Cytologic diagnosis of metastatic melanoma by FNA: A practical review

Abstract

Malignant melanoma (MM) is a highly aggressive neoplasm with a growing worldwide incidence. It is not uncommon that the disease is already metastatic at the time of the first diagnosis. Regional lymph nodes and skin are the first and most common metastatic sites, followed by distant visceral sites (lungs, liver, and central nervous system) and bone. In this clinical setting, fine-needle aspiration (FNA) often represents the first diagnostic approach. FNA is a useful tool to obtain a rapid and accurate diagnosis, in conjunction with ancillary techniques and molecular analysis, as recommended by recent guidelines. The aim of this review was to describe the cytomorphology, immunocytochemical tools, and molecular tools used for the diagnosis of MM metastases on FNA.

Keywords: BRAF; fine-needle aspiration; immunocytochemistry; melanoma; sentinel node.

Figure 1

Fine‐needle aspiration smears of metastatic melanoma are shown. (A) A direct smear shows a branching blood vessel surrounded by numerous melanoma cells. Several diagnostic, dispersed malignant cells are present in the background (May‐Grunwald‐Giemsa stain, original magnification ×100). (B,C) Viable melanoma cells are shown closely clinging to the blood vessel wall (May‐Grunwald‐Giemsa stain; original magnification ×400 in B, ×600 in C). (D) A cell‐block section shows numerous melanoma cells surrounding a central blood vessel (H&E stain, original magnification ×200).

Figure 2

Morphologic features of malignant melanoma metastasis on direct smears are shown, including (A) large epithelioid cells with round‐to‐oval nuclei and abundant, sometimes microvacuolized cytoplasm (May‐Grunwald‐Giemsa stain, original magnification ×400); (B) discohesive plasmocytoid cells with round nuclei and dense cytoplasm, well defined borders, and evident nucleoli (Papanicolaou stain, original magnification ×400); (C) numerous spindle‐shaped cells with oval‐to‐fusiform nuclei and evident cytoplasmatic projections (Papanicolaou stain, original magnification ×400); (D) a small cell component with inconspicuous nucleoli and scarce cytoplasm mixed with a larger cellular component (Papanicolaou stain, original magnification ×400); and (E) malignant multinucleated cells mixed with an epithelioid and plasmocytoid cell population (May‐Grunwald‐Giemsa stain, original magnification ×400).

Figure 3

Melanin pigment is shown in a cytologic sample of malignant melanoma. (A) Melanin pigment may be macroscopically evident on the slide, particularly when abundant. The pigment is abundant in (B) the corresponding smear (May‐Grunwald‐Giemsa stain, original magnification ×400) and (C) cell‐block section (H&E stain, original magnification 400x). Some epithelioid cells are recognized in both cytopreparations, allowing the diagnosis.

Figure 4

This is an overview of malignant melanoma immunocytochemistry on cell‐block sections showing cytoplasmic and nuclear positivity for S100, nuclear positivity for Sry‐related HMg‐box gene 10 (SOX10), cytoplasmic positivity for tyrosinase, cytoplasmic positivity for the melanoma marker antibody HMB45, cytoplasmic positivity for melanoma‐associated antigen recognized by T cells (MART‐1), and nuclear positivity for microphthalmia transcription factor (MiTF) (immunocytochemical stains, original magnification ×400).

Figure 5

The interpretation of immunocytochemistry may be challenging in pigmented cases because the melanin pigmentation may be misinterpreted as viable tumor. In this circumstance, Fast Red immunocytochemical staining may be useful. (Left) In this illustrative case, large cells containing melanin pigment in the cytoplasm are observed in the cell‐block section (H&E stain, original magnification ×600). (Right) Immunocytochemical Melan‐A evaluation with Fast Red shows positive staining in the neoplastic cells; note the negative histiocyte (yellow arrow; immunocytochemical stain, original magnification ×600).

Figure 6

On BRAF immunocytochemistry, granular cytoplasmatic staining is observed in the neoplastic cells (immunocytochemical stain, original magnification ×400).