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Flashcards in Quizes Deck (51):

Well circumscribed, mahogany brown lesion on gross.

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Renal Oncocytoma

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Older gentleman w/ parotid mass

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Salivary Gland Oncocytoma

  • Light pink cytoplasm (due to high number of mitochondria), lots of glands, well-circumscribed
  • Stains w/ PTH (mitochondria)

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Middle aged lady w/ great toe lesion

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Granular Cell Tumor

  • Foamy macrophage-look
  • Pseudoepitheliomatous hyperplasia
  • Pitfall: invasive SCC
  • Benign, although there is a malignant version
  • Stains: S-100 + PAS
  • Commonly: esophagus, tongue


47yo w/ slow growing, mobile, non tender inguinal mass

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Atypical Lipomatous Tumor (Well-Differentiated Liposarcoma)

  • Lockhern cells
  • Foamy histiocytes
  • Cytologic atypia, variation in sizes
  • Lipoblasts
  • May de-differentiate
  • Stains MDM2 + p16
  • FISH (for p16?)

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41 yo F w/ multiple foci of grouped amorphous calcifications on imaging

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Ductal Carcinoma in Situ (DCIS)

  • Equal spacing of cells - "cookie cutter" look.
  • Cells line-up along lumen/glandular spaces - form "Roman briges".
  • Architecture suggestive of DCIS - see Subtypes of DCIS.
  • Nuclear changes: Nuclear enlargement - at least 2-3x size of RBC - key feature.
    • Compared to RBCs to grade DCIS - see Grading DCIS.
    • Compare sizes of nuclei if you cannot find RBCs.
  • Nuclear pleomorphism - important feature.
  • Variants:
    • Solid
    • Cribriform
    • Papillary
    • Micropapillary

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67yo F left perineal/perianal pruritis and inflammation

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High Grade Anal Intraepithelial Lesion/Bowman's Disease

  • Parakeratosis + Hyperkeratosis
  • Papillary dermal inflitrate
  • Cytologic atypia
  • Mites
  • Koilocytes


27yo M mole on R shoulder, discomfort, gets caught and bleeds

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Lobular Capillary Hemangioma (Pyogenic Granuloma)

  • Polypoid or peduculated.
  • Vascular, i.e. many blood vessels, with plump endothelium.
  • Usu. thinned epithelium or ulcerated.
  • Lobular arrangement of vascular (seen at low power)

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45yo F, EMBx

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Late Secretory Phase Endometrium

  • Early secretory phase
    • Features - post-ovulatory day 1-5:
      • Glands: secretory vacuoles.
        • First basal to the epithelial nuclei (infranuclear vacuoles).
        • Then apical to the epithelial nuclei (supranuclear vacuoles).
      • Mitoses may be present - common when vacuoles are subnuclear.
  • Mid secretory phase
    • Features - post-ovulatory day 6-8:
      • Glands: Mucus in glands.
      • Stroma: Edema (empty space around the glands).
  • Late secretory phase
    • Features - post-ovulatory day 9-12:
      • Stroma:
        • Spiral arterioles.
        • Predecidual changes -- mnemonic NEW:
          • Nucleus central.
          • Eosinophilic cytoplasm key feature (may be subtle to the novice).
          • Well-defined cell borders.

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57yo M w/ left parotid gland mass

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Warthin's tumor (papillary cystadenoma lymphomatosis)

  • Nodular blue architecture
  • Dense lymphoid aggregate
  • Oncocytic appearing glands w/ bilayered/pseudostratified look
  • Large central area of necrotic debris
  • Most common malignant salivary gland tumor: mucoepidermoid 

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70 yo M with previously diagnosed pulmonary chondroma, extra-adrenal paraganglioma and this recently discovered stomach mass.

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Gastrointestinal Stromal Tumor (GIST)

Carney's Triad (malignant epithelioid gastric GIST,
pulmonary chondroma, and extra-adrenal paraganglioma)

  • Classically, spindle cell morphology ~ 50% of tumours.
    • May be epithelioid (round) ~40% of tumours.
    • Mixed epithelioid and spindle cell tumours ~10% tumours.
  • +/-Cytoplasmic inclusions - perinuclear.
  • Classically splits the layers of the muscularis propria - as this is where the interstitial cells of Cajal are located.
  • +/-Skenoid fibres - extracellular collagen bundles ~ 2-5 x 60 micrometers - uncommon finding.
    • Not seen in gastric GISTs.
    • High specificity for GIST.
  • Can also be seen in NF Type 1 (von Recklinghausen's)
  • DDx
    • Leiomyosarcoma.
    • Leiomyoma - esp. in the esophagus.
    • Neural tumours.
      • Neurofibroma.
      • Schwannoma (GFAP +ve).
        • GFAP uniformly neg. in GISTs.
    • Desmoid-type fibromatosis.
    • Epstein-Barr virus-associated smooth muscle tumour - very uncommon, in immunoincompetent individuals

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35 yo M w/ recent vasectomy.  Nodule discovered on vas.

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​Vasitis Nodosa

  • Tubules in wall of vas deferens.
    • Lined by columnar/cuboidal epithelium.
      • May have mitotic activity.
      • Nucleoli.
      • Contain sperm - small, dark staining, teardrop-shaped (~1 micrometer) - key feature.
        • The tail is rarely seen completely in the plane of section.
  • +/-Sperm granulomas.
    • Histocytes - abundant foamy cytoplasm.
    • Sperm - small, dark staining, teardrop-shaped (~1 micrometer).
  • Can vary in size
    • Cystic or small
  • Can show perineural invasion
  • DDx:
    • Metastatic carcinoma, especially prostate carcinoma.

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Bladder tumor in 3 year old female

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Embryonal Rhabdomyosarcoma (sarcoma botryoides)

  • Sarcoma botryoides subtype: cambium layer (dense proliferation of immature tumor cells just deep to epithelial surface (shown in previous image)
  • Randomly arranged small cells.
  • Polypoid architecture
  • Myxoid matrix.
  • Strap cells:
    • Tadpole-like morphology.
  • Rhabdomyoblasts - essentially diagnostic.
    • Eccentric nucleus.
    • Moderate amount of intensly eosinophilic cytoplasm.
    • Striations -- if you're really lucky; these are not common.
  • Stains:
    • Desmin +
    • MyoD1 +
  • DDx:
    • Small round cell tumours.
    • Pleuropulmonary blastoma.

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Child with skull mass

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Langerhans Cell Histiocytosis (LCH)

  • Langerhans cells histiocytes - key feature.
    • Clusters of cells (histiocytes) with a reniform (kidney-shaped) nucleus and abundant foamy cytoplasm.
      • Nucleus may look like a "coffee bean", i.e. have nuclear grooves (similar to those in papillary thyroid carcinoma) -- appearance dependent on the rotation of the nucleus. May be called "buttock cells".
      • Chromatin pattern: fine granular, light gray.
  • +/-Eosinophils - often prominent.
  • +/-Fibrosis - common.
  • +/-Other inflammatory cells - neutrophils, plasma cells (uncommon).
  • +/-Multinucleated giant cells - uncommon.
  • Stains:
    • CD1a +ve.
    • S100 +ve.
    • CD207 (AKA Langerin) +ve
  • DDx:
    • Kimura disease - eosinophilia.
    • See lymph node pathology.
    • See lesions with many eosinophils.

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Side of neck mass in 34 yo F

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Branchial Cleft Cyst

  • BLUF: Squamous and respiratory lined epithelium with lymphoid tissue
  • Cystic space lined by squamous epithelium - usually.
    • +/-Inflammation.
  • Connective tissue:
    • +/-Adipose tissue.
    • +/-Cartilage.
    • +/-Bone.
    • +/-Muscle.
  • DDx:
    • Cystic squamous cell carcinoma - may be deceptively benign appearing.
    • Papillary thyroid carcinoma (PTC) arising in a brachial cleft cyst - uncommon, looks like PTC in the thyroid.
    • Epidermal inclusion cyst.


44yo F w/ renal mass

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Renal Oncocytoma

  • Eosinophilic cytoplasm - slightly granular key feature.
  • Cells arranged in nests.
  • Nuclei uniform and round.
  • Slightly enlarged nuclei, but no significant pleomorphism (size variation) - important.
  • Notes:
    • May look like eosinophilic variant of chromophobe RCC -- this is the main DDx.
      • A comparison based on histomorphology: Tabular comparison between ChRCC & oncocytoma.
        • Oncocytoma typically has: no perinuclear clearing, no raisinoid nuclei, rare or no binucleation.
    • May have - according to Trpkov et al.
      • Vascular invasion ~4% of cases.
      • Chromophobe-like foci (<5% of neoplasm) ~12% of cases.
      • Focal clear cell changes ~15% of cases.
      • Hemorrhage.
  • DDx:
    • Chromophobe renal cell carcinoma, eosinophilic variant.
    • Succinate dehydrogenase-deficient renal cell carcinoma - emerging entity as per Vancouver classification - classically has a flocculent cytoplasm, may have oncocytoma-like areas.
    • Papillary renal cell carcinoma, oncocytic variant.
    • Renal hybrid oncocytic/chromophobe tumour.
    • Clear cell renal cell carcinoma, eosinophilic variant.
    • Tubulocystic carcinoma of the kidney.
    • Other renal tumours with eosinophilic cytoplasm

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Pigmented lesion in 24yo M arm


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nevoid melanoma

  • Well circumscribed
  • Not maturing
  • Large, atypical cells
  • Not nested as much as should be, more sheets (nested in this pic)
  • Scattered mitoses


nasal mass in 54 yo M

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Emperopolesis (Rosai-Dorfman Disease)

  • Day of explanation:
    • Histiocytes w vesicular nuclei
    • Lymphocytes passing through macrophages (emperopolesis)
    • Stains: S100 + histiocytes, CD1a - histiocytes
  • Sinus histiocytosis:
    • Histiocytes - abundant.
      • Singular large round nuclei ~2x the size of resting lymphocyte.
        • Prominent nucleolus - visible with 10x objective.
        • Abundant cytoplasm.
    • Emperipolesis (from Greek: em = inside, peri = around, polemai = wander about):
      • Histiocytes contain other whole cells: neutrophils, lymphocytes, plasma cells.
        • The "eaten" cell is within a vacuole; thus, it should have a clear halo around it.
        • Thought to be related to peripolesis; the attachment of a cell to another.
  • DDx:
    • Other specific histiocytoses:
    • Langerhans cell histiocytosis.
    • Erdheim-Chester disease.
    • Infection, e.g. rhinoscleroma (nasopharynx), xanthogranulomatous pyelonephritis.
    • Sinus histiocytosis.
    • Xanthomatous change.

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Polyp in 56yo M

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Tubulovillous Adenoma (TVA) with High Grade Dysplasia (HGD)

  • Day of explanation:
    • Finger like villi
    • Areas of invasive/HG glands into stalk (intramucosal)
    • Surrounding desmoplasia
  • Nuclear changes at the surface of the mucosa - key feature.
  • Size and shape or size change:
    • Cigar-shaped (elongated) nucleus (usu. length:width > 3:1) with nuclear hyperchromasia (more blue).
    • Large round nuclei +/- vesicular appearance (clearing) -- nuclei have white space.
    • Nuclear crowding/pseudostratification - important.
    • +/-Loss of nuclear polarity (nuclei no longer on basement membrane).
    • Loss/decrease of goblet cells (common).
    • Cytoplasmic hyperchromasia.
  • Notes:
    • Nuclear changes deep to the surface are non-neoplastic if normal appearing mucosa (with small round nuclei) is superficial to it; mucosa that is more blue and atypical deep and less blue without nuclear atypia at the surface is said to be "maturing".  Classically, adenomatous polyps have "reverse maturation":
    • The surface is more hyperchromatic (more blue).
    • The base is more mature (more globlet cells, no nuclear changes -- less blue).
    • Ampullary adenomas often have less prominent pseudostratification and fine chromatin.
  • High Grade Changes:
    • Architectural:
      • (gland) cribriforming
      • glandular budding
      • intraluminal papillary tufting
      • sheeting (of epithelium)
      • lamina propria invasion
    • Cytology:
      • loss of nuclear stratification
      • enlarged nuclei
      • loss of cell polarity
      • prominent nucleoli
      • open (clear) chromatin

*NOTE: Image below is negative for HGD.

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Pancreatic mass in 50yo F

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  • Day of explanation:
    • Washed-out look and lilac color on LP
    • Nests of purple cells
    • Zellballen architecture
    • Stains: chromo/synapto +, sustentacular cells
  • Zellballen - nests of cells - key low power feature.
    • Zellballen is "cell balls" in German.
  • Fibrovascular septae and sustentacular cells (structural support cell).
  • Finely granular cytoplasm (salt-and-pepper nuclei).
  • +/-Hemorrhage - very common.
  • DDx:
    • Neuroendocrine tumour - nests surrounded by stroma/do not touch.
    • Pheochromocytoma - paraganglioma of the adrenal gland.
    • Gangliocytic paraganglioma - has schwannian component and ganglion cells, usu. duodenum.

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Incidentally discovered adrenal mass

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Adrenocortical Adenoma

  • Day of explanation:
    • Well circumscribed 
    • Clear cells
    • Benign appearing
  • Classic features:
    • Well-defined cell borders.
    • Clear cells (abundant, finely vacuolated cytoplasm)
    • Polygonal pink cells.
    • Most of the nuclei are bland, central and round.
    • May have foci of necrosis/degeneration and nuclear atypia.
  • Note: In aldosterone producing tumours:
    • May extend outside of the capsule (should not be diagnosed as adrenal cortical carcinoma).
    • No atrophy of non-hyperplastic cortex.
    • May show spironolactone bodies if hypertension treated with spironolactone prior to surgery.
  • DDx:
    • Adrenal cortical nodule.
    • Adrenal cortical hyperplasia.
    • Hyperplasia is multifocal.
    • Adrenal cortical carcinoma - see Weiss criteria below.

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Kid with Neck mass

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Juvenile Xanthogranuloma (JXG)

  • Day of explanation:
    • Lymphohistiocytic proliferation
    • Toutons (circular) giant cells
    • Classically presents with red patches and plaques on head and neck
  • Dermal histiocytes:
    • Abundant cytoplasm - may not be xanthomatous/foam cells.
  • +/-Touton giant cell - key feature.
    • Large multi-nucleated cells where nuclei are distributed at the cell periphery.
  • Notes:
    • Must prove they are non-Langerhans cell histiocytes, esp. if no Touton giant cells.
  • DDx:
    • Langerhans cell histiocytosis.
    • Spitz nevus - uncommon; reported to have Touton cells.
    • Dermatofibroma, aneurysmal - has Touton giant cells and hemosiderin deposition.
    • Tuberculoma.
    • Erdheim-Chester disease - usu. BRAF V600E mutated.
    • Rosai-Dorfman disease - Emperipolesis.
    • Necrobiotic xanthogranuloma - also may have Touton giant cells.

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42yo F w/ pelvic pain and elevated CA-125.  Salpingectomy.

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  • Criteria - need at least 2 / 3 for the diagnosis:
    • Endometrial glands - endometrial glands are classically: circular, with nuclei that are hyperchromatic & cigar-shaped.
    • Endometrial stroma - endometrial stroma is classically: cellular and hyperchromatic (may resemble a lymphocytic infiltration on low power).
    • Hemosiderin-laden macrophages - light brown, may be granular.
  • Notes:
    • The epithelial component (1) may appear cuboidal in cysts or be sloughed-off, i.e. absent.
    • The microscopic correlation of chocolate cyst is: light brown acellular material; this can be considered as a substitute for (3) - hemosiderin-laden macrophages.
    • Epithelial component may have tubal metaplasia.
    • Endometriosis may mimic cancer - see images below.
    • If it is just endometrial type glands - the stroma is missing... it is probably endosalpingiosis.
  • DDx:
    • Adenocarcinoma.
    • Endosalpingiosis - does not have stromal component.
    • In the GI tract, it classically expands the muscularis propria.

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Neuroendocrine tumor of the appendix (Carcinoid)

  • Classically subepithelial/mural.
  • Various growth patterns:
    • Nested (insular).
    • Trabecular.
    • Palisading.
    • Ribbons, rosettes.
    • Fibrous stroma in between cell groups.
  • Cytomorphology:
    • Monotonous appearance with scanty mitoses.
    • Round central nuclei.
    • Stippled chromatin (AKA salt-and-pepper chromatin and coarse chromatin).
    • Eosinophilic granular cytoplasm.
  • DDx:
    • Colorectal adenocarcinoma.
    • Adenocarcinoid.
    • Crypt cell carcinoma, also known as goblet cell carcinoid.
    • Metastatic adenocarcinoma.
    • Normal ganglion cells in the Meissner plexus (submucosa) and Auerbach plexus (located between the inner and outer layers of the muscularis propria).

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19yo F w/ 3.6cm ovarian mass.

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Serous Cystadenofibroma

  • Day of:
    • Ovarian stroma
    • Stromal proliferation bulging into lumen
    • Bland, simple epithelial lining
  • Simple epithelium - key feature - usually with cilia.
  • Cell morphology: columnar, cuboidal or flatted.
  • Absent or minimal nuclear atypia.
  • +/-Rare tufting.
  • +/-Non-branching papillae.
  • +/-Rare mitoses.
  • Note:
    • May have calcifications - uncommon.[6]
  • DDx:
    • Cortical inclusion cyst - <1 cm in size, see mesothelial inclusion cyst.
    • Ovarian serous borderline tumour - branching papillae, tufting, mitoses, nuclear atypia.
    • Note - the following may be lumped with this entity:
    • Serous cystadenofibroma.
    • Adenofibroma.
  • IHC:
    • CK7 +ve.
    • EMA +ve.
    • WT1 +ve.
    • CK20 -ve

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29yo F w/ infertility.  Endometrial curretage.

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    • Plasma cells with in the endometrial stroma - key feature.
      • Usually superficial/close to the luminal aspect.
    • Lymphocytic infiltrate - usually marked.
      • May form lymphoid aggregates - low power finding.
    • +/-Eosinophils - presence should prompt a search for plasma cells.[4]
    • Other findings:
      • +/-Necrosis.
      • Edema - common.
      • Hemorrhage.
    • Notes:
      • One plasma cell is not enough to call it.
    • DDx:
      • Menstrual endometrium - endometrial stromal condensation.
  • ACUTE:
    • Neutrophils clusters (>5 PMNs) in the:
      • Endometrial stroma.
      • Within uterine glands.
    • Notes:
      • Neutrophils are normal in the context of menses.
    • DDx:
      • Menstrual endometrium - less neutrophils. (???)

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29yo F w/ R supraclavicular soft tissue.  What is your interpretation?

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  • Large polygonal/oval cells:
    • Nucleus - central & small.
      • Nucleoli typically prominent.
    • Cytoplasm - multivacuolated, oval, eosinophilic, granular.
  • +/-Prominent blood vessels, central.
  • DDx:
    • Reaction to silicone implant.

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61yo F w/ postmenopausal bleeding.  Endometrial bx.

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Serous Endometrial Carcinoma

  • Architecture - classically papillary.
    • May be glomeruloid, tubulocystic, solid (uncommon).
  • Cytology:Columnar or cuboidal cells.
    • Moderate to marked nuclear pleomorphism - variation of size, shape and staining.
    • Large nuclear size variation between cells often esp. prominent.
    • Singular prominent, classically red, nucleolus.
  • +/-Psammoma bodies.
  • DDx:
    • High-grade endometrioid endometrial carcinoma - uncommon, typically younger age.
    • Clear cell carcinoma of the endometrium - usually have less nuclear pleomorphism and less mitoses.
    • Arias-Stella reaction.
    • Metastatic serous carcinoma.
    • Endometrium with psammoma bodies - no atypical cells.

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70yo M w/ left level 2 (lateral) neck mass and FNA demonstrating "squamous cells".

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Branchial cleft cyst

  • Cystic space lined by squamous epithelium - usually.
    • +/-Inflammation.
  • Connective tissue:
    • +/-Adipose tissue.
    • +/-Cartilage.
    • +/-Bone.
    • +/-Muscle.
  • DDx:
    • Cystic squamous cell carcinoma - may be deceptively benign appearing.
    • Papillary thyroid carcinoma (PTC) arising in a brachial cleft cyst - uncommon, looks like PTC in the thyroid.
    • Epidermal inclusion cyst.

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29yo M w/ pain in left axilla and night sweats, LAN.  What is diagnosis and comment?

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Acute granulomatous lymphadenitis (concern for Bartonella henslae [Cat Scratch Disease])

  • Necrotizing granulomas with:
    • Neutrophils present in microabscess (necrotic debris) - key feature.
      • Microabscesses often described as "stellate" (star-shaped).
  • +/-Multinucleated giant cells.
  • Microorganism consistent with B. henselae.
  • Notes:
    • May involve capsule or perinodal tissue.
  • DDx of stellate abscess in lymph nodes - cat split:
    • Cat-scratch disease.
    • Sporotrichosis.
    • Lymphogranuloma venereum.
    • Tularemia.

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50yo F w/ right, retroperitoneal mass.  Cells positive for CD10, negative for inhibin-A and MART-1.

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Clear Cell Renal Cell Carcinoma (CCRCC)

  • Clear cytoplasm.
    • May have eosinophilic cytoplasm (in high-grade tumours) - usually focal.
  • Delicate branching vasculature - key feature.
    • Often called "chicken wire-like" vasculature.
  • Solid or trabecular pattern.
  • Polygonal cells.
  • Central nucleus.
  • +/-Rhabdoid cells:
    • Eccentric nucleus.
  • Abundant eosinophilic cytoplasm.
  • Notes:
    • Cytoplasm may be eosinophilic.
      • This change is typically focal - other areas have a classic appearance.
    • Chicken wire-like vasculature present - helps distinguish from other tumours.
    • Hyaline bodies common.
      • Not common in papillary RCC.
    • Clear cytoplasm - due to lipid content.
    • Necrosis is independent predictor of outcome - if present in a significant quantity:
      • >30% is significant for pT3a tumours.
      • >20% is significant for pT1-2 pN0 tumours.
  • DDx:
    • Chromophobe renal cell carcinoma.
    • Clear cell papillary renal cell carcinoma.
    • Xp11.2 translocation carcinoma.
    • Adrenocortical carcinoma (ACC)
    • EMA -ve, CKs mostly -ve, inhibin +ve (neg. in RCC).
    • Alveolar soft part sarcoma.
    • Adrenal gland, normal cortex - wispy, vacuolated.
    • Epithelioid angiomyolipoma.

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87yo M w/ dementia fell and broke multiple ribs with splenic lac.  Spleen bx.

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Splenic Marginal Zone Lymphoma

  • Day of:
    • Red and white pulp
      • White pulp expanded (marginal zone)
    • Effaced node included
    • Vague paler areas present
    • Lymphoid tissue in hilar fat
    • Often involved:
      • Spleen
      • Bone marrow
      • Blood
      • Lymph nodes
  • Small (lymphoid) cells that may be plasma cell-like (plasmacytoid):
    • +/-Clockface nucleus.
    • +/-Eccentric nucleus.
  • +/-"Lymphoepithelial lesion" - gastric crypts invaded by a monomorphous population of lymphocytes. Features:Cluster of lymphocytes - three cells or more - key feature.
    • Single lymphocytes don't count.
    • Clearing around the lymphocyte cluster.
      • Not specific for MALT lymphoma, i.e. may be seen in other types of lymphoma.
  • DDx:
    • Other small cell lymphomas.
    • DLBCL - should be a distinctive region at low power

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Duodenal bx in 54yo M

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(Features suggestive of) Celiac Disease

  • Day of:
    • Blunted villi
    • Intraepithelial lymphs at tips
  • Intraepithelial lymphocytes (IELs) - key feature.
    • Should be more pronounced at tips of villi.
    • Criteria for number varies:
      • > 40 IELs / 100 enterocytes (epithelial cells).
      • > 25 IELs / 100 enterocytes (epithelial cells).
  • Loss of villi - important feature.
    • Normal duodenal biopsy should have 3 good villi.
  • Plasma cells - abundant (weak feature).
  • Macrophages.
  • Mitosis increased (in the crypts).
  • +/-Collagen band (pink material in mucosa) - "Collagenous sprue"; must encompass ~25% of mucosa.
  • Notes:
    • If you see acute inflammatory cells, i.e. neutrophils, consider Giardiasis and other infectious etiologies.
    • Biopsy should consist of 2-3 sites. In children it is important to sample the duodenal cap, as it is the only affected site in ~10% of cases.
    • Flat lesions without IELs are unlikely to be celiac sprue.
    • Mucosa erosions are rare in celiac sprue; should prompt consideration of an alternate diagnosis (infection, medications, Crohn's disease).
    • Biagi et al. count twenty cells in five (villi) tips.
  • DDx
    • Giardiasis.
      • Have giardia organisms.
      • Always consider Giardiasis and especially on exams.
    • Crohn's disease.
    • Helicobacter gastritis.
    • Cryptosporidiosis.
    • Whipple's disease (very rare).
      • Abundant macrophages should make one suspicious.
    • Autoimmune enteropathy - pediatric population.
      • Super duper rare.
    • Drugs - e.g. olmesartan

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34yo M w breast mass

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  • Moderate hyperplasia.
  • Glands have more than 2 cell layers.
  • "Budding" - individual cells jut into the lumen - key feature.
  • Buds may be multicellular; however, narrower toward the centre of the lumen.
  • Stromal palor.
  • DDx:
    • Micropapillary DCIS - buds not narrower toward the centre of the lumen.

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Back mass 56yo F

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  • General:
    • Benign.
    • Classically, subscapular in elderly women.
  • Gross Features:
    • Yellow-white, moderate demarcation to surrounding tissue.
  • DDx - shoulder lesions:
    • Desmoplastic fibroblastoma.
    • Pleomorphic lipoma.
  • Microscopic Features:
    • Thick bundles of collagen.
    • Elastin fibres.

PIC: A): Fibrous, collagenous strands intermingled with fat cells (hematoxylin-eosine-staining). B): Collagenous material and roundly shaped elastic fibres, mesenchymal cells with bland nuclei (hematoxylin-eosine-staining). C): Elastic fibres and structures forming discs and globules stained dark brown to black using an elastic stain (Elastica-van-Gieson).

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24yo F possible lipoma left flank

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  • Day of:
    • Rope like collagen
    • shredded carrots/twisted dish rags (nuclei)
    • Peripheral nerve sheath tumor
    • Usually leaves surrounding adnexal structures alone
  • Spindle cells with wavy nuclei without pleomorphism - key feature.
  • Intermixed with wire-like collagen.
    • Often no pattern is apparent.
    • Often described as "shredded carrots".
  • Moderate increase of cellularity vis-a-vis normal dermis.
  • May be poorly or well-circumscribed.
  • +/-Plexiform growth pattern - "bag of worms".
    • Multiple well-circumscribed nests.
    • Suggestive of NF-1
  • Mast cells - one has to look for them at high power.
    • Very useful for confirming the low power suspicion.
  • DDx:
    • Plexiform neurofibroma.
    • Schwannoma - calretinin +ve, CD34 mostly -ve.
    • Dermatofibrosarcoma protuberans (DFSP) - S-100 -ve.
    • Ganglioneuroma.
    • Neurotized melanocytic nevus - melanocyte nests make the diagnosis, otherwise immunostains are needed to differentiate.
      • Usually have more mast cells than neurofibromas

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67yo F, cervical bx

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Endocervical Adenocarcinoma in Situ (AIS), Intestinal Type

  • Day of:
    • Goblet cells in cervix: worry about AIS, intestinal type
    • Hyperchromasia
    • Architectural distortion
  • Nuclear changes - key feature:
    • Variable nuclear stratification.
      • Nuclear crowding/pseudostratification.
    • Nuclear enlargement.
      • Often cigar-shaped nuclei.
    • Coarse chromatin.
    • Small nucleolus or nucleoli.
  • +/-Mitoses.
  • +/-Reduced cytoplasmic mucin.
  • Preservation of glandular architecture.
    • Normal gland spacing - lack of complexity ("lobular pattern").
    • Normal gland depth (subjective).
  • DDx:
    • Tubal metaplasia.
    • Arias-Stella reaction.
    • Endometriosis.
    • Lower uterine segment epithelium - esp. proliferative phase endometrium - mitoses rare, NC ratio normal, stroma different.
    • Endocervical adenocarcinoma - often has paradoxical maturation... paler cytoplasm & nuclei than adjacent AIS.
    • Metastatic adenocarcinoma.
    • Proliferative phase endometrium - endometrial type stroma, cytoplasm not pale staining, no nuclear atypia (smooth nuclear contour, stratified).

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Enlarged LN in neck of 34yo F (be specific)

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Nodular Sclerosing Hodgkin's Lymphoma

  • Day of:
    • Big, blue nodules and interspersed hyaline bands
    • Mixed inflammatory infiltrate
    • Lots of eosinophils
    • Mummified cells (dark purple, look calcified)
    • Hodgkins cells: mononuclear; RS cells: binuclear
    • CD30+, CD15+ (less than 30)
  • Reed-Sternberg cell.
    • Large binucleated cell (>= 45 micrometres).
    • May be multinucleated.
    • May have a horseshoe-like shape.
    • Macronucleolus - approximately the size of a RBC (~8 micrometers).
    • Well-defined cell border.
    • Abundant cytoplasm.
  • Notes:
    • Large mononuclear cells are common (so called "mononuclear RSCs") but not diagnostic.
  • There are four CHL subtypes:
    1. Nodular sclerosis CHL - ~70% of CHL.
      • Mixed cellular background - T cell, plasma cells, eosinophils, neutrophils and histiocytes.
      • Nodular sclerosing fibrosis - thick strands fibrosis.
    2. Mixed cellularity CHL - ~20-25% of CHL.
      • Like nodular sclerosis - but no fibrosis.
      • May be associated with HIV infection.
    3. Lymphocyte-rich CHL - rare.
      • T lymphocytes only (no mix of cells).
    4. Lymphocyte-depleted CHL - rare.
      • May be associated with HIV infection.
    • Memory device:
      • The subtypes prevalence is in reverse alphabetical order.

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Incidental kidney mass in 57yo F

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Angiomyolipoma (AML)

  • Day of:
    • Clearish look of cytoplasm
    • Stains: HMB45, SMA
  • Smooth muscle.
  • Adipose tissue - not always present - key feature.
  • Abundant blood vessels.
  • Note:
    • May have melanin pigment - occasionally extensive.
  • DDx:
    • Retroperitoneal sarcoma.
    • Liposarcoma.
    • Leiomyosarcoma.
    • Renal cell carcinoma with sarcomatoid differentiation.
    • Renal leiomyoma - very rare - desmin +ve, HMB-45 -ve

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Fundic Bx in obese 54yo F

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(Features Suggestive of) Autoimmune Metaplastic Atrophic Gastritis (AMAG)

  • Corpus predominant inflammation - usu. moderate or severe - key feature.
  • Loss of parietal cells.
  • Increased G cells in the antrum.
    • Produce gastrin to stimulate the (missing) parietal cells.
  • Notes:
    • Compare with other types of gastric atrophy.
  • DDx:
    • Gastric neuroendocrine tumour.
  • PIC (reverse): Typical histopathological features of autoimmune atrophic gastritis. A) The antral mucosa shows moderate foveolar hyperplasia (reactive gastropathy) with neither inflammation nor metaplasia. B) The mucosa of the corpus shows absence of parietal cells, intestinal metaplasia (arrows) and pseudopyloric metaplasia (asterisk). A small cluster of surviving oxyntic glands (Oxy) is seen in the lower portion of the mucosa.

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Enlarged mediastinal mass, 64yo F, previously bx

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  • Day of:
    • Bx site changes seen
    • Balls of cells w interspersed vessels
    • "Zellballen" look
    • Lilac color

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Urethral stricture 84yo M (IHC positive: CK7, Racemase, PAX8; IHC negative: PSA)

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Nephrogenic Adenoma

  • Tubular structures - the classic morphology. †
    • Lined by a single cell layer - classically hobnailed. ‡
    • +/-Thick eosinophilic basement membrane.
    • Typically microcystic appearance.
  • Usually associated with chronic inflammation.
  • Notes:
    • May mimic vascular/lymphatic channels - can be sorted-out with IHC.
    • † May be tubulocystic, polypoid, papillary or fibromyxoid.
    • ‡ May be flat.
    • Should not have necrosis or mitoses.
  • DDx:
    • Urothelial carcinoma, microcystic and nested variants.
    • Clear cell adenocarcinoma.
    • Clear cell adenocarcinoma of the urethra.
    • Mesonephroid adenocarcinoma (also known as clear cell carcinoma) - may be deceptively bland.
    • Prostatic adenocarcinoma.
    • Metastatic tumours.
    • Clear cell renal cell carcinoma.
    • Other clear cell tumours.

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62yo F with palate mass.  Most likely diagnosis?

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Polymorphous Low Grade Adenocarcinoma

  • Architecture: often small nests, may be targetoid.
  • Classically has whorling with eye-of-storm & single file.
  • Cytologically monotonous (uniform) with variable architecture - key feature.
    • Nucleus: ovoid & small, small nucleoli, powdery chromatin.
      • Papillary thyroid carcinoma-like appearance.
    • Cytoplasm: eosinophilic.
    • Indistinct cell borders.
  • Note:
    • Always a low-grade tumour - by definition.
  • DDx:
    • Adenoid cystic carcinoma.
    • Pleomorphic adenoma.
    • Cribriform adenocarcinoma of the minor salivary gland

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Rapidly growing cheek mass in 78yo M

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Merkel Cell Carcinoma

  • Neuroendocrine nuclear features - round nucleus, small nucleoli/no nucleolus, stippled chromatin - key feature.
  • Typically medium size cells ~3x resting lymphocyte.
    • May be small or large.
  • Architecture: nests, sheets or trabeculae.
  • Scant cytoplasm.
  • Abundant mitoses. †
  • +/-Nuclear moulding.
    • Nuclei of adjacent cells conform to one another.
  • +/-Tumour infiltrating lymphocytes. ‡
  • Notes:
    • † >10 mitoses/HPF = poor prognosis - definition suffers from HPFitis.
    • ‡ May be associated with a worse prognosis.
  • Merkel cell carcinoma lymph node metastases is difficult to diagnose with routine stains; use of IHC stains are advised.
  • Arise from the epidermis - very rarely in situ.
  • DDx:
    • Basal cell carcinoma - no stippled chromatin, less mitoses active.
    • Cutaneous Ewing sarcoma - sorted-out with immunostains.
    • Lymphoma.
    • Burkitt lymphoma.
    • Metastatic small cell carcinoma.
    • Other small round cell tumours.

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35yo M with inguinal lymphadenopathy.

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Mixed Germ Cell Tumor (Metastatic to Nodes)

  • Depends on the components.
  • Classic appearances:
    • Seminoma: fried egg-like" cells with lymphocytes.
    • Yolk sac tumour: edematous appearing/paucicellular regions, Schiller-Duval bodies.
    • Embryonal carcinoma: moderate-to-marked nuclear atypia with overlapping nuclei and usu. necrosis.
    • Teratoma: cysts with GI like epithelium, cysts with squamous epithelium & keratin (skin), immature cartilage, others.
    • Choriocarcinoma: hemorrhagic, multinucleated cells (syncytiotrophoblasts) and cells with pale cytoplasm (cytotrophoblasts).
  • Notes:
    • If one cannot identify the component... it is probably yolk sac as this has so many different patterns.

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31yo F with a jaw cyst

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Keratocystic Odontogenic Tumor (Formerly OKC)

  • Stratified epithelium (resembling squamous epithelium) with:
    • "Ribbon-like appearance" - important.
      • Typically 8-10 cell layers thick - with relatively uniform thickness.
      • Lacks rete ridges.
    • Palisaded basal cell layer.
  • Parakeratosis (keratinized cells with nuclei) - key feature.
  • Artefactual separation of epithelium from the basement membrane.
  • DDx:
    • Odontogenic cyst.Orthokeratinized odontogenic cyst - usu. dentigerous cyst - has orthokeratosis instead of parakeratosis.
    • Orthokeratosis = keratinized cells no nuclei; parakeratosis = keratinized cell with nuclei.

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11yo F with INI1 negative renal mass.

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Renal Medullary Carcinoma

  • Associated with sickle cell disease and a poor prognosis.
  • Variable architecture:
    • Reticular - classic.
    • Adenoid cystic carcinoma-like appearance:
    • Cystic spaces.
    • Yolk sac-like.
    • Tubular.
  • Desmoplastic stroma - prominent.
  • Inflammation:
    • Lymphocytes.
    • Neutrophils - margination in vessels.
  • DDx:
    • Yolk sac tumour.
    • Collecting duct carcinoma.
    • Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma.

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14yo M with "chest lesion".

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Molluscum Contagiosum

  • A suprabasilar epidermal lesion consisting of "molluscum bodies" -- in other words "molluscum bodies" are found above the stratum basale +/- extension to the skin surface.
    • Molluscum bodies - key feature:
      • Large cells with (granular) eosinophilic cytoplasmic inclusions.
        • The inclusions usually fill the cytoplasm.
        • Inclusions are usually one per cell... but may be multiple.
      • Small peripheral nucleus.
  • +/-Lymphocytes.
  • Notes:
    • Molluscum bodies very vaguely resemble signet ring cells -- but:
      • Cytoplasm is eosinophilic and granular.
      • Nucleus usually smaller than in signet ring cells.
      • Molluscum bodies are only in the epidermis - an uncommon place to find SRCs without finding them elsewhere.
    • The granular eosinophilic cytoplasmic inclusions represents accumulated virons.
    • Molluscum bodies "grow" toward the surface
  • DDx:
    • Nothing really - it is very distinctive.

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32yo M with testicular mass

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Sertoli Cell Tumor

  • Groups of cells in cords or trabeculae (beam-like arrangement).
  • Cells have:
    • Light staining bubbly cytoplasm +/- large cytoplasmic vacuoles.
    • Slightly irregular nucleoli.
    • Granular irregular appearing chromatin.
  • Negatives:
    • Mitoses are rare.
    • No significant nuclear atypia.
  • DDx:
    • Granulosa cell tumour - may be very similar. Often has nuclear grooves.
    • Epithelioid adenomatoid tumour.
    • Sertoli cell nodule.
    • Sertoli-Leydig tumour - esp. in ovary.

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78yo F with breast mass.

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Metaplastic Breast Carcinoma

  • Features - one of the following:
    • Malignant mesenchymal elements - either:
      • Spindle cells.
      • Osseous, chondroid or rhabdoid differentiation.
    • Squamous component.
      • Non-skin squamous cell carcinoma of the breast = metaplastic breast carcinoma.
  • Notes:
    • Calcifications are uncommon.
    • Cytology may be very bland, i.e. it may look very benign.
    • May have minimal mitotic activity.
  • DDx:
    • Fibromatosis.
    • Malignant phyllodes tumour.
    • Primary mammary sarcoma.
    • Mammary myofibroblastoma.
    • Nodular fasciitis.
    • Squamous cell carcinoma of the skin.
    • Malignant melanoma.

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45yo F with renal mass.

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Renal Oncocytoma

  • Eosinophilic cytoplasm - slightly granular key feature.
  • Cells arranged in nests.
  • Nuclei uniform and round.
    • Slightly enlarged nuclei, but no significant pleomorphism (size variation) - important.
  • Notes:
    • May look like eosinophilic variant of chromophobe RCC -- this is the main DDx.
      • A comparison based on histomorphology: Tabular comparison between ChRCC & oncocytoma.
        • Oncocytoma typically has: no perinuclear clearing, no raisinoid nuclei, rare or no binucleation.
  • May have - according to Trpkov et al.:
    • Vascular invasion ~4% of cases.
    • Chromophobe-like foci (<5% of neoplasm) ~12% of cases.
    • Focal clear cell changes ~15% of cases.
    • Hemorrhage.
  • DDx:
    • Chromophobe renal cell carcinoma, eosinophilic variant.
    • Succinate dehydrogenase-deficient renal cell carcinoma - emerging entity as per Vancouver classification - classically has a flocculent cytoplasm, may have oncocytoma-like areas.
    • Papillary renal cell carcinoma, oncocytic variant.
    • Renal hybrid oncocytic/chromophobe tumour.
    • Clear cell renal cell carcinoma, eosinophilic variant.
    • Tubulocystic carcinoma of the kidney.
    • Other renal tumours with eosinophilic cytoplasm.
    • Benign liver.

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38yo F with ovarian mass.

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Mucinous Borderline Tumor of the Ovary

  • Two Types: Intestinal and Endocervical
  • Intestinal Type:
    • Mucinous differentiation:
      • Tall columnar cells with apical mucin - usu. resembles gastric foveolar epithelium.
    • Layering of epithelial cells (stratification).
      • Must be <= 3 cells.
    • +/-Papillary infoldings.
      • Projections into the cystic space.
    • +/-Mild nuclear atypia.
    • +/-Mitoses (focally).
    • Notes:
      • Resembles a villous adenoma of the colon.
      • Borderline component must be >= 10% of the tumour.
      • Lesions with <10% borderline component are known as mucinous cystadenoma of the ovary with focal proliferation or mucinous cystadenoma of the ovary with focal atypia.
    • DDx:
      • Mucinous adenocarcinoma of the ovary.
      • Mucinous cystadenoma of the ovary.
      • Mucinous cystadenoma of the ovary with focal proliferation.
  • Endocervical Type:
    • Cells with mucinous differentiation resembling endocervical epithelium:
    • Tall columnar cells with grey apical mucin.
    • Cells with eosinophilic cytoplasm - known as "pink cells".
    • Ciliated cells.
    • Neutrophils associated with the epithelium/mucin - common.