Distinction of Melanoma In Situ From Solar Lentigo on Sun-Damaged Skin Using Morphometrics and MITF Immunohistochemistry

Abstract

Distinction between melanoma in situ (MIS) and solar lentigo (SL) on chronically sun-damaged skin (CSDS) by hematoxylin and eosin (H&E) criteria alone can be difficult and in frozen section (FS) material, may be virtually impossible without immunohistochemistry (IHC). In this study, we used microphthalmia-associated transcription factor (MITF) IHC-directed image analysis to compare melanocyte nuclear morphometrics of MIS, SL, and sections of sun-damaged skin from redundant tissue acquired during Mohs micrographic surgery. The mean nuclear diameter and melanocytic density figures for MIS were greater than those for SL and CSDS by both independent t-test and analysis of variance statistics. No significant differences in these parameters were found between SL and sun-damaged skin. Cutoff values that favored MIS over SL included melanocyte density ≥10 nuclei per 200 μm, nuclear diameter ≥9 μm, and a product of density and diameter of 80 or more, as each of these values was associated with 100% specificity of MIS diagnosis. Our results suggest that image analysis of melanocytes labeled with MITF IHC can be used to produce morphometric data that distinguish MIS from SL and CSDS. The study was conducted using permanent sections, but previous studies with FSs indicate that the findings would apply to FSs as well. Quantitative assessment of melanocytic parameters using image analysis will likely become increasingly important as an adjunct to conventional histopathology for the diagnosis and surgical management of MIS on sun-damaged skin.

Diagnostic Utility and Comparative Immunohistochemical Analysis of MITF-1 and SOX10 to Distinguish Melanoma In Situ and Actinic Keratosis

“…In actinic keratosis, the melanocytes are concentrated on the tips of the rete ridges, spare the adnexa, are often increased in number but only occasionally display cytologic atypia. 9 On the other hand, the criteria in lentiginous melanocytic hyperplasia in chronic sun-damaged skin are not well defined; it may show effacement of rete ridges, lack symmetry, and often has markedly increased numbers of melanocytes with variable cytological atypia that is histologically similar to melanoma in situ. The use of immunohistochemical stains usually enhances identification of intraepidermal melanocytes at low power magnification; however, this assessment is precluded with the use of cytoplasmic staining melanocytic markers, such as MART-1, because of its extensive labeling of melanocyte dendrites and melanin uptake by adjacent keratinocytes.…”

“…9 As the diagnostic and treatment implications for these lesions are different, immunohistochemical markers are often employed to help assess the density of melanocytes and to differentiate melanoma from its mimics, which on small biopsies may be difficult to discern especially in cases exhibiting atypical melanocytic hyperplasia. 5,8,9 Several immunohistochemical studies, such as S100p, HMB-45, or MART-1, are routinely used to help differentiate melanocytes from adjacent keratinocytes. Nevertheless, the most commonly used adjunct immunohistochemical stain for the diagnosis of melanoma in situ probably is MART-1.…”

Lentigo Maligna and Lentigo Maligna Melanoma: Contemporary Issues in Diagnosis and Management

“…Melan A is more specific, but can fail to stain desmoplastic melanomas [22,23]. MITF, a nuclear stain, has been demonstrated to be useful in distinguishing LM from chronically sun-damaged skin, by demonstrating melanocytic nuclear density of greater than or equal to 9 μm [21]. Mel-5 has also been reported to have excellent efficacy and is thought to provide less collateral staining of nonmelanocytes when used in Mohs surgery as a rapid immunostain [18].…”

“…Additionally, early lesions often demonstrate quite subtle histologic changes. Distinguishing factors between chronically sun-damaged skin and LM include a higher density of melanocytes in LM [21].…”

Expression of Soluble Adenylyl Cyclase in Lentigo Maligna: Use of Immunohistochemistry With Anti–Soluble Adenylyl Cyclase Antibody (R21) in Diagnosis of Lentigo Maligna and Assessment of Margins

“…Pan nuclear staining is also observed in a subset of neoplastic cells in superficial spreading melanomas and nodular melanoma but not to the extent seen in the setting of lentiginous melanomas. These results suggest that, in contrast to the currently available “first generation melanocytic markers” such as S100, microphthalmia transcription factor (MITF) or Mart1/Melan A, 14–18 R21 immunohistochemistry can be used to distinguish melanoma from benign melanocytic proliferations and may be useful in the subclassification of melanoma.…”