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Evidence for human T cell lymphoma-leukemia virus infection of family members of human T cell lymphoma-leukemia virus positive T cell leukemia-lymphoma patients.

Sera of family members of patients from the United States, the Caribbean, and Japan, with human T cell lymphoma-leukemia virus (HTLV) associated T cell malignancies, possess HTLV-specific antibodies directed against internal structural components of HTLV, p24 and p19. The prevalence of antibodies to HTLV is greater in family members than in random healthy donors, which supports the infectious nature of HTLV and its association with particular aggressive T cell malignancies. Expression of HTLV p24 and p19 has also been observed in cultured T cells of some healthy relatives, and intact virus particles have been released from cells of one possibly pre-leukemic family member.

Antibodies, Neoplasm↗

Human lymphoma-lymphoma hybrids and lymphoma-leukemia hybrids. I. Isolation, characterization, cell surface markers, and B-cell markers.

Four new somatic cell hybrids were obtained by fusion of various Burkitt's lymphoma (BL)-derived cell lines that had different selective markers: Raji-P3HR-1, Daudi-Raji, and a P3HR-1-P3HR-1 "autohybrid" derived from two P3HR-1 sublines. In addition, a hybrid was obtained between the Daudi (BL) line and the human leukemia cell line K562. The hybrids were extensively characterized by means of chromosome, isozyme, and HLA surface markers. The phenotypic differences between the parent cell lines allowed some conclusions with respect to the expression of latent Epstein-Barr virus (EBV) genomes, C3 and EBV receptors, and of immunoglobulin and beta 2-microglobulin-HLA expression as well as the influence of the leukemia cell (K562) genome on B-cell properties in the Daudi-K562 hybrid. B-cell and differentiated markers of these hybrids were characterized. High-level expression dominated for the marker C3 and EBV receptors, which showed a good correlation coefficient of 0.84, as was true for Fc receptors and surface immunoglobulin. The Daudi-K562 hybrid showed loss of all B-cell markers but retention of the leukemia cell markers (e.g., hemoglobin synthesis).

Animals↗

Ocular adnexal lymphoma. A clinicopathologic study with identification of lymphomas of mucosa-associated lymphoid tissue type.

PURPOSE: Extranodal marginal zone B-cell lymphoma (low-grade B-cell lymphoma of mucosa-associated lymphoid tissue [MALT] type) is a distinctive type of lymphoma that usually arises in association with mucosa or other epithelial structures and has an indolent clinical course. The frequency and clinical features of MALT lymphomas in the ocular adnexa have not been well studied. METHODS: The authors examined the clinicopathologic features of ocular adnexal lymphoma, identified a subset of cases with MALT characteristics, and determined patient outcome. RESULTS: The 42 patients, 16 men and 26 women age 35-89 years (mean, 64) were followed an average of 4.8 years. Thirty-two patients had ocular adnexal involvement at presentation (primary ocular adnexal lymphoma) and 10 had a history of lymphoma that relapsed in the orbit (secondary ocular adnexal lymphoma). In the primary group, 23 patients had lymphoma confined to the ocular adnexa, 3 had a single lesion that invaded adjacent structures, and 6 had distant spread at the time of presentation. Twenty-five patients achieved a complete remission. Nine patients, including 6 patients whose disease was localized initially, had progression or relapse of disease in distant sites. At last follow-up, 21 patients were free of disease, 9 were alive with disease and 2 had died of lymphoma. In the secondary group, at last follow-up, 1 patient had died of other causes, free of lymphoma, 3 patients were alive with disease and 5 had died of lymphoma (outcome not known in 1 case). Using the recently described revised European-American lymphoma classification, we found 16 MALT lymphomas, 8 diffuse large B cell, 12 follicular center, 3 mantle cell, 1 B-small lymphocytic lymphoma, and 2 unclassifiable low-grade lymphomas. The most common type of primary lymphoma was MALT type (15 of 30 classifiable cases), and the most common secondary lymphoma was follicular center (6 of 10). No increased frequency of conjunctival or lacrimal gland involvement by MALT lymphomas was found. All 33 lymphomas with immunophenotyping were of B lineage. CONCLUSIONS: Ocular adnexal lymphomas are B-cell tumors that develop in older adults, predominantly among women. Primary orbital lymphomas have a favorable prognosis; a high proportion of them have MALT characteristics.

Adult↗

Ocular adnexal lymphoma-comparison of MALT lymphoma with other histological types.

AIMS: To correlate histological features of ocular adnexal lymphoma using the revised European American lymphoma classification (REAL), with stage of disease at presentation, treatment modalities, and patient outcome. MALT lymphoma defines an extranodal marginal zone B cell lymphoma as outlined in the REAL classification. Comparison groups of patients included those with primary ocular adnexal MALT lymphoma versus primary ocular adnexal lymphomas of other types, MALT lymphoma versus non-MALT lymphomas (primary and secondary), and primary ocular adnexal lymphoma (MALT lymphomas and other types) versus secondary ocular adnexal lymphomas. METHODS: A retrospective review of the National Ophthalmic Pathology Laboratory records identified 20 cases of ocular adnexal lymphoma over a 10 year period which were reclassified using appropriate immunohistochemical stains. Patients' medical records were examined for data including stage of the disease at presentation, mode of treatment, and patient outcome. RESULTS: Among the 20 cases identified 14 had primary ocular adnexal lymphomas. 10 of the primary lymphomas had histological features of MALT lymphoma. One case was a primary ocular adnexal T cell lymphoma, one a follicular centre, follicular B cell lymphoma, and two were large cell B cell lymphomas. Six cases had systemic disease, four large B cell, one follicular centre, follicular B cell, and one mantle cell. A significantly higher proportion of patients with MALT lymphomas had early disease (p = 0.005), initially required local treatment (p = 0.005) and were alive at last follow up (p = 0.001) than those without. Two patients with MALT lymphoma had recurrence of lymphoma which responded to further treatment. CONCLUSIONS: Patients with primary ocular adnexal MALT lymphomas present with localised disease requiring local treatment and have a better outcome compared with patients with other types. As a small percentage of these tumours recur, patients should be followed up indefinitely.

Adult↗

REAL classification of malignant lymphomas in the Republic of Korea: incidence of recently recognized entities and changes in clinicopathologic features. Hematolymphoreticular Study Group of the Korean Society of Pathologists. Revised European-American lymphoma.

BACKGROUND: The clinicopathologic characteristics of malignant lymphomas vary according to geography. The aim of this study was to determine the clinical characteristics of malignant lymphomas and the relative frequency in the Republic of Korea of lymphomas belonging to the newly described REAL (revised European-American lymphoma) classification categories. METHODS: The Hematolymphoreticular Study Group of the Korean Society of Pathologists conducted a consensus-based morphologic review of a nationwide collection of 1548 malignant lymphomas, including Hodgkin's disease (HD), diagnosed at 23 institutes over a recent 2-year period. Slides stained with hematoxylin and eosin or other immunohistochemical stains were reviewed. All cases were classified according to the histologic criteria proposed by the International Lymphoma Study Group. Clinical data, including age, gender, and site of disease involvement, were reviewed. RESULTS: The Republic of Korea had lower rates of HD and follicle center lymphoma and higher rates of extranodal lymphoma, diffuse large B-cell lymphoma, and angiocentric lymphoma compared with Western countries. The most frequent subtypes of non-Hodgkin's lymphoma (NHL) were diffuse large B-cell lymphoma, extranodal marginal zone B-cell lymphoma, peripheral T-cell lymphoma, unspecified type, and angiocentric lymphoma, in decreasing order. Compared with a previous nationwide study, the rates for follicular lymphoma and NHL involving the stomach, orbit, and central nervous system were increased. The rate of T-cell NHL in the current study was much lower than that reported in a previous study for the Republic of Korea and was also lower than that reported for other Far East countries. For HD, the relative frequency of nodular sclerosis subtype was higher compared with that in the previous study, and lymphocyte predominance and lymphocyte depletion were lower. CONCLUSIONS: The occurrence rates for various subtypes of malignant lymphoma in the Republic of Korea are distinct from those in Western countries and similar in many ways to those in other countries in the Far East. Compared with other Far East countries, the Republic of Korea has a higher rate of extranodal lymphoma, rare adult T-cell lymphoma, and a relatively low rate of T-cell lymphomas. It appears that over time there have been changes in the relative rates for follicular lymphoma, subtypes of Hodgkin's disease, and gastric and orbital lymphoma. The authors attribute these changes primarily to refined criteria for diagnosing new clinicopathologic entities.

Adolescent↗

T-cell/histiocyte-rich large B-cell lymphoma is a disseminated aggressive neoplasm: differential diagnosis from Hodgkin's lymphoma.

AIMS: An accurate diagnosis of T-cell/histiocyte-rich large B-cell lymphoma needs to take into consideration those forms of Hodgkin's lymphoma also characterized by a predominance of small lymphocytes and histiocytes, i.e. nodular lymphocyte predominance Hodgkin's lymphoma and lymphocyte-rich classical Hodgkin's lymphoma. We have studied the clinical, phenotypic and genetic features of a series of 12 cases of T-cell/histiocyte-rich large B-cell lymphoma along with 18 cases of Hodgkin's lymphoma for comparative purposes. METHODS AND RESULTS: Of the Hodgkin's lymphoma cases, there were 11 lymphocyte predominance type and seven classic type. T-cell/histiocyte-rich large B-cell lymphomas presented usually in advanced stages (III or IV in 11/12 cases), frequently with 'B' symptoms (6/9 cases), and followed a more aggressive course than Hodgkin's lymphoma (4/8 patients died due to the tumour in T-cell/histiocyte-rich large B-cell lymphoma versus 0/15 in Hodgkin's lymphoma). T-cell/histiocyte-rich large B-cell lymphoma cases showed diffuse effacement of the nodal architecture by a proliferation of scattered large atypical B-cells obscured by a background of small T-lymphocytes (more CD8+, TIA1+ than CD57+). Five cases showed also a prominent histiocytic component. The large B-cells expressed CD45 and often EMA (6/10 cases). On the other hand, CD 30, CD15 and latent infection by Epstein-Barr virus (EBV) were generally lacking. bc l6 and CD10 were, respectively, detected in 6/6 and 1/5 cases. Conventional polymerase chain reaction (PCR) showed monoclonal immunoglobulin heavy chain (IgH) gene rearrangements in all T-cell/histiocyte-rich large B-cell lymphomas studied (5/5), but did not detect any case with t(14;18) involving the major breakpoint region (0/4). CONCLUSIONS: The differential diagnosis of T-cell/histiocyte-rich large B-cell lymphoma from Hodgkin's lymphoma is facilitated by the integration of different immunophenotypic, molecular and clinical findings. T-cell/histiocyte-rich large B-cell lymphoma is a monoclonal neoplasm of bc l6+ B-cells with a phenotypic profile similar to lymphocyte predominance Hodgkin's lymphoma, suggesting a germinal centre origin and a possible relation to this disease. Therefore, in order to distinguish it from lymphocyte predominance Hodgkin's lymphoma, characterization of the reactive background, IgH gene rearrangement studies by conventional PCR and clinical features are more useful. In contrast, T-cell/histiocyte-rich large B-cell lymphoma can be distinguished from classical Hodgkin's lymphoma thanks to the presence of monoclonal IgH rearrangement and the CD 30-CD15-CD45+EMA+ immunophenotypic profile of the neoplastic cells in T-cell/histiocyte-rich large B-cell lymphoma.

Adult↗

Distribution of various subtypes of non-Hodgkin's lymphoma in India: a study of 2773 lymphomas using R.E.A.L. and WHO Classifications.

INTRODUCTION: The distribution of the major subtypes of non-Hodgkin's lymphoma (NHL) differs across geographic regions. This is the first study from India that has incorporated immunophenotypic findings while investigating the distribution of NHL subtypes. PATIENTS AND METHODS: All cases diagnosed as NHL between January 1995 and June 1998 in the Department of Pathology and in the Lymphoma Registry, Tata Memorial Hospital, Bombay, were selected for the study. The cases were reviewed by three pathologists and diagnostic problems were discussed by a panel of pathologists with a special interest in lymph node pathology. Of a total of 2831 cases, the diagnosis of NHL was accepted in 2773 cases. RESULTS: B-cell lymphomas formed 79.1% of the NHLs, whereas T-cell lymphomas formed 16.2% of the total. Diffuse large B-cell lymphoma was the most common subtype (34% of all NHLs). Follicular centre-cell lymphomas, B-cell small lymphocytic lymphoma, mantle-cell lymphoma, and marginal zone B-cell lymphomas (including MALT lymphomas) amounted to 12.6%, 5.7%, 3.4%, and 8.2%, respectively. Among the T-cell lymphomas, T-cell lymphoblastic lymphoma, anaplastic large-cell lymphomas of T/null-cell type, and other nodal peripheral T-cell lymphomas accounted for 6%, 4.3%, and 2.9% of all cases, respectively. CONCLUSIONS: The distribution of NHL subtypes in India shows important differences with those from the rest of the world. Follicular lymphoma and mantle-cell lymphoma are less common in India compared to Europe and the USA. Peripheral T-cell lymphomas and T/NK-cell lymphomas of nasal and nasal types, which are common in many other Asian countries, are also less prevalent. T-cell lymphoblastic lymphoma and anaplastic large T/null cell lymphoma are more prevalent in India.

Europe↗

Immunoreactivity of CD99 in non-Hodgkin's lymphoma: unexpected frequent expression in ALK-positive anaplastic large cell lymphoma.

To verify the spectrum of CD99-expressing lymphoid malignancy, an immunohistochemical study for CD99 was carried out in 182 cases of non-Hodgkin's lymphoma, including 21 lymphoblastic lymphomas, 11 small lymphocytic lymphomas, 9 mantle cell lymphomas, 12 follicular lymphomas, 37 diffuse large B cell lymphomas, 18 Burkitt's lymphomas, 28 NK/T-cell lymphomas, 8 angioimmunoblastic T-cell lymphomas, 23 peripheral T-cell lymphomas, unspecified, and 15 systemic anaplastic large cell lymphomas. CD99 was positive in all T-lymphoblastic lymphomas and in 60% of B-lymphoblastic lymphomas. Majority of T and NK cell lymphomas were negative for CD99, except anaplastic large cell lymphomas (ALCLs). Eight of 15 cases (54%) of ALCLs reacted with anti CD99 antibody. Seven of 10 (70%) ALK positive ALCLs expressed CD99, whereas only 1 of 5 (20%) ALK negative ALCLs were positive. Of the mature B-cell lymphomas, 5.4% (2/37) of diffuse large B cell lymphomas and 11.1% (2/18) of Burkitt's lymphomas expressed CD99. In conclusion, CD99 is infrequently expressed in mature B and T cell lymphomas, except ALK-positive ALCL. High expression of CD99 in ALK-positive ALCL is unexpected finding and its biologic and clinical significances have yet to be clarified.

12E7 Antigen↗

Testicular diffuse large cell lymphoma with tubule preservation--molecular genetic evidence of transformation from previous follicular lymphoma.

Testicular lymphomas usually occur in older men and are mostly diffuse large B-cell lymphomas (DLBL). They may be primary manifestation of lymphoma or represent a relapse of a previous non-Hodgkin's lymphoma. This report details a testicular large cell lymphoma, which was proven to be large cell transformation of a low-grade follicular lymphoma biopsied 8 years earlier. Initially, a 38-year old man was diagnosed with cervical lymphadenopathy, and biopsy was interpreted as reactive follicular hyperplasia; no treatment was given, and the lymphadenopathy resolved spontaneously. Eight years later, the patient underwent surgery for a left testicular mass and gastroscopy for gastric symptoms. The patient died 7 months later with evidence for intra-abdominal and central nervous system lymphoma after a brief but temporary response to M-BACOD chemotherapy. Orchiectomy specimen and gastroscopic biopsy showed diffuse large B-cell lymphoma (CD20+), which infiltrated between well-preserved tubules in the testis. Histological comparison with 20 testicular lymphomas without previous lymphoma showed tubule infiltration in all cases, suggesting that the tubule-preserving infiltration pattern could be a histological marker for secondary lymphoma involvement in testis. On re-examination, the lymph node 8 years prior was verified as follicular, predominantly small, cleaved cell lymphoma with bcl2-positive follicles. The earlier follicular lymphoma and the subsequent diffuse large cell lymphoma were analyzed using polymerase chain reaction and showed identical sequences of the t(14;18) translocation and immunoglobulin heavy chain gene rearrangement. Analysis of the VH-gene sequences from the follicular lymphoma revealed sequence heterogeneity consistent with ongoing mutation. However, the transformed diffuse large cell lymphoma had no intraclonal variation, with the sequence matching with one of the subclones from the low-grade follicular lymphoma. These results confirm that the large cell transformation of follicular lymphoma occurs in a single follicular lymphoma cell. This case also indicates that the selection of the transformed clone can be part of the natural history of disease and can occur without exposure to chemotherapy.

Base Sequence↗

Deviated VH4 immunoglobulin gene usage is found among thyroid mucosa-associated lymphoid tissue lymphomas, similar to the usage at other sites, but is not found in thyroid diffuse large B-cell lymphomas.

It remains unclear whether or not diffuse large B-cell lymphomas of extranodal sites arise from mucosa-associated lymphoid tissue (MALT) lymphomas. We studied the clinicopathological features of MALT lymphoma and diffuse large B-cell lymphoma in the thyroid gland, with special reference to VH usage of immunoglobulin gene rearrangement, to clarify the relationships between these two types of lymphomas. In addition, t(11; 18) (q21; q21) translocation was examined by multiplex reverse transcription-polymerase chain reaction. We examined 58 patients with primary thyroid lymphoma: 31 (male seven and female 24) with MALT lymphoma and 27 (male three and female 24) with diffuse large B-cell lymphoma. Interestingly, the sequence of VH genes revealed that the two subtypes differed significantly in their use of the VH4 family (P < 0.05). Of the seven MALT lymphomas, three used the VH4 family and the other four used the VH3 family, whereas eight out of nine diffuse large B-cell lymphoma used the VH3 family, one used the VH1 family, and none used the VH4 family. It was also interesting that, in one diffuse large B-cell lymphoma patient with MALT lymphoma, the diffuse large B-cell lymphoma component used the VH3 family and the MALT lymphoma component used the VH4 family. These data imply that, in a subset of cases, these two subtypes do not share a common origin and that at least some diffuse large B-cell lymphomas have a de novo origin. No t(11; 18) (q21; q21) was detected in thyroid lymphomas, which are different from MALT lymphoma of the stomach, lungs, large intestine and ocular adnexa. This strongly indicated that the presence of t(11; 18) (q21; q21) in MALT lymphoma is organ-specific.

Adult↗

Bone marrow biopsy involvement by non-Hodgkin's lymphoma: frequency of lymphoma types, patterns, blood involvement, and discordance with other sites in 450 specimens.

To evaluate the features of bone trephine biopsy involvement by non-Hodgkin lymphoma, 450 specimens were evaluated for percentage of marrow involvement, pattern of involvement, presence of germinal centers or follicular structures, and discordance with other involved sites. A subset of 197 cases was evaluated for evidence of concurrent peripheral blood involvement. Follicular grade 1 lymphoma (30.4%) was the most common type to involve the marrow, followed by diffuse large B-cell lymphoma (16.0%), mantle cell lymphoma (9.3%), low-grade B-cell lymphoma, not otherwise specified (8.7%), lymphoplasmacytic lymphoma (8.4%), follicular grade 2 lymphoma (7.1%), and mature T- and NK-cell lymphomas (6.4%). A mixed pattern of infiltration was most common, followed by paratrabecular, nodular, diffuse, and interstitial patterns. Greater than 90% of follicular lymphomas had at least a focal paratrabecular infiltration pattern, but this pattern was also seen with other lymphoma types. Interstitial disease infiltration tended to correlate with lymphoplasmacytic lymphoma but was also not specific. The presence of germinal centers or follicular structures was associated with follicular lymphoma in 88% of cases. Discordance between the bone marrow morphology and other tissue sites was observed in 24.9% of cases and was most often seen with follicular or diffuse large B-cell lymphoma. Peripheral blood involvement by lymphoma was observed in 29% of cases, found in all disease groups except for follicular grade 3 lymphoma. This study highlights the frequency of different lymphoma patterns in the marrow, limitations of primary lymphoma classification on biopsy material alone, and the relative frequency of marrow discordance and peripheral blood involvement by marrow lymphoma.

Adolescent↗

Mantle zone lymphoma: a morphometric comparison with centrocytic and immunocytic lymphomas and reactive secondary follicles.

Nuclear size and shape of lymphoid cells were evaluated morphometrically in the mantle zone lymphoma, immunocytic lymphoma, and centrocytic lymphoma, and were compared with those of reactive secondary follicles. Shape factors (forms Ar, Ell, Pe, and Dia) have been used to quantitatively define the most frequent nuclear profiles. One of the testing sets consisted of the nuclei of the light, dark, and mantle regions of reactive nodes, as well as those of the centrocytic lymphoma, immunocytic lymphoma, and the mantle-fashion growth lymphoma. Another testing set was made up of only the three types of lymphoma and was used for evaluating the variability of shapes within these groups by means of a pattern recognition algorithm. The content of reactive T lymphocytes was assessed in all cases by immunohistochemistry. The results of transforming centroid values into geometric shapes by computer modelling indicated that only minor geometric differences existed between the a priori qualitatively chosen nuclear types and those modeled a posteriori by computer. All the nuclear types were found in each of the reactive regions and in each of the lymphomas. However, highly significant differences of distribution were detected among the three categories of lymphoma and between each reactive region and each lymphoma. The cases of centrocytic lymphoma showed constant findings in terms of nuclear composition, while lymphomas with mantle-fashion growth and the examples of immunocytic lymphoma showed significant variability. These observations confirm that the centrocytic lymphoma represents a distinct entity, although its normal counterpart is still unknown, and question the view that the immunocytoma and the mantle zone lymphoma correspond to homogenous categories of non-Hodgkin's lymphomas. In addition, since all the qualitatively and quantitatively detected nuclear types were found in all the reactive regions and in all the lymphomas, albeit with different distributions, it has to be assumed that only numerical differences exist among the various lymphomas and the reactive regions.

Adult↗

The world health organization classification of malignant lymphomas in japan: incidence of recently recognized entities. Lymphoma Study Group of Japanese Pathologists.

New insights into the immunology and genetics of malignant lymphomas have allowed the recognition of new entities and the refinement of previously recognized disease categories. The relative incidence of these subtypes of malignant lymphoma is also known to differ according to geographic location. In order to clarify the current status of malignant lymphomas in Japan and the relative incidences of their subtypes, 3194 patients were classified according to the new World Health Organization (WHO) classification. Among these were 3025 cases (94.71%) of non-Hodgkin's lymphoma (2189 cases (68.53%) of B-cell lymphoma, 796 cases (24.92%) of T-cell lymphoma) and 141 cases (4.41%) of Hodgkin's lymphoma. The incidences of the major subtypes of non-Hodgkin's lymphoma were 33.34% for diffuse large B-cell lymphoma, 8.45% for marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type, 8.05% for plasma cell myeloma, 7.45% for adult T-cell leukemia/lymphoma (ATLL), 6.7% for follicular lymphoma, 6.67% for peripheral T-cell lymphoma of unspecified type, 2.79% for mantle cell lymphoma, 2.6% for nasal and nasal-type T/NK cell lymphoma, 2.35% for angioimmunoblastic T-cell lymphoma, and 2.35% for precursor B-cell lymphoblastic leukemia/lymphoma, in decreasing order. The other subtypes comprised less than 2%, mainly precursor T-cell lymphoblastic lymphoma/leukemia (1.72%), anaplastic large-cell lymphoma of T- and null-cell types (1.53%), and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (1.31%). The incidence of ATLL was influenced by its high percentage (19.20%) in the south-western Japanese island, Kyushu, an endemic area of human T-cell leukemia virus type 1 (HTLV-1), but which appeared to be lower than that in a previous study. The nodular sclerosis and mixed cellularity types of Hodgkin's disease occupied 1.78% and 1.63%, respectively. These data are distinct from those in Western countries and similar in several ways to those in the East, although the relatively high rate of ATLL was attributed to the geographical difference in the etiologic factor, HTLV-1.

Humans↗

Clinical and pathological features in T-cell gastric lymphoma associated with human T-cell leukemia virus type 1 (HTLV-1) in comparison with B-cell gastric lymphoma.

BACKGROUND/AIMS: We investigated clinical features of T-cell gastric lymphomas associated with human T-cell leukemia virus type 1 (HTLV-1). METHODOLOGY: Ninety patients with gastric lymphoma who underwent gastrectomy were included in this study. They were divided into T-cell and B-cell gastric lymphomas according to the immunohistochemical expression of surface T-cell or B-cell markers. Clinicopathological features and surgical outcome were compared between T-cell and B-cell gastric lymphomas. Correlation between T-cell gastric lymphoma and Epstein-Barr virus, p53, MIB-1, and CD44 variant 6 on lymphoma cells was evaluated in 60 patients by in situ hybridization and immunohistochemical examination. Anti-adult T-cell leukemia antigen was evaluated in 74 patients in the blood serum were evaluated. RESULTS: Nine of the 90 patients were classified as T-cell gastric lymphoma. Patients with T-cell gastric lymphoma had significantly more nodal involvement and poorer resectability than those with B-cell gastric lymphoma. Positivity of serum anti-adult T-cell leukemia antigen was significantly higher in T-cell lymphoma patients (100%) than in B-cell lymphoma patients (41%). However, there was no significant difference in Epstein-Barr virus positivity and expression of p53, MIB-1, CD44 variant 6 between T-cell and B-cell lymphomas. The five-year-survival rate in patients with T-cell gastric lymphomas was 0% and whereas that in B-cell gastric lymphoma was 45%, there was a significant difference between the two groups (p < 0.01). Two patients with T-cell lymphoma who underwent emergency gastrectomy died in hospital during follow-up. CONCLUSIONS: The surgical outcome of patients with T-cell lymphoma with anti-adult T-cell leukemia antigen tended to be very poor, despite curative resection. Thus, intensive chemotherapy is recommended for the patients with HTLV-1 associated T-cell gastric lymphoma.

Biomarkers, Tumor↗

Differentiating large cell lymphoma from indolent small B-cell lymphoma in fine needle aspirates using p53, PCNA and transformed lymphocyte count.

OBJECTIVE: To determine the usefulness of proliferating cell nuclear antigen (PCNA), p53 protein expression and transformed lymphocyte count (TLC) as adjunctive tests to differentiate indolent small B-cell lymphoma from large cell lymphoma in fine needle aspiration biopsies. STUDY DESIGN: Aspirates of lymphoproliferative disorders from April 1993 to January 1997 were reviewed. The percentage of TLCs was determined on the Papanicolaou smear. The percentage and intensity of p53 and PCNA immunocytochemical staining was evaluated on cell block sections. These results were compared and correlated with the final diagnoses based on available morphology, flow cytometry and clinical history. RESULTS: There were 40 cases of non-Hodgkin's lymphoma and 12 reactive lymph nodes. Adequate cell blocks were available on 16 large cell lymphomas, 7 grade 1-2 follicular center cell lymphomas, 6 mucosal associated lymphoid tissue lymphomas, 2 small lymphocytic lymphomas and 2 mantle cell lymphomas. Average TLC and p53 nuclear staining was highest in large cell lymphomas (57% TLC and 24% p53), followed by grades 1 and 2 follicular lymphomas (14% TLC and 15% p53) and lowest in other indolent lymphomas (< 10% TLC and < 1% p53). Average PCNA staining was highest in large cell lymphomas (46%) and lowest in small lymphocytic lymphomas (7%); however, TLC was the best parameter for differentiating large cell lymphoma from indolent small B-cell lymphoma. CONCLUSION: TLC differentiated large cell lymphoma from indolent small B-cell lymphoma better than either p53 or PCNA alone or in combination. Significant overlap between categories limits usefulness of these immunocytochemical stains for differentiating these entities.

Biopsy, Needle↗

Breast lymphoma. A B-cell spectrum including the low grade B-cell lymphoma of mucosa associated lymphoid tissue.

We studied the morphologic, immunologic, and clinical features of 31 cases of malignant lymphoma involving the breast. Primary breast lymphoma occurred in nine women with a median age of 69 years (range, 51-87 years); median follow-up was 31 months (range, 9-67 months). Eight cases were low grade, one was high grade, and all expressed B-lineage antigens. Four cases had features of lymphoma of mucosa-associated lymphoid tissue (MALT); three were free of disease after excision alone at 10, 12, and 48 months, whereas the fourth relapsed with transition to immunoblastic lymphoma and died at 25 months. Four patients had follicular lymphomas, three of which relapsed, causing death from active disease at a median of 55 months (range, 25-67 months). One case of small noncleaved cell lymphoma relapsed, causing death at 31 months. Lymphoma secondarily involved the breast in 22 patients (21 women, one man) with a median age of 60 years (range, 39-83 years) at breast relapse; these patients were followed for a median of 88 months (range, 2-271 months) from primary diagnosis and 4 months (range, 0-116 months) from breast relapse. Nineteen patients had prior documented lymphomas (10 nodal or splenic, nine extranodal), and breast involvement most commonly occurred as part of widespread, predominantly nodal disease. Three patients had breast involvement by lymphomas that were generalized at diagnosis or staging. Thirteen cases were low grade (nine follicular), seven intermediate grade, and one high grade; 19 of 20 cases expressed B-lineage antigens, and one expressed T-lineage antigens. Four cases had features of MALT-type lymphoma; in these patients, isolated breast relapses were interspersed with other extranodal relapses, with interim resolution of disease after local or systemic therapy; two were free of disease and two were alive with localized disease on treatment at median follow-up of 60 months (range, 9-91 months). In contrast, 15 of 18 nonMALT lymphomas had widespread disease at breast relapse (median, 29 months; range, 0-259 months); 16 of 18 received systemic therapy, 10 died with active disease, and five of eight had disseminated active disease at last follow-up. Primary breast lymphomas were commonly low grade. The follicular lymphomas had clinical behavior similar to nodal follicular lymphoma. Primary MALT-type lymphomas were a distinct subset with a potential for disease-free survival after local therapy. Secondary breast lymphomas were heterogeneous and more commonly higher grade, although follicular lymphoma was the most common subtype.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

A clinicopathologic study of primary small intestine lymphoma: prognostic significance of mucosa-associated lymphoid tissue-derived lymphoma.

BACKGROUND: It remains unclear whether the presence of mucosa-associated lymphoid tissue (MALT) lymphoma has prognostic implications for patients with primary small intestine lymphoma. METHODS: The clinicopathologic features of 80 patients with primary small intestine lymphoma were examined retrospectively in relation to the presence of MALT lymphoma. Survival was compared univariately and multivariately among the groups divided by clinicopathologic findings. RESULTS: Twenty-one cases (26%) were diagnosed as low grade B-cell lymphoma (15 marginal zone B-cell lymphoma of MALT type, 2 mantle cell lymphoma, and 4 follicle center lymphoma), 46 cases (58%) were diagnosed as high grade B-cell lymphoma (19 secondary large cell lymphoma with a low grade MALT component, 17 diffuse large cell lymphoma without MALT features, 7 Burkitt lymphoma, and 3 lymphoblastic lymphoma), and 13 cases (16%) were diagnosed as T-cell lymphoma. A significantly better survival was noted for patients without colorectal and/or gastric involvement, diffuse infiltration under macroscopy, high grade histology, and perforation. Those patients with MALT type tumors, less advanced stage of disease, B-cell phenotype, benign lymphoid follicular hyperplasia, and radical tumor resectability appeared to have a better survival rate. Based on Cox multivariate analysis, early stage disease and MALT-derived tumors were determined to be independent prognostic factors (P < 0.05). CONCLUSIONS: The presence of MALT-derived lymphoma appears to have a favorable prognosis among patients with primary small intestinal lymphoma.

Adolescent↗

Expression of CXCL13, a chemokine highly upregulated in germinal center T-helper cells, distinguishes angioimmunoblastic T-cell lymphoma from peripheral T-cell lymphoma, unspecified.

The germinal center T-helper cell has been proposed as the cell of origin for angioimmunoblastic T-cell lymphoma. Our recent report of expression of CXCL13, a chemokine critical for germinal center formation and one of the most highly upregulated genes in the germinal center T-helper cell subset, in the majority of angioimmunoblastic T-cell lymphoma cases, provided further support for this theory. To determine the specifity of this marker for angioimmunoblastic T-cell lymphoma, we evaluated CXCL13 expression in 26 nodal-based peripheral T-cell lymphomas and 14 lymph nodes showing paracortical lymphoid hyperplasia. No significant paracortical CXCL13 staining was seen in the reactive lymph nodes. By WHO classification criteria, 20 of the lymphoma cases were considered peripheral T-cell lymphoma, unspecified, and six were reclassified as angioimmunoblastic T-cell lymphoma after immunohistochemical detection of disorganized follicular dendritic cell meshworks. Combining the results of our studies, 31 of 35 angioimmunoblastic T-cell lymphoma cases (89%) showed CXCL13 expression, in contrast to two out of 20 peripheral T-cell lymphoma, unspecified cases (10%). The two peripheral T-cell lymphoma, unspecified cases that were positive for CXCL13 showed a Lennert lymphoma-like histology. While these cases did not meet all histologic criteria for angioimmunoblastic T-cell lymphoma, they did show an increase in EBV-positive B cells, suggesting they may be histologic variants of angioimmunoblastic T-cell lymphoma. In conclusion, CXCL13 expression is a distinctive feature of angioimmunoblastic T-cell lymphoma, providing further support for the germinal center T-helper cell as the cell of origin for this neoplasm. Given its specificity when compared to cases of peripheral T-cell lymphoma, unspecified as well as paracortical lymphoid hyperplasia, it may be a useful marker in the diagnosis of angioimmunoblastic T-cell lymphoma.

Biomarkers, Tumor↗