A 2-year-old Brazilian white male toddler weighing 11.8kg - previously healthy - presented with vomiting after meals, muscular weakness, generalized pain, abdominal cramps, intestinal constipation and inappetence that had begun 25 days prior to his first examination. There was no relevant information about family history.
He was admitted to the pediatric intensive care unit dehydrated, pallid, referring generalized pain, mainly on legs, arms and in abdomen, and was almost unable to walk. At first, the staff thought it could be sepsis or some endocrinological disorder. However, the initial laboratory tests showed heightened ionic calcium levels in the blood (2.95 mmol/L; normal: 1.11 to 1.40 mmol/L). Other laboratory analyses showed hemoglobin: 9.5 g/mL, white blood cell count: 9,460 cells/mm3, platelet count: 206,000/mm3. Urinalysis showed an elevated leukocyte presence (100 leukocytes/field; normal: < 10/field).
As soon as we received the results of the calcium analysis we submitted the patient to a pelvic X-ray to check calcification status. The X-ray revealed substantial osteolysis ( Figure 1).
We started treatment for hypercalcemia with hydration and low doses of furosemide (1mg/kg/day divided into 3 doses, duration 2 days) in order to raise the calcium excretion by the kidneys . We decided to start pamidronate (0.5mg/kg/day, duration 3 days) - a second-generation bisphosphonate class drug - to stop the osteolysis by the inhibition of calcium resorption . The symptoms of hypercalcemia subsided and the patient improved.
Subsequent laboratory analysis showed that PTH was low at 8 pg/mL (normal: 10 to 65 pg/mL), calcitonin was normal at 8 pg/mL (normal: less than 12 pg/mL) and 1, 25(OH) 2D3 was low at 21 ng/mL (normal: 30 to 60 ng/mL).
A myelogram was performed and was compatible with acute leukemia. The immunophenotype showed the presence of immature T-type cells that expressed intracytoplasmic CD3 antigens, CD7, CD5, CD1a and partial terminal deoxynucleotidyl transferase (TdT). The presence of CD45 at moderately high levels and a lack of CD2 expression in the studied cells were also observed.
The patient underwent chemotherapy based on the standard Berlin-Frankfurt-Munich (BMF) protocol for pediatric ALL. Complete clinical remission occurred after the first cycle of chemotherapy. As a result, calcium levels returned to normal (ionic calcium: 1.2 mmol/L).
Seven months after starting treatment, fever and bacteremia occured, with no associated neutropenia. An infectious disease screen was performed (blood and urine cultures included), and chest x-ray revealed multiple dense nodular structures. A CT scan confirmed structures resembling calcium nodules not exceeding 1 cm in diameter with peribronchovascular distribution, affecting both lungs mainly in the inferior lobes ( Figure 2). Plasma calcium levels (ionized calcium: 1.2 mmol/L) were normal at that time. Tests for fungal infection, and specifically for Aspergillus spp., gave negative results. We also tested for Cryptococcus neoformans (agglutination test), Cytomegalovirus spp. (antigenemia), tuberculosis (three gastric lavages) and respiratory viruses (nasal secretion tests), with all negative results. The patient had no respiratory symtoms or hypoxemia. Despite the negative results, while the search for an infectious agent was ongoing, he received empiric antibiotic therapy, cefepime (150mg/kg/day) and vancomycin (60mg/kg/day) for 10 days, and lipossomal amphotericin B (5mg/kg/day) for 7 days.
The patient was free from infectious or respiratory disorders. Therefore we attributed the nodules observed in the CT images ( Figure 2) to previous hypercalcemia which possibly led to a process of pulmonary alveolar calcification. We did not perform a biopsy, since we saw no benefit to the patient of doing so.
Presently the patient is on maintenance chemotherapy with methotrexate (20mg/m2/once a week) and 6-mercaptopurine (50mg/m2/day) completing 106 weeks of treatment.
Thorax CT scan: pulmonary alveolar calcification.