Anaplastic large cell lymphoma, with 1,25(OH)2D3-mediated hypercalcemia: A case report

Abstract

Hypercalcemia due to malignant tumors including malignant lymphomas is relatively common. Among cancer patients with hypercalcemia, humoral hypercalcemia of malignancy is the most common and accounts for about 80% of all cases with hypercalcemia. 1,25-dihydroxyvitamin D_³(1,25(OH)_²D_³)-mediated hypercalcemia is relatively rare. Although malignant lymphoma has been also reported to cause 1,25(OH)_²D_³-mediated hypercalcemia, it is not known whether there is any association between 1,25(OH)_²D_³-mediated hypercalcemia and any specific histological type of malignant lymphoma. We herein report a case of an anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK) -negative with 1,25(OH)_²D_³-mediated hypercalcemia, which has never been previously reported. An 80-year-old Japanese man was admitted to our department due to acute exacerbation of hypercalcemia. He was diagnosed with ALCL, ALK-negative. Serum 1,25(OH)_²D_³ level was high and seemed to be associated with the lymphoma because the serum calcium and 1,25(OH)_²D_³ levels improved in response to chemotherapy. Histological findings showed that many CD68 positive macrophages were observed in the microenvironment of tumor cells. Lymphoma cells or tumor microenvironmental cells may produce 1,25(OH)_²D_³ because several previous reports showed the source of 1,25(OH)_²D_³ can be either lymphoma or tumor microenvironmental cells. Moreover, because 1,25(OH)_²D_³-mediated hypercalcemia has been reported regardless of the specific histological type of lymphoma, tumor microenvironmental cells may be involved in this condition. However, we could not identify the source of 1,25(OH)_²D_³ in this case. The association between 1,25(OH)_²D_³ production and prognosis in malignant lymphomas is yet unknown; further studies are needed to elucidate the clinical characteristics of malignant lymphoma with 1,25(OH)_²D_³-mediated hypercalcemia.

Keywords: 1,25-dihydroxyvitamin D3; anaplastic large cell lymphoma; hypercalcemia.

Fig. 1

Systemic computed tomography (CT) scan images on admission. Systemic CT scan showed lymphadenopathies at (A) right neck, right supraclavicular, superior mediastinal, and right axillary lymph nodes; (B) under tracheal branch; and (C) under tracheal branch. Evident neoplastic bone lesions were not found.

Fig. 2

Pathological images of cervical lymph node biopsy on the 5th hospital day. Hematoxylin-eosin (HE) staining showed large atypical lymphocytes growing in the tissue. Immunostaining revealed that tumor cells were CD3(-), CD20(-), CD4(+), CD8(-), CD30(+), ALK(-), TIA-1(+), PAX5(-), CD68(-), AE1/AE3(-) and Granzyme B(-). CD68-positive histiocytes were observed around the tumor cells.

Fig. 3

Transition of lactate dehydrogenase (LDH), soluble interleukin-2 receptor (sIL2-R), corrected serum calcium (corrected Ca), and 1,25-dihydroxyvitamin D_³ (1,25(OH)_²D_³). Corrected Ca and 1,25(OH)_²D_³ are improved in parallel with LDH and sIL2-R. Day 1 is the date of hospitalization. THP: therarubicin, CPA: cyclophosphamide, VCR: vincristine, PSL: prednisolone, PA: partial response, CR: complete response.

Fig. 4

¹⁸F-fluorodeoxy glucose positron emission tomography (FDG-PET) images after 6th cycle of THP-COP therapy. FDG-PET showed that lymphadenopathy at (A) right neck, right supraclavicular, superior mediastinal, and right axillary lymph nodes; (B) subcarinal lymph nodes; and (C) pancreas head had disappeared. No significant accumulations of FDG were observed (D). We confirmed complete metabolic response.