Immunohistochemistry for PRAME in the Distinction of Nodal Nevi From Metastatic Melanoma

Abstract

The distinction of metastatic melanoma from melanocytic nevi in lymph nodes can on occasion be difficult. As diffuse immunohistochemical (IHC) PRAME (PReferentially expressed Antigen in MElanoma) expression is detected in the majority of primary and metastatic melanomas, but rarely in nevi, we reasoned that PRAME could be a useful adjunct marker for the diagnosis of melanocytes in lymph nodes. In this study, we examined 45 nodal melanocytic deposits comprising 30 nodal nevi and 15 melanoma metastases. The latter were diagnostically not straightforward because they either coexisted with nodal nevi or were present in perinodal fibrous tissue. All nodal nevi (30/30) were negative for PRAME, whereas all melanoma metastases (15/15) were diffusely positive for PRAME IHC. We additionally report the novel use of a PRAME/Melan A dual-label immunostain. Our results show that PRAME IHC may be useful in the assessment of diagnostically challenging nodal melanocytic deposits, such as intraparenchymal nodal nevi, metastases confined to the capsular fibrous tissue, or in the setting of small metastases coexisting with a nodal nevus in the same lymph node.

Figure 1.. Nodal nevus.

Nodal nevic rests present in perinodal fibrous tissue showing bland cytomorphologic features (A, H&E stain) are negative for PRAME IHC (B).

Figure 2.. Nodal nevus.

Capsular, subcapsular, and intraparenchymal nevus (A, H&E; B, Melan A; C, PRAME) showing no immunoreactivity for PRAME.

Figure 3.. Metastatic melanoma to lymph node.

Metastatic melanoma showing markedly atypical cells in perinodal fibrous tissue (A) shows diffuse nuclear labeling for PRAME IHC (B) in tumor cells. Associated melanophages with coarse cytoplasmic melanin pigment are negative for PRAME.

Figure 4.. Nodal nevus and adjacent metastatic melanoma.

Capsular and focally subcapsular nevic rests (left) and adjacent metastatic melanoma present as a single large epithelioid cell within nodal parenchyma (right, arrow) show differential expression of PRAME that is negative in nevic cells and positive in metastatic melanoma (A, Melan A; B, Melan A/PRAME double immunostain). Inset showing double labeling of a metastatic melanoma cell with strong brown nuclear PRAME and red cytoplasmic Melan A; note weak brown nuclear immunoreactivity in few adjacent non-melanocytic cells.