RESUMO
The aim of the present study was to investigate the molecular characteristics of hereditary multiple osteochondromas (HMO) in a subset of Jordanian patients with a focus on the genetic variants of exostosin (EXT1)/(EXT2) and their protein expression. Patients with HMO and their family members were included. Recorded clinical characteristics included age, sex, tumors number and location, joint deformities and associated functional limitations. Mutational analysis of EXT1 and EXT2 exonic regions was performed. Immunohistochemical staining for EXT1 and EXT2 was performed manually using two different commercially available rabbit anti-human EXT1 and EXT2 antibodies. A total of 16 patients with HMO from nine unrelated families were included, with a mean age of 13.9 years. A total of 75% (12/16) of the patients were male and (69%) (11/16) had a mild disease (class I). EXT mutation analysis revealed only EXT1 gene mutations in 13 patients. Seven variants were detected, among which three were novel: c.1019G>A, p. (Arg340His), c.962+1G>A and c.1469del, p. (Leu490Argfs*9). Of the 16 patients, 3 did not harbor any mutations for either EXT1 or EXT2. Immunohistochemical examination revealed decreased expression of EXT1 protein in all patients with EXT1 mutation. Surprisingly, EXT2 protein was not detected in these patients, although none had EXT2 mutations. The majority of Jordanian patients with HMO, who may represent an ethnic group that is infrequently investigated, were males and had a mild clinical disease course; whereas most patients with EXT1 gene mutations were not necessarily associated with a severe clinical disease course. The role of EXT2 gene remains a subject of debate, since patients with EXT1 mutations alone did not express the non-mutated EXT2 gene.
RESUMO
Giant cell tumor of bone is a benign tumor with an aggressive behavior. Its typical subarticular location and high recurrence risk can be associated with significant morbidity. Although benign, it can rarely metastasize especially to the lungs. Also, it can be multicentric in less than 1% of patients. Late malignant transformation, although rare, can occur with a very poor prognosis. This series reports on these unusual and challenging features and management considerations of giant cell tumor of bone. This retrospective study included review of the medical records of patients with a confirmed histopathological diagnosis of giant cell tumor of bone. A total of 25 patients (16 females and 9 males) with a mean age of 34.5 years were included; 22 had primary tumors, while 3 were referred with recurrent tumors. Pain was the most common presenting symptom. Most patients had grade III tumors. Tumors around the knee were the most common. Multicentric tumors were detected in three patients. Twenty-three patients (20 primary giant cell tumor of bone and 3 with recurrence) received treatment. Most patients (15/23) were treated with intralesional curettage with or without adjuvants. Seven patients had wide excision. Recurrence was seen in 45% (9/20) of primary giant cell tumor of bone especially with difficult anatomical locations. Most recurrences occurred more than 4 years after treatment. Pulmonary nodules were detected in four patients; two of them showed resolution during follow-up. One patient developed secondary sarcoma transformation with a fatal outcome. Giant cell tumor of bone was more common in females. Long bones were more affected, especially around the knee. Intralesional curettage was the most frequently used treatment. Recurrence was associated with inadequate tumor resection (especially in difficult anatomical location), younger age, male gender, and advanced local tumor grade. Denosumab can be used in the treatment of pulmonary metastasis, multicentric and recurrent giant cell tumor of bone. Due to late recurrence and malignant transformation, a prolonged follow-up is warranted.