Hepatosplenic T-cell lymphoma


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Synonyms

Hepatosplenic γδ T-cell lymphoma

ICD-O Code

9716/3

Definition

Hepatosplenic T-cell lymphoma is a systemic neoplasm comprised of medium-sized cytotoxic T-cells that show a significant sinusoidal infiltration in the liver, spleen, and bone marrow.

Epidemiology

This lymphoma is rare, comprising less than 5% of all cases, and is most common in young adults and adolescents. A distinct male gender preference has been described.[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=8943863&query_hl=7&itool=pubmed_ExternalLink] Cooke CB, Krenacs L, Stetler-Stevenson M, Greiner TC, Raffeld M, Kingma DW, Abruzzo L, Frantz C, Kaviani M, Jaffe ES. "Hepatosplenic T-cell lymphoma: a distinct clinicopathologic entity of cytotoxic gamma delta T-cell origin." Blood. 1996 Dec 1;88(11):4265-74. PMID: 8943863

Clinical Features

Etiology

The cell of origin for this disease is an immature cytotoxic T-cell clonally expressing the γδ T-cell receptor. This disease is seen more often in immunosuppressed solid organ transplant recipients, an association that has led to the hypothesis that long-term immune stimulation in the setting of immunosuppression is the causative agent. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=8085554&query_hl=10&itool=pubmed_ExternalLink] Ross CW, Schnitzer B, Sheldon S, Braun DK, Hanson CA. "Gamma/delta T-cell posttransplantation lymphoproliferative disorder primarily in the spleen." Am J Clin Pathol. 1994 Sep;102(3):310-5. PMID: 8085554[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11224598&query_hl=12&itool=pubmed_ExternalLink] Macon WR, Levy NB, Kurtin PJ, Salhany KE, Elkhalifa MY, Casey TT, Craig FE, Vnencak-Jones CL, Gulley ML, Park JP, Cousar JB. "Hepatosplenic alphabeta T-cell lymphomas: a report of 14 cases and comparison with hepatosplenic gammadelta T-cell lymphomas." Am J Surg Pathol. 2001 Mar;25(3):285-96. PMID: 11224598

Clinical Presentation

The typical clinical finding in a patient with hepatosplenic T-cell lymphoma is hepatosplenomegaly.[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=2140703&query_hl=14&itool=pubmed_ExternalLink] Farcet JP, Gaulard P, Marolleau JP, Le Couedic JP, Henni T, Gourdin MF, Divine M, Haioun C, Zafrani S, Goossens M, et al. "Hepatosplenic T-cell lymphoma: sinusal/sinusoidal localization of malignant cells expressing the T-cell receptor gamma delta." Blood. 1990 Jun 1;75(11):2213-9. PMID: 2140703

Laboratory Findings

The constellation of thrombocytopenia, anemia, and leukocytosis is common in patients with hepatosplenic T-cell lymphoma. The discovery of neoplastic cells in peripheral blood is often a finding late in the clinical course.

Sites of Involvement

The spleen and liver are always involved, with bone marrow involvement frequently present. Nodal involvement is exceedingly rare.[http://www.iarc.fr/WHO-BlueBooks/BBwebsite/bb3.html] Jaffe E.S., Harris N.L., Stein H., Vardiman J.W. (eds): World Health Organization Classification of Tumors. Pathology and Genetics of Tumours of Haemopoietic and Lymphoid Tissues. IARC Press: Lyon 2001

Morphology

The neoplastic cells in this disorder show a monotonous appearance, with a small amount of cytoplasm and inconspicuous nucleoli.

Spleen and liver

This disease shows a distinct sinusoidal pattern of infiltration which spares the splenic white pulp and hepatic portal triads.

Bone marrow

While the bone marrow is commonly involved, the detection of the neoplastic infiltrate may be difficult due to diffuse, interstitial pattern. Immunohistochemistry can aid in the detection of this lymphoma.

Peripheral blood

Cells of a similar morphology observed in solid organs are observed in peripheral blood.

Molecular Findings

Immunophenotype

The immunophenotype for hepatosplenic T-cell lymphoma is a post-thymic, immature T-cell.

Genetic Findings

Clonal rearrangement of the γ gene of the T-cell receptor is the hallmark of this disease. A few cases have shown rearrangement of the T-cell receptor β gene. Isochromosome 7q has been observed in all cases described so far, sometimes in conjunction with other chromosomal abnormalities such as trisomy 8.[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=9264394&query_hl=16&itool=pubmed_ExternalLink] Alonsozana EL, Stamberg J, Kumar D, Jaffe ES, Medeiros LJ, Frantz C, Schiffer CA, O'Connell BA, Kerman S, Stass SA, Abruzzo LV. "Isochromosome 7q: the primary cytogenetic abnormality in hepatosplenic gammadelta T cell lymphoma." Leukemia. 1997 Aug;11(8):1367-72. PMID: 9264394


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