Sclerozing melanocytic lesions, characterized by either focal or diffuse sclerosis of the dermal component, often with atypical intraepidermal melanocytic proliferation, with an adjacent ordinary dermal nevus, and in most of the cases nevoid morphology of the melanocytes, remain poorly characterized, in particular, the distinction between the sclerosing nevus and melanoma. Attributed to atypical morphology, sclerosing lesions tend to be over diagnosed as melanomas. On the other hand, only sclerosing melanocytic lesions from the less atypical part of the spectrum, with an accompanying nevus have been analyzed in the previous studies. The entire morphological spectrum of sclerosing melanocytic lesions has not been well documented. Our goal was to analyze systematically the morphological spectrum of the sclerosing melanocytic lesions, in particular the distinction between sclerosing nevus and melanoma. With use of the fluorescence in situ hybridization (FISH), we wanted to confirm that both, the sclerosing nevi and sclerosing melanomas are part of the spectrum of the sclerosing melanocytic lesions.
We prospectively collected 90 sclerosing melanocytic lesions in 82 patients (49 men, 33 women, aged from 21 to 89 years). Additional diagnostic investigations were performed retrospectively, when we re-evaluated all the lesions. Based on the morphological features and proliferation activity, determined by a double Ki67/Melan A immunohistochemical staining, and the expression of HMB-45 in the sclerotic part, without knowing the results of the FISH analysis. On re-evaluation, 26 (29% ) lesions were diagnosed as nevi, 19 (21%) as melanomas and 45 (50%) melanoma with an accompanying nevus. In comparison to the original histopathological diagnoses, we reclassified 8 lesions, originally diagnosed as melanomas (without or with an accompanying nevus) as nevus.
The largest lesion diameter was from 2 to 29 mm (median, 9.0 mm; average, 9.7 mm). There was no history of prior trauma or local treatment for any of the lesions. In 13 patients (15.9%), including three patients with multiple sclerosing melanocytic lesions, at least one non-sclerosing superficial spreading melanoma was found. The sclerosis was diffuse in 93 (43%) and focal in 51 (57%) cases; in these later cases, an ordinary nevus was found beneath or adjacent to the sclerotic part. The thickness of the sclerosis ranged from 0.3 to 1.8 mm (median, 0.7 mm). The depth of invasion of 63 invasive melanomas ranged from 0.4 to 1.8 mm (median 0.75 mm) and in 62 (98%) of the cases it corresponded to the thickness of the sclerosis. Pronounced pagetoid spread of melanocytes in the entire thickness of the epidermis above the sclerosis was present in 1 of 26 (4%) nevi and 43 of 64 (67%) of melanomas, with or without an accompanying nevus. Melanoma in situ outside the sclerosis was present in 55 of 64 (86%) melanomas and in none of the nevi. Within sclerosis, maturation was absent in 25 (96%) nevi and 25 (39%) melanomas. Multifocal irregular positivity of HMB-45 in the sclerosis was present in 6 of 19 (32%) nevi and in 31 of 41 (76) melanomas. There were no Ki67-positive nuclei in 15 of 19 (79%) nevi and 16 of 47 (34%) melanomas in the sclerotic component.
The FISH analysis with four probes for diagnosing melanoma (RREB1, MYB, CEP6, CCDN1) was performed in 41 cases in the sclerotic section; it was positive in 14 of 25 lesions (56%) that were morphologically diagnosed as melanomas and in none of the 16 nevi. The FISH results did not differ significantly in relation to the proliferative activity. The FISH analysis was positive in 6 of 8 (75%) lesions without proliferative activity in the sclerotic section and morphologically diagnosed as melanoma. The FISH analysis was negative in all 6 nevi originally diagnosed as melanomas, in which the FISH analysis was performed. During follow-up period (median follow-up of disease recurrence of 19 months and median follow-up of the oveall disease specific survival of 77 months), no progression of the disease that could be attributed to the sclerosing lesions occurred in any of the cases.
The morphological spectrum of sclerosing melanocytic lesions is wide and includes both nevi and melanomas. Most of the lesions meet morphological criteria for the diagnosis of melanoma, in particularly the presence of melanoma in situ outside the sclerosis and marked pagetoid spread above sclerosis, which, in our view, are the most important criteria for the diagnosis of sclerosing melanoma. The FISH results confirm that sclerosing lesions also include melanomas. Due to the diagnostic complexity, some of the sclerosing nevi are incorrectly diagnosed as melanomas in routine practice. According to the results of our study, we propose that FISH analysis with four probes should be included in the diagnostic workup of ambuiogous sclerosing melanocytic lesions. A positive FISH result favors the diagnosis of sclerosing melanoma. In the case of a negative result, a lesion should be labelled on morphological grounds as a "sclerosing melanocytic lesion of unknown malignant potential, more likely a nevus " or "sclerosing melanocytic lesion of unkonown malignant potential, more likely a melanoma."
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