Case Of T-cell Lymphoblastic Lymphoma Research Articles

Histopathology and Immunohistochemical profile of mediastinal lymphoma in Dr. Soetomo General Hospital

Mediastinal lymphoma is a rare tumor. Approximately 10% of primary mediastinal lymphoma occur in mediastinum. In this study we look for sex and age characteristics, histopathology and immunohistochemical profile of mediastinal lymphoma. Data were collected from the Anatomical Pathology laboratory Dr. Soetomo archives from January 2016 to August 2018. Seventeen cases of mediastinal lymphoma were found predominantly in males (76.47 %). The age range was between 17 and 64 years old. Distribution of tumor type was as follows: Non-Hodgkin’s Lymphoma, B-cell type high grade (Ki67 > 30%) 17.65 % and Non-Hodgkin’s Lymphoma, B-cell type low grade (Ki67 <30%) 11.76%, Non-Hodgkin’s Lymphoma, T-cell type high grade 11.76%, Non-Hodgkin’s Lymphoma unknown subtype 35.29%, Classical Hodgkin’s Lymphoma (CHL) 17.65%, T-cell Lymphoblastic Lymphoma (T-LBL) 5.88%. Histologically, Non-Hodgkin’s Lymphoma showed a diffuse pattern consisting of anaplastic lymphoid cells, pleomorphic nuclei, coarse chromatin, thin cytoplasm between fibrotic stroma and the immunohistochemistry profile showed positive for CD20 in NHL B-cell type. CD3 were positive in Peripheral T-cell Lymphoma and T-Lymphoblastic Lymphoma (T-LBL). Classical Hodgkin’s Lymphoma showed large cells (reed-stenberg cells) and Hodgkin’s cells dispersed between an inflammatory background, CD30 were positive in CHL cases. Tdt was positive in T-LBL cases.

Genomic landscape of T-cell lymphoblastic lymphoma.

ObjectiveT-cell lymphoblastic lymphoma (T-LBL) is an aggressive neoplasm of precursor T cells, however, detailed genome-wide sequencing of large T-LBL cohorts has not been performed due to its rarity. The purpose of this study was to identify putative driver genes in T-LBL.MethodsTo gain insight into the genetic mechanisms of T-LBL development, we performed whole-exome sequencing on 41 paired tumor-normal DNA samples from patients with T-LBL.ResultsWe identified 32 putative driver genes using whole-exome sequencing in 41 T-LBL cases, many of which have not previously been described in T-LBL, such as Janus kinase 3 (JAK3), Janus kinase 1 (JAK1), Runt-related transcription factor 1 (RUNX1) and Wilms’ tumor suppressor gene 1 (WT1). When comparing the genetic alterations of T-LBL to T-cell acute lymphoblastic leukemia (T-ALL), we found that JAK-STAT and RAS pathway mutations were predominantly observed in T-LBL (58.5% and 34.1%, respectively), whereas Notch and cell cycle signaling pathways mutations were more prevalent in T-ALL. Notably, besides notch receptor 1 (NOTCH1), mutational status of plant homeodomain (PHD)-like finger protein 6 (PHF6) was identified as another independent factor for good prognosis. Of utmost interest is that co-existence of PHF6 and NOTCH1 mutation status might provide an alternative for early therapeutic stratification in T-LBL. ConclusionsTogether, our findings will not only provide new insights into the molecular and genetic mechanisms of T-LBL, but also have tangible implications for clinical practice.

Characterization of Immunophenotypic Aberrancies in Adult and Childhood Acute Lymphoblastic Leukemia: Lessons from Regional Variation.

Background & Objective:Although the antigen expression patterns of acute lymphoblastic leukemia (ALL) are well known, this study attempted to evaluate commonly used immune markers for immunophenotyping of acute leukemia to set the minimum of necessary diagnostic panels by flow cytometry.Methods:This study evaluated 89 patients referred from all over the country to the Iranian Blood Transfusion Organization (IBTO) in Tehran from 2013 to 2015. We compared the immunophenotype patterns of childhood and adult ALLs including 69(77.5%) B-cell lymphoblastic lymphoma (B-LBL), 2(2.2%) Burkitt’s lymphoma (BL), and 18(20.2%) T-cell lymphoblastic lymphoma (T-LBL) cases using flowcytometry with broad antibody panel.Results:CD19 and CD79a were the most frequent markers for B-LBL while CD7 was the most sensitive marker in T-LBL; the frequency of CD7, CD3, and CD5 antigens were 100%, 38.9%, and 88.9%, respectively. TdT+/CD34+ was significantly higher in adult B-LBLs than children, which indicates blast cells are more immature in adults. In addition, CD10 and cCD79a were significantly higher in children with B-LBL like as CD5 and CD8 in children with T-LBL. Aberrant phenotypes including CD13, CD33, CD7, and CD117 were found in 7(10.1%) cases of B-LBL. These phenotypes were CD117, HLA-DR, and CD33 in 7(38/9%) cases of T-LBL. Expression of CD117 aberrant myeloid antigen was significantly more associated with T-LBL than with B-lineage ALL.Conclusion:Significant differences were observed in antigen-expression patterns between adult and childhood ALLs. Further studies are needed to correlate specific markers with recurrent cytogenetic abnormalities and prognosis with therapeutic response.

Comprehensive Genomic Profiling of Adult T-Cell Lymphoblastic Lymphoma in Chinese Patients

Background: T-cell lymphoblastic lymphoma (T-LBL) is a rare, aggressive neoplasm of precursor T cells that occurs mostly in adolescents and young adults. Extensive genomic analyses of T-LBL have discovered genes encoding adhesion molecules and extracellular matrix proteins in samples from T-LBL patients, with most studies being performed on patients in the Western hemisphere. We sought to define the mutational profile of T-LBL in Chinese patients. Methods: We collected 15 adult T-LBL biopsies from one center in China with confirmed pathologic diagnosis and treatment information. Median cohort age at diagnosis was 26.0 years. The male/female ratio was 13/2. DNA was extracted from formalin-fixed paraffin embedded samples, and targeted deep next generation sequencing (NGS) analyses were performed. Results: Mutation features were revealed in this Chinese T-LBL analysis. NOTCH1 mutations were found in 67% (10/15) of T-LBL patients (pts) with the highest mutation frequency. PHF6 mutations were seen in 53% (8/15) of cases. TP53mutations were seen in 53% (5/15) of T-LBL cases. JAK1 and JAK3 mutations were seen in 27% (4/15)of T-LBL cases respectively. Mutations at histone modification genesincluded SUZ12 (20%, 3/15), EZH2(13%, 2/15), and EP300 (7%,1/15). Other mutations included PTEN(27% 4/15), DNM2 (27% 4/15). Discussion: The aim of our study was to reveal the genomic landscape of Chinese T-LBL. The cohort collection was unbiased, the patients' features were in concordance with previous reports that the disease of T-LBL is mostly found in the young patients and shows male predominance. The most predominant somatic mutation wasNOTCH1, which is also usually seen in T-ALL. Mutations at histone modification genes were also seen in our study. NGS studies have identified epigenetic modifiers mutations as a hallmark of T-LBL, highlighting an attractive therapeutic target in this disease. In summary, this effort has identified novel mutation features in Chinese T-LBLs that can potentially lead to more effective treatments in Chinese population. Disclosures Li: Guangdong Province Hospital: Employment.

T-cell lymphoblastic lymphoma infiltration into the thyroid gland: A rare case report

Lymphomas account for approximately 2% of all malignancies of the thyroid gland. Infiltration of T-cell lymphoblastic lymphoma (T-LBL) into the thyroid gland is rare. This case is presented on account of the rarity of T-LBL infiltration into the thyroid gland. A 22-year-old male, diagnosed case of T-LBL by left cervical lymph node biopsy and immunohistochemistry (IHC) and on chemotherapy, presented with a thyroid swelling after 6 months of diagnosis of T-LBL. Ultrasound imaging of the neck showed symmetrically enlarged thyroid gland. Fine needle aspiration cytology of the thyroid swelling showed infiltration of lymphoma cells into the thyroid gland, which was confirmed with IHC. T-LBL is a high-grade lymphoma which rarely infiltrates the thyroid gland. Intensive chemotherapy regimens and long-term maintenance therapy improve the prognosis of T-LBL.

Primary Analysis of the Effect of Hematopoietic Stem Cell Transplantation in the Treatment of 98 Cases of T Cell Lymphoma

Objective To investigate the effect of hematopoietic stem cell transplantation in the treatment of T cell lymphoma.Methods The clinical data of 98 patients with T cell lymphoma (T-NHL) treated by hematopoietic stem cell transplantation from June 2001 to December 2015 in our center were retrospectively analyzed.Results (1) 98 T-NHL patients, 62 males and 36 females, aged 7-64 years (median age 27 years). Disease subtypes: 30 cases of T-cell lymphoblastic lymphoma, 24 cases of NK / T cell lymphoma, 22 cases of peripheral T-cell lymphoma (PTCL, NOS), 19 cases of variable large cell lymphoma (ALCL), and 3 cases of subcutaneous panniculitic T cell lymphoma. Transplantation type: 55 cases of autologous transplantation, 43 cases of allogeneic transplantation. The follow-up was ended in April 2016, the duration of following-up ranged from 2 to 178 months (median follow-up time was 20 months). (2) 55/98 patients with autologous hematopoietic stem cell transplantation (auto-HSCT), 31 males and 24 females, aged 7-64 years (median age 27 years). Disease subtypes: 19 cases of anaplastic large cell lymphoma (ALCL) , 15 cases of NK / T cell lymphoma, 13 cases of peripheral T-cell lymphoma (PTCL, NOS), 5 cases of T cell lymphoblastic lymphoma, and 3 cases of subcutaneous panniculitic T cell lymphoma. The 3 year overall survival (OS) and disease-free survival (EFS) were 79.6% and 58.4%, respectively. (3) 43/98 patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT), 31 males and 12 females, aged 8-52 years (median age 27 years). Disease subtypes: 25 cases of T lymphoblastic lymphoma, 9 cases of NK / T cell lymphoma, and 9 cases of peripheral T cell lymphoma (PTCL, NOS). Transplant subtypes: 23 cases of haploidentical transplantation, 12 cases of HLA-identical sibling donor transplantation, 6 cases of HLA-identical unrelated donor transplantation, and 2 cases of umbilical cord blood transplantation. The 3 year EFS and OS of allo-HSCT were 58.3% and 56.7%, respectively. (4) 38/55 patients with CR1 status before auto-SCT, 3 year OS and EFS were 82.8% and 60.7% respectively. 17/55 patients with non-CR1 status before auto-HSCT, 3 year OS and EFS were 57.2% and 47.8%. Compared with non-CR1 group, the OS and PFS of CR1 group were better, but failed to show significant statistical difference (p>0.05), which may be related to the less number of cases and sub types of the two groups do not match the correlation. (5) 31/98 cases were young and high-risk patients (age < 60 years, IPI score ≥3).16/31 cases treated with allo-HSCT, the 3 year OS and EFS were 73.1% and 70.5%. 15/31 cases treated with auto-HSCT, the 3 year OS and EFS were 48.4% and 27.8%. The OS and EFS of the two groups were significantly different (P=0.001).Conclusion Hematopoietic stem cell transplantation can improve the efficacy of T cell lymphoma. Auto-HSCT in first complete remission (CR1) enables T-NHL patients with greater benefit. Allo-HSCT can cure some T-NHL patients, which can be considered for the treatment of young and high-risk T-NHL patients. DisclosuresNo relevant conflicts of interest to declare.

Primary orbital precursor T-cell lymphoblastic lymphoma: Report of a unique case.

Primary T-cell lymphoblastic lymphoma (T-LBL) in the eye region is very rare. The present study described a unique case of T-LBL involving the extraocular muscles. A 22-year-old male patient presented with a 3-week history of headache, reduced visual acuity and edema of the left eye. Clinical examination revealed left-sided exophthalmus, periorbital edema, chemosis, and reduced motility of the left eye. A magnetic resonance imaging scan revealed thickening of the left orbital muscles and a positron emission tomography-computed tomography scan also demonstrated activity in a subclavicular lymph node. Histopathological analysis of both lesions revealed infiltration by medium-sized neoplastic lymphoid cells with a high nuclear-cytoplasmic ratio and a high mitotic index. Immunostaining revealed positivity for CD2, CD3, CD99, Tia-1, and GranzymB, and variable positivity for CD4. There was no involvement of the bone marrow. Based on the clinical and histopathological findings, a diagnosis of T-LBL was made. There was no evidence of NOTCH1 mutation or rearrangements of the ETV6 and MLL genes and high-resolution array-based comparative genomic hybridization (arrayCGH) analysis revealed a normal genomic profile. The patient received chemotherapy according to the high-risk NOPHO protocol, followed by myeloablative allogenic bone marrow transplantation. At 35 months after diagnosis, the patient remained in complete first remission, but without light perception on his left eye. To the best of our knowledge, this is the first report of a case of T-LBL involving the extraocular muscles. Although primary T-LBL in the eye region is very rare, our findings demonstrate that lymphoma should be considered in the differential diagnosis of patients with similar symptoms.

Abstract 3092: PTEN mutations correlate with relapse risk in pediatric T-cell lymphoblastic lymphoma patients: Validation of whole exome sequencing results

Abstract Prognosis of T-cell lymphoblastic lymphoma (T-LBL) in children and adolescents is poor in case of relapse, but pathogenetic knowledge of the disease which may lead to the establishment of prognostic parameters is still extremely limited. Recently, it was reported that molecular aberrations like NOTCH1 mutations or loss of heterozygosity at chromosome 6q (LOH6q) significantly correlate with relapse risk and survival in patients with T-LBL treated according to NHL-BFM protocols. PI3-kinase (PI3K) consists of two subunits (PIK3R1 and PIK3CA); its activity is repressed by the tumor suppressor PTEN. Mutations in PIK3R1, PIK3CA and PTEN leading to increased cell proliferation have been reported for different cancer types. Next generation sequencing (NGS) technologies facilitate in-depth genome-wide insight into different types of cancer. We performed NGS of pediatric T-LBL patients and validated results regarding the PI3K pathway in a large cohort of patients with respect to mutational frequencies and prognostic relevance. We analyzed five pediatric T-LBL cases by whole exome sequencing. A total of 107 cases were available for validation of candidate genes. All patients were treated according to NHL-BFM regimen for LBL. A lymphoma-specific aberration in PIK3R1 was identified via whole exome sequencing and verified by Sanger sequencing. Mutation frequencies in selected exons of PIK3R1, PIK3CA and PTEN were investigated in 107 cases. Five patients (5%) showed mutations in PIK3R1, 7 (7%) in PIK3CA, and 16 (15%) in PTEN. In 22% of the cases (24/107), mutations in at least one of the genes could be detected. These aberrations correlated with inferior probability of event-free survival (pEFS) in the analyzed cohort (pEFS at 5 years 0.80±0.05 vs. 0.61±0.10; p&amp;lt;0.02). This depended on mutations in PTEN, as the effect was more prominent when these aberrations were considered separately (pEFS 0.80±0.04 vs. 0.53±0.13; p&amp;lt;0.005). Although PTEN is reported to be transcriptionally repressed by NOTCH1, NOTCH1 mutations seem to set off the negative effect of PTEN mutations on outcome instead of acting synergistically in T-LBL. The pEFS of patients with mutations in both genes was 0.88±0.12 (N=10), whereas patients with mutations in PTEN, but wild-type NOTCH1 (N=6), displayed a significantly inferior pEFS compared to all other patients (0.17±0.15 vs. 0.80±0.04; p&amp;lt;0.0001). Moreover, in a Cox regression model with LOH6q, NOTCH1, PTEN and an interaction term (NOTCH1 WT/PTEN mutated) only the interaction was significant (p=0.001). Thus, we identified mutations in PTEN as another molecular parameter which is significantly associated with prognosis in pediatric T-LBL patients treated according to NHL-BFM protocols. Validation studies on larger series are needed to evaluate the genetic interplay of these alterations and their impact on pediatric T-LBL pathogenesis. Citation Format: Bettina R. Bonn, Andreas Huge, Marius Rohde, Martin Zimmermann, Reinhard Voss, Wilhelm Woessmann, Lorenz Trümper, Claudia Rossig, Heribert Juergens, Jochen Seggewiss, Birgit Burkhardt. PTEN mutations correlate with relapse risk in pediatric T-cell lymphoblastic lymphoma patients: Validation of whole exome sequencing results. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3092. doi:10.1158/1538-7445.AM2014-3092

Precursor T-cell lymphoblastic lymphoma extensively involving the mediastinum, pleura and pericardium: A case report.

Precursor T-cell lymphoblastic lymphoma (T-LBL) is a rare type of malignant lymphoma, with clinical manifestations including diaphragmatic lymph node enlargement, accompanied by local oppression and/or systemic lymphoma symptoms. However, extensive involvement of the mediastinum, pleura and pericardium is rare in T-LBL cases. This is the case report of a T-LBL extensively involving the mediastinum, pleura and pericardium in a 54-year-old woman. The patient complained of anhelation, chest tightness and tiredness for ~3 months. A computed tomography (CT) scan of the chest revealed a diffuse mass of soft tissue density involving the mediastinum, pleura and pericardium. Several thoracocenteses indicated inflammatory changes and cytological examination of the pleural fluid and pleural biopsy under CT guidance identified no heterotypic cells. As 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT imaging revealed a diffused moderate FDG uptake (maximum standard uptake value of 4) by the mediastinum, pleura and cardiac sac, we diagnosed a malignant lymphoma. We subsequently successfully performed needle biopsy under PET/CT guidance according to the PET/CT images and the diagnosis of T-LBL was pathologically confirmed.

T-cell lymphoblastic lymphoma in a child presenting as rapid thyroid enlargement.

The majority of lymphomas of the head and neck in children present as an enlarged cervical lymph node; however, malignant lymphoma arising from the thyroid gland is extremely rare. We report a case of a 12-year-old child who was admitted to our hospital because of a history of rapidly progressive anterior neck swelling. Histopathological studies revealed this case to be T-cell lymphoblastic lymphoma. We performed chemotherapy and the patient has kept recurrence-free survival for 18 months after the beginning of the treatment. This is the 2nd case of T-cell lymphoblastic lymphoma in the thyroid gland in a child.

T-cell lymphoblastic lymphoma of Tenon’s capsule: an unusual presentation

Lymphoid neoplasms of the orbit account for approximately 6-8 % of all orbital tumors and 15 % of all ocular adnexal tumors. We report an unusual case of T-cell lymphoblastic lymphoma occurring in a 30-year-old man, presenting as red, painless, firm swelling in the Tenon's capsule of the eye.

Determination of Frequency of Epstein-Barr Virus in Non-Hodgkin Lymphomas Using EBV Latent Membrane Protein 1 (EBV-LMP1) Immunohistochemical Staining

The presence of Epstein-Barr virus (EBV) in Non-Hodgkin's lymphoma can be identified by immunohistochemistry for detection of EBV latent membrane protein (LMP). The role of EBV as an etiologic agent in the development of non-Hodgkin lymphoma has been supported by detection of high levels of latent membrane protein 1 (LMP-1) expression in tumors. However, no study has been conducted in a Pakistani population up till now to determine the frequency of Epstein-Barr virus positivity. The objective of our study was to determine a value for non-Hodgkin lymphoma patients using EBV LMP-1 immunostaining in our institution. This study was carried out at the Department of Histopathology, Armed Forces Institute of Pathology (AFIP), Pakistan from December 2011 to December 2012. It was a cross sectional study. A total of 71 patients who were diagnosed with various subtypes of NHL after histological and EBV LMP-1 immunohistochemical evaluation were studied. Sampling technique was non-probability purposive. Statistical analysis was achieved using SPSS version 17.0. Mean and SD were calculated for quantitative variables like patient age. Frequencies and percentages were calculated for qualitative variables like subgroup of NHL, results outcome of IHC for EBV and gender distribution. Mean age of the patients was 53.6 ± 16 years (Mean ± SD). A total of 50 (70.4%) were male and 21 (29.6%) were female. Some 9 (12.7%) out of 71 cases were positive for EBV-LMP-1 immunostaining, 2 (22.2%) follicular lymphoma cases, 1 (11.1%) case of T-cell lymphoblastic lymphoma, 4 (44.4%) cases of diffuse large B cell lymphomas, 1 (11.1%) mantle cell lymphoma and 1 (11.1%) angioimmunoblastic T cell lymphoma case. In our study, frequency of EBV in NHL is 12.7% and is mostly seen in diffuse large B cell lymphoma. This requires further evaluation to find out whether this positivity is due to co-infection or has a role in pathogenesis.

Chromosome abnormalities in advanced stage T‐cell lymphoblastic lymphoma of children and adolescents: a report from Japanese Paediatric Leukaemia/Lymphoma Study Group (JPLSG) and review of the literature

T-cell acute lymphoblastic leukaemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) are combined into one category as T lymphoblastic leukaemia/lymphoma in the current World Health Organization (WHO) classification. However, there is still ongoing discussion on whether T-ALL and T-LBL are two separate entities or represent two variant phenotypes of the same disease. Cytogenetic analysis has been used to identify the molecular background of haematological malignancies. To compare the distribution of chromosomal abnormalities of T-ALL and T-LBL, large series of cytogenetic data are required, but are absent in T-LBL in contrast to the abundant data in T-ALL. Among 111 T-LBL cases in our clinical trial, we obtained complete cytogenetic data from 56 patients. The comparison between our cytogenetic findings and those from three published T-LBL studies revealed no significant difference. However, meta-analysis showed that translocations involving chromosome region 9q34 were significantly more common in T-LBL than in T-ALL. In particular, four out of the 92 T-LBL cases, but none of the 523 paediatric T-ALL cases, showed translocation t(9;17)(q34;q22-23) (P=0·0004). Further studies are needed for the possible linkage between abnormal expression of genes located at 9q34 and/or 17q22-23 and the unique 'lymphoma phenotype' of T-LBL.

Synchronous FIP1L1–PDGFRA‐positive chronic eosinophilic leukemia and T‐cell lymphoblastic lymphoma: a bilineal clonal malignancy

Several reports of successful empirical treatment of idiopathic hypereosinophilic syndrome with imatinib led to the recent identification of the FIP1L1-PDGFRA fusion gene rearrangement, which characterizes a distinctive group of chronic eosinophilic leukemias. This fusion gene can be detected in eosinophils, neutrophils, mast cells, T cells, B cells and monocytes in FIP1L1-PDGFRA-positive hypereosinophilic patients suggesting a multilineage involvement. Furthermore, the same FIP1L1-PDGFRA rearrangement was identified in patients with hypereosinophilia and atypical mast cell proliferations, raising the question of a disease with two concomitant lines of differentiation. In addition, a recent report noted two cases with the association of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia and T-cell lymphoblastic lymphoma (T-LBL). We report here the only third case of synchronous chronic eosinophilic leukemia and T-LBL, both associated with a FIP1L1-PDGFRA fusion transcript, confirming the occurrence of such disease and suggesting a clonal proliferation with two lines of differentiation probably arising from a primitive multipotent medullary stem cell.

Treatment with bortezomib in a patient with heavily pretreated refractory T‐cell lymphoblastic lymphoma

T-cell lymphoblastic lymphomas are highly aggressive non-Hodgkin's lymphoma (NHL) and account for approximately 3% of all adult NHL histologies, with poor prognosis. We describe a 38-year-old patient with T-cell lymphoblastic lymphoma, who responds to bortezomib and doxorubincin combination, following a failure of conventional chemotherapy. Two months after treatment, the patient showed near complete remission of the lymphadenopathy. These data suggest a possible synergistic effect with bortezomib in combination with doxorubincin and dexamethasone. To our knowledge, this is the first case of T-cell lymphoblastic lymphoma treated with bortezomib.

Molecular cytogenetic study of 126 unselected T-ALL cases reveals high incidence of TCRβ locus rearrangements and putative new T-cell oncogenes

Chromosomal aberrations of T-cell receptor (TCR) gene loci often involve the TCRalphadelta (14q11) locus and affect various known T-cell oncogenes. A systematic fluorescent in situ hybridization (FISH) screening for the detection of chromosomal aberrations involving the TCR loci, TCRalphadelta (14q11), TCRbeta (7q34) and TCRgamma (7p14), has not been conducted so far. Therefore, we initiated a screening of 126 T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma cases and 19 T-ALL cell lines using FISH break-apart assays for the different TCR loci. Genomic rearrangements of the TCRbeta locus were detected in 24/126 cases (19%), most of which (58.3%) were not detected upon banding analysis. Breakpoints in the TCRalphadelta locus were detected in 22/126 cases (17.4%), whereas standard cytogenetics only detected 14 of these 22 cases. Cryptic TCRalphadelta/TCRbeta chromosome aberrations were thus observed in 22 of 126 cases (17.4%). Some of these chromosome aberrations target new putative T-cell oncogenes at chromosome 11q24, 20p12 and 6q22. Five patients and one cell line carried chromosomal rearrangements affecting both TCRbeta and TCRalphadelta loci. In conclusion, this study presents the first inventory of chromosomal rearrangements of TCR loci in T-ALL, revealing an unexpected high number of cryptic chromosomal rearrangements of the TCRbeta locus and further broadening the spectrum of genes putatively implicated in T-cell oncogenesis.

Pathologic diagnoses of core needle biopsies of the mediastinum

To assess the diagnostic accuracy and to study the histologic typing of mediastinal lesions using core needle biopsies. The histopathology and immunophenotype of 65 mediastinal core needle biopsy specimens were studied retrospectively by light microscopy and immunohistochemical staining (ABC method). Gene rearrangement studies were performed in some of the non-Hodgkin's lymphomas cases using PCR. Follow-up records were also analyzed. Morphologically, all specimens showed a combination of epithelioid cells, lymphoid cells and fibrous tissue in different proportions. The pathologic diagnoses included lymphoma (21 cases), pulmonary carcinoma (20 cases), thymoma (14 cases), thymic carcinoma (4 cases), seminoma (3 cases) and chronic inflammation (1 case). Definitive diagnosis was not possible in 2 cases due to insufficient material. The tumor cells in lymphoma (21 cases) expressed CD20, CD3, TDT, CD30, CD15 or EMA, depending on their histologic subtypes. Tumor cells in the 17 pulmonary carcinoma cases expressed cytokeratin (CK), except 3 cases of small cell carcinoma of lung. Synaptophysin, chromogranin A and neuron-specific enolase were all positive in the 10 cases of small cell carcinoma of lung and 1 case of thymic small cell carcinoma (which was also CD5 negative). The 3 cases of adenocarcinoma of lung showed positivity for thyroid transcription factor-1 (TTF-1) and they were negative for CD5. The 14 thymoma cases expressed CK, CD3 or CD20. The 3 thymic carcinoma cases expressed CK and CD5. Placental-like alkaline phosphatase (PLAP) was positive in 3 seminoma cases which were CK-negative. Immunoglobulin heavy chain gene was rearranged in the 3 cases of diffuse large B-cell lymphoma and 1 B-cell anaplastic large cell lymphoma case. T-cell receptor beta gene was rearranged in 5 T-cell lymphoblastic lymphoma cases. Microscopic assessment of tissue samples from mediastinal core needle biopsies should be made in combination with clinical and radiologic information. Ancillary investigations, including immunohistochemical staining and/or gene rearrangement studie, are needed in both non-lymphoma and lymphoma cases of mediastinum.

T-cell lymphoblastic lymphoma of the lower jaw in a young child: A case report

Among non-Hodgkin's lymphomas occurring in childhood two major histologic subgroups can be identified: (1) Burkitt's lymphoma and (2) T-cell lymphoblastic lymphoma, an uncommon high-grade malignant non-Hodgkin's lymphoma. Although Burkitt's lymphoma with maxillofacial involvement is a well-documented disease, T-cell lymphoblastic lymphoma in the perioral region is rare. An unusual case of T-cell lymphoblastic lymphoma with initial oral manifestation in an 18-month-old child is presented.

Acute Myeloid Leukaemia Following Matched Allogeneic Bone Marrow Transplantation for T-Cell Lymphoblastic Lymphoma.

It is now commonly acknowledged that cells from some acute leukaemias may bear both myeloid and lymphoid markers at diagnosis, or that relapse following initial treatment may occur, with blast cells phenotypically different from those seen at initial diagnosis. Patients showing evidence of bi-linear disease seem to carry a worse prognosis for cure. Here, a case of T-cell lymphoblastic lymphoma is reported, who relapsed with acute myeloblastic leukaemia, following allogeneic bone marrow transplantation. Early diagnosis of disease with lymphoid and myeloid features is therefore warranted, so that intensive treatment programmes may be offered, in anticipation of permanent cure.

Specific Phenotyping of T-Cell Proliferations in Formalin-Fixed Paraffin-Embedded Tissues: Use of Antibodies to the T-Cell Receptor βF1

Antibody beta F1 to a common framework determinant of the beta subunit of the T-cell receptor (TCR) was used as a specific phenotypic marker for T-cell differentiation in malignant lymphomas. Sensitivity of immunoperoxidase staining in paraffin sections was enhanced by pronase pretreatment, overnight incubation of primary antibody in Tween 20, and use of streptavidin horseradish peroxidase complexes to amplify the reaction. All 43 cases of B-cell lymphoma were negative for TCR. Reed Sternberg (RS) cells in 3 of 20 cases of Hodgkin's disease exhibited cell membrane staining for TCR (all nodular sclerosis type), further evidence that some RS cells may be T-cell derived. Twenty-nine of 44 cases of T-cell lymphoma expressed TCR (66%). These included 11 of 12 cases of peripheral T-cell lymphoma (PTCL) of small and mixed cell type, 8 of 9 cases of lymphoepithelioid cell (Lennert's) lymphoma, and 2 of 4 cases of T-cell lymphoblastic lymphoma. Loss of immunoreactivity for TCR occurred in lymphomas of large or activated T-cell type, including 7 of 9 cases of T-cell immunoblastic lymphoma and 3 of 4 cases of large cell PTCL. Antibody beta F1 is a specific and relatively sensitive marker of T-cell phenotype in formalin-fixed paraffin sections of malignant lymphomas.