Epo HL DHTKRF CYcq Yp WG

Www.Medicalstudyzone.
comPathology Revision 1 01 1
PATHOLOGY REVISION 1 ----- Active space -----
Normal Smears 00:00:14
WBC
Granulocytes Agranulocytes
Neutrophil Eosinophil Basophil Lymphocyte Monocyte
Peripheral smear : 00:00:34
Usually contains only mature cells.

• 3-5 lobes.
Platelet Neutrophil • Granules in
cytoplasm.
RBC
Eosinophil
Round cell with
central 1/3 rd • Binucleate
pallor. (Spectacle
shaped).
Monocyte • Brick red
granules.
• Largest WBC.
• Horse shoe shaped
Lymphocyte Basophil
nucleus.
• Smallest WBC. Nucleus obscured by
• Small central blue granules.
nucleus.
Bone marrow (BM) examination :
Bone marrow aspirate :
Contains mature and immature cells.
Cells
Fat globules
Pathology Revision • v1.0 • Marrow 6.5 • 2023

Www.Medicalstudyzone.com
This PDF was created and uploaded by

www.medicalstudyzone.com which is one the
biggest free resources platform for medical
students and healthcare professionals. You can
access all medical Video Lectures, Books in PDF
Format or kindle Edition, Paid Medical Apps and
Softwares, Qbanks, Audio Lectures And Much
More Absolutely for Free By visiting our Website
https://medicalstudyzone.com all stuff are free
with no cost at all.
Furthermore You can also request a specific

Book In PDF Format OR Medical Video Lectures.
2 01 Pathology
----- Active space -----

Bone marrow biopsy :
Cells
RBC
Fat
Bony trabeculae
Bone marrow biopsy
Note :
% cellularity = (100 - Age of the patient).
Bone marrow needles :
Bone marrow needles
Salah’s needle Klima needle Jamshidis needle
Can do aspiration
Side screw present and biopsy using
the same needle
M/C site of bone marrow examination :

• In adults : ASIS or PSIS or Iliac crest.
• In children : Anterior surface of the tibia or shin of tibia.
ASIS : Anterior Superior Iliac spine PSIS : Posterior Superior iliac spine
On aspiration → Dry tap → Then do bone marrow biopsy.

Causes of dry tap
Aplastic anemia Myelofibrosis Hairy cell leukemia AML-M7

Www.Medicalstudyzone.comPathology Revision 1 01 3
WBC Disorders 00:10:20 ----- Active space -----
A. Non Neoplastic Disorders :

Normal TLC : 4,000 - 11,000/mm3.
• Neutrophils : 40-70 %
• Lymphocytes : 15-40 %
• Monocytes : 2-8 %
• Eosinophils : 1-6%
• Basophils : <1%
Note : Increase in TLC (Leukocytosis) → Indicative of infection.
Acute infection
1. Neutrophilia Bacterial infection
Tissue necrosis
Viral infection
2. Lymphocytosis Chronic infection
Tuberculosis
3. Basophilia Myeloproliferative disorder : CML
Allergic reactions (Hay fever, asthma)

Parasitic infection (Hemlinthic)
4. Eosinophilia Malignancy (Hodgkins lymphoma)
Tropical pulmonary eosinophilia
Chronic infection
Inflammatory bowel disease
5. Monocytosis
Rickettsia
Malaria
Extra edge information :

In sepsis :
• Toxic granules.
• Dohle bodies.

4 01 Pathology
Toxic granules Dohle bodies
Thick coarse blue granules Patches of dilated endoplasmic

reticulum
Hypersegmented neutrophils Hyposegmented neutrophils
Hypersegmented neutrophil Hyposegmented neutrophil

(≥ 5 lobes) (<3 lobes)
Seen in Megaloblastic anemia Psuedo pelger huet cell : Seen

(Vitamin B12 deficiency). in Myelodysplastic syndrome.
B. Neoplastic Disorders
Leukemia Lymphoma
(Malignant cells/problem in bone (Has more systemic involvement
marrow or peripheral blood). : LN, Tissues, Spleen).
Acute Chronic Hodgkins Non Hodgkins

lymphoma lymphoma
ALL AML CML CLL

Acute leukemia : 00:21:31 ----- Active space -----

Diagnostic criteria :
• WHO criteria : > 20 % blasts in the peripheral blood or bone marrow.
• FAB criteria : > 30 % blasts in the peripheral blood or bone marrow.
• Exception : Diagnosis can be made even if blast count < 20 % if
Any one of the 3 present
t(15:17) t(8:21) Inv 16
Lymphoblast vs myeloblast :
Lymphoblast Myeloblast
Cell size Small Large
Cytoplasm Scanty Moderate
Granules in
Absent Present
cytoplasm
Auer rods Absent May be present
Faggot cells Absent May be present
Coarse or clumped up Opened up or homogenous
Chromatin
(dark purple) (Pinkish)
Nucleoli Inconspicuous 2-5 prominent nucleoli
PAS : Positive • Myeloperoxidase +ve.
Staining (Dot/Block positivity) • Non specific esterase +ve.
• Sudan Black B +ve.
Auer rod (Most important Cytoplasm :

morphological feature) • Scanty.
• No granules.
Opened up chromatin
Prominent nucleoli Coarse chromatin
Myeloblast Lymphoblast
Myeloblast markers :
CD 13, CD 33, CD 117, MPO +ve.

6 01 Pathology

1. ALL (Acute Lymphoblastic Leukemia) : 00:30:49
Common in younger age group : 2-9 yrs.
C/F :
Hb / TLC Platelet Organ involvement
• Anemia. Increased risk of Bleeding • Hepatosplenomegaly.
• Fatigue. infection. tendency. • CNS, testis, lymph node
can also be involved.
Classification of ALL :
• FAB classification : Based on the morphology (L1, L2, L3)..
Note : Practically difficult to differentiate ALL-L2 from AML.
• WHO Classification :
B- ALL T- ALL
more common. Less common.
Better prognosis. Poor prognosis.
Usually seen in children. Usually seen in adults.
Mediastinal involvement : Absent. Mediastinal involvement : Present.
Loss of function mutation : Gain of function mutation :
• PAX 5. • NOTCH 1 gene.
• E2A.
• RUN X1.
• EBF gene.
• t(12;21).
Peripheral smear : > 20 % lymphoblast
Investigations Special Stain : PAS +ve (Dot and block)
B-ALL CD 19, CD 20, CD 22, PAX 5, TdT

Markers
T-ALL CD 1 , CD 2, CD 3, CD 5, CD 7
IOC : Flow Cytometry.

Peripheral smear- ALL : ----- Active space -----
Hand mirror cells

(Cytoplasmic protrusion) seen in ALL
Hand mirror cells
Note :
AML-M6 is also PAS positive but diffuse PAS +ve as compared to ALL which
shows block/dot positivity.
Prognostic factors :
Feature Good prognosis Bad Prognosis
Age 2-9 yrs <1 yrs, >10 yrs
Sex Males Females
Race Whites Blacks
FAB type L1 (Best prognosis) L2, L3
WHO type B-ALL T-ALL
Organ involvement :
• CNS Not involved Involved
• Testis
• Lymph node
Hyperdiploidy
Hypodiploidy
Cytogenetics (M/C cytogenetic abnormality in ALL).
Trisomy 4, 7, 10 /t(12;21) t(9;22)
Leukocyte count TLC <1,00,000/ml TLC >1,00,000/ml
2. AML (Acute Myeloid Leukemia) : 00:41:33
Average age : 15-39 years.

Features similar to ALL.
Additional features in AML
Gum bleeding/hyperplasia Chloroma DIC

8 01 Pathology

Chloroma :
• In myeloblastoma/granulocytic sarcoma.
• MPO : +ve.
• M/C site : Orbit.
• Color : Greenish.
• Arbiskov cells : Monocytes in chloroma.
Chloroma : Soft tissue
involvement
FAB classification : Based on cell type and degree of differentiation (morphology

of the blast).
FAB classification
M0 Undifferentiated.
M1 AML with minimal maturation.
M2 AML with maturation.
M3 Acute promyelocytic leukemia.
M4 Acute myelomonocytic leukemia.
M4 eos Acute Myelomonocytic leukemia with eosinophilia.
M5 Monocytic leukemia.
M6 Acute erythroid leukemia.
M7 Acute megakaryocytic leukemia.
Salient features :
AML type Salient features
• M/C FAB type.
AML M2 • Translocation : t(8:21).
• M/C associated with chloroma.
• Translocation : t(15:17).
• Associated with DIC.
AML M3 • Maximum Auer rods.
• Rx : All trans retinoic acid or arsenic trioxide.
• Best prognosis.
• Associated with gum bleeding.
• Associated with leukemia cutis.
AML M4, M5
• Non specific esterase +ve.
• AML M4 : Inv 16.
• Also called Di Guglielmo disease.
AML M6
• Diffuse staining with PAS.
• Least common.
• CD 41, CD 61 : +ve.
AML M7 • Associated with Down’s syndrome.
• Associated with myelofibrosis (D/t platelet derived growth factors)
→ Dry tap.

Auer rod Faggot cell MPO positivity in Myeloblast
Criss cross pattern of auer rods
Myeloproliferative Disorders 00:50:29
1. Chronic Myeloid Leukemia :

Middle age to elderly
Massive splenomegaly on clinical examination.
Pathogenesis :
95 % cases :
t(9;22) Philadelphia chromosome
BCR-ABL fusion transcript: 22 kDa
Constitutive Activation of tyrosine kinase
Myeloproliferation
inhibit
CML
Imatinib mesylate ( Gleevac)
Formation of BCR- ABL fusion transcript

10 01 Pathology

Diagnostic criteria of CML in accelerated phase
Persistent spleen size Peripheral Cytogenetic Blast 10-19% in

Thrombocytopenia and WBc blood basophil evidence of blood and/or
(<100 x 109) unrelated to unresponsive >20%. clonal bone marrow.
therapy. to therapy. evolution.
(OR)
Persistent
Thrombocytosis
(>1000 x 109) unresponsive
to therapy.
Note :
Investigations : Massive splenomegaly
• Peripheral smear : causes in India :
• Malaria.
• Kala Azar.
All stages of
myeloid • CML.
maturation • Polycythemia vera.
• Myelofibrosis.
Basophilia
• Gauchers disease.
• Hairy cell leukemia
Peripheral smear looks more like a bone marrow
• Bone marrow aspirate : Contain Pseudo gaucher cells + Sea blue histiocytes.
Pseudo gaucher cells
• FISH : Investigation of choice.
Normal
BCR- ABL fusion (Fusion of red and green)

• NAP Score : Neutrophil Alkaline Phosphatase. ----- Active space -----

a. Normal score : 40-100.
b. Decreased in CML.
Decreased NAP score
Paroxysmal nocturnal hemoglobinuria Myelodysplastic syndrome
Increased NAP Score
Stress Infection Leukemoid reaction Pregnancy Myeloproliferative

disorders other
than CML
Rx of choice in CML : Bone marrow transplantation.
2. Polycythemia vera : 00:59:51
Major criteria Minor criteria

1. Hb 1. Subnormal serum
• > 16.5 g/dl in men. erythropoetin levels.
• > 16.0 g/dl in women.
2. Bone marrow trilineage myeloproliferation
with pleomorphic megakaryocytes.
3. Presence of JAK2 mutation.
Diagnostic criteria : All 3 major criteria or first 2 major + 1 minor criteria
Note :
All other myeloproliferative disorders except CML, the translocation seen is
JAK2 V617F translocation.
3. Essential Thrombocytosis : 01:02:05
Diagnostic criteria : All 4 criteria needed for diagnosis.

• Platelet count ≥ 4,50,000.
• JAK2 V617F mutation or no evidence of reactive thrombocytosis.
• Not meeting WHO criteria for other MPN
• Megakaryocytic proliferation with large and mature morphology; no or little
granulocyte or erythroid proliferation.
12 01 Pathology

4. Myelofibrosis : 01:02:52
Diagnostic Criteria :
Major criteria Minor criteria

1. Atypical megakaryocytic hyperplasia with 1. Leukoerythroblastosis.
reticulin/collagen fibrosis (Due to PDGF 2. Elevated LDH.
elaboration). 3. Anemia.
2. Exclusion of WHO criteria for other 4. Palpable splenomegaly.
myeloproliferative disorders (CML, MDS,
MPDS or PV).
3. JAK2V617F or other clonal markers, if not
rule out other clonal markers.
Investigations :
Peripheral smear Reticulin stain : Silver stain
Tear drop cells (Dacrocytes) Bony Fibrosed fibres :

trabeculae Black
Note :
Leukoerythroblastic blood picture :
Leukoerythroblastic blood
picture also seen in :
• Myelofibrosis.
• Hairy cell leukemia.
• AML-M7.
• Space occupying lesions
of BM.
• Metastatic cancer.
Both immature myeloid and erythroid • Myelopthisic anemia.
cells in blood picture.
Differences between Hodgkin & Non-Hodgkin lymphoma :

Hodgkin Lymphoma Non-Hodgkin Lymphoma
Lymph node Single group of axial nodes (Cervical, Multiple peripheral lymph
involvement mediastinal, para-aortic). nodes.
Spread Contiguous. Non-contiguous.
Mesenteric nodes,
Rarely involved. Commonly involved.
Waldeyer’s ring
Extra nodal
Uncommon. Common.
involvement
Reed Sternberg (RS)
Present/Characteristic. Not present.
cells
Hodgkin’s Lymphomas (HL) 00:01:40
Age : Bimodal distribution (15-20 years & elderly).

C/F : Cervical lymph node enlargement (M/c).
B symptoms : Fever (Pel Ebstein : waxing & waning), night sweats & wt. loss.
Mediastinal involvement → Nodular sclerosing HL (Also seen in T-ALL).
Itching can be present.
Reed-Sternberg (RS) cell :
Reed
sternberg cells
CMV inclusions
Normal
lymphocyte
Popcorn /
LH RS cell
Lacunar RS cell (Lympho Histiocytic)
(Empty space seen)
Nodular sclerosis HL NLPHL

14 02 Pathology

Owl’s eye appearance : Large binucleate cells with prominent eosinophilic macro
nucleoli.
Note : Owl’s eye appearance is also seen in CMV inclusions
Types of HL :
Classical HL Non classical HL
Nodular Mixed Lymphocyte Lymphocyte Nodular lymphocyte
Types
sclerosis cellularity rich depleted predominant HL
M/C M/C in HIV
- -
globally. India. associated.
M:F M=F M>F
Age Young. Biphasic. Elderly. Young.
Lacunar
LH (Popcorn) variant
RS cell variant Present. Present. Present.
seen.
seen.
CD 15, CD 30 : -
Markers CD 15, CD 30 : +
CD 20, BCL 6, EMA : +
EBV Uncommon. Associated. Never associated.
Prognosis 2nd best. Very good. Worst. Best.
Non- Hodgkin’s Lymphomas (NHL) 00:13:10
A. Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma

(SLL) :
When lymph nodes (LN) become involved in CLL → SLL.
Pathogenesis : Del 13q/11q/17p; trisomy 12. Normal lymphocytes
C/F : Elderly (60-70 years) patient with
painless lymphadenopathy & Auto Immune
Hemolytic Anemia (AIHA).
Investigations :
• Absolute lymphocytes > 5000/mm3.
• Peripheral Smear (PS) : Smudge cells/ Smudge
parachute cells/basket cells. cells
• LN biopsy : Proliferation centers
(Pathognomic finding).
• Flow cytometry (IOC) :
Markers : CD 5+, CD 23+, CD 200+.

CLL ALL ----- Active space -----
Seen in young patients. Seen in elderly

PS : Blast cells PS : Normal lymphocytes, smudge cells
CLL CML
Lymphocytes with similar morphology Lymphocytes with different morphologies (College
(Convent girl appearance). girl/ Garden party appearnce).
B. Burkitt’s Lymphoma : 00:18:20

• Disorder of B cells.
• Usually seen in children. Note :
Pathogenesis : n-myc : Neuroblastoma
1. t(8 : 14) or gain of function in c-myc. L-myc : Lung cancer
2. t(2 : 8), t(8 : 22).
Markers : CD 19, CD 20, BCL 6 : +.
Types
African/Endemic Sporadic HIV associated

EBV associated. 15-20 % EBV
Site : Anywhere
Site : Jaw, mandible. associated.
Site : GIT, peritoneum.
HPE of LN biopsy : Starry sky appearance.
Lymphocytes (SKY)
Histiocytes → Macrophages (STAR)
Starry sky appearance

C. Hairy Cell Leukemia : 00:22:00
Disorder of B cells.
Pathogenesis : BRAF V600E mutation.
C/F : Massive splenomegaly.
Investigations :
• CBC : Pancytopenia (Myelofibrosis d/t ↑ Platelet Derived Growth Factor).
• PS : Hairy cells (Cells with hair-like projections → Best seen with phase
contrast microscope).
• Bone marrow (BM) aspiration : Dry tap.
• BM biopsy : Fried egg/honey comb appearance.
• Special stain : Tartrate resistant acid phosphatase (TRAP) +.
• Markers : Annexin A1, CD 25, CD 11c, CD 103 : +.
16 02 Pathology

Note:
• Conditions with BRAF V600E mutation :
1. Hairy cell leukemia.
2. Langerhans cell histiocytosis.
3. Papillary carcinoma thyroid.
4. Pilocytic astrocytoma.
• TGF b is the most fibrogenic cytokine.
• Fried egg appearance also seen in : Fried egg appearance
Oligodendroglioma.
• Annexin 5 is a marker for apoptotic cells.
Hairy cells
Peripheral smear Electron microscopy of hairy cell leukemia

D. Other B cell NHLs :
Follicular Mantle cell Burkitt’s Marginal zone
Features DLBCL
Lymphoma Lymphoma lymphoma Lymphoma
M/C indolent M/C NHL in
Incidence - - -
NHL in the west. India & globally.
BCL6
t(14 : 18), t (8 : 14),
Pathology t(11 : 14). dysregulation, t(11 : 18).
MLL gene. t (2 : 8).
t(14 : 18).
Follicles, small
Small - medium Diffuse Lympho-
centrocytes,
Histology irregular - patterned big, epithelial
larger
lymphocytes. pleomorphic cell. lesions.
centroblasts.
Cyclin D1 +, CD 5+, CD 19 +, CD CD 19 +, CD 20 +,
Markers BCL 2 + CD 43+
CD 23-, SOX 11 + 20+, BCL 6 + BCL 6 +
Seen in H.
pylori
Para-
EBV infection,
trabecular Lymphomatoid
Others associated, - Hashimoto’s
lymphoid polyposis.
jaw/GIT lesion. thyroiditis,
aggregates.
Sjogren’s
syndrome.
Note : CLL is CD5+. CD23+.

E. T cell NHLs : 00:30:33

Mycosis Fungoides /Sezary

Adult T cell Anaplastic Large Cell
Features syndrome / Cutaneous T cell
Leukemia Lymphoma (ALCL)
Lymphoma
Pathology HTLV 1. - ALK gene on ch 2p.
Flower cells/clover
Histology Sezary cells (cerebriform nuclei). Hallmark cells.
leaf cells.
Note : ALK gene mutation is seen in ALCL, Adenocarcinoma of lung,
Inflammatory myofibroblastic tumors.
Plasma Cell Disorders 00:31:35
Plasma Cell :
• Oval cell.
• Eccentric nucleus.
• Cart wheel/clock face chromatin.
• Perinuclear hoff/halo.
A. Multiple Myeloma (MM) :

Tumour of post germinal center B cells.
C/F : • Middle-aged to elderly.
• Fever, pallor, fatigue, abdominal pain.
• Bone pains, pathological fractures.
• ↑ Risk of infections (M/c cause of death).
Diagnostic Criteria of MM :
1. Clonal bone marrow plasma cell ≥ 10 %. OR
Biopsy proven bony or extramedullary plasmacytoma.
Plus
Positive malignancy biomarkers :
• Clonal BM plasma cells ≥ 60%.
• Involved : Uninvolved serum free light chain ratio > 100.
• > 1 focal lesion on MRI.
2. A Myeloma OR
defining event Evidence of end organ damage d/t underlying plasma cell disorder :
• Hypercalcemia
• Renal insufficiency
CRAB features
• Anaemia
• Bone lesions

18 02 Pathology

Investigations :
• PS : RBC rouleaux formation (Stack of coins)
d/t ↑ ESR; no plasma cells seen.
• BM aspiration :
1. Flame cell (Flame shaped immunoglobulin).
2. Mott / Morula cell (Grape like cluster).
3. Russell body.
4. Dutcher body (Intranuclear Ig inclusion). Rouleaux formation
Russel body Dutcher

(intracytoplasmic body
Immunoglobulin)
Mott / Morula cell Russel body Dutcher body
Note : Ig increase : IgG (M/c) > IgA > IgM.

rody
• X-ray findings : Lytic/punched out lesions.
M/c involved bones : Lumbar vertebra.
• Biochemical tests :
1. ↑ S. Calcium → Metastatic calcification.
2. Abnormal kidney function test.
3. Reversed S. Albumin/Globulin ratio. Lytic
lesions
4. ↑ ESR → Rouleaux formation.
5. ↑ S. b2 microglobulin : Most important prognostic factor in MM.
6. Bence Jones proteinuria : Not very specific; Light chain Igs which
precipitate at 40-60°C, disappear on boiling & reappear on cooling.
7. Markers : CD 138 (syndecan 1), CD 56.
• Protein electrophoresis (IOC) :
g-globulin peak seen

B. Other Plasma Cell Disorders: 00:41:07 ----- Active space -----
Disorders Features
>20% plasma cells in the blood
Plasma cell Leukemia
(Normally, no plasma cells seen in blood).
• BM plasma cells >10%.
Smoldering / Asymptomatic
• No CRAB lesions.
myeloma
• S. monoclonal M protein >3gm/dl.
• M/c plasma cell abnormality.
Monoclonal gammopathy of • BM plasma cells <10%.
undetermined significance (MGUS) • No myeloma defining events.
• S. IgG <3gm/dl.
• Increased IgM.
Waldenstrom’s Macroglobulinemia /
• Other features similar to MM.
Hyper viscosity syndrome
• A/s with lymphoplasmacytic lymphoma.
• Associated with MYD 88 mutations.
Langerhans Cell Histiocytosis (LCH) 00:43:16
Proliferation of immature dendritic cells (Langerhans cells).

Pathogenesis : BRAFV600E mutation.
C/F : Hand Schuller Christian disease → Triad of :
• Diabetes insipidus.
• Exophthalmos.
• Calvarial bone defects.
Tennis racket
Investigations : appearance
• Biopsy finding : Coffee bean nuclei.
• Electron microscopy (EM) :
Tennis racket appearance, Birbeck granules. Birbeck
granules
• Markers : Langerin, S-100, CD 1a.
Note : Coffee bean nuclei seen in

• Papillary carcinoma thyroid.
• LCH.
• Brenner’s tumor.
• Chondroblastoma.
• Granulosa cell tumor of ovary.
Coffee bean nuclei

20 02 Pathology
----- Active space ----- Revision Tables 00:46:45
Features ALL AML CLL/SLL CML

Age 2 - 9 years 15 - 39 years Elderly Elderly
CNS, testis & LN
involvement Gum bleeding, Lymphadenopathy, Massive
C/F
Hepatosplenomegaly, chloroma, DIC AIHA splenomegaly
pancytopenia
All stages
> 20% ↑ Lymphocyte count, of myeloid
PS > 20% lymphoblasts
myeloblasts smudge cells maturation,
basophilia
MPO,
Stains PAS + Sudan black B, - -
oil red O
B ALL : CD 19, CD 10,
PAX 5 +
CD 13, CD 33, CD
Markers T ALL : CD 1, CD2, CD CD 5, CD 23 + -
117, MPO +
5, CD 7 +
Both : TdT +
t(8 : 21),
Trisomy 12,
Path - t(15 : 17) t(9 : 22)
del 13q, 17p
inv 16
BM findings in diseases :
Disorder BM Aspiration BM biopsy

ALL >20% Lymphoblasts >20% Lymphoblasts
AML >20% Myeloblasts >20% Myeloblasts
CLL ↑ Lymphoid cells ↑ Lymphoid cells
Pseudo gaucher cells,
CML -
Sea blue histiocytes
Hairy cell leukemia Dry tap Fried egg appearance
LCH - Coffee bean nuclei
Myelofibrosis Dry tap ↑ Fibrosis
Multiple myeloma ↑ Plasma cells -
Aplastic anemia Dry tap ↑ Fat
Megaloblasts : Erythroid
Megaloblastic Anemia precursors with sieve like -
chromatin

RBC 00:00:35
Peripheral smear :
Peripheral smear
Platelet
Eosinophil
Neutrophil
Basophil
RBC (Central 1/3rd pallor)
Lymphocyte
Monocyte
• Stains for peripheral smear : Romanowsky stains.
1. Geimsa stain.
2. Leishman stain.
• Ideal shape of peripheral smear on gross examination : Tongue shaped.
• Anisocytosis : Variation in the size of RBCs.
• Poikilocytosis : Variation in the shape of RBCs.
RBC series :
Proerythroblast
Cell size
Early normoblast (Basophilic) Nuclear size
Intermediate normoblast (Polychromatic)
Late normoblast (Orthochromic)
Reticulocyte No nucleus
RBC
• 1st stage of RBC with no nucleus : Reticulocyte.

• Hb production starts in : Proerythroblast.
• Hb is first seen/visualized in : Intermediate normoblast.

22 03 Pathology

Reticulocytes :
Mature RBC
Reticulocyte
(Bluish meshwork like : Ribosome/RNA)
Supra vital stain
• Staining process : Supra vital staining.

• Supra vital stains : Brilliant cresyl blue, New methylene blue.
• Normal reticulocyte count : 0.5% - 1.5%.
• Conditions :
Reticulocytosis Reticulocytopenia
1. Hemolytic anemia. 1. Aplastic anemia.
2. Acute blood loss.
3. Response to Rx in iron/
B12 deficiency anemia.
Patient Hb
• Corrected reticulocyte count = Retic % x Normal Hb for that age
RBC abnormalities on peripheral smear 00:13:00
Peripheral smear finding Conditions

1. Microcytic hypochromic RBC’s :
• S : Sideroblastic anemia, lead poi-
soning.
• I : Iron deficiency anemia.
• T : Thalassemia.
• A : Anemia of chronic disease (Nor-
mocytic normochromic anemia is
Microcyte (MCV < 80 fL)
(Central pallor > 1/3rd ) also seen).

Peripheral smear finding Conditions ----- Active space -----
2. Macrocytic RBC’s :
• L : Liver disease.
• H : Hypothyroid.
• M : Megaloblastic (B12/folate defi-
ciency anemia).
• C : Cytotoxic drugs.
Macro ovalocyte
3. Pencil cells : • Iron deficiency of anemia.
4. Bite cells :
• G6PD deficiency.
Bite cells
5. Spherocytes :
• Hereditary spherocytosis.
• Autoimmune hemolytic anemia
(M/c cause of spherocytosis).
• Blood transfusion reaction.
• Burns.
Spherocyte
(Absence of central pallor)
6. Burr cell/echinocyte :
• Chronic renal failure.

• Uremia.
• Liver disease.
Burr cell (Blunt

projections)

24 03 Pathology
----- Active space ----- Peripheral smear finding Conditions

7. Spurr cell/acanthocyte :
• Abetalipoproteinemia.
Spur cells (Pointed

spicules )
8. Sickle cell :
• Sickle cell anemia.
Sickle cells
9. Target cell/codocyte :
• Thalassemia.
• Liver disease.
• Iron deficiency anemia.
Target cell
10. Schistocytes/helmet/fragmented
RBC : • Microangiopathic hemolytic ane-
mia (MAHA) :
1. HUS
2. TTP
3. DIC
• Prosthetic cardiac valves.

Peripheral smear finding Conditions ----- Active space -----
11. Tear drop cells/dacrocyte :
• Myelofibrosis.
• Myelodysplastic syndrome (MDS).
• Myelophthisic anemia.
Tear drop cells
12. Heinz bodies/bite cells :
Heinz bodies (Denatured ppt. of Hb)

(Seen on supravital stain)
13. Howell jolly bodies :
• Asplenia.
• Megaloblastic anemia.
• Thalassemia.
Howell jolly bodies
(Remnant of nucleus)
14. Pappenheimer bodies : D/t precipi-

• Sideroblastic anemia.
tation of iron.
15. Rouleaux formation : • Multiple myeloma.
16. Cabot ring :
• Megaloblastic anemia.
• Thalassemia.
Cabot ring (Fig.
of 8 formed from
microtubules)
17. Polychromasia : • Hemolytic anemia.

26 03 Pathology
----- Active space ----- Peripheral smear finding Conditions

18. Basophilic stippling :
• Sideroblastic anemia.
• Lead poisoning.
• Thalassemia.
• Megaloblastic anemia d/t B12 de-
ficiency.
Basophilic stippling
19. Stomatocytes : • Hereditary stomatocytosis.
WBC abnormalities on peripheral smear 00:25:20
Peripheral smear finding Conditions

1. Hypersegmented neutrophil : > 5 lobes. • Megaloblastic anemia.
2. Bilobed neutrophil : Pseudo Pelger Huet • MDS.
cell. • Myelofibrosis.
3. Toxic granules : Dark blue granules.
• Sepsis.
4. Dohle bodies : Patches of dilated ER.
Parasites on peripheral smear 00:33:34
Ring form of
Plasmodium
Microfilaria
Microfilaria Ring form of Plasmodium
Gametocyte of
P. falciparum
LD bodies (seen
in Leishmaniasis)
Gametocyte of P. falciparum
LD bodies : Bone marrow aspirate of a pt. with

massive splenomegaly.

RBC indices 00:00:12
Index MCV MCH MCHC RDW Mentzer index

Definition Average Average mass Average Hb Degree of MCV/ RBC
volume (size) of Hb per red concentration anisocytosis count
of red cells. cell. in a volume of (variation of
packed red red cell size).
cells.
Normal 82 - 96 fL 27 - 32 pg 33 - 37 gm/dl 11 - 14% 13
Significance Microcytic Hypochromic ↑sed in To diff b/w < 13 :
Macrocytic Normochromic Hereditary thalassemia Thalassemia.
Normocytic spherocytosis (Normal)
& iron deficiency > 13 : Iron
anemia (↑sed). deficiency
anemia.
Causes :
Microcytic Normocytic Macrocytic
(MCV < 80 fL) (80 - 100 fL) ( > 100 fL)
• Sideroblastic anemia, • Aplastic anemia. • Liver disease.
lead poisoning. • PNH. • Hypothyroidism.
• Iron deficiency anemia. • Hemolytic anemia. • Megaloblastic anemia
• Thalassemia. • Anemia of chronic disease. d/t B12 deficiency.
• Anemia of chronic disease. • Cytotoxic drugs.
Anemia 00:06:07
↓sed Hb mass/↓sed Hb according to patients age & sex.
Classification of anemia :
1. Hypoproliferative anemia :
• Aplastic anemia.
• Pure red cell aplasia (PRCA).
• Myelophthisic anemia.
2. Deficiency anemia :
• Vit B12 deficiency anemia.
• Iron deficiency anemia.
3. Hemolytic anemia.
28 04 Pathology

Hypoproliferative anemia 00:07:28
1. Aplastic anemia :
D/t to bone marrow suppression (No cells in bone marrow).
H/o of cytotoxic drugs, radiation exposure or viral infection.
C/f :
Anemia : Pallor, fatigue.
Leucopenia : Risk of infections.
Thrombocytopenia : Petechiae, purpura, bleeding.
No splenomegaly.
On investigation :
Pancytopenia
Bone marrow aspiration : Dry tap.
Bone marrow aspirate in
Bone marrow Bx (IOC) : ↓sed cellularity & ↑sed fat. Aplastic anemia
2. Pure red cell aplasia :

↓sed erythroid progenitor/RBC, but TLC & platelet count is normal.
Associated with :
• Parvo virus B19 infection.
• Thymoma.
3. Myelophthisic anemia :
Any space occupying lesion of bone marrow (Like metastasis, TB granuloma).
Clinical picture :
• Tear drop cells on peripheral smear.
• Dry tap on bone marrow aspirate.
Hemolytic anemia 00:13:58
Caused d/t excessive destruction of RBC.

Difference b/w intravascular & extravascular hemolysis :
Feature Intravascular Extravascular
Hepatosplenomegaly +/- ++
Hemoglobinuria + -
Hemosiderinuria + -
S. Haptoglobin Decreased Decreased or normal

General C/f & investigation in intravascular & extravascular hemolysis :

General clinical features Investigations
• Pallor • ↓sed Hb
• Jaundice • Reticulocyte count ↑sed
• Splenomegaly (M/c in extravascular hemolysis) • Unconjugated bilirubin ↑sed
• Gall stones (Pigmented type) • LDH ↑sed
Causes of intravascular & extravascular hemolysis :
Intravascular hemolysis Extravascular hemolysis
• Paroxysmal nocturnal hemoglobinuria (PNH). • Hereditary spherocytosis.
• Paroxysmal cold hemoglobinuria (PCH). • Sickle cell anemia.
• Microangiopathic hemolytic anemia (MAHA). • Thalassemia.
• G6PD deficiency. • Autoimmune hemolytic
• Infections. anemia (AIHA).
• Prosthetic cardiac valves.
Extravascular hemolysis :
Features of extravascular hemolysis :
Feature Hereditary spherocytosis G6PD deficiency Sickle cell anemia
Inheritance AD XLR AR
M=F M>>F M=F
Patho- M/c protein Defect of G6PD : Affects Missense point mutation :
genesis defect : Ankyrin. HMP shunt → ↑H2O2 → Glutamic acid is replaced
Free radical injury → by Valine at 6th position
Most severe Hemolysis of β chain
deficiency : Spectrin. (HbS production).
Clinical • Splenomegaly • Episodic haemolysis • Crisis (Microvascular
features • Pigment gall stones • No splenomegaly occlusion) like
• No gall stones bone pain, fracture,
• Haemoglobinuria chest pain
• H/o chronic infection,
drugs/fava beans intake
Hemolysis Extravascular Both Extravascular
P/S Spherocytes Bite cells, Heinz bodies Sickle cells
Special Osmotic fragility Methaemoglobin Sickling test,
test reduction test Hb electrophoresis, HPLC
Best test Flow cytometric analysis HPLC
Rx Splenectomy Avoid oxidative stress • Hydroxyurea (↑sed
HbF : Reduce sickling).
• Stem cell transplant.
AD : Autosomal dominant ; AR : Autosomal recessive ; XLR : X linked recessive.

30 04 Pathology

Note : Heinz bodies can only be visualized on supravital stains.
Images Description
1. X ray skull
Crew cut appearance
• Due to extramedullary hematopoisis.
• Seen in thalassemia > Sickle cell
anemia.
2. Hb electrophoresis :
Adults :
Hb A : α2 β2 (95% - 97%)
Hb F : α2 γ2 (< 1%)
Hb A2 : α2 δ2 (2% - 3.5%)
3. HPLC
High performance liquid chromatography :
• Best investigation for
hemoglobinopathies.
• It tells about the % of various Hb.
Thalassemia :
Autosomal recessive.
Male = Females.
Thalassemia, sickle cell anemia, G6PD deficiency provide protection against
P. falciparum.
Types of thalassemia :
Beta thalassemia Alpha thalassemia
Cause Reduced β chain synthesis Reduced α chain synthesis
Gene Ch 11 Ch 16
Defect Mostly mutations Mostly gene deletions
Incidence M/c Less common

Beta thalassemia : ----- Active space -----

Types of beta thalassemia :
β thalassemia β thalassemia
Feature β thalassemia major
intermedia minor
Synthesis of
Markedly reduced Moderately reduced Mildly reduced
beta chain
• Severe pallor
• Jaundice • Mild pallor
• Pallor
• Hepatosplenomegaly • Asymptomatic
C/F • Jaundice
• H/o repeated blood • No response to
• Hepatosplenomegaly
transfusion iron therapy
• Chipmunk facies
Hb 3 - 5 gm% 5 - 8 gm% 8 - 10 gm%
• Microcytic hypochromic RBC’s
• Many target cells
P/S Few target cells No target cells
• Basophilic stippling
• Cabot ring
MCV, MCH, MCV, MCH,
All most Normal/
RBC indices MCHC :↓ MCHC : ↓
slightly ↓sed
RDW : Normal RDW : Normal
Iron profile Iron ↑sed (D/t to transfusion) Normal Normal
Hb
↑sed HbF Both ↑sed HbA2 3.5 – 9%
electrophoresis
HPLC ↑sed HbF Both ↑sed ↑sed HbA2
Thalassemic/Chipmunk facies :
Frontal bossing
• D/t extramedullary hematopoiesis
Flat nasal bridge
in skull & facial bones.
Patterns of hemoglobin electrophoresis
Origin HbA2 HbF HbA
Chipmunk facies
Normal
Beta thalassemia trait
Beta thalassemia major

HbS
Sickle cell trait
Sickle cell anemia

32 04 Pathology

Alpha thalassemia :
Types of alpha thalassemia :
Major
Disorder Silent carrier Minor Hb H disease
(Fetal hydrops )
α α/--
Genotype α α/ α - α -/- - - -/- -
OR α -/ α -
MCV Normal Low Low Low
Anemia None Mild Moderate Fatal
• 5% - 30% HbH • Hb Barts & HbH
Hb < 3% Hb Barts 3% - 8% Hb in adults. present.
electrophoresis at birth Barts at birth • 20% - 40% Hb • HbA, HbF & HbA2
Barts at birth are absent.
Golf ball inclusions : Seen in Hb H disease.
Note : Structures seen on supra vital staining :

• Reticulocyte.
• Heinz bodies.
Golf ball inclusions
• Golf ball inclusions.
Investigations in Hb disorders :
• Screening : Hb electrophorosis.
• IOC : HPLC.
• Definitive Dx : Globin gene sequencing.
Intravascular hemolysis :
Paroxysmal nocturnal hemoglobinuria (PNH) :
Only acquired intra corpuscular defect.
Pathogenesis :
Mutation in PIGA gene (Phosphatidyl inositol glycan A)
Reduced synthesis of complement regulatory proteins

CD 55 : Decay accelerating factor (DAF)
CD 59 : Membrane inhibitor of reactive lysis (MIRL)
↑sed complement activation → Intravascular hemolysis

Features :
• Pancytopenia with hypercellular bone marrow.

• Intravascular hemolysis (Nocturnal hemoglobinuria in 30% cases). ----- Active space -----
• Thrombosis (i.e hepatic vein thrombosis).
M/c cause of death : Thrombosis.
Screening test : HAM’s test (Acidified serum lysis test).
Best test : Flow cytometry.
Rx : Eculizumab.
Microangiopathic hemolytic anemia (MAHA) :

Includes :
• Hemolytic uremic syndrome (HUS) : H/o of E.coli O 157 : H7 infection.
• Thrombotic thrombocytopenic purpura (TTP) : Mutation of ADAMTS 13.
• Disseminated intravascular coagulopathy (DIC).
C/f :
• Fever.
• MAHA.
• Thrombocytopenia.
• Renal abnormality (M/c in HUS).
• Neurological abnormality (M/c in TTP).
• Peripheral smear shows schistocytes/helmet cells (Fragmented RBCs).
Deficiency anemia 00:58:08
Iron deficiency anemia (IDA) :

M/c worm causing IDA : Hookworm/Ancylostoma duodenale.
Maximum iron absorption : Duodenum.
Factors influencing absorprtion :
• Increased by : Ascorbic acid, citric acid.
• Decreased by : Calcium, milk, phytates, oxalates, tannates.
Storage form of iron : Hemosiderin.
Transport form of iron : Transferrin.
Master regulator of iron metabolism : Hepcidin (Negative regulator).
H/o GI malignancy in elderly, H/o pica in child.
Plummer Vinson syndrome :

1. Atrophic glossitis.
2. Esophageal webs.
Koilonychia : Spoon
3. IDA. shaped nails in IDA

34 04 Pathology

Iron metabolism :
Investigations in IDA :
P/S : Microcytic hypochromic RBC’s, Pencil cells.
Iron profile :
• S.iron ↓sed.
• S.ferritin ↓sed.
• TIBC ↑sed.
Stains for Iron/hemosiderin : Perl’s stain/Persian blue.
Sideroblastic anemia :
D/t to ↑sed iron overload.
Causes :
• Genetic.
• Anti tubercular drugs like isoniazid.
• Lead poisoning.
On P/S :
Ringed sideroblasts
• Microcytic hypochromic RBC’s. (Blue colour)
• Basophilic stippling (In lead poisoning).
On bone marrow Bx : Ringed sideroblast (Iron granules arranges in ring like
manner around erythroid precursor)
Anemia of chronic disease :

Causes :
• Chronic infections : TB.
• Neoplasms : Multiple myeloma.
• Autoimmune disorders.
• Idiopathic.
Pathogenesis : In chronic infection/neoplasm → ↑sed IL-1, ↑sed IL-6 → ----- Active space -----
↑sed hepcidin → ↓sed iron → Anemia.
On P/S : Normocytic normochromic RBCs > Microcytic hypochromic RBCs.
Differential diagnosis of microcytic hypochromic anemia :

S. Iron S. Ferritin S. TIBC P/S Extra points
RDW ↑
IDA ↓ ↓ ↑ Pencil cells
Mentzer index > 13
Sideroblastic Coarse basophilic Ringed sideroblasts
↑ ↑ ↓
anemia stippling (Bone marrow)
Anemia of
↓ ↑/Normal ↓ - ESR ↑
chronic disease
HbA2 ↑ : 4% - 9%
Thalassemia
Normal Target cells Mentzer index < 13
trait
RDW : Normal
Megaloblastic anemia :
D/t to B12 deficiency.
Site of maximum absorption of B12 : Ileum.
M/c worm causing B12 deficiency anemia : Fish tapeworm/Diphyllobothrium latum.
Causes :
• Veg diet.
• Gastrectomized patients.
• Ileal resection.
C/f :
• Anemia. Knuckle pigmentation
• Beefy tongue.
• Pigmentation of knuckles.
• Neurological complications.
• Pancytopenia with hypercellular marrow.
• ↑sed risk of thrombosis.
Biochemical reactions involving vit B12 :
Reaction involving B12 In B12 deficiency Pathology
↓sed dTMP : Pancytopenia d/t nuclear
1. d UMP d TMP
Thymidine cytoplasm asynchrony.
2. Homocystine Methionine ↑sed Homocystine ↑sed risk of thrombosis.
3. Methyl malonyl coA Succinyl coA Subacute combined
↓sed Succinyl coA
(Used in myelination) degeneration of spinal cord

36 04 Pathology

P/S :
• Macro ovalocytes.
• Hypersegmented neutrophil (>5 lobes).
• Howell Jolly bodies.
• Cabot rings.
On bone marrow aspiration :
Megaloblast (Erythroid precursors with
sieve like chromatin). Bone marrow aspirate : Megaloblasts
Note : Folic acid deficiency anemia : Same as B12 deficiency anemia with
no neurological complication.

Haemostasis 00:00:38
It is interplay of 3 components :
1. Platelets : 1.5-4 lakhs/mL (Normal count).
2. Vascular endothelium.
3. Coagulation cascade.
Primary hemostasis
Step 1 : Platelet adhesion to endothelium.
vWF (Present on endothelium) + GpIb-IX (On platelet).
vwf (On endothelium)
Gp1b-IX (On platelet)

Platelet adhesion Gpllb-IIIa (On platelet)
Step 2 : Platelets aggregate to each other by factor GpIIb-IIIa present on their

surface & form unstable clot.
Blood clot : Aggregation of platelets.
Fibrin + Unstable clot/thrombus : Stable clot/Thrombus.
Platelet aggregation disorders :

Deficiency of factor Disease
GpIb-IX Bernard Soulier syndrome
GpIIb-IIIa Glanzmann thrombasthenia
von Willebrand factor Von Willebrand disease

38 05 Pathology

Secondary hemostasis
The coagulation pathway :
XII : Hageman factor, a serine protease.
Intrinsic pathway XI : Plasma thromboplastin, antecedent serine
protease.
Surface factor IX : Christmas factor, serine protease.
VII : Stable factor, serine protease.
XIII : Fibrin stabilizing factor, a transglutaminase.
PL : Platelet membrane phospholipid.
XII XIIa
XI XIa
Extrinsic pathway
IX IXa VIIa Tissue damage
(VIII, PL, Ca2+)
X Xa X XIII Common
(V, PL, Ca2+) pathway
Prothrombin Thrombin
(Serine protease)
XIII a
Fibrinogen Fibrin Stable fibrin clot
Note : vWF also stabilises factor VIII ( T1/2).

Tests :
a. Extrinsic pathway : Prothrombin time ( in factor VII deficiency).
b. Intrinsic pathway : aPTT/Activated partial prothrombin time ( in
intrinsic factor deficiency).
c. Common pathway factors deficiency : Both PT & aPTT .
Disorders of haemostasis
Bleeding disorder Coagulation disorder
Autosomal mostly. X linked.
Inheritance
Males = Females. M >> F.
Petechiae.
Purpura. Mucosal bleeds.
Clinically
Mucosal bleeds. Ecchymoses.
Prolonged bleeding after injury.

Lab tests Bleeding disorder Coagulation disorder ----- Active space -----
Platelet count
Can be affected. Normal.
Bleeding time
PT
Normal. Can be affected.
aPTT
Immune thrombocytopenic
Example Hemophilia.
purpura (ITP).
Pro-
Plate- Bleed-
Disorder Pathogenesis throm- aPTT Extra points
lets ing time
bin time
Defect of • Platelet
Gp1b-IX aggregation
(Platelet with ristocetin
Bernard Soulier Normal Normal Normal
adhesion is abnormal .
disorder) • Giant platelets.
• Platelet
Defect of aggregation
GpIIb-IIIA with ADP is
Glanzmann’s
(Platelet Normal Normal Normal abnormal.
Thrombasthenia
aggregation) • Bleeding
from umbilical
stump.
• Type 2 hy-
Bone marrow
persenstivity.
aspirate :
• Antiplatelet
ITP Normal Normal Megakaryo-
antibodies
cytes.
against GpIb-
IX/GpIIb-IIIa.
Schistocytes
HUS E. Coli O157:H7,
Normal Normal reticulocyte
(Type of MAHA) Shigella
count.
Schistocytes
TTP Mutation of
Normal Normal reticulocyte
(Type of MAHA) ADAMTS13
count.
Hemophilia A
Deficiency of
(X-linked
factor VIII Normal Normal Normal Factor VIII
recessive)
M>F

40 05 Pathology
----- Active space ----- Pro-

Bleeding
Disorder Pathogenesis Platelets thrombin aPTT Extra points
time
time
Hemophilia B
Factor IX Factor IX
(Christmas Normal Normal Normal
deficiency
disease)
• Factor VIII .
• RIPA
abnormality.
von Willebrand
VwF deficiency Normal Normal • RiCof assay
Disease
(Ristocetin
cofactor) :
Abnormal.
Endothelial
DIC
injury →
(Disseminated • FDP
Activation of
intravascular • D-dimers
coagulation
coagulopathy) :
& fibrinolytic
Type of MAHA.
pathways.
Vitamin K Deficiency of
deficiency factor factor Normal Normal
2, 7, 9, 10.
Vascular
Normal Normal Normal Normal
disorders
RIPA : Ristocetin induced platelet aggregation.
MAHA : Microangiopathic hemolytic anemia.
FDP : Fibrin Degradation Products.
Note :
• M/C cause for Umbilical stump bleeding : Factor x111 deficiency.
• M/C cause of DIC : Obstetric complications like abruptio placenta/septic
abortions.
Types of ITP :
Acute ITP Chronic ITP
Duration <6 months. > 6 months.
Common in Children. Adults.
Preceding h/o Viral infection. No such history.
Steroids &
Treatment Self limiting.
immunosuppressive drugs.

Blood banking 00:16:55 ----- Active space -----
Anticoagulants used :
Anticoagulant Shelf life
CPD (Citrate PO43- dextrose) 21 days
CPD-A (Citrate PO43 dextrose adenine) 35 days
SAG-M (Sodium adenine glucose mannitol) 42 days
Blood components & their storage :

Storage
Blood product Volume Shelf life Use
temp.
Based on
Whole blood 350 mL 2-6 C o
anticoagulant Acute blood loss.
used.
Fresh frozen Multiple coagulation
200 mL
plasma (FFP) factor deficiency.
Cryoprecipitate ≤ -18o C 1 year • Hemophilia A.
(Rich in factor 10-20 • von Willibrand d/s.
VIII, fibrinogen, mL • Factor XIII deficiency.
vWf) • Hypofibrinogenemia.
Random donor 50-70
20-24oC
platelets mL
with 5 days Thrombocytopenia.
Single donor 200-300
agitator
platelets mL
Note :
• I unit of blood : Hb by 1 g%.
• 1 unit of random donor platelets : platelets by 10,00o/MM3.
• 1 unit of single donor platelets : platelets by 30,00o/MM3.
• Blood is screened for : HIV/Hepatitis B/Hepatitis C/malaria/syphilis.
• Infection transmitted by all blood products : Malaria.
• Component most prone to bacterial contamination : Platelets.
• Life span of transfused RBCs : 50–60 days.

42 05 Pathology

Transfusion
Transfusion protocol :
Transfusion should commence within 30 minutes of taking out of fridge.
Completed : 4 hrs.
Size of needle : 18-19G.
Size of micropore filter : 170 microns.
Massive blood transfusion (MBT) :

Replacement of patient’s whole blood volume within 24 hrs.
Complications :
C : Coagulation (Dilutional coagulopathy) DIC (M/C cause of death).
A : Acidosis, alkalosis (More common metabolic alkalosis).
T : Hypothermia.
C : Citrate toxicity (Tingling, numbness).
H : Hyperkalemia (Arrythmias), hypocalcemia.
TRALI (Transfusion related acute lung injury) :

Develops within 6 hrs of transfusion.
Symptoms similar to ARDS like dyspnea, tachypnea.
CXR : Bilateral pulmonary infiltrates & white out appearance.
Pathology : Anti HLA/leucocyte antibodies.
More common with plasma products.
Note : TACO (Transfusion Associated Circulatory Overload) characterised by high
BP (Absent in TRALI).
Practical hematology 00:29:30
Instrument Points
1. Sahli’s Hemoglobinometer
Principle : Hb Acid hematin
(Brown color).
Color of acid hematin is compared
with
the comparator.
Comparator box

2. RBC & WBC pipette ----- Active space -----
For RBCs : Aspirate to 0.5 → Dilute to

Red bead in RBC 101 (DF :202).
pipette For WBCs : Aspirate to 0.5 → Dilute to
11 (DF : 22).
3. wintrobe’s tube
Use : ESR estimation.

Anticoagulant : EDTA.
1 end closed & 1 end opened.

4. Westergren’s tube
Use : ESR estimation.

Anticoagulant : Citrate.
Opened at both ends

5. Neubauer chamber
Diluting fluids :
WBC : Turk’s fluid.
RBC : Dacie & Hayem’s fluid.
Platelet : Rees & Ecker fluid.
Order of blood drawing :

“Be Loving, Respectful, Gracious, Light hearted & Gentle”.
Blood culture → Light blue → Red → Green → Lavender → Grey.

44 05 Pathology

Vacutainers :
Vacutainer
Anticoagulant Uses
color
Purple
• Routine blood tests (CBC’s, Periphera
EDTA. smear).
• ESR by wintrobe’s method.
Blue • Coagulation studies.

Sodium citrate. • ESR estimation by westergren’s method.
• Platelet function assay.
Grey
Potassium oxalate/
Sodium fluoride (Inhibit Blood sugar estimation.
enolase).
Red • Biochemistry.
Clot activator (No gel). • Serology.
• Immunohematology.
Yellow
Acid citrate dextrose. Preserve RBC for blood banking & HLA typing.
Green • Osmotic fragility.

Heparin
• Blood gas analysis.
(Inhibits thrombin
• Immunophenotyping.
activation).

M/C cause of cell injury : Hypoxia (M/C cause of hypoxia : Ischemia).

Cells most sensitive to hypoxia : Neurons.
Cell Adaptations 00:02:12
Examples
Adaptation Definition
Physiological Pathological
• ↑ in size of cell. • Skeletal muscles in Left ventricular
• No change in number body builders. hypertrophy in HTN.
of cells. • Uterus in pregnancy.
Hypertrophy • Seen in permanent/ • Breast in pregnancy
non-dividing cells. & lactation.
• Eg. : Cardiac & skeletal
muscles.
• ↑ in number of cells. • Uterus in pregnancy. • BPH (Benign Prostatic
• Occurs in dividing cells. • Breast in puberty. Hyperplasia).
Hyperplasia
• Liver (Compensatory • Endometrial hyperplasia.
hyperplasia).
• ↓ in size of cell. • Thymus. • Senile atrophy.
• ↓ in number of cells. • Notocord. • Pressure atrophy.
Atrophy (↓ Size of organ). • Ischemic atrophy.
• Mutritional atrophy.
• Disuse atrophy.
Reversible change where • Pseudostratified ciliated columnar epithelium →
one differentiated cell Stratified squamous epithelium (M/C).
Metaplasia
type is converted into • Barrett’s esophasgus.
another. • Myositis ossificans.
Columnar
Stratified Epithelium
Squamous
Epithelium
Goblet cells
Metaplasia
46 06 Pathology

Metaplasia :
Types :
1. Epithelial : Squamous metaplasia in smoking, Barrett’s esophagus.
2. Mesenchymal : Myositis ossificans (Connective tissue metaplasia).
Note : Vitamin A deficiency → Metaplasia.
Barrett’s esophagus :
• Stratified squamous epithelium GERD Columnar epithelium.
• ↑ Risk of : Adenocarcinoma.
• Histological hallmark :
a. Intestinal metaplasia.
b. Goblet cells.
• Special stain : Alcian blue/Mucicarmine. Alcian blue/Mucicarmine
Stratified squamous epithelium
Columnar epithelium with goblet cells
Barrett’s esophagus
Cell Injury 00:15:56
Reversible Cell Injury (RCI) :

Na+ & H2O influx → Cell swelling → Formation of membrane blebs.
M/C organelle affected in RCI : Mitochondria.
M/I morphological feature of RCI : Cell swelling/hydropic change.
Myelin figures : Present (Reversible < Irrreversible cell injury).
Membrane bleb
Myelin
Swelling of
figure
endoplasmic reticulum
& mitochondria
Reversible cell injury

Note : Mitochondria : ----- Active space -----

• M/C organelle affected in RCI.
• Organelle where calcification occurs first.
• Plays a pivotal role in apoptosis.
Irreversible cell injury :

Flocculant amorphous densities (Most important differentiationg feature b/w
reversible and irreversible cell injury).
Nuclear changes :
Most important light microscopic feature.
Changes :
1. Pyknosis (Clumping of chromatin).
2. Karyolysis (Dissolution of nucleus).
3. Karyorrhexis (Fragmentation of nucleus).
Nuclear pyknosis
Cell membrane defects
Large densities
Karyolysis
Karyorrhexis Mitochondrial swelling

Irreversible cell injury
Cell Death 00:22:41
Mechanisms of cell death :

1. Necrosis.
2. Apoptosis.
3. Necroptosis.
4. Pyroptosis.
5. Ferroptosis.
6. Autophagy.

48 06 Pathology

Necrosis :
Type Features Examples
• M/C type. • Heart (M/C organ).
• Occurs in all solid organs (Except brain). • Liver.
• Infarct : Type of coagulative necrosis. • Kidney.
Coagulative
• Considered a type of dry gangrene. • Spleen
• Cell architecture preserved. • Zenker’s degeneration
(Skeletal muscle).
• ↑ Enzymatic activity → Liqufied material. • Brain.
Liquefactive • Considered a type of wet gangrene. • Fungal infections.
• Cell architecture not preserved.
• Cheese-like appearance. • TB.
• Intermediate form b/w coagulative & liquifactive • Histoplasmosis.
Caseous
necrosis. • Blastomycosis.
• Coccidiomycosis.
• Pink, fibrin-like appearance. • Polyarteritis nodosa.
Fibrinoid • Seen in type 2 & 3 hypersensitivity reaction • Malignant HTN.
(Immune complex deposition). • Aschoff nodules
Chalky white deposits seen d/t saponification of • Breast.
Fat fat. • Pancreas.
• Omentum.
2 types : Dry & wet. Seen in limbs d/t
Gangrene
ischemia.
Coagulative necrosis Liquifactive necrosis Caseous necrosis
Fibrinoid necrosis Fat necrosis Gangrene

Apoptosis : ----- Active space -----

Genetically programmed cell death.
M/C organism studied for apoptosis : Caenorhabditis elegans (Nematode).
Most important organelle for apoptosis : Mitochondria.
Pathways Phases Important enzymes Markers
1. Instrinsic. 1. Initiation. 1. Caspases. 1. Annexin V.
2. Extrinsic. 2. Execution. 2. Cytochrome C. 2. CD-95 (For extrinsic
3. Endonuclease. pathway).
Caspases :
a. Initiator caspases : Caspase 8, 9, 10.
b. Executioner caspases : Caspase 3, 6, 7.
Pro-apoptotic factors : Anti-apoptotic factors :

• bax. • bad. • bcl-2. Apoptotic cell
• bak. • PUMA. • bcl-XL.
• bim. • NOXA. • mcl-1.
• bid. • p53.
Note : Annexin A1 is the marker in Hairy cell leukemia.
Difference between necrosis and apoptosis :

Feature Necrosis Apoptosis
• Enzymatic/ischemic • Genetically programmed cell
process. death.
Definition • Passive. • Active.
• Involves group of cells. • Involves single cell.
• Always pathological. • Both physiological & pathological.
Cell size ↑ ↓
Cell membrane Affected Intact
Inflammation Present Absent
Marker None Annexin V, CD-95
Step ladder
PAGE pattern
(Poly-
Acrylamide Smear
Gel
Electrophoresis)

50 06 Pathology
----- Active space ----- Necroptosis : Pyroptosis :

Programmed necrosis. Pyrogen induced apoptosis.
Mechanism : Apoptosis (Genetically Cell death caused by fever &
programmed). infections.
Morphologically : Necrosis (Inflammation +). Mediated by : IL-1.
Mediated by : RIP 1 & 3.
Seen in :
• Mammalian growth plate formation.
• Acute pancreatitis.
• Neurodegenerative diseases.
Entosis : Efferocytosis :
Process in which non-macrophage Process of phagocytosis of
cells eat & kill other cells. apoptotic cell.
Seen in : Autoimmune hepatits. Signalling process : Inhibits
pro-inflammatory cytokines.
Ferroptosis :
Mechanism : Fenton reaction. Role in :
↑ Levels of Fe2+ • Cancer.
↓ • Stroke.
Activates Glutathione dependent defenses • Neurodegenerative disease.
↓
Lipid peroxidation
↓
Loss of membrane permeability & function
↓
Cell death.
Ischemia Reperfusion Injury 00:43:55
Cell damage following reperfusion to an

ischemic area.
Mechanism : Free radical injury.
HPE : Contraction band necrosis.
Contraction band necrosis

Calcification 00:45:08 ----- Active space -----
Definition : Deposition of excess amount of Ca2+.

Types :
Dystrophic Metastatic
Seen in Dead tissues Living tissues
S. Ca2+
Normal ↑↑
“RAT-P” • Bone diseases like multiple myeloma.
• R : Rheumatic vegetation. • Vitamin D related diseases.
Examples • A : Atheromatous plaque. • Sarcoidosis.
• T : TB lymph node. • Milk alkali syndrome.
• P : Psammoma bodies • Parathyroid disorders.
Calcification begins in : Mitochondria.

Special stain for Ca2+ : von Kossa/Alizarin red.
Psammoma bodies :
Foci of dystrophic calcification.
Deposits appear basophilic.
Seen in : “PS-MP”.
• P : Papillary thyroid cancer, RCC.
• S : Serous cystadenocarcinoma ovary.
• M : Meningioma. Psammoma bodies
• P : Prolactinoma.
Pigments 00:50:00
Coloured substances deposited in various tissues.

Types :
1. Exogenous :
a. Tattooing.
b. Anthracosis : Inhaled carbon particles deposited in lungs.
2. Endogenous :
a. Lipofuscin.
b. Hemosiderin.
c. Melanin.

52 06 Pathology

Lipofuscin :
• Aging/wear & tear pigment.
• Perinuclear brown pigmentation.
• Sign of free radical damage (Lipid peroxidation).
• Eg. : Brown atrophy of liver, heart.
Lipofuscin
Hemosiderin :
• Seen in iron overload.
• Eg. :
a. b Thalassemia major (D/t repeated transfusions).
b. Hemochromatosis.
• Golden yellow/brown colour.
• Special stain : Prussian blue/Perl’s stain.
Hemosiderin Prussian blue

Melanin :
• Derived from : Tyrosine.
• Black coloured pigment.
• Special stain : Masson Fontana.
• IHC markers : Melan A, HMB-45, S-100.
Melanin
Cell Aging 00:55:36
Telomere-telomerase hypothesis (Most accepted theory) :

Telomere :
• Short repeat sequence of nucleotides at the end of chromosomes.
• Sequence : TTAGGG.
• Telomere shortens with each cell division → Cell aging.
Telomerase :
• Synthesises telomeres → Inhibits cell aging.
• Known as “Immortality gene”.

Werner syndrome : Premature aging d/t defect in DNA helicase. ----- Active space -----
Hayflick limit : Normally cells undergo 60-70 cell divisions in their life span.
Sirtuins :
• NAD-dependent protein deacetylase.
• ↑ Longevity.
• Plays a role in : DM, cancer, cell aging.
• ↓ Cell aging by :
a. Calorie restriction → ↑ Life span.
b. Wine consumption.
Important Stains in Pathology 00:59:52
Cell/condition Stain
M/C stain in HPE Hematoxylin & eosin (H & E).
M/C stain in hematology Romanowsky stains like Leishman, Giemsa.
Reticulocyte Supravital.
Lymphoblast PAS (Periodic Acid-Schiff).
Monoblast NSE (Neuron Specific Enolase).
Myeloblast NSE, Oil red O, SBB (Sudan Black B).
Hairy cell TRAP (Tartarate Resistant Acid Phosphatase).
Lipid Oil red O, Sudan black.
Iron Prussian blue.
Calcium von Kossa, Alizarin red S.
Glycogen PAS.
Copper Rhodamine, Rubeanic acid.
Mast cell Toluidine blue.
Mucin Mucicarmine, Alcian blue.
Reticulin fibres Silver.
Elastin fibres van Geison.
Collagen Masson trichrome.
Melanin Masson Fonatana.
H. pylori Warthin starry silver.
Cryptococcus India ink.
Fungi Silver methanamine, Gamori methamine, PAS.
Amyloid Congo red.

54 07 Pathology
----- Active space ----- PATHOLOGY REVISION 7
Inflammation 00:00:47
Response of vascularised connective tissue to injury.

Acute inflammation Chronic inflammation
Most important cell Neutrophil Monocyte-Macrophage
4 cardinal signs of inflammation : Given by Celsus.

1. Pain/dolor.
2. Heat/calor.
3. Redness/rubor.
4. Swelling/tumor.
5 sign given by Virchow : Loss of function.
th
Steps of acute inflammation :

Vascular events :
Early transient vasoconstriction (Earliest event) Vasodilation ↑ Vascular
permeability (Most critical event) mediated by histamine stasis (Slowing of
blood flow).
Cellular events :
Margination/pavementing
Rolling (Selectins : E, P, L)
Adhesion (Integrins : β1, β2)
Transmigration/Diapedesis (PECAM1/CD 31)
Chemotaxis
Opsonisation
Phagocytosis

Selectins : ----- Active space -----
Selectin Ligands Distribution

Sialylated Lewis X & Endothelium activated by cytokines
E-selectin
related glycans (IL-1, TNF)
Sialylated Lewis X & Storage granules &
P-selectin
related glycan on PSGL-1 surface of endothelium & platelets
Lymphocytes
L-selectin GlyCAM-1 (HEV), CD 34
(high expression on naive T cell)
Chemotactic factors :
Exogenous : Bacterial cell wall products like N-formyl methionine.
Endogenous : “LIC” → LTB4, IL-8, C5a.
Opsonins :
• C3b.
• Fc fragment of IgG (Most important).
• Serum proteins like fibrinogen, CRP, etc.,
Phagocytosis :
Types :
• O2 dependent (M/C).
• O2 independent.
H202- halide is the most important microbial killing system.
NADPH oxidase -
O2 O2
Bacterium
Pseudopod Phagosome
Phagocytosis
Phagolysosome
Lysosome
Soluble debris
Exocytosis

56 07 Pathology

Leucocyte function defects 00:20:06
Defect Pathogenesis Clinical features

Leucocyte adhesion Recurrent infections, delayed
Defect in β2 integrin
deficiency (LAD) 1 (AR) separation of umbilical stump.
Mutation in
LAD 2 (AR) sialyl lewis X Recurrent infections.
modified glycoprotein
Recurrent infections with
Chronic granulomatous
Defect in catalase +ve organisms.
disease (XLR : M/C,
NADPH oxidase Test done : NBT (Nitro Blue
AR)
Tetrazolium test).
LYST defect, Fever, recurrent infections,
Chediak Higashi
required for albinism, sensorineural
syndrome (AR)
phagolysosome fusion deafness, thrombocytopenia.
AR : Autosomal recessive ; XLR : X linked recessive.
PS of Chediak Higashi syndrome

showing giant granules in neutrophils
Neutrophil Extracellular Traps (NET) :

Extracellular fibrillar meshwork produced by neutrophils at the site of infection.
Release high concentration of anti microbial substances → Prevents the spread
of infection.
Arginine is involved in the production of NET & nitric oxide.
Emperipolesis :
Cell within a cell appearance.
Cell remains viable/live and can exit.
Seen in Rosai Dorfman syndrome, NHL,
hematolymphoid disorders.
New Updates :
• Frustrated phagocytosis : Seen when phagocytes encounter materials which
cannot be easily digested (Eg. : Immune complexes deposited on flat surface
like glomerular basement membrane). ----- Active space -----

• New positive acute phase reactant called thrombopoeitin has been added.
Mediators of inflammation 00:30:24
Cell derived : Plasma derived :

• Histamine. • Coagulation factors.
• Serotonin. • Kinin.
• Platelet activating factor (PAF). • Complement.
• Nitric oxide (NO).
• Cytokines.
• Chemokines.
• Prostaglandins.
• Leukotrienes.
Mediator Function
Histamine
(Source : Mast cells) Vasodilation
Serotonin ↑sed permeability
(Source : Platelets > Basophils)
↑sed platelet aggregation
Platelet-activating factor (PAF) Bronchoconstriction
(Produced by platelets) Vasoconstriction
↑sed permeability
Vasodilation
Nitric oxide (NO)
Smooth muscle relaxation
Aka endothelium derived relaxation factor (EDRF)
Inhibits platelet aggregation
• Stain for mast cell is metachromatic stain (Toluidine blue).
• cGMP pathway : Arginine Nitric oxide synthase NO.
Prostaglandins & leukotrienes :

Cell membrane phospholipids
Phospholipases
Arachidonic acid (20 C)
Cycloxygenase 5-Lipoxygenase

58 07 Pathology

Cyclo-oxygenase pathway :
It leads to the production of prostaglandins, prostacyclins & thromboxane.
• Thromboxane A2 (TXA2) increases platelets aggregation & vasoconstriction.
• Prostacyclin (PGI2) acts opposite to TXA2 (inhibits platelets aggregation &
vasodilation) .
• Prostaglandins (PGD2 & PGE2) are involved in fever, pain, vasodilation &
increases vascular permeability.
Lipoxygenase pathway :
It leads to the production of leukotrienes & lipoxins.
• Lipoxins are anti inflammatory substances.
• Leukotrienes cause bronchoconstriction & increase vascular permeability
(Except LTB4, which is involved in chemotaxis).
Cytokines :
Function Cytokine
Pro inflammatory IL-1, IL-2, IL-4, IL-6, IL-8, IFN γ, TNF α
Anti inflammatory IL-4, IL-6, IL-10, TGF β
Both pro & anti inflammatory IL-4, IL-6
Cancer cachexia TNF α
Granuloma formation IFN γ, IL-12
Fibrosis TGF β, PDGF
Angiogenesis VEGF
Fever IL-1
Eosinophil activation IL-5
Chemokines :
Chemokine Specific for
α chemokine Cysteine-X-cysteine (CXC) Neutrophils. Eg., IL-8
β chemokine Cysteine-cysteine (C-C) MCP-1, Eotaxin, RANTES
γ chemokine C Lymphocytes
δ chemokine CX3C Monocytes & T cells
Note : X denotes any amino acid other than cysteine.
Complement factors :
C3a , C5a : Anaphylatoxins. C5a : Chemotaxis.
C3b : Opsonin. C5b-9 : Membrane attack complex (MAC).
Chronic Inflammation 00:44:28 ----- Active space -----
Granuloma :
Type 1V hypersensitivity reaction.
Epitheloid cells (Macrophages)
Types of giant cells :
Peripheral/horse
Langhans shoe shaped
TB
giant cells arrangement of
nuclei
Haphazard
Foreign body
arrangement of
giant cell
nuclei
Haphazard
Tumor giant cells arrangement of
nuclei
Reed-Sternberg Owl’s eye Hodgkin lymphoma

(RS) cell appearance (RS cell)
Fat vacuoles
Touton giant cell Xanthoma
around nucleus +
Aschoff giant cell RHD

Warthin Finkeldey Intracytoplasmic
Measles
giant cell nuclear inclusions

60 07 Pathology

List of granulomatous disorders :
TB
Caseating granuloma.
Fungal infection like histoplasmosis
Sarcoidosis : Non caseating granuloma.
Lympho granuloma venerum (LGV).
Leprosy.
Tertiary syphilis/gumma.
Cat scratch disease : Stellate/star shaped granuloma.
Wegener’s granulomatosis.
Crohn’s disease.
Berylliosis.
Chronic granulomatous disease.
Granulation tissue :
Neovascularisation is characteristic of granulation tissue.
New blood vessel

formation
Healing 00:53:40
Healing by primary intention :

Occurs in clean, uninfected wounds with no tissue loss.
Eg. : Surgical incision.
Wound contraction is absent.
Healing by secondary intention :

Seen in infected, lacerated wounds with tissue loss.
Wound contraction mediated by myofibroblasts is seen.

Steps in wound healing : ----- Active space -----
0 hr Incision is filled with blood clot.

Within 24 hrs Neutrophils from margins infiltrate the clot.
24-48 hrs Below the scab, continuous thin layer of epithelium is formed.
Neutrophils replaced by macrophages, early granulation tissue
Day 3
is formed. Collagen evident at the margins of incision.
Abundant granulation tissue. Maximum neovascularization.
Day 5
Collagen fibres bridge the incision.
2nd week Proliferation of fibroblasts & accumulation of collagen.
3rd week Scar formation.
A wound regains 70-80% of its tensile strength (never 100% or complete).

62 08 Pathology
----- Active space ----- PATHOLOGY REVISION 8
Neoplasia 00:00:10
Types of neoplasia/tumor
Benign : Malignant :
• Usually ends with -oma • Epithelial origin : Carcinoma.
• Mesenchymal origin : Sarcoma.
Difference b/w benign & malignant tumors :
Feature Benign Malignant
1. Anaplasia (Lack of
Absent Present
differentiation)
• Pleomorphism
• High N/C ratio
(Normal → 1:4)
• Hyperchromatic nuclei - +
• Prominent nuclei
• Loss of polarity
• Abnormal mitosis
2. Rate of growth Slow growing Rapidly growing
3. Encapsulated + -
4. Local invasion Absent Present
5. Metastasis Absent Present
Definitive indicator of malignancy : Metastasis > invasion.

Malignancies which do not metastasize :
1. Basal cell carcinoma.
2. Glioma.
Metastasis
Lymphatic : Hematogenous : Direct seeding :

Mostly by Mostly by Pseudomyxoma
carcinomas sarcomas peritonei

Metaplasia Dysplasia Anaplasia Desmoplasia ----- Active space -----
Reversible change • Disordered growth/ • Lack of Dense

in one cell type to proliferation. differenti- fibrosis in a
another. • Partially reversible. ation. tumor.
Eg : • Basement mem- • Irreversible.
• Cigarette smokers. brane intact.
• Barret’s esophagus. • Aka carcinoma insitu.
Hallmarks of carcinogenesis 00:09:43
1. Self sufficiency in growth signals : Oncogenes.

2. Insensitivity to growth inhibitory signals : Tumor suppressor genes.
3. Limitless replicative potential.
4. Evasion of apoptosis.
5. Sustained angiogenesis.
6. Altered cellular metabolism.
7. Invasion & metastasis.
8. Escape of immune recognition.
Oncogenes :
M/c oncogene affected in human malignancy : RAS
Gene Cancer
C kit GIST
RET (on • Medullary Ca thyroid
chromosome 10) • MEN II syndrome
• Anaplastic large cell lymphoma
ALK (on
• Adeno Ca lung
chromosome 2)
• Inflammatory myofibroblastic tumor
ABL CML
K RAS Colon, pancreatic Ca
H RAS Bladder Ca
N RAS Melanoma
C MYC Burkitt’s lymphoma
L MYC Small cell lung Ca
N MYC Neuroblastoma
NOTCH T cell - ALL
64 08 Pathology

Tumor suppressor genes :
M/c tumor suppressor genes involved in human malignancy : p53.
Gene Chromosome Tumors
Rb 13q Retinoblastoma, osteosarcoma
p53 17p Li Fraumeni syndrome
NF 1 17 Neurofibromas
NF 2 22 Schwannoma, meningiomas
BRCA 1 17 Breast Ca, ovarian Ca
BRCA 2 13 Male breast Ca, female breast Ca & prostate Ca.
WT 1
11 Wilms tumor
WT 2
PTEN 10 Endometrial Ca, Cowden syndrome
VHL 3 Clear cell RCC, Cerebellar hemangioblastoma.
APC 5 FAP (Familial adenomatous polyps), colorectal Ca
PTCH Bcc, Gorlin syndrome
CDH 1 (E Gastric adeno Ca, lobular Ca breast
cadherin)
Tumor markers :
Marker Condition
PSA
Prostate Ca
PAP
Medullary Ca thyroid
Calcitonin
(ACal deposition)
CEA Colon CA, pancreatic Ca
CA 19-9 Colon Ca, pancreatic Ca
HCG Choriocarcinoma
Hepatocellular Ca
AFP
NSGCT like yolk sac tumor
Immunoglobulins Multiple myeloma
CA 125 Ovarian Ca
CA 15-3 Breast Ca
Catecholamines Pheochromocytoma

Immunohistochemical markers : ----- Active space -----
Cell of origin/tumor Marker

Epithelial origin Cytokeratin (CK), P40, P63
Mesenchymal origin Vimentin
Glial GFAP (Glial fibrillary acidic protein)
Skeletal muscle
Desmin, myogenin, myo D1
(Rhabdomyosarcoma)
Vascular Vwf, CD31, VEGF
Neuroendocrine NSE, chromogranin, synaptophysin
Hepatic Hep par1, arginase 3
GIST DOG 1, CD 34, CD 117
Malignant melanoma HMB 45, S 100, melan A
Malignant
Calretinin, CK 5, CK 6
mesothelioma
Ewing’s sarcoma CD 99, MIC 2
Osteosarcoma Osteopontin, osteonectin, osteocalcin
Markers for unknown primary :

CK7/CK20 Profile :
CK 7 CK 20 Condition
+ + Bladder Ca, stomach Ca, pancreatic Ca.
- - HCC, RCC.
+ - Carcinoma involving female genital tract, breast, lung & thyroid.
- + Colorectal Ca.
Paraneoplastic syndromes :
• M/c paraneoplastic syndrome : Hypercalcemia.
• M/c endocrinopathy as a paraneoplastic syndrome : Cushing’s syndrome.
• Tumor producing maximum paraneoplastic syndrome : Small cell carcinoma
of lung.

66 08 Pathology
----- Active space ----- Syndrome Tumor Substance

SIADH Small cell ca lung ADH
Cushing’s
Small cell ca lung ACTH
syndrome
Hypercalcemia SCC lung, Breast Ca PTHrP
Polycythemia RCC Erythropoietin
Migratory Ca pancreas,
-
thrombophlebitis Ca colon
Hypertrophic
pulmonary Small cell ca lung -
osteoarthropathy
Acanthosis Ca stomach, Epidermal growth
nigricans Ca colon factor
Thymoma,
Myasthenia gravis -
Ca lung
Carcinogens 00:33:24
Chemical carcinogenesis :
Chemical Cancer
Polycyclic aromatic
Lung Ca
hydrocarbons
Arsenic Skin Ca
Lung adeno Ca (M/c)
Asbestos
Malignant mesothelioma
Aflatoxin HCC
Beta naphthylamine/
Bladder Ca
azo dyes/benzidine.
Benzene Leukemia, AML
Diethylstilbestreol Clear cell Ca vagina
Polyvinylchloride Hepatic angiosarcoma
Cadmium Prostate Ca

Microbial carcinogenesis : ----- Active space -----
Microbe Pathogenic factor Cancer

Gastric adeno Ca (M/c)
H. Pylori CagA gene
Maltoma (More specific)
E6 (Inactivates P53)
HPV Cervical Ca, anogenital Ca, laryngeal Ca
E7 (Inactivates RB)
HTLV 1 Tax Adult T cell leukemia
HBV HBx HCC
Kaposi’s sarcoma
HHV 8 Primary effusion lymphoma
Multicentric castleman disease
LMP 1 • HL & NHL
EBV EBNA2 • Burkitts lymphoma, nasopharyngeal Ca
• Post transplant lymphoproliferative disorder
Note : Nodular lymphocyte predominant hodgkin lymphoma is never associated

with EBV.
Images in neoplasia 00:37:51
Image Description
1. HPV infection :
Koilocyte :
• Seen in HPV infection.
• Large cell with thick membrane &
raisin like nucleus.
Koilocyte
2. Frozen section machine :
• Frozen section is an intrasurgical
procedure.
• Stains used : Oil red O stain.
• Used to check margins during Sx.
• Not used for definitive Dx.

68 08 Pathology
----- Active space ----- Image Description

3. Cell cycle : • Longest phase of cell cycle : G1.
• Most radiosensitive phase : M > G2.
• Mediators of cell cycle :
1. Cyclin D + CDK 4.
2. Cyclin E + CDK 2.
3. Cyclin A + CDK 2.
4. Cyclin B + CDK 1.
• Ist cyclin to increase in cell cycle :
Cyclin D.
• Last cyclin to increase : Cyclin B.
4. SCC : • Keratin pearls.
• Desmosomes (On high power only).
• IHC : CK, P40, P63.
Keratin pearls
5. Adenocarcinoma :
Glands lined by pleomorphic cells.
6. Small round blue cell tumors • Neuroblastoma. Homer wright

(SRCT) : • Medulloblastoma. rosette
• Hepatoblastoma.
• Retinoblastoma (Flexner winterstein
rosettes seen).
• Nephroblastoma/wilm’s tumor.
• Rhabdomyosarcoma.
• Ewing’s sarcoma/PNET.
Small round blue cells Rosettes • Lymphoma.

Image Description ----- Active space -----
7. Papillary lesion :
• Finger like projection with fibro-
vascular core.
• A/w psammoma bodies.
• Eg : Papillary RCC & thyroid Ca.
8. Cribriform pattern :
• Swiss cheese pattern.

• Eg : Adeno cystic Ca of salivary
glands.
9. Neuroendocrine pattern : Cells with salt & pepper chromatin.

• Pheochromocytoma (Zellballen
pattern).
• Carotid body tumor.
• Paraganglioma.
• Neuroblastoma.
• Small cell Ca of lung.
• Carcinoid tumor.
10. Owl’s eye appearance :
• Reed sternberg cell in hodgkin

lymphoma.
• CMV inclusions.
Reed Sternberg Cell CMV inclusion

70 08 Pathology
----- Active space ----- Image Description

11. Glomeruloid body/Schiller duval body : • Yolk sac tumor (AFP +ve).
• Glioblastoma multiforme.
12. Coffee bean nuclei : • Papillay Ca thyroid.

• Langerhans cell histiocytosis.
• Granulosa cell tumor.
13. Fried egg appearance : • Oligodendroglioma.

• Hairy cell leukemia.

Immunity 00:00:25
Hypersensitivity reactions (HS)
Types :
Type 1/Anaphylactic hypersensitivity :
• Most important cell involved : Mast cells (early phase, stained using toluidine
blue) & Eosinophil (late phase).
• Most important antibody in type 1 HS : IgE.
• Most important cytokine : IL 4, IL 5.
• Earliest mediator : Histamine.
Type 2/Antibody mediated HS :

• Type 5 HS is a variant of type 2 HS in which antibody against receptor
present (eg : Graves disease, myasthenia gravis).
Type 3/Immune complex mediated HS :

• Circulating immune complexes responsible.
Type 4/delayed/cell mediated HS
Examples of HS :
Type 1 HS Type 2 HS
• Hay fever My blood group is Rh positive.
• Bronchial asthma • Myasthenia gravis
• Allergic rhinitis • Blood transfusion reaction
• Allergic dermatitis • Grave’s disease, Goodpasture syndrome
• Food allergy • ITP, Immune hemolytic anemia
• Casoni’s test • Rheumatic fever
• PK reaction • Hyperacute graft rejection
• Anaphylaxis • Pernicious anemia, pemphigus vulgaris

72 09 Pathology
----- Active space ----- Type 3 HS Type 4 HS

SHARP • Tuberculin test
• Serum sickness, SLE (Visceral • Lepromin test
lesions are type 3, hematological • Sarcoidosis
changes are type 2) • Granuloma
• HSP • Acute & chronic graft rejection
• Arthus reaction • Contact dermatitis
• Reactive arthritis • Rheumatoid arthritis (type 4 > type 3)
• PSGN, PAN
Difference between MHC class 1 & class 2

MHC (HLA) Class I MHC (HLA) class Il
Peptide binding domain alpha 1 & 2 Peptide binding domain alpha 1 & beta 1
Present antigen to CD-8 T cells Present antigen to CD -4 T cells
Found on surfaces of all nucleated Found on surface of APCs & activated T
cells cells
Bind with endogenous antigen Bind with exogenous antigen
Encoded by HLA A, B, C Encoded by HLA DP, DQ, DR
• Gene for MHC is located on chromosome 6p.
• For transplantation matching requirement : HLA DR > B > A.
• HLA matching useful in paternity testing.
• Celiac disease a/w HLA DQ 2, HLA DQ 8.
• Behcets disease a/w HLA B5.
Transplants : 00:11:05
Transplant rejection
Type Onset Mechanism Type of HS
Hyperacute Immediate Preformed antibody against donor tissue. 2
Thrombosis & occlusion of graft vessels.
Acute (M/C) Weeks to T cell mediated response against foreign MHC. 4

months Leukocyte infiltration of graft vessels +.
Chronic Months to T cell mediated. 3&4
years Thickening & fibrosis of vessels.
Graft v/s Host Variable Occurs after bone marrow transplant. 4
(GVHD) Skin, gut & liver commonly affected.

• Isograft : Identical twins. ----- Active space -----

• Autograft : Transplant done in same body.
• Allograft : Transplant between different individuals of same species.
• Xenograft : Transplant between different species.
Antibodies in autoimmune conditions

Disease Antibody
Most specific for SLE Anti ds DNA, Anti Smith
Most sensitive for SLE Anti nuclear
Drug induced lupus Anti histone
Neonatal lupus Anti Ro
Diffuse scleroderma Anti scl 1
Limited scleroderma/CREST syndrome Anti centromere
Inflammatory myopathies Anti Jo1
Sjogren syndrome Anti Ro (SS1), Anti La (SS2)
ANA staining pattern
Homogenous Systemic lupus erythematosus

(Anti ds DNA, anti histone) Mixed connective tissue disease
Drug induced lupus
Juvenile idiopathic arthritis
Speckled Systemic lupus erythematosus

(Anti smith, anti RNP, Sjögren’s syndrome
anti SS-A, anti SS-B) Polymyositis/dermatomyositis
Systemic sclerosis/scleroderma
Nucleolar (Anti-RNA) Diffuse systemic sclerosis/

scleroderma
Polymyositis
Centromere (Anti ds DNA) Limited systemic sclerosis/

scleroderma

74 09 Pathology

Immunodeficiency disorders 00:17:15
Disease Primary deficitSecondary Clinically

deficit
Brutons aggamma- Bruton tyrosine Failure of B H.Influenzae &
globulinemia kinase (Btk) cells to mature, Staph aureus
mutation absent plasma infections.
(X linked reces- cells.
sive).
Hyper IgM syndrome Mutation in CD Defect in Recurrent pyogenic
40 L. Immunoglobulin infections.
class switching.
Wiscott Aldrich Mutation in CD8 T cell defi- Eczema
syndrome Wasp protein. ciency. Thrombocytopenia
IgM low. Recurrent infections
IgA & IgE high.
Digeorge syndrome Del 22q11, failure T cell defect. Tetany, cleft lip &
of dev of 3rd & palate.
4th pouch. Heart defects.
Severe combined ADA deficiency. Defect in cyto- Candida &
Immunodeficiency kine signalling. Pneumocystis.
Ataxia ATM gene on ch Both B and T cell Neurologic defects.
telangiectasia 11 mutation. defect. Tumors.
Amyloidosis 00:19:46
• Deposition of pathological proteinaceous extracellular hyaline like substance

in various tissues.
Amyloidosis
Physical nature Chemical nature
X ray crystallography features : Electron microscopy features :

Cross β-pleated sheath structure Non branching fibrils of 7.5-10nm.
(Responsible for apple green
bifringence under polarised light)

Disease/ condition Type of amyloid ----- Active space -----
Primary amyloidosis AL
Secondary amyloidosis AA
Familial Mediterranean fever AA/Apyrin
Familial amyloidotic polyneuropathy ATTR
Senile/ cardiac amyloidosis ATTR
CRF/ long term dialysis A beta 2m
Prion disease Apr
Diabetes mellitus AIAPP
Medullary carcinoma thyroid Acal
Alzheimer's disease A beta
• M/c biopsy site : Abdominal fat pad aspirates.

• Best stain for amyloid : Congo Red.
• Gross stain for amyloid : Lugol’s iodine.
• M/c organ affected : Kidney.
• M/c cause of death in Primary amyloidosis : Cardiac failure.
• M/c cause of death in secondary amyloidosis : Renal failure.
• Earliest part of liver affected by amyloidosis : Space of Disse.
• Sago spleen & lardaceous spleen (when sinuses are affected) are seen in
amyloidosis.
HPE of amylodisis Sago spleen

76 09 Pathology

Genetics 00:27:51
Mendelian modes of inheritance
Autosomal dominant Autosomal recessive

Males = females equally affected Males = females equally affected
Homozygous = Incompetent with life Expressed in homozygous state
Expressed in heterozygous state Heterozygous state acts as a carrier
Usually in adulthood Usually manifests in childhood
Skip generations absent in pedigree Skip generations present
Incomplete penetrance & variable Shows complete penetrance
expressivity
Examples : Examples :
He Has A Very DOMINANT Father • A : Ataxia, Alpha 1 antitrypsin
a. Huntington’s disease deficiency, alkaptonuria
b. Hereditary spherocytosis • B : Beta thalassemia
c. Achondroplasia • C : Congenital adrenal hyperplasia,
d. vWD, Von Hippel Lindau syndrome Cystic fibrosis
e. Dystrophia myotonica • D : Deafness
f. Osteogenesis imperfecta • E : Emphysema (D/t alpha 1
g. Marfan’s syndrome antitrypsin deficiency)
h. Intermittent porphyria • F : Friedreich’s ataxia
i. Neurofibromatosis 1 (NF1) • G : Gaucher’s disease, glycogen
j. Adult onset polycystic kidney storage disease
disease • H : Hemochromatosis,
k. Neurofibromatosis 2 (NF2) Homocystinuria
l. Tuberous sclerosis • I : Inborn errors of metabolism
m. Familial adenomatous polyposis (FAP),
familial hypercholesterolemia

Marfan’s syndrome : ----- Active space -----

Caused by mutations in the fibrillin 1 gene (chromosome 15).
Clinical features :
1. Skeletal defects :
• Dolicocephalic head.
• High arched palate.
• Arm span exceeds height.
• Very tall with hyperextensible joints.
• Pectus excavatum & scoliosis can occur.
2. Ocular defects :
• Ectopia lentis (Superotemporal subluxation of lens).
3. CVS defects :
• Mitral valve prolapse (M/C).
• Aortic dissection (M/C cause of death).
• Aortic regurgitation.
Storage disorders 00:36:31
Lysosomal storage disorders Enzyme deficiency

Sphingolipidoses
Gauchers disease Glucocerebrosidase
Tay sachs disease Hexosaminidase A
Fabry disease Alpha galactosidase A
Krabbe disease Galactocerebrosidase
Niemann pick disease Sphingomyelinase
Mucopolysaccharidoses
Hurler syndrome Alpha L iduronidase
Hunter syndrome Iduronate 2 sulfatase
Taysach’s disease :
Mnemonic : TAYSACH
• T : Taysach’s.
• A : Autosomal recessive. Ballooned neurons
• Y : Young adults.
• S : Spots (History of cherry red spots in macula).
• A : Ashkenazi jews.
• C : CNS deficiency : Lead to ballooned neurons Onion skin appearance on
• H : Hexosaminidase deficiency. EM in taysachs disease.
78 09 Pathology

Niemann pick disease :
• On electron microscopy : Zebra bodies.
Gaucher’s disease :
• M/C lysosomal storage disorder.
Zebra bodies
• Glucocerebrosidase enzyme deficiency.
• C/f : Bone pains, Pathological #, splenomegaly.
• Gauchers cell on BM exam : Crumpled tissue
paper appearance of cytoplasm.
• PAS positive.
• Oil red O positive.
• Prussian blue stain positive.
Gaucher cells
X linked recessive trait :
• Males >>> females.
• Females are usually carriers.
• Only males are affected.
Examples :
Mnemonic : Lady Harding College Girls
Dont Care About Foolish Words
• Lesch Nyhan syndrome.
• Hemophilia A & B, Hunters syndrome.
• Color blindness.
• Duchenne muscular dystrophy.
• Chronic granulomatous disease, color blindness.
• Agammaglobulinemia.
• Fabry’s disease, fragile x syndrome.
• Wiskott aldrich syndrome.
X linked dominant disorders :

• Mother can give the disease to both sons & daughters.
• Father affects only daughters, not sons.
Mnemonic : RAVI.
• Rett’s syndrome.
• Alport syndrome.
• Vitamin D resistant rickets.
• Incontinentia pigmenti.

Barr body (Lyon’s hypothesis) :
Inactivated X chromosome.
Drumstick appearance.
Sample taken for study from buccal mucosa.
Useful in conditions like Turners syndrome.
Barr body
Mitochondrial inheritance 00:43:50

Exclusively maternally inherited.
Organs affected : Brain, eye, skeletal muscles.
Mutation : Heteroplasmy.
Diseases :
• Mitochondrial encephalomyopathy,
lactic acidosis and stroke-like epi-
sodes (MELAS).
• Leigh syndrome.
• Leber hereditary optic neuropathy.
• NARP syndrome.
• Chronic progressive external ophthalmoplegia (CPEO).
Trinucleotide repeat mutation

• CAG amplification : Huntington’s chorea.
• CGG amplifcation : Fragile X syndrome.
• CTG amplification : Myotonic dystrophy.
• GAA amplification : Friedreich ataxia .
Fragile X syndrome :
• X linked disease.
• 2nd M/c genetic cause of mental retardation.
• FMR 1 gene mutation : Increased CGG repeats.
• Normal : 6-55 repeats.
• Full mutation : 200-4000 repeats.
Clinical manifestations :
• Attention & behavioural problems.
• Macroorchidism.
• Anticipation : Severity of disease increases with each successive genera-
tions.
80 09 Pathology

• Premutation in CGG is seen in Fragile X associated primary ovarian failure
along with Fragile X tremor/ataxia.
Genomic imprinting
Prader willi syndrome Angelman syndrome
Ch 15 Ch 15
Maternal silencing Paternal silencing
Paternal deletion Maternal deletion
Maternal disomy Paternal disomy
SNORP gene UBE3A gene
C/f : C/f :
• Mentally retarded. • Happy demeanour (happy puppet).
• Obesity. • Microcephaly.
• Seizures.
Pedigree analysis :
1. Rule out mitochondrial inheritance.
2. Rule out dominant / recessive
• Skip generations present : Recessive.
• Skip generations absent : Dominant.
If recessive :
• Male = female : Autosomal.
• Males >>> females : X linked.
If dominant :
• Father to son transmission present : Autosomal.
• Father to son transmission absent and 100 % daughters affected : X linked.
Chromosomal disorders 00:50:57
Down’s syndrome :
• Trisomy 21 (M/c cause : Meiotic non dysjunc-
tion).
• M/c genetic cause of mental retardation.
• M/c CVS defect is endocardial cushion de-
fects.
• Increased chances of acute leukemia
(AML m7), Alzheimer’s disease.

Patau syndrome : 00:48:31 ----- Active space -----

Trisomy 13.
Defects :
• Scalp defects, microcephaly.
• Microphthalmia.
• Cleft lip and palate (60-80 %)..
• Congenital Heart Disease 80% (VSD,
PDA, and ASD).
• Omphalocele.
• Polydactyly.
• Severe developmental delay and
mental retardation, only 5 % live
longer than 6 months.
Patau syndrome
Edward syndrome :
Trisomy 18, M/c cause is nondisjunction.
Clinical features :
• Prominent occiput.
• Micrognathia.
• Cleft lip and palate.
• Short palpebral fissures.
• Corneal opacities.
• Microopthalmos.
• Low set malformed ears.
Del 22q11/DiGeorge syndrome/Velocardiofacial Edward syndrome

defect :
Mnemonic CATCH 22
Cleft lip/palate �ardiac defect
Abnormal facies Hypocalcemia
Thymic dysplasia 22 : Del22q11
Klinefelter syndrome :
• Extra X chromosomes present (XXY/XXXY).
• Testicular atrophy +, infertility +, tall stature.
• Gynecomastia.

82 09 Pathology

Turner syndrome :
• Loss of X chromosome.
• 45 XO Genotype.
• Clinical features (mnemonic : CLOWNS) :
a. Cardiac, cystic hygroma.
b. Lymphoedema.
c. Streaked ovary.
d. Webbed neck.
e. Wide spaced nipples.
f. Short stature, Short 4th metacarpal.
• M/c cardiac defect : Bicuspid aortic valve.
• M/c cause of death : Coarctation of aorta.
Turner syndrome
karyotype 00:56:22
Chromosomes arranged on the basis of descending order of length.
Normal karyotype Turner syndrome

FISH (Fluorescence in situ hybridization (FISH)) 00:58:28
Normal FISH FISH : Trisomy FISH : t (9:22)
FISH : Monosomy FISH : Her 2 amplification

Pathology Revision 10 10 83
Blood vessels 00:00:55
Histology :
Tunica externa : Connective tissue + vessels.
Tunica media : Smooth muscles.
Tunica intima : Endothelial cells.
Internal elastic lamina : B/w tunica intima & tunica media.
External elastic lamina : B/w Tunica externa & tunica media.
Histology of blood vessel
Sclerosis :
1. Monckeberg’s medial calcific sclerosis :
• Asymptomatic. Ca2+
deposition
• Elderly people. in tunica
Stain for Ca2+ : Von Kossa, Alizarin red. media
Monckenberg’s medial sclerosis
Psamomma bodies → Dystrophic calcification.
2. Arteriosclerosis :
Hyaline arteriosclerosis Hyperplastic arteriosclerosis
Pink homogenous thickening of Concentric laminated thickening (Onion
arteriolar wall. skin appearance).
Seen in : Fibrinoid necrosis is present.
• Benign hypertension. Seen in : Malignant hypertension.
• DM.

84 10 Pathology
----- Active space ----- Onion skin appearance

• Malignant hypertension : Biopsy.
• Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) : Biopsy.
• X-ray of Ewing’s sarcoma.
• Gross specimen of spleen in SLE.
• Electron microscopy of Tay Sach’s disease.
• Primary sclerosing cholangitis : Biopsy.
3. Atherosclerosis :
Risk factors :
Non modifiable Modifiable
Age. Cigarette smoking.
Gender (Males > females). Alcohol.
Type A personality. Obesity, sedentary lifestyle.
Family history. Hyperhomocysteinemia.
Rickettsial infections.
M/c vessel affected : Abdominal aorta > coronary artery > popliteal artery.
Components of atherosclerotic plaque :

• Fibrous cap (Shoulder ) : Smooth muscle cells.
• Necrotic core : Foam cells (Lipid laden mac-
rophages).
Atherosclerotic plaque
Vasculitis 00:12:12
Chapel Hill classification
Large vessel Medium vessel Small vessel

• Giant cell. • Polyarteritis nodosa
Immune complex Pauci immune
• Takayasu. (PAN).
mediated • Wegner’s
• Kawasaki disease.
• HSP. granulomatosis.
• Buerger’s disease.
• SLE. • Microscopic
• Goodpasture polyangitis.
syndrome. • Churg Strauss
syndrome.
P-ANCA C-ANCA ----- Active space -----
Perinuclear Cytoplasmic
Aka anti MPO ANCA. Aka anti PR-3 ANCA.
P-ANCA positive in : C-ANCA positive in :
• Microscopic polyangiitis. • Wegner’s granulomatosis.
• Churg Strauss syndrome.
ANCA : Anti neutrophilic cytoplasmic antibody.
Other conditions with +ve ANCA :

• SLE, RA.
• Sjogren’s syndrome.
• Primary sclerosing cholangitis.
• Ulcerative colitis.
Fibrinoid necrosis
RBCs
HPE of PAN

86
10
Age Vessel affected Clinically Biopsy Extra

Pathology
Giant cell arteritis > 50 years Temporal artery. Headache, jaw claudication Granulomas, giant cells, Raised ESR.
(GCA)/Temporal (MC vasculitis Ophthalmic artery. (Most specific symptom), fragmentation of A/w polymyalgia
arteritis. in adults). Vertebral artery. blindness (If ophthalmic artery internal elastic lamina. rheumatica.
is involved).
Takayasu arteritis/ <40 years. Coronary artery Loss of pulse in the upper Granulomas, giant cells Aka Aortic arch
Pulseless disease. (M/C vessel extremity. syndrome.
affected).
PAN (Type 3 Kidney , heart, GIT. Abdominal pain, hematuria, Transmural necrotizing 30% pts : HbSAg +ve.
Hypersensitivity Lung : never melena. inflammation. A/w mononeuritis
reaction). affected. Fibrinoid necrosis. multiplex.
Kawasaki disease/ Coronary artery Fever, cervical lymph Anti endothelial
Mucocutaneous lymph < 5 years. (M/C vessel nodes, strawberry tongue, antibody +ve.
node syndrome. affected). conjunctivitis, cardiac Common cause of
complications. MI in children.
Buerger’s disease/ Middle age Intermittent claudication, rest Granulomatous inflammation, A/w HLA B5, A9.

Thromboangiitis male smokers. pain, gangrene. neutrophilic microabscess.

obliterans.
Granulomatosis with Any. URTI (Sinusitis, nasal polyp) , Granulomas. 95% c-ANCA positive.
polyangiitis. LRTI (Pneumonia, granulomas),
kidney (RPGN).
Microscopic polyangiitis. Any. Lung, kidney, GIT. Fragmented neutrophils. P ANCA positive.
Churg strauss Bronchial asthma, eosinophilia. Necrotizing granulomas. P ANCA positive.
syndrome.
Causes of granulomatous vasculitis ----- Active space -----

• Wegner’s granulomatosis.
• Takayasu arteritis.
• Churg Strauss syndrome.
• Temporal arteritis.
• Buerger’s disease.
Vascular tumors 00:33:42
1. Hemangioma :
Capillary hemangioma Cavernous hemangioma
More common. Less common.
Involves superficial (or) s/c tissue. Involves deeper tissues.
Proliferation of large number of small Proliferation of large dilated vascular
blood vessels. spaces.
2. Kaposi sarcoma :
Causative organism : HHV-8.
Composed of spindle shaped cells.
Borderline vascular tumor.
Lesions in Kaposi sarcoma

3. Angiosarcoma :
Highly malignant, aggressive sarcoma.
Risk factors :
• Thorotrast.
• Arsenic.
• PVC.
Organ affected : Liver.
IHC markers : vWF, CD 31, VEGF, factor VIII.
HPE of angiosarcoma

88 10 Pathology

Heart 00:37:12
Heart failure cells : Hemosiderin laden

macrophages seen in lungs of Heart
congestive heart failure patient. failure cells
Special stain used for iron/hemosiderin : Perl’s

stain/prussian blue stain.
Nutmeg liver :
Seen in chronic venous congestion of liver (Gross specimen)
Myocardial infarction (MI) 00:40:13
Introduction :
Infarct : Area of coagulative necrosis (Brain → liquefactive necrosis).
2 types of MI :
• Subendocardial infarct : Non ST elevation MI.
• Transmural infarct : ST elevation MI.
M/c vessel affected : LAD > RCA > LCX.
Zone of maximum risk : Apex.
Stain for MI : Triphenyl tetrazolium
chloride (TTC).
MI occured < 12 hours

TTC
Brick red : Normal Pale yellow : MI
TTC stain showing MI

Morphological changes in myocardial infarction
Time Gross features Light microscope Electron microscope
Reversible injury
0 - 1/2 hr None. None. Relaxation of myofibrils, glycogen
loss, mitochondrial swelling.
Irreversible injury
1/2 - 4 hrs None. waviness of fibers at border. Sarcolemmal disruption,
mitochondrial amorphous densities.
4-12 hrs Dark mottling (occasional). Early coagulation necrosis; edema; hemmorhage.
12-24 hrs Dark mottling. Ongoing coagulation necrosis; pyknosis of nuclei; myocyte hypereosinophilia;
marginal contraction band necrosis; early neutrophilic infiltrate.
1-3 days Mottling with yellow tan Coagulation necrosis, with lots of nuclei & striations; brisk
infarct center. interstitial infiltrate of neutrophils.
3-7 days Hyperemic border, central Dsintegration of dead myofibers, with dying neutrophils; Early phagocytosis
yellow tan softening. of dead cells by macrophages at infarct border.
7-10 days Maximally yellow tan and Well developed phagocytosis of dead cells; granulation
soft, with depressed red tissue at margins.
tan margins.

10-14 days Red-gray depressed well established granulation tissue with new blood vessels and collagen
infarct borders. deposition.
2-8 wks Gray-white scar. Increased collagen deposition, with decreased cellularity.
>2 months Scarring complete. Dense collagenous scar.
10
89 Pathology Revision 10

90 10 Pathology

Age of MI :
HPE of MI at 1-3 days : HPE of MI at 7-10 days :

Neutrophilic infiltration. Neovascularisation.
Rheumatic heart disease (RHD) 00:50:50
Age : 5-15 years.

D/t type 2 hypersensitivity reaction.
H/o streptococcal sore throat 2-3 weeks prior (ASO titre ↑).
M/c valve affected : Mitral valve (Acute RHD → MR, chronic RHD → MS).
Least common valve affected : Pulmonary valve.
Modified Jones criteria :

Major criteria :
1. Pancarditis. 3. S/c nodules. 5. Migratory polyarthritis.
2. Erythema marginatum. 4. Sydenham’s chorea.
Morphology of heart in RHD :

• Aschoff bodies : Pathognomonic. Composed of
fibrinoid necrosis, lymphocytes, anitschkow
cells/caterpillar cells.
• Bread & butter pericarditis.
• Fish mouth/buttonhole stenosis. Aschoff body
• Subendocardial jets/McCallum plaques.
Fish mouth stenosis

Vegetations : ----- Active space -----
Non bacterial
Infective Libman sach’s
RHD thrombotic
endocarditis endocarditis
endocarditis
Small, warty Large, infective, Small to medium Seen in SLE. Present
along line of destructive, sized along line of on both sides of valve
closure. friable. closure. leaflets.
Cardiomyopathy 00:59:54
Dilated Hypertrophic Restrictive

cardiomyopathy cardiomyopathy cardiomyopathy
Dilatation of all
Excessive wall thickening Least common.
chambers of heart (M/c).
Causes : M/c cause : Genetic. Causes :
• Idiopathic. Mutation in : • Idiopathic.
• Alcohol. • β myosin heavy chain. • Radiation.
• Postpartum. • Myosin binding protein C. • Amyloidosis (ATTR).
• Adriamycin. M/c cause of sudden • Hemochromatosis.
• Hemochromatosis. cardiac death in young
• Genetic. athletes.
Banana split configuration.

92 10 Pathology
Ninja star nuclei : Seen in DCM d/t Helter skelter arrangement of cardiac
titin gene mutation. myocytes in HCM.
Takotsubo cardiomyopathy/broken heart syndrome :

Type of DCM.
Sudden emotional stress → Sudden release of
catecholamines.
Heart takes the shape of a Japanese octopus trap
(Takotsubo). Takotsubo cardiomyopathy
Tumors of heart 01:06:50
M/c tumor of heart : Secondaries/metastasis.

M/c primary tumor of heart (overall) in adults : Myxoma.
M/c primary tumor of heart in children : Rhabdomyoma.
Rhabdomyoma :
• Has spider cells.
• Seen in association with tuberous sclerosis.
Myxoma :
• Usually involves the left atrium.
• Causes ball valve obstruction.
Stellate
• Biopsy shows stellate cells in a cell
mucopolysaccharide background.
Myxoma
CNS 01:09:10
Alzheimer’s disease :
Common cause of dementia in elderly.
Lobes affected : Frontal, temporal & parietal.

Gross changes Pathological changes ----- Active space -----
• Atrophy of the brain. • Neuritic plaque (Aβ40, Aβ42).

• Widening of sulci & • Neurofibrillary tangles (Hyperphosphorylated tau
gyri. protein).
• Cerebral amyloid angiopathy.
• Hirano bodies : Eosinophilic bodies composed of actin.
Neuritic plaque Neurofibrillary tangle Hirano body
Note : Lewy bodies → Parkinson’s disease.
CNS tumors :
Classification of CNS tumors
Glial tumors : Undifferentiated : Meningeal : Neuronal : Others :

• Astrocytoma. Medulloblastoma. Meningioma. • Neurocytoma. • Lymphoma
• Ependymo- • Ganglioglioma. • Giant cell
ma. • Ganglioneuroma. tumor.
• Oligodendro-
glioma.
Glial tumors are GFAP +ve.

M/c CNS tumor : Secondary/metastasis.
M/c primary brain tumor : Glioma > meningioma.
M/c brain tumor in children : Pilocytic astrocytoma.
M/c malignant tumor of CNS in children : Medulloblastoma.
Pilocytic astrocytoma :
WHO grade 1 tumor. Excellent prognosis.
3 Cs :
Rosenthal
• Seen in children. fibres
• Affects cerebellum.
• Presents as cystic nodules.
Pilocytic astrocytoma
94 10 Pathology

Glioblastoma multiforme (GBM) :
WHO grade 4.
Highly aggressive.
Butterfly tumor.
Affects adults.
HPE : Butterfly tumor HPE of GBM showing
• Geographical necrosis. geographical necrosis
• Serpentine necrosis.
• Glomeruloid body.
Glomeruloid body
Glomeruloid body
• In GBM.
• Schiller duval bodies in yolk sac tumor.
WHO 2016 classification of GBM :

IDH wild type IDH mutant type
Aka Primary glioblastoma Secondary glioblastoma
Age : 55 years (Elderly) Age : 45 years
90% (More common) 10%
Mutations : TERT, EGFR, PTEN, p53 Mutation : p53
Extensive necrosis Less necrosis
Supratentorial Infratentorial
Oligodendroglioma :
Middle age to elderly population.
Fried egg appearance
Chicken wire blood vessels

HPE of oligodendroglioma

Fried egg appearance ----- Active space -----
• Oligodendroglioma.
• Hairy cell leukemia : Bone marrow biopsy.
Ependymoma :
Affects spinal cord, ependymal lining.
Perivascular
pseudorosettes
HPE of ependymoma
Medulloblastoma :
Undifferentiated tumor.
M/c primary malignancy in children.
Location : Posterior fossa.
Highly malignant tumor with CSF drop mets.
HPE : Small, round blue cells forming → Homer
wright rosettes. Homer Wright rosettes
Note :
Homer Wright rosettes : Medulloblastoma, neuroblastoma.
Flexner wintersteiner rosettes : Retinoblastoma.
Perivascular pseudorosettes : Ependymoma.
Meningioma : Psamomma bodies

• Papillary carcinoma thyroid.
Psamomma • Serous cystadenocarcinoma
bodies of the ovary.
• Meningioma.
• Mesothelioma.
• Prolactinoma.

96 10 Pathology

Schwannoma :
Tumor of vestibulocochlear nerve.
NF 2 gene mutation on Chr 22.
GFAP +ve tumors :
Verrocay bodies • Astrocytoma.
• Oligodendroglioma.
Hypercellular area • Ependymoma.
(Antoni A) • Choroid plexus tumor.
Hypocellular area • Glioblastoma.
(Antoni B)
• Medulloblastoma.
Tumor HPE features

Pilocytic astrocytoma Rosenthal fibres, microcysts.
GBM Serpentine necrosis, glomeruloid bodies, butterfly lesion.
Oligodendroglioma Fried egg appearance, chicken wire blood vessels, cal-
cification.
Ependymoma Perivascular pseudorosettes.
Medulloblastoma Small round blue cells, Homer Wright rosettes.
Schwannoma Antoni A, antoni B, verrocay bodies.
Syndromes associated with brain tumors
Syndrome Mutation Clinically
Li Fraumeni syndrome p53 Medulloblastoma
Cowden syndrome PTEN Dysplastic gangliocytoma
Turcot syndrome APC Medulloblastoma
Gorlin syndrome PTCH Medulloblastoma
Dermapathology 01:27:06
Squamous cell carcinoma (SCC) :

HPE : Keratin
• Keratin pearls. pearl
• Desmosomes : Interdigitating bridges.
IHC markers : CK, P40, P63. HPE of SCC

Basal cell carcinoma (BCC) : ----- Active space -----

Aka rodent ulcer.
Does not metastasise.
Presents as a purplish nodule with
telangiectasia.
HPE :
• Nests of basaloid cells (small, blue cells).
• Peripheral pallisading.
Retraction
artefacts
Peripheral
palisading
Malignant melanoma : HPE of BCC
Melanin : Black colored pigment derived
from tyrosine.
Stains for melanin : Masson fontana
stain, dopa reaction.
Marker : HMB 45, Melan A, S-100.
Malignant melanoma
Bullous disorders :
Subcorneal bulla Suprabasal bulla Subepidermal bulla
Pemphigus foliaceous Pemphigus vulgaris Bullous pemphigoid
Pemphigus vulgaris :
Type 2 hypersensitivity reaction : Antibodies against Dsg 1 & 3.
Row of tombstone appearance Immunofluorescence (IF) : Fishnet pattern

98 10 Pathology

Bullous pemphigoid :
Eosinophils IF : Linear pattern
Dermatitis herpetiformis :
A/w celiac disease.
Neutrophilic abscess at
tip of dermal papilla
IF : Granular pattern
P. vulgaris Bullous pemphigoid Dermatitis herpetiformis

Antibody IgG IgG IgA
Bullae Suprabasal Subepidermal Subepidermal
IF Fishnet Linear Granular

Respiratory system 00:00:27
Histology of respiratory tract :

Entire respiratory tract is lined by pseudo stratified ciliated columnar epithelium.
Alveoli :
• Lined by type 1 & type 2 pneumocytes.
• Type 2 pneumocytes produce surfactants.
Alveolar biopsy
Obstructive lung diseases :

A) Emphysema :
Irreversible enlargement of airspaces distal to the terminal bronchiole with
destruction of walls (without fibrosis).
Types of emphysema :
Types Key points
Centrilobular/centriacinar Affects upper lobe of lung.
(M/c type) M/c emphysema associated with smoking.
Panacinar Associated with α 1 anti-trypsin deficiency.

Affects lower lobe of lung.
Para septal/distal acinar Associated with spontaneous pneumothorax.
Irregular Can affect any part of the lung.
TB : Terminal bronchiole; RB : Respiratory bronchiole; A : Alveoli.
Normal air spaces.
Dilated air spaces.
Centrilobular emphysema

100 11 Pathology
----- Active space ----- B) Chronic bronchitis :

Persistent productive cough for atleast
3 consecutive months & 2 consecutive years.
90% of patients are smokers.
Reid index : Ratio of thickness of mucus gland layer
to the thickness of wall (b/w epithelium &
cartilage).
Normal Reid index = 0.4.
It is ↑ in chronic bronchitis (d/t gland hypertrophy).
C) Bronchial asthma :
Pathogenesis : Type 1 hypersensitivity reaction.
Note :
• Most important cell in Type 1 HS reaction : Mast cell.
• Most important cell in late phase : Eosinophil. Curshman spirals
Genetic components :
• Gene for atopy is on chromosome 5.
• Adam 33 is affected.
Sputum microscopy :
• Curshman spirals. Charcot leyden crystals
• Charcot Leyden crystals : Made of eosinophilic
membrane protein called Galectin 10.
• Creola bodies : Sloughed mucus epithelium.
Creola bodies
D) Bronchiectasis :
Dilatation of bronchi & bronchioles.
Kartagener syndrome :
• Aka Immotile Cilia syndrome/primary ciliary dyskinesia.
• Defect in dynein arm of cilia.
• Triad : Bronchiectasis, sinusitis & situs inversus.
Note : Bronchiectasis can lead to AA amyloidosis. Bronchiectasis

Restrictive lung diseases : ----- Active space -----
A) Pneumoconiosis :
Types of pneumoconiosis Images

1. Coalworkers pneumoconiosis :
• Presents as coal macules or coal nodules.
• On Bx : Black pigment (carbon) is seen → D/t anthracosis.
• Affects upper lobe.
Caplan Syndrome : Coal worker’s pneumoconiosis + RA. Anthracosis

2. Silicosis :
• M/C pneumoconiosis in the world.
• Usually affects upper lobe of lungs.
• ↑ risk of TB & lung cancer.
• X-ray : Egg shell calcification.
• Histopathology : Whorled collagen fibres.
• Birefringent silica particles seen on phase contrast
microscopy (used for diagnosis). Whorled collagen fibres
3. Asbestosis :
• Seen in construction workers/shipping industry workers.
• Usually affects lower lobe of lungs.
• 2 types of asbestos fibres :
- Serpentine.
- Amphibole (more carcinogenic).
• Diseases caused by asbestosis : Pleural plaque
- Pleural plaque : M/c & earliest lesion.
- Pleural effusion.
- Lung cancer : M/c malignancy.
• M/c lung malignancy : Lung adenocarcinoma.
• Most specific malignancy : Malignant mesothelioma.
• Tumor marker used for malignant mesothelioma :
Calretinin, CK 5/6.
Asbestos bodies
• Electron microscopy of malignant mesothelioma :
Long slender microvilli or tonofilaments.
• On Bx :
a. Asbestos bodies/ ferruginous bodies → dumbbell
shaped, beaded, fusiform rod-like structure.
These are asbestos fibres coated with iron (Prussian
blue/Pearls stain +ve). EM of malignant
b. Psammoma bodies (+). mesothelioma

102 11 Pathology
----- Active space ----- Causes of psammoma bodies :

• Papillary carcinoma of thyroid. • Meningioma.
• Papillary renal cell carcinoma. • Mesothelioma
• Serous cystadenocarcinoma of ovary. • Prolactinoma.
B) Cryptogenic organizing pneumonia/ Bronchiolitis obliterans organizing

pneumonia (BOOP) : Inflammation
HPE : Masson bodies (loose fibrous plaques). Hemorrhages
Masson body
Granulomatous lung diseases :
A) Sarcoidosis :
Granulomatous disease.
F >> M.
Involves any part of the body.
Hilar lymph nodes enlargement is seen in 95% of pts.
Pathogenesis : Type IV hypersensitivity reaction.
Note : Most important cytokine in type IV HS reaction : IFN gamma/ IL-12.
Biochemical tests :
• ↑ serum calcium : Metastatic calcification.
• ↑ level of ACE enzymes.
HPE :
• Non caseating granulomas.
• Epitheloid cells : Slipper shaped nuclei. Granuloma with giant cells
• Naked granuloma (absence of lymphocytic collar).
• Inclusions :
a. Asteroid bodies.
b. Schaumann bodies : Basophilic d/t calcium concretions.
Asteroid body Schaumann body

B) Tuberculosis : ----- Active space -----

Seen as acid fast bacilli on ZN stain.
HPE of LN biopsy :
• Caseating granulomas with Langhan’s giant cells
(peripheral/ necklace arrangement of nuclei).
Miliary TB/ disseminated TB :
AFB bacilli on ZN stain
• Millet shaped lesions.
• Poor prognosis.
Miliary TB Non caseating granuloma with Langhan’s giant cells
Infections of lung :
A) CMV pneumonitis :
• HPE : Owl’s eye inclusions (intranuclear basophilic
inclusions).
Owl’s eye inclusions
B) COVID 19 :
• HPE :
- Diffuse alveolar damage with inflammation &
mononuclear cells.
- Hyaline membrane deposition.
Hyaline membrane
Lung cancer :
M/c lung cancer : Metastasis.
Squamous cell Small cell
Features Adenocarcinoma Large cell Ca
Ca Ca
Incidence M>F F>M M>F M>F
Location Central Peripheral Central Peripheral
Smoking asso- Strongest Smokers & Non
A/w smoking Non smokers
ciation a/w smoking smokers
Cushings
Paraneoplastic Hypercalcemia Migratory
syndrome Gynecomastia
Syndromes (d/t ↑ PTHrP) thrombophlebitis
SIADH

104 11 Pathology
----- Active space ----- Large cell

Feature SCC Adeno Ca Small cell Ca
Ca
Note :
• M/c paraneoplastic syndrome : Hypercalcemia.
• M/c endocrinopathy associated with paraneoplastic syndrome : Cushings syndrome.
• M/c cancer associated with paraneoplastic syndrome : Small cell lung carcinoma.
Pathogenesis. P53. K RAS, EGFR, ALK. L-myc.
• Small cells.
• Salt & pepper chro-
matin. Large,
Keratin pearls, Glands lined by
H&E • Nuclear moulding. pleomorphic
desmosomes pleomorphic cells
• Azzopardi effect (blu- cells.
ish staining on vessel
wall).
NSE, Synaptophysin,
IHC CK, P63, P40 TTF 1, Napsin A
Chromogranin
• Worst prognosis.
• Chemo sensitive.
Other points • On electron microsco-
py : Dense core neu-
rosecretory granules.
Keratin pearls (SCC) Adeno Ca Small cell lung Ca Large cell lung Ca
Other neuroendocrine tumors with similar microscopy & IHC markers like small
cell lung Ca :
• Pheochromocytoma. • Carotid body tumor.
• Carcinoid tumor. • Medullary Ca of thyroid.
• Paraganglioma.
Bronchioalveolar carcinoma/ Adenocarcinoma insitu :

• HPE : Filigree/lepidic/butterflies on a fence
pattern (tumor cells are present around
bronchioalveolar lining).
Filigree pattern

Carcinoid tumor : ----- Active space -----
• HPE : Salt and pepper chromatin.

• IHC markers : NSE, Synaptophysin, Chromogranin.
• Electron microscopy : Dense core neurosecretory
granules.
Dense core neurosecretory granules
Salivary gland, Head & neck 00:33:09
Salivary Gland :
• Pleomorphic adenoma is a/w : HMGA2 mutation.
• Mucoepidermoid carcinoma is a/w : t(11:19).
• Adenoid cystic carcinoma is a/w : MYB-NF1B gene mutation.
Head & neck :

HPV associated & not HPV associated head and neck cancers :
HPV associated Not HPV associated
Seen in young Seen in elderly
Sexually active A/w smoking, alcohol
M/c site : Oropharynx M/c site : Oral cavity
Non keratinizing SCC Keratinizing SCC
Metastasis : Rare Metastasis : Common
Good prognosis Poor prognosis
P 16 : Positive P 16 : Negative
Female genital system 00:34:47
1. Molluscum contagiosum :
Pearly umbilicated/dome shaped Handerson Patterson (HP bodies) :

nodules Eosinophilic inclusion bodies

106 11 Pathology

2. Genital wart/ Condyloma acuminatum :
Caused by : HPV 6, 11 (low risk HPV).
Note : HPV 16, 18 cause genital
cancers.
HPE : Koilocytes seen (perinuclear
halo, thick membrane, raisin like
nuclei). Cauliflower-like lesions Koilocytes
Pathogenesis :
• HPV produces two proteins : E6 & E7.
• E6 combines with p53, E7 combines with Rb → Inactivation of these tumor
suppressor genes → Lead to cervical intraepithelial neoplasia, cancers.
3. Ovarian tumors :
Surface epithelial : Germ cell tumors : Sex cord stromal tumors : Metastasis :
• Serous. • Dysgerminoma. • Granulosa cell tumor. • Krukenberg’s
• Mucinous. • Chorio carcinoma. • Leydig cell tumor. tumor.
• Clear cell. • Teratoma. • Fibroma.
• Endometrioid. • Embryonal • Thecoma.
• Brenner’s. carcinoma. • Fibrothecoma.
• Yolk sac tumor.
Germ cell tumors are seen both in ovary & testes.
Serous epithelial vs mucinous tumors :
Serous epithelial tumors Mucinous tumors
More common Less common
Usually B/L U/L
R/F : Family history, multiparity R/F : Smoking
Genetics : BRCA 1, BRCA 2, p53 Genetics : K-RAS
Gross appearance : Uniloculated Gross appearance : Multiloculated
HPE : Serous, ciliated columnar HPE : Tall, columnar, non ciliated cells with
epithelial cells mucin
Psammoma bodies present
Psammoma bodies are absent
Psammoma bodies

Brenner’s tumor : Coffee bean nuclei. ----- Active space -----

Benign, solid, U/L tumors.
HPE :
• Nests of cells which resembles bladder
epithelium.
• Dense fibrous stroma.
Coffee bean nuclei.
Urothelium like appearance
Dysgerminoma :
Counterpart of dysgerminoma in testes : Seminoma.
HPE :
• Cells separated by fibrous septa infiltrated with
lymphocytes, plasma cells & giant cells.
• Large polygonal with a central nuclei.
IHC markers :
• Placental alkaline Phosphatase (PLAP) +
• hCG + Fibrous septa
• OCT 3/ 4 +
• Nanog +
Choriocarcinoma :
Seen in elderly.
Gross : Large areas of hemorrhage seen.
HPE :
• Syncytiotrophoblast.
• Cytotrophoblast.
Tumor marker : hCG.
Metastasize to lung as cannon ball mets.
Yolk sac tumor/ endodermal sinus tumor :
Seen in children.
HPE :
• Schiller Duval bodies/ glomeruloid bodies.
Note : Schiller Duval bodies

Glomeruloid bodies seen in :
• Yolk sac tumor.
• Glioblastoma multiforme.

108 11 Pathology

Terratoma/dermoid cyst :
Has derivatives of all 3 germ layers.
HPE : Mixture of elements like neural cells, glands, hair follicle,
bone, cartilage.
Hair follicle
Gross image
Epithelium.
Glands
Bone.
Dermoid cyst
Granulosa cell tumor :

HPE :
• Call Exner bodies.
• Coffee bean nuclei.
Call Exner bodies

Note : Coffee bean nuclei is seen in :
• Papillary Ca thyroid.
• Langerhan’s cell histiocytosis.
• Granulosa cell tumor.
Leydig cell tumor :
HPE : Excess of Reinke’s crystals (yellow rod shaped
crystals).
Reinke’s crystals
Krukenberg’s tumor :
Diffuse gastric Ca metastazing to
ovary (M/c).
Gross : B/L, symmetric ovarian mass.
HPE : Signet ring cells.
Signet ring cells

Tumor Histopathology Marker ----- Active space -----
Serous epithelial tumor Cells with cilia, psammoma bodies CA 125

Yolk sac tumor Schiller Duval bodies AFP, Alpha 1 AT
Teratoma Skin, bone, cartilage, teeth, hair
Chorio Ca Cytotrophoblast, syncitiotrophoblast, no villi hCG +ve
Primitive cells
Embryonal Ca CD30+, CK+
No villi
Call Exner bodies
Granulosa cell tumor
Coffee bean nuclei
Sertoli cell tumor Inhibin
Leydig cell tumor Reinke’s crystal
Cells in nodules with fibrous septa containing
Dysgerminoma PLAP, LDH, hCG
lymphocytes
Brenner’s tumor Transitional epithelium
Krukenberg’s tumor Signet ring cells
Hydatidiform mole :
Partial mole Vs complete mole :
Partial mole Complete mole
Genetics : Single egg fertilized by Genetics : One empty egg fertilized by
more than one sperm. one sperm.
Triploid (69 chromosome). Diploid (46 chromosome).
Fetal parts + Fetal parts absent
Mucosal edema ++ Mucosal edema +
Patchy trophoblastic proliferation Diffuse trophoblastic proliferation
Some villi are normal All the villi are edematous
Minimal risk of choriocarcinoma 2-3% risk of choriocarcinoma
Male genital system 00:52:23
Prostate adenocarcinoma :
Gleason’s score :
Important prognostic factor for prostatic adenocarcinoma.
5 different patterns are given based on the architecture & morphology of the
glands.
Gleason’s score = Primary dominant pattern + Secondary dominant pattern.
Higher primary score indicate poorer prognosis even if a higher secondary score
is present. i.e ( A score of 3+2 is worse than 2+3).

110 11 Pathology

Traditional Gleason score New grading system
group 1
GLEASON 3+3=6 : only well-formed glands Grade 1
GLEASON 3+4=7 : Predominantly well-formed glands Grade 2
GLEASON 4+3=7 : Predominantly poorly-formed Grade 3
GLEASON 4+4=8 : Only poorly- formed∕fused∕cribriform glands Grade 4
GLEASON 9-10 : Lacks gland formation (or with necrosis) with or
Grade 5
without poorly-formed/ fused/ cribriform gland
Breast 00:57:02
Paget’s disease :
HPE : Pagets cells with perinuclear
halo.
Paget’s disease in breast implies
underlying malignancy.
DD : Eczema of breast.
Pagets cells
Morphological classification of breast cancer :
Invasive ductal carcinoma :

M/c type morphologically : Invasive ductal cancer-No special type (IDC-NOS).
IDC is graded using Bloom Richardson score (BR score) based on :
• Cells in ducts/ tubules.
• Degree of pleomorphism.
• Number of mitosis.
Prognosis : Worst.
Tubules
Invasion into
stroma
Invasive ductal cancer

Invasive lobular carcinoma : ----- Active space -----

M/c type pathologically.
Usually B/L and multicentric.
HPE :
• Dyscohesive cells (d/t CDH1 gene →
mutation loss of E-Cadherin).
• Single monomorphic cells.
• Cells are lined one after the other → Single file pattern
Single file pattern or Indian file pattern.
Prognosis : Excellent.
Note : Cancers with loss of E-Cadherin : Invasive lobular Ca of breast, diffuse
gastric adeno Ca.
Mucinous carcinoma :
HPE :
• Extracellular mucin : Pools of mucin with tumor cells.
• Intracellular mucin : Nucleus is pushed to periphery by mucin, creating
a signet ring cell appearance.
Mucin
Signet ring
Medullary carcinoma :
BRCA 1 positive.
HPE :
• Sheets of highly pleomorphic cells.
• ↑ no. of mitosis.
• Lymphoplasmacytic infiltrate.
• Pushing borders.
Molecular classification of breast cancer :

Based on
• Gene expression profiling.
• ER, PR, HER2 neu status

112 11 Pathology

Note :
• ER, PR +ve : Nucleus stained.
• Her2neu +ve : Membrane stained.
Significance :
• If the tumor is ER, PR +ve :
- Responsive to Tamoxifen.
- Good prognosis.
• If the tumor is HER2 neu +ve :
- Responsive to Herceptin/ Trastuzumab.
- Bad prognosis.
Type ER PR Her 2 neu

Luminal A (best prognosis) +ve +ve -ve
Luminal B/ Triple +ve +ve +ve +ve
Her 2 neu +ve -ve -ve +ve
Triple -ve/ Basal like (worst prognosis) -ve -ve -ve
ER+/PR+/HER2- ER+/PR+/HER2+ ER-/PR-/HER2+ ER-/PR-/HER2-
H&E
ER
PR
HER2

Gastrointestinal System 00:00:29
Helicobacter pylori :
Rod shaped bacillus.
Pathogenic factor : Cag A & Vac A.
Diagnosed through antral biopsy.
On biopsy :
• Floating over mucus layer as they
cannot penetrate it.
• Intra epithelial neutrophils.
• Subepithelial plasma cells.
Special stain : Warthin starry silver stain (Bacilli stain black).
Diseases caused by H. pylori :

• Chronic gastritis.
• Gastric adenocarcinoma.
• Marginal zone lymphoma (Maltoma).
Gastric adenocarcinoma (Lauman’s classification) :

a. Intestinal b. Diffuse
Environmental Familial
Gastric atrophy, intestinal metaplasia Blood type A
Men > women Women > men
Increasing incidence with age Younger age group
Poorly differentiated.
Gland formation
Signet ring cells.
Hematogenous spread Transmural/lymphatic spread
Microsatellite instability APC gene Decreased E-cadherin
p53, p16 inactivation

114 12 Pathology

Cancers related to CDH1 gene mutation & loss of E-cadherin mutation :
• Diffuse gastric adenocarcinoma.
• Lobular carcinoma breast.
When gastric adenocarcinoma metastasizes to ovary → Krukenburg’s tumor.
On gross examination :
Linitis plastica (Diffuse type) : Leather bottle appearance
On histopathological examination (HPE) :
Intestinal type Diffuse type : Signet ring cells with

intracellular mucin
Gastrointestinal Stromal Tumor (GIST) :

M/c mesenchymal tumor of stomach.
Pathology : c-kit mutation.
Markers : CD 117.
DOG 1 : Most specific marker.
CD 34.
Spindle & epithelioid cells seen.

Inflammatory bowel disease (IBD) : ----- Active space -----
Feature Crohn’s disease Ulcerative Colitis

Starts from colon, progresses to
Site Ileum, caecum
rectum
HLA HLA DR1 HLA DR2
Risk factor :
Causative Protective
Smoking
Cell CD4 TH1 CD4 TH2
• Skip lesions. • Pseudopolyps & mucosal
• Cobblestone bridges present.
appearance. • Toxic megacolon.
Gross • Transmural. • Submucosal.
features • Pseudopolyps & mucosal
bridges absent.
• Thick rubbery wall.
Microscopy Granuloma present Granuloma absent
Cryptitis/
+ +++
Crypt abscess
+ More prominent
Ulcer
(Deep knife like ulcers). (Superficial broad based ulcers).
Strictures, fissures,
Complications Less common
fistulas, sinuses.
Colon cancer Equal risk of colon cancer
Radiology String sign of Kantor Lead pipe/hose pipe appearance
Anti saccharomyces
Antibodies p-ANCA
cerevisae
Note :
• Most important cell in granuloma : Epithelioid cell (activated macrophage).
• Most important cytokine : IFN γ/IL-12.
• Associated with CD4 TH 1.
• p-ANCA positive vasculitis :
a. Microscopic polyangiitis.
b. Churg Strauss disease.
Crypt abscess
Early onset IBD : Mutation in IL-1 or IL-10 receptor.

116 12 Pathology

Celiac disease :
a.k.a Gluten sensitive enteropathy.
Barley, Rye, Oats, Wheat (BROW) cannot be included in diet.
Site of biopsy : Duodenal biopsy.
MARSH score is used for diagnosis.
Histopathological features :
• Villous atrophy.
• Crypt hyperplasia.
• Intraepithelial lymphocytes.
Antibodies :
• Anti gliadin antibody.
• Anti Tissue Trans Glutaminase (TTG) antibody.
• Anti endomysial antibody.
Increased risk of dermatitis herpetiformis.
Enteropathy associated T-cell lymphoma can be seen.
Whipple’s disease : Giardiasis :

Caused by Tropheryma whipplei.
HPE : Foamy histiocytes Containing PAS
positive organisms in lamina propria.
Giardiasis : Pear shaped

organism over mucus layer
PAS positive organisms

Microvillus inclusion disease (A.k.a Davidson disease) : ----- Active space -----
AR, MYO5B gene (vesicular transport of water & ions).
Clinical feature : Diarrhea.
Biopsy : Tiny eosinophilic inclusions at the apex .
IHC : villin, CD 10.
EM : Inclusion with microvilli.
Peutz Jheger’s syndrome : Eosinophilic inclusions at the apex

AD, LKB1/STK11 gene mutation.
Multiple hamartomatous polyps.
Perioral melanosis/mucosal hyperpigmentation.
Increased risk of pancreatic, breast, thyroid & colon
cancer.
HPE : Arborizing pattern of smooth muscle mixed with
lamina propria → Christmas tree appearance.
Christmas tree appearance
Perioral melanosis
Polyps :
1. Tubular polyp 2. Villous polyp 3. Tubulovillous polyp
Most malignant : Villous polyp & sessile polyps.
Adenocarcinoma colon :
Tumor markers : CEA, CA-19-9.
Adenoma-carcinoma sequence : (Mneumonic : AK-53)
APC → KRAS → p53 → Telomerase.

118 12 Pathology

HNPCC :
Mismatch repair pathway :
Mutation in mismatch repair genes (MLH1, MSH2, MSH6, PMS1, PMS2) → Senile
serrated adenoma (Microsatellite instability) → Carcinoma.
Neuroendocrine tumours 00:29:04
Pheochromocytoma :
HPE :
• Zell ballen pattern seen.
• Cells with salt and pepper chromatin seen.
IHC : NSE, synaptophysin, chromogranin +.
Other tumors with similar IHC profile :
• Carcinoid syndrome.
• Medullary carcinoma thyroid. Pheochromocytoma
• Small cell carcinoma lung.
• Paraganglionoma.
Polycythemia paraganglioma syndrome :

Genetic defect in EPAS 1 →increases HIF 2a.
Can lead to phaeochromocytoma, paraganglioma & polycythemia.
Familial syndromes associated with pheochromocytoma :

Syndrome Gene Other features
Multiple endocrine neoplasia Medullary thyroid carcinoma
RET
type 2A (MEN-2A) Parathyroid hyperplasia
Medullary thyroid carcinoma
Marfanoid habitus
MEN-2B RET
Mucocutaneous
Ganglioneuroma
Neurofibromatosis
Neurofibromatosis, type 1
NF1 Café-au-lait spots
(NF1)
Optic nerve glioma
Renal cell carcinoma
Hemangioblastoma
Von Hippel-Lindau(VHL) VHL
Pancreatic endocrine neoplasm
Paraganglioma (uncommon)

Neuroblastoma : ----- Active space -----

C/f : Child with abdominal tumor.
Gene : N-MYC mutation.
HPE : Small round blue cell tumor.
Cells arranged in Homer Wright rosettes.
Note : Flexner-Wintersteiner rosettes →
Retinoblastoma. Neuroblastoma
Thyroid gland 00:32:25
Normal HPE : Thyroid follicles are filled with colloid & lined
by cuboidal epithelium.
Hashimoto’s thyroiditis : Normal thyroid gland

• HLA associated autoimmune disease.
• On HPE : Lymphoid follicles/aggregates → Increased risk of lymphoma.
• Hurthle cells seen : Cells with abundant eosinophilic granular cytoplasm
(d/t excess of mitochondria).
• Can develop papillary carcinoma of thyroid.
Hashimoto’s thyroiditis
Criteria for adequacy in thyroid FNAC :

At least 6 groups of at least 10 follicular cells, preferably on a single slide.
3 exceptions :
1. Abundant inflammatory cells seen → Thyroiditis.
2. Abundant thick colloid seen → Benign colloid nodule (present as the pres-
ence of abundant colloid reliably identifies most benign processes).
3. Atypical/malignant cells seen → Atypia or malignancy.
120 12 Pathology

Overview of thyroid malignancies :
Feature Papillary Follicular Medullary Anaplastic

Incidence Most common Least common
H/o Radiation, Iodine

Thyroglossal cyst, deficiency,
Risk factor
Hashimotos Multinodular goitre,
thyroiditis. long standing goitre.
Parafollicular
Origin Follicular cells. Follicular cells Follicular cells
cells (C cells).
Metastasis Lymphatic. Hematogenous Both Both
K–RAS
Genetics BRAF, RET-PTC. RET, MEN II. p53
PI3K
Prognosis Best Worst
Papillary,
HPE Orphan Anne nuclei, Follicles Amyloid
Psamomma bodies.
Papillary carcinoma thyroid :

On HPE :
• Papillae.
• Follicles lined with optically clear nuclei
(Orphan Annie nuclei).
• Coffee bean nuclei.
• Nuclear pseudo inclusions.
• Psamomma bodies. Papillae
Psamomma bodies Orphan annie nuclei Coffee bean nuclei
Follicular variant of papillary carcinoma thyroid :

Cells arranged in follicles but nuclear features are that of papillary cancer.

Follicular carcinoma : ----- Active space -----

Cannot be diagnosed by FNAC as FNAC cannot detect
capsular & vascular invasion of tumor.
Medullary carcinoma thyroid : Follicular carcinoma

Gene : RET on chromosome 10.
On HPE : Spindle shaped cells & amyloid present
(ACal amyloid).
Apple green birefringence on polarized
microscopy.
Tumor markers : Calcitonin.
Medullary carcinoma
Bone and soft tissue tumors 00:42:22
Overview of bone tumors :

Tumor Age Location Genetics
Microscopy and gross
X-ray : Codman’s
triangle
Bimodal Metaphysis
Gross : Large, tan
distribution, of long bones,
Osteosaroma RB gene white gritty masses.
10–20 yrs & M/c site : Distal
Microscopy : New bone
elderly femur
formation, lace like
pattern.
Osteochondroma Metaphysis of EXT1, EXT2 gene Gross : Mushroom
(exostosis) long bones defect shaped protrusion
Giant cell tumor F > M, Multinucleated
Lower end of
(osteo- 20 to 50 osteoclast type giant
femur
clastoma) years cells
Axial skeleton, Malignant hyaline,
M>F, 40 Chr. 1p
Chondrosarcoma pelvis, ribs, myxoid cartilage,
years rearrangement
sternum pleomorphic cells
Small, round, blue cells
Diaphysis of with rosettes
Ewings sarcoma <20 yrs t(11:22)
long bones X-ray : Onion skin
appearance

122 12 Pathology
Osteosarcoma : Lace like pattern of Giant cell tumor with multinucleated

new bone formation giant cells
Ewing’s sarcoma : Small round blue Ewing’s sarcoma : PAS positive d/t
cells arranged in rosettes glycogen
Embryonal rhabdomyosarcoma :
Small round blue cell tumors with scanty cytoplasm sometimes arranged in
rosettes. Tadpole cells seen.
IHC : Desmin, myogenin, myo D1.
Renal Pathology 00:47:00
Based on investigations :
Urine examination
Cells Casts Crystals

Casts : Major component is Tamm Horsfall protein produced in ascending loop of
Henle.
Commonly seen casts Associated conditions
Hyaline Normal individual, exercise, stress, fever
RBC Glomerulonephritis
WBC Pyelonephritis
Broad/waxy Chronic renal failure
Lipid/ fatty Nephrotic syndrome
Muddy Brown granular Acute tubular necrosis
Microscopic appearances of various stones : ----- Active space -----
Stone Image
Struvite/staghorn stones :
• Radiopaque.
• Seen in alkaline urine.
• Rectangular/coffin lid appearance.
• Associated with urea-splitting organisms.
Struvite
Cystine stones :
• Radiopaque.
• Seen in acidic urine.
• Hexagonal shaped.
• Very hard stones.
Cystine
Uric acid crystals :
• Radiolucent.
• Seen in acidic urine : Varying shapes
(rhomboids/ parallelograms).
Uric acid crystal
Calcium oxalate mono/dihydrate stones :

• Radiopaque.
• Seen in acidic urine.
• Dumbbell shaped/envelope shaped.
• Most common type of renal calculi.
Ammonium urate stones :

• Radiolucent.
• Associated with laxative abuse.
Ammonium urate

124 12 Pathology

Kidney biopsy :
Kidney biopsy
Light microscopy Electron microscopy Immunofluorescence

(Stains : H & E, PAS, Silver, Congo red).
Electron microscopy :
Type of deposit Seen in
PSGN
Subepithelial RPGN
Membranous Glomerulonephritis
MPGN Type 1
Subendothelial
Lupus nephritis
Intramembranous MPGN Type II
Henoch Schonlein Purpura
Mesangial
IgA nephropathy
Immunofluorescence :
Linear immunofluoresence : D/t Granular immunofluoresence :

basement membrane defect D/t immune complex deposition
Post streptococcal glomerulonephritis :

• Type of nephritic syndrome.
• Type III hypersensitivity reaction.
• Age 5-15 years.
• Occurs 2-4 weeks after streptococcal sore
throat.
IF : Lumpy bumby appearance
• Cola coloured urine seen.
• Light microscopy : Enlarged, hyper-cellular glomeruli.
• Electron microscopy : Subepithelial humps d/t immune complex deposition.
• Immunofluorescence : Lumpy Bumpy appearance.

Rapidly Progressive Glomerulonephritis (RPGN) : ----- Active space -----

RPGN
Type 1 RPGN Type II RPGN Type III RPGN

• Anti GBM associated • Immune complex • Pauci Immune
• Eg : Goodpasture’s associated • Eg: Wegener’s
syndrome • Eg: SLE, Poly Arteritis Granulomatosis
Nodosa
Aka cresentric glomerulonephritis.
Crescents
> 50% glomeruli show cresents.
↑ in number of crescents → Poor prognosis.
Goodpasture’s syndrome : RPGN

Involves lung (hemoptypsis) & Kidney.
Mnemonic : 1, 2, 34.
Type I RPGN (D/t Type II hypersensitivity reaction).
Defect in α 3 chain of type 4 collagen.
Alport syndrome :
Defect in α5 chain of collagen type IV.
C/f : Anterior > posterior lenticonus, renal problems (proteinuria, hematuria &
ESRD), sensorineural hearing loss.
Investigations :
• Cannot be diagnosed on light microscopy.
• Electron microscopy : Basket weave appearance.
Mx : ACE inhibitors (To reduce renal damage & disease progression).
Diabetic nephropathy findings :
Diffuse sclerosis Armani Ebstein lesion : Seen in

(M/c) Nodular glomerulosclerosis/ severe diabetic nephropathy.
Kimmelstein Wilson lesion Glycogen filled vacuoles in tubules.
(most specific finding)

126 12 Pathology

SLE :
Type IV SLE : Diffuse proliferative

glomerulonephritis. Wire loop lesions SLE : Full house effect seen in
seen (M/c finding) immunofluorescence
Note : Cardiac lesion in SLE → Libman Sacks endocarditis.
Malakoplakia :
Purplish concretions known as

Michaelis Gutmann bodies seen
Tumors of the kidney :

Wilm’s tumor :
a.k.a nephroblastoma.
Gene : WT-1 gene on chromosome 11.
Triphasic tumor :
• Small round blue cells.
• mesenchymal component.
Wilm’s tumour
• Blastemal component.
Clear cell RCC :

M/c kidney tumor.
Involves proximal convoluted tubule.
Gene : VHL gene mutation on Chromosome 3p.
HPE : Sheets of cells with clearing.
PAS positive and Oil Red O positive. Clear cell RCC

Papillary RCC : ----- Active space -----

Cancer most associated with patients on long
term hemodialysis.
On HPE, papillae filled with foamy histiocytes &
psamomma bodies seen.
Papillary RCC
Chromophobe RCC :
Arises from the I cells of CD.
HPE : Cells with well defined borders &
perinuclear halo → Plant like appearance
Special stain : Hale’s colloidal iron.
Best prognosis.
Note : Bellini duct carcinoma → Worst prognosis. Chromophobe RCC
Liver pathology 01:05:57
Normal Hepatocyte :
Consists of zone 1, 2, 3, based on distance from portal triad.
Space between hepatocyte and sinusoid : Space of Disse.
Amyloid in the liver first affects space of Disse.
Alcoholic liver disease :

Steatosis (Micro/macrovesicular) → Hepatitis → Cirrhosis.
Macronodular cirrhosis : > 3 mm.
Micronodular cirrhosis : < 3 mm.
Mallory (hyaline) bodies :
Composed of intermediate filaments Ck8 & CK18.
Seen in (Mnemonic : New Indian WATCH) :
• Non Alcoholic Steato hepatitis.
• Indian Childhood Cirrhosis.
• Wilson’s disease. Mallory (hyaline) bodies
128 12 Pathology

• Alcoholic liver disease.
• Tumor (Hepatocellular carcinoma).
• Cirrhosis (Primary Biliary Cirrhosis).
• Hyperplasia (Focal Nodular Hyperplasia).
Metabolic liver diseases :

Hemochromatosis Wilson’s disease α1 antitrypsin deficiency
HFE gene mutation on AR, ATP7B gene mutation AR, Def of a1 AT, gene
Chr 6p on Chr 13 on Chr 14
Pathology
Excessive iron Excess copper ↑ Neutrophil elastase
deposition deposition activity
Bronze skin, DM,
Clinical micronodular cirrhosis, Liver, brain, KF ring Panacinar emphysema,
features DCMP > RCMP, (Descement’s membrane). liver disorder.
hypogonadism
↓ Ceruloplasmin,
↑ Iron, ferritin, red
Investigations ↑ urinary excretion of
TIBC
copper
Hemosiderin deposi- PAS positive
Liver biopsy & Steatosis, hepatitis,
tion, Prussian blue/ diastant resistant
stains rhodamine, orcein.
pearl’s stain. globules.
Hemochromatosis α1 antitrypsin deficiency
Acute and chronic hepatitis :

Ground glass hepatocytes Ballooning degeneration
Conditions & various bodies found on HPE :

Bodies Disorders
Heinz G6PD deficiency
Howell Jolly Post splenectomy, megaloblasticanemia, thalassemia
Pappenheimer Sideroblastic anemia
Russell
Multiple myeloma
Dutcher
Councilman Hepatitis B
Creola Asthma
Asteroid
Sarcoidosis
Schaumann
Ferruginous Asbestosis
Verrocay Schwanomma
Aschoff Rheumatic heart disease
Bunina Amyotrophic lateral sclerosis
Call Exner Granulosa cell tumor
Civatte Lichen planus
Negri Rabies
Lewy Parkinson’s
Hirano Alzheimer’s
Michaelis Gutmann Malakoplakia

Epo HL DHTKRF CYcq Yp WG

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Epo HL DHTKRF CYcq Yp WG

Uploaded by

Copyright:

Available Formats

Www.Medicalstudyzone.

PATHOLOGY REVISION 1 ----- Active space -----

Normal Smears 00:00:14

Neutrophil Eosinophil Basophil Lymphocyte Monocyte

Peripheral smear : 00:00:34

Usually contains only mature cells.

Pathology Revision • v1.0 • Marrow 6.5 • 2023

This PDF was created and uploaded by

Furthermore You can also request a specific

----- Active space -----

Salah’s needle Klima needle Jamshidis needle

M/C site of bone marrow examination :

On aspiration → Dry tap → Then do bone marrow biopsy.

Aplastic anemia Myelofibrosis Hairy cell leukemia AML-M7

Pathology Revision • v1.0 • Marrow 6.5 • 2023

WBC Disorders 00:10:20 ----- Active space -----

A. Non Neoplastic Disorders :

3. Basophilia Myeloproliferative disorder : CML

Allergic reactions (Hay fever, asthma)

Extra edge information :

Pathology Revision • v1.0 • Marrow 6.5 • 2023

----- Active space -----

Toxic granules Dohle bodies

Thick coarse blue granules Patches of dilated endoplasmic

Hypersegmented neutrophils Hyposegmented neutrophils

Hypersegmented neutrophil Hyposegmented neutrophil

Seen in Megaloblastic anemia Psuedo pelger huet cell : Seen

Acute Chronic Hodgkins Non Hodgkins

Pathology Revision • v1.0 • Marrow 6.5 • 2023

Acute leukemia : 00:21:31 ----- Active space -----

t(15:17) t(8:21) Inv 16

Auer rod (Most important Cytoplasm :

Prominent nucleoli Coarse chromatin

Pathology Revision • v1.0 • Marrow 6.5 • 2023

----- Active space -----

Peripheral smear : > 20 % lymphoblast

Investigations Special Stain : PAS +ve (Dot and block)

B-ALL CD 19, CD 20, CD 22, PAX 5, TdT

IOC : Flow Cytometry.

Pathology Revision • v1.0 • Marrow 6.5 • 2023

Peripheral smear- ALL : ----- Active space -----

Hand mirror cells

Hand mirror cells

2. AML (Acute Myeloid Leukemia) : 00:41:33

Average age : 15-39 years.

Gum bleeding/hyperplasia Chloroma DIC

Pathology Revision • v1.0 • Marrow 6.5 • 2023

----- Active space -----

FAB classification : Based on cell type and degree of differentiation (morphology

Pathology Revision • v1.0 • Marrow 6.5 • 2023

----- Active space -----

Auer rod Faggot cell MPO positivity in Myeloblast

Criss cross pattern of auer rods

Myeloproliferative Disorders 00:50:29

1. Chronic Myeloid Leukemia :

BCR-ABL fusion transcript: 22 kDa

Constitutive Activation of tyrosine kinase

Imatinib mesylate ( Gleevac)

Formation of BCR- ABL fusion transcript

Pathology Revision • v1.0 • Marrow 6.5 • 2023

----- Active space -----

Persistent spleen size Peripheral Cytogenetic Blast 10-19% in

Pseudo gaucher cells