Friedman M, Forgione H, Shanbhag V

Needle aspiration of nodal and extranodal metastases of malignant melanoma was evaluated in 74 patients. All patients had the initial diagnosis of malignant melanoma established on surgical biopsy and histologic sections. A 20-cc glass syringe and an 18-gauge needle were used, and the material obtained was stained by the Wright-Giemsa technique. Adequate material was obtained, and a cytologic diagnosis of malignant melanoma was made in 67 patients (90.5%). In seven patients (9.5%) the specimens contained nondiagnostic material. The diversity of cell types, cytoplasm staining affinity and pigmentation is described. Despite the high variability of the cytologic features encountered, malignant melanoma usually can be diagnosed on cytologic smears. Difficulties in recognizing the nonpigmented varieties are emphasized. The procedure was well tolerated, and no complications were seen.

PMID: 6153490, UI: 80126473

Nasiell K, Tani E, Skoog L

Department of Pathology, Karolinska Hospital, Stockholm, Sweden.

The cytological and immunological findings of 81 metastatic melanomas are described. Fine needle aspiration was performed from secondary deposits in lymph nodes (38), subcutaneous and soft tissue (36), abdomen (5), lung (1) from 67 patients with histologically verified malignant melanoma. One patient had disease which had spread into the cerebrospinal fluid. Cytomorphologically the cases were classified as classical (47%), carcinoma-like (22%), spindle cell type (14%), lymphoma like (6%), undifferentiated (6%), myxoid type (3%), and clear cell type (2%). All cases were immunologically characterized using antibodies to S-100, vimentin and cytokeratin. All cases were S-100 positive and the majority (96%) reacted with antibodies to vimentin. A weak heterogenous reactivity to cytokeratin antibody was detected in only eight cases. The HMB45 antibody was applied to 20 cases and 16 (80%) of these tumours were positive. In summary, we found that an immunological characterization was necessary to conclusively diagnose over 50% of metastatic melanomas which presented with an equivocal cytological picture.

PMID: 1932577, UI: 92032641

Basler GC, Fader DJ, Yahanda A, Sondak VK, Johnson TM

Department of Dermatology, University of Michigan Medical Center, Ann Arbor, USA.

BACKGROUND: Prompt and accurate diagnosis of melanoma metastatic to the lymph nodes is important with respect to prognosis and treatment. OBJECTIVE: The purpose of this study was to determine the utility and diagnostic reliability of fine needle aspiration (FNA) of enlarged nodules in lymph node basins in patients with melanoma. METHODS: We retrospectively reviewed the charts of 46 patients with melanoma who underwent a total of 56 FNAs of palpable nodules in lymph node basins. RESULTS: Of the 56 FNAs, 24 showed melanoma, 26 did not demonstrate melanoma, five were inadequate, and one gave inconclusive but suspect results. Findings were confirmed by open biopsy (n = 35) or clinical follow-up (n = 21). Fifty of 56 FNAs (89%) yielded a definitive diagnosis (sensitivity/specificity = 100% in these 50). CONCLUSION: FNA biopsy of enlarged palpable nodules in nodal basins in patients with melanoma is accurate, rapid, and cost-efficient. An algorithm for management of patients with melanoma who have palpable nodes is provided.

PMID: 9091471, UI: 97226340

Kline TS, Kannan V

Fine needle aspiration biopsy cytology (ABC) has proven to be a valuable tool for diagnosis of metastatic and primary melanoma. The ABC of 28 cases was studied and the findings tabulated. Melanin can be verified by Fontana-Masson stain. Additional salient features include cell isolation, anisocytosis, multinucleation, eosinophilic nucleoli, and intranuclear inclusions. Use of all of these cytomorphologic findings will result in accurate diagnosis of melanoma by ABC.

PMID: 7081153, UI: 82203283

Perry MD, Gore M, Seigler HF, Johnston WW

The prognostic and therapeutic decisions in cases of metastatic melanoma depend upon the morphologic documentation of metastatic disease, which may rapidly and accurately be done by fine needle aspiration (FNA) biopsy of clinically suspicious lesions. The tumor cells derived from malignant melanomas demonstrate a wide range of appearances, however, and other neoplasms may be mimicked. Furthermore, additional neoplasms of other types are more frequent in melanoma patients: the possibility of a new primary tumor must be considered if the morphology of the tumor cells is uncharacteristic. Therefore, a study was undertaken to analyze the morphologic changes seen in FNA biopsy specimens from metastatic malignant melanoma and to determine which features could be the most useful in establishing a definitive diagnosis. A total of 174 consecutive cases, comprising 151 malignant aspirates and 23 inconclusive aspirates, were reviewed. The most significant features for identification of melanoma over other tumor types were the cell shape and nuclear position, the presence of numerous isolated neoplastic cells and occasional binucleated or multinucleated cells. Intracellular melanin in neoplastic cells was diagnostic when present, but it was absent in 60% of the cases. Macronucleoli and/or intranuclear cytoplasmic invaginations were characteristic but variable features. Morphology was also found to vary by site and cell type. Lung aspirates were less cellular and more likely to contain melanin. Aspirates of subcutaneous nodules were more often composed of spindle-shaped cells or of other variant cell types. Lymph node aspirates more often yielded epithelioid cells with macronucleoli and/or intranuclear invaginations. Spindle-cell melanomas usually demonstrated inconspicuous nuclei and rarely showed enlarged nucleoli. Epithelioid-cell tumors contained multinucleated cells and areas of cell wrapping more frequently than did spindle-cell tumors. The findings in this study emphasize that a full awareness of the spectrum of morphologic presentations of metastatic melanoma as well as of the clinical history are needed for greater precision in its diagnosis and for avoidance of the pitfall of misdiagnosing nonmelanomas with similar appearances.

PMID: 3461649, UI: 86291878

Layfield LJ, Ostrzega N

Department of Pathology, UCLA Medical Center 90024-1732.

Cytologic smear preparations of fine needle aspirates obtained from 71 patients with biopsy-proven metastatic malignant melanoma were morphologically analyzed. Cell diameter, percentage of cells lying individually, smear cellularity, mitotic rate, percentage of cells with nuclear inclusions and number of giant cells were quantitated. Qualitative estimates of degree of pigmentation, background composition, presence of macrophages, presence of contaminating blood, cell shape, amount and appearance of cytoplasm, prominence of Golgi apparatus, reactivity with the antibody NKI/C-3 and eccentricity of the nuclei were made. While eccentric nuclei, cytoplasmic vacuoles, intranuclear inclusions, high cellularity and cells with abundant cytoplasm were found frequently in smears from malignant melanomas, the presence of reactivity with NKI/C-3, pigment, giant cells, a bloody background and a lack of cell cohesion were the features most commonly associated with smears obtained from patients harboring metastatic melanoma.

PMID: 2675514, UI: 89389698

Riker AI, Panelli MC, Kammula US, Wang E, Wunderlich J, Abati A, Fetsch P, Rosenberg SA, Marincola FM

National Institutes of Health, National Cancer Institute, Surgery Branch, Bethesda, Maryland 20892, USA.

The establishment of melanoma cell lines from fine-needle aspiration biopsies (FNAB) has allowed for an enhanced understanding of the complex interactions that occur between T cells and tumor cells. The technique of FNAB offers the advantage of providing a sequential analysis of the same tumor nodules throughout treatment. The expression of melanoma antigens (MAs) was assessed in fresh melanoma FNAB samples and from tumor cell lines derived from these samples using several different approaches. Cytospin preparations of freshly isolated tumor cell explants were analyzed by immunocytochemistry (ICC), while the daughter cell line was analyzed by fluorescent activated cell sorting (FACS) analysis, and semiquantitative and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR, qRT-PCR). As assessed by these methods, the level of MA expression by the original tumor cell explants correlated with the expression in established in vitro cell lines. Molecular analysis of the established cell lines utilizing PCR technology improved the sensitivity of detection of MA expression. Thus FNAB of melanoma is an efficient and effective method of tissue procurement, capable of generating, sequentially and from the same lesion, fresh tumor cells, tumor infiltrating lymphocytes (TIL), and long-term melanoma cell lines.

PMID: 10468890, UI: 99398233

Simmons TJ, Martin SE

Department of Pathology, University of Southern California School of Medicine, Los Angeles 90033.

The immunoreactivity of alcohol-fixed cell blocks from 15 fine-needle aspiration (FNA) specimens of malignant melanoma was investigated using monoclonal antibodies to keratin and vimentin intermediate filaments, melanoma cytoplasmic antigen (HMB-45), and S-100, as well as polyclonal antibodies to S-100. The results were compared with the immunoprofiles obtained using formalin-fixed surgical specimens from 10 of the same patients. In all cases, immunostaining for keratin was negative and immunostaining for vimentin was positive. Immunostaining for HMB-45 was positive in 13/15 aspirates and in 9/10 surgical specimens. Immunostaining for S-100 protein showed the greatest variability in staining, with 5/15 fine needle aspiration biopsies and 9/10 surgical specimens being positive using the polyclonal antibody and only 1/15 FNA specimens and 7/10 surgical specimens being positive using the monoclonal S-100 reagent. Our findings indicate that immunocytochemical studies can be very useful as an adjunct in the FNA diagnosis of melanoma. Also included in our series is an unusual variant of malignant melanoma, the so-called signet ring melanoma. Given the location of the anal verge, the use of immunocytochemical markers was essential in establishing the correct diagnosis in this case. While S-100 protein is of limited value as a marker of melanoma in alcohol-fixed FNA specimens, a definitive diagnosis of malignant melanoma can be made using a panel of antibodies including keratin, vimentin, and HMB-45.

PMID: 1935517, UI: 92036896

Kapila K, Kharbanda K, Verma K

Department of Pathology, All India Institute of Medical Sciences, New Delhi.

The cytomorphological features of cells from 52 cases of metastatic melanoma obtained by fine needle aspiration cytodiagnosis were studied. Morphologically, 11, 19 and 22 cases were classified as spindle, epithelial, and mixed cell types of metastatic melanoma respectively. There were 34 melanotic and 18 amelanotic melanomas. Besides melanin, the presence of intranuclear cytoplasmic inclusions, eosinophilic macronucleoli and giant cells were helpful in the diagnosis of a melanoma. Where attempted, staining for S-100 protein was positive in all the 19 cases (eight amelanotic and 11 sparsely pigmented melanomas). In addition eight cases of metastatic tumour where a differential diagnosis of poorly differentiated carcinoma or large cell lymphoma was entertained, were also studied for localization of S-100 protein and all were found to be negative. Electron microscopy was performed in five cases and showed the presence of melanosomes and/or premelanosomes.

PMID: 1782361, UI: 92144910

Martinez F, Merenda G, Bedrossian CW

Pathology Associates Medical, Inc., Spokane, WA.

Fine needle aspirates from one of multiple liver nodules revealed a large number of discohesive malignant cells with abundant vacuolated cytoplasm. The patient had had left eye enucleation the year before, for a melanoma with focal areas of clear cell change. Pap stained preparations from the liver FNA displayed well the nuclear features of balloon cell melanoma, including anisonucleosis, prominent nucleoli and intranuclear inclusions. Diff-Quik stain demonstrated best the cytoplasmic features such as distinct cell margins and finely dispersed and sharply delineated clear vacuoles. No pigmentation was noted but melanoma was suspected after the history prompted comparison with the enucleated specimen resected a year previously. A multimodal battery of ancillary methods including electron microscopy (EM) and immunocytochemistry (ICC) allowed the confirmation of balloon-cell melanoma, a rare variant not previously described in the eye. By EM, abundant lipids were identified along with melanin-containing structures resembling melanosomes. S-100 positivity along with negativity for epithelial, lymphohistiocyte and germ cell markers was compatible with melanoma. These findings are consistent with the view that cytologic detection of poorly cohesive, hypervacuolated cells does not exclude the possibility of melanoma. This rare example of a lipid-containing melanoma stresses the value of obtaining good clinical history, comparing FNAs to any pre-existing material and utilizing a multimodal approach to cytologic diagnosis in select cases.

PMID: 1705502, UI: 91153176