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Melanoma is a major malignant cutaneous neoplasm with a high mortality rate. In recent years, the treatment of melanoma has developed dramatically with the invention of new therapeutic agents, including immune checkpoint inhibitors and molecular‐targeted agents. These agents are available as adjuvant therapies for postoperative patients with stage IIB, IIC, and III melanomas. Furthermore, neoadjuvant therapy has been studied in several global clinical trials and has demonstrated promising and favorable clinical efficacy, mainly in patients with palpable regional lymph nodes. A recent large phase III clinical trial investigating early lymph node dissection for sentinel lymph node metastases demonstrated no survival benefits. Based on these data, surgery should be reconsidered as an appropriate treatment modality for melanoma. The need for invasive surgical procedures will be reduced with the invention of effective adjuvant and neoadjuvant therapies and novel clinical trial data on regional lymph node dissection. However, surgery still plays an important role in treating early‐stage melanoma, accurately determining the disease stage, and effective palliative treatment for advanced melanoma. In this article, we focus on surgery for primary tumors, regional lymph nodes, and metastatic sites in an era of remarkably revolutionary drug treatments for melanoma. [ABSTRACT FROM AUTHOR]

Cutaneous squamous cell carcinoma is usually treated with surgery; however, locoregionally advanced cutaneous squamous cell carcinoma can be difficult to resect. Although recent guidelines from Western countries recommend using anti–programmed cell death protein 1 (PD‐1) antibodies, including cemiplimab and pembrolizumab, there are no approved anti–PD‐1 antibodies for locoregional cutaneous squamous cell carcinoma in Asian countries. S‐1 is an oral drug with a low incidence of severe toxicity that can be used for head and neck cancers, including head and neck locoregional cutaneous squamous cell carcinoma, in Japan. We retrospectively evaluated patients with head and neck locoregional cutaneous squamous cell carcinoma treated with S‐1 at two Japanese institutions (2008–2022). The initial dosage was determined by the body surface area (<1.25 m2: 80 mg/day, 1.25–1.5 m2: 100 mg/day, ≥1.5 m2: 120 mg/day) for 28 consecutive days. The outcome measures were objective response rate (ORR), progression‐free survival (PFS), and overall survival (OS). Fourteen patients were included. The ORR was 78%, and the complete response (CR) rate was 64.3%. The median PFS and OS were not reached (NR) (95% confidence interval [CI], 5.9 months–NR) and NR (95% CI, 13.8 months–NR), respectively. The 12‐month PFS and OS rates were 51% and 85%, respectively. Six of the nine patients who achieved CR showed no recurrence during the follow‐up period (median follow‐up, 24.7 months). After CR, three patients experienced recurrence. Among these, two resumed S‐1 treatment and subsequently underwent salvage surgery, resulting in a sustained absence of recurrence. One patient developed lung metastasis and died, although S‐1 therapy was resumed. Only one patient (7.1%) developed grade 3 anemia. S‐1 showed favorable efficacy and low toxicity in patients with head and neck locoregionally advanced cutaneous squamous cell carcinoma. S‐1 may be a good alternative to the anti–PD‐1 antibody for treating head and neck locoregionally advanced squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Background: Anti‐PD‐1‐based immunotherapy is considered a preferred first‐line treatment for advanced BRAF V600‐mutant melanoma. However, a recent international multi‐center study suggested that the efficacy of immunotherapy is poorer in Asian patients in the non‐acral cutaneous subtype. We hypothesized that the optimal first‐line treatment for Asian patients may be different. Methods: We retrospectively collected data of Asian patients with advanced BRAF V600‐mutant melanoma treated with first‐line BRAF/MEK inhibitors (BRAF/MEKi), anti‐PD‐1 monotherapy (Anti‐PD‐1), and nivolumab plus ipilimumab (PD‐1/CTLA‐4) between 2016 and 2021 from 28 institutions in Japan. Results: We identified 336 patients treated with BRAF/MEKi (n = 236), Anti‐PD‐1 (n = 64) and PD‐1/CTLA‐4 (n = 36). The median follow‐up duration was 19.9 months for all patients and 28.6 months for the 184 pa tients who were alive at their last follow‐up. For patients treated with BRAF/MEKi, anti‐PD‐1, PD‐1/CTLA‐4, the median ages at baseline were 62, 62, and 53 years (p = 0.03); objective response rates were 69%, 27%, and 28% (p < 0.001); median progression‐free survival (PFS) was 14.7, 5.4, and 5.8 months (p = 0.003), and median overall survival (OS) was 34.6, 37.0 months, and not reached, respectively (p = 0.535). In multivariable analysis, hazard ratios (HRs) for PFS of Anti‐PD‐1 and PD‐1/CTLA‐4 compared with BRAF/MEKi were 2.30 (p < 0.001) and 1.38 (p = 0.147), and for OS, HRs were 1.37 (p = 0.111) and 0.56 (p = 0.075), respectively. In propensity‐score matching, BRAF/MEKi showed a tendency for longer PFS and equivalent OS with PD‐1/CTLA‐4 (HRs for PD‐1/CTLA‐4 were 1.78 [p = 0.149]) and 1.03 [p = 0.953], respectively). For patients who received second‐line treatment, BRAF/MEKi followed by PD‐1/CTLA‐4 showed poor survival outcomes. Conclusions: The superiority of PD‐1/CTLA‐4 over BRAF/MEKi appears modest in Asian patients. First‐line BRAF/MEKi remains feasible, but it is difficult to salvage at progression. Ethnicity should be considered when selecting systemic therapies until personalized biomarkers are available in daily practice. Further studies are needed to establish the optimal treatment sequence for Asian patients. [ABSTRACT FROM AUTHOR]

Four‐colored fluorescence in situ hybridization (FISH) is an ancillary diagnostic tool for melanoma. However, most studies that have investigated the usefulness of FISH primarily focused on advanced melanomas. The aim of the current study was to evaluate the effectiveness of FISH in distinguishing acral melanoma (AM) in situ from benign acral junctional nevus (AJN), two types of lesions that are difficult to differentiate via traditional clinical means. The authors investigated the usefulness of FISH in 91 acral melanocytic lesions, including 50 lesions with diagnostic discrepancies between dermoscopic and pathologic approaches or difficulty diagnosing between AM in situ and AJN, on the volar skin of Japanese patients. The authors classified the lesions based on the diagnosis of dermatologists and pathologists into four groups: (I) lesions with a unanimous diagnosis by dermatologists and pathologists as AM in situ or AJN (n = 41); (II) lesions with a unanimous diagnosis by dermatologists only as AM in situ or AJN (n = 21); (III) lesions with a unanimous diagnosis by pathologists only as AM in situ or AJN (n = 15); and (IV) all other lesions (n = 14). The dermatologists diagnosed the lesions by clinical and dermoscopic photographs alone, while the pathologists diagnosed the lesions by microscopy of hematoxylin and eosin–stained slides alone. In group I (AM in situ [n = 20] and AJN [n = 21]), four‐colored FISH demonstrated 90% sensitivity and 81% specificity in distinguishing AM in situ from AJN. There was a significant correlation between the FISH results and the unanimous diagnoses by pathologists alone (p = 0.03) in group III. However, FISH results were not significantly correlated with the unanimous diagnoses by dermatologists alone (p = 0.33) in group II. In conclusion, the four‐colored FISH probe kit was useful in distinguishing between AM in situ and AJN and may be an ancillary method when pathologists who are not experts of dermatopathology diagnose melanocytic lesions. [ABSTRACT FROM AUTHOR]

Acral melanoma (AM) and mucosal melanomas (MM) are rare clinical subtypes of melanoma. AM and MM are etiologically, biologically, and molecularly distinct from cutaneous melanoma (CM). Despite the recent development of immune checkpoint inhibitors (ICIs) for the treatment of advanced CMs, the true therapeutic efficacy of ICIs for these rare subtypes remains unclear. Since these subtypes are rare, especially in the Caucasian population, their biological features and corresponding novel therapies are underexplored than those of CM. Even in the larger phase III clinical trials for ICIs, the sample size of patients with AM and MM is limited. Consequently, establishment of standard of care for advanced AM and MM has been challenging. This review covers current update and overview on clinical efficacy of ICIs and ICI‐based therapy for advanced AM and MM, based mainly on the reported clinical trials, prospective observational studies, and retrospective studies, to provide a better understanding of the current landscape of this field. In addition, we discuss the future direction of treatment for those rare clinical subtypes, focusing on issues relevant to dermatology and medical oncology. [ABSTRACT FROM AUTHOR]

Skin cancer patients with clinical nodal disease or whose positive sentinel nodes had great tumor burden remain candidates for regional lymph node dissections. Among these patients, inguinal or ilioinguinal lymph node dissection is frequently required in clinical practice, which is associated with significant postoperative morbidity—including lymphatic leakage. The aim of this retrospective study was to evaluate the efficacy of LigaSure™, an electrothermal bipolar vessel sealing system, in reducing lymphatic leakage in inguinal or ilioinguinal lymph node dissection. In total, 58 patients who received inguinal or ilioinguinal lymph node dissection (conventional group, 48; LigaSure™ group, 10) and shared similar characteristics were included in this study. Lymphatic leakage after drain removal was significantly lower in the LigaSure™ group than that in the conventional group (present ratio, 0% vs. 37%; p = 0.02). The daily lymphatic drainage volume also tended to be lower in the LigaSure™ than that in the conventional group, with significant differences on postoperative day 1 (p = 0.02). Other perioperative outcomes including the operating time, intraoperative blood loss, time to drain removal, duration of hospital stay, flap necrosis, and wound infection showed no significant differences between the two groups. The use of the LigaSure™ in inguinal or ilioinguinal lymph node dissection for the treatment of skin cancer could reduce the incidence of postoperative lymphatic leakage after drain removal. [ABSTRACT FROM AUTHOR]

Basal cell carcinoma is the most common type of skin cancer, and surgical excision with clear margins is the standard of care. Surgical margins are determined based on risk factors (high or low risk) for recurrence according to the National Comprehensive Cancer Network and Japanese basal cell carcinoma guidelines. The clarity of the clinical tumor border (well‐defined or poorly defined) is considered a risk factor, and significant discrepancies in the judgment of clinical tumor borders among dermato‐oncologists may occur. Therefore, we analyzed the dermato‐oncologists' concordance in judging the clinical tumor border of basal cell carcinoma. Forty‐seven dermato‐oncologists (experts: 37; young trainees: 10) participated in this study. The datasets of clinical and dermoscopic photographs of 79 Japanese cases of head and neck basal cell carcinoma were used to determine the concordance in the judgment of clinical tumor border. The probability of the border that was selected more often was used to calculate the rater agreement rate for each dataset. Correct judgment was defined as a more frequently selected border, and the concordance rate of clarity of clinical tumor border for each dermato‐oncologist was calculated based on the definition of the correct judgment. A median concordance rate of 85% or higher for all dermato‐oncologists was predefined as an acceptable rate for clinical use. Of the 79 datasets, rater agreement rates were 80–100%, 60–79%, and 51–59% for 55, 19, and five datasets, respectively. The median concordance rate for all dermato‐oncologists was 86% (interquartile range: 82–89%). There was no significant difference in the concordance rate between the experts and the trainees (median, 87% vs. 85.5%; p = 0.58). The concordance rates of dermato‐oncologists for all datasets were relatively high and acceptable for clinical use. [ABSTRACT FROM AUTHOR]

Summary: Background and objectives: In cutaneous squamous cell carcinoma (cSCC), adherence to guideline‐recommended fixed surgical margins is often difficult, and narrower margins are preferable. This study aimed to evaluate relapse and disease‐specific death with narrower margins for high or very high‐risk cSCC. Patients/Methods: We retrospectively investigated high or very high‐risk cSCC patients who underwent tumor excision. Patients were divided into guideline‐recommended standard margin group (SMG) and narrower‐margin group (NMG). Co‐primary outcomes were local relapse, SCC relapse, and SCC death. Cumulative incidence function (CIF) was used to describe SCC death probability and competing risk mortality. Gray's test was used to compare differences in CIF between the groups. Results: In total, 1,000 patients with cSCC (high‐risk, 570; very high‐risk, 430) were included. In the high‐risk cohort, there were no significant differences in incomplete excision rate (IER) between SMG and NMG (2.6 % vs. 3.0 %, P > 0.99). However, in the very high‐risk cohort, IER in SMG was significantly lower than in NMG (8.9 % vs. 16.2 %, P = 0.03). No significant differences were observed between SMG and NMG for local relapse (high‐risk, P = 0.56; very high‐risk, P = 0.70), SCC relapse (high‐risk, P = 0.30; very high‐risk, P = 0.47), and SCC death (high‐risk, P = 0.23; very high‐risk, P = 0.83). Conclusions: Surgical margin size has limited impact on margin control, relapse, and disease‐specific death in high‐risk cSCC. [ABSTRACT FROM AUTHOR]

Zusammenfassung: Hintergrund und Ziele: Bei kutanen Plattenepithelkarzinomen (PEK) ist die Einhaltung der in Leitlinien empfohlenen festen Resektionsränder oft schwierig und knappere Ränder sind wünschenswert. Ziel dieser Studie war die Bewertung des Auftretens von Rezidiven und krankheitsspezifischen Todesfällen bei knapperen Resektionsrändern für PEK mit hohem oder sehr hohem Risiko. Patienten/Methoden: PEK‐Patienten mit hohem oder sehr hohem Risiko, bei denen eine Tumorexzision durchgeführt wurde, wurden retrospektiv untersucht. Die Patienten wurden in eine Gruppe mit Standardrand gemäß Leitlinienempfehlung (standard margin group, SMG) und eine Gruppe mit knapperen Rändern (narrower‐margin group, NMG) eingeteilt. Gemeinsame primäre Endpunkte waren lokales Rezidiv, PEK‐Rezidiv und PEK‐bedingter Tod. Die Wahrscheinlichkeit eines PEK‐bedingten Tods und konkurrierender Mortalitätsrisiken wurde mittels kumulativer Inzidenzfunktion (CIF) beschrieben. Unterschiede bei der CIF zwischen den Gruppen wurden mit dem Test nach Gray verglichen. Ergebnisse: Insgesamt wurden 1.000 Patienten mit PEK (hohes Risiko, 570; sehr hohes Risiko, 430) eingeschlossen. In der Kohorte mit hohem Risiko gab es keine signifikanten Unterschiede bei der unvollständigen Exzisionsrate (IER) zwischen SMG und NMG (2,6 % vs. 3,0 %, P > 0,99). In der Kohorte mit sehr hohem Risiko war die IER in der SMG jedoch signifikant geringer als in der NMG (8.9 % vs. 16.2 %, P = 0,03). Keine signifikanten Unterschiede zwischen SMG und NMG wurden für Lokalrezidiv (hohes Risiko, P = 0.56; sehr hohes Risiko, P = 0,70), PEK‐Rezidiv (hohes Risiko, P = 0,30; sehr hohes Risiko, P = 0,47) und PEK‐bedingtem Tod (hohes Risiko, P = 0,23; sehr hohes Risiko, P = 0,83) beobachtet. Schlussfolgerungen: Die Größe des Resektionsrands hat einen begrenzten Einfluss auf Randkontrolle, Rezidive und krankheitsspezifischen Tod bei PEK mit hohem Risiko. [ABSTRACT FROM AUTHOR]

Objective/Hypothesis: Middle ear cholesteatoma is characterized by abnormal growth of the keratinizing squamous epithelium of the temporal bone. d‐β‐aspartic acid is the major isomer of d‐aspartic acid found in elderly tissue. We assessed the immunoreactivity to k‐β‐aspartic acid of congenital and acquired middle ear cholesteatomas. Study Design: Case–control studies. Material and Methods: Tissue samples were collected from 21 patients comprising 21 ears with congenital middle ear cholesteatoma and 26 patients comprising 29 ears with acquired type. Their clinical and histopathological features were investigated. We divided the middle ear cholesteatoma samples into three layers: the perimatrix, matrix, and cystic contents. The patterns of immunoreactivity to d‐β‐aspartic acid expression were then assessed immunohistochemically. Results: Two patterns of immunoreactivity to d‐β‐aspartic acid were detected in middle ear cholesteatoma: infiltrative and diffuse. In congenital middle ear cholesteatoma, d‐β‐aspartic acid expression was observed throughout all the layers (perimatrix, matrix, and cystic contents), and immunoreactivity to d‐β‐aspartic acid was dramatically strong in all layers. The expression levels of d‐β‐aspartic acid to the cystic content and perimatrix were significantly higher in congenital middle ear cholesteatoma than in the acquired type. Conclusions: This study showed the expression levels of d‐β‐aspartic acid in middle ear cholesteatoma to differ significantly between congenital and acquired middle ear cholesteatoma. Our results indicate that overexpression of d‐β‐aspartic acid is likely to be involved in the pathogenesis of cholesteatoma, and we speculate that d‐β‐aspartic acid could be a novel biomarker for, and a therapeutic target in, congenital and acquired middle ear cholesteatoma. Level of Evidence: 4 [ABSTRACT FROM AUTHOR]

Computed tomography (CT) revealed a 2.1-cm mass in the right adrenal gland with a low CT value (13 Hounsfield Units). Abbreviations ACTH adrenocortcotropic horome AHF Adreno-hepatic fusion CT Computed tomography CYP11B1 cytochrome P450 family 11 subfamily B member 1 CYP11B2 cytochrome P450 family 11 subfamily B member 2 DST dexamethasone suppression test HCC hepatocellular carcinoma PAC plasma aldosterone concentration SF-1 steroidgenic factor 1 Adreno-hepatic fusion (AHF) is defined as parenchymal adhesions between the liver and right adrenal gland. Moreover, as in the present case, ectopic bile ducts within the adrenal parenchyma sometimes showed cystic changes, and AHF-related intra-adrenal bile duct dilatation has been reported as a possible pathogenesis of right adrenal epithelial cysts.[3] We diagnosed the patient with adrenocortical adenoma arising from AHF. [Extracted from the article]

Angiotensin receptor blockers (ARBs) plus calcium channel blockers (CCBs) are a widely used combination therapy for hypertensive patients. In order to determine which combination was better as the next-step therapy for standard-dose combination of ARBs and CCBs, a combination with high-dose CCBs or a triple combination with diuretics, the authors conducted a prospective, randomized, open-label trial to determine which of the following combination is better as the next-step treatment: a combination with high-dose CCBs or a triple combination with diuretics. Hypertensive outpatients who did not achieve their target blood pressure (BP) with usual dosages of ARBs and amlodipine 5 mg were randomly assigned to treatment with irbesartan 100 mg/amlodipine 10 mg (Group 1: n = 48) or indapamide 1 mg in addition to ARBs plus amlodipine 5 mg (Group 2: n = 46). The primary end point was changes in the systolic BP (SBP) and diastolic BP (DBP) after the 12-week treatment period, while secondary end points were changes in BP after the 24-week treatment period and laboratory values. At 12 weeks, the SBP/DBP significantly decreased from 152.1/83.4 mm Hg to 131.5/76.1 mm Hg in Group 1 and 153.9/82.1 mm Hg to 132.7/75.9 mm Hg in Group 2. Although both groups produced a similar efficacy in reducing the SBP/DBP (-19.2/-9.2 mm Hg in Group 1 and -21.6/-8.8 mm Hg in Group 2; SBP P = .378, DBP P = .825), high-dose CCBs combined with ARBs controlled hypertension without elevation of serum uric acid. These results will provide new evidence for selecting optimal combination therapies for uncontrolled hypertensive patients. [ABSTRACT FROM AUTHOR]

A 70‐year‐old Japanese man with diabetes mellitus was referred to our hospital for treatment of renal dysfunction. Renal biopsy revealed that the tubular basement membrane (TBM) showed extreme thickening histologically, and selective polyclonal immunoglobulin G deposition on the thickened TBM, whereas no immunoglobulin deposition was found in the glomeruli in an immunofluorescence study. In electron microscopy, a powdery type of electron dense material, which was similar to that seen in Randall‐type monoclonal immunoglobulin deposition disease (MIDD), was observed on the tubular epithelial side of the TBM. However, the present case was differentiated from MIDD, because polyclonal deposition with both kappa and lambda deposition on the TBM was observed. Moreover, there was no noticeable glomerular deposition, which is usually found in cases of MIDD. Anti‐TBM disease was also considered as a differential diagnosis, in which polyclonal immunoglobulin deposits selectively on the TBM. However, in the present case, prominent interstitial nephritis was not observed. A similar case with a history of diabetes mellitus has been reported, which was diagnosed as Polyclonal Immunoglobulin G Deposition Disease. No further reports of this case have emerged thereafter; we present this case as the second report supporting this article. [ABSTRACT FROM AUTHOR]

Vitiligo is an autoimmune disorder resulting from the destruction of melanocytes. Several reports indicate the association between vitiligo and treatment response in advanced melanoma during immunotherapy. It has not been investigated, however, if an increase of vitiligo while on treatment with anti‐programmed death 1 (PD‐1) antibodies is associated with more durable responses. The aim of this study is to evaluate the correlation between the vitiligo dynamics and clinical efficacy of anti‐PD‐1 antibodies. This study included advanced melanoma patients who were treated with nivolumab or pembrolizumab and developed vitiligo thereafter. Correlation between vitiligo expansion (defined as an increase of lesion size at two separate time points at least 4 weeks apart) as well as vitiligo extent (body surface area [BSA] affected) and clinical efficacy based on response rate, progression‐free survival and overall survival was assessed. We retrospectively reviewed 29 patients. The median time from the initiation of anti‐PD‐1 antibody to vitiligo onset was 4.3 months in patients who showed a response and 5.5 months in patients who showed no response (P = 0.31). Twelve patients showed vitiligo expansion, and in nine of these patients, vitiligo increased to grade 2 (covering ≥ 10% BSA). Vitiligo expansion and grade 2 vitiligo showed no improvement in treatment response (P = 0.59 and 0.25) but were associated with prolonged progression‐free survival (P = 0.019 and 0.04). Grade 2 vitiligo also showed a trend for prolonged overall survival (P = 0.07). Trend of expansion and larger vitiligo extent may be predictive factors of prolonged survival during anti‐PD‐1 antibody in melanoma patients. [ABSTRACT FROM AUTHOR]

Intestinal necrosis associated with cation exchange resin (CER) is considered related to sorbitol, but it has been reported even in patients receiving CER alone. This study was performed to identify the risk factors of CER‐related intestinal necrosis. The pathological database of 61 end‐stage renal disease patients with surgical intervention for intestinal perforation was reviewed. The correlations between CER treatment and clinicopathological factors were studied among three groups: (i) patients administered CER and with CER at the perforation site (n = 23), (ii) patients administered CER with undetected CER at the perforation site (n = 12) and (iii) patients not administered CER (n = 26). The majority of the perforation site in group 1 was in the sigmoid colon (82.6%) with significantly higher average age and more frequent CER adhesion rates to the mucosa around the perforation site than group 2. The laxative administration rate in group 1 was significantly higher than group 3 and tended to be higher than group 2. The incidence of CER‐related intestinal necrosis was estimated at 0.57%. CER should be used with extreme caution in elderly patients with passage disturbance. [ABSTRACT FROM AUTHOR]

With consideration of the ongoing developments in treatment options for cutaneous melanoma, the Japanese Skin Cancer Society published the first guidelines for cutaneous melanoma in 2007 and later revised them in 2015. Here, we report on an English version of the 2019 Japanese Melanoma Guidelines. In this latest edition, all processes were carried out according to the Grading of Recommendations, Assessment, Development and Evaluation system. A comprehensive published work search, systematic review and determination of recommendations in each clinical question were performed by a multidisciplinary expert panel consisting of dermatologists, a plastic and reconstructive surgeon, and a radiation oncologist. The advent of novel agents, such as immune checkpoint inhibitors and molecular‐targeted agents, has drastically changed the nature of treatment for adjuvant and advanced‐stage diseases among melanoma patients worldwide. Additionally, recent reports of clinical trials regarding surgical procedures and a better understanding of molecular biology and tumor immunology in clinical types of melanoma have had an impact on clinical practise. Based on these viewpoints, eight relevant clinical questions were raised in this report that aim to help clinicians select the appropriate therapeutic approach. [ABSTRACT FROM AUTHOR]

Although epithelioid granulomas typically involve liver parenchyma and/or walls of the tributaries of the portal or hepatic veins, idiopathic granulomatous lesions selectively involving the small hepatic veins have infrequently been reported.1 On rare occasions, sarcoidosis causes Budd-Chiari syndrome through granulomas involving centrilobular parenchyma and large hepatic vein radicle.2 Precise pathogenic mechanisms inducing sarcoidosis are unknown; however, hypotheses strongly suggest it may occur in genetically susceptible individuals due to environmental exposures. Hepatic granulomas are identified in several hepatic diseases such as sarcoidosis, primary biliary cholangitis, and tuberculosis. [Extracted from the article]

Zinc‐finger transcription factors GATA2 and GATA3 are both expressed in the developing inner ear, although their overlapping versus distinct activities in adult definitive inner ear are not well understood. We show here that GATA2 and GATA3 are co‐expressed in cochlear spiral ganglion cells and redundantly function in the maintenance of spiral ganglion cells and auditory neural circuitry. Notably, Gata2 and Gata3 compound heterozygous mutant mice had a diminished number of spiral ganglion cells due to enhanced apoptosis, which resulted in progressive hearing loss. The decrease in spiral ganglion cellularity was associated with lowered expression of neurotrophin receptor TrkC that is an essential factor for spiral ganglion cell survival. We further show that Gata2 null mutants that additionally bear a Gata2 YAC (yeast artificial chromosome) that counteracts the lethal hematopoietic deficiency due to complete Gata2 loss nonetheless failed to complement the deficiency in neonatal spiral ganglion neurons. Furthermore, cochlea‐specific Gata2 deletion mice also had fewer spiral ganglion cells and resultant hearing impairment. These results show that GATA2 and GATA3 redundantly function to maintain spiral ganglion cells and hearing. We propose possible mechanisms underlying hearing loss in human GATA2‐ or GATA3‐related genetic disorders. [ABSTRACT FROM AUTHOR]

Background: The incidence of melanoma among those of an Asian ethnicity is lower than in Caucasians; few large‐scale Asian studies that include follow‐up data have been reported. Objectives: To investigate the clinical characteristics of Japanese patients with melanoma and to evaluate the prognostic factors. Methods: Detailed patient information was collected from the database of Japanese Melanoma Study Group of the Japanese Skin Cancer Society. The American Joint Committee on Cancer seventh Edition system was used for TNM classification. The Kaplan‐Meier method and Cox proportional hazards model were used to estimate the impact of clinical and histological parameters on disease‐specific survival in patients with invasive melanoma. Results: In total, 4594 patients were included in this analysis. The most common clinical type was acral lentiginous melanoma (40.4%) followed by superficial spreading melanoma (20.5%), nodular melanoma (10.0%), mucosal melanoma (9.5%), and lentigo maligna melanoma (8.1%). The 5‐year disease‐specific survival for each stage was as follows: IA = 98.0%, IB = 93.9%, IIA = 94.8%, IIB = 82.4%, IIC = 71.8%, IIIA = 75.0%, IIIB = 61.3%, IIIC = 41.7%, and IV = 17.7%. Although multivariate analysis showed that clinical classifications were not associated with survival across all stages, acral type was an independent poor prognostic factor in stage IIIA. Conclusions: Our study revealed the characteristics of melanoma in the Japanese population. The 5‐year disease‐specific survival of each stage showed a similar trend to that of Caucasians. While clinical classification was not associated with survival in any stages, acral type was associated with poor survival in stage IIIA. Our result might indicate the aggressiveness of acral type in certain populations. [ABSTRACT FROM AUTHOR]

Histiocytic sarcoma (HS) is a rare hematopoietic tumor that mainly involves extranodal sites, including the intestinal tract, skin, soft tissues and other organs. It is well known as an aggressive neoplasm that shows a poor response to therapy. However, a subset of patients with resectable disease has shown a favorable outcome with surgical treatment. Primary cutaneous HS is exceedingly rare and, to date, its long‐term prognosis has thus not been well described. Here, we highlight two cases of primary cutaneous HS that showed long‐term survival. Case 1 was a healthy 47‐year‐old woman who found a 12‐mm tumor on her forehead. Case 2 was a 66‐year‐old woman, under follow up of a myxoid liposarcoma in her leg, who presented with a 25‐mm tumor in her hypothenar eminence. Histologically, the tumors in both cases had a smooth outline with proliferating atypical tumor cells that showed histiocytic differentiation as revealed by immunohistochemistry with antibodies to CD68 (KP‐1) and lysozyme in case 1; and CD68, lysozyme and CD163 in case 2. Tumor cells in case 1 had a monotonous appearance. After complete resection, cases 1 and 2 have survived for 10 and 4 years, respectively, without recurrence. To date, such patients are relatively long follow‐up cases of survival from HS and highlight how a clear outline of the primary cutaneous HS tumor may be associated with its resectability and be an important factor in the assessment of its curability. [ABSTRACT FROM AUTHOR]

Background: There is limited evidence of parametric MR mapping to characterize carotid plaques associated with cerebral ischemic events.Purpose: To explore the apparent diffusion coefficients (ADCs) and longitudinal relaxation rates (R1 ) of carotid plaques, including areas of hemorrhage, lipid-rich/necrotic core (LR/NC) without hemorrhage, and fibrous tissue (Fbr) STUDY TYPE: Prospective.Subjects: Twelve patients who underwent carotid endarterectomy.Field Strength/sequence: R1 was measured using double angle Look-Locker acquisition on 3T systems. Single-shot spin-echo echo-planar imaging with fat suppression and outer-volume suppression (OVS-DWEPI) with b values of 10 and 500 s/mm2 was used for diffusion-weighted imaging.Assessment: A phantom study using diluted gadolinium solutions and polyvinyl alcohol solutions was used to validate the two protocols. Regions of interest (ROIs) were manually outlined on MR images for areas of LR/NC, hemorrhage, and Fbr based on histological cross-sections. Pixel-based R1 and ADC values in the ROIs were plotted for each component. The probability density function of the plots determined the optimum contours to separate the three components in the ADC-R1 plane. The LR/NC, hemorrhage, and Fbr regions were mapped on MR images based on the above results and compared to histological results.Statistical Tests: The R1 values of the phantom measurements were tested using Bland-Altman analysis. The accuracies of the MRI classification were calculated.Results: R1 values <8 s-1 calculated using our method agreed with those calculated using an inversion-recovery fast-spin-echo sequence (error, ≤0.1 s-1 ). ADC values obtained using OVS-DWEPI were 4.1% higher than those obtained using standard echo-planar imaging. LR/NC (R1 , 0.4-1.2 s-1 ; ADC, 0-1.5 μm2 /ms), hemorrhage (R1  ≥ 1.5 s-1 ; ADC, 0.5-1.5 μm2 /ms), and Fbr (R1 , 0.2-0.8 s-1 ; ADC, 1.5-2.9 μm2 /ms) were separated on the plots. The accuracies of MRI classification were LR/NC, 0.86; hemorrhage, 0.79; and Fbr, 0.77.Conclusion: The combination of ADC and R1 values measured using our method enabled differentiation among LR/NC, hemorrhage, and Fbr.Level Of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1657-1667. [ABSTRACT FROM AUTHOR]

Both glandular papilloma (GP) and sclerosing pneumocytoma (SP) are rare tumors in the lung. We herein report an extremely rare case of coexistence of these two uncommon tumors. The patient was a 40‐year‐old Japanese woman with no chief complaint. A solitary nodule of the lung was detected using chest computed tomography. The transbronchial biopsy revealed that the tumor histologically corresponded to GP. The patient subsequently underwent partial resection of the right upper lobe. Histological examination of the resected specimens further revealed that the mass contained two different and independent elements and displayed typically histological features of GP and SP. Molecular analysis further revealed the presence of BRAF V600E and AKT1 E17K mutations in GP, whereas only AKT1 mutation was detected in SP. To our knowledge, this is the first case of coexistence of GP and SP in the bronchiole harboring common AKT1 mutation and different BRAF V600E mutational status. [ABSTRACT FROM AUTHOR]

Background The number of very elderly patients who require surgery for cutaneous tumors is increasing. However, there is limited information on the safety of cutaneous surgery in such patients. Methods To evaluate the safety of cutaneous surgery in patients 90 years of age and older, we retrospectively reviewed the elderly patients who underwent surgery for cutaneous tumors under local anesthesia. Consecutive patients 90 years of age and older and 75-80 years old were included in the elderly group and the control group. Results The elderly and control groups included 104 and 106 patients, respectively. The mean age of the patients was 93.4 years (range, 90-101 years) in the elderly group and 77.4 years (range, 75-80 years) in the control group. The preoperative performance status was significantly worse in the elderly group than in the control group ( P < 0.001). The surgical time was not significantly different between the two groups ( P = 0.09). The occurrences of intraoperative and postoperative complications were not significantly different between the two groups ( P = 0.19 and P = 0.07, respectively). Conclusions The result of the present study indicates that cutaneous surgery for very elderly patients 90 years of age and older is as safe as for patients ranging in age from 75-80 years old. [ABSTRACT FROM AUTHOR]

p62/sequestosome 1 (p62) is a multi-domain protein that functions as a receptor for ubiquitinated targets in the selective autophagy and serves as a scaffold in various signaling cascades. p62 have been reported to be up-regulated in several human malignancies, but the biological roles and significance of p62 are still poorly understood in colorectal carcinoma. We immunohistochemically evaluated p62 in 118 colorectal adenocarcinoma and 28 colorectal adenoma cases. We used four colon carcinoma cells ( HCT8, HT29, COLO320, and SW480) in the in vitro studies. p62 immunoreactivity was detected in 11% of colorectal adenoma cases and 31% of adenocarcinoma cases, while it was negligible in the normal epithelium. The immunohistochemical p62 status was significantly associated with synchronous liver metastasis, and it turned out to be an independent adverse prognostic factor in colorectal cancer patients. Following in vitro studies revealed that HCT8 and HT29 cells transfected with p62-specific si RNA showed significantly decreased cell proliferation activity, whereas COLO320 and SW480 cells transfected with p62 expression plasmid showed significantly increased cell proliferation activity. The p62-mediated cell proliferation was not associated with the autophagy activity. These findings suggest that p62 promotes the cell proliferation mainly as a scaffold protein, and that the p62 status is a potent prognostic factor in colorectal carcinoma patients. [ABSTRACT FROM AUTHOR]

Cutaneous squamous cell carcinoma is the second common cutaneous cancer, especially in the elderly. Sentinel lymph node biopsy is generally performed in breast cancers and cutaneous melanomas to detect occult nodal metastases. The benefit of sentinel lymph node biopsy in improving cutaneous squamous cell carcinoma prognosis is doubtful. One hundred and sixty-nine patients who underwent treatment for cutaneous squamous cell carcinoma between 2004 and 2015, and who were followed up for at least 6 months or developed metastases within the follow-up period were included. Forty-nine patients underwent sentinel lymph node biopsy, whereas 120 patients did not, including 13 who exhibited clinical lymph node metastases before treatment. Of these 49 patients, nine (18.4%) presented with sentinel lymph node metastasis, which occurred after treatment in three (6.1%) of them (false-negative). Among the 107 patients who did not undergo lymph node biopsy, 12 (11.2%) developed post-treatment metastases. The metastasis-free and disease-specific survival rates were not significantly different in those who did or did not undergo sentinel lymph node biopsy. Patients with clinical lymph node metastases had a higher risk compared with those without. Patients with T2-T4 tumors had a higher risk compared with those with T1 tumors. When selecting for those with T2 tumors or greater, the same lack of relationship was observed. In conclusion, in this small retrospective cohort, in patients with cutaneous squamous cell carcinoma, there were no significant differences in metastasis-free and disease-specific survival rates between those who did or did not undergo sentinel lymph node biopsy, regardless of T staging. [ABSTRACT FROM AUTHOR]

Vitiligo is occasionally seen in melanoma patients. Although several studies indicate a correlation between vitiligo occurrence and clinical response in melanoma patients receiving immunotherapy, most studies have included heterogeneous patient and treatment settings. The aim of this study is to investigate the correlation between the occurrence of vitiligo and clinical benefit of nivolumab treatment in advanced melanoma patients. We retrospectively reviewed unresectable stage III or IV melanoma patients treated with nivolumab. Of 35 melanoma patients treated with nivolumab, 25.7% (9/35) developed vitiligo during treatment. The time from the start of nivolumab treatment to occurrence of vitiligo ranged 2-9 months (mean, 5.2). Of nine patients who developed vitiligo, two (22.2%) had a complete response to nivolumab and two (22.2%) had a partial response. The objective response rate was significantly higher in patients with vitiligo than in patients without vitiligo (4/9 [44.4%] vs 2/26 [7.7%]; P = 0.027). The mean time to vitiligo occurrence in patients achieving an objective response was significantly less than that in patients who showed no response (3.1 vs 6.8 months, P = 0.004). Vitiligo occurrence was significantly associated with prolonged progression-free and overall survival (hazard ratio, 0.24 and 0.16; 95% confidence interval, 0.11-0.55 and 0.03-0.79; P = 0.005, and 0.047, respectively). At the 20-week landmark analysis, however, vitiligo was not associated with a statistically significant overall survival benefit ( P = 0.28). The occurrence of vitiligo during nivolumab treatment may be correlated with favorable clinical outcome. [ABSTRACT FROM AUTHOR]

Breast cancer patients have a generally increased risk of developing second cancers. The object of this study was to clarify the increased as well as decreased incidence of cancers in breast cancer patients using autopsy cases. 164 211 autopsy cases in the Annual of Pathological Autopsy Cases in Japan from 2002 to 2010 were analyzed for multiple primary cancer (MPC). Female MPC cases (4222 cases) were selected. We investigated the cancer incidence observed in breast cancer associated MPC. The Chi-squared test was used for analysis. All P-values were two-sided, and differences at P < 0.05 were considered significant. Breast cancer associated MPC showed a significantly increased incidence of ovarian, pancreatic, and skin cancer (Odds Ratio [95 % confidence interval (CI)]) = 1.464 [1.03, 2.08], 1.414 [1.08, 1.85] and 2.092 [1.28, 3.41]), and a decreased incidence of colorectal and cervical cancer (OR [95 % CI]) = 0.732 [0.60, 0.90], 0.605 [0.38, 0.96]). Our findings of an increased incidence of malignancies in breast cancer associated MPC cases were consistent with the results of previous population-based studies. This study is the first study to analyze massive autopsy data on MPC which provide new evidence clinically and pathologically. [ABSTRACT FROM AUTHOR]

Varicose veins are treated at multiple clinical departments, but as patients often visit the dermatology clinic first due to leg ulcers, the present Guidelines for the Management of Lower Leg Ulcers/Varicose Veins were prepared in consideration of the importance of the dermatologist's role. Also, the disease concept of chronic venous insufficiency or chronic venous disorders and the CEAP classification of these disorders are presented. The objective of the present guidelines is to properly guide the diagnosis and treatment of lower leg ulcers/varicose veins by systematically presenting evidence-based recommendations that support clinical decisions. [ABSTRACT FROM AUTHOR]

HTTP is recognized as the most widely used protocol on the Internet when applications are being transferred more and more by developers onto the web. Due to increasingly complex computer systems, diversity HTTP automated software (autoware) thrives. Unfortunately, besides normal autoware, HTTP malware and greyware are also spreading rapidly in web environment. Consequently, network communication is not just rigorously controlled by users intention. This raises the demand for analyzing HTTP autoware communication behaviour to detect and classify malicious and normal activities via HTTP traffic. Hence, in this paper, based on many studies and analysis of the autoware communication behaviour through access graph, a new method to detect and classify HTTP autoware communication at network level is presented. The proposal system includes combination of MapReduce of Hadoop and MarkLogic NoSQL database along with xQuery to deal with huge HTTP traffic generated each day in a large network. The method is examined with real outbound HTTP traffic data collected through a proxy server of a private network. Experimental results obtained for proposed method showed that promised outcomes are achieved since 95.1% of suspicious autoware are classified and detected. This finding may assist network and system administrator in inspecting early the internal threats caused by HTTP autoware. [ABSTRACT FROM AUTHOR]

Mucinous cystic neoplasms (MCNs) are generally defined as cyst-forming epithelial neoplasms that arise in the pancreas and harbor characteristic ovarian-type stroma beneath the epithelium. In this study, we compared the immunoreactivity of steroid-related factors in these subepithelial stromal cells in MCNs to those in intraductal papillary mucinous neoplasms (IPMNs) to further characterize this unique MCN ovarian-type stroma through evaluation of sex steroid biosynthesis. Twenty MCNs and twenty IPMNs were examined. Immunoreactivity of steroid hormone receptors, including estrogen receptor (ERα and ERβ), progesterone receptor (PR, PR-A, and PR-B), and androgen receptor (AR), was more frequently detected in MCN ovarian-type stromal cells than in IPMN stromal cells ( P < 0.01). The H-scores (mean ± SD) of steroidogenic factor (SF)-1 were also significantly higher in MCNs (112.3 ± 33.1) than in IPMNs (0.9 ± 1.2) ( P < 0.01). The steroidogenic enzymes cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), cytochrome P450 17 alpha-hydroxylase (P450c17) and 3β-hydroxysteroid dehydrogenase (3β-HSD) showed immunoreactivity in 9/20 (45.0 %), 15/20 (75.0 %) and 13/20 (65.0 %), respectively, of ovarian-type stroma from MCN cases. These results demonstrate that the ovarian-type stroma of MCNs can express steroidogenic enzymes. Thus, the ovarian-type stroma of MCNs can produce sex steroids that may also act on these cells. [ABSTRACT FROM AUTHOR]

Tumors harboring osteoclast-like giant cells (OGCs) at extraosseous site are extremely rare. These rare tumors have been detected most frequently in the pancreas and few pulmonary tumors harboring OGCs have been previously reported. In addition, the genetic profiles of these tumors have remained virtually unknown. Therefore, we report a case of pulmonary adenocarcinoma harboring OGCs in which k-ras mutation and immunohistochemical study of proteins associated with OGCs were examined. The case was a 70-year-old man, who demonstrated a pulmonary mass associated with unusual radiological features. Histopathologically, three different cell types, mucinous adenocarcinoma cell, OGC and mononuclear cell were detected. OGCs were immunohistochemically negative for epithelial markers and positive for histiocytic markers but mononuclear cells were immunopositive for epithelial markers. In addition, both mononuclear and adenocarcinoma cells had the same k-ras mutation profiles and mononuclear cells were immunohistochemically positive for macrophage colony-stimulating factor (M-CSF), one of the factors associated with OGC differentiation. Therefore, mononuclear cells were considered to be derived from neoplastic epithelium and OGCs could represent non-neoplastic cells. In addition, M-CSF locally produced could promote the differentiation of OGCs. [ABSTRACT FROM AUTHOR]

Inguinal lymph node dissection (ILND) for skin cancer is associated with a high incidence of wound complications. The traditional skin approaches are associated with a high risk of wound/flap necrosis of the inguinal skin, which leads to wound dehiscence and wound infection. We report a novel approach for ILND without inguinal skin incision for patients with invasive extramammary Paget disease (EMPD) to minimize the wound complications inherent in conventional ILND. We totally performed this procedure in 3 patients with invasive EMPD with inguinal nodal metastases. No patient had complications, including flap necrosis, wound dehiscence, or wound infection. Our novel surgical approach would retain the vascular supply because there was no inguinal skin incision, preventing postoperative wound complications. In addition, ILND was easily performed with satisfactory exposure of the surgical field. However, the number of patients was small and the follow-up period was short. Further evaluation of a larger case series with longer follow-up is essential to investigate the effect, safety, and indications for this novel approach. [ABSTRACT FROM AUTHOR]

Subungual melanomas ( SUM) are rare, and amputation is often required. Non-amputative wide local excision ( WLE) of the nail unit with the periosteum of the distal phalanx, followed by skin graft, has been accepted for in situ or SUM of 0.5 mm or less thickness. However, previous reports have included a limited number of cases, and not all more than 0.5-mm thick SUM exhibit invasion or attachment to the distal phalanx. The aim of the present study was to investigate the local recurrence and prognosis for in situ, minimally invasive and invasive SUM that were treated using WLE. We retrospectively reviewed 50 patients with in situ ( n = 48) or minimally invasive SUM ( n = 2) ( in situ or minimally invasive group) and 12 patients with more than 0.5-mm thick invasive SUM (invasive group) who were treated using WLE. All patients survived the follow-up period (24-207 months), although four patients with in situ SUM experienced local recurrence at the lateral margin and re-excision was required. In the invasive group, no patients experienced local recurrence, although one patient (8.3%) developed nodal metastasis at 86 months and regional lymph node dissection was required. WLE may provide acceptable local control for in situ and intermediate thickness SUM, without compromising the vital prognosis. However, a larger randomized prospective study with long-term follow up is required to evaluate adequately the risks associated with a non-amputative WLE for in situ and invasive SUM. [ABSTRACT FROM AUTHOR]

Artifacts in the process of specimen preparation are frequent in ultrastructural evaluation of renal biopsy. We hypothesized that the common practice of wrapping kidney biopsy specimens in saline-soaked gauze to prevent the drying of the specimens could be the major factor of artifacts. In this study, whole kidneys from two male Sprague- Dawley rats were used. Before fixation, fresh small cubes of kidney tissue were macerated in saline ( Saline group) or hypoelectrolytic isoosmotic solution for infusion ( HISI group) ( Sorita T3 or SOLDEM 3A) for 10 or 30 min. Then, the specimens were processed by 1% OsO4 in 0.1 M phosphate buffer ( pH 7.4) and embedded by EPON 812 for ultramicroscopic analysis. In the Saline group, ultrastructural examination revealed swollen podocyte, swollen capillary protuberance of the mesangium into the glomerular capillary loop, tubular cells with swollen mitochondria and microvilli, and the smooth muscle cells in the arteriolar wall with marked vacuolar degeneration were detected after 10 min maceration in saline and these findings become more pronounced after 30 min maceration. However, in the HISI group, these artifacts were not identified or limited within 30 min. It is postulated that HISI solution could prevent the artifacts, and be used for soaking and wrapping instead of physiologic saline solution. [ABSTRACT FROM AUTHOR]

Prediction of subsequent risks of breast carcinoma ( BC) development in intraductal papilloma ( IDP) has remained controversial with the exception of atypical papilloma ( AP). The potential value of immunohistochemistry ( IHC) of cytokeratin 5/6 [ CK5/6] and p63 have been proposed but its standardization has also remained controversial. We studied 17 patients initially diagnosed as IDP or AP who subsequently developed BC with 34 age-matched controls. We compared histological features, results of IHC (estrogen receptor [ ER], progesterone receptor [ PR], human epidermal growth factor receptor 2 [ HER2], p63, CK5/6, Ki67), and ultrasound findings. Univariate conditional logistic regression analysis revealed that the status of both CK5/6 and p63/ CK5/6 were significantly associated with subsequent BC development ( P < 0.05). BC development in CK5/6 positive patients was 17.9% and p63/ CK5/6 double positive patients 8.6%, respectively. Ultrasound evaluation was not significantly associated with any of the parameters examined and subsequent carcinoma development. Despite CK5/6 positivity, the subsequent incidence of BC development was nearly 20%. However p63/ CK5/6 double positive status could predict a significantly lower subsequent carcinoma incidence, indicating a more accurate prognostic utility. Combining p63/ CK5/6 with histological findings could be easily applied and could predict the subsequent BC development of the patients diagnosed as IDP at biopsy. [ABSTRACT FROM AUTHOR]

Basal cell carcinoma ( BCC) is a common malignant skin tumor. However, BCC that arise at the umbilicus is rare. We present three cases of umbilical BCC. Each BCC was excised at a different depth level, and all deep surgical margins were negative. All patients had no evidence of local recurrence or metastasis during the follow-up periods (12, 24, and 52 months). Reviewing the reported cases of umbilical BCC, the BCC cells did not seem to invade into the umbilical scar in most cases, and the deepest invasion levels of tumor cells were up to the middle layer of the subcutaneous tissue. However, the dermatological surgeons have to consider the possibility of surgical excision down to and including the umbilical attachment to the peritoneum, and intraoperative margin assessment should be necessary to avoid the risk of excessive or incomplete excision. [ABSTRACT FROM AUTHOR]

The great majority of the cases clinically diagnosed as primary aldosteronism ( PA) have been caused by aldosterone-producing adenoma ( APA) or idiopathic hyperaldosteronism ( IHA). The differential diagnosis of both subtypes of PA is important due to the different therapeutic modes but clinically it is sometimes difficult. It is also important to understand the morphological features of these two subtypes with special emphasis upon differences of the status for aldosterone biosynthesis. In the last decade, molecular mechanisms of PA including the aberrant expression of G-protein coupled receptors ( GPCRs), key regulators of the intracellular calcium signaling pathway and somatic mutations of ion channels, have been revealed and our understanding of the molecular pathways involved in excessive aldosterone production has been markedly advanced. In addition, newly developed monoclonal antibodies specific to the isoform of adrenal steroidogenic enzymes have demonstrated the novel profiles of adrenal steroidogenesis in PA. These novel findings indicate that the molecular mechanisms on the onset and pathophysiology of PA are more complicated than previously considered and further clarification of clinical relevance of these findings is required at this juncture. [ABSTRACT FROM AUTHOR]

Subungual melanoma ( SUM) is rare and represents approximately 2-3% and 20% of all cutaneous melanomas in Caucasians and Asians, respectively. Amputation has usually been performed for invasive SUM; however, not all invasive SUMs invade or attach to the distal phalanx. To investigate the possibility of non-amputative surgery for patients with invasive SUM, the distances between the deepest base of the melanoma cells and the bony surface in the surgical specimens of invasive SUM were measured. Thirty surgical specimens of invasive SUM were retrospectively reviewed. The contents of the specimens were as follows: 14 first toes, 10 thumbs, three second fingers, two third fingers, and one fifth finger. Four specimens showed bone invasion, and the tumor was attached to the bone in four specimens. The tumor-to-bone distance exceeded 0.9 mm in all the specimens with thicknesses <4 mm. In the non-ulcerated SUMs (nine specimens), only one SUM specimen showed bone attachment. There was a higher likelihood of bone attachment or invasion when tumor thickness (TT) exceeded 4 mm (Pearson chi-square test, P = 0.009; Fisher exact test, P = 0.004; student t test, 0.033). Univariate and multivariate analysis also revealed that thick TT had a statistically significant affect (odds ratio 1.807 and 1.865, 95% CI 1.11-3.01 and 1.11-3.13, P = 0.023 and 0.018). Non-amputative surgery may be possible for SUM tumors that are of intermediate-thickness. However, there has been little evidence demonstrating survival with non-amputative surgery for invasive SUM. A large, randomized, prospective clinical study is required to address this issue. [ABSTRACT FROM AUTHOR]

Lipomas are common, benign, small-sized, soft-tissue tumors. However, giant lipomas are uncommon and the tumor size can cause pain and nerve compression syndrome. The axilla is an extremely rare location for development of giant lipomas. We report two cases of axillary giant lipoma. A 47-year-old man (case 1) and a 42-year-old woman (case 2) presented with a large mass in the axillary region. Case 2 had tenderness in the shoulder and numbness in the upper arm. Magnetic resonance imaging of each tumor showed a homogenous soft-tissue mass in the axillary region, suggestive of lipoma. In case 2, the tumor extended from the axilla to the supraclavicular region and split and compressed the neurovascular bundle. Each lesion was successfully excised surgically without serious complications and recurrence. In case 2, the tenderness and numbness disappeared. Histologically, each lesion was composed of multilobulated, mature adipose cells, which led to a diagnosis of benign lipoma. Axillary giant lipoma is preferably excised surgically to avoid damage caused by tumor compression to the major vessels or nerves, to offer better local control and to establish a correct final diagnosis. [ABSTRACT FROM AUTHOR]