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Summary: Background: Taxanes are the current first‐line treatment for advanced cutaneous angiosarcoma (CAS) for patients who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity. However, no effective second‐line therapy for such patients has been established. Methods: We designed a single‐arm prospective observational study of eribulin mesylate (ERB) administered at a dose of 1·4 mg m−2 on days 1 and 8 in a 21‐day cycle. Patients with advanced CAS who were previously treated with a taxane and were scheduled to begin ERB treatment were enrolled. The primary endpoint was overall survival (OS) and the secondary endpoints were response rate (RR), progression‐free survival (PFS) and toxicity assessment. Results: We enrolled a total of 25 patients. The median OS and PFS were 8·6 months and 3·0 months, respectively. The best overall RR was 20% (five of 25). In total, 16 grade 3/4 severe adverse events (SAEs) occurred; however, all patients recovered. Patients who achieved partial response or stable disease as best response had longer OS than those with progressive disease (median OS not reached and 3·3 months, respectively; P < 0·001). Patients who did not experience SAEs showed longer OS than those who did (median OS 18·8 months and 7·5 months, respectively; P < 0·05). Patients with distant metastasis had shorter median OS than those with locoregional disease, but without statistically significant difference. Conclusions: ERB showed a promising RR and is a potential candidate for second‐line treatment for patients with CAS, after treatment with taxanes. However, owing to the occurrence of SAEs in over half of the participants, caution should be exercised regarding ERB use in elderly patients. What is already known about this topic? Taxanes are the current first‐line treatment for patients with advanced cutaneous angiosarcoma (CAS) who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity.No effective therapy for taxane‐resistant CAS has been established thus far.Eribulin suppresses microtubule polymerization and elicits an antitumour effect similar to that of taxanes. What does this study add? In our single‐arm prospective observational study to evaluate the efficacy of eribulin for treating patients with advanced CAS who previously received taxanes, the median overall survival and progression‐free survival were 8·6 and 3·0 months, respectively.Response rates at weeks 7, 13 and 25 were 20%, 17% and 14%, respectively.Although 16 grade 3/4 severe adverse events occurred, all patients recovered.Eribulin showed a promising response rate and is a potential candidate for second‐line treatment in CAS after taxane treatment. Linked Comment:Smrke and Benson. Br J Dermatol 2020; 183:797–798. What is already known about this topic? Taxanes are the current first‐line treatment for patients with advanced cutaneous angiosarcoma (CAS) who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity.No effective therapy for taxane‐resistant CAS has been established thus far.Eribulin suppresses microtubule polymerization and elicits an antitumour effect similar to that of taxanes. What does this study add? In our single‐arm prospective observational study to evaluate the efficacy of eribulin for treating patients with advanced CAS who previously received taxanes, the median overall survival and progression‐free survival were 8·6 and 3·0 months, respectively.Response rates at weeks 7, 13 and 25 were 20%, 17% and 14%, respectively.Although 16 grade 3/4 severe adverse events occurred, all patients recovered.Eribulin showed a promising response rate and is a potential candidate for second‐line treatment in CAS after taxane treatment. Linked Comment:Smrke and Benson. Br J Dermatol 2020; 183:797–798. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitor-induced vitiligo in advanced melanoma could be related to increased levels of CCL19 In addition to development of vitiligo, compared with baseline, CCL19 at day 42 was significantly higher in patients with advanced melanoma showing objective response ( I P i = 0-01) (Fig. a). As our study analysed CCL20 during anti-PD1 antibody treatment, the mechanisms underlying the development of vitiligo differ from those in previous reports that analysed a single time point in conventional vitiligo. [Extracted from the article]

Summary: ‘Pseudoprogression’ is often seen in patients with melanomas who are treated with immune checkpoint inhibitors such as nivolumab or ipilimumab. We sometimes evaluate metastatic lesions by imaging tests such as computed tomography (CT) or positron emission tomography‐CT. ‘Pseudoprogression’ usually occurs upon the initial administration, which may make it difficult for the physician to determine the disease condition. In our two cases of metastatic melanoma treated with nivolumab (antiprogrammed cell death‐1 antibody), we examined the ultrasonography (US) of target lesions that could be accessed from the body surface, such as those of the regional lymph node or subcutaneous metastasis. In both cases, the US revealed a lesion approximately 10% greater in size after 40–50 days of nivolumab administration, even though the blood flow inside the tumour was reduced by about 20% within 50 days. From about 100 days after blood flow reduction was detected by US, the tumours began to decrease in size. However, contrast CT was unable to detect the association between tumour size and tumour blood flow. The present cases suggest that US could be a powerful tool for differentiating between ‘pseudoprogression’ and real progressive disease in patients treated with cancer immunotherapies such as those involving immune checkpoint inhibitors. The misdiagnosis of progressive disease can lead to unnecessary alterations to the current treatment. Therefore, the US findings in our study could be clinically useful and educational for physicians. [ABSTRACT FROM AUTHOR]

Interferon ( IFN)-alfa as an adjuvant therapy has been found to improve relapse-free survival in patients with malignant melanoma ( MM). However, the efficacy of IFN-beta has not been studied in detail. This study evaluated the contribution of adjuvant IFN-beta therapy to improvements in the prognosis of patients with MM. We reviewed 63 patients with resected stage II/ III primary MM at our institution. Of these, 36 had been treated with IFN-beta adjuvant therapy (subcutaneous injection, 3 × 106 IU/day, 10 days), while 27 patients had undergone observation alone. In comparisons of all patients (stage II/ III), overall survival and relapse-free survival were significantly better in the IFN-beta group than in the observation group ( P < 0.001 for both). The 75-month overall survival rate was 41.2% in the observation group and 68.7% in the IFN-beta group. Adjuvant therapy with IFN-beta may become a new treatment option for patients with stage II/ III MM. [ABSTRACT FROM AUTHOR]

Phototherapy is a useful noninvasive therapy, but it can induce cutaneous malignant tumours, including squamous cell carcinoma ( SCC) and basal cell carcinoma ( BCC). We report on a 79-year-old man who had long-standing mycosis fungoides for 40 years, which had been treated with psoralen ultraviolet A therapy for 37 years at a dose of approximately 5000 J/cm2. Approximately 6 years before presentation, numerous types of cutaneous malignancies, including actinic keratosis, BCC and SCC, had begun to develop all over the patient's body. We hypothesized that he was experiencing a pathogenesis similar to patients with xeroderma pigmentosum ( XP), and we therefore assessed his DNA repair capacity. Based on these investigations, the patient was eventually diagnosed as non- XP, even though we detected that his DNA repair capacity was slightly lower than that of normal controls, which may have led to the skin cancers. We speculate that multiple skin malignancies can be induced by long-term phototherapy in patients with slightly impaired DNA repair capacity. [ABSTRACT FROM AUTHOR]

Recessive dystrophic epidermolysis bullosa ( RDEB) is a severe hereditary mechanobullous disease resulting from mutations in the COL7A1 gene, coding for type VII collagen. Patients with RDEB tend to develop squamous cell carcinomas ( SCCs) at sites of chronic ulceration or scarring on the whole body. Distinguishing SCC from benign hyperkeratotic lesions is often difficult, not only clinically but also histologically in patients with RDEB. We investigated several matrix metallopeptidase ( MMP) subtypes by comparing the DNA amplification microarray findings between evident SCCs and benign hyperkeratotic lesions in the same patient with RDEB. We report that MMP13 was found to be strongly positive in SCCs but negative in benign hyperkeratotic lesions. We found that there is an evident difference in the transitional area between SCCs and benign hyperkeratotic lesions. We propose that MMP13 may be a useful differentiating marker between SCC and benign hyperkeratotic lesions in RDEB. [ABSTRACT FROM AUTHOR]

Eight Thoroughbred horses were used to examine the effects of grass hay intake on the fiber digestion and the retention time of digesta in the total gas-trointestinal tract and the hindgut segments. The horses were randomly assigned to 2 groups and offered 2.0 (high intake [HI]) or 1.3 kg DM/(100 kg BW-d; low intake [LI]) of timothy hay in equal amounts every 3 h for 17 d. The digestibility and total tract mean retention time of digesta (tMRT) in the total gastrointestinal tract were measured from d 11 to d 15. To measure the mean retention time of digesta in each hindgut segment (sMRT), the horses were euthanized on d 17, after being fed a series of hay markers that were labeled with different rare earth elements. The digesta were collected from the ileum, cecum, right ventral colon (RVC), left ventral colon (LVC), left dorsal colon, right dorsal colon (RDC), and small colon (SC) to measure fiber digestibility, sMRT, VFA concentration, and fibrolytic activities. The digestibility ofNDF and ADF in the total gastrointestinal tract was lower (P < 0.01) for HI than for LI. The cumulative disappearance of NDF and ADF from the ileum to the LVC attained 90% of total tract digestion regardless of hay intake. Values did not differ according to treatments in the ileum and the cecum but were lower (P < 0.01) for HI than for LI in the postcecal segments. This was caused by the smaller increase in the cumulative NDF and ADF disappearance from the cecum to the RVC for HI than for LI. The solid phase tMRT was shorter (P = 0.04) for HI than for LI. Although sMRT in the RDC and SC were shorter (P = 0.04 and P < 0.01, respectively) for HI than for LI, no differences were observed in the other hindgut segments. There was no difference between treatments in the total VFA concentration, VFA proportions, or the specific activity of carboxymethyl cellulase and xylanase in each hindgut segment. The fibrolytic activity for the cecum and RVC were greatest and decreased beyond the LVC. A clear relation between mean retention time and fiber digestion was observed in the total gastrointestinal tract, but the segments where a difference in sMRT was detected because of the intake were not the same as those with the fiber digestibility depression. Although the reduction in total tract fiber digestibility with increased feed intake was clearly shown to occur between the cecum and RVC, which were the main segments for fiber digestion, it could be explained neither by the sMRT nor by the fibrolytic activity in these segments. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 79-year-old man with eccrine angiomatous hamartoma (EAH) and has a history of a reddish nodule on the intergluteal cleft that are enlarged and become prone to bleeding. The patient had also hypertension and diabetes. It has been speculated that chronic mechanical irritation of EAH is caused by angioleratomas. The tumour had surgically removed after the physical examination had been done.

We report a case of invasive SCC arising from multiple lesions of Bowen’s disease with right inguinal lymph-node metastasis. Assessment of superficial lymph-node involvement by real-time tissue elastography before surgery was found to be more useful than other noninvasive conventional methods. Histologically, the metastatic tumour cells were located asymmetrically in a small section of the cortical area of the right node, and this result was comparable with the elastographic findings. Additionally, we found that the presence of an asymmetrical cortical area with high elasticity should be included in the determination of metastatic involvement in small lymph nodes. It has high predictive values in the differentiation of benign and malignant superficial lymph nodes in patients with clinically node-negative skin cancer. More cases are needed to validate this efficiency in differentiating benign from malignant lymph-node status, but if confirmed, it may have an important role in the diagnosis of high-risk cutaneous squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Aims: To detect quantitatively the total bacteria and Streptococcus mutans in dental plaque by real-time PCR with prbac, Sm and GTF-B primers, and to compare their presence with the prevalence of dental caries in Japanese preschool children. Methods and Results: Human dental plaque samples were collected from the labial surfaces of the upper primary central incisors of 107 children. The dental status was recorded as dft by WHO caries diagnostic criteria. Positive dt and dft scores by the Sm or GTF-B primer were significantly higher than negative scores ( P < 0·01). The proportions of Strep. mutans to the total bacteria from sound, and sound and/or filled upper primary incisors were significantly lower than those from decayed or filled, and decayed incisors, respectively ( P < 0·01). Conclusions: The ratios of Strep. mutans to total bacteria in plaque detected by real-time PCR with Sm and GTF-B primers were closely associated with the prevalence of dental caries in Japanese preschool children. Significance and Impact of the Study: These assays may be useful for the assessment of an individual's risk of dental caries. [ABSTRACT FROM AUTHOR]

Mucin core protein ( MUC) 5 AC is a gel-forming glycoprotein that is expressed in different types of tumour cells. MUC5 AC expression in cultured cells is regulated through the extracellular matrix and through remodelling by other membranous proteins such as type IV collagen ( COL4) and E-cadherin. However, it has not been elucidated whether COL4 and E-cadherin affect MUC5 AC expression in tumours in vivo. Here, by analysing a single individual with concomitant neoplasms in the skin [extramammary Paget disease ( EMPD)] and the stomach (gastric cancer), we show that MUC5 AC expression is reduced in COL4 and membranous E-cadherin-expressing EMPD specimens whereas MUC5 AC is not abolished in gastric cancer with COL4 negativity and E-cadherin cytoplasmic localization. As the EMPD and gastric cancer specimens were derived from a single patient, each specimen had the same genetic background. These in vivo results support previous in vitro studies which showed that COL4 and E-cadherin downregulated MUC5 AC expression. Our study suggests that concomitant neoplasms in different organs of the same individual can serve as a strong tool for uncovering functional diversity in tumour markers in distinct cancer cells. [ABSTRACT FROM AUTHOR]

Primary mucinous carcinoma of the skin (PMCS) is a rare cutaneous malignant neoplasm; its regional node metastasis is also rare. Currently, positron emission tomography-computed tomography (PET-CT) is known to be a useful tool to search for early metastatic lesions in various carcinomas. However, PET-CT is not always specific for head and neck lesions because of physiological uptake in the brain, palatine tonsil, salivary gland, thyroid etc. Herein we present two cases of head and neck PMCS in which metastasis was diagnosed accurately by PET-CT. In these cases, nodal uptake of fluorodeoxy-D-glucose (FDG) histopathologically proved PMCS metastasis, verifying the utility of PET-CT in detail. A surgeon was involved in the verification to compare the histopathological manifestations with the imaging results. Histopathologically, two of 13 nodes were positive in case 1, and one of 41 nodes was positive in case 2. These positive nodes were completely in accordance with the FDG uptake findings with no false negative findings. In treating PMCS on head and neck lesions, PET-CT may be useful in the preoperative assessment when planning the extent of resection. [ABSTRACT FROM AUTHOR]

The article presents the case study of a 74-year-old man who reported pain due to a lesion on his left shoulder. The clinical findings through Ultrasonograph scan revealed a hyper-vascular multiloculated cyst-like mass and Dermoscopy showed the area dilated. The skin biopsy for Histopathological findings showed two nodules along with dilated veins. Based on the data, the disease was concluded as a Glomus tumor whose symptoms are pain, tenderness, and sensitivity to temperature variation.

A new monoclonal antibody which recognizes plasma cells was developed by utilizing two myeloma cell lines, KMS12PE (12PE) and KMS12BM (12BM), established from the pleural effusion and bone marrow, respectively, of the same patient. Since 12BM expresses CD20, CD38, and PCA-1 antigens, while 12PE has lost CD20, 12PE is considered to be phenotypically more mature than 12BM. The 12PE cells were used to immunize a BALB/c mouse and a MoAb was produced which was more reactive to 12PE than to I2BM. Thus, a clone, D2, was obtained. On Western blotting, D2 detected a single band of 54 kD under both reduced and non-reduced conditions. This antigen was not detected by Western blotting in peripheral blood lymphocytes that had been stimulated with pokeweed mitogen (PWM) for 7 days or in those not so stimulated. On flow cytometry, D2 detected a myeloma cell line, RPMI 8226. Another myelomacell line, U266. was negative for D2 antigen. Staining various cell lines by D2 and other anti-plasma cell antibodies, PCA-1 and CD38, showed that D2 is distinct from PCA-1 and CD38. The fresh myeloma cells of 14 myeloma patients were stained by D2 and for other plasma cell antigens. D2 strongly stained three samples obtained from patients with clinically aggressive myeloma, while CD38 stained all cases except one. PCA-1 was positive in nine samples and negative in five. PCA-1 expression was observed in plasma cells obtained from pleural effusion and peripheral blood, while PCA-1-negative cases were not found in such samples, suggesting that PCA-1 expression was related to extramedullary invasion. The morphology of the myeloma cells, classified according to Greipp's criteria, showed that there was no correlation between plasma cell antigen expression and plasma cell morphology. Analysis of D2 antigen expressions should provide more information about the heterogeneity of myeloma cells. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 32-year-old woman diagnosed with approximately 30 millimeter (mm) palpable tumour in diameter on the pubic mound. The conducted Doppler ultrasonography showed abundant flow of blood and hypervascularity within the tumour. Information regarding the solitary fibrous tumour (SET) is also mentioned.

The article describes the cases of Japanese female patients who developed pseudolymphoma on the lips. The patients presented several clinical conditions including a firm. well-demarcated and asymptomatic erythematous papules, dense filtrates of mononuclear cells and increased eosinophils. A discussion on pseudolymphoma in mucous membranes, the pathomechanism of pseudolymphoma and the effect of metals on the lip is offered.

The article offers information on the efficacy of nivolumab monotherapy against acral lentiginous melanoma and mucosal melanoma in Asian patients. It mentions the early clinical trials showed that treatment with anti-programmed death (PD)-1 agents, such as nivolumab and pembrolizumab, led to marked improvements in the prognosis of patients with advanced melanoma; and also mentions the efficacy of anti-PD-1 agents in Asian populations remains unclear.

An association between seborrhoeic keratosis (SK) and malignant tumours is considered to be rare. We observed a case of eccrine porocarcinoma and Bowen's disease (BD) occurring synchronously, forming one lesion in a SK on the abdomen. It is controversial whether malignant neoplasms arising in SK occur only by chance or if pre-existing SK plays a role in pathogenesis. This case suggests an implication of pre-existing SK in the subsequent development of both BD and eccrine porocarcinoma. [ABSTRACT FROM AUTHOR]

The article presents a case of 80-year-old Japanese man patient presented with a 4-year history of a nodule suspected to be angiosarcoma. Physical examination of nodules revealed bordered lesion with several nodules within the lesion. Histopathological examination of the same nodule showed widely dilated vascular channels, microthrombi and endothelial papillary structure. Nodules in the port-wine stain had dermoscopic features resembling those of pyogenic granuloma.

The article describes the case of a 78-year-old man with hypothyrodism associated with cessation of nivolumab treatment for unresectable malignat melanoma. Topics discussed include the discontinuance of the patient's nivolumab treatment due to chronic heart failure, the supportive care given to the patient, and the percentage of patients treated with PD-1 inhibitors who demonstrate hypothyroidism.

The article describes the case of a 76-year-old woman who developed vulvar basal cell carcinoma (BCC) with adhesion of the labia majora and minora. Topics discussed include physical examination which showed an asymptomatic, subcutaneous nodule, and histological findings which revealed some nests composed of basophilic hair germ cell-like cells connected to the epidermis.

Linked Article: Fujimura et al. Br J Dermatol 2018; 179:1392–1395. [ABSTRACT FROM AUTHOR]

The article presents a case study of an 80-year-old Japanese woman who was treated with tyrosine kinase inhibitor pazopanib for end-stage angiosarcoma (AS) of the scalp. Topics discussed include the history of dementia of the patient, the association of pleural effusion (PE) with AS metastasis, and the use of computed tomography (CT) and magnetic resonance imaging (MRI).

The article presents a case study of a 92-year-old man who was presented with dark-violaceous lesions on the dorsa of his both hands. Topics discussed include the several conditions revealed by histopathological test which include hyperkeratosis of horny cells with parakeratosis, acanthosis, and interface dermatitis, the diagnosis of pellagra, and the mental changes and gastrointestinal symptoms resulting to diarrhoea, dementia, and dermatitis.

The article presents a case study of a 77-year-old woman having a 4-month history of a tumour on her left temporal region. Ultrasound elastography showed a demarcated lesion having high elasticity at the cystic low-echolic area's centre. Histopathology specimens showed a subcutaneous tumour with cystic and haemorrhagic spaces. Immunohistochemical results revealed the tumour cells to be positive for CD68 and desmin.

A letter to the editor is presented regarding melanonychia caused by Stenotrophomonas maltophilia.

Background Hidradenitis suppurativa (HS) is a chronic follicular occlusive disease with characteristic recurrent draining sinuses, skin abscesses and disfiguring scars, mainly involving the axilla, groin, perianal and perineal regions. While most HS cases are nonfamilial, familial cases showing autosomal dominant inheritance have been reported. Recently, loss-of-function mutations in the genes encoding γ-secretase have been identified as a cause of familial HS in the Chinese and British populations. Objectives To identify mutations in the genes encoding γ-secretase in Japanese patients with familial and nonfamilial HS. Methods Two affected and three unaffected individuals from a Japanese family with familial HS and nine patients with nonfamilial HS were recruited. We conducted mutation analysis of the γ-secretase genes in Japanese patients with familial and nonfamilial HS. Results A novel splice site mutation in the nicastrin gene NCSTN, one of the six key component genes encoding γ-secretase, was identified in the patients with familial HS. Neither unaffected individuals in the family nor 100 ethnically matched control alleles carry this mutation. None of the nine patients with nonfamilial HS carry nonsense, frameshift or splice site mutations in this gene. Conclusions A novel splice site mutation, c.582+1delG, in NCSTN was identified in the familial patients with HS. We also reveal for the first time that a γ-secretase gene mutation is not linked to the development of nonfamilial HS. These results would further pave the way to a better understanding of the contribution of γ-secretase and other genes to the pathogenesis of HS and to the development of a new therapeutic strategy for HS. [ABSTRACT FROM AUTHOR]