Dermatofibrosarcoma protuberans. A study of 148 patients.

INTRODUCTION: Dermatofibrosarcoma protuberans (DFSP) is the most common sarcoma of the skin. Although distant metastases are infrequent, DFSP is highly aggressive locally with frequent local recurrences. It has been reported that the presence within the tumour of areas histopathologically mimicking fibrosarcoma may increase the risk of recurrence. OBJECTIVE: To review the clinical features of our patients with DFSP and the factors associated with recurrence of the tumour, focusing on the presence of fibrosarcomatous areas. METHODS: Retrospective study of patients with DFSP diagnosed in 1990-2021 in a tertiary university hospital. The medical records were reviewed to obtain the following data: age, sex, tumour location, diameter, and evolution time, presence of fibrosarcomatous areas, development of recurrence, and follow-up. Factors possibly associated with disease-free survival were analyzed with Kaplan-Meier method and multivariate Cox regression. RESULTS: 148 patients (74 women/74 men, mean age 46.28 years, SD 14.431) were included in the study. Tumours involved head and neck in 15 cases, thorax in 31, abdomen in 16, upper back in 43, lower back in 10, upper extremities in 10, and lower extremities in 23. Fibrosarcoma-like areas were observed in 16 tumours (10.81%) . In 17 patients (11.49%) recurrences were observed (13 local recurrences, 3 lung metastasis, and 1 local recurrence with lung metastasis). Fibrosarcomatous DFSP recurred more frequently than classic DFSP (50% vs. 6.82%, respectively), and its disease free survival was significantly lower (p<0.001). In multivariate Cox regression the presence of fibrosarcomatous areas was the only factor influencing disease free survival. CONCLUSIONS: It is important to identify the fibrosarcomatous variant since it recurs more frequently and has lower recurrence-free survival. Distant metastases, mainly in the lung, are also more frequent in fibrosarcomatous DFSP.

Molecular Profile of Subungual Melanoma: A MelaNostrum Consortium Study of 68 Cases Reporting BRAF, NRAS, KIT, and TERT Promoter Status.

BACKGROUND: Subungual melanoma (SM) is an unusual type of melanocytic tumor affecting the nail apparatus. The mutational prevalence of the most prominently mutated genes in melanoma has been reported in small cohorts of SM, with unclear conclusions on whether SM is different from the rest of melanomas arising in acral locations or not. Hence, the molecular profile of a large series of SM is yet to be described. OBJECTIVES: The aim of this study was to describe the molecular characteristics of a large series of SM and their association with demographic and histopathological features. METHODS: Patients diagnosed with SM between 2001 and 2021 were identified from six Spanish and Italian healthcare centers. The mutational status for BRAF, NRAS, KIT, and the promoter region of TERT (TERTp) were determined either by Sanger sequencing or next-generation sequencing. Clinical data were retrieved from the hospital databases to elucidate potential associations. RESULTS: A total of 68 SM cases were included. Mutations were most common in BRAF (10.3%) and KIT (10%), followed by NRAS (7.6%), and TERTp (3.8%). Their prevalence was similar to that of non-subungual acral melanoma but higher in SM located on the hand than on the foot. CONCLUSIONS: To date, this study represents the largest cohort of SM patients with data on the known driver gene mutations. The low mutation rate supports a different etiopathogenic mechanism for SM in comparison of non-acral cutaneous melanoma, particularly for SM of the foot.

Sarcoidosis Induced by Atezolizumab Presenting With Xanthelasma Infiltration.

ABSTRACT: Sarcoidosis induced by anti-PD1 or anti-PDL1 agents such as atezolizumab has recently been reported. It has been suggested that the predilection of sarcoidosis to affect scars is due to the presence of antigens or foreign bodies that can serve as a stimulus for granuloma formation. However, to the best of our knowledge, sarcoidosis-specific skin lesions have not to date been reported involving xanthelasma. We report a patient who developed specific lesions of sarcoidosis infiltrating some xanthelasmata 6 months after starting treatment with atezolizumab. A 69-year-old woman was referred to the dermatology department for infiltration of xanthelasmata. The patient was being treated with atezolizumab for metastatic uterine carcinosarcoma. Cutaneous biopsy from an infiltrated xanthelasma and from still yellow, no infiltrated xanthelasma showed differing proportions of foamy histiocytes and sarcoid granulomas. On physical examination, erythemato-marronaceous papules clustered on both knees, and not previously detected by the patient, were observed. The biopsy showed sarcoid dermal granulomas with foreign bodies. A chest computerized tomography scan was consistent with intrathoracic involvement of sarcoidosis. Endobronchial ultrasound-guided transbronchial needle aspiration of a mediastinal lymphadenopathy showed epithelioid cell granulomas. Histopathologically, the foamy histiocytes of xanthelasma seem to be replaced by or evolve to epithelioid cells to form sarcoid granulomas. The possible pathogenic mechanism is discussed. Dermatologists and dermatopathologists should bear in mind that sarcoidosis can present as infiltration of pre-existing xanthelasmata.