Hypercalcemia may indicate Richter's syndrome: report of four cases and review.
BACKGROUND
Hypercalcemia has rarely been reported in patients with Richter's syndrome (RS). In this article, the authors report four cases with complementary pathophysiologic examinations.


METHODS
Four patients with hypercalcemia that indicated RS were admitted to the study unit between 1980 and 1994 with the following diagnoses: transformation of mixed follicular lymphoma, Waldenstrom's macroglobulinemia, and chronic lymphocytic leukemia, respectively, in 3 men ages 60 to 73 years, and chronic lymphocytic leukemia in a woman 73 years of age. Radiologic and histologic features were reported. Circulating levels of parathormone-related peptide (PTHrP), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were measured.


RESULTS
Radiologic skeletal abnormalities were found in three of three cases: osteopenia twice and multifocal osteolysis once. All four patients had large cell lymphoma (LCL). Bone resorption assessed histomorphometrically was elevated in two of two cases. Serum TNF-alpha and IL-6 levels were high in three of three and one of three cases, respectively. Elevated values were also found in four patients with LCL but without hypercalcemia. The serum PTHrP level was increased in the only hypercalcemic patient tested and values were normal in the three control patients.


CONCLUSIONS
Hypercalcemia arising in a patient with a low grade lymphoproliferative disorder may indicate RS. Hypercalcemia is due to increased bone resorption, which may be caused by the secretion of osteoclast-stimulating factors by the LCL invading the bone marrow. Independently, TNF-alpha and/or IL-6 were unlikely causative factors of hypercalcemia in the patients in this study; however, synergism with PTHrP was suspected in one case.
Beaudreuil
J
J
Service de Médecine Interne, Université Paris-Nord, France.
Lortholary
O
O
Martin
A
A
Feuillard
J
J
Guillevin
L
L
Lortholary
P
P
Raphael
M
M
Casassus
P
P
D000368:Aged; D001862:Bone Resorption; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology* / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications* / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000150:complications*; D008297:Male; D008875:Middle Aged; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000378:metabolism; D013577:Syndrome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D008258:Waldenstrom Macroglobulinemia / Q000150:complications
C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha