T-cell prolymphocytic leukemia

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]

Synonyms and Keywords: T-cell chronic lymphocytic leukemia; "Knobby" type of T-cell leukemia; T-prolymphocytic leukemia/T-cell lymphocytic leukemia- Kiel; T-PLL

Overview

T-cell-prolymphocytic leukemia (also known as T-PLL) is a rare, mature T-cell leukemia with aggressive behavior and predilection for blood, bone marrow, lymph nodes, liver, spleen, and skin. T-cell prolymphocytic leukemia was first described by Catovsky in 1973. There is no classification system for T-cell prolymphocytic leukemia. The inversion of chromosome 14 (14q11) has been associated with the development of T-cell prolymphocytic leukemia. T-cell prolymphocytic leukemia is very rare, and it represents 2% of all small lymphocytic leukemias in adults. T-cell prolymphocytic leukemia is more commonly observed among young adult patients aged between 30 to 40 years old. Males are slightly more affected with are more commonly affected with T-cell prolymphocytic leukemia than females. Laboratory findings consistent with the diagnosis of T-cell prolymphocytic leukemia, include: high lymphocyte count (> 100 x 109/L), anemia, thrombocytopenia, and negative HTLV-1 serology. There are no specific imaging findings associated with T-cell prolymphocytic leukemia. Prognosis is generally poor, and the median survival time of patients with T-cell prolymphocytic leukemia is approximately 7 months. The mainstay of therapy for T-cell prolymphocytic leukemia is alemtuzumab (anti-CD52). However, T-cell prolymphocytic leukemia is often resistant to therapy. Autologous and allogeneic stem cell transplants is the mainstay of therapy for patients who achieve remission.

Historical Perspective

  • In 1973, T-cell prolymphocytic leukemia was first described by Catovsky.[1]
  • In 1994, T-cell prolymphocytic leukemia was described as a separate entity from other large grandular lymphocytic disorders.[2]

Classification

  • Morphologically T-cell prolymphocytic leukemia has three variants:[3]
    • Typical (75 percent)
    • Small cell variant (20 percent)
    • Cerebriform (Sézary cell-like) variant (5 percent)

Pathophysiology

  • T-cell prolymphocytic leukemia arises from mature (post-thymic) T-cell, which is normally involved in in cell-mediated immunity.
  • The inversion of chromosome 14 (14q11) has been associated with the development of T-cell prolymphocytic leukemia.
  • Patients with T-cell prolymphocytic leukemia have TCR gene rearrangements for the γ and δ chains.
  • Mutations of chromosome 8 are seen in approximately 75% of patients.
  • On gross pathology, characteristic findings of T-cell prolymphocytic leukemia, include:[3]
  • No remarkable findings
  • On microscopic histopathological analysis, characteristic findings of T-cell prolymphocytic leukemia, include:[3]
  • The immunophenotype CD4+/CD8- (present in 60% of cases)
  • The immunophenotype CD4+/CD8+ (present in 25%)
  • The immunophenotype CD4-/CD8+ (15% of cases)

Immunophenotype

  • T-cell prolymphocytic leukemia cells express different markers including:
    • CD52 (strongly)
    • Pan-T cell markers such as:
      • CD2
      • CD3 (might be low or high level)
      • CD7
    • Oncogene TCL1
    • CD4+/CD8- (present in 60% of cases)
    • CD4+/CD8+ (present in 25%, unique for T-cell prolymphocytic leukemia)
    • CD4-/CD8+ (15% of cases)
    • Negative terminal deoxynucleotidyl transferase (TdT)

Genetic

  • There are many chromosomal abnormalities in T-cell prolymphocytic leukemia, which mostly involve chromosome 14. Different types of genetic abnormalities are as follows:
    • Inv(14)
    • t(14;14)(q11;q32)
    • t(X;14)(q28;q11) which involves a homolog of TCL1, MTCP1 (mature T cell proliferation 1 gene)
    • idic(8p11)
    • t(8;8)
    • Trisomy 8q
    • Del(12p13)
    • Abnormalities in chromosome 6
    • Abnormalities in chromosome 17
    • Deletion of TP53 gene
    • Deletions of or missense mutations at the ataxia telangiectasia mutated (ATM) locus 11q23

Causes

  • Common causes of T-cell prolymphocytic leukemia, include:[3]
  • Genetic mutations (e.g. Trisomy 8, chromosomal abnormalities)

Differentiating T-cell Prolymphocytic Leukemia from Other Diseases

Epidemiology and Demographics

  • T-cell prolymphocytic leukemia is very rare, and it represents 2% of all small lymphocytic leukemias in adults.
  • The incidence of T-cell prolymphocytic leukemia increases with age; the median age at diagnosis is 65 years.[3]
  • Patients with ataxia telangiectasia and T-cell prolymphocytic leukemia are young adults; the median age at diagnosis is 30 years.
  • Males are slightly more affected with T-cell prolymphocytic leukemia than females.
  • There is no racial predilection for T-cell prolymphocytic leukemia.

Risk Factors

  • There are no risk factors associated with the development of T-cell prolymphocytic leukemia.[3]

Screening

There is insufficient evidence to recommend routine screening for T-cell prolymphocytic leukemia.

Natural History, Complications and Prognosis

  • The majority of patients with T-cell prolymphocytic leukemia are symptomatic at the time of diagnosis.
  • Early clinical features include fever, fatigue, and lymphadenopathy.
  • If left untreated, patients with T-cell prolymphocytic leukemia may progress to develop multiple organ failure.
  • Common complications of T-cell prolymphocytic leukemia, include:[3]
  • Prognosis is generally poor, and the median survival time of patients with T-cell prolymphocytic leukemia is approximately one to two years.[3]
  • Patients with CD45RO+/CD45RA- immunophenotype tend to have a more indolent course.
  • It seems following factors are associated with worse prognosis:
    • Increased expression of TCL1
    • Increased activity of the serine-threonine kinase AKT

Diagnosis

Diagnostic Study of Choice

  • There are no established criteria for the diagnosis of T-cell prolymphocytic leukemia. Patients with T-cell prolymphocytic leukemia are diagnosed by clinical presentation, pathology evaluation of the peripheral blood and bone marrow. Flow cytometry and immunostains should be performed to diagnose a T cell immunophenotype.

History and Symptoms

  • Symptoms of T-cell prolymphocytic leukemia may include the following:[3]

Physical Examination

  • Patients with T-cell prolymphocytic leukemia usually appear pale and malnourished.
  • Physical examination may be remarkable for:[3]

Laboratory Findings

  • Laboratory findings consistent with the diagnosis of T-cell prolymphocytic leukemia, include:[3]
  • High lymphocyte count (> 100 x 109/L)
  • Anemia
  • Thrombocytopenia
  • Negative human T lymphotropic virus (HTLV) serology
  • Peripheral Blood Smear demonstrated predominance of lymphocytes:
    • Typical variant:
      • Medium-sized lymphocytes
      • Condensed chromatin and a visible nucleolus
      • Round nucleus
      • Slightly basophilic cytoplasm
      • Cytoplasmic protrusion
    • Small cell variant
      • Small tumor cells with condensed chromatin
      • Small nucleolus visible by electron microscopy
    • Cerebriform (Sézary cell-like) variant
      • Irregular nuclear outline
      • Similar to cerebriform nucleus of Sézary cells seen in mycosis fungoides

Electrocardiogram

There are no ECG findings associated with T-cell prolymphocytic leukemia.

X-ray

There are no x-ray findings associated with T-cell prolymphocytic leukemia. However, an x-ray may be helpful in the diagnosis of complications of T-cell prolymphocytic leukemia, which include pleural effusion and lung involvement.

Echocardiography or Ultrasound

There are no echocardiography findings associated with T-cell prolymphocytic leukemia.

Ultrasound may be helpful in the diagnosis of T-cell prolymphocytic leukemia. Findings on an ultrasound suggestive of/diagnostic of T-cell prolymphocytic leukemia include hepatomegaly and splenomegaly.

CT scan

CT scan may be helpful in the diagnosis of T-cell prolymphocytic leukemia. Findings on an CT scan suggestive of/diagnostic of T-cell prolymphocytic leukemia include hepatomegaly and splenomegaly.

MRI

There are no MRI findings associated with T-cell prolymphocytic leukemia.

Other Imaging Findings

There are no specific imaging findings associated with T-cell prolymphocytic leukemia.[3]

Other Diagnostic Studies

Flow cytometry and immunohistopathology must be done to diagnose T-cell prolymphocytic leukemia.

Treatment

Medical Therapy

  • The mainstay of therapy for T-cell prolymphocytic leukemia, include:[3]
  • T-cell prolymphocytic leukemia is often resistant to therapy.

Surgery

  • Autologous and allogeneic stem cell transplants is the mainstay of therapy for patients who achieve remission.

Primary Prevention

  • There are no established measures for the primary prevention of T-cell prolymphocytic leukemia.

Secondary Prevention

  • There are no established measures for the secondary prevention of T-cell prolymphocytic leukemia.

References

  1. Catovsky D, Galetto J, Okos A, Galton DA, Wiltshaw E, Stathopoulos G (August 1973). "Prolymphocytic leukaemia of B and T cell type". Lancet. 2 (7823): 232–4. PMID 4124423.
  2. Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC (September 1994). "A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group". Blood. 84 (5): 1361–92. PMID 8068936.
  3. 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 Graham RL, Cooper B, Krause JR (2013). "T-cell prolymphocytic leukemia". Proc (Bayl Univ Med Cent). 26 (1): 19–21. PMC 3523759. PMID 23382603.

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