Ovarian neoplasm
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This document provides an overview of ovarian neoplasms, discussing their classification, histopathology, immunohistochemistry, and other characteristics. The major groups include surface epithelial tumors, sex cord-stromal tumors, germ cell tumors, and metastatic tumors. Surface epithelial tumors include serous, mucinous, endometrioid, clear cell, seromucinous, and Brenner tumors. Sex cord-stromal tumors comprise granulosa cell tumor, thecoma, Sertoli-Leydig cell tumor, and steroid cell tumor. Germ cell tumors are dysgerminoma, yolk sac tumor, embryonal carcinoma, choriocarcinoma, teratoma. Risk factors, tumor markers, gross
Ovarian neoplasm
- 1. An Overview Of Ovarian Neoplasm Dr. Gaurav Kumar Dr. Sumaira Qayoom KING GEORGES MEDICAL UNIVERSITY
- 2. Classification of ovarian neoplasm • 4 major groups 1- Surface epithelial tumors 2- Sex cord - Stromal tumors 3- Germ cell tumors 4- Metastatic tumors
- 3. Surface epithelial tumors • Serous tumor • Mucinous tumor • Seromucinous tumor • Endometriod tumor • Clear cell tumor • Brenner tumor
- 4. Sex cord- stromal tumor • Granulosa cell tumor • Fibroma – Thecoma group tumor • Sertoli - Leydig cell tumor • Steroid cell tumor
- 5. Germ cell tumor • Dysgerminoma • Yolk sac tumor • Embryonal tumor • Choriocarcinoma • Teratoma
- 6. Risk factors • Patient characteristics • Increasing age • Family history of breast carcinoma • Genetic factors • BRCA 1/2 mutations • HNPCC syndrome • Environmental factors • Obesity • High fat diet
- 7. Contd.. • Reproductive factors • Nulliparity • Early menarche • Late menopause • Infertility • Polycystic ovarian syndrome • Endometriosis • OCPs • HRT
- 9. Gross based approach of ovarian mass Gross appearance Probable diagnosis Smooth walled cyst with serous/mucinous content Serous/ Mucinous cystadenoma Cyst with thick hemorrhagic content Endometriosis Cyst with hair, teeth with pultaceous material Teratoma Solid mass with surface nodularity carcinoma Solid, fibrous with mucinous cyst Fibroma/thecoma Bilateral solid multinodular ovaries Krukenberg tumor
- 10. Histomorphological approach • Where is the tumor arising? Central location -- think GCTs and SCST. Surface of ovary -- think surface epithelial tumor. If no surface is apparent... possibly obliterated by tumor. • Spindle cell morphology? Consider sex cord stromal tumors. • Nests of cells? Consider Brenner tumour. • Gland-like structures? Endometrioid carcinoma. Granulosa cell tumour.
- 11. Surface epithelial tumors • Classified into 6 types on the basis of cell types • Each types classified into 3 subtypes – benign borderline and malignant
- 12. • Benign tumors • Epithelium with benign nuclear features and differentiated cytoplasm, No stratification • No invasion Benign tumors adenofibromacystadenoma cystadenofibroma cystic Cystic + solid Atleast 25% solid solid
- 13. • Borderline tumors • Cytologic atypia • No invasion • Distinction between borderline and malignant tumor is the presence of invasion in the malignant
- 14. • Serous borderline tumor(SBOT) - Cystic serous tumor with >10 % BOT architecture • Serous cystadenoma with focal proliferation(atypia) - Cystic serous tumor with BOT fraction <10 % • Microinvasive SBOT- ≥ 1 invasive foci is ≤5mm foci in greatest dimension
- 15. Familial ovarian cancer syndrome Hereditary breast & ovarian cancer syndrome (HBOCS) • High grade serous carcinoma • BRCA 1/2 Hereditary nonpolyposis colorectal cancer syndrome (Lynch syndrome) • Clear cell carcinoma • Endometroid carcinoma
- 16. Serous tubular intraepithelial carcinoma Epithelial atypia in FT Germline mutation in BRCA1/2 No Germline mutation in BRCA1/2 Normal FT Detachment of FT epithelium & lodged on the surface
- 18. Serous tumors • Benign • Cystadenoma • Adenofibroma • Surface papilloma • Borderline • Serous BOT/ Atypical proliferating tumor • SBOT, micropapillary type/ serous low grade carcinoma • Malignant • Serous low grade carcinoma • Serous high grade carcinoma
- 22. Histological criteria for serous borderline tumor • Epithelial hyperplasia in the form of • Stratification • Tufting • Cribriform • Micropapillary arrangements • Atypia (mild to moderate) • Detached cell clusters • Minimal mitotic activity • Absence of destructive stromal invasion
- 23. • Divided into 2 types – Typical (90%) • Classic branching papillary architecture • Epithelial tufts overlying the papillae – Micropapillary (10%) • Diffuse proliferation of tumor cells in elongated thin micropapillae • Length 5 times the width • Arising directly from papillae
- 24. Malignant serous tumor • Nuclear atypia • Mitotic activity • Stratification • Glandular complexity • Papillary fronds • Stromal invasion
- 25. • Stromal invasion can be – Single cells or in compact nests – Micropapillae and complex papillary fronds – Inverted micropapillae – Cribriform – Glandular – Solid LOW GRADE vs HIGH GRADE • Mild to moderate nuclear atypia (<3 fold variation in size and shape) • Mitosis – <12 /10 HPF
- 27. Low grade serous carcinoma High grade serous carcinoma
- 28. HGSC with slit like spaces HGSC with gland formation Pattern in HGSC a. Papillary b. Micropapillary c. Slit like d. Glandular e. Microcystic f. Transitional
- 29. Mucinous tumors • Less common (20%) • Bilateral 10-20% • Predominantly benign and borderline • Viscous mucoid material • Epithelium- intestinal (goblet cells)
- 31. Mucinous cystadenoma Mucinous borderline tumor Mucinous carcinoma
- 32. IHC Serous tumor • CK7/20 (+/-) • WT1 + • P16 + • ER + • p53 + • PAX 8 + Mucinous tumor • CK7/20 (+/+ or -) • p16 (v) • ER (-/focal positive) • CEA+ • Endocrine cells: – Serotonin – ACTH – Gastrin – somatostatin
- 33. Seromucinous tumor • Previously considered as a variant of mucinous tumor • Also called endocervical type mucinous tumor • Serous part- papillary architecture • Mucinous part- tall non ciliated cells with basally located nuclei and abundant mucin • ARID1A mutation
- 34. Seromucinous borderline tumor With prominent edema in stroma Prominent intracellular mucin
- 35. Endometroid tumor • Benign • Endometriosis cyst • Endometroid cystadenoma • Endometroid cystadenofibroma • Borderline • Endometroid borderline tumor • Malignant • Endometroid carcinoma
- 36. • 10% • Grossly- cystic or solid • Hemorrhagic> serous/mucinous • Papillae- generally absent • Microscopically- similar to endometroid adenocarcinoma
- 37. Villoglandular pattern Villi and gland lined by endometroid epithelum
- 38. • Endometrial carcinoma resembling sex cord stromal tumor – small and tubular neoplastic glands – Old aged patients – Absence of endocrine manifestations – Foci of squamous metaplasia – Negativity for inhibin 50% of tumor – foci of squamous metaplasia
- 39. Clear cell tumor • <5% • Cells have clear cytoplasm, majority are malignant • a/w endometriosis & endometrial CA • Predominantly cystic with solid • Higher grade
- 40. High nuclear grade, hobnail pattern Nuclei protrude into lumina Clear Cytoplasm - Glycogen, mucin or fat PAS + diastase resistance hyaline globules
- 41. Oxyphilic cytoplasm Stromal hyalinization
- 42. Brenner tumor • Benign • Brenner tumor • Borderline • Borderline brenner tumor/ atypical proliferating brenner tumor • Malignant • Malignant brenner tumor
- 43. • Resembles transitional cell neoplasm of urinary tract • 1-2% • ~50 yrs • Sometimes sign of hyperestronism (postmemopausal bleeding or endometrial hyperplasia) • Strong association with mucinous tumor
- 45. Malignant brenner Borderline brenner
- 47. Malignant mixed mullerian tumor • Resembles grossly and microscopically resembles in every respect of its uterine counterpart • Homologous variety – nonspecific malignant stroma • Heterologous variety – malignant heterologous elements • Hyaline droplets containing alpha 1 Antitrypsin in cytoplasm of tumor cells • Also called carcinosarcoma
- 48. • Carcinomatous : – Serous – Endometroid – Squamous – Clear cell • Sarcomatous: – Chondrosarcoma – Osteosarcoma – Rhabdosarcoma
- 49. Germ cell tumor • Origin: germ cell • 15-20% • Children & young adult • Younger the patient, more likely the GCT is malignant
- 51. Parameters Dysgerminoma Yolk sac tumor Embryonal carcinoma choriocarcinoma Age Young, ~30 yrs Childern & young adult ~19 yrs Young , ~ 15 yrs Young to middle age Laterality Right, Bilateral 15% U/L U/L U/L Gross cut surface Solid & grey 15cm, smooth & glistening surface, partially cystic 17cm, smooth & glistening surface, partially cystic Tan, hemorrhagic with necrosis H/g & necrosis occasional predominant predominant predominant
- 52. Microscopy Dysgerminoma Yolk sac tumor Embryonal carcinoma choriocarcinoma arrangement Well defined nests, separated by fibrous strand Microcystic areas l/b cuboidal cells Solid sheets & nests of large primitive cells Admixture of cytotrophoblasts and syncytiotrophobl asts others • Prominent nucleoli • Clear cytoplasm • Infiltrated by T lymphocytes • Schiller duval bodies • PAS + hyaline globules Can be arranged in papillae, Syncytiotrophobl ast like cells scattered in b/g • Radiosensitiv e • a/w hypercalcemi a
- 53. Dysgerminoma
- 54. Yolk sac tumor
- 55. Embryonal carcinoma Papillary pattern, sheets and nests of large primitive cells
- 56. Choriocarcinoma
- 57. SALL-4+ OCT-4 + OCT 4 - CD30+ PLAP+ SOX-2+ PLAP+ CD117+ βHCG +/- Sox 2+AFP+ Glypican 3+ GATA-3+ Embryonal Carcinoma Dysgermin oma Immature teratoma Yolk sac tumor SALL-4 – βHCG GATA-3 Choriocarcino ma
- 58. Immature malignant teratoma • Malignant ovarian germinal tumor • Mixture of embryonal & adult tissue (3 germ layers) • Main component – neuroepithelial • Mesoderm also common
- 59. Grading • Grade I: Benign – rare foci of immature neuroepithelial tissue (<1LPF in any slide) • Grade II: Malignant – Occasional foci of immature neuroepithelial tissue with mitosis, (not exceeding 3 LPF in any slide) • Grade III: Malignant – Few / no mature tissue – Numerous neuroepithelial elements merging with stroma (4 or more LPF)
- 60. Mature cystic teratoma • 20% of all ovarian neoplasm • 88% unilateral • Multiple mature elements • Cystic: keratin, sebum, hairs • Fetiform teratoma: resembling human organ • Rokitansky’s protuberance: solid projection from inner cystic wall (covered with hair)
- 61. • Ectodermal derivatives: 100% • Mesodermal derivatives: 93% • Endodermal derivatives: 71% • May coexist with brenner tumor
- 62. Sex Cord stromal tumor Parameter s Adult GCT Juvenile GCT Thecoma Fibroma Sertoli- leydig cell tumor Steroid cell tumor Age Childbeari ng 1st 2 decade Menopaus al group After puberty Young Any age A/w hyperestre nism Isosexual precocity Estrogenic manifestati on Gorlin syndrome Meigs syndrome Androgen excess, reinke crystalloid Virlizing syndrome Gross Smooth lobulated, tan to yellow same Encapsulat ed, solid, YELLOW color Solid lobulated and white Solid - cystic Yellow IHC / Special stain Oil red O, FOXl2, inhibin vimentin Keratin, SOX 9, inhibin, calretinin, WT1 SF-1, Inhibin, calretinin FOXL2, ER,PR
- 63. Parameters Adult GCT Juvenile GCT Thecoma Fibroma Sertoli- leydig cell tumor Steroid cell tumor microscopy Grooving of nuclei No grooving, Large tumor cells, nuclear atypia Fascicles of spindle cells, centrally placed nuclei, pale pink cytoplasm Closely packed spindle stromal cells Large round cells, eosinophili c or vacuolated cytoplasm pattern Microfollicu lar, macrofolllic ular, solid Diffuse, macrofollic ular Storiform pattern Variant Cellular, Mitotically active WD - tubules, both sertoli and leydig cells MD- aggregates of sertoli cells + occ leydig cells PD- sarcomatoid Pure – no leydig cells Retiform- coexist with formation resembling rete of ovary or testis MEYER’S grading
- 64. Granulosa cell tumor Adult granulosa cell tumor Juvenile granulosa cell tumor
- 65. Thecoma fibroma
- 66. Sertoli-leydig cell tumor PD/ SarcomatoidWD
- 68. Primary and secondary ovarian tumors • 7% • 50% are bilateral • Predominantly from Gastrointestinal tract (stomach), colon, appendix, breast, uterus. • Krukenberg tumor- usually B/L Stomach (70%) gross: solid multiodular enlargement microscopic: signet ring cells
- 69. Primary ovarian mucinous tumor Mucinous tumors metastatic to ovary Usually large (>15cm) Often small (<10cm) U/L, multicystic with smooth capsule B/L, forming nodules with surface A borderline component is present Borderline component absent Growth is glandular and expansive Growth is infiltrative Dirty necrosis (colorectal metastasis) IHC Primary ovarian adenocarcinoma Metastatic colorectal carcinoma CK7 Diffuse + +/-, focal CK20 Usually negative (except in mucinous tumor) Diffuse + CDX2 variable Diffuse + Diffuse CK7 and focal CK20 – ovarian primary Focal CK7 and diffuse CK20 - colorectal primary
- 70. TNM staging • pT1- limited to ovaries (one or both) or F.T(s) pT1a: limited to one ovary (intact capsule) / FT pT1b: limited to both ovaries (intact capsule)/ FT pT1c: C1- surgical spill C2- capsule ruptured before surgery or tumor on surface of ovary/ FT C3- malignant cells in ascites/ peritoneal washing • pT2- involving one or both ovary/FT with pelvic extension pT2a: onto uterus/FT/Ovary pT2b: onto other pelvic structure • pT3: outside pelvic cavity pT3a: microscopic extrapelvic peritoneal mets pT3b: macroscopic peritoneal mets beyond pelvis (<2cm) pT3c: macroscopic peritoneal mets beyond pelvis (>2cm)
- 71. • Regional Lymph Nodes (pN) pN0: No regional lymph node metastasis pN0(i+): Isolated tumor cells in regional lymph node(s) no greater than 0.2 mm pN1: Positive retroperitoneal lymph nodes only (histologically confirmed) pN1a: Metastasis up to and including 10 mm in greatest dimension pN1b: Metastasis more than 10 mm in greatest dimension
- 73. References • Rosai and Ackerman’s Surgical Pathology , 11th Edition • WHO classification of tumors of Breast and Female Genital organ • Meinhold-Heerlein, I., Fotopoulou, C., Harter, P. et al. Arch Gynecol Obstet (2016) 293: 695. https://doi.org/10.1007/s00404-016-4035-8
- 74. Question 1 True about brenner tumor ? a) Contain squamous epithelium and adnexal structures. b) Contain fibrous tissue and transitional epithelium. c) May be associated with virilization d) Most often are bilateral
- 75. 2- 40-year-old nulliparous woman with no significant medical history presents with dyspnea and abdominal distention for 1 month. The patient has a right-sided hydrothorax, ascites, and a large ovarian mass. Surgery is performed to remove the ovarian mass, and the patient's ascites and pleural effusion resolve promptly. What is the most likely diagnosis? a)Metastatic colon cancer b)Metastatic lung cancer c)Metastatic ovarian cancer d)Meigs syndrome
- 76. Question 3 52-year-old patient undergoes a biopsy of the ovary, with the results shown in figure. Which of the following additional findings would you most expect to see in this patient?
- 77. a) Mature teratoma b) Increased AFP level c) Endometrial hyperplasia d) Vaginal atrophy
- 78. Question 4 Sections from a solid-cystic uniliateral ovarian tumor in a 30-year old female show a tumor composed of diffuse sheets of small cells with occasional nuclear grooving and scant cytoplasm. No Call-Exner bodies are seen. The ideal immunohistochemistry panel would include: a) Vimentin, inhibin, CD45 b) Desmin, S-100, SMA, cytokeratin c) Chromogranin, CD45, CD99 d) CD45, synaptophysin,
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