Kitazawa Riko, Kitazawa Sohei, Kajimoto Kazuyoshi, Sowa Hideaki, Sugimoto Toshitsugu, Matsui Tosimitsu, Chihara Kazuo, Maeda Sakan
Division of Molecular Pathology Kobe University Graduate School of Medicine, Kobe, Japan.
Pathol Int. 2002 Jan;52(1):63-8. doi: 10.1046/j.1440-1827.2002.01314.x.
Multiple myeloma is a plasma cell neoplasia often associated with multiple skeletal lesions and hypercalcemia. Several cytokines, including interleukin (IL)-1, IL-6 and tumor necrosis factor-beta (TNF-beta), derived from myeloma cells are thought to accelerate osteoclastic bone resorption and cause hypercalcemia through a paracrine mechanism. We report on a case of a 69-year-old man with multiple myeloma associated with hypercalcemia and advanced osteolytic lesions. After bisphosphonate treatment and MP (melphalan and prednisolone) therapy, the patient's serum calcium level was successfully but transiently recovered to the normal range. Biochemical analysis showed a remarkable increase in serum parathyroid hormone-related protein (PTHrP; 3.7 pmol/L) and IL-6 (22.0 pg/mL). On the other hand, parathyroid hormone and 1alpha,25(OH)2 vitamin D3 were suppressed. By immunohistochemistry and in situ hybridization on aspiration-biopsied bone marrow clot sections, PTHrP mRNA and protein were detected in the cytoplasm of myeloma cells. The rate of PTHrP-positive myeloma cells was estimated to be at least one-third. Since PTHrP can, as an endocrine factor, systemically act on bone and kidney, hypercalcemia in this case might have been caused through both local osteolytic hypercalcemia and humoral hypercalcemia of malignancy mechanisms.
多发性骨髓瘤是一种浆细胞肿瘤，常伴有多处骨骼病变和高钙血症。骨髓瘤细胞产生的几种细胞因子，包括白细胞介素（IL）-1、IL-6和肿瘤坏死因子-β（TNF-β），被认为通过旁分泌机制加速破骨细胞骨吸收并导致高钙血症。我们报告一例69岁男性，患有多发性骨髓瘤并伴有高钙血症和晚期溶骨性病变。在双膦酸盐治疗和MP（美法仑和泼尼松龙）治疗后，患者的血清钙水平成功但短暂恢复到正常范围。生化分析显示血清甲状旁腺激素相关蛋白（PTHrP；3.7 pmol/L）和IL-6（22.0 pg/mL）显著升高。另一方面，甲状旁腺激素和1α,25(OH)2维生素D3被抑制。通过对抽吸活检骨髓凝块切片进行免疫组织化学和原位杂交，在骨髓瘤细胞的细胞质中检测到PTHrP mRNA和蛋白。PTHrP阳性骨髓瘤细胞的比例估计至少为三分之一。由于PTHrP作为一种内分泌因子可全身作用于骨骼和肾脏，该病例中的高钙血症可能是通过局部溶骨性高钙血症和恶性肿瘤的体液性高钙血症机制共同引起的。
