Primary effusion lymphoma

Primary effusion lymphoma
SpecialtyHematology, oncology, virology
CausesChronic viral infection with KSHV/HHV8 or HIV
PrognosisGuarded

Primary effusion lymphoma (PEL) is classified as a diffuse large B cell lymphoma. It is a rare malignancy of plasmablastic cells that occurs in individuals that are infected with the Kaposi's sarcoma-associated herpesvirus (i.e. KSHV/HHV8). Plasmablasts are immature plasma cells, i.e. lymphocytes of the B-cell type that have differentiated into plasmablasts but because of their malignant nature do not differentiate into mature plasma cells but rather proliferate excessively and thereby cause life-threatening disease.[1] In PEL, the proliferating plasmablastoid cells commonly accumulate within body cavities to produce effusions (i.e. accumulations of fluid), primarily in the pleural, pericardial, or peritoneal cavities, without forming a contiguous tumor mass.[2] In rare cases of these cavitary forms of PEL, the effusions develop in joints, the epidural space surrounding the brain and spinal cord, and underneath the capsule (i.e. tightly woven collagen fibers) which forms around breast implants.[1] Less frequently, individuals present with extracavitary primary effusion lymphomas, i.e., solid tumor masses not accompanied by effusions.[3] The extracavitary tumors may develop in lymph nodes, bone, bone marrow, the gastrointestinal tract, skin, spleen, liver, lungs, central nervous system, testes, paranasal sinuses, muscle, and, rarely, inside the vasculature and sinuses of lymph nodes.[1] As their disease progresses, however, individuals with the classical effusion-form of PEL may develop extracavitary tumors and individuals with extracavitary PEL may develop cavitary effusions.[4]

PEL typically occurs in individuals who are immunocompromised, i.e., individuals whose immune system is weakened and therefore less able to fight infectious agents and cancers. This weakening is ascribed to KSHV/HHV8 infection that is commonly further promoted by concurrent human immunodeficiency virus (i.e. HIV) infection, prior organ transplantation,[4] the decline in immunity that develops with aging,[1] and/or cirrhosis of the liver due to hepatitis B or C virus.[5] The plasmacytoid cells in PEL are also commonly infected with the Epstein-Barr virus (i.e. EBV). EBV is a known cause of various Epstein-Barr virus-associated lymphoproliferative diseases including various B-cell lymphomas. However, the role of this virus in the development of PEL is not clear,[4] although some studies suggest that EBV infection cooperates with KSHV/HHV8 infection to promote the development and/or progression of this disease.[3]

Formally, PEL is defined by the World Health Organization, 2016 as a KSHV/HHV8-positive[6] and KSHV/HHV8-driven large B-cell lymphoma. This lymphoma also belongs to a group of lymphoid neoplasms with plasmablastic differentiation that involve malignant plasmablasts but differ from PEL in the types of tissues where they accumulate, the gene abnormalities they carry, and/or the predisposing conditions involved in their development.[1] More than 50, 30, and 60% of all PEL cases, respectively, develop in individuals who already have KSHV/HHV8-positive Kaposi's sarcoma, human herpesvirus 8-associated multicentric Castleman disease,[7] and/or (especially in HIV-positive individuals) evidence of bearing EBV-infected plasmablasts.[2]

Primary effussion lymphoma is an extremely aggressive cancer that is highly resistant to various chemotherapy treatments. It has carried a median survival time of ~5 months,[8] with overall survival rates at 1, 3, and 5 years of only 30, 18, and 17%, respectively. In many cases, however, this high mortality reflects, at least in part, the lethality of its underlying predisposing diseases, particularly HIV/AIDS in HIV-infected individuals. New treatment strategies, including those directed at its underlying predisposing diseases, may improve the prognosis of PEL.[9]

  1. ^ a b c d e Chen BJ, Chuang SS (March 2020). "Lymphoid Neoplasms With Plasmablastic Differentiation: A Comprehensive Review and Diagnostic Approaches". Advances in Anatomic Pathology. 27 (2): 61–74. doi:10.1097/PAP.0000000000000253. PMID 31725418. S2CID 208039484.
  2. ^ a b Korkolopoulou P, Vassilakopoulos T, Milionis V, Ioannou M (July 2016). "Recent Advances in Aggressive Large B-cell Lymphomas: A Comprehensive Review". Advances in Anatomic Pathology. 23 (4): 202–43. doi:10.1097/PAP.0000000000000117. PMID 27271843. S2CID 205915174.
  3. ^ a b Rezk SA, Zhao X, Weiss LM (September 2018). "Epstein-Barr virus (EBV)-associated lymphoid proliferations, a 2018 update". Human Pathology. 79: 18–41. doi:10.1016/j.humpath.2018.05.020. PMID 29885408. S2CID 47010934.
  4. ^ a b c Shimada K, Hayakawa F, Kiyoi H (November 2018). "Biology and management of primary effusion lymphoma". Blood. 132 (18): 1879–1888. doi:10.1182/blood-2018-03-791426. PMID 30154110. S2CID 206957482.
  5. ^ El-Fattah MA (December 2017). "Clinical characteristics and survival outcome of primary effusion lymphoma: A review of 105 patients". Hematological Oncology. 35 (4): 878–883. doi:10.1002/hon.2372. PMID 27859456. S2CID 21614181.
  6. ^ Zanelli M, Zizzo M, Bisagni A, Froio E, De Marco L, Valli R, Filosa A, Luminari S, Martino G, Massaro F, Fratoni S, Ascani S (April 2020). "Germinotropic lymphoproliferative disorder: a systematic review". Annals of Hematology. 99 (10): 2243–2253. doi:10.1007/s00277-020-04024-3. PMID 32307569. S2CID 215819914.
  7. ^ Sukswai N, Lyapichev K, Khoury JD, Medeiros LJ (January 2020). "Diffuse large B-cell lymphoma variants: an update". Pathology. 52 (1): 53–67. doi:10.1016/j.pathol.2019.08.013. PMID 31735345. S2CID 208142227.
  8. ^ Gonçalves PH, Uldrick TS, Yarchoan R (September 2017). "HIV-associated Kaposi sarcoma and related diseases". AIDS. 31 (14): 1903–1916. doi:10.1097/QAD.0000000000001567. PMC 6310482. PMID 28609402.
  9. ^ Arora N, Gupta A, Sadeghi N (July 2017). "Primary effusion lymphoma: current concepts and management". Current Opinion in Pulmonary Medicine. 23 (4): 365–370. doi:10.1097/MCP.0000000000000384. PMID 28399009. S2CID 4514140.