Indolent T-Lymphoblastic Proliferation in Idiopathic Multicentric Castleman Disease.

Benign and polyclonal proliferation of immature T cells in a lymph node with preserved morphological architecture is called indolent T-lymphoblastic proliferation (iT-LBP). Although overall rare, they have been described in association with both benign and malignant disorders including Castleman disease. We report the first case of idiopathic multicentric Castleman disease associated with iT-LBP, all previous reports of iT-LBP in Castleman disease were unicentric. A 37-year-old-male presented with 3 months of fevers and B-symptoms and was found to have enlargement of multiple bilateral lymph node sites on both sides of diaphragm along with splenomegaly. Anemia, elevated C-reactive protein, hypoalbuminemia, and elevated interleukin-6 levels were present. Biopsy of a lymph node showed features suggestive of idiopathic multicentric Castleman disease and iT-LBP. Bone marrow biopsy was unremarkable. Siltuximab and steroids were used to treat the condition.

LIM domain only 2 (LMO2) expression distinguishes T-lymphoblastic leukemia/lymphoma from indolent T-lymphoblastic proliferations.

AIMS: An indolent T-lymphoblastic proliferation (iT-LBP) is a benign, reactive expansion of immature terminal deoxynucleotidyl transferase (TdT)-positive T cells found in extrathymic tissues. iT-LBP can be challenging to distinguish from malignant processes, specifically T-lymphoblastic lymphoma (T-LBL), given the overlapping clinical and histological features. Recently, it has been shown that LIM domain only 2 (LMO2) is overexpressed in T-LBL but not in reactive immature TdT+ T cells in the thymus. On the basis of these findings, the aim of this study was to investigate the expression of LMO2 by using immunohistochemistry and its role in differentiating iT-LBPs from T-LBLs. METHODS AND RESULTS: We retrospectively identified cases of iT-LBP and T-LBL from the pathology archives of four institutions. Seven iT-LBP cases (including five new cases that have not been reported in the literature) and 13 T-LBL cases were analysed. Clinical, morphological, immunophenotypic and molecular data were analysed. Immunohistochemical staining with LMO2 was performed on all iT-LBP and T-LBL cases. A review of five new iT-LBP cases showed similar morphological, immunophenotypic and molecular features to those of previously reported cases. All iT-LBP cases were negative for LMO2 (0/7), whereas 92% of T-LBL cases (12/13) expressed LMO2; the sensitivity was 92% (confidence interval 64-100%) and the specificity was 100% (confidence interval 59-100%). CONCLUSION: We confirm previously published findings that iT-LBP cases show highly overlapping morphological and immunophenotypic features with T-LBL. Importantly, LMO2 expression is a sensitive and specific marker with which to rule out iT-LBP.

[Indolent T-lymphoblastic proliferation in association with localized Castleman disease: A case report]. / Maladie de Castleman localisée avec prolifération lymphoblastique T indolente.

Herein we report the case of a 41-year-old woman who presented with pelvic pain. Magnetic Resonance Imaging exhibited a single pelvic mass, measuring 50mm long axis, alongside the right iliac vessels. Histological examination of the excision specimen showed a lymphoid tumor with features of localized Castleman disease, hyaline vascular type. Moreover we identified multiple interfollicular dark clusters, composed of cells morphologically resembling cortical thymocytes. Their immunophenotype was consistent with an intermediate stage of T-cell differentiation, with the expression of CD3, CD4, CD8, TdT, CD1a, CD99, CD2, CD5, CD7 and CD10, with 40% Ki67. After integration of clinical and molecular data, the retained diagnosis was an indolent T-cell lymphoblastic proliferation associated with hyaline vascular localized Castleman disease. The clinical course confirmed the indolent nature of the proliferation, despite a late local recurrence at 7 years of the initial diagnosis, without histological modification, due to an incomplete initial resection surgery.

Indolent T-lymphoblastic proliferation concomitant with acinic cell carcinoma mimicking T-lymphoblastic lymphoma: case report and literature review.

AIMS: Indolent T-lymphoblastic proliferation (iT-LBP) is a non-clonal benign condition showing extrathymic proliferation of T-lymphoblasts positive for CD3, CD4, CD8, and TdT. Isolated iT-LBP has been observed, but the majority of iT-LBPs have been seen in conjunction with other disorders, including Castleman disease, hepatocellular carcinoma, follicular dendritic cell tumours, angioimmunoblastic T-cell lymphoma, myasthenia gravis, and acinic cell carcinoma (ACC). The clinical course of iT-LBP is indolent, and no therapy is usually required. A major concern is misdiagnosis as T-lymphoblastic lymphoma, and a correct diagnosis of iT-LBP often requires not only pathological analysis but also careful monitoring of the clinical course. The aim of this study was to broaden the knowledge of pathologists and physicians concerning this as yet not well-recognised entity. METHODS AND RESULTS: We report a case of iT-LBP concomitant with ACC, along with a literature review of all 14 cases of iT-LBP reported to date. CONCLUSIONS: iT-LBP should always be considered as a differential diagnosis of T-lymphoblastic lymphoma, as the two disorders show extremely similar traits.

Indolent T-lymphoblastic proliferation with fibrolamellar hepatocellular carcinoma developed after colorectal adenocarcinoma: a case report.

Objective: Indolent T-lymphoblastic proliferation (iT-LBP) is a non-neoplastic disease with an indolent clinical course, manifesting as hyperplasia of immature extrathymic T-lymphoblastic cells. Isolated iT-LBP has been observed, but the majority of iT-LBP cases has been seen in conjunction with other diseases. iT-LBP is easily misdiagnosed as T-lymphoblastic lymphoma/leukemia, and understanding the disease of indolent T-lymphoblastic proliferation may prevent misdiagnosis and missed diagnosis in pathological diagnosis. Case presentation: We report a case morphology, immunophenotypic, and molecular features of iT-LBP combined with fibrolamellar hepatocellular carcinoma developed after colorectal adenocarcinoma and review relevant literature. Conclusion: iT-LBP combined with fibrolamellar hepatocellular carcinoma developed after colorectal adenocarcinoma is relatively rare and should always be considered as a differential diagnosis of T-lymphoblastic lymphoma and scirrhous hepatocellular carcinoma as the two disorders show highly similar clinical features.

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

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.

Indolent T-lymphoblastic proliferation: a report of three cases.

Indolent T-lymphoblastic proliferation (iT-LBP) is the extrathymic proliferation of nonclonal TdT + T cells and is typically associated with lymphoid disorders. Although one study revealed that iT-LBP occurred in angioimmunoblastic T-cell lymphoma, no other lymphoma-related cases have been reported. Here, we report three cases of concurrent iT-LBP and benign or malignant lymphoid disorders. The first patient had bilateral cervical lymph node enlargement, and the resected lymph node showed polyclonal precursor T-cells distributed between benign hyperplastic lymphoid follicles. In the second case, iT-LBP occurred in peripheral T-cell lymphoma with a follicular growth pattern, showing that precursor T-cells were distributed between neoplastic follicles composed of CD4 + and CXCL13 + T-cells. In the third case, polyclonal precursor T-cells were distributed between the neoplastic follicles of follicular lymphoma. In summary, our results indicate an association between iT-LBP and reactive lymphoid hyperplasia (case 1) and lymphoma (cases 2 and 3).

Hepatocellular carcinoma with immature T-cell (T-lymphoblastic) proliferation.

Indolent T-lymphoblastic proliferation has been rarely reported in the upper aerodigestive tract. The lymphoid cells associated with this condition have the morphological and phenotypical features of immature thymocytes. However, their pathogenesis and biology are unknown. We present an unusual type of tumor infiltrating lymphocytes in a case with hepatocellular carcinoma, presumed to be a T-lymphoblastic proliferation. A 58-yr-old female patient presented with indigestion and a palpable epigastric mass. The abdominal computed tomography revealed a mass in the S6 region of the liver. A hepatic segmentectomy was performed. Microscopic examination showed dense isolated nests of monomorphic lymphoid cells within the tumor. Immunohistochemically, the lymphoid cells were positive for CD3, terminal deoxymucleotide transferase (TdT) and CD1a. In addition, they showed dual expression of CD4 and CD8. The polymerase chain reaction used to examine the T-cell antigen receptor gamma gene rearrangement showed polyclonal T-cell proliferation. This is the second case of hepatocellular carcinoma combined with indolent T-lymphoblastic proliferation identified by an unusual tumor infiltrating lymphocytes.

Indolent T-lymphoblastic proliferation associated with Castleman disease and low grade follicular dendric cell sarcoma: report of a case and review of literature.

Indolent T-lymphoblastic proliferation (IT-LBP) is referred to as extrathymic immature TDT+T-cell hyperplasia, non-neoplastic lesion, often misdiagnosed as T-lymphoblastic lymphoma and overtreated. We report a case of a 20-year-old male patient with a right adrenal gland mass, diagnosed as indolent T-lymphoblastic proliferation (IT-LBP) associated with hyaline vascular Castleman disease (HV-CD) and low grade follicular dendric cell sarcoma (LG-FDCS). The case is a rare combination of finding, and it is the first case occurring in adrenal gland. IT-LBP is a clinically indolent disease, requiring no treatment, often associated with other tumors. Because of the high ki67 index, IT-LBP is easily misdiagnosed as T-lymphoblastic lymphoma, causing overtreatment. Understanding the biological behavior, treatment, prognosis and the associated diseases of IT-LBP is important.

Hepatic carcinoma with indolent T-lymphoblastic proliferation (iT-LBP).

Although indolent T-lymphoblastic proliferation (iT-LBP) in the extrathymic location have been shown to be a distinct clinicopathologic entity, carcinoma composed iT-LBP are rare. We retrospectively analyzed the clinicopathological features of 7 hepatic carcinoma cases with iT-LBP. There were 5 male and 2 female patients, aged from 37-54 (mean 47) years. All patients had a clinical history of chronic hepatitis B viral infection with high serum AFP level. Microscopically, these carcinomas were characterized by admixed with increased amounts of fibrous and small lymphocytes composed of regressive germinal centers. Immunohistochemically, in lymphoid tissues, some TDT+ cells were highlighted in the CD3+ area. These lymphoblasts localized predominantly between the cords of the carcinoma and interfollicular regions, diffused or only focal presented more than 50 TdT+ lymphoblasts/HPF. No EBV infection cells and T-cell antigen clonal rearrangement was detected. 3/4 cirrhotic patients developed HCC recurrence, while the 4-y survival rate was 100% in non-cirrhosis patients. It-LBP is a rare unusual proliferation and easily be misdiagnosed in HC patients. It does not seem to be associated with a specific HCC type. If HC companied with numerous small lymphocytes infiltration and showed high Ki67 index, a primary HC with iT-LBP should be considered in the lists of diagnosis.

Benign TdT-positive cells in pediatric and adult lymph nodes: a potential diagnostic pitfall.

Benign terminal deoxynucleotidyl transferase (TdT)-positive cells have been documented in a variety of nonhematopoietic tissues. Scant data are, however, available on their presence in nonneoplastic lymph nodes. This study is aimed to (1) characterize the presence/distribution of benign TdT-positive cells in pediatric and adult reactive lymph nodes and (2) define the phenotype and nature of such elements. This retrospective study considered 141 reactive lymph nodes from pediatric and adult patients without history of neoplastic disease. TdT-positive cells were characterized by immunohistochemical and morphometric analyses, and their presence was correlated with the clinical-pathological features. The nature of TdT-positive cells was investigated by (1) double immunostaining for early lymphoid cell markers and (2) assessment of TdT expression in fetal lymph nodes. Sparse TdT-positive cells were documented in all pediatric cases and in most (76%) adult lymph nodes. TdT-positive cell density was higher in children than adults (15.9/mm2 versus 8.6/mm2; P < .05). TdT positivity did not correlate with any clinical or histological parameter, and double immunostaining disclosed a phenotype compatible with early lymphoid precursors (positivity for CD34 and CD10, and variable expression of CD7). A very high TdT-positive cell density (802.4/mm2) was reported in all fetal lymph nodes. In conclusion, TdT-positive cells are a common finding in pediatric and adult lymph nodes. The interstitial distribution and low number of such cells allow for the differential diagnosis with precursor lymphoid neoplasms. The high density in fetal lymph nodes and the phenotype of such cells suggest their belonging to an immature lymphoid subset gradually decreasing with age.

Indolent T-lymphblastic proliferation: report of a case involving the upper aerodigestive tract.

T-lymphoblastic lymphoma (T-LBP) is a high-grade malignant lymphoma, which possesses the characteristic of high metastasis and high mortality without treatment. We are presenting a special T-lymphoblastic proliferation involving in the oropharynx, nasopharynx, sinus and trachea in a patient with local involved about 15-years without systemic dissemination. The immunophenotype of this case was similar to T-LBP. The proliferous cells were positive for terminal deoxynucleotidyl transferase (TdT), CD3, and appeared co-expression CD4 and CD8. No clonal rearrangements of TCRγ and/or TCRß gene were detected. Indolent T-lymphoblastic proliferations rarely occurred or unusually could not be diagnosed, combing with the relevant literature and clinically indolent manifestation, we interpreted this case as indolent T-lymphoblastic proliferation (iT-LBPs). So far, the mechanism of the T-lymphoblastic proliferations is still uncertain and requires further study.

Hepatocellular Carcinoma with Immature T-Cell (T-lymphoblastic) Proliferation

Indolent T-lymphoblastic proliferation has been rarely reported in the upper aerodigestive tract. The lymphoid cells associated with this condition have the morphological and phenotypical features of immature thymocytes. However, their pathogenesis and biology are unknown. We present an unusual type of tumor infiltrating lymphocytes in a case with hepatocellular carcinoma, presumed to be a T-lymphoblastic proliferation. A 58-yr-old female patient presented with indigestion and a palpable epigastric mass. The abdominal computed tomography revealed a mass in the S6 region of the liver. A hepatic segmentectomy was performed. Microscopic examination showed dense isolated nests of monomorphic lymphoid cells within the tumor. Immunohistochemically, the lymphoid cells were positive for CD3, terminal deoxymucleotide transferase (TdT) and CD1a. In addition, they showed dual expression of CD4 and CD8. The polymerase chain reaction used to examine the T-cell antigen receptor gamma gene rearrangement showed polyclonal T-cell proliferation. This is the second case of hepatocellular carcinoma combined with indolent T-lymphoblastic proliferation identified by an unusual tumor infiltrating lymphocytes.