Recalcitrant Cutaneous Mastocytosis Treated With Genetically Informed Targeted Therapy: A Case Report.

Mastocytosis, a clonal proliferation of mast cells commonly involving the skin and bone marrow, has a varied clinical presentation ranging from cutaneous lesions to systemic disease. Cutaneous mastocytosis is managed symptomatically, but systemic mastocytosis is treated with targeted therapy against the mutated receptor tyrosine kinase c-KIT, the pathogenic driver of mastocytosis. However, there are no guidelines for the treatment of cutaneous mastocytosis refractory to symptomatic management. We herein report a method to select genetically informed therapy for symptomatic and recalcitrant cutaneous mastocytosis. Case presentation: We performed a mutational analysis of dermal mast cells after enrichment by laser capture in a 23-year-old woman with recalcitrant cutaneous mastocytosis. The analysis revealed a aspartic acid to valine substitution at codon 816 (D816V) mutation in the protein c-KIT. Based on these results, we initiated treatment with the multi-kinase/KIT inhibitor midostaurin, a treatment effective against the D816V c-KIT mutation. After 3 months of treatment, the patient exhibited a reduction in the number and size of cutaneous lesions and reported resolution of pruritus and decreased severity of other mast cell-related symptoms. Discussion: The treatment of mastocytosis relies heavily on whether the disease is limited to the skin or systemic. However, there are no guidelines for cutaneous mastocytosis that does not respond to symptomatic management. In the present report describing a patient with recalcitrant cutaneous mastocytosis, we describe a strategy in which skin mutational analysis is used to guide the selection of targeted therapy. Conclusion: Performing mast cell mutational analyses in the skin provides a means to select targeted therapy for symptomatic and refractory cutaneous mastocytosis.

Dermal fibroblasts promote cancer cell proliferation and exhibit fibronectin overexpression in early mycosis fungoides.

BACKGROUND: Mycosis fungoides (MF) is caused by proliferation of malignant T-cells in the skin and may progress to involve blood, lymph nodes, and viscera. While the skin microenvironment is essential for the initiation and progression of MF in early stages, little is known about the impact of skin stroma on the growth and survival of malignant lymphocytes. OBJECTIVE: We investigated the effect of dermal fibroblasts and their product, fibronectin, on the survival and proliferation of malignant MF cells. METHODS: Fibroblasts and malignant MF CD4 T-cells were isolated from skin of patients with early-stage MF. Fibroblast-lymphocyte co-culture experiments and lymphocyte cultures on fibronectin-coated plates were established utilizing the cells derived from lesional skin, blood, and MF cell lines. The survival and proliferation rates of lymphocytes were assessed via Annexin V and carboxyfluorescein succinimidyl ester assays respectively. Additionally, integrin and fibronectin expressions in MF skin were assessed via immunofluorescence. RESULTS: We found that dermal fibroblasts increased the proliferation rates of MF cells, but not normal skin or blood CD4 T-cells. However, fibroblasts did not rescue MF cells from apoptosis in co-cultures. In MF skin, we found an overexpression of a fibronectin isoform not normally found in healthy skin. MF cells expressed fibronectin-binding integrins and adhered to fibronectin but did not exhibit adhesion-mediated survival via fibronectin-integrin interactions. CONCLUSION: Overall, our results suggest a direct role for fibroblasts, independent of fibronectin-mediated adhesion, in promoting MF cell proliferation. These findings have implications in understanding and targeting the malignant skin stromal microenvironment in cutaneous lymphomas.

Erbium:YAG laser augments the penetration of cryotherapy.

Cryotherapy is commonly used during dermatologic practice. Several modifications such as an "add-on" to topicals or intralesional applications have been already defined to enhance efficacy. The aim of this study is to test our hypothesis that ablative laser application before cryotherapy would increase the depth of freezing.Throughout this experiment, target points received either cryotherapy alone or a combination of erbium:yttrium-aluminum garnet (erbium:YAG) laser and cryotherapy. Freezing durations of 10 (C10), 20 (C20), and 30 seconds (C30) were investigated. Erbium:YAG laser groups received equal high energy shots with different pulse durations (100 µs versus 1500 µs) before freezing. The treatment points were arranged on the peripheral side of porcine skin specimens, and dermoscopic images revealing the iceball visible from the lateral side were immediately captured. Repeated experimental results were compared by Wilcoxon's test. The comparison of the vertical length of the iceball between the three different freezing durations of 10 seconds, 20 seconds, and 30 seconds was statistically significant (p<0.05). The vertical length of the iceball was higher in both laser groups receiving 30-second freezing (mean ± SD: 4.32±0.53, 3.9±0.38 for micro-short pulse (MSP) and extra-long pulse (XLP), respectively) when compared with 30-second freezing alone (mean ± SD:3.51±0.44) (p=0.016). The two laser settings did not reveal a difference for the penetration of 30-second freezing (p=0.122). In this study, through visual monitorization of the iceball, erbium:YAG laser is found to augment the penetration of cryotherapy. The defined combination regimen has the potential to ameliorate treatment outcomes of cryotherapy.

Acrochordons and autoimmunity: Significance of preconceptional counseling.

BACKGROUND: Acrochordons are benign hypertrophic lesions of the skin of which the pathophysiology is unclear. OBJECTIVE: This study aimed to examine the association of acrochordons with autoimmune disorders in patients with a poor obstetric history. METHODS: This retrospective cohort involved 350 female patients with poor obstetric history who were included in a preconceptional care program to investigate risk factors for obstetric complications. These patients were further investigated for the co-existence of autoimmune disorders (defined by either a diagnosis of autoimmune diseases or autoimmune antibody positivity) and acrochordons. RESULTS: An autoimmune disorder was present in 55.7% (195/350) of the patients. The rate of acrochordons was significantly higher in patients with autoimmune disorders (n= 195) compared to the control group (n= 155) (8.21% versus 2.58%, respectively) (p= 0.043). When the autoimmune disease positive (n= 58) and autoimmune antibody-positive (n= 137) groups were separately analyzed, acrochordons were found more frequently in the autoimmune disease group (p= 0.004). However, there was no statistically significant co-occurrence of autoimmune antibody positivity and the presence of skin tags (p= 0.135). CONCLUSION: There may be immune system-related biological mechanisms underlying the pathogenesis of acrochordons. Preconceptional counseling is beneficial for women with poor obstetric history and acrochordons.

Sparsity of dendritic cells and cytotoxic T cells in tumor microenvironment may lead to recurrence in basal cell carcinoma.

BACKGROUND: Antitumor immune response affects tumor growth. The effect of antitumor immune response on recurrence has been poorly studied in basal cell carcinoma (BCC). OBJECTIVES: To investigate the effects of the peritumoral immune infiltrate on BCC recurrence. METHODS: A total of 30 BCC patients without recurrence and 29 BCC patients with recurrence were included in this retrospective study. Non-recurrent tumor samples as well as primary and recurrent tumor samples from the recurrent group were stained immunohistochemically with anti-CD4, CD8, CD25, FOXP3, CD68, CD163, and CD1a antibodies. Immune infiltrates were semiquantitatively evaluated. RESULTS: BCC tumor microenvironment was rich in CD4+ cells. CD163 expression was higher than CD68. In primary tumors of the recurrent group, CD8 expression was significantly lower than CD4 expression. CD1a expression was lower in primary tumors of the recurrent group than in nonrecurrent tumors. CONCLUSIONS: Our results suggest the existence of an immunosuppressive microenvironment in BCC. Lower CD8+ T-cell numbers and sparsity of dendritic cells in primary tumors of recurrent patients suggest further immunosuppression in the tumor microenvironment and an increase in recurrence risk. This is the first study that evaluates and compares tumor immune microenvironments of primary and recurrent BCC lesions with several markers and investigates the role of antitumor immunity on BCC recurrence.

Clinical characteristics of pediatric hidradenitis suppurativa: a cross-sectional multicenter study of 140 patients.

Hidradenitis suppurativa (HS) rarely affects pediatric patients. The literature on pediatric HS patients is scarce. This is a cross-sectional study based on case note review or interviews and clinical examination of 140 pediatric patients undergoing secondary or tertiary level care. Patients were predominantly female (75.5%, n = 105) with a median age of 16. 39% reported 1st-degree relative with HS. Median BMI percentile was 88, and 11% were smokers (n = 15). Median modified Sartorius score was 8.5. Notable comorbidities found were acne (32.8%, n = 45), hirsutism (19.3%, n = 27), and pilonidal cysts (16.4%, n = 23). Resorcinol (n = 27) and clindamycin (n = 25) were the most frequently used topical treatments. Patients were treated with tetracycline (n = 32), or oral clindamycin and rifampicin in combination (n = 29). Surgical excision was performed in 18 patients, deroofing in five and incision in seven patients. Obesity seemed to be prominent in the pediatric population and correlated to parent BMI, suggesting a potential for preventive measures for the family. Disease management appeared to be similar to that of adult HS, bearing in mind that the younger the patient, the milder the disease in majority of cases.

Secondary Cutaneous Dissemination of Peripheral T-Cell Lymphoma With T-Follicular Helper Phenotype as a Patient's Fourth Primary Malignancy.

Peripheral T-cell lymphomas expressing follicular helper T-cell (TFH) markers have recently been identified. Although this type of lymphomas consist of malignant proliferation of T-cells, they may also exhibit B-cell clonality. We report a case of a 72-year-old woman with multiple erythematous to violaceous nonscaling plaques and tumors on her trunk. Histopathological analysis revealed a dense infiltration of medium-to-large-sized atypical cells throughout the entire dermis. The result of immunohistochemical analysis showed that the infiltrating T-cells expressed programmed death-1 (PD-1), CD10, Bcl-6, CD3, CD4, CD2, and CD5. The infiltrate also contained scattered atypical large B-cells. Based on the clinical appearance and the histopathological findings, we diagnosed the patient with secondary cutaneous dissemination of peripheral T-cell lymphoma with expression of a T-follicular helper phenotype.