A 64-year-old Japanese woman wasreferred to uswith erosionson the lipsand erythematous macules on the trunk and extremities. She had undergone right lateral temporal bone resection,postoperative radiation therapy, and chemotherapy for the right external auditory canal cancer one year before. The eruptionsoccurred 12 daysafter administering nivolumab for recurrence. The eruptions were diagnosed as nivolumab-induced Stevens-Johnson syndrome, an immune-related adverse event with clinical and histopathological features. The lesions were cured after applying steroid pulse therapy, plasma exchange, and intravenous immunoglobulin. To date, six cases of Stevens-Johnson syndrome and one case of toxic epidermal necrosis due to nivolumab have been reported in Japan. To prevent poor prognosis due to nivolumab-associated immune-related adverse events, immediate diagnosis and intensive treatment are required. It would be necessary to accumulate similar case series to establish appropriate management for nivolumab-induced severe immune-related adverse events. Skin Research, 21 : 1-5, 2022

A 77-year-old woman presented with painful erythematous nodules on the anterior aspect of the right lower limb. They regressed by topical corticosteroids without ulceration ; however, shortly afterwards, new similar lesions appeared on the medial aspect nearby the previous lesions. They progressed to the posterior aspect and became refractory. A skin biopsy revealed lobular granulomatous panniculitis without caseous necrosis. She had a past medical history of pulmonary tuberculosis 27 years ago. She underwent an interferon-gamma release assay test and a tuberculin reaction test, both of which were positive. Although active tuberculous lesions were not found in other organs, she was treated with tuberculostatic drugs in consultation with pulmonologists. The lesions showed a good clinical response and regressed in about 3 months. Therefore, she was diagnosed with erythema induratum of Bazin (EI). Recently, reports of atypical cases of EI are increasing in Japan. It is suspected that this trend may be related to an increase in the aging population of patients and changes in their immune status by immunosuppressant and underlying diseases. In the present study, the atypical clinical presentation was associated with the advanced age and the medical history of the patient, as she had developed malignant tumors twice in the past. Furthermore, the diagnosis and recovery were delayed because the lesions were unilateral and seemed to be in a remission. Therefore, it is crucial to be familiar with characteristics of EI,including atypical cases, for early intervention. Skin Research, 21 : 6-9, 2022

We experienced two cases of multiple basal cell carcinomas (BCCs) in proximity to one another on one side of the neck. Both patients were referred to us on suspicion of malignant melanoma with intransit metastases. In the first case, we were unable to distinguish the lesions from malignant melanoma preoperatively. They were found to be BCCs after resection of all the lesions as a single mass. As we experienced the first case and some of the lesions of the second case were superficial ones, we diagnosed the lesions of the second case as BCCs. Multiple BCCs in proximity should be recognized as a disease that requires differentiation from malignant melanoma with in-transit metastases. Skin Research, 21 : 10-14, 2022

A 66-year-old Japanese man had well-defined erythema and erosions on the left inguinal and the scrotum 10 years before. He visited his local doctor and was diagnosed with extramammary Paget’s disease (EMPD) by skin biopsy. The patient underwent tumor resection with a 1-cm margin and lymphadenectomy in the left inguinal region at our hospital. Histopathological examination revealed a diagnosis of EMPD pT2N2M0 Stage IIIb. One year and 3 months after surgery, FDG-PET/CT showed intra-abdominal metastasis, and monthly docetaxel therapy was initiated. No visceral metastasis was found ; however, dysarthria and dyskinesia of the left upper extremity were observed after 34 courses of monthly docetaxel treatment. Contrast-enhanced magnetic resonance imaging showed a solitary mass, which was clinically diagnosed as a brain metastasis of EMPD. Craniotomy and brain tumor resection were performed, because it was a solitary mass and he was suffering from neurological symptoms. His neurological symptoms improved after the surgery. We summarize previous case reports of EMPD with brain metastasis and discuss whether craniectomy and brain tumor resection are effective for improving quality of life in these patients. Skin Research, 21 : 15-19, 2022

Abstract : An 88-year-old man presented with an erythematous nodule measuring 25×20 mm on his right cheek at the initial examination, which was noticed 2 months previously. It was histopathologically diagnosed as diffuse large B-cell lymphoma (DLBCL). Immunohistological examination revealed that the nodule was double-expressor lymphoma positive for bcl-2 and c-myc with a poor prognosis. Fluorodeoxyglucose-positron emission tomography/computed tomography revealed another lymphoma lesion in the maxillary paranasal sinus. Based on these results and due to his old age, hematologists in our hospital judged that standard combination chemotherapy for DLBCL was not suitable for him. However, due to the rapidly growing nodule, he had difficulty opening his right eye. Thus, oral administration of low-dose etoposide and surgical resection of the tumor was performed as palliative care. He received additional radiation therapy on his cheek and maxillary paranasal sinus. Thereafter, although some lesions in the maxillary paranasal sinus remain, he is alive with good performance status, showing no recurrence of lymphoma on his cheek. Surgical resection may be a treatment option for localized cutaneous lesions, although DLBCL is high grade and shows poor prognosis markers. Skin Research, 21 : 20-26, 2022

Case 1 : A 70-year-old man presented with a painful nodule on his right shoulder. The lesion, 30 cm in diameter, was characterized by a dark red necrotic plaque that was surrounded by numerous pus-filled bumps. The patient was diagnosed with a carbuncle, admitted, and treated with infusion antibiotic therapy. On the 13th day after admission, the patient underwent tissue debridement. From the 20th to the 30th day post-admission, he received negative pressure wound therapy with instillation therapy and dwelling time (NPWT-id), followed by a full-thickness skin graft. Eighty days after admission, complete epithelialization had occurred. Case 2 : A 74-year-old man presented with a lesion that was similar to Case 1. A dark red necrotic carbuncle, 23 cm in diameter, was on his left shoulder and was surrounded by numerous pus-lled bumps. After admission, the patient underwent the same treatment plan : antibiotic infusion, debridement, NPWT-id, and a full-thickness skin graft. Eighty days after admission, epithelialization was complete. Previous studies reported that the majority of patients with large carbuncles also had severe diabetes. For this reason,patients with these lesions tend to experience severe symptoms and require early treatment. In recent years, NPWT has become the preferred treatment for large-sized carbuncles. However, the disadvantage of NPWT is that it cannot be performed until the infection is controlled. By including instillation therapy and dwelling time to NPWT, we were able to provide a rapid approach to both wound healing and infection treatment. Both patients experienced wound healing with good granulation tissue formation within a short period of time. NPWT-id is an effective method of treatment for large carbuncles. Skin Research, 21 : 27-33, 2022

A 69-year-old womanwas referred to us for erythema and bullae onthe upper extremities and the back that appeared a month before. Oral antibiotics prescribed by a local dermatologist under the putative diagnosis of infectious impetigo were ineffective. Physical examination revealed erosions,crusts, and pigmentation associated with faint erythema, and tense bullae on the back and upper extremities. Skinbiopsy revealed subepidermal bullae with regenerated epidermis. The direct immunofluorescence of the skin sample disclosed linear deposition of C3 at the dermo-epidermal junction. Chemiluminescent enzyme immunoassay (CLEIA) for BP180 NC16A, desmoglein-1, and desmoglein-3, and enzyme-linked immunosorbent assay (ELISA) for BP230 showed negative results ; however, ELISA for the full-length BP180 triplet was positive. Immunoblotting using human epidermal extracts as substrate uncovered positivity at 230 kDa BP230. The patient had been taking oral dipeptidyl peptidase-4 (DPP-4) inhibitors for 4.5 years (linagliptin for 2 years and then teneligliptin for 2.5 years). Oral prednisolone (15 mg/day) and minocycline (50 mg/day) were started, and teneligliptin was stopped nine days later. As the eruption showed remarkable improvement, the prednisolone was tapered off at day 50 after the first visit. No recurrence of bullous disorder was observed. The DPP-4 inhibitor-associated bullous pemphigoid (DPP-4i-BP) is reported to be relatively mild, often negative for anti-BP180 NC16A autoantibodies in CLEIA/ELISA,and sometimes positive for the full-length BP180 triplet. In addition, anti-BP230 antibodies were positive only by immunoblotting. Previous studies reported that the anti-BP230 antibodies may be associated with blistering in mice and human ; thus, further study is required to elucidate the role of anti-BP230 antibodies in DPP-4i-BP. Skin Research, 21 : 34-38, 2022

Abstract : A 71-year-old woman noticed a cutaneous tumor on her right axilla about 30 years before the first visit, and underwent tumor resection performed by her local doctor 12 years previously. Although the tumor recurred a year later, she received no additional treatment. Chest computed tomography was performed for cough, which showed multiple nodules in her bilateral lungs. Histological examination of a biopsy specimen from the cutaneous tumor on the axilla revealed adenoid cystic carcinoma. Thus, she was referred to our hospital. On her first visit, she presented with a red tumor measuring 45×30 mm on her right axilla. We diagnosed her with primary cutaneous adenoid cystic carcinoma with local recurrence and metastasis of not only lymph nodes but also bilateral lungs. We performed surgical resection of the cutaneous tumor as palliative care and treated the lung metastasis with docetaxel for 1 year. Afterward, due to the development of a serious urinary tract infection and the gradual expansion of lung metastasis despite chemotherapy,docetaxel treatment was ceased, and only follow-up observation was performed without additional treatment. She died of adenoid cystic carcinoma 5 years after the first visit. Primary cutaneous adenoid cystic carcinoma is a relatively rare disease and has a better prognosis than adenoid cystic carcinoma arising from salivary gland. However, previous studies reported primary cutaneous adenoid cystic carcinomas with local recurrence and distant metastasis similar to our case. Local recurrence and distant metastasis sometimes develop after more than 5 years. Thus, we should treat primary cutaneous adenoid cystic carcinoma with resection with enough surgical margin and careful observation for a long period. Skin Research, 21 : 39-45, 2022

We report a case of Rosai-Dorfman disease (RDD). A 62-year-old Japanese male noticed a subcutaneous mass on the neck six months prior to his first visit. He was examined byhis family doctor because of subcutaneous masses on the chest and back. The familydoctor took a skin excision, which revealed large foamy histiocytes in the dermis. Large histiocytes were diffusely infiltrated and emperiporesis, in which morphologicallypreserved leukocytes are trapped in the cytoplasm of histiocytes, was observed. The patient was referred to our department for suspicion of RDD. On his first visit to our department, two subcutaneous masses on the right upper arm were excised under local anesthesia for diagnostic purposes. Histopathological examination revealed similar histological findings as those of his previous doctor. From the deep dermis to the fat tissue,S-100 and CD68 stain showed positive, and CD1a stain showed negative histiocytes. The results of these immunohistochemical tests were consistent with RDD. The diagnosis was confirmed. The patient is currentlybeing followed up every3 months, and has passed 2 years without organ compression or airwayinvolvement. In the cases reported between 2014 and 2019 in Japan, about half of the cases were in women aged 45 years or older and skin lesion was found in 20%, followed by the neck lesion in 15%. In the U.S.A., RDD is often reported to occur at a young age ; however, in Japan, there are manyreports of elderlypatients with RDD ; thus, there maybe racial or regional differences. This present patient is a rare case of systemic RDD in Japan. Skin Research, 21 : 46-52, 2022