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      Staged Excision of Lentigo Maligna of the Head and Neck: Assessing Surgical Excision Margins With Melan A, SOX10, and PRAME Immunohistochemistry

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          Abstract

          Background:

          Staged excision has emerged as a superior treatment option for lentigo maligna (LM) of the head and neck when compared with conventional wide local excision. Assessing surgical excision margins for remaining LM poses a diagnostic challenge.

          Objectives:

          To determine whether immunohistochemical (IHC) staining with SOX10 and preferentially expressed antigen in melanoma (PRAME) aids in diagnosing LM on excision margins compared with conventional hematoxylin and eosin and Melan A IHC staining.

          Methods:

          This study included cases of LM of the head and neck treated with staged excision. Histological findings were reviewed according to standard criteria for the diagnosis of LM and compared with the results after IHC staining for Melan A, SOX10, and PRAME.

          Results:

          The cohort consisted of 35 sections. Based on hematoxylin and eosin and Melan A IHC staining, 23 sections were diagnosed as LM by the initial pathologist. Further staining with SOX10 IHC showed only 8 to be consistent with a diagnosis of LM and 9 revealing features of actinic melanocyte hyperplasia. PRAME was positive in 5 of the 8 cases of LM and negative in all 9 cases of actinic melanocyte hyperplasia ( P = 0.009). The presence of melanocyte nests ( P = 0.29) and pagetoid spread ( P = 0.003) was the most reliable histological findings distinguishing LM from its mimics.

          Conclusion:

          SOX10 is a more specific and sensitive marker for melanocytes when assessing for LM on excision margins compared with Melan A. The addition of PRAME can be useful to confirm or exclude the diagnosis in challenging cases.

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          Most cited references41

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          PRAME Expression in Melanocytic Tumors

          PRAME (PReferentially expressed Antigen in MElanoma) is a melanoma-associated antigen that was isolated by autologous T cells in a melanoma patient. While frequent PRAME mRNA expression is well documented in cutaneous and ocular melanomas, little is known about PRAME protein expression in melanocytic tumors. in this study we examined the immunohistochemical expression of PRAME in 400 melanocytic tumors, including 155 primary and 100 metastatic melanomas, and 145 melanocytic nevi. Diffuse nuclear immunoreactivity for PRAME was found in 87% of metastatic and 83.2% of primary melanomas. Among melanoma subtypes, PRAME was diffusely expressed in 94.4% of acral melanomas, 92.5% of superficial spreading melanomas, 90% of nodular melanomas, 88.6% of lentigo maligna melanomas, and 35% of desmoplastic melanomas. When in situ and nondesmoplastic invasive melanoma components were present, PRAME expression was seen in both. Of the 140 cutaneous melanocytic nevi, 86.4% were completely negative for PRAME. immunoreactivity for PRAME was seen, albeit usually only in a minor subpopulation of lesional melanocytes, in 13.6% of cutaneous nevi, including dysplastic nevi, common acquired nevi, traumatized/recurrent nevi, and Spitz nevi. Rare isolated junctional melanocytes with immunoreactivity for PRAME were also seen in solar lentigines and benign nonlesional skin. Our results suggest that immunohistochemical analysis for PRAME expression may be useful for diagnostic purposes to support a suspected diagnosis of melanoma. it may also be valuable for margin assessment of a known PRAME-positive melanoma, but its expression in nevi, solar lentigines, and benign nonlesional skin can represent a pitfall and merits further investigations to better assess the potential clinical utility of this marker.
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            The meaning of surgical margins.

            In an effort to define the pathological term surgical margins, 11 pathologists were interviewed regarding the meaning of the term margins. In addition, 25 plastic surgeons were queried regarding their decisions based on pathology reports of margins. We found nonuniformity of processing specimens and ambiguity in the use of the term close when describing specimen margins. Among the plastic surgeons there was also variability of opinion regarding handling of patients with pathology reports with close or involved margins and a lack of appreciation of the differences and the meanings of various methods of processing tissue.
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              Immunohistochemistry for PRAME in the distinction of nodal nevi from metastatic melanoma

              The distinction of metastatic melanoma from melanocytic nevi in lymph nodes can on occasion be difficult. Since diffuse immunohistochemical PRAME 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, while all melanoma metastases (15/15) were diffusely positive for PRAME immunohistochemistry (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.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                The American Journal of Dermatopathology
                Ovid Technologies (Wolters Kluwer Health)
                0193-1091
                2023
                February 2023
                December 7 2022
                : 45
                : 2
                : 107-112
                Affiliations
                [1 ]Division of Dermatology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Academic Hospital, Cape Town, South Africa;
                [2 ]Skinmatters Mohs and Reconstructive Unit, Club Surgical Centre, Hazelwood Pretoria and Summerhill Surgical Centre, Somerset West; and
                [3 ]Division of Anatomical Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University and National Health Laboratory Service, Tygerberg Academic Hospital, Cape Town, South Africa.
                Article
                10.1097/DAD.0000000000002354
                36669074
                f3fb5900-be54-4867-87b9-3fbe2a9cacbd
                © 2022
                History

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