The Accuracy of Detecting Melanoma on Frozen Section Melanoma Antigen Recognized by T Cells 1 (MART-1) Stains and on Permanent Sections of Previously Frozen Tissue: A Prospective Cohort Study.

To the Editor: Mohs micrographic surgery (MMS) for melanoma is controversial because of concerns about the accuracy of detecting melanoma on frozen sections. This study's primary analysis examined the sensitivity and specificity of detecting melanoma using hematoxylin and eosin (H&E) and melanoma-associated antigen recognized by T cells (MART-1) frozen sections compared with permanent sections. The secondary analysis evaluated whether frozen section specimens can be subsequently processed for permanent sections without diminishing diagnostic accuracy. This Institutional Review Board-approved prospective study enrolled consecutive consenting adults (aged >18 years) with biopsy-proven in situ or invasive melanoma treated with MMS with frozen section MART-1 immunohistochemical stains (MMS-IHC) from 2016 to 2018. All melanomas were excised with a previously published MMS-IHC protocol.1Etzkorn J.R. Sobanko J.F. Elenitsas R. et al.Low recurrence rates for in situ and invasive melanomas using Mohs micrographic surgery with melanoma antigen recognized by T cells 1 (MART-1) immunostaining: tissue processing methodology to optimize pathologic staging and margin assessment.J Am Acad Dermatol. 2015; 72: 840-850Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar Two opposing vertical sections were isolated from the melanoma debulking excision (Fig 1) . One specimen (frozen-to-permanent) was processed for frozen sections, then thawed and processed for permanent sections. The opposing study specimen (direct-to-permanent) was immediately fixed in formalin for permanent sections. All frozen sections were stained with both H&E and MART-1 and were evaluated by a single Mohs micrographic surgeon. All permanent sections were stained with H&E, but MART-1 was ordered at the discretion of the dermatopathologist. Permanent sections were evaluated by 1 of 5 dermatopathologists, who were blinded to the interpretation of the Mohs micrographic surgeon and whether or not the specimen had been previously frozen. Pathologic interpretations were categorized into 4 groups: (1) malignant; (2) benign; (3) qualified malignant; (4) qualified benign (see Supplemental Table I for definitions, available via Mendeley at https://data.mendeley.com/datasets/hrjjcr43nx/1). A positive result (melanoma detected) was defined as diagnosis of “malignant” or “qualified malignant.” A negative result (melanoma not detected) was defined as diagnosis of “benign” or “qualified benign.” Tissue samples from 169 consecutive patients, comprising 119 melanoma in situ (70.4%) and 50 invasive melanomas (29.6%) were evaluated (Table I). The primary analysis showed that the Mohs micrographic surgeon detected melanoma on frozen sections (test specimen) with a sensitivity of 95.3% (95% confidence interval [CI], 89.6%-98.1%) and a specificity of 95.1% (95% CI, 82.2%-99.2%) compared with the dermatopathologist's permanent section interpretation of the same study specimen (frozen-to-permanent; gold standard) (Fig 1).Table ICharacteristics of the study cohortVariable∗Data are presented as number of patients (%) or as mean (range).Number of Patients (%) (N = 169)Sex Male104 (62) Female65 (38)Age, y67.7 (37-101)Preoperative diagnosis Melanoma in situ119 (70)Lentigo maligna type65Superficial spreading1Acral lentiginous1Not specified52 Invasive melanoma50 (30)Lentigo maligna30Superficial spreading14Nodular3Not specified3Depth of invasion, mm <141 1-27 >2-41 Not specified1Anatomic location Head and neck147 (87) Hands or feet5 (3) Pretibial leg4 (2.3) Trunk or extremity (nonacral, non-pretibial)13 (7.7)∗ Data are presented as number of patients (%) or as mean (range). Open table in a new tab The secondary analysis showed that dermatopathologists detected melanoma on the frozen-to-permanent sections (test specimen) with a sensitivity of 98.3% (95% CI, 93.6%-99.7%) and a specificity of 89.6% (95% CI, 76.6%-96.1%), compared with their own interpretation of the direct-to-permanent sections (gold standard) (Fig 1). Of the 15 total discordant diagnoses from both analyses, 12 involved specimens with a qualified diagnosis, indicating the challenge of diagnosing these specimens (Supplemental Fig 1). This study shows that Mohs micrographic surgeons detect melanoma on H&E and MART-1 frozen sections with high accuracy compared with dermatopathologists' interpretation of permanent sections. It also shows that dermatopathologists detect melanoma on permanent sections of previously frozen tissue with high accuracy compared with specimens sent directly for permanent sections. Therefore, Mohs micrographic surgeons can thaw challenging frozen sections for second opinions with diagnostically accurate permanent sections. Diagnostic discordances are expected for challenging melanocytic tumors.2Piepkorn M.W. Longton G.M. Reisch L.M. et al.Assessment of second-opinion strategies for diagnoses of cutaneous melanocytic lesions.JAMA Netw Open. 2019; 2: e1912597Crossref PubMed Scopus (15) Google Scholar, 3Santillan A.A. Messina J.L. Marzban S.S. Crespo G. Sondak V.K. Zager J.S. Pathology review of thin melanoma and melanoma in situ in a multidisciplinary melanoma clinic: impact on treatment decisions.J Clin Oncol. 2010; 28: 481-486Crossref PubMed Scopus (57) Google Scholar, 4Gonzalez M.L. Young E.D. Bush J. et al.Histopathologic features of melanoma in difficult-to-diagnose lesions: a case-control study.J Am Acad Dermatol. 2017; 77: 543-548.e1Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar Although this study is limited by its single-center design, it demonstrates that MMS-IHC is a reliable technique to detect melanoma. It supports the use of MMS-IHC for precise microscopic margin-directed excision of in situ and invasive melanoma. None disclosed.