Immunohistochemistry for PRAME in Dermatopathology

Abstract

Preferentially expressed antigen in melanoma (PRAME) is a tumor-associated antigen first identified in a melanoma patient and found to be expressed in most melanomas as well as in variable levels in other malignant neoplasms of epithelial, mesenchymal, or hematolymphoid lineage. Detection of PRAME expression in formalin-fixed paraffin-embedded tissue is possible by immunohistochemistry (IHC) with commercially available monoclonal antibodies. In situ and invasive melanoma frequently show a diffuse pattern of nuclear PRAME immunoreactivity which contrasts with the infrequent and typically nondiffuse staining seen in nevi. In many challenging melanocytic tumors, results of PRAME IHC and other ancillary tests correlate well, but not always: The tests are not interchangeable. Most metastatic melanomas are positive for PRAME, whereas nodal nevi are not. Numerous studies on PRAME IHC have become available in the past few years with results supporting the value of PRAME IHC as an ancillary tool in the evaluation of melanocytic lesions and providing insights into limitations in sensitivity and specificity as well as possible pitfalls that need to be kept in mind by practicing pathologists.

Figure 1.

Melanoma in situ with diffuse 4+ immunoreactivity for PRAME (A, H&E stain; B, PRAME IHC; original magnification, 50x).

Figure 2.

Primary melanoma. (A) H&E stain showing in situ and invasive melanoma. (B) Both in situ and invasive melanoma are strongly and diffusely immunoreactive for PRAME (original magnification, 50x).

Figure 3.

(A) Desmoplastic melanoma, pure type (H&E). (B) Sox10 immunostain highlights the subtle melanoma in situ and scattered spindle tumor cells in the dermis in a fibrotic stroma (C) while PRAME shows immunoreactivity in only a subset of the in situ component and it is mostly negative in the invasive tumor cells (original magnification, 60x).

Figure 4.

PRAME immunoreactivity in a nevus. (A) Compound melanocytic nevus with architectural disorder showing (B) a subset of PRAME-positive melanocytes at the dermoepidermal junction and in the superficial dermis. Note the melanin pigment within adjacent keratinocytes which at lower magnification could give a false impression of more extensive PRAME nuclear expression in melanocytes (if using a brown chromogen); examination at medium and high magnification prevents this potential pitfall (A, H&E; B, PRAME IHC; original magnification 90x).

Figure 5.

(A) Melanoma in situ and invasive associated to nevus. (B) IHC for PRAME stains only intraepidermal and superficially invasive melanoma cells and is negative in the associated nevus (A, H&E; B, PRAME IHC; original magnification 90x).

Figure 6.

PRAME IHC in a challenging melanocytic tumor. (A) Atypical predominantly dermal melanocytic neoplasm with nevoid features, impaired maturation, and rare mitotic figures (seen in D). (B) PRAME immunostain diffusely highlights tumor cells. (C) SNP-array showed several genomic aberrations including segmental gains in chromosome 1q, gain and loss of segments in chromosome 3q, segmental losses in chromosome 5q, low level gain of chromosome 6, segmental loss of chromosome 9q, segmental losses in chromosome 11p and 11q, segmental loss of chromosome 12q, loss of chromosome 16q, low level segmental gain in chromosome 18q, and segmental loss of chromosome 22q. (A and D, H&E original magnifications 50x and 200x, respectively; B, PRAME IHC; original magnification 50x; chr= chromosome, seg= segmental).

Figure 7.

(A) Metastatic melanoma present in a lymph node. (B) PRAME IHC diffusely highlights tumor cells (A, H&E; B, PRAME IHC; original magnification 15x).

Figure 8.

Melanocytic deposits in a sentinel lymph node for melanoma. (A) Foci of subcapsular metastatic melanoma are present and show co-labeling of red cytoplasmic Melan A and brown nuclear PRAME in tumor cells. (B) The same sentinel lymph node also showed capsular nevic rests highlighted only by Melan A (note absence of brown/DAB nuclear stain for PRAME). The lower aspect of (A) and (B) show scattered non-specific variable PRAME immunoreactivitv in inflammatory cells of background lymph node parenchyma. (A and B, Melan A/PRAME double immunostain; original magnification 200x).

Figure 9.

Primary acquired melanosis with high grade atypia/conjunctival melanoma in situ with diffuse 4+ immunoreactivity for PRAME (A, H&E stain; B, PRAME IHC; original magnification 50x).

Figure 10.

Ulcerated metastatic synovial sarcoma to skin with diffuse 4+ immunoreactivity for PRAME and also positive with IHC for SS18-SSX (A, H&E stain; B, PRAME IHC; C, SS18-SSX IHC; original magnification 60x).