Hepatosplenic T cell lymphoma
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- Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Jogeet Singh Sekhon, M.D. [2]
Synonyms and Keywords: Hepatosplenic γδ T-cell lymphoma, Hepatosplenic gamma delta T-cell lymphoma, HSTCL
Synonyms and keywords:
Overview
Hepatosplenic t cell lymphoma is a rare type of non Hodgkins lymphoma that occurs in states of immunosupression such as post organ transplant and treatment of inflammatory bowel disease. Hepatosplenic T cell lymphoma was discovered by Farcet et al in 1990. It is also known as ‘gamma-delta hepatosplenic T-cell lymphoma. The lymphoma is characterized by malignant T-cell proliferation in the sinusoids of the liver, sinuses and red pulp of the spleen, and sinuses of the bone marrow. The incidence of hepatosplenic t cell lymphoma is 0.3 per 100000 individuals per year. If left untreated, patients can develop liver failure, pancytopenia or spleen rupture. Biopsy of the tumor is the gold standard diagnostic test for diagnosing hepatosplenic t cell lymphoma. Chemotherapy including CHOP is the mainstay of the treatment alongwith bone marrow transplant and radiation therapy.
Historical Perspective
Hepatosplenic T cell lymphoma was discovered by Farcet et al in 1990.
Classification
There is no established system for the classification of hepatosplenic t cell lymphoma.
Pathophysiology
- Hepatosplenic T-cell lymphoma is a peripheral T-cell lymphoma, a type of non Hodgkin's lymphoma[1].
- It is also known as ‘gamma-delta hepatosplenic T-cell lymphoma[2].
- It usually occurs in young men with history of immunosuppression including solid organ transplantation[3].
- Patients with inflammatory bowel disease receiving immunosuppressants and anti-tumor necrosis factor-α agent are also at risk for developing hepatosplenic T-cell lymphoma.
- The T-cell receptor consists of either a gamma delta or aplha beta entity on their cell surface which are a part of the innate immune system[4][5].
- Gamma delta T cells represent the first line of defense against bacterial peptides, such as heat-shock proteins.
- Gamma delta T cells are CD4 and CD8 negative, but CD56 positive which is NK cell marker.
- Gamma delta cells respond to a stimuli and are responsible for lymphokine production and proliferation.
- Gamma delta cells are predominantly located in the spleen, liver sinusoids and intestinal epithelium.
- 75 % of the cases are of gamma delta phenotype and the rest are apha beta phenotype.
- Chronic antigen stimulation in states of immunosuppression is responsible for the development of the lymphoma.
- Isochromosome of the long arm of chromosome 7 is a genetic abnormality described in hepatosplenic t cell lymphoma. It could also be in association with trisomy 8 and a loss of a sex chromosome.
- Mutations in SETD2, INO80, TET3 and STAT5B occur exclusively in hepatosplenic t cell lymphoma as compared to other T and B cell lymphoma types.
- The lymphoma is characterized by malignant T-cell proliferation in the sinusoids of the liver, sinuses and red pulp of the spleen, and sinuses of the bone marrow.
- Splenic involvement is characterized by diffuse involvement of the red pulp with small-to-medium-sized atypical lymphocytes.
- The atypical lymphocytes are present within the cords and sinuses of the red pulp.
- There occurs a complete loss of the white pulp.
- The liver also shows sinusoidal infiltration by neoplastic lymphoid cells.
- The bone marrow is characterized by neoplastic cells in the sinusoids.
- Bone marrow infiltration results in pancytopenia.
- The lymphoma cells are typically CD2+, CD3+, CD4−, CD5−, CD7+, CD8− CD42+, CD52+, CD76+, CD82+ with either gamma-delta or alpha-beta T-cell phenotypic receptor expression.
- It manifests as hepatosplenomegaly without peripheral lymphadenopathy.
- Pancytopenia and abnormal liver functions are the laboratory findings.
- Histology and immunohistochemistry of the tumor biopsy shows portal and sinusoidal infiltration by atypical small-to-medium sized lymphocytes with hyperchromatic nuclei and low mitotic activity.
Causes
Common causes of hepatosplenic t cell lymphoma are[6][7]:
- Inflammatory bowel disease
- Organ transplant patients (reciever)
- Immunosuppressive medications
- Thiopurines
- Infliximab
- Cyclophosphamide
- Vincristine
- Doxorubicin
Differentiating hepatosplenic t cell lymphoma from Other Diseases
Epidemiology and Demographics
- The incidence of hepatosplenic t cell lymphoma is 0.3 per 100000 individuals per year.
- It occurs in younger group of patients, most cases falling in 20-40 years of age group.
- Men are more affected than the females.
Risk Factors
Common risk factors include:
- Autoimmune diseases
- Patients on immunosuppresant medications.
- Patients on chemotherapy.
- Inflammatory bowel disease
- Organ transplant patients.
Screening
There is insufficient evidence to recommend routine screening for hepatosplenic t cell lymphoma.
Natural History, Complications, and Prognosis
Natural history
- Patients have a history of immunosupression such as inflammatory bowel disease under treatment or organ transplant[8].
- The mean age group is 35 years and most of the patients are males.
- Initial symptoms are fever, weight loss, night sweats and then progress to more severe symptoms depending on the organ involvement but there is no lymphadenopathy.
- Patients also present with symptoms of liver, spleen and bone marrow dysfunction.
- If left untreated, patients can develop liver failure, pancytopenia or spleen rupture.
Complications
- Hepatomegaly
- Hepatic failure
- Portal vein thrombosis
- Splenomegaly
- Splenic infarction
- Spleen rupture
- Splenic vein thrombosis
- Anemia
- Thrombocytopenia
- Neutropenia
- Neurological dysfunction if metastasizes to brain.
- Intestinal perforation
- Intestinal obstruction
Prognosis
- The prognosis is very poor, with patients dying within 2-3 years of diagnosis even after recieving treatment[9].
Diagnosis
Diagnostic Study of Choice
- Biopsy of the tumor is the gold standard diagnostic test for diagnosing hepatosplenic t cell lymphoma[10].
- CT scan and PET scan are used to assess the spread of the lymphoma.
Symptoms
The most common symtoms are[11]:
- Fever
- Weight loss
- Night sweats
- Pain abdomen
- Jaundice
- Fatigue
- Recurrent infections
- Bleeding
Physical Examination
Temperature
- Fever is often present
Skin
Thorax
- Pleural effusion
- Chest tenderness
Abdomen
- Splenomegaly
- Hepatomegaly
- Ascites
- Abdomen tenderness
Extremities
- Bone tenderness
Laboratory Findings
- Biopsy of the tumor:
- Histology - small-to intermediate sized T lymphocytes infiltrate the sinusoids of the liver and the splenic red pulp.
- Flow cytometry and immunophenotyping - The lymphoma cells are typically CD2+, CD3+, CD4−, CD5−, CD7+, CD8− CD42+, CD52+, CD76+, CD82+ with either gamma-delta or alpha-beta T-cell phenotypic receptor expression[12].
- Karyotyping - Isochromosome of the long arm of chromosome 7 is a genetic abnormality described in hepatosplenic t cell lymphoma. It could also be in association with trisomy 8 and a loss of a sex chromosome[13].
- Bone marrow biopsy; The bone marrow is characterized by neoplastic cells in the sinusoids.
- Complete blood count; Pancytopenia
- Liver function tests: Deranged LFT
- Elevated transaminases
- Hyperbilirubinemia
- Hypoproteinemia
- Elevated alkaline phosphatase
- Elevated PT/INR
Electrocardiogram
There are no ECG findings associated with hepatosplenic t cell lymphoma.
X-ray
There are no x-ray findings associated with hepatosplenic t cell lymphoma but pleural effusion might be present.
Echocardiography or Ultrasound
- There are no echocardiography findings associated with hepatosplenic t cell lymphoma.
- On ultrasound of abdomen:
CT scan
Tumor mass can be seen in liver or spleen or both.
MRI
Tumor mass can be seen in liver or spleen or both.
Other Imaging Findings
PET scan: On PET scan, tumor mass can be seen in liver or spleen or if it has metastatsized to any other organ.
Treatment
Medical Therapy
- Induction therapy[14]
- Consolidation therapy
- Radiation therapy
- Allogenic bone marrow transplant[15]
- Autologous bone marrow transplant
- Additional medications given during chemotherapy
Surgery
Surgical intervention is not recommended for the management of hepaosplenic t cell lymphoma.
Primary Prevention
There are no established measures for the primary prevention of hepatosplenic t cell lymphoma.
Secondary Prevention
There are no established measures for the secondary prevention of hepatosplenic t cell lymphoma.
References
- ↑ Armitage JO (2017). "The aggressive peripheral T-cell lymphomas: 2017". Am J Hematol. 92 (7): 706–715. doi:10.1002/ajh.24791. PMID 28516671.
- ↑ Brandt PH, Rahmat LT, Ali SS (2019). "A rare case of hepatosplenic gamma-delta T-cell lymphoma and secondary hemophagocytic lymphohistiocytosis". Clin Case Rep. 7 (1): 164–169. doi:10.1002/ccr3.1924. PMC 6333078. PMID 30656034.
- ↑ Choi Y, Jeon SY, Yoo WH (2018). "Hepatosplenic T-Cell Lymphoma Arising in a Patient Treated With Tumor Necrosis Factor-α Inhibitors for Ankylosing Spondylitis". J Clin Rheumatol. doi:10.1097/RHU.0000000000000805. PMID 29933321.
- ↑ Gowda L, Foss F (2019). "Hepatosplenic T-Cell Lymphomas". Cancer Treat Res. 176: 185–193. doi:10.1007/978-3-319-99716-2_9. PMID 30596219.
- ↑ Gaulard P, Bourquelot P, Kanavaros P, Haioun C, Le Couedic JP, Divine M; et al. (1990). "Expression of the alpha/beta and gamma/delta T-cell receptors in 57 cases of peripheral T-cell lymphomas. Identification of a subset of gamma/delta T-cell lymphomas". Am J Pathol. 137 (3): 617–28. PMC 1877506. PMID 1698028.
- ↑ Yabe M, Miranda RN, Medeiros LJ (2018). "Hepatosplenic T-cell Lymphoma: a review of clinicopathologic features, pathogenesis, and prognostic factors". Hum Pathol. 74: 5–16. doi:10.1016/j.humpath.2018.01.005. PMID 29337025.
- ↑ Gallamini A, Stelitano C, Calvi R, Bellei M, Mattei D, Vitolo U; et al. (2004). "Peripheral T-cell lymphoma unspecified (PTCL-U): a new prognostic model from a retrospective multicentric clinical study". Blood. 103 (7): 2474–9. doi:10.1182/blood-2003-09-3080. PMID 14645001.
- ↑ Falchook GS, Vega F, Dang NH, Samaniego F, Rodriguez MA, Champlin RE; et al. (2009). "Hepatosplenic gamma-delta T-cell lymphoma: clinicopathological features and treatment". Ann Oncol. 20 (6): 1080–5. doi:10.1093/annonc/mdn751. PMC 4092251. PMID 19237479.
- ↑ Yabe M, Medeiros LJ, Tang G, Wang SA, Ahmed S, Nieto Y; et al. (2016). "Prognostic Factors of Hepatosplenic T-cell Lymphoma: Clinicopathologic Study of 28 Cases". Am J Surg Pathol. 40 (5): 676–88. doi:10.1097/PAS.0000000000000614. PMID 26872013.
- ↑ International Non-Hodgkin's Lymphoma Prognostic Factors Project (1993). "A predictive model for aggressive non-Hodgkin's lymphoma". N Engl J Med. 329 (14): 987–94. doi:10.1056/NEJM199309303291402. PMID 8141877.
- ↑ Saito T, Matsuno Y, Tanosaki R, Watanabe T, Kobayashi Y, Tobinai K (2002). "Gamma delta T-cell neoplasms: a clinicopathological study of 11 cases". Ann Oncol. 13 (11): 1792–8. PMID 12419753.
- ↑ Boulland ML, Kanavaros P, Wechsler J, Casiraghi O, Gaulard P (1997). "Cytotoxic protein expression in natural killer cell lymphomas and in alpha beta and gamma delta peripheral T-cell lymphomas". J Pathol. 183 (4): 432–9. doi:10.1002/(SICI)1096-9896(199712)183:4<432::AID-PATH942>3.0.CO;2-4. PMID 9496260.
- ↑ Jonveaux P, Daniel MT, Martel V, Maarek O, Berger R (1996). "Isochromosome 7q and trisomy 8 are consistent primary, non-random chromosomal abnormalities associated with hepatosplenic T gamma/delta lymphoma". Leukemia. 10 (9): 1453–5. PMID 8751461.
- ↑ Simon A, Peoch M, Casassus P, Deconinck E, Colombat P, Desablens B; et al. (2010). "Upfront VIP-reinforced-ABVD (VIP-rABVD) is not superior to CHOP/21 in newly diagnosed peripheral T cell lymphoma. Results of the randomized phase III trial GOELAMS-LTP95". Br J Haematol. 151 (2): 159–66. doi:10.1111/j.1365-2141.2010.08329.x. PMID 20738307.
- ↑ Han X, Zhang W, Zhou D, Ruan J, Duan M, Zhu T; et al. (2017). "Autologous stem cell transplantation as frontline strategy for peripheral T-cell lymphoma: A single-centre experience". J Int Med Res. 45 (1): 290–302. doi:10.1177/0300060516676725. PMC 5536587. PMID 28222648.