Negative E-cadherin expression on bone marrow myeloma cell membranes is associated with extramedullary disease.

Background: The loss of E-cadherin expression and the induction of N-cadherin are known as hallmarks of the epithelial-to-mesenchymal transition, an essential initial step in the process of metastasis in solid tumors. Although several studies have reported expressions of these cadherins in patients with multiple myeloma (MM), their clinical significance is unknown as MM cells are non-epithelial. Methods: In this study, we examined the expression of E- and N-cadherins by immunohistochemistry using bone marrow (BM) biopsy specimens from 31 newly diagnosed MM patients and in subsequent biopsy specimens from six of these. Results: Negative E-cadherin expression on BM myeloma cell membranes was significantly associated with the presence of soft-tissue masses arising from bone lesions and breaking through the cortical bone, referred to as extramedullary disease (EMD). Conclusions: Given the aggressive nature of EMD, our study suggests that screening for E-cadherin using BM immunohistochemistry is one measure that could predict the development of EMD in patients with MM.

Surface CD3-negative monomorphic epitheliotropic intestinal T-cell lymphoma.

Intestinal T/NK-cell lymphomas include enteropathy-associated T-cell lymphoma (EATL), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), indolent T-cell lymphoproliferative disorders of the GI tract (ITCLPD), extranodal NK/T-cell lymphoma, nasal type (ENKTL), and intestinal T-cell lymphoma NOS (ITCL-NOS). Here we describe a case of surface CD3-negative MEITL. A 63-year-old Japanese female had a tumor located in the conglomerated ileum, which formed multiple mass lesions. The resected tissue showed a diffuse infiltration of monomorphic medium-sized lymphocytes with epitheliotropism. Flowcytometry using a fresh specimen of the tumor revealed positivity for CD7, CD8, CD38, and CD56, but not surface CD3. On immunohistochemistry, the tumor showed positivity for cytoplasmic CD3, CD8, CD56, TIA-1, Granzyme B, and perforin. EBER with in situ hybridization was negative. Moreover, H3K36me3, which is negative in MEITL with SETD2-mutation, was positive. This is an important case of MEITL due to its oncogenesis.

Disappearance of recurrent thymic epithelial tumor following corticosteroid and cyclosporine treatment: A case report.

Thymic epithelial tumors (TETs) are considered orphan neoplasms, and treatment options for recurrent or metastatic stages are limited. Here, we have reported a case of recurrent TET that showed complete remission after receiving high-dose corticosteroids followed by low-dose corticosteroids and cyclosporine. No recurrence was observed for the next 2 years. The effects of corticosteroids on the TET and the associated pure red cell aplasia led to adjustment of the diagnosis from thymic carcinoma to thymoma. Low-dose corticosteroids and cyclosporine might be the reason for remission maintenance.

Clinical characteristics of patients with B-cell lymphoma enrolled in clinical trials for aggressive lymphoma in Japan: Japan Clinical Oncology Group - Lymphoma Study Group study - JCOG0108A.

The clinical characteristics of B-cell lymphoma (BCL) were studied through the combined analysis of six clinical trials conducted by the Japan Clinical Oncology Group - Lymphoma Study Group (JCOG-LSG) for aggressive lymphoma in the 1990s, before the introduction of rituximab. Through a central pathological review, 829 patients were diagnosed with BCL according to the World Health Organization classification and treated with doxorubicin-containing combination chemotherapies. Of these patients, 642, 104, 30, and 24 patients were diagnosed with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL), respectively. The overall survival (OS) of FL and MZL patients was higher than that of patients with DLBCL and MCL. The OS of the MCL patients was higher than that of DLBCL patients in the first 5 years, but MCL had the lowest survival after 5 years. The OS of DLBCL patients was clearly stratified by the international prognostic index and showed data compatible with that of aggressive lymphoma in the pre-rituximab era. These results established the clinical aspects of BCL in a large number of patients treated in prospective studies during the pre-rituximab era in Japan.

[IPSILATERAL SYNCHRONOUS MUCINOUS TUBULAR AND SPINDLE CELL CARCINOMA AND CLEAR CELL PAPILLARY RENAL CELL CARCINOMA: A CASE REPORT AND REVIEW OF THE LITERATURE].

Renal cell carcinoma (RCC), the most common solid lesion of the kidney, accounts for approximately 2%-3% of all malignancies among adults. Clear cell carcinoma and papillary cell carcinoma are the most common types of renal tumors. Some case reports have described synchronous benign and malignant tumors in the same kidney. In particular, angiomyolipoma and RCC in patients with tuberous sclerosis (TSC) and non-TSC have been reported many times in the literature. However, unilateral concordance of malignant renal tumors is very rare; thus, only few cases have been reported in the literature.Here we report the case of a 58-year-old male who had ipsilateral synchronous mucinous tubular and spindle cell carcinoma (MTSCC) and clear cell papillary renal cell carcinoma (CCPRCC). Both cancers are rare and relatively recently defined subtypes of RCC. Additionally, both were successfully treated using partial nephrectomy. MTSCC has been a distinct entity in the World Health Organization classification of kidney tumors since 2004. The classic type of MTSCC is characterized by small elongated tubules lined with clear cuboidal or spindle cells with mucinous stroma. Neoplastic cells always exhibit low-grade histological features. However, unclassified variants of MTSCC, such as mucin-poor, papillary, high-grade, and sarcomatoid variants, have also been reported. MTSCC is considered to have a relatively good prognosis, but some patients with poor prognoses have recently been reported. CCPRCC is a recently recognized entity and represents the fourth most common variant of RCC. It has unique morphological and immunohistochemical features and shows indolent clinical behavior. Microscopically, CCPRCC may mimic other RCCs with clear cell features, such as clear cell RCC, translocation RCC, and papillary RCC, with clear cell changes. In 2006, CCPRCC was described as a subtype of renal tumors in patients with end-stage renal disease. However, currently, CCPRCC has also been shown to occur in kidneys with normal function.To the best of our knowledge, this is the first report of ipsilateral synchronous MTSCC and CCPRCC, which we present with a review of the pertinent literature.

Epithelioid Hemangioma of the Thoracic Spine: A Case Report and Review of the Literature.

Context: Osseous epithelioid hemangioma is uncommon, and reports of epithelioid hemangiomas of the spine are especially rare.Study Design: Case report.Findings: A 43-year-old male was referred to our department with progressive gait disturbance. CT scans showed a lucent mass in the vertebral body at the T3 level. MRI of the thoracic spine showed a strongly enhanced mass compressing the spinal cord. The patient underwent laminectomy from T2 to T4, debulking of the tumor, and posterior fusion from T1 to T5. After the operation, the patient's neurological status improved significantly, and he was able walk without assistance. Histological examination determined that the tumor was an epithelioid hemangioma. The patient was treated with 40 Gy radiation for local control of the tumor. The patient could walk without difficulty 12 months after the surgery.Conclusion: This is a rare example of an epithelioid hemangioma that developed in the thoracic spine and compressed the spinal cord, and was treated successfully.

Invasive Solid Papillary Carcinoma of the Nipple With Pagetoid Extension and Nodal Metastasis.

We report a case of invasive solid papillary carcinoma (SPC) of the nipple with Pagetoid extension to the skin and lymph node metastasis. SPC is an uncommon primary breast cancer accounting for less than 1% of all breast cancers. Only 2 cases occurring in the nipple have been reported. However, both cases were without Pagetoid extension or lymph node metastasis. The presently reported tumor consisted of irregularly shaped solid cell nests with delicate fibrovascular cores. The tumor cells had round nuclei with low-grade atypia and eosinophilic cytoplasm. Neuroendocrine differentiation was confirmed by immunohistochemical positivity for CD56, synaptophysin, and chromogranin A. Immunohistochemistry also confirmed the absence of myoepithelial cells around the tumor cell nests. Therefore, a diagnosis of invasive SPC was made. Additionally, tumor cell deposits in the intramammary and axillary lymph nodes were identified, and these deposits had the same histological characteristics as the invasive SPC of the nipple. The invasiveness of SPC can be difficult to determine. However, the tumor cell nests in the current case exhibited a retraction artifact, which is known to be associated with invasive carcinoma and a poor prognosis, as well as morphological patterns that have been previously identified as characteristic of invasive SPC. Although SPC is widely recognized as having a favorable outcome, the existence of exceptionally aggressive cases occurring in the nipple must be recognized. Additional cases of invasive SPC of the nipple are needed to analyze the clinicopathological correlation.

Dataset for reporting of thymic epithelial tumours: recommendations from the International Collaboration on Cancer Reporting (ICCR).

AIMS: The International Collaboration on Cancer Reporting (ICCR) is a not-for-profit organization formed by the Royal Colleges of Pathologists of Australasia and the United Kingdom, the College of American Pathologists, the Canadian Association of Pathologists-Association Canadienne des Pathologists in association with the Canadian Partnership Against Cancer, and the European Society of Pathology. Its goal is to produce standardized, internationally agreed, evidence-based datasets for use throughout the world. METHODS AND RESULTS: This article describes the development of a cancer dataset by the multidisciplinary ICCR expert panel for the reporting of thymic epithelial tumours. The dataset includes 'required' (mandatory) and 'recommended' (non-mandatory) elements, which are validated by a review of current evidence and supported by explanatory text. Seven required elements and 12 recommended elements were agreed by the international dataset authoring committee to represent the essential information for the reporting of thymic epithelial tumours. CONCLUSIONS: The use of an internationally agreed, structured pathology dataset for reporting thymic tumours provides all of the necessary information for optimal patient management, facilitates consistent and accurate data collection, and provides valuable data for research and international benchmarking. The dataset also provides a valuable resource for those countries and institutions that are not in a position to develop their own datasets.

Mesenchymal tumours of the mediastinum--part I.

The mediastinum is an anatomically defined space in which organs and major blood vessels reside with surrounding soft tissue elements. The thymus is an important organ in the mediastinum, and many of the masses encountered in the mediastinum are related to this organ. Most neoplasms diagnosed in the mediastinum are epithelial tumours (thymomas and thymic carcinomas), lymphomas or germ cell tumours. In contrast, soft tissue tumours of the mediastinum are rare. In 1963, Pachter and Lattes systematically reviewed soft tissue pathology of the mediastinum, covering the hitherto described [2, 226, 227] In this review, based on the 2013 WHO classification of soft tissue tumours and the 2015 WHO classification of tumours of the lung, pleura, thymus and heart, we provide an updated overview of mesenchymal tumours that may be encountered in the mediastinum.

Mesenchymal tumours of the mediastinum--part II.

This is the second part of a two-part review on soft tissue tumours which may be encountered in the mediastinum. This review is based on the 2013 WHO classification of soft tissue tumours and the 2015 WHO classification of tumours of the lung, pleura, thymus and heart and provides an updated overview of mesenchymal tumours that have been reported in the mediastinum.

The 2015 World Health Organization Classification of Tumors of the Thymus: Continuity and Changes.

This overview of the 4th edition of the World Health Organization (WHO) Classification of thymic tumors has two aims. First, to comprehensively list the established and new tumor entities and variants that are described in the new WHO Classification of thymic epithelial tumors, germ cell tumors, lymphomas, dendritic cell and myeloid neoplasms, and soft-tissue tumors of the thymus and mediastinum; second, to highlight major differences in the new WHO Classification that result from the progress that has been made since the 3rd edition in 2004 at immunohistochemical, genetic and conceptual levels. Refined diagnostic criteria for type A, AB, B1-B3 thymomas and thymic squamous cell carcinoma are given, and it is hoped that these criteria will improve the reproducibility of the classification and its clinical relevance. The clinical perspective of the classification has been strengthened by involving experts from radiology, thoracic surgery, and oncology; by incorporating state-of-the-art positron emission tomography/computed tomography images; and by depicting prototypic cytological specimens. This makes the thymus section of the new WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart a valuable tool for pathologists, cytologists, and clinicians alike. The impact of the new WHO Classification on therapeutic decisions is exemplified in this overview for thymic epithelial tumors and mediastinal lymphomas, and future perspectives and challenges are discussed.

Breast carcinoma metastasis to meningioma in the thoracic spine: A case report and review of the literature.

CONTEXT: Systemic metastasis to a primary tumor of the central nervous system is uncommon. Breast carcinomas metastasizing to a possibly preexisting meningioma in the spine are reported very rarely. STUDY DESIGN: Case report. FINDINGS: A 69-year-old female was referred to us with progressive gait disturbance. She had undergone a total mastectomy for carcinoma of the right breast 11 years previously. A magnetic resonance imaging of the thoracic spine showed an intra- and extradural spinal cord tumor. The patient underwent resection of the tumor via laminectomy from T2 to T4. After the operation, the patient's neurological status improved significantly, and she was able to walk without assistance. Histological examination showed the tumor to be a fibrous-type meningioma within a metastatic breast cancer tumor. The patient underwent 40 Gy radiation treatment for local control of the tumor. However, the tumor recurred locally 7 months after the surgery. The patient died of carcinomatous pleurisy 13 months after the surgery. CONCLUSION: This case illustrates that a primary meningioma in the thoracic spine can be a recipient of breast cancer metastasis, which may alter the treatment strategy.

Preoperative parameters to predict incidental (T1a and T1b) prostate cancer.

INTRODUCTON: Prostate cancer has been found incidentally in transurethral resection of the prostate (TURP) specimens without prior diagnosis in 5% to 13% of the patients. We evaluated whether incidental prostate cancer (stages T1a and T1b) could be predicted preoperatively. METHODS: TURP was performed in 307 patients between 2006 and 2011. Patient age, prostate-specific antigen (PSA) level, total prostate volume, transitional zone volume, PSA density, history of needle biopsy, and pathological diagnosis on TURP specimen were assessed. We analyzed the association between these parameters and prostate cancer detection. RESULTS: Incidental prostate cancer was found in 31 patients (10.1%), and 13 cases (4.2%) had cancer with T1b and/or Gleason ≥7. Multivariate analysis demonstrated that age ≥75 years (odds ratio [OR] 2.58, p = 0.022), prostate volume ≤50 cc (OR 4.11, p < 0.001), and the absence of preoperative needle biopsy despite PSA ≥4 ng/mL (OR 2.65, p = 0.046) were independent risk factors. In patients who had 2 or 3 of these risk factors, incidental prostate cancer and cancer with T1b and/or Gleason ≥7 were observed in 25% to 50% and 16% to 25% cases, respectively. CONCLUSIONS: Older patient age, small prostate volume, and the absence of previous needle biopsy (despite a high PSA level) might be independent risk factors for detecting incidental prostate cancer, although external validation is warranted to confirm our results.

ITMIG consensus statement on the use of the WHO histological classification of thymoma and thymic carcinoma: refined definitions, histological criteria, and reporting.

INTRODUCTION: The 2004 version of the World Health Organization classification subdivides thymic epithelial tumors into A, AB, B1, B2, and B3 (and rare other) thymomas and thymic carcinomas (TC). Due to a morphological continuum between some thymoma subtypes and some morphological overlap between thymomas and TC, a variable proportion of cases may pose problems in classification, contributing to the poor interobserver reproducibility in some studies. METHODS: To overcome this problem, hematoxylin-eosin-stained and immunohistochemically processed sections of prototypic, "borderland," and "combined" thymomas and TC (n = 72) were studied by 18 pathologists at an international consensus slide workshop supported by the International Thymic Malignancy Interest Group. RESULTS: Consensus was achieved on refined criteria for decision making at the A/AB borderland, the distinction between B1, B2, and B3 thymomas and the separation of B3 thymomas from TCs. "Atypical type A thymoma" is tentatively proposed as a new type A thymoma variant. New reporting strategies for tumors with more than one histological pattern are proposed. CONCLUSION: These guidelines can set the stage for reproducibility studies and the design of a clinically meaningful grading system for thymic epithelial tumors.

[A case of endocrine cell carcinoma of the ascending colon with liver metastasis treated with hepatectomy after excision of the primary lesion and systemic chemotherapy].

A 77-year-old man who complained of melena was admitted to our department. Colonoscopy revealed a type 2 tumor in the hepatic flexure of the ascending colon. Biopsy examination revealed a poorly differentiated adenocarcinoma. Abdominal computed tomography(CT)revealed 3 tumors within the posterior segment of the right hepatic lobe. Initially, a right hemicolectomy was performed. Immunohistochemically, the tumor was diagnosed as an endocrine cell carcinoma. After surgery, a capecitabine, oxaliplatin, and bevacizumab(CapeOX/BEV)regimen was administered. However, after 5 chemotherapy courses, abdominal CT revealed enlargement of the 3 tumors in the posterior segment of the right hepatic lobe. There was no metastasis besides the liver metastasis. The patient underwent a radical hepatectomy of the posterior segment. At 8 months post-surgery, the patient remains alive and well. Endocrine cell carcinoma of the colon and rectum is usually malignant and is associated with a very poor prognosis because of rapid hematogenous or lymphogenous metastasis. Effective multimodal treatment regimens, including surgery and new chemotherapies such as molecular targeted therapies, should be established to improve the prognosis of patients with endocrine cell carcinomas of the colon and rectum.

Histopathological characteristics of stenosing flexor tenosynovitis in diabetic patients and possible associations with diabetes-related variables.

PURPOSE: To compare the histopathological findings of stenosing flexor tenosynovitis (SFTS) in diabetic patients with those in nondiabetic patients and to analyze the predominant characteristics of SFTS in diabetic patients by statistical methods. METHODS: We included 63 patients (63 specimens) who underwent excision of A1 pulleys for SFTS. A total of 38 patients (38 digits) were diabetic and 25 (25 digits) were nondiabetic. We obtained specimens from the proximal one-third of each A1 pulley and analyzed them by histological and immunohistochemical methods. After we identified the predominant histopathological characteristics of SFTS in patients with diabetes, we performed multiple logistic regression analysis to examine the possible associations between the histopathological characteristics and diabetes-related variables. RESULTS: We divided histopathological findings into 3 types in both diabetic and nondiabetic groups. Types 1 and 2 showed fibrocartilage metaplasia including fibrocartilage-like cells surrounded by basophilic extracellular substances. Type 2 was characterized by the presence of granulation tissue in the middle layer, which was not recognized in type 1. The granulation tissue contained newly formed microvessels, stromal cells, a small number of inflammatory cells, and extracellular matrix that showed myxomatous degeneration. Type 3 showed a decrease in fibrocartilage-like cells with surrounding extracellular eosinophilic substances, which was similar to hyaline degeneration. The histopathological features of type 2 were found in 68% of the diabetic group and in 28% of the nondiabetic group. This difference was statistically significant. The findings of type 2 were significantly associated with the severity of diabetic retinopathy and hemoglobin A1c values in the diabetic group. CONCLUSIONS: Type 2 findings were more frequent in the diabetic group than in the nondiabetic group. A pathomechanism to accelerate neovascularization and hypercellularity in the granulation tissue in the middle layer of A1 pulley may exist, especially in diabetic patients with severe retinopathy and poorly controlled hyperglycemia.

Positive posterior margin of needle biopsy cores is an independent predictor for extracapsular extension in retropubic radical prostatectomy.

OBJECTIVE: To introduce the new preoperative parameter as a predictor for extracapsular extension (ECE), we defined the presence of tumor at the stump of the rectum side on prostate needle biopsy as a positive posterior margin (PPM), and speculated that PPM is related to ECE. METHODS: This retrospective study was conducted in 230 patients who underwent prostate needle biopsy and retropubic radical prostatectomy between 2001 and 2011. We analyzed the association between their clinicopathological parameters and ECE. RESULTS: Multivariate analysis showed that the Gleason score (P = .023, odds ratio [OR] 1.433), serum prostate-specific antigen (PSA, P = .013, OR 1.040), clinical stage (P = .018, OR 2.162), and PPM (P = .013, OR 2.253) were significant independent predictors for ECE. Next, using these 4 preoperative risk factors, we were able to accurately predict their ECE. Patients with 0 or 1 risk factor had a low probability of ECE (13.0% and 18.5%, respectively). In contrast, the majority of patients who had 3 or 4 risk factors were found to have ECE (80.1% and 71.4%, respectively). CONCLUSION: The data suggest that the Gleason score, serum PSA, clinical stage, and PPM may be independent predictors for the existence of ECE. This suggests that the posterior margin in biopsy specimens is a more reliable and clinically useful parameter when making decisions concerning the choice of treatments.

Histopathologic profiles of coronary atherosclerosis by myocardial bridge underlying myocardial infarction.

OBJECTIVE: Anatomic properties of myocardial bridge (MB) are sometimes responsible for myocardial infarction (MI) through the changes in the atherosclerosis distribution in the left ascending coronary artery (LAD). The purpose of this study was to investigate histopathologic profiles of atherosclerotic lesions resulting from the MB presence in the LAD in the MI cases. METHODS: In 150 consecutive autopsied MI hearts either with MBs [MI(+)MB(+); n = 67] or without MBs [MI(+)MB(-); n = 83] and 100 normal hearts with MBs [MI(-)MB(+)], LADs were consecutively cross-sectioned at 5-mm intervals. The most advanced intimal lesion and unstable plaque-related lesion characteristics (UPLCs) in each section were histopathologically evaluated in conjunction with the anatomic properties of the MB, such as its thickness, length, location, and MB muscle volume burden (MMV: the total volume of MB thickness multiplied by MB length). RESULTS: The MB showed a significantly greater thickness (P = 0.0090), length (P = 0.0300), and MMV (P = 0.0019) in MI(+)MB(+) than in MI(-)MB(+). Mean age of acute MI cases was significantly younger (P = 0.0227) in MI(+)MB(+) than in MI(+)MB(-). Frequency of plaque fissure/rupture in the proximal LAD was significantly higher in acute MI cases of MI(+)MB(+) than in MI(+)MB(-). UPLCs tended to be located proximally in MI(+)MB(+) and frequent 2.0 cm or more proximal to the MB entrance in MI(+)MB(+). CONCLUSION: In MI(+)MB(+), UPLCs tend to be located more proximally, and a plaque in the LAD proximal to the MB is prone to rupture, resulting in MI at younger age.

Phase II study of cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) therapy for newly diagnosed patients with low- and low-intermediate risk, aggressive non-Hodgkin's lymphoma: final results of the Japan Clinical Oncology Group Study, JCOG9508.

The regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone, known as CHOP therapy, has been established as the standard treatment for aggressive non-Hodgkin's lymphoma (NHL). Although patients categorized as low (L) and low-intermediate (L-I) risk using the International Prognostic Index have favorable prognoses in Western countries, the efficacy and safety of CHOP therapy has not been prospectively evaluated in Japan. We conducted a phase II study of CHOP in L and L-I risk Japanese patients, evaluating overall survival (OS) as the primary endpoint. A total of 213 patients were enrolled and treated with eight courses of CHOP. Efficacy was evaluated in 168 eligible patients (L risk, 87; L-I risk, 81). Five-year OS rates in all eligible, L, and L-I risk patients were 68 % [95 % confidence interval (CI): 61-76 %], 73 % (95 % CI: 63-82 %), and 64 % (95 % CI: 53-74 %), respectively. The major toxicity observed was grade 4 neutropenia (64 %). Grade 4 non-hematological toxicities were observed as follows: one case each of paralytic ileus, convulsions, hypoxemia due to interstitial pneumonia, and reactivated fulminant hepatitis B. These results show reasonable efficacy and safety of the CHOP regimen in Japanese patients with lower risk aggressive NHL (UMIN-CTR Number C000000053).