Sandbox: T-cell prolymphocytic leukemia
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
- T-cell prolymphocytic leukemia was first described by Catovsky in 1973.

# Classification
- There is no classification system for T-cell prolymphocytic leukemia.

# 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  and  chains.
- Mutations of chromosome 8 are seen approximately 75% of patients.
- On gross pathology, characteristic findings of T-cell prolymphocytic leukemia, include:
- No remarkable findings
- On microscopic histopathological analysis, characteristic findings of T-cell prolymphocytic leukemia, include:
- The immunophenotype CD4+/CD8- (present in 60% of cases)
- The immunophenotype  CD4+/CD8+ (present in 25%)
- The immunophenotype  CD4-/CD8+ (15% of cases)
Pan-T antigens
- CD2 negative
- CD3 negative
- CD7 negative
- TdT positive
- CD1a  positive

# Causes
- Common causes of T-cell prolymphocytic leukemia, include:
- Genetic mutations (e.g. Trisomy 8, chromosomal abnormalities)

# Differentiating T-cell Prolymphocytic Leukemia from Other Diseases
- T-cell prolymphocytic leukemia must be differentiated from other diseases that cause lymphadenopathy, hepatomegaly, and fever, such as:
- Sezary syndrome
- Cutaneous T cell lymphoma
- Angioimmunoblastic T cell lymphoma
- B-cell prolymphocytic leukemia

# Epidemiology and Demographics
- T-cell prolymphocytic leukemia is very rare, and it represents 2% of all small lymphocytic leukemias in adults.

## Age
- T-cell prolymphocytic leukemia is more commonly observed among patients aged between 30 to 40 years old.
- T-cell prolymphocytic leukemia is more commonly observed among young adults.

## Gender
- Males are slightly more affected with are more commonly affected with T-cell prolymphocytic leukemia than females.

## Race
- 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.

# 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:
- Graft-versus-host disease (allogeneic transplant)
- Infections
- Bleeding
- Prognosis is generally poor, and the median survival time of patients with T-cell prolymphocytic leukemia is approximately 7 months.

# Diagnosis

## Symptoms
- Symptoms of T-cell prolymphocytic leukemia may include the following:
- Fever
- Weight loss
- Night sweats

## Physical Examination
- Patients with T-cell prolymphocytic leukemia usually appear pale and malnourished.
- Physical examination may be remarkable for:
- Hepatomegaly
- Splenomegaly
- Generalized lymphadenopathy
- Skin infiltration
Peripheral Blood Smear
- Medium-sized lymphocytes
- Single nucleoli and basophilic cytoplasm
- The nuclei are usually round to oval in shape,
- Irregular nuclear outline that is similar to the cerebriform nuclear shape seen in Sezary syndrome.
- A small cell variant comprises 20% of all T-PLL cases, and the Sezary cell-like (cerebriform) variant is seen in 5% of cases

## Laboratory Findings
- Laboratory findings consistent with the diagnosis of T-cell prolymphocytic leukemia, include:
- High lymphocyte count (> 100 x 109/L)
- Anemia
- Thrombocytopenia
- Negative HTLV-1 serology

## Imaging Findings
- There are no specific imaging findings associated with T-cell prolymphocytic leukemia.

# Treatment

## Medical Therapy
- The mainstay of therapy for T-cell prolymphocytic leukemia, include:
- Alemtuzumab (anti-CD52)
- 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.

## Prevention
- There are no primary preventive measures available for T-cell prolymphocytic leukemia.