Castleman disease is a rare lymphoproliferative condition that has a strong association with several cancers.  It has also been associated with human herpesvirus 8 (HHV-8) and human immunodeficiency virus (HIV).1 The primary pathology of Castleman disease resides within the lymph nodes, where they become highly vascular and hyalinized or contain excessive amounts of plasma cells. Interleukin 6 (IL-6) also appears to play a role in causing a pro-inflammatory reaction that assists in lymph node hyper-proliferation. 

When HHV-8 is involved, many of the lymph nodes have an increased risk of transforming to active lymphomas.  Regardless of the type or co-infection, the basic pathophysiology in Castleman disease is hyperplastic lymph nodes in the setting of an inflammatory environment and the consequences that follow.

Castleman disease can be either unicentric or multicentric. In patients with unicentric Castleman disease, the affected lymph nodes are isolated and not widespread throughout the body; in this form, there is no association with HHV-8.  The most commonly affected areas are within the lung and mediastinum. Patients with unicentric disease are typically younger and do well with surgery and/or radiation therapy to the affected lymph nodes.  On the other hand, patients with multicentric disease are typically older and male, not to mention, there is a stronger association between multicentric disease and HIV. 

Based on these characteristics—how is Castleman disease diagnosed? Typically, the gold standard for diagnosing this condition is through a lymph node biopsy.  A chest x-ray followed by a computed tomography scan of the chest, abdomen, or pelvis usually aids in finding the most appropriate lymph node to biopsy. If there is difficulty in choosing the most appropriate lymph node, the supraclavicular and axillary lymph nodes are often biopsied. 

Incidence of Castleman disease has been reported with several cancers, including Kaposi sarcoma (KS), non-Hodgkin lymphoma (NHL) and Hodgkin Lymphoma (HL).  Since KS and Castleman disease are independently affiliated with HHV-8, it is not surprising that they sometimes occur together.2 Almost 15% of patients with multicentric Castleman disease have KS; however, the occurrence of Castleman disease  can be as high as 70% in patients who are also infected with HIV.  Up to 20% of multicentric patients can develop or present with NHL; these patients have a much higher mortality rate than if they had either condition independently.  There is also an association between both unicentric and multicentric disease with HL, although the incidence is much less than with KS and NHL.

In terms of treatment options—what is the best option? Surgery is a curative option in unicentric disease, although that is not the case in multicentric disease due to a more diffuse distribution throughout the body.  Patients with multicentric Castleman disease will often need chemotherapy, although the most efficacious regimen has yet to be proven.  

While Rituximab is one of the more common agents used, although the use of etoposide, vinblastine, and steroids have also been reported.  Lymphoma regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) and CVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasone) have also been used with some success. Additional research and enhanced recognition of this condition will serve to better determine optimal treatment options moving forward.


References

1. Larroche C, Cacoub P, Soulier J, et al. Castleman’s disease and lymphoma: report of eight cases in HIV-negative patients and literature review. Am J Hematol. 2002 Feb;69(2):119-26.
2. Bower M, Newsom-Davis T, Naresh K, et al. Clinical Features and Outcome in HIV-Associated Multicentric Castleman’s Disease. J Clin Oncol. 2011 Jun 20;29(18):2481-6. doi: 10.1200/JCO.2010.34.1909. Epub 2011 May 9.