A Case of Vesiculobullous Dermatomyositis with Anti-NXP-2 Antibody without Malignancy.

Vesiculobullous dermatomyositis (VD) is a rare manifestation of dermatomyositis (DM) and has been suggested to be associated with malignancy. Although the myositis-specific autoantibodies are associated with distinct clinical presentations of DM, those associated with VD remain unclear. Here, we present the case of a 54-year-old man with VD who tested positive for anti-nuclear matrix protein 2 (NXP-2) antibody, one of the DM-specific autoantibodies. Serological and histopathological findings did not support autoimmune blistering disease. Physical and histological findings suggested that the severe edema in combination with the interface dermatitis of DM contributed to blister formation. Although a systemic examination was performed, no evidence of malignancy was found. Following initiation of immunosuppressive therapy, the patient showed significant improvement in both skin lesions and myositis. This case represents the first report of anti-NXP-2-positive VD without malignancy or autoimmune blistering disease. Subcutaneous edema, a characteristic feature of anti-NXP-2-positive DM, could be related to the formation of VD.

Proteasome inhibitor-associated histiocytoid Sweet's syndrome: Clinical and histological similarities to Nakajo-Nishimura syndrome suggest a potential mechanism.

Histiocytoid Sweet's syndrome (HSS) is a variant of Sweet's syndrome (SS) that clinically resembles SS but differs histologically by infiltrates, predominantly composed of immature cells of the myeloid lineage. Medications such as proteasome inhibitors have been reported to cause HSS but there has been little discussion on the underlying mechanism. Here we report two cases of HSS associated with a proteasome inhibitor. Both patients were on ixazomib for the treatment of multiple myeloma and presented with acute erythematous plaques on the upper half of the body. Pathological findings were consistent with HSS. Similarities between proteasome inhibitor-induced HSS and Nakajo-Nishimura syndrome, an inherited inflammatory disease, can be identified both clinically and histologically, suggesting a potential explanation of the mechanism behind proteasome inhibitor-associated HSS.

[Mononeuropathy multiplex caused by cutaneous arteritis diagnosed by skin biopsies for emerging atypical erythema on upper limbs following neurological symptoms: a case report].

A 33-year-old female was admitted to our department complaining of multifocal paresthesia and weakness of the upper and lower extremities that had developed over the previous three months. She had also been undergoing treatment for atopic dermatitis with dupilumab, an anti-interleukin 4/13 receptor antibody. A nerve conduction study revealed multifocal axonal sensorimotor neuropathy of bilateral limbs. On admission, a small erythema appeared on her right forearm, but it was atypical for vasculitic skin lesions due to its location and time course. Nonetheless, a biopsy revealed medium-sized vessel vasculitis. The patient was therefore diagnosed with vasculitic neuropathy caused by cutaneous arteritis. Methylprednisolone pulse therapy with prednisolone and azathioprine markedly improved her symptoms. A skin biopsy is useful when mononeuropathy multiplex is suspected, even if the skin findings are atypical for vasculitic rash.

Alopecia areata: What's new in the diagnosis and treatment with JAK inhibitors?

Alopecia areata (AA) affects individuals of all ages and is intractable in severe relapsing cases. Dermatologists and other healthcare providers should consider AA in the medical context and prioritize treatment. Several randomized controlled clinical studies on Janus kinase (JAK) inhibitors with different specificities for the treatment of AA are ongoing. These studies have encouraged us to appreciate the importance of a definitive diagnosis and accurate evaluation of AA before and during treatment. Following our previous review article in 2017, here we provide the second part of this two-review series on the recent progress in the multidisciplinary approaches to AA from more than 1800 articles published between July 2016 and December 2022. This review focuses on the evaluation, diagnosis, and treatment of AA. We also provide the latest information on the safety and efficacy of JAK inhibitors for the treatment of AA and describe their mechanisms of action.

Neutrophilic epitheliotropism, proposed as an auto-inflammatory condition of neutrophilic urticarial dermatosis including Schnitzler syndrome, is also observed in Japanese cases.

Schnitzler syndrome (SchS) is a rare autoinflammatory disease characterized by bone pain, recurrent fever, leukocytosis, and elevated C-reactive protein, along with an urticaria-like rash and monoclonal immunoglobulin (Ig)M or IgG gammopathy. Notably, the condition is distinguished by a relatively persistent recurrent urticarial-like rash. Histopathological features observed in the skin comprise diffuse neutrophil infiltration into the dermis, absence of dermal edema, and vascular wall degeneration, all of which classify SchS as a neutrophilic urticarial dermatosis (NUD). Accumulated histological data from skin biopsies of patients with NUD have revealed a sensitive histopathological marker for NUD, acknowledged as neutrophilic epitheliotropism, which has been proposed as reflecting an autoinflammatory condition. In this report, we present three SchS patients: two men (ages 55 and 68) and a woman (age 75), all displaying neutrophilic epitheliotropism in their skin biopsy specimens. Additionally, a review of eight previously reported SchS cases in Japan identified neutrophilic epithliotropism in five cases. These findings suggest that the inclination of neutrophils toward the epithelial tissue could aid in confirming diagnoses of NUD in most cases that need to be differentiated from conventional urticaria. Consequently, we emphasize that acknowledging neutrophilic epithelial predilection as a hallmark of NUD is critical for expediting early diagnosis and appropriate treatment for SchS.

Alopecia areata: What's new in the epidemiology, comorbidities, and pathogenesis?

BACKGROUND: Alopecia areata (AA) is a common, acquired, and nonscarring type of hair loss that affects people of every generation and is intractable in severe and relapsing cases. Patients with AA, especially those with greater scalp involvement, have poor health-related quality-of-life scores. PURPOSE: Following our previous review article in the April 2017 issue of the Journal of Dermatological Science, we aim to provide a pair of review articles on recent progress in multidisciplinary approaches to AA. MAIN FINDINGS: We found more than 1800 publications on AA from July 2016 to December 2022. CONCLUSIONS: In this review, we focused on the latest information on the epidemiology, comorbidities, and pathogenesis of AA.

Incidental finding of extramammary Paget's disease during active surveillance for early-stage prostate cancer in a prostate biopsy.

Introduction: Skin tissue contamination within transcutaneous visceral organ biopsies is seldom found. We encountered a rare case of extramammary Paget's disease incidentally diagnosed by prostate biopsy during active surveillance for prostate cancer. Case presentation: A 71-year-old Japanese patient was diagnosed with prostate cancer, and active surveillance was selected. After 1 year, prostate biopsy was performed by a transperitoneal approach, and 16 biopsy cores were taken. One biopsy core contained skin tissue showing extramammary Paget's disease. Careful skin examination confirmed the presence of an extramammary Paget's disease lesion in the left perineum, and curative surgical resection was performed. Recurrence and metastasis did not occur after 6 months of follow-up. Conclusion: Although the perianal region is a common site of extramammary Paget's disease, early-stage extramammary Paget's disease is often asymptomatic. Thus, during a transcutaneous biopsy, it is important to consider the appearance of the skin and the pathological features of migrating skin tissue.

Constant small-cell changes and variable LEF1 expression in DUSP22-rearranged primary cutaneous anaplastic large-cell lymphoma: Analysis of the repeated biopsies of three patients.

DUSP22-rearranged primary cutaneous anaplastic large-cell lymphoma (pcALCL) has a biphasic histological pattern defined by large dermal atypical lymphocytes and epidermotropic small lymphocytes resembling pagetoid reticulosis, but the positivity rate of the biphasic pattern in DUSP22-rearranged pcALCL is unknown. Immunohistochemically, LEF1 expression in >75% of tumor cells is associated with DUSP22-rearrangement (DUSP22-R) in systemic ALCL. However, whether this association applies to pcALCL remains unclear. To analyze these pathological clues for screening DUSP22-R, we reviewed 11 skin biopsies from three patients with DUSP22-rearranged pcALCL. All specimens showed a biphasic pattern, of which three showed nonpagetoid infiltration of the epidermis. In all lesions, small-cell changes of tumor cells were observed not only within the epidermis but also under the epidermis. LEF1 positivity rates varied by lesion (range: 30%-90%, mean: 59.6%) with only three patients expressing LEF1 in more than 75% of tumor cells. In conclusion, the biphasic pattern was a constant finding in DUSP22-rearranged pcALCL, but it was not always pagetoid reticulosis-like. The recognition of small-cell change outside the epidermis may be helpful in diagnosing DUSP22-rearranged pcALCL. However, LEF1 expression was variable and its diagnostic usefulness may be limited.

Cutaneous arteritis with intimal fibrin ring and immature myeloid cell infiltrate: lymphocytic thrombophilic arteritis or histiocytoid polyarteritis nodosa?

The ongoing debate on whether lymphocytic thrombophilic arteritis (LTA) is a separate disease or a type of polyarteritis nodosa (PAN) has yet to be settled. In this study, we analyzed the nature of infiltrating cells in LTA to resolve this controversy. Skin biopsies from five female patients (mean age 29.4 years, age range 16-45 years) diagnosed with LTA were immunostained for CD3, CD20, CD68, lysozyme, myeloid cell nuclear differentiation antigen, myeloperoxidase, and PU.1. Immunohistochemistry revealed that the majority of mononuclear cells in all five cases were not lymphocytes but myelomonocytic cells. Given that the infiltrating cells are of the myelomonocyte lineage including immature myeloid cells, PAN was deemed the more appropriate diagnosis for the five cases rather than LTA. Whether PAN with immature myeloid cells (histiocytoid PAN) is the same disease as conventional PAN with mature neutrophils requires further investigation.

Acute generalized exanthematous pustulosis during apalutamide treatment in a patient with prostate cancer.

Introduction: Acute generalized exanthematous pustulosis is a type of severe cutaneous drug adverse reaction. While apalutamide is known for its high incidence of cutaneous adverse events, it remains unknown whether acute generalized exanthematous pustulosis can develop during apalutamide treatment. Case presentation: A 72-year-old man with metastatic castration-sensitive prostate cancer developed small erythema on the face and trunk after 41 days of apalutamide treatment. Three days later, apalutamide was discontinued. However, 9 days after the discontinuation of apalutamide, the patient had a high fever with hemodynamic instability and showed diffuse erythema throughout the body with numerous small pustules. Skin biopsy revealed subcorneal and intraepidermal pustules admixed with many eosinophils, which led to the diagnosis of acute generalized exanthematous pustulosis. The skin rash improved in 14 days with systemic corticosteroid administration. Conclusion: We present the first case of a skin rash with clinical features of acute generalized exanthematous pustulosis during apalutamide treatment.

Maturing papillomatous nevoid melanoma in the scalp mimicking recurrent melanocytic nevus: A case report of previously undescribed subtype of nevoid melanoma.

Nevoid melanoma is a subtype of melanoma that histologically resembles a melanocytic nevus. Two subtypes have been proposed for nevoid melanoma, namely papillomatous and maturing. Here, we report the case of a 67-year-old woman who developed two nevoid melanomas on her scalp with composite histological features of papillomatous and maturing subtypes after electrocautery of a nearby solitary scalp papule. The histology of both lesions was very similar, papillary in shape, and both comprised two melanocyte populations, including large atypical melanocytes and small non-atypical melanocytes. Whole-exome sequencing was performed in one of the two lesions, which revealed a high mutation burden (17 mutations/megabase) with co-deletion of CDKN2A. Additional immunohistochemistry revealed that the large and small melanocytes in both lesions were completely negative for p16 and MTAP. A final diagnosis of nevoid melanoma was made. To our knowledge, this is the first report of a nevoid melanoma with both features of papillomatous and maturing subtypes. Pathologists should be aware of this subtype of melanoma to avoid misdiagnosis as a mitotically active melanocytic nevus. In this case, immunohistochemistry for p16 and MTAP, in addition to molecular analysis, helped in the final diagnosis.

Giant Pilomatrical Tumor With Broad Epidermal Components: An Example of Histological Diversity and a Potential Diagnostic Pitfall of Tumors With Pilomatrical Differentiation.

ABSTRACT: The diagnosis of pilomatricoma, the most common matrical tumor, is generally straightforward; however, it exhibits diverse histology associated with various morphological stages and several clinical variants, and matrical differentiation can occur in various neoplastic diseases. A 56-year-old man was admitted to our hospital to resect an 11.0-cm skin tumor on his right shoulder. Because of its large size and surface irregularities, including multiple erosions and ulcers, cutaneous malignancies were clinically suspected. Histologically, the tumor formed numerous nodules with marked matrical differentiation in the superficial to deep dermis. Although the tumor was macroscopically asymmetrical and irregular, each nodule was microscopically round-shaped and consisted of basaloid cells without marked atypia, atypical mitoses, or lymphovascular invasion. Immunohistochemically, the tumor cells were positive for beta-catenin, LEF-1, and PHLDA-1, consistent with their pilomatrical differentiation. We diagnosed the case as a giant pilomatrical tumor with uncertain malignant potential, considering its "contradictory" features, namely, the worrisome histoarchitecture, such as the asymmetrical silhouette, but bland-looking cytological appearance. Unlike typical pilomatrical tumors, this tumor contained numerous epidermal components with features similar to those of the dermal components, resulting in a unique macroscopic and histological appearance. Our case broadens the known histological diversity of pilomatrical tumors.