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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