Follicular Small Cleaved Cell Research Articles

Common Symptoms - Different Diseases: Coexistence of Neurosyphilis and Non-Hodgkin's Lymphoma

We describe the case of a 32-year-old man with generalized lymphadenopathy who was diagnosed with a low-grade follicular small-cleaved cell lymphoma. The patient developed hearing loss, tinnitus and cerebrospinal fluid (CSF) pleocytosis attributed to central nervous system (CNS) infiltration by his malignancy, while receiving chemotherapy with vincristine, cyclophosphamide and prednisone. Despite intrathecal chemotherapy with methotrexate, the CSF pleocytosis persisted. Neurosyphilis was suspected because of prior history of gonorrhea and was confirmed with serologic studies of blood and CSF and from the decline of the anti-treponemal antibody titers with appropriate antibiotic therapy. Syphilis should be considered in the differential diagnosis of patients with generalized lymphadenopathy and neurologic signs or symptoms.

PROGNOSTIC FACTORS IN LOW GRADE LYMPHOMA (Study of 278 Cases)

Non-Hodgkin's lymphomas are a diverse group of tumours which show morphologically a heterogenous wide spectrum of disease complexes and often unpredictable response to treat­ment. Clinically they vary from fulmi­nate conditions to chronic indolent processes (Jelliffe, 1986). According to the Working Formu­lation, the NHLs are grouped into three broad prognostic categories, low, intermediate and high grade dis­eases. Low grade NHLs are com­posed of three histologic subtypes by the Working Formulation: small lym-phocytic (SLL), follicular small cleaved cell (FSCL) and follicular mixed small cleaved and large cell (FML). Whereas radiotherapy is potiential-ly curative in localized disease (stage I and II), the most appropriate man­agement of wide-spread lymphoma remains controversial. Current thera­peutic modalities range from a cau­tious Watch and Wait approach, through chemotherapy of moderate intensity, to aggressive muftidrug regi­mens combined with total nodal irradi­ation (Young et al., 1988 and Port-lock, 1990). The aim of this work is review of different treatment modalities of newly diagnosed low grade NHL patients with analysis of the prog­nostic factors for response and survival.

Clinicopathological Analysis of Follicular Lymphoma with a Polyploid Karyotype

The prognostic significance of specific cytogenetic abnormalities in follicular lymphoma (FL) is an area of ongoing research. A small percentage of FL are characterized by a polyploid karyotype. Several studies have analyzed ploidy level to determine its role as an independent prognostic factor in non-Hodgkins lymphoma, with equivocal results, mostly using DNA flow cytometry to ascertain ploidy status. We have performed cytogenetic analyses on 180 cases of FL with a t(14;18) diagnosed between 1980 and 1995. Cases were divided into a polyploid group (20 cases) and a non-polyploid group (160 cases), polyploidy defined as a modal chromosome number of 58 or greater. Each group included examples of the 3 subtypes of FL, [Working Formulation]: 1) follicular small cleaved cell (FSC), 2) follicular mixed, small and large cell (FM), and 3) follicular large cell (FLC). The median follow-up time was 38.5 months. The histological subclassification of the polyploid group revealed much less FSC (30% vs 66%, p < 0.004) and much more FLC (25% vs 4%, p < 0.003) than the non-polyploid group, implying histological progression may occur in parallel with the development of polyploidy. Recognized clinical prognostic factors were evenly distributed between the two groups and no survival difference was detected. We show that polyploidy as determined by classical cytogenetics is present in different frequencies across the subtypes of FL with a t(14;18), but is not an independent prognostic factor for survival in FL.

Lymphoid cell aggregates: A useful clue in the fine‐needle aspiration diagnosis of follicular lymphomas

Among the various types of lymphoma, follicular lymphoma (FL) is known to have significant limitations in cytologic diagnosis by the fine-needle aspiration (FNA) method. The diagnostic accuracy (DA) for non-Hodgkin's lymphoma (NHL) by FNA was evaluated by review of 82 cases of histologically proved NHL after prior FNA. The DA for all NHLs was 66% (54/82), and that for low-grade lymphomas, including small lymphocytic lymphoma, follicular small-cleaved cell lymphoma, and follicular mixed cell lymphoma, was 71% (12/17). The DA for FL was 69% (11/16). Review of individual surgical and cytologic materials from FLs revealed a tendency to show fibrosis in the cytologically false-negative group and diffuse areas of lymphoma in the true-positive group. The presence of “aggregation” of uniform lymphoid cells, probably due to cell adhesions with the support of dendritic reticulum cells, was seen in 55% of true-positive FL (6/11). In contrast, only 28% of true-positive diffuse large cell lymphomas (5/18) showed a mild degree of aggregation, and none of 7 cases of true-positive diffuse small-cleaved cell lymphoma showed this feature. The aggregation of cells was not pathognomonic of FL, but its presence with a homogeneous cellular constituent and the paucity of tingible-body macrophages helped us to predict FL. Also, it was a feature distinguishing FL from diffuse small-cleaved cell lymphoma (P = 0.025). Diagn. Cytopathol. 1997;17:467–471. © 1997 Wiley-Liss, Inc.

Lymphoid cell aggregates: A useful clue in the fine-needle aspiration diagnosis of follicular lymphomas

Among the various types of lymphoma, follicular lymphoma (FL) is known to have significant limitations in cytologic diagnosis by the fine-needle aspiration (FNA) method. The diagnostic accuracy (DA) for non-Hodgkin's lymphoma (NHL) by FNA was evaluated by review of 82 cases of histologically proved NHL after prior FNA. The DA for all NHLs was 66% (54/82), and that for low-grade lymphomas, including small lymphocytic lymphoma, follicular small-cleaved cell lymphoma, and follicular mixed cell lymphoma, was 71% (12/17). The DA for FL was 69% (11/16). Review of individual surgical and cytologic materials from FLs revealed a tendency to show fibrosis in the cytologically false-negative group and diffuse areas of lymphoma in the true-positive group. The presence of "aggregation" of uniform lymphoid cells, probably due to cell adhesions with the support of dendritic reticulum cells, was seen in 55% of true-positive FL (6/11). In contrast, only 28% of true-positive diffuse large cell lymphomas (5/18) showed a mild degree of aggregation, and none of 7 cases of true-positive diffuse small-cleaved cell lymphoma showed this feature. The aggregation of cells was not pathognomonic of FL, but its presence with a homogeneous cellular constituent and the paucity of tingible-body macrophages helped us to predict FL. Also, it was a feature distinguishing FL from diffuse small-cleaved cell lymphoma (P = 0.025).

A PCR ANALYSIS OF BCL-2 GENE REARRANGEMENT IN NODAL AND EXTRANODAL NON-HODGKINS-LYMPHOMA (NHL) - SOME UNUSUAL OBSERVATIONS IN SAUDI PATIENTS

Non-Hodgkin's lymphoma (NHL) is the most common malignancy referred to our institute which is the largest tertiary referral cancer centre in Saudi Arabia, The proportion of follicular low grade NHL appears to be extremely small in this population (<5% of all NHL). To date, there is no data available regarding any correlation between bcl-2 gene rearrangement and different cell types of nodal and extranodal NHLs in Saudi patients. We used a sequential polymerase chain reaction (PCR) technique to determine the frequency of bcl-2/J(H) recombination occurring via the major breakpoint region (mbr) in 16 GI tract NHLs including 4 MALT lymphomas and 13 follicular (nodal) NHLs. The results showed only 2/13 (15%) nodal follicular NHLs with bcl-2/J(H) fusion DNA whereas 9/16 (56%) of the extranodal NHLs with at least 2 of them exhibiting MALT characteristics were positive for the bcl-2 gene rearrangement. A breakdown of the proportion of extranodal NHLs of different cell types showing bcl-2 rearrangement via mbr was as follows: 5/8 diffuse large non-cleaved cell (DLNCC), 1/3 diffuse small cleaved cell (DSCC), 1/1 follicular small cleaved cell (FSCC) and 2/4 MALTs. The PCR amplified bcl-2/J(H) fusion DNA from 5 randomly selected tumors (2 MALTs, 1 DLNCC, 1 DSCC and 1 nodal follicular lymphoma) were cloned and sequenced. All 5 of them showed different bcl-2/J(H) N-regions confirming the clonality of each tumor sample. The data indicating a very low incidence of bcl-2 translocation in nodal follicular NHLs and a surprisingly high incidence of it in extranodal NHLs are intriguing, and quite contrary to the findings in Western patients. These unusual observations warrant further studies and may suggest that different genetic events are involved in the development of extranodal NHLs including MALT and follicular center-cell NHLs in Saudi patients.

Recurrent abnormalities of chromosome bands 10q23-25 in non-Hodgkin's lymphoma.

Many nonrandom chromosome abnormalities have been associated with non-Hodgkin's lymphomas (NHL). Some of these are nonspecific changes seen in many different histologic subtypes. We describe a series of abnormalities of chromosome bands 10q23-25 seen in 159 consecutive NHL patients with abnormal cytogenetic findings. The proportion of karyotypes with abnormalities of 10q varied from 3% among the immunoblastic lymphomas to 67% in the diffuse large cleaved cell lymphomas. Seventeen (10.7%) had abnormalities of 10q23-25. All but one of these were B-cell tumors. The abnormalities consisted of six deletions and 11 translocations. Sixteen of the 17 patients had the 10q abnormality when cells were first karyotyped. The remaining patient acquired the 10q abnormality in the third of a series of biopsies. In the follicular histologic subtypes [follicular small cleaved cell (FSC), follicular mixed small cleaved and large cell (FM), and follicular large cell noncleaved (FL-NC)], abnormalities of 10q were found in nine patients, all in association with abnormalities of 14q32. Seven of these were associated with the t(14;18)(q32;q21). Overall, 10q23-25 abnormalities were observed in 11.9% (8/67) of low-grade [small lymphocytic (SL), FSC, and FM] lymphoma cases. DNA was available from five patients with abnormalities of 10q and was probed for rearrangements with the HOXII (TCL3) oncogene probe. As expected, we did not find such rearrangements in these five patients with B-cell tumors. Abnormalities of 10q23-25 have been reported previously in NHL but not at this frequency.

Alfacalcidol is a nontoxic, effective treatment of follicular small-cleaved cell lymphoma

Thirty-four patients with progressive low grade non-Hodgkin's lymphoma were treated with 1 microgram oral alfacalcidol daily. Complete response was seen in four patients and a partial response in four patients with an overall response rate of 24%. Median duration of response was 14 months. Disease stabilised in ten other patients (29%) and 16 patients (47%) had tumour progression. In the sub-group of patients with follicular, small-cleaved cell-lymphoma the overall response to treatment was 29%. Apart from one patient who had a mild transitory elevation of serum calcium there was no recorded toxicity from alfacidol. These results indicate that alfacalcidol has significant antitumour activity in patients with low grade non-Hodgkin's lymphoma of the follicular, small-cleaved cell type.

Common Acute Lymphoblastic Leukemia‐associated Antigen (CALLA)‐positive B cell lymphoma

We analyzed the expression of common acute lymphoblastic leukemia-associated antigen (CALLA) in 134 cases of non-Hodgkin's lymphoma of the B cell type using an immunohistochemical method. The incidence of CALLA expression in B cell lymphomas was higher in follicular lymphomas (29%) than in diffuse lymphomas (15%). Malignant lymphoma (ML), follicular small cleaved cell (FSC) according to the histologic type, showed a considerably high incidence of CALLA (43%), whereas ML, diffuse small cleaved cell (DSC) displayed a very low incidence (5%). These findings suggest the possibility that these two morphologically similar lymphomas may be derived from distinct populations of B cells [CALLA+-germinal center (GC) cells, CALLA- -germinal center (GC) cells or mantle zone (MZ) cells]. In addition, one case of DSC expressed surface immunoglobulin D (SIgD) and alkaline phosphatase (ALPase) as well as CALLA. This indicates that CALLA-positive small cleaved cell lymphoma expressing SIgD or ALPase may represent neoplastic proliferation of CALLA-positive MZ cells of secondary follicles in lymph nodes.

Long‐term results of treatment of patients with follicular lymphomas

The management of patients with follicular lymphoma is controversial, particularly in those with follicular small cleaved cell (FSCC) or nodular poorly differentiated lymphoma (NPDL). Some advocate no treatment until symptoms arise, while others prefer to treat with intensive combination regimens and others with single agents. We reviewed the long-term effects of two types of combination chemotherapy on relapse-free survival and survival on 91 patients (88 were stages III-IV) who had received no previous chemotherapy. Those patients with FSCC lymphoma obtaining a complete remission had a significantly longer median survival than did those obtaining a partial remission (13 years versus 2 years). An adriamycin-containing regimen appeared to be the key factor in obtaining a complete remission in FSCC after taking into consideration prognostic factors. Not only was the complete response rate significantly higher for patients receiving adriamycin, but so too was the median survival and relapse-free survival. BCG immunotherapy appeared to be important in preventing relapse in some of the complete responders with NPDL who received adriamycin.

Liver biopsy immunotyping to characterize lymphoid malignancies.

To determine the feasibility of liver biopsy immunotyping to characterize hepatic lymphoid malignancies, we employed a panel of monoclonal antibodies on snap-frozen hepatic tissue from 18 patients. Six patients proved to have a histologic diagnosis of lymphoid malignancy. By using free avidin and biotin-blocking reagents to block endogenous biotin, followed by standard immunochemistry, immunotyping was successful in all six cases. Serial section typing allowed delineation of complex B cell phenotypes. Furthermore, architecture was preserved allowing discernment of disease patterns (e.g., sinusoidal, hairy cell leukemia vs. portal, follicular small-cleaved cell lymphoma. Unexpectedly, we found striking expression of common ALL antigen in normal bile canaliculi, which may prove of diagnostic or therapeutic relevance. This study establishes the utility of immunohistochemical techniques applied to hepatic biopsies as a valuable adjunct to histologic diagnosis as well as a tool in revealing the immunobiology of the liver.

Immunoregulatory Leu-7+ and T8+lymphocytes in B-cell follicular lymphomas

Lymphocyte subpopulations were profiled in lymph nodes and tonsils showing follicular hyperplasia and in follicular lymphomas with monoclonal antibodies on frozen tissue sections. Immunoregulatory lymphocyte subsets identified with T8 and Leu-7 monoclonal antibodies were quantified within the follicular centers (FC) of the nonneoplastic tissue and neoplastic follicles of the lymphomas with an optical grid defining a unit surface area (USA) of 0.04 mm2. T8+ cells were essentially confined to the interfollicular areas, with a few cells occupying the FC of the nonneoplastic specimens (mean, two and five cells/USA for tonsils and benign lymph nodes, respectively). Although lymphomas exhibited a similar pattern of distribution of T8+ cells, 17 T8+ cells/USA were observed in the follicular small cleaved cell (FSCL) group and eight T8+ cells/USA within the follicular mixed small cleaved and large cell (FML) group. Leu-7+ cells were almost entirely confined to the FC of the nonneoplastic tissues and increased (mean, 17 and 19 cells/USA for tonsils and benign lymph nodes, respectively) compared with the T8+ population. Variable distributions of Leu-7+ cells were found in the FSCL group, with a mean of 16 cells/USA. Very few Leu-7+ cells were present in the FML group. Natural killer cells and/or cytotoxic/suppressor T lymphocytes may play an immunoregulatory role in modulating the growth of follicular lymphomas.