Pictures for Arab board exam

lymphomatoid granulomatosis

characterized by angiocentric and angioinvasive lymphoid infiltrates with fibrinoid necrosis of the
vessel walls and widespread necrosis of the surrounding parenchyma
Alkaptonuria
 Adenoid cystic carcinoma
• A primary salivary gland or minor salivary gland of upper aerodigestive tract carcinoma characterized by its
biphasic ductal and myoepithelial differentiation.
• Grows in tubular, cribriform, and/or solid patterns: solid pattern is associated with adverse outcome
• 60% - 90% carry MYB-NFIB or MYBL1-NFIB fusion
• More common (60% of all tumors) in minor salivary gland, especially those in oral cavity but may also
occur in sinonasal tract, nasopharynx, oropharynx and trachea
• Among major salivary glands, the most common affected site is the parotid gland
• Frequent perineural invasion.
• Lung is most common site of distant metastasis.
• Ductal component is typically positive for CK7 and CAM 5.2
• Myoepithelial component is positive for myoepithelial markers,
e.g. SMA, S100, calponin, p40, p63, GFAP and cytokeratins
• Other positive stains: c-KIT (CD117)
• MYB overexpression is a sensitive but nonspecific immunomarker for adenoid cystic carcinoma
Myoepithelial component is positive for myoepithelial markers, Ductal component is typically positive for
e.g. SMA, S100, calponin, p40, p63, GFAP and cytokeratins CK7 and CAM 5.2
Myoepithelial component is positive for myoepithelial markers, Ductal component is typically positive for
e.g. SMA, S100, calponin, p40, p63, GFAP and cytokeratins CK7 and CAM 5.2
Myoepithelial component is positive for myoepithelial markers, Ductal component is typically positive for
e.g. SMA, S100, calponin, p40, p63, GFAP and cytokeratins CK7 and CAM 5.2
Circular islands of abundant very small cells
Adenoid cystic carcinoma
Sample pathology report

• Left parotid, parotidectomy:

• Adenoid cystic carcinoma, solid, cribriform and tubular pattern (see
synoptic report)

• Comment: Solid component accounts for 20% of total tumor volume.

• In breast
• Start with p63, then CK5/6
 Rosai-Dorfman disease
• Rosai-Dorfman disease, also called sinus histiocytosis with massive lymphadenopathy, is a disorder of
massive lymph node involvement that may also involve extranodal sites.
• Histologically, large histiocytes are present with abundant pale eosinophilic cytoplasm and mildly atypical
round vesicular nuclei.
• The background shows lymphocytophagocytosis (emperipolesis) in a background of mature lymphocytes
and plasma cells.
• The histiocytes are immunoreactive for S100 and CD68
and negative for CD1a.

Lymph node : Distinctive features are:

• emperipolesis,
• plasma cells,
• distention of nodal sinuses.
Emperipolesis
Liver biopsy : The hepatocyte plates are atrophied, and there is massive deposition of eosinophilic extracellular amyloid (arrow) along the sinusoids in the space of
Disse. ( hx of dialysis)
Ovarian tumor
 Solitary fibrous tumor (keratin-)

Express:

CD34
Diffuse and strong CD34
(nonspecific) Vimentin

BCL2

Markedly collagenous stroma ("ropey collagen") with irregularly

STAT6 immunohistochemistry highly
distributed thick walled "staghorn" vessels and bland spindle
sensitive and specific surrogate for NAB2-
cells
STAT6 gene fusion
Gross: Composed of dense, gray-white fibrous tissue with firm, whorled cut surface (like uterine leiomyoma),
large tumors may be cystic and hemorrhagic

Cut section of the excised tumor revealing an

encapsulated solid fleshy mass with whorling
 Synovial sarcoma (PAN-CK+/ EMA+)

BCL2+,

CD99+

TLE1+, cytokeratin+, EMA+, BCL2+, CD99+

Has a characteristic chromosomal translocation t(X;18)(p11;q11) involving genes SS18 and
either SSX1, SSX2 or SSX4
Synovial sarcoma (PAN-CK+/ EMA+) S100+
TLE1+, cytokeratin+, EMA+, BCL2+, CD99+

CD99+

BCL2+
Mesothelioma
 Distinguishing pleural malignant mesothelioma from lung
adenocarcinoma

• Epithelial markers that are usually present in both tumors:

( EMA, Pan-CK).

• Markers usually expressed in carcinoma but not in mesothelioma:

MOC31, Ber-EP4, CEA, CD15, MUC4, Claudin-4,

• Markers usually expressed in mesothelioma but not in carcinoma:

Calretinin, WT1, CK5/6, D2-40

Calretinin CK5/6 CEA MOC31

Asbestosis

fibrous pleural plaque

 Gross diagnosis?

Sarcoidosis – Honeycombing

Prominent honeycombing is present in the

lower lobes accompanied by fibrosis and some
honeycombing in the upper lungs.
Honeycombing consists of cystically dilated
airways separated by scar tissue resembling the
honeycomb of bees. It is a non-specific end
stage of many types of interstitial lung disease
Q: Lung tumor , pt has hx of GIST, this condition associated
with……..

Carney traid:

• Pulominary chondroma
• GIST
• Paragnglioma
Paragnglioma
 Paraganglioma
Macroscopy (A) tumor nodule brownish lobulated surface and soft consistency of 60 x
45 x 31 mm.
Microscopy (B) tumor proliferation of spindle cells with ovoid nuclei chromatin
stippling "salt and pepper" and large finely granular basophilic cytoplasm.
GIST DOG1, KIT, CD34
 GIST in
stomach
•Carney triad: GIST, pulmonary chondroma,
paraganglioma

•Carney-Stratakis syndrome: GIST and

paraganglioma

•Familial: germline mutations

in KIT or PDGFRα autosomal dominant

•DOG1 is usually positive in cases of GIST

negative C-KIT.
Gastric GIST: Risk of Disease Progression

Size ≤ 5 mitoses per 50 HPF > 5 mitoses per 50 HPF

> 10 cm Moderate High
> 5 to ≤ 10
Low High
cm
> 2 to ≤ 5 cm Very low Moderate
≤ 2 cm No No
• pT0: No evidence of primary tumor .
• pT1: Tumor 2 cm or less
• pT2: Tumor more than 2 cm but not more than 5 cm
• pT3: Tumor more than 5 cm but not more than 10 cm
• pT4: Tumor more than 10 cm in greatest dimension
• Because of the advent of small-molecule kinase inhibitor therapy in the treatment of GIST , it has become
imperative to distinguish GIST from its histologic mimics, mainly:
leiomyoma, leiomyosarcoma, schwannoma, and desmoid fibromatosis

• For the initial work up of GIST, a basic immunohistochemical panel including CD117 (KIT), DOG1 (Ano1),
Desmin, S100 protein and CD34 is recommended.
• GISTs are immunoreactive for KIT (CD117) (approximately 95%) and/or DOG1(>99%).

• Most KIT-negative / DOG1 positive GISTs are gastric or extra-visceral GISTs and almost invariably harbor a
platelet-derived growth factor receptor A (PDGFRA) mutation.

• Since succinate dehydrogenase (SDH)-deficient GISTs have specific implications ,

• it is recommended to screen all gastric GISTs for loss of SDH by immunohistochemistry, usually best
accomplished by staining for SDHB, which is loss in all subtypes of SDH-deficient GISTs
Coccidioidomycosis
• Infection caused by breathing in the microscopic
fungal spores from the air.
• Diagnostic: Suppurative granulomas containing
spherules.
• Spherules are usually present in association with
histiocytic neutrophilic infiltrate or rarely within
the hyperplastic squamous epithelium.
Sites:
• Lungs
• Skin
• Disseminated
 Blastomycosis
• Due to Blastomyces dermatitidis, a spherical, double-
contoured, 12 micron yeast that reproduces by
budding
• Granulomatous and neutrophilic infiltrate
• Fungi are within giant cells
• Blastomyces dermatitidis is a 12 micron, spherical,
double-contoured yeast with broad based buds
 Pneumocystis jiroveci
• Pneumocystis Carinii Pneumonia (PCP), now referred to as Pneumocystis Jirovecii Pneumonia is a fungal
infection that most commonly affects the immunocompromised and, in some cases, can be severely life-
threatening.
• Typically, patients at risk are those with any underlying disease states that alter host immunity such as those
with cancer, the HIV, transplant recipients, or those taking immunosuppressive therapies and medications.

Pneumocystis jiroveci cysts.

GMS stain for Pneumocystis carinii.
 Cytology: Foamy alveolar cast

• Acelluar foamy casts containing debris.

• Silver stain demonstrate cup shaped
organisms that lacking budding.
• Pnumocystis have an outer round cyst,
which contain comma-shaped trophozoites.
• On pap stain , the organisms are not visible
except as negative image
• Silver stain as GMS are at best
demonstrating the cup shaped cyst and
internal comma-shaped trophozoites.
Foamy alveolar cast
 Cryptococcus neoformans

GMS stain. Encapsulated variably sized yeasts with thin walls noted on
H&E stain.
 Cryptococcus neoformans

Encapsulated variably sized yeasts with thin walls Identifying variably sized encapsulated yeasts with narrow
noted on PAS stain. based budding morphologically consistent
with Cryptococcus species
 Key words :
Nocardia asteroides

lung abscess,
ulcerative colitis,
steroid

grocott's
methenamine silver
stain
 Grocott-stain

• Grocott stain demonstrates numerous thin, Grocott-stained cytological preparation reveals thin,
filamentous, lamifying bacteria.
filamentous and lamifying argyrophilic bacteria, strongly
• N. asteroides is an opportunistic pathogen for
immunocompromised hosts.
suggestive of nocardiosis.
 Key words : Nocardia (fite stain .gonccret)

lung abscess, ulcerative colitis, steroid

Necrotizing inflammation (abscess formation) is filamentous bacteria are Gram-positive

observed (HE
 Nocardia Gram stain

Modified acid fast stain shows weakly acid fast

branching, filamentous bacilli

Numerous long, thin, Gram positive filaments are

present. Although the appearance of the
filaments is similar to those of Actinomyces,
Nocardia do not form colonies in tissue.
They are usually seen within abscesses.
Sometimes the filaments of Nocardia stain
An acid fast stain demonstrates a long filamentous organism in the positive with acid fast stains.
center that is dark red. This is typical for Nocardia infection
• Histologically, Nocardia has delicate (< 2 microns in thickness) filaments with pronounced branching.
• Actinomyces in contrast has a similar filamentous appearance, albeit with slightly thicker, straighter, and
less-branched filaments.
• Since the histologic appearance of Nocardia is similar to other Actinomycetes family members, culture
and biochemical testing is necessary for definitive diagnosis/identification.
• Nocardia organisms are classically weakly acid-fast. This characteristic may help to
distinguish Nocardia from negative Actinomyces (which is modified-acid-fast-negative ).

Actinomyces
 Pulmonary emphysema is defined as the "abnormal
permanent enlargement of the airspaces distal to the
terminal bronchioles accompanied by destruction of the
alveolar wall and without obvious fibrosis".

Four variants:

1-Centrilobular emphysema
2-Panacinar emphysema
3-Paraseptal emphysema
4-irregular emphysema

presence of centrilobular emphysema in

the upper zones of the lungs.
1-Centrilobular: associated with long standing tobacco use.
2-Panacinar: associated with alf-1 antitrypsin deficiency.
3-Paraseptal
4-irregular: occurs at periphery and of large scar and focal lesions.
 Centrilobular emphysema :
associated with long standing tobacco use and
smoking.
Upper lobe
 Panacinar emphysema:

associated with alf-1 antitrypsin deficiency

Lower Lobe
paraseptal emphysema

associated with Spontaneous pneumothorax

 Lymphangioleiomyomatosis

The image demonstrates innumerable small regular

lung cysts diffusely distributed throughout the
lungs,
Lymphangioleiomyomatosis (exprse melanocytes and smooth muscle
markers)
In lungs, LAM shows proliferation of plump spindle-shaped myoid cells arranged in short fascicles
around arterioles, venules, and lymphatics which cause thickening of alveolar septa.
PEComatous Tumors & Tuberous Sclerosis:
• Lymphangiomyomatosis, clear cell sugar tumor of lung (PEComa) and
pecomatosis belong to the PEComatous family of tumors.
inflammatory myofibroblastic
tumor (ALK+)
Placenta:
Liver
 Cavernous hemangioma

Well circumscribed and nonencapsulated large mass with a red-brown color, focal honeycombed appearance,
sponge-like consistency and foci of fibrosis.
Cavernous hemangioma
Focal nodular hyperplasia
• Focal nodular hyperplasia (FNH) is the second most common tumor of the liver,
after hemangioma.

• This tumor characteristically is a solitary (80%), subcapsular, nodular and bulging

mass, light brown to yellow (usually lighter than the surrounding liver), with a
central stellate scar from which broad fibrous septa radiate outwards .

• It is usually well circumscribed, but not encapsulated.

• Occur in non-cirrhotic liver.
Focal nodular hyperplasia

1- satellite scar

2- ductular reaction and inflammation

in fibrous septae.

3-Glutamine synthetase: patchy and

map-like pattern

DDx : hepatocellular adenoma

Hepatocyte plates are 1 - 2 cells thick and

are supported by an intact reticulin
framework
 Nodular regenerative hyperplasia (NRH)

-Micro nodular cirrhosis without fibrosis.

-Lead to portal HTN.
-No fibrous septa between nodules ( atrophic
hepatocytes)

Nodular regenerative hyperplasia (NRH) is characterized by

diffuse replacement of liver by small nodule
 Trichrome Stain

Trichrome stain highlights the nodules.

By definition, there are no fibrous septa between

the nodules in nodular regenerative hyperplasia
 Reticulin stain should be obtained in all cases of
unexplained portal hypertension

Reticulin stain highlights the nodules.

The reticulin network is compressed in the parenchyma

between the nodules.

Reticulin stain is very useful for the diagnosis as the

nodularity in NRH can be subtle.
• No Fibrous Septa

• Trichrome stain shows absence of fibrous septa

at the periphery of the nodules.
This distinguished NRH from cirrhosis.

• Focal sinusoidal dilatation can be seen in NRH.

• The hepatocytes between the nodules are

compressed and atrophic.
 Hepatocellular adenomas
• Benign
• Occur in non-cirrhotic liver.
• Detected incidentally with abdominal image.
• Pain due to rapid growing .
• Rapture of adenoma leads to intra abdominal bleeding
• Associated with oral contraceptive (estrogen) and anabolic steroids.
• Cessation of exposure to sex hormones often can lead to full
regression.
• Subtypes…> related to risk of malignant transformation.
 Hepatocellular adenomas
1- HNF1-a inactivated hepatocellular adenomas: (often fatty) LFABP absence in this adenoma :
diagnostic
No risk of malignant transformation.
Common in women
OCP implicated in some

B-catenin: nuclear staining is a

2- B –Catenin activated hepatocellular adenomas: (cytologic dysplasia) diagnostic

very high risk malignant transformation and should be resected even when asymptomatic Glutamine synthetase:
Men and women diffuse positive
associated with OCP and anabolic steroid

3-Infammatory hepatocellular adenomas: ( telanegctatic vessel, inflammation and ductular reaction)

Small high risk malignant transformation and should be resected even when asymptomatic C-reactive protein
and
Men and women serum Amyloid A
Associated with non-alcoholic fatty liver disease.
HCC
mutation in gp130……. (IL-6 mediated JAK-STAT signaling)
Smooth outer surface
 • well defined border

• Partially encapsulated masses of uniform ,

bland looking hepatocyts .
• unpaired arteries
• no central veins or bile ducts.

• In reticulin stain: the hepatocyte plates are

still only 1-2 cell thickness (every cell
touches -the reticulin).
 HNF1-a inactivated hepatocellular adenomas

HNF1A mutated hepatocellular adenoma: high power HNF1A mutated hepatocellular adenoma: reticulin stain
view showing marked fat accumulation in lesional highlights intact reticulin framework with 1 - 2 cell thick hepatic
hepatocytes plates and loss of reticulin around steatotic hepatocytes
 HNF1-a inactivated hepatocellular adenomas

negative nuclear immunohistochemistry staining for beta catenin in immunohistochemistry staining for glutamine synthetase show
lesional hepatocytes; instead positive membranous staining is seen. patchy positivity in few lesional hepatocytes
B –Catenin activated hepatocellular adenomas

focal pseudoacinar architecture.

 Infammatory hepatocellular adenomas

high power view showing sinusoidal dilatation and positive immunohistochemistry staining for SAA
inflammation characteristic of HA-I subtype.
Hepatoblastoma

Frequent activation of the WNT signaling pathway. Involving

mutation in APC gene.

Pts with familial adenomatosis polyposis frequent develop

hepatoblastoma.

Chromosomal abnormalities.

beckwith wiedemann syndrome.

Hepatoblastoma
 Hepatoblastoma

Hepatoblastoma with fetal component (clear Fetal pattern hepatoblastoma with small peripheral nests; these
cytoplasmatic cells) nests usually have low proliferative activity and thus are more
resistant to chemotherapy
B-catanin
Hepatoblastoma, embryonal pattern (black arrows) and fetal patterns (blue arrows)
Hepatoblastoma, embryonal pattern (black arrows), fetal pattern (blue arrows) and cholangioblastic pattern (red arrows)
HCC in cirrhotic liver

HCC appear grossly as:

1- unifocal large mass.
2-multifocal widely distributed nodules varying in size.
3-diffuse infiltiraive cancer.
 Polyclonal CEA, villin and CD10 reveal
canalicular pattern in HCC

• Immunohistochemical staining patterns of CD10

and pCEA.
A, Enhanced CD10 canalicular staining seen in a
HCC (400x).
B, Enhanced pCEA canalicular staining in a HCC
(400x).

C, Linear canalicular staining pattern for CD10 in

nonneoplastic liver tissue (400x).

D, Linear canalicular staining pattern for pCEA in

nonneoplastic liver tissue (400x).
Positive staining was also noted in scattered
inflammatory cells for pCEA.
Fibrolamellar HCC in non cirrhotic liver
 Fibrolamellar HCC
Diagnosis
Combination of
• Compatible histomorphology
• Appropriate immunophenotype (CK7, CD68 positive) or detection of key genomic events
(DNAJB1 PRKACA, PRKACA rearrangement, PRKACA amplification, PRKAR1A loss)

CK7 HepPar
• Characteristically no underlying chronic liver disease
• Eosinophilic tumor cells characterized by ample granular cytoplasm
• Intratumoral fibrosis
• Recurrent protein kinase A oncogenic driver abnormalitie
• Serum alpha fetoprotein is classically not elevated

• > 95% of cases harbor the oncogenic DNAJB1-PRKACA fusion gene

formed by intrachromosomal deletion on chromosome 19
Typical fibrolamellar carcinoma results.

• (a) Typical fibrolamellar carcinoma. The

neoplastic cells are characterized by abundant
eosinophilic cytoplasm, nuclei with open
chromatin, and prominent nucleoli.
• The tumor cells form trabecula which are
separated by bands of fibrosis.

• (b) Cytokeratin 7 is positive in the tumor cells.

• (c) A CD68 immunostain shows characteristic

cytoplasmic staining.

• (d) PRKACA break apart FISH in a typical

fibrolamellar carcinoma.

The FISH result is positive. The tumor cells show

separate green signals and intact yellow signals
(due to overlapping red and green signals)
 Associated with
infantile polycystic
kidney disease
• Ductal plate malformation consistent with congenital
hepatic fibrosis.

• portal tracts diffusely demonstrate ductal plate

malformations consisting of bile duct structures with
irregular contours and regions of mild dilatation.

• Portal tracts / fibrous septa are without significant

inflammation.
• The figure showed zone 3
necrosis.

• If acetaminophen dose is
severe , the injury with
extend to zone 2 and
periportal hepatocytes ,
resulting in acute hepatic
failure
 Biliary Atresia
• Biliary atresia is defined as a complete or partial obstruction of the lumen of the extrahepatic biliary tree within the first 3
months of life.
• Biliary atresia is the single most frequent cause of death from liver disease in early childhood and accounts for 50% to 60% of
children referred for liver transplantation.
• When biliary atresia is unrecognized or uncorrected, cirrhosis develops within 3 to 6 months of birth.

• Two major forms of biliary atresia are recognized:

*The fetal form: accounts for as many as 20% of cases and is commonly associated with other anomalies Include situs inversus
malrotation of abdominal viscera, interrupted inferior vena cava, polysplenia, and congenital heart disease.

*The perinatal form: ( more commomn) , in which a presumed normally developed biliary tree is destroyed following birth.
-The etiology of perinatal biliary atresia remains unknown.
-viral infection and autoimmune reactions are leading suspects. Reovirus, rotavirus, and CMV have been implicated in some
cases.
• Type I: disease is limited to the common duct .
• Type II : disease in right and/or left hepatic bile ducts .
• Type III : in which there is also obstruction of bile ducts at or above the porta
hepatis.

NOTE:
• When the disease is (type I) or (type II) the disease is surgically correctable
(Kasai procedure).
• Unfortunately, 90% of patients have type III biliary atresia, These cases are
not correctable.
• female predominate.
• Infants with biliay atresia present with neonatal cholestasis.
• Initially normal stools change to acholic stools.
• At the time of presentation, serum bilirubin values are usually in the range of 6 to 12 mg/dL
• only moderately elevated aminotransferase and alkaline phosphatase levels.
• Moreover, in most patients, bile ducts within the liver are initially patent, but then are progressively destroyed.
• The salient features of biliary atresia include inflammation and fibrosing stricture of the hepatic or
common bile ducts
• periductular inflammation also progresses into the intrahepatic bile ducts leading, to progressive destruction
of the intrahepatic biliary tree.
• On liver biopsy, florid features of extrahepatic biliary obstruction evident in about two thirds of cases.
(bile ductular prolferation , cholestasis, portal edema)
• inflammatory destruction of intrahepatic ducts leads to duct paucity, often without the accompanying ductular
reactions, edema and neutrophils characteristic of obstruction.
 Giant cell transformation

Neonatal giant cell hepatitis (NGCH) is an important diagnostic

consideration in infants who present with jaundice.
Neonatal hepatitis
• General nonspecific changes:

• Lobular changes:
• giant cell transformation (hepatocytes containing 4 - 10 nuclei),
• variable lobular inflammatory infiltrate and necrosis (spotty, confluent to bridging),
• canalicular ± hepatocellular bilirubinostasis,
• extramedullary hematopoiesis

• Portal tract changes: variable portal mononuclear inflammatory infiltrate

GBM
Chief Complaints:
• Headaches
• Nausea
• Seizures

Clinical Workup:
• Often crosses hemispheres through corpus callosum: “butterfly” lesion
• Lesions enhance with contrast on imaging
• Histology:
• “Pseudopalisading tumor cells” can be seen on a brain biopsy
• Necrosis and hemorrhage in the center of the tumor
• GFAP positive on immunofluorescence
Question # 1
• A 60 year old male comes to the ER after the new consent of generalized tonic-clonic seizures. His partner explains that for the
past few weeks he has been complaining of headaches, nausea, and weakness. He has even been experiencing the
headaches at night, and they have become so severe that they wake him up from his sleep. The patients past medical history
is unremarkable other then a diagnosis of osteoarthritis. He is admitted to the hospital for further workup. He develops septic
shock from a hospital acquired pneumonia and passes away. A brain section is performed and shown below:

What is the likely diagnosis in this patient?

Explanation # 1

Brain lesion + areas of necrosis/hemorrhage seen on

gross histology = GBM
Question #2
• A 70 year old male is brought to the emergency room after he undergoes new tonic-clonic seizures. His brother explains that
recently the patent underwent personality changes to the point that he is a “entirely new person”. A CT-scan of the head
reveals the presence of a single brain lesion that enhances with contrast. It is found on the left hemisphere of the
brain, and crosses over to the right side through the corpus callosum. What is the likely diagnosis in this patient?

• Explanation # 2
• Brain lesion + enhances with contrast + butterfly lesion (crosses corpus callosum) = GBM
Question # 3
• A 65 year old male develops the new consent of headaches. An MRI is performed and reveals the presence of a intracranial
mass that is biopsied for further analysis. Light microscopy from the lesion is shown below:

Explanation # 3

Brain lesion + pseudopalisading tumor cells on histology = GBM

GBM
Lymphangiectasia/ Waldmann disease

Markedly dilated lymphatics

A 10 year old presented with bilateral edema of the legs and
diarrhea. Laboratory evaluation showed hypoalbuminemia
and hypogammaglobinemia. No other abnormality was
identified.
Capsule endoscopy performed showed white granular surface
in the small intestine.
A biopsy was performed which showed dilated spaces in the
mucosa and submucosa.
PAS stain performed is negative.
What is the most likely cause of the patient's underlying
condition?

A. Crohn's disease
B. Primary lymphangiectasia
C. Ulcerative colitis
D. Whipple disease

answer :
B. Primary lymphangiectasia
Kayexalate (sodium polystyrene
sulfonate) in sorbitol is used to treat
hyperkalemia

Symptoms are from sorbitol, given orally though NG

tube or as an enema, may crystallize in esophagus,
stomach or duodenum and produce endoscopic ulcers
and erosions resembling carcinoma or Candida

Kayexalate is classically purple and angulated on

H&E with a fish scale texture.
It appears black after AFB staining.

Kayexalate crystal:

H&E : Purple
PAS/PAS-D : Purple
ZN/AFP stain : Black
used to treat hyperphosphatemia
in patients with chronic kidney
disease.

it can be distinguished from

Kayexalate by its two tone
appearance on H&E (pink
centrally, yellow peripherally)
and its less harsh angulation
Bile acid sequestrants:
opaque orange polygonal / rhomboid
crystals;
usually no fish scale appearance;
may be spherical

AFB: bile acid sequestrants appear

dull yellow
• Which of the following microscopically identifiable medication materials
typically shows a two tone appearance with a fish scale pattern on H&E?

• A. Cholestyramine
• B. Crospovidone
• C. Sevelamer
• D. Sodium polystyrene sulfonate

Answer:
• C. Sevelamer
Inherited cancer Syndromes
 Inherited cancer Syndromes
i. Autosomal dominant cancer syndrome.
ii. Familial cancers
iii. Autosomal recessive cancer syndrome
o Bloom syndrome
o Franconi anemia
o Ataxia telangiectasia
o xeroderma pigmentosum
 Inherited cancer Syndromes
i. Autosomal dominant cancer syndrome.
• Inheritance of single mutant gene increases the risk of development of cancer.
• Mnemonic:
Very Rich, Cute and Nice Men Hereditarily Like Familiar Female
o Von Hippel lindau syndrome
o Retinoblastoma.
o Cowden syndrome
o Neurofibromatosis 1 and 2, Nevoid basal cell carcinoma
o Melanoma, MEN 1 and 2.
o Heretaitary nonpolyposis colon cancer
o Li-Fraumeni syndrome + LKB1 gene in Peutz Jegher syndrome.
o Familial adenomatous polyposis
o Ovarian and breast tumor
Von Hippel-Lindau disease
• Autosomal dominant disorder.
• VHL (tumor suppressor gene) >>>> gremlin mutation>>>>>In chromosome 3p.

• characterized by:
1. hemangioblastomas of the cerebellum and retinal angioma
2. cysts of the liver and pancreas, and kiney.
3. pheochromocytoma and renal cell carcinoma.
 Von Hippel-Lindau disease
Hemangioblastoma (grade I/IV)
• is a slow growing and indolent tumor which, for CNS tumors, is graded I of IV (benign) by the World Health
Organization (WHO).
• � It represents 1-2% of intracranial tumors, and is often in the cerebellum.
• � Other sites include the spinal cord and meninges.

• strongly associated with mutations of the von Hippel-Lindau (VHL) gene at 3p25-26, either as part of von Hippel-
Lindau disease (25% of cases) or due to a sporadic mutation of the VHL gene.
• � Loss of the VHL gene causes increased production of vascular endothelial growth factor, leading to richly
vascular tumors such as hemangioblastoma, pheochromocytoma and clear cell type of renal cell carcinoma.
• � Increased production of erythropoietin causes polycythemia.
 Von Hippel-Lindau disease
Hemangioblastoma (grade I/IV)
• Grossly, hemangioblastomas are usually well circumscribed mural nodules within a large, fluid filled cyst.
• � If a frozen section is requested, be sure to submit tissue from the mural nodule which contains the tumor, not from the cyst
wall.

• Histologically, the tumor is composed of a proliferation of capillaries of variable size, with large, neoplastic stromal cells
containing pink to clear foamy cytoplasm with PAS+ vacuoles containing lipid.
• � The nuclei are hyperchromatic, but there no prominent pleomorphism or nucleoli or other atypical features.
• � There is no necrosis and no/rare mitotic figures.
• � There may be associated mast cells .
• � The cyst wall often has gliosis and Rosenthal fibers.
Pineoblastoma
• Grade IV of IV
• Second most common pineal gland tumor after germ cell tumor
• Usually age 20 years or less
• Frequent CNS metastases or spinal seeding, which is the main cause of death
• 5 year survival is 58%
• Poor prognostic factors:
• 7+ mitotic figures/10 HPF
• Presence of necrosis
• No neurofilament staining
• Pineal gland tumor like seminoma CD117+
 Retinoblastoma
• RB gene (tumor suppressor gene) >>>> located In chromosome 13q 14.
• Familial RB is inherited Autosomal dominant associated with Osteosarcoma.
• Most common primary intraocular malignancy in children.
• Involved both eyes with pineal gland>>> called trilateral retinoblastoma
• Pineoblatoma in associated with retinoblastoma is primary tumor.
• Osteosarcoma, the comments secondary malignancy associated with retinoblastoma
• Retinoblastoma is a prime example of tumor which is associated with Loss of
heterozygosity.
 Cowden syndrome
• Characterized by hamartomas as well as an increased lifetime risk of
breast, thyroid, uterine, and other cancers. ( colonic lipoma,
ganglioneuroma, fibroma, adenoma)
• mutations in PTEN.
• Autosomal dominant.
• tricholemmoma is a benign tumour originating from the outer root sheath
of the hair follicle.

Cowden's disease displaying typical

trichilemmomas on the bilateral dorsal hands
Neurofibromatosis Type 1
Code for neurofibromatosis Type 1 in exam:
• Cafe au lait macules: hyperpigmented lesions with either smooth or irregular
borders.
• Neurofibromas: short, sessile, or pedunculated lesions throughout the body. Usually
are present in multiples.
• Lisch nodules: pigmented hamartomas in the iris.

• What causes it: singe gene mutation in the NF1 gene (chromosome 17).
• Inheritance pattern: autosomal dominant.
• Associated conditions:
• Eye: optic nerve glioma, Lisch nodules
• Bony abnormalities: sphenoid dysphasia, congenital psuedoarthrosis,
scoliosis
• Other associated tumors: meningioma, astrocytoma, glioma,
pheochromocytoma
Question # 1
• A 13 year old boy is brought to the clinic because of a history of a learning disability and hyperactivity. His
teacher explains that she feels he has a short attention span. His father explain that the child can not
concnetratre on his homework. The patient has had a generalized tonic-clonic seizure about 8 years ago.
An exam shows 10 lesions with a coffee-stain appearance on the chest and abdomen. There are
small areas of increased pigmentation on the axial and there are also many small skin tags seen on the
back, chest, and the abdomen. What is the most likely diagnosis in this patient?
• Explanation: Cafe au lait macules = neurofibromatosis Type 1

Question # 2
• A 3 year old girl is brought to the clinic because her father has noticed that she has developed several
brown colored spots over her back since brith. The patient’s mother also has similar spots as well as
several 1 cm lumps under the skin, and scoliosis as well. A dermatological exam reveals that the patient
has four 1.5 cm brown macules over her back. What is the likely diagnosis?
• Explanation: Cafe au lait macules = neurofibromatosis Type 1
 Li Fraumeni syndrome
• Autosomal dominant
• Usually due to p53 mutation ( tumor suppressor
gene ).

• soft tissue sarcomas, osteosarcoma,

-breast cancer,
-brain tumors,
-leukemia and
-adrenocortical carcinoma
 Sertoli cell tumor

Peutz–Jeghers syndrome assocciated with Non-GI

tumors include:

• Sex cord tumor with annular tubules

(SCTAT) of the ovary
• Sertoli cell tumor of the testis
• Breast carcinoma
• Adenoma malignum of the cervix
 Peutz–Jeghers syndrome
• Autosomal dominant
• mutations in STK11/LKB1. ( tumor suppressor gene)
• characterized by the development of
-benign hamartomatous polyps in the gastrointestinal tract
-and hyperpigmented macules on the lips and oral mucosa (melanosis)
 Gardner's syndrome
• mutation in the APC tumor suppressor gene.
• Autosomal dominant .
• A variant of familial adenomatous polyposis (FAP) with prominent
extraintestinal manifestations.
Desmoid fibromatosis
• Features of FAP and extraintestinal lesions, including
-desmoid fibromatosis
-bone osteomas and
-fibromas

bone osteomas
Gorlin syndrome/ Basal cell nevus syndrome
• germline mutations in the human homolog of the patched (PTCH) gene .
• Autosomal dominant

• Criteria for evaluation, "triggers" for screening:

-Odontogenic keratocysts in children < 20 years of age
-BCC in persons < 20 years of age
-Palmar or plantar pits
-Lamellar calcification of the falx cerebri
-Medullobastoma with desmoplastic histology in combination with any of the other major or minor
criteria
Palmar or plantar pits Odontogenic keratocysts
 Gorlin syndrome

• A. Axial CT image shows hypodense areas in relation to the right mandibular body separated by hyperdense
septae.
• B. Coronal CT image shows the lesion involving the right half of maxilla including maxillary sinus.
• C. Axial CT image shows calcification of falx cerebri
pectus deformity

Sprengel's deformity (also known as high

scapula or congenital high scapula
•
Major criteria:
● Multiple (>2) basal cell carcinomas or one under 20 years
● Odontogenic keratocysts of the jaws proven by histopathology
● Palmar or plantar pits (3 or more)
● Bilamellar calcification of the falx cerebri
● Bifid, fused or markedly splayed ribs
● First degree relatives with this syndrome
•

Minor criteria:
● Macrocephaly determined after adjustment for height
● Congenital malformation: cleft lip or palate, frontal bossing, "coarse face", moderate of severe hypertelorism
● Other skeletal abnormalities: sprengel deformity, marked pectus deformity, marked syndactyly of the digits
● Radiological abnormalities: bridging of the sella turcica, vertebral anomalies such as hemivertebrae, fusion or elongation
of the vertebral bodies, modeling defects of the hands and feet, or flame-shaped lucencies of the hands or feet
● Ovarian fibroma
● Medulloblastoma
 Ataxia telangectasia
• Autosomal recessive cancer syndrome ( defect
in DNA repair)
• Present in first decade in life
• Progressive telangectatic lesions
• Defect in cerebella function + nystagmus.
• Recurrent pulmonary infection ( bronchiecatasis)
• Thymic hyperplasia .
• Cellular and humeral immunodefiecny ( IgA
and IgG2)
• DM1
• Most striking neuropathic change include:
• Loss purkinji
• Granules and basket cells in cerebellar cortex.
• syndrome of watery diarrhea associated with hypokalemia and
achlorhydri…………. VIPoma
Glucagonoma syndrome
• (necrolytic migratory erythema, diabetes mellitus, weight loss, anemia, angular stomatitis)

• Necrolytic migratory erythema: skin rash of legs, perineum, groin; rash becomes blisters
with central clearing, heals with hyperpigmentation but without scarring in 7 - 14 days

Necrolytic migratory erythema

• Sample pathology report
• Pancreas and duodenum, Whipple procedure:
• Pancreatic neuroendocrine tumor, WHO grade 1 (see synoptic report and
comment)
• Comment: The patient’s clinical history of necrolytic migratory erythema is
noted. This may be due to glucagon secretion by this tumor, which would
make it a glucagonoma. Immunohistochemical stains for synaptophysin and
chromogranin are positive and the Ki67 index is approximately 1.2%.
Fabry disease:
• Neuropathic pain
• Hypohidrosis: decreased sweating
• Skin findings: both angiokeratomas and telangiectasis develop on the skin
• Cardiac rhabdomyoma associated with Tuberous sclerosis.
Nail-patella syndrome
• Patients are also at risk for kidney disease and glaucoma.
• present with mutations of the LMX1B gene.
• is characterized by abnormalities of the nails, knees, elbows, and pelvis.
• Autosomal dominant.

Triangular lunulae
 Birt-Hogg-Dubé syndrome
•Autosomal dominant.
•mutation of the Folliculin gene (FLCN)
•multiple folliculomas on head and neck and trichodiscomas.
•Renal cell Tumor (renal oncocytoma, hybrid oncocytic chromophobe tumor and carcinoma)
•lung cysts and spontaneous pneumothorax

Hybrid oncocytic - chromophobe tumor

Muir-Torre syndrome
• Variant of Lynch syndrome with skin manifestations
• More common in men
• cutaneous sebaceous neoplasms (including sebaceous adenoma, sebaceoma and sebaceous
carcinoma) or keratoacanthomas.
• germline mutations in a DNA mismatch repair gene: most commonly MSH2.
1-Muir-Torre syndrome is considered a clinical variant of what syndrome?
A. Cowden syndrome
B. Juvenile polyposis syndrome
C. Li-Fraumeni syndrome
D. Lynch syndrome

2-Which of the following is a typical manifestation of Muir-Torre syndrome?

Cylindroma
E. Desmoid fibromatosis
F. Sebaceous adenoma
G. Trichilemmoma

Answer 1 :D. Lynch syndrome

Answer 2: C. Sebaceous adenoma
 Sweet syndrome
• Also called acute febrile neutrophilic dermatosis
• Abrupt onset of tender or painful erythematous plaques and nodules on the face and extremities and less commonly on the
trunk, in association with fever (usually), malaise and a neutrophil leukocytosis
• Associated with AML, less often with solid malignancies
• Often females, any age but rare in childhood
• Unknown etiology, but may represent immunological hypersensitivity reaction

• Signs and symptoms of Sweet's syndrome include:

-Fever
-Painful small red bumps on your arms, face, neck or back
 Epididymis
• Connects efferent ductules to vas deferens.
• Has head, body and tail.
• Composed of columnar cells (tall, ciliated with PAS+ nuclear inclusions), clear cells and basal contractile cells (actin
positive)
• May have "monster" cells similar to seminal vesicle (no significance ) J

• Tubules have thick muscular coat.

• Nonpathologic morphologic variations:

• Intranuclear eosinophilic inclusions: 72%, usually older patients
• Lipofuscin pigment: 33% usually in efferent ducts and associated with obstructive changes
• Cribriform hyperplasia: 42% usually NOT in normal testis
• Paneth cell-like metaplasia: 8% with hyalin-like globules that are positive for PAS with and without diastase digestion, associated
with obstructive changes
• Nuclear atypia: 14% similar to that in seminal vesicles, associated with older age .
Rheumatoid nodule - subcutis
Gout

White deposits around the distal interphalangeal

joint an in the surrounding soft tissue of the skin
Gout
Psudogout
 cholesterol crystals in synovial fluid

Cholesterol crystals are a rare finding in synovial fluid but have been reported in cases of rheumatoid arthritis
 cholesterol crystals in synovial fluid
• No relationship was found between synovial fluid accumulation of cholesterol crystal and previous intra-
articular corticosteroid therapy, intra-articular hemorrhage, or generalized arteriosclerosis.
• The results suggest that local factors are most important in the development of synovial fluid cholesterol
crystals, but the exact mechanisms are unknown.
• The presence of cholesterol crystals in synovial fluid should suggest a severe persistent synovitis, knowledge
of which may be helpful in diagnosis and planning therapy.
Paget's Disease of Bone (Oseitis Deformans)
Cotton Wool” Appearance of Paget's Disease
DDX:

f multiple myeloma and multiple

Intracranial Langerhans Cell Histiocytosis
Symptomatic ,untreated primary hyperparathyroidism:

• 1.Osteoporosis

• 2.Brown tumors

• 3.Osteitis fibrosa cystica.

Brown tumor
Osteopetrosis (marble bone disease)
NORMAL

Mineralized bone is green

osteoid is orange
osteomalacia

The orange-staining osteoid covers many surfaces and is

thicker than normal.
 Fetal human woven bone.

Goldner’s trichrome stained section. Magnification ×100, green mineralized bone, pink osteoid tissue.
(B) Bone histological sections observed under polarized light, same section as in ( a ), illustrating the woven aspect of
primary bone.
(C) Adult bone with lamellar collage
Woven bone
• Immature (streamer) bone due to haphazard (random) arrangement of collagen fibers, found
during growth, healing, repair, infections or in some neoplasms
• Highlighted with polarized light or reticulin stain
• Abnormal in adults and associated with fibrous dysplasia or other causes of accelerated bone
turnover

Lamellar bone
• Layered bone with concentric parallel lamellae
• Gradually replaces woven bone
• Normal type of bone found in adult skeleton
• Stronger than woven bone
nephrogenic adenoma
• Nonneoplastic localized or diffuse, papillary, tubular or cystic metaplastic changes of the
urothelium in response to chronic infection, calculi, injury or prolonged catheterization.

• Characterized by a single layer of cuboidal or hobnail epithelial cells with clear or eosinophilic
cytoplasm and small, discrete nuclei without prominent nucleoli.

• Nonneoplastic reactive metaplastic lesion with tubular, glandular, papillary or cystic architecture
and surrounded (at least focally) by thick basement membrane

• Most cases confined to lamina propria..

• May mimic urothelial carcinoma, clear cell or prostatic adenocarcinoma.
Kidney
Visceral epithelium
Post-infectious glomerulonephritis

• Lumpy bumpy (granular) deposition of IgG, IgM

and C3 in peripheral glomerular loops
or starry scar immunofluoresenc

Granular IgG and C3………> NOT linear

Sub epithelail humps
Good pasture syndrome

Linear IgG and C3

 Good pasture syndrome

High power of the lung biopsy shows recent

intraalveolar hemorrhage intermixed with shows extensive hemorrhage in this lung biopsy
macrophages.
This feature helps differentiate it from intraoperative
hemorrhage
chronic glomerulonephritis
 Nephrotic syndrome

Accumulation of lipid in
Membranous nephropathy. proximal tubular cells ( lipoid
Minimal change disease. (most common in children) (2-6 year old) nephrosisi)
Focal Segmental Glomerulosclerosis (most common in adult)
Membranoproliferative glomerulonephritis (MPGN) type I
Membranous nephropathy

Granular IgG and C3

Sub-epithelial
deposit
Effacement of foot process of podocytes
Spikes on silver stain
 Jones stain

NOTE:
• Jones' stain, also Jones stain, is a methenamine silver-
Periodic acid-Schiff stain used in pathology.
• It is also referred to as methenamine PAS which is
commonly abbreviated MPAS.
• It stains for basement membrane and is widely used in the
investigation of medical kidney diseases.
• The Jones stain demonstrates the spiked GBM, caused by
sub-epithelial deposits, seen in membranous nephropathy.

In pathology, the reticulin stain, is a popular staining method

in histology. It is used to visualize reticular fiber and used
extensively in liver histopathology
 Diffuse
Granular and linear
IgG and C3
Subepithelail deposit
Membranous nephropathy

Effacement of foot process of podocytes

Sub-epithelial deposit
This is membranous nephropathy

What is the next step?

 It is necessary in any patient to first rule out the secondary causes.

• Drug. ( Penicillamine, captopril, glod, NSID)

• Underlying malignant tumor. (colon, lung, melanoma)
• SLE.
• Infections (chronic hepatitis B, hepatitis C, Syphillis, schistosomiasis, malarai)
• Autoimmune disorder. ( thyrodidtis)

primary membranous nephropathy :

• Autoimmune formation against Phosphlipase A2 receptor
• Associated with HLA-DQA1
• deep vein thrombosis.
•
membranous nephropathy
• Non- selective proteinuria.
• Not respond to steroid.
What is the clinical utility of identifying anti-PLA2R antibodies in a patient with membranous
nephropathy?

A. It is characteristic of primary membranous nephropathy and evaluation for an underlying

neoplasm or autoimmune disorder is not needed
B. It suggests an underlying autoimmune disorder
C. It suggests an underlying malignancy
D. It supports a diagnosis of secondary membranous nephropathy

A. It is characteristic of primary membranous nephropathy and evaluation for an underlying neoplasm or

autoimmune disorder is not needed.
Focal Segmental Glomerulosclerosis (FSGS)
Deposit of IgM and C3 at
sclerotic area and
mesangium

On left, graphic illustration of a normal glomerulus; on right graphic illustration of glomerulus with
FSGS (perihilar)
Good bcz Response to
steroid
Focal Segmental Glomerulosclerosis (FSGS)
• Non- selective proteinuria.
• Not respond to steroid.

• High incidence of recurrence in transplant patients

• Affect all age group
• Children have better prognosis than adults.
Electron microscopy showed glomerular capillary loop with diffuse podocyte foot
process effacement (arrow).
 HIV-associated nephropathy

HIV-associated nephropathy with glomerulosclerosis in a HIV-associated nephropathy with collapsing lesion

focal and segmental pattern with collapse of the characterized by segmental collapse of the HIV-associated nephropathy with tubloreticular
glomerular tuft and cystic changes of the tubules filled glomerular tuft and hyperplasia of overlying visceral inclusions (electron microscopy
with proteinaceous material (Jones silver stain) epithelial cells with cytoplasmic protein droplets
(Jones silver stain)
Membranoproliferative glomerulonephritis
(MPGN)
 Membranoproliferative glomerulonephritis
(MPGN)
• Glomerular basement membrane tram-tack or double contour or splitting appearance.
• Pt have nephritic on nephrotic syndrome.
MPGN type 1 MPGN type2

Granular pattern of IgG and C3 Garnular and Linear of C3 only

C1q + C4 No IgG.

Sub-endothelial deposit Intra-membranous deposit

Seen with :
HBV, HCV, HIV
CLL , lymphoma
Toxoplasmosis
 IgA Nephropathy (Berger disease): commonest nephritis in the
world

•Occur 3-4 days after

infection

•Normal complement
level

Mesangial immune deposits

The IgA is deposited mainly within the mesangium, which then
increases mesangial cellularity as shown at the arrow.
a picture, from the actual kidney biopsy of someone with IgA Nephropathy. Shown is a single filter
in which the actual IgA deposits have been stained florescent green
This is IgA nephropathy, and the immunofluorescence pattern
demonstrates positivity with antibody to IgA. Note that the pattern
is that of mesangial deposition in the glomerulus.
Henoch Schönlein purpura (IgA vasculitis)
IgA vasculitis usually causes a skin rash most prominent over the buttocks and
behind the lower legs. (purpura)
 Fibrillary GN

Deposition of IgG (usually polytypic) and

infiltrative fibrils with a diameter of 12 - 24 nm
by electron microscopy

Most cases (95%) are Congo red negative; rare

Congo red positive ones are reported.

Poor prognosis.

The disease recur in kidney transplant.

Jones methenamine silver
Trichrome
• Mesangial and variable capillary wall staining for polyclonal IgG and C3 is most common.
• in a small number of patients, light chain restriction (usually kappa) is seen
• Robbins: selective depostion of plyclonal IgG, often of IgG4, complement C3 and Ig kappa and Ig lambda light
chain.
Electron microscopy description
• Mesangial and variable capillary
wall deposits of randomly
organized fibrils that range from
10 - 30 nm in diameter
• A patient presents with nephrotic range proteinuria with normal serology.
Assays for cryoglobulin are negative. A kidney biopsy is performed, showing
mesangial expansion by Congo red negative material that is brightly positive for
IgG (polyclonal) and c3. Electron microscopy reveals randomly arranged fibrils
within the glomerular mesangium and focally within the basement membrane.
The fibrils measure 13 - 16 nm in diameter. What is the best diagnosis?
A. Amyloidosis
B. Fibrillary glomerulonephritis
C. Fibronectin glomerulopathy
D. Immunotactoid glomerulopathy

answer :
• B. Fibrillary glomerulonephritis
other
• Good pasture syndrome
• Microscopic polyangiitis.
• Wegners granulomatosis.

These three conditions can be histological similar and characterized by

foci of glomerular necrosis and crescent formation.
In severe cases, there is more necrosis, fibrin deposition, and extensive
formation of epithelial crescent
Alport syndrome

Splitting and lamellation of basement membrane

Alport syndrome
• Due to defects in collagen IV synthesis affecting basement membranes, caused by mutations in COL4A3,
COL4A4 and COL4A5 genes, important structural component of basement membranes in kidney, inner ear,
eye
• Nephritis, subtle nerve deafness (55%, seen in adults), eye disorders (15 - 30%, anterior lens dislocation,
posterior cataracts, corneal dystrophy)
• Called hereditary nephritis if no hearing or vision defects

Diagnosis:
• skin or kidney biopsy; if necessary, can use skin biopsy for analysis of COL4A5 gene for X linked cases .
• and peripheral WBC analysis of COL4A3 and COL4A4 for autosomal recessive.
Immunofluorescence description
• Negative or segmental staining for alpha 3, 4 and 5 collagen in glomerular
basement membrane (normals have strong continuous staining);
• negative for alpha 5 collagen in skin biopsies (positive in normals)
• Negative for immunoglobulin and complement.
 Multiple myeloma

the figures show Bence- jones tubular casts appear as pink to blue amorphous masses.
some time concentrically laminated and often fractured.
This finding s consistent with myeloma kidney
Myeloma Kidney
This silver stain demonstrates a double contour to many basement membranes, or the "tram-
tracking" that is characteristic of membranoproliferative glomerulonephritis (MPGN) that
results from basement membrane reduplication.
• Transplant glomerulopathy (TG) is a morphologic lesion of renal allografts that is characterized
histologically by duplication and/or multilayering of the glomerular basement membrane (GBM)

Silver staining highlighting double contouring of the glomerular capillary wall

C4d deposition is indictor of antibody
mediated (humeral) graft rejection
 No
immunoglobulin
or complement
deposit in GBM

C4d deposition is indictor of antibody

mediated (humeral) graft rejection
 Chancroid: Caused by Haemophilus ducreyi, a small gram negative rod

• Sexually transmitted disease caused by Haemophilus ducreyi which produces a painful genital ulcer and
inguinal adenopathy.
• Cofactor for HIV transmission

Regional adenopathy
Slightly raised flat disc with central ulceration
Gentian violet stain
Lymphogranuloma venereum
• Sexually transmitted disease caused by Chlamydia trachomatis, an obligate
intracellular parasite.

• Inguinal syndrome: painless papule or ulcer at inoculation site appears and

rapidly disappears
 Granuloma annulare
• Sections demonstrate palisaded histiocytes forming granulomas with peripheral
lymphocytes and central eosinophilic material.

Which interstitial extracellular substance would you expect to be most prevalent in this granulomatous dermatosis?
Mucin
Granuloma annulare
Granuloma annulare
• Benign, self limited dermatosis characterized by erythematous papules and plaques, classically in
an arciform or annular configuration.

• 2 classic morphologic patterns

• Palisaded granulomas with central necrobiosis (collagen degradation) with peripheral
histiocytes and admixed lymphocytes
• Histiocytes intercalating among collagen bundles with interstitial mucin

• Associations with hyperlipidemia and diabetes mellitus

• No proven treatment for this recurring, idiopathic disease
Hailey-Hailey disease
• Autosomal dominant. ( mutation in ATPC1 gene)

• intraepidermal vesicles located predominately in intertriginous area

( armit and inguinal)
• Ovarain tumors
Sex cord tumor
Juvenile Granulosa cell tumor
Q: 3 Y/O pt with enlarged breast and ovarian mass?

Loose edematous areas with

abortive follicles
Compact spindle cell areas with
hemangiopericytoma like pattern
 Juvenile Granulosa cell tumor
Q: pt with enlarged breast and ovarian mass?

• Diffuse or macrofollicular patterns with microcysts containing eosinophilic secretions, tumor cells
either have scant cytoplasm or are luteinized
• Round / oval hyperchromatic nuclei with small nucleoli, irregular nuclear contours
• No / rare nuclear grooves; high mitotic rate (mean 7/10 HPF)
• Has follicles with irregular size and shape, no Call-Exner bodies, brisk mitotic activity and can
have areas of higher grade atypia
• 90% FOXL2 mutation negative

• Adult granulosa cell tumor: more regularly shaped follicles with basement membrane
material, prominent nuclear grooves and no hyperchromasia
• Granulosa cell tumor-adult:
often unilateral

• Solid yellow mass.

• Solid and cystic tumor

• Granulosa cell tumor-adult:
often unilateral
Angulated, pale nuclei with nuclear
grooves.
•FOXL2 immunostain is a sensitive (80%) and specific (99%)
marker for sex cord stromal tumors (SCST), superior to α
inhibin and calretinin and is positive in almost all SCST (98%)
•Inhibin A: more specific marker
•Calretinin
•EMA -
 Ovary
Germ cell tumors

• Yolk sac tumor

Yolk sac tumor

Smooth, nodular exterior

Ovarian yolk sac tumor with a fleshy, gelatinous
protruding cut surface and focal hemorrhage.
Yolk sac tumor
OCT3/4 often negative in yolk sac tumors (9% are positive). but positive in all dysgerminomas.
Yolk sac tumor
AFP (gold standard, patchy expression)

OCT3/4 is positive in all dysgerminomas but most often negative in yolk sac tumors (9% are positive).

Hepatoid varient
Salivary gland
Features of papillary cystadenoma
lymphomatosum ( warthin tumor) seen in
the image:
• Oncocytes.
• Well-defined cell border.
• Granular cytoplasm.
• Nucleoli.
• Lymphocytes.
• Necrotic material (cyst contents)
Salivary gland
 Pleomorphic adenoma

Fluffy fibromyxoid material & cells and

single (plasmacytoid-like) myoepithelial
cells
Actinomycetes
 Brain
• Malaria

Frontal section of the formalin-fixed brain reveals multiple Congested capillary vessels show stasis of red cells
hemorrhagic spots in the basal ganglia and white matter. The deposited with coarse malaria pigment (HE).
brain tends to be brown-colored (gross findings
CMV in CNS:
• Severe hemorrhagic necrotizing ventriculo-encephalitis.
• Microencephaly with hydrocephalus.
• In immunosuppressive patient.
 B: Cortical area with subarachnoid
encephalitis, parenchymal cells with
CMV cytopathic effect, and a focus of
neutrophilic abscess (arrow)
Rabies

Negri body in infected neuron

Neuron without Negri bodies
HIV encephalitis:

Multinucleated cells, inflammatory cells, and necrosis are

evident.
 Pick disease.
• a type of frontotemporal dementia, a neurodegenerative disease
• The very marked frontal lobe atrophy and temporal lobe
atrophy seen
Alzheimer's disease
• Alzheimer's disease, there is more marked atrophy seen superiorly and laterally, with sparing of the
occipital region
• The cerebral atrophy seen here mainly in the frontal and parietal regions is characterized by narrowed
gyri along with widened sulci.
• The progressive cortical atrophy with Alzheimer disease leads to compensatory dilation of the cerebral
ventricles known as "hydrocephalus ex vacuo".
This is dry artifact
 cornflakes artifacts

Remove air bubble while

mounting
• Toxoplasmosis
• But we have to R/O TB
non casteating granuloma
Tongue biopsy:
Leprosy……..wade stain