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Biomedical subjects

H Rappaport

Publications and source records attributed to H Rappaport.

At least 55 records · Page 3Linked to original sources

Peripheral T-cell lymphoma. A case report demonstrating morphologic heterogeneity and progression, and atypical immune reactions.

Peripheral T-cell lymphomas (PTCL) comprise a morphologically heterogeneous group of non-Hodgkin's lymphomas. The authors report on PTCL occurring in a 13-year-old girl, in whom they were able to evaluate histologic material from 11 biopsy specimens obtained during her 8-month clinical course. These biopsy specimens demonstrated morphologic progression from atypical immune reactions and diffuse mixed cell lymphoma observed at different anatomic sites during early stages of the disease to pleomorphic large cell lymphoma with erythrophagocytic tumor cells at the time of her death. Morphologic variability of PTCL that may occur during the course of a patient's illness was demonstrated, and discordant histologic findings in biopsy specimens obtained simultaneously from different anatomic sites was noted. The morphologic evolution of PTCL was expressed, in sequential biopsy specimens, by a progressive cellular pleomorphism with the appearance of large, often bizarre lymphoid cells. This was associated with the gradual diminution and disappearance of the B-cell areas and epithelioid histiocytic reactions which were present initially in the biopsy specimens. The findings suggest that some of the various morphologic descriptions of PTCL given in the literature may represent transient histologic expressions of the lymphoma at various stages in its natural history.

Adolescent↗

Further evidence that "malignant angioendotheliomatosis" is an angiotropic large-cell lymphoma.

Malignant angioendotheliomatosis is a rare, generally fatal disease characterized by a multifocal proliferation of neoplastic mononuclear cells within the lumens of small blood vessels. Although the disease primarily involves the vasculature of the skin and central nervous system, vascular involvement of other organs may occur and may produce a variety of clinical findings. Some early investigators concluded that malignant angioendotheliomatosis was a neoplasm of endothelial cells, but recently others have suggested that it is of hematopoietic origin. We have studied three patients with the disease and have characterized the immunophenotype of the neoplasm on cryostat-cut fresh-frozen tissues. A detailed antigenic phenotyping of neoplastic lymphoid cells showed that one patient had the immunophenotype T11+, Leu-1+, Leu-3+, Leu-2+, B1-, B2-, SIg-, LN1-, LN2-, the predominant phenotype for peripheral T-cell lymphoma; the others had T11-, Leu-1-, Leu-3-, Leu-2-, B1+, B2+, SIg+, LN1+, LN2+, consistent with a B-cell-derived lymphoma. On the basis of our results, we suggest that angiotropic (intravascular) large-cell lymphoma would be more appropriate than malignant angioendotheliomatosis as a name for this disease.

Adult↗

Do therapists bias their ratings of patient functioning under peer review?

The present study was an attempt to examine the rating bias of therapists participating in an evaluation of an experimental quality assurance system at a community mental health center. The test program was intended to identify patients who demonstrated lack of progress or poor level of functioning after two months of treatment, and to employ a clinical assessment process by independent clinicians to evaluate problems in the quality of care. It was believed that the therapists knowledge that they might have their clinical work assessed would lead to biased ratings of more severe symptomatology in their patients. The results of this study partially supported the hypothesis. Patients in the peer review system were rated as more dysfunctional at admission on Psychological Functioning than patients in the control groups. No differences, however, were found on Basic Life Functioning, Anti-Social Behavior, or Mental Processes. The implications for these results relative to psychotherapy research, quality assurance, and program evaluation are discussed.

Adult↗

Angiotropic large cell lymphoma of the prostate gland: an immunohistochemical study.

Malignant angioendotheliomatosis (MAE) is a rare disorder characterized by the intravascular proliferation of neoplastic mononuclear cells. Until recently, the cell of origin was uncertain; some investigators reported MAE to be lymphomatous in nature, while others claimed it to be of endothelial derivation. In the present unusual case, MAE was an incidental findings in the prostate of a patient with prostatic adenocarcinoma; it is shown to be a lymphoma of B-cell origin.

Aged↗

Tissue Na, K, and Ca changes in regional cerebral ischemia: their measurement and interpretation.

A simple and reliable method of quantifying tissue damage is described. This method, based on atomic absorption spectroscopic determinations of Na, K, and Ca concentrations in small brain samples, was applied to the rat middle cerebral artery occlusion model (MCAo). At the infarct site by 24 hours, Na concentration more than doubled, Ca concentration increased by greater than 70%, and K concentration fell nearly 80%; these changes are consistent with a greater than 80% disruption of cells. A remarkable acceleration of ionic shifts occurred between 4 and 6 hours after MCAo. At 4 hours, only 20-30% of the ionic shifts found at 24 hours had occurred; by 6 hours, 80-100% of the ionic shifts found at 24 hours had taken place. Since the measurements reflect ionic movement into and out of the tissue, they are likely to represent irreversible tissue damage. Although blood brain barrier breakdown may have contributed to an increased rate of ionic shifts, large ionic gradients must have been present between the extracellular space and the vascular compartment at 4-6 hours to drive the ionic shifts. Our results suggest an upper time limit of 4 hours for treatments of acute ischemic tissue damage in the rat MCAo model. The methods and analytical approach described may be useful for determining the time window for therapeutic intervention in acute CNS injuries, as well as for evaluating treatment effects.

Acute Disease↗

Detection of lymphocyte antigens in tissues placed in transport medium. Comparison with cryostat fresh-frozen section technic. An immunologic study of 56 cases.

It has been suggested recently that use of a transport medium (Michel's medium) satisfactorily preserves the antigenicity of surface markers on lymphocytes for immunologic evaluation. Transport medium has been reported to be especially useful when immediate preparation of a specimen for immunologic study is not possible. Because adverse conditions such as changes in temperature during the transport of fresh-frozen tissue may markedly alter immunologic markers, it is desirable to transport fresh tissue in a medium that does not adversely affect the immunoreactivity of the tissue antigens. Therefore, we undertook a comparative study in which we compared cryostat-cut, fresh-frozen sections and tissues fixed in transport medium. The specimens were obtained from 56 consecutive patients who had various malignant lymphomas and benign lymphoid disorders. The results of our study indicate that the morphologic and immunologic findings obtained from the frozen sections that had been maintained in the transport medium (Michel's) may be confusing and may be interpreted inaccurately. This study also confirms our previous observation that the inconclusive or spurious results occasionally obtained with cell suspension technics can be avoided if the immunohistochemical technics are applied to cryostat-cut, fresh-frozen sections. We conclude that immunohistochemical study of cryostat-cut fresh-frozen sections remains the technic of choice for the identification and evaluation of both the morphologic and immunologic characteristics of tissues involved by lymphoproliferative diseases.

Antibodies, Monoclonal↗

Leu-M1 antigen in human neoplasms. An immunohistologic study of 400 cases.

Several studies have shown that the Leu-M1 antigen, a monocyte/granulocyte-related marker, is consistently expressed by the neoplastic cells of patients with Hodgkin's disease (HD). It has been suggested that reactivity of Reed-Sternberg cells with Leu-M1 can be used in support of a morphologic interpretation of HD, and that it is helpful in the differential diagnosis of HD from morphologically similar lesions. To evaluate the significance of the Leu-M1 positivity of Reed-Sternberg cells in the diagnosis of HD, we investigated the distribution of Leu-M1 antigen in a series of patients with HD, non-Hodgkin's lymphomas, and nonhematopoietic neoplasms. We were able to demonstrate the presence of Leu-M1 antigen not only in the majority of patients with HD, but also in 12 of 18 (67%) peripheral T-cell lymphomas, as well as in a variety of nonhematopoietic neoplasms, which included 113 of 199 carcinomas, most of them (58%) adenocarcinomas. Only one of 34 sarcomas showed a focal positive reaction. Leu-M1-related antigen was not detected in any of 18 mesotheliomas, 15 germ cell tumors, 13 melanomas, three schwannomas, or three astrocytomas. Our study indicates that Leu-M1 positivity has no value in supporting the diagnosis of HD in situations where the histologic diagnosis of HD is doubtful. However, since anti-Leu-M1 reacted positively in the majority of adenocarcinomas but was absent in mesotheliomas, melanomas, and most sarcomas, this antigen could serve as a new marker that may be helpful in situations in which carcinoma is a part of the differential diagnosis.

Adenocarcinoma↗

Leukopenic chronic T cell leukemia mimicking hairy cell leukemia: association with human retroviruses.

We report two cases of a T cell lymphoproliferative disease not previously described, with cytologic and clinical features similar to those associated with Galton's "prolymphocytic" leukemia (PL). Our patients, like those with Galton's PL, had massive splenomegaly and minimal or absent hepatomegaly and lymphadenopathy. In contrast, however, our patients had leukopenia, as well as low percentages of leukemic cells in the peripheral blood and in the bone marrow. In splenic imprints, the nuclear chromatin pattern of most of the leukemic cells was intermediate between those of mature lymphocytes and those of lymphoblasts, and the nuclei contained single, centrally located, conspicuous nucleoli. In sections of the spleen, the leukemic cells diffusely infiltrated the red pulp in a pattern strikingly similar to that of hairy cell leukemia; however, when the leukemic cells were studied cytochemically, the cytoplasmic acid phosphatase positivity was punctate and tartrate-sensitive. The leukemic cells were sheep erythrocyte rosette-positive and expressed T cell-associated antigens. Initially, both patients responded well to therapeutic splenectomy. One patient received combination chemotherapy after splenectomy and is alive and well 24 months after diagnosis. The other patient was in complete clinical remission for one year after splenectomy and received chemotherapy at relapse. He died, however, 23 months after splenectomy, with disseminated disease. IgG antibody titers against human T lymphotropic virus type I (HTLV-I) were detected in one patient and against HTLV-II in the other. The leukemia in these patients represents a distinct clinicopathologic entity within the spectrum of peripheral T cell lymphoproliferative diseases that includes Galton's PL of T cell derivation, T cell chronic lymphocytic leukemia, T cell hairy cell leukemia, and adult T cell leukemia/lymphoma.

Adult↗

Dermatopathic lymphadenopathy. An immunophenotypic comparison of cases associated and unassociated with mycosis fungoides.

Documenting focal mycosis fungoides in lymph node biopsies that exhibit dermatopathic lymphadenopathy is morphologically difficult. Since mycosis fungoides is a lymphoma with the phenotype of mature T cells, usually of the T-helper class, the authors investigated whether there are alterations in the ratio of Leu 3a (T-helper):Leu 2a (T-suppressor) cells in dermatopathic lymphadenopathy in order to determine the significance of immunologic markers as a possible solution to the problem. Ten lymph node biopsy specimens with diagnostic evidence of dermatopathic lymphadenopathy, but not of mycosis fungoides, were studied with the use of fresh-frozen section immunohistochemistry (FS), cell suspensions (CS), or both; five of the specimens came from patients with known cutaneous mycosis fungoides, and the other five came from patients without mycosis fungoides. The mean Leu 3a/Leu 2a ratio was 7.0 +/- 1.06 (SE) in all 10 cases of dermatopathic lymphadenopathy studied by FS and 6.9 +/- 1.14 in the 6 cases studied by CS. These ratios were significantly higher (P less than 0.001) than the mean Leu 3a/Leu 2a ratios of 2.9 +/- 0.29 (FS) and 2.4 +/- 0.22 (CS) in control lymph nodes exhibiting nonspecific reactive follicular hyperplasia, but were comparable to the mean Leu 3a/Leu 2a ratio of 5.9 obtained in two lymph node biopsies with unequivocal involvement by mycosis fungoides. Despite the increase in Leu 3a staining cells in dermatopathic lymphadenopathy, however, there were no essential differences in the Leu 3a/Leu 2a ratios between patients with and those without known mycosis fungoides. The use of other antibodies reactive with T cells, such as anti-Leu 8, anti-Leu 9, and anti-Tac also did not aid in this discrimination. The results indicate that determination of the Leu 3a/Leu 2a ratio and use of other conventional T-cell monoclonal antibodies do not provide conclusive evidence in support of a presumptive or early diagnosis of mycosis fungoides in a lymph node which fails to show histologic evidence of the disease.

Animals↗

Acceleration of age-associated immune decline and mortality by early repeated administration of bestatin to C57BL/6 mice.

The effect of chronic treatment with an immunostimulating agent, bestatin, on age-associated immune decline was assessed in C57BL/6 mice. Animals were given weekly doses of bestatin (100 micrograms/mouse, i.p.) from 7 months of age until death, and immune responses (natural killer cell activity, T cell cytotoxicity in vitro and in vivo, delayed-type hypersensitivity reaction, lymphoproliferative responses to mitogens, production of interleukin-2, macrophage functions) were tested at 11, 15, and 20 months. Most of the functions were reduced in 15-17-month-old mice, but evidence of reduced macrophage activities appeared only in limiting conditions (low lipopolysaccharide stimulation for interleukin-1 production and low concentration of macrophages in the cytostatic test). Bestatin administration produced a transient increase in natural killer (NK) cell activity and in vivo T cell cytotoxicity, followed (15-20 months of age) by a depression of NK and T cell-mediated responses. Only macrophage functions were stimulated in 20-month-old bestatin-treated mice. This unresponsiveness coincides with an accelerated mortality of bestatin-treated mice and a significant increase in the number of spontaneous tumor-bearing animals. The stimulation of T cells by bestatin seems to be mediated by a primary activation of macrophages to release immune mediators. Several reasons for the bestatin-induced immunodepression can be postulated including a high dose of bestatin, leading to toxicity or unresponsiveness; induction of suppressor cells; and overproliferation of T cells due to the mitogenic activity of bestatin, which may act as a promoting factor for tumor development.

Adjuvants, Immunologic↗

Monocytoid B-cell lymphoma. A novel B-cell neoplasm.

Monocytoid B lymphocytes (MBLs), originally described as part of the histologic picture of toxoplasmic lymphadenitis, have been recognized as a reactive component in a variety of lymph node disorders. The authors now report 3 cases of non-Hodgkin's lymphoma in which a multidisciplinary approach allowed them to confirm the existence of a malignant lymphoma composed of the neoplastic counterpart of the MBLs found in nonneoplastic disorders. In all 3 cases, the lymphoma was composed of a relatively monomorphous infiltrate of atypical MBLs that had rather uniform-appearing nuclei and had well-defined, moderately abundant pale cytoplasm. The pattern of lymph node involvement in all 3 cases was predominantly sinusoidal and interfollicular. The neoplastic lymphoid cells were strongly positive for B-cell-restricted antigens; the light- and heavy-chain phenotypes were kappa-IgM (2 cases) and kappa-IgG (1 case). In all 3 cases, rearrangement of heavy- and/or light-chain genes was clearly identified by Southern blot hybridization. The name "monocytoid B-cell lymphoma" is proposed for this newly described malignant B-cell neoplasm.

Aged↗

Studies of the bone marrow in polycythemia vera and the evolution of myelofibrosis and second hematologic malignancies.

The PVSG study is unique in that it is prospective and composed of 432 patients randomized to three treatment arms. This study also provides the opportunity for serial studies of numerous sequential biopsies. Large numbers of cases with sequential biopsies covering the entire long course are essential to appreciate the full spectrum of tissue changes in this disease. The PVSG was initiated in 1967 and in mid-1985 approximately one third of the patients are alive and on protocol. For these reasons, the results must still be considered preliminary. Pretreatment biopsies from patients randomized in the PVSG have been analyzed for total cellularity, megakaryocyte concentration, and reticulin content. Considerable variation in these elements was found in these biopsies. Sequential posttreatment biopsies from these patients have also been studied and correlated with the clinical course of the disease. None of the morphologic parameters analyzed was shown to be of prognostic significance. Early in the course of PV the marrow reticulin content is almost always normal. The length of the developmental stage is unknown and the precise timing of the clinical onset may be difficult. Therefore, the 11% of patients that showed a significant increase in reticulin on initial evaluation may have had PV longer than was indicated clinically. If large numbers of sequential biopsies are studied, an increase in reticulin content can frequently be demonstrated during the active phase of the disease and before the onset of the spent phase. Currently 39 patients (9%) have developed the spent phase, or PPMM. PPMM occurred in about the same incidence in the patients treated with myelosuppressive therapy as by phlebotomy alone, the spent phase occurring in 16 patients treated by phlebotomy alone, 11 with chlorambucil, and 12 with 32P. The course of the reticulin fibrosis is slowly progressive. There is some evidence for regression in a few patients in the erythrocytotic phase, but sampling variation cannot be completely ruled out. At this time in the study, AL has developed in 37 patients (8.6%). The incidence of AL is quite low in the phlebotomy group (three cases). Presumably this represents the natural incidence in PV unmodified by therapeutic agents. The frequency is approximately equal and quite high in the chlorambucil and 32P groups. There are 19 cases in the chlorambucil-treated group and 15 in the 32P-treated group. The leukemias that developed in the PV patients occurred either de novo or following PPMM.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗

Pulmonary lymphomas and other pulmonary lymphoid lesions. A clinicopathologic and immunologic study of 64 patients.

Sixty-four patients with lymphoid lesions involving the lung were separated into three groups. In 32 patients, the predominant lymphoid cell population consisted of small, mature-appearing round lymphocytes with or without plasmacytoid features. This group, designated small lymphocytic proliferation (SLP), represents a heterogeneous group of pulmonary lymphocytic lesions including small lymphocytic lymphoma, lymphocytic interstitial pneumonia, and lymphoid hyperplasia (pseudolymphoma). Thirteen SLP patients were identified as having small lymphocytic lymphoma on the basis of monoclonality, progressive disease in other sites, or both. This group was morphologically identical to the remainder of the SLP patients, except for a higher incidence of plasmacytoid features (P = 0.003) and a greater degree of mast cell infiltration (P less than 0.05). Four of these 13 patients subsequently developed an aggressive large cell lymphoma resulting in death in three patients. The median survival for all of the SLP patients has not yet been reached. Patients in whom a monoclonal cell population could be established showed a slightly worse prognosis of borderline statistical significance (P = 0.09); however, the presence of a serum monoclonal gammopathy conveyed a significantly worse prognosis (P = 0.003). The remaining two groups of patients had various forms of malignant lymphoma other than the small lymphocytic type. One group of 12 patients, designated as having presumed primary lymphoma limited to one or both lungs (PL), had a prolonged course with a median survival of 117 months. The remaining 20 patients had disseminated lymphoma also involving lung (DL); DL patients had a shorter median survival of 33 months.

Adolescent↗

Enzymatic differences between chronic lymphocytic leukemia and prolymphocytic leukemia.

Chronic lymphocytic leukemia and prolymphocytic leukemia of the B-cell immunophenotype are closely related disorders, but differ in their cytomorphologic and clinical features. In an attempt to differentiate further between these two forms of leukemia, we measured adenosine deaminase and purine nucleoside phosphorylase activities by using a linked-enzyme spectrophotometric assay on peripheral-blood leukemic cells from seven patients with chronic lymphocytic leukemia, three patients with prolymphocytic leukemia, and one patient with prolymphocytoid transformation of chronic lymphocytic leukemia. By using discriminant analysis, we were able to distinguish the two groups only on the basis of purine nucleoside phosphorylase activity (F1,9; p less than 0.001). The purine nucleoside phosphorylase activity in leukemic cells with prolymphocytic cytomorphology was significantly elevated (mean = 58.6 nM/min/mg protein) compared to the activity in leukemic cells with lymphocytic cytomorphology (mean = 25.6 nM/min/mg protein). There was only one patient with chronic lymphocytic leukemia who was assigned to the prolymphocytic leukemia group on the basis of her purine nucleoside phosphorylase activity. Our study suggests that purine nucleoside phosphorylase activity in leukemic cells may be useful in the distinction of prolymphocytic leukemia from chronic lymphocytic leukemia, and that it may be an enzymatic marker for the early detection of prolymphocytoid transformation of chronic lymphocytic leukemia.

Adenosine Deaminase↗

Multicentric angiofollicular lymph node hyperplasia: a clinicopathologic study of 16 cases.

A clinicopathologic analysis of 16 cases of multicentric angiofollicular lymph node hyperplasia (MAFH) was performed. Histologically, the disease was characterized by recognizable lymph node architecture that was at least partially intact, by paracortical hyperplasia with prominent vascular proliferation, and by numerous evenly distributed, apparently benign germinal centers of various types, usually including some typical hyaline-vascular centers. At the onset of the disease, 12 patients had the plasma cell (PC) type of MAFH, three patients had the hyaline-vascular (HV) type, and one patient presented with PC and HV types at separate sites. Transitions between the PC and HV types were observed in two cases. Immunologic studies demonstrated polyclonal populations of plasma cells in the lymph nodes of all patients and the absence of suppressor T lymphocytes in the one patient tested. Clinically, the patients had constitutional symptoms, multicentric lymphadenopathy, hepatosplenomegaly in many cases, and abnormal laboratory findings, including anemia, polyclonal hypergammaglobulinemia, and bone marrow plasmacytosis. The 16 patients were placed in four different clinical groups based on presentation and course: stable disease, chronic relapsing disease, aggressive disease, and development of malignant lymphoma. Ten of the 16 patients died (median survival, 26 months; range, eight to 170 months). Multicentric angiofollicular lymph node hyperplasia appears to be a variant of classic angiofollicular lymph node hyperplasia (Castleman's disease) and is associated with significant morbidity and mortality.

Adult↗

Neoplastic B cells with cerebriform nuclei in follicular lymphomas.

Three cases of follicular lymphoma in which the follicular center cells exhibited pronounced nuclear irregularities, i.e., convoluted and cerebriform shapes, are described. The cytoplasm in B5-fixed sections was scanty to abundant and showed pale to clear staining, with interlocking cell borders. Although the architectural pattern in these cases suggested B-cell lymphoma, the cytologic features suggested a T-cell phenotype. Immunologic studies of frozen sections by immunohistochemical techniques in all three cases, as well as cell suspension studies in two cases, showed that the follicular center cells, including those with convoluted and cerebriform nuclei, were clearly monoclonal B cells, as evidenced by the presence of only one immunoglobulin light chain on the surfaces. The results of this study suggest that the follicular architectural pattern is a more reliable predictor of the immunologic phenotype than are the cytologic features.

Aged↗

Monocytoid B lymphocytes: their relation to the patterns of the acquired immunodeficiency syndrome (AIDS) and AIDS-related lymphadenopathy.

It was shown recently that monocytoid cells express B-cell-restricted antigens and polyclonal surface immunoglobulins, and the term monocytoid B lymphocytes (MBL) has thus been offered as a more appropriate designation. Although most commonly seen in toxoplasmic lymphadenitis, MBL have been observed in a variety of reactive and neoplastic conditions involving lymph nodes. In the present study MBL were found in 17 of 22 lymph nodes from 20 patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related lymphadenopathy. In all 17 samples, the MBL were found in lymph nodes with florid reactive follicular hyperplasia, and they were geographically close to the hyperplastic lymphoid follicles. However, MBL were not detected in lymph nodes showing involuted follicles or lymphocyte depletion. The disappearance of MBL apparently parallels the progressive involution of secondary follicles. Leu-3+/Leu-2+ (T-helper/T-suppressor) ratios were studied in 14 lymph node cell suspension samples and ten peripheral blood samples. The lymph node Leu-3+/Leu-2+ ratios were significantly lower in AIDS-related lymphadenopathy than in non-AIDS-related reactive follicular hyperplasia (P less than 0.001); the peripheral blood ratios were decreased in nine of the ten cases. The diminished T-helper status in patients with AIDS and AIDS-related lymphadenopathy may be relevant to the immunopathogenesis of follicular involution and, indirectly, to the disappearance of MBL.

Acquired Immunodeficiency Syndrome↗

Small lymphocytic lymphoma. Morphologic and immunologic progression.

The large cell lymphoma (LCL) that occurs in patients with chronic lymphocytic leukemia (Richter's syndrome) has generally been shown to be of the same light chain type as the original chronic lymphocytic leukemia (CLL). The authors now report on a patient with diffuse well-differentiated lymphocytic lymphoma (WDL) of the kappa light chain type who in the course of his illness first had the blood picture of CLL and then developed malignant lymphoma of large cell ("histiocytic") type, which expressed lambda light chains. Despite an extensive multiparameter investigation, we could not determine with certainty whether the presence of two morphologically and immunologically different lymphomas represented proliferation of two distinctly separate clones or whether it represented clonal evolution of the disease with an alteration in immunoglobulin light chain associated genes. The results of the study, however, suggest that the development of lymphoma with expression of a different immunoglobulin light chain may not necessarily indicate the occurrence of a second primary. This study also illustrates the necessity for sequential lymph node biopsies to document progression of disease in patients with low-grade lymphoproliferative disorders and indicates that the immunologic phenotype of a B-cell neoplasm in a given patient should not be assumed to remain constant.

Antigens, Surface↗