NONO::TFE3 fusion cutaneous epithelioid and spindle cell tumor: A case series.

The NONO::TFE3 fusion has been described in MiT family translocation renal cell carcinomas as well as extracutaneous perivascular epithelioid cell tumors (PEComas). PEComas are known to express myogenic and melanocytic markers but SOX10 and p63 positivity has never been reported. We report two primary cutaneous tumors that morphologically and molecularly fit PEComas, both harboring the NONO::TFE3 fusion, but with an unusual immunophenotype of SOX10 and p63 positivity. One case was on an 80-year-old male's finger, and the other one was on a 72-year-old female's thigh. Both were well-circumscribed multinodular dermal tumors composed of nests of monotonous epithelioid to spindled cells with pale to vacuolated cytoplasm, some of which were arranged around blood vessels. Both tumors were positive for SOX10, S100, and p63, focally positive for Melan-A, and negative for myogenic markers. There are very little data regarding the molecular findings of primary cutaneous PEComas. While the NONO::TFE3 fusion has been identified in extracutaneous PEComas, it has never been reported in primary cutaneous cases. We believe these cases represent a previously undescribed subtype of cutaneous tumor which shows some immunophenotypic expression of melanocytic markers and we named these cases NONO::TFE3 fusion cutaneous epithelioid and spindle cell tumor. Further, we raise the question of whether this tumor should fall under the rubric of PEComa because of its morphology, partial expression of melanocytic markers, and the presence of the NONO::TFE3 fusion, or whether these tumors represent a separate novel class of tumors since the immunophenotypic expression of SOX10 and p63 is unusual for PEComas.

Long-Term Efficacy of Dupilumab in Alopecia Areata.

BACKGROUND Dupilumab is a relatively new immune-modulating drug that has transformed the way clinicians treat common immunologic conditions, including atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis. Blocking signaling molecules involved within the Th2 immune response, dupilumab is a proven effective treatment for moderate to severe atopic dermatitis - a condition whose disease pathogenesis is heavily linked to the dysregulation of this immunologic pathway. Interestingly, dupilumab has found broader clinical utility, showing efficacy in treating other distinct dermatologic diseases, including alopecia areata. CASE REPORT A 16-year-old White male with a past medical history of moderate atopic dermatitis presented to our clinic with complete scalp hair, eyebrow, and eyelash loss. At this time, the patient was given a clinical diagnosis of alopecia totalis. Understanding that dupilumab has been previously used for treatment in adults of this specific autoimmune condition, we started this adolescent patient on dupilumab to concomitantly treat his atopic dermatitis and alopecia areata. The patient gradually experienced complete regrowth of his hair and almost complete resolution of his atopic dermatitis. Three years after starting dupilumab, the patient remains without signs of alopecia totalis. CONCLUSIONS This case report demonstrates the long-term efficacy of dupilumab use in alopecia areata. More investigation is required to understand dupilumab's broadening clinical indications. Additionally, this case highlights the complex relationship between dysregulation of the Th2 response and autoimmunity. Crosstalk between immune pathways within the disease spectrum of alopecia areata may explain why dupilumab has been reported to both treat and exacerbate alopecia areata.

High Estrogen States in Hereditary Angioedema: a Spectrum.

Sex differences have been well documented within hereditary angioedema (HAE) over the past several decades. Females often experience more frequent and more intense attacks compared to their male counterparts. Additionally, elevated estrogen levels-as seen in pregnancy and use of oral contraceptives-is a widely known trigger for angioedema attacks. In this review article, we will outline how estrogens' downstream effects increase bradykinin, a potent vasodilator and key mediator of HAE. Estrogen-dependent HAE is a rare disorder that provides insight into the relationship between HAE and estrogens. Females affected by this subtype of HAE only experience attacks when under "high estrogen states," such as during pregnancy and when taking exogenous estrogens (most commonly, oral contraceptives). This unique phenotype has been documented in individuals with an activating Factor XII mutation. Thus, based on this clear genotype-phenotype relationship, we conclude that Factor XII may be key in our understanding of estrogens' role in HAE. Lastly, we propose that the sex differences seen in HAE be viewed as a spectrum from exacerbation to underlying genetic mutations in Factor XII.