Cases Of Lymphoblastic Lymphoma Research Articles

Myasthenia gravis and lymphoblastic lymphoma involving the thymus: A rare association

Myasthenia gravis (MG) is an autoimmune neuromuscular junction disease. An association between thymic epithelial neoplasms and MG is well known. However, it is rarely associated with hematologic malignancies. In particular, very few cases of lymphoblastic lymphoma (LL) involving the thymus and MG have been reported.

Clinicopathological Study of Primary Pediatric Gastrointestinal Lymphomas.

Background:Primary gastrointestinal lymphomas (PGIL) are uncommon in children and account for <5% of all pediatric malignancies. The objective of our study was to analyze the prognostic factors of pediatric PGILs with reference to its histological subtypes, stage, and outcomes using immunohistochemistry.Materials and Methods:Twenty cases were studied over 11 years. Clinicopathological profiles, histological details, and immunohistochemical (IHC) profiles were analyzed.Results:The mean age at the presentation was 6 years. Using IHC stains (CD CD10, CD19, CD20, CD3, terminal deoxynucleotidyl transferase, BCL 2 and 6, PAX 5, and MUM1), diffuse large B-cell lymphoma (DLBCL) was most prevalent (45%), followed by Burkitt lymphoma (35%) and lymphoblastic lymphoma (20%). DLBCLs (9) were classified using the Han's algorithm. Six were activated B-cell and 3 were germinal center B-cell subtypes. The cases of lymphoblastic lymphoma and those in Stage I disease had the best prognosis.Conclusion:Pediatric PGILs have variable presentation, outcomes, and diverse treatment modalities depending on the histological subtypes. A panel of IHC stains can be a useful adjunct for the categorization and prognosis of pediatric PGILs.

T-cell lymphomas in a tertiary care center of Mangalore

The clinicomorphology and immunohistochemical features of T-cell lymphomas have been documented. The aim of the study was to evaluate the spectrum of clincopathological features of T-cell lymphoma with immunohistochemistry correlation in a tertiary care center. The present study was conducted on 19 biopsy specimens received from the Department of Pathology, Kasturba Medical College, from referral hospitals of Mangalore city. Cases of nodal and extranodal T-cell lymphomas diagnosed between January 2012 and December 2015 were selected with evaluation of clinical data, histomorphological features, and immunophenotyping. Appropriate panel of antibodies was chosen after morphological evaluation of the cases. Of the 19 cases of T-cell lymphomas, 14 were nodal disease and 5 were extranodal disease. Among the nodal lymphomas, five were primary peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), four were cases of lymphoblastic lymphoma, three were cases of angioimmunoblastic T-cell lymphomas, and two were cases of anaplastic large-cell lymphoma anaplastic lymphoma kinase (ALK) negative. In extranodal disease, two were mycosis fungoides of skin, one case each of subcutaneous panniculitis-like T-cell lymphoma, T-cell lymphoblastic lymphoma of tonsil, and T-cell lymphoma of the stomach. The diagnosis and subclassification of PTCLs is necessary for therapeutic and prognostic purposes.

Clinical Features and Prognosis of 74 Cases of Lymphoblastic Lymphoma

Clinical Features and Prognosis of 74 Cases of Lymphoblastic Lymphoma

Lymphoma with mediastinal bulky masses: a clinical analysis of 17 cases

Objective To analyze the clinical characteristics, pathological types, treatment modalities of lymphoma patients with mediastinal bulky masses. Methods The clinical data of 17 lymphoma patients with mediastinal bulky masses from January 2010 to January 2017 in Beijing Friendship Hospital were analyzed retrospectively. Results All the patients were pathologically diagnosed, including 6 cases of primary mediastinal large B-cell lymphoma, 5 cases of lymphoblastic lymphoma, 3 cases of Hodgkin lymphoma and 3 cases of other non-Hodgkin lymphoma. Four cases with bulky disease were treated with combined chemoradiotherapy regimen, 7 cases were treated with combined chemotherapy, 5 cases were treated with combined chemotherapy regimens followed by autologous bone marrow transplantation and 1 case was treated with high dose chemotherapy followed by allogeneic stem cell transplantation. The effects were evaluated after the final treatments. Twelve patients achieved complete remission, 1 case achieved partial remission, 1 case achieved stable disease, 1 case achieved progressive disease and 3 cases died. Conclusions The prognosis of lymphoma patients with mediastinal bulky masses is related with histopathology and treatment response. Combined treatment modalities including chemoradiotherapy regimen and chemotherapy regimen followed by autologous or allogeneic stem cell transplantation are helpful to improve treatment effects. Key words: Lymphoma; Mediastinal neoplasms; Biomedical research

Endoscopic Ultrasound-Guided Fine Needle Aspiration Biopsy for Diagnosis of Intra-Abdominal Lymphoma without Accessible Peripheral Lymphadenopathy

Introduction: Endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) is considered the procedure of choice for the diagnosis and staging of intra-abdominal non-Hodgkin’s lymphoma (NHL) without accessible peripheral lymphadenopathy. However, diagnosis and subclassification lymphoma by FNAB is often challenging due to variable cellularity and lack of architecture. Recent advances of ancillary techniques such as immunohistochemical staining, flowcytometry (FCM), fluorescence in situ hybridization (FISH) analysis and molecular analysis allowed classify lymphoma more precisely, although sufficient information can be obtained through this procedure remained undetermined. The present study was performed to evaluate the yield of EUS-FNAB using a standard 19 or 22-gauge needle for diagnosis and subclassification of lymphoma, assessing the feasibility of immunohistological, FCM, molecular and cytogenetic assessments.Methods: Between April 2008 and July 2014, 90 patients with malignant lymphoma who had an intra-abdominal mass without accessible peripheral lymphadenopathy underwent EUS-guided fine needle aspiration biopsy at our hospital. All patients received positron emission tomography/computed tomography and had 2-deoxy-2-(18F)fluoro-D-glucose-avid lesions in abdomen before examination. The aspirated materials were processed for flowcytometry (FCM), molecular analysis of immunoglobulin heavy (IgH) and T-cell receptor (TCR) gene rearrangement, cytogenetic analysis by conventional G banding, and FISH analysis, in addition to standard histopathological studies. Patients’ baseline data, including age, sex, laboratory examinations, imaging studies, and final diagnosis of lymphoma, were collected and examined to determine the feasibility and sensitivity for diagnosis and subclassification of lymphoma.Results: The mean of the diameter of mass was 37mm (9.7-149mm). Among the 90 patients, conventional G banding, FCM analysis, standard cytogenetic analysis, and FISH were successfully performed in 67 (74%), 78 (87%), 44 (49%), and 58 (64%) cases, respectively. G banding analysis were successful in 45 patients (67%) that showed normal karyotype in 5 cases (7%), t(14;18)(q32;q21) in 7 cases (10%), t(8;14)(q24;q32) in one case, and complex abnormality in 32 cases (48%), respectively. FCM analysis showed immunoglobulin light chain restriction in 48 cases (62%) and were diagnosed as B-cell lymphoma. FCM could not determine the T-cell clonality. Molecular analyses for TCR and/or IgH receptor rearrangements were successful in 35 patients (83%), 31 rearranged in IgH and 4 rearranged in TCR, respectively. There were 32 cases with IgH/Bcl2 fusions by FISH analysis, 26 cases in follicular lymphoma (FL) and 6 cases in diffuse large B-cell lymphoma (DLBCL), respectively. IgH/Bcl6 fusion was seen in 2 case of DLBCL and IgH/C-myc fusion was seen in 1 case of Burkitt lymphoma (BL). Finally, our cohort included 82 B-cell lymphomas (91%) and 8 T-cell lymphomas (9%). Subclassification of lymphoma in accordance with WHO system included 40 cases of FL, 39 cases of DLBCL, one case of BL, 2 cases of lymphoblastic lymphoma, 7 cases of peripheral T cell lymphoma not specified, and one case of angioimmunoblastic lymphoma. Although all of the outpatients were hospitalized until the day after biopsy, there were no serious complications related to this procedure like bleeding, perforation, ileus, and infection.Conclusions: EUS-FNAB using a standard 19 or 22-gauge needle is safe and feasible and has high diagnostic value for subclassification of intra-abdominal lymphoma without accessible peripheral lymphadenopathy. With the use of simultaneous immunophenotyping, molecular, and cytogenetic studies, lymphoma subclassification was possible in most of the cases. DisclosuresNo relevant conflicts of interest to declare.

Solitary Lymphoblastic Lymphoma of the Thoracic Spine

Non-Hodgkin's lymphoma rarely originates from bone, and even more infrequently from a vertebral body. Lymphoblastic lymphoma is a rare type of non-Hodgkin's lymphoma, and results from an abnormality in adaptive immune cells. A 27-year-old man presented with a two-month history of night sweats, weight loss, and severe back pain. Radiological studies demonstrated an osteolytic lesion compressing the subarachnoid space at the T11 level. Posterolateral fusion with decompression was performed and a pathologic examination confirmed lymphoblastic lymphoma of the B-cell precursor type. To our knowledge, this is the first report of solitary lymphoblastic lymphoma from B-cell precursors in of the thoracic spine. Herein, we discuss the presenting symptoms and the management of this rare case of lymphoblastic lymphoma.

Primary lymphoma of breast: a clinicopathologic and prognostic study of 40 cases

To study the clinicopathologic features and prognosis of primary lymphoma of breast. Forty cases of primary breast lymphoma, diagnosed according to the 2008 World Health Organization classification of hematopoietic and lymphoid tumors, were retrospectively studied. Immunohistochemistry was performed by SP method. The follow-up data were analyzed. (1) All the patients were females and the median age was 47 years. Unilateral and bilateral breast involvement were noted in 36 and 4 patients, respectively. The number of tumor were 31 cases (77.5%, 31/40) less than 3, and 9 cases (22.5%, 9/40) were 3 and more than 3. According to Ann Arbor staging system, 33 cases (82.5%) were in stage I to II and 7 cases (17.5%) in stage III to IV. The level of LDH in 9 cases (24.3%, 9/37) went up. For ECOG scores, 34 cases (85.0%) were 0 to 1 score and 6 cases (15.0%) were more than 2 scores. With respect to international prognostic index, 83.8% (31/37) were of score 0 to 2 and 16.2% (6/37) were of score 3 and more than 3. The axillary lymph nodes of 21 patients (53.8%, 21/39) were involved by the malignancy. (2) Histologically, 38 cases (95.0%, 38/40) were classified as B-cell lymphoma [including 27 cases (67.5%) of diffuse large B-cell lymphoma, 8 cases (20.0%) of mucosa-associated lymphoid tissue lymphoma, 2 cases of follicular lymphoma and 1 case of lymphoplasmacytic lymphoma]. The remaining cases included one case of peripheral T-cell lymphoma and one case of lymphoblastic lymphoma. Immunohistochemically, expression of CD20+/- CD79a were demonstrated in the 38 cases (95.0%) of B-cell lymphoma. The staining for CK was negative in all cases. In 33 cases, the positive rates of MUM-1, bcl-6 and bcl-2 were 57.6% (19/33), 30.3% (10/33) and 72.7% (24/33), respectively. Three cases were germinal center B cell phenotype and 21 cases were non-germinal center B cell phenotype. (3) Follow-up information was available in 37 patients (92.5%, 37/40). Twenty-three patients (62.2%, 23/37) were still alive and fourteen ones (37.8%, 14/37) died. For the 27 cases with diffuse large B-cell lymphoma, the five-year and disease-free survival rates were 48.0% and 36.0%, respectively. Primary breast lymphoma is a rare disease entity. Diffuse large B-cell lymphoma is the commonest histologic type and the majority show a non-germinal center B cell phenotype. The level of LDH, number of tumor and international prognostic index are of prognostic significance.

Gastric Helicobacter species as a cause of feline gastric lymphoma: A viable hypothesis

Gastric Helicobacter spp. are associated with chronic inflammation and neoplastic transformation in humans as well as domestic and laboratory species. The present study examined the association of Helicobacter heilmannii ( Hhe) infection in pet cats with feline gastric mucosa associated lymphoid tissue (MALT) lymphoma. Tissues were collected via gastric biopsy or at necropsy from 47 pet cats with clinical signs of gastrointestinal disease, including vomiting and inappetance, and classified as gastritis (14/47), lymphoma (31/37), or normal (2/47). Tissues positive for argyrophilic organisms with Warthin–Starry stain (29/47) were assessed by fluorescent in situ hybridization (FISH) for the presence of Hhe strains 1–4 as well as with a fifth probe that detected Helicobacter salomonis, Helicobacter bizzozeronii, or Helicobacter felis. A significant association of positive Warthin–Starry status with Hhe infection was found in cases of sick cats (22/29; p < 0.05 by Chi-square; χ 2 = 7.034). Interestingly, a significant association between Hhe status and a diagnosis of lymphoblastic or lymphocytic lymphoma was observed as well in a subset of 24 Warthin–Starry positive lymphoma cases: of lymphoblastic lymphoma cases, 13/17 were positive for Hhe ( p < 0.05; χ 2 = 4.854). Hhe strains 2 and 4 were most commonly found (18/29 and 17/29, respectively) among sick cats, although a higher than expected number of cats was also positive for Hhe1, which initial reports have described as rare in cats and common in humans. The association found between a positive Hhe status with the presence of feline gastric lymphoma, especially lymphoblastic lymphoma, argues for the need to conduct prospective studies to better identify the frequency and strain distribution of Hhe infection in both healthy and clinically ill cats, particularly those cats with gastric lymphoma.

Autologous peripheral blood stem cell transplantation in first remission in adult patients with Burkitt and lymphoblastic lymphoma: A single center phase-II study

16517 Background: Optimal therapeutic modality and duration of adult Burkitt and lymphoblastic lymphoma (LL) are still unknown. Despite long-lasting and intensive chemotherapy administration, post-therapy relapses are common. Methods: In this single center phase-II prospective study, high-dose therapy (HDC) and autologous peripheral blood stem cell transplantation (APSCT) was done during the first remission following induction and consolidation therapy for 18 patients with Burkitt (n: 5) and LL (n: 13) without bone marrow and central nervous system involvement at presentation. Cyclophosphamide, vincristine, prednisolone, adriamycin with or without L-asparaginase induction regimen was followed by dexamethasone, cytarabine, and cisplatin consolidation therapy with total body irradiation and cyclophoshamide conditioning. Results: Mean patient age was 24.6 (range: 21–55) years and male to female ratio was 5 to1. 44% (8/18) of the patients were in the intermediate and high-risk groups of International Prognostic Index. Median treatment duration until APSCT was 104 days (range: 87–128). 83% and 17% of the patients were in complete and partial remission before transplantation. One patient with Burkitt lymphoma out of 5 (20%) and 6 patients with LL out of 13 (46%) have died of progression. Overall survival (OS) at 113-month follow-up for all patients was 59.03% with 59.26% of disease-free survival (DFS). However, LL cases revealed OS and DFS rates of 50.35% and 50.77%, respectively. Only one early death (5.5%) was noted due to liver toxicity following HDC and APSCT. Conclusions: In conclusion, this single center phase-II study reveals an acceptable toxicity, short treatment period and high survival rate in adult Burkitt and LL cases, suggesting APSCT to be a good treatment option in the first remission. No significant financial relationships to disclose.

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.

Combined applications of fine needle aspiration cytology and Flow cytometric immunphenotyping for diagnosis and classification of non Hodgkin Lymphoma

Aims and objectivesIn this present study we have evaluated the feasibility of sub-classification of non-Hodgkin's lymphoma (NHL) cases according to World Health Organization's (WHO) classification on fine needle aspiration cytology (FNAC) material along with flow cytometric immunotyping (FCI) as an adjunct.Materials and methodsIn this five years study, only cases suggested or confirmed as NHL by FNAC were selected and FCI was performed with a complete panel of antibodies (CD3, CD2, CD 4, CD5, CD8, CD7, CD10, CD19, CD20, CD23, CD45, κ and λ) by dual color flow cytometry. Both cytologic findings and FCI data were interpreted together to diagnose and sub-classify NHL according to WHO classification. Wherever possible the diagnoses were compared with cytology.ResultsThere were total 48 cases included in this study. The cases were classified on FNAC as predominant small cells (12), mixed small and large cells (5) and large cells (26). In five cases a suggestion of NHL was offered on FNAC material and these cases were labeled as NHL not otherwise specified (NHL-NOS). Flow cytometry could be performed in 45 cases (93.8%) and in rest of the three cases the material was inadequate because of scanty blood mixed aspirate. Light chain restriction was demonstrated in 30 cases out of 40 cases of B-NHL (75%). There were 15 cases each of κ and λ light chain restriction in these 30 cases. With the help of combined FCI and FNAC, it was possible to sub-classify 38 cases of NHL (79%) according to WHO classification. Combined FNAC and FCI data helped to diagnose 9 cases of small lymphocytic lymphoma (SLL), 2 cases of mantle cell lymphoma (MCL), 4 cases of follicular lymphoma (FL), 17 cases of diffuse large B lymphoma (DLBL) and 6 cases of lymphoblastic lymphoma. Histopathology diagnosis was available in 31 cases of NHL out of which there were 14 recurrent and 17 cases of primary NHL. Out of 15 DLBL cases diagnosed on FCI and FNAC, histology confirmed 14 cases and one of these cases was diagnosed as Burkitt's lymphoma on histology. Cases of FL (4), SLL (3) and MCL (2) were well correlated with histopathology. Out of the five cases suggestive of NHL on cytology, histopathology was available in four cases. Histology diagnosis was given as DLBL (1), SLL (1), anaplastic large cell lymphoma (1) and FL transformed into large cell NHL (1). Considering histopathology as gold standard, diagnostic specificity of combined FNAC and FCI was 100% (31/31) and sensitivity in sub-classification was 83.8% (26/31).ConclusionFNAC combined with FCI may be helpful in accurately sub-classifying NHL according to WHO classification. Many of the subtypes of NHL such as FL and MCL which were previously recognized as a pure morphologic entity can be diagnosed by combined use of FNAC and FCI. Other ancillary investigations such as chromosomal changes, cell proliferation markers etc. may be helpful in this aspect.

CD26, together with cell surface adenosine deaminase, is selectively expressed on ALK-positive, but not on ALK-negative, anaplastic large cell lymphoma and Hodgkin's lymphoma

CD26/dipeptidyl peptidase IV is a cell surface antigen with multiple biological functions. Although its involvement in tumor biology has been suggested, the significance of its expression in malignant lymphoma has not been clarified in detail. This study examined the expression of CD26 and cell surface adenosine deaminase (ADA) in 42 cases of Hodgkin's lymphoma (HL) and T-cell lymphoma by immunohistochemistry on frozen sections. CD26 was expressed in three of 14 cases of HL, in four of eight cases of anaplastic large cell lymphoma (ALCL), in two of nine cases of peripheral T-cell lymphoma, in one of six cases of lymphoblastic lymphoma and in none of three cases of adult T-cell lymphoma/leukemia. Expression of cell surface ADA was fully correlated with the expression of CD26 and expression of CD26/ADA in ALCL and HL was also completely correlated with the expression of p80 and epithelial membrane antigen. Of 10 CD26-positive patients, seven had fever and elevated CRP at initial diagnosis and over a median follow-up of 61 months (range, 7 – 152 months) only three survived. This study suggested that CD26 is selectively expressed on ALK-positive, but not on ALK-negative, ALCL and HL. This is also the first report to demonstrate that ADA is coexpressed with CD26 on the cell surface of malignant neoplasms in vivo.

Cytogenetic Findings in Pediatric T-Lymphoblastic Lymphomas: One Institution's Experience and a Review of the Literature

Cytogenetic analyses of lymphomas commonly reveal nonrandom chromosomal abnormalities, but there are relatively few reports in childhood lymphoblastic lymphoma (LL). We retrospectively reviewed G-banded karyotypic analyses performed at Arkansas Children's Hospital between 1990 and 2004. Six children (2 to 20 years old) had LL that presented as mediastinal or cervical masses and had a T-cell immunophenotype and clonal abnormalities. The cytogenetic findings in these 6 patients were as follows: 46,XX,-7,inv(9)(p11q12),der (12)t(7;12)(q11.2;p13),t(16;18)(p13.1;q21),+22 in patient 1; 47,XX,+9,del(9)(q11q22)x2 in patient 2; 72-119, XY,+X,+1,+1, inv(2) (p11q13),-3,+5,+6,+7,+10,-12,-16, -21,-21,-22,+mar in patient 3; 48,XY,+5,+20,t(7;9) (q32;q34) in patient 4; 47 approximately 48,XX,der(10)t(10;14)(q23; q11.2),+12, del(12)(p12)x2, -14,del(16)(q22q22),+?add (19)(p13.3) in patient 5; and 48 approximately 49,XY,+7,+8,t(11;19) (q23;p?13.3),+der(19)t(11;19)[cp20] in patient 6. Eleven chromosome breakpoints in 6 of our patients (7q11, 12p13, 16p13, 18q21, 9q11, 2p11, 2q13, 7q32, and 7q23) have been reported in other patients with acute lymphoblastic leukemia or LL and involved regions containing TEL, ABL, E2A, MLL, and T-cell receptor-alpha genes. A review of the cytogenetic findings of these and other cases of LL reveals that clonal aberrations are common and most frequently involve T-cell receptor gene regions. The aberrations show some features similar to those of acute lymphoblastic leukemia and are not unique to LL, thus furnishing additional evidence of the equivalence of these two diseases. The cytogenetic features of LL may be helpful in the diagnosis of pediatric lymphomas and undifferentiated neoplasms.

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.

Emmprin, a cell surface inducer of matrix metalloproteinases (MMPs), is expressed in T-cell lymphomas.

Degradation of the extracellular matrix by matrix metalloproteinases (MMPs) is a crucial step in tumour invasion and metastasis. In human carcinomas, tumour cell-fibroblast interactions (TFIs) have been demonstrated to play a role in the up-regulation of MMP levels in tumours, and emmprin is a surface molecule on tumour cells that stimulates nearby fibroblasts to produce MMP-1, 2, and 3. T-cell lymphomas frequently show extranodal organ involvement and skin invasion, but a role for TFIs in their invasion has not been examined in detail. This study investigated TFIs in T-cell lymphomas with special reference to emmprin expression and MMP production. Immunohistochemically, only germinal centre cells and some histiocytes expressed emmprin in non-neoplastic lymph nodes (ten cases), while all T-cell lymphomas [14 cases of adult T-cell leukaemia/lymphoma (ATLL), six cases of lymphoblastic lymphoma, seven cases of anaplastic large cell lymphoma, and nine cases of angio-immunoblastic T-cell lymphoma] expressed emmprin strongly and diffusely. FACS analysis of peripheral blood from normal individuals revealed that small fractions of B-cells, T-cells, and monocytes expressed emmprin, whereas emmprin-expressing T-cells were much increased in number, and expressed this protein to a higher level, in ATLL patients. In vitro co-cultures of emmprin-positive HTLV-1-transformed lymphocytes (MT-2) and emmprin-negative human fibroblasts enhanced the production of pro-MMP-2 (gelatinase A) and active MMP-2, compared with cultures of either cell type alone. This stimulation was inhibited by an activity-blocking peptide against emmprin. Moreover, in histopathological sections from patients with ATL skin involvement, MMP-2 was demonstrated in fibroblasts around infiltrating ATL cells, but not in fibroblasts in non-diseased areas. In conclusion, emmprin is overexpressed by T-lymphoma cells, when compared with normal counterparts, and facilitates MMP-2 production via interactions with fibroblasts, which could play a role in stromal invasion by lymphoma cells.

Non-B, non-T neoplasms with lymphoblast morphology: further clarification and classification.

We studied the morphologic, immunohistochemical, and clinical characteristics of 158 cases of lymphoblastic lymphoma. Based on immunophenotyping and cell lineage, cases were classified into B-cell type (CD20,CD19 or CD79a+, n = 53), T-cell type (surface CD3+, n = 84), and non-B, non-T type (B cell marker- and surface CD3-, n = 21). The latter group was further divided based on immunohistochemistry into: 1) CD7+ stem cell lymphoma (CD7+SCL) [CD4-, CD7+, CD33+/-, CD56-], 2) blastic natural killer cell lymphoma (B-NKL) [CD4-, CD7+/-, CD33-, CD56+, CD123-], 3) myeloid/NK precursor cell leukemia (M/NKL) [CD4-, CD7+, CD33+, CD56+], and 4) CD4+CD56+ hematodermic malignancy (CD4+CD56+) type [CD4+, CD7+/-, CD33-, CD56+, CD123+]. The CD7+SCL and M/NKL types frequently exhibited bone marrow invasion and mediastinal masses. All CD4+CD56+ types were associated with skin lesions. B-NKL type is included into Blastic NK lymphoma in new World Health Organization classification with CD4+CD56+ type. But the cases of B-NKL were more reminiscent of CD7+SCL or M/NKL type than the CD4+CD56+ type, both clinically and histologically. We propose that blastic NK lymphoma, a disease entity in the new WHO classification, should be divided into two types based on phenotypes and clinical features. The non-B, non-T lymphomas exhibited poorer prognoses, similar to that of B-cell lymphomas, than T-cell type tumors (P = 0.009). Among the 21 tumors, the prognosis of the four subtypes did not differ significantly; however, cases receiving aggressive chemotherapy and stem cell transplantation had a more favorable prognosis than those receiving only traditional chemotherapy and radiation therapy (P = 0.0089).

Myasthenia Gravis and Lymphoblastic Lymphoma Involving the Thymus: A Rare Association

Myasthenia gravis (MG) is an autoimmune neuromuscular junction disease. An association between thyrnic epithelial neoplasms and MG is well known. However, it is rarely associated with hematologic malignancies. In particular, very few cases of lymphoblastic lymphoma involving the thymus and MG have been reported. Here we report a case T-cell lymphoblastic lymphoma involving the thymus who developed MG after the initial diagnosis. The patient initially presented with a mediastinal mass which was diagnosed as lymphoblastic lymphoma. MG was diagnosed during leukemic relapse in this patient and was based on clinical presentation and neurophysiologic studies including single fiber electromyography (EMG) and repetitive nerve stimulation tests. In contrast to the other cases with such an association, the myasthenic symptoms presented nine months after the diagnosis of lymphoma by thymectomy. The patient had a highly aggressive clinical course and was resistant to various chemotherapy regimens.

Precursor B-cell lymphoblastic lymphoma: a predominantly extranodal tumor with low propensity for leukemic involvement.

Precursor B-cell lymphoblastic lymphoma (B-LBL) is uncommon and accounts for less than 10% of cases of lymphoblastic lymphoma. We collected 25 cases of B-LBL, occurring in children and adults, and report the clinical and histologic features. Patients with concurrent precursor B-cell acute lymphoblastic leukemia (B-ALL) or a history thereof were excluded. There was no evidence of bone marrow disease at the time of diagnosis in 23 patients; two patients had focal (<5%) involvement. Immunophenotypic analysis was performed in all cases using flow cytometry or immunohistochemical methods. The treatment and survival data available for a subset of patients with B-LBL were compared with those from a series of patients with B-ALL at our institution. The median age was 20 years (range, 5-68 yrs); 22 (88%) patients were younger than 35 years of age. There were 17 males and 8 females. The primary sites of disease were skin (nine cases), bones (five cases), soft tissue (four cases), lymph nodes, (three cases), breast (two cases), stomach and colon (one case), and mediastinum (one case). Clinical stage was stage I in 13 cases, stage II in seven cases, stage III in three cases, and stage IV in two cases. Histologically, each neoplasm was diffuse and composed of small to medium-sized lymphoid cells with blastic nuclear chromatin and a high mitotic rate. All cases were positive for B-cell antigens and terminal deoxynucleotidyl transferase. Thirteen (76.4%) of 17 cases analyzed were positive for CD10 and 13 (54.1%) of 24 cases assessed were positive for CD20. Of 14 patients with available survival data, all achieved complete clinical response after combination chemotherapy (13 patients) or surgical excision followed by local irradiation (one patient). Five (35.7%) patients subsequently relapsed, including the patient who had received only irradiation, and four of these patients died after a median survival time of 60 months. None of the patients had leukemia, although one patient developed extensive bone marrow involvement. Nine patients remained in complete remission and were alive at the last follow up (range, 6-144 months). Unlike precursor T-cell lymphoblastic lymphoma, which commonly involves lymph nodes and the mediastinum, B-LBL usually involves extranodal sites, most often the skin, and rarely presents as a mediastinal mass. With aggressive chemotherapy, patients with precursor B-LBL rarely develop leukemia and appear to have a better prognosis than do patients with B-ALL.

CD56 and terminal deoxynucleotidyl transferase positive cutaneous lymphoblastic lymphoma

Sir, Recently, lymphoblastic lymphomas of putatively immature or progenitor natural killer (NK)‐cell lineage have been reported.1–4 These lymphomas possess particular characteristic features, including positivity for CD56 and terminal deoxynucleotidyl transferase (TdT), negativity for Epstein–Barr virus (EBV), and no rearrangements of T and B cell immunoassociated genes.2–4 This report provides a description of a rare case of lymphoblastic lymphoma expressing an NK cell phenotype and with initial expression in the skin. A 39‐year‐old Japanese man was referred to our hospital in September 1998, complaining of multiple, indurated, slightly reddish plaques up to the size of a thumb‐tip; the plaques were located on his left cheek, forearms and trunk (Fig. 1a). The patient first became aware of a plaque on his left forearm in April 1996. Further lesions developed on his left cheek, right forearm and trunk during March 1998. A biopsy specimen obtained from the nodule on his back revealed diffuse proliferation of neoplastic cells, which were medium‐sized and had irregularly folded delicate nuclear membranes, fine chromatin, and tiny nucleoli (Fig. 1b). Angiocentric features were not seen in the biopsy section. The majority of lymphocytes were positive for TdT and CD56, but negative for CD2, CD3, CD4, CD5, CD8, CD16, CD20, CD25, CD30, CD34, CD45RO, CD57 and myeloperoxidase (MPO). The neoplastic cells were negative for EBV‐encoded latent membrane protein‐1 by immunohistochemistry, and negative for EBV‐encoded small RNAs by in situ hybridization. Immunogenotyping showed germline configurations for the T‐cell receptor Cβ1 gene and T‐cell receptor Jγ gene chain constant regions and the immunoglobulin heavy‐chain gene in the skin specimen. A PCR assay was performed to detect the EBV genome, and Southern blotting analysis was performed to test for the EBV terminal repeat; both tests were negative in the skin specimen. In addition, transmission electron microscopy revealed a few membrane‐bound electron‐dense granules measuring 200–500 nm in diameter in the cell cytoplasm.