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Immediate breast reconstruction (IBR) is a standard option for breast cancer patients, although its utility in patients with advanced breast cancer requiring neoadjuvant chemotherapy (NAC) is debatable. We assessed the short-term complications and long-term prognosis of IBR after NAC. We retrospectively analyzed 1135 patients with IBR and/or NAC between 2010 and 2018, 43 of whom underwent IBR after NAC. Twenty-five patients underwent reconstruction with a tissue expander (TE) followed by silicon breast implantation, 5 with a latissimus dorsi muscle transfer flap, and 13 with a deep inferior epigastric perforator flap. Complete surgical resection with a free margin confirmed by a pathological assessment was achieved in all patients. The evaluation of the short-term complications indicated no cases of total flap necrosis, two cases of partial flap necrosis, and one case of wound infection. Only one case required postponement of subsequent therapy due to partial flap necrosis. A long-term evaluation indicated no local recurrence, although distant metastasis was observed in 4 cases, 3 patients died, and TE removal after post-mastectomy radiotherapy (PMRT) was performed in 2 of 11 TE cases. IBR may be a viable option in patients with advanced breast cancer who achieve complete surgical resection after NAC.

Purpose Four clinical active surveillance trials including LORIS, COMET, LORD and LORETTA, are being conducted to assess whether women with low-risk ductal carcinoma in situ can safely avoid surgery. The present study aimed to determine the rate of upstaging to invasive cancer among patients with a preoperative diagnosis of ductal carcinoma in situ and to evaluate the incidence of upstaging in patients meeting the eligibility criteria for four active surveillance clinical trials. Methods The present study initially enrolled 180 patients with 183 calcifications who received the diagnosis of ductal carcinoma in situ by biopsy. Patients were classified as eligible for four clinical trials according to the respective inclusion criteria. Results In total, 152 patients with 155 calcifications were analyzed. Of these, 32 (21%) were upstaged to invasive disease based on the final pathological analysis of surgical specimens. Of the 152 patients, 53 (35%), 90 (59%), 24 (16%) and 34 (22%) met the eligibility criteria for the LORIS, COMET, LORD and LORETTA trial, respectively. Among patients with low-risk ductal carcinoma in situ, 10 (19%), 14 (16%), 6 (25%) and 4 (12%) patients were upstaged to invasive disease in LORIS, COMET, LORD and LORETTA, respectively. The upstaging to pT1b or higher rates were 2% (1/53), 3% (3/90), 0% (0/24) and 3% (1/34) in LORIS, COMET, LORD and LORETTA, respectively. Conclusions The upstaging rate in patients eligible for the clinical active surveillance trials was 12–25%. Although the rate of upstaging to pT1b or higher was low, further studies are required to determine the rates of upstaging to invasive cancer and the risk factors among patients with low-risk ductal carcinoma in situ.

Introduction The purpose of this study was to clarify the clinicopathological features of patients with false-negative fine needle aspiration cytology (FNAC) and to determine the factors associated with negative FNAC. Methods Patients with negative FNAC from January 2010 to December 2019 were included. The patients with positive sentinel nodes (SN) were divided into two groups: micrometastasis (≤2 mm) group and macrometastasis (>2 mm) group. The clinicopathological characteristics were compared between the two groups using the χ2 test. Results A total of 165 patients with negative FNAC were included; 52 (31.5%) had positive SNs. Of the 52 patients, 13 (25%) had micrometastasis and the remaining 39 (75%) had macrometastasis. Of the 113 patients with negative SNs, none had metastases found in non-SNs. No significant differences were observed in age, cT stage or subtype, and preoperative ultrasound findings between the two groups. Conclusions The false-negative rate of FNAC was high (31.5%). Micrometastatic disease was seen in patients with negative FNAC, and this might be the cause of false-negative FNAC results.

The American College of Surgeons Oncology Group (ACOSOG) Z1071 trial assessed the accuracy of sentinel lymph node biopsies in clinically node-positive patients who underwent neoadjuvant chemotherapy (NAC). Axillary ultrasound (US) images after NAC were reviewed, and the accuracy of classifying nodes into six types according to the ACOSOG Z1071 trial was determined. This study included 69 patients who underwent NAC followed by curative surgery for breast cancer including axillary lymph node dissection between January 2010 and July 2019. All patients were pathologically confirmed as being initially node positive. Lymph nodes were retrospectively classified into one of six types based on the appearance of the nodal cortex and hilum. Types I and II were classified as having normal nodal morphology, whereas types III, IV, V, and VI were classified as having suspicious nodal morphology. These node types on US images after NAC were compared between patients with an axillary complete response (Ax-pCR) and those with residual metastatic lymph nodes (Ax-non-pCR) using Chi-square tests. Twenty-four (35%) of the 69 patients achieved Ax-pCR. Patients with nodes classified as type I or II were more likely to achieve Ax-pCR (83% vs. 36%, p = 0. 0002). The classification of six node types was associated with nodal status.

Epstein–Barr virus (EBV)‐associated gastric cancer (EBVaGC), whose prognosis remains controversial, is diagnosed by in situ hybridization of EBV‐derived EBER1/2 small RNAs. In The Cancer Genome Atlas (TCGA) Stomach Adenocarcinoma (STAD) project, the EBV molecular subtype was determined through a combination of multiple next‐generation sequencing methods, but not by the gold standard in situ hybridization method. This leaves unanswered questions regarding the discordance of EBV positivity detected by different approaches and the threshold of sequencing reads. Therefore, we reanalyzed the TCGA‐STAD RNA sequencing (RNA‐seq) dataset including 375 tumor and 32 normal samples, using our analysis pipeline. We defined a reliable threshold for EBV‐derived next‐generation sequencing reads by mapping them to the EBV genome with three different random arbitrary alignments. We analyzed the prognostic impact of EBV status on the histopathological subtypes of gastric cancer. EBV‐positive cases identified by reanalysis comprised nearly half of the cases (49.6%) independent from infiltrating lymphocyte signatures, and showed significantly longer overall survival for adenocarcinomas of the ‘not‐otherwise‐specified’ type [P = 0.016 (log‐rank test); hazard ratios (HR): 0.476; 95% CI: 0.260–0.870, P = 0.016 (Cox univariate analysis)], but shorter overall survival for the tubular adenocarcinoma type [P = 0.005 (log‐rank test); HR: 3.329; 95% CI: 1.406–7.885, P = 0.006 (Cox univariate analysis)]. These results demonstrate that the EBV positivity rates were higher when determined by RNA‐seq than when determined by EBER1/2 in situ hybridization. The RNA‐seq‐based EBV positivity demonstrated distinct results for gastric cancer prognosis depending on the histopathological subtype, suggesting its potential to be used in clinical prognoses., We reanalyzed the large‐scale RNA sequencing (RNA‐seq) dataset of gastric cancer (The Cancer Genome Atlas‐Stomach Adenocarcinoma). Epstein–Barr virus (EBV)‐positive cases identified by reanalysis encompassed almost half of the cases, and showed longer overall survival for adenocarcinomas of the ‘not‐otherwise‐specified’ type, but shorter overall survival for the intestinal type. Thus, the RNA‐seq‐based EBV positivity might be useful in clinical prognoses.

Pathological diagnosis of dermal melanocytic tumors is often problematic owing to histological resemblance. Recently, cutaneous melanocytoma with CRTC1-TRIM11 (CMCT) was added to this category. However, only six cases have been reported so far. We herein present a case of a 77-year-old Japanese man with CMCT. The patient presented a nodule in the right thigh and underwent surgical resection. Histological examination indicated a well-demarcated 6 × 5 mm-sized tumor nodule in the dermis and subcutis. The tumor was amelanotic, consisting of uniform nests and fascicles of spindled, or epithelioid cells. The melanocytic nature was evident by immunohistochemistry. The CRTC1-TRIM11 fusion was detected by TRIM11 immunostaining, chromogenic in situ hybridization, and RT-PCR/direct sequencing. He has been free from the tumor for 1 year after additional resection. The main differential diagnosis of CMCT includes primary and metastatic dermal malignant melanomas (MM) and dermal/subcutaneous clear cell sarcoma (CCS). Additionally, histological overlap with paraganglioma-like dermal melanocytic tumor was considered. Although some investigators argue that CMCT is a variant of CCS, we think it should be separated from CCS, and subcutaneous/dermal CCS should be confined to tumors with EWSR1-ATF1/ CREB1 fusion. However, longer follow-up and more case studies are needed for revealing the true prognosis of CMCT.

We identified a Japanese patient with Lynch syndrome with a novel large germline deletion of chromosome 2p16-21, including the EPCAM, MSH2, and KCNK12 genes. The proband was a 46-year-old man with ascending colon cancer. The clinical significance of germline KCNK12 gene deletion, which encodes one of the subfamilies of two-pore-domain potassium channels, is still unknown.

Peritoneal metastases of hepatocellular carcinoma (HCC) are occasionally observed, but rupture of such metastases is rare. We report a resected case with a single ruptured peritoneal HCC metastasis. A 57-year-old man with chronic hepatitis C underwent hepatic resection twice for hepatocellular carcinoma. Recurrence in S3 was found, and the tumor was treated by radiofrequency ablation therapy (RFA). One month after RFA, plane computed tomography (CT) showed a nodule with a diameter of 5 cm near the upper pole of the spleen, and the serum alpha-fetoprotein (AFP) level remained high. The patient was admitted to hospital, with a chief complaint of abdominal pain 4 days after the CT scan, and diagnosed with intra-abdominal hemorrhage caused by a ruptured peritoneal HCC metastatic nodule. We performed semi-urgent surgery, including splenectomy and peritoneal metastasis resection, and the patient was discharged on the 10th postoperative day. Histopathological examination of the nodule confirmed HCC metastasis. The patient is alive with no evidence of recurrence as of 1 year and 6 months after the operation, with AFP levels remaining within the normal range.

A paraganglioma is a tumor originating in the sympathetic or parasympathetic nervous system. Its diagnosis may sometimes be confusing if it occurs in an atypical site. We described herein a case of a peripancreatic paraganglioma originating in the greater omentum. An asymptomatic, 61-year-old, female patient was referred to our hospital for detailed examination of a peripancreatic mass detected incidentally on computed tomography (CT). The differential diagnosis was a neuroendocrine neoplasm (NEN), and a biopsy using EUS-FNA was performed. Histologically, the tumor cells showed proliferation in solid cell nests and were positive for CD56, chromogranin A, and synaptophysin. These findings and the hypervascularity of the tumor on imaging studies were compatible with NEN. Since the imaging studies did not clearly demonstrate the continuity of the tumor with the pancreas, laparoscopic tumor resection without a pancreatectomy and sampling of the enlarged peripancreatic lymph nodes were planned as treatment. The absence of continuity with the pancreas was later confirmed by intraoperative observation, and the resection was carried out as planned. The resected tumor was pathologically considered as NEN at first in agreement with the preoperative diagnosis. However, several histological findings (such as a zelleballen-like growth pattern, pseudo-inclusion, and strong nuclear atypia compared with the cells' proliferative ability) were atypical for NEN, and paraganglioma was included in the differential diagnosis. Additional immunostainings of S-100 and AE1/AE3 were performed, leading to the final diagnosis of paraganglioma. Paragangliomas should be included in the differential diagnosis of an intraperitoneal mass of uncertain identity with hypervascularity.

Here, we report a case of successful surgical resection of expansive-growth acinar cell carcinoma. A 59-year-old man was referred to a local hospital with abdominal distention. CT revealed a large abdominal tumor. Subsequently, he was referred to our hospital. Physical examination showed a large tumor on his left upper abdomen without tenderness. CT revealed an enhanced 18 cm-sized expansive-growth tumor on the left flank, suggesting a primary pancreatic tumor. EUS-FNA yielded a diagnosis of adenocarcinoma. Imaging findings were not typical for pancreatic ductal carcinoma. We performed distal pancreatectomy with splenectomy, transverse colon resection, and proximal gastrectomy. Pathological findings revealed a tumor, measuring 19.5×16.5×15.5 cm, originating from the pancreatic body, positive for trypsin, chymotrypsin, and elastase, consistent with a diagnosis of acinar cell carcinoma, pT3, N0, M0. Four courses of adjuvant chemotherapy with S-1 were provided, and the patient is currently alive without recurrence for 10 months.

The clinical and pathological features of sporadic microsatellite instability-high (MSI) colorectal cancer (CRC) are still unclear. The present study aimed to clarify the clinicopathological features of sporadic MSI CRC in comparison with those of Lynch syndrome (LS) exploratorily. The present study was a single-center, retrospective cohort study. Sporadic MSI CRC was defined as MSI CRC with aberrant promoter hypermethylation of the MLH1 gene, while hereditary MSI CRC was defined colorectal cancer in patients with LS. In total, 2653 patients were enrolled; of these, 120 (4.5%) had MSI CRC, 98 had sporadic MSI CRC, and 22 had LS. Patients with sporadic MSI CRC were significantly older (p

To improve the poor prognosis of pancreatic ductal adenocarcinoma (PDAC), the diagnosis of early-stage PDAC is essential. In particular, the diagnosis of high-grade intraepithelial pancreatic neoplasia/carcinoma in situ (HG-PanIN/CIS) is the best option. However, it is almost impossible to directly observe HG-PanIN/CIS. Thus, identifying a secondary imaging finding due to the disorder is important. Focal pancreatic parenchymal atrophy (FPPA) and hypoechoic area have been reported as preferred secondary signs. We studied 50 patients to clarify the effectiveness of FPPA in diagnosing HG-PanIN/CIS. Most patients had the opportunity to undergo further examination due to the presence of a cyst. Among the 50 patients, 23 (46%) had positive results for serial pancreatic-juice aspiration cytologic examination (SPACE), which has high sensitivity and specificity for diagnosing PADC; 20 of the 23 (87.0%) patients underwent surgery to resect the pancreatic part including the FPPA. Distal pancreatectomy and pancreatoduodenectomy were performed in 19 patients and one patient, respectively. In 13 of the 20 (65%) patients, histopathological examination revealed HG-PanIN/CIS in the pancreatic ductal epithelium of the resected specimens. FPPA could indicate HG-PanIN/CIS, but not satisfactorily. One of the factors for the unsatisfactory results might be the difficulty in identifying FPPA in the pancreatic head area. On the other hand, a pancreatic cyst, especially in the area of FPPA, could lead to the diagnosis of HG-PanIN/CIS. The size of the cyst does not affect the diagnosis of HG-PanIN/CIS.

Primary gastric squamous cell carcinoma (SCC) is a rare histological subtype of gastric cancer. Here, we report the first case of primary gastric verrucous carcinoma (VC), a well-differentiated variant of SCC. Gastroscopy revealed a papillary polypoid lesion at the posterior wall of the upper gastric body and isolated squamous epithelium at the greater curvature of the fornix in a 78-year-old woman. Endoscopic submucosal dissection was performed. Microscopically, the lesion comprised very well-differentiated squamous epithelium with minimal atypia and exhibited coarse papillary structure and bulbous epithelial downgrowth with submucosal invasion. Conventional SCC or adenocarcinoma components were not included, and the lesion was surrounded by the metaplastic intestinal mucosa. Human papillomavirus infection was not detected. Although the pathogenesis of primary gastric SCC remains controversial, here, the disease is suggested as having originated from squamous epithelium. Knowledge of primary gastric VC and difficulty in diagnosing it using surface biopsy is necessary.

We report a case of pulmonary metastasis from hilar cholangiocarcinoma successfully treated by stereotactic body radiotherapy. The patient was a 70-year-old woman who underwent extended left hemi-hepatectomy with bile duct reconstruction for hilar cholangiocarcinoma at the age of 67. Pathological diagnosis indicated a well-differentiated adenocarcinoma. We followed up the patient without adjuvant chemotherapy. Nineteen months after the initial resection, a solitary pulmonary metastasis was detected in the right upper lobe. The patient received gemcitabine plus cisplatin(GC)therapy. After 4 courses of GC therapy, the size of the pulmonary metastasis was unchanged. Therefore, we performed a thoracoscopic wedge resection. Pathological diagnosis indicated that the pulmonary metastasis originated from the cholangiocarcinoma. Fifteen months after the pulmonary resection, another solitary pulmonary metastasis was detected in the left lower lobe. As the patient refused further chemotherapy, we performed stereotactic body radiotherapy(SBRT)(50 Gy/4 Fr). An adverse event of Grade 1 radiation pneumonitis was observed. The metastasis disappeared after SBRT. Twenty-eight months after SBRT and 70 months after the initial surgery, the patient is alive without recurrence.

Although Stenotrophomonas maltophilia causes substantial morbidity and mortality in immunocompromised patients, it has not been described as a causal pathogen of neutropenic enterocolitis (NEC). We describe the first case of histologically-confirmed NEC caused by S. maltophilia accompanied by bacteremia and pneumonia after salvage chemotherapy for acute myeloid leukemia relapse following a second hematopoietic stem cell transplantation. S. maltophilia should be included as a pathogenic organism of NEC in severely immunocompromised patients to prevent a delayed diagnosis, which carries a high risk of inappropriate antimicrobial selection and fatal outcome.

The field of immunotherapy has recently focused on cancers with microsatellite instability (MSI). These cancers include both Lynch-syndrome-associated tumors, which are caused by mismatch repair (MMR) germline mutations, and sporadic MSI tumors, which are mainly attributed to MLH1 promoter methylation. The present study aimed to clarify differences in the histological and PD-L1 expression profiles between these two types of MSI cancers in Japanese patients. Among 908 cases of colorectal cancer treated via surgical resection from 2008 to 2014, we identified 64 MSI cancers, including 36 sporadic MSI and 28 Lynch-syndrome-associated cancers, using a BRAF V600E mutation analysis and MLH1 methylation analysis. Of the latter subgroup, 21 (75%) harbored MMR germline mutations. The following were more frequent with sporadic MSI than with Lynch syndrome associated cancers: poor differentiation (50.0 vs. 7.1%, P = 0.0002), especially solid type (30.6 vs. 3.6%, P = 0.0061); medullary morphology (19.4 and 0%, P = 0.015), Crohn-like lymphoid reaction (50.0 vs. 25.0%, P = 0.042), and PD-L1 expression (25.0 vs. 3.6%, P = 0.034). However, the groups did not differ in terms of the mean invasive front and intratumoral CD8-positive cell densities. In a logistic regression analysis, PD-L1 expression correlated with poor differentiation (odds ratio: 7.65, 95% confidence interval: 1.55–37.7, P = 0.012), but not with the difference between sporadic MSI cancer and Lynch-syndrome-associated cancer (odds ratio: 4.74, 95% confidence interval: 0.50–45.0, P = 0.176). Therefore, compared with Lynch-syndrome-associated cancers, sporadic MSI cancers are more frequently solid, poorly differentiated medullary cancers that express PD-L1.

A 70s man underwent transurethral resection of the bladder tumor(TURBT)at a previous hospital. The pathological diagnosis was urothelial carcinoma pT1. Nine months later, recurrence appeared in the bladder and he underwent repeated TURBT. The pathological diagnosis was also pT1 and he was administered 8 courses of intravesical BCG therapy. Fourteen months after the first operation, computed tomography scans showed new lesions in the liver. Therefore, he was referred to our hospital. Because biopsy from the hepatic lesion confirmed the diagnosis of metastatic urothelial carcinoma, he received 10 courses of gemcitabine plus cisplatin(GC)and radiofrequency ablation. However, daughter nodule and enlargement of the main tumor were revealed on MRI 33 months after the initial TURBT. After 5 courses of pembrolizumab that limited the potential for hepatic metastases, he had no evidence of other metastatic sites and underwent laparoscopic right hepatectomy. There was no viable carcinoma in the pathological specimens of the hepatic lesions. Six months after hepatectomy, the patient has a high quality of life without any recurrence.

Objectives Diagnosing high-grade intraepithelial neoplasia without invasion, traditionally referred to as carcinoma in situ (CIS), is essential for improving prognosis. We examined the imaging findings of patients with and without CIS to identify significant aspects for the diagnosis of CIS. Methods Forty-six patients strongly suspected of early pancreatic cancer without nodule on imaging (CIS group, n = 27; non-malignant group, n = 19) were retrospectively evaluated according to ten factors of computed tomography/magnetic resonance imaging (CT/MRI), endoscopic ultrasonography (EUS), and endoscopic retrograde cholangiopancreatography (ERCP) using hierarchical cluster and univariate analyses. Results Two clusters were formed by hierarchical cluster analysis. One cluster consisted of 83.3% CIS cases with similar image findings such as focal pancreatic parenchymal atrophy (FPPA) on CT/MRI, main pancreatic duct (MPD) stricture surrounded by hypoechoic areas on EUS, and MPD stricture with upstream MPD dilation on ERCP. On univariate analysis, the CIS and non-malignant groups had FPPA on CT/MRI in 15 (55.6%) and 3 (15.8%) cases (p = 0.013), and MPD stricture surrounded by hypoechoic areas on EUS in 20 (74.1%) and 4 (21.1%) cases (p = 0.001), respectively. MPD stricture surrounded by hypoechoic areas was observed in 80% (12/15) of CIS cases with FPPA on CT/MRI and correlated with FPPA. Moreover, FPPA and MPD stricture surrounded by hypoechoic areas had histopathologically observed fibrosis or fat replacement due to pancreatic parenchymal atrophy. Conclusions FPPA and MPD stricture surrounded by hypoechoic areas are significant findings for the diagnosis of CIS.

In breast cancer, FoxP3-positive tumor-infiltrating lymphocytes (FoxP3+ TILs) vary depending on lymph node status, histological grade, and subtype. All these studies have compared the numbers of FoxP3+ TILs among different hosts, but recruitment of FoxP3+ TILs might depend on each individual's immune environment and each tumor's biological characteristics. In the present study, FoxP3+ TIL numbers were investigated in patients with synchronous bilateral breast cancer (SBBC) to determine the factors that affect FoxP3+ TIL recruitment in the same anti-tumor immune environment.Patients diagnosed with SBBC who underwent curative surgery at two institutions were enrolled in this study. Patients who underwent primary systemic therapy or who were diagnosed with ductal carcinoma in situ or who had distant metastases at diagnosis were excluded. The average numbers of Foxp3+ TILs were determined from the scores of five high-power microscopic fields (HPF). The associations between Foxp3+ TIL numbers and the clinicopathological features of bilateral breasts in a single individual were examined.Nuclear grade (NG) (p = 0.007) and subtype (p = 0.03), but not size (p = 0.18) and axillary lymph node (p = 0.23) were significantly associated with increase of FoxP3 + TIL numbers by univariate analysis. Further, only NG was a statistically significant clinicopathological factor for change in the number of FoxP3+ TILs by multivariate analysis (p = 0.046) CONCLUSIONS: There was no relationship between FoxP3+ TIL numbers and cancer progression as reflected in tumor size and axillary lymph node in patients with SBBC. Aggressive biological factors, especially high NG, were significantly related to enhanced recruitment of FoxP3+ TILs.

Neoadjuvant imatinib may prevent tumor rupture and the need for extended surgery by reducing the tumor size by approximately 35%, especially for large gastric gastrointestinal stromal tumors(GISTs), as shown in a previous phase Ⅱ study (Kurokawa et al. BJC 2017); however, the use ofneoadjuvant imatinib is not prevalent in clinical practice. Herein, we report a large gastric GIST that was successfully treated with neoadjuvant imatinib. A 74-year-old woman complained ofabdominal pain, and abdominal computed tomography(CT)revealed a 14 cm oval tumor in the left upper abdominal cavity. Gastric biopsy revealed that the tumor was a GIST. The patient also had a small lung tumor that was diagnosed as a primary lung carcinoma in the right upper lobe. We performed neoadjuvant imatinib for 6 months as the primary treatment. After 7 months ofimatinib administration, CT revealed that the GIST decreased in size but the lung cancer was slightly enlarged. Therefore, we performed right upper lung lobectomy and continued imatinib therapy for an additional 3 months. After a total of9 months ofneoadjuvant imatinib treatment, we performed partial gastrectomy combined with splenectomy without tumor rupture. The patient is scheduled to continue imatinib therapy for a total of 3 years.

Background The objective of this study was to evaluate the accuracy of fine needle aspiration cytology (FNAC) of axillary lymph nodes (LN) in breast cancer, to compare the results of FNAC and pathological examination, and to distinguish patients with 1 to 2 metastatic LNs from those with ≥3 metastatic LNs in patients with FNAC-positive patients. Patients and methods This study included 198 breasts of 196 patients with breast cancer who underwent FNAC and surgery for the primary and axilla without neoadjuvant chemotherapy from January 2010 to August 2016. Axillary nodal status was assessed by ultrasound (US), and whether FNAC-positive had three or more suspicious LNs on US imaging was examined. Results The results of FNAC were positive in 75 (38%), negative in 97 (49%), suspicious in 2 (1%), indeterminate in 5 (2.5%), and insufficient in 19 patients (9.5%). FNAC sensitivity, specificity, positive predictive value, and negative predictive value were 62.6%, 100%, 100%, and 62.0%, respectively. Whereas 53% (18/34) of patients with false-negative FNAC had one metastatic LN on final pathology, 61% (47/77) patients who were FNAC-positive had three or more metastatic LNs. In the FNAC-positive patients, all patients had ≥3 metastatic LNs if they had ≥3 suspicious LNs on US imaging. Conclusion Patients with positive cytology were more likely to have ≥3 positive LNs compared to false-negative cytology patients. Patients with ≥3 abnormal LNs on US and positive FNAC might require axillary dissection.

Serial pancreatic juice aspiration cytologic examination (SPACE) by nasopancreatic tube placement can give us an opportunity to diagnose early-stage pancreatic cancer with higher sensitivity and specificity compared with conventional pancreatic cytology by one-time pancreatic juice aspiration or pancreatic duct brushing. We performed SPACE in a patient with persistent pancreatic duct stricture (PDS) with gradually advancing pancreatic parenchyma atrophy (PPA) in the pancreas tail. The result of SPACE was suggestive of pancreatic carcinoma, and distal pancreatectomy was performed. Histopathological examination of the resected specimen revealed carcinoma in situ of the pancreas. The present case could indicate that any PDS becomes a candidate for SPACE especially in a patient with PPA, although the PDS remains unchanged for a long period.

Aims Although desmoplastic fibroblastoma (DFB) and fibroma of tendon sheath (FTS) are well-established entities, they may show overlapping clinicopathological features. In addition, cytogenetic data showing a shared 11q12 rearrangement in a small number of cases suggest a close link between these entities. A recent microarray study revealed up-regulation of FOSL1 mRNA in DFBs with 11q12 rearrangement. The aim of this study was to clarify the relationship between DFB and FTS. Methods and results We tested 42 cases diagnosed originally as either DFBs or FTSs for interobserver concordance based on the existing histological criteria and correlated the diagnosis with FOSL1 immunohistochemistry. In addition, FOSL1 gene status was determined by chromogenic in-situ hybridization (CISH). Using joint histological evaluation, 41 of 42 tumours were classified unanimously by three pathologists into 25 DFBs and 16 FTSs, whereas only one case received discordant opinions. Immunohistochemically, all DFBs showed diffuse, strong FOSL1 nuclear immunoreactivity (25 of 25, 100%), while none of the FTSs showed such overexpression. None of the selected 42 DFB mimics overexpressed FOSL1. FOSL1 was not rearranged in seven DFBs tested by CISH. Conclusions We confirm here that DFB and FTS are two distinct entities that can be distinguished using the existing histological criteria. This distinction corresponds perfectly with FOSL1 immunohistochemical expression status, and diffuse strong FOSL1 expression specific to DFBs sharpens the border between the two categories. FOSL1 overexpression in DFB may not be caused directly by FOSL1 gene rearrangement. FOSL1 may also be a diagnostic aid for differentiating DFB from other histological mimics.

Background Evasion of the immune system is one of the hallmarks of malignant tumors, and recently blocking of such evasion has been used in clinical practice for the treatment of some types of cancers. Recruitment of regulatory T cells (Tregs), which express the specific marker Foxp3, is an established mechanism of escaping from the immune system. In breast cancer, it has been reported that the number of Tregs differs widely among breast cancer subtypes, and that patients who have many Tregs around the tumor tend to have a poor prognosis. However, the factors that are important for the recruitment of Tregs are not well known. Thus, factors that depend on the host (e.g., age or comorbidity), on the tumor (e.g., subtype, grade, or stage), or on measurement error might be the cause of the observed differences in the number of Tregs. In this study, we investigated the numbers of Tregs in simultaneous bilateral breast cancer patients in order to determine the factors that influence the recruitment of Tregs, while excluding differences in individuals as much as possible. Material and methods Patients who had breast cancer in both breasts and who underwent simultaneous surgery between January 2005 and September 2015 at two institutions were enrolled in this study. Patients who underwent primary systemic therapy who were diagnosed with ductal carcinoma in situ, or who were stage IV were excluded. The average numbers of Foxp3-positive (Foxp3+cells) were determined from scores of five high-power fields (HPFs). The association between the difference in Foxp3+ cell number between each breast in a single individual and clinicopathological features was examined. Results Seventy patients were included in this study. Their ages ranged from 39-85 (median 54) years old. Ninety five percent of the tumors were invasive ductal carcinoma non-special type. Eighty eight (62.9%), 43 (30.7%), and 9 (6.4%) of the tumors were T1, T2, and ≥T3, respectively, and 102 (72.9%) of the tumors were node-negative. Regarding nuclear grade (NG), 104 (74.3%), 21 (22.1%), and 7 (5%) of the tumors were NG1, 2, and 3, respectively. As for subtype, 124 (88.6%), 9 (6.4%), and 7 (5%) were ER-positive and HER2-negative(ER+/HER2-), ER-positive or negative and HER2-negative(ER±/HER2+), and ER-negative and HER2-negative(ER-/HER2-), respectively. The numbers of Foxp3+ cells ranged from 0 to 39.8 (median 3.3)/HPF, and difference in Foxp3+ cell number between each breast in a single individual ranged from 0 to 34 (median 3.9)/HPF. Differences in tumor size and node status in individuals did not impact on the number of Foxp3+ cells. However, the number of Foxp3+ cells in tumors that were NG3 (P=0.00098) or ER±/HER2+ or ER-/HER2- type (P=0.00586) were statistically significantly increased compared with tumors that were NG1/2 or ER+/HER2- type in the same host. Furthermore, the difference of Foxp3+ cells between each tumor in a single individual were quite small regarding tumor size and node status in 53 patients who had similar NG and subtype tumors in both breasts. Conclusions The number of Foxp3+ cells showed no relationship with tumor size, or lymph node status in simultaneous bilateral breast cancer patients. High NG, ER±/HER2+ or ER-/HER2- type of the tumor were involved with enhancement of the recruitment of Tregs. Citation Format: Goto R, Hirota Y, Aruga T, Horiguchi S, Tazawa S, Nakamura S, Takimoto M. The numbers of Foxp3 positive cells in simultaneous bilateral breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-05-17.

High-grade pancreatic intraepithelial neoplasia (HG PanIN)/carcinoma in situ (CIS) in the pancreatic body and tail can induce parenchymal atrophy through chronic inflammatory changes presenting as a Hypoechoic area on EUS (Hypocho) or focal pancreatic parenchymal atrophy (FPPA) on computed tomography (CT) and magnetic resonance imaging (MRI). We herein discussed two patients with a hypoechoic area in the pancreatic head and neck on EUS resembling pancreatic ductal adenocarcinoma (PDAC). The lesions consisted of dense fibrosis and fat infiltration with pancreatic parenchymal atrophy around the HG PanIN/CIS in the main pancreatic duct (MPD), which penetrated the lesion and showed mild stenosis and upstream dilation. CT and MRI were unable to visualize the lesions. A specimen was obtained from one lesion by fine-needle aspiration under EUS (EUS-FNA) guidance for histopathological and cytological analysis, but the tests returned negative for adenocarcinoma. However, serial pancreatic-juice aspiration cytologic examination (SPACE) revealed adenocarcinoma in both lesions, prompting surgical resection. Histopathological examination revealed non-invasive HG PanIN/CIS in the MPD surrounded by dense fibrosis and fat deposition in the area of parenchymal atrophy. The CIS was restricted to the area of parenchymal atrophy.These two cases are noteworthy in illustrating a hypoechoic area appearing on EUS as a tumor-like lesion resembling PDAC. EUS-FNA has recently been used histopathologically to diagnose a pancreatic lesion. However, in the present and similar cases, EUS-FNA can only reveal secondary changes due to CIS unless the pancreatic duct covered by the CIS is accidentally punctured. We should bear in mind that CIS can appear as a hypoechoic area resembling PDAC on EUS, and that SPACE is the best method for diagnosing CIS in such cases.

Adenomyoepithelioma (AME) of the male breast is a rare tumor characterized by biphasic proliferation of gland epithelial cells and myoepithelial cells. Though pleomorphic adenoma (PA) is also known to be an epithelial-myoepithelial tumor in the breast, and these tumors are considered to exist on the same spectrum by some authors, to the best of our knowledge, there have been no reports of a clear transition from AME to PA in the male breast. Therefore, the case of an 85-year-old man with AME with PA-like components is presented.

Transplantation-associated thrombotic microangiopathy (TA-TMA) is an important complication of hematopoietic stem cell transplantation. To date, information regarding the organs that are affected by TA-TMA as confirmed histologically remains limited; the clinicopathologic differences between renal TA-TMA and intestinal TA-TMA have not been examined despite being the well-known and commonly affected sites of TA-TMA. We therefore examined 165 autopsied patients after hematopoietic stem cell transplantation and compared the clinicopathologic factors of renal and intestinal TA-TMA. It was clear that 38 (23%) of our patients had TA-TMA. In the TA-TMA cases, the kidney (61%) and intestine (53%) were commonly affected, and the ileum and right colon were vulnerable. Other organs that we found to be affected by TA-TMA included the stomach (8%), gallbladder (5%), and oral cavity, pharynx, esophagus, liver, heart, urinary bladder, and ureter (all at 3%), and symptoms thought to be caused by TA-TMA of these organs were not observed in any patient. Histologically, TA-TMA only affected the arteriole, or small arteries, regardless of the organ, and the veins or larger arteries were not affected at all. In the kidney, the glomerular capillary was also affected, and mesangiolysis and double contours of the basement membranes were often in evidence. The histologic overlap of renal and intestinal TA-TMA was rare (13%), and the patients in the intestinal TA-TMA group exhibited more frequency of a history of intestinal acute graft-versus-host disease (GVHD) during the clinical course compared with that of the renal TA-TMA group (80% versus 22%, P = .0016). Although TA-TMA can affect many other organs, the frequency of these ancillary events was low, and the clinical effect may have been small. Our results suggest that in comparison to renal TA-TMA, intestinal GVHD could be more closely associated with intestinal TA-TMA as a risk factor.

Ciliated muconodular papillary tumors are benign lesions located in the peripheral lung field. Recent studies revealed BRAF and epidermal growth factor receptor gene mutations and anaplastic lymphoma kinase gene rearrangement. Five ciliated muconodular papillary tumors were screened for the BRAF V600E and EGFR mutations via polymerase chain reaction. Immunohistochemical analysis was performed for the detection of the BRAF V600E and anaplastic lymphoma kinase proteins, as well as other markers including phosphorylated extracellular signal-regulated protein kinase. Three tumors (60%) harbored the BRAF V600E mutation. Immunohistochemical analysis confirmed this mutation in all of the tumor cell types. EGFR mutation and immunoactivity of the anaplastic lymphoma kinase protein were not detected. Phosphorylated extracellular signal-regulated protein kinase was negative both in the cytoplasm and nucleus of the BRAF V600E–positive tumors. Mucin 1, mucin 4, thyroid transcription factor 1, and cytokeratin 7 were positive, and mucin 5AC was partially positive, whereas napsin A and cytokeratin 20 were negative. Ciliated muconodular papillary tumor may originate from the terminal bronchioles, and the status of ERK activation reflects its benign behavior.

Backgrounds: Endoscopic ultrasonography (EUS) is used to observe the stricture of the main pancreatic duct (MPD) and in diagnosing pancreatic cancer (PC). We investigate the findings on EUS by referring to the histopathological findings of resected specimens. Materials and Methods: Six patients with carcinoma in situ (CIS) and 30 patients with invasive carcinoma of 20 mm or less were included. The preoperative EUS findings were classified as follows. A1: Simple stricture type—no findings around the stricture; A2: Hypoecho stricture type—localized hypoechoic area without demarcation around the stricture; A3: Tumor stricture type—tumor on the stricture; B: Dilation type—the dilation of the pancreatic duct without a downstream stricture; C: Parenchymal tumor type—tumor located apart from the MPD. Results: Classes A1 and A2 consisted of 2 CISs, and 4 invasive carcinomas included two cases smaller than 5 mm in diameter. Most of the cancers classified as A3 or C were of invasive carcinoma larger than 5 mm in diameter. All cancers classified as B involved CIS. Serial pancreatic-juice aspiration cytologic examination (SPACE) was selected for all types of cases, with a sensitivity of 92.0%, while EUS-guided fine needle aspiration cytology (EUS-FNA) was only useful for invasive carcinoma, and its sensitivity was 66.7%. Conclusions: Stricture without a tumor could be a finding for invasive PC and pancreatic duct dilation without a downstream stricture could be a finding indicative of CIS. Carcinoma smaller than 5 mm in diameter could not be recognized by EUS. SPACE had a high sensitivity for diagnosing small PC.

Idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) is a rare and poorly understood ischemic colitis that occurs in the rectosigmoid colon of predominantly young, previously healthy, male patients. A 76-year-old Japanese man presented to our hospital with a 1-year history of worsening diarrhea, lower abdominal pain, and weight loss (−6 kg). Laboratory evaluation revealed white blood cell count of 13 200/μL, C-reactive protein level of 2.0 mg/dL (normal range, 0.0–0.3), and negative results for stool culture (including Clostridium difficile). Colonoscopy showed circumferential and edematous narrowing of the sigmoid colon with deep longitude ulceration. Biopsy was done and examination of the specimen demonstrated no specific ischemia. The patient was treated with bowel rest, antibiotics, and i.v. fluids; however, his symptoms worsened. Finally, sigmoidectomy was carried out. Histological examination demonstrated significant myointimal hyperplasia of mesenteric veins leading to thickening and stenosis of the venous lumen. Therefore, the final diagnosis was IMHMV. Three months following sigmoidectomy, he was asymptomatic.

Gastric carcinoma with enteroblastic differentiation (GCED) is a rare variant of gastric carcinoma, and a part of GCED produces alpha-fetoprotein. GCED is characterized by cells with clear cytoplasm and a tubulopapillary and solid growth pattern resembling those in the primitive gut. GCED is typically overlaid by a conventional adenocarcinoma (CA) component, implying that CA in the mucosa differentiates into GCED during tumor invasion and proliferation. We present the case of a 73-year-old woman with a 10-mm superficial elevated lesion and a slight central depression at the anterior wall of the lower gastric body. Endoscopic submucosal dissection revealed tumor cells having clear cytoplasm and severely atypical nuclei characteristic of GCED. The growth pattern was predominantly solid and trabecular but included submucosal layer invasion and limited tubular growth. Atrophic pyloric mucosa without intestinal metaplasia surrounded the tumor. Immunohistochemically, the tumor cells were positive for AFP, GPC3, and SALL4. The present patient showed a purely enteroblastic differentiation without a CA component despite the presence of early cancer, indicating that few cases of GCED may arise de novo in the gastric mucosa. GCED is more aggressive compared with CA; therefore, pathologists should be aware that GCED without CA can appear in biopsy specimens of early cancer while making an accurate diagnosis.

The base excision repair gene MUTYH is the causative gene of colorectal polyposis syndrome, which is an autosomal recessive disorder associated with a high risk of colorectal cancer. Since few studies have investigated the genotype–phenotype association in Japanese patients with MUTYH variants, the aim of this study was to clarify the clinicopathological findings in Japanese patients with MUTYH gene variants who were detected by screening causative genes associated with hereditary colorectal polyposis. After obtaining informed consent, genetic testing was performed using target enrichment sequencing of 26 genes, including MUTYH. Of the 31 Japanese patients with suspected hereditary colorectal polyposis, eight MUTYH variants were detected in five patients. MUTYH hotspot variants known for Caucasians, namely p.G396D and p.Y179D, were not among the detected variants.Of five patients, two with biallelic MUTYH variants were diagnosed with MUTYH-associated polyposis, while two others had monoallelic MUTYH variants. One patient had the p.P18L and p.G25D variants on the same allele; however, supportive data for considering these two variants ‘pathogenic’ were lacking. Two patients with biallelic MUTYH variants and two others with monoallelic MUTYH variants were identified among Japanese colorectal polyposis patients. Hotspot variants of the MUTYH gene for Caucasians were not hotspots for Japanese patients.

Background The aim of this study was to clarify clinicopathological features, frequencies of molecular biomarkers, and prognoses in Japanese colorectal cancer patients and compare them with right-sided colon cancer (RCC) and left-sided colorectal cancer (LCRC). Methods We consecutively selected 575 colorectal cancer patients who underwent surgical resection from 2008 to 2011. RCC was located from the cecum to the transverse colon, and LCRC was located from the splenic flexure to the rectum. Frequencies of KRAS gene mutation, BRAF gene mutation, microsatellite instability (MSI), l18qLOH and CpG island methylator phenotype (CIMP) were statistically analyzed between groups. Results Tumors were located in the RCC in 26.3% of patients and in the LCRC in 73.7%. Elderly patients, females and advanced diseases were significantly more frequent in the RCC group than in the LCRC group. However, venous invasion was significantly more frequent in LCRC than in RCC. Between groups, BRAF mutant type, KRAS mutant type, MSI and CIMP+ were significantly more frequent in RCC, whereas 18qLOH was significantly more frequent in LCRC. In overall survival, RCC demonstrated poor prognosis compared with LCRC; however, age, gender, stage, lymphatic invasion, KRAS status and BRAF status rather than tumor location were independent prognostic factors. In addition, the independent prognostic factors in RCC were different from those in LCRC in each stage. However, the consistency between OS and DFS was not observed in this study, excluding lymphatic invasion in LCRC. Conclusion Comparing RCC with LCRC, RCC is different from LCRC in clinicopathological features, molecular biomarkers and prognostic factors in Japanese colorectal cancer patients. Since the proportions of molecular biomarkers of CRC in this study are different from Western CRCs, further studies are required to clarify the clinicopathological differences between Japanese CRCs and Western CRCs.

The proband was a 32-year-old man with sparse type of familial adenomatous polyposis with fundic gland and duodenal polyps and congenital hypertrophy of the retinal pigment epithelium without osteoma, dental abnormalities and desmoid tumors. Direct DNA sequencing did not detect germline mutations in any APC exon. However, using the multiplex ligation-dependent probe amplification method, we detected germline deletions of all APC exons. Using dual-color fluorescence in situ hybridization, we identified germline deletion of locus 5q22.1-22.2 that includes APC. Analysis of colorectal tumors identified somatic APC mutations in the cluster region in all polyps, but no loss of heterozygosity was detected in any polyp.

Angiofibroma of soft tissue is a recently described soft tissue tumor that is characterized by fibroblastic spindle tumor cells with arborizing capillary proliferation. Cytogenetically, it harbors a specific fusion gene involving the nuclear receptor coactivator 2 (NCOA2) gene. We report here additional new pathological and cytogenetic features. A soft tissue tumor in the left thigh of 73-year-old female was investigated. Microscopically, histiocytoid tumor cells were scattered in an edematous background with branching capillary proliferation. Immunohistochemically, we identified that the tumor cells were positive for histiocytic markers such as CD68 and CD163. Rearrangement of the NCOA2 gene was detected successfully by chromogenic in situ hybridization; however, abnormal signal patterns were observed in only a small subset of tumor cells. Unlike typical tumors with bland spindle cells, the present tumor needs to be distinguished from myxoid, dendritic and clear cell tumors. This case may suggest that angiofibroma of soft tissue is not in the center of the fibroblastic/myofibroblastic tumor group, but rather shows a fibrohistiocytic nature. We also found intratumor genetic heterogeneity, which is uncommon for a translocation-associated tumor. Therefore, careful evaluation is required to detect the gene rearrangement in this tumor entity.