Small Cleaved Cell Research Articles

Successful treatment of recurrent follicular B-cell lymphoma with clarithromycin, prednisolone, and cyclophosphamide

Successful treatment of recurrent follicular B-cell lymphoma with clarithromycin, prednisolone, and cyclophosphamide

A newly established human lymphoma cell line, FL-18, carrying a 14;18 translocation.

A new human cell line named FL-18, carrying a 14;18 translocation [t(14;18)(q32;q21)], was established from a Japanese patient with follicular small cleaved cell lymphoma. The established FL-18 cells had monoclonal surface immunoglobulins (IgG-kappa) and were negative for Epstein-Barr virus nuclear antigens. The high-resolution banding technique indicated the breakpoints of chromosomes 14 and 18 involved in the characteristic 14;18 translocation to be at sub-bands 14q32.3 and 18q21.3, respectively. The FL-18 cell line should be useful for studying oncogenic events associated with 14;18 translocation and karyotype evolution.

Follicular Lymphoma With Small Intestinal Involvement Detected by Double-Balloon Enteroscopy

1 57-year-old woman was referred for further examination of a duodenal lesion. She was asymptomatic and physical ndings were normal. Laboratory data revealed no abnormal ndings. Upper gastrointestinal endoscopy revealed multiple ranules with a white color in the second portion of the duoenum. Biopsy specimens showed lymphoid follicles with a onotonous population of small-cleaved cells in the mucosa nd the immunohistochemical staining was positive for CD20, D10, and bcl-2 (Figure A) and negative for CD5. Thus, a iagnosis was made of follicular lymphoma (FL), grade 1, by a ematopathologist. Colonoscopic examination revealed no abormal findings. To investigate the initial spread and pattern of he small intestinal involvement, double-balloon enteroscopy DBE) was performed. DBE findings revealed multiple small ranules at the jejunum (Figure B). Biopsy specimens, which ere taken under DBE, also revealed FL, grade 1. Computerized omography of the chest and abdomen, gallium scintigraphy, nd bone marrow aspirate were normal. Based on these findngs, FL had arisen not only in the duodenum but also the ejunum. The lymphoma was evaluated as stage IE (involvement f a single lymph node region/lymphoid structure and involveent of a single extranodal site). Systemic chemotherapy was erformed because her lymphoma was not localized. The paient was treated with a combination of cyclophosphamide, oxorubicin, vincristine, prednisone, and rituximab. Sixteen onths after this chemotherapy, DBE revealed the disappearnce of lymphoma. FLs in the duodenum, which we encountered, have been eported with increasing frequency.1 However, it has been difcult to investigate whether FLs are involved extensively in the mall intestine or not. As we report here, DBE enables us to mprove the diagnostic yield in identifying small intestinal nvolvement of FL and to decide the optimal therapy.

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.

The histologic classification of 602 cases of feline lymphoproliferative disease using the National Cancer Institute working formulation.

Case information and histologic slides for 688 admissions of feline tissues from 12 veterinary institutions were assembled and reviewed to determine tissues obtained by biopsy or necropsy, age and sex of cat, tumor topography, feline leukemia viral antigen status, histologic frequency of mitoses, diagnosis, presence of necrosis, and presence and degree of sclerosis. Histologic sections were examined to place the lesions in one of the diagnostic categories of the National Cancer Institute working formulation (NCI WF) for lymphomas or lymphoid leukemia. Correlations between the various factors determined were tested using contingency tables and chi-square analysis to provide a statistical comparison between the levels of observations determined by case examination with the numbers expected from chance alone. Significant correlations (P < or = 0.05) were found between diagnosis and tumor topography, the frequency of mitoses, necrosis, sclerosis, and age, between mitoses and necrosis, topography, age, and feline leukemia viral infection status, between topography and necrosis and age, and between leukemia viral status and age. Significant correlations between diagnosis and tumor topography included a greater than expected number of cases of acute and chronic lymphoid leukemia and multicentric distribution of tumor. Small cell lymphomas were more frequent than expected in enteric and cutaneous areas and less frequent than expected in mediastinal, renal, and multicentric areas. In contrast, the high-grade small noncleaved type of lymphomas was found significantly more frequently than expected in the mediastinum and less frequently than expected in enteric tissues. In comparing diagnosis and frequency of mitoses, the lymphomas classified as low grade by the NCI WF were significantly more frequent than expected in the lower categories (0-2/100x) of mitoses, and those classified as high-grade lymphomas were more frequent than expected in the higher categories (4-8/1OOx) of mitoses. In comparing diagnosis and sclerosis, diffuse sclerosis was more frequent than expected for the intermediate grade lymphomas of mixed cell type and for the high-grade lymphomas of the immunoblastic polymorphous type. In comparing diagnosis and locally extensive necrosis, this feature was more frequently observed than expected for cases of intermediate grade lymphoma of the small-cleaved cell category and for the high-grade lymphoma of the immunoblastic cell type. In comparing mitoses and necrosis, the lower grade lymphomas were, in general, characterized by a lower frequency of mitoses and a lower incidence of necrosis then would be expected from chance alone. In contrast, the higher grade lymphomas were characterized by more frequent mitoses and a higher incidence of necrosis. In tests comparing mitoses and tumor topography, lymphomas of the alimentary tract were more frequently observed than expected in the category with the lowest level of mitoses (0-1/100x), whereas lymphomas of the mediastinum and kidney were more frequently observed than expected in the categories with a higher level (4-20/ 100x) of mitoses.

Cicatrizing conjunctivities associated with paraneoplastic lichen planus

PURPOSE: To report two cases of cicatrizing conjunctivitis associated with paraneoplastic lichen planus. METHODS: Case reports. RESULTS: Two patients were examined because of redness and discomfort in both eyes. A 63-year-old woman with follicular, small-cleaved cell lymphoma had cicatrizing conjunctivitis, stomatitis, vulvitis, and skin lesions. A 25-year-old man with malignant thymoma had cicatrizing conjunctivitis, erosive stomatitis, and penile papules. Histopathologic studies of conjunctiva and skin biopsy specimens in the first patient and labial biopsy specimens in the second revealed lichen planus. CONCLUSION: Paraneoplastic lichen planus is a possible cause of cicatrizing conjunctivitis associated with inflammatory skin and mucous membrane disease.

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).

Immunolocalization of the ICE/Ced-3–Family Protease, CPP32 (Caspase-3), in Non-Hodgkin's Lymphomas, Chronic Lymphocytic Leukemias, and Reactive Lymph Nodes

AbstractImmunohistochemical analysis of the apoptosis-effector protease CPP32 (Caspase-3) in normal lymph nodes, tonsils, and nodes affected with reactive hyperplasia (n = 22) showed strong immunoreactivity in the apoptosis-prone germinal center B-lymphocytes of secondary follicles, but little or no reactivity in the surrounding long-lived mantle zone lymphocytes. Immunoblot analysis of fluorescence-activated cell sorted germinal center and mantle zone B cells supported the immunohistochemical results. In 22 of 27 (81%) follicular small cleaved cell non-Hodgkin's B-cell lymphomas, the CPP32-immunopositive germinal center lymphocytes were replaced by CPP32-negative tumor cells. In contrast, the large cell component of follicular mixed cells (FMs) and follicular large cell lymphomas (FLCLs) was strongly CPP32 immunopositive in 12 of 17 (71%) and in 8 of 14 (57%) cases, respectively, whereas the residual small-cleaved cells were poorly stained for CPP32 in all FLCLs and in 12 of 17 (71%) FMs, suggesting that an upregulation of CPP32 immunoreactivity occurred during progression. Similarly, cytosolic immunostaining for CPP32 was present in 10 of 12 (83%) diffuse large cell lymphomas (DLCLs) and 2 of 3 diffuse mixed B-cell lymphomas (DMs). Immunopositivity for CPP32 was also found in the majority of other types of non-Hodgkin's lymphomas studied. Plasmacytomas were CPP32 immunonegative in 4 of 12 (33%) cases, in contrast to normal plasma cells, which uniformly contained intense CPP32 immunoreactivity, implying downregulation of CPP32 in a subset of these malignancies. All 12 peripheral blood B-cell chronic lymphocyte leukemia specimens examined were CPP32 immunopositive, whereas 3 of 3 small lymphocytic lymphomas were CPP32 negative, suggesting that CPP32 expression may vary depending on the tissue compartment in which these neoplastic B cells reside. The results show dynamic regulation of CPP32 expression in normal and malignant lymphocytes.

Immunolocalization of the ICE/Ced-3–Family Protease, CPP32 (Caspase-3), in Non-Hodgkin's Lymphomas, Chronic Lymphocytic Leukemias, and Reactive Lymph Nodes

Immunohistochemical analysis of the apoptosis-effector protease CPP32 (Caspase-3) in normal lymph nodes, tonsils, and nodes affected with reactive hyperplasia (n = 22) showed strong immunoreactivity in the apoptosis-prone germinal center B-lymphocytes of secondary follicles, but little or no reactivity in the surrounding long-lived mantle zone lymphocytes. Immunoblot analysis of fluorescence-activated cell sorted germinal center and mantle zone B cells supported the immunohistochemical results. In 22 of 27 (81%) follicular small cleaved cell non-Hodgkin's B-cell lymphomas, the CPP32-immunopositive germinal center lymphocytes were replaced by CPP32-negative tumor cells. In contrast, the large cell component of follicular mixed cells (FMs) and follicular large cell lymphomas (FLCLs) was strongly CPP32 immunopositive in 12 of 17 (71%) and in 8 of 14 (57%) cases, respectively, whereas the residual small-cleaved cells were poorly stained for CPP32 in all FLCLs and in 12 of 17 (71%) FMs, suggesting that an upregulation of CPP32 immunoreactivity occurred during progression. Similarly, cytosolic immunostaining for CPP32 was present in 10 of 12 (83%) diffuse large cell lymphomas (DLCLs) and 2 of 3 diffuse mixed B-cell lymphomas (DMs). Immunopositivity for CPP32 was also found in the majority of other types of non-Hodgkin's lymphomas studied. Plasmacytomas were CPP32 immunonegative in 4 of 12 (33%) cases, in contrast to normal plasma cells, which uniformly contained intense CPP32 immunoreactivity, implying downregulation of CPP32 in a subset of these malignancies. All 12 peripheral blood B-cell chronic lymphocyte leukemia specimens examined were CPP32 immunopositive, whereas 3 of 3 small lymphocytic lymphomas were CPP32 negative, suggesting that CPP32 expression may vary depending on the tissue compartment in which these neoplastic B cells reside. The results show dynamic regulation of CPP32 expression in normal and malignant lymphocytes.

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.

Chromosome studies in the non-Hodgkin's lymphomas: the role of the 14;18 translocation.

The 14;18 translocation [t(14;18)] is the most common chromosome abnormality noted in the non-Hodgkin's lymphomas (NHL). Although the translocation is seen in various histologic subtypes, it is most commonly associated with the follicular lymphomas, especially the small-cleaved cell (FSC) and mixed-cell (FM) subtypes. The translocation breakpoint has been cloned and DNA probes from the junction on chromosome 18 can now be used to detect the genetic consequences of the translocation in tumors with few dividing cells. This will allow a more precise classification of this subset of lymphomas and should lead to better understanding of the biology of this category of lymphomas. Finally, these insights will help in the development of more effective and possibly less toxic therapy.

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.

Sclerosing variants of follicular center cell lymphomas presenting in the retroperitoneum.

A study of 22 patients with sclerosing variants of follicular center cell lymphoma (FCCL) presenting as a retroperitoneal mass is reported. These FCCL variants comprise 74% of retroperitoneal non-Hodgkin's lymphoma presentations. A partial intranodal follicular growth pattern was present in each case, and marked sclerosis of a distinctive pattern was associated with extensive perinodal lymphomatous infiltration. Small cleaved cells (SCC) predominated in five cases, large cleaved cells (LCC) in 14, and large noncleaved cells (LNCC) in three. Eighty percent of patients with SCC predominance were Stage I-II, compared to 50% of those with LCC predominance; all three LNCC cases were Stage IV. High stage was attained primarily by renal invasion or infiltration out the mesenteric root into gut or omentum; only three patients had biopsy proven extraabdominal disease. Combined modality therapy achieved an 88% complete or partial remission rate in patients with SCC and LCC predominance; all three LNCC patients died.

Non-hodgkin's lymphoma phenotyping: Problems in the use of heterologous and monoclonal antibodies

Cell suspensions or frozen sections of lymph node biopsies from 32 patients with non-Hodgkin's lymphoma (NHL) were studied for sheep erythrocyte (E)-binding under three conditions (E standard, E AET, E gravity), F c and C receptors, immunoglobulin (Ig) heavy and light chain class and reactivity with heterologous antisera to T cells (T-LCL), HLA-D (Ia-like) and common acute lymphocytic leukemia (c-ALL) antigens. Selected B and T cell lymphomas were also tested for reactivity with the monoclonal antibodies OKT 3, OKT 4, OKT 6, OKT 8, OKT 11A, Leu-1, leu-2a, Leu-3a, Leu-4 and Leu-7. There were 26 B and 6 T lymphomas. Most B lymphomas were μ+ (81%), χ+ (77%) and 31% were μ+ δ+. One of the T lymphomas arose in a patient with antecedent follicular small-cleaved (B) cell lymphoma. The most accurate marker for characterizing the immunologic phenotype in NHL was the clonal excess of χ+ or λ+ cells. Neither E standard, E AET, E gravity or T-LCL were consistently reliable as sole reagents in identifying T-cell lymphomas, their individual scores often being lower than those of monoclonal pan-T cell reagents. HLA-D (Ia-like) antigen was noted in 89% of B and 50% of T lymphomas. The corresponding values for c-ALL antigen were 12 and 33%, respectively. The comparative scores in T-lymphomas between OKT 4 and Leu-3a for “helper-inducer” (HE) cells and OKT 8 and Leu-2a for “suppressor-cytotoxic” (SU) cells were not uniformly consistent. Four T lymphomas had a mixed HE/SU cell phenotype, one was HE, and another SU. Anti-T reactivity was detected in the neoplastic follicles of six of seven follicular lymphomas. The percentage of anti-T reactive cells within positive neoplastic follicles was usually small (5–15%) and of the same order as that noted within reactive lymphoid follicles (5–30%). High numbers (50–100%) of cells from five small lymphocytic B, three diffuse small cleaved cell B and six T cell lymphomas were also positive with one or more anti-T reagents, suggesting the presence of cross-reactive antigens that make phenotyping of lymphomas with monoclonal antibodies problematic. Reactivity with the monoclonal antibody Leu-7 (HNK-1), a putative NK-specific reagent, was seen in one of five B and three of five T lymphomas.