Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Primer
  • Published:

Castleman disease

Nature Reviews Disease Primers volume 7, Article number: 84 (2021) Cite this article

Subjects

Abstract

Castleman disease (CD), a heterogeneous group of disorders that share morphological features, is divided into unicentric CD and multicentric CD (MCD) according to the clinical presentation and disease course. Unicentric CD involves a solitary enlarged lymph node and mild symptoms and excision surgery is often curative. MCD includes a form associated with Kaposi sarcoma herpesvirus (KSHV) (also known as human herpesvirus 8) and a KSHV-negative idiopathic form (iMCD). iMCD can present in association with severe syndromes such as TAFRO (thrombocytopenia, ascites, fever, reticulin fibrosis and organomegaly) or POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder and skin changes). KSHV-MCD often occurs in the setting of HIV infection or another cause of immune deficiency. The interplay between KSHV and HIV elevates the risk for the development of KSHV-induced disorders, including KSHV-MCD, KSHV-lymphoproliferation, KSHV inflammatory cytokine syndrome, primary effusion lymphoma and Kaposi sarcoma. A CD diagnosis requires a multidimensional approach, including clinical presentation and imaging, pathological features, and molecular virology. B cell-directed monoclonal antibody therapy is the standard of care in KSHV-MCD, and anti-IL-6 therapy is the recommended first-line therapy and only treatment of iMCD approved by the US FDA and EMA.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Common pathogenic mechanisms in KSHV-MCD and other KSHV-associated diseases.
Fig. 2: Unicentric Castleman disease.
Fig. 3: Histological features of the plasma cell variant of iMCD.
Fig. 4: KSHV-MCD and KSHV-MCD with concurrent KS.
Fig. 5: The management of UCD.
Fig. 6: Management of iMCD.

Similar content being viewed by others

References

  1. IARC. A Review of Human Carcinogens. Part B: Biological Agents Vol. 100 (IARC, 2012).

  2. Castleman, B. & Towne, V. W. Case records of the Massachusetts General Hospital: Case No. 40231. N. Engl. J. Med. 250, 1001–1005 (1954).

    CAS  PubMed  Google Scholar 

  3. Keller, A. R., Hochholzer, L. & Castleman, B. Hyaline-vascular and plasma-cell types of giant lymph node hyperplasia of the mediastinum and other locations. Cancer 29, 670–683 (1972).

    CAS  PubMed  Google Scholar 

  4. Kessler, E. Multicentric giant lymph node hyperplasia. A report of seven cases. Cancer 56, 2446–2451 (1985).

    CAS  PubMed  Google Scholar 

  5. van Rhee, F. et al. International evidence-based consensus diagnostic and treatment guidelines for unicentric Castleman disease. Blood Adv. 4, 6039–6050 (2020).

    PubMed  PubMed Central  Google Scholar 

  6. Soulier, J. et al. Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman’s disease. Blood 86, 1276–1280 (1995).

    CAS  PubMed  Google Scholar 

  7. Carbone, A., De Paoli, P., Gloghini, A. & Vaccher, E. KSHV-associated multicentric Castleman disease: A tangle of different entities requiring multitarget treatment strategies. Int. J. Cancer 137, 251–261 (2015). This review focuses on the aetiopathogenic role of co-infection by herpesviruses (KSHV and EBV) in PLWH.

    CAS  PubMed  Google Scholar 

  8. Ramaswami, R. et al. Characteristics and outcomes of KSHV-associated multicentric Castleman disease with or without other KSHV diseases. Blood Adv. 5, 1660–1670 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Carbone, A., Cesarman, E., Spina, M., Gloghini, A. & Schulz, T. F. HIV-associated lymphomas and gamma-herpesviruses. Blood 113, 1213–1224 (2009).

    CAS  PubMed  Google Scholar 

  10. Polizzotto, M. N., Uldrick, T. S., Hu, D. & Yarchoan, R. Clinical manifestations of Kaposi sarcoma herpesvirus lytic activation: multicentric Castleman disease (KSHV-MCD) and the KSHV inflammatory cytokine syndrome. Front. Microbiol. 3, 73 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Kojima, M. et al. Clinical implications of idiopathic multicentric Castleman disease among Japanese: a report of 28 cases. Int. J. Surg. Pathol. 16, 391–398 (2008). The paper suggests that at variance with iMCD in the Western world, the chronic course of the disease in Japan appears to be related to negativity for HHV8 infection.

    PubMed  Google Scholar 

  12. Bélec, L. et al. Human herpesvirus 8 infection in patients with POEMS syndrome-associated multicentric Castleman’s disease. Blood 93, 3643–3653 (1999).

    PubMed  Google Scholar 

  13. Vega, F., Miranda, R. N. & Medeiros, L. J. KSHV/HHV8-positive large B-cell lymphomas and associated diseases: a heterogeneous group of lymphoproliferative processes with significant clinicopathological overlap. Mod. Pathol. 33, 18–28 (2020). This review focuses on the current diagnosis of HHV8-associated lymphoproliferative disorders ranging from MCD to frank lymphomas.

    PubMed  Google Scholar 

  14. Bower, M. How I treat HIV-associated multicentric Castleman disease. Blood 116, 4415–4421 (2010).

    CAS  PubMed  Google Scholar 

  15. Dispenzieri, A. & Fajgenbaum, D. C. Overview of Castleman disease. Blood 135, 1353–1364 (2020). The advent of effective retroviral therapy and the use of rituximab in HHV8-MCD have improved outcomes in HHV8-MCD. Anti-IL-6-directed therapies are highly effective in many iMCD patients but additional therapies are required for refractory cases.

    PubMed  Google Scholar 

  16. Gopal, S. et al. Multicentric Castleman’s disease in Malawi. Lancet 384, 1158 (2014).

    PubMed  PubMed Central  Google Scholar 

  17. Cohen, A. B. et al. Clinical characteristics, treatment patterns, and overall survival of real-world patients with idiopathic multicentric Castleman disease. J. Clin. Oncol. 39, 7048–7048 (2021).

    Google Scholar 

  18. Simpson, D. Epidemiology of Castleman disease. Hematol. Oncol. Clin. North. Am. 32, 1–10 (2018).

    PubMed  Google Scholar 

  19. Oksenhendler, E. et al. The full spectrum of Castleman disease: 273 patients studied over 20 years. Br. J. Haematol. 180, 206–216 (2018). The study demonstrates that, although patients with iMCD and HHV8-associated MCD displayed similar clinical characteristics, the disease was more aggressive in HHV8-associated MCD, particularly in PLWH.

    CAS  PubMed  Google Scholar 

  20. van Rhee, F. et al. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease. Blood 132, 2115–2124 (2018). The purpose of this paper is to establish a consensus for treatment guidelines based on the severity of iMCD.

    PubMed  PubMed Central  Google Scholar 

  21. Murakami, M. et al. Clinicopathologic characteristics of 342 patients with multicentric Castleman disease in Japan. Mod. Rheumatol. 30, 843–851 (2020).

    CAS  PubMed  Google Scholar 

  22. Gopal, S. et al. Characteristics and survival for HIV-associated multicentric Castleman disease in Malawi. J. Int. AIDS Soc. 18, 20122 (2015).

    PubMed  PubMed Central  Google Scholar 

  23. Patel, M. et al. in Immunopathology and Immunomodulation (ed. Metodiev, K.) 247–259 (IntechOpen, 2015).

  24. Parez, N., Bader-Meunier, B., Roy, C. C. & Dommergues, J. P. Paediatric Castleman disease: report of seven cases and review of the literature. Eur. J. Pediatr. 158, 631–637 (1999).

    CAS  PubMed  Google Scholar 

  25. Borocco, C. et al. The French paediatric cohort of Castleman disease: a retrospective report of 23 patients. Orphanet J. Rare Dis. 15, 95 (2020). Unlike adult CD, which may be associated with HIV and HHV8 infection, paediatric CD could be favoured by primary activation of innate immunity and may affect life expectancy less.

    PubMed  PubMed Central  Google Scholar 

  26. Leroy, S. et al. Multicentric Castleman disease in an HHV8-infected child born to consanguineous parents with systematic review. Pediatrics 129, e199–e203 (2012).

    PubMed  PubMed Central  Google Scholar 

  27. Masaki, Y. et al. Epidemiological analysis of multicentric and unicentric Castleman disease and TAFRO syndrome in Japan. J. Clin. Exp. Hematop. 59, 175–178 (2019).

    PubMed  PubMed Central  Google Scholar 

  28. Munshi, N. et al. Use of a claims database to characterize and estimate the incidence rate for Castleman disease. Leuk. Lymphoma 56, 1252–1260 (2015).

    PubMed  Google Scholar 

  29. Iftode, N., Rădulescu, M. A., Aramă, Ș. S. & Aramă, V. Update on Kaposi sarcoma-associated herpesvirus (KSHV or HHV8) — review. Rom. J. Intern. Med. 58, 199–208 (2020).

    PubMed  Google Scholar 

  30. Chihara, D. et al. Differences in incidence and trends of haematological malignancies in Japan and the United States. Br. J. Haematol. 164, 536–545 (2014).

    PubMed  Google Scholar 

  31. Powles, T. et al. The role of immune suppression and HHV-8 in the increasing incidence of HIV-associated multicentric Castleman’s disease. Ann. Oncol. 20, 775–779 (2009).

    CAS  PubMed  Google Scholar 

  32. Zhang, L. et al. Clinical spectrum and survival analysis of 145 cases of HIV-negative Castleman’s disease: renal function is an important prognostic factor. Sci. Rep. 6, 23831 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Gonçalves, P. H., Uldrick, T. S. & Yarchoan, R. HIV-associated Kaposi sarcoma and related diseases. AIDS 31, 1903–1916 (2017).

    PubMed  Google Scholar 

  34. Cesarman, E. et al. Kaposi sarcoma. Nat. Rev. Dis. Prim. 5, 9 (2019).

    PubMed  Google Scholar 

  35. Mesri, E. A., Cesarman, E. & Boshoff, C. Kaposi’s sarcoma and its associated herpesvirus. Nat. Rev. Cancer 10, 707–719 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Dispenzieri, A. et al. The clinical spectrum of Castleman’s disease. Am. J. Hematol. 87, 997–1002 (2012). The paper supports the concept of four categories of CD, namely (1) unicentric CD (91%), (2) multicentric CD associated with the osteosclerotic variant of POEMS syndrome (90%), (3) multicentric CD without POEMS syndrome (65%), and (4) multicentric CD with POEMS syndrome without osteosclerotic lesions (27%).

    PubMed  PubMed Central  Google Scholar 

  37. Weisenburger, D. D., Nathwani, B. N., Winberg, C. D. & Rappaport, H. Multicentric angiofollicular lymph node hyperplasia: a clinicopathologic study of 16 cases. Hum. Pathol. 16, 162–172 (1985).

    CAS  PubMed  Google Scholar 

  38. Chang, K. C. et al. Monoclonality and cytogenetic abnormalities in hyaline vascular Castleman disease. Mod. Pathol. 27, 823–831 (2014).

    CAS  PubMed  Google Scholar 

  39. Li, Z. et al. Recurrent PDGFRB mutations in unicentric Castleman disease. Leukemia 33, 1035–1038 (2019).

    PubMed  PubMed Central  Google Scholar 

  40. Nabel, C. S. et al. Virome capture sequencing does not identify active viral infection in unicentric and idiopathic multicentric Castleman disease. PLoS ONE 14, e0218660 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Fajgenbaum, D. C., van Rhee, F. & Nabel, C. S. HHV-8-negative, idiopathic multicentric Castleman disease: novel insights into biology, pathogenesis, and therapy. Blood 123, 2924–2933 (2014).

    CAS  PubMed  Google Scholar 

  42. Goodman, A. M. et al. Novel somatic alterations in unicentric and idiopathic multicentric castleman disease. Eur. J. Haematol. https://doi.org/10.1111/ejh.13702 (2021).

    Article  PubMed  Google Scholar 

  43. Nagy, A. et al. Next-generation sequencing of idiopathic multicentric and unicentric Castleman disease and follicular dendritic cell sarcomas. Blood Adv. 2, 481–491 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Lim, J. Y. et al. DNMT3A haploinsufficiency causes dichotomous DNA methylation defects at enhancers in mature human immune cells. J. Exp. Med. 218, e20202733 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Yoshimi, A. et al. Genetic basis for iMCD-TAFRO. Oncogene 39, 3218–3225 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Baker, T. S. et al. A novel FAS mutation with variable expressivity in a family with unicentric and idiopathic multicentric Castleman disease. Blood Adv. 2, 2959–2963 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Fajgenbaum, D. C. & June, C. H. Cytokine storm. N. Engl. J. Med. 383, 2255–2273 (2020). The review describes the role of the cytokine storm in MCD.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. van Rhee, F., Stone, K., Szmania, S., Barlogie, B. & Singh, Z. Castleman disease in the 21st century: an update on diagnosis, assessment, and therapy. Clin. Adv. Hematol. Oncol. 8, 486–498 (2010).

    PubMed  Google Scholar 

  49. van Gameren, M. M. et al. Effects of recombinant human interleukin-6 in cancer patients: a phase I-II study. Blood 84, 1434–1441 (1994).

    PubMed  Google Scholar 

  50. Gherardi, R. K. et al. Elevated levels of interleukin-1 beta (IL-1 beta) and IL-6 in serum and increased production of IL-1 beta mRNA in lymph nodes of patients with polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome. Blood 83, 2587–2593 (1994).

    CAS  PubMed  Google Scholar 

  51. Lee, M. et al. Multicentric Castleman’s disease with an increased serum level of macrophage colony-stimulating factor. Am. J. Hematol. 54, 321–323 (1997).

    CAS  PubMed  Google Scholar 

  52. Nishi, J. et al. Expression of vascular endothelial growth factor in sera and lymph nodes of the plasma cell type of Castleman’s disease. Br. J. Haematol. 104, 482–485 (1999).

    CAS  PubMed  Google Scholar 

  53. Pierson, S. K. et al. ACCELERATE: a patient-powered natural history study design enabling clinical and therapeutic discoveries in a rare disorder. Cell Rep. Med. 1, 100158 (2020).

    PubMed  PubMed Central  Google Scholar 

  54. Pierson, S. K. et al. Plasma proteomics identifies a ‘chemokine storm’ in idiopathic multicentric Castleman disease. Am. J. Hematol. 93, 902–912 (2018).

    CAS  PubMed  Google Scholar 

  55. Fajgenbaum, D. C. et al. Identifying and targeting pathogenic PI3K/AKT/mTOR signaling in IL-6-blockade-refractory idiopathic multicentric Castleman disease. J. Clin. Invest. 129, 4451–4463 (2019).

    PubMed  PubMed Central  Google Scholar 

  56. An, J., Lichtenstein, A. K., Brent, G. & Rettig, M. B. The Kaposi sarcoma-associated herpesvirus (KSHV) induces cellular interleukin 6 expression: role of the KSHV latency-associated nuclear antigen and the AP1 response element. Blood 99, 649–654 (2002).

    CAS  PubMed  Google Scholar 

  57. Pai, R. L. et al. Type I IFN response associated with mTOR activation in the TAFRO subtype of idiopathic multicentric Castleman disease. JCI Insight 5, e135031 (2020).

    PubMed Central  Google Scholar 

  58. Pierson, S. K. et al. Discovery and validation of a novel subgroup and therapeutic target in idiopathic multicentric Castleman disease. Blood Adv. 5, 3445–3456 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Arenas, D. J. et al. Increased mTOR activation in idiopathic multicentric Castleman disease. Blood 135, 1673–1684 (2020).

    PubMed  PubMed Central  Google Scholar 

  60. Endo, Y. et al. Mediterranean fever gene variants modify clinical phenotypes of idiopathic multi-centric Castleman disease. Clin. Exp. Immunol. 206, 91–98 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Endo, Y. et al. Idiopathic multicentric Castleman disease with novel heterozygous Ile729Met mutation in exon 10 of familial Mediterranean fever gene. Rheumatology 60, 445–450 (2021).

    PubMed  Google Scholar 

  62. Endo, Y. et al. Successful canakinumab treatment for activated innate response in idiopathic Castleman’s disease with multiple heterozygous MEFV exon 2 variants. Clin. Immunol. 219, 108547 (2020).

    CAS  PubMed  Google Scholar 

  63. Du, M. Q. et al. Kaposi sarcoma-associated herpesvirus infects monotypic (IgM lambda) but polyclonal naive B cells in Castleman disease and associated lymphoproliferative disorders. Blood 97, 2130–2136 (2001).

    CAS  PubMed  Google Scholar 

  64. Dupin, N. et al. Distribution of human herpesvirus-8 latently infected cells in Kaposi’s sarcoma, multicentric Castleman’s disease, and primary effusion lymphoma. Proc. Natl Acad. Sci. USA 96, 4546–4551 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Parravicini, C. et al. Differential viral protein expression in Kaposi’s sarcoma-associated herpesvirus-infected diseases: Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. Am. J. Pathol. 156, 743–749 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Totonchy, J. et al. KSHV induces immunoglobulin rearrangements in mature B lymphocytes. PLoS Pathog. 14, e1006967 (2018).

    PubMed  PubMed Central  Google Scholar 

  67. Jacobs, S. R. et al. The viral interferon regulatory factors of kaposi’s sarcoma-associated herpesvirus differ in their inhibition of interferon activation mediated by toll-like receptor 3. J. Virol. 87, 798–806 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Dittmer, D. P. & Damania, B. Kaposi sarcoma-associated herpesvirus: immunobiology, oncogenesis, and therapy. J. Clin. Invest. 126, 3165–3175 (2016).

    PubMed  PubMed Central  Google Scholar 

  69. Uldrick, T. S. et al. High-dose zidovudine plus valganciclovir for Kaposi sarcoma herpesvirus-associated multicentric Castleman disease: a pilot study of virus-activated cytotoxic therapy. Blood 117, 6977–6986 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Bhatt, A. P. et al. A viral kinase mimics S6 kinase to enhance cell proliferation. Proc. Natl Acad. Sci. USA 113, 7876–7881 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Anders, P. M. et al. Human herpesvirus-encoded kinase induces B cell lymphomas in vivo. J. Clin. Invest. 128, 2519–2534 (2018).

    PubMed  PubMed Central  Google Scholar 

  72. Cannon, J. S. et al. Heterogeneity of viral IL-6 expression in HHV-8-associated diseases. J. Infect. Dis. 180, 824–828 (1999).

    CAS  PubMed  Google Scholar 

  73. Parravicini, C. et al. Expression of a virus-derived cytokine, KSHV vIL-6, in HIV-seronegative Castleman’s disease. Am. J. Pathol. 151, 1517–1522 (1997).

    CAS  PubMed  Google Scholar 

  74. Staskus, K. A. et al. Cellular tropism and viral interleukin-6 expression distinguish human herpesvirus 8 involvement in Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. J. Virol. 73, 4181–4187 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Polizzotto, M. N. et al. Human and viral interleukin-6 and other cytokines in Kaposi sarcoma herpesvirus-associated multicentric Castleman disease. Blood 122, 4189–4198 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Oksenhendler, E. et al. High levels of human herpesvirus 8 viral load, human interleukin-6, interleukin-10, and C reactive protein correlate with exacerbation of multicentric Castleman disease in HIV-infected patients. Blood 96, 2069–2073 (2000).

    CAS  PubMed  Google Scholar 

  77. Aoki, Y., Tosato, G., Fonville, T. W. & Pittaluga, S. Serum viral interleukin-6 in AIDS-related multicentric Castleman disease. Blood 97, 2526–2527 (2001).

    CAS  PubMed  Google Scholar 

  78. An, J., Sun, Y., Sun, R. & Rettig, M. B. Kaposi’s sarcoma-associated herpesvirus encoded vFLIP induces cellular IL-6 expression: the role of the NF-kappaB and JNK/AP1 pathways. Oncogene 22, 3371–3385 (2003).

    CAS  PubMed  Google Scholar 

  79. Deng, H., Chu, J. T., Rettig, M. B., Martinez-Maza, O. & Sun, R. Rta of the human herpesvirus 8/Kaposi sarcoma-associated herpesvirus up-regulates human interleukin-6 gene expression. Blood 100, 1919–1921 (2002).

    CAS  PubMed  Google Scholar 

  80. Chadburn, A. et al. HHV8/KSHV-positive lymphoproliferative disorders and the spectrum of plasmablastic and plasma cell neoplasms: 2015 SH/EAHP Workshop Report-Part 3. Am. J. Clin. Pathol. 147, 171–187 (2017).

    PubMed  PubMed Central  Google Scholar 

  81. Gasperini, P., Sakakibara, S. & Tosato, G. Contribution of viral and cellular cytokines to Kaposi’s sarcoma-associated herpesvirus pathogenesis. J. Leukoc. Biol. 84, 994–1000 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Suda, T. et al. HHV-8 infection status of AIDS-unrelated and AIDS-associated multicentric Castleman’s disease. Pathol. Int. 51, 671–679 (2001).

    CAS  PubMed  Google Scholar 

  83. Kawabata, H. et al. Clinical features and treatment of multicentric Castleman’s disease: a retrospective study of 21 Japanese patients at a single institute. J. Clin. Exp. Hematop. 53, 69–77 (2013).

    PubMed  Google Scholar 

  84. Tosato, G. et al. Monocyte-derived human B-cell growth factor identified as interferon-beta 2 (BSF-2, IL-6). Science 239, 502–504 (1988).

    CAS  PubMed  Google Scholar 

  85. Murakami, M. et al. Critical cytoplasmic region of the interleukin 6 signal transducer gp130 is conserved in the cytokine receptor family. Proc. Natl Acad. Sci. USA 88, 11349–11353 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Nicholas, J. et al. Kaposi’s sarcoma-associated human herpesvirus-8 encodes homologues of macrophage inflammatory protein-1 and interleukin-6. Nat. Med. 3, 287–292 (1997).

    CAS  PubMed  Google Scholar 

  87. Chatterjee, M., Osborne, J., Bestetti, G., Chang, Y. & Moore, P. S. Viral IL-6-induced cell proliferation and immune evasion of interferon activity. Science 298, 1432–1435 (2002).

    CAS  PubMed  Google Scholar 

  88. Giffin, L. & Damania, B. KSHV: pathways to tumorigenesis and persistent infection. Adv. Virus Res. 88, 111–159 (2014).

    PubMed  PubMed Central  Google Scholar 

  89. Giffin, L., West, J.A. & Damania, B. Kaposi’s sarcoma-associated herpesvirus interleukin-6 modulates endothelial cell movement by upregulating cellular genes involved in migration. mBio 6, e01499-15 (2015).

    PubMed  PubMed Central  Google Scholar 

  90. Nishi, J. & Maruyama, I. Increased expression of vascular endothelial growth factor (VEGF) in Castleman’s disease: proposed pathomechanism of vascular proliferation in the affected lymph node. Leuk. Lymphoma 38, 387–394 (2000).

    CAS  PubMed  Google Scholar 

  91. Aoki, Y. et al. Angiogenesis and hematopoiesis induced by Kaposi’s sarcoma-associated herpesvirus-encoded interleukin-6. Blood 93, 4034–4043 (1999).

    CAS  PubMed  Google Scholar 

  92. Brousset, P., Cesarman, E., Meggetto, F., Lamant, L. & Delsol, G. Colocalization of the viral interleukin-6 with latent nuclear antigen-1 of human herpesvirus-8 in endothelial spindle cells of Kaposi’s sarcoma and lymphoid cells of multicentric Castleman’s disease. Hum. Pathol. 32, 95–100 (2001).

    CAS  PubMed  Google Scholar 

  93. McNamara, R. P. et al. Extracellular vesicles from Kaposi sarcoma-associated herpesvirus lymphoma induce long-term endothelial cell reprogramming. PLoS Pathog. 15, e1007536 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. O’Hara, A. J. et al. Pre-micro RNA signatures delineate stages of endothelial cell transformation in Kaposi sarcoma. PLoS Pathog. 5, e1000389 (2009).

    PubMed  PubMed Central  Google Scholar 

  95. Said, J. et al. in WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (eds Swerdlow, S. H. et al) 325–329 (IARC, 2017).

  96. Moore, P. S., Boshoff, C., Weiss, R. A. & Chang, Y. Molecular mimicry of human cytokine and cytokine response pathway genes by KSHV. Science 274, 1739–1744 (1996).

    CAS  PubMed  Google Scholar 

  97. Sarek, G. et al. Reactivation of the p53 pathway as a treatment modality for KSHV-induced lymphomas. J. Clin. Invest. 117, 1019–1028 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Uldrick, T. S. et al. An interleukin-6-related systemic inflammatory syndrome in patients co-infected with Kaposi sarcoma-associated herpesvirus and HIV but without multicentric Castleman disease. Clin. Infect. Dis. 51, 350–358 (2010).

    CAS  PubMed  Google Scholar 

  99. Caro-Vegas, C. et al. Runaway Kaposi sarcoma-associated herpesvirus replication correlates with systemic IL-10 levels. Virology 539, 18–25 (2020).

    CAS  PubMed  Google Scholar 

  100. Tamburro, K. M. et al. Vironome of Kaposi sarcoma associated herpesvirus-inflammatory cytokine syndrome in an AIDS patient reveals co-infection of human herpesvirus 8 and human herpesvirus 6A. Virology 433, 220–225 (2012).

    CAS  PubMed  Google Scholar 

  101. Boutboul, D. et al. Treatment and outcome of unicentric Castleman disease: a retrospective analysis of 71 cases. Br. J. Haematol. 186, 269–273 (2019).

    PubMed  Google Scholar 

  102. Zhang, M. Y. et al. UCD with MCD-like inflammatory state: surgical excision is highly effective. Blood Adv. 5, 122–128 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Zhen, J. F. et al. Clinical analysis of unicentric Castleman’s disease with paraneoplastic pemphigus and bronchiolitis obliterans. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 39, 492–498 (2017).

    PubMed  Google Scholar 

  104. Fajgenbaum, D. C. et al. International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. Blood 129, 1646–1657 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Teruya-Feldstein, J. et al. Expression of human herpesvirus-8 oncogene and cytokine homologues in an HIV-seronegative patient with multicentric Castleman’s disease and primary effusion lymphoma. Lab. Invest. 78, 1637–1642 (1998).

    CAS  PubMed  Google Scholar 

  106. Haq, I. U. et al. The clinical application of plasma Kaposi sarcoma herpesvirus viral load as a tumour biomarker: results from 704 patients. HIV Med. 17, 56–61 (2016).

    CAS  PubMed  Google Scholar 

  107. Polizzotto, M. N. et al. Clinical features and outcomes of patients with symptomatic Kaposi sarcoma herpesvirus (KSHV)-associated inflammation: prospective characterization of KSHV inflammatory cytokine syndrome (KICS). Clin. Infect. Dis. 62, 730–738 (2016). KICS may be an unrecognized cause of morbidity and mortality in patients with KSHV-MCD.

    CAS  PubMed  Google Scholar 

  108. Lurain, K. et al. Viral, immunologic, and clinical features of primary effusion lymphoma. Blood 133, 1753–1761 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Fujimoto, S. et al. Tentative diagnostic criteria and disease severity classification for Castleman disease: a report of the research group on Castleman disease in Japan. Mod. Rheumatol. 28, 161–167 (2018).

    PubMed  Google Scholar 

  110. Iwaki, N. et al. Elevated serum interferon gamma-induced protein 10 kDa is associated with TAFRO syndrome. Sci. Rep. 7, 42316 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Polizzotto, M. N. et al. 18F-fluorodeoxyglucose positron emission tomography in Kaposi sarcoma herpesvirus-associated multicentric Castleman disease: correlation with activity, severity, inflammatory and virologic parameters. J. Infect. Dis. 212, 1250–1260 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Gloghini, A., Dolcetti, R. & Carbone, A. Lymphomas occurring specifically in HIV-infected patients: from pathogenesis to pathology. Semin. Cancer Biol. 23, 457–467 (2013).

    CAS  PubMed  Google Scholar 

  113. Chadburn, A. et al. Immunophenotypic analysis of the Kaposi sarcoma herpesvirus (KSHV; HHV-8)-infected B cells in HIV+ multicentric Castleman disease (MCD). Histopathology 53, 513–524 (2008).

    CAS  PubMed  Google Scholar 

  114. Oksenhendler, E. et al. Multicentric Castleman’s disease in HIV infection: a clinical and pathological study of 20 patients. AIDS 10, 61–67 (1996).

    CAS  PubMed  Google Scholar 

  115. Cronin, D. M. & Warnke, R. A. Castleman disease: an update on classification and the spectrum of associated lesions. Adv. Anat. Pathol. 16, 236–246 (2009).

    PubMed  Google Scholar 

  116. Naresh, K. N., Trivedi, P., Horncastle, D. & Bower, M. CD20 expression in the HHV-8-infected lymphoid cells in multicentric Castleman disease. Histopathology 55, 358–359 (2009).

    PubMed  Google Scholar 

  117. Naresh, K. N., Rice, A. J. & Bower, M. Lymph nodes involved by multicentric Castleman disease among HIV-positive individuals are often involved by Kaposi sarcoma. Am. J. Surg. Pathol. 32, 1006–1012 (2008).

    PubMed  Google Scholar 

  118. Liu, A. Y. et al. Idiopathic multicentric Castleman’s disease: a systematic literature review. Lancet Haematol. 3, e163–e175 (2016).

    PubMed  Google Scholar 

  119. Stone, K. et al. Interleukin-6 receptor polymorphism is prevalent in HIV-negative Castleman disease and is associated with increased soluble interleukin-6 receptor levels. PLoS ONE 8, e54610 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Fayand, A. et al. Epidemiology of Castleman disease associated with AA amyloidosis: description of 2 new cases and literature review. Amyloid 26, 197–202 (2019).

    CAS  PubMed  Google Scholar 

  121. Ohzono, A. et al. Clinical and immunological findings in 104 cases of paraneoplastic pemphigus. Br. J. Dermatol. 173, 1447–1452 (2015).

    CAS  PubMed  Google Scholar 

  122. Raza, H. A. et al. Unicentric Castleman disease complicated by paraneoplastic bronchiolitis obliterans and pemphigus. Respir. Med. Case Rep. 25, 129–132 (2018).

    PubMed  PubMed Central  Google Scholar 

  123. Gerald, W., Kostianovsky, M. & Rosai, J. Development of vascular neoplasia in Castleman’s disease. Report of seven cases. Am. J. Surg. Pathol. 14, 603–614 (1990).

    CAS  PubMed  Google Scholar 

  124. Castleman, B., Iverson, L. & Menendez, V. Localized mediastinal lymph-node hyperplasia resembling thymoma. Cancer 9, 822–830 (1956).

    CAS  PubMed  Google Scholar 

  125. Lachmann, H. J., Gilbertson, J. A., Gillmore, J. D., Hawkins, P. N. & Pepys, M. B. Unicentric Castleman’s disease complicated by systemic AA amyloidosis: a curable disease. QJM 95, 211–218 (2002).

    CAS  PubMed  Google Scholar 

  126. Yoshizaki, K. et al. Pathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman’s disease. Blood 74, 1360–1367 (1989).

    CAS  PubMed  Google Scholar 

  127. van Rhee, F. et al. Siltuximab for multicentric Castleman’s disease: a randomised, double-blind, placebo-controlled trial. Lancet Oncol. 15, 966–974 (2014).

    PubMed  Google Scholar 

  128. Casper, C. et al. Analysis of inflammatory and anemia-related biomarkers in a randomized, double-blind, placebo-controlled study of siltuximab (anti-IL6 monoclonal antibody) in patients with multicentric Castleman disease. Clin. Cancer Res. 21, 4294–4304 (2015).

    CAS  PubMed  Google Scholar 

  129. Nishimoto, N. et al. Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease. Blood 106, 2627–2632 (2005).

    CAS  PubMed  Google Scholar 

  130. Morra, D. E. et al. Predictors of response to anti-IL6 monoclonal antibody therapy (siltuximab) in idiopathic multicentric Castleman disease: secondary analyses of phase II clinical trial data. Br. J. Haematol. 184, 232–241 (2019).

    CAS  PubMed  Google Scholar 

  131. Fajgenbaum, D. C. et al. Insufficient evidence exists to use histopathologic subtype to guide treatment of idiopathic multicentric Castleman disease. Am. J. Hematol. 95, 1553–1561 (2020).

    PubMed  Google Scholar 

  132. Gholam, D., Vantelon, J. M., Al-Jijakli, A. & Bourhis, J. H. A case of multicentric Castleman’s disease associated with advanced systemic amyloidosis treated with chemotherapy and anti-CD20 monoclonal antibody. Ann. Hematol. 82, 766–768 (2003).

    PubMed  Google Scholar 

  133. Ocio, E. M. et al. Efficacy of rituximab in an aggressive form of multicentric Castleman disease associated with immune phenomena. Am. J. Hematol. 78, 302–305 (2005).

    PubMed  Google Scholar 

  134. Ide, M., Kawachi, Y., Izumi, Y., Kasagi, K. & Ogino, T. Long-term remission in HIV-negative patients with multicentric Castleman’s disease using rituximab. Eur. J. Haematol. 76, 119–123 (2006).

    CAS  PubMed  Google Scholar 

  135. Mian, H. & Leber, B. Mixed variant multicentric Castleman disease treated with rituximab: case report. J. Pediatr. Hematol. Oncol. 32, 622 (2010).

    PubMed  Google Scholar 

  136. Chen, L. Y. C., Skinnider, B. F., Wilson, D. & Fajgenbaum, D. C. Adrenalitis and anasarca in idiopathic multicentric Castleman’s disease. Lancet 397, 1749 (2021).

    PubMed  Google Scholar 

  137. Akiyama, M., Kaneko, Y. & Takeuchi, T. Tocilizumab for the treatment of TAFRO syndrome: a systematic literature review. Ann. Hematol. 99, 2463–2475 (2020).

    CAS  PubMed  Google Scholar 

  138. Fujimoto, S. et al. Optimal treatments for TAFRO syndrome: a retrospective surveillance study in Japan. Int. J. Hematol. 113, 73–80 (2021).

    CAS  PubMed  Google Scholar 

  139. Masaki, Y. et al. 2019 Updated diagnostic criteria and disease severity classification for TAFRO syndrome. Int. J. Hematol. 111, 155–158 (2020).

    PubMed  Google Scholar 

  140. Dispenzieri, A. How I treat POEMS syndrome. Blood 119, 5650–5658 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  141. Kuwabara, S., Dispenzieri, A., Arimura, K., Misawa, S. & Nakaseko, C. Treatment for POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome. Cochrane Database Syst. Rev. 2012, CD006828 (2012).

    PubMed Central  Google Scholar 

  142. Gavriatopoulou, M. et al. European Myeloma Network recommendations on diagnosis and management of patients with rare plasma cell dyscrasias. Leukemia 32, 1883–1898 (2018).

    PubMed  Google Scholar 

  143. Gerard, L. et al. Prospective study of rituximab in chemotherapy-dependent human immunodeficiency virus associated multicentric Castleman’s disease: ANRS 117 CastlemaB Trial. J. Clin. Oncol. 25, 3350–3356 (2007).

    CAS  PubMed  Google Scholar 

  144. Bower, M. et al. Brief communication: rituximab in HIV-associated multicentric Castleman disease. Ann. Intern. Med. 147, 836–839 (2007).

    PubMed  Google Scholar 

  145. Hoffmann, C. et al. Improved outcome with rituximab in patients with HIV-associated multicentric Castleman disease. Blood 118, 3499–3503 (2011).

    CAS  PubMed  Google Scholar 

  146. Gerard, L. et al. Rituximab decreases the risk of lymphoma in patients with HIV-associated multicentric Castleman disease. Blood 119, 2228–2233 (2012).

    CAS  PubMed  Google Scholar 

  147. Pria, A. D. et al. Relapse of HHV8-positive multicentric Castleman disease following rituximab-based therapy in HIV-positive patients. Blood 129, 2143–2147 (2017).

    PubMed  Google Scholar 

  148. Casper, C., Nichols, W. G., Huang, M. L., Corey, L. & Wald, A. Remission of HHV-8 and HIV-associated multicentric Castleman disease with ganciclovir treatment. Blood 103, 1632–1634 (2004).

    CAS  PubMed  Google Scholar 

  149. Berezne, A., Agbalika, F. & Oksenhendler, E. Failure of cidofovir in HIV-associated multicentric Castleman disease. Blood 103, 4368–4369 (2004).

    CAS  PubMed  Google Scholar 

  150. Senanayake, S. et al. Multicentric Castleman’s disease treated with antivirals and immunosuppressants. J. Med. Virol. 71, 399–403 (2003).

    PubMed  Google Scholar 

  151. Ramaswami, R. et al. Tocilizumab in patients with symptomatic Kaposi sarcoma herpesvirus-associated multicentric Castleman disease. Blood 135, 2316–2319 (2020).

    PubMed  PubMed Central  Google Scholar 

  152. Oksenhendler, E. et al. High incidence of Kaposi sarcoma-associated herpesvirus-related non-Hodgkin lymphoma in patients with HIV infection and multicentric Castleman disease. Blood 99, 2331–2336 (2002).

    CAS  PubMed  Google Scholar 

  153. Marcelin, A. G. et al. Rituximab therapy for HIV-associated Castleman disease long-term remission of Kaposi sarcoma-associated herpesvirus-related multicentric Castleman disease with anti-CD20 monoclonal antibody therapy. Blood 102, 2786–2788 (2003).

    CAS  PubMed  Google Scholar 

  154. Karass, M., Grossniklaus, E., Seoud, T., Jain, S. & Goldstein, D. A. Kaposi sarcoma inflammatory cytokine syndrome (KICS): a rare but potentially treatable condition. Oncologist 22, 623–625 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Talat, N., Belgaumkar, A. P. & Schulte, K. M. Surgery in Castleman’s disease: a systematic review of 404 published cases. Ann. Surg. 255, 677–684 (2012).

    PubMed  Google Scholar 

  156. Sitenga, J., Aird, G., Ahmed, A. & Silberstein, P. T. Impact of siltuximab on patient-related outcomes in multicentric Castleman’s disease. Patient Relat. Outcome Meas. 9, 35–41 (2018).

    PubMed  PubMed Central  Google Scholar 

  157. van Rhee, F. et al. Patient-reported outcomes for multicentric Castleman’s disease in a randomized, placebo-controlled study of siltuximab. Patient 8, 207–216 (2015).

    PubMed  PubMed Central  Google Scholar 

  158. Vernon, M. et al. Deriving health utility values from a randomized, double-blind, placebo-controlled trial of siltuximab in subjects with multicentric Castleman’s disease. Curr. Med. Res. Opin. 32, 1193–1200 (2016).

    CAS  PubMed  Google Scholar 

  159. Slade, A. et al. Patient reported outcome measures in rare diseases: a narrative review. Orphanet J. Rare Dis. 13, 61 (2018).

    PubMed  PubMed Central  Google Scholar 

  160. Casper, C. et al. The Multicentric Castleman’s Disease (MCD)-Symptom Scale (MCD-SS): development and validation of a patient-reported outcome (PRO) measure for an ultra-orphan disease. Value Health 17, A535 (2014).

    CAS  PubMed  Google Scholar 

  161. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02817997 (2016).

  162. Guerit, E., Arts, F., Dachy, G., Boulouadnine, B. & Demoulin, J. B. PDGF receptor mutations in human diseases. Cell Mol. Life Sci. 78, 3867–3881 (2021).

    CAS  PubMed  Google Scholar 

  163. Brandt, S. J., Bodine, D. M., Dunbar, C. E. & Nienhuis, A. W. Dysregulated interleukin 6 expression produces a syndrome resembling Castleman’s disease in mice. J. Clin. Invest. 86, 592–599 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  164. Suthaus, J. et al. HHV-8-encoded viral IL-6 collaborates with mouse IL-6 in the development of multicentric Castleman disease in mice. Blood 119, 5173–5181 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Nishimura, Y. et al. Validated international definition of the thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly clinical subtype (TAFRO) of idiopathic multicentric Castleman disease. Am. J. Hematol. 96, 1241–1252 (2021).

    PubMed  Google Scholar 

  166. Wang, H. W., Pittaluga, S. & Jaffe, E. S. Multicentric Castleman disease: where are we now? Semin. Diagn. Pathol. 33, 294–306 (2016).

    PubMed  PubMed Central  Google Scholar 

  167. Gonzalez-Farre, B. et al. HHV8-related lymphoid proliferations: a broad spectrum of lesions from reactive lymphoid hyperplasia to overt lymphoma. Mod. Pathol. 30, 745–760 (2017).

    CAS  PubMed  Google Scholar 

  168. Bower, M. et al. British HIV association guidelines for HIV-associated malignancies 2014. HIV Med. 15, 1–92 (2014).

    PubMed  Google Scholar 

  169. Olszewski, A. J., Fallah, J. & Castillo, J. J. Human immunodeficiency virus-associated lymphomas in the antiretroviral therapy era: analysis of the National Cancer Data Base. Cancer 122, 2689–2697 (2016).

    CAS  PubMed  Google Scholar 

  170. El-Fattah, M. A. Clinical characteristics and survival outcome of primary effusion lymphoma: a review of 105 patients. Hematol. Oncol. 35, 878–883 (2017).

    PubMed  Google Scholar 

  171. Shimada, K., Hayakawa, F. & Kiyoi, H. Biology and management of primary effusion lymphoma. Blood 132, 1879–1888 (2018).

    CAS  PubMed  Google Scholar 

  172. Castillo, J. J. et al. Prognostic factors in chemotherapy-treated patients with HIV-associated plasmablastic lymphoma. Oncologist 15, 293–299 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

M. Bor. is supported by NIH grants 2UM1CA121947-09, 5U01-I068636 and R25TW011215. B.D. is supported by NIH grants DE028211, CA096500, CA254564, CA239583 and CA163217. M.N.P. is supported by the Australian National Health and Medical Research Council and by the Cancer Institute of New South Wales. The authors would like to thank the patients and their families for sharing their experiences as outlined in Box 6.

Author information

Authors and Affiliations

  1. Centro di Riferimento Oncologico (CRO), IRCCS, National Cancer Institute, Aviano, Italy

    Antonino Carbone

  2. S. Maria degli Angeli Hospital, Pordenone, Italy

    Antonino Carbone

  3. Unit of Internal Medicine, University of Zimbabwe Faculty of Medicine and Health Sciences, Harare, Zimbabwe

    Margaret Borok

  4. Department of Microbiology and Immunology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA

    Blossom Damania

  5. Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy

    Annunziata Gloghini

  6. Clinical Hub for Interventional Research, John Curtin School of Medical Research, The Australian National University, Canberra, NSW, Australia

    Mark N. Polizzotto

  7. Castleman Disease Collaborative Network, Philadelphia, PA, USA

    Raj K. Jayanthan

  8. Center for Cytokine Storm Treatment & Laboratory, University of Pennsylvania, Philadelphia, PA, USA

    David C. Fajgenbaum

  9. National Centre for HIV Malignancy, Chelsea & Westminster Hospital, London, UK

    Mark Bower

Authors
  1. Antonino Carbone
    View author publications

    Search author on:PubMed Google Scholar

  2. Margaret Borok
    View author publications

    Search author on:PubMed Google Scholar

  3. Blossom Damania
    View author publications

    Search author on:PubMed Google Scholar

  4. Annunziata Gloghini
    View author publications

    Search author on:PubMed Google Scholar

  5. Mark N. Polizzotto
    View author publications

    Search author on:PubMed Google Scholar

  6. Raj K. Jayanthan
    View author publications

    Search author on:PubMed Google Scholar

  7. David C. Fajgenbaum
    View author publications

    Search author on:PubMed Google Scholar

  8. Mark Bower
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Introduction (A.C.); Epidemiology (M. Bor.); Mechanisms/pathophysiology (B.D. and A.G.); Diagnosis, screening and prevention (M.N.P.); Management (D.C.F. and M. Bow.); Quality of life (R.K.J. and D.C.F.); Outlook (M. Bow.); Overview of Primer (A.C.)

Corresponding author

Correspondence to Antonino Carbone.

Ethics declarations

Competing interests

M. Bow. received speaker honoraria from Gilead sciences, BMS, MSD, Janssen and ViiV. M.N.P. received speaker honoraria from Gilead Sciences and research funding from BMS, Celgene, Janssen and ViiV (to the institution, outside the area of the submitted work). D.C.F. has received research funding from EUSA Pharma and Janssen Pharmaceuticals, the study drug from Pfizer for a clinical trial of sirolimus in Castleman disease, and two provisional patents pending on the diagnosis and treatment of Castleman disease. The other authors declare no competing interests.

Additional information

Peer review information

Nature Reviews Disease Primers thanks M. Ide, who co-reviewed with T. Koga; J. Li, T. Schulz; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Carbone, A., Borok, M., Damania, B. et al. Castleman disease. Nat Rev Dis Primers 7, 84 (2021). https://doi.org/10.1038/s41572-021-00317-7

Download citation

  • Accepted:

  • Published:

  • Version of record:

  • DOI: https://doi.org/10.1038/s41572-021-00317-7

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer