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This is the first case of follicular T-cell lymphoma (FTCL) presenting as methotrexate-associated lymphoproliferative disorders (MTX-LPDs). A 69-year-old man treated rheumatoid arthritis with methotrexate presented with cervical swelling, hoarseness and fever. Imaging studies revealed multiple lymphadenopathy and lymphoma was suspected. Lymph node biopsy was performed to confirm the diagnosis. Pathologically, the lymph node was composed of atypical lymphocytes with a follicular growth pattern and area of necrosis. Immunohistochemical examination showed the atypical lymphocytes were positive for CD3, CD4, programmed cell death protein 1, and inducible T-cell co-stimulator. These findings are consistent with FTCL. During hospitalization, the patient's fever subsided and cervical lymphadenopathy improved, probably due to discontinuation of MTX. Here we presented the first case of FTCL presenting as MTX-LPDs. The T-cell phenotype MTX-LPDs are relatively rare and accounts for only 3.4%-6.3% of all MTX-LPD cases. Therefore, detailed clinicopathological features have not been clarified sufficiently. It is hoped that similar cases should be accumulated and studied to better understand the clinical and pathological features of this condition.

Endometrial stromal sarcoma (ESS) is a rare mesenchymal tumor of the uterus that accounts for 7–25% of uterine sarcomas and

This is the first reported case of follicular T-cell lymphoma (FTCL) that primarily developed in the extranodal site of the right submandibular gland. An 86-year-old man was detected with a right cervical mass suspected to be malignant lymphoma during his physical examination. Imaging studies revealed that the mass was a submandibular gland tumor. The tumor was excised for diagnosis and treatment. Pathologically, the tumor was composed of densely aggregated lymphocytes with a follicular growth pattern. The immunohistochemical investigation showed that the lymphoma cells expressed CD3, CD4, programmed cell death protein 1, BCL6, chemokine (C-X-C motif) ligand 13, and BCL2. Staining of the follicular dendritic cell revealed its meshwork structure limited in the germinal center. Monoclonal rearrangement of the T-cell receptor was detected using polymerase chain reaction. These findings are consistent with the characteristics of FTCL. Here, we describe the first reported case of extranodal counterpart of FTCL of the submandibular gland. Accumulation and investigation of such extranodal cases is essential.

A pathological evaluation is one of the most important methods for the diagnosis of malignant lymphoma. A standardized diagnosis is occasionally difficult to achieve even by experienced hematopathologists. Therefore, established procedures including a computer-aided diagnosis are desired. This study aims to classify histopathological images of malignant lymphomas through deep learning, which is a computer algorithm and type of artificial intelligence (AI) technology. We prepared hematoxylin and eosin (H&E) slides of a lesion area from 388 sections, namely, 259 with diffuse large B-cell lymphoma, 89 with follicular lymphoma, and 40 with reactive lymphoid hyperplasia, and created whole slide images (WSIs) using a whole slide system. WSI was annotated in the lesion area by experienced hematopathologists. Image patches were cropped from the WSI to train and evaluate the classifiers. Image patches at magnifications of ×5, ×20, and ×40 were randomly divided into a test set and a training and evaluation set. The classifier was assessed using the test set through a cross-validation after training. The classifier achieved the highest levels of accuracy of 94.0%, 93.0%, and 92.0% for image patches with magnifications of ×5, ×20, and ×40, respectively, in comparison to diffuse large B-cell lymphoma, follicular lymphoma, and reactive lymphoid hyperplasia. Comparing the diagnostic accuracies between the proposed classifier and seven pathologists, including experienced hematopathologists, using the test set made up of image patches with magnifications of ×5, ×20, and ×40, the best accuracy demonstrated by the classifier was 97.0%, whereas the average accuracy achieved by the pathologists using WSIs was 76.0%, with the highest accuracy reaching 83.3%. In conclusion, the neural classifier can outperform pathologists in a morphological evaluation. These results suggest that the AI system can potentially support the diagnosis of malignant lymphoma.

Adult T-cell leukaemia/lymphoma (ATL) patients have a poor prognosis. Here, we investigated the impact of TP53 gene mutations on prognosis of ATL treated in different ways. Among 177 patients, we identified 47 single nucleotide variants or insertion-deletions (SNVs/indels) of the TP53 gene in 37 individuals. TP53 copy number variations (CNVs) were observed in 38 patients. Altogether, 67 of 177 patients harboured TP53 SNVs/indels or TP53 CNVs, and were categorized as having TP53 mutations. In the entire cohort, median survival of patients with and without TP53 mutations was 1·0 and 6·7 years respectively (P < 0·001). After allogeneic haematopoietic stem cell transplantation (HSCT), median survival of patients with (n = 16) and without (n = 29) TP53 mutations was 0·4 years and not reached respectively (P = 0·001). For patients receiving mogamulizumab without allogeneic HSCT, the median survival from the first dose of antibody in patients with TP53 mutations (n = 27) was only 0·9 years, but 5·1 years in those without (n = 42; P < 0·001). Thus, TP53 mutations are associated with unfavourable prognosis of ATL, regardless of treatment strategy. The establishment of alternative modalities to overcome the adverse impact of TP53 mutations in patients with ATL is required.

This study provides an overview of the epidemiology and secular trends of malignant lymphoma in Japan. Using data from clinics and hospitals throughout Japan, we analyzed 9426 cases of malignant lymphoma diagnosed in 2007‐2014. We show that the proportion of follicular lymphoma and methotrexate‐associated lymphoproliferative disorder increased during this time, as did the onset age for follicular lymphoma and diffuse large B‐cell lymphoma. Significant increases in onset age for follicular lymphoma and diffuse large B‐cell lymphoma were observed in both men and women (all P values

// Joji Shimono 1, 3 , Hiroaki Miyoshi 1 , Fumiko Arakawa 1 , Kensaku Sato 1 , Takuya Furuta 1 , Reiji Muto 1 , Eriko Yanagida 1 , Yuya Sasaki 1 , Daisuke Kurita 1 , Keisuke Kawamoto 1 , Koji Nagafuji 2 and Koichi Ohshima 1 1 Department of Pathology, Kurume University, School of Medicine, Kurume, Japan 2 Department of Hematology, Kurume University, School of Medicine, Kurume, Japan 3 Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan Correspondence to: Hiroaki Miyoshi, email: miyoshi_hiroaki@med.kurume-u.ac.jp Keywords: dendritic cell neoplasm; histiocytic sarcoma; survival; prognostic factor; BRAF Received: June 05, 2017 Accepted: September 21, 2017 Published: October 19, 2017 ABSTRACT Histiocytic and dendritic cell neoplasms are rare and poorly studied. We report the clinical characteristics and prognostic factors in such cases in Japan. We investigated the clinical characteristics and survival in 87 adult patients with histiocytic and dendritic cell neoplasms. Fifty patients had histiocytic sarcoma, 12 had Langerhans cell histiocytosis, 11 had follicular dendritic cell sarcoma, 8 had Langerhans cell sarcoma, 6 had interdigitating cell sarcoma and 1 had indeterminate dendritic cell sarcoma. The median follow-up period was 18.0 (range: 9.6-71.8) months, and median overall survival (OS) was 23.5 months . The 2-year OS rate was 49.2% . In the multivariate analysis, elevated lactate dehydrogenase (LDH) ( p =.004), ECOG performance status (PS) 2-4 ( p =.006), and Ann Arbor stage III-IV ( p =.008) affected OS. Stratification by elevated LDH, ECOG PS 2-4, and Ann Arbor stage III-IV allowed classification of patients into low risk, intermediate risk, and high risk groups. The same classification was applicable for HS and non-HS categories. In the rare neoplasms of histiocytic and dendritic cell sarcoma, ECOG PS, Ann Arbor stage, and LDH are important prognostic factors for predicting survival.

Methotrexate (MTX) carries a risk of lymphoproliferative disorders (LPDs), but MTX-associated LPDs (MTX-LPDs) can resolve spontaneously after MTX withdrawal. However, the precise clinicopathologic features of MTX-LPD remain unclear. We aimed to investigate the clinicopathologic characteristics, outcomes, and prognostic factors for histologic types of MTX-LPD. Paraffin-embedded tissue samples of 219 patients with MTX-LPD were analyzed. In total, 30,33,106, and 26 had reactive lymphoid hyperplasia (RH), polymorphic-LPD (Poly-LPD), diffuse large B-cell lymphomas (DLBCLs), and classic Hodgkin lymphoma (CHL), respectively. The clinicopathologic features of RH, Poly-LPD, DLBCLs, and CHL were as follows: extranodal involvement: 13.8% (4/29), 36.4% (12/33), 69.5% (73/105), and 15.4% (4/26); Epstein-Barr virus encoded RNA positivity: 55.2% (16/29), 71.9% (23/32), 45.3% (48/106), and 76.9% (20/26); necrosis: 0% (0/29), 51.5% (17/33), 34.3% (36/105), and 12.0% (3/25); and Hodgkin Reed-Sternberg-like cells: 17.2% (5/29), 50% (14/28), and 19.8% (21/106). The median duration from MTX withdrawal to the time of disease regression was 10.4, 3.0, 4.2, and 2.7 months for RH, Poly-LPD, DLBCLs, and CHL. After MTX withdrawal, progression-free survival was the greatest for RH, followed by for Poly-LPD, DLBCL, and CHL (all P

Cryptococcosis is an invasive fungal infection in immunocompromised patients. The clinicopathological characteristics of cryptococcal lymphadenitis are not well known. We analyzed three cases of cryptococcal lymphadenitis and compared their characteristics with those in previous reports. Two patients were human immunodeficiency virus (HIV) carriers, and one patient was a human T-cell leukemia virus type-1 (HTLV-1) carrier. The age of the HTLV-1 carrier with cryptococcosis was much higher than that of the HIV-1 carriers. CD4-positive cell counts in peripheral blood were 5.8/μL (Case 1) and 79.9/μL (Case 2) in the HIV carriers and 3285/μL in the HTLV-1 carrier (Case 3). According to flow cytometric analysis of the lymph nodes of Cases 1, 2, and 3, 50.0%, 87.1%, and 85.9%, respectively, of the T-cells were CD3; 9.8%, 16.3%, and 75.8%, respectively, were CD4; and 35.5%, 77.3%, and 10.2%, respectively, were CD8. Cryptococcus neoformans was detected in tissue culture in all patients. Although gelatinous lesions and numerous fungal cocci were observed in the two HIV patients, the granuloma formation was small. Gelatinous formation and granuloma formation were observed in the HTLV-1 carrier. Necrosis was observed in all cases. In previous reports, granuloma formation, epithelioid cells, and necrotic lesions were observed in most cases. Most of the patients were also immunosuppressed. However, no HTLV-1 carrier was detected. In conclusion, lymphadenopathy in a HTLV-1 carrier may suggest the presence of cryptococcal lymphadenitis. The frequency of cryptococcosis in HTVL-1 carriers may increase with increase in the long-term survival rate of HTLV-1 carriers.

Extranodal NK/T-cell lymphoma, nasal type (ENKTL) is a subtype of non-Hodgkin lymphoma with a poor prognosis. Although first-line treatments for patients with localized ENKTL have been established, there is no gold standard treatment for patients with advanced ENKTL and refractory and/or relapsed disease. Anti-CD30 antibody-based therapy, including brentuximab vedotin (BV), has been shown to target malignant lymphomas with CD30 expression. In particular, this therapeutic agent has recently been suggested to be effective for Hodgkin lymphoma and mature T-cell lymphoma. However, the efficacy of BV toward ENKTL has not yet been established. Therefore, we investigated the expression of CD30 in a large cohort to evaluate BV as a potential treatment for ENKTL. In this study, 97 Japanese patients with newly diagnosed ENKTL between January 2007 and December 2015 were enrolled. Flow cytometry and immunohistochemistry were performed for the evaluation of CD30 expression. If the cut-off value of CD30 expression is 1% or more, there were 55 positive cases (56.5%). According to the localization of lesion, the frequency of CD30 expression was significantly higher in the non-nasal type than in the nasal type (P = .0394). No differences were observed in almost all clinical characteristics between CD30-positive cases and CD30-negative cases. In addition, the expression of CD30 was not a prognostic factor for either overall survival or progression-free survival. In conclusion, frequent expression of CD30 in ENKTL suggests anti-CD30 antibody-based therapy may be an effective treatment.