- Email: [email protected]
What is your diagnosis?
Indian Journal of Rheumatology 2010 June Volume 5, Number 2; pp. 93–94
PG Forum
What is your diagnosis? Unusual cause of osteomalacia Jagannath Rao1, IR Varaprasad2, L Rajasekhar3, T Gangadhar4, C Sundaram5, G Narsimulu6, SV Venkatratnam7 A 46-year-old male presented with body pain for three years. It started as a pain in both feet and progressed to involve the chest wall and low back in a few months. A year later, he developed polyarthralgias. His symptoms deteriorated. He needed support for walking. He also reported nasal stuffiness over the last 2 years. Systemic examination was normal except for generalized bony tenderness. Haematologic investigations were normal. His blood urea and serum creatinine were normal. His serum calcium was normal (8.7 mg/dL), phosphorous low (1.6 mg/dL), alkaline phosphatase and bone alkaline phosphatase isoenzyme elevated (950 and 540 U/L, respectively). His 24-hour urine phosphate excretion was elevated (1.7 gm, normal less than 1 gm). Serum intact PTH levels were normal. Radiographs of the pelvis showed linear lucency involving the right iliac wing and small lucencies in the left femoral head. A skeletal scintigraphy scan showed multiple insufficiency fractures, consistent with metabolic bone disease. Tumour imaging using Tc MIBI radionuclide scanning was done, and revealed non-specific uptake of tracer at right shoulder joint and sinuses.
Figure 1 CT of paranasal sinus showing a mass lesion involving ethmoid and sphenoid sinuses on right side.
ANSWER Examination by nasal endoscope revealed a growth in the right superior meatus of the nostril. A contrast-enhanced computerized tomogram imaging of paranasal sinus (PNS) region showed a mass lesion involving ethmoid and sphenoid sinuses on right side, measuring 56 × 20 × 28 mm (Figure 1). The lesion had lobulated margins and eroded the bony septa. An excisional biopsy of the lesion was done that was consistent with malignant haemangiopericytoma (Figure 2). 1
Figure 2 Histopathology of the lesion consistent with malignant haemangiopericytoma.
Associate Professor Department of Radiotherapy, 2Senior Resident, Department of Rheumatology, 3Associate Professor, Department of Rheumatology and Radiotherapy, 4Associate Professor, Department of Nephrology, 5Professor and Head, Department of Pathology, 6Professor and Head, Department of Rheumatology, 7Professor and Head, Department of Radiation Oncology All from Nizam’s Institute of Medical Sciences, Hyderabad. Correspondence: Rajasekhar, email: [email protected]
94
Indian Journal of Rheumatology 2010 June; Vol. 5, No. 2
Rao et al
The patient had oncogenic osteomalacia due to malignant haemangiopericytoma. Oncogenic osteomalacia is primarily described in adults, but can also occur in children and adolescents. It is characterized by proximal muscle weakness, bone pains and fractures. The characteristic laboratory parameters are hypophosphataemia, hyperphosphaturia and inappropriately normal/low plasma 1,25(OH)2D3 concentration.1 Haemangiopericytoma is the most dominant histologic diagnosis noted. The tumours secrete phosphatonins, factors involved in the regulation of phosphate homeostasis such as the secreted frizzle-related protein 4 (sFRP-4), the fibroblast growth factors 7 and 23 (FGF-7/-23) or the matrix extracellular phosphoglycoprotein (MEPE).2 These factors upregulate the renal sodium phosphate co-transporter, resulting in renal phosphate wasting. Locating an occult tumour is best done by Octreotidelabelled In-111 nuclear scintigraphy scan as the tumour expresses somatostatin receptors.3 This should be followed by CT or MRI of the specific site. One report recommends careful imaging of the nasal sinuses as a part of the work-up of cases of oncogenic osteomalacia.4 Surgical removal of the primary tumour to prompt reversal of the symptoms, biochemical abnormalities and healing of the bone disease.5 Malignant varieties require postoperative irradiation. In inoperable tumours, phosphate wasting may be relieved by treatment with somatostatin analogues.6 Our patient received external radiation treatment for the lesion at a dose of 63 Gy/35#, 5# a week for seven weeks. The treatment planning was done by using contrast-enhanced
computerized tomogram of the paranasal sinuses and 3dimensional treatment planning system with wedge and appropriate shielding to the contralateral lens with cobalt 60 machine. At follow-up after 3 months, the patient showed good symptomatic relief in pain and CT scan of PNS showed good regression of the lesion.
ANSWERS TO THE RHEUMATOLOGY QUIZ (page 90)
†
1d*, 2a, 3c**, 4b†, 5c††, 6c†††, 7c, 8b§, 9a§§, 10a§§§ *More than 90% on HRCT and autopsy, FVC < 80% in 25–40% **Oesophagus is the commonest site, one third have constipation
REFERENCES 1.
2.
3.
4.
5.
6.
Clunie GP, Fox PE, Stamp TC. Four cases of acquired hypophosphataemic (‘oncogenic’) osteomalacia. Problems of diagnosis, treatment and long-term management. Rheumatology (Oxford) 2000; 39: 1415–21. Woznowski M, et al. Oncogenic osteomalacia, a rare paraneoplastic syndrome due to phosphate wasting—a case report and review of the literature. Clin Nephrol 2008; 70: 431–8. Rhee Y, et al. Oncogenic osteomalacia associated with mesenchymal tumour detected by indium-111 octreotide scintigraphy. Clin Endocrinol (Ox) 2001; 54: 551–4. Kenealy H, Holdaway I Grey A. Occult nasal sinus tumours causing oncogenic osteomalacia. Eur J Intern Med 2008; 19: 516–9. Folpe AL, et al. Most osteomalacia-associated mesenchymal tumors are a single histopathologic entity: an analysis of 32 cases and a comprehensive review of the literature. Am J Surg Pathol 2004; 28: 1–30. Seufert J, et al. Octreotide therapy for tumor-induced osteomalacia. N Engl J Med 2001; 45: 1883–8.
DLBCL in RA is usually unrelated to EBV Light headedness is usually due to vertebral artery involvement ††† Pelvic involvement is usually asymmetric § First generation use PPD, most but not all non-tubercular mycobacteria are excluded by second generation tests §§ BCP presents as tendonitis, usually acute §§§ Infiltrates are usually asymmetric, although bilateral ††
PG Forum
What is your diagnosis? Unusual cause of osteomalacia Jagannath Rao1, IR Varaprasad2, L Rajasekhar3, T Gangadhar4, C Sundaram5, G Narsimulu6, SV Venkatratnam7 A 46-year-old male presented with body pain for three years. It started as a pain in both feet and progressed to involve the chest wall and low back in a few months. A year later, he developed polyarthralgias. His symptoms deteriorated. He needed support for walking. He also reported nasal stuffiness over the last 2 years. Systemic examination was normal except for generalized bony tenderness. Haematologic investigations were normal. His blood urea and serum creatinine were normal. His serum calcium was normal (8.7 mg/dL), phosphorous low (1.6 mg/dL), alkaline phosphatase and bone alkaline phosphatase isoenzyme elevated (950 and 540 U/L, respectively). His 24-hour urine phosphate excretion was elevated (1.7 gm, normal less than 1 gm). Serum intact PTH levels were normal. Radiographs of the pelvis showed linear lucency involving the right iliac wing and small lucencies in the left femoral head. A skeletal scintigraphy scan showed multiple insufficiency fractures, consistent with metabolic bone disease. Tumour imaging using Tc MIBI radionuclide scanning was done, and revealed non-specific uptake of tracer at right shoulder joint and sinuses.
Figure 1 CT of paranasal sinus showing a mass lesion involving ethmoid and sphenoid sinuses on right side.
ANSWER Examination by nasal endoscope revealed a growth in the right superior meatus of the nostril. A contrast-enhanced computerized tomogram imaging of paranasal sinus (PNS) region showed a mass lesion involving ethmoid and sphenoid sinuses on right side, measuring 56 × 20 × 28 mm (Figure 1). The lesion had lobulated margins and eroded the bony septa. An excisional biopsy of the lesion was done that was consistent with malignant haemangiopericytoma (Figure 2). 1
Figure 2 Histopathology of the lesion consistent with malignant haemangiopericytoma.
Associate Professor Department of Radiotherapy, 2Senior Resident, Department of Rheumatology, 3Associate Professor, Department of Rheumatology and Radiotherapy, 4Associate Professor, Department of Nephrology, 5Professor and Head, Department of Pathology, 6Professor and Head, Department of Rheumatology, 7Professor and Head, Department of Radiation Oncology All from Nizam’s Institute of Medical Sciences, Hyderabad. Correspondence: Rajasekhar, email: [email protected]
94
Indian Journal of Rheumatology 2010 June; Vol. 5, No. 2
Rao et al
The patient had oncogenic osteomalacia due to malignant haemangiopericytoma. Oncogenic osteomalacia is primarily described in adults, but can also occur in children and adolescents. It is characterized by proximal muscle weakness, bone pains and fractures. The characteristic laboratory parameters are hypophosphataemia, hyperphosphaturia and inappropriately normal/low plasma 1,25(OH)2D3 concentration.1 Haemangiopericytoma is the most dominant histologic diagnosis noted. The tumours secrete phosphatonins, factors involved in the regulation of phosphate homeostasis such as the secreted frizzle-related protein 4 (sFRP-4), the fibroblast growth factors 7 and 23 (FGF-7/-23) or the matrix extracellular phosphoglycoprotein (MEPE).2 These factors upregulate the renal sodium phosphate co-transporter, resulting in renal phosphate wasting. Locating an occult tumour is best done by Octreotidelabelled In-111 nuclear scintigraphy scan as the tumour expresses somatostatin receptors.3 This should be followed by CT or MRI of the specific site. One report recommends careful imaging of the nasal sinuses as a part of the work-up of cases of oncogenic osteomalacia.4 Surgical removal of the primary tumour to prompt reversal of the symptoms, biochemical abnormalities and healing of the bone disease.5 Malignant varieties require postoperative irradiation. In inoperable tumours, phosphate wasting may be relieved by treatment with somatostatin analogues.6 Our patient received external radiation treatment for the lesion at a dose of 63 Gy/35#, 5# a week for seven weeks. The treatment planning was done by using contrast-enhanced
computerized tomogram of the paranasal sinuses and 3dimensional treatment planning system with wedge and appropriate shielding to the contralateral lens with cobalt 60 machine. At follow-up after 3 months, the patient showed good symptomatic relief in pain and CT scan of PNS showed good regression of the lesion.
ANSWERS TO THE RHEUMATOLOGY QUIZ (page 90)
†
1d*, 2a, 3c**, 4b†, 5c††, 6c†††, 7c, 8b§, 9a§§, 10a§§§ *More than 90% on HRCT and autopsy, FVC < 80% in 25–40% **Oesophagus is the commonest site, one third have constipation
REFERENCES 1.
2.
3.
4.
5.
6.
Clunie GP, Fox PE, Stamp TC. Four cases of acquired hypophosphataemic (‘oncogenic’) osteomalacia. Problems of diagnosis, treatment and long-term management. Rheumatology (Oxford) 2000; 39: 1415–21. Woznowski M, et al. Oncogenic osteomalacia, a rare paraneoplastic syndrome due to phosphate wasting—a case report and review of the literature. Clin Nephrol 2008; 70: 431–8. Rhee Y, et al. Oncogenic osteomalacia associated with mesenchymal tumour detected by indium-111 octreotide scintigraphy. Clin Endocrinol (Ox) 2001; 54: 551–4. Kenealy H, Holdaway I Grey A. Occult nasal sinus tumours causing oncogenic osteomalacia. Eur J Intern Med 2008; 19: 516–9. Folpe AL, et al. Most osteomalacia-associated mesenchymal tumors are a single histopathologic entity: an analysis of 32 cases and a comprehensive review of the literature. Am J Surg Pathol 2004; 28: 1–30. Seufert J, et al. Octreotide therapy for tumor-induced osteomalacia. N Engl J Med 2001; 45: 1883–8.
DLBCL in RA is usually unrelated to EBV Light headedness is usually due to vertebral artery involvement ††† Pelvic involvement is usually asymmetric § First generation use PPD, most but not all non-tubercular mycobacteria are excluded by second generation tests §§ BCP presents as tendonitis, usually acute §§§ Infiltrates are usually asymmetric, although bilateral ††