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Proliferative activity examined by Ki67 labeling index (LI) plays pivotal role for managing gastrointestinal neuroendocrine tumor (GI-NET). Few reports indicated the intra-patient heterogeneity of Ki67-LI among metastatic tumor sites. We report a case of brain and orbital metastases from GI-NET that showed discrepancy of the Ki67-LI. A 71 year-old woman who was diagnosed as GI-NET with liver and bone metastases and performed medical therapy, had headache, right exophthalmos, and pain of right eye and was referred to our department. Magnetic resonance image revealed that tumors in the left occipital region and right orbit. We diagnosed as metastatic brain and orbital tumors from GI-NET. Surgical removal of both symptomatic lesions was performed and the diagnosis was pathologically confirmed. Immunohistochemical studies revealed the discrepancy of the Ki67-LI of the lesions (brain tumor: 8% versus orbital tumor: 22%). Sampling of multiple metastatic sites may prevent underestimate tumor proliferative activity.

We describe a rare case of newly discovered pulmonary metastases and surgical confirmation 12 years after initial surgery for a pheochromocytoma. A 61-year-old asymptomatic man was referred because of an abnormal shadow in the right lung field upon chest radiography. Computed tomography (CT) showed two well-demarcated tumors in the basal segment of the right lung. Twelve years previously, he underwent right adrenalectomy and was pathologically diagnosed as having a benign pheochromocytoma. Thereafter, he received a medical check-up annually. To confirm the diagnosis of two pulmonary tumors, video-assisted thoracic surgery was done and wedge resection of the right lower lobe completed. Pathology studies revealed these tumors as pulmonary metastases from the pheochromocytoma, which indicated that the true diagnosis was a malignant pheochromocytoma. Patients with a benign pheochromocytoma should continue to undergo careful monitoring for a long time after the initial surgical procedure. Thoracic surgeons should be aware of the possibility of pulmonary metastases even if >10 years have passed since initial resection of a benign pheochromocytoma.

We report a case of cystic meningioma at the left cerebellopontine angle (CPA). Magnetic resonance imaging demonstrated both solid and cystic components in the tumor. The cystic component appeared slightly hyperintense compared to cerebrospinal fluid on fluid-attenuated inversion recovery (FLAIR) imaging. A hypointense tubular structure was identified in the cystic component on 3D driven equilibrium sequencing. These imaging findings are unusual for cystic meningioma. However, awareness of these unusual imaging features is important to determine appropriate treatment strategies although cystic meningioma at the CPA is extremely rare.

Immune checkpoint inhibitors with chemotherapy have been shown to exhibit remarkable efficacy for advanced non‐small‐cell lung carcinoma and are under investigation as an induction therapy. However, the significance of preoperative therapy with pembrolizumab + chemotherapy for surgically resectable non‐small‐cell lung carcinoma still remains unclear. Here, we report a case of stage IIIB non‐small‐cell lung carcinoma that underwent salvage surgery after three cycles of pembrolizumab + carboplatin + nab‐paclitaxel. Computed tomography revealed the remarkable decrease in tumor volume by 81%. A pathological examination showed that viable neoplastic cells were observed in, Significance of preoperative therapy with pembrolizumab + chemotherapy for surgically resected non‐small‐cell lung carcinoma still remains unclear. This regimen showed a drastic response in a case of stage IIIB non‐small‐cell lung carcinoma that underwent salvage surgery after three cycles. A pathological examination showed that viable neoplastic cells were observed in

The differentiation between major histological types of lung cancer, such as adenocarcinoma (ADC), squamous cell carcinoma (SCC), and small-cell lung cancer (SCLC) is of crucial importance for determining optimum cancer treatment. Hematoxylin and Eosin (H&E)-stained slides of small transbronchial lung biopsy (TBLB) are one of the primary sources for making a diagnosis; however, a subset of cases present a challenge for pathologists to diagnose from H&E-stained slides alone, and these either require further immunohistochemistry or are deferred to surgical resection for definitive diagnosis. We trained a deep learning model to classify H&E-stained Whole Slide Images of TBLB specimens into ADC, SCC, SCLC, and non-neoplastic using a training set of 579 WSIs. The trained model was capable of classifying an independent test set of 83 challenging indeterminate cases with a receiver operator curve area under the curve (AUC) of 0.99. We further evaluated the model on four independent test sets—one TBLB and three surgical, with combined total of 2407 WSIs—demonstrating highly promising results with AUCs ranging from 0.94 to 0.99.

A 52-year-old woman was diagnosed as having anti-centromere antibody (ACA)-positive primary Sjögren syndrome (pSS). Eight years later, she visited our hospital because she had developed dyspnoea. She was diagnosed as having pulmonary arterial hypertension (PAH) with pulmonary veno-occlusive disease on the basis of the results of right heart catheterisation, a severe decrease in diffusing capacity of the lung for carbon monoxide (D

Epstein–Barr virus (EBV)‐associated gastric cancer (GC) is associated with a high degree of DNA methylation. However, the association between chemotherapy susceptibility and tumor DNA methylation in advanced diseases remains unclear. The comprehensive DNA methylation status of GC cells obtained from an advanced EBV‐associated GC (EBVGC) case, in which complete response to S‐1 plus cisplatin chemotherapy was achieved, was analyzed using a DNA methylation microarray. We compared DNA methylation of GC cells with public data and identified genes with higher methylation in EBVGC cell lines than in normal gastric cells, and genes in which methylation was increased by EBV. Of these genes, ABCG2, AHNAK2, BCL2, FZD1, and TP73 are associated with published evidence for resistance to 5‐fluorouracil and cisplatin. Silencing of these genes may be associated with hypersensitivity to chemotherapy., Here, we report an analysis of comprehensive DNA methylation of gastric cancer (GC) cells obtained from an advanced Epstein–Barr virus (EBV)‐associated GC case, which showed complete response to standard chemotherapy, using the latest DNA methylation microarray platform (Illumina Infinium MethylationEPIC BeadChip). We compared DNA methylation of GC cells with public data and identified genes in which methylation was increased by EBV.

Background: M2-like/repair macrophages are thought to contribute to fibrotic process of idiopathic pulmonary fibrosis (IPF). We analyzed the association between pulmonary accumulation of M2-like macrophages and survival in IPF patients. Methods: Lung tissues were obtained by surgical lung biopsy from patients with IPF (n=16), nonspecific interstitial pneumonia (NSIP, n=8) and control subjects (n=14). Samples were also obtained at autopsy from 9 patients who died of acute exacerbation (AE) of IPF. Lung specimens and/or human peripheral blood mononuclear cells-derived macrophages were evaluated by immunohistochemistry for expression of CD68 (pan-macrophage marker), CD163, and CD204 (M2-like macrophage markers), and by in situ mRNA hybridization and ELISA for production of transforming growth factor-β1 (TGF-β1). Results: CD68 + , CD163 + , and CD204 + cell counts and CD163 + /CD68 + and CD204 + /CD68 + cell ratios were comparable in IPF and NSIP lung tissues and significantly higher than in control tissues. IPF-AE lung samples contained significantly elevated CD68 + and CD163 + cell counts and CD163 + /CD68 + cell ratio compared with IPF samples, whereas CD204 + cell counts and CD204 + /CD68 + cells ratio did not differ. High CD163 + /CD68 + and CD204 + /CD68 + cell ratios were significantly associated with shorter overall survival and time-to-AE in IPF patients. In vitro -differentiated human CD163 + and CD204 + macrophages both secreted TGF-β1; however, the novel IPF drug pentraxin 2/serum amyloid protein could suppress secretion only by CD204 + macrophages. Conclusions: Pulmonary accumulation of CD163 + and CD204 + macrophages is associated with worse clinical course in IPF patients. Suppression of macrophage activation and TGF-β1 secretion may be a potential therapeutic target for IPF.

Background: Adult T-cell leukemia/lymphoma (ATLL) frequently involves the gastrointestinal (GI) tract, and patients mainly show an aggressive clinical course despite of intensive cytotoxic treatments. We investigated the characteristic clinicopathological and endoscopic features of GI ATLL. Methods: This was a retrospective analysis of 61 GI tract lesions in 54 ATLL patients. Results: Thirty-six (67%) patients were classified as having lymphoma-type ATLL and 18 (33%) patients were classified as having acute-type with leukemic changes. Examined ATLL lesions in the stomach and intestine (small intestine and colorectum) were 40 (66%) and 21 (34%), respectively. Gastric ATLL lesions were frequently found in the lymphoma-type (29/38; 76%) compared with the acute-type lesions (11/23; 48%; P=0.023). Intestinal ATLL lesions were frequent in the acute-type (12/23; 52%) compared with the lymphoma-type lesions (9/38; 24%; P=0.023). Endoscopically, tumor-forming type lesions were significantly more frequent in lymphoma-type ATLL lesions (29/38 lesions; 76%) compared with acute-type lesions (10/23; 44%; P=0.0096). The superficial spreading-type was significantly more frequent in acute-type lesions (12/23 lesions; 52%) compared with lymphoma-type lesions (3/38; 8%; P=0.0003). Additionally, gastropathy-, enteropathy-, or proctocolitis-like lesions were distinct features, mainly in the acute type (9/23 lesions; 39%). Twenty three of 39 tumor-forming-type lesions (59%) were significantly composed of pleomorphic or anaplastic large cell lymphoma, and 13 of 15 superficial spreading-type lesions (87%) were significantly composed of pleomorphic medium-sized cells (P=0.007, in each). Six patients (11%) who were estimated as having primary GI ATLL based on restricted clinical stages, showed a significantly better overall survival (OS) compared with the 48 advanced-stage patients (P=0.017). Twenty patients with solitary tumor-forming-type lesions showed a significantly better OS than 17 patients with the multiple tumor-forming-type (P=0.015) and five with the mucosal-thickening-type lesions (P=0.04). Twenty-six patients with pleomorphic or anaplastic large cell ATLL showed a significantly better prognosis compared with 28 patients with pleomorphic medium-sized ATLL (P=0.034). Conclusions: ATLL predominantly involves the stomach. Leukemic behavior of ATLL had a large influence on the tumor location and endoscopic features of GI tract lesions. Gastropathy-, enteropathy-, and proctocolitis-like lesions showed additional distinct characteristics. Primary GI ATLL in the early clinical stages, solitary tumor-forming-type lesions and large tumor cells showed better prognostic factors than other factors, respectively.

Background: Advances in neurosurgical techniques and neuroimaging resolution questions the modern-day reliability of the Simpson grade for predicting meningioma recurrence. Therefore, we evaluated the reliability of predictors for recurrence and outcomes in detail in patients with non-skull base meningiomas (NSBMs). Methods: We retrospectively analyzed data from consecutive 175 NSBMs underwent surgical resection. We performed Kaplan–Meier analyses of recurrence-free survival (RFS) according to Simpson and World Health Organization (WHO) grades. Predictors of RFS and clinical deterioration were estimated by univariate and multivariate analyses. Correlation between the Simpson grade and change in Karnofsky Performance Scale scores was assessed by Fisher's exact test. Results: Log-rank tests revealed significant correlations of both the Simpson and WHO grades with RFS for the overall cohort, convexity, and falx/tentorium meningioma. Unlike patients undergoing Simpson grade I and II resections, RFS in patients with WHO grade I and II/III tumors differed significantly from the early postoperative stage. Multivariate analysis identified tumor size, Simpson grade, and MIB-1 labeling index as significant predictors of RFS. Clinical deterioration was more frequent among patients undergoing less aggressive resection. Tumor location was the only significant predictor of clinical deterioration. Conclusions: Our findings indicate that tumor size, Simpson and WHO grades, and MIB-1 labeling index are significant predictors of NSBM recurrence. Moreover, the risk of recurrence markedly decreases within the follow-up duration of 80 months. Aggressive resection appears to minimize the risk of recurrence without evidence of clinical deterioration. Follow-up schedules should be based on the WHO grade and extent of resection. Keywords: Meningioma, Non-skull base, Outcome, Recurrence, Simpson grade, WHO grade

Microvascular invasion (MVI) is recognized as a risk factor for early recurrence of hepatocellular carcinoma (HCC) within the Milan criteria after curative treatment.One hundred eleven consecutive patients with HCC within the Milan criteria who underwent hepatic resection were retrospectively reviewed. Independent preoperative predictors of MVI were identified, and a scoring system was developed using significant predictors.MVI was identified in 51 of 111 patients (46%). Multivariate analysis identified the following independent predictors of MVI: alpha-fetoprotein (AFP) of 95 ng/mL (odds ratio [OR], 9.87; 95% confidence interval [95% CI], 2.24-56.8; P = 0.002), des-γ-carboxy prothrombin (DCP) of 55 mAU/mL (OR, 5.50; 95% CI, 2.09-15.4; P 0.001), tumor size of 2.8 cm (OR, 6.10; 95% CI, 2.07-20.0; P 0.001), and non-smooth tumor margin in the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) (OR, 5.34; 95% CI, 1.84-16.9; P = 0.002). A clinical scoring system was developed using these four variables. Within a total possible score of 0 to 4, the prevalence of MVI with a score of 0, 1, 2, 3, and 4 was 4.5%, 24.0%, 45.5%, 91.7%, and 100%, respectively (P 0.001). The area under the curve of the scoring system was 0.865 based on the receiver operating characteristic curve analysis of the prediction score.Our clinical scoring system, consisting of AFP, DCP, tumor size, and tumor margin in Gd-EOB-DTPA-enhanced MRI, can be valuable for predicting MVI in HCC within the Milan criteria before curative treatment.

Background Systemic Epstein-Barr virus+ T-cell lymphoma (sEBV+ TCL) occurs in childhood and young adults, and is exceptionally rare in older adults. Methods We investigated clinicopathological features in 16 patients of various ages with systemic EBV+ CD8+ T-lymphoproliferative diseases. Results Eight younger patients and four of eight older adults had sEBV+ CD8+ TCL, with invasion by medium-sized to/or large atypical lymphocytes primarily in bone marrow and lymph nodes, hemophagocytic lymphohistiocytosis (HLH), and progressive clinicopathological course. A further two patients demonstrated EBV+ node-based CD8+ large TCL without HLH, while the remaining two had the systemic form of chronic active EBV infection (sCAEBV) with CD8+ small lymphocytes. Past history of sCAEBV-like lesions was observed in one sEBV+ TCL patient (8.3%). Immunohistologically, in 12 sEBV+ TCL patients, atypical lymphocytes were positive for phosphate signal transducer and activator of transcription 3 (66.7%), CMYC (83.3%), and p53 (75%). Strong reactions of programmed cell death-ligand (PD-L)1+ tumor or non-neoplastic cells were detected in nine sEBV+ TCL patients (75%). Clonal peaks of the T-cell receptor (TCR) γ gene were detected in eight sEBV+ TCL patients by polymerase chain reaction. Four younger patients in sEBV+ TCL (33.3%) are in remission with chemotherapies including etoposide, and three of the four underwent allogeneic stem cell transplantation (SCT). Conclusion sEBV+ CD8+ TCL was observed in younger and older adults with less history of sCAEBV. HLH, tumor cell atypia, immunohistological findings, and progressive clinical course were characteristic of sEBV+ CD8+ TCL. Prompt chemotherapy and SCT induced tumor regression in sEBV+ CD8+ TCL patients.

Background: Systemic Epstein-Barr virus+ CD8+ T-cell lymphoma (sEBV+ CD8+ TCL) occurs in childhood and young adults, and exceptionally rare in older individuals. Methods: We investigated clinicopathological features in 16 patients of various ages with systemic EBV+ CD8+ T-lymphoproliferative diseases. Results: Eight younger and four of eight older patients had sEBV+ CD8+ TCL, with invasion by medium-sized to/or large atypical lymphocytes primarily in bone marrow and lymph nodes, hemophagocytic lymphohistiocytosis (HLH), and progressive clinicopathological course. Other two patients demonstrated EBV+ node-based CD8+ large TCL without HLH, while the remaining two had systemic form of chronic active EBV infection (sCAEBV) with CD8+ small lymphocytes. Past history of sCAEBV-like lesions was observed in one sEBV+ TCL patient (8.3%). Immunohistologically, in 12 sEBV+ TCL patients, atypical lymphocytes were positive for phosphate signal transducer and activator of transcription 3 (66.7%), CMYC (83.3%), and p53 (75%). Programmed cell death-ligand (PD-L)1+ tumor cells and strong reaction of PD-L1+ non-neoplastic cells were detected in nine sEBV+ TCL patients (75%). Clonal peaks of the T-cell receptor (TCR)γ gene were detected in eight sEBV+ TCL patients by polymerase chain reaction. Four younger patients in sEBV+ TCL (33.3%) are in remission with cytotoxic therapies including etoposide, and the three underwent allogeneic stem cell transplantation (SCT). Conclusion: sEBV+ CD8+ TCL was observed in younger and older patients with less history of sCAEBV. HLH, tumor cell atypia, immunohistological findings, and progressive clinical course were characteristic in sEBV+ CD8+ TCL. Prompt cytotoxic treatments and SCT induced tumor regression in sEBV+ CD8+ TCL patients.

Tumors originating from the nipple-areolar complex of the breast are rare. We herein report the case of a patient with metachronous bilateral areolar methotrexate (MTX)-associated lymphoma. The patient was a 67-year-old woman who presented with a rapidly enlarging tumor in the areolar region of her left breast. She had a long history of rheumatoid arthritis and had taken MTX for many years. On ultrasonography, the tumor showed well-demarcated margins and hyper-vascularity. On magnetic resonance imaging, the tumor showed a homogeneous low-to-moderate signal intensity that was similar to that of the nipple on both T1- and T2-weighted imaging; the diffusion was significantly reduced on diffusion-weighted images. The tumor showed a medium-plateau pattern on dynamic contrast-enhanced imaging. No necrotic change was observed. Based on the imaging findings, we considered the tumor to have originated from the areola. According to the internal homogeneity, the rapid growth and hyper-cellularity, the potential diagnoses included a small round cell tumor (including malignant lymphoma) and a mesenchymal neoplasm (especially leiomyoma or leiomyosarcoma, which frequently originate from the areolar region). An excisional biopsy of the tumor was performed. The pathological diagnosis was diffuse large, non GC B-cell lymphoma that we suspected was associated with MTX. The tumor shrank rapidly after the withdrawal of MTX. After three months, we detected a B-cell lymphoma of the same type originating in the contralateral areola. We compared the characteristics of the imaging findings of the MTX-associated lymphoma with the nipple-areolar or periareolar tumors and primary breast lymphoma.

Pilocytic astrocytoma is a less aggressive form of glial tumor that commonly occurs in the pediatric population, and its malignant transformation is extremely rare. Here, we report an elderly case of malignant small cell glioma with hemorrhage coexistent with a calcified pilocytic astrocytoma component. An 80-year-old male was found to have a right cerebellar non-enhanced tumor with hematoma adjoining a calcified nodule. The lesion was surgically removed, and a histological examination verified that the tumor was a malignant small cell glioma with hemorrhagic change and the calcified nodule showed features of pilocytic astrocytoma. Genetic analyses revealed no glioma-relevant genetic alterations such as IDH and BRAF mutations. Although calcification is generally observed in slowly growing gliomas, the aggressive clinical course of calcified cerebellar pilocytic astrocytoma has been previously reported. Our extremely rare case shows that careful follow-up is necessary even for calcified pilocytic astrocytomas.

BACKGROUND: M2-like/repair macrophages are thought to contribute to fibrotic process of idiopathic pulmonary fibrosis (IPF). We analyzed the association between pulmonary accumulation of M2-like macrophages and survival in IPF patients. METHODS: Lung tissues were obtained by surgical lung biopsy from patients with IPF (n=16), nonspecific interstitial pneumonia (NSIP, n=8) and control subjects (n=14). Samples were also obtained at autopsy from 9 patients who died of acute exacerbation (AE) of IPF. Lung specimens and/or human peripheral blood mononuclear cells-derived macrophages were evaluated by immunohistochemistry for expression of CD68 (pan-macrophage marker), CD163, and CD204 (M2-like macrophage markers), and by in situ mRNA hybridization and ELISA for production of transforming growth factor-β1 (TGF-β1). RESULTS: CD68(+), CD163(+), and CD204(+) cell counts and CD163(+)/CD68(+) and CD204(+)/CD68(+) cell ratios were comparable in IPF and NSIP lung tissues and significantly higher than in control tissues. IPF-AE lung samples contained significantly elevated CD68(+) and CD163(+) cell counts and CD163(+)/CD68(+) cell ratio compared with IPF samples, whereas CD204(+) cell counts and CD204(+)/CD68(+) cells ratio did not differ. High CD163(+)/CD68(+) and CD204(+)/CD68(+) cell ratios were significantly associated with shorter overall survival and time-to-AE in IPF patients. In vitro-differentiated human CD163(+) and CD204(+) macrophages both secreted TGF-β1; however, the novel IPF drug pentraxin 2/serum amyloid protein could suppress secretion only by CD204(+) macrophages. CONCLUSIONS: Pulmonary accumulation of CD163(+) and CD204(+) macrophages is associated with worse clinical course in IPF patients. Suppression of macrophage activation and TGF-β1 secretion may be a potential therapeutic target for IPF.

8536 Background: Lung cancer is the leading cause of cancer-related death in many countries, and its prognosis remains unsatisfactory. Since treatment approaches differ substantially based on the subtype, such as adenocarcinoma (ADC), squamous cell carcinoma (SCC) and small cell lung cancer (SCLC), an accurate histopathological diagnosis is of great importance. However, if the specimen is solely composed of poorly differentiated cancer cells, distinguishing between histological subtypes can be difficult. The present study developed a deep learning model to classify lung cancer subtypes from whole slide images (WSIs) of transbronchial lung biopsy (TBLB) specimens, in particular with the aim of using this model to evaluate a challenging test set of indeterminate cases. Methods: Our deep learning model consisted of two separately trained components: a convolutional neural network tile classifier and a recurrent neural network tile aggregator for the WSI diagnosis. We used a training set consisting of 638 WSIs of TBLB specimens to train a deep learning model to classify lung cancer subtypes (ADC, SCC and SCLC) and non-neoplastic lesions. The training set consisted of 593 WSIs for which the diagnosis had been determined by pathologists based on the visual inspection of Hematoxylin-Eosin (HE) slides and of 45 WSIs of indeterminate cases (64 ADCs and 19 SCCs). We then evaluated the models using five independent test sets. For each test set, we computed the receiver operator curve (ROC) area under the curve (AUC). Results: We applied the model to an indeterminate test set of WSIs obtained from TBLB specimens that pathologists had not been able to conclusively diagnose by examining the HE-stained specimens alone. Overall, the model achieved ROC AUCs of 0.993 (confidence interval [CI] 0.971-1.0) and 0.996 (0.981-1.0) for ADC and SCC, respectively. We further evaluated the model using five independent test sets consisting of both TBLB and surgically resected lung specimens (combined total of 2490 WSIs) and obtained highly promising results with ROC AUCs ranging from 0.94 to 0.99. Conclusions: In this study, we demonstrated that a deep learning model could be trained to predict lung cancer subtypes in indeterminate TBLB specimens. The extremely promising results obtained show that if deployed in clinical practice, a deep learning model that is capable of aiding pathologists in diagnosing indeterminate cases would be extremely beneficial as it would allow a diagnosis to be obtained sooner and reduce costs that would result from further investigations.

9025 Background: Lung cancer is one of the leading causes of cancer-related death worldwide, and its histopathological diagnosis is crucial for deciding on optimum treatment strategies. Recently, artificial intelligence (AI) models have been widely shown to be useful in various medical fields, particularly image and pathological diagnoses; however, AI models for the pathological diagnosis of pulmonary lesions that have been validated in large-scale test sets are yet to be seen. Methods: We trained a convolution neural network based on the Efficient Net B3 architecture to classify carcinoma from whole slide images (WSIs) using a training dataset of 3640 images. WSI diagnoses were available. We used a transfer learning approach, in which the starting weights were obtained from a pre-trained model on ImageNet. The model was then trained on our dataset using multiple instance learning, a semi-supervised learning approach. To classify a WSI, the model was applied in a sliding window fashion with an input tile size of 512x512 and a stride of 256. The maximum probability was then used as a WSI diagnosis. Results: We evaluated our model on a total of 2680 WSIs originating from five independent sources (two hospitals in Japan and three public datasets from around the world). The model achieved a Receiver Operator Curve Area Under the Curves (ROC AUCs) of 0.974, 0.974, 0.996, 0.988, and 0.981, respectively. Conclusions: We successfully established a reliable AI model for differentiating between lung carcinoma and non-neoplasm with a high ROC AUC on five independent test sets. If used in clinical practice, our model could help reduce the burden on pathologists and be useful for diagnosing pulmonary lesions in areas in which there are shortages of pathologists. Further prospective multicenter studies are warranted in order to validate the results obtained in the current study.

A 75-year-old man diagnosed with ileal gastrointestinal tumor with peritoneal dissemination was subjected to salvage treatment with regorafenib at 120 mg/day. Following the initiation of the treatment, liver dysfunction appeared on day 28, and continued to worsen despite termination of the treatment. Since no increase in the levels of serum immunoglobulins of the patient was observed, and negative results were obtained for the analysis of viral markers and autoantibodies, a diagnosis of regorafenib-induced hepatitis was suggested. In consequence, the patient received steroid pulse therapy and continuous administration of prednisolone, without sufficient improvement. Liver biopsy revealed interface hepatitis with prominent plasma cell infiltration, suggesting regorafenib-induced autoimmune hepatitis. The patient was then administered azathioprine and prednisolone, which improved the hepatic injury. The present case represents the first report of successful treatment of regorafenib-induced severe hepatic injury by the use of an immunosuppressant.

To investigate the imaging characteristics of rare ductal adenoma of the breast, we evaluated the detailed imaging findings and correlated them with the pathologic features of the ductal adenomas. In particular, we describe in detail the imaging findings derived from "pseudoinvasion," one of the histological features unique to this tumor.We reviewed the imaging findings including magnetic resonance imaging (MRI) in three patients with ductal adenomas of the breast and correlated the findings with the detailed histological features.All patients exhibited well-demarcated nodules with smooth margins on mammography. On ultrasonography, two patients exhibited mural nodules within cysts. The bases of mural nodules protruded into the mammary glands. On contrast-enhanced MRI, these margins were smooth. Histologically, the bases showed foci of tumor cells scattered into collagenous materials (pseudoinvasion), the tumor foci were located along the collagen fibers; therefore, the margins were smooth.Distinguishing ductal adenoma from invasive carcinoma is an urgent issue. A clear margin of 'pseudoinvasion' on MRI is both a unique finding and a useful diagnostic clue.

Purpose Ultrasound (US) elastography provides information regarding tissue hardness and is expected to become a novel diagnostic tool for breast disease. In contrast, magnetic resonance (MR) images reflect the tissue characteristics. Fibrosis of the stroma of breast diseases may affect their hardness. We investigated the correlation among elasticity score (ES) and signal intensity of short Tau inversion recovery MR images, enhancement ratio, apparent diffusion coefficient (ADC), and the fibrosis in the breast lesions. Materials and methods We reviewed the findings of US elastography and MR imaging from 41 consecutive patients with breast lesions (25 invasive ductal carcinoma, 3 fibroadenoma, 1 phyllodes tumor, 2 ductal hyperplasia, 2 primary malignant lymphoma, 3 mastopathy, 1 metastasis, 1 tubular adenoma, 1 ductal carcinoma in situ, 1 diabetic mastopathy, and 1 intraductal papilloma). In each patient, elastography images were classified based on Tsukuba ES. We calculated the ratio of signal intensity of the lesion to the muscle on short Tau inversion recovery images (L/M ratio), enhancement ratio of early to precontrast and early to delayed images, and ADC for each lesion. The ES and MR findings were correlated with the degree of fibrosis (based on Masson trichrome stain). Results The ES significantly correlated with the L/M ratio (P = 0.0306) and the ADC (P = 0.0256). The stromal fibrosis also correlated with ES (P = 0.0023), the L/M ratio (P = 0.0344), and enhancement ratio of the early-to-delayed images (P = 0.049). Conclusions The ES and L/M ratio are correlated significantly with each other, and they are correlated with the fibrosis. These results suggest that they will provide the information on the fibrosis and may help the diagnosis of breast lesions.

We illustrate the magnetic resonance imaging features of 3 cases of rare ovarian Mullerian mixed epithelial borderline tumor (MEBT) and identify important diagnostic clues based on their detailed histologic, morphologic, and clinical features. Mullerian mixed epithelial borderline tumor has good prognosis, and adequate management is essential. In order to avoid unnecessary aggressive treatment, radiologists should become familiar with the imaging findings of MEBT. To the best of our knowledge, no articles have described the detailed images of MEBT.

Smoldering-type and chronic-type adult T-cell leukemia/lymphomas (ATLL) patients have relatively indolent clinical courses, but often progress into aggressive lymphoma-type and acute-type disease. We examined the roles of transcription factor C-MYC and its ubiquitin ligase FBXW7 in tumor tissues from 137 patients with ATLL. Immunohistochemical tests showed ≥50% of lymphoma cells in 78.7% (48/61) of lymphoma-type, and 64.9% (24/37) of acute-type samples expressed C-MYC, significantly higher than was seen in smoldering-type (3.6%) and chronic-type (9.1%) samples (P

Objective To identify risk factors of biochemical recurrence after radical prostatectomy in high-risk patients. Methods A total of 191 high-risk prostate cancer patients according to the D'Amico classification treated with radical prostatectomy at a single institution between April 2000 and December 2013 were enrolled. The pathological evaluation including intraductal carcinoma of prostate was reassessed, and the clinical and pathological risk factors of biochemical recurrence were analyzed. Results The median follow up after radical prostatectomy was 49 months. The 5-year biochemical recurrence-free survival rate after radical prostatectomy in high-risk prostate cancer patients was 41.6%. Initial prostate-specific antigen, pathological Gleason score, seminal vesicle invasion, extraprostatic extension and intraductal carcinoma of the prostate were significantly associated with biochemical recurrence-free survival. The 5-year biochemical recurrence-free survival rates in patients with zero, one, two and three of these risk factors were 92.9%, 70.7%, 38.3% and 28.8%, respectively. In patients with four or more factors, the biochemical recurrence-free survival rate was 6.1% after 18 months. Conclusions In D'Amico high-risk patients treated with radical prostatectomy, risk factors for biochemical recurrence can be identified. Patients with fewer risk factors have longer biochemical recurrence-free survival, even among these high-risk cases.

Carcinosarcoma is a rare neoplasm with epithelial and mesenchymal components. We herein report the case of a 68-year-old male with a carcinosarcoma of the gallbladder. Preoperative examinations revealed the gallbladder cancer infiltrating the liver with a multinodular mass with a portal vein tumor thrombus through the right anterior branch of the portal vein. Extended right hepatectomy with portal thrombectomy was performed. Histologically, the tumor comprised a distinct adenocarcinoma and pleomorphic mononuclear cell components. The adenocarcinoma mainly lined the gallbladder lumen, forming irregular papillary glands. The pleomorphic mononuclear cells formed the majority of the tumor. Immunohistochemical analysis revealed that the pleomorphic mononuclear component was strongly positive for vimentin and slightly positive for cytokeratin. These findings suggested that the mononuclear cells formed a degenerated neoplasm of adenocarcinoma cells. The pathological diagnosis was carcinosarcoma of the gallbladder. After curative surgery, adjuvant chemotherapy with gemcitabine chloride was conducted for 3 years. The patient was alive for 5 years without recurrence after resection. The present case showed the longest reported survival among patients with advanced stage carcinosarcoma.

Objective The distribution of intraductal carcinoma of the prostate (IDC-P) and other intraductal lesions associated with IDC-P was evaluated in the cancer foci on radical prostatectomy specimens. Materials and methods We reviewed slide in 412 cases treated by radical prostatectomy without neoadjuvant therapy. Mapping study was performed with regard to IDC-P, other intraductal lesions associated with IDC-P and invasive carcinoma. Results We identified 98 cases (23.8%) and 102 cancer foci associated with IDC-P. In these all cancer foci, IDC-P was associated with invasive carcinoma and other intraductal neoplastic lesions with tufting, micropapillary and loose cribriform patterns were contiguous and admixed with IDC-P in 83 cancer foci (81.4%). There were lesions with invasive carcinoma around the IDC-P in 95 cancer foci (93.1%) and lesions without invasive carcinoma around IDC-P in 66 foci (64.7%). The latter lesions existed in the marginal areas of the cancer foci in 63 (61.8%) and in the central areas of the cancer foci in 14 (13.7%). In 5 cancer foci (4.9%), volume of IDC-P was larger than that of invasive carcinoma. Conclusions The distribution of IDC-P with dense cribriform and solid patterns varied in cancer foci, and intraductal lesions with tufting, micropapillary and loose cribriform patterns were frequently seen in area contiguous and admixed with IDC-P. The latter lesion may be low grade morphology of IDC-P, although the lesions could not be distinguished from high grade prostatic intraepithelial neoplasia.

To investigate the magnetic resonance (MR) imaging characteristics of malignant primary breast lymphoma (PBL), including features on diffusion-weighted imaging (DWI).The MR findings of three patients were reviewed retrospectively at our institutions. The signal intensity, shape, enhancement pattern, and DWI findings were examined and correlated with the histologic features. We also reviewed the MR findings of cases of PBL reported in the literature.The tumors in our cases showed early enhancement with penetrating vessels on early-phase dynamic MR images and a strong high signal intensity on DWI. The tumors had a cerebroid appearance and septal enhancement on delayed contrast-enhanced MR images, and we speculate that the fibrous tissue seen in the tumors may correspond to septal enhancement. After chemotherapy, all lesions decreased in size, while the ADCs were increased. All of the cases reported in the literature showed early or avid enhancement; this finding was similar to that observed in our cases.Although based on a small number of cases, we suggest that strong enhancement with penetrating vessels in masses on early images of dynamic MR, strong high intensity on DWI, a cerebroid appearance, and septal enhancement are useful diagnostic clues for a diagnosis of PBL.

OBJECTIVE. The purpose of this article is to describe CT findings of miscellaneous pulmonary conditions that mimic lung cancers, especially primary cancers, to improve diagnosis of pulmonary lesions. Brief descriptions of patient clinical information and pathologic findings will be included and correlated with imaging findings in actual cases. CONCLUSION. A wide variety of pulmonary conditions present imaging features that mimic those of primary lung cancers and are difficult to differentiate from cancer. Awareness of these conditions with an understanding of their pathologic background and careful attention to the clinical information will help achieve correct diagnoses.

Sixty-four cases of malignant lymphoma involving the liver were examined. Of these, 20 cases were histologically confirmed to be primary hepatic B-cell lymphoma. Twelve of these 20 cases were diffuse large B-cell lymphoma (DLBCL) and eight cases were mucosa-associated lymphoid tissue (MALT) lymphoma. Of the 12 cases of DLBCL, six were immunohistologically positive for CD10 and/or Bcl6 (indicating a germinal center phenotype), six were positive for Bcl2, and five were positive for CD25. Eight of the 12 DLBCL cases (66.7%) and two of the eight MALT lymphoma cases (25%) had serum anti-hepatitis C virus (HCV) antibodies and HCV RNA. The incidence of HCV infection was significantly higher in the hepatic DLBCL cases than in systemic intravascular large B-cell cases with liver involvement (one of 11 cases, 9.1%) and T/NK-cell lymphoma cases (one of 19 cases, 5.3%) (p

Aim: We have recently reported that hyperdynamic state of retinoid metabolism, which may lead to the shortage of retinoid, is observed in patients with non-alcoholic fatty liver disease (NAFLD). Hepatic iron overload, which causes production of reactive oxygen species (ROS), is also frequently seen in NAFLD patients. The aim of the study is to examine iron state and retinoid metabolic state simultaneously, and to clarify the relationship between two disorders. Methods: Thirty-six persons, comprising 17 patients with simple steatosis (SS), 11 with NASH, and 8 normal controls (N), were examined on hepatic expression of iron metabolism-related genes including hemojuvelin (HJV), hepcidin (HEPC), transferrin receptor 1 and 2 (TfR1, TfR2), ferroportin (FPN), neogenin (NEO) and ferritin heavy chain (FtH) and hepatic iron contents in addition to expression 51 genes which is involved in retinoid metabolism and antioxidative action. Results: In patients with NAFLD, expression of HJV, TfR2, FPN, TfR1, FtH, SOD and catalase was increased, compared with that in N. In addition, hepatic iron content, which was increased in NASH, was correlated with expression level of TfR2. Expression of cellular retinoid binding protein (CRBP1), alcohol dehydrogenase 1 (ADH1) and cytochrome P450 26A1(CYP26A1) was significantly correlated with that of HJV, TfR2 and FPN, respectively. Conclusion: The results of the present study suggest that the reasons responsible for iron accumulation in NASH in the present study may partly be due to enhanced expression of TfRs, especially TfR2, and hyperdynamic state of retinoid metabolism is closely related to iron metabolism in the disease.

Objective A metastatic lymph node commonly becomes enlarge; however, there is limited data available with regard to the direct measurement of lymph nodes and their clinicopathologic characteristics. Methods The size of dissected lymph node was quantified in a total of 848 nodes with metastasis and 10,462 nodes without metastasis from 454 patients with lung cancer who underwent a pulmonary resection with lymph node dissection. Results The short axis and the volume of the metastatic lymph nodes were significantly greater than those of the nonmetastatic ones. The smaller the lymph node, the less frequently the lymph nodes were metastatic; however, the ratios of nodes smaller than the fifth largest lymph node with metastasis of adenocarcinoma and squamous cell carcinoma were 21.8 to 26.2%, respectively. When the hilar and mediastinal lymph node stations were examined, 1.14 to 4.00% of the lung cancer patients had lymph node metastasis in small lymph node despite having no metastases in the largest and second largest lymph nodes. Conclusions The small lymph nodes in the hilar or mediastinal stations frequently had metastases of carcinoma even though largest and second largest lymph nodes were negative for metastases, especially in adenocarcinoma cases. Surgical oncologists should, therefore, perform systemic lymph node dissection, and not sampling, during a pulmonary resection of lung cancer.