PRAME Immunocytochemistry for the Diagnosis of Melanoma Metastases in Cytological Samples

Abstract

(1) Background: Fine-needle aspiration cytology is often used for the pre-operative diagnosis of melanoma metastases. The diagnosis may not be confidently established based on morphology alone, and immunocytochemistry is mandatory. The choice of the most advantageous immunocytochemical antibodies is critical, as the sample may be scant, and the presence of pigmented histiocytes may be confounding. However, the diagnostic performance of melanocytic markers in this setting is poorly investigated. Moreover, PRAME (preferentially expressed antigen in melanoma) recently emerged as a novel marker for the diagnosis of melanoma. The current work aimed to evaluate the sensitivity and specificity of PRAME for the diagnosis of melanoma metastases in cytological samples, compared to other melanocytic markers. (2) Methods: PRAME, S100, Melan-A, HMB45 and SOX10 were tested on cell block sections of 48 cases of melanoma metastases diagnosed from cytological samples, and 20 cases of reactive lymphadenopathy. (3) Results: S100 and SOX10 showed the highest sensitivity (100%), while the sensitivity of PRAME was 85.4%. PRAME, Melan-A, SOX10 and HMB45 showed a specificity of 100%, while the specificity of S100 was lower (85%), as it marked some histiocytes. (4) Conclusion: PRAME immunocytochemistry is highly specific for the diagnosis of melanoma metastasis from a cytological sample, but is less sensitive compared with other melanocytic markers.

Keywords: HMB45; Melan-A; PRAME; S100; SOX10; immunocytochemistry; melanoma metastasis.

Figure 1

Distribution of staining scores for the immunocytochemistry antibodies. Immunocytochemical stains for S100, Melan-A, SOX10, HMB45 and PRAME were performed in 48 cytological samples of melanoma metastases. S100 and SOX10 were positive in all cases (100%). Melan-A, HMB45 and PRAME were negative in 1 (2.1%), 5 (10.4%) and 7 (14.6%) cases, respectively. SOX10 showed the best diagnostic performance, as strong positivity was observed in 46 (95.8%) cases.

Figure 2

Immunohistochemistry in a case of heavily pigmented melanoma metastasis (A–E), and in a case of slightly pigmented melanoma metastasis (F–J) ((A,F): PRAME, (B,G): SOX10, (C,H): S100, (D,I): Melan-A, and (E,J): HMB45). ((A–J): immunostain, original magnification 400×).

Figure 3

Inguinal lymph node fine-needle aspiration cytology: (A) direct smear: cell aggregate consisting of medium–large-sized cells with irregular nuclear membrane and large eosinophilic cytoplasm. In this context, only a few small lymphocytes are recognized. Morphologically, these aspects are not clearly identifiable with a macrophage–lymphocyte complex (May Grunwald Giemsa stain, 400×). (B) Cell block section: medium-sized cells with round–oval nuclei, sometimes incised and granular cytoplasm, eosinophilic. Small, mature lymphocytes are also present (hematoxylin and eosin stain, original magnification 400×). (C) S100 immunostaining in this cell aggregate is positive; PRAME and SOX10 are negative (S100 immunostain, original magnification 400×).