Familial Paget’s disease accounts for about 20% of PDB cases, and it is often found to segregate in an autosomal dominant pattern. Mutations of p62/sequestosome 1 gene (SQSTM1/p62) account for familial forms of PDB.
It is well known that the presentation of familial PDB is most frequently poliostotic than in sporadic cases, and that levels of alkaline phosphatase are frequently higher.
From PDB diagnosis, patient was treated with antireabsorptive therapy. There are four general indications for treatment of Paget’s disease: symptoms due to metabolically active Paget’s disease such as bone pain or neurological syndromes; patient planning to undergo elective surgery on a pagetic site; the management of hypercalcemia, a rare occurrence following prolonged immobilization; finally, some investigators believe that treatment is indicated as an attempt to decrease local progression and reduce the risk of future complications. Nowadays pharmacological treatment is based upon the use of bisphosphonates.
Bisphosphonates approved by the US Food and Drug Administration for the treatment of Paget’s disease include pamidronate, which is given intravenously, and etidronate, tilu- dronate, alendronate and risedronate, all of which are taken orally. Clodronate, though not approved for treatment of Paget’s disease in many countries, has been successfully used. Daily infusions of clodronate 300 mg for 5 days have showed the ability to significantly reduce disease activity. Our patient was repeatedly treated with clodronate infusions with a satisfying clinical and biochemical response during the past years.
Investigators have recognized that secondary resistance to individual bisphosphonates can occur. Therefore, it may be necessary for a patient to use more than one bisphosphonate in long-term management of the disease. In this patient, after the diagnosis of osteosarcoma was made, we used pamidronate to obtain both an antiresorptive effect and a reduction of pain.
It is important to search and diagnose all familial cases of Paget’s disease of bone in order to treat them and to avoid the occurrence of future severe complications in these subjects. In fact, a number of complications may result from Paget’s disease. Of these, the most devastating is a transformation of the bone that becomes cancerous. Osteosarcoma or other types of sarcoma occurs in less than 1 percent of patients with Paget’s disease, with a significantly higher rate than in non-PDB individuals. Malignant complication is mostly described over 70 years of age, after a large number of years from PDB diagnosis, and it is often rapidly progressive with early metastasis and death.
Osteosarcoma is the most common type of Paget’s sarcoma. Skeletal distribution of these tumors mirrors that of Paget’s disease. A patient presents with the sudden onset of a mass and/or severe pain at the site of previously-asymptomatic Paget’s disease. Frequently, this presents as a pathologic fracture. Pain is the most reliable indicator of malignant transformation in Paget’s disease.
Figure 2 – Histologic features of bone biopsy: osteoid matrix in which there is a proliferation of spindle cells with atypia, with irregular nuclei.
In the case of our patient, the symptom of presentation was bone pain, at first misdiagnosed as a possible reactivation of the pagetic lesion, but subsequently suspected as a malignant evolution.
On radiograph, there is development of a radiolucent, destructive process within a well-established area of pagetic bone. The early, destructive phase of Paget’s can be confusing. Multiple, small radiolucencies are less suggestive than a single, large area. The lucencies must be clearly destructive and progressive to reliably indicate malignant transformation. On isotope scan, it is often difficult to distinguish between the increased uptake in the lesion and that seen in Paget’s disease. This study is not helpful unless there is a dramatic change.
Preoperative evaluation of the extent of local disease was performed with MRI. Don’t let the pharmacy companies beat you. Buy cheap ventolin inhalers online
Diagnosis is based and confirmed on biopsy (Figure 2). Microscopic features are strikingly varied within a single lesion. Areas of high-grade, classic osteosarcoma can usually be found but are often overshadowed by other areas of undifferentiated spindle cells, fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, and even giant cell tumor. For this reason, some prefer to call the lesion “Paget’s sarcoma” rather than osteosarcoma. The lesional cells often infiltrate the adjacent, Pagetic bone, and plugs of tumor are frequently seen within the large, vascular channels peculiar to Pagetic b o n e .
After the diagnosis of sarcoma has been made, a thorough search for evidence of intrathoracic disease should be performed because pulmonary nodules are the most common site of metastatic disease for both soft tissue and bone sarcomas. If chest radiographic findings are normal, chest computed tomography should be performed. The discovery of metastatic disease clearly influences decisions about the need to subject the patient to aggressive local therapy to achieve long-term local control.
Surgical treatment, when possible, is indicated. Radical margins, usually amputation, are required for reliable, local control. The prognosis, even with local control, is dismal. In our patient the site of the lesion would have required a destructive operation, furthermore, the presence of pulmonary metastasis contraindicated surgical excision. Chemotherapy is currently used, but when dealing with os- teosarcoma in Paget’s disease, response to chemotherapy is generally much less positive than with classic osteosarcoma. It seldom provides meaningful alteration in the rapid, downhill course and is often devastating to the remaining lifestyle in this age group. Two randomized clinical studies have documented significant benefit using adjuvant chemotherapy in patients presenting with osteogenic sarcoma.
In conclusion, at the moment prognosis of bone sarcoma in PDB remains generally poor due to late and difficult diagnosis, high grade of malignancy of the tumors, difficulties at their surgical removal and the old age of patients. The particularity of the case presented above was the early occurrence of bone sarcoma in a case of polyostotic Paget’s disease with a family history segregating in an autosomal dominant pattern.