Tatsuya Kaji

Hypocomplementemic urticarial vasculitis arising in a patient with immunoglobulin G4-related disease.

Hypocomplementemic urticarial vasculitis (HUV) has been defined as a syndrome associated with urticarial lesions caused by leukocytoclastic vasculitis. It has been observed in patients with systemic lupus erythematosus and related conditions. Immunoglobulin G4 (IgG4)‐related disease is a lymphoproliferative disorder characterized by sclerosing pancreatitis, retroperitoneal fibrosis, sclerotic cholangitis, acute interstitial nephritis, and Mikuliczs disease, and associated with elevated levels of IgG4 and hypocomplementemia. Various cutaneous lesions may occur in IgG4‐related disease.

Usefulness of serum 5-S-cysteinyl-dopa as a biomarker for predicting prognosis and detecting relapse in patients with advanced stage malignant melanoma.

With the recent development of novel molecular targeted drugs for advanced stage malignant melanoma (MM), including RAF and mitogen‐activated protein kinase kinase inhibitors and immune checkpoint blockers, the early detection of relapse is important for managing patients with MM. In this study, we retrospectively analyzed two conventional serum biomarkers, 5‐S‐cysteinyl‐dopa and lactate dehydrogenase, in patients with MM (n = 140) who were treated at a single Japanese institute from June 2007 to June 2015. At the initial hospital visit, serum 5‐S‐cysteinyl‐dopa levels were significantly increased in patients with stages III (n = 38) and IV (n = 20) MM compared with patients with stages 0–II (n = 62) MM. In addition, in patients with stages III and IV MM, serum 5‐S‐cysteinyl‐dopa levels of more than 15.0 nmol/L at initial hospital visit correlated with a poor prognosis. In 11 of 14 patients whose disease progressed during follow up (mostly from stages III–IV), serum 5‐S‐cysteinyl‐dopa levels exceeded the normal limit of 10.0 nmol/L during the clinical detection of distant metastases. These results indicate the usefulness of measuring serum 5‐S‐cysteinyl‐dopa levels at initial hospital visit and during follow up for early and effective therapeutic interventions using newly developed molecular targeted drugs.

Comparative study on driver mutations in primary and metastatic melanomas at a single Japanese institute: A clue for intra- and inter-tumor heterogeneity

BACKGROUND Searching for driver mutations in melanoma is critical to understanding melanoma genesis, progression and response to therapy. OBJECTIVES We aimed to investigate the frequency and pattern of driver mutations in Japanese primary and metastatic melanomas including cases of unknown primary origin, in relation to their clinicopathologic manifestations. METHODS Seventy-seven samples from 60 patients with melanoma were screened for 70 driver mutations of 20 oncogenes by Sequenom MelaCarta MassARRAY, and the results for primary and metastatic melanomas were compared. RESULTS Of 77 tissue samples, BRAF V600E was detected in 21 samples (27%), CDK4 R24C in 7, EPHB6 G404S in 6, BRAF V600K in 2, NEK10 E379K in 2, and CDK4 R24H, NRAS Q61K, NRAS Q61R, KRAS G12A, KIT L576P, KIT V559A, ERBB4 E452K, and PDGFRA E996K in one sample each. No driver mutations related to the MAPK cascade including RAS and BRAF were detected in the chronically sun-damaged (CSD) group of melanoma. Dual or triple driver mutations were found in four of 40 (10%) samples from the primary melanomas, and three of 37 (8%) of the metastatic melanomas. Fourteen of 26 (54%) samples of non-CSD melanoma, and 3 of 6 (50%) melanomas of unknown primary origin had the BRAF V600E mutation. Mutations in membrane-bound receptors including KIT, ERBB4 and EPHB6 were detected in 8 of 77 (10%) samples. Of 17 pairs of primary and metastatic melanomas from the same patient, the primary mutation pattern was changed to a novel one in three cases, and only one of the plural mutations in the primary melanoma was found in the metastatic lesions in two cases. CONCLUSIONS BRAF V600E is a predominant mutation in non-CSD melanoma and melanomas of unknown primary origin. Mutational heterogeneity may exist in the primary melanoma (intra-tumor heterogeneity), and between the primary and metastatic lesions (inter-tumor heterogeneity).

Prognostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with cutaneous angiosarcoma: A retrospective study of 18 cases

Cutaneous angiosarcoma (CAS) is a rare soft tissue sarcoma with rapid growth and poor prognosis. We retrospectively analyzed the data of 18 patients with CAS who underwent 18F‐Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) at the initial visit to the Department of Dermatology, Okayama University Hospital from September 2006 to March 2016. In the univariate survival analysis, patients with high standardized uptake values (SUVmax) of the primary tumor showed significantly poorer prognosis than those with low SUVmax. Early assessment of prognosis using PET/CT may predict patient survival and is useful in the selection of therapeutic strategies.

Clinical outcomes of primary cutaneous anaplastic large cell lymphoma: data from a single Japanese centre

aspect of the fingers; this was associated with drug-resistant chronic angular stomatitis and typical seborrheic dermatitis. Laboratory findings, including complete blood count, erythrocyte sedimentation rate, urea, creatinine, thyroid stimulating hormone, fasting glucose, transaminases, and total bilirubin, were within the normal range. HBV and HCV serology were negative. Immunological work up, including antinuclear antibodies, anti-Ro/SSA and La/SSB antibodies, and rheumatoid factor, was normal. Liver ultrasound and Doppler ultrasound of the upper limbs were also normal; in addition, the electromyogram performed did not show any abnormalities. Serological tests for syphilis were negative, however, HIV antibodies were detected using an enzyme-linked immunosorbent assay, confirmed by western blotting. The blood CD4-lymphocyte count was 392/ L; HIV RNA viral load reached 107,000 copies/ L. The patient attributed his primary HIV infection to sexual intercourse, two years before. A combination of anti-HIV therapy with darunavir (a protease inhibitor), ritonavir (a booster for other protease inhibitors), and tenofovir/emtricitabine (a combination of two nucleoside inhibitors) was initiated. Marked improvement of the PE and resolution of dysesthesia were seen within two months. The viral load decreased significantly after treatment initiation. PE can be a manifestation of various infectious diseases, including HBV or HCV [1, 3, 4], arboviruses [5], and myelopathy associated with human T-lymphotrophic virus type 1 infection [6, 7]. PE has also been described in patients with brucellosis and trichinellosis [8, 9], however, to our knowledge, PE secondary to HIV infection has never been described before. A similar syndrome called “red-finger syndrome”, manifesting with well-demarcated distal erythema of the fingers and toes, has been described in patients co-infected with HIV and HCV [10]. The authors speculated that vascular reactions might be induced by immunological disturbances induced by HCV and liver disease. The physiopathology of PE is unknown. It could be due to capillary dilatation in the palms and high circulating oestrogen levels, or to stimulation of parasympathetic nerve fibres due to neuropathy secondary to some viral infections (such as HIV). PE can be a manifestation of HIV infection. Its recognition as a cutaneous sign of HIV infection is important, as HIV screening could lead to early diagnosis, early control of the disease, and could prevent further infections.

Sentinel lymph node biopsy for 102 patients with primary cutaneous melanoma at a single Japanese institute.

Sentinel lymph node biopsy (SLNB) is a widely accepted standard procedure for patients with clinically localized melanoma. Melanoma prevalence and Clarks subtype differ between Asians and Caucasians. Here, we evaluated our experience on SLNB for cutaneous melanoma in a Japanese population. SLNB was performed for patients with melanoma between July 2000 and June 2014. We retrospectively analyzed 102 patients regarding association of clinicopathological features with sentinel lymph node (SLN) status, melanoma‐specific survival (MSS) and disease‐free survival (DFS). A positive SLN was significantly associated with primary Breslow thickness. Compared with 43 patients with negative SLN, 59 patients with positive SLN had significantly shorter MSS (5‐year survival rate, 94.3% vs 63.2%; P = 0.0002) and DFS (5‐year survival rate, 92.7% vs 63.4%; P = 0.0004). According to our subgroup analyses, nine patients with positive non‐SLN had significantly shorter MSS compared with 32 patients with negative non‐SLN (5‐year survival rate, 32.4% vs 68.5%; P = 0.0273). The survival of 51 Japanese patients with acral lentiginous melanoma (ALM) was not inferior to the survival of patients with other Clarks subtype. Breslow thickness is an important factor for both MSS and DFS, and the status of SLN is the most predictive prognostic factor in Japanese patients with clinically localized melanomas, as in case of Caucasians. Features of ALM may be different between Asians and Caucasians.