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Immune checkpoint inhibitors (ICI), including monoclonal antibodies to programmed death 1, programmed death ligand 1, and cytotoxic T lymphocyte-associated antigen 4, have provided great therapeutic benefits for cancer patients at advanced stages. However, the introduction of ICI frequently results in the development of immune-related adverse events (irAE) through activation of autoreactive T cells. Here, we present three cases of cancer patients with cutaneous irAE, including development of de novo psoriasis and exacerbation of pre-existing psoriasis. Interestingly, these patients shared an altered histological feature characterized by loss of epidermal CD1a

A 76-year-old man was admitted to our hospital with Guillain-Barré syndrome (GBS), presenting with facial palsy, dysarthria, and dysphagia as Grade 3 immune-related adverse events (irAEs) due to pembrolizumab administration for Stage IV lung adenocarcinoma. Although prednisolone (1 mg/kg) was started for GBS due to the irAE, dark erythema and skin eruptions appeared on the patient’s torso. Then erosion was observed on 18% of the body surface area and skin biopsy was performed. Finally, the patient was diagnosed with Stevens-Johnson syndrome/toxic epidermal necrosis overlap. Intravenous immunoglobulin therapy was started, and the skin symptoms improved, with the erosion becoming epithelial. He died of aspiration pneumonia related to GBS, although his neurological symptoms had improved after steroid and intravenous immunoglobulin therapy. This is the first reported case of pembrolizumab-induced GBS and Stevens–Johnson syndrome/toxic epidermal necrosis overlap. It is necessary to be careful that the possibility of other severe irAEs may occur simultaneously.

A 32-year-old Japanese man presented to our hospital with a 5-month history of painful nodules on the fingers. He had previously developed left atrial myxoma followed by cerebral embolism and had undergone resection of the cardiac tumor 4 months before his first visit. His family history was unremarkable. Physical examination showed subcutaneous nodules 4 to 17 mm in size on all finger pads (Figure 1A and 1B). The tumors were smooth and as hard as cartilage. Hand radiographs showed irregularly shaped subcutaneous calcification corresponding to the nodules (Figure 2), and postoperative examination of the 3-dimensional computed tomographic reconstruction indicated the tumors more clearly (Figure 3). Physical examination and diagnostic imaging detected no tumors in other sites, including the lower extremities. The blood test results, including endocrine examination, were unremarkable. Figure 1. Subcutaneous nodules on all finger pads: the left …

Background Bullous pemphigoid (BP) is the most common autoimmune blistering disease. BP180 is the primary autoantigen of BP, and in a portion of BP cases, BP230 is the only target of autoantibodies. Such BP is called BP230-type BP. BP230-type BP tends to show milder clinical phenotypes than conventional BP, but the reason is unclear. The pathogenic roles of autoantibodies and complement activation have been shown in conventional BP, but the distribution of IgG subclasses and the degree of complement deposition in BP230-type BP remain unclear. Objective To compare the distribution of IgG subclasses and the degree of complement deposition in BP230-type BP with those in conventional BP with autoantibodies to BP180 and BP230 (BP180-BP230-type BP). Methods The diagnosis of BP was confirmed by the histopathology of the lesions, the deposition of IgG and complement in the perilesional skin and the presence of circulating autoantibodies to BP180 and BP230. The disease severity was determined by bullous pemphigoid disease area index. The deposition of IgG subclasses and complement deposition were examined by direct immunofluorescence of the perilesional skin in 6 BP230-type BP cases and 11 BP180-BP230-type BP cases. Results Sixty seven percent of BP230-type BP cases show a mild clinical phenotype. All BP230-type BP cases and 82% of BP180-BP230-type BP cases were found to demonstrate the clear deposition of IgG4 at the basement membrane zone of skin specimens. Notably, the deposition of IgG1 and IgG3 was faint or negative in all of the BP230-type BP cases, whereas they were clearly detected in 91% and 64% of the BP180-BP230-type BP cases, respectively. The deposition of complement C3 tended to be weaker in BP230-type BP than in BP180-BP230-type BP. Conclusion The mild clinical phenotype of BP230-type BP may correlate with the weaker deposition of IgG1, IgG3 and complement in the skin lesions.

Punctate palmoplantar keratoderma type 1 (PPKP1) is a rare autosomal dominant disorder of keratinization, clinically characterized by punctate keratotic papules affecting the palmoplantar skin. Loss-of-function mutations in AAGAB have recently been reported as a cause of PPKP1. Despite the discovery of the genetic cause of PPKP1, pathogenesis-based therapies are still unavailable. Moreover, little is known about the effectiveness of treatments for PPKP1. In this study, we analyzed a Japanese woman with PPKP1 and identified a novel frame-shift mutation c.195_198del4 (p.Lys66Phefs*43) in AAGAB. Moreover, low-dose etretinate was effective in improving the PPKP1 lesions in our patient. Our published work review identified only eight cases of PPKP1 with successful response to topical or systemic treatments. Notably, six of the cases were successfully treated with systemic retinoids. Thus, this study clearly provides further evidence that PPKP1 is caused by AAGAB mutations and that systemic retinoids are the most promising current treatment for PPKP1.

Background/purpose We report the current status of patients who underwent augmentation cystoplasty (AC) at least 20 years previously. Methods Surgical history, incidence of urinary tract infection (UTI) and bladder stones, vesicoureteral reflux (VUR), urine cytology, renal function, a colon cancer tumor marker (carcinoembryonic antigen: CEA), and patient outcomes were assessed. Results Forty patients who underwent AC (mean age: 34.4 years; mean follow-up time: 24.3 years) were analyzed. Mean age at AC was 11 years. Incidence of bladder stones was 30%. There were no incidences of carcinoma after AC, and CEA levels were not increased. Ureteral reimplantation (URI) was performed in 21 patients. URI performed at the same time as AC was successful in 14 cases (93%) and unsuccessful in 1 (7%) because of persistent VUR. UTI developed after AC in only 1 patient (2.5%) with persistent VUR. This patient required unilateral nephrectomy 18 years after the AC because of repeated UTIs. Thirty-four patients (85%) were employed, and 4 (10%) were married. Two of the 19 female patients (11%) had experienced pregnancy and delivery. Five patients (13%) had mental disorders. Conclusion Ultra long-term follow-up suggests that AC is a safe procedure with manageable sequelae, although some mental health issues remain. Type of study Case series with no comparison group. Level of evidence Level IV.

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BRAF inhibitors have been licensed for the treatment of unresectable or metastatic BRAF-mutated melanomas. In Japan, the BRAF inhibitor vemurafenib has been available since December 2014. Several adverse events induced by BRAF inhibitors have been reported, such as Stevens-Johnson syndrome, toxic epidermal necrosis, squamous cell carcinoma, secondary melanoma, and hand-foot syndrome. Recently, inflammatory skin lesions clinically resembling erythema nodosum have been reported as side effects that may lead to treatment discontinuation. In this report, we described the first Japanese case of erythema nodosum-like lesions induced by vemurafenib and discussed the countermeasures to this adverse reaction. Dose reduction or interruption of BRAF inhibitors should be considered on a case-by-case basis because the condition may resolve spontaneously or under symptomatic treatment. We postulate that erythema nodosum-like lesions can be controlled by careful follow-up and supportive care.

Posterior polymorphous corneal dystrophy (PPCD) is an autosomal dominant disorder characterized by corneal endothelial abnormalities, which can lead to blindness due to loss of corneal transparency and sometimes glaucoma. We mapped a new locus responsible for PPCD in a family in which we excluded the previously reported PPCD locus on 20q11, and the region containing COL8A2 on chromosome 1. Results of a 317-marker genome scan provided significant evidence of linkage of PPCD to markers on chromosome 10, with single-point LOD scores of 2.63, 1.63, and 3.19 for markers D10S208 (at (circumflex)theta = 0.03), D10S1780 (at (circumflex)theta = 0.00), and D10S578 (at (circumflex)theta = 0.06). A maximum multi-point LOD score of 4.35 was found at marker D10S1780. Affected family members shared a haplotype in an 8.55 cM critical interval that was bounded by markers D10S213 and D10S578. Our finding of another PPCD locus, PPCD3, on chromosome 10 indicates that PPCD is genetically heterogeneous. Guttae, a common corneal finding sometimes observed along with PPCD, were found among both affected and unaffected members of the proband's sib ship, but were absent in the younger generations of the family. Evaluation of phenotypic differences between family members sharing the same affected haplotype raises questions about whether differences in disease severity, including differences in response to surgical interventions, could be due to genetic background or other factors independent of the PPCD3 locus.

Helicobacter cinaedi causes gastroenteritis and bacter-aemia, particularly in immunocompromised individuals. Although cellulitis is sometimes reported to accompany infection by this pathogen, the cutaneous manifestations are poorly understood. To clarify the characteristic cutaneous features, 47 cases of H. cinaedi bacteraemia experienced at Sapporo City General Hospital as nosocomial infection were retrospectively evaluated. Thirty-four percent (16 cases) of the patients showed cutaneous lesions. They all had sudden onset of erythemas accompanied by high temperature. The most common cutaneous manifestations were found to be superficial cellulitis, which results in painful erythemas or infiltrated erythematous plaques on the extremities. These skin lesions can be an early clinical indicator of H. cinaedi bacteraemia in the setting of nosocomial infection.

Purpose: To report a novel mutation of the OPA1 gene in a Japanese family with optic atrophy type 1 (OPA1) and to describe the clinical features of this family. Methods: Standard ocular examinations were performed on the proband and his two affected sons. The DNA sequence of all exons and splice sites of the OPA1 gene was determined to detect mutations. Results: The proband and his sons had a heterozygous mutation of the OPA1 gene in the third nucleotide of intron 12 (IVS12+3A→T). Clinically, each patient had reduced visual acuity (onset within the first 6 years of life) and optic nerve pallor. The proband showed bilateral central scotomas and generalized dyschroatopsia. This is the first report of OPA1 gene mutation in Japanese patients with familial optic atrophy. Conclusions: A mutation of the OPA1 gene was detected in a Japanese family with OPA1, which follows the same pattern as reported in Western countries. It is suggested that mutations of the OPA1 gene contribute to the development of optic nerve atrophy regardless of ethnic groups. Screening for the OPA1 gene mutation will be useful for diagnosis of OPA1 in Japanese patients.

We report a case of bullous erythema multiforme caused by an exotic wood, pao ferro (Machaerium scleroxylon). A 25-year-old female, a luthier (guitar maker) who often handles a variety of woods, developed bullous erythema multiforme. A patch test confirmed a positive reaction to one of the exotic woods, pao ferro. A subsequent accidental short contact with pao ferro 5 months following the first incidence induced a similar exudative erythema. Exotic woods such as pao ferro should be added to the list of contact allergens that can induce bullous erythema multiforme.

Multiple endocrine neoplasia type 1 (MEN1) is a familial cancer syndrome inherited as an autosomal dominant trait. Various heterozygous germline mutations of the responsible gene, MEN1, have been identified within its exons in many, but not all, affected individuals. We here demonstrate, by DNA polymorphism analysis and gene dosage analysis with polymerase chain reaction (PCR), a large heterozygous germline MEN1 deletion in a kindred with MEN1, in whom no mutation could be detected in the PCR-amplified exons. The deletion spanned an at least 7 kb region containing the entire MEN1 gene. These findings indicate that a large germline deletion of the MEN1 gene, which escapes detection in PCR-based sequence analysis, should be considered as a potential cause of MEN1.

Multiple endocrine neoplasia type 1 (MEN1) is an autosotnal dominant familial cancer syndrome. The responsible gene MEN1 has recently been isolated, and its germline mutations have been identified in affected individuals in the United States, Canada and Europe. We screened for MEN1 mutations by direct nucleotide sequencing of all protein‐coding regions, and identified five distinct germline mutations in five among six Japanese kindreds with familial MEN1 or familial hyperparathyroidism. The mutations were dispersed across the gene. These findings suggest that, because of the absence of an obvious founder effect, the entire MEN1 gene region should be examined for germline mutations in the probands of MEN1 and related syndromes in Japanese families.

We describe a Japanese patient with cutaneous plasmacytosis whose clinical course we observed for 5 years. We also review 26 patients with this condition, including 24 Japanese and two non-Japanese, reported in detail. This review revealed that this condition has characteristic clinical and pathologic features and should be considered a distinct clinical entity. The reason for the predominant occurrence of cutaneous plasmacytosis in Japanese patients is unknown.

A malignant epithelioid schwannoma occurred on the right second toe of a 30-year-old Japanese man. It was a firm, flesh-colored, benign-appearing nodule and measured 13 x 9 mm in diameter and 6 mm in height. To our knowledge, this is the first case of malignant epithelioid schwannoma occurring on the toe. Histopathology was characterized by a circumscribed nodule in the dermis that predominantly consisted of atypical large epithelioid cells with some spindle cells whose proliferation was similar to that of the Verocay bodies seen in ordinary schwannoma. Fontana-Masson staining demonstrated no melanin pigment in the tumor at the light microscopic level. The eosinophilic cytoplasm contained abundant glycogen and was positive for S-100 protein and HMB-45, as usually seen in melanomas. Electron microscopy revealed that there was an abundance of long-spacing collagen in the extracellular matrix, and the cells contained numerous dense-cored granules. But no definite melanosomes were observed in any stage. As far as we are aware, this is the first case of a malignant epithelioid schwannoma showing HMB-45 positivity.

Linear IgA/IgG bullous dermatosis (LAGBD) is an auto-immune blistering disease characterized by the local accumulation of IgA- and IgG-class anti-basement membrane autoantibodies. It typically presents as a generalized pruritic vesiculobullous eruption. No cases of localized LAGBD have yet been reported. We report a case of a 78-year-old man with LAGBD localized to the perianal area. The patient complained of suffering from persistent ulcers around the anus for more than 3 years. Physical examination revealed several blisters and ulcers up to 2-cm in diameter around the anus. No lesions were found elsewhere on the body. Histological analysis of a skin biopsy revealed subepidermal blistering, while direct immunofluorescence showed the linear deposition of IgA and IgG antibodies at the dermoepidermal junction. Indirect immunofluorescence of normal human skin whose layers had been separated using 1M NaCl showed the binding of both IgA and IgG to the epidermal side. Immunoblotting demonstrated the presence of circulating IgA and IgG autoantibodies that bound to a 120-kDa protein. This is the first case of localized LAGBD whose skin lesions were restricted to the perianal region.

OPA1 mutations are known to cause autosomal dominant optic atrophy (ADOA), and some types of OPA1 mutations also cause auditory neuropathy. In the present study, we evaluated the vestibular dysfunction that accompanied auditory neuropathy in a patient with an OPA1 mutation. A caloric test failed to elicit nystagmus or dizziness in either ear. Vestibular evoked myogenic potentials (VEMPs) in the right ear were characterized by a normal biphasic waveform. In contrast, no VEMPs were evoked in the left ear. Model building suggested that the OPA1 mutation, p.R445H, indirectly distorts the catalytic structure of the GTPase reaction center and decreases GTPase activity. The patient complained of instability while walking or moving but thought these symptoms were caused by visual dysfunction. This is the first report of a detailed evaluation of vestibular dysfunction in a patient with an OPA1 mutation. This case suggests that vestibular dysfunction may be involved in motor instability in patients with an OPA1 mutation, even when patients do not complain of vestibular symptoms. Based on this case, we suggest that vestibular evaluation should be performed in auditory neuropathy patients carrying an OPA1 mutation, even if the patients are free of symptoms of vestibular dysfunction.

We describe a 10-month-old boy with 22q13 deletion syndrome. Chromosomal analysis showed a partial duplication of 22p11.2-pter and a terminal deletion of 22q13.31-qter. Maternal chromosomal analysis showed a pericentric inversion of chromosome 22, with breakpoints at p11.2 and q13.31 [inv(22)(p11.2q13.31)]. The deleted chromosome resulted from a recombinant chromosome inherited from his mother. This is a rare case of 22q13 deletion syndrome associated with parental pericentric inversion of chromosome 22.

Adult T-cell leukemia/lymphoma (ATLL) often involves the skin. Cases with skin lesions without either leukemic nor lymph node involvement have been categorized into a cutaneous type. While the clinical manifestations of the cutaneous-type ATLL are variable, including multiple papules, nodules, plaques, or erythroderma, a solitary skin nodule alone is rare, and only 2 cases have been reported in the literature. We present a 58-year-old Japanese patient with cutaneous-type ATLL that presented as a large, solitary skin nodule as the sole clinical feature. The skin tumor was completely resolved after treatment with x-ray and electron beam irradiation.

To report recurrent mutation of the KIF21A gene in three Japanese families in which some members have congenital fibrosis of the extraocular muscles type 1 (CFEOM1), and to describe the clinical characteristics of the families. Standard ocular examinations were performed on 18 normal and affected members of three unrelated families. To detect mutations, we determined the DNA sequence of exons 8, 20, and 21 and the splice sites of the KIF21A gene. All affected members had a heterozygous mutation of the KIF21A gene in exon 21 (R954W). Clinically, each patient had congenital bilateral ptosis, an infraducted primary position of each eye, and the inability to raise either eye above midline. The KIF21A gene mutation R954W was detected in the patients with CFEOM1 screened in this study, all of whom were Japanese, reflecting similar reports from Europe, America, the Middle East, and Japan. We suggest that mutations of the KIF21A gene contribute to the development of CFEOM1 regardless of ethnicity. We also found that the delimitation of the KIF21A gene mutation site enabled us to efficiently detect the KIF21A gene mutation despite the large number of KIF21A gene exons. Jpn J Ophthalmol 2005;49:443–447 © Japanese Ophthalmological Society 2005

Elastofibroma is an uncommon fibroelastic tumor or tumorlike process that usually occurs between the scapula and the chest wall of elderly patients. This condition is rarely reported in the dermatologic literature, because it infrequently arises in the skin or within the subcutaneous tissue. We present a 78-year-old man with 15 separate subcutaneous nodules on the buttocks and upper extremities together with bilateral subscapular nodules. All specimens taken from different lesions were histologically confirmed as elastofibromas. As far as we know, this case with 17 distinct elastofibromas demonstrates the largest number ever reported in a single patient. Although the pathomechanism of the occurrence of multiple elastofibromas is unknown, it should be included in the differential diagnosis of multiple subcutaneous nodules.

Purpose To evaluate the clinical history, histopathology, and genetics of posterior polymorphous corneal dystrophy (PPMD) in a woman with a prominent retrocorneal membrane. Design Observational case report and genetic analysis of her family, UM:139. Methods Records were reviewed from a case and associated family members. The diagnosis of PPMD was based on clinical examination, immunohistochemical staining, electron microscopy, and screening of genetic markers from regions previously reported to be associated with PPMD. Results Over 17 years, the proband with PPMD had 25 ocular procedures performed for glaucoma, cataract, cornea, retina, and postoperative problems. A prominent retrocorneal membrane grew onto the crystalline lens and intraocular lens (IOL). Histopathology revealed stratified epithelial-like cells on iris from an iridectomy and stratified corneal endothelium on a corneal button. Electron microscopy on the cornea revealed microvilli, tonofilaments, and desmosomes consistent with endothelial transformation, which was confirmed by positive anticytokeratin (CK) AE1/AE3 and CAM 5.2 immunoreactivity. Negative immunoreactivity in epithelium and positive in endothelium with anti-CK 7 supported the diagnosis of PPMD rather than epithelial downgrowth. Multiple relatives were affected with PPMD with apparent autosomal dominant inheritance, but surprisingly, the PPMD, congenital hereditary endothelial dystrophy 1 (CHED1) and CHED2 loci on chromosome 20 and the collagen, type VIII, α-2 (COL8A2) gene were excluded by linkage and haplotype analyses. Conclusions We are unaware of previous PPMD reports describing the unusual feature of a retrocorneal membrane extending onto the crystalline lens and IOL. In addition, this family suggests another PPMD locus.

We describe an unusual case of hidradenoma papilliferum on the chest of a man and discuss the rare sites of the tumor.

Purpose To report a novel mutation of the OPA1 gene in a Japanese patient with optic atrophy and to describe the clinical features of the patient. Design Observational case report. Methods Genomic DNA was extracted from leukocytes of four unrelated Japanese patients with optic atrophy. All the exons and splice sites of the OPA1 gene were amplified by polymerase chain reaction and directly sequenced. Results One patient with optic atrophy had a heterozygous Arg445His mutation in the OPA1 gene. The Arg445His mutation was detected neither in 110 control subjects nor in the patient's healthy family members. Conclusions A novel mutation of the OPA1 gene, similar to those reported in Western countries, was detected in a Japanese patient with optic atrophy. Mutations of the OPA1 gene may contribute to the development of optic nerve atrophy in Japanese cases of optic atrophy.

Background: Although various mucocutaneous manifestations have been reported in patients infected with HIV by sexual transmission or intravenous drug use, the prevalence and characteristics of skin disorders in HIV-positive hemophiliacs coinfected with hepatitits C virus (HCV) have rarely been described. Objective: The purpose of this study was to clarify the characteristics of skin disorders in HIV-positive hemophiliacs and to identify differences in comparison with other HIV-positive groups. Methods: A prospective study of the prevalence of mucocutaneous manifestations in 110 Japanese hemophiliacs (53 HIV-positive hemophiliacs including 24 AIDS and 57 HIV-negative hemophiliacs) was performed from July 1997 to July 1998. Result: None of the hemophiliacs developed Kaposi’s sarcoma or sexually transmitted skin diseases. Eosinophilic folliculitis was observed in 3 AIDS patients. The incidence of folliculitis, common warts, seborrheic dermatitis, generalized eczema, oral candidiasis and herpes zoster was higher in HIV-positive than in HIV-negative hemophiliacs (p < 0.05). Although anti-HCV antibody was positive in all HIV-positive hemophiliacs, HCV-related dermatoses such as lichen planus and porphyria cutanea tarda were not observed. Conclusion: Although Kaposi’s sarcoma and sexually transmitted skin diseases such as molluscum contagiosum, condyloma, and scabies are frequently associated with HIV, they were not found in the HIV-positive hemophiliacs in our study. HIV infection-related mucocutaneous manifestations are influenced not only by the presence of HIV but also by other factors such as the mode of transmission and sexual habit.

c PURPOSE: To screen a population with primary openangle glaucoma for mutations in the gene that encodes the trabecular meshwork inducible glucocorticoid response protein (TIGR), also known as myocilin (MYOC). c METHODS: Ophthalmologic information was collected for study subjects with primary open-angle glaucoma and their relatives. Mutation screening of 74 primary openangle glaucoma probands was conducted by sequencing TIGR/MYOC coding sequence and splice sites. c RESULTS: In 23 families we detected 13 nonsynonymous sequence changes, nine of which appear to be mutations likely to cause or contribute to primary openangle glaucoma. Two mutations, Arg272Gly and Ile499Ser, and one nonsynonymous sequence variant, Asn57Asp, are novel. We found mutations in nine of 25 juvenile glaucoma probands (36%) and two of 49 adultonset glaucoma probands (4%). Age classification of families rather than individual probands revealed mutations in three of nine families with strictly juvenile primary open-angle glaucoma (33%), and no mutations in 39 families with strictly adult-onset primary open-angle glaucoma (0%). In families with mixed-onset primary open-angle glaucoma containing both juvenile primary open-angle glaucoma and adult-onset primary open-angle glaucoma cases, we found mutations in eight of 26 families (31%). c CONCLUSIONS: Our data suggest that Gly252Arg, Arg272Gly, Glu323Lys, Gln368STOP, Pro370Leu, Thr377Met, Val426Phe, Ile477Asn, and Ile499Ser are likely to play roles that cause or contribute to the etiology of autosomal dominant primary open-angle glaucoma. Our finding of more TIGR/MYOC mutations in families with mixed-onset primary open-angle glaucoma than in the families with strictly adult-onset primary open-angle glaucoma implies that the presence of relatives with juvenile primary open-angle glaucoma in a family could be used as a basis for identifying a subset of the population with adult-onset primary open-angle glaucoma with higher prevalence of TIGR/MYOC mutations. To address this issue, and to refine estimations of mutation prevalence in these age-defined subpopulations, prospective study of a larger population ascertained entirely through adult-onset primary open-angle glaucoma probands will be needed. (Am J Ophthalmol 2000;130: 165‐177. © 2000 by Elsevier Science Inc. All rights reserved.)

Germline MEN1 gene mutations are responsible for multiple endocrine neoplasia type 1 (MEN1), a dominantly inherited cancer syndrome. We identified a MEN1 germline mutation 894-9 G --> A in three MEN1 patients from two unrelated families. This mutation was not present in any of the 100 blood samples from normal volunteers. The wild type MEN1 sequence was lost in the patient's pancreatic tumor. Abnormal mRNA was identified in the tumor, which retained an intronic sequence indicating aberrant mRNA splicing at a newly created splicing acceptor site. These findings indicate that this nucleotide substitution is, though previously reported to be a polymorphism, a causative splicing mutation.

Choriocarcinoma is a malignant growth of trophoblastic cells characterized by secretion of human chorionic gonadotropin. Choriocarcinoma usually arises from fetal trophoblasts and rarely arises from germ cells in the testis or ovary or derives from dedifferentiation of other carcinomas. Skin metastasis of choriocarcinoma is rare: only seven cases have been reported in the English and Japanese literature. We report the case of a 22-year-old Japanese man with pure choriocarcinoma of the testis who developed skin metastases that presented as multiple reddish nodules. Microscopic examination of both the primary lesion of the testis and the cutaneous metastasis demonstrated the typical histologic features of pure choriocarcinoma. The patient died 3 months after the initial onset of skin metastasis. Review of the literature indicates that skin metastasis of choriocarcinoma usually occurs as a nodular lesion with the histologically typical feature of the primary disease and signals of poor prognosis.

Purpose : To report a novel mutation of the typel optic atrophy(OPA1) gene in a Japanese family with OPA1 and to describe the clinical features of this family. Methods : Standard ocular examinations were performed on the proband and his two affected sons. The DNA sequence of all exons and splice sites of the OPA1 gene was determined to detect mutations. Results : The proband and his sons had a heterozygous mutation of the OPA1 gene in the third nucleotide of intron 12(IVS12+3A→T). Clinically, each patient had reduced visual acuity (onset within the first 6 years of life) and optic nerve pallor. The proband showed a central scotoma and generaact lized dyschromatopsia. This is the first report of OPA1 gene mutation in Japanese patients with familial optic atrophy. Conclusions: A mutation of the OPA1 gene was detected in a Japanese family with OPA1, which follows the same pattern as reported in Western countries. It is suggested that mutations of the OPAL gene contribute to the development of optic nerve atrophy regardless of ethnic groups. Screening for the OPA1 gene mutation will be useful for diagnosis of OPA1 in Japanese patients.

Photoallergy to vitamin B6 is very rare; only a few cases of contact dermatitis and one case of photosensitive dermatitis due to pyritinol have been reported. We report here the first case of photoallergy drug eruption due to pyridoxine hydrochloride. A 71-year-old man developed papulo-squamous erythemata which were confined to sun-exposed sites. Photopatch testing, together with the clinical course, was helpful in reaching the initial diagnosis; this was confirmed by an oral challenge test. Photoallergic drug eruption due to vitamin B6 should be considered a rare cause of photosensitive dermatitis.