Follicular Dendritic Cell Sarcoma With Indolent T-Lymphoblastic Proliferation Is Associated With Paraneoplastic Autoimmune Multiorgan Syndrome

Abstract

Nonclonal expansions of immature T cells outside of the thymus, termed indolent T-lymphoblastic proliferation (iT-LBP), have been identified in rare lymphoproliferative disorders. We report that iT-LBP is a frequent finding in cases of follicular dendritic cell sarcoma (FDCS), and shows an association with paraneoplastic autoimmune multiorgan syndrome (PAMS). We studied 31 cases of FDCS by paraffin immunohistochemistry using antibodies to CD21, CD23, CD35, clusterin, CXCL13, podoplanin, CD3, CD4, CD8, CD20, CD1a, and TdT. Chart review was performed to characterize the clinical behavior including evidence of autoimmune disease. FDCS occurred in a wide variety of nodal and extranodal sites. Fourteen of 31 (45%) cases contained immature TdT-positive T cells; in 5 cases these cells were numerous and present throughout the tumor. Four of these 5 patients with numerous immature T cells developed autoimmune disease, clinically categorized as PAMS and/or myasthenia gravis. PAMS persisted after tumor resection, causing severe morbidity and mortality. These findings suggest that the neoplastic follicular dendritic cells can recruit or foster the proliferation of immature T cells and that these cells may play a role in mediating PAMS. Recognition of iT-LBP in FDCS is important to avoid misdiagnosis as thymoma or T-lymphoblastic lymphoma, and may predict serious autoimmune complications in some patients.

Follicular Dendritic Cell Sarcoma With Co-Expression of CD4 and CD30 Mimics Anaplastic Large Cell Lymphoma

“…The patient we reported here did not have any significant past medical history including Castleman disease. Interestingly, Walters et al reported that nearly half of FDCS cases demonstrated indolent T-lymphoblastic proliferation, and some of these patients developed autoimmune diseases (21). However, we did not observe TdT-positive T-cells in both specimens from our patient, and no evidence was found to suggest an autoimmune disease in our patient.…”

Intra-abdominal inflammatory pseudotumor-like follicular dendritic cell sarcoma associated with paraneoplastic pemphigus: A case report and review of the literature

“…This characteristic suggests that intra-abdominal FDC sarcomas may indicate a poor prognosis. Furthermore, in six cases, FDC sarcomas caused PNP were coexisting with myasthenia gravis (MG)[ 4 , 5 , 13 , 14 , 19 , 21 ]. Paraneoplastic neurologic syndromes are even rarer than other syndromes, occurring in approximately 0.01% of patients with cancer[ 33 ].…”

“…Previous reports have revealed that diseases associated with PNP predominantly underlie B-cell lymphoproliferative diseases, for example, non-Hodgkin lymphomas, chronic lymphocytic leukemia, and Castleman disease, such that 84% of neoplasms are associated with PNP[ 31 ]. Interestingly, we found that Castleman disease was involved in eight cases of PNP-associated FDC sarcoma (Table 1 )[ 4 , 8 , 19 , 21 , 24 , 26 , 29 ]. In China, PNP is frequently found in association with Castleman’s tumors[ 36 ].…”

“…Paraneoplastic pemphigus (PNP), which was first described in 1990, is a rare and life-threatening mucocutaneous autoimmune disease that is associated with underlying neoplasms, especially lymphoproliferative disorders[ 3 ]. A total of 32 cases of FDC sarcomas associated with the occurrence of PNP have been previously reported (Table 1 )[ 4 - 30 ]. Only two case wherein an IPT-like FDC sarcoma is an underlying neoplasm of PNP have been described[ 20 , 31 ].…”

Flow cytometric features of incidental indolent T lymphoblastic proliferations

“…Despite this classic paradigm for T‐cell maturation, recent studies have suggested that T‐cell maturation can occur outside the thymus, specifically in the tonsil (McClory et al, ) and in extrathymic locations after bone marrow transplantation (Holland et al, ). Recently, benign immature lymphoid cells (often a mix of cytoplasmic CD3+/TdT+ and lineage undefined TdT+ cells) have been identified in tissues from a number of reactive and neoplastic entities including Castleman disease and angioimmunoblastic T‐cell lymphoma (AITL) and rarely in association with B‐cell lymphomas, follicular dendritic sarcomas (Walters et al, ), and nonhematopoietic neoplasms (Ohgami et al, ). Despite the use of immunofluorescence and immunohistochemistry to evaluate coexpression of CD3 and TdT, a complete description of coexpression of antigens on these cells is lacking.…”