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| Pathological findings in human autoimmune lymphoproliferative syndrome |
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| Author(s): Lim MS, Straus SE, Dale JK, Fleisher TA, Stetler-Stevenson M, Strober W, Sneller MC, Puck JM, Lenardo MJ, Elenitoba-Johnson KSJ, Lin AY, Raffeld M, Jaffe ES |
| Source: AMERICAN JOURNAL OF PATHOLOGY Volume: 153 Issue: 5 Pages: 1541-1550 Published: NOV 1998 |
| Times Cited: 89 References: 34 |
| Abstract: The defects in lymphocyte apoptosis that underlie the autoimmune lymphoproliferative syndrome (ALPS) are usually attributable to inherited mutations of the CD95 (Fas) gene. In this report, we present the histopathological and immunophenotypic features seen hi the lymph nodes (n = 16), peripheral blood (n = 10), bone marrow (n = 2), spleen (n = 3), and liver (n = 2) from 10 patients with ALPS, Lymph nodes showed marked paracortical hyperplasia. Interfollicular areas were expanded and populated by T cell receptor-alpha beta CD3(+) CD4(-)CD8(-) (double-negative, DN) T cells that were negative for CD45RO. CD45RA(+) T cells were increased in all cases studied. The paracortical infiltrate was a result of both reduced apoptosis and increased proliferation, as measured by in situ detection of DNA fragmentation and staining with MIB-1, respectively. The paracortical proliferation may be extensive enough to suggest a diagnosis of malignant lymphoma. Many of the paracortical lymphocytes expressed markers associated with cytotoxicity, such as perforin, TIA-1, and CD57, CD25 was negative. in addition, most lymph nodes exhibited florid follicular hyperplasia, often with focal progressive transformation of germinal centers; in some cases, follicular involution was seen. A polyclonal plasmacytosis also was present, The spleens were markedly enlarged, more than 10 times normal size. There was expansion of both white pulp and red pulp, with increased DN T cells. DN T cells also were observed in Liver biopsies exhibiting portal triaditis, In the peripheral blood, the T cells showed increased expression of HLA-DR and CD57 but not CD25, CD45RA(+) T cells were increased in the four cases studied. Polyclonal B cell lymphocytosis with expansion of CD5(+) B cells was a characteristic finding, Taken together, the histopathological and immunophenotypic findings, particularly in lymph nodes and peripheral blood, are sufficiently distinctive to suggest a diagnosis of ALPS. Of note, two affected family members of one proband developed lymphoma (T-cell-rich B-cell lymphoma and nodular lymphocyte predominance Hodgkin's disease, respectively). |
| Document Type: Article |
| Language: English |
| Reprint Address: Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, NIH, Bldg 10,Room 2N 202,10 Ctr Dr,MSC-1500, Bethesda, MD 20892 USA |
Addresses:
1. NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA
2. NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA
3. NIAID, Warren Grant Magnuson Clin Ctr, Clin Invest Lab, Bethesda, MD 20892 USA
4. NIAID, Warren Grant Magnuson Clin Ctr, Immunoregulat Lab, Bethesda, MD 20892 USA
5. NIAID, Warren Grant Magnuson Clin Ctr, Immunol Lab, Bethesda, MD 20892 USA
6. Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD USA |
| Publisher: AMER SOC INVESTIGATIVE PATHOLOGY, INC, 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA |
| Subject Category: Pathology |
| IDS Number: 135ME |
| ISSN: 0002-9440 |
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