Distinction of Primary Ovarian MuciDistinction of Primary Ovarian Mucinous Tumors and Mucinous Tumors nous Tumors and Mucinous Tumors

Metastatic to the OvaryMetastatic to the OvaryA Practical Approach With Guidelines for Prediction of Primary Site for MetastaseA Practical Approach With Guidelines for Prediction of Primary Site for Metastase

s of Uncertain Origins of Uncertain Origin

Russell Vang, MD, and Brigitte M. Russell Vang, MD, and Brigitte M. Ronnett, MDRonnett, MDPathology Case Reviews Pathology Case Reviews • Volume 11, Number 1, January/Februa• Volume 11, Number 1, January/Februa

ry 2006ry 2006

CASE PRESENTATION

33y/o, female33y/o, femaleA right ovarian cyst A right ovarian cyst No history of cervical diseasesNo history of cervical diseaseslaparoscopic salpingo-oophorectomyspongy and papillary tissue measuring 1

2.5 cm in aggregate

FIGURE 1 FIGURE 1

FIGURE 1.FIGURE 1. variably sized cysts lined by stratified and tufted mucinous epithelium separated by ovarian stroma as well as areas having confluent glandular growth.

FIGURE 2.FIGURE 2. atypical, hyperchromatic nuclei with numerous mitotic figures and apoptotic bodies and intraglandular cribriform growthand intraglandular cribriform growth

→→Primary ovarian atypical proliferative (borderline) mucinous tumor with intraepithelial carcinoma.

P16:+, HPV 16: +Endocervical and endometrial curettage

s: dendocervical adenoCA→→→Metastatic endocervical adenocar

cinoma

GENERAL FEATURES OF METASTASES

INVOLVING THE OVARIES

8% of malignant ovarian neoplasms From nongynecologic sites are 11 times more

common ( esp. GI tract ) Characteristic gross features 1. Smaller size (often less than 10 cm)2. Bilateral involvement3. Nodular growth pattern4. Presence of tumor on the surface and/or in th

e superficial cortex of the ovary. 5. Solid and compress the surrounding ovarian

stroma.

Characteristic microscopic features 1. Infiltrative growth pattern with stromal

desmoplasia2. Nodular growth pattern with involvem

ent of the ovarian surface and superficial cortex

3. Hilar and lymphvascular space involvement.

PATHOLOGIC AND IMMUNOHISTOCHEMICAL FEATURES OF PRIMARY OVARIAN MUCINOUS TUMORS Atypical Proliferative (Borderline) Mucinous

Tumors of Gastrointestinal Type and Mucinous Carcinomas

Stage I unilateral 19 to 20 cm Internal surfaces are generally smooth Intraepithelium CK7:+, CK:20:variable, always negetive Dpc4:+, CEA:+, ER 、 PR 、 CA125 ： +/-

（（ GI typeGI type ）） Intraglandular epithelial proliferation but lacks glandular confluenIntraglandular epithelial proliferation but lacks glandular confluence or infiltrative growth (a). diffuse expression of CK7 (b) patchy expression of CK2ce or infiltrative growth (a). diffuse expression of CK7 (b) patchy expression of CK20 (c).0 (c).

(Gastrointestinal) type. glandular/cribriform growth pat(Gastrointestinal) type. glandular/cribriform growth pattern. tern.

Teratoma: Negative for CK7 (c) and diffusely positive for CK20 (d).Teratoma: Negative for CK7 (c) and diffusely positive for CK20 (d).

Colorectal Adenocarcinomas Unilateral***Unilateral*** 11 to 15 cm Cystic or solid. Hemorrhage and necrosis Endometrioid-like appearance Abundant extracellular mucin (colloid carcinom

a) or signet ring cell differentiation. “Garland pattern” of “dirty necrosis” CK7CK7 ：： -, CK20-, CK20 ：： +, Dpc4+, Dpc4 ：： ++ Rectum, right side, high grade: more CK7

Nodular growth pattern (a), glands infiltrating within a desmoplastic stroma (b), Nodular growth pattern (a), glands infiltrating within a desmoplastic stroma (b), or display a “garland pattern” with “dirty necrosis” (c). Other tumors simulaor display a “garland pattern” with “dirty necrosis” (c). Other tumors simulate primary ovarian mucinous tumors when they exhibit confluent glandular (d) te primary ovarian mucinous tumors when they exhibit confluent glandular (d) or villoglandular (e) growth patterns lacking infiltrative growth.or villoglandular (e) growth patterns lacking infiltrative growth.

CK7CK7 ：： -(f) -(f) CK20CK20 ：： + (g) + (g) Occasionally, a colOccasionally, a colorectal adenocarcinorectal adenocarcinoma can simulate a oma can simulate a primary ovarian mucprimary ovarian mucinous tumor (h) inous tumor (h) Patchy expression Patchy expression of CK7 (i) combined of CK7 (i) combined with diffuse expressiwith diffuse expression of CK20 (j) distingon of CK20 (j) distinguishes these colorectuishes these colorectal tumors from primal tumors from primary ovarian tumorsary ovarian tumors

PancreaticobiliaryAdenocarcinomas

BilateralBilateral7-13cm7-13cmMultiloculated mucinous cystic massesCompress surrounding ovarian stromaCK7 ： +, CK20 ： variableDpc4 lost: pancreas→50%, the others→3

4%CA125 ： +/-

Glands haphazardly infiltrating a desmoplastic stroma (a) and surface/superficial coGlands haphazardly infiltrating a desmoplastic stroma (a) and surface/superficial cortical involvement by a nodular plaque of carcinoma (b); however, some carcinomas rtical involvement by a nodular plaque of carcinoma (b); however, some carcinomas can grow in glandular (c) or villoglandular (d) patterns without stromal invasion, simcan grow in glandular (c) or villoglandular (d) patterns without stromal invasion, simulating an atypical proliferative (borderline) mucinous tumor of gastrointestinal typulating an atypical proliferative (borderline) mucinous tumor of gastrointestinal type.e.

Diffuse expression of CK7 (e) and focal/patchy expression of CK20 (f), similar to Diffuse expression of CK7 (e) and focal/patchy expression of CK20 (f), similar to primary ovarian mucinous tumors. Approximately half of tumors show loss of expprimary ovarian mucinous tumors. Approximately half of tumors show loss of expression of Dpc4 (g) [the background stroma serves as an internal positive control], ression of Dpc4 (g) [the background stroma serves as an internal positive control], which distinguishes them from primary ovarian mucinous tumors. which distinguishes them from primary ovarian mucinous tumors.

Gastric AdenocarcinomasBilateralSolidSignet ring cell carcinoma, typically with

in a hypercellular ovarian stroma (“Krukenberg tumor”).

CK7>CK20, alwaysDpc4:+

signet ring cells within a hyper-cellular ovarian stroma signet ring cells within a hyper-cellular ovarian stroma (a). Not infrequently, the ovarian stroma contains ill-de(a). Not infrequently, the ovarian stroma contains ill-defined nodular hypercellular areas containing numerous fined nodular hypercellular areas containing numerous signet ring cells juxtaposed with hypocellular edematosignet ring cells juxtaposed with hypocellular edematous regions (b). us regions (b).

Appendiceal Tumors (Secondary OvarianInvolvement by Low-Grade Adenomatous

Mucinous Neoplasms Associated WithPseudomyxoma Peritonei and Metastatic

Adenocarcinomas)BilateralRight sideSmall than 10cmAbundant dissecting extracellular mucin

(pseudomyxoma ovarii)Signet ring cells within a hypercellular st

roma (“Krukenberg tumor”)Adenocarcinoid type CK7 ： -, typically, CK20 ： +, Dpc4:+

intestinal-type glandular pattern (a), a goblet cell carcinoid/adenocarcinoid pattern (b), classic signet ring cell pattern (c).intestinal-type glandular pattern (a), a goblet cell carcinoid/adenocarcinoid pattern (b), classic signet ring cell pattern (c).

The tumor can simulate a primary ovarian mucinous tumor (a), but lack of expressThe tumor can simulate a primary ovarian mucinous tumor (a), but lack of expression of CK7 (b) combined with diffuse expression of CK20 (c) distinguishes these tumion of CK7 (b) combined with diffuse expression of CK20 (c) distinguishes these tumors from primary ovarian mucinous tumors. ors from primary ovarian mucinous tumors.

Endocervical Adenocarcinomas

Unilateralmean size of 13 cm‘’usual type”→ HPV-related, glands ex

hibiting endometrioid and/or mucinous differentiation

Minimal deviation adenocarcinoma (adenoma malignum) unrelated to HPV, very welldifferentiated mucinous glands

CK7:+,CK20:-, Dpc4:+, P16,HPV:+(usual type)

Confluent villoglandular patterns, simulating primary ovarian atypical prConfluent villoglandular patterns, simulating primary ovarian atypical proliferative mucinous tumors and well-differentiated carcinomas (a). The oliferative mucinous tumors and well-differentiated carcinomas (a). The HPV-related type of endocervical adenocarcinoma is typically composed HPV-related type of endocervical adenocarcinoma is typically composed of epithelium exhibiting a hybrid of endometrioid and mucinous differenof epithelium exhibiting a hybrid of endometrioid and mucinous differentiation, composed of pseudostratified columnar cells with hyperchromattiation, composed of pseudostratified columnar cells with hyperchromatic elongated nuclei, numerous mitotic figures in the luminal half of the cic elongated nuclei, numerous mitotic figures in the luminal half of the cell, and basal apoptotic bodies (arrows) (b). ell, and basal apoptotic bodies (arrows) (b).

Diffuse strong expression of p16 (both nuclear and cytoplasDiffuse strong expression of p16 (both nuclear and cytoplasmic) (c) is characteristic and is associated with the presence mic) (c) is characteristic and is associated with the presence of high-risk HPV DNA, which can be detected by in situ hybriof high-risk HPV DNA, which can be detected by in situ hybridization (d). dization (d).

GUIDELINES FOR DISTINGUISHING PRIMARY OVARIAN MUCINOUS TUMORS FROM

METASTATIC MUCINOUS TUMORS IN THE OVARY AND FOR PREDICTING PRIMARY SITE

FOR METASTATIC CARCINOMAS OF UNKNOWN ORIGIN

Intraoperative ConsultationWhether the patient has had any other d

ocumented tumorsExtraovarian disease, bilateral tumor, gr

oss or microscopic nodularity, garland pattern necrosis, or signet ring cells→gastrointestinal tract

Mucinous ascites (pseudomyxoma peritonei) →evaluate and remove the appendix.