Comparison of Follicular Helper T-Cell Markers with the Expression of the Follicular Homing Marker CXCR5 in Peripheral T-Cell Lymphomas-A Reappraisal of Follicular Helper T-Cell Lymphomas.

Peripheral T-cell lymphomas (PTCLs) expressing multiple follicular T helper (TFH) cell-related antigens are now classified as TFH lymphomas (TFHL), including angioimmunoblastic, follicular, and not otherwise specified (NOS) types. CXCR5 is the TFH cell-defining chemokine receptor that, together with its ligand CXCL13, plays a critical role in the development of follicles and the positioning of TFH and B cells within follicles. A comprehensive immunomorphologic study was performed to investigate the expression pattern of CXCR5 in a large cohort of nodal PTCLs, particularly those with a TFH cell phenotype, and to compare its expression with six other TFH cell-related antigens. We found that CXCR5 is widely expressed in neoplastic TFH cells, except in TFHL-NOS, and represents a specific marker of this lymphoma entity. Our results suggest that CXCR5 directs the distribution of neoplastic T cells in the affected lymph nodes and may influence the formation of the pathognomic pathological FDC network.

[What should we know about cardiac amyloidosis? From clinical signs to treatment]. / Mit kell tudnunk a cardialis amyloidosisról? A tünettantól a kezelésig.

Systemic amyloidosis is a rare disease, in which the heart involvement is rather frequent and determines survival remarkably. Regarding the disease and organ involvement, new diagnostic procedures help to establish the diagnosis and to start the adequate treatment as soon as possible. Cardiac involvement is more likely to be characterised by monoclonal immunglobulin free light chain (AL amyloidosis) type and transthyretin type. In case of AL amyloidosis, heart involvement can lead to serious consequences. Biomarker assessments for cardiac function are important to determine disease severity at the beginning and to measure response to the treatment. In case of amyloidosis, the incidence of the heart involvement grows with age. The prevalence is not known exactly, but probably there are more cases than recognised. The authors present the clinical signs and diagnostic methods, emphasizing the importance of the cardiac examination methods. Orv Hetil. 2017; 158(46): 1811-1818.

[Incidence and treatment of extranodal natural killer/T-cell lymphoma nasal type. Hungarian experiences]. / Nasalis típusú extranodalis natural killer T-sejtes lymphoma hazai elofordulása és kezelésével szerzett tapasztalatok.

INTRODUCTION: Extranodal natural killer/T (NK/T) cell lymphoma, nasal type (ENKTL) represents a rare subtype of T-cell lymphomas with aggressive clinical behavior according to WHO 2016 classification. AIM: ENKTL has distinctive geographic distribution with higher incidence in Asia and Latin America (10% of all non-Hodgkin lymphoma cases), than in Europe and North America (<1%). ENKTL tipically origins from nasopharynx and upper aerodigestive tract. Anthracycline-based chemotherapy regimens are largely ineffective in the treatment of ENKTL. METHOD: Our aims were to evaluate the incidence and treatment strategies of ENKTL patients in Hungarian Haematological Centres between 2003 and 2015. Altogether 20 patients with ENKTL were treated in the 4 haematological hospitals (male:female ratio 12:8, with median 49.5 years of age). RESULTS: Ten patients had localized (stage I-II) disease at the time of the diagnosis. Seventeen patients were treated with chemotherapy (11/CHOP, CHOP-like, 2/HyperCVAD, 1/ProMACECytaBom, 1/SMILE, 2/others), which was completed with involved-field radiation therapy (IFRT) (40-46 Gy) in 6 cases were used. After first-line therapy 9 patients achieved complete remission (CR), 3 patients had partial remission (PR), 3 patients had progressive disease (PD), and 2 patients had stable disease (SD). Median follow-up was 32 (3-113) months. Five patients received second-line therapy for progressive or recurrent disease [2/DHAP, 1/VIM, 1/HyperCVAD, 1/ProMACECytaBom]. None of the patients achieved CR after second-line therapy. Two patients have undergone autologous hematopoietic stem cell transplantation (HSCT) after the first CR. CONCLUSION: ENKTL treatment is more effective with nonanthracycline-containing regimens. L-asparaginase containing chemotherapy and concurrent or sequential chemo-radiotherapy improves survival and CR rates. Orv Hetil. 2017; 158(41): 1635-1641.

[Large granular lymphocytic leukemia. A rare disease with personalized treatment options]. / Nagy, granulált citoplazmájú lymphocytás leukaemia. Ritka betegség, személyre szabott kezelési lehetoségekkel.

INTRODUCTION: Large granular lymphocyte leukemia is rare, mainly chronic disease. The most common complication is neutropenia, but other immune-mediated cytopenia may also occur. There are no unified treatment recommendations and initiation of treatment mainly depends on the severity of the symptoms. AIM: The aim of the authors was to analyze the main steps of the diagnosis and the necessity and outcome of treatment in their patients diagnosed with large granular lymphocyte leukaemia. METHOD: The authors retrospectively analyzed the data of 17 large granular lymphocyte leukemia patients. RESULTS: Of the 17 patients, 7 patients required treatment because of transfusion dependent anemia (4 patients) or neutropenia (3 patients). In 4 patients corticosteroid was given (supplemented with cyclosporine in one patients), while the other patients received anti-CD52 (one patient), low dose methotrexate (one patient) and combined chemotherapy (one patient). Five patients achieved partial response, and two patients died in sepsis. CONCLUSIONS: In this cohort only a smaller proportion of patients required therapy. Immunosuppression can be successful, but the effect in most cases was temporary. The most serious complication was sepsis, which is associated with a significant risk of mortality in cases with neutropenia.

[Long-term survival after nasal NK/T cell lymphoma]. / Nazális NK/T-sejtes lymphoma hosszú túlélése.

The nasal NK/T cell lymphoma is a rare, extranodal non-Hodgkin lymphoma in western civilizations, which has poor prognosis. The Epstein-Barr virus can be detected in tumor cells in nearly all cases. There are no definite treatment guidelines in our days. There is no significant difference in survival between radiotherapy and chemotherapy according to Asian studies. In this case study we show our diagnostic procedures, our treatment options and we present the summary of this illness based on the data found in the literature.

[Refractory sprue--precursor lesion of enteropathy type T-cell lymphoma--a clinicopathological case report]. / Refrakter sprue mint az enteropathia típusú T-sejtes lymphoma prekurzor laesiója--klinikopatológiai esetismertetés.

INTRODUCTION: Refractory sprue is characterised by distinctive morphologic alterations and the emergence of clonal intraepithelial lymphocytes. AIM: In this case report the authors emphasize the importance of histopathology in the diagnosis of refractory sprue. METHODS: The sequential biopsies from this patient have been investigated with routine histology, immunohistochemistry and molecular genetics for T-cell clonality analysis. RESULTS: The severely cachectic patient presenting with malabsorption syndrome has been diagnosed with celiac disease through a duodenal biopsy, and the CD8 negativity of the intraepithelial lymphocytes suggested the possible diagnosis of refractory sprue. Azathioprine and glucocorticoid therapy was administered due to the failed jejunal feeding and gluten-free diet, resulting in clinically complete, morphologically partial remission. Intestinal T-cell lymphoma developed in the ileocecal region within two years after the first clinical presentation. DISCUSSION: Refractory sprue and the enteropathy-type T-cell lymphoma constitute a disease spectrum. The reported case shows how a simple method can provide crucial information in the diagnosis of refractory sprue.

Plasmoblastic lymphoma associated with human immunodeficiency virus.

Plasmoblastic lymphoma (PBL) is a subtype of the diffuse large B-cell lymphoma, typically present as extranodal disease associated with human immune deficiency virus (HIV) infection. PBLs are often the initial manifestation of AIDS. Here we present a case of PBL concerning the oral cavity. A 34-year-old woman presented a tumor in the oral cavity that involved the maxilla and gingiva (confirmed by CT-scan). The gingival biopsy showed a massive infiltration by large lymphoid cells with round, vesicular nuclei, prominent nucleoli, fine chromatin and an significant amount of basophilic cytoplasm which express CD79a, CD138, cytoplasmic lambda light chain and LCA, without staining for CD20, CD38, CD3 and CTK. Serological analysis confirmed HIV positivity. PBLs lack most B-lineage markers, but many express CD79a in at least some of the cells, therefore generate difficulties in differential diagnosis. Overall assessment and correlation of the histopathological and immunohistochemical features with the clinical findings and serology investigation are the most helpful diagnostic tools and can lead to the final diagnosis.

Optimization of PCR amplification for B- and T-cell clonality analysis on formalin-fixed and paraffin-embedded samples.

In many cases, particularly in retrospective studies, only formalin-fixed and paraffin-embedded (FFPE) tissue samples are available for molecular studies. DNA recovered from FFPE tissues generally consists of fragmented small target sequences with chemical alterations. Clonality analysis is not easy on FFPE samples, in fact, it requires even more experience than that of performed on fresh samples or is more complicated than most genomic PCR amplifications for somatic genes. In our study, we have performed a multi-parameter PCR evaluation investigating immunoglobulin heavy chain gene (IgH) and T-cell receptor gamma gene (TCRgamma) rearrangements on non-purified crude lysates of FFPE samples, in order to establish the significance of different variables on performance of PCR amplification. The results showed that a slight decrease in the concentration of primers in combination with a slight increase in MgCl2 and Taq polymerase concentrations, as well as the use diluted crude template and a standard amount of dNTPs can be the modifications of choice while adjusting IgH and TCRgamma clonality tests on poor quality DNA FFPE samples. Using our improved protocol, 74% (17/23) of the tested B-cell lymphomas and 68% (31/46) of the tested T-cell lymphomas demonstrated monoclonal PCR product, proving the applicability of our optimized method. Our experience may be of help during the optimization process in technically difficult cases as well as to determine which parameters and how should be changed to minimize false-negative and false-positive results.

Left ventricular rigid body rotation in a diffuse large B-cell lymphoma patient with cardiac involvement: A case from the three-dimensional speckle-tracking echocardiographic MAGYAR-Path Study.

Secondary myocardial involvement by diffuse large B-cell lymphoma is a rare occurrence. Left ventricular (LV) twist is considered an essential part of LV function. In normal circumstances LV twist results from the movement of two orthogonally oriented muscular bands of a helical myocardial structure with consequent clockwise rotation of the base and counterclockwise rotation of the apex. Three-dimensional (3D) speckle-tracking echocardiography (3DSTE) has been found to be feasible for non-invasive 3D quantification of LV wall motion and rotational mechanics. The present report aimed to assess LV twisting motion in a patient with diffuse large B-cell lymphoma with positron emission tomography/computer tomography-proven cardiac involvement by 3DSTE. During 3DSTE, reduction in some segmental radial, longitudinal, circumferential, area and 3D LV strains were found. Apical and basal LV rotations were found to be in the same counterclockwise direction, confirming near absence of LV twist - so-called rigid body rotation.

Hepatosplenic gammadelta T-cell lymphoma with ring chromosome 7, an isochromosome 7q equivalent clonal chromosomal aberration.

Hepatosplenic T-cell lymphoma is a rare, clinically aggressive lymphoma. Most cases represent a neoplasm of mature non-activated gammadelta T cells. Isochromosome 7q i(7)(q10) is thought to be the primary cytogenetic abnormality of this disease. In this paper, we describe a hepatosplenic gammadelta T-cell lymphoma case, with clonal ring chromosome 7 exemplifying an isochromosome 7q equivalent clonal aberration. A 62-year-old female patient presented with thrombocytopenia, isolated hepatosplenomegaly, and extremely high levels of LDH. Bone marrow work-up demonstrated a sinusoidal cytotoxic T-cell infiltrate with blastic features, while molecular studies verified monoclonal rearrangement for both TCR gamma and TCR delta genes. Cytogenetics revealed clonal abnormalities including ring chromosome 7, trisomy 8, and der(19), while FISH analysis detected 7q amplification with partial deletion of 7p in ring chromosome 7. To the best of our knowledge, this is the first reported T-cell lymphoma case with ring chromosome 7.

Clinical and Molecular Diagnostic Evaluation of Systemic Mastocytosis in the South-Eastern Hungarian Population Between 2001-2013--A Single Centre Experience.

Systemic mastocytosis (SM) is a rare chronic myeloproliferative neoplasm with only limited epidemiologic data published so far. We aimed to analyze the clinical and molecular diagnostic features, and the prognosis and cumulative incidence of SM cases in a cohort of south-eastern Hungarian patients of 13 year follow up. In the period 2001-2013, 35 consecutive SM cases were diagnosed in our regional centre. Immunophenotype, KIT D816V mutation frequency and clinical characteristics, and the prognosis impact of clinical subtypes were tested and compared with published data. Indolent SM (ISM) was diagnosed in 14 patients, SM with an associated clonal hematologic non-mast cell lineage disease (SM-AHNMD) in 15 patients and aggressive SM (ASM) in 6 patients. The KIT D816V mutation was found in 11/14 (78%) of the ISM cases, in 12/15 (80%) of the SM-AHNMD cases and in 5/6 (83%) of the ASM cases. The life expectancy of ISM patients was better, whereas the SM-AHNMD and ASM groups exhibited a reduced median survival. The cumulative incidence for 13 year of the SM was 0.27/10,000. We detected lower 13 year cumulative SM incidence than of published epidemiologic data due to in our analyses involved only those patients who had bone marrow biopsy and histopathologically confirmed SM. This clinical overview clearly showed that the clinical characteristics differ between ISM (UP, anaphylaxis and osteoporosis) and SM-AHNMD/ASM (cytopenia, eosinophilia and splenomegaly).

[Agranular CD4+/CD56+ haematodermic neoplasm (Precursor haematologic neoplasm)]. / Agranularis CD4+/CD56+ haematodermiás daganat (Prekurzor hematológiai daganat).

The agranular CD4+/CD56+ haematodermic neoplasm (so-called blastic NK-cell lymphoma) represents a distinct clinicopathologic entity and it is characterised by its clinical presentation (skin tropism, bone marrow involvement with or without leukemic phase, very poor prognosis) and the common expression of the T helper CD4 as well as the NK cell marker CD56. The authors present an 86 year old male patient with hemorrhagic macules, plaques and hemorrhagic flat nodules mainly on the trunk without any complaints. The skin biopsy revealed an agranular CD4+/CD56+ hematodermic tumor. During the medical check-up and the 18 months long follow-up they did not find any internal involvement including the bone marrow. In their case they revealed the cutaneous form of the hematodermic tumor which is considered to be a new and interesting manifestation of aleukemic leukemia cutis.

Pattern of MEF2B expression in lymphoid tissues and in malignant lymphomas.

Myocyte enhancer binding factor 2 B (MEF2B) is a member of the evolutionary conserved transcription family MEF2. MEF2B has been shown to directly control biological activity of the B cell lymphoma 6 (BCL6) gene in germinal center (GC) B cells. To validate MEF2B as an immunohistochemical marker, we studied a large consecutive series of hyperplastic lymphoid tissues (n = 38) and malignant lymphoproliferative conditions (n = 471), including all major categories of B and T cell neoplasms. In hyperplastic lymphoid tissues, MEF2B staining revealed intense and crisp nuclear expression confined to GC B cells. Unlike BCL6, MEF2B was not detected in follicular T cells. In addition, weak nuclear staining of plasma cells was noted. MEF2B staining labeled neoplastic cells of follicular lymphoma both in common and variant cases as well as in bone marrow biopsies with high sensitivity, while it was almost consistently negative in marginal zone lymphoma. Consistent MEF2B expression was found in Burkitt lymphoma and nodular lymphocyte predominant Hodgkin lymphoma as well as in the large majority of cases of mantle cell lymphoma and diffuse large cell B cell lymphoma. MEF2B protein expression showed a statistically significant association with that of BCL6 in cases of diffuse large B cell lymphoma, not otherwise specified. We conclude that MEF2B is a valuable marker of normal GC B cells, potentially useful in differential diagnosis of small B cell lymphomas.

A comprehensive immunophenotypic marker analysis of hairy cell leukemia in paraffin-embedded bone marrow trephine biopsies--a tissue microarray study.

Hairy cell leukemia (HCL) is an uncommon B cell lymphoproliferation characterized by a unique immunophenotype. Due to low number of circulating neoplastic cells and 'dry tap' aspiration, the diagnosis is often based on BM trephine biopsy. We have performed a consecutive immunohistochemical analysis to evaluate diagnostic usefulness of various HCL markers (CD11c, CD25, CD68, CD103, CD123, CD200, annexin A1, cyclin D1, DBA.44, HBME-1, phospho-ERK1/2, TRAP, and T-bet) currently available against fixation resistant epitopes. We analyzed tissue microarrays consisting of samples gained from 73 small B-cell lymphoma cases, including hairy cell leukemia (HCL) (n = 32), HCL variant (HCL-v) (n = 4), B-cell chronic lymphocytic leukemia (B-CLL) (n = 11), lymphoplasmacytic lymphoma (LPL) (n = 3), mantle cell lymphoma (MCL) (n = 10), splenic diffuse red pulp small B cell lymphoma (SDRPL) (n = 2), splenic B cell marginal zone lymphoma (SMZL) (n = 8), and splenic B cell lymphoma/leukemia, unclassifiable (SBCL) (n = 3) cases. The HCL cases were 100% positive for all but 2 (DBA.44 and CD123) of these markers. Annexin A1 showed 100% specificity and accuracy, which was followed by CD123, pERK, CD103, HBME-1, CD11c, CD25, CD68, cyclin D1, CD200, T-bet, DBA.44, and TRAP, in decreasing order. In conclusion, our results reassured the high specificity of annexin A1 and pERK, as well as the diagnostic value of standard HCL markers of CD11c, CD25, CD103, and CD123 also in paraffin-embedded BM samples. Additional markers, including HBME-1, cyclin D1, CD200, and T-bet also represent valuable tools in the differential diagnosis of HCL and its mimics.

Increased sensitivity of B-cell clonality analysis in formalin-fixed and paraffin-embedded B-cell lymphoma samples using an enzyme blend with both 5'-->3' DNA polymerase and 3'-->5' exonuclease activity.

Polymerase chain reaction (PCR)-based detection of immunoglobulin heavy chain (IgH) gene rearrangement for determination of B-cell clonality needs to be simple but optimally sensitive. Efficient IgH PCR analysis can be hampered by sequence variability in the template DNA, despite of the use of degenerative primers. To improve sensitivity of the B-cell clonality analysis in formalin-fixed and paraffin-embedded (FFPE) tissues, we have performed framework three-area (FR3)/joining gene (JH) IgH PCR utilizing an enzyme blend (r Tth DNA Polymerase, XL) providing both 5'-->3' polymerase and 3'-->5' exonuclease activities. The DNA samples were extracted from FFPE biopsies of 43 mature B-cell lymphoma cases of so-called germinal center and post-germinal center origin, including 6 nodal follicular lymphomas (FL), 15 gastric mucosa-associated lymphoid tissue (MALT) lymphomas, and 22 gastric diffuse large B-cell lymphomas (DLBCL). Of the cases, 31 (17 DLBCL and 14 MALT lymphoma) represented small endoscopic biopsies. Serial dilutions of target DNA were applied to avoid inconsistent bands that may be seen when the input amount of template is too low, which can be the case when DNA is extracted from FFPE endoscopic gastric biopsies. Using conventional Taq polymerase, consistent monoclonal product was found in 53% (23/43) of the cases (FL: 67%; MALT lymphoma: 47%; DLBCL: 55%). The r Tth polymerase showed reproducible monoclonal pattern in 72% (31/43) of the cases (FL: 67%; MALT lymphoma: 73%; DLBCL: 73%); the sensitivity is compatible with one that can be detected with conventional FR3/JH PCR in fresh/frozen tissues. In conclusion, the r Tth DNA polymerase greatly improves sensitivity of FR3/JH PCR in FFPE biopsies of mature B-cell lymphomas, most probably by increasing the primer matches during PCR amplification.

Analysis of immunoglobulin H gene rearrangement by polymerase chain reaction in primary central nervous system lymphoma.

OBJECT: Diagnosing primary central nervous system lymphoma (PCNSL) may be difficult either because of a paucity of tumor cells in the brain biopsy specimens or a failure to demonstrate monoclonality on immunomorphological studies. Monoclonality can also be demonstrated by amplification of the rearranged immunoglobulin H genes by polymerase chain reaction (PCR) to the framework region (FR)3 and FR2 complementarity determining region (CDR)-III and CDR-II of these genes. The PCR method is feasible with formalin-fixed, paraffin-embedded biopsy material and has proven to be helpful in the diagnosis of non-Hodgkin lymphoma on biopsy samples obtained from various locations in the body. Nevertheless, few studies have addressed the value of this method in the context of PCNSL. In the present study, the contribution of both FR3 single and FR2 seminested PCR procedures for confirming the diagnosis of PCNSL was estimated retrospectively in 30 cases of PCNSL and in three cases of epidural lymphoma. METHODS: Twenty-eight cases of immunophenotypically confirmed PCNSL and two of suspected lymphoma were studied. Tissue specimens obtained in 22 cases of other cerebral diseases, among which were various inflammatory conditions. were used as negative controls. In 18 (60%) of 30 cases the results of FR3 PCR demonstrated monoclonality, whereas FR2 PCR showed monoclonality in 12 cases (40%). In 11 cases FR3 PCR yielded monoclonal patterns and FR2 PCR did not, whereas reversibly in five cases FR2 PCR proved monoclonality and FR3 PCR failed to do so. Adding the results of FR3 to those of FR2 PCR, monoclonal patterns were obtained in 23 (77%) of 30 cases. In both cases in which lymphoma was suspected but not proven immunomorphologically, FR3 PCR revealed monoclonality, as did FR2 PCR in one case. In all 22 control lesions either polyclonal patterns were seen or no consistent patterns were obtained. In the PCNSL group, older age of patients and multifocal presentation of lesions on neuroimaging were significantly associated with worse survival. No correlation between histological subtype and clinical outcome was elucidated. CONCLUSIONS: The application of FR3 and FR2 PCR is a useful additional tool in making the diagnosis of PCNSL. Moreover, in some cases the PCR method may be essential in distinguishing neoplasia from reactive conditions.

Monoclonal antibody HBME-1 reacts with a minor subset of B cells with villous surface and can be useful in the diagnosis of hairy cell leukemia and other indolent lymphoproliferations of villous B lymphocytes.

The Hector Battifora mesothelial epitope-1 (HBME-1) monoclonal antibody has been generated against human mesothelioma cells and recognizes a biochemically unknown membrane epitope. We have accidentally found that the HBME-1 reacts with scattered lymphocytes showing villous surface in hyperplastic lymphoid tissue. To evaluate its reactivity pattern, we have performed a consecutive immunohistochemical study in nonneoplastic bone marrow and lymphoid samples (n = 40), as well as in malignant lymphoproliferations (n = 427), including hairy cell leukemia (HCL) (n = 72), HCL variant (HCL-v) (n = 13), splenic diffuse red pulp small B cell lymphoma (SDRPL) (n = 8), splenic B cell marginal zone lymphoma (SMZL) (n = 59), and splenic B cell lymphoma/leukemia, not further classifiable on bone marrow morphology (SBCL) (n = 37) cases. The staining pattern of HBME-1 was compared to DBA.44. HBME-1(+) villous lymphocytes were constantly detected in low number in nonneoplastic lymphoid tissues. With multicolor immunofluorescence staining, HBME-1(+) lymphocytes showed a CD20(+)/CD79a(+)/IgM(+) B cell phenotype. In B cell lymphoproliferations of villous lymphocytes, HBME-1 reactivity was demonstrated in 96 % of HCL, 39 % of HCL-v, 50 % of SDRPL, 12 % of SMZL, and 19 % of SBCL cases. Nodal and extranodal marginal zone lymphoma cases were positive in 12 % of the cases. A small minority (4 %) of the other B cell lymphomas and no T cell lymphoma revealed tumor cell reactivity with HBME-1. In conclusion, our study has established that HBME-1 reacts with a minor subset of B lymphocytes and a small proportion of B cell lymphomas, which has not been described previously. We suggest that HBME-1 can be a useful marker in the diagnosis of HCL and other indolent lymphoproliferations of villous B lymphocytes.

Primary uterine NK-cell lymphoma, nasal-type: a unique malignancy of a prominent cell type of the endometrium.

Natural killer (NK) cells host in the human endometrium with dedicated role in reproductive physiology. Interestingly, malignant transformation of these specialized cells has not been presented thus far. Here we report a primary endometrial NK-cell lymphoma of a 48 year-old patient presenting with irregular bleeding. The endometrial curetting showed a dense lymphomatous infiltrate demonstrating highly infiltrative aggressive features with characteristic angiocentric, partially angiodestructive growth pattern and accompanying focal necroses. The lymphoma cells displayed a CD3ε/CD56/TIA-1/granzyme-B-positive and CD5/CD4/CD8/TCRγδ-negative immunophenotype, proved to be positive for Epstein-Barr virus by EBER in situ hybridization, and revealed no clonal T-cell receptor gene rearrangement. The diagnosis of uterine extranodal NK-cell lymphoma, nasal-type was made. Clinically, the disease was limited to the uterus at diagnosis, but progressed rapidly, and the patient died within 5 months due disseminated lymphoma, irrespective of intensive chemotherapy. Genuine NK-cell lymphomas occurring in the uterus as primary site seem to be rare making the therapeutic decisions extremely complicated.

Amplification of thymosin beta 10 and AKAP13 genes in metastatic and aggressive papillary thyroid carcinomas.

Papillary thyroid carcinoma (PTC) is the most common well-differentiated thyroid cancer. Although the great majority of the cases exhibit an indolent clinical course, some of them develop local invasion with distant metastasis, and a few cases transform into undifferentiated/anaplastic thyroid carcinoma with a rapidly lethal course. To identify gene copy number alterations predictive of metastatic potential or aggressive transformation, array-based comparative genomic hybridization (CGH-array) was performed in 43 PTC cases. Formalin-fixed and paraffin-embedded samples from primary tumours of 16 cases without metastasis, 14 cases with only regional lymph node metastasis, and 13 cases with distant metastasis, recurrence or extrathyroid extension were analysed. The CGH-array and confirmatory quantitative real-time PCR results identified the deletion of the EIF4EBP3 and TRAK2 gene loci, while amplification of thymosin beta 10 (TB10) and Tre-2 oncogene regions were observed as general markers for PTC. Although there have been several studies implicating TB10 as a specific marker based on gene expression data, our study is the first to report on genomic amplification. Although no significant difference could be detected between the good and bad prognosis cases in the A-kinase anchor protein 13 (AKAP13) gene region, it was discriminative markers for metastasis. Amplification in the AKAP13 region was demonstrated in 42.9% and 15.4% of the cases with local or with distant metastasis, respectively, while no amplification was detected in non-metastatic cases. AKAP13 and TB10 regions may represent potential new genomic markers for PTC and cancer progression.