Malignant transformation of phosphaturic mesenchymal tumor: a case report and literature review

Abstract

Phosphaturic mesenchymal tumor, mixed connective tissue variant (PMT-MCT) causes tumor-induced osteomalacia (TIO). Most cases follow a benign clinical course, with rare occurrences of malignant transformation. We report a case of malignant PMT-MCT and review previous malignant cases to identify predictive factors for transformation. A 13-yr-old female, who presented with hypophosphatemic rickets, elevated serum intact fibroblast growth factor 23 (FGF23) levels, and a nodule in the back, received a diagnosis of TIO because of the benign PMT histopathology. After resection of the primary tumor, regular imaging analyses did not indicate any relapse. At 17 years of age, a tumor developed in the left leg and increased in size. The resected tumor showed a histopathology of pleomorphic sarcoma positive for the TP53 mutation. Despite amputation of the affected leg, the patient died due to multiple metastases at 18 years of age. A literature review revealed that 14 out of 15 reported malignant PMT-MCT tumors occurred in adults, and found no predictive factors for malignant transformation and treatment outcome. Changes in size or number of the tumors along with intact FGF23 levels have been considered as the only sign of malignant transformation. This pediatric case report and literature review indicate the need for prolonged regular monitoring for PMT-MCT.

Keywords: FGF23; malignant phosphaturic mesenchymal tumor-mixed connective tissue variant (PMT-MCT); tumor-induced osteomalacia.

Fig. 1.

(A) Plain X-ray images of bilateral knee joints of the patient at 11 yr of age: arrow heads indicate the rachitic changes. (B) Hematoxylin-eosin staining of the primary tumor: The histopathology of the tumor shows proliferation of spindle to oval-shaped cells with mild nuclear atypia and eosinophilic cytoplasm arranged in fascicular pattern with an absence of mitosis. (C) Immunohistochemical staining of fibroblast growth factor 23 (FGF23) shows immunopositive reactivity of the tumor cells for FGF23. (D, E) ⁶⁸Ga-DOTATOC-PET CT imaging revealed multiple tumors in the lung fields, right forearm, right thigh and left tibia (arrows).

Fig. 2.

Sequential levels of serum fibroblast growth factor 23 (FGF23) levels during the observation. FGF23 levels were plotted from the sampled sites of upper extremity (○), right upper extremity (), left upper extremity (), right lower extremity (×), and left lower extremity (+). Serum FGF23 levels increased to 3100 pg/ml despite the resection of lesions in the trapezius muscle, right thigh and left tibia, and decreased to 1180 pg/ml prior to amputation of her left leg. Values higher than 800 pg/ml were measured after dilution of the samples; hatched area indicates the standard range of FGF23 in healthy subjects (16–69 pg/ml). Surgical intervention has been indicated in the upper panel of the figure, and clinical events have been shown below the horizontal axis.

Fig. 3.

(A) The swollen left leg (arrow head) shows (B) histopathology of the tumor in the leg at 17 yr of age. Tumor shows a diffuse sheet-like growth pattern with oval to spindle-shaped or polygonal cells possessing hyperchromatic and pleomorphic nuclei and occasional multinucleated giant cells. Numerous mitotic figures have been identified. (C) CT scan image of the abdomen shows a large mass at the head of pancreas (arrow heads). (D) PET CT scan image of body shows multiple positive lesions in the left lung, head of pancreas, right ovary and left inguinal lymph nodes (arrows). (E) CT scan image of the brain shows a mass measuring 35 mm × 29 mm, suggesting intracranial metastasis (arrow heads).