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| Discussion |
CLINICAL
PROFILE:
A 32-year-old man came with complaints of generalized weakness and bilateral hip pain since one year.
Radiographs of the pelvis with both the hips performed elsewhere was normal (Fig. 1).
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Fig 1 |
The pain increased gradually and progressively over a period of sixth months and progressed to such an extent that the patient was bedridden since the past one month. The patient was referred to the orthopedic department of our hospital. A repeat radiograph of the pelvis with hips was performed.
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Fig 2 |
The radiograph reveals diffuse osteopenia. There is cortical thinning with hazy and indistinct margins involving both femoral shafts. Looser‘s zones involving the infero-medial aspect of femoral necks on both sides are seen. There is mild reduction in the joint space - predominantly involving superior compartment of both the hip joints
On the basis of the above findings, a diagnosis of osteomalacia was made.
To confirm the diagnosis and to evgaluate the cause of osteomalacia, biochemical assays were performed. The serum phosphorus level was low and alkaline phosphatase level was elevated. Serum calcium and the parathyroid hormone levels were normal.
The patient was treated with vitamin D, calcium and phosphorus. However, there was no symptomatic or radiological improvement. The serum phosphorus levels remained persistently low.
In the mean time, an MRI of both hips was performed.
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Fig 3 |
MRI reveals generalised osteopenia with a linear T1 hypointense signal along the antero-superior margin of the right femoral head suggestive of a crescent. A fracture of right femoral neck with sclerosis of the fractured margins and incomplete sub-capital fracture of left femoral neck is seen. There is was mild flattening of the left femoral head. These findings suggested avascular necrosis of the femoral heads stage II on right side and stage III on left side.
Based on these findings, a diagnosis of Vitamin D resistant osteomalacia was made and a PET scan was done to rule out occult tumour.
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Fig 4 |
The PET scan reveals a 2.2 cm diameter hypermetabolic nodule on medial side of the upper 1/3 of the right thigh.
The diagnosis of oncogenic osteomalacia was suggested which was confirmed by markedly raised serum FGF- 23 levels (673 RU/ml).
For accurate localization and characterization of the nodule, MRI of the thigh was performed.
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Fig. 5 STIR Coronal |
Fig. 6 T1 W Axial |
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Fig. 7 Post contrast T1 Coronal fat suppressed |
Fig. 8 Post contrast T1 Axial fat suppressed |
The study reveals a T2 /STIR hyperintense lobulated soft tissue lesion in the subcutaneous tissues of antero-medial aspect of right upper thigh. It measures 2.5 x 1.9 cms in size (Fig.5). .It appears isointense on T1W images (Fig. 6) and shows intense near homogenous postcontrast enhancement (Fig. 7 & 8). These findings are s/o a mesenchymal benign soft tissue neoplasm.
The lesion was excised. The patient improved symptomatically by around 40% on follow up on 10 th day of operation. The phosphorus level became normal; however the alkaline phosphatase levels were mildly raised. The histopathological diagnosis of the tumor was fibrous histiocytoma.
DIAGNOSIS : Oncogenic osteomalacia with avascular necrosis of both femoral heads secondary to a fibrous histiocytoma of the right thigh.
Clinical features: The most common presenting complaints are generalized weakness, bone pain and multiple pathologic fractures. In children, it can also lead to skeletal deformities, growth retardation, and gait problems. Stress and insufficiency fractures are the prominent features .
Pathophysiology: Oncogenic osteomalacia is an unusual syndrome that is characterized by multiple biochemical abnormalities, such as hypophosphatemia, hyperphosphaturia, and low levels of plasma 1, 25-dihydroxyvitamin D. These patients present with bone and muscle pain and severe muscle weakness. . A patient with osteomalacia-rickets not caused by poor nutrition should be suspected of having tumor-induced disease.
A rare soft tissue tumor is a part of this clinical-pathologic syndrome characterized by renal phosphate wasting. Tumors producing this syndrome secrete a substance appears to be a phosphaturic peptide, "phosphatonin" which acts at the level of the proximal renal tubule, inhibiting sodium-dependent phosphate transport that inhibits the renal tubular reabsorption of phosphates, which produces a cascade of biochemical abnormalities. By virtue of this property, it belongs to the family of paraneoplastic syndromes.
A humoral substance caused the osteomalacia; the factor FGF-23 (one of the fibroblastic growth factors) is elevated in oncogenic osteomalacia.
Tumors that cause osteomalacia are often small, slow-growing, vascular, and benign; they are associated with a variety of histologic types and are commonly mesenchymal in origin. Hemangiopericytoma is the most dominant histologic diagnosis noted in tumor induced osteomalacia; however malignant tumors have occasionally been reported. Based on their histologic features, they have been sub-divided into 4 types:
1) Phosphaturic mesenchymal tumor, mixed connective tissue type (PMTMCT)
2) Osteoblastoma-like tumors
3) Ossifying fibroma-like tumors
4) Nonossifying fibroma-like tumors
Fibroblast growth factor 23 belongs to the mesenchymal origin family, and the measurement of serum FGF-23 has been found to be of considerable importance in facilitating early diagnosis.
A meticulous search for small any lump or bump in the body should be instituted. Mesenchymal tumors can occur in almost any location. Approximately 53% occur in bone, 45% occur in soft tissues, and 2% occur in skin. Skin and soft-tissue masses may be readily diagnosed on physical examination. However, bone lesions may be difficult to diagnose.
Laboratory findings:
Hyperphosphaturia
Hypophosphatemia
Normal serum calcium
Decreased serum 1, 25 dihydroxyvitamin D3
Radiological findings:
If a phosphate wasting syndrome is suggested, then radiographs to evaluate for osteopenia, osteomalacia, or hyperparathyroidism are indicated. Although plain films cannot yield histologic data, looser zones are very suggestive of osteomalacia.
An important aspect of patient management is to locate the tumor. CT and/or MRI (often followed by MR angiography). These are the main imaging tools used to determine tumor location. There is high sensitivity of MR imaging in confirming the presence of bone and soft-tissue pathologies in the absence of positive findings on standard imaging. However, whole-body CT and MRI have their own limitations. Nuclear scintigraphy has emerged as a very useful and economical tool to detect and determine the site of these tumors. Once the site is identified, regional CT and/or MRI are performed to further characterize the tumor.
Many of these tumors express somatostatin receptors that regulate secretory activity, as has been shown by other similar neuroendocrine tumors. Octreotide-labeled In-111 scanning has been successfully used for the detection of such tumors.
The role of [18]-fluorodeoxyglucose positron emission tomography (PET) imaging is well established with encouraging results. However, PET scans usually do not include the limbs. It is mandatory to include the limbs in the field, as these tumors are common in the limbs and can be easily missed.
Treatment: Supportive treatment with calcitriol and phosphate will improve the osteomalacia and the muscle weakness. A complete resection of the tumor will result in cure.
Follow up: All the biochemical and clinical features revert to normal within few days after excision of the tumor. However, radiological improvement lags behind the clinical improvement.