The HV-CD variant represents 80% to 90% of all cases of localized or unicentric CD (17,24,25). This variant occurs over a broad age range and, in most studies, males and females are equally affected (25,26). If patients with HIV infection are excluded, HV-CD occurs in younger patients than does plasma cell variant CD. Hyaline vascular CD usually presents as a large mass involving a lymph node (or group of lymph nodes). Symptoms, when present, are related to the size of the mass and compression of contiguous structures, such as the airways with shortness of breath, or vascular compression that can lead to esophageal varices (25,27). Laboratory abnormalities, other than elevated serum LDH levels in a subset of patients, are rare. Systemic symptoms are also rare (17,25). Many patients are completely asymptomatic, and HV-CD is incidentally discovered as a mass or widened mediastinum by routine chest radiograph. The mediastinum is a common site of involvement, but other lymph node groups are also often involved. In most patients, HV-CD occurs in lymph nodes above the diaphragm, but abdominal lymph nodes can be involved in a subset of cases (24,25,26). The so-called stroma-rich variants of HV-CD (discussed later) tend to occur only in adults and particularly involve abdominal lymph nodes (22). The localized nature of HV-CD usually allows complete surgical excision, which is curative (17,24,25,26). Radiation therapy also has been used in patients in whom complete surgical excision could not be performed (28,29).

The PC variant of CD accounts for 10% to 20% of localized or unicentric cases of CD (17,25). The PC-CD occurs over a broad age range, but patients tend to be older than those with HV-CD. No gender preference is noted (25,26). Any lymph node group can be involved, but the mediastinum is involved less frequently than in patients with HV-CD (26). Patients with PC-CD can be asymptomatic, but systemic symptoms and laboratory abnormalities have been reported in a subset of patients (17,25,26). The symptoms most commonly reported include fever, night sweats, weight loss, and malaise. Laboratory studies most commonly show anemia or thrombocytopenia, and serum IL-6 levels are increased. In one patient with PC-CD, anemia was shown to be associated with a circulating antierythropoietic factor (30).

However, as obvious histologic overlap occurs between localized PC-CD and multicentric CD (MCD), with the latter usually symptomatic, it is unclear how frequently patients with localized PC-CD have symptoms. Particularly in the older literature, before MCD was described, it is possible that some patients with PC-CD had multicentric disease that was not recognized as such. For example, cases of localized PC-CD have been associated with peripheral neuropathy (26). As neuropathy is common in POEMS syndrome, and POEMS syndrome is much more commonly associated with MCD (20), it seems possible that some cases of MCD have been under-recognized in the past. Alternatively, the definition of MCD is inadequate in the sense that some patients who initially present with unicentric disease go on to develop multicentric involvement.

For asymptomatic patients with localized PC-CD, surgical excision appears to be adequate (17,24). Surgical excision alone for symptomatic patients with PC-CD is often inadequate (25,26). In one Mayo Clinic study, such patients were treated with chemotherapy and steroids with a good response (26). However, the presence of neuropathy in patients with PC-CD was associated with very poor prognosis (26). These data reinforce the possibility that some cases of symptomatic “localized” PC-CD reported previously had, in fact, multicentric involvement or went on to develop multicentric disease.

Multicentric CD has become well known in the clinical setting of HIV infection, in which the disease is typically florid and associated with HHV-8 infection (4,7,31). However, MCD also occurs and was initially described in patients without known evidence of HIV infection (32,33). As the name indicates, MCD is a systemic disease characterized by multiple sites of involvement. Histologically, most patients with MCD have lymph node biopsy specimens that show findings most consistent with the PC variant (26,31,32,33). Rare cases of MCD that were classified as HV-CD are also described (26). It is uncertain if these cases have mixed features with prominent hyaline-vascular lesions, or if they were true examples of HV-CD.

Lymphadenopathy is virtually constant in patients with MCD, either peripheral or abdominal; mediastinal lymph nodes also can be involved (31,32,33). B-type symptoms (fever, night sweats, weight loss) occur in over 95% of patients. Splenomegaly (∼75%) and hepatomegaly (∼50%) are common, and edema, body cavity effusions, skin rash, and neurologic changes can occur in a small subset of patients. Laboratory abnormalities also occur in most patients with MCD. Elevated erythrocyte sedimentation rate, anemia, thrombocytopenia, polyclonal hypergammaglobulinemia, and elevated serum levels of IL-6, LDH, and C-reactive protein are common. Patients with MCD can be associated with POEMS syndrome or HIV infection. A distinctive skin tumor, glomeruloid hemangioma, can occur in patients with MCD and POEMS syndrome (34). Patients with MCD also have a higher risk of coexistent chronic infections and can be associated with Kaposi sarcoma, with the latter much more common in HIV-positive patients (17,35). Patients with MCD also and may subsequently develop malignant lymphoma (32,33).

Patients with MCD require therapy. Combination chemotherapy and steroids have been used with some success in patients without evidence of neuropathy, POEMS syndrome, or HIV infection (26,32,33). For MCD patients with these associated conditions, innovative treatment strategies are required as prognosis is generally poor (17,26,31).