Ovarian lesions

Ovarian lesions

1. OVARIAN LESIONS Presented by Dr. Varughese George Moderator : Dr. Uma Devi

2. NON-NEOPLASTIC OVARIAN LESIONS

3. Congenital Lesions and Ectopic Tissues Absent Ovary Lobulated , Accessory, and Supernumerary Ovary Adrenal Cortical Rests Uterus-Like Ovarian Mass Splenic–Gonadal Fusion Ectopic prostatic tissue

4. Adrenal cortical rest within mesovarium Splenic–gonadal fusion - A nodule of splenic tissue is contiguous with the surface of the ovary Supernumerary ovary in MRKH Syndrome Absent left ovary and distal portion of the left Fallopian tube

5. Infections Bacterial Pelvic inflammatory disease (PID) of bacterial origin accounts for most ovarian infections. Ovarian involvement by PID is almost always secondary to salpingitis and typically takes the form of a tuboovarian abscess. A mixed flora with a preponderance of anaerobic organisms is typically recovered from the contents of the abscess Tuboovarian abscess. Lining consists of inflammatory debris with subjacent granulation tissue

6. Infections Bacterial Xanthogranuloma of ovary . Inflammatory reaction consists predominantly of foamy histiocytes Ovarian xanthogranuloma , sectioned surface Rarely, a chronic ovarian abscess may result in a tumor-like mass , variably designated ovarian xanthogranuloma

7. Infections Bacterial Malacoplakia of ovary - Mixed inflammatory infiltrate with epithelioid histiocytes , some containing Michaelis–Guttman bodies. Associated with E coli and Enterococcus faecalis . Actinomycosis of ovary - A colony of actinomyces ( sulfur granule ) is surrounded by a purulent exudate .

8. Infections Bacterial Tuberculosis Tuberculous oophoritis is uncommon and usually secondary to tuberculous salpingitis . Leprosy rarely involves the female genital tract. the ovary is the most commonly involved gynecologic site. In chronic forms of leprous oophoritis , a chronic inflammatory cell infiltrate and fibrosis are seen, and bacilli usually are demonstrable. Syphilis Syphilitic involvement of the ovary is very rare. Luetic oophoritis has been described in congenital, secondary, and tertiary forms of the disease.

9. Infections Parasitic Ovarian involvement by Enterobius vermicularis . Microscopic diagnosis showed cystic lesions with a cellular membrane and the scolices in the daughter cyst  Macroscopic appearance of the resected hydatid cyst

10. Inflammation Granulomatous reaction on ovarian surface potentially mimicking a malignant tumor . Yellowish-brown granular deposits on ovarian surface, representing implants of keratin derived from an endometrial adenocarcinoma with squamous differentation Foreign body reaction to keratin implants on ovarian serosal surface. There was a coexistent endometrial adenocarcinoma with squamous differentiation , confined to the uterus

11. Inflammation Gallstone implanted on ovarian surface Postcautery carbon pigment granuloma in ovary. Note black carbon pigment. Palisading histiocytes are seen at the bottom and right.

12. Inflammation Isolated palisading granuloma of ovary Cortical granuloma . Circumscribed collection of lymphocytes, spindle cells, and an occasional multinucleated giant cell lie within the ovarian stroma

13. Non- neoplastic Lesions of the Follicular and Stromal Elements Lining consists of an inner layer of granulosa cells and an outer layer of theca interna cells( reticulin ). Follicular cyst Follicular cysts measure 2.5 to 10 cm in diameter and contain serosanguineous fluid.

14. Non- neoplastic Lesions of the Follicular and Stromal Elements A prominent inner layer of connective tissue is present . Corpus luteum cyst Corpus luteum cyst. Note the convoluted yellow lining

15. Non- neoplastic Lesions of the Follicular and Stromal Elements Higher-power view of lining cells showing marked nuclear hyperchromasia and atypicality . Luteinized cells with abundant eosinophilic to clear cytoplasm line a cyst (upper) and lie within its fibrous wall (lower). Note focal nuclear atypicality . Large solitary luteinized follicle cyst of pregnancy and puerperium

16. Polycystic ovary disease. Superficial cortical fibrosis and multiple cystic follicles are present Multiple cystic follicles lie beneath the superficially fibrotic cortex. A cystic follicle is lined by non-luteinized granulosa cells and an outer, thicker layer of luteinized theca interna cells Polycystic Ovary Syndrome

17. Stromal hyperplasia . (a) diffuse proliferation of ovarian stromal cells within the cortex& medulla is seen. (b)absence of follicular derivatives Stromal hyperthecosis . (a) A nest of luteinized stromal cells is present within the ovarian stroma . (b) Calretinin immunostain highlighting luteinized stromal cells

18. Massive Ovarian Edema The involved ovary in massive edema is enlarged, soft and fluctuant, ranging from 5.5 to 35 cm. The ovary has a shiny, white, smooth exterior as a result of a white and fibrotic superficial cortex and a sectioned surface that is edematous or gelatinous and exudes watery fluid The edematous ovarian stroma separates several corpora fibrosa Luteinized stromal cells are present

19. Ovarian Fibromatosis Bilateral ovarian fibromatosis . Convoluted external surface with patchy areas of white, fibrous tissue (right ovary) Fibrotic spindle cell proliferation invests follicular structures within the cortex Fibrotic ovarian stroma surrounds a preantral follicle Characterized by a fibromatoid proliferation of collagen-producing spindle cells that typically surrounds normal follicular structures and thickens the superficial cortex

20. Ovarian Endometriosis Multiple, hemorrhagic lesions involve the ovarian surface Microscopically, composed of endometrial glands, endometrial stroma , and fresh and old hemorrhagic foci with accumulation of hemosiderin -laden macrophages.

21. Autoimmune oophoritis Poorly understood disorder characterized microscopically by lymphocytic and plasma cell infiltration in relation to developing follicles but not primordial follicles. results in primary ovarian failure with either primary or secondary amenorrhea. Many of the reported cases have been associated with adrenal failure (Addison disease), hypothyroidism, or both conditions. Lymphoplasmacytic infiltrate of ovary in oophoritis .

22. NEOPLASTIC OVARIAN LESIONS

23. WHO Classification Surface Epithelial Ovarian Tumors Serous tumors Serous cystadenoma , adenofibroma Serous tumor of borderline malignancy (of LMP) Serous adenocarcinoma Mucinous tumors Mucinous cystadenoma Mucinous tumor of borderline malignancy (of LMP) Mucinous adenocarcinoma Endometrioid tumors Endometrioid cystadenoma , adenofibroma Endometrioid tumor of borderline malignancy (of LMP) Endometrioid adenocarcinoma Clear cell tumors Clear cell adenofibroma , cystadenoma Clear cell tumor of borderline malignancy (of LMP) Clear cell adenocarcinoma

24. WHO Classification Surface Epithelial Ovarian Tumors Transitional cell tumors Brenner tumor Brenner tumor of borderline malignancy (proliferating) Malignant Brenner tumor Transitional cell carcinoma (TCC) (non-Brenner type) Squamous cell tumors Mixed epithelial tumors (specify components) Benign Of borderline malignancy (of low malignant potential) Malignant Undifferentiated carcinoma

25. Serous tumors Most common subtype of surface epithelial tumors. Occur in women aged 30 to 40 years. Majority of serous tumors are benign(60%). 15% are borderline (also known as LMP or atypical proliferating) tumors. 25% are malignant. The neoplastic epithelium, particularly in benign & borderline tumors, resembles fallopian tube epithelium and contains ciliated and secretory cells. The cystic spaces contain serous or serosanguineous fluid.

26. Smooth outer and inner surfaces of the cystic formations Inner aspect of serous cystadenoma showing papillary structures protruding within Serous cystadenoma Single layer of bland-looking epithelial cells lining one of the cystic structures of a serous cystadenoma . Serous cystadenomas are the commonest benign ovarian neoplasms and are derived from surface epithelium. They are typically smaller than their mucinous counterparts, are bilateral in up to 30% of cases

27. Serous cystadenofibroma The tumor slightly lobulated and made up of cystic and solid structures. The tumor is firm and hard on cut section. It is yellowish gray. The cystic spaces show a smooth inner lining.  The stroma is composed of dense, fibrous tissue and dilated cyst-like glands lined with cuboidal epithelial cells.  solid neoplasms composed of tough, rubbery tissue with interspersed glandular spaces.

28. Serous tumor of borderline malignancy Inner aspect of an ovarian borderline serous neoplasm. Numerous papillary projections facing the lumen can be appreciated. Borderline or low malignant potential serous tumors are lined by a complex branching papillary epithelium, without stromal invasion . Tumors show some or all of the features associated with carcinoma but lack definite stromal invasion , i.e. irregular or destructive stromal infiltration by small glands or sheets of cells

29. Serous tumor of borderline malignancy Peritoneal implants associated with borderline tumors are classified as non-invasive or i nvasive Nests of neoplastic serous epithelium are surrounded by a markedly desmoplastic stroma ; however, the entire implant is well circumscribed without invasion of the surrounding adipose tissue. Nests of neoplastic serous epithelium irregularly infiltrate the muscularis propria of the bowel wall.

30. Serous tumor of borderline malignancy Two additional architectural patterns may be seen: micropapillary & cribriform Long, thin, papillae emanate directly from stromal cores giving a “medusa head” appearance. The tips of papillae fuse to form cribriform structures.

31. Serous tumor of borderline malignancy with microinvasion Borderline serous neoplasm with foci of microinvasion represented by clusters of cells with abundant eosinophilic cytoplasm. The center of the photo shows small nests and individual cells with abundant eosinophilic cytoplasm surrounded by a clefted space and desmoplastic stroma . This is accompanied in about half of the cases with lymphovascular invasion

32. Serous cystadenocarcinoma The tumor is predominantly solid, with multiple papillary excrescences, necrotic and hemorrhagic areas. Grossly, the tumors are large and friable with multiloculated cysts and polypoid growths.

33. Serous cystadenocarcinoma Low-grade serous carcinoma. Nests of serous carcinoma with minimal cytologic atypia and a low mitotic rate (< 12 mitoses/1 0 high power fields) High-grade serous carcinoma. The tumor forms papillary structures and slit-like spaces. There is marked cytologic atypia and abnormal mitotic figures. This tumor invades omental adipose tissue. ● Vimentin positive ● CA-125 positive ● > 60% of high-grade tumors and < 10% of low-grade tumors are positive for p53 ● WT-1 positive

34. Serous psammocarcinoma A rare form of serous adenocarcinoma Ovarian surface is bosselated with breach in capsule. Cut section shows solid with variegated areas and >50% of the tumor showing gritty yellowish areas of calcification Tumor showing destructive invasion of stroma no more than moderate cytologic atypia abundant psammoma bodies in at least 75% of the papillae no areas of solid growth > 15 cells.

35. Mucinous tumors 2 nd common subtype of surface epithelial tumors. Majority of mucinous tumors are benign(80%). 10% are borderline (also known as LMP or atypical proliferating) tumors. 10% are malignant. The neoplastic epithelium resembles intestinal (goblet cells with intracytoplasmic mucin ), gastric ( foveolar ), or endocervical (apical mucin with no cilia) epithelium. All mucinous neoplasms should be well sampled for its heterogeneity and focal malignant component.

36. Mucinous cystadenomas Tumors are usually unilateral, multiloculated , and large(up to 50 cm). They have a smooth external surface and are filled with thick viscous secretions. The cut surface reveals unilocular or multilocular mucin -filled cysts of varying size. Outer and inner aspect

37. Mucinous cystadenomas Cyst wall lined by a single layer of tall columnar cells with clear cytoplasm and bland basal nuclei, most often of intestinal type. In this instance, the lining of mucinous cystadenoma resembles endocervical epithelium.

38. Mucinous tumor of borderline malignancy Gross appearance of a mucinous ovarian neoplasm that had borderline features at the microscopic level. Grossly, these tumors have thick cyst walls sometimes with papillary excrescences. These tumors do not demonstrate destructive stromal invasion.

39. Mucinous tumor of borderline malignancy Borderline mucinous tumor, intestinal type. Mucinous epithelium lines complicated glands and papillae. Borderline mucinous tumor, endocervical type with detached buds of epithelium and hierarchical branching pattern. Usually associated with acute inflammatory infiltrate and frequently arises in the setting of endometriosis. Note the absence of stromal invasion.

40. Mucinous tumor of borderline malignancy with intraepithelial carcinoma with microinvasion The neoplastic cells have cytologic features of malignancy with marked cytologic atypia and large nucleoli. No stromal invasion is present. Mucinous borderline tumor is present on the right with small nests of more eosinophilic invasive tumor in a desmoplastic stroma toward the center. These foci should not exceed 3 mm in greatest linear extent or 10 mm² in area

41. Mucinous cystadenocarcinoma The tumor is predominantly solid, but some mucin -containing cystic spaces can still be appreciated. The ovary is replaced by a solid, haemorrhagic mass composed of multiple papillae and locules , containing viscid fluid.

42. Mucinous cystadenocarcinoma These large areas of crowded neoplastic mucinous glands shows an expansile pattern of mucinous adenocarcinoma Complex architecture and obvious nuclear atypia in mucinous cystadenocarcinoma . The expansile pattern shows crowded glands, little stroma , and, sometimes a cribriform architecture. The destructive pattern shows single glands or individual cells invading >3 mm in two linear dimensions or >10 10 mm² in area. ● Vimentin - negative ● CK7 and 20 - positive ● CEA: positive cytoplasmic staining

43. Approximately 5% of women with a mucinous ovarian tumor will present with pseudomyxoma peritonei Mucinous neoplasms often cause appendiceal distention (A) because of massive Accumulation of extracellular mucin within the lumen(B). The neoplasms may spread to the serosal surfaces of the viscera (C) or form gelatinous tumor deposits in the omentum (D).

44. Mucinous neoplasms typically display a circumferential growth pattern in the appendiceal mucosa with a variable papillary architecture (A). The tumor cells contain abundant cytoplasmic mucin and enlarged, hyperchromatic nuclei that are basally located, with minimal cytologic atypia (B). Peritoneal mucin deposits contain scant strips and clusters of mucin -containing epithelial cells (C) that are cytologically low grade, similar to the neoplastic cells present in the appendix (D)

45. Metastatic adenocarcinoma from the colorectum will show abundant luminal karyorrhectic debris (dirty necrosis), a garland pattern of glands lining cystic spaces, an abrupt transition between viable and necrotic epithelium Immunopositivity for CK20 and CEA Immunonegativity for CK7 and CA125 Metastatic adenocarcinoma

46. Endometrioid Tumors Majority of endometrioid tumors of the ovary are carcinomas. 10% to 20% are associated with endometriosis. 15% have a concomitant endometrioid tumor of the endometrium . Squamous differentiation may be seen in all types of endometrioid tumors.

47. Endometrioid (cyst) adenofibroma Solid fibrous tumors that average 8- 10 cm in diameter. The cut surfaces are tan or white and contain small cysts ranging from a few mm to several cms in diameter. Tubular or cystic glands lined by a single layer of benign endometrial-type cells surrounded and separated by dense fibrous stroma .

48. Endometrioid Carcinoma Only 10% to 20% are bilateral. Both tumors show a combination of solid and cystic appearances measuring 10-20cm. The solid areas can be firm or soft and are gray or tan. Areas of hemorrhage and necrosis are common.

49. Endometrioid Carcinoma Well-differentiated endometrioid carcinoma of ovary with focally villoglandular structures and tubular glands composed of a stratified layer of epithelial cells with smooth luminal borders. Well-differentiated endometrioid ovarian carcinoma with extensive squamous metaplasia Vimentin positive in malignant tumors

50. Borderline endometrioid tumor The glandular pattern is similar to that seen in complex hyperplasia of the endometrium . The tumor cell nuclei show only mild atypia . Note the immature squamous metaplasia in the center of the field.

51. Clear cell tumors Comprises of 5% of ovarian tumors. Age > 50 years Nulliparous women Associated with endometriosis of ovary Vast majority are frank adenocarcinomas . Benign and borderline tumors are rare.

52. Clear cell carcinoma The tumor is predominantly cystic, but it contains several mural nodules.

53. Clear cell carcinoma Tumor cells have abundant clear cytoplasm, significant nuclear atypia , and hyalinized stromal cores. The nuclei frequently jut into luminal spaces, a pattern referred to as “ hobnailing .” ● PAS highlights abundant glycogen in clear cells ● Mucin negative ● α-Fetoprotein (AFP) rarely stains positive ● Cytokeratin positive

54. Brenner tumor Constitute 1% and 2% of all ovarian tumors. Usually unilateral and incidental finding. About 5% are bilateral. Average age at presentation is approximately 50 years. Sometimes accompanied by signs of hyperestrinism  uterine bleeding from endometrial hyperplasia in postmenopausal women. Slow rate of growth. Ascites is rare.

55. Benign Brenner tumor Well circumscribed, firm, pale yellow or gray-white, solid fibrous tumors. Occasional Brenner tumors are partly cystic. Firm white to tan whorled cut surface, may show cystic spaces and calcification.

56. Benign Brenner tumor This benign tumor is composed of nests of cells of oval or polygonal epithelial cells resembling urothelial cells of the bladder with bland, longitudinally grooved nuclei in a fibromatous stroma . The epithelial nests may have central cystic spaces that may or may not be lined by mucinous epithelium.

57. Borderline Brenner tumor Usually unilateral. They are circumscribed white or tan tumors that are considerably larger than benign Brenner tumors with diameter ranges from 8-30 cm. Most are partially or largely cystic with polyps or friable papillae projecting into the lumens of cysts or in some cases growing as nests of cells in a fibromatous background.

58. Borderline Brenner tumor The tumor is composed of papillary structures lined by stratified urothelial epithelium resembling low-grade urothelial carcinoma

59. Malignant Brenner tumor Large, partly cystic tumors with an average diameter of 15 cm. Cut sections show small cysts as well as are gray, white yellow, or tan solid regions which frequently contain calcifications.

60. Malignant Brenner tumor The tumor is composed of nests of epithelial cells resembling high-grade urothelial carcinoma invading the stroma .

61. Transitional Cell Carcinoma Solid and cystic mass that averages 10 cm in diameter with irregular nodular surface. Cut section shows grayish white solid areas with areas of haemorrhage , necrosis & few cystic spaces. Tumor might extends beyond the capsule.

62. Transitional Cell Carcinoma Nests and islands of malignant transitional cells infiltrate a desmoplastic stroma . ● Cytokeratin 8/18 positive ● Cytokeratin 20 negative

63. Malignant mixed müllerian tumor Resembles grossly and microscopically in every respect its more common uterine counterpart The tumors are large, variegated, solid and cystic, with hemorrhagic and necrotic areas.

64. Malignant mixed müllerian tumor The mesenchymal component may be A. homologous to the female genital tract ( e.g.,smooth muscle, endometrial stroma ) Or B,C. heterologous elements not normally found in the female genital tract {e.g., in the form of bone and cartilage ( B) or skeletal muscle (C) , fat} A B C Reticulin , CK, EMA and Vimentin + ve

65. Squamous Cell Carcinoma Invasive squamous cell carcinoma in the ovary is most commonly due to malignant transformation of a mature cystic teratoma Microphotograph of right ovary showing malignant squamous cells with Keratin Pearls and areas of necrosis. 

66. Undifferentiated Carcinomas Grossly, a large, predominantly solid tumor with foci of hemorrhage and necrosis. Most are bilateral. Solid sheet of anaplastic malignant cells with large nuclei, prominent nucleoli, and numerous mitotic figures. Frequently show positive staining for p16, WT-1 and frequently for p53

67. WHO Classification Germ Cell Ovarian Tumors Primitive germ cell tumors Dysgerminoma Yolk sac tumor Embryonal Carcinoma Polyembryoma Non-gestational choriocarcinoma Mixed germ cell tumor Biphasic/ triphasic teratoma Mature teratoma Solid Cystic Fetiform teratoma (homunculus) Monodermal teratoma and somatic -type tumors associated with dermoid cysts. Thyroid tumor group Struma ovarii Benign Malignant.

68. Dysgerminoma Large and solid tumors with a smooth external surface and a lobulated gray-tan cut surface. Special attention should be directed to hemorrhagic and cystic areas. Dysgerminoma constitutes < 1% of all ovarian tumors & approximately 5% of malignant ones Most patients are young, aged 20-30 years.

69. Dysgerminoma Large and solid tumors with a smooth external surface and a lobulated gray-tan cut surface. Special attention should be directed to hemorrhagic and cystic areas. Dysgerminoma constitutes < 1% of all ovarian tumors & approximately 5% of malignant ones Most patients are young, aged 20-30 years.

70. Tumor is composed of nests of large, round tumor cells with abundant clear cytoplasm, separated by a lymphohistocytic stroma . Dysgerminoma with a large syncytiotrophoblastic giant cell Dysgerminoma ● Placental alkaline phosphatase (PLAP) and vimentin positive ● Cytokeratin is usually negative and EMA is negative ● PAS highlights glycogen-rich cytoplasm of tumor cells

71. Yolk Sac Tumor Grossly, tumors are unilateral and large, with a smooth external surface. Cut surface shows yellow to tan solid and cystic areas with areas of hemorrhage necrosis and cystic degeneration. Also known as endodermal sinus tumors, occur in young women, usually with an associated elevated serum alpha fetoprotein (AFP) level. Yolk sac tumors grow rapidly and have often spread outside the ovary at the time of diagnosis.

72. Yolk Sac Tumor Microcystic pattern Tumor composed of small cystic spaces lined by cuboidal to columnar cells with clear cytoplasm and large hyperchromatic nuclei Endodermal sinus pattern This pattern features characteristic Schiller-Duvall bodies (rounded fibrovascular papillae containing a single central vessel and lined by columnar tumor cells) usually immunopositive for expression of keratins, alpha-1-antitrypsin, glypican 3, AFP, CK, PAS

73. Embryonal carcinoma Grossly, these tumors are large (approx.17cm) Their external surface is smooth and glistening. Cut surface is predominantly solid and variegated, with extensive areas of necrosis and hemorrhage. Rare neoplasm in the ovary & is often a component of mixed germ cell tumors. Half of cases occur in prepubertal girls, and half have elevated beta-HCG levels. Tumor is composed of sheets of large anaplastic cells with pale cytoplasm. Immunopositive for CD30, cytokeratin , PLAP, SALL4, and OCT 3/4.

74. Polyembryoma Bulky, unilateral solid mass with areas of hemorrhage and necrosis. The tumor is composed of embryoid bodies showing amniotic cavity(right), embryonic disk (center), and atypical yolk sac (left) A very rare, highly malignant tumor. Usually a component of a mixed germ cell tumor. ● AFP highlights yolk sac component and hepatic elements ● α1-Antitrypsin may highlight yolk sac component of embryoid bodies and hepatic elements ● HCG highlight syncytiotrophoblastic elements

75. Non-gestational Choriocarcinoma A large unilateral solid purple-red tumor with a friable, hemorrhagic and necrotic cut surface.

76. Non-gestational Choriocarcinoma composed of two cell populations : Cytotrophoblast – Mononucleated , large, rounded cells with pale cytoplasm present centrally in tumor mass – Positive for hCG • Syncytiotrophoblast – Large basophilic, multinucleated , vacuolated cells with irregular outlines, varying shape. – Nuclei are hyperchromatic , pleomorphic Dilated vascular sinusoids, which are the source of the massive hemorrhage are also present. • Vascular invasion is prominent in some cases Cytotrophoblast composed of medium-sized cells are situated centrally Syncytiotrophoblast composed of very large multinucleated cells are situated peripherally

77. Mixed germ cell tumors 10% of germ cell tumors. Most common combination is dysgerminoma and yolk sac tumor

78. Mature Teratoma Most common ovarian germ cell tumor. Occur more often in adult women of reproductive age. Grossly, they are usually cystic with a single solid nodule that may contain fat, teeth, bone, and many other tissue types. Cyst usually contain hair, soft yellow sebaceous debris. Microscopically, mature tissue from all three germ layers Ectoderm - skin or central nervous system elements Mesoderm - smooth muscle, teeth, bone Endoderm - respiratory epithelium, GI epithelium, thyroid Dermoid cyst refer to mature cystic teratomas lined by squamous epithelium that containing skin appendages may be present

79. Mature Teratomas Mature solid teratoma has a predominantly solid gross appearance, but multiple small cystic areas also are present Well-developed teeth in ovarian mature cystic teratoma . Admixture of sebum and hair within the cavity of an ovarian mature cystic teratoma .

80. Mature Teratomas This mature teratoma , or dermoid cyst, has an epithelial lining with adjacent skin appendages. This mature teratoma contains central nervous system tissue (right), salivary gland tissue (center), and cartilage (left).

81. Fetiform teratoma (homunculus) Extremely rare teratomas in which an ovarian cyst contains a structure resembling a malformed human fetus (homunculus). Most occur in the 3 rd or 4 th decade. Absence of umbilical cord & normal extremities.

82. Immature Teratomas rapidly growing unilateral malignant tumors that occur in children and young adults. Typically have solid and cystic components. Solid areas are generally more extensive than in a mature teratoma . Microscopically, they contain immature or primitive tissue (derived from any or all three germ cell layers) usually mixed with areas of mature tissue. The most common immature element is neuroectodermal and consists of rosettes, masses, or tubules of primitive neural cells

83. Immature Teratomas Round, oval, or lobulated , soft or firm solid mass, which frequently contains cystic structures with solid areas present in the cyst wall covered by an ill defined capsule. • The cut surface is usually variegated, trabeculated , and lobulated , varying in color from gray to dark brown. The most common immature element in immature teratoma is neuroepithelium which typically forms rosettes as shown in the figure or tubules, and less commonly sheets of primitive neuroepithelium . Neural markers, including chromogranin and synaptophysin ; GAFP and S-100 protein highlight neuroectodermal tissue

84. Monodermal teratomas Teratomas in which all the tissue is derived from one germ cell layer. Struma ovarii is the most common monodermal teratoma and consists of mature thyroid tissue, including follicles and colloid Secondary changes such as hyperplasia, adenoma, and even carcinoma may be seen.

85. Struma ovarii Varies in size (< 10 cm) The external surface is usually smooth. Cut surface may be composed entirely of light tan, glistening thyroid tissue. Hemorrhage, necrosis, and foci of fibrosis may be present. Solid tumors with small amounts of colloid appear less glistening and more fleshy. Some tumors may be cystic The thyroid tissue is represented by the solid areas.

86. Struma ovarii The tumor is composed of mature thyroid tissue consisting of acini of various sizes, lined by a single layer of columnar or flattened epithelium. The acini contain eosinophilic , PAS-positive colloid . Thyroglobulin and TTF-1 can be identified in the epithelial cells by immunohistochemistry The thyroid tissue, which has a microscopically unremarkable appearance, is sharply delimited from the ovarian stroma .

87. Carcinoid tumor of the ovary Mean diameter of 10 cm. The external surface is smooth or bosselated . The cut surface is predominantly solid, firm, tan to yellow, and homogeneous. Primary ovarian carcinoid tumor with a trabecular pattern of growth. There is a great resemblance to carcinoid tumors of lung and rectum.

88. Strumal carcinoid Gross appearance of strumal carcinoid showing a variegated appearance resulting from the admixture of carcinoid tumor and struma ovarii . Microscopical sections showing intimate admixture of thyroid follicles and carcinoid trabecula .

89. WHO Classification Sex cord- stromal Tumors Granulosa-stromal cell tumors Granulosa cell tumor group Adult granulosa cell tumor Juvenile granulosa cell tumor Thecoma-fibroma group Thecoma , not otherwise specified Typical Luteinized Fibroma Cellular fibroma Fibrosarcoma Stromal tumor with minor sex cord elements Sclerosing stromal tumor Signet-ring stromal tumor Unclassified ( fibrothecoma ) Sertoli-stromal cell tumors Sertoli-Leydig cell tumor group Well differentiated Of intermediate differentiation Variant with heterologous elements (specify type) Poorly differentiated ( sarcomatoid ) Variant with heterologous elements (specify type) Retriform Variant with heterologous elements (specify type) Sertoli cell tumor Stromal-Leydig cell tumor

90. WHO Classification Sex cord- stromal Tumors Sex cord- stromal tumors of mixed or unclassified cell types Sex cord tumor with annular tubules Gynandroblastoma (specify components) Sex cord- stromal tumor, unclassified Steroid cell tumors Stromal luteoma Leydig cell tumor group Hilus cell tumor Leydig cell tumor, non- hilar type Leydig cell tumors, not otherwise specified Steroid cell tumor, not otherwise specified Well differentiated Malignant Germ cell tumors

91. Granulosa cell tumors Adult granulosa cell tumors Grossly the tumor has cystic and solid components. Tumors have a smooth, lobulated outline and a predominantly solid cut surface. The color is usually gray, but it may be yellow in areas of luteinization Cysts filled with straw-colored/ mucoid /bloody fluid may be present admixture of solid and cystic areas. solid cut surface. Predominantly cystic

92. Granulosa cell tumors Adult granulosa cell tumors Diffuse pattern The tumor is composed of diffuse sheets of neoplastic granulosa cells. Trabecular pattern Cords of granulosa cells course through the stroma .

93. Granulosa cell tumors Adult granulosa cell tumors Macrofollicular pattern Granulosa cells line large cystic spaces. Microfollicular pattern Granulosa cells lining small cystic spaces.

94. Granulosa cell tumors Adult granulosa cell tumors Gyriform pattern Granulosa cells form undulating, single-file cords. Grooved nuclei Granulosa cells with little cytoplasm and round or angulated nuclei with longitudinal nuclear grooves.

95. Granulosa cell tumors Adult granulosa cell tumors Call- Exner bodies Granulosa cells palisade around eosinophilic hyaline material. These structures are also seen in normal developing follicles. Bizarre nuclei Occasional tumors exhibit marked cytologic atypia but no associated mitotic activity. This is thought to represent a degenerative phenomenon.

96. Granulosa cell tumors Juvenile granulosa cell tumor Solid and cystic tumor in which the cysts may contain hemorrhagic fluid. The solid component typically is yellow-tan or gray, and occasionally exhibits extensive necrosis, hemorrhage, or both. Multiloculated cysts in cystic tumors

97. Granulosa cell tumors Juvenile granulosa cell tumor The tumor is composed of solid sheets of cells with abundant eosinophilic cytoplasm which form occasional follicle-like spaces. The nuclei are larger and more pleomorphic than those of adult granulosa cell tumor. The nuclei of juvenile granulosa cell tumors do not show grooves.

98. Granulosa cell tumors Adult v/s juveline granulosa cell tumors

99. Fibroma Most common of the sex cord- stromal tumors. Occurs in perimenopausal women and are not hormonally active. Usually unilateral, which occur almost invariably after puberty. Assoicated with Meig’s Syndrome and Gorlin’s syndrome. Tumors are solid, and lobulated with a firm, white-gray cut surface. Cystic degeneration sometimes occurs.

100. Fibroma Tumor composed of interlacing bundles of spindled cells without atypia or mitotic activity. It commonly exhibits bundles of collagen. Tumor cells stain diffusely positive for vimentin and are usually negative for inhibin .

101. Thecoma Unilateral solid tumors found most often in postmenopausal women > 65 years. Hyperestrogenic symptoms are present in 50% to 80% of cases. range in size from small, impalpable tumors to large, solid masses from 5–10 cm. Cut section shows a lobulated solid yellow/white mass with occasional cystic change and foci of hemorrhage and necrosis.

102. Nests or fascicles of lipid-laden cells with cleared cytoplasm and collagen bundles. Oil Red 0 fat stains highlights the intracellular lipid. Thecoma Luteinized thecoma This tumor is composed of luteinized cells with abundant eosinophilic cytoplasm. Tumor is positive for inhibin .

103. Sertoli cell tumors Rare, low-grade, nonfunctioning tumors that occur in women of child-bearing age. Accounts for approximately 4% of Sertoli-stromal cell tumors Associated with Peutz-Jeghers syndrome Tumor composed of closely packed tubules separated by fibrous stroma . The tubules are lined by cuboidal to columnar cells with abundant pale eosinophilic cytoplasm with little atypia or mitotic activity. Yellow-tan, solid, lobulated tumors. ● Cytokeratin and inhibin positive ● EMA negative

104. Sertoli-Leydig cell tumors Sertoli–Leydig cell tumor The tumor (left) is soft and ‘spongy’. Edematous polypoid structures project into the lumen of another neoplasm that was more cystic (right) Sertoli–Leydig cell tumor with retiform pattern The sectioned surface of the neoplasm is solid yellow and lobulated . Sertoli–Leydig cell tumor with mucinous heterologous Elements The sectioned surface of the tumor is mostly mucoid with a minor solid yellow component

105. Sertoli-Leydig cell tumors Well-differentiated tumors are composed of closely packed hollow tubules of cuboidal Sertoli cells. Leydig cells with abundant eosinophilic cytoplasm and small round nuclei are present between the tubules at the bottom. Intermediate differentiation Cords of small tubules of Sertoli cells are interspersed with Leydig cells. Poorly differentiated tumors are composed of sheets of poorly differentiated cells resembling sarcoma. Leydig cells are present but often difficult to find.

106. Sertoli-Leydig cell tumors Sertoli-Leydig cell tumor, lipidized Leydig cells. The Leydig cells have cleared cytoplasm. Sertoli-Leydig cell tumor with heterologous elements. Cords of Sertoli cells are seen on the (right). Heterologous elements in the form of glandular structures lined by mucinous epithelium are seen on the (left). Sertoli-Leydig cell tumor with retiform areas. The tumor forms papillary structures with dense fibrovascular cores.

107. Stromal luteomas Always <3 cm in diameter and are unilateral. Tumor is well circumscribed, solid, and usually gray-white or yellow. One third of them have red or brown areas or are uniformly so Stromal luteoma Sheets of polygonal cells with eosinophilic cytoplasm are surrounded by normal ovarian stroma .

108. Leydig cell tumors Large cells with abundant, eosinophilic cytoplasm are arranged with “nucleus-free” areas. Note the Reinke's crystal . A light brown colored tumor mass with The cut surface showing yellow-brownish areas with areas of hemorrhage. ● Inhibin positive

109. Hilus cell tumor A sharply circumscribed brown-black nodule is present in the ovarian hilus Clusters of tumor cells with abundant eosinophilic cytoplasm and little intracellular lipid; cytoplasmic lipochrome pigment may be abundant. The cells usually are distributed diffusely,separated by nucleus-free eosinophilic zones. Fibrinoid necrosis of vessel walls, and focal bizarre nuclei seen.

110. Steroid cell tumor, not otherwise specified Tumors are solid, well circumscribed, and lobulated . The cut surfaces typically are yellow or orange if large amounts of intracytoplasmic lipid are present. Necrosis, hemorrhage, and cystic degeneration are observed. Tumor composed of large cells with abundant granular cytoplasm separated by a vascular stroma . Reinke's crystals are absent

111. Sclerosing stromal tumor Tumor is firm to rubbery and white with areas of cystic degeneration. Cellular areas consisting of spindle cells (lower left) and round cells with vacuolated cytoplasm alternate with edematous areas (upper left) and collagenous areas (right) to give a pseudolobular appearance.

112. Sex cord tumors with annular tubules Large, yellow-orange, unilateral, predominantly solid tumor Ring-shaped tubules with a double layer of nuclei surround eosinophilic , acellular material.

113. Gynandroblastoma Gynandroblastoma showing granulosa cell, sertoli cell, stromal cell components Tumor composed mainly of a uniloculated cyst with a yellowish solid portion (arrow). The cystic contents are composed of a yellowish-brown serous fluid An extremely rare ovarian sex cord tumor that has an unusual histological morphology composed of solid small uniform cells that resemble granulosa cells of the ovary, and cordlike and tubular formations that resemble the sex cords of a testis.

114. Gonadoblastoma Tumor is usually small with a yellow to gray cut surface and areas of calcification. Tumor consists of admixed primitive germ cells and sex cord- stromal derivatives (which resemble immature granulosa Cells and sertoli cells) surrounded by abundant basement membrane-like material, often with calcification. A complex neoplasm composed of a mixture of  gonadal elements  such as large primordial germ cells, immature  Sertoli cells or  granulosa cells of the sex cord, and gonadal   stromal cells. 

115. Small cell carcinoma of ovary, hypercalcemic type Diffuse sheets of small, closely packed round cells with scant cytoplasm, small hyperchromatic nuclei with irregular chromatin clumps, small but identifiable nucleoli The cut section shows fleshy cream-colored tissue with focal hemmorhage and necrosis

116. Primary hematopoietic malignancies Extremely rare Secondary ovarian involvement may be seen in up to one-half of all lymphomas. Tumors are generally bilateral with a fleshy cut surface. Microscopically, they resemble their nodal or marrow counterparts. The most common lymphoma with secondary involvement of the ovary is diffuse large B-cell lymphoma containing sheets of large noncohesive cells that have irregular nuclear contours and increased mitotic activity. Malignant lymphoma of Burkitt type with massive ovarian involvement .

117. Primary ovarian tumors of mesenchymal origin. Vascular tumors Hemangioma Lymphangioma low-grade angiosarcoma Tumors of striated muscle origin Rhabdomyoma rhabdomyosarcoma Neural tumors Neurofibromas Schwannomas Ganglioneuromas Primary ovarian myxomas

118. Krukenberg tumors of ovary Typical gross appearance of Krukenberg tumors of ovary. The involvement is bilateral and the tumors are characterized by a multinodular outer appearance. Numerous signet ring cells are present in a highly fibrous stroma , either individually or in small nests. Presence of intracellular mucin evidenced by Meyer mucicarmine stain

119. References Kumar V, Abbas AK, Aster JC. Robbins basic pathology e-book. Elsevier Health Sciences; 2017. Myers JL. Rosai and Ackermans Surgical Pathology-2 Volume Set. Elsevier-Health Sciences Division; 2017. Hull ME, Hunphrey PA, Pfeifer JD. Washington manual of surgical pathology. Young RH, Scully RE, Kurman RJ. Blaustein's pathology of the female genital tract. RJ Kurman , L. Hedrick Ellenson , and BM Ronnett , Eds. 2011:786. Fletcher CD. Diagnostic Histopathology of Tumors: 2-Volume Set with CD-ROMs. Elsevier Health Sciences; 2007 Mar 29.