31. T and NK cell lymphomas

From greek.doctor

Introduction

T/NK cell lymphomas are a rare type of non-Hodgkin lymphomas, accounting for only 10-20% of cases. They are generally more aggressive than the B-cell non-Hodgkin lymphomas. Most of these lymphomas originate from T-cells, while only a few originate from NK-cells.

Several subtypes exist:

  • Precursor T-cell lymphomas
    • Precursor T-cell lymphoblastic leukaemia/lymphoma
  • Cutaneous T-cell lymphomas
    • Mycosis fungoides
    • Sézary syndrome
  • Nodal T-cell lymphomas
    • Peripheral T-cell lymphoma not otherwise specified
    • Anaplastic large cell lymphoma
    • Angioimmunoblastic T-cell lymphoma
  • Extranodal T-cell lymphoma
    • Extranodal NK/T cell lymphoma, nasal type
    • Enteropathy-associated T-cell lymphoma
    • Hepatosplenic T-cell lymphoma
  • Leukaemic T-cell lymphomas
    • Adult T-cell leukaemia
    • Large granular lymphocyte leukaemia

As you can see are there many types, but we’ll only discuss the most important ones.

CD3 and CD5 are surface markers that are present on many T-cell lymphomas.

Precursor T-cell lymphomas

Acute lymphoblastic leukaemia/lymphoma (ALL) is a type of neoplasm that can cause acute leukaemia or acute lymphoma. The tumor is composed of lymphocyte precursors. Two subtypes exist, according to which cell type is originates from:

  • Precursor B-cell lymphoblastic leukaemia/lymphoma (B-ALL) – originates from B-cell precursors
  • Precursor T-cell lymphoblastic leukaemia/lymphoma (T-ALL) – originates from T-cell precursors

All types of acute leukaemia (B-ALL, T-ALL and acute myeloid leukaemia (AML)) have similar clinical features:

  • Anaemia – due to suppressed bone marrow
  • Thrombocytopaenia – due to suppressed bone marrow
  • Bone pain – due to bone marrow expansion
  • Lymphadenomegaly, splenomegaly, hepatomegaly – due to dissemination of leukaemic cells – mostly in ALL, not in AML

ALL is the most frequent cause of leukaemia in childhood, accounting for 80% of cases. The incidence peaks at 4 years old.

B-ALL usually develops in the bone marrow and manifest as leukaemia, as B-cells mature in the bone marrow. B-ALL is more common that T-ALL.

The t(9;22) translocation of BCR-ABL, also known as the Philadelphia chromosome, is found in many cases of ALL and signifies worse prognosis. A t(12;21) translocation signifies better prognosis. Hyperploidity (presence of abnormal number of chromosomes per cell) is common; it signifies a better prognosis.

B-ALL technically doesn’t belong to this topic, but I included it here to compare B-ALL and T-ALL.

T-ALL usually develops in the thymus and manifest as mediastinal lymphoma, as T-cells mature in the thymus. However, these thymic lymphomas rapidly progress into leukaemia and therefore usually presents similarly as B-ALL, just with a mediastinal mass.

Translocations of the TCR gene (the gene for the T-cell receptor) are involved in T-ALL. NOTCH1 and TALI mutations also common.

Cutaneous T-cell lymphomas

Mycosis fungoides is a chronic, indolent, epidermotropic (only affects the skin) CD4+ cell lymphoma that only occurs in the epidermis. It’s more frequent in elderly men around 60 years. It manifests as a non-specific rash that progresses into a plaque and later to a proper tumor. The tumors tend to be mushroom-shapes, which gives the condition its name. Histology may show so-called Sézary cells infiltrating the epidermis.

Sézary syndrome is an advanced stage of mycosis fungoides. At this stage has the cancer spread to lymph nodes, and there may be Sézary cells in the peripheral blood (leukaemia).

Nodal T-cell lymphomas

Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) is the most common subtype of nodal T-cell lymphomas. Its name comes from the fact that most nodal T-cell lymphomas are unclassifiable; if a nodal T-cell lymphoma doesn’t belong in any of the other subgroups is it considered a not otherwise specified type.

PTCL-NOS lymphomas may occur in the spleen, liver, bone marrow, lymph node or as leukaemia.

Anaplastic large cell lymphoma is a type of nodal T-cell lymphoma. It commonly involves a mutation in the ALK gene, in which case anti-ALK treatments are effective. ALK negative tumors also exist. As these lymphoma cells are anaplastic, they have a very bad prognosis. Extranodal involvement is common and the tumour is CD30+.

Angioimmunoblastic T-cell lymphoma derives from follicular CD4+ T-cells. It’s one of the most common T-cell lymphomas. It’s more common in elderly. There is disseminated lymphadenomegaly, and B symptoms are common.

Extranodal T-cell lymphomas

Extranodal NK/T cell lymphoma, nasal type (ENKL) can develop from NK cells (more common) or T-cells. As the name suggests the lymphoma commonly arises in the nose. This mass may perforate the septum, block the nose or cause epistaxis. It’s associated with EBV and usually presents with B symptoms.

Other potential causes for septum perforation are cocaine abuse or granulomatosis with polyangiitis (Wegener’s)

Enteropathy associated T-cell lymphoma develops intraepithelially, commonly in the GI-tract, where it is associated with coeliac disease. It may cause ulceration and perforation.

Hepatosplenic T-cell lymphoma originates from γδ T-cells and not from αβ T-cells (the normal type of T-cell). As the name suggests it commonly affects the liver and spleen and causes hepatosplenomegaly.

Leukaemic T-cell lymphomas

Adult T-cell leukaemia is a highly aggressive cancer that is caused by infection by HTLV-1. This cancer is endemic in the Caribbean and southern Japan. It causes leukaemia.

Large granular lymphocyte leukaemia is a chronic, indolent neoplasm characterised by the presence of large granular lymphocytes in the blood. It mostly affects elderly.