Castleman disease (angiofollicular lymph node hyperplasia) is a rare, heterogeneous lymphoproliferative disorder of lymph nodes. It most commonly arises in the mediastinum (60-70%) but can occur in any lymph node station including cervical, axillary, retroperitoneal, and mesenteric locations. Histopathologically, it is classified into two main subtypes: hyaline-vascular type (90% of cases, solitary, asymptomatic, hypervascular mass) and plasma cell type (10% of cases, multicentric, systemic symptoms, generalized lymphadenopathy). HHV-8 (human herpesvirus-8) infection plays a key role in the pathogenesis of multicentric Castleman disease, particularly in HIV-positive patients. The hyaline-vascular type is usually curable by surgical resection, while the plasma cell/multicentric type requires systemic therapy and carries a risk of lymphomatous transformation. Idiopathic multicentric Castleman disease (iMCD) is recognized as a distinct clinical entity managed with IL-6 pathway-targeted therapies (siltuximab, tocilizumab).
Age Range
20-50
Peak Age
35
Gender
Equal
Prevalence
Rare
The pathogenesis of Castleman disease varies by subtype. In the hyaline-vascular type, abnormal vascular proliferation and hyalinized germinal centers develop in lymph node follicles; prominent capillary proliferation is seen in the interfollicular zone ('lollipop sign' histology). This intense neovascularization underlies the prominent homogeneous arterial phase enhancement on imaging — the dense capillary network allows rapid accumulation of iodinated/gadolinium-based contrast agents. The feeding artery is typically enlarged and visible on CT angiography and conventional angiography, confirming the hypervascular nature. In the plasma cell type, overproduction of IL-6 (interleukin-6) plays a central role — IL-6 triggers polyclonal plasma cell proliferation, B-cell activation, and systemic inflammatory response. IL-6's upregulation of vascular endothelial growth factor (VEGF) expression increases capillary permeability, leading to systemic findings including hepatosplenomegaly, ascites, pleural effusion, and generalized edema. In HHV-8-positive multicentric type, viral IL-6 (vIL-6) production additionally contributes. On MRI, T2-weighted images may show flow voids and heterogeneous hyperintensity due to intense vascularity. Calcification (particularly central or arciform) is seen in the hyaline-vascular type and reflects dystrophic calcification.
The combination of a well-circumscribed solitary mass with intense homogeneous arterial phase enhancement and an enlarged feeding artery entering from one side is the signature finding of hyaline-vascular type Castleman disease. This combination has high specificity in the differential diagnosis of mediastinal hypervascular masses.
In hyaline-vascular type Castleman disease, intense, homogeneous, and avid enhancement is seen in the arterial phase. Enhancement typically shows >80 HU increase and may approach the density of adjacent vascular structures. Small lesions tend to be homogeneous, while larger lesions may show mild heterogeneity. This intense enhancement reflects the rich capillary network and neovascularization within the mass. Enhancement persists in the portal venous phase (persistent enhancement) — rapid washout is not seen.
Report Sentence
Well-circumscribed solitary mass in the mediastinum demonstrating marked homogeneous hypervascular enhancement in the arterial phase with persistent enhancement in the portal venous phase; hyaline-vascular type Castleman disease should be primarily considered.
In hyaline-vascular type Castleman disease, an enlarged feeding artery entering one side of the mass is identified. This artery typically originates from internal mammary artery, bronchial artery, or intercostal artery branches in mediastinal masses. It is clearly visible on CT angiography and confirms the hypervascular nature of the mass. Multiple feeding arteries may be present in some cases. This finding is critically important for preoperative planning and embolization decisions.
Report Sentence
An enlarged feeding artery is seen entering the inferolateral surface of the mass, supporting the hypervascular nature of the lesion and consistent with Castleman disease.
Central or arciform (arc-shaped) calcification pattern is seen in 10-30% of hyaline-vascular type Castleman disease cases. Calcification typically concentrates in the center of the mass and may form a 'target' or 'bull's-eye' pattern. This calcification pattern reflects dystrophic calcification occurring in hyalinized germinal centers and regressed follicles. Peripheral calcification is rare, and central localization has diagnostic value. It is detected on non-contrast CT and may be masked on contrast-enhanced series.
Report Sentence
Arciform/central calcification is seen in the center of the mass; this is evaluated as a supportive finding for the diagnosis of hyaline-vascular type Castleman disease.
On T2-weighted MR images, Castleman disease shows heterogeneous hyperintense signal. Prominent flow voids (signal voids) are seen within the mass due to intense vascularity — this finding reflects dilated vascular structures within the mass. In hyaline-vascular type, homogeneous to mildly heterogeneous T2 hyperintensity is typical, while plasma cell type may show more pronounced heterogeneity. Areas of necrosis or cystic degeneration may present as focal high T2 signal foci.
Report Sentence
The mass shows heterogeneous hyperintense signal on T2-weighted images with multiple flow voids within the mass indicating intense vascularity.
On T1-weighted pre-contrast images, Castleman disease shows isointense or mildly hypointense signal relative to muscle. After gadolinium-based contrast agent injection, marked and avid enhancement is seen in the early arterial phase — the MR equivalent of CT arterial phase enhancement. Enhancement may be homogeneous (small lesions) or mildly heterogeneous (large lesions). Enhancement persists in delayed phases (persistent pattern). On dynamic contrast-enhanced MR, a rapid rise with slow washout pattern is typical.
Report Sentence
The mass shows isointense signal to muscle on T1-weighted images with marked homogeneous enhancement in the early arterial phase and persistent enhancement pattern in delayed phases.
On ultrasonography, Castleman disease typically appears as a well-defined, homogeneous hypoechoic solid mass. In hyaline-vascular type, the mass usually has uniform echotexture with homogeneous internal echoes. Calcification foci may appear as hyperechoic spots. The mass is clearly demarcated from surrounding tissues, and a capsule-like hyperechoic rim (pseudocapsule) may be visible.
Report Sentence
Well-defined, homogeneous hypoechoic solid mass is seen on ultrasonography; focal calcification foci are identified within the internal structure.
On color Doppler ultrasonography, Castleman disease exhibits a markedly hypervascular pattern. Intense internal vascularity and central feeding vessel structures are seen within the mass. Power Doppler demonstrates diffuse vascular signal throughout the mass. Spectral Doppler may show low-resistance arterial flow pattern (RI <0.6), confirming the rich vascular bed.
Report Sentence
Color and power Doppler ultrasonography demonstrates markedly hypervascular pattern with central feeding vessel structure within the mass; low-resistance arterial flow is identified on spectral Doppler.
On FDG PET-CT, FDG uptake of Castleman disease varies by subtype. Hyaline-vascular type typically shows low to moderate FDG uptake (SUVmax 2-5). Plasma cell/multicentric type demonstrates high FDG uptake (SUVmax >5-10) — IL-6-mediated inflammatory activity increases metabolic activity. In multicentric type, generalized lymphadenopathy regions, spleen, and bone marrow involvement may be detected. PET-CT is valuable for evaluating the extent of multicentric type and monitoring treatment response.
Report Sentence
Low to moderate FDG uptake is detected in the mass on PET-CT (SUVmax: X), consistent with hyaline-vascular type Castleman disease; clinical correlation is recommended to exclude multicentric type.
Criteria
Accounts for 90% of cases. Solitary, well-circumscribed mass. Histologically shows hyalinized germinal centers, regressed follicles, prominent interfollicular vascular proliferation ('lollipop sign'). Usually asymptomatic or local compressive symptoms.
Distinct Features
Prominent homogeneous hypervascular enhancement in arterial phase on CT, feeding artery, central/arciform calcification. Avid enhancement and flow voids on MRI. Surgical resection is curative. Low FDG uptake.
Criteria
Accounts for 10% of cases. Usually multicentric. Histologically shows polyclonal plasma cell infiltration, hyperplastic germinal centers. Systemic symptoms: fever, night sweats, weight loss, anemia, hypergammaglobulinemia.
Distinct Features
Generalized lymphadenopathy, hepatosplenomegaly, ascites/pleural effusion. Multiple enlarged lymph nodes with mild to moderate enhancement on CT. High FDG uptake. Elevated IL-6, HHV-8 positivity.
Criteria
Simultaneous involvement of two or more lymph node stations. Divided into HHV-8-positive MCD and idiopathic MCD (iMCD). TAFRO syndrome is a subtype of iMCD.
Distinct Features
Lymphadenopathy at multiple stations, hepatosplenomegaly, effusions on CT. Widespread high FDG uptake on PET-CT. Treatment: siltuximab, tocilizumab, rituximab. Risk of lymphomatous transformation (5-10%).
Criteria
Associated with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes). Usually shows plasma cell or mixed histology.
Distinct Features
Sclerotic bone lesions, polyneuropathy findings, skin hyperpigmentation. Combination of osteosclerotic bone lesions + lymph node enlargement + hepatosplenomegaly on CT supports POEMS diagnosis.
Distinguishing Feature
Hodgkin lymphoma typically shows conglomerate lymphadenopathy, heterogeneous enhancement, and necrosis; Castleman disease's intense homogeneous enhancement and feeding artery sign are distinguishing. Calcification in Hodgkin occurs post-treatment, while central calcification in Castleman may be seen pre-treatment.
Distinguishing Feature
Non-Hodgkin lymphoma typically shows homogeneous, mild to moderate enhancement — distinctly different from the intense hypervascular enhancement in Castleman. Feeding artery sign is not seen in NHL.
Distinguishing Feature
Sarcoidosis shows bilateral symmetric hilar and mediastinal lymphadenopathy — different from Castleman's solitary mass pattern. 'Lambda sign' and lung parenchymal involvement strongly support sarcoidosis.
Distinguishing Feature
Carcinoid tumor can also be hypervascular but typically contains an endobronchial component and is related to airways. Calcification in carcinoid shows eccentric pattern while Castleman shows central/arciform pattern. Feeding artery sign is not expected.
Distinguishing Feature
Reactive lymphadenopathy typically shows preserved hilar structure, oval shape, and mild enhancement. Feeding artery sign, central calcification, and prominent flow voids are not seen.
Urgency
routineManagement
surgicalBiopsy
NeededFollow-up
specialist-referralHyaline-vascular type is cured by surgical resection — preoperative embolization may reduce intraoperative bleeding. Plasma cell/multicentric type requires systemic therapy: siltuximab (anti-IL-6), tocilizumab (anti-IL-6R), rituximab. Excisional or core biopsy is required for definitive diagnosis. Long-term follow-up is necessary in multicentric type due to risk of lymphomatous transformation (5-10%).
Surgical resection is curative in unicentric Castleman disease with excellent prognosis. Multicentric Castleman disease presents with systemic symptoms (fever, weight loss, anemia, hypergammaglobulinemia, elevated IL-6) and carries risk of lymphoma transformation. HHV-8 positive multicentric Castleman (especially HIV-associated) is treated with anti-CD20 (rituximab) or anti-IL-6 (siltuximab/tocilizumab).