A 72-yr-old Korean woman presented in February 2003 with recent enlargement of inguinal LNs in association with fatigue and weight loss of 2 kg in 3 months. She had a previous history of microscopic hematuria 20 yr ago, and hyperthyroidism 15 yr ago. In February 2001, an iron deficiency anemia refractory to iron supplementation and polyclonal gammopathy was found during the preoperative workup for a cataract operation. In October 2001, she was referred to the rheumatology outpatient clinic for evaluation of autoantibody positivity, and a diagnosis of pSS was made based on ocular and oral sicca symptoms for 30 yr, positive Schirmer test, salivary gland involvement on salivary scintigraphy, and FANA (1:160+, speckled pattern), and rheumatoid factor (26.7 IU/mL) positivity. Anti-SSA/SSB were negative. Salivary gland biopsy was not performed.
Physical examination revealed cachexic woman with pale conjunctiva and multiple inguinal LN enlargement. Laboratory investigations showed a hemoglobin of 7.9 g/dL, white cell count of 6,800/µL, platelet of 399,000/µL, and MCV of 73.3 fL. ESR was 56 mm/hr and C-reactive protein was 13.0 mg/dL. She had a total protein of 10 g/dL with 7.1 g/dL of globulin. β2-microglobulin was elevated to 3,490 ng/dL. Serum electrophoresis demonstrated a polyclonal pattern with increased amount of IgG (4,610 mg/dL) and IgA (681 mg/dL). In the BM aspirate, plasma cells were 18.2% of the nucleated cells. BM biopsy revealed normocellular marrow with multifocal increase of plasma cells that were normal in morphology and maturation (). LN biopsy revealed extensive infiltration of plasma cells (). The LN plasma cells were also normal in morphology and maturation, and immunostaining stained equally for both kappa and lambda light chains. Expression of CD27 on CD19+
peripheral blood B cells enables the grouping of B cells into 3 populations; CD27-
naïve B cells, CD27+
memory B cells, and CD27high
plasma cells (4
). Immunofluorescence staining of the peripheral B cells revealed marked increase of CD19+
plasma cells and significant reduction of CD19+
memory B cells ().
Fig. 1 Bone marrow biopsy (A) and lymph node biopsy (B) specimens. BM biopsy revealed normocellular marrow with multifocal increase of plasma cells. Lymph node biopsy shows profound germinal center reaction with infiltration of plasma cells (H&E stain, (more ...)
Fig. 2 Immunofluorescence staining of CD27 on CD19+ peripheral blood B cells at baseline (A) and 3 months after treatment (B). At baseline, there was marked increase of CD19+/CD27high plasma cells and significant reduction of CD19+/CD27+ memory B cells. After (more ...)
A diagnosis of reactive plasmacytosis in associated with pSS was made. Immunosuppressive therapy with high-dose glucocorticoid and cyclophosphamide 500 mg IV pulse fortnightly was initiated with concerns for malignant transformation. After completion of 6 cycles of cyclophosphamide pulse therapy, constitutional symptoms improved and lymphadenopathy regressed. Her hemoglobin level improved to 10.9 g/dL and MCV was 84.8 fL. Total protein and globulin decreased to 8.2 g/dL and 4.9 g/dL, respectively. IgG, IgA, β-2 microglobulin also decreased in significant amount with IgG 2,350 mg/dL, IgA of 573 mg/dL, and β2 microglobulin 2,630 ng/mL. Upon follow up immunofluorescence staining of the peripheral B cells, reduction of memory B cells with abnormal plasmacytosis was no longer observed (). The patient is doing clinically well on methylprednisolone 4 mg/day and azathioprine 100 mg/day without any evidence of lymph node enlargement and malignant transformation up to present.