Case 96-2

History/Physical Findings:

A 68-year-old black woman was evaluated for weight loss (30 pounds over 6 months) and cervical lymphadenopathy of six weeks duration.

Physical examination showed diffuse palpable peripheral lymphadenopathy. There was no organomegaly or palpable abdominal masses.

Pathology:

A fine needle aspirate (FNA) of the lymph node suggested lymphoid hyperplasia. Immunophenotypic analysis of the FNA demonstrated a mixture of T-cells and polyclonal B-cells.

A lymph node biopsy (SP-A) was obtained and a diagnosis of "atypical lymphoid hyperplasia consistent with angioimmunoblastic lymphadenopathy" was made. H&E sections and Wright's stained touch prep are shown below.

Serum protein electrophoresis did not reveal a dysproteinemia. Immunophenotypic analysis of the nodal material demonstrated a mixture of T-cells and polyclonal B-cells. To detect the presence of clonal lymphoid populations which might escape detection by flow cytometric techniques, Southern blot analysis of the nodal material was performed (So-A).

Southern blot analysis is shown above. DNA was extracted from the lymph node (SP-A) and digested with Eco RI, Bam HI, and Hind III. Southern blots of the restriction fragments were hybridized with probes to the joining regions of the immunoglobulin heavy chain gene and to the T-cell receptor beta-chain gene. Germline immunoglobulin heavy chain genes were identified (data not shown). Although the blot of the T cell receptor beta chain gene was considered nondiagnostic: germline configuration was seen with Bam HI (lane 3), but one to two rearranged bands with Eco RI (lane 6) and two rearranged bands with Hind III (lane 9) were identified. The results of the JB probe were considered suspicious, but not diagnostic for a T cell clonal population.

There was no history of fever, chills, night sweats, cough, nausea or vomiting following a diagnosis of AILD (SP-A). The patient was treated with prednisone, 30 mg/day to which there was complete resolution of her palpable lymphadenopathy within approximately two months. After tapering the steroids, her lymphadenopathy recurred in a widespread fashion including both bilateral cervical chain supraclavicular lymph nodes and extensive abdominal and mediastinal lymphadenopathy as well as splenomegaly.

A second lymph node biopsy (SP-B) and a bone marrow biopsy were obtained four months after the initial diagnosis.

The bone marrow biopsy ( H&E sections above) showed several discrete hypercellular foci of Leder-negative lymphoid cells. These cells had large, highly irregular nuclei, fine chromatin, and one or two densely staining nucleoli. Flow cytometric analysis of the marrow aspirate revealed a lymphocytosis with a T cell:B cell ratio of approximately 10:1. These cells expressed the T-cell markers CD3, CD5, and CD7. While approximately 50% of these T cells expressed CD 8, less than two percent expressed CD 4, indicating the presence of a population with aberrant loss of an MHC receptor.

The second lymph node biopsy, while similar to the first node biopsy had increased numbers of the large atypical immunoblasts. The pleomorphic, highly atypical cells frequently formed clusters and were often hyperlobated (best seen in the H&E X100 and the CD 3 stained sections). Immunophentypic analysis of the nodal material (SP-B) also identified a predominance of T-cells and no evidence for a clonal population of B-cells. H&E sections and immunohistochemistry for CD 20; CD 45RO; and CD 3 are shown above.

Southern blot analysis of the bone marrow showed germline heavy chain immunoglobulin genes. However, distinct non-germline restriction fragments were detected with the probe to the T-cell receptor beta chain gene (lanes 4,7,10). Furthermore, the fragments obtained correlate with those seen in the analysis (S-A) four months previously. While the earlier studies were considered nondiagnostic, this second study confirms the presence of a clonal T-cell population. This study together with the morphologic findings in the marrow and lymph node is diagnostic of a peripheral angioimmunoblastic T-cell lymphoma (see References) and shows that the clonal population was present at the time of morphologic diagnosis of AILD.

Diagnosis:

References:

• Harris NL, Jaffe ES, Stein H: A Revised European-American Classification of Lymphoid Neoplasms: A Proposal From the International Lymphoma Study Group. Blood 84:1361-1392, 1994.

   

• Nakamura S, Suchi T, Koshikawa T, et al: Clinicopathologic Study of 212 Cases of Peripheral T-Cell Lymphom Among the Japanese. Cancer 72:1762-1972, 1993.

   

• Chott A, Augustin I, Wrba F, et al: Peripheral T-Cell Lymphomas: A Clinicopathologic Study of 75 Cases. Hum Pathol 21:1117-1125, 1990.

Contributors:

Donald J. Innes, Jr., M.D.
Department of Pathology
University of Virginia Health System

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