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Flashcards in Missed Questions: Surgical Pathology Deck (23)
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Young patient with Li-Fraumeni and distal femur lesion on radiography.




  • Cells with malignant features (e.g. nuclear membrane irregularities, marked nuclear size differences, mitoses) surrounded by delicate strands of osteoid.
    • Osteoid on H&E: pink, homogenous, “glassy”.
    • Tumours typically very cellular - when compared to normal bone.
  • +/-Large (multinucleated) osteoclast-like giant cells.
  • DDx:
    • Chondrosarcoma.
    • Phosphaturic mesenchymal tumour, mixed connective tissue type.
    • Others.

Mass on back of middle aged male.



Spindle Cell Lipoma

  • Aligned bland spindled cells adjacent to fat.
  • Rope-like collagen bundles - key feature.
    • May be described as “shreaded wheat”.
  • +/-Myxoid component.
  • +/-Staghorn-like vessels.
  • Notes:
    • May overlap with pleomorphic lipoma.
  • DDx:
    • Neurofibroma.
    • Spindle cell liposarcoma - extremely rare.
    • Myxoid liposarcoma
      • Has lipoblasts and prominent plexiform vascular pattern

GI biopsy. What is the molecular aberation in this lesion?


Microsatellite Instability (MLH1) (Sessile Serrated Adenoma)

  • Other molecular aberations seen include BRAF and excessive methylation (CpG Island Methlator Phenotype; CIMP)
  • Serrated epithelium at the surface and deep in the crypts.
    • Saw-tooth appearance, epithelium has jagged appearing edge.
  • Crypt dilation at base with serrations - key feature.
    • Very common – anecdotally the most sensitive feature.
  • “Boot”-shape or “L”-shaped glands.
    • Shape may be similar to a hockey stick.
  • Horizontal crypts = crypt long axis parallel to the muscularis mucosae.
  • Crypt branching.
  • Submucosal lipoma or pseudolipoma is often seen in associated with SSA.
  • Perineuriomas are also seen in a small proportion of cases
  • Minimal extent criteria - number of abnormal crypts with the above features:
    • German Society of Pathology proposal: at least two abnormal crypts – crypts do not have to be adjacent.
    • An expert panel lead by Rex states that one unequivocally altered crypt should prompt calling SSA.
    • The 4th edition of the WHO blue book requires - depending on what you read:
      • Three adjacent crypts to be abnormal.
      • Two or three adjacent crypts to be abnormal.
      • The 5th edition is likely to make a single crypt sufficient for diagnosis.

What are the three (3) most common translocations and gene-fusions associated with Ewings Sarcoma/PNET?

  1. t(11;22)(q24;212) : EWSR1-FLI1
  2. t(21;22)(q22;q12) : ESWR1-ERG
  3. t(7;22)(p22;q12) : EWSR1-ETV1

Abdominal mass in adolescent male.

What is are the two (2) most common translocations and gene fusions associated with this lesion?


t(11;22)(p13;q12) : EWSR1 - WT1

t(21;22)(q22;q12) : EWSR1 - ERG

(Desmoplastic Small Round Cell Tumor)


Young male kicked in the knee. Swelling did not subside after several weeks. Radiology demonstrated a mass and a biopsy was taken.

What are the most common translocation and gene fusion associated with this tumor?


t(X; 18)(p11; q11) : SS18 - SSX1 SS18-

t(X; 18)(p11; q11) : SSX2 SS18 - SSX4

(Synovial Sarcoma)

  • Comes in three (histologic) flavours:
  1. Spindle cell sarcoma (monophasic) with features of hemangiopericytoma, i.e. staghorn vessels.
  2. Biphasic synovial sarcoma:
    • Spindle cells with features of hemangiopericytoma.
    • Epitheliod glands or nests.
  3. Primitive round cell type.
  • Features:
    • Herring bone or vesicular pattern - key feature.
    • Spindle cells.
    • +/-Glandular component - typically more pink.
    • +/-Calcification - uncommon.
      • Extensive calcification = better prognosis.[5]
  • DDx:
    • MPNST.
    • Can be difficult.
  • IHC (positive):
    • Vimentin +ve.
    • EMA +ve.
    • BCL2 +ve.
    • CD99 +ve.
  • Others:
    • Beta-catenin +ve ~30-70%.
    • Cyclin D1 ~50%.
    • TLE1 +ve nuclear staining; not specific for synovial sarcoma.
  • Molecular:
    • t(X;18)(p11.2;q11.2).[14]
      • SYT/SSX fusion gene.
    • Several SSX genes - cannot be differentiated with standard karyotyping:
      • SSX1.
      • SSX2 - better survival, rarely seen in biphasic tumours.
      • SSX4 - uncommon.

60 year old female with AUB and pelvic mass on imaging.

IHC: CD10 +, H-Caldesmon -

What is the most common translocation and gene fusion for this lesion?


t(7; 17)(p15; q21) : JAZF1 - SUZ12

(Endometrial Stromal Sarcoma)

  • Highly cellular islands with a wavy irregular border.
    • Border has finger-like projections/tongue-like projections.
    • Benign uterine smooth muscle between islands of tumour cells.
  • Epithelioid cells.
  • High NC ratio.
  • Thin blood vessels within islands of cells.
    • Tumour cells pallisade around the vessels.
  • Notes:
    • Vaguely resembles the stroma of proliferative endometrium.
    • Low mitotic rate - predictive of good outcome.
  • DDx:
    • Leiomyoma.
    • Endometrial stromal nodule (no LVI and interface may not have more than three (3) finger-like projections that are >/= 3mm).
    • Uterine leiomyosarcoma.
    • Undifferentiated endometrial sarcoma (previously known as high-grade endometrial stromal sarcoma) - necrosis and nuclear atypia.
    • Uterine tumour resembling an ovarian sex cord stromal tumour.

Young male with persistent, slow-growing nodular mass on trunk.

What is the most common translocation and gene fusion associated with this lesion?


t(17; 22)(q22; q13) : COL1A1 - PDGFB

(Dermatofibrosarcoma Protuberans [DFSP])

  • Dermal spindle cell lesion with storiform pattern.
    • Spokes of the wheel-pattern.
  • Contains adipose tissue within the tumour – key feature.
    • Described as “honeycomb pattern” and “Swiss cheese pattern”.
  • Notes:
    • Adnexal structure within tumour are preserved – this is unusual for a malignant tumour – important.
  • DDx:
    • Dermatofibroma - main DDx - has entrapment of collagen bundles at the edge of the lesion.
    • Dermatomyofibroma.
    • Nodular fasciitis.
  • DDx of storiform pattern:
    • DFSP.
    • Dermatofibroma.
    • Solitary fibrous tumour.
    • Undifferentiated pleomorphic sarcoma.
  • Subtypes:
    • Pigmented DFSP (Bednar tumour).
    • Myxoid DFSP.
    • Myoid DFSP.
    • Granular cell DFSP.
    • Sclerotic DFSP.
    • Atrophic DFSP,
    • Giant cell fibroblastoma.
    • DFSP with fibrosarcomatous areas.
  • IHC:
    • CD34 +ve.
      • Usually negative in dermatofibroma.
    • Factor XIIIa -ve.
      • Usually positive in dermatofibroma.
    • S-100 -ve (screen for melanoma).
    • Caldesmin -ve (screen for muscle differentiation).

Cervical Biopsy. Diagnosis?


Endocervical Adenocarcinoma, gastric-type

  • Well-formed glands lined by cells with voluminous clear or eosinophilic cytoplasm and distinct cell borders.
  • Not HPV associated.
  • Lack high mitotic rate and apoptotic bodies (contrary to HPV associated adenocarcinomas).
  • IHC:
    • CEA +
    • p16 - (usually, esp. in low grade)
    • ER -

Picture: A, curetting of low grade gastric type adenocarcinoma of cervix. B, focal CDX2 positivity. C and D, negative for ER and p16, resp.


What are the two (2) most common translocations and gene fusions associated with this uncommon soft tissue tumor?


t(12;22)(q13;q12) : EWSR1 - ATF1

t(2;22)(q33;q12) : EWSR1 - CREB1

(Clear Cell Sarcoma)

  • Architecture: sheeting or fascicular (bundles) arrangement.
    • Fibrous septae - between tumour cells.
  • Tumour cells uniform (low pleomorphism) - spindle-shaped or epithelioid:
    • Classically have clear cytoplasm.
    • Prominent nucleoli - basophilic - key feature.
    • +/-Binucleation.
  • DDx:
    • Malignant melanoma.
    • PEComa.
    • Carcinoma.

What are the two (2) most common translocations and gene fusions of this extraskeletal lesion, arising in the soft tissue of an adult forearm?


t(9;22)(q22;q12) : EWSR1 - NR4A3

t(9;17)(q22;q11) : TAF2NNR4A3

(Extraskeletal Myxoid Chondrosarcoma)

  • Microscopic: Features:
    • Chordoma-like:
      • Myxoid background.
      • Small cells with eosinophilic cytoplasm.
  • DDx:
    • Chondroid syringoma - These are dermal based, circumscribed and much smaller.
    • Parachordoma.
    • Chordoma. (???)
    • Myxoid liposarcoma.
    • Metastatic myxoid carcinoma.

Kidney tumor in young child.

What is the translocation and gene fusion associated with this tumor?


t(12;15)(p13;q25) : ETV6 - NTRK3

(Congenital Mesoblastic Nephroma)

  • General
    • Almost exclusively in infants.
    • Subclassified:
      • Classic.
      • Cellular.
      • Mixed.
  • Gross
    • Renal sinus infiltration - common.
  • Microscopic
    • Classic
      • Spindle cells in fascicles.
      • Infiltrative border.
    • Cellular
      • Plump cells with vesicular nuclei.
      • Well-defined border.
      • Mitotically active.
    • Mixed
      • Like the name implies - both classic pattern and cellular pattern areas are present.

*BELOW: cellular variant


Mesenteric lesion in the region of the small bowel in a young adult; SMA +.

What are the two (2) most common translocations and gene fusions?


t(1;2)(q25;q23) : TPM3 - ALK

t(2;19)(q23;q13) : TPM4 - ALK

(Inflammatory Myofibroblastic Tumor)


10 year old male who was kicked in the knee 6 months ago. Continued swelling and pain. Diagnosis?



  • Abundant extracellular material - pink on H&E stain - looks vaguely like cartilage.
  • Sometimes described as ‘immature cartilage’ (very narrow DDX for this type of cartilage)
  • Chondroblasts:
    • Nuclear morphology variable: ovoid, folded or grooved.
    • Moderate-abundant eosinophilic cytoplasm.
  • +/-Calcification surrounds the cell nests (“chickenwire” appearance) - classic feature.
    • Cell nests have a thin pale blue rimming.
  • +/-Giant cells.
    • May lead to confusion with giant cell tumour of bone.
    • Not infrequently associated with an aneurysmal bone cyst (33%).
  • DDx:
    • Giant cell tumour of bone.
    • Chondroma.
    • Well-differentiated chondrosarcoma.
    • Chondromyxoid fibroma - also has ‘immature cartilage’
    • Aneurysmal bone cyst - dont forget that these may be secondary to another lesion.
  • IHC:
    • S100 +ve
    • Vimentin +ve

Postmenopausal female w/ endometrial polyp. Diagnosis?


Clear cell carcinoma of the endometrium

  • Features:
    • Clear cells - with moderate nuclear pleomorphism - key feature.
    • Classically clear cells… but not always.
    • Hobnail pattern – apical cytoplasm > cytoplasm on basement membrane.
    • Usually tubular/cystic, may be solid or papillary.
    • Papillae may be pseudopapillae – with edema instead of vessels.
  • Notes:
    • May have psammoma bodies - esp. in papillary area; may lead to confusion with serous carcinoma.
  • DDx:
    • Serous endometrial carcinoma - usually has more nuclear pleomorphism, esp. cell size variation.
    • High grade endometrioid endometrial carcinoma - have non-clear areas.
    • Arias-Stella reaction - esp. in the context of pregnancy.
    • Papillary cystadenoma - benign; bland nuclei.
  • DDx weird stuff:
    • PEComa.
    • Epithelioid leiomyosarcoma.
  • IHC:
    • p53 - (unlike uterine serous carcinoma)
    • ER -
    • PR -

45 year old male with headache. Brain bx.



  • Common CNS infection: granular appearing ball ~ 2x the size of resting lymphocyte.
  • Toxoplasma gondii - pathogenic; causes toxoplasmosis.
    • Protozoa.
    • A TORCH infection.
  • Microscopic:
    • Tachyzoites (Invasive form):
      • Crescent-shaped organisms that are 2-3μm wide by 4-8μm long.
    • Bradyzoites:
      • Are founded within the tissue cysts and are shorter than tachyzoites.
    • Oocysst:
      • Ovoid shape that measures 10μm to 12μm and contains four sporozoites.
  • Histopathological features depend on location in body.

What ‘category’ would you place this dermatitis into?

What is a good Ddx for this category?


Vacuolar Interface Dermatitis (Graft vs. Host Disease)

  • DDx:
    • Erythema multiforme.
    • Lichen sclerosus.
    • Fixed drug eruption.
  • Others:
    • Graft versus host disease.
    • Dermatomyositis.
    • Systemic lupus erythematosus.
    • Morbillifrom viral exanthem.
  • Additional:
    • Phototoxic dermatitis.
    • Acute radiation dermatitis.
    • Erythema multiforme-like drug eruption.
    • Lichen sclerosis et atrophicus.
    • Erythema dyschromicum perstans (ashy dermatosis).
  • Super lame mnemonic Danny G & SLE:
    • Dermatomyositis, GVHD, SLE, Lichen sclerosus, Erythema multiforme.

Renal biopsy in a chronically ill patient. Diagnosis?


Focal Segmental Glomerulosclerosis

  • General:
    • Presents as nephrotic syndrome.
    • Does not respond to steroids (unlike MCD).
    • Usually less rapid onset than MCD.
    • Fibrosis usually takes some time.
  • Etiology
    • Primary:
      • Mutations in the podocin gene NPHS2
      • Other mutations: ACTN4, TRPC6, CD2AP
      • May be familial.
  • Secondary:
    • HIV, parvovirus B19.
    • Drug use.
    • Reduced renal mass.
  • Notes:
    • Primary FSGS needs ~70-80% foot process effacement.
  • Microscopic Features:
    • Partial sclerosis of less than 50% of glomeruli.
    • +/-Adhesions between the glomerular tuft and Bowman’s capsule.
    • +/-Glomerular enlargement.
  • DDx:
    • Minimal change disease.
    • C1q nephropathy.

Sexually active middle aged male. Frequent marijuana smoker. What is the diagnosis and what is the etiology?


Squamous Cell Carcinoma, Basaloid Variant

Caused by high risk HPV (16/18/31/etc)

  • The pathologic features of HPV-positive tumours are different from HPV-negative tumours in the following:
    • They are not associated with surface dysplasia or keratinisation.
    • They exhibit lobular growth.
    • They have infiltrating lymphocytes.
    • Basaloid variants are common.
  • HPV-positive tumours are usually well differentiated and the basaloid tumours have good prognosis
  • Marijuana use is an independent risk factor for HPV-related head and neck SCC, possibly due to its immunomodulatory effects

What stromal breast lesions are CD34+?

  1. Pseudoangiomatous Stromal Hyperplasia (PASH)
  2. Phyllodes tumor
  3. Fibroadenoma

Submitted as “Products of Conception”.



Very Early Complete Hydatidiform Mole

  • Variation in villous size
  • Subtle scalloping with bulbus projections
  • Marked stromal cellularity and rare cisterns

10 year old male with pain and swelling of forearm. BTE resection performed.



Aneurysmal Bone Cyst

  • Destructive, expansile benign neoplasm of bone characterized by multiloculated, blood-filled cystic spaces
  • Microscopic Features:
    • Bony trabeculae or osteoid tissue.
    • Osteoclast giant cells.
      • Multi-nucleated giant-cells with round randomly arranged nuclei.
    • Benign spindle cells (fibroblasts) - surround bone/adjacent to the giant cells - important.
    • Blood +/- surrounded by giant cells.
  • DDx:
    • Giant cell tumour of bone - the nuclei of the cells surrounding the giant cells are similar to those in the giant cells (round nuclei).
    • Telangiectatic osteosarcoma.
    • Other giant cell lesions.

58 year old homeless male with nephropathy and yellowed skin.

Needle core biopsy - Diagnosis?


Hepatitis B

  • Lobular inflammation - this is non-specific finding.
    • Hepatocyte necrosis:
      • Necrotic hepatocytes look a lot like neutrophils - however:
        • Cytoplasm is more pink.
        • Round apoptotic bodies.
  • Ground glass hepatocytes - important.
  • DDx:
    • Hepatitis C.
    • Autoimmune hepatitis.
    • Primary biliary cirrhosis without granulomas.
    • Drug reaction.
      • Pseudo-Lafora bodies in patients on disulfiram (anatabuse) can result in ground glass hepatocytes.
  • Associated pathology
    • Polyarteritis nodosa (PAN).
    • Membranoproliferative glomerulonephritis.
    • Membranous nephropathy.
    • Cirrhosis.
    • Hepatocellular carcinoma.