Prognosis of CDKN2A germline mutation in patients with familial melanoma: a systematic review and meta-analysis.

Familial melanoma is defined as melanoma occurring in two or more first-degree relatives by the WHO. Germline mutations are isolated in a subset of them. It is well known that CDKN2A is the most frequently mutated high-risk gene in familial melanoma, however, the prognosis it confers to patients who carry its mutations is still controversial. This review aims to assess whether germline mutations imply a worse prognosis in patients with familial melanoma. A systematic review and meta-analysis were conducted by searching the electronic databases PubMed/MEDLINE, EMBASE, and Cochrane Library. Data from 3 independent populations were eventually included in the meta-analysis, involving 291 cases and 57 416 controls. The results of this systematic review and meta-analysis suggest that there is a tendency for patients with germline mutations in the CDKN2A gene to have a worse overall survival (HR = 1.30, 95% CI = 0.99-1.69, P  = 0.05) and melanoma-specific survival (HR = 1.5, 95% CI = 0.97-2.31, P  = 0.07). Carrier patients would not only have more incidence of melanoma and a higher risk of a second melanoma, but they also seem to have a worse prognosis. The inclusion of gene panel testing in clinical practice and the collaboration within consortia are needed to provide further evidence on the prognosis of these patients.

Emerging subcutaneous mycoses by opportunistic filamentous fungi: A retrospective study in Northwest Spain.

BACKGROUND: Subcutaneous mycoses caused by opportunistic filamentous fungi are emerging infections in developed countries due to the longer survival of immunocompromised patients. The evidence published in relation to subcutaneous mycoses is fundamentally based on case reports and small case series. METHODS: We performed an observational retrospective study of subcutaneous mycoses caused by opportunistic filamentous fungi diagnosed at our institution between 2017 and 2022. This study aims to estimate the incidence rate of subcutaneous mycoses, identify which fungal species are involved, and analyse which clinical variables predispose to infection and if any are associated with mortality. RESULTS: Fifteen patients met the inclusion criteria. The median age was 61 years (range 27-84), and 80% of them were males. Alternaria spp. were the most common fungi. Two other organisms were frequently isolated: Scedosporium apiospermum and Fusarium solani. Among patients infected with F. solani, 66.7% died. The most common clinical presentation was suppurative nodules in the lower limbs and the main risk factors for infection were immunosuppressants, corticosteroids, previous trauma and transplantation, but they were not particularly associated with increased mortality. A statistically significant association with mortality was only found in the case of positive blood culture (p = <.001). CONCLUSIONS: Phaeohyphomycosis has a lower risk of dissemination, especially when compared to subcutaneous mycoses caused by hyalohyphomycetes. It is important to convey the severity of these skin infections to the physicians involved in the treatment and follow-up of susceptible patients to avoid misdiagnosis and delays in the treatment, especially in the case of hyalohyphomycosis.

Treatment Options for Multinucleate Cell Angiohistiocytoma: A Case Series and Review of the Literature.

BACKGROUND: Multinucleate cell angiohistiocytoma (MCAH) is an unusual fibrohistiocytic proliferation in the dermis with vascular hyperplasia. Numerous clinicopathological studies of MCAH have been published, but little has been written in relation to treatment. OBJECTIVES: The aim of the present study is to review the therapeutical approaches for MCAH in the literature and to report the results of the different therapies followed at our institution. METHODS: A literature review was conducted including all MCAH published cases that followed any therapy. Search terms included "multinucleate cell angiohistiocytoma" or "MCAH" and "treatment" or "therapy". Also, all cases of MCAH treated at our institution from 2010 to 2020 are reported. RESULTS: The literature search revealed 16 cases of MCAH treated with any of the therapeutic options. At our institution, 9 patients have been treated of MCAH between 2010 and 2020. Over 75% of them were female, and the median age was 56 years (range 47-73). More than 50% had lesions on the dorsum of the hands. Surgical excision was indicated in 2 patients, ablative CO2 laser was used in 1 patient and the 6 remaining ones followed vascular-targeted therapies (PDL and IPL). A satisfactory cosmetic result was achieved in all of them. CONCLUSIONS: We propose PDL therapy as a first-line treatment for MCAH since it achieves satisfactory esthetic results, while being well-tolerated. Selecting those amenable patients according to morphologic characteristics may be useful to avoid unsuccessful therapies. In MCAH with predominant fibrous stroma, surgery or CO2 laser may be the best option.

PUVA therapy in persistent cutaneous histiocytosis: Case report and literature review.

BACKGROUND: Cutaneous and mucocutaneous histiocytosis (group C) comprise a wide variety of entities affecting skin and/or mucosae. Although they are considered as reactive proliferations, their exact pathophysiology remains unknown and, therefore, they lack a specific treatment. AIMS: The aim of this study is to review the evidence on cases of histiocytosis treated with UVB and/or UVA and to report a new case of relapsing group C histiocytosis that has been successfully treated with PUVA therapy. MATERIALS & METHODS: We have conducted a review of the literature published over the last 40 years on the treatment of histiocytosis with phototherapy in the online PubMed database. We also describe a new case of successful treatment of histiocytosis with PUVA therapy. RESULTS: Our patient was a 27-year-old man with persistent outbreaks of cutaneous histiocytosis over the previous 8 years. He responded successfully to PUVA therapy, and no relapse has been detected after one year of follow-up. DISCUSSION: Self-involution is usual in group C histiocytosis, so conservative management is usually the first approach. Relapsing cases pose a therapeutic challenge. Reported treatment options for these patients include isotretinoin, cryotherapy, immunosuppressants, low-dose chemotherapy, CO2 laser, radiotherapy, and surgery. Phototherapy and photochemotherapy have been used in a small number of patients with considerable success. The main limitation to provide firm recommendations on histiocytosis therapy is the absence of solid evidence, as the articles published are mainly case reports with a short follow-up. In our patient, despite the short follow-up we have considered photochemotherapy to be effective since no spontaneous remission had been achieved in the previous 8 years. CONCLUSION: PUVA therapy could be a safe and effective option to treat persistent cutaneous manifestations in patients with histiocytosis, although more evidence is required to support this statement.

Treatment of progressive nodular histiocytosis: a case report.

Background: Progressive nodular histiocytosis (PNH) is an extremely rare type of non-Langerhans cell histiocytosis, characterized by the emergence of hundreds small to large cutaneous papulonodules without spontaneous remission. It can be life-threatening if pharyngeal and laryngeal mucosa were involved, just as we reported in this case. Disfigurement and disabling are common, whereas current treatment options are of limited efficacy. At present, about 20 reported cases can be found through a PubMed search, fewer with treatment options. In this article, we report a unique case of a patient diagnosed with PNH, in whom regorafenib had a remarkably curative effect. Case Presentation: We present the case of a 21-year-old man who developed lesions on his face, trunk, limbs, and exceptionally in the pharyngeal and laryngeal mucosa. Immunohistochemistry showed diffuse CD68 positivity and scattered S-100 positivity, while CD1α, smooth muscle actin (SMA) and B-Raf proto-oncogene, serine/threonine kinase (BRAF) were negative. Histopathological and biochemical examinations confirmed the diagnosis of PNH. The patient underwent facial lesion resections; however, the lesions recurred rapidly within 1 month. In December 2019, treatment with a small multi-kinase inhibitor, regorafenib (120 mg daily for 3 weeks on, and 1 week off), was initiated, and the patient's progress was monitored. After 10 days of administration, the patient's facial lesions began to gradually alleviate, and after 1 month, the lesions in the trunk, limb, and especially the face continued to subside even further. In 2021, the regorafenib dose was subsequently adjusted to 40 mg daily, with intermittent administration. No abnormalities were observed in the routine blood tests, liver, and kidney function results during the follow-ups to date. Presently, the patient's overall condition is good, the lesions are gradually improving, and the patient has returned to normal life and work. Conclusions: This clinical report supports the future exploration of regorafenib treatment in patients with PNH.