Indolent T‐lymphoblastic proliferation: A systematic review of the literature analyzing the epidemiologic, clinical, and pathologic features of 45 cases

Abstract

An indolent T‐lymphoblastic proliferation (iT‐LBP) is a rare benign disorder characterized by an abnormal expansion of immature T‐cells, which morphologically can mimic malignancy. Since the first case was described in 1999, dozens more have been reported in the literature. However, the epidemiologic, clinical, pathologic, and biologic features of this disease have not been well described. Here, we retrospectively reviewed all known cases reported in the literature to better understand this entity. A PubMed search up to January 2022 highlighted 25 papers describing cases/case series of iT‐LBP, one of which was a case presentation in a slide workshop. Except for 9 of the cases in one of the papers, where it was evident that the number of CD3+/TdT+ cells were too few to conform with a diagnosis of iT‐LBP, all papers and all the cases reported were included in the study amounting to a total of 45 cases. Clinicopathologic characteristics were analyzed using descriptive statistics and frequencies. Our analysis highlighted the previously known association with Castleman disease and Castleman‐like features and underlined its association with dendritic cell proliferations in general, as well as uncovering high frequency of concurrence with hepatocellular carcinoma and autoimmune diseases, most notably myasthenia gravis, paraneoplastic pemphigus and paraneoplastic autoimmune multiorgan syndrome. Furthermore, the co‐expression of CD4 and CD8 and high prevalence of extranodal disease and recurrences were other less well described features that were revealed.

sTRBC1 and cyTRBC1 Expression Distinguishes Indolent T-Lymphoblastic Proliferations From T-Lymphoblastic Leukemia/Lymphoma

“…Although the true nature of these TdT + T cells has not been determined yet, several hypotheses of the pathogenesis of iT-LBP have been proposed. 6 iT-LBPs might arise from extrathymic T-cell progenitors that proliferate in certain niches or conditions or may originate from T-lymphoblasts released from the thymus and homed to extrathymic sites such as lymph nodes. There may also be an association between iT-LBPs with autoimmune conditions or paraneoplastic syndromes.…”

“…Since that first reported case by Velankar et al 2 in 1999, several distinct instances of iT-LBP have been described, 1,3–5 often in association with Castleman disease, follicular dendritic cell tumors/sarcomas, hepatocellular carcinomas, peripheral T-cell lymphoma, or as an isolated finding. Although the true nature of these TdT + T cells has not been determined yet, several hypotheses of the pathogenesis of iT-LBP have been proposed 6 . iT-LBPs might arise from extrathymic T-cell progenitors that proliferate in certain niches or conditions or may originate from T-lymphoblasts released from the thymus and homed to extrathymic sites such as lymph nodes.…”

“…I ndolent T-lymphoblastic proliferation (iT-LBP) is a rare, benign, and reactive proliferation of nonclonal immature TdT + T cells found in extrathymic tissues. [1][2][3][4][5][6] Unlike the aggressive neoplasm characterized by an immature T-precursor phenotype and high incidence of mediastinal involvement known as T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL), 7,8 iT-LBP does not require therapy. However, the overlapping clinical and histologic features make it challenging to distinguish iT-LBP from T-ALL/LBL.…”

An Approach to Nodal T- and NK-Cell Lymphomas—A Systemic Review

“…Indolent T-lymphoblastic proliferation occurring as tiny clusters or confluent sheets of lymphoid cells morphologi-cally consistent with thymocytes has been noted by itself or in association with other benign and malignant lesions. 4,48 These thymocyte-like cells express TdT and may be misdiagnosed as T-lymphoblastic leukemia/lymphoma. However, IT-LBP does not obscure the architecture of nodes and is devoid of monoclonal TCR gene rearrangement.…”