Lymphoma with hypercalcemia

Case Reports in Endocrinology, 2014

The most common cause of hypercalcemia in hospitalized patients is malignancy. Primary hyperparathyroidism most commonly causes hypercalcemia in the outpatient setting. These two account for over 90% of all cases of hypercalcemia. Hypercalcemia can be divided into PTH-mediated and PTH-independent variants. Primary hyperparathyroidism, familial hypocalciuric hypercalcemia, familial hyperparathyroidism, and secondary hyperparathyroidism are PTH mediated. The most common PTH-independent type of hypercalcemia is malignancy related. Several mechanisms lead to hypercalcemia in malignancy-direct osteolysis by metastatic disease or, more commonly, production of humoral factors by the primary tumor also known as humoral hypercalcemia of malignancy that accounts for about 80% of malignancy-related hypercalcemia. The majority of HHM is caused by tumor-produced parathyroid hormone-related protein and less frequently production of 1,25-dihydroxyvitamin D or parathyroid hormone by the tumor. We r...

Clinical Lymphoma Myeloma and Leukemia, 2018

Introduction: The etiology of hypercalcemia in non-Hodgkin lymphoma (NHL) is most often attributed to either elevated serum levels of 1,25-dihydroxycholecalciferol (calcitriol) or parathyroid-related protein (PTHrP). In a single center retrospective review we evaluated the incidence of and outcomes associated with hypercalcemia in NHL. Methods: Medical records of patients with a histologically confirmed diagnosis of NHL and at least one episode of hypercalcemia were evaluated for demographic and lymphoma-specific factors including response to therapy and overall survival. Results: Fifty-four patients with NHL met inclusion criteria. The majority of patients (57.4%) had diffuse large B-cell lymphoma, and of these 70% were of the non-germinal center subtype. Approximately half (42.6%) of the included cases had serologic investigation into the etiology of hypercalcemia but only 17 (31.5%) patients had both a serum PTHrP and calcitriol level properly collected. Of the 17 cases in which both a serum calcitriol and PTHrP were collected, the majority (61.1%) were found to have neither an elevation of serum calcitriol nor an elevation in PTHrP. The degree of calcitriol elevation was found to correlate with worse progression free (p = 0.04) but not overall survival. Conclusions: The major mechanism by which non-Hodgkin lymphoma patients develop hypercalcemia is not mediated by calcitriol or PTHrP. Hypercalcemia is most prevalent in DLBCL patients of the non-germinal cell subtype. Patients with calcitriolmediated hypercalcemia have a trend toward worse outcomes, suggesting that calcitriol may be a marker of high-grade lymphoma, transformation to such, or a surrogate for more advanced disease.

Journal of the Medical Association of Thailand = Chotmaihet thangphaet, 2007

Examine the clinical and biochemical features including serum intact PTH (iPTH) and plasma PTH-related peptide (PTHrP) levels in patients with malignancy-associated hypercalcemia (MAHC). Forty-eight patients with histopathological or cytological proven malignancies and MAHC who were admitted to Siriraj Hospital were studied. The malignancies that caused MAHC were squamous cell carcinoma (45.8%), non-squamous cell solid tumors (31.3 %), and hematological malignancies (22.9%). Most patients (93.8%) had advanced stage malignancies. Corrected serum total calcium (cTCa) levels were 10.8-19.1 mg/dL (13.6 +/- 2.4) and severe hypercalcemia was observed in 17 cases (40.5%). Serum iPTH levels were 0.95-17.1 pg/mL (3.9 +/- 3.6). Most patients had suppressed serum iPTH levels of < 10 pg/mL. Plasma PTHrP levels were 0.2-44.0 pmol/L (3.8 +/- 6.8). There were 27 cases (56.3%) that had humoral hypercalcemia of malignancy (HHM) with plasma PTHrP levels of > 1.5 pmol/L, and 22 cases had squamou...

Annals of Hematology, 2020

The prognostic significance of hypercalcemia in lymphoma has only been studied on small series to date. We conducted a retrospective, monocentric, matched-control study that aimed to compare the outcome of patients diagnosed with any histological subtype of lymphoma associated with hypercalcemia, at diagnosis or relapse, with a group of controls matched for histological and prognostic factors. Sixty-two and 118 comparable patients treated between 2000 and 2016 were included in hypercalcemia and control cohorts, respectively. Hypercalcemia was found mainly at diagnosis (71%) in higher-risk patients (prognosis scores ≥ 3, 76%) and those with diffuse large B cell lymphoma (67.7%), stage III/IV disease (91.9%), and elevated LDH (90.3%). Twoyear progression-free survival (PFS) was shorter in the hypercalcemia than control cohort [30.1% (95% confidence interval (95% CI) 18.3-41.9) vs 63.9% (95% CI 5.1-72.7), p < 0.001]. Two-year overall survival (OS) was 40.6% (95% CI 28.1-53.1) and 77.7% (95% CI 70.1-85.3) in the hypercalcemia and control cohorts, respectively (p < 0.001). Hypercalcemia was independently associated with poor PFS [HR = 2.5 (95% CI 1.4-3.5)] and OS [HR = 4.7 (95% CI 2.8-7.8)] in multivariate analysis. Among the 40 patients who received autologous stem cell transplantation (ASCT), hypercalcemia was still associated with shorter OS [2year OS: 65% (95% CI 40.1-89.9) vs 88.0 (95% CI 75.3-100), p = 0.04]. Hypercalcemia may be associated with chemoresistance, given its impact on PFS and OS. Hence, these data suggest that alternate strategies for lymphoma patients with hypercalcemia should be developed.

T-Cell Leukemia, 2011

Journal of medical case reports, 2018

Angioimmunoblastic T cell lymphoma is a rare malignancy, accounting for only 2% of all non-Hodgkin lymphomas, first described in the 1970s and subsequently accepted as a distinct entity in the current World Health Organization classification. Due to the paucity of this disease, there is still no identifiable etiology, no consistent risk factors, and the pathogenesis remains unclear. An 83-year-old Caucasian man presented to an emergency department with palpitations and was found to have atrial fibrillation. During his hospitalization, he was found to have asymptomatic hypercalcemia with corrected calcium of 11.7. Ten days later while in rehabilitation, he started complaining of progressive fatigue and altered mental status was noted. He was found to have a calcium level of 15.5 and was admitted to the intensive care unit for management and further workup. He was found at that time to have, parathyroid hormone: &lt; 1; 25 hydroxyvitamin D: 74; 1,25 dihydroxyvitamin D: 85.4; angiotens...

The American Journal of Medicine, 1978

American Journal of Pathology, 2001

The majority of patients with adult T-cell leukemia/ lymphoma (ATL) resulting from human T-cell lymphotropic virus type-1 (HTLV-1) infection develop humoral hypercalcemia of malignancy (HHM). We used an animal model using severe combined immunodeficient (SCID)/beige mice to study the pathogenesis of HHM. SCID/beige mice were inoculated intraperitoneally with a human ATL line (RV-ATL) and were euthanized 20 to 32 days after inoculation. SCID/beige mice with engrafted RV-ATL cells developed lymphoma in the mesentery, liver, thymus, lungs, and spleen. The lymphomas stained positively for human CD45RO surface receptor and normal mouse lymphocytes stained negatively confirming the human origin of the tumors. The ATL cells were immunohistochemically positive for parathyroid hormone-related protein (PTHrP). In addition, PTHrP mRNA was highly expressed in lymphomas when compared to MT-2 cells (HTLV-1-positive cell line). Mice with lymphoma developed severe hypercalcemia. Plasma PTHrP concentrations were markedly increased in mice with hypercalcemia, and correlated with the increase in plasma calcium concentrations. Bone densitometry and histomorphometry in lymphoma-bearing mice revealed significant bone loss because of a marked increase in osteoclastic bone resorption. RV-ATL cells

British Journal of Haematology, 1996

The incidence of hypercalcaemia and its association with humoral mechanisms involving parathyroid hormone-related protein (PTHrP), parathyroid hormone (PTH), or 1,25(OH) 2 vitamin D were assessed in a prospective study of patients admitted to a clinical haematology unit. Hypercalcaemia was detected in 18/165 patients, and was due to primary hyperparathyroidism in 3/17 patients in whom results of humoral mediator assessments were obtained. In the other patients, hypercalcaemia was associated in nine instances with myeloma, in five with B-cell non-Hodgkin's lymphoma (NHL), and in one with myeloid neoplasia. No evidence was obtained of a humoral mechanism involving 1,25(OH) 2 vitamin D, but elevated circulating levels of PTHrP, comparable with those in humoral hypercalcaemia of malignancy, were present in 2/4 patients with NHL, and in 3/9 with myeloma. The relationship between presence or absence of elevated circulating PTHrP, and presence or absence of hypercalcaemia during the course of treatment, indicated PTHrP was involved in the production of hypercalcaemia. Such an association raises the possibility that PTHrP released by neoplastic cells in these disorders acts in a paracrine manner to produce local bone resorption, and when produced in greater amounts causes elevated circulating levels which make an additional humorally-mediated contribution to the development of hypercalcaemia.

Hormone and Metabolic Research

Hypercalcemia of malignancy is the most common life-threatening metabolic disorder in patients with advanced stage cancers and is a sign of poor prognosis. It usually presents with markedly elevated calcium level and is severely symptomatic. It is associated with hematological malignancies, such as multiple myeloma, non-Hodgkin lymphoma, leukemias and solid cancers, particularly renal and breast carcinomas as well as squamous cell carcinomas of any organ. Several mechanisms have been implicated in the development of hypercalcemia of malignancy amongst them the osteolytic related hypercalcemia, parathyroid hormone-related peptide (PTHrP) mediated hypercalcemia, extrarenal 1,25 dixydroxyvitamin D (calcitriol) mediated hypercalcemia and parathyroid hormone (PTH) related hypercalcemia either ectopic in origin or in patients with parathyroid carcinoma. Clinical history and and physical examination could point towards the correct diagnosis confirmed by the above-mentioned biochemical medi...