General Pathology

- Increase stress : Hypertrophy : increase ptn synthesis and gene activation + production
of organells like mitochondria
- Hyperplasia and hypertrophy occur together except permenant tissues like cardiac
myocytes / sk. Ms / nerve
- Pathological hyperplasia à cancer except BPH
- Decrease stress ? atrophy : decrease cell number : apoptosis
- Decrease cell size ? ubiquin proteome / Autophagy : lyozomal destruction
- CHANGE stress : metaplesia
- Metaplasia occurs by REPROGRAMMING of stem cells , and it’s REVERSIBLE like GERD
- Apocrine metaplasia in breast ? NOT PRECANCEROUS
- ATRA = All Trans Retinoic Acid : for AML
- Myoscitis ossificans is an example of mesenchymal metaplasia
- BONE is normal and distinct separation of bone and muscle, NOT osteosarcoma
- Dysplasia is REVERSIBLE
- Stress exceeds the cell ability to adapt? INJURY
- Hypoxia is low oxygen delivery
- Hypoxemia is low blood oxygen
- Ischemia decrease BLODD FLOW in artery or vein ( eg: Budd Chiari Synd)
- MCC of budd chiari is PRV – hypercoaggulable state in SLE
- Any Increase PACO2 like COPD à PAO2 will decrease
- CO : normal PaO2 – SaO2 decreased !
- EARLY sign of CO is Headache
- Newborns are susceptible to metHB , Chocolate colored blood + cyanosis
- Ischemia : 1- damage Na K Pumb 2- failure Ca pump : increase Ca inside 3- anaerobic
glycolysis
- REVERSIBLE = SWELLING : eg : loss of micro villi / membrane blebbing due to swelling /
Swelling of RER à release of ribosomes à decrease ptn synthesis
- IRREVERSIBLE = membrane damage ( release of enzymes) eg : cardiac enzymes in MI
and liver enzymes in LCF
- Also calcium enters the cells
- Damage of mitoch membrane and release of cyt.c
- Calcium and lysozomal enzyme ? = irreversible
- Cell DEATH ? = Loss of nucleus
- Necrosis = Large GROUP of cells + Inflammation / Always pathologic “not like apoptosis”
- Red infarction : Loosely organized + Blood must RE-ENTER the tissue
- Liquifactive necrosis ? Enzymes
- Brain ( by microglial cells) / abscess ( neutrophils enzymes) / pancreatitis ( pancreas
itself) NOT fat necrosis “ surrounding”
- Fat necrosis : Saponification in pancreatitis / breast trauma ( mass : inflammatory
response : giant cells fat and calcification)
- Saponification : fat + Calcium : example if dystrophic calcification ( like psammoma
bodies )
- Serum calcium is normal in dystrophic “dead tissue” Vs. metastatic calcification :
calcium or po4 is High .. one of the causes is cancer but metastatic calcification itself is
NOT CANCER
- Fibrinoid necrosis : malignant HTN + Vasculitis
- 30 yr old with fibrinoid necrosis ? not malignant HTN, not vasculitis : THINK
preeclampsia in placental vessels ##
- Apoptosis energy dependant – maybe physiological
- Dying cells shrink : becomes eosinophilic , apoptotic bodies removed by macrophages
- Caspasses break CYTOSKELETON – activates Endonucleases breaks DNA
- Fas Ligand bing CD95 (Fas receptor) à T cell selection / TNF
- CD8 + also apoptosis
- Free radical has an unpaired electron on the outer orbit
- O à O2- à H2 O2 à OH à H2O : one electron at a time
- radiation hits water in tissue generates free radicals , hydroxyl free radicals is the MOST
DAMAGING
- copper and iron also free radicals : Iron do the Fenton reaction : OH free radical
- inflammation / acetaminophen
- Free radicals : Peroxidize the lipids / oxidizes Proteins and DNA (oncogenesis)
- Elimination of Free radicals : Antioxidants A,C,E / Metal carriers : transferring for Iron
and ceruloplasmin for copper / ENZYMES
- SOD – catalase – GTH peroxidase
- CCL4 : in dry cleaning industry à CCl3 in P450 in the liver à decrease ptn synthesis à loss
of apolipoproteins à FATTY LIVER
- Reperfusion injury : return of O2 and inflammatory cells = free radicals : in cardai
catheterization
- Amyloid : misfolded protein that deposits in EXTRACELLULAR space (outside) à damage
- Multiple proteins not one kind à all are B-pleated sheet configuration
- Tends to deposit around blood vessels ( see image)

SYSTEMIC AMYLOIDOSIS :

- Primary amyloidosis : AL chain due to plasma cell dyscriasis : increase Light chain >
heavy chain
- Secondary Amyloidosis : SAA = systemic derived amyloid associated
- APR “ chronic inflammation” = malignancy / RA / familial mediterranian fever ?
- FMF : dysfunction of neutrophils : episodes of fever and inflammation à involves serosal
surface ( pericardium / peritoneum) à APR is SAA à deposit as amyloid
- Findings : Nephrotic / restrictive CM / tongue enlargement / HSM / intestine
enlargement and malabs
- REQUIRES BIOBSY from abd fat pad and rectum ( easy to optain )
- AMYLOID CANNOT BE REMOVED

LOCALIZED AMYLOIDOSIS :

- Single organ
- Non-mutated transthyritin : Senile cardiac : Asymptomatic and 25% in people >80%
- Mutated ? FAMILIAL AMYLOID CARDIOMYOPATHY : restrictive / African Americans
- NIDDM – excess insulin à Amylin which is derived from insulin à deposit
- Alzheimer : AB amyloid protein à derived from amyloid precursor ptn present on chr 21
( early onset)
- Dialysis ? B2 microglobulin ( in joints) : MHC1 support ##
- Calcitonin in medullary thyroid : WITHIN tumor à biopsy

-------------------------

- Inflammation is due to 1) Infection 2) Tissue Necrosis

- Goal is eliminate infection OR remove necrotic debris
- inflammation is Innate : limited specificity
- Toll like Receptors ? on innate immunity cells : recognize PAMPs [ pathogen associated
molecular pattern] : example is CD14 recognize LPS
- TLR activation à up-regulation of NF-kB
- VD occurs at arterioles , permeability is at capillary end
- PGE2 – FEEEVER and pain
- Diagram : LTC4 , LTD4 , LTE4 : VC and bronchospasm : increase permeability
- Mast cells activated by : 1) tissue trauma – C3A, C4A , IgE
- Mast cells : 1) PREFORMED histamine 2) LATE RESPONSE by Leukotrienes
- C5a , C3a àmast cell degranulation
- C5a à chemotactic for PNL , C3b à opsonins
- Hageman factor : from liver : from inflammation : coagulation and DIC
- Dolor via PGE2 and bradykinin
- Rubor and calor : from VD : histamine / PGs / bradykinin
- Tumor : histamine and tissue damage : from post capillary venules
- Fever : MACROPHAGES : IL1 and TNG àincrease COX activity In hypothalamus à PGE2 à
increase set point
- 1) margination : slowing blood flow AT POSTCAPILLARY VENULES
- 2) Rolling : sialyl lewis x and selectins :
- P-selectins from Weibel Palade bodies “ VWF + P-selectin”
- E-selectins : upregulated by TNF and IL-1
- 3) firm Adhesion : CAM : cellular adhesion molecules bing Integrins on leucocytes
- CAM : activated by TNF , IL1
- Integrins activated by LTB4 and C5a
- LAD ? lack of CD 18 ni nutrophils to clear the tissue and fascilitate umbilical cord
separation à delayed
- Increased circulating neutrophils ? normally 50% are stuck in the vessels of the lung
( called marginated pool _ , in LAD : marginated pool will be released in the blood
- Recurrent bac infection that Lack pus bcz no PNL
- 4) Transmigration : POST CAPILLARY VENULES
- 5) chemotaxis : C5a IL8 LTB4 and bacterial product
- 6) Phagocytosis : enhanced by opsonins
- Pseudopods from neutrophils or macrophage : form Phagosome à moves ( in a road of
trafficking by microtubules) to fuse with Lysozome à Phagolysozome
- Chediac Higashi : no microtubules à no phagolysozomes
- Nutropenia dt failure of division and cytokinesis
- Giant granules in leucocytes : piling up bcz they cannot migrate to periphery
- Defective primary hemostasis : platelets migration
- Melanocytes : can form pigment , but it cannot be moves to keratinocyes ! ( one
melanocyte = 25 keratinocytes) so it’s partial
- Peripheral neuropathy : cannot maintain integrity of periphery dt decrease moving
- 7) destruction of phagocytosed material : oxygen dependant and oxygen independent
- HOCL “ bleach” is the product of MPO
- Most bacteria have H2O2 à can be used by MPO in CGD
- Except catalase +ve : destroy H2O2
- -ve Nitroblue tetrazolium test : No NADPH = No Blue color
- MPO deficiency ?? Asymptomatic but maybe candida infection / NbT test is POSITIVE
- O2 independent : enzymes like Lysozyma and MBP “less effective”
- 8) Resolution : PNL die via apoptosis and form Pus
- 9) the phase of Macrophages ( 2-3 days) via the same ways à phagocytosis : PRIMARY
MECHANISM is Enzymatic killing by Lysozymes
- Release cytokines:
- Resolution by IL-10 and TGF B
- Continue : IL-8 à recruit MORE neutrophils à so there maybe ACUTE inflammation for 8
weeks : there’s still neutrophils
- If it cannot handle it ?? summon lymphocytes and chronic inflammation
- Granuloma = epithelioid histiocytes [ macrophages with abundant pink cytoplasm]
- NOT NECESSAIRELY : giant cells / rim of lymphocytes
- Non caseating : foreign material “ wood – breast implant” / sarcoidosis / Beryllium in
NASA / Crohn / Cat-Scratch ( stellate shaped granuloma )
- Caseating Granuloma : do AFP stain look for TB / GMS stain to look for fungus
- Granuloma = macrophage + TH1
- Macrophage secrete IL-12 à TH1 à Inf gamma à convert macrophage to histiocytes
- SCID : cytokine receptor def / ADA / MHC II
- Stem-cell transplant ##
- Bruton’s :Bacteria / enterovirus / giardia
- CVID : risk of autoimmune
- IgA def : especially in celiac diseases
- WASP gene = Wiskot Aldrich Syndrome Protein
- Lebman sacks ? SLE : vegetations on BOTH sides of the valve : characteristic
- SLE : Pancytopenia
- FALSLY elevated PTT : à the patient is actually hypercoaggulable
- DVT and Budd chiari / stroke / placental thrombosis
- Can’t chew a cracker “dry” / dirt in my eye / dental caries : Sjogren Synd
- Anti-SSA and Anti-SSB : anti Ribonucleoprotein
- Sjogren associated with RA
Sjogren à Parotitis à risk of B-Cell Lymphoma ## Unilateral swelling late in the disease
course
- Scleroderma ? No peristalsis à solids and liquids
- Serum antibodies against U1 ribonucleoprotein ? MIXED CT DISORDER
- Healing = Regeneration (same tissue : depend on type of tissues) + Repair ( scar)
- BM stem cells ? CD34+
- Stable tissue : Liver and kidneys
- Permenant tissue ? ONLY REPAIR by fibrous scar in ms / cardiac / neuron
- Repair ? permenant tissue / stem cells have been damaged
- Bone = type one / Cartwolage = type two
- Regeneration and repait ?? Paracrine signaling
- FGF ? Angiogenic ## and skeletal development
- Vit C : important of cross linking between hydroxyl
- Hypertrophic scar : excess SCAR tissue
- Keloid : WAYY out of proportion to the wound à ear lobe à type III

NEOPLASIA

- Unregulated, irreversible and monoclonal [ proved by G6PD isoforms on chromosome

X / androgen receptor isoforms]
- Polyclonal = hyperplasia
- Clonality of B cells is by light chain , kappa or lambda ( polyclonal : the K:L is STILL 3:1 )
- K:L is 20 : 1 ?? MONOCLONAL à lymphoma
- Both benign and malignant are monoclonal
- Lymphocytes à NO BENIGN
- Lung cancer is the most killer dt no improvement in screening
- 30 divisions occur before clinical symptoms
- With each division à mutations à more aggressive
- Depend on site : eg : pancrease is late : worst prognosis
- Carcinogens are agents that damage DNA
- Grains in Africa ? aspergillous à aflatoxins
- Arsenic ? Sq cell carcinoma of Skin / Lung cancer “ cig smoke” / angiosarcoma of liver
- Most important carcinogen in cig smoke is Polycyclic hydrocarbon
- Naphthylamine : in cig smoke : urothelial carcinoma of the bladder
- Nickel à lung cancer
- AML / CML / papillary carc of thyroid : Ionizing radiation à hydroxyl free radicals
- NON-Ionizing radiation ? UVB à BCC / Sq cell carcinoma / melanoma
- Proplem in Xeroderma
- myc translocated to ON location à macrophage eating dying cells à starry sky
- cyclin D à Mantle cell lymphoma : G1 à S
- expansion of the mantle : region next to the follicle
- CDK-4 à melanoma
- Hyperchromasia : increase nucleus
- The ABSOLUTE DIFFERENCE is that benign tumors NEVER METASTASIZE
- Immunohistochemistry : antibody that bind the cell to identify it
- Like “ keratin / vimentin / …..
- Used to classify tumors
- Chromogranin : good : carcinoid / bad : Small cell carcinoma
- Downregulation of E-Cadherin : attached to laminin and destruct BM
- BM : collagen 4 + laminin
- Attach to fibronectin then BV/ lymph
- Omental cacking : very thick in ovarian cancer

-----------------

BLOOD

- VC of vessel : sympathertic and Endothelin release

- VWF : Weibel Palade bodies
- Qualitative ?? NO PETICHIEA
- ITP = IgG against GP IIB/IIIA
- Spleen makes antibodies, and they coat platelets, then macrophages ALSO in the spleen
eat them
- Chronic ITP : eg SLE / women in child bearing age
- ITP : increase magakaryocytes ( to compensate)
- ADAMTS 13 : cuts down VWF polymer into monomers à deficient in TTP
( autoantibodies / autoimmune in adult female )
- Abnormal platelet adhesion à PLATELET microthrombi
- E.coli O157:H7 à verotoxin damages endothelial cells and damages ADAMTS 13
- Qualitative : BSS – Glanzman – aspirin – Uremia “ decrease function”
- BSS : platelets are lacking GP – 1B à platelets live shorter à mild thrombocytopenia à
compensatory increased size of platelets “ Big suckers”
- Coagg factor inhibitor ? usually Abs to factor VIII
- Distinguish between hemophalia : mixing study : adding normal plasma : if corrected
PTT then it’s hemophilia not coagg factor inhibitor
- VWF deficiency : abnormal ristocetin test
- Desmopressin increase release of VWF from W-P bodies
- LCF : 1) decrease production of coagg factors, 2) decrease epoxide reductase = decrease
activation of Vit K
- Large volume transfusion = dilution of coagg factors
- Heparin complex with PF4 à forms Abs à destroyed à fragments can activate other
platelets à coagulation
- Adenocarcinoma à mucin à activate coagg cascade
- D-Dimer : is the split product of fibrin ( which means there were excess fibrin)
- Plasmin cleaves Fibrin AND fibrinogen AND /knocks out coagg factors AND block platelet
aggregation
- Radical prostatectomy ?? à release of urokinase à anticoagg
- Liver cirrhosis ?? à decrease antiplasmin àanticoagg
- Increased fibrinoGEN split products BUT NOT D-DIMERES ( bcz no fibrin )
- D_DIMERS is the difference between it and DIC ###
- ANTEMORTUM CLOT : 1) attached 2) lines of zhan
- Endothelium releases Heparin Like Molecule “ HLM”
- Endothelium releases thrombomodulin : modulates thrombin that it can activates
protein C ##
- Vit B12 deficiency can lead to thrombosis dt increased homocysteine
- Protein C&S deficiency : skin necrosis with warfarin à usually knocks out C & S faster
and elrllier that 2,7,9,10 , so there will be INCREASED coagg factors à coagulation and
thrombosis à this is why we give heparin
- In AT III def : you give HIGH DOSES of heparin to activate the limited AT III à then give
coumarin to maintain and stop heparin then
- Atherosclerotic embolus : cholesterol crystals “picture”
- Caisson’s diseases = gas embolus causing BONE NECROSIS
- Amniotic fluid à baby skin gets shed off periodically so the amniotic fluid embolus will
contain keratin debris and squamous cells ## picture
- PE is usually silent 1) dual blood supply 2) small and self resolve
- Symptoms ? 2) large or medium sized artery 2) pre-existing Cardiopulmonary problems (
dual blood supply is not protective )
- Spiral CT : vascular filling defects in lung / Doppler in DVT / D-Dimers elevated
- Hemorrhagic bcz second blood supply “ blood re-enter” / loosely organized tissue
- Saddled embolus ? saddled to occlude BOTH branches of PA : electomechanical
dissociation ( there’s contraction bubt no blood is pumped)

ANEMIA:

- Microcytosis is due to an Extra division “ to maintain a nice pink cell”

- Ferroportin is the iron regulator NOT intestinal cells
- For every 3 TF à one carries Iron
- TIBC : how much TF – saturation : how many TF carrying Iron
- Decrease ferritin ß\\à always increased TIBC “ the liver senses and produces more
transferring”
- Increased TIBC / BUT decrease saturation
- INITIALLY normocytic anemia : good RBCs but few of them
- Pica : psychological drive to get iron : chewing on dirt
- IDA : INCREASED FEP free erythrocyte protoporphyrin
- They will give you a lymphocyte to compare size
- ACD ?? increased ferritin / ergo : decreased TIBC
- Decrease serum iron / decreases saturation / increase FEP
- Sideroblastic = decrease protoporphyrin
- Ringed sideroblast : Iron is present in MITOCHONDRIA
- Congenital : ALAS def
- Acquired : Alcoholism ( mitochondrial poison) / Lead ( ALAD and ferrochelatase) / Vit B6
( ALAS )
- High ferritin bcz macrophage will eat all the iron from the sideroblast ( SAME IRON
PROFILE as hemochromatosis)
- Thalassemia carries protection against pl. falciparum
- Normally 4 alpha alleles on chr 16
- Knock out 2 near genes ? cis [ worse] [ in Asians] [ ass with severe thalassemia in
offspring] [ high rate of spontaneous abortion]
- Knock out2 genes opposite ? trans [ less severe] [ Africa]
- 3 gene deletion ? no problem in foetus à after that à risk of HbH à tetra beta Hb
damages RBCs
- 4 gene deletion à tetramer of gamma chain à lethal in utero
- B- thalassemia : alpha tetramers damages RBCs à destruction In the spleen
- NO HBA à there’s HBA2 and HBF
- Macrocytic anemia : one less division
- Hypersegmented neutrophils = greater than 5 lobes
- Vit B-12 bind to ( R-Binder) from salivary gland
- Vit B-12 released in intestine by protease of pancrease and bind Intrinsinc factor
- Complex goes to ileum and absorbed
- Parietal cells = Proton Pumps / Pink “ not like blue chief cells” / Pernicious anemia
- Vit B12 def in pancreatic deficiency ? not released from R-Binder
- Methyl-malonic acid accumulation in B-12 ? à neuropathy and SCD
- Reticulocytes = RNA in cytoplasm
- A decreased RBCs mass may induce falsly increased Reticulocytes à so corrected
reticulocytes
- Corrected = Reticulocytes X hct/normal hct
- Spleen in normocytic extravascular hemolysis will have hypertrophy
- Intravascular ? bing to haptoglobin and send it back to spleen to re-use à so decreased
haptoglobim “ but it’s not enough”
- Hemoglobinemia / Hemoglubinuria / hemosedrinurea “ tubular cells contain iron – die
and slough off – days over à urine”
- Spherocytosis : inherited defects in membrane teathering protein : spectrin / Ankyrin /
band 3.1
- Increased RDW / parvo B19 crisis
- Splenectomy : anemia resolves but spherocytes PERSIST / howell jelly bodies
- HbS POLYMERIZE in acidosis / dehydration / hypoxia à this is not covalent binding
- HbF prevent against sickling à so use Hydroxyurea
- Extravascular hmolyisis / intravascular bcz membrane damage
- Target cells bcz membrane damage à blebs
- Sickling is usually reversible à if irreversible à vaso-occlusive crisis
- Maybe : Acute chest syndrome : occlusion of pulmonary vessels : aggravated by
pneumonia “ classic finding – most common cause of death “
- Gross hematuria and ptn urea ? à think renal papillary necrosis
- Sickle cell trait ? 55% HbA and 43% HbS and 2% HbA2
you need MORE than 50% HbS to sicke à so they don’t sickle
but in EXTREME HYPOXIA they can sickle à microscopic hematuria à eventually
decreased ability to concentrate urine
- Metabisulfite test : screen for HbS : +ve for BOTH trait and diseases
- HbC à LySine
- PNH : ACQUIRED defect of myloid stem cells ( RBCs / granulocytes / platelets) à GPI
protein which fixes CD55 (DAF : Decay Accelerating Factor) and CD59 ( MIRL :
Membrane inhibitor of Reactive Lysis )
- Shallow breathing at night à resp acidosis à complement activation
- Sucrose test : SCREEN : activate complement and induce hemolysis
- MCC of death : thrombosis à bcz destruction of platelets à fragments activate coagg
pathway
- AML develop in 10% ( it’s easy to acquire new mutation im myloid stem cells)
- African G6PD : mild decrease / Mediterranean : marked decrease of enzyme
- G6PD will not be available for the whole life of RBCs
- Heinz Preparation ? used to show hemoglobin aggregates à SCREENING
- Bite cells ? macrophages will take a bite with Hb Aggregates
- Warm IgG antibodies ? lose excess membranes à SPHEROCYTOSIS !
- SLE / CLL / drugs 1) penicillin : antibody binds to it 2) methyldopa à forms antibody
- IgM ? cold agglutinin à fixes complement à MAC
Mycoplasma / IMN
- Direct coombs : does the patient has RBC ALREADY coated ?
indirect : does the patient have Antibodies in the serum ?
- Myelophthisic disorder : fibrosis / granuloma / anything that occupies BM

BLOOD CELLS

- Neutropenia : from drugs à Rx is GM-CSF or G-CSF

- Neutrophilic leukocytosis ? infection / tissue necrosis / cushing
- Immature neutrophlis in left shift ? decreased CD16 ( which is the Fc receptor) which
means they are not functional correctly
- Eosinophilia ? allergy / parasitic infestation / HODGKIN’s ?? By IL-5 ##
- Basophilia ? à associated with CML ###
- Lymphocytes Leukocytosis ? à viral infection / Bordetella Pertussis ?? exception bcz it
produce Lymphocytosis blocking factor à inhibit Lymphocytes from entering LNs à
remain in the blood
- Generalized LAD in IMN ? T cells à in para-cortex
- Splenomegaly ? in PALS
- Atypical lymphocytes : 1) much bigger nucleus than adjacent RBCs 2) abundant blue
cytoplasm à resemble monocytes
- Spleen rupture à avoid sports for 1 year
- Rash with PCN
- Dormancy in B-cells
- Blast = large / little cytoplasm /punched out nucleus ( nucleolus)
- MPO crystallize to form Auer Rods à marker for myeloblasts
- tDt is a marker for Lymphoblast ( dna polymerase à in the nucleus )
- B-ALL à CD 10 / 19 / 20 / 22
T-ALL CD2 à CD 8 ( NO CD 10 ##)
- T-ALL à Thymic mass “ lymphoma” Teenagers
- Acute monocytic leukemia ? à GUMS ##
- Acute Megakaryoblastic Leukemia à lack MPO à Down’s Syndrome before the age of
Five ##
- Myelodysplastic syndrome à blasts less than 20% with cytopenias
- CLL : B lymphocytes à CD-5 ( normally on T not B ) and CD20
- CLL à can transform to diffuse large B-cell lymphoma ( enlargement of LNs and Spleen )
- In HCL à Splenomagealy is due to expansion of RED PULP
Dry tap ? bcz BM is fibrosed
No LN enlargement ( bcz TRAPPED in BM and in Red bulp)
- Respond to ADA (-) = Cladribine ( 2-CDA)
- Adult T-cell Lymphoma à there’s RASH nad Lytic bone lesions with hypercalcemia ( don’t
jump to MM)
- Neoplastic T- cells in epidermis à in mycosis fungoides is called Pautrier microabscesses
- Spread to the blood à Sezary syndrome à ceribriform nuclei
- MPD à all myeloid cells increase à but one in particular increases more
- Complications à 1) hyperuricemia 2)marrow fibrosis 3) transform to acute leukemia
- CML à BASOPHILS ##
- In CML à the mutation MUST be in a stem cell .. so the mutation maybe in the
Myelocytic stem cell à AML (2/3) / OR it can be in Hematopoeitic stem cell à ALL (1/3) ie
: Both can be correct
- CML chch : 1) LAP negative [ bcz they are inactive] 2) Basophils 3) t(9;22)
- PRV à thrombosis à Budd-Chiari
- PRV : mat cells à itching after bathing “ classic”
- Thrombocytosis : maybe ETC / IDA
- RARELY leukemia and RARELY fibrosis
- No significant risk of hyperuricemia “ just pieces of cytoplasm “
- IMF à PDGF à Megakaryocytes
- Splenomegaly and extramedullary hematopoeisis à leucoerythroblastic smear “ no
control of size and more immature cells in blood”
- Extramedullary is not sufficient
- Teardrop à stretch as they try to leave BM

LYMPHADENOPAHY

- Paracortex hyperplasia in viral / follicles in RA and early HIV

- LNs draining cancer ?? Sinus histiocytosis
- Lymphoma  lymph cells that form a mass
- Small lymphocytes = well differentiated
- In follicular lymphoma : the follicles contains cells that may fail somatic hypermutation
– they need apoptosis but BCL-2 anti apoptotic
- Translocate from chr 18 to Ig heavy chain on chr 14
- Rituximab  anti CD-20
- Can progress to large B-Cll lymphoma “ enlarging LN”
- Anti-apoptotic = no macrophages in follicles to clear the failed cells ( no tangible body
macrophages”
- Region immediately adjascent to follicle ?  Mantle cell lymphoma
- Marginal zone lymphoma  associated with chronic inflammatory state [ hashimoto /
sjogren / h,Pylori ]
- C-myc drives peoduction and growth  translocated to Ig heavy chain on chr 14
- Diffuse large  no follicle or whatever diffuse
- Sporadically or progressed from follicular
- B symptoms are due to cytokines ##
- Nodular sclerosis : neck or mediastinal LNs in females
- RS cells in spaces  lacunar cells
- Mixed cellularity : EOSINOPHILS  called in by IL-5
- MM  high serum Il-6 often elevated : important growth factor for plasma cells
- MM activates RANK receptors in osteoclasts
- Normal serum ptn electrophoresis : the spike is LESS than Albumin – in MM : in SPEP
[Serum Protein Electrophoresis] : M spike is higher than Albumin and narrow
- Usually IgG or IgA
- Increased IgG  decrease charge between RBCs  stick together  Roleaux formation
- Primary AL Amyloidosis bcz extra light chain
- MGUS in elderly  may develop MM
- Waldenstrom macroglobulinemia  this Is Lymphoma  macro bcz IgM is large
- Viscocity of the blood increases but no lytic bone lesions or kidney
- ttt with Plasmaphoresis
- histiocytosis : CD 1a+ and S100+
- people’s name = malignant / malignant = skin rash / 2 people = less than 2 yrs / three
people = more than 3 yrs
-

CVS

- Intima “Endothelium on BM” / Media “ sm.ms” / Adventitia : CT

- Vasculitis : 1) NS symptoms 2)ischemia
- Ischemia bcz 1)inflammation = tissue factor = thrombosis 2) heal by fibrosis
- Giant cell arteritis : classically ESR is > 100
- Giant cell arteritis : Granulomatous “ giant cell”
- It’s segmental  so you do biobsy  even if it’s negative it doesn’t exclude
- Takayasu ? LESS than 50 yrs old
- Medium vessels = muscular artery “ supply organs like Renal artery”
- PAN : fibrinoid necrosis  fibrosis  form NODES
- String of pearls appearance ? varying stages ( aneurism / fibrosis / aneurism / firbosis /
….)
- A kid with MI ? think Kawasaki
- Rx ? Aspirin and IVIG  NO steroids
- This is interesting bcz the C/P looks like viral illness and you shouldn’t give bcz Rye’s
syndrome
- Aspirin bcz inhibits COX and inhibit aggregation and protects them from thrombosis in
coronaries
- P- ANCA = perinuclear anti nutrophils cytoplasmic antibody
- C-ANCA = cytoplasmic Anti nutrophils cytoplasmic antibody
- Wagners = Microscopic Polyangitis except : 1) P-ANCA 2) no nasopharynx 3) no
granuloma
- Churg Vs Microscopic both have P-ANCA BUT Churg strauss : 1) eosinophilia 2)
granuloma 3) Asthma
- HSP? IgA deposition in mesangium of kidney
- Follows URT infection  because it generates IgA ##
- RAS in old male ? atherosclerosis / in female : Fibromuscular dysplasia
- Atherosclerosis : Intima of small and large sized vessels
- Artriolosclerosis : narrowing of small Bl.Vs
- Monkeberg : Media
- Rupture atherosclerotic plaque occurs at the neck ##
- Hyaline artrioloscleorosis : proteins : pink staining ( DM / benign HTN)
- Glomerular scarring : due to hyaline nephroscleorosis
- Hyperblastic : smooth muscle hyperplasia  flea bitten kidney and ARF
- Aortic dissection : 1) damage to intima 2) blood goes into media
- Need per-existing weakening of media and a lot o stress “ eg : HTN in proximal Aorta”
- HTN = narrowing of vasa vasorum
- Aneurism  sisrbts laminar blood flow  activates coagg cascade
- >5 cm aneurism  RUPTURE
- Triad of ( hypotention / pulsatile abd mass / flank pain)
- Usually dt atherosclerosis of Abd aorta
- Angina = REVEERSIBLE injury “ no necrosis”
- Unstable angina  INCOMPLETE occlusion of coronary a.
- MI : complete occlusion > 20 minutes ( thrombus of pirenzimital )
- Fibrinolysis --. Calcium enters the cell  contraction bands
- You only get fibrinous pericarditis with TRANSMURAL infarction
- Necrisos  dark coloration / inflammation  yellow / granulation  red / fibrosis and
scar  white
- Fetal Alcohol Syndrome  VSD  cri du chat
- Paradoxical embolus : from Right side  ASD  Left side
- PGE : KEEps PDA open
- TGA  meternal Diabetes
- Infantile coarctation : associated with PDA , occurs proximal to PDA
- Presented with lower extremity cyanosis / Turner Syndrome
- Adult coarctation : distal to ductus artriosus : hypotention in low etremitis  and
bicusbid aortic valve
- RF = molecular mimicry against M protein and endocardium
- Erhtyema marginatum : red at the margins
- Scarring of the valve  fish mouth appearance
- RHD Vs wear and tear AS stenosis : 1) in RHD there’s ALWAYS MS 2) RHD there’s fusion
of the valves
- pulmonary congestion  hge  macrophages  HF cells are in the lung
- septic embolization in SBE  jenway and osler / ACD
- Trans-eophageal-echo -> TEE : see vegetations in SBE
- Sterile vegetations  hypercoagg state or adenocarcinoma
- Libman sacks ? MV  regurgitation
 - DCM  regurgitations “ stretch of rings” / arrhythmia “stretch of conducting systems”
- DCM  pregnancy
- Myocarditis can cause DCM
- Ttt : Transplant only
- Congenital HOCM -- > AD : genetic mutations in sarcomere proteins
- HOCM : myocardial fibrils with disarray
- RCM = CHF “ blood accumulated backwards”
- Heart is permenant cells , so the only tumor is mesenchymal “ myxoma”
- Rhabdomyoma is a hamartoma
- Metastasis is more common than primary tumors  pericardium  pericardial effusion
-
-
-
-
-
-
-

: GI

- Behchet syndrome : apthus ulcers + genital ulcers after viral infection : no etiology
known
- Hairy leukoplakia ? on the lateral side NO dysplasia
- True leukoplakia is dysplasia vs candidiasis : scrab test
- Erythroplakia : vascularized leukoplakia [ more suggestive to dysplasia]
- Pleomorphic adenoma = stromal + epithelial
- MW syndrome : painful hematemesis
- Esoph varices ? painless hematemesis : MCC of death in cirrhoso [ with DIC]
- Chronic gastritis is type IV HPY , pernicious anemia is type II HPY !!!!!
- Celiac disease : DQ2 and DQ8
- Celiac is IgA deficient because it’s deposited and form dermatitis
- EATL : enteropathy associated T cell lymphoma : associated with celiac
- pANCA : think about UC
- smoking increases risk of chron’s and protects from UC
- RECTAL SUCTIO BIOBSY : not normal mucosal biobsy in hirchsbrung . to be able to truly
look at ganglia
- Aspirin : decrease COX , decrease adenoma carcinoma sequence
- Sessile is more dangerous and villous is more dangerous
- Pancreas : Liquifactive necrosis + fat necrosis of the surrounding adipose tissue
- Hypocalcemia dt use of calcium in saponification
- Pancreatitis  Shock dt digestion of Bl.Vs  hge and shock
- Chronic pancreatitis ? no elevated enzymes  all cells are destroyed
 - Pancreatic adenocarcinoma  DUCTAL carcinoma
- Thin elderly male that suddenly developed DM ? think cancer pancreas
- Estrogen stimulate HMG coA reductase / increase LPL receptors in the liver
- Gall bladder to the right scapula
- Biliary colic is dt contraction of GB on an obstructed duct
- Phototheraby doesn’t conjugate bilirubin, it just makes it soluble
- Viral hepatitis : UCB increase dt damage of hepatocytes / CB increases dt damage of bile
ductules
- Acute hepatitis : hepatic lobules / chronic hepatitis ? portal tracts
- Fibrosis in cirrhosis by TGF-beta from stellate cells
- Coagulopathy in cirrhosis ? decrease activity of epoxide reductase
- Mallory bodies are damaged intermediate filaments in hepatocytes
- Hemochromatosis : brown pigment in hepatocytes
DD : lipofuscin : wear and tear pigment / iron
do Prussian blue
- Wilson’s : inability to incorporate copper in ceruloplasmin / can’t put it into bile  build
in hepatocytes  free radicals
- Primary sclerosing cholangitis : peri-ductal fibrosis with onion-skin [ figure]
- P-ANCA / UC association ##
- Hypoglycemic child , elevated LFTs , N, V : check history for Reye’s
- Rupture adenoma – bcz it’s subcapsular
- Aspergilous  aflatoxins  mutations in P53 mutations ##
- HCC  vein  increase risk of budd chiari
- Nodular free edge of liver ? metastasis

REPRODUCTIVE

- unilateral lesion in the side of the vulva adjascent to vaginal canal  bartholin cyst “
painful”
- HPV  vulva / vagina / cervix = lower tract
- HPV : low risk = condyloma  6/11
HPV high risk = Dysplasia and carcinoma  16/18/31/33
- Risk is due to DNA sequence [ DNA virus ]
- Lichen sclerosis : parchement like vulva  postmenauposal women
BENIGN – slightly increased risk of sq cell carcinoma
- Lichen simplex chronicus  opposite : hyperplasia of sq epithelium dt chronic irritation
and scratching
BENIGN – NO increased risk
- Sq cell carcinoma in vulva  resembles leukoplakia  do biobsy
- Maybe HPV related “ VIN  carcinoma ‘ 16/18 /3 1 / 33
- Non HPV  long standidn lichen sclerosis [ elderly women larger than 70 yrs ]
- Extramammary paget’s diseases : malignant epithelial cells in the epidermis
- DD : carcinoma Vs. Melanoma  do stains
- Pagets  Pas +ve / Keratin +ve / s100 –ve
Melanoma  PAS –ve / Keratin –ve / S100 +ve
ONLY epithelial cells make mucus and PAS +ve ##
- Paget’s diseases in the nipple  usually there’s a cancer in the breast
Vulva ? usually NO cancer in the lower genital tract
- Adenosis ; persistence of columnar epithelium in the lower part of the vagina ## DES use
- These women are high risk for  celar cell adenocarcinoma
- Mass protruding from vagina / penis  child  think rhabdomyosarcoma [ picture]
- Malignant cell is Rhabdomyoblast 1) cytoplasmic cross-straiation / +ve for Desmin or
Myoglobim ##
- VAIN ? vaginal intraepithelial neoplasia ( Vs VIN : vulvar )
- HPV infection – cleared by immunity  only PERSISTENT infection with HIGH risk may
do CIN
- High risk ? produce E6 [ X p53] and produce E7 [ X Rb ]
- Rb bing E2F  no Rb ? E2F free  progression of cell cycle
- Cervical carcinoma : bleeding or pain after intercourse
- Immunodeficiency is highly associated with high risk HPV [ AIDS defining lesion ]
- Cervix : squamous AND adeno are possible , however squamous is more common , but
BOTH can occur and BOTH are related to hPV
- Cerial cancer may invade through uretine wall into bladder / ureter and for
hydronephrosis
- PAP smear is sensitive – colposcopy is specific
THEN Biobsy
- PAP smear is at transformation zone ##
PAP doesn’t detect adenocarcinoma as well ## much more difficult to detect
- The prevalence of cervical ADENOcarcinoma has not reduced , only squamous ##
- Quadrivalent vaccine 6/11/16/18 – 5 yrs protection
- PAP smears are still uses “ other strains ##
- Endometrium : functionalis layers sheds , Basalis persitis  regenerates
Asherman syndrome  damage to basalis eg by excessive D&C
- DUB ? anovulatory cycle :
proliferative phase – no secretory phase – no shedding - another proliferative phase on
top of the last one – cells grow beyond blood supply – necrosis and dysfunctional
bleeding
- Endometritis – retained parts of the placenta
- Chronic endometritis – have to see plasma cells
- Endometrial polyp : protrusion of endometirum : result of Tamoxifen bcz it’s agonist
on the breast
- Endometriosis : (((GLANDS + STOMA )))
- Endometriosis increases the risk of carcinoma at the site of endometriosis – especially at
the ovary ##
- Endomatrial hyperplasia – unopposed estrogen : GLANDS ONLY relative to the stroma
##
- Endometrioid ? the cancer endometrium looks pretty much like the normal
endometrium  usually from the hyperplastic endometrium – usually in age of 50
- OTHER type is sporadic : from atrophic endometrium  papillary serous ## occur in
elderly ## p53 mutation
- Psammoma bodies may arise in sporadic type
- Leiomyoma is realted to Estrogen and shrinks after menopause
- Multiple is MOSTLY benign NOT leiomyosarcoma
- White whorly masses and multiple and Pre-menopause : benign Vs he and necrosis and
single nad post menopause
- Leiomyomas are asymptomatic ( may be bleeding / infertility / pelvic mass )
- Leiomyosarcoma :
 De-novo NOT from leiomyoma
 Post menopausal not like leiomyoma
 SINGLE lesion with he and necrosis
 mitotic activity and cellular atypia
- maybe hge in CL  CL hgic cyst
- Ovarian tumors : epithelial / sex cord / germ cells
 Surface Epithelial : Present LATE , and vague symptoms
CA-125
(35-40) benign
(60-70) malignant
1) Cystadenoma : flast lining of the cells : single layer ( serous / mucinous )
2) Cystadenocarcinoma : multiple complex cysts and shaggy lining not smoothe
( serous / mucinous )
cells invade into cT
post menopausal women
BRCA 1 mutation  serous carcinoma of the ovary / fallopian tube also ##
3) Border line tumors : but metastatic potentials
4) Endometrioid histology : usually malignant , 50% have separate carcinoma in
the endometrium as well : check there
5) Brenner tumor : Bladder like
 Germ cell
Reproductive age ( 15-30 )
1) Fetal tissue : Cystic teratoma
Benign , except of 1) immature teratoma ( usually neuro ectoderm) 2) if the
tissue contains cancer itself [ somatic malignancy]
struma ovarii : contains thyroid tissue : THrx with mass In the ovary
 2) Fetal tissue : Embryonal carcinoma : primitive and aggressive with early
metastasis
3) Germ cells : Dysgerminoma : oocytes : large cells with central nuclei
Most common type , resembles seminoma
LDH tumor marker
4) Yolk sac : Endodermal sinus tumore  MC in kids
produces AFP
schiller duval bodies : glomerular like
5) Placental : Choriocarcinoma
NO VILLI  just the trophoblast
EARLY HGIC spread : programmed to invade
poor response to chemo ?? ##

 Sex-Cord
resemble granulose and theca cells ( vs : Leydig and sertoli )
1) Granulosa theca cell tumor : produces Estrogen : usually in child with precocious
puberty / adult with heavy menses / elderly with postmenopausal tumor
2) Sertoli-Leydig cell tumor ? may develop in female dt common origin - contain
Reinke crystals : pink cells with crystals
produce androgen
3) Fibroma : fibroblasts  meigs’ syndrome
 Metastasis
1) Kruckenberg tumor : Classically but not only : Gastric cancer diffuse type : signet
ring cells ( maybe breast in lobular carcinoma – colon cancer )
mucinous tumor ? ask if it’s primary or metastatic
one ovary : more likely primary / both ovaries : metastatic
2) Pseudomyxoma peritonei : mucin within peritoneum : jelly belly
usually a tumor within the appendix  metastasize to the ovary [ appendix /
ovary / peritoneum ]

- MC site in ectopic pregnancy : fallobian tube dt scar 1) PID 2) endometriosis

- lower quadrant Abd pain weeks after missed period
- vaginal bleeding / cramp pain / pass fetal tissues
- placenta previa : preview of the placenta
- preeclapsia is realted mainly to placenta – fibrinoid necrosis in placental vessels
- SIDS : 1 month to 1 year : usually during sleep
- Snow strom in hydatiform mole ? bcz grape masses full of fluid : black and white
- Complete mole :
 Completely molar with no fetal
  Completely involves the villi
 Compeletely involves ALL the villi
 Complete risk for carcinoma
- Choricarcinoma 1) complication of gestation or mole or even normal preg 2)
SPONTANEOUS germ cell tumor
- Gestational way responds well to chemo , BUT germ cell tumor NOT RESPONSIVE to
chemo ## HY

Penis

- Hypospadius : failure of fusion of urethral folds

- Epispadius : abnormality of genital tubercle
- Orchitis : Chlamydia D-K / NG in child
E.coli and pseudomonas
Mumps
Autoimmune ( DD TB : acid fast and necrotizing granuloma)
- Torsion : twist of the cord : artery patent vein collapsed : blood get in but no out --?
Hgic infarct
Adolescent with sudden onset and absent cremastric reflex
- Testicular tumors : only SC or Germinal
- Testicular tumors are NOT biobsied 1) it will seed to scrotum 2) mostly Germ cell tumors
and are malignant
 Germ cell tumors : Seminoma and non seminoma
 Seminoma : large cells with clear cytoplasm and central nuclei = dysgerminoma
Mass is homogenous with no hge or necrosis
May produce HCG
 Embryonal carcinoma :
hge and necrosis
CTX may result in differentiation
AFP or HCG
 Yolk sac tumor
AFP and shiller duval body “glomeruloid like “
 Choricarcinoma
B-HCG : resemble TSH so can cause hyperthyroidism
You don’t get villi : only trophoblasts
Tiny mass is primary and metastasis is large “ against logic”
 Teratoma
AFP or B-HCG
 Mixed
Prognosis upon the worst
 Sex cord
  Leydig cell
produce androgen and precocious pubery
Reinke crystals
 Sertoli cell
tubules – clinically silent
- Testicular tumors : 15-40 : germ cell 95% / >60% is lymphoma
- Prostatitis = orchitis organisms
- BPH may cause blebing of the bladder
- PSA is elevated : produced by glands : extra glands ? slight elevation
- 5-alpha reductase take months
- Prostatic adenocarcinoma clinically silent bcz it’s peripheral and post away from urethra
so no obstruction
- Screen by DRE / PSA from 4-10 or higher
- Gleason grading : architecture alone not nucleus : the higher score the worse prognosis

ENDOCRINE

- In prolactinoma : no galactorrhea in males bcz they have no sufficient glandular tissue

and lobules
- Octeriotide : blocks response of Ant Pit to GHRH
- Sheehan : no lactation / loss of Pubic hair dt loss of Androgen bcz no LH
- Empty sella : herniation of SAH into sella leading to death of Ant pituitary
- SIADH : Hyponatremia and mental changes ( vs water deprivation )
- Thyroxin : hyperglycemia
- Grave’s : woman in child bearing age
- Grave’s diseases : scalloping of the colloid : space between colloid and the edge of the
follicle
- Thyrotoxicosis : my use steroids to maintain the circulation
- Dyshormogentic goiter ? deficiency in Peroxidase enzyme ( mostly )  hypothyroidism
- Myxodema  GAG deposition in the larynx “ deep voice” and tongue
- Hashimoto : destryoy thyroid follicles  some will leak into the blood giving
hyperthyroidism , then goes back to normal and less than normal
- Hashimoto : antithyroglobulin and anti microsomal
- Germinal centers  form marginal zone  may develop lymphoma
- Hurthle cells : large cells with eosinophilic cytoplasm
- Subacute granulomatous thyroiditis : tender and NO hypothyroidism
- Reidel : maybe fibrosis of local structures
- Reidel ? young patients / Old age ? anaplastic carcinoma
- Radioactive I  increased in nodular goter or graves / decrease in carcinoma or
adenoma
- Then DO FNA , not true cut biopsy bcz it’s very bloody
- Follicular carcinoma ALSO has a capsule BUT carcinoma invade the capsule
 - FNA cannot distinguish  MUST see the capsule ##
- Follicular carcinoma like blood metastasis
- Ret mutation ? prophylactic thyroidectomy
-
- PTH activates osteoblasts which in turn activated osteoclasts ##
- Hyperpara  MCC parathyroid adenoma
- Hyperpara  hypercalcemia  enzyme activator  pancreatitis ##
- High PTH  osteitis fibrosa cystic
- Why ALP elevation when you bone resorbtion ? bcz it first activates osteoBlasts
- Pseudohypopara : KKDD , proplem in Gs protein  hypocalcemia with increased PTH
- DM : hyperkalemia but low total potassium bcz it’s escreted in urine
- So ttt : replace potassium
- Osmotic damage : schwan cells / pericytes of retinal bl vs “ he” / lens
- Cushing : gluconeogenesis : high glucose : excess insulin : increase fat storage on face /
trunk / back
- Htn bcz upregulated alpha-1 reeptors
- Sac of blood adrenal : waterhouse fridrichson syndrome
- Lung cancer lovers to go to the adrenal

BREAST

- Breast develop in the milk line ( from axilla to vulva) can develop anywhere
- TDLU : Terminal duct lobule unit : Functional unit : lobule secrete , ducts deliver
- Duct and lobules : inner luminal layer and outer myoepithelial layer
- Breast is hormone sensitive : develop after menarche / tenderness during menses /
hyperplasia in pregnancy / atrophy after menopause
- Galactorrhea is not realted to breast cancer
- Acute mastitis : staph dt fissures due to lactation
Continue drainage “ continue to feed the child” and use dicloxacillin
- Pericuctal mastitis : subarelolar duct inflammation / usually in smokers bcz loss of vit A
and loss of speciality of epithelium / sq metaplasia and keratin plugs the duct /
inflamataion
fibrosis and nipple retraction [ vs breast cancer ]
- Mammary duct ectasia : inflammation of the wall of duct  dilatation [ ectasia ] 
green brown nipple discharge and maybe a mass
multiparous post menopausal woman [ vs cancer ]
Biopsy : chronic inflammation and plasma cells
- Fat necrosis : maybe minor trauma and biopsy show calcifications and giant cells
- Fibrocystic change : pre-menopausal women
change : bcz it’s related to changing hormonal levels
cysts are blue in color : blue domed appearance ##
 BENIGN – NO RISK OF CANCER : fibrosis / cyst / apocrine metaplasia [ this is an
exception of metaplasia : no cancer risk]
some carry risk of INVASIVE CARCINOMA IN BOTH BREASTS ?
* ductal hyperplasia : excess number of cells [ X2 risk ]
* Sclerosing adenosis : too many glands + fibrosis and hardening  often calcified [ X2
risk ]
* Atypical hyperplasia : Atypical cells in ducts / or in lobules : ductal or lobular
hyperplasia [ X5 risk ]
- Intra ductal papilloma : benign variant has BOTH layers : epithelial cells and
myoepithelial cells  post menopausal woman with bloody nipple discharge
papillary carcinoma ?? NO myoepithelial cells ##
- Fibroadenoma : most common tumor in premenopausal women
wel demarcated and mobile
- Phyllodes : similar to fibroadenoma  but overgrowth of the fibers and leaf like
projections [ post menopausal women  can get cancer ]
- Cancer : first degree relative : sister / mother / daughter
- DCIS  only in the duct  walks it’s way into the terminal duct and the nipple ? Paget’s
disease
Invade  invasive ductal carcinoma
- LCIS  invade = invasive lobular carcinoma
- DCIS :
no mass – detected as calcification on top of dead cells [ vs fat necrosis / sclerosing
adenosis ]
Paget’s disease of the breast  THERE WILL be a cancer somewhere in the breast
- INVASIVE DUCTAL :
 tubular : tubule like structures with ONE layer and Desmoplastic stroma 9 CT
supporting the tumor)  good prognosis bcz tumor cells a re bound by stroma
 mucinous : good prognosis bcz malignant cells bound by mucus
 inflammatory : looks like infection and acute mastitis but not responsive by
antibiotics [[ see after 10 days ]]
cancer in dermal lymphatics ( must see clinical and EM )
poor prognosis bcz it’s already seeding
 Medullary carcinoma : high grade [ in BRCA1 mutations]
- LCIS
by chance : no mass or calcification
lacks E-cadherin : so cells are separated or not attached to each other due to mutation
of cadherin gene
usually multifocal and bilateral
use Tamoxifen  low risk for development of invasive
- INVASIVE LOBULAR
invade in SINGLE file pattern [ single from each other bcz no E-cadherin ] NO ductal
 structures ##

- Metastasis is most important, but most patients don’t appear with metastasis , so most
useful is Nodal affection
- Sentinel : inject dye and see the 1 st LN affected  not to remove NORMAL LNs
- HER 2 neu is a cll SURFACE – Estrogen is cytoplasmic that goes to the nucleus
- Tripple negative ( ER / PR / HER 2neu )  poor prognosis
- BRCA 2 – breast cancer in males
- Male : usually ductal carcinoma bcz no lobules aslan
BRCA2 and kleinfilter
-

CNS

- NTD : low folate PRIOR to conception

- Syrngomyelia : P/T on both sides – may be LMNL if expands – maybe lateral horn and
horner’s syndrome
- Familial ALS ? Zinc copper superoxide dismutase mutation
- Meningitis is inflammation of leptomeninges : ie pia and arachnoid
- Bacterial meningitis : PUS  may press on the brain causing herniation
- Cerebral Vascular diseases :
 Global cerebral ischemia :
 mild ( conusion like in insulinoma )
 severe ( vegetables )
 moderate ( infarcts and watershed area)  laminar necrosis : present in lines
[ cerebellum or hippocampus ]

 Ischemic stroke :
 Thrombotic  PALE infarction at the periphery [ bcz you cannot lyse the
thrombus it will reform ]
 Embolic : when embolus gets lysed  hgic infarction
 Lacunar : hyaline arteriolosclerosis in small Bl.vs  deep areas
 Intracerebral hge :
 rupture charcot bouchard aneurism
 SAH : berry anurism lack media layer in branching point ##
- MLD  cannot degrade mylin – acumilate in lysozomes
- Adrenoleukodystrohpy : demylinating diseases : failure of adding coA to long chain fatty
acids  fatty acids accumulate and damage adrenal gland and white matter
- JC virus  immunodeficiency activates it  PMLE
- Apo E4  increase risk of beta amyloid [ 4 >2 ]
Apo E2  decreased risk of Beta amyloid
 - DS ? APP is present on chromosome 21 , they have extra chr 21 and extra APP
- Familial : presinillin 1 mainly mutation ( also presinillin 2 )
- Brain atrophy ? ventricles dilate to fill the space  Ex Vaco
- A-Beta amyloid may deposit on blood vessels of the brain  Amyloid angiopathy
- TAU protein : hyperphosphorylated  cannot organize microtubules  neurofibrillary
tangles
- Vascular dementia : damage of brain areas ( 3,5,6 pyramidal neurons and hippocampus )
 2nd MCC of dementia
- MPTP can result in Parkinson’s
- Parkinson’s dementia ?  LATER not EARLY
Early ? Lewy bodies in cortex  lewy body dementia not parkinson’s
- Striatum ? it got a striate running in between ( internal capsule )
- Anticipation ? further expansion of tnr in SPERMATOGENESIS
- LP improves normal pressure hydrocephalus
increased CSF bcz decreased absorbtion of CSF in arachnoid villi [ unknown reason] –
stretch corona radiate
- Prion ? beta pleated sheets
- How can you get beta pleated ptn ? sporadic / inherited / Transmitted [ CJD : ( maybe
corneal transplant ) RAPID dementia and patient die within a year + startle
myoclonus [ involuntary ms contraction wit minimal stimuli ] and ataxia / spike wave
complexes on EEg ]
- Variant CJD ? mad cow
Familial fatal insomnia ? inherited with exaggerated startle response
-
- 50% Glial cells : atrocytes – oligodendrocyes – ependymal cells
- 50% neurons + meningothelial cells
- Meningeoma : female > male bcz it’s related to Estrogen
- Compresses but doesn’t invade
- Medulloblastoma  Drop metastasis : to spinal cord

MSK

- Activating mutation in FGF3  inhibit cartilage

- OI : blue sclera : exposure of choroidal veins
- Acidic environment is necessary to remova Ca from bone ##
CA is required to produce acid  CA deficience ? in osteopetrosis : failure of resorbtion
- Tie in with RTA ##
- Alkaline environment is required to add Ca to bone ( Alk phosphatase )
- Paget’s disease starts by osteoclasts
- Lytic bone surrounded by sclerosis  osteomylitis
- Osteoma : fascial bone / Gardner Syndrome
- Osteoid osteoma : osteoblasts tumor surrounded by active bone
Diaphysis of long bone
cortex of long bone
bone pain resolves with Aspirin
- Osteoblastoma :
vertebra
pain doesn’r respond to ASA
- Chondroma : small bones of hands and feet
- Chondrosarcoma : pelvis or femur
- Pannus is inflamed granulation tissue in RA [ bl vs / fibriblast / myofibroblast]
Myofibroblasts contract causing deformities
Systemic manifestaions
- Dermatomyoscitis : may get malar rash
- Dermatomyoscitis : Perimysium inflammation with perifascicular atrophy of the muscle
Polymyoscitis : no skin  Endomysial inflammation
- Dystrophin links cytoskeleton to extracellular matrix
- CK is elevated in Duchene dt damage of ms fibers
- Lambert-Eaton :
 Improves with ms use
 Eyes are spared
 Anticholinergics are of no use
 Resolves with resection of cancer
- Rhabdomyosarcoma : desmin positive and rhabdomyoblast
- Stratum spinosum : DESMOSOMES
- Acne : hormone related increase in sebum – excess keratin block the follicle
( comedones)
- Probionibacterium acnes : infection of acne : use benzoyl peroxides antimicrobial
- Psoriasis : associated with HLA-C
- acanthosis : increase spinosum and epidermal hyperplasia
- Parakeratosis / neutrophils in coneum : munro abscess / elongated paplillae with
thinning above them , exposure of bl. Vs [ asupitz]
- Ttt : steroids + PUVA : psoralin + UVA
- Lichen planus : Pruritic papules, purple , polygonal , planar
- Inflammation of dermal epidermal junction  sawtoothe appearance
wicham stria
associated with hep c
- Pemphigus : basal cells is intact
- Wall of blister rupture easily bcz not all layers over blisters
- Separation bcz IgG gainst desmoglein  component of desmosome  separation :
Acantholysis of strarum spinosum
- Immunohistochemistry :IgG surrounding keratinocytes  fishnet appearance ##
 - Bullous pemph : not rupture easily “ wall is entire epidermis”
oral mucosa is spared
- Dermatitis herpetiformis : resembles little blisters of herpes  IgA deposits ( against
gluten )
- Erythema multiforme : mycoplasma / HSV / malignancy
Target lesion : necrosis of center
- EM + oral mucosa + fever = SJS
- Severe SJS = TEN ‘ drug’ with sloughing of skin
- Pseudocysts in seborrhic keratosis : contains pink keratin ## coin like stuck on lesions
- Vitiligo  autoimmune destruction of melanocytes
- In lighter individual ? failure to tan
- Albinism : Melanocytes are normal  problem with tyrosinase
- Freckles  darker in sun lightdt increase number of Melanosomes NOT melanocytes
[ organelle in melanocytes ]
- Melasma : mask like pigmentation of cheeks : pregnancy
- Nevus have hair mostly, but melanoma destroys skin and hair follicles
- Acquired nevus 
starts in a child as Junctional
then progresses to dermis [ compound]
then junctional disappears and remains the intradermal [ most common in adults ]
- Lentigo maligna : lentiginous means remain in d-epidermal junction  excellent
prognosis
- Superficial spreading : good prognosis
- Nodular melanoma : Early vertical phase  push epidermis up  nodules
- Acral lentiginous  palms and soles  not related to sun  black people
- Scalded skin syndrome : separation is at stratum granulosum : very superficial
Vs TEN : dermal epidermal junction  very deep
-

NUTRITION

- Kwash : liver ptn decrease , muscle ptn is relatively unchanged

- Anorecia / bullemia : MCC of death is Vfib dt hypokalemia
- In hyervitaminosis A : skin is yellow but sclera is normal unlike jaundice
- Alkalinephosphatase dephosphorylates pyrophosphate which normally inhibits bone
mineralization
- Epoxide reductase activates vitamin K
- Bitot’s spots in Vit A deficiency
 - High fiber diet : decrease Estrogen deconjugation / binds lipocholic acid which colon
cancer / increase fecal bacteria in fermentable type / increase stool freq

Renal :

- Unilateral renal agenesis : later on life there’s hyper filtration syndrome and Renal
failure
- Dysplastic kidney ? cysts with wall containing cartilage : NON INHERITED !! don’t confuse
with ADPKD
- Medullary cystic : shrinken kidnys + cysts in MEDULLA
- Most important in interstitial nephritis is eosinophilic cell casts
- Very important : in MCD there is effacement of foot processes because of cytokines,
in Hodgkin’s Lymphoma there’s a huge amount of cytokines which is responsible for
the B symptoms such as fever, night sweats, ……
- in type II MPGN : there’s antibody to C3 convertase which decrease serum C3 and
increase c3a and c3b
- DM nephropathy ? NEG of efferent, so ACEi decrease it and good prognosis
- Bladder cancer : 2 pathways :
 Papillary pathway: start LG à HG à invade
 Flat pathway : start HG à invade + EARLY p53 mutation
- Bladder adenocarcinoma ?
 urachal remnants at the dome of the bladder
 Cystitis glandularis : cystitis followed by metaplasia
 Bladder esxtophy

Respiratory :

- Nasal polyps : allergic rhinitis / Cystic fibrosis / Aspirin intolerance

- Angiofibroma : in adolescent males : epistaxis
- African children and Chinese young adult : EBV NP carcinoma : epithelial cells [keratin]
on a background of lymphocytes
- Laryngotracheobronchitis : parainfluenza virus
- Vocal cord nodules : degenerate myxoid tissue : singers
- Laryngeal papilloma is single in adult , multiple in children [ hpv] LOW risk of carcinoma
- TB meningitis ? BASE of meninges
- Smokers : cenrtiacinar emphysema in upper lobes
- Alpha-1 antitrypsin deficiency : accumulation of unfolded protein in liver ER ## [picture]
- PiM is normal allele , PiZ is the mutant
- Heterozygotes ? normal except if smoking
- Homozygote : panacinar + cirrhosis
- They will NOT have mucus cough
- Very thin patients
- IL-5 calls in eosinophils
- Bronchiactasis : Amyloidosis
- TGF-B induce ILF
- Beryllium : In miners / aerospace NASA : non-caseating granuloma in the lungs and hilar
LNs, various organ : NOT SARCOIDOSIS :Berryliosis
- Sarcoidosis ? lacrimal and salivary glands : mimic sjogren’s
- Insulin inhibit surfactant “ in GDM”
- Free radicals : ROP + damage to the lung with bronchopulmonary dysplasia
- Sq cell carcinoma : keratin pearls / Intercellular bridges
- Broncioloalveolar cell carcinoma : clara cell tumour , consolidation like on imaging , LM [
pic] excellent prognosis
- Lung loves to metastasize to adrenal gland