Hypercalcemia and huge splenomegaly presenting in an elderly patient with B-cell non-Hodgkin's lymphoma: a case report
© Ghazi et al; licensee BioMed Central Ltd. 2010
Received: 23 October 2009
Accepted: 19 October 2010
Published: 19 October 2010
Hypercalcemia is the major electrolyte abnormality in patients with malignant tumors. It can be due to localized osteolytic hypercalcemia or elaboration of humoral substances such as parathyroid hormone-related protein from tumoral cells. In hematological malignancies, a third mechanism of uncontrolled synthesis and secretion of 1-25(OH)2D3 from tumoral cells or neighboring macrophages may contribute to the problem. However, hypercalcemia is quite unusual in patients with B-cell non-Hodgkin's lymphoma.
An 85-year-old Caucasian woman presented with low grade fever, anorexia, abdominal discomfort and fullness in her left abdomen for the last six months. She was mildly anemic and complained of fatigability. She had huge splenomegaly and was hypercalcemic. After correction of her hypercalcemia, she had a splenectomy. Microscopic evaluation revealed a malignant lymphoma. Her immunohistochemistry was positive for leukocyte common antigen, CD20 and parathyroid hormone-related peptide.
Immunopositivity for parathyroid hormone-related peptide clearly demonstrates that hypersecretion of a parathyroid hormone-like substance from the tumor had led to hypercalcemia in this case. High serum calcium is seen in only seven to eight percent of patients with B-cell non-Hodgkin's lymphoma, apparently due to different mechanisms. Evaluation of serum parathyroid hormone-related protein and 1-25(OH)2D3 can be helpful in diagnosis and management. It should be noted that presentation with hypercalcemia has a serious impact on prognosis and survival.
Hypercalcemia is the major electrolyte abnormality in patients with malignant tumors. It can be due to skeletal invasion, known as localized osteolytic hypercalcemia or elaboration of humoral substances such as parathyroid hormone-related protein (PTHrP) from tumoral cells. In hematological malignancies, a third mechanism, uncontrolled synthesis and secretion of 1-25(OH)2D3 from tumoral cells or neighboring macrophages, may contribute to the problem [1, 2].
Hypercalcemia is common in patients with hematological malignancies. About 30% of patients with multiple myeloma and 60% of patients with T-cell non-Hodgkin's lymphoma (NHL) experience hypercalcemia due to osteolytic mechanisms or PTHrP hypersecretion respectively. By contrast, hypercalcemia is seen in only seven to eight percent of patients with B-cell NHL , mostly due to uncontrolled endogenous production of 1-25(OH)2D3 from tumor cells. Hypercalcemia that is secondary to elaboration of PTHrP in patients with B-cell NHL is quite unusual and, according to the best of our knowledge, limited numbers of such patients have been observed [3–7].
In our case report, we present the case of an 85-year-old Iranian woman who had huge splenomegaly and hypercalcemia. She was finally proven to have a PTHrP-producing B-cell lymphoma of her spleen.
An 85-year-old Iranian, Caucasian woman presented with low grade fever, anorexia, abdominal discomfort and fullness in her left abdomen for the last six months. An abdominal computed tomography (CT) scan performed six months previously revealed a filling defect in her spleen, which was interpreted as a splenic cyst. No specific treatment was done at that time.
Laboratory data of the patient on admission
4-10.8 × 103/ml
24 h Urine Calcium
<120 mg/24 h
Immunohistochemistry immunopositivity for PTHrP clearly demonstrates that hypersecretion of the PTH-like substance from the tumor had led to hypercalcemia in this case. Contrary to Adult T-cell leukemia/lymphoma (ATLL) in which hypercalcemia is common and almost always secondary to PTHrP hypersecretion, high serum calcium is seen in only seven to eight percent of patients with B-cell NHL, apparently due to different mechanisms. Majumdar in his study on 112 patients with B-cell NHL showed that eight patients (7.1%), six with high grade and two with low grade disease had elevated serum calcium levels . Most patients had stage 3 and 4 (Stage 3: NHL is in two lymph node groups, with/without partial involvement of an extranodal organ or site above and below the diaphragm. Stage 4: NHL is extensive (diffuse) in one organ or site, with/without NHL in distant lymph nodes.) and survived between two to 11 months after the appearance of hypercalcemia. No explanation about the etiology of hypercalcemia was given in that paper.
Clinical and laboratory data of B-cell NHL patients with hypercalcemia due to PTHrP hypersecretion
died after 3 months
Wada et al, 1992
Hamihara et al, 1996
Ranganath et al, 1998
died after 2 months
Uno et al, 1998
Daroszewski et al, 1999
Knobel et al, 2001
died at hospital
Schottker et al, 2006
died at hospital
Takasaki et al, 2006
Ghazi et al, 2008
Serum PTH and 1-25(OH)2D3 were low in most cases due to suppression of the parathyroid glands and renal α-hydroxylase secondary to hypercalcemia.
It is also evident that hypercalcemia is a manifestation of advanced disease and, as with other cases of humoral hypercalcemia of malignancy (HHM), points to a poor prognosis. All the patients, except our patient who is still in remission, died between two to 11 months after the appearance of hypercalcemia.
We conclude that although hypercalcemia is rare in patients with B-cell NHL, it should be properly diagnosed and urgently treated. The evaluation of serum PTHrP and 1-25(OH)2D3 can be helpful in diagnosis and management. It should also be noted that presentation with hypercalcemia has a serious impact on prognosis and survival.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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