Pathological findings in human autoimmune lymphoproliferative syndrome

Megan S. Lim; Stephen E. Straus; Janet K. Dale; Thomas A. Fleisher; Maryalice Stetler-Stevenson; Warren Strober; Michael C. Sneller; Jennifer M. Puck; Michael J. Lenardo; Kojo S.J. Elenitoba-Johnson; Albert Y. Lin; Mark Raffeld; Elaine S. Jaffe

doi:10.1016/S0002-9440(10)65742-2

Pathological findings in human autoimmune lymphoproliferative syndrome

Megan S. Lim, Stephen E. Straus, Janet K. Dale, Thomas A. Fleisher, Maryalice Stetler-Stevenson, Warren Strober, Michael C. Sneller, Jennifer M. Puck, Michael J. Lenardo, Kojo S.J. Elenitoba-Johnson, Albert Y. Lin, Mark Raffeld, Elaine S. Jaffe^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

199 Scopus citations

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 in 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-αβ 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).

Original language	English
Pages (from-to)	1541-1550
Number of pages	10
Journal	American Journal of Pathology
Volume	153
Issue number	5
DOIs	https://doi.org/10.1016/S0002-9440(10)65742-2
State	Published - Nov 1998
Externally published	Yes

Access to Document

10.1016/S0002-9440(10)65742-2

Cite this

Lim, M. S., Straus, S. E., Dale, J. K., Fleisher, T. A., Stetler-Stevenson, M., Strober, W., Sneller, M. C., Puck, J. M., Lenardo, M. J., Elenitoba-Johnson, K. S. J., Lin, A. Y., Raffeld, M., & Jaffe, E. S. (1998). Pathological findings in human autoimmune lymphoproliferative syndrome. American Journal of Pathology, 153(5), 1541-1550. https://doi.org/10.1016/S0002-9440(10)65742-2

@article{9ff377810db34b9983545268fcbd6fc3,

title = "Pathological findings in human autoimmune lymphoproliferative syndrome",

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 in 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-αβ 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).",

author = "Lim, {Megan S.} and Straus, {Stephen E.} and Dale, {Janet K.} and Fleisher, {Thomas A.} and Maryalice Stetler-Stevenson and Warren Strober and Sneller, {Michael C.} and Puck, {Jennifer M.} and Lenardo, {Michael J.} and Elenitoba-Johnson, {Kojo S.J.} and Lin, {Albert Y.} and Mark Raffeld and Jaffe, {Elaine S.}",

note = "Funding Information: M.S. Lim is a recipient of a clinical fellowship from the Medical Research Council of Canada, Alberta Heritage Foundation for Medical Research, and the Fogarty Visiting Fellowship from the National Institutes of Health. ",

year = "1998",

month = nov,

doi = "10.1016/S0002-9440(10)65742-2",

language = "English",

volume = "153",

pages = "1541--1550",

journal = "American Journal of Pathology",

issn = "0002-9440",

number = "5",

}

TY - JOUR

T1 - Pathological findings in human autoimmune lymphoproliferative syndrome

AU - Lim, Megan S.

AU - Straus, Stephen E.

AU - Dale, Janet K.

AU - Fleisher, Thomas A.

AU - Stetler-Stevenson, Maryalice

AU - Strober, Warren

AU - Sneller, Michael C.

AU - Puck, Jennifer M.

AU - Lenardo, Michael J.

AU - Elenitoba-Johnson, Kojo S.J.

AU - Lin, Albert Y.

AU - Raffeld, Mark

AU - Jaffe, Elaine S.

N1 - Funding Information: M.S. Lim is a recipient of a clinical fellowship from the Medical Research Council of Canada, Alberta Heritage Foundation for Medical Research, and the Fogarty Visiting Fellowship from the National Institutes of Health.

PY - 1998/11

Y1 - 1998/11

N2 - 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 in 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-αβ 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).

AB - 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 in 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-αβ 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).

UR - http://www.scopus.com/inward/record.url?scp=0031737954&partnerID=8YFLogxK

U2 - 10.1016/S0002-9440(10)65742-2

DO - 10.1016/S0002-9440(10)65742-2

M3 - Article

C2 - 9811346

AN - SCOPUS:0031737954

SN - 0002-9440

VL - 153

SP - 1541

EP - 1550

JO - American Journal of Pathology

JF - American Journal of Pathology

IS - 5

ER -

Pathological findings in human autoimmune lymphoproliferative syndrome

Abstract

Access to Document

Fingerprint

Cite this