Chromosomal and immunophenotypic patterns in T cell acute lymphoblastic leukemia (T ALL) and lymphoblastic lymphoma (LBL)

In this study of 33 T cell acute lymphoblastic leukemia (T ALL) and 17 lymphoblastic lymphoma (LBL) patients, no relevant differences between the two groups were observed in clinical characteristics, response to therapy, and survival. We found translocations involving 14q11, 7q35, or 7p15, where T cell receptor alpha and delta, beta, and gamma subunit genes reside, in 20 patients (40%). Most of these translocations were seen with equal frequency in T ALL and LBL, indicating that, in a large proportion, the two diseases are different manifestations of the same lymphoblastic disorder. However, other translocations, such as t(9;17)(q34;q23), occurred only in LBL, perhaps pointing to the existence of subsets of LBLs that are distinct from T ALL. On the basis of karyotype, 50 patients could be classified into three groups: 20 patients with 14q11, 7q35, or 7p15 translocations (group A); 20 with other translocations, and/or deletions (group B); and 10 with normal diploidy (group C). There was no difference in survival time between any two of the three groups.     

Angiomatoid malignant fibrous histiocytoma with extensive lymphadenopathy simulating Castleman's disease

We report the association in a 10-year-old boy of an angiomatoid malignant fibrous histiocytoma (AMFH) of the left thigh with ipsilateral inguinal, pelvic and extensive retroperitoneal lymphadenopathy, and severe systemic manifestations. These include growth retardation, fever, severe anemia, hypergammaglobinemia, and hypoalbuminemia. At ultrastructural level the tumor was characterized by an abundance of myofibroblasts, occasional histiocytes, and small vessels with marked reduplication of the basal lamina. Biopsies of the inguinal and abdominal lymph nodes showed follicular hyperplasia and massive plasmacytosis indistinguishable from Castleman's disease (giant lymph node hyperplasia) of plasma cell type. The radical surgical excision of the primary tumor in the thigh resulted in the disappearance of the abdominal lymphadenopathy and a marked reduction in size of the pelvic lymph nodes with marked decrease of the gammaglobulins, thus proving that the nodal lesions were the expression of a reactive process to the tumor rather than a coincidental independent lymphoproliferative disorder. Retroperitoneal and pelvic node dissection was performed 1 year after the radical excision of the thigh tumor because of persistent pelvic lymphadenopathy and failure of serum immunoglobulins M and A to return to normal level, with a recent peak of IgA to twofolds that of normal value. Metastatic AMFH was found in the three pelvic nodes. One month postoperatively IgA returned to near normal level whereas IgM remained slightly elevated.     

bcl-2 and other genomic alterations in the prognosis of large-cell lymphoma

Approximately half the patients with diffuse or follicular large-cell or mixed large- and small-cell lymphoma enter a prolonged remission or are cured after receiving combined-drug therapy. It has been unclear, however, why the other half do not respond. We evaluated 54 previously untreated patients with diffuse lymphoma and 20 with follicular lymphoma, all of whom had a large-cell component and Stage II through IV disease, subsequently treated with combined chemotherapy. Different recurrent genomic defects were associated with differences in the response to treatment. Among the 54 patients with diffuse lymphoma, all 12 patients with a duplication of chromosome 3p had a complete clinical remission after a median follow-up of 39 months (11 patients survived). In contrast, all seven patients with a duplication of chromosome 2p had a partial response or no response to treatment and a median survival of six months (all died). Among the 20 patients with follicular lymphoma, all 5 patients with duplication 3p or +3 had a complete clinical remission (all survived), and 3 of 4 patients with duplication 2p or +2 had no response or a partial response to treatment and died. Twenty-three patients with B-cell non-immunoblastic lymphoma or follicular lymphoma who had a bcl-2 oncogene rearrangement had a poorer response to therapy (7 of 23 with complete remission) than the patients without bcl-2 rearrangement (21 of 26 with complete remission). We conclude that in large-cell or mixed-cell lymphoma, duplication of chromosome 3p is associated with a relatively good prognosis and duplication of chromosome 2p or bcl-2 oncogene rearrangement is associated with a relatively poor prognosis. Because such multiple recurrent genomic defects are also common in most other types of cancer, they may have general prognostic importance.     

T-helper cell lymphoma involving the lymph nodes and skin. A clinical, morphologic, and immunohistochemical analysis of five cases

The clinical, morphologic, and immunohistochemical features of 5 cases of peripheral T-cell lymphoma with lymph node and skin involvement are reported. All patients were male and presented with generalized lymphadenopathy and skin lesions. Lymph node biopsy specimens showed a diffusely growing, pleomorphic, atypical lymphoid infiltrate composed of markedly irregular small and large cells. The stroma consisted of plasma cells, eosinophils, epithelioid histiocytes, and an increased number of small blood vessels. A similar neoplastic infiltrate was observed in the cutaneous nodules that developed in three patients. Immunohistochemistry on frozen tissue sections of lymph nodes using a broad panel of monoclonal antibodies revealed that the neoplastic cells were reactive with anti-T-cell antibodies, the majority of them belonging to the helper/inducer T-cell subset. Stromal plasma cells contained polyclonal immunoglobulins. It is concluded that the malignant lymphoma of peripheral helper/inducer T-cell origin observed in these five patients represents a variant of a mixed, blastic/cell T-cell lymphoma, characterized by a peculiar stromal component and skin involvement.     

Angioimmunoblastic lymphadenopathy and related disorders: a retrospective look in search of definitions

The recent report of an immunoblastic lymphadenopathy (IBL)-like T cell lymphoma has rekindled questions about the nature, reactive or neoplastic, of IBL, angioimmunoblastic lymphadenopathy (AIL), and lymphogranulomatosis X (LgX) and blurred the criteria for their diagnosis. We looked in the literature and our own data for a categorization of AIL (IBL, LgX) and related disorders, needed for future prospective studies. Specific differences in the original histologic definitions and discordant immunophenotypic data may warrant the separate consideration of AIL, IBL and LgX and their subdivision into predominantly T cell or B cell lesions. DNA hybridization and cytogenetic studies of the processes sharing histologic features of AIL (IBL, LgX) demonstrate a continuum of disorders from purely reactive to frankly malignant, which may be categorized as follows: (1) those without evidence of clonality by any of three parameters (immunophenotypic, immunogenotypic, and cytogenetic), for which only the term AIL (IBL, LgX) might be reserved; (2) those with evidence of clonality by all parameters, or AIL (IBL, LgX)-like lymphomas; and (3) those that, due to any discordance among the three parameters, do not fit into either of the above categories, and for which the term AIL (IBL, LgX)-like dysplasias is proposed. This intermediate group seems to be composed of unstable lymphoproliferative conditions, in which a predominant component of normal cells coexists with clonal population(s) that may either disappear with time or selectively proliferate and develop into frank lymphoma.     

The distinction of Hodgkin's disease from anaplastic large cell lymphoma.

In this session there seemed to be general agreement on the existence of anaplastic large cell lymphoma (ALCL) as an entity defined by a characteristic morphology and by diffuse expression of the Ki-1 (CD30) antigen. The discussion indicated the lack of specific immunophenotypic and genotypic markers for such a neoplasm and the variability of the clinical patterns associated with it: these include a childhood form, an adult cutaneous form, and an adult nodal disease. While typical cases of ALCL are clearly distinct (by pathologic, cytogenetic, and clinical criteria) from Hodgkin's disease (HD), there is a variety of histologic and immunophenotypic patterns that overlap those of ALCL and HD; most of these would be classified as HD, lymphocyte depletion (LD) or nodular sclerosis (NS), syncytial subtype. No agreed-upon criteria were found that could consistently define these patterns, nor was an agreement possible on whether they are part of a continuum unifying ALCL and HD or phenotypically similar expressions of different diseases.     

Detection of Epstein-Barr virus sequences in Hodgkin''s disease by the polymerase chain reaction.

The authors examined paraffin-embedded lymph node biopsies from 65 cases of Hodgkin's disease for the presence of Epstein-Barr virus (EBV) DNA, using the highly sensitive polymerase chain reaction technique. Overall 40% of the cases were positive for EBV DNA; there were no statistically significant differences in the frequency of EBV positivity among the different subtypes of Hodgkin's disease. These results are in agreement with those of previous studies that employed less sensitive detection techniques and suggest that EBV either is present in pathologic tissues only in some phases of the evolution of Hodgkin's disease or is a pathogenetic factor involved in only a portion of cases.     

Clonal rearrangement for immunoglobulin and T-cell receptor genes in systemic Castleman's disease. Association with Epstein-Barr virus

Castleman's disease is a morphologically and clinically heterogeneous lymphoproliferative disorder. Both a localized benign variant and an aggressive form with systemic manifestations have been described. To investigate the differences between these variants of Castleman's disease, the authors analyzed lymph node DNA from 4 patients with the localized type and 4 with the systemic type of Castleman's disease for immunoglobulin and T-cell receptor gene rearrangements. The role of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) was also studied by viral genomic DNA probes. They detected clonal rearrangements in 3 of the 4 patients with the systemic variant of Castleman's; no patients with localized disease had rearrangements. Copies of EBV genome were also detected in 2 of the 3 patients with clonal rearrangements. These results suggest that systemic Castleman's disease is a disorder distinct from the classical localized variant in that it may evolve into a clonal lymphoproliferation.     

Bone marrow manifestations of peripheral T-cell lymphoma. A study of 30 cases

Morphologic and clinical features of 30 patients with peripheral T-cell lymphoma (PTCL) were studied with particular attention to bone marrow and blood manifestations. Twenty-four (80%) patients had marrow involvement with lymphoma in trephine biopsies at initial diagnosis; two other patients subsequently developed marrow involvement. The bone marrow lesions were diffuse in 58% of the cases and focal, nonparatrabecular in 42%. A morphologic spectrum of lymphoma cells was seen with cases classified into small cell, mixed cell, and large cell/immunoblastic lymphoma. The bone marrow lesions were characterized by a heteromorphous population of lymphocytes, prominent vascularity with endothelial cell proliferation, reticulin fibrosis, and a polycellular infiltrate composed of plasma cells, eosinophils, and histiocytes. The histopathologic features in bone marrow biopsies were not pathognomonic for PTCL; the differential diagnosis may include non-Hodgkin's lymphomas of B-cell type, polymorphous reactive lymphoid lesions, including those from patients with acquired immune deficiency syndrome (AIDS), angioimmunoblastic lymphadenopathy, Hodgkin's disease, and systemic mastocytosis. The patients ranged in age from 13 to 81 years (median, 61 years) and generally presented with constitutional symptoms, lymphadenopathy, and hepatosplenomegaly. Abnormalities in one or more hematologic parameters were common and, in general, related to the degree of bone marrow involvement. Hypocalcemia was found in 40% of the patients studied and hypercalcemia in 4%. The median survival for PTCL patients was 11 months. Patients with small cell lymphoma, large cell/immunoblastic lymphoma, and marked eosinophilia had the shortest median survivals.     

Characteristic karyotypic pattern in T-cell lymphoproliferative disorders with reactive "angioimmunoblastic lymphadenopathy with dysproteinemia-type" features

We report the clinical, histological, immunophenotypic, and cytogenetic findings in ten patients with T-cell lymphoproliferative disorders demonstrating reactive "angioimmunoblastic lymphadenopathy with dysproteinemia (AILD)-type" features. Fifteen available specimens were diagnosed as atypical hyperplasias (four) or malignant lymphomas (11). The latter were classified as AILD-type (five), T-zone (four), lymphoepithelioid (one), and low-grade, unclassified lymphoma (one). Despite the histologic differences, all these lesions shared minor nuclear atypicalities and reactive AILD-type features such as prominent vascularity, plasma cells, eosinophils, macrophages, and residual germinal centers. All lesions were immunophenotyped as predominantly T cell. The chromosome pattern was characterized by the frequent presence of karyotypically unrelated abnormal clones and/or cells with nonclonal chromosome abnormalities, a large population of normal mitotic cells, and a high incidence of trisomies 3 and 5. Sequential cytogenetic and histologic studies in five patients revealed that atypical hyperplasia and lymphoma with AILD-type features shared the same cytogenetic characteristics, ie, an unstable coexistence of normal mitotic cells and small-clonal and/or nonclonal abnormal cells, and that histologic transformation from low-grade lymphoma to immunoblastic lymphoma was accompanied by a selective proliferation of abnormal clonal cells. The AILD-type histology and the characteristic karyotypic pattern may be the expression of a specific pathogenesis and may warrant the separation of these neoplasias from other peripheral T-cell lymphomas.