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Primary effusion lymphoma (PEL)

Aggressive HIV-associated large B-cell non-Hodgkin lymphoma (NHL) with an aggressive phenotype.

Aggressive HIV-associated large B-cell non-Hodgkin lymphoma (NHL) with an aggressive phenotype.

  • Main characteristic of PEL: Neoplastic effusions in body cavities without detectable tumor masses
  • PEL is rare: ~4% of HIV-associated NHL and < 1% of non-HIV-related lymphomas
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Visual abstract of primary effusion lymphoma (PEL) | Lurain, K., Polizzotto, M. N., Aleman, K., Bhutani, M., Wyvill, K. M., Gonçalves, P. H., … Uldrick, T. S. (2019). Viral, immunologic, and clinical features of primary effusion lymphoma. Blood, 133(16), 1753–1761. https://doi.org/10.1182/blood-2019-01-893339

History

PEL was first described in 1989 as an AIDS-related lymphoma in which patients with the disease developed further weakness and cachexia with a large malignant pleural effusion. In 1995, Cesarman et al identified KSHV in tumour cells of AIDS-related lymphoma with malignant effusion, and Nador et al called HHV8-associated lymphoma whose main tumour was present in the body cavity fluid PEL in 1996.

Aetiology

Viral infection (∼80%):

  • Kaposi sarcoma herpesvirus (KSHV)/human herpesvirus-8 (HHV8)
    • Aetiologic agent of PEL as well as Kaposi sarcoma and a form of multicentric Castleman disease (KSHV-MCD)
      • PEL may have concurrent Kaposi sarcoma and/or KSHV-MCD
  • Epstein-Barr virus (EBV) co-infection

Pathophysiology

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The schema of the proposed mechanism of PEL development: HHV8/KSHV-infected B cells acquire the characteristics of neoplastic change, such as immune evasion, drug resistance, antiapoptosis, cell cycle progression, and cytokine stabilization. | Color coding is as follows: viral proteins (light blue), transcription factors (lavender), kinase (light green), enzyme (blue), and proteins (magenta). | BCL10, B-cell lymphoma/leukemia 10; BCR, B-cell receptor; CARD11, caspase recruitment domain–containing protein 11; MALT1, mucosa-associated lymphoid tissue lymphoma translocation protein 1; TNFR, TNF receptor. | Illustration by Patrick Lane, ScEYEnce Studios. | Shimada, K., Hayakawa, F., & Kiyoi, H. (2018). Biology and management of primary effusion lymphoma. Blood, 132(18), 1879–1888. https://doi.org/10.1182/blood-2018-03-791426

Clinical features

Typically presents in middle-aged patients infected with HIV or harboring other immunocompromised states, such as recipients of solid-organ transplants, patients with cirrhosis, and in the elderly, often in HHV8 endemic areas.

Lymphomatous effusions in body cavities (formerly called body cavity lymphoma) usually without extracavitary tumour masses and the clinical symptoms depend on the cavities involved.

  • M/C sites: Pleural, peritoneal, and pericardial cavities
  • Dyspnea (from pleural or pericardial effusion)
  • Abdominal distention from ascites (from mass effects of malignant effusions)

Extracavitary PEL (rare):

  • Extracavitary sites: Intestinal tract, skin, lung, central nervous system, and lymph nodes

Diagnosis

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Working case definition of KICS. CTCAE, Common Terminology for Adverse Events. | Working case definition of KICS. CTCAE, Common Terminology for Adverse Events.

Biopsy:

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Solid primary effusion lymphoma (Solid PEL) tumor. (A) Starry-sky pattern. (B) Numerous mitoses. (C) Solid PEL cells, like PEL cells, show anaplastic/plasmablastic cytologic features, and some resemble Reed-Sternberg cells. (D-F) Immunohistochemical studies reveal that the tumor cells are CD20-negative (D), CD138-positive (E), and human herpes virus 8-positive (labeling for latent nuclear antigen 1) (F). | Kim, Y., Park, C. J., Roh, J., & Huh, J. (2014). Current concepts in primary effusion lymphoma and other effusion-based lymphomas. Korean Journal of Pathology, 48(2), 81–90. https://doi.org/10.4132/KoreanJPathol.2014.48.2.81

Differential diagnosis:

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Main differential diagnoses of primary effusion lymphoma | HHV8, human herpesvirus 8; HIV, human immunodeficiency virus; HCV, hepatitis C virus; EBV, Epstein-Barr virus; sIg, surface immunoglobulin; cIg, cytoplasmic immunoglobulin; IgH, immunoglobulin heavy chain gene rearrangement. | Kim, Y., Park, C. J., Roh, J., & Huh, J. (2014). Current concepts in primary effusion lymphoma and other effusion-based lymphomas. Korean Journal of Pathology, 48(2), 81–90. https://doi.org/10.4132/KoreanJPathol.2014.48.2.81
  • PEL-like lymphoma or HHV8− effusion-based lymphoma:
    • Morphologically similar to PEL
  • Pyothorax-associated lymphoma
  • DLBCL with chronic inflammation

Management

Chemoimmunotherapy (CI):

  • R-CHOP regimen (cures 50%‐60% cases):
    • Rituximab
    • Cyclophosphamide (adv effect: hemorrhagic cystitis)
    • Doxorubicin
    • Vincristine (adv. effect: peripheral neuropathy)
    • Prednisone

Combination antiretroviral therapy (cART)

Treatment of concurrent HIV-infection

Autologous stem cell transplant (ASCT)

For relapse/refractory cases

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