1. RECENT WHO
CLASSIFICTION OF OVARIAN
NEOPLASMS
(IN DETAIL ABOUT SURFACE
EPITHELIAL TUMORS)
-BY DR. B. RAGHASUDHA
1ST PG
MENTOR : DR. DIVIJA ,M.D
DEPARTMENT OF PATHOLOGY ,
GOVERNEMT MEDICAL COLLEGE,
KADAPA.
6. • sex cord stromal tumors:
• Pure stromal tumors
• Fibroma, NOS
• Cellular fibroma
• Thecoma
• Luteinized thecoma associated
with sclerosing peritonitis
• Sclerosing stromal tumor
• Microcystic stromal tumor
• Signet ring stromal tumor
• Leydig cell tumor
• Steroid cell tumor, NOS
• Malignant steroid cell tumor
• Fibrosarcoma
• Pure sex cord tumors
• Adult granulosa cell tumor
• Juvenile granulosa cell
tumor
• Sertoli cell tumor, NOS
• Sex cord tumor with annular
tubules
• Mixed sex cord stromal
tumors
• Sertoli-Leydig cell tumor
• Well differentiated
• Moderately differentiated
• Poorly differentiated
• Retiform
• Sex cord stromal tumor, NOS
• Gynandroblastoma
7. • Germ cell tumors
• Teratoma, benign
• Immature teratoma, NOS
• Dysgerminoma
• Yolk sac tumor
• Embryonal carcinoma
• Choriocarcinoma, NOS
• Mixed germ cell tumor
• Monodermal teratomas and
somatic type tumors arising
from a dermoid cyst
• Struma ovarii, NOS
• Struma ovarii, malignant
• Strumal carcinoid
• Teratoma with malignant
transformation
• Cystic teratoma, NOS
• Germ cell sex cord stromal
tumors
• Gonadoblastoma
• Dissecting gonadoblastoma
• Undifferentiated gonadal tissue
• Mixed germ cell - sex cord
stromal tumor, unclassified
8. • Miscellaneous tumors
• Rete cystadenoma,
adenoma and
adenocarcinoma
• Wolffian tumor
• Solid pseudopapillary
tumor
• Small cell carcinoma of the
ovary, hypercalcemic type
• Wilms tumor
• Tumor-like lesions
• Follicle cyst
• Corpus luteum cyst
• Large solitary luteinized
follicle cyst
• Hyperreactio luteinalis
• Pregnancy luteoma
• Stromal hyperplasia and
hyperthecosis
• Fibromatosis and massive
edema
• Leydig cell hyperplasia
9. SEROUS TUMORS :
1.SEROUS CYSTADENOMA ,ADENOFIBROMA AND SURFACE PAPILLOMA:
• AGE - women of reproductive age
• SITE - Ovary, less commonly fallopian tube
• PATHOGENESIS: DNA – copy number changes – stromal and epithelial cells(rarely )
• CLINICAL FEATURES - Generally asymptomatic
One of the more common ovarian tumors to undergo torsion
• CA-125 levels – mildly elevated.
10. GROSS :
• CYSTADENOMA :3 - 10 cm (but can be up to 30 cm),
smooth glistening surface,Uni to multilocular cysts,
watery clear to pale yellow cyst fluid.
•CYSTADENOFIBROMA: cysts surrounded by
variable amount of solid area.
14. SEROUS BORDERLINE TUMOR :
• AGE : Median age - fifth decade.
• SITE : Ovary- bilateral (30%),fallopian tubes and peritoneal surfaces.
• PATHOGENESIS: progression from serous cystadenoma / cystadenofibroma
with BRAF / KRAS mutations → SBT → LGSC.
• CLINICAL FEATURES: asymptomatic / nonspecific pelvic or abdominal pain
/ compression effect on adjacent tissues (constipation, dysuria)
• CA-125 ,CEA,CA19-9- elevated.
15. SEROUS BORDERLINE TUMOR GROSS :
• >5cm , Intracystic –lined by excrescences, Exophytic – surface involvement
-papillary outgrowth resembling clusters of small berries
16. SEROUS BORDERLINE TUMOR MICROSCOPY :
Conventional SBT : hierarchically branching
papillae lined by heterogenous population
of cells, terminating in epithelial tufts.
Papillae arborizing into small papillae , lined
by pseudostratified ciliated columnar
epithelim.
19. LOW GRADE SEROUS CARCINOMA
• AGE : Median age - fifth to sixth decades.
• SITE : Ovary- bilateral.
• PATHOGENESIS: Precursor lesion is - borderline serous tumor.
• CLINICAL FEATURES: Abdominal pain / swelling/ incidental
finding/ most patients present with advanced stage disease
• CA-125 - elevated.
20. LGSC GROSS
• Often bilateral, fine papillary, nodular growth , little to no necrosis,
calcification in the ovary and extraovarian lesions can be extensive
21. LGSC MICROSCOPY
Uniform / homogeneous population of small cells with scant cytoplasm showing
glandular, micropapillary, cribriform pattern, low mitotic index: < 12 mitotic figures per 10
high power fields, Psammoma bodies are frequent
23. HIGH GRADE SEROUS CARCINOMA
• AGE :Mean age: 63 years.
• SITE : Tubo-ovarian, peritoneum
• PATHOGENESIS: Hereditary predisposition in 15 - 20% of cases
involving BRCA genes:
• BRCA1 and BRCA2 germline mutations.
• CLINICAL FEATURES: Abdominal distension / bloating / pain, nausea,
anorexia / early satiety, back pain, urinary incontinence, advanced disease
at presentation in ~80% of cases
• CA-125 - elevated.
24. HGSC GROSS
• Often bilateral, variable in size; often large, ~30% of cases with grossly normal
ovary or surface nodules < 1 cm, exophytic with solid or papillary growth, solid
areas tan to white with necrosis and hemorrhage, serous / bloody fluid filled cysts
• Fallopian tube can be grossly involved at fimbriated end
27. MUCINOUS TUMORS
1.MUCINOUS CYSTADENOMA AND ADENOFIBROMA:
• AGE : Median age 50 years (range 13 - 79)
• SITE : Ovary- unilateral, rarely retroperitoneal.
• PATHOGENESIS: May arise from mature teratoma (possible
germ cell origin) or Brenner tumor, KRAS mutation - 68%
• CLINICAL FEATURES: Abdominal distention with or without
palpable mass, abdominal or pelvic pain
• CA125 – rarely elevated.
28. GROSS :
• Cystadenoma: Uni or multilocular cyst with variably size, filled with
dense, viscous, sticky, gelatinous material, no solid areas or papillary
excrescences, mean size 10 cm, rarely > 30 cm
31. MUCINOUS BORDERLINE TUMOR:
• AGE : Mean age: 45 years
• SITE : Ovary- unilateral, rarely retroperitoneal.
• PATHOGENESIS: May arise from mucinous cystadenoma
• Also associated with Brenner tumor and mature cystic teratoma
• CLINICAL FEATURES: Symptoms related to pelvic mass
• CA125,CEA,CA19-9 – elevated.
32. MUCINOUS BORDERLINE TUMOR GROSS:
• Mean size-22 cm; some tumors can measure as large as 50 cm, cysts are
multiloculated with mucinous contents and smooth external surface, solid
areas and necrosis may be present.
33. MUCINOUS BORDERLINE TUMOR
MICROSCOPY
•Complex architecture with tufting &villous formation :Epithelium resembles low grade dysplasia of the intestine with
goblet cells, neuroendocrine cells and occasional Paneth cells, neoplastic cells have hyperchromasia, crowding,
stratification and mitotic activity,Glands with luminal mucin.
•INTESTINAL TYPE : Resembles high grade dysplasia of intestines, no stromal invasion
35. MUCINOUS CARCINOMA
• AGE : Mean age: 55 years
• SITE : Ovary- unilateral, rarely retroperitoneal.
• PATHOGENESIS: May arise from mucinous borderline tumor,
• Also associated with Brenner tumor and mature cystic teratoma
• CLINICAL FEATURES: Symptoms related to pelvic mass,
advanced stage disease is very rare.
• CA125,CEA,CA19-9 – elevated.
36. MUCINOUS CARCINOMA GROSS
• Tumors – typically large, unilateral, with solid and cystic areas with an
intact smooth outer surface and mucoid contents.
37. MUCINOUS CARCINOMA MICROSCOPY
• Stromal invasion; also more solid growth, atypia, stratification, papillae, loss of glandular architecture, greater
complexity of glands than borderline tumors
• Stromal invasion: infiltrative: with disorderly penetration of stroma by neoplastic glands, single cells or cell clusters,
may have desmoplastic response expansile :with complex arrangement of glands, cysts or papillae lined by malignant
epithelium with minimal or no intervening stroma with a broad, sharply defined border
38. •POSITIVE STAINS :
• CEA
• CK7
• CK20
• CA125 (weak)
•NEGATIVE STAINS :
WT1
ER
PR
39. ENDOMETRIOD TUMORS :
1.ENDOMETRIOD CYTSADENOMA AND ADENOFIBROMA:
• AGE :seen in postmenopausal women.
• SITE : Ovary.
• PATHOGENESIS: endometrioid cystadenomas may represent
endometriotic cysts without obvious endometrial type stroma.
• Adenofibroma associated with endometriosis.
• CLINICAL FEATURES: abnormal vaginal bleeding, abdominal
pain, incidental finding.
41. MICROSCOPY
• Cystadenoma:
• Variable dilated Cyst lined by benign endometrioid epithelium without endometrial stroma
• Adenofibroma:
• Widely spaced benign endometrioid glands associated with fibromatous stroma
42. ENDOMETRIOD BORDERLINE TUMOR
• AGE : mean age : 45-55yrs
• SITE : Ovary, unilateral.
• PATHOGENESIS: associated with endometriosis and
endometriod adenofibroma.
• CLINICAL FEATURES: symptoms related to a pelvic mass,
incidental finding.
44. ENDOMETRIOD BORDERLINE TUMOR
MICROSCOPY
• Adenofibromatous – glands are crowded ,vary in size, resembles atypical hyperplasia. Nuclei shows mild to
moderate cytological atypia with low mitotic activity .
• Intracystic – proliferation of endometriod glands with intracystic papillary growth embedded in a fibrous
stroma.
45. ENDOMETRIOD CARCINOMA :
• AGE : mean age : 55yrs
• SITE : Ovary, unilateral.
• PATHOGENESIS: associated with endometriosis.
• Most common molecular alterations: WNT / beta catenin
signaling pathway , PI3K pathway.
• CLINICAL FEATURES: symptoms are abdominal distention and
pain.
• CA 125 elevated.
46. ENDOMETRIOD CARCINOMA GROSS:
• Usually unilateral; only 5% bilateral, cystic with solid component and areas
of haemorrhage, with or without polypoid nodule in endometriotic cyst
• Mean tumor size: 11 cm (range: 3 - 22 cm)
47. ENDOMETRIOD CARCINOMA
MICROSCOPY
• Most common morphologic pattern is confluent (back to back) glands,stromal invasion is
usually by expansion; rarely, destructive stromal invasion can be observed
• Squamous metaplasia (morules or keratin pearls), cytoplasmic mucin, intracytoplasmic
vacuoles, oncocytic changes, clear cell changes and cilia and sex cord-like elements
(sertoliform) can be observed
49. CLEAR CELL TUMORS :
1.CLEAR CELL CYSTADENOMA AND ADENOFIBROMA:
• AGE : median age – sixth decade .
• SITE : Ovary, unilateral.
• PATHOGENESIS: associated with endometriosis.
• CLINICAL FEATURES: symptoms of pelvic mass, incidental
findings.
50. GROSS :
• Size- 3.5 to 26cm,Unilateral, solid fibromatous mass with small cystic
spaces , outer surface smooth , lobulated
51. MICROSCOPY :
• Small to medium sized widely spaced glands in a fibromatous stroma, cells – flat to low cuboidal
with clear or eosinophilic cytoplasm, nuclei are small without chromatin abnormality, mitotic
activity is absent.
52. CLEAR CELL BORDERLINE :
• AGE : postmenopausal women .
• SITE : Ovary, unilateral.
• PATHOGENESIS: associated with endometriosis.
• CLINICAL FEATURES: symptoms of pelvic mass, incidental
findings.
53. CLEAR CELL BORDERLINE GROSS :
• Predominantly solid, white-tan mass
• May have small or large cysts, imparting a honeycomb cut
surface
56. CLEAR CELL CARCINOMA :
• AGE : mean age – 56 yrs.
• SITE : Ovary, unilateral.
• PATHOGENESIS: associated with paraneoplastic –
hypercalcemia,venous thromboembolism, Endometriosis, lynch
syndrome.
• CLINICAL FEATURES: symptoms of pelvic mass, incidental
findings.
• CA125 elevated.
57. CLEAR CELL CARCINOMA GROSS :
• Usually unilateral, mean size 13 cm (range 0.8 - 35 cm),mainly
cystic, with fleshy nodules protruding into the cyst lumen, cyst may
contain chocolate brown fluid, solid areas also seen.
58. CLEAR CELL CARCINOMA MICROSCOPY
• Papillary: simple non branching papillae lined by cuboidal in single layer
• Tubulocystic: Variably sized tubules and cysts, with or without intraluminal dense
eosinophilic secretions and out pouchings, lined by a single layer of hobnail, cuboidal or
flattened cells
59. • Solid architecture :sheets or nested clusters of polyhedral cells
separated by delicate septa exhibiting clear to eosinophilic
cytoplasm, intracytoplasmic hyaline bodies .
61. SEROMUCINOUS TUMORS :
• SEROMUCINOUS CYSTADENOMA AND ADENOFIBROMA :
• AGE : mean age – 62yrs.
• SITE : Ovary, unilateral, bilateral-40%cases.
• PATHOGENESIS: unknown.
• CLINICAL FEATURES: symptoms of pelvic mass, incidental
finding.
62. GROSS AND MICROSCOPY :
• Adenofibroma: predominantly solid, dense fibrous cut surface.
• Prominent fibromatous hypocellular stroma with widely spaced glands lined by Cell types: mucinous (endocervical in appearance),
serous (ciliated), endometrioid (nonserous, nonciliated), hybrid morphology (serous and mucinous)
• Cystadenoma : unilocular, sometimes multilocular.
63. SEROMUCINOUS BORDERLINE TUMOR:
• AGE : 34-39yrs.
• SITE : Ovary, unilateral, bilateral -30%cases.
• PATHOGENESIS: loss of ARID1A expression.
• CLINICAL FEATURES: symptoms of pelvic mass, incidental
finding.
64. GROSS AND MICROSCOPY :
• Typically a cyst with smooth outer lining and internal papillary excrescences,Tumors range in size from 1.8 - 18 cm;
mean size is 9 cm
• SBT- hierarchical branching papillae, with variable edematous or fibrous stromal cores, few neutrophils are seen the
stroma.
66. BRENNER TUMORS
• AGE : 5th and 6th decades.
• SITE : Ovary.
• PATHOGENESIS: cell of origin -controversial.
• CLINICAL FEATURES:
• Benign Brenner tumors -usually asymptomatic
• Borderline and malignant Brenner tumors - usually present
with findings secondary to an adnexal mass.
67. BRENNER TUMORS GROSS
• Benign Brenner tumor: Small (usually < 2 cm), circumscribed, fibrous tumor with
a uniform cut surface, calcifications may be present
• Borderline and malignant Brenner tumor: Smooth surface, larger (usually > 10
cm) with fleshy, polypoid masses projecting into cystic cavity
68. BRENNER TUMOR MICROSCOPY
• BENIGN : nests of bland transitional epithelium within fibromatous stroma,transitional cells
have uniform oval nuclei and may have a longitudinal nuclear groove,there may be
mucinous epithelium at the center of the nests, with microcyst formation
69. • BORDERLINE:Papillary architecture with papillae covered by multilayered transitional epithelium, variable cytological
atypia; usually low grade.
• MALIGNANT: Stromal invasion by carcinoma with transitional cell features, with irregular nests of cells and single cells
in an infiltrative pattern
