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Perivascular epithelioid cell tumors, also known as PEComas, are rare mesenchymal tumors composed mainly of epithelioid cells found in perivascular tissue. PEComas occur most frequently in the kidney, uterus, the gastrointestinal tract, liver, and retroperitoneum; those originating in the biliary tree are extremely rare. We report a case of benign PEComa of the cystic duct with positive TFE3 staining on immunohistochemistry.A 66-year-old woman was referred for a 20 mm mass adjacent to the common bile duct discovered incidentally on abdominal ultrasound. Laboratory data including tumor markers were unremarkable. The tumor appeared to arise from the cystic duct, showed early enhancement, and compressed the common bile duct on imaging studies. Endoscopic ultrasound-guided fine-needle aspiration revealed round- and spindle-shaped atypical cells with eosinophilic cytoplasm and brown deposits suggestive of melanin granules. Histological examination of the resected specimen revealed a tumor consisting of epithelioid cells forming an alveolar structure, with melanin pigmentation. Immunohistochemistry was positive for HMB-45 and TFE3, consistent with benign pigmented PEComa of the cystic duct. Melanotic, myogenic, and TFE3 staining are helpful when diagnosing PEComas arising in unusual locations.

KRAS mutation is a major driver of pancreatic carcinogenesis and will likely be a therapeutic target. Due to lack of sensitive assays for clinical samples of pancreatic cancer with low cellularity, KRAS mutations and their prognostic association have not been fully examined in large populations. In a multi-institutional cohort of 1162 pancreatic cancer patients with formalin-fixed paraffin-embedded tumor samples, we undertook droplet digital PCR (ddPCR) for KRAS codons 12/13/61. We examined detection rates of KRAS mutations by clinicopathological parameters and survival associations of KRAS mutation status. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) and overall survival (OS) were computed using the Cox regression model with adjustment for potential confounders. KRAS mutations were detected in 1139 (98%) patients. The detection rate did not differ by age of tissue blocks, tumor cellularity, or receipt of neoadjuvant chemotherapy. KRAS mutations were not associated with DFS or OS (multivariable HR comparing KRAS-mutant to KRAS-wild-type tumors, 1.04 [95% CI, 0.62-1.75] and 1.05 [95% CI, 0.60-1.84], respectively). Among KRAS-mutant tumors, KRAS variant allele frequency (VAF) was inversely associated with DFS and OS with HRs per 20% VAF increase of 1.27 (95% CI, 1.13-1.42; p

This study evaluated the efficacy of adjuvant chemotherapy (AC) for intraductal papillary mucinous carcinoma (IPMC).We retrospectively analyzed patients who underwent pancreatectomy for invasive IPMC from January 2007 to June 2020. We evaluated outcomes of AC in the entire cohort and in patients with known prognostic factors.A total of 51 patients with invasive IPMC underwent surgery, of which 35 received AC. In the entire cohort, there was no significant difference in median overall survival (OS) between the AC and surgery alone (SA) group [hazard ratio (HR)=0.54; p=0.232]. For patients with poorly differentiated adenocarcinoma, median OS was significantly longer in the AC group (HR=0.27; p=0.022). For patients with lymph node metastasis, median OS was significantly higher in the AC group (HR=0.07; p0.001).AC may be effective for selected invasive IPMC patients.

Purpose After the popularization of serum immunoglobulin G4 (IgG4) measurement and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in our institute, surgical resection for non-neoplastic diseases of the pancreas became less common. Although the incidence of such false-positive cases was clarified in the 10-year period after introduction of these measures (2009–2018), these data were not compared with the 30 years before 2009 (1979–2008). This study was performed to determine the percentage of autoimmune pancreatitis (AIP) that was included during the latter period and how the numbers of false-positive cases differed between the two periods. Methods From 1979 to 2008, 51 patients had clinical suspicion of pancreatic carcinoma (false-positive disease). Among these 51 patients, 32 non-alcoholic patients who had tumor-forming chronic pancreatitis (TFCP) were clinically, histologically, and immunohistochemically compared with 11 patients who had TFCP during the latter 10-year period. Results Retrospective IgG4 immunostaining of TFCP revealed 14 (43.8%) cases of AIP in the former 30 years versus 5 (45.5%) in the latter 10 years. There were 32 (6.7%) cases of TFCP among 675 patients in the former 30 years and 11 (0.9%) among 1289 patients in the latter 10 years. Conclusions When the TFCP ratio of pancreatic resections and the AIP ratio of TFCPs were compared between the two periods, the TFCP ratio was 4.7% versus 0.9% and the AIP ratio was 43.8% versus 45.5%, respectively. These findings indicate that IgG4 measurement and EUS-FNA are imperative for the diagnosis of TFCP.

Primary pancreatic lymphomas are extremely rare, accounting for 0.1-0.5% of malignant lymphomas and about 0.2% of primary pancreatic tumors. They occur most commonly in the pancreatic head of elderly males, with diffuse large B-cell lymphoma being the most common subtype. Primary pancreatic follicular lymphoma is the most commonly reported primary pancreatic indolent lymphoma, accounting for 9-14% of primary pancreatic lymphomas. We report two cases of primary pancreatic follicular lymphoma treated with obinutuzumab, a second-generation humanized anti-CD20 monoclonal antibody, and bendamustine. One was diagnosed by endoscopic ultrasound-guided fine-needle aspiration, while the other required laparoscopic lymph node sampling to reach a diagnosis. Both achieved complete response with induction therapy and opted for maintenance therapy with obinutuzumab. We also conducted a literature review of primary pancreatic follicular lymphoma cases reported over the last 30 years.

Purpose It is rare to find surgically-resectable metastatic lesions that are limited to the pancreas, by preoperative imaging. In this retrospective study, we reviewed the histopathologic findings in pancreatic surgical resection specimens to determine the factors that contribute to the prognostic improvement of surgical treatment for pancreatic metastases. Methods From 1979 to 2018, 43 patients underwent pancreatic resection for metastatic tumors in the Department of Hepato-Biliary-Pancreatic Surgery of the Cancer Institute of the Japanese Foundation for Cancer Research. Survival curves were created using the Kaplan–Meier method, and comparisons of survival were performed using the log-rank test.Results Primary tumors comprised renal cell carcinoma (RCC), colorectal carcinoma (CRC), and miscellaneous malignancies (MM) in 23, 9, and 11 cases, respectively. Histopathologically, the patterns of metastases were classified as hematogenous (32), lymphatic (8), and peritoneal (3). Regarding the prognosis after metastasectomy of the pancreas, there were significant differences for disease-free interval (< 5 years versus ≥5 years) and primary tumor (RCC versus CRC/MM). The rate of secondary or accompanying lymph node metastasis around the main metastasis was 5/9 (56%) for CRC, 5/11 (45%) for MM, and 1/23 (4%) for RCC. Conclusion Survival outcomes are more favorable for disease-free intervals ≥ 5 years, pancreatic metastasis from RCC, and with lymphatic metastasis. Lymph node dissection is not strictly necessary for the surgical removal of pancreatic metastasis from RCC, whereas this is highly recommended for patients with metastasis from CRC or MM.

Helicobacter pylori (HP) is a major etiologic driver of diffuse-type gastric cancer (DGC). However, improvements in hygiene have led to an increase in the prevalence of HP-naïve DGC; that is, DGC that occurs independent of HP. Although multiple genomic cohort studies for gastric cancer have been conducted, including studies for DGC, distinctive genomic differences between HP-exposed and HP-naïve DGC remain largely unknown. Here, we employed exome and RNA sequencing with immunohistochemical analyses to perform binary comparisons between 36 HP-exposed and 27 HP-naïve DGCs from sporadic, early-stage, and intramucosal or submucosal tumor samples. Among the samples, 33 HP-exposed and 17 HP-naïve samples had been preserved as fresh-frozen samples. HP infection status was determined using stringent criteria. HP-exposed DGCs exhibited an increased single nucleotide variant burden (HP-exposed DGCs; 1.97 [0.48-7.19] and HP-naïve DGCs; 1.09 [0.38-3.68] per megabase; p = 0.0003) and a higher prevalence of chromosome arm-level aneuploidies (p 0.0001). CDH1 was mutated at similar frequencies in both groups, whereas the RHOA-ARHGAP pathway misregulation was exclusive to HP-exposed DGCs (p = 0.0167). HP-exposed DGCs showed gains in chromosome arms 8p/8q (p 0.0001), 7p (p = 0.0035), and 7q (p = 0.0354), and losses in 16q (p = 0.0167). Immunohistochemical analyses revealed a higher expression of intestinal markers such as CD10 (p 0.0001) and CDX2 (p = 0.0002) and a lower expression of the gastric marker, MUC5AC (p = 0.0305) among HP-exposed DGCs. HP-naïve DGCs, on the other hand, had a purely gastric marker phenotype. This work reveals that HP-naïve and HP-exposed DGCs develop along different molecular pathways, which provide a basis for early detection strategies in high incidence settings. © 2022 The Authors. The Journal of Pathology published by John WileySons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Synovial sarcoma is a high-grade soft tissue sarcoma that occurs primarily in the deep soft tissue of extremities, and primary colorectal synovial sarcoma is extremely rare. In this report, we present a synovial sarcoma mostly located within the mucosa of the sigmoid colon. The patient was a man in his forties with a germline deletion in the MSH2 gene. He had experienced undifferentiated pleomorphic sarcoma of the left forearm 7 years before and adenocarcinoma of the transverse colon 6 years before, both of which were successfully treated and exhibited no recurrence to date. A surveillance colonoscopy for Lynch syndrome revealed the tumor which had a submucosal tumor-like appearance with central erosion and endoscopic resection was performed. Histologically, it was composed of monotonous proliferation of spindle cells arranged in cellular fascicles; these findings were compatible with monophasic fibrous synovial sarcoma. In the tumor cells, the presence of the SS18-SSX1 fusion gene was confirmed. Protein expression of mismatch repair genes was intact in the tumor cells, indicating the association between microsatellite instability and synovial sarcoma was weak. The present case highlights a rare primary site of synovial sarcoma in a patient with Lynch syndrome.

Hereditary diffuse gastric cancer (HDGC) is a rare autosomal dominant syndrome associated with an increased risk of developing Lauren's diffuse-type gastric carcinoma and lobular breast carcinoma. Although signet-ring cell carcinoma (SRCC) in situ (SRCC-pTis) has been reported as a characteristic lesion in HDGC cases with CDH1 germline mutations (CDH1 pathogenic variant), and a precursor of conventional intramucosal SRCC (SRCC-pT1a), its histopathologic features and specificity have not been sufficiently clarified. Here, we examined gastrectomy samples from 6 Japanese HDGC patients with CDH1 germline mutation, belonging to 4 families, and analyzed SRCC lesions histologically and immunohistochemically. Of the 274 foci found in the 6 samples, SRCC-pT1a accounted for 225 lesions (range: 8 to 107, mean 45.7 lesions per patient), while 46 foci were of SRCC-pTis (range: 1 to 15, mean 7.67 foci per patient). All SRCC-pTis foci were observed in the fundic gland area and on the superficial side of the mucosa. Histologically, tumor cells of SRCC-pTis were found between normal foveolar epithelial cells and the basement membrane, following a typical pagetoid spread pattern. Immunohistochemically, E-cadherin expression was lost in SRCC-pTis (27/28, 96.4%) more frequently than in SRCC-pT1a (95/197, 48.2%; P

Neoadjuvant treatment has significant survival benefits for patients with pancreatic cancer. However, local recurrence remains a serious issue, even after neoadjuvant treatment. This study investigated local recurrence after pancreaticoduodenectomy and determined the optimal resection level after neoadjuvant treatment.This retrospective study analyzed consecutive patients who underwent pancreaticoduodenectomy for borderline resectable pancreatic cancer after 4 cycles of neoadjuvant treatment-gemcitabine plus nab-paclitaxel between April 2015 and March 2020. Patients with borderline resectable-artery pancreatic cancer were classified according to the dissection level around the artery: level 3 group, hemi-, or whole circumferential arterial nerve plexus was dissected; and level 2 group, the nerve plexus was preserved.Fifty-six patients with borderline resectable-artery pancreatic cancer underwent pancreaticoduodenectomy after neoadjuvant treatment (level 3 group, n = 40; level 2 group, n = 16). The resection level in the level 2 group was changed based on post-neoadjuvant treatment computed tomography images or intraoperative frozen section diagnosis. The overall and local recurrence rates were significantly higher in the level 2 group than in the level 3 group (overall recurrence, 93.8% vs 70.0%; P = .037) (local recurrence, 50.0% vs 5.0%; P.001). Ten patients experienced local recurrence, of which 8 belonged to the level 2 group. Among them, 4 patients were confirmed as cancer-negative by surgical margin analysis or intraoperative frozen section diagnosis but experienced recurrence around the arteries.For treating borderline resectable-artery pancreatic cancer, changing the resection level based on post-neoadjuvant treatment computed tomography images increased the risk of local recurrence. All patients with borderline resectable-artery should undergo level 3 dissection, regardless of the response to neoadjuvant treatment.

A 67-year-old woman underwent distal pancreatectomy for pancreatic cancer. Recurrence in the form of lung metastasis was discovered eight months after surgery, and chemotherapy was initiated. Two years after the surgery, she was admitted for the evaluation of melena. Esophagogastroduodenoscopy revealed multiple subepithelial lesions with ulceration from the gastric body to the fornix. The histopathology of biopsy specimens was consistent with ductal adenocarcinoma, which appeared similar to the resected pancreatic cancer. The patient was diagnosed with multiple gastric metastases of pancreatic cancer. We herein report a case of pancreatic cancer with multiple gastric metastases that occurred after surgery for pancreatic tail cancer.

Acquired isolated hypoganglionosis is a rare intestinal neurological disease, which presents in adulthood with the clinical symptoms of chronic constipation. A 39-year-old man underwent laparoscopic low anterior resection and covering ileostomy for locally advanced-rectal cancer. A 6-month course of postoperative adjuvant chemotherapy was completed, followed by closure of the ileostoma. After the closure, he developed severe colitis which required 1-month of hospitalization. Mucosal erosions and pseudo-membrane formation were evident on colonoscopy and severe mucosal damage characterized by infiltration of inflammatory cells and crypt degeneration were pathologically confirmed. Even after the remission of the colitis, he suffered from severe constipation and distention. At 4 years after the stoma closure, he decided to undergo laparoscopic total colectomy. Histopathologically, the nerve fibers and ganglion cells became gradually scarcer from the non-dilated to dilated regions. Immunohistochemical staining examination confirmed that the ganglion cells gradually decreased and became degenerated from the normal to dilated region, thereby arriving at the final diagnosis of isolated hypoganglionosis. The patient recovered without any complications and there has been no evidence of any relapse of the symptoms. We present a case of acquired isolated hypoganglionosis-related megacolon, which required laparoscopic total colectomy, due to severe enterocolitis following stoma closure.

Rectal multiple neuroendocrine tumors (M-NETs) are rare, with only few epidemiologic reports on the topic. Therefore, their clinicopathological features are not completely known, and the appropriate treatment strategy has not been established. This study aimed to compare the clinicopathological malignant potential (lymphatic or venous invasion-positive and lymph node metastasis rates) of M-NETs with that of solitary NETs (S-NETs). We retrospectively investigated 369 patients with NETs of the rectum. Patients who underwent colonoscopy at the Cancer Institute Hospital between January 1979 and 2016 and diagnosed with S-NETs were included, and S-NETs were found in 348 patients. Patients with M-NETs were classified into two groups as follows: patients with

Patients with pancreatic cancer (PC) have poor prognosis and a high incidence of recurrence. Since further treatment is applicable for specific recurrent events, it is important to predict recurrence patterns after surgery. This study aimed to identify and predict early and late recurrence patterns of PC using a histology-based machine learning model.Patients who underwent upfront curative surgery for PC between 2001 and 2014 were included. The timing of recurrence and prognosis of each first recurrence site were examined. A histology-based supervised machine learning method, which combined convolutional neural networks and random forest, was used to predict the recurrence and respective sites of metastasis. Accuracy was evaluated using area under the receiver operating characteristic curve (AUC).In total, 524 patients were included. Recurrence in the liver accounted for 47.8% of all recurrence events in the first year after surgery. Meanwhile, recurrence in the lung occurred later and could become apparent more than 5 years post-surgery, with indications for further surgery. In terms of substantial distant organ metastases, liver and lung metastases were identified as representative early and late recurrence events. The predictive AUCs of the machine learning model for training and test data were 1.000 and 0.861, respectively, and for predicting nonrecurrence were 1.000 for both.We identified the liver and lung as early and late recurrence sites, which could be distinguished with high probability using a machine learning model. Prediction of recurrence sites using this model may be useful for further treatment of patients with PC.

Pancreatic cancer is the fourth leading cause of cancer-related death in Japan. Pancreatic cancer is categorized as resectable, borderline resectable, or unresectable based on the degree of adjacent vascular invasion and the presence of distant metastases. Neoadjuvant chemotherapy with gemcitabine and S-1 (NAC-GS) has recently become a standard option for resectable pancreatic cancer in Japanese patients. According to previous reports, GS is considered to be relatively safe and feasible treatment for Japanese patients, including the elderly. However, NAC-GS is occasionally associated with severe adverse events which may ultimately render the patient unfit for surgery. A 60-year-old man with resectable pancreatic cancer suffered from severe necrotic enteritis during NAC-GS, which required surgical resection. Considering the time course and histological findings of the resected bowel, S-1 was believed to be the causative agent. The low urinary dihydrouracil to uracil ratio also suggested possible dihydropyrimidine dehydrogenase deficiency, which may have hindered the metabolism of S-1 and contributed to the development of necrotic enteritis. Life-threatening enteritis occurs in approximately 0.3% of all patients who receive S-1. As initial symptoms are non-specific, patients should be instructed to lower the hurdle for contacting the hospital during NAC-GS.

Background. A higher Ki-67 labeling index is associated with a poorer prognosis in gastroenteropancreatic neuroendocrine neoplasms. It has also been proposed that the Ki-67 labeling index may increase during disease progression from the primary site to metastatic sites. Although biopsy specimens are used to measure the Ki-67 labeling index, heterogeneity in lesions is thought to affect the assessment of the Ki-67 labeling index. To overcome tumor heterogeneity, we evaluated the variability in the Ki-67 labeling index between primary lesions and hepatic metastases by analyzing only surgically resected specimens. Methods. We conducted a single-center retrospective study to analyze the variability in the Ki-67 labeling index and the change in tumor grade between the primary site and metastatic hepatic sites in 19 patients diagnosed with gastroenteropancreatic neuroendocrine neoplasms at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from 1998 to 2018. Both the primary site and metastatic hepatic sites were surgically resected. Results. Among the 19 patients with gastroenteropancreatic neuroendocrine neoplasms, 12 patients (63%) showed higher levels of the Ki-67 labeling index at metastatic hepatic sites than at the primary site. The median Ki-67 labeling index levels for the primary lesion and metastatic hepatic lesions were 5% and 10%, respectively. The Ki-67 labeling index levels were significantly elevated in the metastatic hepatic lesions compared to the primary lesion ( P = .002). Conclusions. This study addressed the heterogeneity of the Ki-67 labeling index by analyzing only surgically resected specimens. We observed a statistically significant increase in the Ki-67 labeling index in hepatic metastases compared to the primary lesion.

Microsatellite instability (MSI) is categorized by mutation frequency: high MSI (MSI-H), low MSI (MSI-L) and microsatellite stable (MSS). MSI-H tumors have a distinct immunogenic phenotype, with immunotherapies using checkpoint inhibitors already approved for the treatment of MSI-H gastroesophageal adenocarcinoma (GEA); this is not observed for MSI-L or MSS. Here, we tested the hypothesis that MSI-L tumors are also a distinct phenotype and potentially immunogenic. MSI-PCR assays (BAT25, BAT26, BAT40, D2S123, D5S346 and D17S250) were performed on 363 Epstein-Barr virus-negative, surgically resected esophagogastric junction (EGJ) adenocarcinoma samples. Tumors were characterized as MSI-H (≥2 markers), MSI-L (1 marker) or MSS (0 markers). CD8+ cell counts, PD-L1 and HER2 expression levels, TP53 mutations, epigenetic alterations and prognostic significance were also examined. All pathological and molecular experiments were conducted using serial, whole-tumor sections of chemo-naive surgical specimens. MSI-H and MSI-L were assigned to 28 (7.7%) and 24 (6.6%) cases, respectively. Compared to MSS cases, MSI-L cases had significantly higher intratumoral CD8+ cell infiltration (P = .048) and favorable EGJ cancer-specific survival (multivariate hazard ratio = 0.35, 95% CI, 0.12-0.82; P = .012). MSI-L tumors were also significantly associated with TP53-truncating mutations as compared to MSI-H (P = .009) and MSS (P = .012) cases, and this trend was also observed in GEA data from The Cancer Genome Atlas (TCGA). Indel mutational burden among TCGA MSI-L tumors was significantly higher than that of MSS tumors (P = .016). These results suggest that MSI-L tumors may have a distinct tumor phenotype and be potentially immunogenic in EGJ adenocarcinoma.

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

A 55-year-old man visited our hospital for a detailed examination of a gastric submucosal tumor that was first detected 10 years prior. The tumor continued to grow and had developed a depressed area in its center. A histopathological examination of biopsy specimens revealed gastric adenocarcinoma of the fundic gland type (GA-FG). It was diagnosed as T2 based on the invasion depth as determined by white-light endoscopy and endoscopic ultrasonography. A total gastrectomy with lymphadenectomy was performed and a GA-FG in the mucosa and submucosa was confirmed histopathologically. However, there was a gradual transition to an infiltrative tubular adenocarcinoma with poorly differentiated components in the muscular and subserosal layers. Metastasis was identified in a dissected lymph node (LN). This is the first report of a GA-FG progressing to an aggressive cancer with LN metastasis. These findings modify our understanding of the pathophysiology of GA-FG.

Among the various diagnostic modalities for small bowel hemangioma, video capsule endoscopy (VCE) and double-balloon enteroscopy (DBE) can be recommended as part of the work-up in patients with obscure gastrointestinal bleeding (OGIB). DBE is superior to VCE in the accuracy of diagnosis and therapeutic potential, while in most cases total enteroscopy cannot be achieved through only the antegrade or retrograde DBE procedures. As treatment for small bowel bleeding, especially spout bleeding, localization of the lesion for the decision of DBE insertion facilitates early treatment, such as endoscopic hemostatic clipping, allowing patients to avoid useless transfusion and the worsening of their disease into life-threatening status. Applying endoscopic India ink marking prior to laparoscopic surgical resection is a particularly useful technique for more minimally invasive treatment. We report two cases of small bowel hemangioma found in examinations for OGIB that were treated with combination of laparoscopic and endoscopic modalities.

Objectives Serrated lesions of the colorectum often have complex histological morphology, and some groups include subtypes with different molecular biology. This study aimed to characterize serrated lesions with heterogeneous histology that was dominated by a traditional serrated adenoma (TSA) component. Methods Representative lesions were selected based on both endoscopic and histological features. If a lesion had more than one component, each of the different structural parts was considered as a separate sample. DNA was extracted from 177 samples of 60 lesions and amplified to screen for BRAF and K/NRAS mutations. Results Heterogeneous TSA samples were classified into four categories: sessile serrated lesion with TSA (SA-1); TSAs with microvesicular hyperplastic polyp (SA-2); TSAs with unclassified adenoma, characterized by tubulo-serrated histology (SA-3); and TSAs with conventional adenomas (SA-4). On endoscopy, SA-1 lesions had sessile-elevated morphology with the small reddish elevations; SA-2 lesions had a pedunculated appearance with a whitish mucosal component at the stalk; SA-3 lesions had a sessile-elevated component surrounded by flat spreading margins; and SA-4 lesions had mixed adenomatous morphology. Eighteen of the 19 category SA-1 and -2 lesions (95%) had BRAF mutations, and all of the SA-3 and -4 lesions had K/NRAS mutations. Conclusions Traditional serrated adenomas were classified into two phenotypes according to their molecular characteristics: microvesicular serrated subtypes with BRAF mutations (SA-1 and -2 lesions) and subtypes containing tubulo-serrated/conventional adenoma with K/NRAS mutations (SA-3 and -4 lesions). Each subtype had characteristic macroscopic and microscopic morphologies and was distinct on endoscopy.

An 85-year-old woman was transported to our emergency room by ambulance with a complaint of slurred speech. Neurological examination revealed dysarthria only. We considered that lingual edema identified on physical examination might have influenced dysarthria. However, we were unable to perform sufficient evaluation, since she could not open her mouth widely or push the tongue out beyond the lips. We considered the incidence of acute cerebrovascular disease because of the acute onset, and performed emergency brain MRI. Imaging revealed that although no abnormality was present in the brain parenchyma, edema of the tongue and soft palate was evident on T2-weighted sagittal imaging. We confirmed the dysarthria was caused by tongue edema due to angioedema. In addition, we diagnosed angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema, because ACEI had been started 2 months earlier as pharmacotherapy for hypertension. Tongue swelling due to angioedema should be considered when examining patients with dysarthria.

The risk of malignancy in inflammatory myopathy patients is well recognized. However, the incidence of germ cell tumor (GCT) with inflammatory myopathy is low, and most reported cases of GCT also exhibit testicular tumors. Therefore, a case of extragonadal GCT with dermatomyositis (DM) is reported in the current study to better understand this paraneoplastic syndrome. A 53-year-old man presented with bilateral cervical lymph node enlargement. A lymph node biopsy showed embryonal carcinoma, and computed tomography showed multiple lymph node and lung metastases. A period of one month after bleomycin, etoposide and cisplatin (BEP) chemotherapy, this patient developed an erythematous eruption over the extensor surfaces of bilateral fingers, or Gottron's sign and facial erythema. The patient was diagnosed with DM with a positive anti-TIF-1γ-antibody result. High-dose prednisolone was effective, and there has been no evidence of cancer recurrence for over one year. The literature review identified 17 cases of GCT with inflammatory myopathy that have been reported so far, and it was indicated that this is the first case of extragonadal GCT with DM following chemotherapy. This case highlights the importance of monitoring after the completion of cancer treatment, as distinctive dermal and muscular symptoms should cause us to consider the possibility of paraneoplastic inflammatory myopathy.