Discussion
Hypercalcemia is a relatively common clinical problem. Among all causes of hypercalcemia, primary hyperparathyroidism and malignancy are the most common, accounting for greater than 90 percent of cases [5]. It is often not difficult to differentiate both conditions, as malignancy is usually clinically evident by the time hypercalcemia appears, and patients with hypercalcemia of malignancy usually have higher calcium concentrations and are more symptomatic than those with primary hyperparathyroidism [5].
Our patient presented with a malignant hypercalcemia with low parathyroid hormone and normal calcitriol levels along with hyperphosphatemia and increased rPTH. After performing a thoraco-abdominal scan, our first hypothesis was a solid tumor but the origin was difficult to determine. The presence of an extensive abdominal calcinosis and adenopathies prompted us to initially suspect a gastrointestinal origin. To establish the diagnosis, and after medical discussion, a peritoneal carcinosis nodule biopsy was performed and found to be consistent with diffuse large-cell B lymphoma once the patient was already in the intensive care unit. This result was not expected as calcitriol was normal, he presented a non-hypermetabolic splenomegaly linked with his known CMML and rPTH was increased.
Diffuse large B cell lymphoma (DLBCL) is the most frequent subtype of lymphoma in western countries [6,7]. However, the prevalence of hypercalcemia and its prognostic value remain unclear. Previous studies in NHL reported a prevalence of hypercalcemia ranging from 7-14%, but these studies included different subtypes and often considered the development of hypercalcemia during the entire disease course and not only at diagnosis. [6] In contrast, Gauchy et al conducted a study showing that hypercalcemia is not uncommon in newly diagnosed DLBCL and was associated with a poor clinical outcome [6]. Abadi et al also reported a prevalence of 18% in the novo DLBCL patients from two referral centers [2].
Regarding the etiology of hypercalcemia, some patients with DLBCL may present with hypercalcemia secondary to hyperparathyroidism and not lymphoma related. Previous studies have shown that levels of calcitriol are often increased in these patients [1,2], but this was not the case in the patient reported. Notably, it is rare to find ectopic secretion of PTH by a neoplastic clone as the cause of hypercalcemia [2]. The presence of low levels of calcitriol and increased levels of PTHrP made us search initially for a solid tumor delaying the diagnosis and therefore the specific treatment. Hypercalcemia secondary to the production of PTHrP as seen in our case is unusual [1,2], with only limited cases reported.
Another intriguing clinical feature of this case was the development of Diffuse large B cell lymphoma in a patient previously diagnosed with CMML. CMML arises from the combination of hypersensitivity of myeloid precursors to granulocyte‐macrophage colony‐stimulating factor, myeloid cell dysplasia, and ineffective hematopoiesis [8]. There are only a few cases in which CMML is associated with other hematological conditions, including lymphoproliferative diseases such as monoclonal gammopathy of uncertain significance (MGUS), monoclonal B‐cell lymphocytosis (MBL), multiple myeloma (MM), and non‐Hodgkin T‐ and B‐cell lymphomas as in this case [8,9]. CMML is an uncommon myeloid disorder that is rarely associated with NHL[8]. Romano et al described a case with synchronous chronic myelomonocytic leukemia and diffuse large b-cell lymphoma[8].
Conclusions: The etiologic diagnosis of hypercalcemia is a challenge in clinical practice, especially when the initial results are not in favor of what is described in the literature, often leading to a delay in diagnosis, treatment, and poorer prognosis. Hypercalcemia in newly diagnosed patients with diffuse large B lymphoma may be due, albeit rarely, to PTHrP production and is associated with a worse prognosis. Coexistence of chronic myelomonocytic leukemia and diffuse large B lymphoma is unusual.
Conflicts of Interests: The Authors declare that there are no competing interests.
Patient Consent : Authors obtained the consent from the patient’s family.