| T-cell-prolymphocytic leukemia |
| Classification and external resources |
Prolymphocyte |
| ICD-O: |
M9834/3 |
| MeSH |
D015461 |
T-cell-prolymphocytic leukemia (T-PLL) is a mature T-cell leukemia with aggressive behavior and predilection for blood, bone marrow, lymph nodes, liver, spleen, and skin involvement.[1] T-PLL is a very rare leukemia, primarily affecting adults over the age of 30. It represents 2% of all small lymphocytic leukemias in adults.[2] Other names include T-cell chronic lymphocytic leukemia, "knobby" type of T-cell leukemia, and T-prolymphocytic leukemia/T-cell lymphocytic leukemia.[1]
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Contents
- 1 Etiology
- 2 Signs and symptoms
- 3 Morphology
- 4 Molecular findings
- 4.1 Immunophenotype
- 4.2 Genetic findings
- 5 Treatment
- 6 Prognosis
- 7 Epidemiology
- 8 References
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Etiology
It is postulated that the originating cell line for this disease is a mature (post-thymic) T-cell.[1]
Signs and symptoms
Patients typically have systemic disease at presentation, including hepatosplenomegaly, generalized lymphadenopathy, and skin infiltrates.[1]
Due to the systemic nature of this disease, leukemic cells can be found in peripheral blood, lymph nodes, bone marrow, spleen, liver, skin.[1] A high lymphocyte count (> 100 x 109/L)along with anemia and thrombocytopenia are common findings. HTLV-1 serologies are negative, and serum immunoglobins are within normal limits with no paraproteins present.[1]
Morphology
In the peripheral blood, T-PLL consists of medium-sized lymphocytes with single nucleoli and basophilic cytoplasm with occasional blebs or projections. The nuclei are usually round to oval in shape, with occasional patients having cells with a more irregular nuclear outline that is similar to the cerebriform nuclear shape seen in Sézary syndrome.[3] A small cell variant comprises 20% of all T-PLL cases, and the Sézary cell-like (cerebriform) variant is seen in 5% of cases.[3]
Marrow involvement is typically diffuse with morphology similar to what is observed in peripheral blood.[1] In the spleen, the leukemic cell infiltrate both the red pulp and white pulp, and lymph node involvement is typically diffuse through the paracortex.[1] Skin infiltrates are seen in 20% of patients, and the infiltrates are usually dense and confined to the dermis and around the skin appendages.[2]
Molecular findings
Immunophenotype
T-PLL has the immunophenotype of a mature (post-thymic) T-lymphocyte, and the neoplastic cells are typically positive for pan-T antigens CD2, CD3, and CD7 and negative for TdT and CD1a. The immunophenotype CD4+/CD8- is present in 60% of cases, the CD4+/CD8+ immunophenotype is present in 25%, and the CD4-/CD8+ immunophenotype is present in 15% of cases.[2]
Genetic findings
Clonal TCR gene rearrangements for the γ and δ chains are typically found. The most frequent chromosomal abnormality is the inversion of chromosome 14, specifically inv 14(q11;q32). This is found in 80% of cases, while 10% of cases show a reciprocal translocation of chromosome 14 (t(14;14)(q11;q32)).[4]
[5] Also, abnormalities of chromosome 8 are seen approximately 75% of patients, including idic (8p11), t(8;8)(p11-12;q12), and trisomy 8. [6]
Treatment
Most patients with T-cell prolymphocytic leukemia require immediate treatment.[7]
T-cell prolymphocytic leukemia is difficult to treat, and it does not respond to most available chemotherapeutic drugs.[7] Many different treatments have been attempted, with limited success in certain patients: purine analogues (pentostatin, fludarabine, cladribine), chlorambucil, and various forms of combination chemotherapy regimens, including cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), cyclophosphamide, vincristine, prednisone (COP), and vincristine, doxorubicin, prednisone, etoposide, cyclophosphamide, bleomycin (VAPEC-B).
Alemtuzumab (Campath), an anti-CD52 monoclonal antibody that attacks white blood cells, has been used in treatment with greater success than previous options.[7] In one study of previously treated people with T-PLL, people who had a complete response to alemtuzumab survived a median of 16 months after treatment.[7]
Some patients who successfully respond to treatment also undergo stem cell transplantation to consolidate the response.[7]
Prognosis
T-PLL is an aggressive disease, and patients are not expected to live normal lifespans. Before the recent introduction of better treatments, such as alemtuzumab, the median survival time was 7.5 months after diagnosis.[7] More recently, some patients have survived five years and more, although the median survival is still low.
Epidemiology
About four men are diagnosed with this disease for every three women.[8] Despite its overall rarity, it is also the most common type of mature T cell leukemia.[9]
References
- ^ a b c d e f g h Elaine Sarkin Jaffe, Nancy Lee Harris, World Health Organization, International Agency for Research on Cancer, Harald Stein, J.W. Vardiman (2001). Pathology and genetics of tumours of haematopoietic and lymphoid tissues. World Health Organization Classification of Tumors. 3. Lyon: IARC Press. ISBN 92-832-2411-6. http://books.google.com/?id=XSKqcy7TUZUC.
- ^ a b c Matutes E, Brito-Babapulle V, Swansbury J, et al. (1991). "Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia". Blood 78 (12): 3269–74. PMID 1742486.
- ^ a b Matutes E, Garcia Talavera J, O'Brien M, Catovsky D (September 1986). "The morphological spectrum of T-prolymphocytic leukaemia". Br. J. Haematol. 64 (1): 111–24. doi:10.1111/j.1365-2141.1986.tb07579.x. PMID 3489482.
- ^ Brito-Babapulle V, Catovsky D (1991). "Inversions and tandem translocations involving chromosome 14q11 and 14q32 in T-prolymphocytic leukemia and T-cell leukemias in patients with ataxia telangiectasia". Cancer Genet. Cytogenet. 55 (1): 1–9. doi:10.1016/0165-4608(91)90228-M. PMID 1913594.
- ^ Maljaei SH, Brito-Babapulle V, Hiorns LR, Catovsky D (1998). "Abnormalities of chromosomes 8, 11, 14, and X in T-prolymphocytic leukemia studied by fluorescence in situ hybridization". Cancer Genet. Cytogenet. 103 (2): 110–6. doi:10.1016/S0165-4608(97)00410-X. PMID 9614908.
- ^ Sorour A, Brito-Babapulle V, Smedley D, Yuille M, Catovsky D (2000). "Unusual breakpoint distribution of 8p abnormalities in T-prolymphocytic leukemia: a study with YACS mapping to 8p11-p12". Cancer Genet. Cytogenet. 121 (2): 128–32. doi:10.1016/S0165-4608(00)00239-9. PMID 11063795.
- ^ a b c d e f Dearden CE, Matutes E, Cazin B, et al. (September 2001). "High remission rate in T-cell prolymphocytic leukemia with CAMPATH-1H". Blood 98 (6): 1721–6. doi:10.1182/blood.V98.6.1721. PMID 11535503. http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=11535503.
- ^ Matutes Estella (1998). "T-cell prolymphocytic leukemia, a rare variant of mature post-thymic T-cell leukemias, has distinct clinical and laboratory characteristics and a poor prognosis". Cancer Control Journal 5 (1). http://www.moffitt.org/moffittapps/ccj/v5n1/article2.html.
- ^ Valbuena JR, Herling M, Admirand JH, Padula A, Jones D, Medeiros LJ (March 2005). "T-cell prolymphocytic leukemia involving extramedullary sites". Am. J. Clin. Pathol. 123 (3): 456–64. doi:10.1309/93P4-2RNG-5XBG-3KBE. PMID 15716243. http://www.medscape.com/viewarticle/501092.
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Hematological malignancy/leukemia histology (ICD-O 9590–9989, C81–C96, 200–208)
Lymphoid/Lymphoproliferative, Lymphomas/Lymphoid leukemias (9590–9739, 9800–9839)
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B cell
(lymphoma,
leukemia)
(most CD19
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By development/
marker
|
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TdT+
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- ALL (Precursor B acute lymphoblastic leukemia/lymphoma)
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CD5+
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mantle zone (Mantle cell)
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CD22+
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- Prolymphocytic
- CD11c+ (Hairy cell leukemia)
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CD79a+
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- germinal center/follicular B cell (Follicular
- Burkitt's
- GCB DLBCL
- Primary cutaneous follicular lymphoma)
marginal zone/marginal-zone B cell (Splenic marginal zone
- MALT
- Nodal marginal zone
- Primary cutaneous marginal zone lymphoma)
|
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RS (CD15+, CD30+)
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- Classic Hodgkin's lymphoma (Nodular sclerosis)
- CD20+ (Nodular lymphocyte predominant Hodgkin's lymphoma)
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PCDs/PP
(CD38+/CD138+)
|
- see immunoproliferative immunoglobulin disorders
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|
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By infection
|
- KSHV (Primary effusion)
- EBV (Lymphomatoid granulomatosis
- Post-transplant lymphoproliferative disorder)
- HIV (AIDS-related lymphoma)
- Helicobacter pylori (MALT lymphoma)
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|
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Cutaneous
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- Diffuse large B-cell lymphoma
- Intravascular large B-cell lymphoma
- Primary cutaneous marginal zone lymphoma
- Primary cutaneous immunocytoma
- Plasmacytoma
- Plasmacytosis
- Primary cutaneous follicular lymphoma
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T/NK
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T cell
(lymphoma,
leukemia)
(most CD3
|
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By development/
marker
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- TdT+: ALL (Precursor T acute lymphoblastic leukemia/lymphoma)
- prolymphocyte (Prolymphocytic)
- CD30+ (Anaplastic large-cell lymphoma
- Lymphomatoid papulosis type A)
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Cutaneous
|
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MF+variants
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- indolent: Mycosis fungoides
- Pagetoid reticulosis
- Granulomatous slack skin
aggressive: Sézary's disease
- Adult T-cell leukemia/lymphoma
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|
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Non-MF
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- CD30-: Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma
- Pleomorphic T-cell lymphoma
- Lymphomatoid papulosis type B
CD30+: CD30+ cutaneous T-cell lymphoma
- Secondary cutaneous CD30+ large cell lymphoma
- Lymphomatoid papulosis type A
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Other peripheral
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- Hepatosplenic
- Angioimmunoblastic
- Enteropathy-associated T-cell lymphoma
- Peripheral T-cell lymphoma-Not-Otherwise-Specified (Lennert lymphoma)
- Subcutaneous T-cell lymphoma
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By infection
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- HTLV-1 (Adult T-cell leukemia/lymphoma)
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NK cell/
(most CD56)
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- Aggressive NK-cell leukemia
- Blastic NK cell lymphoma
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T or NK
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- EBV (Extranodal NK-T-cell lymphoma/Angiocentric lymphoma)
- Large granular lymphocytic leukemia
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Lymphoid+myeloid
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- Acute biphenotypic leukaemia
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Lymphocytosis
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- Lymphoproliferative disorders (X-linked lymphoproliferative disease
- Autoimmune lymphoproliferative syndrome)
- Leukemoid reaction
- Diffuse infiltrative lymphocytosis syndrome
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| Cutaneous lymphoid hyperplasia |
- Cutaneous lymphoid hyperplasia with bandlike and perivascular patterns
- Cutaneous lymphoid hyperplasia with nodular pattern
- Jessner lymphocytic infiltrate of the skin
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cell/phys/auag/auab/comp, igrc
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