Introduction: Metastatic melanoma (MM) is an uncommon finding in serous effusion specimens with a highly variable cytomorphology. Methods: We reviewed specimens submitted over a 19-year period to determine (a) the range of cytologic findings in effusion specimens from melanoma patients and (b) the cytologic presentation and immunoprofile of MM in effusion specimens. Results: Of 123 serous effusion specimens from patients with clinical notes of melanoma, 59% were reported negative for malignancy, 16% were reported with a non-melanoma malignancy, 19% MM, and 6% atypical, MM not excluded. Pleural fluids were twice as likely to be reported as MM than peritoneal samples. Review of 44 cases with confirmed MM showed the most common cytologic pattern was epithelioid. Most (88%) cases contained mainly dispersed plasmacytoid cells, but many (61%) also contained malignant cells arranged in loose groups. Rare cases also had spindle cells, giant bizarre cells, small lymphoid-like cells, or cells with large hard-edged vacuoles, mimicking other metastatic malignancies. MM cases containing predominantly plasmacytoid cells often mimicked reactive mesothelial cells. As well as being composed of cells of similar size, features such as bi- and multinucleation, round nuclei, mild anisokaryosis, nucleoli, and loose groups were common to both. Features seen more commonly in MM than reactive cells included large nucleoli (95%) and intranuclear cytoplasmic inclusions (41%), binucleate “bug-eyed demons,” and small punctate vacuoles on the air-dried preparations. Pigment was identified in 36% of cases. Immunohistochemistry (IHC) is a valuable aid in confirming the cell type. The sensitivity for the most commonly used melanoma markers was as follows: S100 84% (21/25), pan-melanoma 100% (19/19), HMB45 92% (11/12), Melan A 92% (11/12), SOX10 91% (10/11). No staining was reported for calretinin (0/21), AE1/AE3 (0/11), EMA (0/16), Ber-Ep4 (0/13). Discussion: Effusion specimens from patients with a history of melanoma are frequently (40%) malignant but almost as likely to be reported as a nonmelanoma malignancy as MM. The cytology of MM may mimic a wide range of other metastatic malignancies but also often closely resembles reactive mesothelial cells. It is important to be aware of this latter pattern so that IHC markers can be applied.

Keywords:
Melanoma, Metastatic malignancy, Cytology, Serous effusion
1.
Garbe C, Leiter U. Melanoma epidemiology and trends. Clin Dermatol. 2009;27(1):3–9.
https://doi.org/10.1016/j.clindermatol.2008.09.001
2.
Australian Institute of Health and Welfare 2021. Cancer in Australia 2021. Cancer series no. 133. Cat. no. CAN 144. Canberra: AIHW.
3.
Patel JK, Didolkar MS, Pickren JW, Moore RH. Metastatic pattern of malignant melanoma: a study of 216 autopsy cases. Am J Surg. 1978;135(6):807–10.
https://doi.org/10.1016/0002-9610(78)90171-x
4.
De la Monte SM, Moore GW, Hutchins GM. Patterned distribution of metastases from malignant melanoma in humans. Cancer Res. 1983;43(7):3427–33.
5.
Chen JTT, Dahlmash NS, Ravin CS. Metastatic melanoma to the thorax. AJR. 1987;137:293–8.
6.
Ribu DL, Shield PW, Bligh JF. The varied presentation of metastatic melanoma in fine needle aspiration cytology of the breast. Cytopathology. 2012;23(4):256–62.
https://doi.org/10.1111/j.1365-2303.2011.00883.x
7.
Johnston WW. The malignant pleural effusion. A review of cytopathologic diagnoses of 584 specimens from 472 consecutive patients. Cancer. 1985;56(4):905–9.
https://doi.org/10.1002/1097-0142(19850815)56:4%3c905::aid-cncr2820560435%3e3.0.co;2-u
8.
Sears D, Hadju SJ. The cytologic diagnosis of malignant neoplasms in pleural and peritoneal effusions. Acta Cytol. 1987;31:97.
9.
Beaty M, Fetsch P, Wilder AM, Marincola F, Abati A. Effusion cytology of malignant melanoma. A morphologic and immunocytochemical analysis including application of the MART-1 antibody. Cancer. 1997;81(1):57–63.
https://doi.org/10.1002/(sici)1097-0142(19970225)81:1%3c57::aid-cncr12%3e3.0.co;2-b
10.
Longatto Filho A, de Carvalho LV, Santos Gd C, Oyafuso MS, Lombardo V, Bortolan J, et al. Cytologic diagnosis of melanoma in serous effusions. A morphologic and immunocytochemical study. Acta Cytol. 1995;39(3):481–4.
11.
Niemann TH, Thomas PA. Melanoma with signet-ring cells in peritoneal fluid. Diagn Cytopathol. 1995;12:243–4.
12.
Walts AE. Malignant melanoma in effusions: a source of false-negative cytodiagnoses. Diagn Cytopathol. 1986;2:150–3.
https://doi.org/10.1002/dc.2840020210
13.
Izban KF, Candel AG, Hsi ED, Selvaggi S. Metastatic melanoma of the vulva identified by peritoneal fluid cytology. Diagn Cytopathol. 1999;20(3):152–5.
https://doi.org/10.1002/(sici)1097-0339(199903)20:3%3c152::aid-dc7%3e3.0.co;2-d
14.
Ikeda K, Tate G, Iezumi K, Suzuki T, Kitamura T, Mitsuya T. Effusion cytomorphology and immunocytochemistry of malignant melanoma: five cases of melanotic melanoma and one case of amelanotic melanoma. Diagn Cytopathol. 2009;37(7):516–21.
https://doi.org/10.1002/dc.21054
15.
Murali R, Loughman NT, McKenzie PR, Watson GF, Thompson JF, Scolyer RA. Cytological features of melanoma in exfoliative fluid specimens. J Clin Pathol. 2009;62(7):638–43.
https://doi.org/10.1136/jcp.2009.065599
16.
Gupta RK, Lallu S. Cytodiagnosis of amelanotic metastatic malignant melanoma: an immunocytochemical study. Diagn Cytopathol. 1997;16(3):238–41.
https://doi.org/10.1002/(sici)1097-0339(199703)16:3%3c238::aid-dc9%3e3.0.co;2-b
17.
Clevenger J, Joseph C, Dawlett M, Guo M, Gong Y. Reliability of immunostaining using pan-melanoma cocktail, SOX10, and microphthalmia transcription factor in confirming a diagnosis of melanoma on fine-needle aspiration smears. Cancer Cytopathol. 2014;122(10):779–85.
https://doi.org/10.1002/cncy.21458
18.
Mohamed A, Gonzalez RS, Lawson D, Wang J, Cohen C. SOX10 expression in malignant melanoma, carcinoma and normal tissues. Appl Immunohistochem Mol Morphol. 2013;21(6):506–10.
https://doi.org/10.1097/PAI.0b013e318279bc0a
© 2023 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2023
You do not currently have access to this content.