Ovary Flashcards

Question

Fibroma

Answer 1

* Benign stromal tumor * Fibroblastic cells * Variably collagenous stroma **Macro:** * Well circumscribed mass with smooth, lobulated surface * Firm, chalky, solid, white to yellow-white to tan-yellow cut surface that may be whorled * Frequent oedema resulting in softer consistency * Mean size 6 cm * Usually unilateral (< 10% bilateral) * Cystic degeneration in ~25% of cases * Calcifications in ~10% of cases **Micro:** * Spindled or ovoid cells * Abundant collagen * Bland nuclear features **Variants:** * Cellular Fibroma --> Cellular with scant collagen, mild atypia, increased mitoses * Mitotically Active Cellular Fibroma * Minor Sex Cord Elements **IHC:** WT1 SF1 FOXL2 (no mutation) Inhibin: 50% of cases, often focal or weak Vimentin CD56 ER/PR SMA Reticulin: differentiates fibroma (individual pericellular reticulin staining pattern) from diffuse type of adult granulosa cell tumor (nested reticulin staining pattern) **Syndromes:** * Gorlin Syndrome --> if young and bilateral * Meig's Syndrome --> Fibroma + Ascites + Pleural Effusion (resolve after removal of ovarian tumour)

Answer 2

* Ovarian stromal neoplasm * Almost always benign * Usually occurs in postmenopausal women who present with uterine bleeding **Macro:** * Usually unilateral * Most are < 5 cm * Solid, yellow and lobulated or white with focal yellow areas * Occasional cystic change and hemorrhage * Necrosis is rare **Micro:** * Sheets of uniform cells * Pale greyish-pink cytoplasm * Cytologically bland * Reticulin surrounds individual cells **IHC:** Inhibin Calretinin Reticulin stain shows a pericellular pattern SF1 FOXL2 WT1 CD56 Vimentin Oil red O in lipid rich cells

Answer 3

* Ovarian stromal tumor composed of steroid cells with malignant potential * Mostly unilateral * Half of cases have androgenic manifestations --> hirsuitism **Macro:** * Wide size range * Unilateral (95%) * Solid, well circumscribed, occasionally lobulated * Sections from yellow-orange (lipid rich) to red-brown (lipid poor) to dark brown-black (abundant lipochrome pigment) * Occasionally with necrosis, hemorrhage and cystic degeneration **Micro:** * Architectural pattern: diffuse (most common) but occasionally in nests, cords, pseudoglandular and follicle-like arrangements * Stroma: usually sparse (85%) but may be fibrotic or hyalinized, rarely edematous or myxoid * Polygonal to rounded tumor cells with distinct cell borders, central nuclei and moderate to abundant cytoplasm * Tumor cell cytoplasm: eosinophilic and granular (lipid poor) to vacuolated and spongy (lipid rich); * Lipochrome pigment present (40%) **IHC:** Inhibin Calretinin SF1 MelanA Androgen receptor (64%) Vimentin (75%) CD99

Answer 4

* Benign steroid cell tumor composed of polygonal cells with abundant eosinophilic cytoplasm and Reinke crystals * Postmenopausal occurrence * Predominantly located in the ovarian hilus, close to nerve fibers * Often lobulated or nodular growth * Reinke cytoplasmic crystals present * Secretes androgens --> masculisation **Micro:** * Unencapsulated neoplasms * Smooth or irregular borders located in the hilus, next to nonmedullary nerve fibers * Round to polygonal cells with abundant eosinophilic or vacuolated cytoplasm and round nuclei with small nucleoli * Reinke crystals: eosinophilic, cytoplasmic rod, rectangular or hexagonal crystals * Lipochrome pigment is common * May have cytoplasmic pseudoinclusions or bizarre nuclear atypia **IHC:** Inhibin Calretinin MelanA MITF SF1 CD99

Answer 5

* Low grade indolent malignant neoplasm originating from granulosa cells of the ovarian follicles * 20-30% chance of local recurrence, 5-20 years after diagnosis * Secretes Oestrogen --> Menorrhagia, PMB, Amenorrhea **Micro:** * Scant, pale architecture * Grooved nuclei * Varied architecture --> Sheet-like, trabecular, ribbon-like, microfollicullar * Call-Exner bodies filled with pink secretions * Frequent mitoses **Molecular:** FOXL2 point mutations **IHC:** * FOXL2 immunostain is a sensitive (80%) and specific (99%) marker for sex cord stromal tumors (SCST) * SF1: most sensitive marker for this as well as most common sex cord stromal tumors * Inhibin A: more specific marker * Calretinin * **Reticulin: shows lack of pericellular staining and highlights nests or large groups of granulosa cells and vessels, helps differentiate diffuse pattern from fibroma / thecoma ** * Low molecular weight cytokeratin (CAM5.2, AE1 / AE3): 30 - 60%, usually dot-like or globoid perinuclear pattern * S100: 50% * CD99: 70% * Vimentin, WT1, CD56 and SMA

Answer 6

* Sex cord stromal tumor composed of primitive appearing granulosa cells with follicular and solid growth patterns * Sex cord stromal tumor with primitive granulosa cell differentiation * Solid and follicular growth * Almost always occurs in patients younger than 30 years * Lacks the FOXL2 somatic mutation seen in adult granulosa cell tumor * Usually stage IA and associated with a favorable prognosis **Macro:** * Usually unilateral with a smooth surface * Mean size 12.5 cm * Multiloculated, cystic and solid tumor with yellow-white solid areas * May have hemorrhage and necrosis **Micro:** * Cells are round, abundant oesinophilic cytoplasm * NO GROOVES * Macrofollicular * Basophillic secretions * Frequent mitoses **Molecular:** NO FOXL2 mutations **IHC:** Inhibin Calretinin SF1 WT1 FOXL2 BRG1 (SMARCA4) (retained)

Answer 7

* Distinctive variant of sex cord stromal tumor * Characterized by sharply circumscribed nests composed of ring-like tubules that encircle basement membrane-like material * 2 types: sporadic and syndromic, the latter is associated with Peutz-Jeghers syndrome **Macro:** **Nonsyndromic tumors:** * Unilateral masses ranging in size from several millimeters to 3 cm * Solid, tan to yellow * Cysts may be seen and occasionally may predominate **Syndromic tumors:** * Bilateral and multifocal lesions * Often microscopic; may not be grossly visible * Gritty texture may be noted if there is a mass **Micro:** * Syndromic and nonsyndromic tumors have similar morphology * Variably size round nests of sharply delineated simple and complex tubules * Tubules contain basement membrane-like material, which may also be present around the tubules * Cells are columnar with clear cytoplasm * Antipodal nuclei. Tumors associated with Peutz-Jeghers syndrome: * Calcifications within the tubules may be seen * May be associated with endocervical gastric type adenocarcinoma (adenoma malignum) Nonsyndromic / sporadic tumors: * May focally transition to granulosa or Sertoli cell morphology * Cytologic atypia and mitotic activity may rarely be seen * May be hyalinized **IHC:** Calretinin WT1 Inhibin SF1 FOXL2 CD56

Answer 8

* Accounts for < 0.5% of all ovarian neoplasms * Common in young patients --> mean age of 25 * Composed of sex cord (Sertoli cells) and stromal (Leydig cells) elements * May occur sporadically or in patients with DICER1 syndrome **3 molecular subtypes:** **DICER1 mutant:** * Younger age * Moderately / poorly differentiated * Retiform or heterologous elements **FOXL2 c.402C>G (p.Cys134Trp) mutant:** * Postmenopausal patients * Moderately / poorly differentiated * No retiform or heterologous elements **DICER1 / FOXL2 wildtype:** * Intermediate age * No retiform or heterologous elements * Including all well differentiated tumors **Micro:** * Well differentiated * Moderately differentiated * Poorly differentiated * Histologic grade and subtype correlates with clinical behaviour * Sertoli-Leydig cell tumour with heterologous elements (Rhabdomyoblasts) * Sertoli-Leydig cell tumour with retiform variant * Intestinal metaplasia may be seen. **IHC:** * General sex cord proteins, such as inhibin, calretinin, SF1, FOXL2, CD56, WT1 and CD99 * Vimentin and pancytokeratin * MelanA / MART1 in Leydig cells * CK20 and CDX2 in heterologous intestinal type mucinous epithelium * AFP, arginase and HepPar1 in hepatoid elements * Reticulin histochemical staining may be helpful in differentiating Sertoli-Leydig cell tumor (completely absent or nested pattern) from fibromas and thecomas (individual pericellular reticulin network) * Absence of reticulin staining is not specific for Sertoli-Leydig cell tumors, as adult granulosa cell tumors and epithelial ovarian tumors also show the same staining pattern

Answer 9

* Varients of protein encoded by DICER1 gene on chromosome 14 * DICER1 syndrome is a rare, inherited genetic disorder that increases the risk of developing tumors * Autosomal dominant **Tumors** * **Pleuropulmonary blastoma:** A cystic lung tumor that may transform into an invasive tumor if not diagnosed and treated early. * **Multinodular goiter (MNG):** A non-cancerous thyroid condition in which there are multiple nodules throughout the thyroid. * **Cystic nephroma:** A non-cancerous kidney tumor. * **Sertoli-Leydig cell tumor: **An ovarian tumor that is more common in females with a faulty DICER1 gene. **Other conditions** * Goiter (an enlarged thyroid) * Polyps in the colon may also occur. Inheritance

Answer 10

* Benign stromal tumor * Pseudolobular appearance resulting from alternating cellular and hypocellular areas **Macro:** * Typically unilateral * Well circumscribed * White-yellow variegated solid mass * Often edema and cysts * Hemorrhage, calcifications and rarely necrosis may be seen **Micro:** * Moderately cellular pseudo-lobuiles with numerous thin-walled vessels. * Cellular areas --> fibroblasts and lip-laden vaculolated cells * Separated by oedematous connmective tissue or dense collagenous stroma * Sclerosis is present within the nodules * Rare mitoses **Molecular:** GLI2 rearrangements in 81% FHL2 is the most common gene partner **IHC:** Inhibin calretinin FOXL2 CD10 smooth muscle actin Diffuse TFE3 expression in a subset of tumors

Answer 11

1. Pulmonary Type 2. Hypercalcaemic Type --> More common **Hypercalcaemic Type** * Young women * Unilateral * Associated with paraneoplastic hypercalcaemia * Undifferentiated tumour * Diffuse growth of small, monotonous cells with scant cytoplasm * Often focal macro follicle-like spaces * Often a component of larger cells with more cytoplasm * Very aggressive **IHC:** Diffuse WT1 Focal CK and EMA Loss of nuclear **SMARCA4 / BRG1** expression **Pulmonary Type** * Must exclude a metastasis * Older women * Often bilateral with extra-ovarian spread * Diffuse growth of smnall cells with scant cytoplasm * Salt and Pepper chromatin, and moulding * Losts of mitoses and apoptotic bodies * Poor prognosis

Answer 12

* Dysgerminoma * Yoke Sac Tumours * Embryonal Carcinoma * Choriocarcinoma * Teratoma * Struma Ovarii

Answer 13

* Malignant primitive germ cell tumor with no specific type of differentiation * Most common germ cell tumour (Female seminoma) * Most common in children and young women * Usually unilateral * Elevated serum LDH * Rarely elevated hCG * Excellent prognosis with chemotherapy **Micro:** * Sheets or nests of uniform cells with clear or eosinophilic cytoplasm and distinct cell membranes * Nuclei are rounded, often with angulated edges * Tumor often separated by fibrous septae containing cytotoxic T cells and epithelioid histiocytes that can extend into tumor **Molecular:** Majority have isochrome 12p ckit mutations **IHC:** SALL4 OCT3/4 --> nuclear positivity D2-40 CD117 PLAP

Answer 14

* Most common before the age of 30 * Usually unilateral ovarian mass with predilection for right ovary * Usually occurs as a pure form or rarely as a component of a mixed germ cell tumor * Numerous morphologic patterns, with the hallmark Schiller-Duval bodies * Elevated serum alpha fetoprotein (AFP) * Usually favorable clinical outcomes due to chemosensitivity * Pure hepatoid and glandular intestinal types associated with poorer prognosis **Molecular:** Chromosome 12 abnormalities, usually isochromosome 12p **Micro:** * Multiple patterns * Most common --> reticular/microcystic * Schiller-Duval bodies --> A central blood vessel surrounded by layers of tumor cells, contained in a cystic space **IHC:** SALL4: marker of primitive germ cell differentiation AFP: highly specific but 60% sensitive, often patchy / focal and weak Glypican 3: less specific but stronger expression PLAP HNF1β Pancytokeratin GATA3: positive in reticular / microcystic, papillary and polyvesicular vitelline patterns but not in the glandular pattern HepPar1: positive in glandular and hepatoid patterns CEA, albumin: positive in hepatoid pattern TTF1: positive in foregut / respiratory pattern CDX2: positive in glandular intestinal type pattern Villin: positive in reticular / microcystic and glandular intestinal type patterns

Answer 15

* Primitive appearing ovarian tumor that is histologically similar to embryonal carcinoma of the testis * Often a component in a malignant mixed germ cell tumor of the ovary; the pure form is exceedingly rare * May show serum elevation of AFP or βhCG with positive pregnancy test * Aggressive but respond to chemotherapy **Micro:** * Similar to embryonal carcinoma of the testis * Often mixed with other malignant germ cell tumor components * Sheets and nests of large, primitive pleomorphic cells with abundant cytoplasm * Round nuclei with coarse membranes, at least 1 prominent nucleolus and brisk mitotic activity * Occasional papillae and gland morphology * Syncytiotrophoblast-like tumor cells are seen (hCG+) around sheets of tumor cells or within stroma * Hyaline globules, similar to yolk sac tumor, may also be present * Glandular pattern may mimic endometrial carcinoma or glandular morphology of a yolk sac tumor **Molecular:** Isochrome 12p **IHC:** SALL4, OCT 3/4 and SOX2 nuclear positivity CD30 membranous positivity OCT 3/4 more sensitive than CD30 but can also be expressed in dysgerminoma AE1 / AE3 βhCG positive in syncytiotrophoblastic cells AFP may be expressed in both tumor cells and hyaline globules CD30 expression might decrease after chemotherapy

Answer 16

* Rare primary ovarian tumor; < 1% of primitive ovarian germ cell tumors * May develop from: * Ovarian pregnancy (gestational choriocarcinoma), * Germ cell tumor (pure or mixed, non-gestational choriocarcinoma) or * Surface epithelial tumor with choriocarcinomatous differentiation * Markedly elevated bHCG --> monitoring helps predict reecurrence and response to therapy * Non-gestational choriocarcinomas are difficult to treat --> unresponsive to chemotherapy * Mets to lungs, liver, bone, and viscera are common at diagnosis **Micro:** * Composed of cytotrophoblast, intermediate trophopblast and multinucleated syncytiotrophoblast around periphery of blood channels **IHC:** Cytokeratin, CD10, human placental lactogen, EMA Syncytiotrophoblasts are hCG+

Answer 17

* Composed of tissues form 2-3 germs layers * Often and cystic and unilateral * Common elements --> skin with adnexal structures, cartilage, GI, Brain **Types:** * Mature (benign) * Immature (malignant) * Teratoma with malignant transformations * Monodermal teratomas --> struma ovarii --> mostly/all thyroid * Carcinoid --> resemble well-differentiated NET tumours of GI tract **Mature Teratoma** * Mature tissue representing at least 2 embryonic layers * If malignant transformation (rare), prognosis is related to the type of malignancy * Most common ovarian tumor (20% of all ovarian tumors, 95% of all ovarian germ cell tumors) * Reproductive age * 10% bilateral **Immature Teratoma** * Malignant germ cell tumor of the ovary composed of cells from the 3 germ layers and containing variable amounts of mature and immature tissue * Affects mostly young females < 20 years old * Grossly solid ovarian tumor mass with necrosis and hemorrhage on cut sections * Grading is based on the amount of immature neuroepithelium * Can have associated nodal or peritoneal gliomatosis (presence of mature neural tissue), which increases risk of recurrence * Grading and stage are the most important factors for prognosis and prognosis is greatly improved after chemotherapy **Struma Ovarii** * Ovarian teratoma either composed predominantly or exclusively of benign thyroid tissue or with any amount of malignant thyroid tissue * Most common thyroid malignancy to occur in struma ovarii is papillary thyroid carcinoma, followed by follicular carcinoma **Macro:** * Typically unilateral * <10cm * Smooth surfaced * Solid, brown or green-brown * Fibrous septa * Fluid-filled cysts containing brown-green gelatinous fluid **Micro:** * Mature thyroid tissue or adenoma with small and large follicles lined by a layer of columnar, cuboidal, or flattened epithelium * May show changes similar to thyroid gland --> hyperplasia or thyroiditis **IHC:** * PAS higfhlights colloid * Thyroglobulin highlights thyroglobulin in the struma component **Monodermal teratomas: carcinoid tumour:** * Primary carcinoid rumours of the ovary are associated with other teratomatous elements in 85-90% cases * Most commonly insular carcinoid * 30 to 80 years * Carcinoid syndrome --> flushing, diarrhoea, abdo cramping, cardiac involvement * Elevated urinary 5-hydroxyindole acetic acid **Micro:** * Insular carcinoid resembles midgut carcinoid --> discrete groups of small uniform cells separated by fibrous stroma. * Nuclei with coarse chromatin * Rare mitoses * Associated with other teratomatous components **IHC:** * Chromogranin * Synaptophysin * NSE positive

Answer 18

**PLAP** * All **SALL4** * All **LIN28** * All **OCT3/4** * Dysgerminoma * Embyronal Carcinoma **SOX2** * Embryonal Carcinoma * Immature Teratoma **D2-40** * Dysgerminoma * Choriocarcinoma **CD30** * Embyronal Carcinoma **AFP** * Yolk Sac * Immature Teratoma **Glypican-3** * Yolk Sac * Immature Teratoma * Choriocarcinoma **B-hCG** * Choriocarcinoma

Ovary Flashcards

(42 cards)