Lymphomatoid papulosis types D and E: a multicentre series of the French Cutaneous Lymphomas Study Group.

BACKGROUND: Lymphomatoid papulosis (LyP) type D (LyP D) and type E (LyP E) have recently been described in small series of cases or isolated case reports. AIM: To further describe the clinical and histological features of LyP D and E based on a retrospective multicentre study. METHODS: The clinical and histopathological features of 29 patients with an initial diagnosis of LyP D or LyP E were retrospectively assessed using standardized forms. RESULTS: After exclusion of 5 cases, 24 patients (14 LyP D, 10 LyP E) were enrolled in the study. The median follow-up was 2.5 years (range 1 month to 13 years). LyP D was characterized by multiple recurrent self-regressing small papules that developed central erosion or necrosis, whereas LyP E presented as papulonodular lesions that rapidly evolved into necrotic eschar-like lesions > 10 mm in size. Epidermal changes were more frequent in LyP D, whereas dermal infiltrates were deeper in LyP E. Anaplastic cytology was rare and the DUSP22 rearrangement was never observed. Two patients (8%) had an associated cutaneous lymphoma. CONCLUSION: LyP D and E have distinct clinical findings and may be associated with other cutaneous lymphomas.

Evaluation of large clinically atypical vulvar pigmentation with RCM: atypical melanosis or early melanoma?

BACKGROUND: Vulvar melanosis can occasionally be clinically challenging by mimicking an early melanoma. OBJECTIVE: To report our experience of initial evaluation and follow-up in this peculiar subset of vulvar melanosis using reflectance confocal microscopy (RCM). METHODS: We retrospectively evaluated 18 consecutive cases referred for atypical vulvar pigmentation or for which melanoma was considered and that underwent both RCM examination and histopathological assessment. In 13 cases with available dermoscopic pictures, RCM classification was compared to dermoscopic diagnosis, and in all cases, the density of melanocytes was evaluated on biopsies using MelanA immunostaining. RESULTS: Among the 18 atypical pigmented lesions, 17 vulvar melanosis and one melanoma were histologically determined. RCM concluded a benign vulvar melanosis in 10 of 17 cases, whereas dermoscopy did so in three of 12 cases. RCM identified the only early malignant lentiginous melanoma. In several cases of vulvar melanosis, RCM could identify foci of melanocytic hyperplasia in an otherwise benign pattern. CONCLUSIONS: In this clinically and dermoscopically challenging subset of vulvar pigmentations, RCM appears relevant for initial extensive evaluation, especially to target initial biopsy sampling, and to perform non-invasive monitoring of foci of melanocytic hyperplasia.

[Zosteriform cutaneous metastasis in melanoma]. / Mélanome avec métastases cutanées zostériformes.

INTRODUCTION: Cutaneous metastases are common in patients with malignant melanoma. In rare cases, they are distributed on a dermatome, in which case they are known as zosteriform metastases. OBSERVATION: We report the case of a patient with zosteriform metastasis of a malignant melanoma, progressing unfavourably despite surgical excision and immunotherapy. DISCUSSION: The physiopathology of this condition continues to be poorly understood.

Predictors of responses to immune checkpoint blockade in advanced melanoma.

Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we retrospectively observed, in eight cohorts enrolling 190 MMel patients treated with ipilimumab, that PD-L1 expression on peripheral T cells was prognostic on overall and progression-free survival. Moreover, detectable CD137 on circulating CD8+ T cells was associated with the disease-free status of resected stage III MMel patients after adjuvant ipilimumab + nivolumab (but not nivolumab alone). These biomarkers should be validated in prospective trials in MMel.The clinical management of metastatic melanoma requires predictors of the response to checkpoint blockade. Here, the authors use immunological assays to identify potential prognostic/predictive biomarkers in circulating blood cells and in tumor-infiltrating lymphocytes from patients with resected stage III melanoma.

Mucosal melanoma: clinical, histological and c-kit gene mutational profile of 86 French cases.

BACKGROUND: Mucosal melanomas are rare and highly aggressive tumours. Few studies evaluated mucosal melanomas of locations other than the head and neck region, and other than those of the Asian population. OBJECTIVES: The objective of this study was to analyse the clinical and histological features, as well as the mutational status of c-kit and b-raf gene of mucosal melanoma in any localization in a French series. METHODS: We investigated clinical (sex, age, performance status, survival, treatment of the patients and lack of pigmentation of the tumours) and histopathological features (ulceration, Breslow's index, mitotic rate), as well as the mutational status of c-kit and b-raf of 86 mucosal melanomas diagnosed in 15 years in four French University Hospitals. RESULTS: Most melanomas affected women (72%) and the genital region (46.5%). A fifth of melanomas were amelanotic. 81% of melanomas had a Breslow's index ≥1, whereas all glans melanomas, and most vulvar melanomas had a Breslow index ≤1 mm. Overall survival was 54% at 3 years; 11.6% of the 43 tested mucosal melanomas were c-kit-mutated while the 15 tested genital melanomas were not. The c-kit gene mutation did not influence the overall survival. Age ≥ 50, amelanotic type and performance status ≥1 were not poor prognostic factors in our series. CONCLUSION: This study confirmed that mucosal melanomas are rare and could be difficult to diagnose being often amelanotic and in hidden sites. Most melanomas were thick at the diagnosis, but glans and vulvar melanomas were thinner probably because of their greater visibility. The frequency of the c-kit mutation varied depending on the initial tumour site. In our series, the prognosis was poor, independently from c-kit mutations and the patient's general health and age. The presence of metastasis at diagnosis was associated with a worse prognosis indicating the importance of an early diagnosis.

[Malignant transformation of an eccrine spiradenoma]. / Transformation maligne d'un spiradénome eccrine.

INTRODUCTION: Malignant eccrine spiradenoma is a rare and aggressive tumor, developed on the epithelium of eccrine sweat glands. Typically, it occurs after malignant transformation of benign eccrine spiradenoma, but sometimes it happens de novo. OBSERVATION: We report a case of malignant eccrine spiradenoma in a 62-year-old woman. The patient presented a rapid increase in size of a long-standing tumoral lesion of her forearm. There was no secondary lesion on the chest, abdomen or pelvis at the CT-scanner. Cutaneous biopsy of the lesion was performed and showed a carcinoma with no contact with epidermis. On this biopsy, we could not affirm if the tumor was a metastatic process or a primary tumor of the skin. Histologic examination of the surgical removal of the tumor showed an undifferentiated carcinoma with adjacent nodules of eccrine spiradenoma. Immunohistochemical assessment of Ki67 expression showed a weak expression (5%) in the benign spiradenoma nodules and a high rate expression (80%) in the malignant neoplasm. The final diagnosis was an undifferentiated carcinoma arising from preexisting benign spiradenoma. DISCUSSION: Malignant eccrine spiradenoma is not frequent and is rarely described in the international literature that may lead to diagnostic difficulties.

Comparative histological analysis of drug-induced maculopapular exanthema and DRESS.

BACKGROUND: Cutaneous adverse drug reactions frequently present as a benign maculopapular exanthema (MPE) with a rapid healing. Sometimes systemic signs are present, which could represent a more severe or systemic MPE (sMPE) or even be the initial phase of a drug reaction with eosinophilia and systemic symptoms (DRESS). Histopathology associated with MPE, sMPE and DRESS has not been well characterized. OBJECTIVES: To study the cutaneous histopathological changes associated with MPE, sMPE and DRESS. METHODS: A retrospective clinicopathological analysis of 13 cases of MPE, 13 of sMPE and 45 of DRESS, collected in one centre from 2005 to 2013. RESULTS: The number of histopathological changes per section increased gradually from MPE to sMPE and DRESS. Prevalence of spongiosis, dermal lymphocytes, eosinophils and neutrophils did not differ between MPE, sMPE and DRESS. Keratinocyte damage, rare in MPE, was regularly found in sMPE and frequent in DRESS. The density of the inflammatory infiltrate increased progressively from MPE to sMPE and DRESS. Atypical lymphocytes were absent in MPE, present in sMPE and more frequent in DRESS. Deep dermal involvement and leukocytoclastic vasculitis were only observed in DRESS. LIMITATIONS: This was a retrospective study. CONCLUSIONS: Numerous histopathological changes per section in drug-induced exanthema should alert for a more severe form of cutaneous adverse drug reactions, i.e. DRESS.