Ovarian tumors Ancillary methods

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1 Ovarian tumors Ancillary methods Ovarian tumor course Oslo, 24-25/11/14 Prof. Ben Davidson, MD PhD Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway Division of Pathology

2 Ancillary methods in ovarian pathology Genetic/genomic approaches not in routine use Ploidy limited applications, not widely accepted HPV analysis for suspected cervical ca. metastasis Immunohistochemistry Morphology is the basis for correct diagnosis

3 Ploidy Flow cytometry vs. image analysis Suggests higher risk, not diagnostic Current indications at NRH: Sex cord/stromal tumors (Granulosa, Sertoli-Leydig) Borderline tumors (all types) Stage I ovarian carcinoma

4 Ploidy

5 Main differentials Epithelial tumor (mainly adenocarcinoma) histotype Primary vs. metastatic adenocarcinoma Adenocarcinoma vs. germ cell tumor vs. sex cord stromal tumor Rare entities

6 Main differentials Epithelial tumor (mainly adenocarcinoma) histotype Primary vs. metastatic adenocarcinoma Adenocarcinoma vs. germ cell tumor vs. sex cord stromal tumor Rare entities

7 Differentiating ovarian AC of various histology ER: positive in the majority of SC + EC, negative in MC and CCC WT1: positive in the majority of SC, negative in EC, MC and CCC p53: aberrant expression in the majority of HGSC and TCC and in some EC, variable in CCC, negative in LGSC and MC p16: diffuse expression in SC and TCC, patchy in EC, variable in CCC mcea: positive in MC, may focally stain EC, negative in SC and CCC CDX2: positive in MC, may focally stain EC, negative in SC and CCC

8 Differentiating ovarian AC of various histology HNF1β: positive in CCC, may stain some EC, negative in SC and MC Napsin A: positive in CCC, negative in EC, SC and MC ARID1A: lost in CCC and in EC, positive in SC and MC PTEN: lost in EC, positive in CCC, SC and MC GATA3, S100P and p63: Brenner tumor markers (also Uroplakin III and Thrombomodulin?) Chromogranin A: positive in neuroendocrine adenoca. and small cell ca. Synaptophysin: positive in neuroendocrine adenoca. and small cell ca.

9 HGSC PAX8 WT1 CK7

10 ER HGSC CEA CDX2 CK20

11 HGSC + undifferentiated carcinoma WT1 WT1 Division of Pathology

12 Retroperitoneal metastasis origin? CK8 Ber-EP4 mcea PAX8 WT1

13 CCC vs. HGSC

14 WT1 CCC vs. HGSC HNF1β WT1 HNF1β

15 CCC lung met. TTF1 HNF1β PAX8 Napsin A

16 Division of Pathology Brenner borderline tumor

17 Brenner borderline tumor WT1 PAX8 CK7 CK20 Division of Pathology

18 Neuroendocrine carcinoma

19 Neuroendocrine carcinoma CK7 Villin Chromogranin A Synaptophysin

20 Main differentials Epithelial tumor (mainly adenocarcinoma) histotype Primary vs. metastatic adenocarcinoma Adenocarcinoma vs. germ cell tumor vs. sex cord stromal tumor Rare entities

21 Case 1 A 41-year old female, medical history unknown Right-sided ovarian mass (30 cm, 4.5 kg) Pre-operative right-sided pleural effusion: Reactive Operated October 2010 Division of Pathology

22 Division of Pathology Histology - ovary

23 Division of Pathology Histology - ovary

24 Division of Pathology Histology - ovary

25 IHC CK7 CK20 ER CDX2 CEA Villin Division of Pathology

26 Other findings Metastasis in right pericolic area No tumor in left ovary, fallopian tubes, uterus, appendix, 19 intestinal and 22 abdominal lymph nodes Division of Pathology

27 Case 2 A 70-year old female Right-sided colectomy 2010 Tumor in left ovary (3.5 cm) Operated June 2011 Division of Pathology

28 Division of Pathology Histology - ovary

29 Division of Pathology Histology - colon

30 CDX2 IHC CK20 CEA CK7 Division of Pathology

31 Case 3 A 63-year old female Sarcoma in corpus uteri in curettage, leiomyosa. and rhabdomyosa. (carcinosa.?) Enlarged right ovary (4.5 cm) Division of Pathology

32 Division of Pathology Histology - uterus

33 Division of Pathology Histology - ovary

34 Division of Pathology Histology- ovary

35 IHC CK7 CK20 ER CDX2 CEA Division of Pathology

36 Breast carcinoma metastasis GCDFP-15 Mammaglobin Her2 SISH WT1 PAX8

37 Main differentials Epithelial tumor (mainly adenocarcinoma) histotype Primary vs. metastatic adenocarcinoma Adenocarcinoma vs. germ cell tumor vs. sex cord stromal tumor Rare entities

38 Most useful markers EMA (carcinoma) Inhibin (sex cord stromal tumors) Calretinin (sex cord stromal tumors) FOXL2 (sex cord stromal tumors) SF-1 (sex cord stromal tumors) Melan A (Sertoli-Leydig cell tumors) SALL4 (germ cell tumors) D2-40 (dysgerminoma) c-kit/cd117 (dysgerminoma) OCT3/4 (dysgerminoma) AFP (yolk sac tumor) HCG (choriocarcinoma)

39 Granulosa cell tumor Calretinin Inhibin

40 Immature teratoma SOX2 SOX2

41 Dysgerminoma c-kit c-kit c-kit

42 Mixed germ cell tumor AFP AFP PLAP HCG

43 Mixed germ cell tumor OCT3/4 OCT3/4 D2-40 D2-40

44 Mixed germ cell tumor Glypican-3 Glypican-3

45 Main differentials Epithelial tumor (mainly adenocarcinoma) histotype Primary vs. metastatic adenocarcinoma Adenocarcinoma vs. germ cell tumor vs. sex cord stromal tumor Rare entities

46 Entities Mesenchymal tumors (sarcomas and other) Hematological cancers Melanoma Mesothelioma Unclassifiable malignant tumors

47 Spindle cell tumor panel Actin Desmin SMA S100 EMA Pan-cytokeratin CD31 CD34 CD68 CD99

48 DLBCL Bcl-2 CD20 CD10

49 DLBCL CD138 Ki-67 MUM1 CD45

50 Mesothelioma Calretinin D2-40 CK7 WT1

51 Ovarian tumor

52 Omentum

53 Immunohistochemistry- referring lab Cytokeratin (AE1/AE3): negative CK8: negative NSE: positive Calretinin: negative Chromogranin: negative Synaptophysin: negative OVARY WITH EPITHELIAL TUMOR WITH NEUROENDOCRINE DIFFERENTIATION, M/P PRIMARY OMENTAL METASTASIS

54 New IHC AE1/AE3 Vimentin Synaptophysin HMB-45 Melan A

55 Final diagnosis OVARY AND OMENTUM WITH MALIGNANT MELANOMA, PROBABLY METATSASES

56 Non-classifiable

57 Vimentin Non-classifiable AE1/AE3 PGR ER

58 Summary Morphology is basis IHC is the main adjunct Large panels are not a good starting point Primary and metastatic tumors should be considered Not all cases can be decisively classified

59 Thank you for your attention

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