1. Distinction of Primary Ovarian Mucinous Tumors and Mucinous Tumors Metastatic to the Ovary A Practical Approach With Guidelines for Prediction of Primary Site for Metastases of Uncertain Origin
Russell Vang, MD, and Brigitte M. Ronnett, MD
Pathology Case Reviews • Volume 11, Number 1, January/February 2006

2. CASE PRESENTATION 33y/o, female A right ovarian cyst
No history of cervical diseases
laparoscopic salpingo-oophorectomy
spongy and papillary tissue measuring 12.5 cm in aggregate

3. 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.

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

5. →→Primary ovarian atypical proliferative (borderline) mucinous tumor with intraepithelial carcinoma.
P16:+, HPV 16: +
Endocervical and endometrial curettages: dendocervical adenoCA
→→→Metastatic endocervical adenocarcinoma

6. 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
Smaller size (often less than 10 cm)
Bilateral involvement
Nodular growth pattern
Presence of tumor on the surface and/or in the superficial cortex of the ovary.
Solid and compress the surrounding ovarian stroma.

7. Characteristic microscopic features
Infiltrative growth pattern with stromal desmoplasia
Nodular growth pattern with involvement of the ovarian surface and superficial cortex
Hilar and lymphvascular space involvement.

8. 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：+/-

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

10. (Gastrointestinal) type. glandular/cribriform growth pattern.

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

12. Colorectal Adenocarcinomas
Unilateral***
11 to 15 cm
Cystic or solid. Hemorrhage and necrosis
Endometrioid-like appearance
Abundant extracellular mucin (colloid carcinoma) or signet ring cell differentiation.
“Garland pattern” of “dirty necrosis”
CK7：-, CK20：+, Dpc4：+
Rectum, right side, high grade: more CK7

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

14. CK7：-(f)
CK20：+ (g)
Occasionally, a colorectal adenocarcinoma can simulate a primary ovarian mucinous tumor (h)
Patchy expression of CK7 (i) combined with diffuse expression of CK20 (j) distinguishes these colorectal tumors from primary ovarian tumors

15. Pancreaticobiliary Adenocarcinomas
Bilateral
7-13cm
Multiloculated mucinous cystic masses
Compress surrounding ovarian stroma
CK7：+, CK20：variable
Dpc4 lost: pancreas→50%, the others→34%
CA125：+/-

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

17. 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 expression of Dpc4 (g) [the background stroma serves as an internal positive control], which distinguishes them from primary ovarian mucinous tumors.

18. Gastric Adenocarcinomas
Bilateral
Solid
Signet ring cell carcinoma, typically within a hypercellular ovarian stroma (“Krukenberg tumor”).
CK7>CK20, always
Dpc4:+

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

20. Abundant dissecting extracellular mucin (pseudomyxoma ovarii)
Appendiceal Tumors (Secondary Ovarian Involvement by Low-Grade Adenomatous Mucinous Neoplasms Associated With Pseudomyxoma Peritonei and Metastatic Adenocarcinomas)
Bilateral
Right side
Small than 10cm
Abundant dissecting extracellular mucin (pseudomyxoma ovarii)
Signet ring cells within a hypercellular stroma (“Krukenberg tumor”)
Adenocarcinoid type
CK7：-, typically, CK20：+, Dpc4:+

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

22. The 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 tumors from primary ovarian mucinous tumors.

23. Endocervical Adenocarcinomas
Unilateral
mean size of 13 cm
‘’usual type”→ HPV-related, glands exhibiting endometrioid and/or mucinous differentiation
Minimal deviation adenocarcinoma (adenoma malignum) unrelated to HPV, very welldifferentiated mucinous glands
CK7:+,CK20:-, Dpc4:+, P16,HPV:+(usual type)

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

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

26. Intraoperative Consultation
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 Consultation
Whether the patient has had any other documented tumors
Extraovarian disease, bilateral tumor, gross or microscopic nodularity, garland pattern necrosis, or signet ring cells→gastrointestinal tract
Mucinous ascites (pseudomyxoma peritonei) →evaluate and remove the appendix.