YAP1::MAML2 fusions in poromatosis: A report of two patients.

Poromatosis is a rare condition characterized by the development of multiple poromas, mainly reported in patients with a history of malignancy. Recently, frequent YAP1::MAML2 and YAP1::NUTM1 fusions have been described in poromas and porocarcinomas. To date, the molecular features of poromatosis have been investigated in one patient only, wherein the poromas harbored YAP1::MAML2 fusions. Herein, we present two additional cases of poromatosis with YAP1::MAML2 fusions. Case 1: An 81-year-old woman presented with nine papules on the scalp, trunk, and extremities persisting for a year. She had a history of breast cancer, with no information on the treatment. Seven papules were excised. Case 2: A 65-year-old woman presented with 21 lesions on her trunk and lower extremities persisting for 2 years. She had been diagnosed with breast cancer 11 years prior and had undergone partial mastectomy, radiotherapy, chemotherapy, and endocrine therapy. Four lesions were excised. All 11 lesions in both patients were histopathologically similar: anastomosing cords and strands extending from the epidermis, and poroid and cuticular cell proliferation with interspersed small ducts. The tumors showed diffuse nuclear expression of YAP1 N-terminus and loss of YAP1 C-terminus expression. No lesions showed NUT immunopositivity. Sanger sequencing identified YAP1::MAML2 fusions in the poromas of both patients.

Immunogenicity of varicella-zoster virus vaccine by different routes of administration: Comparable vaccination efficacy of one-fifth dose intradermal vaccination to conventional subcutaneous vaccination.

BACKGROUND: The live attenuated varicella-zoster virus (VZV) vaccine is used for the prevention of chickenpox and herpes zoster; however, there have been few studies on the immunogenicity of intradermal vaccination. OBJECTIVE: To compare the immunogenicity between subcutaneous and intradermal VZV vaccination. METHODS: Thirty healthy participants aged 50-75 who developed erythema less than 10 mm in diameter in VZV skin test were examined. Thirteen participants received full dose of VZV vaccine subcutaneously and 17 participants received one-fifth dose of vaccine intradermally. Immunogenicity to VZV was determined by VZV skin test reaction, proliferation of VZV-specific memory T cells, levels of VZV-specific serum antibody, and cytokine production from peripheral blood cells. RESULTS: VZV skin test reaction was similar between two groups. VZV-specific memory T cells were significantly increased only in the intradermal injection group. The increase of VZV-specific memory T cells correlated with Th1, Th2 and Th17 cytokines and cytotoxic molecules. No serious adverse events were observed in either group after vaccination. CONCLUSION: Intradermal injection with one-fifth dose VZV vaccine showed a similar or greater effect on VZV-specific cellular immunostimulation than conventional subcutaneous injection. These findings suggest that one-fifth dose intradermal vaccination may have a comparable preventive effect to conventional subcutaneous injection.

Serum Soluble OX40 as a Diagnostic and Prognostic Biomarker for Drug-Induced Hypersensitivity Syndrome/Drug Reaction with Eosinophilia and Systemic Symptoms.

BACKGROUND: Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe adverse drug reaction commonly associated with the reactivation of human herpesvirus 6 (HHV-6). There are currently no adequate biomarkers for the early diagnosis and detection of DIHS/DRESS. Notably, OX40 (CD134) has an important role in allergic inflammation and functions as a cellular receptor for HHV-6 entry. We previously reported that the membrane-bound form of OX40 in CD4+ T cells was upregulated in DIHS/DRESS. OBJECTIVE: We sought to investigate the clinical significance of serum soluble OX40 (sOX40) in DIHS/DRESS. METHODS: Serum sOX40 levels in patients with DIHS/DRESS (n = 39), maculopapular exanthema/erythema multiforme (n = 17), Stevens-Johnson syndrome/toxic epidermal necrolysis (n = 13), or autoimmune bullous diseases (n = 5), and levels in healthy volunteers (n = 5) were examined by enzyme-linked immunosorbent assay. Copy numbers of HHV-6, HHV-7, and cytomegalovirus in peripheral blood mononuclear cells were quantified using real-time PCR. RESULTS: Serum sOX40 levels in patients with DIHS/DRESS in the acute stage were elevated in parallel with high OX40 expression on CD4+ T cells. Serum sOX40 levels were significantly positively correlated with disease severity and serum levels of thymus and activation-regulated chemokine, IL-5, and IL-10. Human herpesvirus 6-positive patients had higher sOX40 levels than did HHV-6-negative patients, and serum sOX40 levels were correlated with HHV-6 DNA loads. CONCLUSIONS: Serum sOX40 levels can be a useful diagnostic marker for DIHS/DRESS that reflect disease severity. Elevated serum sOX40 levels also predict HHV-6 reactivation in patients with DIHS/DRESS.

Facial pustules due to drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms may histopathologically mimic eosinophilic pustular folliculitis: A case report.

Pustules with facial and/or neck edema is one characteristic feature of drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) at the early stage. Although several retrospective histopathologic studies on DIHS/DRESS have been reported, the detailed histopathologic findings of facial pustules for DIHS/DRESS are unavailable. We herein report a case of DIHS/DRESS with facial pustules that was histopathologically similar to eosinophilic pustular folliculitis (EPF). Eosinophilic infiltration into expanded follicles and sebaceous glands, which is highly characteristic of EPF, was detected in pustules due to DIHS/DRESS in this case. There are numerous pathophysiological similarities between DIHS/DRESS and EPF, which may cause their histopathologic similarity. Our findings suggest that facial pustules of DIHS/DRESS may histopathologically mimic EPF.