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.

1.
Garbe C, Leiter U. Melanoma epidemiology and trends. Clin Dermatol. 2009;27(1):3–9.
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.
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.
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.
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.
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.
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.
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.
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.
16.
Gupta RK, Lallu S. Cytodiagnosis of amelanotic metastatic malignant melanoma: an immunocytochemical study. Diagn Cytopathol. 1997;16(3):238–41.
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.
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.
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