Missed Questions: Surgical Pathology

Question 1

Young patient with Li-Fraumeni and distal femur lesion on radiography.

Diagnosis?

Answer 1

Osteosarcoma

• 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.

Question 2

Mass on back of middle aged male.

Diagnosis?

Answer 2

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

Question 3

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

Answer 3

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.

Question 4

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

Answer 4

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

Question 5

Abdominal mass in adolescent male.

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

Answer 5

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

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

(Desmoplastic Small Round Cell Tumor)

Question 6

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?

Answer 6

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.

Question 7

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?

Answer 7

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.

Question 8

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

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

Answer 8

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).

Question 9

Cervical Biopsy. Diagnosis?

Answer 9

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.

Question 10

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

Answer 10

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.

Question 11

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

Answer 11

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.

Question 12

Kidney tumor in young child.

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

Answer 12

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

Question 13

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?

Answer 13

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

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

(Inflammatory Myofibroblastic Tumor)

Question 14

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

Answer 14

Chondroblastoma

• 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

Question 15

Postmenopausal female w/ endometrial polyp. Diagnosis?

Answer 15

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 -

Question 16

45 year old male with headache. Brain bx.

Answer 16

Toxoplasma

• 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.

Question 17

What ‘category’ would you place this dermatitis into?

What is a good Ddx for this category?

Answer 17

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.

Question 18

Renal biopsy in a chronically ill patient. Diagnosis?

Answer 18

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.

Question 19

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

Answer 19

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

Question 20

What stromal breast lesions are CD34+?

Answer 20

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

Question 21

Submitted as “Products of Conception”.

Diagnosis?

Answer 21

Very Early Complete Hydatidiform Mole

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

Question 22

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

Diagnosis?

Answer 22

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.

Question 23

58 year old homeless male with nephropathy and yellowed skin.

Needle core biopsy - Diagnosis?

Answer 23

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.