Herein, we report on a case of a 70-year-old man with a primary high-grade myxofibrosarcoma (MFS) in the anterior mediastinum. A computed tomography (CT) scan of the patient's chest revealed a heterogeneous mass lesion. On magnetic resonance imaging (MRI), the mass lesion exhibited heterogeneous low signal intensity with focal high signal intensity on T1-weighted images, and high signal intensity with cystic lesions on T2-weighted images. There were no signs of adipose tissue or calcification in the chest CT or MRI findings. Tumor resection was performed for the diagnosis and treatment. The resected mass was composed of myxoid and solid areas. The myxoid areas revealed atypical spindle cells with abundant myxoid matrix. The solid areas showed atypical spindle cell proliferation with numerous mitoses and multinucleated atypical cells. MDM2 gene amplification was not found in the tumor using fluorescent in situ hybridization method. Thus, the tumor was diagnosed as myxofibrosarcoma. Post-operative radiation therapy was administered to the mediastinum. However, the patient died from locally recurrent disease 1-year after surgery. Our case confirms the existence of MFS in the mediastinum and shows its poor prognosis and rapid progression.

A calcifying fibrous pseudotumor (CFPT) is a rare benign lesion that often presents in the upper and lower extremities of children and young adults. In the present report, we describe a case of a small CFPT arising from the epicardium (visceral pericardium) in a 32-year-old woman. The tumor presented as a 25-mm polypoid mass protruding into the pericardial cavity, without extending into the myocardium. A complete resection was performed, and the patient has not experienced any relapse for more than 2 years. On histological examination, the lesion contained densely hyalinized collagen with psammomatous and dystrophic calcifications, as well as patchy chronic inflammatory infiltrate. The localization in the epicardium with no involvement of the myocardium was confirmed by the elastic stain. Amyloid was negative by the Congo red stain. On immunohistochemical analysis, the lesional cells indicated diffuse positive staining for vimentin and factor XIIIa and focal positive staining for CD34, but did not indicate positive staining for other pertinent antigens such as cytokeratins, calretinin, desmin, α-smooth muscle actin, ALK, and estrogen and progesterone receptors as well as IgG4 in plasma cells. To our knowledge, only three cases of CFPT in the heart have been reported in the literature, all of which developed in young females as a large mass involving the epicardium; the lesion also extended to the parietal pericardium in two cases. Moreover, all cases presented with few symptoms, despite the large lesion. In the present case, the CFPT developed also in a young woman, but the lesion was much smaller than those previously published and was localized in the visceral serous membrane of the heart. The findings of this case suggest a potential preferable site of origin of CFPTs of the heart.

Aims: Extranodal natural killer (NK)/T-cell lymphoma (NKTL), comprising nasal NKTL and extranasal NKTL (ENKTL), is associated with Epstein-Barr virus (EBV). A bimodal age distribution was noted in NKTL patients. We examined the clinicopathological differences between two age groups of ENKTL patients (n = 23) and compared the findings with those of aggressive NK cell leukaemia (ANKL; n = 10) and monoclonal chronic active EBV infection-associated T/NK-cell lymphoproliferative disorders [chronic active EBV infection/TNK-lymphoproliferative disorders (CAEBV/TNK-LPD)] of NK-cell type (n = 45).Methods and results: Distinct differences existed between elderly (>50 years; n = 13) and younger (<= 50 years; n = 10) ENKTL patients; the latter showed a higher disease stage (P = 0.0286), worse performance status (P = 0.0244), more frequent B symptoms (P = 0.0286) and more frequent liver, spleen and bone marrow involvement (P = 0.0222, 0.0005 and 0.0259, respectively). Few clinicopathological differences existed between younger ENKTL and ANKL patients. Patients with monoclonal CAEBV/TNK-LPD of NK-cell type (n = 45) showed features similar to those in younger ENKTL/ANKL patients, except a more juvenile onset of CAEBV-related symptoms and better prognosis. However, the onset age of overt leukaemia/lymphoma in CAEBV/TNK-LPD patients and overall survival thereafter were similar to those in younger ENKTL/ANKL patients.Conclusions: ENKTL (<= 50 years) is distinct from that in elderly patients and may encompass ANKL and overlap in the clinicopathological profile with NK-cell type CAEBV/TNK-LPD.

Thymic carcinoma is a rare tumor. The most common histological subtype is squamous cell carcinoma, and only a few cases of thymic adenocarcinoma have been reported. A case of papillary adenocarcinoma of thymic origin that coexisted with type AB thymoma as a separate nodule is presented herein. The patient was found to have an abnormal mediastinal shadow on chest X-ray. A computed tomography scan revealed a round, 6.5-cm-diameter mass in the right anterior mediastinum. The preoperative diagnosis was thymoma, and thymothymectomy was performed. On pathological examination, two tumors, which were diagnosed as papillary adenocarcinoma and type AB thymoma, respectively, were present in the thymus without any connection with each other. The patient has been alive without any signs of recurrence for 11 years after surgery. We diagnosed the adenocarcinoma in this case was a primary thymic carcinoma.

HistopathologyVolume 56, Issue 2 p. 265-269 Peripheral pulmonary papillary/glandular neoplasms with ciliated cells and a component of well-differentiated adenocarcinoma: report of three tumours Yoshifumi Arai, Yoshifumi Arai Department of Pathology, Nagoya City University, School of Medicine, Nagoya, JapanSearch for more papers by this authorShigeki Shimizu, Shigeki Shimizu Department of Pathology, Nagoya City University, School of Medicine, Nagoya, Japan Department of Pathology, Memorial Sloan-Kettering, Cancer Centre, New York, NY, USASearch for more papers by this authorTadaaki Eimoto, Tadaaki Eimoto Department of Pathology, Nagoya City University, School of Medicine, Nagoya, JapanSearch for more papers by this authorShin– Ichi Shimizu, Shin– Ichi Shimizu Division of Pathology, Clinical Laboratory, Seirei Hamamatsu General HospitalSearch for more papers by this authorYoshiro Otsuki, Yoshiro Otsuki Division of Pathology, Clinical Laboratory, Seirei Hamamatsu General HospitalSearch for more papers by this authorHiroshi Kobayashi, Hiroshi Kobayashi Division of Pathology, Clinical Laboratory, Seirei Hamamatsu General HospitalSearch for more papers by this authorHiroshi Ogawa, Hiroshi Ogawa Seirei Mikatahara General Hospital, Hamamatsu, JapanSearch for more papers by this authorWilliam D Travis, William D Travis Department of Pathology, Memorial Sloan-Kettering, Cancer Centre, New York, NY, USASearch for more papers by this author Yoshifumi Arai, Yoshifumi Arai Department of Pathology, Nagoya City University, School of Medicine, Nagoya, JapanSearch for more papers by this authorShigeki Shimizu, Shigeki Shimizu Department of Pathology, Nagoya City University, School of Medicine, Nagoya, Japan Department of Pathology, Memorial Sloan-Kettering, Cancer Centre, New York, NY, USASearch for more papers by this authorTadaaki Eimoto, Tadaaki Eimoto Department of Pathology, Nagoya City University, School of Medicine, Nagoya, JapanSearch for more papers by this authorShin– Ichi Shimizu, Shin– Ichi Shimizu Division of Pathology, Clinical Laboratory, Seirei Hamamatsu General HospitalSearch for more papers by this authorYoshiro Otsuki, Yoshiro Otsuki Division of Pathology, Clinical Laboratory, Seirei Hamamatsu General HospitalSearch for more papers by this authorHiroshi Kobayashi, Hiroshi Kobayashi Division of Pathology, Clinical Laboratory, Seirei Hamamatsu General HospitalSearch for more papers by this authorHiroshi Ogawa, Hiroshi Ogawa Seirei Mikatahara General Hospital, Hamamatsu, JapanSearch for more papers by this authorWilliam D Travis, William D Travis Department of Pathology, Memorial Sloan-Kettering, Cancer Centre, New York, NY, USASearch for more papers by this author First published: 23 December 2009 https://doi.org/10.1111/j.1365-2559.2009.03463.xCitations: 18Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume56, Issue2January 2010Pages 265-269 RelatedInformation

Background. Thymic carcinoma is a rare tumor. Limited data are available regarding the effectiveness of treatment and the prognosis of thymic carcinoma. The present study aimed to clarify the prognostic factors in patients who underwent resection.Methods. The study retrospectively reviewed 21 patients (15 men, 6 women) with thymic carcinoma who had undergone resection at Niigata University Hospital.Results. Masaoka stage was II in 4 patients, III in 9, IVa in 2, and IVb in 6. Histologic subtypes were squamous cell carcinoma in 14 patients, adenocarcinoma in 2, atypical carcinoid in 3, and undifferentiated carcinoma in 2. Histologic grade by degree of differentiation was low in 4 tumors, intermediate in 12, and high in 5. Treatment comprised resection alone in 6 patients and resection along with multimodal therapies in 15. Complete resection was achieved in 14 (67%). Eight patients died of tumor. Recurrence was documented in 7 of 14 patients with complete resection, and 5 received additional treatment. The overall 5-year survival rate was 61.1%, and the disease-free 5-year survival rate was 66.8% for the 14 with complete resection. By multivariate analysis, Masaoka stage and histologic grade were significant independent prognostic factors for overall survival.Conclusions. The surgical outcome of patients with thymic carcinoma depends on the Masaoka stage and histologic grade. Patients with early Masaoka stage and low or intermediate histologic grade had favorable prognoses. (Ann Thorac Surg 2010;89:912-7) (C) 2010 by The Society of Thoracic Surgeons

Purpose: Mucoepidermoid carcinoma (MEC) is the most frequently detected primary malignancy of the salivary gland and is characterized by a marked variation in prognosis. In the present study, we investigated the prognostic significance of p27(Kip1), Ki-67, and CRTC1 (also called MECT1, TORC1, and WAMTP1)-MAML2 fusion in MEC.Materials and Methods: MEC cases (n = 101) were examined for p27(Kip1) and Ki-67 expression using immunohistochemistry and for CRTC1-MAML2 fusion transcript using reverse transcriptase-polymerase chain reaction.Results: p27(Kip1), Ki-67, and the CRTC1-MAML2 fusion transcript were expressed in 71, 31, and 34 of the 101 cases, respectively. p27(Kip1) and CRTC1-MAML2 fusion were associated with favorable clinicopathologic tumor features and Ki-67 with aggressive clinicopathologic features. Multivariate Survival analyses were performed that included the following 10 clinicopathologic factors: age, gender, tumor site, tumor size, nodal metastasis, clinical stage, histologic grade, p27 expression, Ki-67 expression, and CRTC1-MAML2 fusion. For disease-free Survival, only p27(Kip1) expression was significant as an independent prognostic factor. For overall survival, p27(Kip1) expression, CRTC1-MAML2 fusion, and tumor size were significant. In each analysis, p27(Kip1) and CRTC1-MAML2 fusion were independent of the clinical stage. Ki-67 expression was not selected in either multivariate analysis.Conclusions: p27(Kip1) and CRTC1-MAML2 fusion were associated with favorable clinicopathologic tumor features, and both were useful in predicting the overall Survival of patients with MEC. For disease-free survival, p27(Kip1) might be the most useful prognostic factor. In contrast, Ki-67 might not be a very powerful prognostic indicator for either Survival point. (C) 2009 American Association of Ored and Maxillofacial Surgeons J Oral Maxillofac Surg 67:1432-1441, 2009

Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the prostate is rare, and only five cases have been reported. Reported herein is a new case that has involved a 9 year follow up. A 79-year-old man was treated with transurethral resection (TUR) for a mass of the right prostatic lobe, and followed up under a diagnosis of benign prostatic hyperplasia with atypical lymphoid infiltration. Seven years later TUR was again performed for a right lobe mass. The lesion was diagnosed as a relapsed MALT lymphoma after detailed histological and immunoglobulin heavy chain gene analyses of the initial and relapsed lesions. Interestingly, lymphoepithelial lesions were observed only infrequently in this tumor. The API2-MALT1 fusion, a gene alteration specific to MALT lymphoma, was absent. The patient had stage IA disease at the time of tumor relapse, and has been alive and well for the 2 years after the second TUR. The present case suggests that despite tumor recurrence, prostatic MALT lymphoma is indolent, and function-preserving therapy is warranted.

BACKGROUND:Overexpression of KIT, a tyrosine kinase receptor protein encoded by the proto-oncogene c-kit, is observed in human neoplasms such as gastrointestinal stromal tumors (GISTs), myeloproliferative disorders, melanoma and seminoma. In patients with GIST, overexpression of mutated KIT within the tumor is predictive of response to molecular targeted therapy using imatinib. However, the role of KIT expression in thymic carcinoma is not fully understood.METHODS:Thymic epithelial tumors from 37 patients (17 thymic carcinomas and 20 thymomas) were examined. Immunohistochemical staining with anti-KIT polyclonal antibody and anti-CD5 was performed. Mutation analyses in the juxtamembrane domains, exons 9 and 11, and in the tyrosine kinase domains, exons 13 and 17, were undertaken using polymerase chain reaction (PCR) and direct DNA sequencing in KIT-positive samples.RESULTS:KIT- and CD5-positive staining was observed only in thymic carcinoma. Percentage of positive staining was 100% in squamous cell carcinoma, with no positive staining in other histologies, including atypical carcinoid. Mutation analysis of the KIT gene was performed in 11 squamous cell carcinomas, 1 adenocarcinoma and 1 adenosquamous cell carcinoma. None of the tested samples showed mutations in any of the four exons.CONCLUSIONS:Squamous cell carcinoma of the thymus frequently expressed KIT and CD5 proteins, whereas other tumors did not. Unlike GIST, overexpression of KIT does not necessarily indicate gene mutation in thymic carcinoma. KIT and CD5 appear useful for evaluating and subtyping thymic epithelial tumors.

AIMS:To investigate neuroendocrine (NE) differentiation in gastric signet ring cell carcinoma (SRCC) using chromogranin A (CgA) as an indicator of a well-differentiated NE phenotype and to determine its relationship to cell type, stage and prognosis. METHODS AND RESULTS:102 SRCCs were categorized into five subtypes according to the predominant cell type in the World Health Organization classification. 38 cases (37.3%) showed focal or diffuse CgA positivity. The positive cells were mostly histiocytoid and eosinophilic SRCC cells and some were classical SRCC cells. Small cell and anaplastic-type SRCC cells were only rarely immunopositive. There was no significant relationship between CgA expression and the extent of invasion or presence of metastasis. However, a significant positive correlation existed between CgA positivity and favourable prognosis, with a tendency for greater positivity to be associated with better overall survival. Multivariate analysis showed expression of CgA to be an independent prognostic factor. CONCLUSION:CgA expression is restricted to certain tumour cell types and may help to predict prognosis in gastric SRCCs.

Aims: To evaluate proliferation and apoptosis in high-grade sarcomas of the extremities before and after preoperative radio-hyperthermo-chemotherapy (RHC) and to determine the relationship between these parameters and treatment outcomes.Methods and results: Pre- and post-RHC specimens of 41 soft tissue and bone tumours were immunohistochemically stained for minichromosome maintenance protein (MCM) 2 and caspase 3 as proliferation and apoptosis markers, respectively, based on a preliminary study comparing them with conventional markers. Indices were calculated as a percentage of positive cells by counting tumour cells in the most frequently labelled areas. MCM2, caspase 3 and MCM2/caspase 3 (growth) indices were 45.3 +/- 21.9%, 4.1 +/- 7.1% and 82.9 +/- 104.5, respectively, in pre-RHC specimens and 35.4 +/- 30.8%, 39.2 +/- 34.6% and 5.3 +/- 11.7, respectively, in post-RHC specimens. Response scores showed positive correlation with pre-RHC MCM2 and post-RHC caspase 3 indices, inverse correlation with post-RHC MCM2 and post-RHC growth indices and no correlation with prognosis. Multivariate analysis revealed high pre-RHC MCM2 and high post-RHC growth indices as significant unfavourable prognostic factors.Conclusions: High proliferative activity in untreated sarcoma may predict good response to neoadjuvant therapy, but poor prognosis, whereas a high growth index, i.e. high proliferation:apoptosis ratio in a post-neoadjuvant therapy tumour specimen may indicate poor response and poor prognosis.

HistopathologyVolume 52, Issue 3 p. 409-411 Sarcomatoid carcinoma of the thymus arising in metaplastic thymoma S Moritani, S Moritani Department of Pathology and Clinical Laboratories, Nagoya Medical Centre, NagoyaSearch for more papers by this authorS Ichihara, S Ichihara Department of Pathology and Clinical Laboratories, Nagoya Medical Centre, NagoyaSearch for more papers by this authorK Mukai, K Mukai Department of Diagnostic Pathology, Tokyo Medical University, TokyoSearch for more papers by this authorY Seki, Y Seki Department of Thoracic Surgery, Nagoya Medical CentreSearch for more papers by this authorS Inoue, S Inoue Department of Thoracic Surgery, Nagoya Medical CentreSearch for more papers by this authorA Yasuda, A Yasuda Department of Thoracic Surgery, Nagoya Medical CentreSearch for more papers by this authorS Hakiri, S Hakiri Department of Thoracic Surgery, Nagoya Medical CentreSearch for more papers by this authorY Yatabe, Y Yatabe Department of Pathology and Molecular Diagnostics, Aichi Cancer CentreSearch for more papers by this authorT Eimoto, T Eimoto Department of Pathology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, JapanSearch for more papers by this author S Moritani, S Moritani Department of Pathology and Clinical Laboratories, Nagoya Medical Centre, NagoyaSearch for more papers by this authorS Ichihara, S Ichihara Department of Pathology and Clinical Laboratories, Nagoya Medical Centre, NagoyaSearch for more papers by this authorK Mukai, K Mukai Department of Diagnostic Pathology, Tokyo Medical University, TokyoSearch for more papers by this authorY Seki, Y Seki Department of Thoracic Surgery, Nagoya Medical CentreSearch for more papers by this authorS Inoue, S Inoue Department of Thoracic Surgery, Nagoya Medical CentreSearch for more papers by this authorA Yasuda, A Yasuda Department of Thoracic Surgery, Nagoya Medical CentreSearch for more papers by this authorS Hakiri, S Hakiri Department of Thoracic Surgery, Nagoya Medical CentreSearch for more papers by this authorY Yatabe, Y Yatabe Department of Pathology and Molecular Diagnostics, Aichi Cancer CentreSearch for more papers by this authorT Eimoto, T Eimoto Department of Pathology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, JapanSearch for more papers by this author First published: 05 February 2008 https://doi.org/10.1111/j.1365-2559.2007.02960.xCitations: 18Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume52, Issue3February 2008Pages 409-411 RelatedInformation

Aims: To investigate the clinicopathological features of six unusual cases of nodal CD56+ and Epstein-Barr virus (EBV)+ T/natural killer (NK)-cell lymphoma, a putative nodal counterpart of nasal NK/T-cell lymphoma (nodal T/NK-cell lymphoma of nasal type) in comparison with nasal NK/T-cell lymphoma with secondary lymph node involvement (n = 24) and peripheral T-cell lymphoma (PTCL) of cytotoxic molecule (CTM)+ and EBV+ type (n = 21).Methods and results: All cases of nodal T/NK-cell lymphoma of nasal type exhibited diffuse infiltration of pleomorphic medium-sized to large tumour cells, reminiscent of those in CTM+ EBV+ PTCL. The tumour cells had a typical phenotype of nasal NK/T-cell lymphoma: CD2+, CD3 epsilon+, CD4-, CD5-, CD56+, T-cell intracellular antigen-1+, granzyme B+, perforin+ and EBV+. However, four of six cases demonstrated clonal T-cell receptor gamma-gene rearrangement on polymerase chain reaction analysis, unlike nasal NK/T-cell lymphoma. Comparison of clinical parameters and overall survival among the three groups demonstrated only minor differences.Conclusions: Nodal T/NK-cell lymphoma may occupy the grey zone between extranodal nasal-type NK/T-cell lymphoma and nodal CTM+ PTCL in a spectrum of NK to T-cell lymphomas that are EBV+. The close relationship between NK/T-cell lymphomas and cytotoxic T-cell lymphomas was also substantiated.

In anaplastic large-cell lymphomas positive for anaplastic lymphoma kinase (ALK) protein, the ALK gene is most commonly fused to the NPM gene, and less commonly to TPM3, TFG, ATIC, and other rare genes. Although this lymphoma is generally associated with a favorable clinical outcome, 25% of the patients die of the disease within 5 years. In this study, we developed three assays, all of which can be used with archival formalin-fixed, paraffin-embedded tissues: (1) a sensitive reverse transcription-polymerase chain reaction (RT-PCR) assay for various X-ALK fusion genes, (2) a 5′ rapid amplification of cDNA ends (RACE) assay to identify unknown fusion partners, and (3) a real-time RT-PCR assay to quantify the amount of the NPM-ALK fusion transcript. In 26 cases of ALK+ anaplastic large-cell lymphoma, the RT-PCR assay showed that the ALK was fused to NPM in 21 cases, to TPM3 in three, and to TFG in one. The 5′ RACE assay detected ATIC-ALK fusion in the remaining case. The real-time quantitative RT-PCR assay showed that the NPM-ALK transcript was over expressed in four of 20 quantifiable cases. Patients with NPM-ALK overexpression showed a significantly unfavorable overall survival compared with those with a low expression of this transcript. The RT-PCR and 5′ RACE assays developed here may be useful for identification of known and unknown gene partners fused to the ALK gene. Overexpression of the NPM-ALK fusion transcript may be associated with a poor prognosis of the patients with ALK+ anaplastic large-cell lymphomas.

Little is known about the role of chemokines and their receptors interaction, which are essential for recruitment of selective lymphocyte subsets during inflammation, in the pathogenesis of idiopathic nonspecific interstitial pneumonia (NSIP). Recent studies have revealed Th1 and Th2 cells preferentially employ the chemokine receptors, CXCR3 and CCR4, respectively, in the process of accumulation into inflammatory sites. We evaluated the CXCR3 and CCR4 expression on infiltrated lymphocytes in lung tissues of 12 NSIP cases and 10 idiopathic pulmonary fibrosis (IPF) cases in our previous study. The number of CXCR3 positive lymphocytes of NSIP patients was significantly greater than that of IPF patients (261.1±145.1 vs. 64.9±27.0, P<0.01). The number of CCR4 positive lymphocytes of NSIP patients was significantly lower than that of IPF (9.5±8.3 vs.62.6±26.9, P<0.01). The CXCR3 to CCR4 ratio of NSIP patients was significantly greater than that of IPF patients (47.9±45.9 vs. 1.11±0.40, P<0.01). The differences of CXCR3 positive, CCR4 positive lymphocyte counts, and of CXCR3/CCR4 ratio between cellular and fibrosing NSIP were not significant. These results suggest that a Th1 pattern of chemokine receptor expression predominates in the lung interstitium of patients with NSIP but, in IPF patients, CCR4 might be relatively predominant, in contrast to the finding in NSIP patients, and that Th1/Th2 balance might be an important factor in the pathogenesis of NSIP.

We report here the development of a polyclonal antibody for human equilibrative nucleoside transporter 1 (hENT1) and assess the expression of hENT1 in non-small cell lung cancer (NSCLC) patients who were treated with gemcitabine-containing chemotherapy. hENT1 expression was analyzed by immunohistochemical staining in 24 NSCLC biopsy samples of formalin-fixed, paraffin-embedded tissues. The hENT1-positive staining in NSCLC samples was significantly associated with response to gemcitabine-containing chemotherapy. Responses to gemcitabine-containing chemotherapy were evident in none of the seven patients with no hENT1 expression. These results indicate that the absence of hENT1 expression may be useful to predict NSCLC patients who will not respond to gemcitabine-containing chemotherapy.

The majority of gastric mucosa-associated lymphoid tissue (MALT) lymphomas are successfully treated with Helicobacter pylori eradication alone. However, certain subsets of these tumors are resistant to the eradication treatment. As API2-MALT1 fusion is a feature of one of these subsets, we divided gastric MALT lymphomas into three groups: eradication-responsive and API2-MALT1 fusion-negative (Group A), eradication-resistant and fusion-negative (Group B), and eradication-resistant and fusion-positive (Group C). To characterize further gastric MALT lymphomas, we analyzed VH genes, which do not change in the course of tumor progression, by extensive subcloning of the monoclonal PCR products of 45 cases. VH3-23 and VH3-30 were preferentially used in Group A tumors (14/23 cases, 61%) as compared with Group B (1/10 cases, 10%, P=0.0094) and Group C (2/12 cases, 17%, P=0.017). Tumors of Groups B and C used variegated VH fragments, and no dominant VH fragments were noted. Somatic mutation was detected in most of the cases. Ongoing mutation was detected in 3/45 cases (7%), when assessed according to strict criteria for a confirmed mutation. These findings suggest that inflammation-dependent tumors (Group A) may be derived from a highly restricted, probably H. pylori-associated, B cell subset and may not often progress to those that are inflammation-independent (Groups B and C). Although considered to be common in this tumor, ongoing mutation may be infrequent when assessed by strict criteria.

Aims: To compare cell proliferation markers, minichromosome maintenance protein 2 (MCM2) and Ki67, in minimally invasive follicular carcinoma (MIFC) and follicular adenoma (FA) of the thyroid and among MIFCs with different diagnostic criteria.Methods and results: Twenty-two MIFCs and 20 FAs were immunohistochemically stained for MCM2 and Ki67. The MIFCs were subdivided into six Group 1 tumours with both capsular and vascular invasions, seven Group 2 tumours with vascular invasion only and nine Group 3 tumours with capsular invasion only. The MCM2 and Ki67 indices were calculated, counting more than 1000 tumour cells in the most frequently positive areas. In total and Groups 1-3 MIFCs and in FAs, the average MCM2 index was 26.7 +/- 11.0, 28.4 +/- 8.6, 26.3 +/- 14.8, 25.9 +/- 8.4 and 10.7 +/- 4.5, respectively, whereas the average Ki67 index was 2.07 +/- 1.65, 1.93 +/- 2.02, 2.49 +/- 1.38, 1.84 +/- 1.5 and 1.78 +/- 0.92, respectively. There was a significant difference in the MCM2 index, but not in the Ki67 index, between each category of MIFCs and FA (P < 0.01). However, neither the MCM2 index nor the Ki67 index showed a statistically significant difference among the subgroups of MIFC.Conclusions: MCM2, but not Ki67, is a helpful marker for differentiating MIFC from FA. The tumour cell proliferative activity supports the histological criteria based on diagnosing MIFC by either capsular or vascular invasion only.

Hassall's corpuscles are regular structures in the medulla of the normal thymus and in non-neoplastic thymic conditions, e.g. in multilocular thymic cysts. In thymomas, however, they are inconsistently found, and are believed to indicate medullary differentiation of WHO type B1-3 thymomas. We present five organotypical thymomas resembling WHO type B2 and B3 thymomas, but with an abundance of Hassall's corpuscles. We wonder whether this exceedingly rare observation might herald a distinct entity. Four tumors were asymptomatic, incidental findings and of low Masaoka stage (I or II) [20] . One patient suffered from myasthenia gravis which disappeared upon surgical removal of the thymus, while all other patients had no concomitant autoimmune disease. Two patients had a relapse-free follow-up of 12 and 2 years, respectively, upon curative surgery, and another tumor was an autopsy finding; follow-up data of two more recent cases was not yet available. The neoplastic epithelium other than Hassall's corpuscles was arranged either in a cortical type B2 pattern or in type B3 solid cords. In all examples, there was cyst formation, inflammatory reaction and repair, indicative of a long-standing condition. Immature T cells were present in all instances. "Corpuscular thymomas" morphologically resemble WHO type B2 and B3 thymomas, but appear biologically indolent and are rarely associated with myasthenia gravis. Whether they qualify for a separate entity has to be proven by larger series, including genetic studies.

Thymic MALT lymphoma shows certain distinctive features among MALT lymphomas, such as expression of IgA isotype, consistent lack of API2–MALT1 gene fusion, and very strong association with autoimmune disease, especially Sjogren's syndrome. To help clarify the nature of the clonal lymphoid infiltrates, we analysed the usage and somatic hypermutation of the Ig heavy chain variable region ( V H ) genes in nine different cases. The V H rearrangement was potentially functional in all cases and was restricted to the V H 3 family. V H usage was biased toward V H 3‐30 (five cases) and V H 3‐23 (three cases) segments, which have both been frequently expressed by autoimmune B cells. Somatic hypermutation was absent in five cases. Fewer than the expected replacement mutations were found in the framework regions in two cases, indicating a negative antigen selection pressure. Ongoing mutation was absent in all cases. D segment usage was varied, whereas J H segment usage was restricted to J H 4 . The observed patterns of V H usage and mutations suggested that specific antigens may play a pathologically relevant role in the genesis or progression of thymic MALT lymphoma. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.