Kyosuke Oishi

A crucial role of L-selectin in C protein-induced experimental polymyositis in mice.

To investigate the role of adhesion molecules in C protein–induced myositis (CIM), a murine model of polymyositis (PM).

A case of aseptic meningitis without neck rigidity occurring in a metastatic melanoma patient treated with ipilimumab

A 59-year-old male was referred with several black nodules on a burn scar on his head (figure 1A). The clinical diagnosis was in-transit metastases of malignant melanoma, and the primary lesion had already regressed. He also had right enlarged neck lymph nodes. We performed wide dissection of the original site of head and lymph node dissection. Figures 1B , C show the results of the histopathological examination. No tumour cells were observed in the epidermis. Pathological findings confirmed the [...]

Spitz nevus on the sole of the foot presenting with transepidermal elimination

A 10-year-old Japanese girl presented with a rhomboid-shaped brown macule, 4x3 mm in size, on the sole of the right foot. Dermoscopic examination revealed a number of black dots and globules on the ridges of the skin, marking an area of symmetrical brown pigmentation. On the periphery, a streak-like arrangement of black dots/globules on the brown pigmentation was observed along the ridges, simulating a “starburst” pattern. The lesion was excised and histological examination showed a symmetrical wedge-shaped compound melanocytic lesion that consisted of junctional and intradermal nests of a mixture of large spindle and epithelioid cells. None of the cells were atypical, and maturation of the cells with increasing depth was observed. From these findings, a diagnosis of Spitz nevus was made. Transepidermal elimination of nevus cell nests was observed and there were small groups of degenerated melanin-laden cells in the cornified layer. Masson Fontana stain revealed fine melanin deposits in the nevus cells of the junctional and intradermal nests, as well as heavy melanin deposits in the small groups of degenerated cells in the cornified layer. The distribution of melanin may contribute to a unique dermoscopic finding in this case.

Aggressive Digital Papillary Adenocarcinoma With Multiple Organ Metastases: A Case Report and Review of the Literature

Abstract: Aggressive digital papillary adenocarcinoma (ADPA) is a rare sweat gland neoplasm with a high recurrence rate and metastatic potential. In this study, the authors describe a case that originally appeared to benign spiradenoma, but took an ominous course eventually resulting in the diagnosis of ADPA. A 73-year-old woman developed a gradually growing nodule on the second toe of her left foot, which she had first noticed 4 years previously. An excisional biopsy was performed followed by histological examination. The authors initially considered the tumor to be a benign spiradenoma and did not perform reexcision. However, she experienced local recurrence 24 months later, and multiple pulmonary metastasis 31 months later. On histological examination, both the primary and locally recurrent tumors were found to be composed of discrete and well-circumscribed solid nodules, lacking cystic space. All tumors (the primary tumor, locally recurrent tumor, and lung metastases) presented with a pattern of fused back-to-back tubular structures and myoepithelial differentiation confirmed by immunohistochemical examination. On the basis of these findings, the authors finally diagnosed ADPA with multiple pulmonary metastases. The patient underwent chemotherapy, but died of disease 49 months later. This case highlights the importance of high clinical suspicion of ADPA when digital lesions present.

Increased interleukin-9 levels in sera, muscle and skin of patients with dermatomyositis

Dermatomyositis (DM) is an autoimmune connective tissue disorder characterized by the inflammation of striated muscle. Interleukin (IL)-9 was initially identified as one of the T-cell growth factors and is mainly produced by activated T-helper (Th)2 lymphocytes. However, its role in DM currently remains unknown. In this study, we aim to examine serum IL-9 levels and the expression of IL-9 in the muscle and skin tissues of patients with DM. Serum samples were obtained from 40 Japanese patients with DM. Anti-TIF1 antibody (Ab) was positive in 13 patients, anti-MDA5 Ab in 10, anti-ARS Ab in 10 and anti-Mi-2 Ab in seven. All samples were collected at their first visit or before treatment and stored at 70°C before being used. Specific enzyme-linked immunosorbent assay kits were used to measure the serum levels of IL-9 (eBioscience, San Diego, CA, USA). Immunohistochemical staining of the skin and muscle specimens were performed using rabbit antihuman IL-9 (Abcam, Cambridge, UK), rabbit anti-IL-17A (Santa Cruz Biotechnology, Santa Cruz, CA, USA) and mouse antihuman CD4 (4B12) (Dako, Glostrup, Denmark) Ab. All study participants provided written informed consent. The protocol was approved by Kanazawa University Hospital. Serum IL-9 levels were significantly higher in DM patients than in controls (6.4 17.8 vs 1.7 4.4 pg/mL, P < 0.05) (Fig. 1a). A significant difference was observed in serum IL-9 levels between patients with and those without anti-Mi-2 Ab (29.9 36.1 vs 1.6 1.9 pg/mL, P < 0.001) (Fig. 1b). IL-9 levels were elevated in four out of 40 (10%) patients with DM. The age at disease onset was younger in patients with elevated IL-9 levels than in those with normal IL-9 levels (P = 0.005) (Table S1). This difference may be explained by the fact that the age at disease onset was significantly younger in patients with anti-Mi-2 Ab than in those without anti-Mi-2 Ab (P < 0.05). In laboratory findings, serum creatine kinase (CK) levels were significantly higher in patients with elevated IL-9 levels than in those with normal IL-9 levels (P = 0.0202). Serum levels of aldolase were also significantly higher in patients with elevated IL-9 levels than in those with normal IL-9 levels (P = 0.0242). All four patients with elevated IL-9 levels were positive for anti-Mi-2 Ab and had higher CK levels (Table S2). On the other hand, two out of three anti-Mi-2 Ab-positive patients had higher CK levels but normal IL-9 levels (Table S2). We then examined IL-9 expression in affected muscle and skin lesions. Patients with elevated serum IL-9 levels had a larger number of IL-9 cells in muscle and skin lesions (Fig. 1c). Sequential histological sections revealed that IL-9 cells were also positive for CD4. IL-17 cells were not observed in either muscle or skin tissues in patients with elevated serum IL-9 levels (data not shown). Interleukin-9 contributes to the proliferation of CD4 T cells and increases the production of IL-17 by promoting the proliferation of Th17 cells, which, in turn, produce IL-9. IL-17 has been shown to play an important role in the pathogenesis of immune-mediated inflammatory myopathies. Increased IL-17 levels have been reported in the sera and muscles of DM patients. However, IL-17 cells were not observed in both muscle and skin tissues in this study, suggesting that other pathways independent of Th17 and IL-17 are involved. IL-9 may also contribute to the infiltration of CD4 cells into muscle tissue. IL-9 production by CD4 T cells was previously shown to be enhanced in the presence of transforming growth factor-b and IL-4. In this study, CD4IL-9 T cells in both the skin and muscle tissues were infiltrated in DM patients by elevated serum IL-9 levels. Thus, IL-9 may play an important role in the development of DM. All four patients with elevated serum IL-9 levels tested positive for anti-Mi-2 Ab. Although it currently remains unclear whether elevations in serum IL-9 levels are a specific immune phenomenon for anti-Mi-2 Ab, myositis-specific autoantibodies may be related to different molecular pathways. For example, anti-Jo-1 Ab may activate the type I interferon system and these sera contain higher levels of B-cell-activating factor than other idiopathic inflammatory myopathy subsets. Because this study included a small number of patients with anti-Mi-2 Ab, we need to emphasize that the current data are of a preliminary nature. Further studies are required in order to clarify the role of IL-9 in the development of muscle and skin inflammation.

Two cases of pemphigus vulgaris in remission showing high titer of anti-desmoglein 3 antibodies

1 Kwon CW, Land AS, Smoller BR, Scott G, Beck LA, Mercurio MG. Bullous pemphigoid associated with nivolumab, a programmed cell death 1 protein inhibitor. J Eur Acad Dermatol Venereol 2017; 31: e349–e350. 2 Bandino JP, Perry DM, Clarke CE, Marchell RM, Elston DM. Two cases of anti-programmed cell death 1-associated bullous pemphigoid-like disease and eruptive keratoacanthomas featuring combined histopathology. J Eur Acad Dermatol Venereol 2017; 31: e378–e380. 3 Ishii N, Teye K, Fukuda S et al. Anti-desmocollin autoantibodies in nonclassical pemphigus. Br J Dermatol 2015; 173: 59–68. 4 Gallo E, Garcia-Martin P, Fraga J et al. Paraneoplastic pemphigus with eosinophilic spongiosis and autoantibodies against desmocollins 2 and 3. Clin Exp Dermatol 2014; 39: 323–326. 5 Tanaka M, Hoashi T, Ichiyama S et al. Eczematous reactions mimicking psoriasiform dermatitis induced by nivolumab for advanced lung cancer. Australas J Dermatol 2018; https://doi.org/10. 1111/ajd.12868

Case of anti-transcriptional intermediary factor-1-positive dermatomyositis associated with breast cancer developing over 10 years

Dear Editor, Dermatomyositis (DM) is characterized by inflammatory myopathy and distinct cutaneous findings. The clinical manifestations of DM are heterogeneous, with varying degrees of myositis, skin rash, and accompanying symptoms such as interstitial lung disease and internal malignancy. Recently, antitranscriptional intermediary factor-1c (TIF-1c) antibodies have been identified in cases with cancer-associated DM. A 66-year-old Japanese woman was aware of a tumor of the right breast 10 years before the first visit, but chose to leave it untreated and did not receive a biopsy. She visited our hospital in September 2015 with chief complaints of dysphagia, muscle weakness and skin rash for 1 month. Physical examination revealed muscle weakness and skin rash, including heliotrope rash (Fig. 1a), Gottron’s sign, V-neck/shawl sign, periungual erythema and nail fold bleeding. Furthermore, she presented a hardened skin-colored nodule, fixed to the underlying tissues, measuring 10–13 cm, on her right breast (Fig. 1b, c). Laboratory examinations showed elevated levels of creatine kinase (864 U/L) and aldolase (9 U/L). Tumor marker tests revealed elevated levels of serum carcinoembryonic antigen, cancer antigen 15-3, and NCC-ST-439. Anti-TIF-1 antibodies were detected by immunoprecipitation assay. Muscle biopsy and electromyogram were not conducted because of poor general condition. Computed tomography showed multiple lymph nodes, liver and bone metastases. Biopsy from the tumor on her right breast revealed invasive ductal carcinoma (solid tubular type; Fig. 1d). In addition, immunohistochemical staining resulted in triple-negative breast cancer, which is defined by the lack of protein expression of estrogen receptor,

Pilomatricoma presenting with localized alopecia

A 5-year-old Japanese girl presented with a 4-month history of a solid dermal tumor on the left side of her forehead. She had neither diathesis for autoimmune disorders nor family history of alopecia areata. Her left eyebrow and vellus hairs around the tumor had been lost as the tumor grew. Examination revealed a 1 cm, bluish, solid, dermal tumor surrounded by a 5-cm diameter alopecia, where the left eyebrow and the vellus hairs on the forehead were missing (figure 1A). A presumptive clinical diagnosis [...]