Ovarian mucinous lesions Ovarian mucinous …

1 5/25/20131 Ovarian mucinous lesions : Common diagnostic dilemmasKaruna Garg, MDUniversity of California San Francisco Intestinal or usual type Seromucinous(Endocervicalmucinous or Mullerianmucinous) typeOvarian mucinous lesionsOvarian mucinous lesions : problematic issues mucinous cystadenomaversus borderline tumor mucinous borderline tumor versus carcinoma Primary mucinous tumors versus metastasis Pseudomyxomaperitonei site of origin, classification and clinical outcomes Effective handling of mucinous Ovarian lesions at frozen section Mural nodulesMucinous cystadenomaversus borderline tumor5/25/20132 mucinous cystadenomaversus borderline tumorSignificanceBorderline tumors are usually cystadenomaversus borderline tumorAssess for epithelial proliferation Sample well If less than 10% -cystadenomawith focal epithelial atypia/proliferation Clinical outcome similar to cystadenoma If >10% -borderline tumorMucinous cystadenomaMucinous cystadenofibroma5/25/20133 mucinous cystadenofibromaMucinous cystadenoma with Brenner tumorMucinous cystadenofibroma with

2 Focal epithelial proliferationMucinous cystadenofibroma with focal epithelial proliferation5/25/20134 mucinous borderline tumorMucinous borderline tumorMucinous borderline tumorMucinous borderline tumor versus carcinoma5/25/20135 mucinous borderline tumor versus carcinomaSignificance- Carcinomas always staged- Small risk of extra- Ovarian disease- mucinous borderline tumors are benign and should be stage 1A (if considering an advanced stage borderline tumor or borderline tumor with implants-exclude metastasis) mucinous borderline tumor Microinvasion Intraepithelial carcinomaMucinous borderline tumorMicroinvasion No single invasive focus should measure >5 mm or 10 mm2 Multiple foci can occur Prognosis similar to borderline tumors (one recent study shows higher risk of recurrence)Microscopic.

3 mucinous borderline tumor with microinvasionMucinous borderline tumor with microinvasion5/25/20136 mucinous borderline tumor with microinvasionMucinous borderline tumorIntraepithelial carcinoma High grade nuclear atypia Prognosis similar to borderline tumors (one recent study suggests higher risk of recurrence) mucinous borderline tumor with intraepithelial carcinomaMicroscopic: mucinous borderline tumor with intraepithelial carcinomaMucinous borderline tumor with intraepithelial carcinoma5/25/20137 Ovarian mucinous carcinoma Unequivocal invasion >5 mm (10 mm2) Two patterns of invasion:- Expansile(confluent cribriform/glandular pattern) more common- Infiltrative (worse prognosis) (should exclude metastasis)Microscopic: Primary mucinous carcinomaOvarian mucinous carcinoma: expansile invasionOvarian mucinous carcinoma: expansile invasionMicroscopic: Primary mucinous carcinomaOvarian mucinous carcinoma: expansile invasion5/25/20138 Ovarian mucinous carcinoma.

4 Destructive stromal invasionImmunophenotypeof primary Ovarian mucinous tumors CK7++ CK20+(83%) CDX2+ (40%-less frequently positive in primary Ovarian mucinous tumors) PAX-8+(50%) ER/PR- WT1-CK7>>CK20 Immunophenotypeof primary Ovarian mucinous tumorsTumor typePrimary Ovarian mucinous tumors(n=42)CK7+/CDX2-25 (60%)CK7+/CDX2+15 (36%)CK7-/CDX2+2 (5%)CK7-/CDX2-0 (-)CK7+/CK20-7 (17%)CK7+/CK20+33 (79%)CK7-/CK20+2 (5%)CK7-/CK20-0 (-)Vang, et al. Mod Pathol 2006 Primary versus metastatic mucinous neoplasms of the ovary5/25/20139 Primary versus metastasis Can be challenging Metastatic mucinous carcinomas to the ovary can be highly deceptive Sometimes metastatic involvement of the ovary is the primary presentation of a mucinous tumor without clinical evidence of an extra- Ovarian lesion Immunohistochemistry of limited helpOvarian mucinous carcinoma Uncommon <3% of all Ovarian carcinomas Predominantly stage 1 Extra- Ovarian disease rareOvarian mucinous carcinoma Metastatic mucinous carcinomas are more common Metastatic mucinous carcinomas can simulate Ovarian

5 mucinous carcinoma, borderline tumor or cystadenomaby radiology and pathologyOvarian mucinous carcinoma 44 cases of advanced stage mucinous carcinomas 61% reclassified as likely metastasis True advanced stage primary Ovarian mucinous carcinomas rare ( ) Advanced stage Ovarian mucinous carcinomas highly lethal and survival shorter than serousZaino RJ, et al. Cancer 20115/25/201310 HER2 in Ovarian mucinous carcinomas Low response rates to carbotaxol Her2 amplification in 18% mucinous carcinomas and borderline tumors No association with prognosis Patients may respond to trastuzumab therapyMcAlpine et al, BMC Cancer 2009 Primary versus metastasisSignificance- Prognosis- Therapy 1999 Lippincott Williams & Wilkins, Inc.

6 Published by Lippincott Williams & Wilkins, of Diagnostic Criteria and Behavior of Ovarian Intestinal-Type mucinous Tumors: Atypical Proliferative (Borderline) Tumors and Intraepithelial, Microinvasive, Invasive, and Metastatic , Maureen; Ronnett, Brigitte; Kurman, RobertAmerican Journal of Surgical Pathology. 23(6):617-635, June 10 . Survival analysis of Ovarian mucinous tumors. There is a statistically significant difference in survival between atypical proliferative tumors (with and without microinvasion), primary mucinous carcinomas, and metastatic carcinomas (p = , log rank test).Primary versus metastasis: prognosis5 year survival:Primary versus metastasis: therapy Surgery- Primary Ovarian cancer: comprehensivesurgical staging and debulking- Metastasis: No staging Chemotherapy.

7 Different agents (move toward treating mucinous tumors by histology rather than site of origin)5/25/201311 PrimaryMetastasisLateralityUnilateralBil ateralSize>10 cm>12 cm<10 cm<12 cmSurface involvementAbsentPresentStageUsually stage IAdvanced stagePrimary versus metastasisGross featuresLee et al, Am J Surg Pathol2003 Seidmanet al, Am J Surg Pathol2003 Yemelyanovaet al, Am J Surg Pathol2008 Primary versus metastasisGross algorithm: -Bilateral tumors of any size, unilateral <13 cm: Metastatic-Unilateral > 13 cm: PrimaryApplication of this algorithm correctly identified 98% of primary tumors and 82% metastasesCommon exceptions: Colorectal and endocervical carcinomasPrimary versus metastasis: pitfallsGross:Metastatic mucinous tumors can be - Unilateral- Large- Grossly multicystic - Smooth surfacePrimaryMetastasisPattern of growth ExpansileNodularDestructive stromal invasionNoYesOvarian hilar involvementNoYesLymphovascularinvasionNo YesMicroscopic surface mucinNoYesSignet ring cellsNoYes/NoPseudomyxomaperitonei and ovariiNoYesPrimary versus metastasisMicroscopic features5/25/201312 Metastatic colon carcinoma.

8 Nodular, desmoplasia, infiltrative growth patternMetastatic colon carcinoma: Surface involvementMetastatic gastric carcinoma: Signet ring cellsMetastatic colon carcinoma: Lymphovascularinvasion5/25/201313 Primary versus metastasis: pitfallsMicroscopic: Maturation phenomenon Metastatic mucinous carcinomas can simulate- mucinous cystadenoma- Borderline mucinous tumor- Borderline mucinous tumor with intraepithelial carcinoma - Borderline mucinous tumor with microinvasionMetastatic pancreatic carcinoma - mimicking mucinous cystadenomaMetastatic endocervical adenocarcinoma mimicking mucinous borderline tumorPrimary versus metastasis Heterogeneous Highly differentiated areas adjacent to malignant areas Look for foci that may be suggestive of metastasis Consider submitting 2 sections per cm in difficult casesSampling is key!

9 5/25/201314 PseudomyxomaperitoneiPseudomyxoma peritonei (PMP) Clinical entity Abundant extracellular peritoneal mucin May or may not contain epithelial cells Associated with a heterogeneous group of pathologic lesionsPseudomyxoma peritonei (PMP)Two broad categories:1. Low grade: Disseminated peritoneal adenomucinosis(DPAM)2. High grade: Peritoneal mucinouscarcinomatosis(PMCA)Pseudomyxoma peritonei (PMP)DPAM (Disseminated peritoneal adenomucinosis)PMCA (Peritoneal mucinous carcinomatosis)CellularityScantModerate to abundantCytologic atypiaMinimalModerate to markedMitotic activityRareOccasional to abundantLymph node involvementRareFrequentParenchyma organ involvementRareFrequentSite of originAppendix- Cystadenoma-Hyperplastic polyp- Villous adenomaAppendix/colon- Carcinoma5 and 10 year survival75% and 68%14% and 3%Ronnett et al, Am J Surg Pathol 1995 Ronnett et al, Cancer 20015/25/201315 Pseudomyxoma peritonei (PMP)Problems:1.

10 Pathologic terminology- Lack of consensus- Disseminated peritoneal adenomucinosis(DPAM) = Well differentiated adenocarcinoma = Low grade appendiceal mucinous neoplasm (LAMN) = Pseudomyxomaperitonei2. PMP frequently involves ovaries, but virtually never originates therePseudomyxoma peritonei (no epithelium)Pseudomyxoma peritonei: Low grade epitheliumPseudomyxoma peritonei: Low grade epithelium5/25/201316 Pseudomyxoma peritonei: High grade epithelium with signet ring cellsPseudomyxoma peritonei (PMP)Take home message:-Most cases of PMP are of appendiceal or intestinal origin- Ovarian involvement is secondaryException: mucinous tumors arising in Ovarian teratomasOvarian mucinous tumors associated with mature cystic teratomas- 2-11% of mature cystic teratomas- Teratoma component may be focal1.