A fatal case of pleural osteosarcoma mimicking mesothelioma in Paget's disease of bone

K. Chakravarty, I. T. Saeed1 and R. W. Fowler2

Departments of Rheumatology, 1Histopathology and 2Chest Medicine, Harold Wood and Old Church Hospitals, Gubbins Lane, Romford, Essex, UK

Correspondence to: K. Chakravarty, Department of Rheumatology, Harold Wood Hospital, Gubbins Lane, Romford, Essex, UK. E-mail: kuntal{at}talk21.com

SIR, Pulmonary involvement due to pagetic osteosarcoma is exceedingly rare and pleural secondaries from a primary vertebral pagetic osteosarcoma have not been reported in the literature. We describe a case of metastatic pleural disease arising from primary pagetic osteosarcoma of the spine that was misdiagnosed as pleural mesothelioma.

A 77-yr-old ex-smoker was admitted with a short history of increasing breathlessness, a dry cough and weight loss. He had suffered from well-controlled epilepsy from a very young age. He also had a long history of polyostotic Paget's disease of bone, which was diagnosed when he developed a pathological fracture of the femoral shaft. He had not received any specific treatment for Paget's until recently, when he had a good response to his pain with intravenous pamidronate (90 mg).

On examination he looked pale with a kyphoscoliosis. There were no palpable lymph nodes or thyroid enlargement. Clinical examination suggested a left pleural effusion which was confirmed by chest radiograph and computed tomographic (CT) scan. The scan also showed dense irregular pleural thickening with a calcification pattern commonly seen in a malignant mesothelioma with sarcomatous degeneration.

Haematological investigations showed a normocytic normochromic anaemia (haemoglobin: 10.5 g/dl), with raised white cell count and normal erythrocyte sedimentation rate. Serum alkaline phosphatase was 2414 IU/l (normal range: 0–100 IU/l), with normal serum calcium and phosphate levels. Results of other biochemical tests including urea, creatinine, liver function, thyroid stimulating hormone, C-reactive protein and parathyroid hormone were within the normal range. Microbiological investigations including blood, sputum and urine culture were negative. A flexible bronchoscopy and microbiological and cytological investigations were all normal, including screening for acid-fast bacilli. A pleural tap revealed blood-stained exudative fluid with a total protein of 43 g/l. A pleural biopsy showed a mixture of sarcomatoid and epitheloid malignant cells with deposition of osteoid. Although stains for mesothelioma were negative, this tumour was thought to represent a biphasic malignant mesothelioma with osteoid metaplasia. Artificial pleurodesis with tetracycline produced only a transient improvement. Five weeks later the patient was re-admitted with massive right pleural effusion and died after a few days.

Autopsy showed a tumour involving left parietal and visceral pleura invading the left lung on its outer pleural surface with firm calcified and ossified tumour tissue extending into lung parenchyma in the form of bony trabeculae (Fig. 1). Partially calcified tumour nodules varying from 0.5 to 2 cm were found on the outer surface of the right lung. Further examination of the L2 vertebra revealed changes of osteosarcoma in the background of Paget's disease.



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FIG. 1. The autopsy tissue from the vertebral biopsy showing the expanded osteoid tissue of Paget's disease of bone with evidence of tumorous involvement due to osteosarcoma. The inset on the left-hand side shows the pleural tissue with similar malignant cells to those seen in the bone biopsy.

 
Sarcomatous change in Paget's disease of bone is well recognized and occurs in less than 10% of cases [1]. Our patient had a sarcomatous change in the lumbar vertebra, with extra-osseous osteosarcoma infiltrating the pleura, which in life was interpreted as sarcomatous degeneration of a malignant mesothelioma. Subsequent autopsy revealed the true nature of the metastatic osteosarcoma with additional evidence of tumour nodules on the apparently normal-looking lung.

Pulmonary osteosarcoma is extremely uncommon, particularly in Paget's disease of bone [2]. Most common sites of pagetic osteosarcoma are, in order of frequency, femur, humerus, innominate bones, skull and tibia [3]. Sarcomatous changes in vertebral Paget's are rarely seen [4] and in one large series only 15% had changes of sarcoma [5].

Primary osteosarcoma metastasizing to lung is recognized to cause well-circumscribed spherical nodules giving the typical appearance of cannonball shadows [6]. Primary osteosarcoma presents with pulmonary metastasis in only 10% of cases, while mortality is 70% in such patients [7]. Pulmonary secondaries arising from osteosarcoma of Paget's disease have been described only in three cases in the literature [8] and our case is unique in that the patient presented with extensive pleural involvement, and the pulmonary deposits were detected only at autopsy.

It is interesting to note that although our patient had an ante-mortem diagnosis of mesothelioma with osteoid differentiation in the background of a polyostotic Paget's disease, there was no history of exposure to asbestos at any stage. A recent report suggests that it is worth re-examination of the tissue with anti-mesothelial cell markers as sarcomatous degeneration in a mesothelioma may not be easily differentiated from a secondary osteosarcoma in the pulmonary or pleural tissue [9]. The literature to date describes 12 case reports of metastatic osteosarcoma in pre-existing Paget's disease, of which three appeared to involve the lung. Our patient is the first case to show such pleural involvement and this clearly demonstrates the need to consider this diagnosis much earlier in patients with Paget's disease of bone presenting with pleural involvement.

The authors have declared no conflicts of interest.

References

  1. Kanis JA. Pathology and treatment of Paget's disease of bone, 2nd edn. UK: Martin Dunitz Publishers, 1998.
  2. Jeffrey GM, Price CHG et al. The metastasis patterns of osteosarcoma. Br J Cancer 1975;32:87–107.[ISI][Medline]
  3. Murray P, Jacobson et al. The radiology of skeletal disorders, 2nd edn, Vol. 1. London: Churchill Livingstone, 1977.
  4. Huang IL, Cohen NJ et al. Clinical orthopedics and related research—osteosarcoma complicating Paget's disease. No. 141. Philadelphia: J. P. Lippincott, 1979.
  5. Lichtenstein L. Bone tumors, 3rd edn. St. Louis: Mosby, 1965.
  6. Crow J, Slavin G, Kreel L et al. Pulmonary metastasis: a pathologic and radiologic study. Cancer 1981;47:2595–602.[ISI][Medline]
  7. McKenna RJ, Schwinn CP, Soong KY et al. Osteogenic sarcoma arising in Paget's disease. Cancer 1964;17:42.
  8. Weiss L, Gilbert HA. In: Pulmonary metastasis. Boston: G. K. Hall & Co., 1978:100–3.
  9. Andrion A, Mazzuco G, Bernardi P et al. Sarcomatous tumor of the chest wall with osteochondral differentiation—Evidence of mesothelial origin. Am J Surg Pathol 1989;13:707–11.
Accepted 29 April 2003





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