Description
Castleman disease, also known as Castleman’s disease or angiofollicular lymph node hyperplasia, is a rare and complex group of disorders characterised by lymphoproliferation. It presents as lymphadenopathy, frequently in the mediastinum, and is associated with a wide range of clinical manifestations.
Pathogenesis
The pathogenesis is not completely understood, however, it is believed to involve an abnormal response to antigens with subsequent lymphoproliferation. In some cases, there is an association with human herpesvirus 8 (HHV-8), particularly in HIV-positive patients.
Subtypes
The disease comprises two primary forms:
- Unicentric (localised, 75-90% of cases)
- Multicentric
Epidemiology, Risk Factors & Associations
- There are two major forms: unicentric (localised) and multicentric Castleman disease. Unicentric is more common (75-90%).
- The disease can occur at any age, but most patients are diagnosed in their 30s to 40s.
- Multicentric Castleman disease has a significant association with HIV and HHV-8.
- Unicentric Castleman disease is not associated with these viruses and has no specific risk factors identified.
Clinical Features
- Patients with unicentric Castleman disease often present with asymptomatic lymphadenopathy, or symptoms related to mass effect.
- Multicentric Castleman disease presents with systemic symptoms such as fever (30-40%), fatigue, night sweats, and weight loss.
- There can be widespread lymphadenopathy and hepatosplenomegaly
Associated conditions include:
- POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, and Skin changes) – associated with multicentric Castleman disease
- Kaposi’s sarcoma – Castleman disease is associated with the human herpesvirus-8 (HHV-8), which is also a causative agent of Kaposi’s sarcoma, leading to an increased risk.
Complications
- Malignant transformation: Castleman disease, particularly the multicentric form, is associated with an increased risk of lymphoma (both non-Hodgkin’s and Hodgkin’s types).
- Paraneoplastic syndromes: Symptoms such as fever, night sweats, weight loss, and anemia, which can be debilitating, often accompany the multicentric form.
- Infections: As Castleman disease can cause an immunocompromised state, affected individuals may be susceptible to opportunistic infections.
- Systemic inflammatory response syndrome (SIRS): This may be triggered in severe cases of Castleman disease due to overactive immune response.
- Organ dysfunction: Multicentric Castleman disease can lead to multiple organ dysfunction due to widespread lymphadenopathy and systemic inflammation. The liver, kidneys, and lungs are commonly affected.
- POEMS syndrome: Characterised by Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes, POEMS syndrome is associated with multicentric Castleman disease.
- Kaposi’s sarcoma: Castleman disease is associated with the human herpesvirus-8 (HHV-8), which is also a causative agent of Kaposi’s sarcoma, leading to an increased risk.
Pathological Features
Histopathology
- There are two primary histological types: the hyaline-vascular type (comprising 90% of unicentric cases) and the less common plasma cell type.
- The hyaline-vascular type is characterised by angiofollicular lymph node hyperplasia, small hyaline-vascular follicles, and interfollicular capillary proliferation.
- The plasma cell type has similar features with the addition of sheets of plasma cells in the interfollicular areas.
Radiological Features
General Features
- Castleman disease presents as well-defined, round or oval lymph node masses which demonstrate intense homogenous enhancement due to their vascular nature.
- Unicentric Castleman disease – A solitary mass is typically found in the mediastinum or the neck.
- Multicentric Castleman disease – Generalised lymphadenopathy.
CT
- Unicentric: Well-defined, homogeneous, intensely enhancing nodal mass, typically in the mediastinum.
- Multicentric: Diffuse lymphadenopathy, hepatosplenomegaly, and possibly pleural or pericardial effusion.
MRI
- T1: Isointense to muscle
- T2: Hyperintense
- Gd+: Strong enhancement.
Grading and Staging
Staging is not typically used for Castleman disease. The most critical distinction is between unicentric and multicentric disease, which have markedly different prognoses and treatment approaches.
Diagnosis
Diagnosis is typically confirmed by histological examination of an excised lymph node.
Differential Diagnosis
- Lymphoma: Has a more aggressive appearance on imaging, typically lacks the intense vascular enhancement of Castleman disease.
- Sarcoidosis: May present with lymphadenopathy, but usually has bilateral hilar lymphadenopathy and lung involvement.
- Infectious lymphadenopathy: Often associated with systemic symptoms of infection, and usually resolves with treatment of the underlying infection.
Management
- Unicentric Castleman disease is generally treated with surgical resection, which is often curative.
- Multicentric Castleman disease treatment is more complex and may involve corticosteroids, chemotherapy, rituximab, and antiviral therapy for associated HHV-8 infection.