Jerome S. Burke

Lymphoid Neoplasia Associated with the Acquired Immunodeficiency Syndrome (AIDS): The New York University Medical Center Experience with 105 Patients (1981-1986)

We identified 105 patients with lymphoid neoplasia associated with the acquired immunodeficiency syndrome (AIDS) at the New York University Medical Center from 1981 through 1986: 89 had non-Hodgkin lymphoma; 13, Hodgkin disease; and 3, chronic lymphocytic leukemia. Immunophenotypic and antigen receptor gene rearrangement analysis showed the B-cell origin of all non-Hodgkin lymphomas studied and the clonal suppressor-cytotoxic T-cell subset origin of the chronic lymphocytic leukemias. We classified 69% of the non-Hodgkin lymphomas as high grade (small, noncleaved and large cell, immunoblastic-plasmacytoid) and 31% as intermediate grade (diffuse large cell). Each histopathologic category was correlated with distinct clinical features, including a statistically significant difference in median survival. Patients with Hodgkin disease had an atypical, aggressive clinical course, whereas patients with T-cell chronic lymphocytic leukemia had an indolent clinical course. These studies show the clinical, morphologic, and immunophenotypic spectrum of AIDS-associated lymphoid neoplasia, that the natural history of Hodgkin disease is altered in patients with AIDS, and support the Centers For Disease Controls recent revision in diagnostic criteria for AIDS to include intermediate-grade diffuse, aggressive non-Hodgkin lymphomas occurring in patients seropositive for human immunodeficiency virus.

Lymphoid hyperplasia and malignant lymphoma occurring in the ocular adnexa orbit conjunctiva and eyelids a prospective multiparametric analysis of 108 cases during 1977 to 1987

We performed a prospective multiparametric correlative clinical, histopathologic, and immunologic analysis of 117 ocular adnexal lymphoid proliferations developing in 108 patients between October 1977 and July 1987. The ocular adnexal lymphoid proliferations were distributed among the 108 patients as follows: orbit 69 (64%), conjunctiva 30 (28%), and eyelids nine (8%). The 117 ocular adnexal lymphoid proliferations were classified as follows: polyclonal lymphoid hyperplasia, 32 (22 orbit, nine conjunctiva, one eyelid) (27%); monoclonal B cell lymphoma, 81 (48 orbit, 25 conjunctiva, eight eyelid) (69%); null cell lymphoma, one (orbit) (1%); and histologically indeterminate, three (one each: orbit, conjunctiva, eyelid) (3%). Patients presenting with ocular adnexal polyclonal lymphoid hyperplasia and monoclonal B cell lymphoma, and patients developing unilateral and bilateral ocular adnexal lymphoid proliferations did not differ significantly with respect to age, sex, presenting complaints, duration of symptoms, or ophthalmic findings. Classifying ocular adnexal lymphoid proliferations into benign and malignant categories by histopathologic criteria and into polyclonal and monoclonal B cell categories by immunophenotypic criteria was not useful in predicting eventual outcome, including the occurrence of extraocular lymphoma. However, the clinicopathologic characteristics did differ according to the anatomic site of involvement and histopathology of the ocular adnexal lymphoid proliferations. Lymphoid infiltrates of the conjunctiva were associated with a lower incidence of extra-ocular lymphoma (20%) than were those of the orbit and eyelid, 35% and 67%, respectively (statistically significant, P less than .03). Ocular adnexal small lymphocytic and intermediate lymphocytic lymphomas were less often associated with extra-ocular lymphoma than were ocular adnexal lymphomas of all other histologic types, 27% and 46%, respectively (P less than .09). However, the single most important and statistically significant prognostic factor in these patients was the extent of disease at the time of presentation with an ocular adnexal lymphoid proliferation (P less than .001). Eighty-six percent of patients presenting with a unilateral or bilateral clinical stage lE ocular adnexal lymphoid proliferation, regardless of the histopathology or the immunophenotype, had a benign indolent clinical course and failed to develop ocular or extra-ocular lymphoma during a median follow-up period of 51 months. The results of this study substantially improve our understanding of extranodal small lymphocytic proliferations in general, and those of the ocular adnexa in particular.

Clonally related follicular lymphomas and histiocytic/dendritic cell sarcomas: evidence for transdifferentiation of the follicular lymphoma clone

Rare cases of histiocytic and dendritic cell (H/DC) neoplasms have been reported in patients with follicular lymphoma (FL), but the biologic relationship between the 2 neoplasms is unknown. We studied 8 patients with both FL and H/DC neoplasms using immunohistochemistry, fluorescence in situ hybridization (FISH) for t(14;18), and polymerase chain reaction (PCR)/sequencing of BCL2 and IGH rearrangements. There were 5 men and 3 women (median age, 59 years). All cases of FL were positive for t(14;18). The H/DC tumors included 7 histiocytic sarcomas, 5 of which showed evidence of dendritic differentiation, and 1 interdigitating cell sarcoma. Five H/DC tumors were metachronous, following FL by 2 months to 12 years; tumors were synchronous in 3. All 8 H/DC tumors showed presence of the t(14;18) either by FISH, or in 2 cases by PCR with the major breakpoint region (MBR) probe. PCR and sequencing identified identical IGH gene rearrangements or BCL2 gene breakpoints in all patients tested. All H/DC tumors lacked PAX5, and up-regulation of CEBPbeta and PU.1 was seen in all cases tested. These results provide evidence for a common clonal origin of FL and H/DC neoplasms when occurring in the same patient, and suggest that lineage plasticity may occur in mature lymphoid neoplasms.

Use of anti-inflammatory and non-narcotic analgesic drugs and risk of non-Hodgkin's lymphoma (NHL) (United States)

Objective: To examine whether exposures to anti-inflammatory and non-narcotic analgesic drugs are associated with risk of non-Hodgkins lymphoma (NHL). Methods: A case–control study was conducted among women living in upstate New York. The study involved 376 cases of NHL identified through the New York State Cancer Registry and 463 controls randomly selected from the Medicare beneficiary files and New York State drivers license records. Information regarding use of common medications in the past 20 years and potential confounding variables was obtained by telephone interview. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using an unconditional logistic regression model. Results: There were non-significant increases in risk associated with ever use of cortisone injections and oral cortisone (OR = 1.44 (Cl 0.98–2.11) for injections and 1.21 (CI 0.73–2.00) for oral cortisone, although there was no clear dose–response relationship with either type. On the other hand, the risk of NHL progressively increased with the frequency of use of non-steroidal anti-inflammatory and non-narcotic analgesic drugs (NSAID/NNAD) (p-value for trend 0.008). Women who used any of these medications daily for more than 10 years had an OR of 1.90 (CI 1.01–3.57), compared with those who used it less than once a month on average. The risk associated with long-term use was most pronounced for ibuprofen, intermediate for aspirin, and least for acetaminophen. Conclusions: Because the population-attributable risk associated with NSAID/NNAD use is potentially large, our results need to be verified in further epidemiologic studies.

Personal and occupational exposure to organic solvents and risk of non-Hodgkin's lymphoma (NHL) in women (United States)

Objectives: The authors assessed whether home and occupational exposure to organic solvents is associated with risk of NHL in women.Methods: A population-based, incidence case-control study was conducted in upstate New York, involving 376 NHL cases and 463 population controls selected from the Medicare beneficiary files and State driver’s license records. Exposure information was obtained by telephone interview. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using an unconditional logistic regression model, adjusting for a number of risk factors for NHL.Results: Overall, history of exposure to organic solvents was not associated with the risk of NHL. A statistically significant increase in risk associated with occupational exposure was observed only for the subjects whose first exposure occurred before 1970 (OR=1.87, 95% CI 1.03–3.40). When occupational and home exposures to paint thinners/turpentine were combined and analyzed together, the risk of NHL associated with any exposure, compared to no exposure at either job or home, was a statistically significantly increased (OR=1.46, 95% CI: 1.05–2.03). This observation was more pronounced for B-cell lymphoma and for low-grade lymphoma with ORs of 1.52 (95 CI: 1.08–2.14) and 2.20 (95% CI; 1.42–3.41), respectively.Conclusions: The results of this case-control study do support of a major role of organic solvents in the development of NHL among women currently living in the US. However, relatively intensive exposure in past occupations and use of paint thinners/turpentine may deserve further investigation.

Pesticide Product Use and Risk of Non-Hodgkin Lymphoma in Women

A population-based, incidence case–control study was conducted among women in upstate New York to determine whether pesticide exposure is associated with an increase in risk of non-Hodgkin lymphoma (NHL) among women. The study involved 376 cases of NHL identified through the State Cancer Registry and 463 controls selected from the Medicare beneficiary files and state driver’s license records. Information about history of farm work, history of other jobs associated with pesticide exposure, use of common household pesticide products, and potential confounding variables was obtained by telephone interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using an unconditional logistic regression model. The risk of NHL was doubled (OR = 2.12; 95% CI, 1.21–3.71) among women who worked for at least 10 years at a farm where pesticides were reportedly used. When both farming and other types of jobs associated with pesticide exposure were combined, there was a progressive increase in risk of NHL with increasing duration of such work (p = 0.005). Overall cumulative frequency of use of household pesticide products was positively associated with risk of NHL (p = 0.004), which was most pronounced when they were applied by subjects themselves. When exposure was analyzed by type of products used, a significant association was observed for mothballs. The associations with both occupational and household pesticides were particularly elevated if exposure started in 1950–1969 and for high-grade NHL. Although the results of this case–control study suggest that exposure to pesticide products may be associated with an increased risk of NHL among women, methodologic limitations related to selection and recall bias suggest caution in inferring causation.

History of antibiotic use and risk of non-Hodgkin's lymphoma (NHL)

A population‐based, incidence case‐control study was conducted among women in upstate New York to determine whether histories of certain infections and antibiotic use are associated with risk of non‐Hodgkins lymphoma (NHL). Our study involved 376 cases of NHL identified through the New York State Cancer Registry and 463 controls selected from the Medicare beneficiary files and state drivers license records. Information about use of common medications including antibiotics, history of selected infectious diseases and potential confounding variables was obtained by telephone interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using an unconditional logistic regression model. There was a progressive increase in risk of NHL with increasing frequency and duration of systemic antibiotic use, as assessed over the period of 2–20 years before the interview. The ORs for the highest exposure categories, ≥36 episodes and ≥366 days of use, were 2.56 (95% CI 1.33–4.94) and 2.66 (95% CI 1.35–5.27), respectively. These associations were primarily due to antibiotic use against respiratory infections and dental conditions. Moreover, the association with frequency of antibiotic use for respiratory infections was pronounced for marginal zone B‐cell lymphoma and for respiratory tract lymphoma. Analyses by class of antibiotics did not suggest that a general cytotoxic effect of antibiotics was responsible for these increased risks. Although recall bias and selection bias remain potential concerns in our study, the results are generally consistent with the hypothesis that persistent infection/inflammation predisposes individuals to the development of NHL. However, a direct role of antibiotics in NHL induction has not been ruled out.

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.

Hemangiopericytoma of the esophagus

A case of hemangiopericytoma arising in the esophagus is described. The light microscopic features were typical, and ultrastructural examination confirmed the presence of pericyte-like cells and excluded smooth muscle and fibroblastic differentiation. Areas of necrosis and a focus of mitotic activity within the tumor suggested the possibility of an uncertain future course.