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.