Kana Yasukawa

Kikuchi's disease and the skin: case report and review of the literature

We report scattered indurated erythematous lesions that presented in an 18‐year‐old Japanese man with Kikuchis disease (KD; histiocytic necrotizing lymphadenitis). A skin biopsy showed a proliferation of histiocytes and abundant nuclear debris without the presence of neutrophils, which is characteristic of KD. The specific dermatological and pathological details of KD have been yet to be fully described. In order to assess the typical skin features of KD better, we have reviewed all the previously well‐documented reports of such lesions. As the clinical and histopathological cutaneous findings in KD are so heterogeneous, it is important that scattered indurated erythematous lesions should be included as one of the possible cutaneous manifestations of this disease.

Primary Cutaneous Adenoid Cystic Carcinoma With Lymph Node Metastasis

We report on a case of primary cutaneous adenoid cystic carcinoma with local recurrence and lymph node metastasis. The patient was a 52-year-old Japanese woman. The initial cutaneous lesion was a skin-colored, centrally elevated, thumb-sized nodule with hair loss on the scalp in the right side of the parietal region. Three and half years after the initial combined treatment consisting of surgery and irradiation, a recurrent nodule on the left side of the parietal region of the scalp and a lymph node metastasis with perinodal tissue involvement in the left retroauricular area were discovered. In the literature on primary cutaneous adenoid cystic carcinoma, the average age in the 37 cases reported, including the present case, is 58.1 years, and 23 of the patients are women. Thirty-two percent of the carcinomas (12 cases) occur on the scalp and 16% (6 cases) on the breast. The average size of the tumors in the 24 documented cases is 3.2 cm. The local recurrence rate is 51% (19 cases). Distant metastasis to the lungs and pleura are recorded in three cases. Lymph node metastasis is recorded only in two cases including the present case. Multiple modalities including surgery, irradiation, and chemotherapy should be used for this locally aggressive and potentially metastasizing carcinoma.

Dominant and Recessive Compound Heterozygous Mutations in Epidermolysis Bullosa Simplex Demonstrate the Role of the Stutter Region in Keratin Intermediate Filament Assembly

Keratin intermediate filaments are important cytoskeletal structural proteins involved in maintaining cell shape and function. Mutations in the epidermal keratin genes, keratin 5 or keratin 14 lead to the disruption of keratin filament assembly, resulting in an autosomal dominant inherited blistering skin disease, epidermolysis bullosa simplex (EBS). We investigated a large EBS kindred who exhibited a markedly heterogeneous clinical presentation and detected two distinct keratin 5 mutations in the proband, the most severely affected. One missense mutation (E170K) in the highly conserved helix initiation peptide sequence of the 1A rod domain was found in all the affected family members. In contrast, the other missense mutation (E418K) was found only in the proband. The E418K mutation was located in the stutter region, an interruption in the heptad repeat regularity, whose function as yet remains unclear. We hypothesized that this mutated stutter allele was clinically silent when combined with the wild type allele but aggravates the clinical severity of EBS caused by the E170K mutation on the other allele. To confirm this in vitro, we transfected mutant keratin 5 cDNA into cultured cells. Although only 12.7% of the cells transfected with the E170K mutation alone showed disrupted keratin filament aggregations, significantly more cells (30.0%) cotransfected with both E170K and E418K mutations demonstrated keratin aggregation (p < 0.05). These transfection assay results corresponded to the heterogeneous clinical findings of the EBS patient in this kindred. We have identified the first case of both compound heterozygous dominant (E170K) and recessive (E418K) mutations in any keratin gene and confirmed the significant involvement of the stutter region in the assembly and organization of the keratin intermediate filament network in vitro.

Leuprorelin acetate granulomas: case reports and review of the literature.

Summary  Leuprorelin acetate, an agonist of gonadotropin‐releasing hormone (GnRH), is indicated in the treatment of prostate cancer. Recently, depot formulations of leuprorelin acetate have been widely used. We report three patients who showed a granulomatous reaction after treatment using a leuprorelin acetate 3‐month depot formulation. These patients presented with 5–6‐cm subcutaneous nodules at injection sites, which developed after the depot type was changed from a 1‐month to a 3‐month formulation. Skin biopsy showed epithelioid cells and foreign body giant cells containing round, translucent microspheres which formed sarcoidal granulomas. Changing to other GnRH agonists resulted in no further problems. We have reviewed the previous reports of leuprorelin acetate‐induced granuloma formation. The formation of such granulomas may be related to the polymers that allow slow release after injection, or leuprorelin acetate itself may be responsible. The depot injection methods using leuprorelin also seem to have a causal effect in granuloma formation. Dermatologists need to know that depot leuprorelin acetate may cause a granulomatous reaction which produces a subcutaneous nodule that might be misdiagnosed as a malignant tumour.

Epidermolysis bullosa simplex in Japanese and Korean patients: genetic studies in 19 cases

Background  Epidermolysis bullosa simplex (EBS) comprises a group of hereditary bullous diseases characterized by intraepidermal blistering caused by mutations in either keratin gene, KRT5 or KRT14. Significant correlation between the position of mutations within these proteins and the clinical severity of EBS has been noted. A recent report showed EBS cases in Israel had unique genetic features compared with European or U.S.A. associated families, which suggests that the ethnic and geographical features of EBS patients may be different.

Genetic studies of 20 Japanese families of dystrophic epidermolysis bullosa

AbstractDystrophic EB (DEB) is clinically characterized by mucocutaneous blistering in response to minor trauma, followed by scarring and nail dystrophy, and is caused by mutations in the COL7A1 gene encoding type VII collagen. DEB is inherited in either an autosomal dominant (DDEB) or recessive (RDEB) fashion. DDEB basically results from a glycine substitution mutation within the collagenous domain on one COL7A1 allele, while a combination of mutations such as premature stop codon, missense, and splice-site mutations on both alleles causes RDEB. In this study, mutation analysis was performed in 20 distinct Japanese DEB families (16 RDEB and four DDEB). The result demonstrated 30 pathogenic COL7A1 mutations with 16 novel mutations, which included four missense, five nonsense, one deletion, two insertion, one indel, and three splice-site mutations. We confirmed that Japanese COL7A1 mutations were basically family specific, although three mutations, 5818delC, 6573+1G>C, and E2857X, were recurrent based on previous reports. Furthermore, the Q2827X mutation found in two unrelated families would be regarded as a candidate recurrent Japanese COL7A1 mutation. The study furthers our understanding of both the clinical and allelic heterogeneity displayed in Japanese DEB patients.

Subcutaneous nodules on the buttocks as a manifestation of dialysis‐related amyloidosis: a clinicopathological entity?

Summary  While β2‐microglobulin amyloidosis occurring in patients undergoing long‐term dialysis is frequently associated with joint involvement, skin lesions have rarely been encountered. We report a 57‐year‐old man with extensive subcutaneous amyloid deposition forming large nodules on the buttocks; the patient had been on maintenance dialysis for 28 years. Although this condition is rare, a review of the literature indicates that the majority of such lesions occur around the buttock region.

Metastatic Cutaneous Plasmacytoma: A Case Report Associated with IgA λ Multiple Myeloma and a Review of the Literature of Metastatic Cutaneous Plasmacytomas Associated with Multiple Myeloma and Primary Cutaneous Plasmacytomas

We present the case of a 67‐year‐old Japanese woman with immunoglobulin A lambda (IgA λ) multiple myeloma (MM). She had firm nodular cutaneous lesions on the trunk and scalp without adjacent bone involvement. The patient was diagnosed as having IgA λ MM of stage IIIA with 52% plasmacytosis in the bone marrow six months before the appearance of the cutaneous lesions. The abnormal plasma cells showed moderate to marked dysplasia in both the bone marrow and skin lesions. The abnormal plasma cells in the bone marrow exhibited abnormal karyotypes: 41, XX, der (1) t (1p; 1q), −4, −10, −14, −16, −17, 17p+, that differed from the “unfavorable” karyotype reported previously.

Penile hybrid verrucous-squamous carcinoma associated with a superficial inguinal lymph node metastasis.

A 62-year-old Japanese man who presented with penile carcinoma is reported. The initial exophytic neoplasm excised from the coronal sulcus and prepuce on the abdominal side of the penis was diagnosed histologically as verrucous carcinoma. Twenty-six months after the primary operation, an epithelial neoplasm recurred within the scar of the primary operation. The neoplasm histologically showed verrucous carcinoma and multiple invasive foci of conventional squamous cell carcinoma in the advancing edge of the tumor, as such representing a hybrid verrucous-squamous carcinoma. A lymph node metastasis in the left superficial inguinal lymph node occurred 4 months after the second operation. A total bilateral inguinal lymphadenectomy was performed and revealed no other lymph node metastases. The patient is alive without local recurrence or evidence of metastases in pelvic lymph nodes or visceral organs 2 years after the resection of the hybrid verrucous-squamous carcinoma. The initial verrucous carcinoma, recurrent hybrid verrucous-squamous carcinoma, and metastatic lymph node were negative for human papillomavirus DNA type 6, 11, 16, 18, and 33 sequences by dot blot hybridization of polymerase chain reaction products. The characteristics of hybrid verrucous-squamous carcinoma and importance of lymph node metastasis in penile carcinoma are discussed.

The spectrum of cutaneous lymphomas in Japan: a study of 62 cases based on the World Health Organization Classification

Background:  The relative incidence of malignant lymphoma subtypes differs according to geographic location. This study investigated the epidemiology of cutaneous lymphoma subtypes in Japan and compared it with other countries.