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

Lezcano, Cecilia; Pulitzer, Melissa; Moy, Andrea P.; Hollmann, Travis J.; Jungbluth, Achim A.; Busam, Klaus J.

doi:10.1097/pas.0000000000001393

Cited by 83 publications

(134 citation statements)

References 24 publications

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“…More recently, PRAME has been described to be a helpful marker in distinguishing nodal nevi from metastatic melanoma, but it needs to be validated in larger series. 29 Finally, this study also showed that expert pathology review…”

Section: Histopathological Evaluation Of Snsupporting

confidence: 58%

Challenges in sentinel node pathology in the era of adjuvant treatment

Franke

Madu

Bierman

et al. 2020

Journal of Surgical Oncology

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Background With the approval of adjuvant therapy for stage III melanoma, accurate staging is more important than ever. Sentinel node biopsy (SNB) is an accurate staging tool, yet the presence of capsular nevi (CN) can lead to a false‐positive diagnosis. Patients and Methods Retrospective analysis of the American Joint Committee on Cancer 7th edition stage IIIA melanoma patients who were treated at our institute between 2000 and 2015. SNB slides were reviewed for this study by an expert melanoma pathologist. Results Of 159 eligible patients, 14 originally diagnosed with metastatic melanoma merely had CN (8.8%). Another two merely had melanophages (1.3%). Thus, 10.1% of SNs were considered false positive after revision. In 12 patients, the SN tumor burden was originally reported as larger than 1 mm but turned out to be less than 1 mm. Four patients originally reported as SN tumor burden less than 1 mm before revision turned out to have larger than 1 mm. These patients might have been over‐ or undertreated in the current era of adjuvant therapy for stage III melanoma. Conclusions Distinguishing metastatic melanoma from benign CN and melanophages can be a diagnostic challenge. We plead for an expert pathologists' review, especially when using the SNB + results to determine treatment consequences.

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Section: Histopathological Evaluation Of Snsupporting

confidence: 58%

Challenges in sentinel node pathology in the era of adjuvant treatment

Franke

Madu

Bierman

et al. 2020

Journal of Surgical Oncology

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“…We note that the threshold for defining diffuse staining in our cohort (60%) differs from the cutoff of 75% established by Lezcano et al 14,15,19 Six of our 24 non‐spitzoid melanomas (25%), none of which were desmoplastic, would be considered non‐diffuse with the higher cutoff, and no Spitz nevi would have shown diffuse expression. Given that rare examples of diffuse PRAME staining in non‐malignant spitzoid neoplasms reinforce the need to perform additional studies for definitive classification in this diagnostic category, we selected a threshold that prioritized the ability of PRAME to discriminate between benign and malignant non‐spitzoid neoplasms.…”

Section: Discussionmentioning

confidence: 60%

“…A summary of PRAME results by type of lesion is provided in We note that the threshold for defining diffuse staining in our cohort (60%) differs from the cutoff of 75% established by Lezcano et al 14,15,19 Six of our 24 non-spitzoid melanomas (25%), none of which were desmoplastic, would be considered non-diffuse with the higher In summary, this study expands on the diagnostic utility of PRAME by demonstrating its lack of diffuse expression in atypical but benign melanocytic proliferations, facilitating their distinction from melanoma. This study also reinforces that PRAME expression in spitzoid neoplasms should be interpreted in the context of histopathologic features, and correlation with cytogenetic and/or molecular studies may be required for diagnostic classification.…”

Section: Resultsmentioning

confidence: 79%

“…PRAME was first identified in tumor‐reactive T‐cell clones in patients with cutaneous melanoma 1 . Although PRAME has been shown to be overexpressed in a variety of malignancies, 4‐11 it has reliably shown utility in distinguishing between diagnostically straightforward benign and malignant melanocytic proliferations, 14 including distinction of capsular nevi from metastatic melanoma within lymph nodes 15 . With the inclusion of histopathologically indeterminate melanocytic proliferations or those with mixed features (ie, well‐circumscribed and nevoid architecture but with severe cytologic atypia, mitotic activity, poor maturation, and/or ulceration), our study sought to examine the ability of PRAME expression to assist in the classification of diagnostically challenging melanocytic proliferations.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies by Lezcano et al characterized PRAME immunohistochemistry in a variety of melanocytic tumors, including benign melanocytic nevi, primary and metastatic melanoma, melanoma in situ, nodal nevi, and other benign melanocytic proliferations. 14,15 This valuable work highlighted the utility of PRAME immunohistochemistry in melanoma diagnosis via examination of largely histopathologically unequivocal benign and malignant melanocytic proliferations.…”

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confidence: 98%

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PRAME expression in melanocytic proliferations with intermediate histopathologic or spitzoid features

et al. 2020

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Background: PRAME (PReferentially expressed Antigen in MElanoma) has shown utility in distinguishing melanoma from benign melanocytic lesions, but knowledge of its expression pattern in intermediate melanocytic and spitzoid proliferations is limited. Methods: Immunohistochemical expression of PRAME was examined in 112 melanocytic proliferations with intermediate histopathologic or spitzoid features. Results: Any intensity of nuclear PRAME staining in at least 60% of lesional melanocytes was determined as the best threshold for diffuse staining in this cohort. Nearly all non-spitzoid melanomas (23/24; 95.8%) demonstrated diffuse PRAME expression. PRAME was completely negative in 95.6% (43/45) of mitotically-active nevi, traumatized nevi, nevi with persistent/recurrent features, and dysplastic nevi. Most Spitz nevi (15/20) and atypical Spitz tumors (10/13) entirely lacked PRAME expression. One Spitz nevus, one atypical Spitz tumor, and one spitzoid melanoma (1/2) demonstrated diffuse PRAME expression. Conclusions: Although diffuse PRAME expression is generally limited to malignant melanoma, benign Spitz nevi and atypical Spitz tumors can infrequently express diffuse PRAME. PRAME immunohistochemistry can be useful in the evaluation of atypical melanocytic proliferations with intermediate histopathologic features but should be interpreted with caution in the setting of spitzoid neoplasms.

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PRAME protein expression in DICER1‐related tumours

Thorner

Chong

Nadaf

et al. 2022

The Journal of Pathology CR

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DICER1 syndrome is an autosomal dominant tumour predisposition syndrome usually affecting persons under 30 years of age. Many of the associated benign and malignant lesions occur almost exclusively in DICER1 syndrome. One such tumour, pituitary blastoma (pitB), overexpresses PRAME 500x above control levels. PRAME (PReferentially expressed Antigen in MElanoma) is expressed in malignancies that are not DICER1-related (e.g. melanoma). To address whether PRAME expression is part of the DICER1 phenotype, or simply a feature of pitB, a series of 75 DICER1-mutated specimens and 33 non-mutated specimens was surveyed using immunohistochemistry for PRAME, together with EZH2, which complexes with PRAME. In DICER1-mutated specimens, positive staining for PRAME was only seen in malignant tumours; 7 of 11 histological types and 34/62 individual tumours were positive, while non-tumourous lesions were always negative. Pleuropulmonary blastoma (PPB) showed a continuum in staining, with type I lesions being PRAME negative (n = 7) but all type II and type III lesions PRAME positive (n = 7). Similarly, cystic nephroma (CN) was negative (n = 8), with anaplastic sarcoma of the kidney being positive (n = 2). However, one atypical CN with mesenchymal cell proliferation was PRAMEpositive. Embryonal rhabdomyosarcoma (RMS) with DICER1 pathogenic variants (PVs) was positive for PRAME (5/6), but the same tumour type without DICER1 PVs was also positive (9/15). Staining for EZH2 corresponded to that seen with PRAME, validating the latter. This study leads us to conclude that (1) PRAME expression occurs in two-thirds of DICER1-related malignancies; (2) PRAME may be a marker for the progression that certain DICER1-related lesions are thought to undergo, such as PPB and CN; and (3) PRAME expression in some tumours, such as RMS, appears to be an intrinsic feature of the tumour, rather than specifically related to DICER1 PVs. Therapy directed against PRAME may offer novel treatment options in patients with the DICER1 syndrome.

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

Cited by 83 publications

References 24 publications

Challenges in sentinel node pathology in the era of adjuvant treatment

Challenges in sentinel node pathology in the era of adjuvant treatment

PRAME expression in melanocytic proliferations with intermediate histopathologic or spitzoid features

PRAME protein expression in DICER1‐related tumours

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