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Bone Case 14 Answers

1) Describe the 3 major abnormalities

(i) There is raised uptake in several ribs, T9 vertebral body, the right humerus and left femoral neck
(ii) There is markedly raised renal uptake
(iii) There is diffuse pulmonary uptake, producing a negative cardiac silhouette

2)What is the most likely pathophysiological explanation for them?

The skeletal uptake is compatible with multiple bony metastases. However, the diffuse, organ-specific soft tissue uptake is unlikely to be due to soft tissue metastases. There are whole host of causes associated with isolated increased pulmonary uptake and a similar number of processes that cause isolated increased renal uptake. However, the combination of lung and renal uptake makes this overwhelmingly likely to be due to so-called metastatic calcification due to hypercalcaemia.

In this case, it is most likely due to malignant hypercalcaemia. This usually involves a protein called parathyroid-related peptide (PTH-rP). This has a very similar structure to normal parathormone (PTH), and hence identical action on parathormone receptors. Consequently, PTH-rP releases calcium into the bloodstream. PTH-rP is a protein normally widely expressed in the human body with a markedly different physiological role. In normal adults, it has little significant physiological role. It is not normally systemically released as its actions seem confined to intracellular signalling, particularly during breast milk expression and fetal bone development. Indeed, Jansen's metaphyseal dysplasia is associated with PTH-rP gene mutations.

PTH-rP is released locally by malignant cells as they directly invade bone with subsequent release of calcium. It may also be released systemically to cause a paraneoplastic effect. Indeed, such patients can have a clinical syndrome which is very similar to that of hyperparathyroidism. Many different solid tumours can release it, the most frequent being squamous cell carcinomas. It seems to be a feature of relatively undifferentiated tumours and even in the absence of metastatic disease it is associated with a poorer prognosis.

The hypercalcaemia probably causes hydroxyapatite crystal deposition in lung and kidney. These then absorb bone imaging agents as avidly as bone, producing the raised uptake.

3) Name some common associated conditions

Isolated renal uptake is covered in Bone Case 2. Isolated pulmonary uptake is rare (incidence in one series of 0.04%) but can be divided into two categories

(i) Metastatic calcification (due to hypercalcaemia of benign and malignant causes)

(ii) Dystrophic calcification (due to healing granulomas or in amyloid)

(The very rare pulmonary alveolar microlithiasis is at the bottom of that list)

The top three causes of hypercalcaemia sufficient to cause lung uptake (in no particular order) are

  • Malignant hypercalcaemia

  • Chronic renal failure causing hyperparathyroidism

  • Primary hyperparathyroidism due a parathyroid adenoma

There are a vast number of small print causes of hypercalcaemia that have been associated with pulmonary uptake including Multiple Myeloma and vitamin D intoxication.

4. Are these abnormalities likely to be visible on other imaging modalities?
Naturally, the bone metastases may show up if there is either sclerosis or >50% loss of the bone texture, or in the case when there are pathological fractures of the ribs.

However, the soft tissue calcification is often microscopic and therefore difficult to visualize on other imaging modalities. Gallium-67 uptake has been described presumably relating to inflammation. Long-standing benign disease may produce a variety of non-specific findings which are best seen on High-Resolution CT rather than conventional chest radiography.

5. Are these abnormalities likely to be symptomatic?

Obviously the bone metastases can cause pain by either irritating the sensitive surrounding periosteum or cause insufficiency fractures. The soft tissue deposition is rarely symptomatic to cause tissue dysfunction - it is a bit of an anoraky "fascinoma".

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The text is entirely the opinion of the author and does not necessarily reflect that of RUH NHS Trust or the Bristol Radiology Training Scheme. Website content devised by Paul McCoubrie.