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Introduction: Basal cell carcinoma (BCC) is a common skin cancer that rarely metastasizes but can deeply infiltrate local tissues. The small number of unresectable BCC cases makes it difficult to conduct clinical trials, resulting in delays in the development of effective drugs for BCC. Cancer gene panel testing has led to an increasing number of new treatment proposals for patients with solid tumors for whom no standard treatment is available. Case Presentation: We described a case of unresectable BRCA1 L63*-mutated BCC invading the parietal bone, which was successfully treated with cisplatin and fluorouracil. Conclusion: Our present case suggests that comprehensive mutation analysis by gene panel testing is important in advanced BCC because genes other than those involved in the hedgehog signaling pathway can be driver genes.

Abstract The debates over the requirement of the International Code of Nomenclature for algae, fungi, and plants (ICNafp) for a viable specimen to represent the name-bearing type material for a species or infraspecific taxon have a long history. Taxonomy of fungi commonly studied as living cultures exemplified by yeasts and moulds, strongly depend on viable reference material. The availability of viable cultures is also particularly useful for several groups of filamentous and dimorphic fungi. While the preservation of metabolically inactive cultures is permitted and recommended by the ICNafp, there is room for improvement. Below, we review the history and current status of cultures as the name-bearing type material under the Code. We also present a roadmap with tasks to be achieved in order to establish a stable nomenclatural system that properly manages taxa typified by viable specimens. Furthermore, we propose setting up rules and defining the nomenclatural status of ex-type cultures under Chapter F, the section of the ICNafp that includes provisions specific to names of fungi.

Introduction: Capicua transcriptional repressor (CIC)-DUX4 rearranged sarcoma is a subtype of CIC-rearranged sarcomas composed of undifferentiated Wilms’ tumor 1 (WT1)+, CD99+ round cells with recurrent CIC gene rearrangement. The diagnosis of CIC-rearranged sarcoma remains challenging, and the prognosis of CIC-rearranged sarcomas is poor. Case Presentation: In this report, we described a case of CIC-DUX4 rearranged sarcoma presenting in the skin, expressing WT1 and CD99 in a dot-like pattern. In addition, the assessment of genomic alterations using genome panel testing was useful to confirm the accurate diagnosis. Conclusion: Our present case suggests that widespread use of genomic panel testing in the future may lead to early treatment and improve the prognosis of CIC-rearranged sarcomas.

Introduction: Chemoradiotherapy with taxanes is well-recognized as a first-line therapy for cutaneous angiosarcoma (CAS), but second-line therapy for CAS is still controversial. Case Presentation: In this report, we described a 75-year-old Japanese case of recurrent, tumor mutation burden-high CAS on the scalp treated with pembrolizumab. Our present case survived for 1 year despite of taxane refractory CAS with mediastinal lymph node metastasis, though the administration of anti-PD-1 Abs alone could not fully suppress the tumor progression of CAS. Conclusion: Since various factors such as pro-angiogenic molecules are correlated with the tumor progression in CAS, the administration of anti-PD-1 Abs alone could not fully suppress the tumor progression of CAS. Further novel anticancer drugs are needed in the future for the treatment of CAS.

Abstract Bexarotene is often administered to phototherapy‐resistant early cutaneous T‐cell lymphoma (CTCL) patients as one of the first‐line therapies in real‐world practice. Since bexarotene reduces the expression of CCR4 in CTCL cells and CCL22 to decrease serum CCL22 levels, bexarotene inhibits the migration of CTCL cells, as well as other CCR4+ cells, such as cytotoxic T cells and regulatory T cells, in the lesional skin of CTCL. In this report, the efficacy of bexarotene in 28 cases of CTCL, as well as its correlations with immunohistochemical profiles of tumour‐infiltrating leucocytes (TILs), was retrospectively investigated. The overall response rate at 1 and 4 months for the total cohort was 70.8% (95% CI, 50.6%–86.3%) and 47.8% (95% CI, 29.2%–67.0%), respectively. The disease control rate for the total cohort at 4 months was 65.2% (95% CI, 44.8%–81.3%). The mean event‐free survival for all patients was 4.1 months (0.3–68.5 months). In addition, the immunoreactive cells were calculated using digital microscopy, suggesting that the ratio of CD25+ cells among TILs was significantly increased in patients who responded to bexarotene (p = 0.0209), whereas there were no significant differences in the ratios of CD8+ cells, granulysin+ cells, and Foxp3+ cells among TILs between responder and non‐responder patients. Collectively, the ratio of CD25 expression among TILs might be a predictive biomarker for the efficacy of bexarotene.

Abstract Background The use of spinal instrumentation is an established risk factor for postoperative infection. To address this problem, we prepared silver‐containing hydroxyapatite coating, consisting of highly osteoconductive hydroxyapatite interfused with silver. The technology has been adopted for total hip arthroplasty. Silver‐containing hydroxyapatite coating has been reported to have good biocompatibility and low toxicity. However, no studies about applying this coating in spinal surgery have addressed the osteoconductivity and direct neurotoxicity to the spinal cord of silver‐containing hydroxyapatite cages in spinal interbody fusion. Aim In this study, we evaluated the osteoconductivity and neurotoxicity of silver‐containing hydroxyapatite‐coated implants in rats. Materials & Methods Titanium (non‐coated, hydroxyapatite‐coated, and silver‐containing hydroxyapatite‐coated) interbody cages were inserted into the spine for anterior lumbar fusion. At 8 weeks postoperatively, micro‐computed tomography and histology were performed to evaluate the osteoconductivity of the cage. Inclined plane test and toe pinch test were performed postoperatively to assess neurotoxicity. Results Micro‐computed tomography data indicated no significant difference in bone volume/total volume among the three groups. Histologically, the hydroxyapatite‐coated and silver‐containing hydroxyapatite‐coated groups showed significantly higher bone contact rate than that of the titanium group. In contrast, there was no significant difference in bone formation rate among the three groups. Data of inclined plane and toe pinch test showed no significant loss of motor and sensory function in the three groups. Furthermore, there was no degeneration, necrosis, or accumulation of silver in the spinal cord on histology. Conclusions This study suggests that silver‐hydroxyapatite‐coated interbody cages produce good osteoconductivity and are not associated with direct neurotoxicity.

Bexarotene is a third-generation retinoid X receptor-selective retinoid that has been approved for use in the treatment of cutaneous T-cell lymphomas (CTCLs). Since the objective response rate of bexarotene is relatively high, with no racial differences, bexarotene can be administered to patients with phototherapy-resistant early CTCL as one of the first-line therapies in real-world clinical practice. Although various adverse events caused by bexarotene have been reported, there have been no reports of drug eruptions caused by bexarotene. One of the possible reasons is that it is difficult to distinguish a drug eruption from recurrence of CTCL, histologically. In this report, drug eruptions in 2 patients with CTCL treated with bexarotene diagnosed by quantitative analysis of immunohistochemical staining by digital microscopy are described.

Abstract Cutaneous angiosarcoma (CAS) is rare and most previous studies of CAS have been small case series, and randomized, phase II studies of CAS are limited. Since treatment options for CAS are controversial, and because only paclitaxel should be recommended based on high‐level evidence, it is important to evaluate the efficacy of another taxane‐derived agents, docetaxel, in real‐world practice. The efficacy and safety profiles of chemoradiotherapy using taxane‐based agents, docetaxel and paclitaxel, were retrospectively examined in the maintenance setting in 90 Japanese CAS patients, including 35 docetaxel‐treated cases and 55 paclitaxel‐treated cases. Overall survival and dose duration time of the patient group treated with docetaxel was equivalent to that with paclitaxel, even in the cohorts with metastasis. Adverse events due to docetaxel and paclitaxel were observed in 77.1% and 69.1% of cases, respectively. The incidence ratio of total severe adverse events tended to be higher in the docetaxel‐treated group (40.0%) than in the paclitaxel‐treated group (23.6%). Peripheral neuropathy occurred only in the paclitaxel‐treated group, whereas high‐grade interstitial pneumonia developed only in the docetaxel‐treated group. In addition, we also evaluate 19 patients selected other taxanes, 17 patients selected eribulin methylate, 11 patients pazopanib, and 2 patients selected nivolumab as second‐line chemotherapy. The efficacy of a monthly docetaxel regimen is equivalent to a three‐weekly paclitaxel regimen evaluated by Overall survival and DDT, even in the cohorts with metastasis, and it is a tolerable protocol for CAS as a maintenance therapy in the Japanese population.

Although microcystic adnexal carcinoma (MAC) recurs and expands locally without metastases to the lymph nodes and other organs, its biological behavior remains unknown. In this report, a case of a giant MAC on the back treated with radical excision and curative radiation therapy and its characteristic dermoscopic findings are presented. In addition, immunohistochemical staining showed the expression of matrix metalloproteinase (MMP) 28 on the tumor cells and MMP12 and periostin in the stroma. The present case suggests the possible biological behaviors of MAC and might provide a possible target for the treatment of MAC in the future.

Abstract Background Numerous patients who receive hemodialysis (HD) undergo total knee arthroplasty (TKA) due to advanced knee joint arthritis. However, there are few studies that describe the clinical outcomes and complications of TKA in HD patients. This study investigated the mid-term results of TKA in patients undergoing HD. Methods This single-center retrospective study compared clinical and surgical outcomes following TKA in patients who were receiving HD with those who were not. We used propensity scores to match 21 knees of 18 patients who received HD to 706 knees of 569 patients who had not received HD, from a total of 727 knees (587 patients) that underwent primary unilateral TKA. The clinical outcomes were evaluated using the American Knee Society Score-knee (AKSS-knee) and AKSS-function scores. The primary surgical outcome measure was the number of knees with postoperative complications. Results In both the HD and non-HD groups, postoperative AKSS-knee and function scores significantly improved when compared to preoperative values. Postoperative AKSS-knee and function scores were not significantly different between the groups. The number of knees with postoperative complications was larger in the HD group than the non-HD group within the first postoperative month, 0–12 months, 12–24 months, 0–24 months, and two years after surgery. Additionally, in the HD group, more complications occurred in the first month than any subsequent month in the two years after surgery. Conclusions TKA improves AKSS-knee and function scores equivalently for HD patients and non-HD patients. However, HD patients develop more complications after TKA, especially within the first month. Therefore, surgeons who perform TKA for HD patients should obtain informed consent after explaining the possible complications, and HD patients should be carefully observed following TKA.

Abstract Background The number of total hip arthroplasties (THAs) performed for patients undergoing dialysis is increasing. However, there are few reports of cementless THA for patients undergoing dialysis. This study investigated the mid-term to long-term results of hydroxyapatite (HA)-coated cementless THA for dialysis patients. Methods This single-center, retrospective study enrolled dialysis patients undergoing primary HA-coated cementless THA. A total of 24 patients (30 hips) were included in the final analyses. The Harris hip score and radiographic results were assessed preoperatively and during the final follow-up examination. Postoperative complications and mortality rates were recorded. The mean follow-up period was 109 months (range, 60–216 months). Results The total Harris hip score significantly improved from 40 to 84 points. The overall cumulative survival rates with revision as the endpoint were 100% at 5 years and 90.4% at both 10 and 15 years. Stress shielding was observed in 24 hips (80%). No deaths were related to the primary THA. Complications included periprosthetic fracture for one patient (3.3%), blood transfusion for nine patients (30%), shunt blockage for two patients (6.7%), deep infection for one patient (3.3%), and dislocation for two patients (6.7%). Conclusions HA-coated cementless THA resulted in good mid-term outcomes for patients undergoing dialysis with no mortality risk. However, the procedure involved a relatively high perioperative risk of blood transfusion.

Anti-PD-1 antibodies (Abs) are among the optimal adjuvant therapies for melanoma at high risk of recurrence, especially BRAF wild-type melanoma, but the anti-tumour effects of anti-PD-1 Abs in the adjuvant setting for acral melanoma have not been evaluated previously. The aim of this study was to analyse the efficacy and safety profiles of anti-PD-1 Ab monotherapy in the adjuvant setting in an Asian population including a high ratio of acral melanoma. The efficacy and safety profiles of anti-PD-1 Ab monotherapy in the adjuvant setting were retrospectively analysed in 78 Japanese patients with advanced melanoma, including 31 cases (40%) of acral melanoma. Overall relapse-free survival was 60.3% (47 of 78 cases, 95% confidence interval (CI) 49.2–70.4%), and 39.7% of patients (31 of 78 patients, 95% CI 29.6–50.8%) relapsed during the adjuvant PD-1 Ab treatment. Six cases (7.9%) discontinued the protocol due to serious adverse events. One case (1.3%) discontinued the protocol due to trauma. The relapse-free survival of acral melanoma was 25.8%, whereas that of high cumulative sun damage was 60.0%, and that of low cumulative sun damage was 57.1%. The acral type had a significantly lower 12-month relapse-free survival than other cutaneous types (p = 0.029). The acral type appeared to be an independent prognostic factor on multivariate analysis (p = 0.015). Adverse events due to anti-PD-1 antibody were observed in 37.1% overall. The results of this study suggest that anti-PD-1 Ab therapy in the adjuvant setting is less effective for acral melanoma than for other cutaneous types.

Abstract Objective We developed a silver-containing hydroxyapatite (Ag-HA) coating to prevent periprosthetic joint infection (PJI). Methicillin-resistant Staphylococcus aureus (MRSA) is the main PJI-causing bacteria. Previously, we had reported the combined effect of Ag-HA coating and vancomycin (VCM) on MRSA biofilm formation 24 h after MRSA inoculation. In this study, we investigated the time-dependent efficacy of Ag-HA coating and VCM on MRSA biofilm formation on Ti discs in vitro by three-dimensional confocal laser scanning microscopic analysis. Results For the Ti VCM and HA VCM groups, the total biofilm volumes per area at 96 h after MRSA inoculation were significantly larger than those at 48 h after MRSA inoculation, respectively (p

Abstract Background Of late, periarticular analgesic injection (PAI) has become a common alternative treatment for pain following total hip arthroplasty (THA). However, the systemic effects of PAI containing corticosteroids in patients subjected to THA have not been investigated. This study evaluated the analgesic efficacy and systemic effects of PAI containing a corticosteroid in patients subjected to THA. Methods This single-center, retrospective cohort study enrolled patients undergoing unilateral, primary THA. A total of 197 patients (200 hips) were included in the final analyses, with 87 hips in the PAI group and 113 hips in the control group. Numeric Rating Scale (NRS) and laboratory data were assessed preoperatively and on postoperative days (POD) 1 and 7. Pearson’s correlation coefficients were obtained to assess the correlations between the D-dimer level on POD 7 and each outcome measure on POD 1. Results The postoperative white blood cell count (WBC) was significantly higher in the PAI group than in the control group. Postoperative NRS, creatine phosphokinase (CK), and C-reactive protein (CRP) levels were significantly lower in the PAI group. D-dimer levels were significantly lower in the PAI group on POD 7. Postoperative aspartate transaminase (AST), alanine aminotransferase, blood urea nitrogen, and creatinine levels were within reference ranges. D-dimer levels on POD 7 showed a significant negative correlation with WBC on POD 1 (r=-0.4652) and a significant positive correlation with the NRS score and AST, CK, CRP, and D-dimer levels on POD 1 (r = 0.1558, 0.2353, 0.2718, 0.3545, and 0.3359, respectively). Conclusions PAI containing a corticosteroid may be an effective treatment for pain and inflammation after THA, and it does not seem to cause drug-induced liver or kidney injury. Moreover, corticosteroid PAI can may accelerate early ambulation, which prevents the elevation of postoperative D-dimer levels, and may reduce the risk of deep venous thrombosis.

Since the cost of molecular biological methods for Spitzoid neoplasms is expensive, the number of institutes that employ these methods might be limited. Preferentially expressed antigen in melanoma (PRAME) is a tumor-associated antigen that is useful to distinguish melanoma from other melanocytic disorders, including pediatric Spitzoid tumors that are difficult to diagnose by conventional methods alone. In this report, we report a case of PRAME-expressing juvenile Spitzoid melanoma with lymph node metastasis. Unexpectedly, there were few PRAME-expressing cells in the primary tumor, whereas most metastatic tumors expressed PRAME in the metastatic lymph node. These observations might suggest that, in Spitzoid melanomas, a limited number of melanoma cells possess metastatic potential and that metastatic lesions possess clonality.

Since the incidence of mucosal melanoma is higher in the Japanese population compared to Caucasians, and since mucosal melanoma possesses a lower mutation burden compared to cutaneous melanoma, the efficacy of anti-PD1 antibody (Ab) monotherapy for mucosal melanoma is limited. Therefore, other targeting molecules that enhance the anti-tumor effects of immune checkpoint inhibitors are needed. In this report, we present a case with anti-PD1 Ab-resistant recurrent malignant melanoma of the nasal cavity successfully treated with nivolu­mab, ipilimumab plus denosumab combination therapy.

Abstract pH homeostasis in the chloroplast is crucial for the control of photosynthesis and other metabolic processes in plants. Recently, nuclear‐encoded Day‐Length‐dependent Delayed Greening1 (DLDG1) and Fluctuating‐Light Acclimation Protein1 (FLAP1) that are required for the light‐inducible optimization of plastidial pH in Arabidopsis thaliana were identified. DLDG1 and FLAP1 homologs are specifically conserved in oxygenic phototrophs, and a DLDG1 homolog, Ycf10, is encoded in the chloroplast genome in plant cells. However, the function of Ycf10 and its physiological significance are unknown. To address this, we constructed ycf10 tobacco Nicotiana tabacum mutants and characterized their phenotypes. The ycf10 tobacco mutants grown under continuous‐light conditions showed a pale‐green phenotype only in developing leaves, and it was suppressed in short‐day conditions. The ycf10 mutants also induced excessive non‐photochemical quenching (NPQ) compared with those in the wild‐type at the induction stage of photosynthesis. These phenotypes resemble those of Arabidopsis dldg1 mutants, suggesting that they have similar functions. However, there are distinct differences between the two mutant phenotypes: The highly induced NPQ in tobacco ycf10 and the Arabidopsis dldg1 mutants are diminished and enhanced, respectively, with increasing duration of the fluctuating actinic‐light illumination. Ycf10 and DLDG1 were previously shown to localize in chloroplast envelope‐membranes, suggesting that Ycf10 and DLDG1 differentially control H+ exchange across these membranes in a light‐dependent manner to control photosynthesis.

Nivolumab plus ipilimumab combined therapy is one of the promising drugs that enhance the anti- immune response in patients with advanced melanoma. Therefore, to increase its response rate is of great interest to dermatologists. Recent reports suggested that, since CD8+ T cells after the administration of ICIs increase the RANKL expression to induce an immunosuppressive tumor microenvironment in melanoma, denosumab might enhance the anti-tumor effects of immune checkpoint inhibitors, such as nivolumab and ipilimumab. In this report, we present a case of multiple metastatic melanoma with nivolumab, ipilimumab plus denosumab combined therapy.

Objective. To improve postoperative pain management, several authors have described the use of periarticular injection (PAI) or intra-articular injection (IAI) following total hip arthroplasty (THA). However, no comparative studies examining the results between PAI and IAI following THA have been published. This study aimed to evaluate the analgesic and anti-inflammatory effects of PAI and IAI following THA. Methods. This single-center, retrospective cohort study enrolled patients who underwent unilateral primary THA. A total of 278 patients (281 hips) were included in the final analyses, with 112 patients (113 hips) in the control group, 85 patients (87 hips) in the PAI group, and 81 patients (81 hips) in the IAI group. Numeric rating scale (NRS) scores and laboratory data were assessed preoperatively and on postoperative days (POD) 1 and 7. Results. NRS scores, creatine phosphokinase, and C-reactive protein levels in the PAI and IAI groups were significantly lower than those in the control group on POD 1 and 7. D-dimer levels were significantly lower in the PAI and IAI groups than in the control group on POD 7. The white blood cell count was significantly higher in the PAI and IAI groups than in the control group on POD 1 and 7. Aspartate transaminase, alanine aminotransferase, blood urea nitrogen, and creatinine levels were within the reference ranges in all three groups at all time points. NRS scores and laboratory data showed no significant differences between the PAI and IAI groups at all time points. Conclusion. PAI and IAI have equivalent analgesic and anti-inflammatory effects. Considering the technical challenges of PAI, IAI may be preferable because of its simplicity in the case of using a closed suction drain.

The prevention of surgical site infections is directly related to the minimization of surgical invasiveness, and is in line with the concept of minimally invasive spine therapy (MIST). In recent years, the incidence of postoperative infections has been increasing due to the increased use of spinal implant surgery in patients at high risk of infection, including the elderly and easily infected hosts, the limitations of poor bone marrow transfer of antibiotics, and the potential for contamination of surgical gloves and instruments. Thus, the development of antimicrobial implants in orthopedic and spinal surgery is becoming more and more popular, and implants with proven antimicrobial, safety, and osteoconductive properties (i.e., silver, iodine, antibiotics) in vitro, in vivo, and in clinical trials have become available for clinical use. We have developed silver-containing hydroxyapatite (Ag-HA)-coated implants to prevent post-operative infection, and increase bone fusion capacity, and have successfully commercialized antibacterial implants for hip prostheses and spinal interbody cages. This narrative review overviews the present status of available surface coating technologies and materials; describes how the antimicrobial, safety, and biocompatibility (osteoconductivity) of Ag-HA-coated implants have been demonstrated for commercialization; and reviews the clinical use of antimicrobial implants in orthopedic and spinal surgery, including Ag-HA-coated implants that we have developed.

Objectives. This study investigated the relationship between quality of life (QOL) and several factors, including pain assessments, in patients with rheumatoid arthritis (RA). Methods. This cross-sectional, single-center study enrolled 85 patients with RA. The variables investigated included demographic characteristics, the 28-joint disease activity score with C-reactive protein (DAS28-CRP), painDETECT questionnaire (PDQ), pain self-efficacy questionnaire (PSEQ), and pain catastrophizing scale (PCS). QOL was measured using the Japanese validated version of the European Quality of Life questionnaire with five dimensions and five levels (EQ-5D-5L). Results. The use of oral steroids and oral analgesics was significantly associated with low EQ-5D-5L scores (P

Distal trochanteric transfer (DTT) has been widely performed to treat developmental dysplasia of the hip or Perthes disease. Total hip arthroplasty (THA) following DTT in patients with hip osteoarthritis is one of the most challenging procedures for hip surgeons, because great care must be taken regarding anatomical abnormalities of the greater trochanter and the soft tissue attached to the greater trochanter. To the best of our knowledge, there are no reports on THA after DTT. We herein report two cases of patients who underwent THA post DTT using cementless components. After THA, both patients developed abduction temporary contraction because of leg length extension and gluteus medius hypertension. However, in both cases, the contraction was reversible within two months and the final clinical result was good. Therefore, THA can be considered an effective and safe choice for treating osteoarthritis after DTT.

Human T-cell leukemia virus type 1- (HTLV-1-) associated arthritis is a relatively common disease. However, tenosynovitis owing to adult T-cell leukemia-lymphoma (ATL) is a rare condition. To the best of our knowledge, there have been no reports of tenosynovitis caused by conversion to acute ATL from one of the other ATL types. We present the case of a 60-year-old woman with rheumatoid arthritis (RA) with bilateral wrist tenosynovitis owing to the conversion to acute ATL from one of the other ATL types. She had swelling around the bilateral wrist joint under well controlled RA inflammation. She had no symptoms, physical findings, or laboratory findings indicative of conversion to acute ATL from one of the other ATL types. She underwent tenosynovectomy on the volar and dorsal sides of the left wrist joint to diagnose the cause of swelling around the bilateral wrist joint. Pathological analysis revealed diffuse proliferation of medium-sized atypical CD4(+) lymphocytes. Interestingly, she was diagnosed with wrist tenosynovitis caused by an acute ATL type. This diagnosis suggested that clinicians must consider ATL in connection with atypical wrist tenosynovitis in HTLV-1-endemic areas.

Keratoacanthoma centrifugum marignatum (KCM) is a rare variant of keratoacanthoma, which is characterized by the dense infiltration of inflammatory cells throughout the dermis, especially around the keratinocytic islands. Therefore, it is sometimes difficult to differentiate between KCM and cutaneous T-cell lymphomas. In this report, we describe a case of KCM with spontaneous regression that showed dense infiltration of CD3+CD8+ T cells. Our present case suggested the importance of investigating tumor-infiltrating lymphocytes to avoid the misdiagnosis of KCM as cutaneous T-cell lymphoma.

A 94-year-old man consulted our hospital due to a rapidly growing tumor on the left cheek. The histological diagnosis of the tumor was basal cell carcinosarcoma, which was composed of intermingled epithelial and mesenchymal components. The former was basal cell carcinoma, while the latter was spindle cell sarcoma. The tumor was completely resected with a 3-mm margin and the patient remained free of local recurrence or distinct metastasis for 2 years. We report here a case of cutaneous basal cell carcinosarcoma and a review of the literature.

Pigmented epithelioid melanocytoma (PEM), also known as an animal-type melanoma, is a distinctive group of melanocytic tumors with a more favorable prognosis than conventional melanoma. Since tumor-associated macrophages (TAMs) extend in the premetastatic lymph nodes in several cancers, we hypothesized that the lower rate of lymph node metastasis in PEM might be correlated with the phenotypes of TAMs. Therefore, in this report, we further investigate the subpopulation of TAMs in PEM, revealing that the main population of TAMs in histiocytic lesion is CD163+CD206+PD-L1+ M2-polarized macrophages. In addition, since the PD-L1-expressing CD205+ dendritic cells are also detected in histiocytic lesions, the PD-L1-expressing TAMs and dendritic cells might suggest favorable prognostic factors in patients with PEM.

Radiation-associated angiosarcoma (RAAS) is a type of radiation-associated sarcoma (RAS) that develops at the previous field of radiation in breast cancer patients. Although several reports have suggested a poor prognosis for RAAS, the 5-year overall survival of RAAS is better than that of cutaneous angiosarcoma (CAS), suggesting that the prognostic factors of RAAS and CAS might be different, at least in part. In this report, we describe a case of RAAS, and employed immunohistochemical (IHC) staining of PD-L1 and MMP9 as well as periostin, IL-4, and CD163. Interestingly, IHC staining revealed that the RAAS in our case was positive for PD-L1 and negative for MMP9. Moreover, the predominant stromal factor of our case was periostin, suggesting that TAMs in the present case was not immunosuppressive, but an inflammatory subtype. These results might explain, at least in part, the better prognosis of RAAS compared to CAS.

Bexarotene is a third-generation retinoid X receptor-selective retinoid that is widely used for the early treatment of advanced-stage cutaneous T-cell lymphomas. In this report, we describe a case of successful treatment of advanced primary cutaneous peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) with oral bexarotene monotherapy. After the administration of oral bexarotene at a dose of 300 mg/m2/day, all skin lesions and lymph nodes regressed, and complete remission was achieved for 1 year. Our case suggested that bexarotene monotherapy could be one of the possible therapies for the treatment of primary cutaneous PTCL-NOS.

Since the efficacy of ipilimumab on nivolumab-resistant advanced melanoma is extremely low, additional supportive therapy for anti-PD-1 antibody therapy-resistant advanced melanoma is needed. Although several supportive therapies that enhance the antitumor immune response of anti-PD-1 antibodies have already been reported, unexpected immune-related adverse events were detected at the same time. In this report, we describe a patient with advanced melanoma treated with nivolumab followed by intensity-modulated radiotherapy, which might have triggered bullous pemphigoid (BP). Although several cases of BP developing in anti-PD-1 antibody-treated patients have already been reported, in this report, we shed light on the possible pathogenesis of BP developing in a patient treated with nivolumab through M2 macrophages.

Simultaneous or sequential, planned administration of ipilimumab could significantly enhance the antitumor effects of nivolumab in advanced melanoma patients. On the other hand, the efficacy of ipilimumab for nivolumab-resistant advanced melanoma is extremely poor. Therefore, additional supportive therapy for anti-PD-1 antibody therapy-resistant advanced melanoma has been widely investigated. In this report, we describe a case of multiple in-transit melanomas developing in a nivolumab-resistant patient successfully treated with ipilimumab in combination with imiquimod. Our present case suggested a possible therapy for nivolumab-resistant multiple in-transit melanomas using ipilimumab in combination with topical imiquimod.

Mogamulizumab induces cytotoxicity against CCR4+ lymphoma cells by antibody-dependent cell-mediated cytotoxicity in advanced cutaneous T-cell lymphoma patients. Since the efficacy of mogamulizumab in mycosis fungoides (28.6%) is lower than that in Sézary syndrome (47.1%), reagents that enhance the antitumor immune response induced by mogamulizumab are needed to further optimize its use for the treatment of erythrodermic mycosis fungoides. In this report, we present a case of erythrodermic mycosis fungoides successfully treated with mogamulizumab followed by etoposide monotherapy.

The diversity of sporocarp-inhabiting fungi (SCIF) was examined using six samples of xylarialean fungi from two different forests in Ibaraki Prefecture, Japan: a moist forest in the Sakuragawa area and an urban dry forest in the Tsukuba area. These fungi were enumerated using direct observation and dilution plate methods. We obtained 44 isolates, and careful morphological and molecular phylogenetic studies of these isolates revealed that approximately 30% of the operating taxonomic units were undescribed or cryptic species related to known fungi. Although typical mycoparasitic fungi, such as helotialean fungi and Trichoderma spp., were not isolated, the genera Acremonium, Acrodontium, and Simplicillium were detected. Comparisons of SCIF communities between the two forests suggested that the number of isolated species in the Sakuragawa area was lower than that in the Tsukuba area. Soil-borne fungi, such as Aspergillus, Beauveria, Penicillium, and Talaromyces, or polypores/corticioid mushrooms, are frequently detected in the Tsukuba area. Factors affecting SCIF communities in the two forests are discussed. Some noteworthy fungi are briefly described with notes on taxonomy, ecology, and molecular phylogeny.

Acquired ichthyosis (AI) is a reactive cutaneous manifestation that can be associated with malignant hematological disease, including cutaneous T-cell lymphoma (CTCL). Since it is difficult to distinguish AI from ichthyosiform mycosis fungoides, to select the treatment for CTCL with ichthyosis-like appearance and to evaluate its efficacy is sometimes challenging. In this report, we describe a case of primary cutaneous peripheral T-cell lymphoma not otherwise specified presenting AI successfully treated with oral bexarotene. In the present case, the administration of oral bexarotene was not only effective for lymphoma cells infiltrating ulcers and nodules, but it also eliminated AI.

Primary cutaneous apocrine carcinoma (PCAC) is a rare and highly aggressive cutaneous adnexal type of tumor that has a high metastasis rate and a poor prognosis. Although there are several case reports describing the successful treatment of PCAC with chemoradiotherapy or molecular targeting therapy, no standard therapy for the treatment of advanced PCAC has been established yet. Since receptor activator of nuclear factor kappa-B ligand (RANKL) is expressed in cancers of apocrine origin, leading to immunosuppression at the tumor site, we hypothesized that targeting RANKL with denosumab might be useful for the treatment of PCAC. In this report, we describe a case with advanced PCAC on the scrotum successfully treated with systemic chemotherapy using carboplatin and paclitaxel, and radiotherapy followed by denosumab.

Both long-term administration of immunosuppressive agents and chronic inflammatory conditions, such as autoimmune disease, could be risk factors for the development of cutaneous squamous cell carcinoma (cSCC). In this report, we present a case of recurrent multiple cSCC on the scalp in a patient with juvenile dermatomyositis who had been administered cyclosporine and Predonine since she was a 1-year-old infant. Interestingly, immunohistochemical staining revealed IL-17-producing cells adjacent to IL-17R-expressing atypical keratinocytes. Our present case suggested that IL-17/IL-17R signaling might contribute to the carcinogenesis of cSCC.

Ipilimumab, in combination with nivolumab, is one of the promising drugs that enhance the anti-tumor immune response of patients with advanced melanoma. Since the co-administration of nivolumab with ipilimumab in the neoadjuvant setting expands melanoma-reactive T cells at the primary site of melanoma and has a high rate of histological complete response, the pre-surgical administration of this combination could be the optimal therapy for unresectable advanced melanoma. In this report, a case of unresectable advanced melanoma treated successfully with administration of nivolumab with ipilimumab before primary tumor resection is presented. In addition, CD8+ T cells increased among the tumor-infiltrating lymphocytes that were surrounding melanoma cells and caspase 3+ cells. The present case suggests that pre-surgical administration of nivolumab with ipilimumab could be the optimal therapy for the treatment of unresectable advanced melanoma.

Anti-programmed cell death protein 1 (PD1) antibodies are in wide use for the treatment of various cancers. PD1 antibody-based immunotherapy, co-administration of nivolumab and ipilimumab, is one of the optimal immunotherapies, especially in advanced melanoma with high tumor mutation burden. Since this combined therapy leads to a high frequency of serious immune-related adverse events (irAEs) in patients with advanced melanoma, biomarkers are needed to evaluate nivolumab efficacy to avoid serious irAEs caused by ipilimumab. This study analyzed baseline serum levels of CXCL5, CXCL10, and CCL22 in 46 cases of advanced cutaneous melanoma treated with nivolumab. Baseline serum levels of CXCL5 were significantly higher in responders than in non-responders. In contrast, there were no significant differences in baseline serum levels of CXCL10 and CCL22 between responders and non-responders. These results suggest that baseline serum levels of CXCL5 may be useful as a biomarker for identifying patients with advanced cutaneous melanoma most likely to benefit from anti-melanoma immunotherapy.

Spontaneous flexor tendon rupture is rare, occurring most commonly in the little finger or flexor pollicis longus. To the best of our knowledge, there have been no reports of spontaneous flexor tendon rupture due to primary distal radioulnar joint (DRUJ) osteoarthritis (OA). We present a case of spontaneous flexor tendon rupture in the index finger due to primary DRUJ OA in a 71-year-old female farmer. Surgical exploration confirmed that, at the wrist joint level, the flexor digitorum profundus of the index finger had undergone degeneration and complete rupture. The flexor digitorum superficialis of the index finger was elongated and thinned. A bony spur toward the volar side was covered with synovial fluid from a pinhole-sized perforation of the capsule. The combination of direct friction from the DRUJ spur and the matrix metalloproteinases in the synovial fluid from the perforation of the DRUJ capsule may have caused the spontaneous flexor tendon rupture. Palmar-side symptoms associated with DRUJ OA should be carefully examined because of the risk of spontaneous flexor tendon rupture.

Since nivolumab significantly prolongs survival in patients with metastatic melanoma, the number of patients administered nivolumab is increasing, but only 30–40% of patients who received nivolumab monotherapy experienced objective tumor regression. Therefore, enhancing its anti-tumor immune response is of great interest to dermato-oncologists. In this report, we present a case of multiple metastatic melanomas in the lung successfully treated with nivolumab (2 mg/kg every 3 weeks for 12 weeks) followed by ipilimumab (3 mg/kg every 3 weeks for 9 weeks), but with severe liver dysfunction.

Antibodies against programmed cell death protein 1, such as nivolumab and pembrolizumab, are widely used for treating various cancers, including advanced melanoma. Nivolumab significantly prolongs survival in patients with metastatic melanoma, and sequential administration with lipilimumab may improve outcomes when switched at the appropriate time. Biomarkers are therefore needed to evaluate nivolumab efficacy soon after first administration. This study analyzed serum levels of soluble cluster of differentiation 163 (sCD163) in 59 cases of advanced cutaneous melanoma and 16 cases of advanced mucosal melanoma treated using nivolumab. Serum levels of sCD163 were significantly increased after 6 weeks in responders compared to non-responders after initial administration of nivolumab for cutaneous melanoma. In contrast, no significant difference between responders and non-responders was seen among patients with non-cutaneous melanoma. These results suggest that sCD163 may be useful as a biomarker for selecting patients with advanced cutaneous melanoma most likely to benefit from anti-melanoma immunotherapy.

The crystal structures of dichloridopalladium(II), -platinum(II) and -rhodium(III) complexes containing 8-(diphenylphosphanyl)quinoline, (SP-4)-[PdCl2(C21H16NP)], (1) [systematic name: dichlorido(8-diphenylphosphanylquinoline)palladium(II)], (SP-4)-[PtCl2(C21H16NP)]·CH2Cl2, (2) [systematic name: dichlorido(8-diphenylphosphanylquinoline)platinum(II) dichloromethane monosolvate], and (OC-6–32)-[RhCl2(C21H16NP)2]PF6·0.5CH2Cl2·0.5CH3OH, (3) [systematic name: cis-dichloridobis(8-diphenylphosphanylquinoline)rhodium(III) hexafluoridophosphate dichloromethane/methanol hemisolvate] are reported. In these complexes, the phosphanylquinoline acts as a bidentate ligand, forming a planar asymmetrical five-membered chelate ring. The palladium(II) and platinum(II) complex molecules in (1) and (2), respectively, show a typical square-planar coordination geometry and form a dimeric structure through an intermolecular π–π stacking interaction between the quinolyl rings. The centroid–centroid distances between the stacked six-membered rings in (1) and (2) are 3.633 (2) and 3.644 (2) Å, respectively. The cationic rhodium(III) complex in (3) has a cis(Cl),cis(P),cis(N) (OC-6–32) configuration of the ligands, in which two kinds of intramolecular π–π stacking interactions are observed: between the quinolyl and phenyl rings and between two phenyl rings, the centroid–centroid distances being 3.458 (2) and 3.717 (2) Å, respectively. The PF6− anion in (3) is rotationally disordered, the site occupancies of each F atom being 0.613 (14) and 0.387 (14). The CH2Cl2 and CH3OH solvent molecules are also disordered and equal site occupancies of 0.5 are assumed.

Merkel cell carcinoma (MCC) is an aggressive, cutaneous, neuroendocrine carcinoma and, in rare cases, occurs with Bowen's disease (BD). In this report, we describe a case of MCC concurrent with invasive BD and compare the profiles of tumor-infiltrating leukocytes in the lesional skin of MCC and invasive BD. Interestingly, immunohistochemical study revealed significant numbers of CD8+ cells and caspase 3-expressing cells in the same areas of invasive BD and MCC. Our present case suggests that MCC concurrent with invasive BD might have a good prognosis because of the substantial number of CD8+ cells in the tumor.

Invasive extramammary Paget's disease (EMPD) is highly metastatic to lymph nodes and other organs, including bone, and when metastatic lesions have expanded beyond the inguinal lymph node, it is difficult to cure. In this report, we present a case of multiple metastasized, receptor activator of nuclear factor kappa-B ligand-expressing EMPD in the pelvic lymph nodes successfully cured with continuous administration of bisphosphonate risedronate sodium after intensive CyberKnife radiotherapy and docetaxel monochemotherapy. Our present case suggested the usefulness of bisphosphonates as a maintenance therapy for metastatic invasive EMPD after the intensive chemoradiotherapy.

Keratoacanthoma (KA) is a benign keratinocytic neoplasm that spontaneously regresses after 3-6 months and shares features with well-differentiated squamous cell carcinoma (SCC). An increased incidence of both KA and non-melanoma skin tumor, including SCC, is seen among immunosuppressed, organ-transplant recipients. In this report we describe a case of KA accompanied by multiple lung SCCs developing in a renal transplant recipient.

Eccrine porocarcinoma is a rare type of skin cancer that originates from eccrine sweat glands or acrosyringium and mainly occurs in the elderly. In this report, we describe an 85-year-old Japanese woman with eccrine porocarcinoma that metastasized to a cervical lymph node who was cured with CyberKnife radiosurgery. Because our patient had a high risk of perioperative complication, standard surgical therapy with a wide margin was impractical. Our present study suggests the novel possibility of using CyberKnife for the treatment of inoperable metastatic porocarcinoma.

Angiosarcoma (AS) is a highly aggressive vascular tumor that spreads widely throughout the skin. Since AS tends to recur locally and metastasize early, an additional intensive therapy is necessary. In this report, we describe an 83-year-old man with recurrent AS that metastasized to the right external auditory meatus, who achieved complete remission with CyberKnife and weekly administration of bisphosphonate risedronate sodium. Results of the present study might suggest the novel possibility of using CyberKnife with weekly administration of bisphosphonate risedronate sodium for the treatment of inoperable metastatic AS.

Low calorific value of lignite, mostly attributed to high moisture content, undermines usability of this low rank coal. Upgrading the quality of this energy carrier, which benefits coal-fired power plant's thermal efficiency, can be effectively realized by means of drying. The kinetics of superheated steam drying was studied for 30 mm spherical samples from Belchatow lignite mine in Poland. The experiment featured simultaneous and continuous measurements of weight and temperature. The drying kinetics, described by curves of moisture content, drying rate and temperature profile, were evaluated using the data acquired. The appearance of the sample throughout the process was video-recorded. Widespread cracking and shrinkage, which differ depending on the conditions, along with series of droplets typical for larger sample, were observed. The examined particles were suitable for predictions of thermodynamically derived drying rate and time, as proposed in the previous study for 5 and 10 mm particles from the same coal deposit. However, in comparison they exhibited more uniform density distribution. On the basis of experimental results and material properties, the numerical model of drying process was applied. Simulated drying behavior was consistent with empirical observations. Extensive investigation, revealing features of variously-sized samples as well as diameter dependence on drying process, is required for purposes of designing industrial drying system dedicated to specific type of coal.

We describe a case of basosquamous cell carcinoma arising from a 52-year-old Japanese renal transplantation recipient (RTR). In the present case, we investigated the immunohistochemical profiles of tumor-infiltrating lymphocytes, focusing on cytotoxic granules, granulysin-bearing cells and immunosuppressive cells, such as regulatory T cells and tumor-associated macrophages. Our present study suggests some of the possible mechanisms for the carcinogenesis of cutaneous malignancy in RTRs.

We describe a 49-year-old Japanese woman with cutaneous squamous cell carcinoma (SCC) developing from recessive dystrophic epidermolysis bullosa (RDEB). Interestingly, immunohistochemical staining revealed dense infiltration of CD163+ M2 macrophages and numerous Foxp3+ regulatory T cells (Tregs) around the tumor. Since the contribution of immunosuppressive factors (e.g. TGFβ) to the carcinogenesis of SCC from RDEB was recently reported, our present findings suggest one of the possible contributions of immunosuppressive cells, such as CD163+ M2 macrophages and Tregs, to the carcinogenesis of SCC from RDEB.

Pseudolymphomatous folliculitis (PLF), which clinically mimicks cutaneous lymphoma, is a rare manifestation of cutaneous pseudolymphoma and cutaneous lymphoid hyperplasia. Here, we report on a 45-year-old Japanese woman with PLF. Dermoscopy findings revealed prominent arborizing vessels with small perifollicular and follicular yellowish spots and follicular red dots. A biopsy specimen also revealed dense lymphocytes, especially CD1a+ cells, infiltrated around the hair follicles. Without any additional treatment, the patient’s nodule rapidly decreased. The presented case suggests that typical dermoscopy findings could be a possible supportive tool for the diagnosis of PLF.