Central Nervous System T-cell Lymphoma Research Articles

NCOG-08. A RARE PRIMARY CNS T-CELL LYMPHOMA CASE: 12-YEAR FOLLOW-UP AFTER CHEMOTHERAPY

Abstract INTRODUCTION Primary central nervous system (CNS) T-cell lymphoma (PCNSTL) is a rare hematological malignancy. There is mere literature to guide the treatment. CASE REPORT This study is an update on our previously reported case at SNO in 2012 after a 12-year follow-up, detailing the long-term outcome of our chemotherapy treatment for a case of PCNSTL. In 2011, a 26-year-old immunocompetent patient presented with severe headache, vomiting, and lethargy. The brain MRI found more than a dozen masses on his bilateral cerebral hemispheres. Brain biopsy discovered T-cell lymphoma. The patient was started biweekly high-dose-methotrexate (HD-MTX) in 2011. After three doses, there was no noticeable improvement on his brain MRI. His treatment was switched to HD-MTX plus high dose cytarabine regimen (Ferreri et al, The Lancet, 2009). The patient could not tolerate cytarabine; thus, was changed back to HD-MTX. The patient responded to the rest of HD-MTX well. He completed 8 doses of biweekly HD-MTX induction therapy and 2 doses of monthly HD-MTX maintenance therapy. His brain MRI showed complete resolution of enhancement on one-year follow-up image. The patient has been off-treatment and monitored under surveillance of brain MRIs since 2012. He has had no lymphoma recurrence over the past 12 years. His physical functions have been preserved with a Karnofsky Performance Status scale of 80%. Neuropsychological evaluations in 2015, 2018, and 2023 showed mild cognitive impairment with gradual improvements in his working memory and semantic fluency. His Mini-Mental Status Exam scores have remained stable to mild improvement, recording 27/30 in 2015, 26/30 in 2018, 27/30 in 2023 and 28/30 in 2024. DISCUSSION The patient, who is now 38 years old, has surpassed a 12-year survival mark. Our experience emphasizes the feasibility of treating PCNSTL through chemotherapy only, which might be potentially beneficial in surviving and preserving major aspects of brain function.

Primary Central Nervous System T- Cell Lymphoma of the Brain in An Immunocompetent Patient

Primary Central Nervous System T- Cell Lymphoma of the Brain in An Immunocompetent Patient Primary central nervous system (PCNS) T-cell lymphoma is a rare disease and rarer if it is seen in immunocompetent patients. The PCNS lymphoma makes up 1-7% of primary brain tumors. PCNS T-cell lymphoma accounts for about 2% of all PCNS lymphoma and almost 99% are seen in immunocompromised patients (Latta et al 2010, Batchelor et al 2003). Here, we report a case of PCNS T-cell lymphoma in an elderly patient who is immunocompetent. The radiological findings, histopathological studies, and reviews of the current literature of this rare condition are discussed.

A Case Report of Primary Central Nervous T-Cell Lymphoma in an Immunologically Competent Patient

Primary central nervous system (CNS) lymphomas are relatively rare, with the most common subtype being diffuse large B-cell lymphoma. Primary CNS T-cell lymphomas (PCNSTL) represent less than 5% of CNS lymphomas [1-2].

Primary central nervous system T-cell lymphoma in children and adolescents: a clinicopathological analysis of five cases

Objective: To study the clinicopathological characteristics, and further understand primary central nervous system T-cell lymphoma (PCNSTCL) in children and adolescents. Methods: Five cases of PCNSTCL in children and adolescents were collected from December 2016 to December 2021 at the First Affiliated Hospital of Zhengzhou University. The clinicopathological characteristics, immunophenotypic, and molecular pathologic features were analyzed, and relevant literatures reviewed. Results: There were two male and three female patients with a median age of 14 years (range 11 to 18 years). There were two peripheral T-cell lymphomas, not otherwise specified, two anaplastic large cell lymphoma, ALK-positive and one NK/T cell lymphoma. Pathologically, the tumor cells showed a variable histomorphologic spectrum, including small, medium and large cells with diffuse growth pattern and perivascular accentuation. Immunohistochemistry and in situ hybridization showed CD3 expression in four cases, and CD3 was lost in one case. CD5 expression was lost in four cases and retained in one case. ALK and CD30 were expressed in two cases. One tumor expressed CD56 and Epstein-Barr virus-encoded RNA. All cases showed a cytotoxic phenotype with expression of TIA1 and granzyme B. Three cases had a high Ki-67 index (>50%). T-cell receptor (TCR) gene rearrangement was clonal in two cases. Conclusions: PCNSTCL is rare, especially in children and adolescents. The morphology of PCNSTCL is diverse. Immunohistochemistry and TCR gene rearrangement play important roles in the diagnosis.

Diagnosis, prevention and treatment of central nervous system involvement in peripheral t-cell lymphomas.

Non-Hodgkin lymphomas with T-cell immunophenotype encompass a heterogeneous group of infrequent neoplasms that follow variable clinical courses but prevalently include aggressive behavior and high mortality rates. The involvement of the central nervous system (CNS) is an uncommon event in T-cell lymphomas, with wide variability among the different disease entities. CNS can be affected either at initial diagnosis or at recurrence, and both forms are considered "secondary CNS T-cell lymphoma". Given the low incidence of secondary CNS T-cell lymphoma, related literature is sparse, contradictory, and primarily constituted by small case series and single case reports. However, reported studies uniformly suggest high mortality rates related to this event. Therefore, to improve our ability to identify high-risk patients and offer them successful CNS prophylaxis or timely and effective treatment once the event has occurred may prevent CNS-related T-cell lymphomas deaths. For example, some entities like aggressive adult T-cell leukemia/lymphoma, extranodal natural killer/T-cell lymphoma, and other peripheral T-cell lymphomas with involvement of two or more extranodal organs are prone to CNS dissemination and should be considered for personalized CNS prophylaxis. The level of evidence suggesting an increased risk of CNS recurrence for other T-cell lymphomas and for other risk factors is lower. Published case series show that, following the example of aggressive B-cell lymphomas, patients with T-cell lymphomas and putative increased CNS risk receive different forms of prophylaxis, mostly methotrexate and cytarabine delivered by intrathecal and/or intravenous routes, with varied success. To date, achievements in the treatment of CNS involvement in patients with aggressive B-cell lymphoma were not replicated in secondary CNS T-cell lymphomas, and identification of effective therapies remains an urgent research target. This review is focused on clinical findings, diagnosis, treatment, and prognosis of patients with T-cell lymphoma experiencing CNS dissemination either at presentation or relapse. It aims to provide logical and, oftentimes, evidence-based answers to the most common questions on the most probable risk factors to CNS involvement in patients with T-cell lymphoma, the indications and strategies to prevent this life-threating event, and the management of patients with CNS disease.

Primary and secondary central nervous system mature T- and NK-cell lymphomas

Primary central nervous system (CNS) mature T- and NK-cell lymphomas are rare, only comprising 2% to 3% of all primary CNS lymphomas. Among them, peripheral T-cell lymphoma, not otherwise specified, anaplastic large cell lymphoma (ALCL), and extranodal NK/T-cell lymphoma (ENKTL) are the commonly reported histological subtypes. Secondary CNS T-cell lymphoma generally affects about 5% of patients with T- or NK-cell lymphoma, with some exceptions. Acute and lymphomatous subtypes of adult T-cell leukemia/lymphoma (ATLL) have high risk of CNS progression, may affect up to 20% of patients; ALK-positive ALCL with extranodal involvement >1 also has high risk of CNS progression. However, the impact and the optimal methodology of CNS prophylaxis remain unclear in systemic T-cell lymphomas. There are little data on the treatment strategy of primary and secondary CNS T-cell lymphoma. Treatment strategy derived from B-cell CNS primary lymphoma is generally used; this includes induction therapy with high-dose methotrexate-based regimens, followed by high-dose chemotherapy with autologous stem cell transplant in fit patients. There are unmet needs for patients who are not fit for intensive chemotherapy. The prognosis after CNS progression in T-cell lymphoma is dismal with the median overall survival of less than 1 year. New agents targeting T-cell lymphomas are emerging and should be tested in patients with mature T- and NK-cell lymphoma who suffer from CNS involvement.

Primary central nervous system T-cell lymphoma: An analysis from the surveillance, epidemiology, and end results program

BackgroundPrimary central nervous system T-cell lymphoma (PCNSTCL) is a rare neoplasm with few data regarding its common features and survival characteristics. ObjectiveTo explore the Surveillance, Epidemiology, and End Results 18 (SEER 18) database to determine the epidemiology of PCNSTCL. MethodsThe SEER 18 registry database was queried to identify patients diagnosed with PCNSTCL from 1973 to 2014 and extract their information. Age-specific rates and Kaplan-Meier overall survival (OS) were calculated. A Cox proportional hazards model was applied to investigate relationships between various demographic/treatment variables and OS. ResultsThe age-specific incidence rates were higher in the older population (≥60 years). Among 59 PCNSTCL cases from the SEER 18, the mean age at presentation was 55.8 years (SD, ±17.95), with a male predominance (1.36:1.00). The median follow-up was 8 months, and the median OS was 8 months (SE, ±4.162). The 1-, 3-, and 5-year OS was 46.3% [95% CI, 33.4%–59.2%], 32.8% [20.3%–45.3%], and 32.8% [20.3%–45.3%], respectively. Seventeen of the 59 patients survived at last follow-up. Patients < 60 years had a greater 3-year OS compared with patients ≥ 60 years (52.6% [33.6%–71.6%] vs 13.9% [1.4%–26.4%]. Multivariate analysis has demonstrated that only age at diagnosis (≥60/<60 years) exhibited a significant relationship with OS (HR, 3.495 [1.688–7.235];p = 0.001). Sex (female/male) was observed to have a doubted trend towards significance (HR, 0.487 [0.231–1.030]; p = 0.060). ConclusionsPCNSTCL is generally of poor prognosis but younger age at diagnosis (<60 years) predicts a better prognosis.

Clinicopathological features of primary central nervous system T-cell lymphomas

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of primary central nervous system T-cell lymphomas (TPCNSL), and to analyze its biological behavior and prognosis. Methods: Three cases of TPCNSL were collected from September 2014 to September 2019 in the First Affiliated Hospital of Nanjing Medical University. They were evaluated by HE, immunohistochemistry (IHC) and molecular genetics, and the relevant literature was reviewed. Results: Among the 6 816 brain tumors, 97 were primary central nervous system lymphomas (PCNSL), including 3 TPCNSL. There were two male and one female patients, aged 60, 67, and 82 years. Clinically, they were presented with varying degrees of limb numbness and unstable gait. Microscopically, the tumor cells were distributed diffusely or around blood vessels. They showed significant atypia and brisk mitotic activity. By IHC, they were positive for LCA, CD3, CD43, TIA-1, and perforin. Two of three cases were positive for CD5 and granzyme B. T-cell receptor gene rearrangement was clonal. EBER in situ hybridization was negative. The patients were followed for 1 to 6 months; one patient received chemotherapy and died of recurrence 3 months after surgery. One patient died of recurrence 5 months after operation alone. One patient remained recurrence and metastasis free more than 4 months post surgery. Conclusions: PCNSL is uncommon, and most are B-cell lymphomas, while T-cell lymphomas are even rarer. As the latter may show atypical clinical manifestations, diverse histologic morphology and poor prognosis, early diagnosis and timely treatment are particularly important for patients to improve survival.

Magnetic Resonance Imaging Characteristics of Primary Central Nervous System T-cell Lymphoma

Magnetic Resonance Imaging Characteristics of Primary Central Nervous System T-cell Lymphoma

Primary CNS T-cell Lymphomas: A Clinical, Morphologic, Immunophenotypic, and Molecular Analysis.

Primary central nervous system (CNS) lymphomas are relatively rare with the most common subtype being diffuse large B-cell lymphoma. Primary CNS T-cell lymphomas (PCNSTL) account for <5% of CNS lymphomas. We report the clinical, morphologic, immunophenotypic, and molecular characteristics of 18 PCNSTLs. Fifteen cases were classified as peripheral T-cell lymphoma, not otherwise specified, 2 of which were of γδ T-cell derivation and 1 was TCR silent; there was 1 anaplastic large cell lymphoma, ALK-positive and 2 anaplastic large cell lymphoma, ALK-negative. Median age was 58.5 years (range, 21 to 81 y), with an M:F ratio of 11:7. Imaging results showed that 15 patients had supratentorial lesions. Regardless of subtype, necrosis and perivascular cuffing of tumor cells were frequently observed (11/18 cases). CD3 was positive in all cases but 1; 10/17 were CD8-positive, and 5/17 were CD4-positive. Most cases studied had a cytotoxic phenotype with expression of TIA1 (13/15) and granzyme-B (9/13). Polymerase chain reaction analysis of T-cell receptor γ rearrangement confirmed a T-cell clone in 14 cases with adequate DNA quality. Next-generation sequencing showed somatic mutations in 36% of cases studied; 2 had >1 mutation, and none showed overlapping mutations. These included mutations in DNMT3A, KRAS, JAK3, STAT3, STAT5B, GNB1, and TET2 genes, genes implicated previously in other T-cell neoplasms. The outcome was heterogenous; 2 patients are alive without disease, 4 are alive with disease, and 6 died of disease. In conclusion, PCNSTLs are histologically and genomically heterogenous with frequent phenotypic aberrancy and a cytotoxic phenotype in most cases.

Clinicopathologic Features of Adult T-cell Leukemias/Lymphomas at a North American Tertiary Care Medical Center

Human T-cell lymphotropic virus type 1 is associated with adult T-cell leukemia/lymphoma (ATLL). Published series of ATLLs seen at a United States medical institution are rare. We present the features of 4 ATLLs diagnosed at our North American tertiary care medical center from 1990 to 2012. Despite the absence of a history of origin from an endemic region, all our ATLLs demonstrated evidence of human T-cell lymphotropic virus type 1 infection. Central nervous system (CNS) involvement by ATLL was uncommon in our series, and represented only 1.6% (1/64) of all CNS B-cell or T-cell lymphomas diagnosed over a 20+ year period at our institution. Review of the medical literature reveals that the majority of CNS-involved ATLLs present with the lymphoma or acute subtype, and complete remission is difficult to achieve in these cases. CNS involvement frequently occurs with a systemic disease, which carries an aggressive clinical course with poor prognosis. In addition, CNS involvement by ATLL can be the initial presentation or seen with relapsed disease, can be the only site or be associated with other tissue sites of involvement, and may manifest with variable clinical signs/symptoms. Our retrospective study reveals that ATLLs are rare mature T-cell lymphomas in a native North American population, but the clinical and histopathologic features of ATLLs from this nonendemic region are similar to those seen from other endemic regions. Early recognition of these rare ATLLs involving uncommon sites, such as the CNS, will help optimize treatment for these infrequent mature T-cell lymphomas.

Adult T-cell lymphoma/leukemia presenting as isolated central nervous system T-cell lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is a T-cell neoplasm, associated with infection by the retrovirus human T-lymphotropic virus type 1 (HTLV-1). Central nervous system (CNS) involved by ATLL is often occurred in advanced disease, such as acute and lymphomatous variants. On the other hand, isolated CNS lymphoma is rare. We repot a 50-year-old woman who presented with multiple infiltrative brain lesions on the magnetic resonance (MR) imaging. Results of initial biopsy of brain tumor indicated CNS vasculitis. The patient received one course of high-dose methotrexate and MR imaging of brain revealed remission of infiltrative lesions. Two years later, new brain lesions were detected. Histopathologic examination of specimens via craniotomy revealed T-cell lymphoma. The patient responded poorly to subsequent chemotherapy, and salvage whole-brain irradiation was performed. Six months later, the patient had hepatosplenomegaly, hypercalcemia, and multiple lymphocytes with a cloverleaf appearance in circulation. Results of flow cytometry analysis of peripheral blood indicated ATLL and antibodies to human T-lymphotropic virus type 1 (HTLV-1) were detected. Clinicians should screen HTLV-1 infection when patients are diagnosed with peripheral T-cell lymphoma. Combined antiviral therapy and intensive chemotherapy may improve the outcomes of ATLL.

Primary Central Nervous System T-Cell Lymphoma in a Common Dolphin (Delphinus delphis)

This report describes the pathological findings in an adult female short-beaked common dolphin (Delphinus delphis) stranded alive in the Canary Islands. Necropsy examination revealed the presence of a nodular neoplastic growth in the central nervous system (CNS) at the level of the thalamus. Microscopical examination revealed the mass to be a lymphoma and immunohistochemical labelling demonstrated a T-cell origin. No significant lesions were observed in other organs, including lymphoid organs. This is the first report of a primary T-cell lymphoma in the CNS in cetaceans.

Primary Central Nervous System T-Cell Lymphoma of the Brain

Primary central nervous system (PCNSL) T-cell lymphoma is a very rare extra nodal non-Hodgkin's lym- phoma (NHL) tumor arising from the central nervous system. The incidence of this disease is increasing globally in part due to larger numbers of immunocompromised patients. There are no pathognomonic clinical or radiographic features of T-cell PCNSL. Brain biopsy is generally necessary for tissue diagnosis in order to direct appropriate treatment and coun- sel patients on prognosis. We report our experience in an immunocompetent patient who presented with a several week history of progressive encephalopathy. The imaging findings, histopathological studies, treatment and review of the cur- rent literature of this rare condition are discussed.

Primary Central Nervous System T-Cell Lymphoma in Aids Patients: Case Report and Literature Review

According to the published data, most primary central nervous system lymphomas (PCNSLs) are B-cell lymphomas; primary T-cell lymphomas are rare. In a search of the MEDLINE database, we found only 6 cases of primary T-cell PCNSL. Here, we present the case of a 43-year-old man with AIDS, not on highly active antiretroviral therapy, who presented with focal neurologic symptoms and was found on magnetic resonance imaging to have multiple brain lesions. A biopsy showed T-cell lymphoma, and the patient was subsequently treated with whole-brain radiation, to marked clinical response. Reported cases from the literature of primary T-cell PCNSL in AIDS patients are summarized in this review.

Central nervous system T-cell lymphoma in acquired immunodeficiency syndrome

Central nervous system T-cell lymphoma in acquired immunodeficiency syndrome

A 76‐YEAR‐OLD MAN WITH COGNITIVE AND NEUROLOGICAL SYMPTOMS

A 76-year-old man presented with cognitive symptoms, followed by headache and weakness of the lower limbs and left arm. The clinical course was progressive but fluctuating. On magnetic resonance imaging (MRI), a contrast-enhancing lesion 1 cm in diameter was seen in the left temporal lobe. This lesion became attenuated and a new contrast-enhancing lesion 1 x 2 cm was seen in the left frontal lobe on a subsequent MRI. Following additional tests, treatment with corticosteroids for presumptive neurosarcoidosis was started, however, he soon expired. At autopsy, there was a tumor-like mass in the left frontal lobe. Pathologic evaluation revealed a primary T-cell lymphoma of the central nervous system (CNS). CNS T-cell lymphomas may be difficult to diagnose, even histologically, due to their frequent small cell morphology and lack of significant atypia.

Periventricular Spread of Primary Central Nervous System T-cell Lymphoma in a Cat

A 9-year-old domestic shorthaired cat with clinical signs of neurological disease was determined to have primary T-cell lymphoma of the central nervous system (CNS) on necropsy examination. Microscopically, neoplastic lymphocytes were distributed in the CNS parenchyma bilaterally around the cerebral ventricles, third ventricle, mesencephalic aqueduct, fourth ventricle and central canal of the spinal cord. The neoplastic infiltration was associated with complete loss of ependymal cells and marked astrocytosis. A large, solitary neoplastic lesion was present in the parenchyma around the central canal of the spinal cord at the level of the 13th thoracic vertebra. Immunohistochemically, the majority of neoplastic cells expressed CD3 and many also labelled for proliferating cell nuclear antigen (PCNA) and Ki-67. This is, to our knowledge, the first report of periventricular spread of primary CNS T-cell lymphoma in animals.

Primäres zerebelläres T-Zell-Lymphom

Primary central nervous system T-cell lymphomas are rare and have to be differentiated from reactive lesions. It is therefore essential to use all possible tools to establish the diagnosis, including immunohistochemistry, molecular genetic analysis, and/or cytogenetic methods. In this paper we present the case of a primary cerebellar T-cell lymphoma in a 50-year-old man; a clonal T-cell receptor gene rearrangement was documented. After two cycles of methotrexate therapy the patient developed Pneumocystis carinii-induced pneumonia, dying 10 weeks after his diagnosis. The autopsy did not reveal any residual tumour.

Primary central nervous system T-cell lymphoma in a cat.

A 5-year-old intact male Persian cat was presented with progressive neurologic deficits, hyperesthesia, hyperreflexia, ataxia, and intention tremors, which resulted in death. Serologic tests for feline leukemia virus and feline immunodeficiency virus infection were negative. Neurohistologic examination revealed the presence of pleomorphic cellular infiltrates in cerebral leptomeninges and around parenchymal vessels. The majority of infiltrating cells were uniformly immunostained using an antiserum directed against T cells. Immunohistochemical examination of paraffin-embedded brain sections for the antigens of canine distemper virus, herpesvirus, Borna virus, and Toxoplasma gondii were negative. Histologic and immunohistochemical studies revealed a primary central nervous system T-cell lymphoma affecting the brain.