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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary bone marrow lymphomata are infrequent; most of them are of B-cell origin, and those of a T-cell lineage produce mainly both hypercalcemia and osteolytic lesions apparently due to abnormal production of osteoclast-activating factor. We report a 15-year old patient with a primary bone marrow lymphoma: 85% of his infiltrating malignant lymphocytes displayed cytoplasmic mu-chains compatible with a pre-B phenotype. The cells failed to display the CALLA/CD 10 antigen. Serum calcium was 7.5 mEq/L (range 4-5 mEq/L); the bone biopsy of an osteolytic lesion disclosed a large-cell, diffuse non-Hodgkin's lymphoma. No malignant cells were found in the peripheral blood and there were no enlarged lymph nodes. The patient was treated with 6 courses of chemotherapy: hydroxyldaunorubicin, vincristine and prednisone (HOP). Complete remission was achieved and the patient was placed on continuation chemotherapy with daily six-mercaptopurine and weekly methotrexate, together with HOP pulses every three months. The hypercalcemia disappeared together with the fever and the bone pain: the patient has been followed 6 months. Data on this case are discussed together with those previously published in regard to the low prevalence of bone lesions in primary B-cell lymphomas of the bone marrow, and to the similarity of this B-cell malignancy to others that produce both hypercalcemia and bone lesions, i.e. multiple myeloma.
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PMID:[Hypercalcemia and osteolytic lesions associated with pre-B-cell primary lymphoma of the bone marrow. A case report]. 227 Mar 71

A 73-year-old man was admitted into the hospital because of lumbago in October, 1986. Laboratory examination on admission showed anemia, an IgA-kappa Bence Jones proteinemia. The bone marrow picture disclosed a marked involvement by the neoplastic cells, followed by leukemic conversion 2 weeks later. The leukemic cells displayed a lymphoblastoid appearance on light microscopy, but rather compatible with plasma cells on electron microscopy, showing some strands of rough endoplasmic reticulum and a prominent Golgi apparatus in the cytoplasm. The cells expressed a wide spectrum of surface markers, including those of plasma cell (PCA-1, OKT10), B cell (B1, sIg) and CALLA. Reverse hemolytic plaque assay disclosed the immunoglobulin production of monoclonal kappa chain, but a heavy chain production was recognized only in a small proportion of the cells. Under the diagnosis of multiple myeloma, he was treated with vincristine, cyclophosphamide, and prednisolone. But he died of renal failure complicating hypercalcemia after only three months of the admission in accordance with previous reports that CALLA-positive myeloma was associated with poor prognosis. This case may also represent the clinical, morphological and phenotypic diversity in multiple myeloma.
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PMID:[CALLA-positive leukemic multiple myeloma of IgA-kappa type]. 250 77

A case of plasma cell leukaemia of non-producer type is described. The patient presented with typical clinical features of plasma cell myeloma, including multiple osteolytic lesions, hypercalcaemia, renal failure and reduced polyclonal immunoglobulins, except that M-component was not detected in either the serum or urine. Morphological examinations showed a plasmacytoid appearance of the neoplastic cells, while immunological studies failed to detect cytoplasmic immunoglobulin or secretory capacity. The surface phenotype of CD38+, PCA-1+, DR-, CD20-, CD24-, CD9-, CD10- and surface immunoglobulin- was compatible with mature plasma cells. Chromosomal analysis showed the 14q+ marker due to translocation (6;14) and deletion of the short arm of chromosome 1. Analysis of immunoglobulin genes revealed the presence of heavy chain gene rearrangement, but the light chain genes, both kappa and lambda, remained in germline configuration. Such defective immunoglobulin gene rearrangement may be responsible for the failure of immunoglobulin biosynthesis and secretion by the neoplastic plasma cells. Furthermore, it is suggested that the morphological and phenotypic development of B cells may not necessarily depend on immunoglobulin light chain gene rearrangement, and that the oncogenic event in myeloma may occur at an earlier stage of B cell differentiation.
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PMID:Plasma cell leukaemia of non-producer type with missing light chain gene rearrangement. 313 42

A novel human EBV-negative B-cell line, designated DOBIL-6, was established from a patient with non-secretary myeloma. The DOBIL-6 cell has cytoplasmic gamma protein and expresses CD19, 20, 38, 45RO, VLA-4 and PCA-1 antigens, but lacks CD10, 45RA and VLA5 antigens. Chromosome analysis showed that DOBIL-6 cells had many complex structural abnormalities, including t(11;4) (q13;q32), which were consistent with that of the fresh tumour cells. Interestingly, abundant interleukin-6 (IL-6) and parathyroid hormone-related protein (PTHrP) accumulated in the culture supernatant of DOBIL-6 cells. Hypercalcaemia and splenomegaly associated with plasma cell proliferations which resulted in the expansion of the light zones in the follicles were observed in DOBIL-6 transplanted nude mice. RT-PCR analysis detected mRNA for PTHrP, and IL-6 as well as its receptor (GP80) in DOBIL-6 cells. Treatment of the DOBIL-6 cells with neutralizing anti-IL-6 antibody inhibited their growth in a dose-dependent manner, whereas the addition of exogenous IL-6 stimulated it in serum-depleted conditions. These findings suggest that both IL-6 and PTHrP are produced in DOBIL-6 cells, and that IL-6 promotes its growth by an autocrine mechanism. Since IL-6 is known to stimulate not only the growth of B-cell neoplasms but also osteoclastic bone resorption by cooperating with PTHrP, this simultaneous production of IL-6 and PTHrP might be synergistically linked and play a role in the development of hypercalcaemia of the patient. The DOBIL-6 cell is a useful tool to clarify the mechanism of hypercalcaemia associated with mature B-cell neoplasms.
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PMID:A novel mature B-cell line (DOBIL-6) producing both parathyroid hormone-related protein and interleukin-6 from a myeloma patient presenting with hypercalcaemia. 967 42

A 9-month-old infant presented with hypercalcemia and lytic bone lesions. Suspicion for malignancy led to a bone marrow examination, which showed replacement of the marrow by a small round blue cell infiltrate. Flow cytometric analysis of these cells showed an unusual immunophenotype in that these cells were dim CD45, HLA-DR, and CD10 positive, but CD19, CD20, CD79a, and CD34 negative. Southern blotting showed clonal rearrangement of immunoglobulin heavy chain (IgH) which confirmed a diagnosis of precursor B acute lymphoblastic leukemia (ALL). He received supportive treatment with hydration and pamidronate, but had recurrent episodes of hypercalcemia. Once the correct diagnosis of ALL was established, the patient was treated with an infantile ALL chemotherapeutic regimen and the hypercalcemia resolved. This case highlights the usefulness of immunoglobulin gene rearrangement studies in atypical cases of ALL.
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PMID:CD19 negative precursor B acute lymphoblastic leukemia presenting with hypercalcemia. 1517 Aug 92

Hypercalcemia in childhood acute lymphoblastic leukemia (ALL) is rare and occasionally associated with parathyroid hormone-related protein (PTHrP). However, the pathogenesis of PTHrP-independent hypercalcemia remains unclear. We report two children with precursor B ALL who had marked hypercalcemia (15.8 and 16.6 mg/dl, respectively) and disseminated osteolysis. Serum tumor necrosis factor-alpha (TNF-alpha) and IL-6 were markedly elevated, whereas 1,25(OH)(2) vitamin D(3), intact PTH and PTHrP were decreased or undetected. Analysis of urinary deoxypyridinoline (DPY) or bone biopsy of the osteolytic lesion showed an increased bone resorption, and administration of bisphosphonate improved the hypercalcemia. Patients had ALL with immunophenotype positive for CD10, CD34, and HLA-DR but negative for CD19 and obtained remission with chemotherapy. These findings suggest that increased osteoclastic bone resorption via stimulation with TNF-alpha and IL-6 may be mechanism causing PTHrP-independent hypercalcemia in some patients with precursor B ALL lacking CD19 expression.
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PMID:PTHrP-independent hypercalcemia with increased proinflammatory cytokines and bone resorption in two children with CD19-negative precursor B acute lymphoblastic leukemia. 1649 89

In hypophosphatemic rickets, there are both inherited and acquired forms, where X-linked dominant hypophosphatemic rickets (XLH) is the most prevalent genetic form and caused by mutations in the phosphate-regulating endopeptidase (PHEX) gene. XLH is associated with growth retardation and bone deformities. The renal tubular cells have an important role in calcium and phosphate metabolism, where the 1alpha-hydroxylase enzyme metabolizes the conversion of 25 (OH)-vitamin D to potent 1,25 (OH)2-vitamin D, whereas the sodium-phosphate transporter controls tubular phosphate reabsorption. The pathophysiological defect in XLH is speculated to cause an increase in a circulating phosphate regulating hormone termed phosphatonin (fibroblast growth factor 23 is the primary phosphatonin candidate), which leads to inhibition of 1alpha-hydroxylase, and simultaneously to inhibition of the sodium-phosphate transporter domain NPT2c leading to parathyroid hormone-independent phosphaturia. Hence, current treatment of XLH is 1,25 (OH)2-vitamin D or the vitamin D analog alfacalcidol and elementary phosphorus. Unfortunately, patients with XLH may develop nephrocalcinosis, secondary or tertiary hyperparathyroidism, and in some situations also hypertension and cardiovascular abnormalities. We describe a patient with XLH caused by a novel missense mutation in the PHEX gene, who on treatment with alfacalcidol and oral phosphate had normal growth and minimal bone deformities, but who subsequently developed moderate nephrocalcinosis, significant hyperparathyroidism, hypercalcemia, renal failure, and hypertension. We also report the use of the calcimimetic drug cinacalcet in the successful treatment of hypercalcemia and hyperparathyroidism.
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PMID:A case of X-linked hypophosphatemic rickets: complications and the therapeutic use of cinacalcet. 1877 77

Hypercalcemia usually results in nonspecific constitutional symptoms, although it can also manifest as a life threatening metabolic emergency. It is an uncommon albeit well recognized biochemical feature of childhood malignancies including acute leukemia. The pathogenesis of hypercalcemia and its implications in terms of long-term outcome are not yet fully understood. Most of the children presenting with acute lymphoblastic leukemia and hypercalcemia tend to be in older age groups and have an absence of blasts in the peripheral blood film. The chromosomal translocation 17;19 seems to be more frequent in children who present with hypercalcemia but the presence of hypercalcemia by itself does not seem to be closely linked to prognosis. Some of the less common immunophenotypes in the form of CD19 negativity and CD10 positivity have also been observed in hypercalcemic patients. In this study, we shall illustrate this clinical problem using the details of 2 patients with hematologic malignancy who were found to be hypercalcemic at presentation. We shall also review the literature with particular emphasis on the pathogenesis of hypercalcemia, its associations, and relationship to outcome.
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PMID:Hypercalcemia in acute lymphoblastic leukemia: an overview. 1964 91

Hypercalcemia is a rare complication of hematological malignancy in children. An 8-year-old girl with CALLA (+) Pre-B-cell ALL developed hypercalcemia during bone marrow relapse. She had nausea, vomiting, leg pain, polyuria, polydipsia, and muscle weakness. At the time of relapse, the ionized calcium level was 1.99 mmol/L. Rehydration with 0.9% saline and furosemide and methylprednisolone (MP) treatment were used for the treatment of hypercalcemia. The serum ionized calcium level increased to 2.2 mmol/L despite hydration, furosemide, and MP treatment. Then, a single-dose pamidronate (1 mg/kg/dose) was administered. Despite pamidronate treatment, the calcium level continued to rise. Next, calcitonin at a dose of 8 IU/kg/dose, 4 doses per day, was added to the treatment. After commencement of calcitonin treatment, her ionized calcium level decreased to normal reference ranges. In conclusion, because of the postponed effect of bisphosphonate treatment, pamidronate and calcitonin combination is an effective treatment option in the early resolution of malignancy-related hypercalcemia.
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PMID:Severe Hypercalcemia in a Child With Acute Lymphoblastic Leukemia Relapse: Successful Management With Combination of Calcitonin and Bisphosphonate. 2690 50

BACKGROUND Paraneoplastic hypercalcemia is a well-described complication associated with a variety of malignancies. However, its incidence in gynecological malignancies is low. CASE REPORT A 53-year-old woman presented with progressive abdominal distention and irregular vaginal bleeding of several weeks' duration. A contrast CT abdomen and pelvis was significant for a mass in the lower uterine/cervical region, multiple peritoneal and omental masses, enlarged pelvic and paraaortic lymph nodes, and large-volume ascites. A pelvic exam revealed a fungating vaginal mass, with biopsy showing a high-grade tumor with immunohistochemical staining positive for vimentin, CD10, and cyclin D1, consistent with endometrial stromal sarcoma. During her hospitalization, the patient became increasingly lethargic. Workup showed severe hypercalcemia and evidence of acute kidney injury. The patient did not have evidence of bony metastatic disease on imaging studies. Further laboratory evaluation revealed an elevated PTHrP of 301 pg/mL (nl 14-27), a depressed PTH level of 3 pg/mL (nl 15-65), and a depressed 25-OH vitamin D level of 16 ng/mL (nl 30-100), consistent with humoral hypercalcemia of malignancy. The patient was treated with pamidronate, calcitonin, and intravenous fluids. She eventually required temporary hemodialysis and denosumab for refractory hypercalcemia, which improved her electrolyte abnormalities and clinical status. CONCLUSIONS Uterine malignancies of various histologies are increasingly recognized as a cause of humoral hypercalcemia. They are an important differential diagnosis in a woman with hypercalcemia and abnormal vaginal bleeding or abdominal symptoms.
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PMID:Humoral Hypercalcemia in Uterine Cancers: A Case Report and Literature Review. 2805 13


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