Five novel mutations in SASH1 contribute to lentiginous phenotypes in Japanese families.

SASH1 has been reported as a causal gene of lentiginous phenotypes with and without heredity, including an autosomal dominant type characterized by lentigines predominantly on sun-exposed areas such as the face and limbs. Recently, cases of dyschromatosis with SASH1 mutations have been reported worldwide; however, only one case has been reported from Japan. Here, we analyzed six Japanese patients who characteristically showed many lentigines on sun-exposed areas, using next-generation sequencing. We identified five novel heterozygous mutations in SASH1 (p.I586M, p.S531Y, p.R644W, p.T525R, and p.S516I) in our patients and their families. The p.R644W substitution identified in two unrelated families was the first mutation located in the sterile alpha motif 1 (SAM1) domain. The degree and location of the lentigines were variable across individuals, even if they shared the same SASH1 mutation. All mutations were predicted to be deleterious by six different algorithms used to evaluate the functional impact of a variation. In addition, immunohistopathological findings and RNA sequencing results suggested that SASH1 mutations were associated with an increase in the number of melanocytes, acceleration of melanogenesis, and upregulated hair keratin expression.

The detection of Propionibacterium acnes signatures in granulomas of lupus miliaris disseminatus faciei.

Lupus miliaris disseminatus faciei (LMDF) is a papular eruption that occurs on adults' faces, predominantly on the lower eyelids. Histologically, the granulomatous lesions are primarily situated around the hair follicles, particularly the superficial region/infundibula. Its etiology remains to be elucidated. Recently, Propionibacterium acnes (P. acnes) has been suspected as a cause of sarcoidosis. In light of the sarcoid-like reactions that are present in LMDF, we hypothesized that P. acnes may also be implicated in granulomas associated with the disease. We evaluated nine DNA samples from granulomatous lesions from the skin of patients with LMDF. We used laser capture microdissection to extract DNA from these regions. Polymerase chain reaction was performed to amplify segments of the 16S ribosomal RNA of P. acnes, and the P. acnes gene was clearly detectable in all nine DNA samples. The gene was also detected in samples from normal-appearing skin, but these bands were faint in all samples. The results of the present study suggest that P. acnes plays a pathogenetic roles in LMDF.

Aggressive digital papillary adenocarcinoma on the palm with pulmonary metastases.

A 41-year-old Japanese male had aggressive digital papillary adenocarcinoma with pulmonary metastases. He had an asymptomatic, solitary, dome-shaped, skin-colored firm nodule on his left palm for half year. The tumor consisted of multiple lobules of anaplastic epithelial cells with central necrosis. The neoplastic cells were immunohistochemically positive for cytokeratin and S-100 protein. Two years after the lesion was removed, pulmonary nodular lesions were found on chest X-ray. On histopathological examination, the pulmonary biopsy specimens showed lobular proliferation of acantholytic tumor cells and some ductal structures associated with papillary projections. Five years after the initial removal of the lesion, the patient was referred to our hospital because of a recurrent skin nodule on his left palm. The recurrent skin tumor was found to have lobular proliferation of anaplastic cells. On immunohistochemistry, the pulmonary metastasis and the palmar skin nodules were identical. The tumor was diagnosed as an aggressive digital papillary adenocarcinoma. This report is a rare case of aggressive digital papillary adenocarcinoma that was diagnosed based on the histopathology of the pulmonary metastases, which showed ductal structures associated with papillary projections.

Primary mediastinal large B-cell lymphoma: a single-institution clinical study in Japan.

Several clinicopathologic studies of primary mediastinal large B-cell lymphoma (Med-DLBCL) have been reported from Western countries; however, only a few series of at most 10 cases are available in Japan. To further clarify the Med-DLBCL occurring in Japan, we analyzed the clinical features of 28 patients with Med-DLBCL diagnoses who were treated at the National Cancer Center Hospital between 1982 and 2002. The median age was 37 years (range, 18-80 years). The ages of 16 male patients ranged widely from 18 to 80 years, whereas the 12 female patients appeared to show a single age peak at 20 to 40 years. Only 13 patients (46%) achieved a complete response with initial treatments, mostly by CHOP-like regimens (cyclophosphamide, doxorubicin, vincristine [Oncovin], and prednisolone) followed by radiotherapy. The estimated 3-year overall and failure-free survival rates were 32% and 33%, respectively, indicating the relatively unfavorable prognosis of the patients in our series. The following factors were found to be significantly associated with shortened survival prospects: age >60 years, serum lactate dehydrogenase level greater than normal, performance status >1, and presence of bulky mediastinal mass. In conclusion, the clinical features of Japanese patients with Med-DLBCL may be different from those with the disease in Western countries. Because this investigation was a single-institution study with a limited number of patients, however, multicenter confirmatory studies are needed.

EBV-positive Burkitt lymphoma as a late-onset posttransplantion lymphoproliferative disorder after allogeneic stem cell transplantation.

Posttransplantation lymphoproliferative disorder (PTLD) is one of the well-recognized complications after allogeneic stem cell transplantation (SCT). It generally occurs early after SCT, and only a few reports of late-onset cases are available. We report a 58-year-old male patient who developed lymphoma 4 years after allogeneic SCT for chronic myeloid leukemia. The presence of c-myc translocation and Epstein-Barr virus-encoded RNA in the lymphoma cells, without rearrangement of the 3'-bcr region, confirmed the histopathologic diagnosis of Burkitt lymphoma. DNA chimerism analysis revealed that the lymphoma cells were of donor origin. The patient achieved complete response with intensive chemotherapy. To our knowledge, this is the first report of Burkitt lymphoma as a PTLD occurring after allogeneic SCT.

Enteropathy-type T-cell lymphoma showing repeated small bowel rupture and refractoriness to chemotherapy: a case report.

The majority of gastrointestinal lymphomas arise in the stomach, whereas lymphomas occurring in the intestine are relatively rare and a limited fraction of them show the T-cell phenotype with clinical manifestations similar to de novo celiac disease. Enteropathy-type T-cell lymphoma is extremely rare in Japan, presumably owing to the very low incidence of celiac disease among the Japanese population. Here, we report a 66-year-old Japanese male who was diagnosed as having enteropathy-type T-cell lymphoma preceded by diarrhea and intermittent bloody stool for over 1 year. He was admitted to our hospital as an emergency case because of panperitonitis due to intestinal perforation. After immediate partial small-bowel resection, cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy was started. However, the disease was highly refractory and was exacerbated with leukemic transformation. Subsequent salvage chemotherapy could not be completed because of the formation of spontaneous jejuno-abdominal fistula, followed by fatal septic shock. Particular attention should be paid to the peculiar clinical manifestations of enteropathy-type T-cell lymphoma such as malnutrition, frequent intestinal perforation and refractoriness to chemotherapy.