Madoka Kato

Prognostic significance of L-type amino acid transporter 1 (LAT1) expression in cutaneous melanoma.

Amino acid transporters play a crucial role in the development and invasiveness of cancer cells. However, it remains unclear whether or not the expression of L-type amino acid transporter 1 (LAT1) has prognostic significance in patients with cutaneous melanoma. A total of 128 patients with cutaneous melanoma were evaluated. Tumor sections were stained by immunohistochemistry for LAT1, CD98, Ki-67, and microvessel density determined by CD34 and p53. We also analyzed 30 specimens of patients with melanocytic nevi as negative controls. LAT1 and CD98 were highly expressed in 58% (75/128) and 75% (97/128), respectively. The rates of positivity for LAT1 in the melanocytic nevi were 0% (0/30). The expression of LAT1 was associated significantly with tumor thickness, T factor, CD98 expression, cell proliferation (Ki-67), and microvessel density (CD34). By Spearman’s rank test, LAT1 expression was correlated with CD98, Ki-67, and CD34. By univariate analysis, tumor thickness, ulceration, disease staging, LAT1, and CD34 showed a significant relationship with overall survival and disease-free survival. Furthermore, a multivariate analysis confirmed that LAT1 was an independent prognostic factor for predicting a poor prognosis. This study had a small sample size. LAT1 can serve as a significant prognostic factor to predict a poor outcome and it may therefore play an important role in the aggressiveness of cutaneous melanoma.

Detection of human papillomavirus (HPV) in patients with squamous cell carcinoma and the clinical characteristics of HPV-positive cases.

The association between human papillomavirus (HPV) and squamous cell carcinoma (SCC) has been reported; however, the prevalence of HPV infection varies, and the clinical characteristics of HPV‐positive cases remain unknown.

An Autosomal Recessive Mutation of DSG4 Causes Monilethrix through the ER Stress Response

Monilethrix is a hair shaft anomaly characterized by beaded hair with periodic changes in hair thickness. Mutations in the desmoglein 4 (DSG4) gene reportedly underlie the autosomal recessive form of the disease. However, the pathogenesis and cellular basis for the DSG4 mutation-induced monilethrix remained largely unknown. We report a Japanese female patient with monilethrix. Observation of her hair shaft by means of transmission electron microscopy showed fewer desmosomes and abnormal keratinization. Genetic analysis revealed a homozygous mutation, c.2119delG (p.Asp707Ilefs*109), in the DSG4 gene, which was predicted to cause a frameshift and premature termination in the intracellular region of the DSG4 protein. The mutation has not been reported previously. In the patients hair shaft, we detected reduced but partial expression of the mutant DSG4 protein. Cellular analyses demonstrated that the mutant DSG4 lost its affinity to plakoglobin and accumulated in the endoplasmic reticulum (ER). The amounts of mutant DSG4 were increased by proteasome inhibitor treatment, and the expression of an ER chaperone, GRP78/BiP, was elevated in the patients skin. Collectively, these results suggest that the dysfunctional mutated DSG4, tethered in the ER, undergoes ER-associated degradation, leading to unfolded protein response induction, and thus ER stress may have a role in the pathogenesis of monilethrix.

Pigmented condyloma acuminatum.

We herein report a case of pigmented condyloma acuminatum in the genital region. A histopathological examination revealed keratinocyte proliferation, papillomatosis and basal pigmentation. Cellular atypia was rarely observed. The patient also had ordinary skin‐colored nodules on the coronal sulcus. Polymerase chain reaction amplification with consensus primers for human papillomavirus (HPV) and subsequent sequencing confirmed an infection of HPV type 6. Pigmented condyloma acuminatum is not rare; however, making the differential diagnosis between bowenoid papulosis and seborrheic keratosis is sometimes difficult. The mechanism of pigmentation in such cases remains unknown and requires further investigation. HPV typing is a useful method for diagnosing the disease.

Bowenoid papulosis successfully treated with imiquimod 5% cream

A 24‐year‐old healthy Japanese female was diagnosed as having bowenoid papulosis in the genital area. The histopathological findings revealed acanthosis, papillomatosis, dyskeratotic cells and clumping cells with mild atypical nuclei. Human papillomavirus type 16 was detected in the lesion. The lesion was successfully treated with topical imiquimod 5% cream after 2 months. Imiquimod 5% cream is a potentially effective treatment modality for lesions that are difficult to treat with surgical excision.

Case of familial Michelin tire baby syndrome

1 Pernet C, Bessis D, Savignac M, Tron E, Guillot B, Hovnanian A. Genitoperineal papular acantholytic dyskeratosis is allelic to HaileyHailey disease. Br J Dermatol 2012; 167: 210–222. 2 Lee JH, Kim YC, Lew W. A case of focal acantholytic dyskeratosis occurring on both the lip and the anal canal. Yonsei Med J 2003; 44: 166–168. 3 Burge SM, Wilkinson JD. Darier-White disease: a review of the clinical features in 163 patients. J Am Acad Dermatol 1992; 27: 40–50. 4 Verbov JL. Palmar lesions in familial benign pemphigus. Br J Dermatol 1969; 81: 77. 5 Lipoff JB, Mudgil AV, Young S, Chu P, Cohen SR. Acantholytic dermatosis of the crural folds with ATP2C1 mutation is a possible variant of Hailey-Hailey Disease. J Cutan Med Surg 2009; 13: 151–154.

Alopecia in a patient with Vogt–Koyanagi–Harada disease

Dear Editor, Vogt–Koyanagi–Harada (VKH) disease is a rare systemic disease characterized by bilateral uveitis, meningitis, auditory symptoms and skin manifestations, such as vitiligo, poliosis and alopecia. Alopecia occurs in up to 73% of patients at an early stage of the disease and is usually diffuse, although it may be patchy. Alopecia usually heals after a variable period; however, it sometimes relapses. We herein report a case of diffuse alopecia complicated by VKH disease in a patient who was successfully treated with pulse corticosteroid therapy. A 24-year-old woman was admitted to the department of ophthalmology with a 2-month history of fever and gradually decreased visual acuity in October 2010. Ophthalmologically, both bilateral uveitis and a sunset fundus were confirmed. The diagnosis of VKH disease was established, and 1 g methylprednisolone was administrated i.v. for 3 days, followed by oral prednisolone at a dose of 30 mg/day, which was gradually tapered to 5 mg/day. In November 2010, diffuse alopecia with poliosis developed, and the patient was referred to our department in August 2011. She had also noted several lesions of vitiligo 1 month earlier. A physical examination revealed diffuse alopecia, poliosis (Fig. 1a) and some lesions of vitiligo on the forearm (Fig. 1b). Easy hair loss was noticed; however, we did not see any black dots or tapering or broken hair. A skin biopsy was not performed. The results of routine laboratory examinations were almost within normal limits. We diagnosed her as having diffuse alopecia and vitiligo complicated with VKH disease. Hair loss was obvious. After consulting an ophthalmologist, we initiated treatment with 0.5 g of pulse corticosteroid therapy for 3 days. Although the newly grown hair remained white to gray, the patient’s hair loss gradually improved (Fig. 1c). After 6 months of follow up, the vitiligo on the dorsum of the hand had disappeared. During 2 years of follow up, there has been no recurrence of alopecia, although poliosis is still present. The pathogenesis of VKH disease is thought to involve an autoimmune response to melanocytes. The histopathological features observed in patients with alopecia associated with VKH disease are identical to those seen in patients with alopecia areata; however, prominent pigment release suggests that the primary target cells are melanocytes. Recently, a few reports concerning alopecia associated with VKH disease have been published. Igawa et al. reported that pulse corticosteroid therapy is effective not only for ocular symptoms, but also for alopecia. Pulse corticosteroid therapy is a well-established treatment for alopecia areata.

Successful treatment of genital Bowen's disease with imiquimod 5% cream.

A 64-year-old Japanese woman was diagnosed as having Bowen’s disease on the vulva. The histopathological findings revealed papillomatosis, koilocytosis and clumping cells with atypical nuclei. Human papillomavirus DNA was not detected on polymerase chain reaction using consensus primers. The lesion was successfully treated with topical imiquimod 5% cream after two months. Histopathologically, no atypical cells were observed after treatment. Imiquimod can be a potential treatment modality for lesions that are difficult to treat with surgical excision.

Giant Condyloma Acuminatum in the Axilla

© 2015 The Authors. doi: 10.2340/00015555-1935 Journal Compilation

Persistent prurigo nodularis in HIV-infected patient responsive to antiretroviral therapy with raltegravir.

Dear Editor, A 37-year-old Japanese man was diagnosed with HIV infection in 2003. He was hospitalized with severe bipolar disorder in our hospital in August 2012. He was referred to our department with multiple eruptions on his extremities. Physical examination revealed numerous brown hyperkeratotic nodules with severe itch on his extremities (Fig. 1a). Skin lesions persisted in spite of treatment with topical steroid. Abnormal laboratory results included low white blood cell counts (2200/lL; normal, 4000–9600), low platelet counts (73 9 10/lL; normal, 160–350) and extremely low CD4 cell counts (1/lL; normal, 330–5472). Serum HIV was positive with significantly high viral load (215 884 copies/mL). Peripheral blood human herpes virus 8 DNA and Treponema pallidum particle agglutination assay were negative. Histopathological examination of a nodule on the knee showed hyperkeratosis, acanthosis, papillomatosis and perivascular infiltration of lymphocytes (Fig. 1b). Abnormal proliferation of endothelial cells was not observed. CD8 cells were slightly observed in dermis (Fig. 1c), however, CD4 cells were not. Based on clinicopathological findings, a diagnosis of persistent prurigo nodularis associated with HIV infection was established. Topical steroid was continued and treatment with antiretroviral therapy (ART) with lamivudine, zidovudine and raltegravir was initiated in September 2012. After the treatment started, multiple nodules improved gradually, along with a decrease in levels of viral load. Within 2 months of starting ART, most of the multiple nodules had disappeared with postinflammatory pigmentation (Fig. 1d), and viral load fell below measurable limits. Improvement was maintained during a 3-month followup period. Skin lesions often develop in association with HIV infection, reflecting the immunocompromised status of the individuals. Huang et al. reported that candidiasis (25.8%), eczema (19.2%), prurigo nodularis (13.8%), dermatophyte infections (10.6%) and herpes zoster (9.4%) were most common in 796 Chinese patients with HIV infection. In two studies, 1.8% and 6.5% of HIV-infected individuals in Nairobi were found to have prurigo nodularis. It is more frequently seen in patients with CD4 cell counts below 50/lL. Consistent with this finding, our patient also had extremely low CD4 cell counts. Treatment of prurigo nodularis in HIV-infected patients is challenging due to the recalcitrant nature and the possible risk of immunosuppressive therapy in these patients. Thalidomide reduces the symptoms of prurigo nodularis in (a) (d)