Q.H. Siraj ( Department of Nuclear Medicine, Royal Free Hospital, London. )
A.J.W. Hilson ( Department of Nuclear Medicine, Royal Free Hospital, London. )
A. Millar ( University Department of Medicine, Royal Free Hospital, London. )
J.S. Dooley ( University Department of Medicine, Royal Free Hospital, London. )
A variety of primary and secondary soft-tissue neoplasms may accumulate bone-seeking agents. We present a 99Tcm methylene diphosphonate bone scan demonstrating extra-osseous tracer uptake in a retroperitoneal liposarcoma with photon-deficiency in a cystic area of the tumour and displacement of the right kidney across the mid-line to the left.
A 57-year-old male Caucasian suffered from increasingly severe Parkinson’s disease over the last 14 years. In 1987, he developed a psychotic illness related to Bromocriptine and had a seizure with no recurrence. He was admitted in 1992 forassessment of his Parkinson’s disease. On examination, the patient was thin with no palpable nodes, had gross ankle oedema upto his mid-thighs, blood pressure was 120/80 mmHg, chest was clear and cardiovascular system was normal, apart from an ejection systolic murmur. Central nervous system examination revealed no abnormalities (apart from known Parkinson’s disease). Abdominal exanunation revealed a palpable mass in the right hypochondrium, extending down to the iliac crest, which moved partially with respiration. A provisional diagnosis of possible polycystic kidney disease was made. The patient had no symptoms related to the mass but had noticed a vague ache in the right abdomen had lost 9Kg in weight over the last two years. Initial investigations showed hypochromic normocytic anaemia with a Hb of 11.1 g/dl and semm iron at 7 umol/l (normal range 11-36). The erythrocyte sedimentation rate was 26 nun h4. Serum biochemistry was normal. Aiphafetoprotein, beta HCG and prostatic specific antigen were normal. ANA was positive but other autoantibodies were negative. Chest X-ray revealed no abnonnality. Computed tomography (CT) showed a large soft-tissue mass occupying the right abdomen with some areas of cystic change (Figure 1).
The right kidney had been displaced to the anterior abdominal wall. A bone scan (Figure 2)
was carried out, which showed clear-cut uptake of tracer within the known retroperitoneal mass, a photopenic area corresponding the cystic necrotic region seen on the CT and displacement of the right kidney. There was no evidence of bone metastases. Biopsy of the mass showed a mixoid of loose fibrous stroma containing mainly scattered polymorphic and a few hypochromic variably sized cells with multinucleated cells. Occasional lymphoblast like cells were also identified. The appearance was in keeping with a low-grade sarcoma or possible liposarcoma. Angiography earned out prior to consideration for surgery, showed compression of the retro-hepatic cava with possible thrombosis. The tumour was relatively avascular with its blood supply arising mainly from the lumbar plexus. On surgery, a massive (7000 gm) retroperitoneal mass with focal areas of haemorrhage and necrosis and a large central cystic space (65 mm in diameter) was excised. The tumour was seen to be displacing the liver, in.fenorvena cava and the right kidney. Histopathology confirmed a retroperitoneal pleomorphic liposarcoma.
Following the introduction of 99TCm labelled diphosphonates in the early 1970s1, bone scintigraphy has now become the most frequently performed nuclear medicine test. Due to it’s excellent in vivo stability and rapid blood clearance with resultant high bone-to-soft tissue ratio, 99Tcm methylene diphosphonate (MDP) has become the current radiopharmaceutical of choice2. The excellent clearance of 99Tcm-MDP from normal soft tissues allows detection of abnormal extra-skeletal accumulation in a variety of non-osseous pathological conditions, both benign and malignant3. Accumulation of bone-seeking agents has been demonstrated in several primary and secondary soft-tissue neoplasms4. Liposarcomas are primary soft-tissue malignant neoplasms of mesenchymal origin, which develop in tissues where lipoblastic cells are found. Soft-tissue accumulation of 99TCm-MDP in liposarcomas of the lower extremities has been reported5,6. The basic mechanism (s) underlying the uptake of bone agents by soft- tissue neoplasms is still not clearly understood. The major proposed mechanisms include tumour calcification, regional hypervascularity and enhanced vascular permeability. There is a strong correlation between the calcium content in the soft tissue and 99Tcm-MDP retention. Extra-osseous calcium is found associated with collagen, osteoid matrix and other organic substrates. MDP acts as a ligand adsorbing onto tissue calcium, localising 99Tcn’ in the mineral phase with no significant organic substrate interaction7. Blatt and workers have pointed out that immature collagen can be found in liposarcomas. possibly affecting radiopharmaceutical uptake5 . Most soft-tissue sarcomas accumulate 99Tcm_ MDP due to calcification, hypervascularity or both4. According to Chew and Hudson, the mechanism of uptake is not dependent on the calcification in the tumour, but is presumed secondary to angiographic and histologic hypervascularity of liposarcomas6. The initial phase üf 99Tcm-MDP concentration in normal tissues is directly related to blood flow and vascularity. Although regional perfusion is the primary determinant of abnormal 99Tcm-MDP delivery, increased perfusion alone cannot account for the high uptake of 9TCm-MDP in soft tissue neoplasms8. Other proposed factors causing diffusion of the tracer through the walls of the abnormal capillaries leading to significantly higher tissue concentrations of 99Tcm-MDP include a change in the sympathetic tone that may open local vascularplexuses and an alteration in the normal capillary permeability by vasoactive compounds and neovascularisation9. Tumour necrosis10 and ischaemia11 have also been implicated. Ischaemic damage to cellular membranes results in rapid intracellular influx of calcium, which precipitates within the mitochondna. Denatured proteins act as further substrates for calcium deposition. In the present case, there was no evidence of tumour ihypervascularity seen on angiography. The accumulation of 99Tcm- MDP in this case may therefore be related to tumour calcification, immature collagen, altered capillary permeability, or a combination of the above mechanisms.
1. Subramanian, G. and McAfee, J.G. A new complex for skeletal imaging. Radiology, 1971 ;99: 192-96.
2. Subramanian 3., McAfee, J.G., Blair, R.J. et al. Tc-99m methylene diphos phonate: Superior agent for skeletal imaging: comparison with other technetium complexes. J. Nucl Med., 1975;16:744-55.
3. Silberstein, E.B. and McAfee, 3G. In differential diagnosis in Nuclear Medicine, Ed. Silberstein, E.B. and McAfee, J.G.: New York, McGraw Hill, 1984, pp. 300-18.
4. Chew. ES.. Hudson, TM., Enneking, W.F. et al. Radionuclide imaging of soft tissue neoplasms. Semin. Nuci. Med. 198;11:266- 76
5. Blatt, C J Hayt, D.B., Desai, M. et al. Soft-tissue sarcoma. Imaged wit technetiurn-99m pyrophosphate. N.Y. State J. Med., 1977;77:211 8-2119.
6. Chew, F. S. and Hudson, T.M. Radionuclide imaging of lipoma and liposarcoma. Radiology, 1980;136:741-45.
7. Francis, MD., Furguson, D.L., Toffe, A.J. et al. Comparative evaluation of three diphosphonstes: In vivo absorption (C- 14 labeled)and in vivo osteogenic uptake (Tc-99m compkxed). J. Nuel. Med., 1980;21 :1185-89.
8. Lavender, J.P., Khan, R.A. and Hughes, S.P. Blood flow and tracer uptake in normal and abnormal canine bone: comparison with Sr-85 microspheres, Kr-81m and Tc-99m MDP. J. Nucl. Med., 1979;20:413-18.
9. Sagar, VV., Piccone, J.M. and Charkes, N.D. Studies of skeletal tracer kinetics. III. Tc-99m (Sn) methylene diphosphonate uptake in the canine tibia as a function of blood flow. 3. Nucl. Med., 1979;20: 1257-61.
10. Senda, M., Tamak, N., Torizuka. K. et al. Accumulation of Tc-99m methylene diphosphonate in calcified metastatic lesions of the liver from colonic carcinoma. Clin. Nucl. Med., 1985;10:9-12.
11. Gentili, A., Miron, S.P. and Bellon, EM. Nonosseous accumulation of bone-seeking radiopharmaceuticals. Radiographics, 1990; 10:871-81.