HIV-associated plasmablastic lymphoma: lessons learned from 112 published cases.

Plasmablastic lymphoma (PBL) is a distinct subtype of non-Hodgkin B-cell lymphoma, originally described with a strong predilection to the oral cavity of human immunodeficiency virus (HIV)-infected individuals. Data regarding patient age and gender, HIV status, initiation of and response to highly active antiretroviral therapy (HAART), tumor extent, pathology, treatment, and outcome were extracted from 112 cases of PBL identified in the literature. The median age at presentation was 38 years with a male predominance of 7:1, and the median CD4+ count was 178 cells/mm(3). PBL presented on average 5 years after diagnosis of HIV. Common primary sites of presentation included the oral cavity, gastrointestinal tract, and lymph nodes. Most cases presented with either stage I or stage IV disease. There was a variable expression of B-cell markers in tumor cells, but plasma cell markers were expressed in all cases. EBV was detected in 74%. Chemotherapy was used to treat 55% patients and was combined with radiotherapy in 21% cases. Complete response was obtained in 66% of treated cases; the majority of these responses were seen after CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). The refractory/relapsed disease rate was 54%. Death occurred in 53% of patients, with a median overall survival of 15 months. Sex, CD4+ count, viral load, clinical stage, EBV status, primary site of involvement, and use of CHOP failed to show an association with survival. PBL is an aggressive B-cell lymphoma that presents in both oral and extra-oral sites of chronically HIV-infected immunosuppressed young men.

Changing incidence of AIDS-related Kaposi sarcoma and non-Hodgkin lymphoma in Ontario, Canada.

OBJECTIVE: To examine the influence of the AIDS epidemic on the incidence of Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL) in Ontario. METHODS: Age-standardized incidence rates for KS and NHL from 1981 to 2000 were calculated from the population-based Ontario Cancer Registry. AIDS cases were extracted from Ontario Ministry of Health and Long-Term Care reports. HIV death data were obtained from the Ontario Cancer Registry. RESULTS: KS was a rare cancer before the 1980s; however, incidence increased sharply between 1985 and 1995 by 13.8% per year. Thereafter, incidence rates fell close to those in the early 1980s. NHL incidence in males increased steadily during the 1980s at 3.2% per year and then slowed beyond 1990. In males aged 30-44, NHL incidence rose from 1981 to 1990 (8.8% per year) and then fell (-2.5%) thereafter. NHL and KS cases represented one-third of HIV deaths. CONCLUSIONS: The AIDS epidemic, the introduction of antiretroviral therapies, and the decrease in HIV infection rates explain the rise and decline of KS incidence in Ontario. NHL incidence trends are more complex, although the AIDS epidemic explains the trends observed in younger men (in whom AIDS is more common), and for the AIDS-related subtypes.

Trends in Kaposi's sarcoma and non-Hodgkin's lymphoma incidence in the United States from 1973 through 1998.

BACKGROUND: The incidence of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL) in the general population has markedly increased since the onset of the AIDS epidemic in 1981. However, during the 1990s, the dynamics of the AIDS epidemic changed, as human immunodeficiency virus (HIV) infection rates slowed and effective antiretroviral therapies were introduced. We examined the impact of these changes on the general population incidence of KS and NHL. METHODS: Age-standardized incidences for KS and NHL from 1973 through 1998 were obtained from nine population-based cancer registries that participate in the Surveillance, Epidemiology and End Results (SEER) program. RESULTS: During the mid-1990s, KS incidence declined sharply in all nine registries. Decreases in KS incidence were most evident in San Francisco, where KS rates among white men had risen from 0.5 per 100 000 people per year in 1973 to between 31.1 and 33.3 from 1987 through 1991 and then declined to 2.8 in 1998. With background NHL incidence in the general population being much higher than that for KS, changes in incidence related to the AIDS epidemic were most evident in subgroups at high risk of AIDS. In San Francisco, NHL rates among white men rose from 10.7 in 1973 to a peak of 31.4 in 1995 and then declined to 21.6 in 1998. NHL types that were most highly AIDS-associated declined most steeply, whereas the incidence of NHL types not associated with AIDS was either stable or increasing. CONCLUSION: Changes in KS and NHL incidence since the mid 1990s may reflect declines in the number of individuals with AIDS and improved immune function in such individuals following the introduction of effective antiretroviral therapies in the 1990s. Notably, non-AIDS-associated NHL incidence has continued to increase steadily through 1998.

Human immunodeficiency virus-related lymphoma: relation between clinical features and histologic subtypes.

PURPOSE: Non-Hodgkin's lymphoma occurs frequently in patients with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). We determined the association between the clinical and histologic features of HIV-related lymphoma. SUBJECTS AND METHODS: We reviewed the medical records of 291 patients with noncerebral HIV-related lymphoma who had been treated in multicenter trials coordinated by the Groupe d'Etude des Lymphomes de l'Adulte between 1988 and 1997. This study was performed mainly before the availability of combination antiretroviral therapy. RESULTS: The main histologic subtypes were centroblastic lymphoma in 131 patients (45%), immunoblastic lymphoma in 39 patients (13%), and Burkitt's lymphoma (including the classical form and the variant with plasmacytic differentiation) in 115 patients (40%). Burkitt's lymphoma was the most aggressive form, whereas immunoblastic lymphoma occurred in severely immunodeficient patients. Two-year survival after enrollment was 15% in immunoblastic lymphoma, 32% in Burkitt's lymphoma, and 31% in centroblastic lymphoma (P = 0.006), but multivariate analysis did not confirm the independent prognostic value of histologic subtype. Instead, five independent pretreatment factors increased the risk of mortality: age 40 years or older [relative risk (RR) = 1.5; 95% confidence interval (CI), 1.1 to 2.1; P = 0.005], elevated serum lactate dehydrogenase level (RR = 1.5; 95% CI, 1.1 to 2.1; P = 0.02), having a diagnosis of AIDS before lymphoma (RR = 1.8; 95% CI, 1.2 to 2.6; P = 0.006), CD4(+) cell count less than 100 x 10(6)/L (RR = 1.8; 95% CI, 1.3 to 2.6; P = 0.0004), and impaired performance status (RR = 2.4; 95% CI, 1.7 to 3.4; P <0.0001). CONCLUSION: Several pretreatment characteristics of HIV-related lymphoma were linked to the histologic form, but HIV disease parameters other than those of lymphoma were the main determinants of outcome, so the histologic features of the lymphoma were not associated with prognosis.

Incidence of primary extranodal lymphoma involving gastrointestinal tract by histological type at Ilorin.

We report 21 cases of primary extranodal lymphoma of the gastrointestinal tract over a period of 10 years (1986-1995) at the Department of Morbid Anatomy and Histopathology, University of Ilorin Teaching Hospital, Ilorin, Kwara State of Nigeria. This represents 6% of the total gastrointestinal tract malignancies diagnosed during same period. All were Non Hodgkin's Lymphoma. The ages ranged from 4 to 60 years, while the mean age was 23 years. Male to female ratio was 4:3. The anatomic sites involved were stomach 4, (19%), small intestine 13, (62%), and large intestine 4, (19%). There was no single case of rectal lymphoma. The histological types were Burkitt's lymphoma 9 (42.8%), diffuse mixed (small and large) cells 4 (19.1%), diffuse large cells 4 (9.1%), small lymphocytic cells, 2 (9.5%) and large immunoblastic cells 2 (9.5%). All the cases of Burkitt's lymphoma occurred under 20 years of age. Distribution into prognostic groups (grades) according to working formulation for clinical usage was low grade, 2 (9.5%), intermediate grade, 8 (38.1%) and High grade, 22 (52.4%). We conclude that extranodal malignant lymphoma involving the gastrointestinal tract is not rare and should be considered for differential diagnosis in gastrointestinal tract malignancies.

Pathology with clinical correlations of primary central nervous system non-Hodgkin's lymphoma. The Massachusetts General Hospital experience 1958-1989.

BACKGROUND: Primary central nervous system non-Hodgkin's lymphoma (NHL-CNS) is an enigmatic disease of uncertain origin. At the Massachusetts General Hospital, 104 patients with NHL-CNS were seen from 1958 through 1989. An impression of changes in the frequency of diagnosis, character of the tumors, and therapy for this disease prompted this study of the pathologic features, clinical data, and natural history of this tumor in these 104 patients. METHODS: Histologic slides (neurosurgical specimens and autopsy tissues) were available for 99 patients. The tumors were classified by the Working Formulation classification. Immunostaining data and all clinical data were retrieved from the relevant offices and hospital charts. RESULTS: Primary central nervous system non-Hodgkin's lymphoma tripled in frequency (5.66 cases per year in 1978-89 versus 1.75 cases per year in 1958-77) and now represents 6.6% of all primary brain neoplasms (versus 3.3% before 1978; chi 2 = 17.52, P < 0.01). For the 99 tumors histologically classified, 89% were high grade. Intermediate grade lymphomas, once the second most common subtype, have disappeared since 1983. All tumors had diffuse architecture; 77% (including all 11 patients with acquired immune deficiency syndrome) were large cell subtypes. Two cases were intravascular lymphoma. With one exception, all of the 41 tumors evaluated were B-cell types; 32 of 40 had monotypic surface immunoglobulin. There was 1 T-cell lymphoma. Of 64 tumor recurrences, 29 were at the initially defined site; 12 were in the leptomeninges, 29 were in other sites in the neuraxis, and 8 were in systemic sites. Systemic metastases have not occurred since 1984. Median survival for the 68 patients who survived after diagnostic surgery and for whom follow-up information could be obtained was 19 months; 9 months for those with high grade tumors and 30.5 months for those with intermediate grade tumors. This difference was not significant (P = 0.13). A separate set of seven patients had focal tumorlike lymphoid infiltrates composed of benign-appearing lymphocytes, which were associated with good long term survival. The differential histologic diagnosis of NHL-CNS was occasionally difficult, and the spectrum of this differential was broader than generally stated. CONCLUSIONS: Primary central nervous system non-Hodgkin's lymphoma has increased in frequency even in nonimunocompromised patient populations. This increase has been accompanied by the disappearance of intermediate grade histologic types, suggesting a fundamental shift in the biology of the neoplasms. The introduction of chemotherapeutic regimens appears to have altered the natural history such that systemic metastases outside the central nervous system no longer occur, and there are now some long term survivors of this formerly uniformly fatal disease.

Primary cerebral lymphoma: an argument for the use of adjunctive systemic chemotherapy.

Eleven patients with primary cerebral lymphoma were treated at a single institution over a 5 year period. Patient characteristics were typical of this rare disease. One patient died prior to receiving treatment and of the remaining 10, all received cranial irradiation and in addition, five received systemic cyclophosphamide, adriamycin, vincristine and prednisolone (CHOP) chemotherapy. Of the six patients who are alive and disease-free, five received the combined modality therapy. The median survival for those patients receiving cranial irradiation alone was 18 months and for the combined modalities was 25+ months. Combination systemic chemotherapy, in addition to cerebral irradiation, may convey a survival benefit in patients with primary cerebral lymphoma but this requires further investigation with multicentre, prospective randomized trials.

AIDS-associated non-Hodgkin lymphoma.

Non-Hodgkin lymphoma is associated with HIV infection. We investigated the epidemiology and aetiology of AIDS-related non-Hodgkin lymphoma by analysing data from cases reported to the Centers for Disease Control, Atlanta, USA, up to June 30, 1989. During this period 97,258 AIDS cases were reported, of whom 2824 (2.9%) had non-Hodgkin lymphoma. The condition was about 60 times more common in AIDS patients than in the general US population. 1686 cases were immunoblastic lymphoma, 548 primary lymphoma of the brain, and 590 Burkitt's lymphoma, a condition which is not normally associated with immunosuppression. The proportion of AIDS patients with immunoblastic lymphoma increased from 0% in those under 1 year old to 3.5% in those aged 50 or more. Primary lymphoma of the brain was constant at 0.6% for all ages. The frequency of Burkitt's lymphoma increased from zero in infants to a peak at 10-19 years of age (1.8%). Each type of lymphoma was twice as common in whites as in blacks and in men as in women. Lymphoma was most common in patients with haemophilia or clotting disorders and least common in those born in the Caribbean or Africa who had acquired HIV by heterosexual contact. Epidemiological data suggested that whilst infectious agents (eg, Epstein-Barr virus) may be associated with development of non-Hodgkin lymphomas in AIDS patients there was probably no single cause for all the types of lymphoma. Perhaps the most puzzling question is why Burkitt's lymphoma is commonly associated with HIV infection but not with other types of immunosuppression.