Baseline patient characteristics are described in Table 1. The median age was 54 years (range, 13-75), and 22 patients were male. All patients had been diagnosed since 2000, except for 2 who were diagnosed in the 1990s. The hyaline vascular variant (HVV) (N=11, 39%) of CD was the most frequent histologic subtype. Frequently observed signs and symptoms seen at diagnosis included hepatomegaly or splenomegaly, fever, edema, ascites, and pleural effusion. Sixteen patients (57%) had disseminated disease (i.e., involvement of both sides of the diaphragm), whereas 11 (39%) patients had limited disease (involvement of a single side of the diaphragm). In 1 patient, disease extent could not be exactly estimated because imaging studies for the abdomen and pelvis were not performed.

One patient had concurrent polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma-proliferative disorder, and skin changes (POEMS) syndrome accompanying polyneuropathy, IgG λ monoclonal gammopathy, splenomegaly, edema, skin pigmentation, and adrenal insufficiency. Two other patients had monoclonal gammopathy, each with IgM λ and IgA λ, but not accompanying polyneuropathy. Despite the absence of 1 mandatory diagnostic criterion, these 2 patients had other features of POEMS syndrome, including extravascular volume overload, organomegaly, and endocrinopathy (adrenal insufficiency and/or pituitary insufficiency). According to a recently proposed concept, these patients might be classified as having a CD variant of POEMS [10]; therefore, 3 patients (11%) in our study cohort had related POEMS syndrome or its variants. One patient had a history of Kaposi's sarcoma treated with radiation therapy.

The laboratory results obtained at diagnosis are summarized in Table 2. Nineteen of 27 tested patients (70%) had anemia. An antiglobulin test was conducted in 8 patients with anemia, and 7 (87%) were positive for the assay. One showed elevation of the reticulocyte productive index and decreasing haptoglobin, both of which were consistent with autoimmune hemolytic anemia. This patient also had autoimmune thrombocytopenia, leading to the diagnosis of Evans syndrome. Thrombocytopenia was also observed in 30% of the other patients. C-reactive protein and erythrocyte sedimentation levels were elevated in 83% and 93% of patients, respectively, and lactate dehydrogenase and β2 microglobulin levels were elevated in 52% and 76% of patients, respectively.

Bone marrow examination was performed in 19 patients, 10 of whom (53%) showed reactive plasmacytosis. One patient fulfilled the criteria for asymptomatic multiple myeloma. Three patients tested positive in the PCR assay for HHV-8 among the 10 tested. Four patients were examined with tissue immunohistochemistry (IHC), and 1 patient was positive for HHV-8. Two of these patients underwent both of the tests; 1 showed a negative result on both tests, whereas the other was positive in the PCR assay but negative in the IHC test.

Extravascular volume overload was significantly associated with several clinical factors, including disseminated disease extents (P=0.01), and constitutional symptoms-fever, weight loss, and/or night sweats (P=0.006), organomegaly (P=0.02), and hypoalbuminemia (P=0.04).

Best responses to initial therapy are summarized in Table 3. As the first-line treatment, cytotoxic chemotherapy was administered to 11 patients (39%); the most common regimen was a cyclophosphamide, doxorubicin, vincristine, and prednisolone combination (CHOP, N=7). Among 7 patients who received CHOP, 5 completed 6 cycles of chemotherapy, 1 was transferred to another hospital after 2 cycles, and 1 was lost to follow up after 1 cycle. Other patients were treated with cyclophosphamide, vincristine, and prednisone (CVP; without doxorubicin from CHOP, N=3) and rituximab plus CHOP (N=1). Among those who underwent CVP chemotherapy, rituximab was added from the second to sixth cycles in a patient with Evan's syndrome (N=1). The other 2 patients who were treated with CVP received 3 cycles and 5 cycles, respectively. In a patient with POEMS syndrome, 1 cycle of rituximab plus CHOP was followed by 6 cycles of a melphalan and prednisolone combination because of financial problems. Among those patients who underwent chemotherapy or chemoimmunotherapy, 5 achieved complete response (CR), 2 achieved partial responses (PR), and the remaining 3 achieved stable disease. The response was not evaluated in 1 patient because of loss of clinical follow up. Glucocorticoid alone was used in 6 (21%) patients, 2 of whom achieved CR and 3 of whom experienced PR. The remaining patient could not be evaluated. The duration of glucocorticoid treatment was variable, ranging from 2 weeks with daily administration to 16 months with intermittent dosing. One patient received interferon-alpha at 3 million units per week for 15 weeks with prednisolone and achieved CR. Five patients were treated with excision, and 1 of them underwent postoperative radiation therapy. The other 5 patients (32%) were treated using a "watch and wait" strategy without systemic therapy. The patients who underwent surgery or surveillance did not initially have constitutional symptoms, except for 1 who presented with fever that resolved without treatment. All of the patients treated with local therapy had disease on a single side of the diaphragm. Two patients who were not administered specific therapy (i.e., watch and wait strategy) had diseases on both sides of the diaphragm. The overall response rates (CR+PR) in patients who underwent systemic therapy (i.e., cytotoxic chemotherapy, glucocorticoid, or interferon-α) was 72% (13/18).

At the time of analysis, 10 of the 28 patients had died. Two died from secondary lymphoma, each with T-cell lymphoma with leukemic manifestation and high-grade B-cell lymphoma. Three died from disease progression. The cause of death was unknown in 5 patients because of follow-up loss. Among those 10 dead patients, 7 had diseases on both sides of the diaphragm and 6 had clinical features related to extravascular fluid accumulation.

With a median follow-up of 67 months (range, 1-162 months), the 5-year OS rate of all patients was 77% (95% confidence interval [CI], 69-86); it was 100% in those who underwent local therapy and 70% (95% CI, 59-82) in those who were given systemic therapy. When we excluded 2 patients from the systemic therapy group given rituximab, the 5-year OS rate was 66% (95% CI, 54-79).

Univariate analyses for potential prognostic factors were performed (Table 4). Patients with extravascular fluid accumulation, such as peripheral edema, ascites, and/or pleural effusion (5-year OS rates 56% vs. 94%, P=0.04) and disseminated disease extent (5-year OS rates 73% vs. 91%, P=0.03) were associated with poor survival (Fig. 1). Elevation of β2 microglobulin was marginally associated with poor survival (5-year OS rates, 58% vs. 100%; P=0.10). Other clinicopathologic factors, including patient gender, age, histopathologic types, existence of organomegaly, hypoalbuminemia, anemia, thrombocytopenia, and elevated lactate dehydrogenase, were not significantly associated with their survival. HHV-8 positivity by either PCR or IHC also was not correlated with their survival (P=0.25). Because of the small sample size, multivariate analysis was not performed in this study.