Tomohiko Narita

Serological aggravation of autoimmune thyroid disease in two cases receiving nivolumab.

Nivolumab, a blockade of programmed cell death 1, is now administrated for advanced malignant melanomas. Nivolumab‐associated adverse events include organ‐specific autoimmune disorders; autoimmune thyroid disease, vitiligo and insulin‐dependent diabetes. However, predisposed persons are currently unknown. Here, we report serological aggravation of autoimmune thyroid disease in two cases receiving nivolumab: one with Hashimoto disease and another with probable subclinical Hashimoto disease. We should verify if nivolumab‐related hypothyroidism and hyperthyroidism are predisposed to occur in euthyroid individuals with subclinical autoimmune thyroid disease.

Phylloid Hypermelanosis and Melanocytic Nevi with Aggregated and Disfigured Melanosomes: Causal Relationship between Phylloid Pigment Distribution and Chromosome 13 Abnormalities

The mosaic pattern of phylloid hypomelanosis is mostly associated with chromosome 13 abnormalities. Recently, 1 case of hypermelanosis in a phylloid pattern has been described. We describe a 29-year-old Japanese male with mental retardation, phylloid hypermelanosis and histopathologically and ultrastructurally peculiar melanocytic nevi, which were associated with 3 aberrant chromosome 13 cell lines. The karyotyping of 30 peripheral blood lymphocytes showed 46,XY,r(13)(p11.2q34) in 21 cells, 45,XY,–13 in 7 cells and 46,XY,dic r(13)(p11.2q34) in 2 cells. Immunohistochemical staining with HMB45 showed a positive reaction to basal keratinocytes in phylloid hypermelanosis. HMB45 staining reacted to the nevus cells and keratinocytes in the melanocytic nevi. Electron microscopy of a specimen excised from a melanocytic nevus showed an unusual finding of aggregated and disfigured melanosomes in the keratinocytes. This case suggests that chromosome 13 abnormalities may be related to the development of phylloid hypermelanosis and the bizarre melanosomes in the keratinocytes of melanocytic nevi.

Concomitant development of photoallergic contact dermatitis from ketoprofen and allergic contact dermatitis from menthol and rosin (colophony) in a compress

A 14-year-old Japanese man playing baseball almost everyday visited us with a rectangular-shaped severe painful bullous and erythematous macular lesion on the left wrist, after using compresses, Mohrus Tape (Hisamitsu Pharmaceutical Co. Inc., Tosu, Japan) for 7 days. The compress contains ketoprofen, menthol, and hydrogenated rosin glycerol ester. The patient had no personal or familial history of atopic dermatitis. He had not previously used any other topical ointment or cream including ketoprofen. He had no personal history of contact dermatitis due to adhesives, tapes, and powder for ballplayers. Themanufacturers provided us with all the ingredients prepared with the same concentration in the compress. The patch and photopatch testing was done as reported previously (1) with irradiation to one side with 4 J/cm of broadbandultravioletA,with readings at D1, D2, and D3 after irradiation. Reactions are shown in Table 1.

Variants in melanogenesis-related genes associate with skin cancer risk among Japanese populations.

Human skin color is known to be associated with the risk of cutaneous cancer. Some reports indicated that pigmentation‐related gene variants were associated with cutaneous cancer risk in Caucasian populations, but there are no similar reports in East Asian populations. This study aimed to evaluate the association between pigmentation‐related genes and the risk of skin cancer in Japanese populations. We studied the associations between 12 variants of four pigmentation‐related genes and melanin index variations in 198 Japanese patients with skin cancer and compared these findings to those of 500 Japanese controls by using multiple logistic regression analysis. Furthermore, we analyzed an independent sample of 107 Japanese patients with skin cancer. A non‐synonymous variant, H615R in the oculocutaneous albinism 2 gene (OCA2), was associated with the risk of malignant melanoma in the Yamagata group (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.17–0.86; P = 0.020). Another non‐synonymous variant, A481T in OCA2, was associated with the risk of squamous cell carcinoma and actinic keratosis in the Osaka group (OR, 3.16; 95% CI, 1.41–7.04; P = 0.005). In malignant melanoma cases, the minor allele in OCA2 H615R might have induced the development of lesions in sun‐exposed skin (OR, 26.32; 95% CI, 1.96–333; P = 0.014). Our results suggest that some OCA2 variants are definite risk factors for the onset of cutaneous cancer in Japanese populations.

Two children with a mild or moderate piebaldism phenotype and a father without leukoderma in a family with the same recurrent missense mutation in the kinase domain of KIT

ejd.2011.1350 Auteur(s) : Tomohiko Narita1 naoiso@med.kindai.ac.jp, Naoki Oiso1, Kazuyoshi Fukai2, Tomonori Motokawa3, Masahiro Hayashi4, Kouji Yokoyama3, Yutaka Hozumi4, Akira Kawada1, Tamio Suzuki4 1 Kinki University Faculty of Medicine Dermatology Department, 377-2 Ohno-Higashi, Osaka-Sayama 589-8511, Japan 2 Osaka City University Graduate School of Medicine Dermatology Department, Osaka 3 Cutaneous Drug Research Department, POLA Chemical Industries Inc, Yokohama 4 Yamagata University School [...]

Pterygium inversum unguis: aberrantly regulated keratinization in the nail isthmus.

The nail unit is constructed of distinctly regulated components. Recently, Perrin proposed a functionally distinct region, the nail isthmus, located between the nail bed and hyponychium. The nail isthmus presents a profile of keratin expression in transition from the nail bed to the hyponychium. It has a peculiar mode of keratinization, with a compartment of pale and nucleated corneocytes. It closely adheres to the inferior border of the nail plate, including its distal free edge. Perrin stated that the strong adhesion of the nail plate and the nail bed is replaced by an effective sealing of the thin, pale, tongue-like parakeratotic extension of the nail isthmus and the nail plate. Pterygium inversum unguis is a nail abnormality characterized by the persistent adherence of the distal portion of the nail bed to the ventral surface of the nail plate, resulting in a subungual extension of the hyponychium and obliteration of the distal groove. It presents as noticeable subungual keratotic thickening between the hyponychium and ventral nail plate. A 16-year-old boy presented with aberrant nails on the second, third and fourth fingers of both hand. The nails wee painful, and the patient had difficulty cutting the fingernails because of the pain. The malformation had been present since childhood. On physical examination, excess tissue was found in the semi-hard keratinized structure in the region separating the free nail plate and the groove (Fig. 1a). The toenails were normal in appearance. On histological examination of a longitudinal specimen taken from the second finger of the left hand, we found a wide lesion produced by the semi-hard keratinized structure; a marked, highly eosinophilic, keratinized substance attaching the distal and visceral nail plate, including the nail s distal free edge, with distinct, pale and nucleated corneocytes; and a whorled keratinized substance in the horny layer of the fingertip, which was markedly eosinophilic (Fig. 1b). Two other cases of pterygium inversum unguis have been histopathologically investigated. Neither had an obvious association between the nail plate and skin, either because the specimen was only partial, or the nail plate was separated from the skin. To our knowledge, our case is the first to show the relationship between the nail plate and the transition from the nail bed to the hyponychium via the nail isthmus. We believe that the eosinophilic keratinized substance with pale and nucleated corneocytes attached to the ventral surface of the nail plate is derived from the nail isthmus. The whorled keratinized substance with marked eosinophilia, which extended into the horny layer of the fingertip was produced by the semi-hard (a)

The histopathological feature of the nail isthmus in an ectopic nail.

The nail unit has a unique structure. It has been recently proposed that the nail isthmus as a transitional zone between the most distal part of the nail bed and the hyponychium. A 7-year-old Japanese boy presented with an ectopic nail, an additional and independent miniature nail on the digital pulp of the right fifth finger. We studied the expression of a series of keratin in longitudinal specimens and showed the histopathological manifestation in the nail isthmus. This region in the ectopic nail is subdivided into 2 parts: a proximal and narrow part anchored to the nail plate and a distal and wide part with a semihard keratinized structure.

Imiquimod-induced vitiligo-like depigmentation over multiple solar keratosis in a patient with vitiligo

Individuals with vitiligo have a low risk of developing non-melanoma skin cancer [1, 2]. Previous studies have reported imiquimod-induced vitiligo-like depigmentation in patients with genital warts and superficial basal cell carcinomas [3, 4]. Here, we report a case of persistent vitiligo-like depigmentation caused by topical application of imiquimod 5% cream for multiple solar keratosis in a patient with non-segmental vitiligo.A 67-year-old man was referred to us in July 2010 with an 11-year history [...]

Dermoscopy for malignant melanoma of the nipple and the areola

ing this case have been described. In two cases, including the present case, the skin tumors arose on non-sun-exposed skin without any precursor lesion. While imatinib can exert a therapeutic effect on SCC lesions, in another two cases of SCC, one of lesions was newly developed and another rapidly progressed even during imatinib administration. In head and neck SCC (HNSCC) cells, imatinib mesylate solubilizes membrane-bound heparin-binding epidermal growth factor-like growth factor, resulting in the activation of epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase 1/2 and Src kinase. The imatinib-induced activation of the EGFR signaling system upregulates invadopodia-dependent invasion of HNSCC cells via negative regulation of Abl kinase, which is related to worsened prognosis. In addition, STAT3 activation plays a critical role in SCC progression and upregulates PDPN by the EGFR-STAT3 pathway stimulating SCC invasion. We analyzed p-STAT3 and PDPN, and both markers as well as a proliferative marker, Ki-67, were markedly upregulated in the tumor nests of the deep dermis (Fig. 1d–f). This indicates that both invasive and proliferative activities are stimulated possibly by the EGFR signaling pathway. Although imatinib mesylate can be effective for several skin tumors, cutaneous SCC may be more invasive during the imatinib therapy. Dermatologists should be aware of the unique adverse effect, which could be profoundly associated with the keratinocyte tumor biology. CONFLICT OF INTEREST: None declared.

Lymph node metastatic melanoma from ungual melanoma: Identification of somatic mutations in KIT and LZTR1

Dear Editor, Acral lentiginous melanoma (ALM) including ungual melanoma does not differ from non-ALM in its biological behavior. However, ALM has a different genetic background from non-ALM; infrequent BRAF mutations and frequent KIT mutations. A 56-year-old Japanese man was referred to us in June 2010 with a blackish eruption on the right first fingertip (Fig. 1a,b). He had first noticed it 1.5 years previously. A biopsy with a 5-mm margin showed atypical cells (Fig. 1c,d). Computed tomography (CT) and positron emission tomography (PET) detected no metastatic lesions. The blackish nodule was diagnosed as ALM (ungual melanoma) (T3bN0M0, stage IIB). The right first finger was excised due to his willingness. No sentinel lymph node was detected. Three courses of dacarbazine, nimustine, vincristine and interferon-b were administrated. In February 2016, CT revealed swelling in the right axial lymph node. PET detected no other metastatic lesions. An excision of the lymph node showed atypical cells (Fig. 1e,f), suggesting metastatic melanoma. The patient provided written informed consent to participate in the study according to a protocol approved by the Genetic Ethics Committee of Kindai University Faculty of Medicine. We performed whole-exome sequencing of DNA from the tumor and whole blood as reported. Libraries were sequenced with a mean depth of 139 for the tumor and 105 for whole blood. Raw variant calls were filtered out using the following criteria: (i) single nucleotide polymorphisms found in whole blood DNA; (ii) quality score of less than 100; and (iii) read depth of less than 5. Detailed information was added by the CLC Genomics Workbench version 9.0.1 (CLC bio Japan, Tokyo, Japan). The Integrative Genomics Viewer (IGV 2.3; Broad Institute, Cambridge, MA, USA) was used to visualize the read alignments and check for the possibility of sequencing errors. We detected 50 somatic mutations, including a