Castleman Disease (CD)

At a glance

A lymphoproliferative disorder characterized by either uni- or multicentric occurrence of large, benign, hyperplastic lymph nodes associated with a wide variety of clinical symptoms.

Synonyms

Castleman Tumor; Angiofollicular Lymph Node Hyperplasia; Angiomatous Lymphoid Hamartoma; Lymphatic Hamartoma; Giant Lymph Node Hyperplasia; Giant Benign Lymphoma. Included: TAFRO Syndrome (an acronym that stands for Thrombocytopenia, Ascites/Anasarca, Fever, Reticulin fibrosis in bone marrow, Organomegaly, and normal amounts of γ-globulin); Thrombocytopenia, Ascites/Anasarka, Fever, Reticulin Fibrosis in Bone Marrow, Organomegaly, Normal Amounts of γ-globulin Syndrome, or Castleman-Kojima Syndrome.

History

Named after the American pathologist Benjamin Castleman, who first described this condition in 1954 in a 40-year-old patient who presented with an anterior mediastinal mass. Two years later, he reported a small case series of 13 patients.

Incidence

Approximately 7,000 new cases are diagnosed each year in the United States alone and more than 1,000 patients have been described in the literature. CD can present at any age, but unicentric CD (UCD), which accounts for approximately half of all CD cases, is most common in the third and fourth decade of life. Multicentric CD (MCD), ie, Human Herpes Virus-8-associated multicentric CD (HHV8-MCD), and idiopathic MCD (iMCD, cause unknown), each accounts for at least one-quarter of all CD patients and typically affect people in their fifth to sixth decade of life.

Classification

CD can be classified either based on the three types of centricity of the lesions (UCD, HHV8-MCD, or iMCD) or the now favored system based on the four histopathological variants, ie, hypervascular (formerly known as hyaline-vascular), plasmacytic/plasma cell, plasmablastic, and mixed type (see below).

• Hypervascular Type: Accounts for approximately 90% of all cases and is typically associated with UCD, involving a single lymph node or lymph node group (in up to 90% of UCD). Histologically, the lymph node in the hypervascular type of CD is characterized by regressed germinal centers with a prominent, penetrating, hyalinized vessel (referred to as lollipop lesion), surrounding concentric rings of small lymphocytes in expanded mantle zones (onion-skin like), and vascular proliferation with perivascular hyalinization in the interfollicular regions. Proliferation of dysplastic follicular dendritic cells is common, and follicular dendritic cell tumors/sarcoma may be associated with this type of CD. The hypervascular CD carries the best prognosis, followed by plasma cell CD, while it is worst for the plasmablastic variant (HHV-8–associated CD).

• Plasma Cell Type: Accounts for less than 10% of all CD cases and is more often associated with MCD than UCD, and has a higher probability than the hypervascular type to be associated with systemic symptoms (eg, fever, malaise, night sweats, splenomegaly) and abnormal laboratory findings (eg, hypergammaglobulinemia, elevated serum interleukin-6, anemia, thrombocytopenia). Compared to the hypervascular type, the plasma cell type histologically shows better ...