Castleman disease, also known as angiofollicular lymph node hyperplasia or giant lymph node hyperplasia, is an uncommon benign B-cell lymphoproliferative condition. It can affect several regions of the body but is commonly described as a solitary mediastinal mass.
There are two distinct subtypes of Castleman disease:
unicentric Castleman disease
- more common
- localized, and locally treated
- associated with minimal symptoms
multicentric Castleman disease
- usually in the context of HIV infection
- systemic disease characterized by diffuse lymphadenopathy, anemia, splenomegaly, and systemic inflammatory symptoms
Unicentric Castleman disease typically occurs in children and young adults (3rd and 4th decades), with a slight female predominance (1.4:1) 15.
Multicentric Castleman disease, on the other hand, occurs in an older population (5th and 6th decades), with a slight male predominance 15. HIV is a relevant risk factor for this condition, and it has been demonstrated that all the HIV patients with multicentric Castleman disease are coinfected with the human herpesvirus 8 (HHV-8).
Unicentric Castleman disease is usually asymptomatic and incidentally found on routine exams for other reasons. Depending on the anatomical site, a painless lymphadenopathy may be noted.
Multicentric Castleman disease has an exuberant clinical presentation due to the systemic inflammation, with symptoms such as fevers, night sweats, fatigue, and weight loss, and clinical signs of generalized lymphadenopathy, hepatosplenomegaly, and fluid retention.
Hematological abnormalities such as anemia, elevated inflammatory markers, hypergammaglobulinemia, and hypoalbuminemia are commonly found in patients with multicentric Castleman disease 15.
The disease is of unknown etiology, but the most widely accepted theory is that Castleman disease is a chronic low-grade inflammatory process. The interleukin 6 in unicentric Castleman disease and both interleukin-6 and HHV-8 in multicentric Castleman disease are demonstrated to play a critical role in pathogenesis and symptomatology of the disease 15.
The disease is characterized by hypervascular lymphoid hyperplasia. There are also several recognized subtypes based on histopathology 1-2:
- hyaline vascular
- most common ~90%, corresponding to most cases of the unicentric Castleman disease
- most commonly found in the mediastinum
- classically appears as an avidly enhancing mediastinal mass at CT and MRI
- increased numbers of small hyalinised blood vessels within and between the lymphoid follicles, which show obliteration of the medullary sinuses
- “onion-skinning” arrangement of the small lymphocytes of the mantle zones, forming concentric rings around the germinal center
- plasma cell
- often multicentric
- hyperplastic follicles of varying sizes, which show patent medullary sinuses
- less enhancing
- may be more symptomatic 5
- HHV-8–associated Castleman disease 8
- multicentric Castleman disease not otherwise specified
Castleman disease is an exclusion diagnosis usually made by excisional biopsy of an affected lymph node. Alternatively, core needle biopsy can be performed when the excision is not possible 15.
The distribution is as follows:
- thorax: ~70%
- abdomen/pelvis and retroperitoneum: 10-15%
- neck: 10-15%
Multicentric Castleman disease may involve all of the above and is associated with a more complicated clinical course with systemic symptoms including fever and organomegaly.
- POEMS syndrome
- osteosclerotic myeloma
- Kaposi sarcoma
- AIDS: especially multicentric 9
- amyloidosis 10
- chordoid meningioma 16
Thoracic lesions may present as mediastinal masses. Additional findings include the following 19:
- displacement of adjacent structures due to mass effect
- ipsilateral pleural effusion
- periosteal reaction
Both hyaline-vascular and plasma cell types present as hypoechoic masses and nodules 17. The ultrasonographic findings are non-specific and indistinguishable from other causes of lymphadenopathy. Doppler examination of hyaline-vascular type may reveal exuberant vascularity with predominantly peripheral flow, prominent penetrating feeding vessels entering the hilum, and low-resistance arterial wave pattern 18.
For mediastinal lesions: CT chest
- commonly seen as a solitary mediastinal mass, infiltrative mass, multiple lymph nodes or rarely as matted lymphadenopathy (with or without a dominant mass) in a single mediastinal compartment
- typical arborising calcification may be seen within the mass in 15% of cases
- hyaline vascular type typically shows intense homogeneous enhancement following contrast
- dynamic CT demonstrates early rapid enhancement with washout in the delayed phase
- plasma cell type are multicentric and are less enhancing 8
For abdominal lesions: CT abdomen
- most commonly, a single well-defined abdominal mass
- location is variable and includes retroperitoneum, mesentery, and porta hepatis 3
- enhancement is homogeneous, or in larger lesions (>5 cm) may demonstrate central hypoattenuation consistent with necrosis.
- variable pattern of calcification, including arborising calcification.
For multicentric disease: multi-region CT
- bilateral hilar and mediastinal lymphadenopathy
- centrilobular nodules
- diffuse abdominal lymphadenopathy
General signal characteristics include the following:
- T1: iso to hyperintense relative to skeletal muscle
- T1 C+ (Gd): shows enhancement
- T2: arborising calcification may be seen as low signal
- low values on ADC may be encountered 13-14
Small studies have shown that active Castleman disease is avid on FDG-PET 12. Discrimination between uni- and multicentric disease, mapping of the extent of disease and monitoring disease progression seems possible, especially if confirmed in larger series 7,12.
Treatment and prognosis
For unicentric Castleman disease treatment is surgical, with good prognosis (can be curative).
Multicentric Castleman disease may be treated with any combination of surgery, chemotherapy and prednisolone 6. Available treatments include also antiviral strategies (targeting HHV-8), and monoclonal antibody therapies targeting CD20 or IL-6 15. Prognosis is relatively poorer.
Patients with multicentric Castleman disease and POEMS syndrome are usually treated with high-dose immunosuppressive agents and steroids. If immunosuppression fails, autologous peripheral blood stem cell transplantation is recommended 19.
History and etymology
The condition was first described by Benjamin Castleman in 1954 4.
For mediastinal lesions, consider the differential by location:
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- 4. Castleman B, Towne VW. CASE records of the Massachusetts General Hospital Weekly Clinicopathological Exercises: Case 40011. N. Engl. J. Med. 1954;250 (1): 26-30. doi:10.1056/NEJM195401072500107 - Pubmed citation
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- 12. Lee ES, Paeng JC, Park CM et-al. Metabolic characteristics of Castleman disease on 18F-FDG PET in relation to clinical implication. Clin Nucl Med. 2013;38 (5): 339-42. doi:10.1097/RLU.0b013e3182816730 - Pubmed citation
- 13. Oida Y, Shimizu K, Mukai M et-al. FDG-PET and diffusion-weighted MR imaging appearance in retroperitoneal Castleman's disease: a case report. Clin Imaging. 2008;32 (2): 144-6. doi:10.1016/j.clinimag.2007.08.020 - Pubmed citation
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- 16. Kepes JJ, Chen WY, Connors MH et-al. "Chordoid" meningeal tumors in young individuals with peritumoral lymphoplasmacellular infiltrates causing systemic manifestations of the Castleman syndrome. A report of seven cases. Cancer. 1988;62 (2): 391-406. Pubmed citation
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- 18. Mahmood N, Suresh HB, Swethadri GK et-al. Ultrasound and Doppler findings in a rare case of Castleman's disease of the parotid. Dentomaxillofac Radiol. 2010;39 (1): 54-6. doi:10.1259/dmfr/77931198 - Free text at pubmed - Pubmed citation
- 19. Kligerman SJ, Auerbach A, Franks TJ et-al. Castleman Disease of the Thorax: Clinical, Radiologic, and Pathologic Correlation: From the Radiologic Pathology Archives. Radiographics. 2016;36 (5): 1309-32. doi:10.1148/rg.2016160076 - Pubmed citation