Primary esophageal lymphoma: a diagnostic challenge.

In this issue of the Southern Medical Journal, Dr. C. Namal Weeratunge's article entitled "Primary Esophageal Lymphoma: A Diagnostic Challenge in Acquired Immunodeficiency Syndrome" (1) reports two cases of primary esophageal lymphoma in patients with acquired immunodeficiency syndrome (AIDS). The first cases of AIDS-related non-Hodgkin lymphomas (NHL) were described in 1982. (2,3) NHL is now recognized as the second most common neoplasm in human immunodeficiency virus (HIV)-infected individuals and the most common neoplasm occurring among HIV-infected intravenous drug users and hemophiliacs. (4,5)

Primary esophageal lymphoma is rare, with fewer than 25 cases reported in the past 25 years. As the authors report, only 12 have been previously reported in association with HIV-seropositive patients. However, AIDS-related primary esophageal lymphoma should be considered in the differential diagnosis of a patient with AIDS who presents with dysphagia and an ulcerated esophageal mass. Esophagoduodenoscopy with biopsy is required in these patients to establish a definitive diagnosis and to rule out the possibility of an infectious cause of the mass. Endoscopic biopsies may demonstrate a false-negative rate of up to 30%. In one study from the Mayo Clinic, 27 patients with lymphoma involvement of the esophagus were identified. (6)

In general, involvement of the esophagus is most commonly a result of contiguous spread from the proximal stomach, adjacent mediastinal lymph nodes, or cervical lymph nodes. The gastrointestinal tract is second only to the central nervous system as the most common site of extranodal involvement by AIDS-related NHL, as approximately 30% of patients have gastrointestinal tract involvement at presentation, (7) and the vast majority have involvement at postmortem examination. (8) Three patients had primary esophageal lymphoma. Esophagoduodenoscopy established the diagnosis in all but five patients, necessitating surgical exploration to establish a diagnosis.

The successful management of patients with NHL depends first and foremost on accurate hematopathologic interpretation with selected special studies for confirmation. These malignancies are primarily of lymphocytic origin, and each histologic subtype is believed to arise from a monoclonal expansion of specific lymphoid subsets. Monoclonality may be established by such studies as cell surface markers, cytogenetics, and rearrangements of B-cell immunoglobulin or T-cell receptor genes. The Working Formulation of the NHLs, cited extensively in Weeratunge's literature review, clarified pathologic classification by identifying three prognostic groups, low-, intermediate-, and high-grade lymphomas, and by using terminology that suggests cell of origin. The current classification scheme of both Hodgkin lymphoma and NHL was published in 2001 as the international standard for classification of hematologic malignancies. (9) This classification includes primary effusion lymphoma, a rare and unusual subset of AIDS-related NHLs first described by Knowles et al (10) that grow primarily in the pleural, pericardial, or abdominal cavities as lymphomatous effusions, usually in the absence of a tumor mass. The cases reviewed in this article would be classified under the category of "mature B-cell neoplasms" in the current classification format.

Further work is necessary to develop a complete understanding of the cause and pathogenesis of NHL in the setting of HIV infection. AIDS-related NHL is an important biologic model for investigating the development and progression of high-grade NHLs and NHLs that develop in immunodeficient hosts. The causes are yet to be identified, but as Higginson (11) has said, "Accurate pathologic diagnosis is a prerequisite for the meaningful investigation of disease." We have the accurate diagnosis; now for the meaningful investigation.

Accepted August 18, 2003.

Copyright [c] 2004 by The Southern Medical Association

0038-4348/04/9704-0331

Please see "Primary Esophageal Lymphoma: A Diagnostic Challenge in Acquired Immunodeficiency Syndrome" on page 383 of this issue.

References

1. Weeratunge CN. Primary esophageal lymphoma: a diagnostic challenge in acquired immunodeficiency syndrome. South Med J 2004;97:383--387.

2. Doll DC, List AF. Burkitt's lymphoma in a homosexual. Lancet 1982;1:1026--1027 (letter).

3. Ziegler JL, Drew WL, Miner RC, et al. Outbreak of Burkitt's-like lymphoma in homosexual men. Lancet 1982;2:631-633.

4. Beral V, Peterman T, Berkelman R, et al. AIDS-associated non-Hodgkin lymphoma. Lancet 1991;337:805-809.

5. Knowles DM, Chadburn A. Lymphadenopathy and the lymphoid neoplasms associated with acquired immune deficiency syndrome, in Knowles DM (ed): Neoplastic Hematopathology. Philadelphia, Lippincott Williams & Wilkins, 2001, ed 2, pp 987-1089.

6. Orvidas LJ, McCaffrey TV, Lewis JE, et al. Lymphoma involving the esophagus. Ann Otol Rhinol Laryngol 1994;103:843-848.

7. Knowles DM, Chamulak GA, Subar M, et al. Lymphoid neoplasia associated with the acquired immunodeficiency syndrome (AIDS): the New York University Medical Center experience with 105 patients (1981-1986). Ann Intern Med 1988;108:744-753.

8. Loureiro C, Gill PS, Meyer PR, et al. Autopsy findings in AIDS-related lymphoma. Cancer 1988;62:735-739.

9. Jaffe ES, Harris NL, Stein H, et al (eds). WHO Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France, IARC Press, 2001.

10. Knowles DM, Inghirami G, Ubriaco A, et al. Molecular genetic analysis of three AIDS-associated neoplasms of uncertain lineage demonstrates their B-cell derivation and the possible pathogenetic role of the Epstein-Barr virus. Blood 1989;73:792-799.

11. Higginson J. The role of the pathologist in environmental medicine and public health. Am J Pathol 1977;86:460-484.

Keith J. Kaplan, MD

Reprint requests to Keith Kaplan, MD, Walter Reed Army Medical Center, Department of Pathology, 6900 Georgia Ave. NW, Washington, DC 20307. Email: [e-mail]