Bruce Raphael

Non-Hodgkin's lymphoma in 90 homosexual men: relation to generalized lymphadenopathy and the acquired immunodeficiency syndrome

We describe the histologic and clinical features of non-Hodgkins lymphoma diagnosed between January 1980 and December 1983 in 90 homosexual men from San Francisco, Los Angeles, Houston, and New York. The median age was 37 years, with an age distribution identical to that for cases of AIDS reported to the Centers for Disease Control. Sixty-two per cent of the patients had high-grade (aggressive) subtypes of lymphoma, 29 per cent had subtypes of intermediate grade, and 7 per cent had low-grade subtypes. Histologic subtypes and malignant cell phenotypes were consistent with a B-cell origin. All but two men had extranodal lymphoma: central-nervous-system, bone-marrow, bowel, and mucocutaneous sites were most commonly involved. Thirty-five of 66 evaluable men (53 per cent) had complete responses to combination chemotherapy or radiotherapy or both, and thus far, 19 (54 per cent) of them have had a relapse. Mortality and morbidity were closely related to prodromal manifestations; death or illness have occurred in 19 (91 per cent) of the 21 men who presented with AIDS, in 26 (79 per cent) of the 33 who presented with generalized lymphadenopathy, and in 5 (42 per cent) of the 12 who had no prodromal manifestations. Mortality rates analyzed according to histologic grade were higher than currently reported rates in other patient populations. Kaposis sarcoma or severe opportunistic infections characteristic of AIDS developed in 14 of 33 men (42 per cent) who presented with generalized lymphadenopathy and in 3 of 12 (33 per cent) without prodromal manifestations. We conclude that non-Hodgkins lymphoma in members of an AIDS risk group is a serious manifestation of AIDS and the AIDS-related complex.

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.

Thrombotic thrombocytopenic purpura associated with human immunodeficiency virus type 1 (HIV-1) infection

The cases of 14 patients with thrombotic thrombocytopenic purpura admitted to one institution after 1980 were reviewed. Three of the fourteen cases occurred in patients with the acquired immunodeficiency syndrome (AIDS)-related complex and one occurred in a patient with probable human immunodeficiency virus (HIV) infection. The diagnosis in all four cases had been made after 1985. The association of thrombotic thrombocytopenic purpura with HIV infection was judged to be statistically significant on the basis of the proportion of patients with AIDS among the general population of patients admitted to the same institution during the same period. The fact that this association is only now being recognized suggests that there may be a long incubation period for thrombotic thrombocytopenic purpura or that the association is a rare one recognized now only because of the increased number of persons with AIDS.

Adrenal insufficiency as a complication of the acquired immunodeficiency syndrome.

Excerpt Since the acquired immunodeficiency syndrome was recognized in 1980, various malignancies, infections, and immunologic defects have been found in the affected population. Recently, adrenal ...

Large-cell variants of mantle cell lymphoma: cytologic characteristics and p53 anomalies may predict poor outcome.

Large‐cell variants are uncommon in mantle cell lymphoma (MCL). Here we describe the pathologic and clinical findings in five patients with large‐cell lymphoma related to MCL (L‐MCL), and compare them to a group of classic small‐cell MCL (s‐MCL) cases.

Systemic lupus erythematosus and angioimmunoblastic lymphadenopathy: Case report and review of the literature

A NGIOIMMUNOBLASTIC lymphadenopathy (AIL) is a non-neoplastic, proliferative disorder of lymphocytes characterized clinically by fever, generalized lymphadenopathy, hepatosplenomegaly, skin rash, polyclonal hypergammaglobulinemia, and frequently, Coombs positive hemolytic anemia. Histologically, normal lymph node architecture is distorted by a lymphoplasmacytic infiltrate, accompanied by finely arborizing blood vessels and often by the interstitial deposition of an amorphous eosinophilic material.“2 There are many similarities between AIL and connective tissue disease, especially systemic lupus erythematosus (SLE). That these conditions can exhibit similar clinical manifestations and pathogenic mechanisms has been noted in the literature. jV4 For example, the presence of various autoantibodies, including ANA, has been documented in AIL.‘-” On the other hand, we have been able to find only two cases in which clinical AIL and SLE seemed to have occurred simultaneously.8~‘3 By contrast, our patient had longstanding connective tissue disease, starting as mixed connective tissue disease (MCTD) which evolved into classical SLE, and ultimately died from AIL. The unusual nature of this case prompted us to review the association of SLE to AIL.

Sustained, durable responses with alemtuzumab in refractory angioimmunoblastic T-cell lymphoma.

Angioimmunoblastic T-cell lymphoma (AITL) was first described in the 1970s as a clinical syndrome characterized by lymphadenopathy, hepatosplenomegaly, anemia, and hypergammaglobulinemia [1,2]. Pathological features include effacement of lymph node architecture by a polymorphic infiltrate of plasma cells, eosinophils, and histiocytes. Mediumsized lymphocytes with clear cytoplasm surround extensive vascular proliferation [3]. Immunohistochemistry demonstrates areas of CD3þ T cells with CD4þ predominance and proliferation of follicular dendritic cells. T-cell gene rearrangement demonstrates clonality. Although the etiology of AITL is uncertain, there is a clear association with Epstein–Barr virus (EBV), where EBV load correlates with histological progression and clinical severity of disease [4]. As a rare subtype of non-Hodgkin lymphoma (NHL), it represents only 2% of all such cases. It is a diagnosis of the elderly associated with a poor prognosis, with median survival less than 36 months and 5-year survival of approximately 30% [5]. Clinically, patients commonly suffer from immune dysfunction, including autoimmune disease and infections [6]. There is no standard treatment for AITL. Although most patients initially respond to steroids and high-dose combination chemotherapy, they frequently relapse within short time intervals [7]. There have been reports using cyclosporine A, fludarabine, methotrexate, thalidomide, and bevacizumab, with mixed results [8–12]. Alemtuzumab is an unconjugated, non-modulating, humanized monoclonal antibody that binds to the CD52 antigen [13]. CD52 is a cell surface glycoprotein expressed on the surface of lymphocytes, monocytes, and macrophages, but not hematopoietic stem cells. Expression occurs in higher densities on malignant T cells. The mechanism of action of alemtuzumab is not completely known, but it is hypothesized to induce cell death through complement-mediated cytolysis, antibody-dependent cellular cytotoxicity, and apoptosis [14,15]. Here we report on three patients with relapsed AITL who achieved sustained, durable responses with alemtuzumab. A 73-year-old female was noted to have abnormal lymph node and bone marrow architecture 4 years prior to her diagnosis of AITL. In 2001, she was found to have a lymph node with focal infiltrates of polyclonal plasma cells and a hypercellular bone marrow with atypical lymphocytes, with increased eosinophils and plasma cells (7%), which were polyclonal. By 2005 she had similar bone marrow findings, but lymph node evaluation revealed a predominance of T cells with prominent vascular component and positive T-cell receptor gamma chain gene rearrangement. Based on her diagnosis of AITL, she received combination chemotherapy composed of adriamycin, vincristine, cyclophosphamide, and prednisone (CHOP) (Table I), but relapsed within 7 months. She was subsequently treated with cytoxan and prednisone and then gemcitabine with prednisone from November 2006 until May 2007, with neither regimen offering a significant clinical benefit. By June 2007, she presented with fevers, weight loss, splenomegaly (11 cm6 13 cm), and lactate dehydrogenase (LDH) of 1292 U/L (313–618 U/L). She was started on alemtuzumab 30 mg infusion three times per week. The patient received antibiotic prophylaxis

Postchemotherapy Histiocyte-Rich Pseudotumor Involving the Spleen

We report 2 cases of splenic postchemotherapy histiocyte-rich pseudotumor. Each patient had a history of diffuse large B-cell lymphoma, treated with multiagent chemotherapy. Computed tomography scans performed on both patients showed splenic masses. A positron emission tomography scan performed on 1 patient showed increased metabolic activity. The preoperative diagnosis in both patients was recurrent lymphoma, prompting splenectomy. The splenectomy specimens showed multiple, tan-white, firm nodules, up to 3.5 cm in diameter, that were histologically composed of central necrotic B cells (CD20+/CD3-), consistent with necrotic lymphoma, surrounded by numerous lipid-laden (xanthomatous) histiocytes. Clinical staging studies at the time of splenectomy showed no other sites of disease. We conclude that these histologic and immunophenotypic findings represent chemotherapy-induced tumor necrosis with a florid histiocytic reaction mimicking residual viable lymphoma. Others have used descriptive terminology or the term xanthomatous pseudotumor for these lesions that have been only rarely reported in the spleen previously.

Malignant lymphoma in homosexual men : Relationship to Acquired Immune Deficiency Syndrome (AIDS)

The definition of AIDS has encompassed the diagnosis of opportunistic infection (OI) or Kaposi’s sarcoma (KS) arising in certain populations without any previously known immunologic defects [1]. As of April 2, 1984, 3954 patients fulfilling the criteria for AIDS had been reported to the Centers for Disease Control in Atlanta, Georgia. The largest single risk group identified consists of males with homosexual or bisexual practices constituting 71.3% of the total cases, followed by intravenous (iv) drug users, Haitians, and hemophiliacs. Malignancies other than KS, particularly lymphomas have been well known to complicate a variety of genetically determined or induced immunodeficiency states [2–4] . B-cell proliferations including primary central nervous system (CNS) high grade lymphomas are represented with greater than expected frequency; however, Hodgkin’s disease and the whole spectrum of acute leukemias, also have been linked to immunodeficiencies.

Leukemic mantle cell lymphoma and chronic lymphocytic leukemia: a rare composite lymphoma and literature review

Composite lymphomas are rare entities that either represent a collision of two separate lymphomas, or one lymphoma that expresses two distinct phenotypes. Mantle cell lymphoma has been reported in some composite lymphomas, but when combined with chronic lymphocytic leukemia, it can be difficult to recognize because of the phenotypic overlap of these two entities. We report a case of a 75-year-old male with a slowly progressing lymphocytosis, but who was otherwise asymptomatic. Flow cytometry revealed two different populations, one showing bright Lambda positivity and CD5(+), while the other was positive for both lambda and kappa and was CD5(+). Subsequently, cytogenetics revealed two different populations, one with a trisomy 12 and the other with a t(11;14). Additionally, immunohistochemistry on a bone marrow biopsy showed SOX-11 to be negative and cyclin D1 to be positive on scattered lymphocytes. This was consistent with a composite lymphoma of leukemic mantle cell lymphoma and chronic lymphocytic lymphoma.