T-Cell Prolymphocytic Leukemia: Diagnosis, Pathogenesis, and Treatment.

T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive neoplasm of mature T-cells. Most patients with T-PLL present with lymphocytosis, anemia, thrombocytopenia, and hepatosplenomegaly. Correct identification of T-PLL is essential because treatment for this disease is distinct from that of other T-cell neoplasms. In 2019, the T-PLL International Study Group (TPLL-ISG) established criteria for the diagnosis, staging, and assessment of response to treatment of T-PLL with the goal of harmonizing research efforts and supporting clinical decision-making. T-PLL pathogenesis is commonly driven by T-cell leukemia 1 (TCL1) overexpression and ATM loss, genetic alterations that are incorporated into the TPLL-ISG diagnostic criteria. The cooperativity between TCL1 family members and ATM is seemingly unique to T-PLL across the spectrum of T-cell neoplasms. The role of the T-cell receptor, its downstream kinases, and JAK/STAT signaling are also emerging themes in disease pathogenesis and have obvious therapeutic implications. Despite improved understanding of disease pathogenesis, alemtuzumab remains the frontline therapy in the treatment of naïve patients with indications for treatment given its high response rate. Unfortunately, the responses achieved are rarely durable, and the majority of patients are not candidates for consolidation with hematopoietic stem cell transplantation. Improved understanding of T-PLL pathogenesis has unveiled novel therapeutic vulnerabilities that may change the natural history of this lymphoproliferative neoplasm and will be the focus of this concise review.

Current understandings on T-cell prolymphocytic leukemia and its association with TCL1 proto-oncogene.

T-cell prolymphocytic leukemia (T-PLL) is a rare mature T cell leukemia with aggressive clinical course, poor response to conventional therapies and high mortality rates. Classical cytogenetics and various genetic techniques have observed complex karyotypes and associated genes involved in the molecular pathogenesis of T-PLL, among which the proto-oncogene T-cell leukemia/lymphoma 1 (TCL1) as a hallmark of malignancy is hyper-activated and abnormally expressed in many T-PLL cases. Progress has been made to identify the presence of chromosomal rearrangements and subsequent changes in key molecular pathways typically involving Akt, which may hint cytogenetic mechanisms underlying the pathogenesis of T-PLL and indicate new treatment targets. In this article, we describe current insights of T-PLL with an emphasis on the potential role of TCL1 gene disorders and TCL1-Akt interactions in cell transformation and disease progression, followed by discussion on current treatment options and novel therapeutic approaches based on cytogenetics, which still remains to be explored for the effective management of T-PLL and other TCL1-driven hematological malignancies.

T-cell chronic lymphocytic leukemia or small-cell variant of T-cell prolymphocytic leukemia: a historical perspective and search for consensus.

There is a rich history behind the extinct entity 'T-cell chronic lymphocytic leukemia (T-CLL)' and the now-established replacement, small-cell variant of T-cell prolymphocytic leukemia (T-PLL-sv). Herein, we review the history of the events, observations, and discussions that led to this replacement. We also provide a systematic analysis of all previously reported cases of T-PLL-sv as well as our four new additional cases. Despite the higher frequency of a normal karyotype and perhaps an overrepresented CD4(-) CD8(-) immunophenotype among these patients (compared to T-PLL in general) as well as bland morphology (that makes them superficially appear more similar to B-CLL), we argue that the current World Health Organization (WHO)-based classification as T-PLL-sv is adequate and should continue for the time being. Morphologically, T-PLL-sv represents approximately one-fifth of all T-PLL cases. However, morphology alone does not determine the clinical course and should not be the basis for clinical decision making and prognostication. We propose a clonal evolution model in which mature T-cell leukemias classified in the past as T-CLL are perhaps T-PLL diagnosed early in the course of the disease. Future research using next-generation sequencing, comparative genomic hybridization, and molecular array studies, including serial analyses of individual cases over time, is needed to better identify this rarely diagnosed, inherently controversial form of T-cell leukemia.

Xantomas planos normolipémicos y micosis fungoide / Normolipemic plane xanthomas and mycosis fungoides

Los xantomas planos difusos normolipémicos se caracterizan por la presencia de placas amarillentas en párpados, cuello, parte superior del tronco, glúteos y flexuras. En la histología se objetivan histiocitos espumosos en la dermis. Aproximadamente la mitad de los casos se asocia a trastornos hematológicos. Raramente se han descrito en el contexto de linfomas cutáneos de células T. Presentamos el caso de una paciente con micosis fungoide tumoral que desarrolló xantomas planos normolipémicos coincidiendo con la aparición de nuevas lesiones de linfoma. Revisamos la literatura inglesa sobre la rara asociación de xantomas y linfomas cutáneos de células T

Diffuse normolipemic plane xanthomas are characterized by the presence of yellowish plaques on the eyelids, neck, upper trunk, buttocks and flexures. Histology shows foamy histiocytes in the dermis. Approximately half of all cases are associated with hematological disorders. On rare occasions, they have been described in the context of cutaneous T-cell lymphomas. We present the case of a female patient with tumor-stage mycosis fungoides who developed normolipemic plane xanthomas coinciding with the appearance of new lymphoma lesions. We review English-language literature regarding the rare association of xanthomas and cutaneous T-cell lymphomas

T-cell large granular lymphocyte leukemia of donor origin after allogeneic bone marrow transplantation.

A 39-year-old man with chronic myeloid leukemia in accelerated phase underwent allogeneic bone marrow transplantation (BMT). At 6 months after BMT, lymphocytosis (WBC count, 23,100/microL [23.1 x 10(9)/L]; 80% (0.80) large granular lymphocytes [LGLs]) occurred. The LGLs were CD3+CD4-CD8+, with clonally rearranged T-cell receptor gamma gene, and of donor origin, as shown by analysis of polymorphic microsatellite markers. Epstein-Barr virus was not present. The diagnosis, therefore, was consistent with T-cell large granular lymphocytic (T-LGL) leukemia. Corticosteroids controlled the LGL count, but progressive pancytopenia led to death 4 months later. Retrospective analysis showed that the T-LGL leukemia apparently had arisen as early as 3 months after BMT. The distinguishing features of this case included donor origin, neoplastic nature, and the aggressive fatal outcome.