Endgames Picture Quiz

A case of progressive bilateral pitting oedema

BMJ 2015; 350 doi: https://doi.org/10.1136/bmj.h3 (Published 20 January 2015) Cite this as: BMJ 2015;350:h3
  1. Fatima Alves Pereira, foundation year 1 doctor1,
  2. Matthew Di Capite, foundation year 1 doctor2,
  3. David Thompson, consultant interventional radiologist3,
  4. Matt Hayes, consultant urologist 4,
  5. Kate Akester, consultant in acute and general medicine5
  1. 1Department of Acute Medicine, Southampton General Hospital, Southampton, UK
  2. 2Department of General Surgery, Southampton General Hospital, Southampton, UK
  3. 3Department of Radiology, Southampton General Hospital, Southampton, UK
  4. 4Department of Urology, Southampton General Hospital, Southampton, UK
  5. 5Department of Acute Medicine, Southampton General Hospital, Southampton, UK
  1. Correspondence to: F Alves Pereira fda22{at}cantab.net

A 68 year old man presented with a two month history of progressive shortness of breath. He had previously been able to swim three times a week, but was now becoming short of breath on climbing stairs. His associated symptoms included orthopnoea, swollen ankles, weight gain, and anorexia. He was being treated with simvastatin for hypercholesterolaemia and diltiazem for hypertension and had never smoked.

On examination, he was plethoric, his pulse was regular at 84 beats/min, and his blood pressure was 138/72 mm Hg. Heart sounds were normal and his jugular venous pressure was not raised, although he had pitting oedema to the mid thighs. Findings on respiratory examination included a respiratory rate of 20 breaths/min, with dullness to percussion and associated reduced breath sounds over the right lung base. His abdominal examination was unremarkable.

Laboratory tests showed haemoglobin 129 g/L (reference range 130-170), mean cell volume 79.4 fL (80-100), and creatinine 127 μmol/L (80-115). All other blood test results, and an electrocardiogram, were unremarkable. Chest radiography showed mild cardiomegaly and echocardiography showed well preserved left ventricular size and function. As a result, computed tomography with contrast of his chest, abdomen, and pelvis was performed (figure).

Figure1

Reformatted curved coronal section through the abdomen

Questions

  • 1. What abnormalities can be seen on the computed tomogram?

  • 2. How does the condition labelled A present?

  • 3. How would you classify the lesions labelled A?

  • 4. How would you manage this condition?

Answers

1. What abnormalities can be seen on the computed tomogram?

Short answer

The computed tomogram shows a small renal mass in the right kidney (A) and a large filling defect within a grossly dilated suprarenal inferior vena cava (B).

Long answer

The computed tomogram shows a small renal mass in the right kidney that probably represents a renal cell carcinoma (RCC), and a grossly dilated suprarenal inferior vena cava containing a large heterogeneous mass (tumour thrombus) extending from the right renal vein to the cavo-atrial junction. The right kidney also shows poor enhancement of its cortex, presumably secondary to renal vein obstruction.

The causes of acquired thrombosis of the inferior vena cava can be loosely classified under two broad headings—bland thrombus or tumour thrombus. Bland thrombus commonly arises from deep vein thrombosis of the lower limbs or pelvis, often in association with hypercoaguable states (cancer), foreign bodies (inferior vena cava filters or catheters), compression by retroperitoneal or other neoplastic lesions (lymph nodes), or profound stasis. In such cases the inferior vena cava tends to be minimally dilated by the thrombus, and the associated precipitating abnormality is often clearly apparent.1

Although almost any neoplastic lesion can invade or infiltrate the inferior vena cava and be associated with thrombus, RCC is the most common cancer associated with this “tumour thrombus.” Other tumours that tend to invade the inferior vena cava include hepatocellular carcinoma, adrenocortical cancer, and Wilms’s tumour. Tumour thrombus often shows continuity with the primary tumour, neovascularity on multiphase computed tomography, and a greatly dilated inferior vena cava. The invading tumour causes damage to the endothelium, which in turn leads to activation of the clotting cascade. In these cases, however, tumour thrombus can be a misnomer, because the expanding tissue is mostly made up of tumour, with relatively little frank thrombus.2

2. How does the condition labelled A present?

Short answer

Incidental presentation is becoming more common with the increasing usage of abdominal imaging, such as ultrasonography, computed tomography, and magnetic resonance imaging. Other potential presentations include haematuria, flank pain, abdominal mass, constitutional symptoms, and paraneoplastic manifestations.

Long answer

RCC has a 2:1 male preponderance and usually presents between the ages of 60 and 70 years. Partly because of the increased availability of imaging, currently it most often presents incidentally. As with other cancers, symptoms at presentation can be local, systemic, or both. Local features include the classic triad of haematuria, abdominal mass, and flank pain. Systemic features may be a result of metastatic spread or paraneoplastic syndromes.3 Interestingly, a variety of paraneoplastic syndromes, both endocrine or non-endocrine, can arise from RCC. Endocrine examples include hypercalcaemia (owing to secretion of parathyroid hormone related peptide), hypertension (as a result of increased renin production) and polycythaemia (as a result of increased production of erythropoietin). Non-endocrine paraneoplastic syndromes are much rarer, and examples include amyloidosis and neuromyopathies.4

3. How would you classify the lesions labelled A?

Short answer

RCC is divided into a diverse group of subtypes on the basis of its morphology and cytogenetics. The three main forms are clear cell, papillary, and chromophobe.

Long answer

RCC can be classified on the basis of histological appearance and cytogenetic abnormalities. The familial variants of renal cancer, such as in Von Hippel-Lindau (VHL) syndrome, have helped to elucidate the molecular genetics of this cancer.

Most (75-80%) RCCs are clear cell carcinomas. Macroscopically these appear yellow because of their high lipid and glycogen content, and they are often located at the poles of the kidney. Microscopically they have clear or granular cytoplasm under haematoxylin and eosin staining.5 These tumours arise from the epithelium of the proximal nephron.6 The VHL gene, found on the short arm of chromosome 3, acts as a tumour suppressor gene and encodes a protein that is part of the ubiquitin ligase complex, which is involved in targeting other proteins for degradation. Most (98%) clear cell tumours—whether sporadic or familial—are associated with loss of sequences of the short arm of chromosome 3.5

The next most common subtype is papillary RCC, which also arises from the proximal nephron and makes up 10-15% of renal cancers. In contrast to clear cell RCCs, these are often multifocal, with a papillary growth pattern and macroscopic areas of necrosis and haemorrhage. In addition, papillary RCCs are not associated with 3p deletions, but exhibit karyotype abnormalities such as trisomy 7, 16, and 17, as well as loss of chromosome Y in male patients.5 There is also a familial form, caused by activating mutations in the MET oncogene. Those affected develop late onset, multiple, bilateral papillary tumours.7

The third most common subtype is chromophobe RCC, which makes up 5% of renal cell carcinomas.5 Macroscopically these are well circumscribed and encapsulated tumours. Microscopically they have prominent cell membranes, appearing plant like, and they often have a perinuclear halo. Genetically these tumours may have loss of multiple chromosomes.5 Of note, the histopathological distinction between the benign renal oncocytoma and chromophobe RCC can be challenging.8

Outside these three main forms, there are other rarer types such as carcinoma of the collecting ducts of Bellini. In surgical case series, about 4-5% of renal tumours cannot be assigned to a particular category and are termed unclassified RCCs.7

4. How would you manage this condition?

Short answer

Management depends on TNM (tumour, node, metastasis) staging and the patient’s performance status. Partial or radical nephrectomy is likely to be curative for organ confined tumours, and a range of systemic targeted agents are available for metastatic disease.

Long answer

The spectrum of RCC is wide and therefore a range of treatment options are available, including radical nephrectomy, nephron sparing surgery, ablative therapies, and systemic treatments for metastatic disease.

Management depends on tumour stage, including the presence or absence of metastases, comorbidities, and patient preference. Important factors regarding the radiological TNM stage of the primary tumour include its size, whether it is limited to the kidney, and any extension into adjacent vessels or perirenal fat.

Surgical management can be divided into partial nephrectomy or radical nephrectomy. Partial nephrectomy should be considered for small renal tumours (T1a, where the tumour is ≤4 cm in greatest dimension and limited to the kidney) and is preferred in patients with a single kidney, pre-existing renal insufficiency, and those with bilateral involvement. Partial nephrectomy can be performed as open surgery, laparoscopically, or robotically. Outcomes of partial nephrectomy are equivalent to radical nephrectomy for small T1a renal tumours, with a 10 year cancer specific survival greater than 95%.9

Radical nephrectomy is the traditional standard treatment for localised RCC. It involves removing the kidney, adrenal gland, perirenal fat, and Gerota’s fascia, along with regional lymph node dissection. However, for tumours less than 7 cm in diameter, evidence shows that partial nephrectomy has an equal cancer specific survival.9 Radical nephrectomy is indicated when disease is more extensive and, for example, the inferior vena cava is affected.10

Because of the increasing number of asymptomatic RCCs being discovered incidentally, ablative therapy for small tumours, using either radiofrequency ablation or cryoablation has been developed as an alternative option. The advantages of this treatment include reduced morbidity, particularly in certain patient groups such as older people, who may not tolerate surgical treatment. Radiofrequency ablation is usually performed percutaneously under computed tomography image guidance with local or general anaesthetic.11 Selective arterial embolisation of RCCs may also be performed. This can be done preoperatively, as well as in the palliative setting, such as in treating persistent haematuria.12

It may not always be in the patient’s best interests to operate immediately. A meta-analysis found that the average growth rate of a small renal mass was 0.28 cm per year and that only about 1% developed metastasis during a median follow-up of 27 months (range 12-152).13 In another study, elderly patients with small tumours (T1a) died from other causes, mainly related to cardiovascular disease.11

Several systemic treatments are now available for metastatic disease. Originally, these were immunotherapy based interferon α and high dose interleukin cytokine treatments. Novel targeted molecular based therapies, which include tyrosine kinase inhibitors, inhibitors of vascular endothelial growth factor, and mTOR (mammalian target of rapamycin) inhibitors are more efficacious and have a better side effect profile. Cytoreductive nephrectomy should be considered in patients with good performance status; it also has a role in palliative treatment for control of pain and bleeding from the primary tumour.14 Finally, radiotherapy is useful for bone metastases but does not have a role as primary treatment. Response rates to chemotherapy are poor.10

Patient outcome

Magnetic resonance imaging was used to further characterise the lesions and a computed tomography guided biopsy of the inferior vena cava tumour thrombus (using a transfemoral venous approach) was performed to achieve a definitive diagnosis. Magnetic resonance imaging confirmed extensive inferior vena cava tumour thrombus (14 cm in length) and the biopsy provided tissue consistent with an RCC. A nuclear medicine scan showed that the relative function of the right kidney was only 11%. The options were explained and discussed with the patient and he decided that, despite the risks, he wished to undergo surgery. Surgery aimed to resect the inferior vena cava tumour and the right kidney from which it arose. The extensive inferior vena cava tumour thrombus was extracted through a longitudinal inferior vena cavotomy, using extensive liver mobilisation and cardiopulmonary bypass to facilitate surgical excision, without the need for vascular grafting. When the tumour thrombus was extracted from the inferior vena cava, it became clear that there was just tumour invasion, with no evidence of clot. The histopathological diagnosis from the resected right kidney and inferior vena cava tumour was of a clear cell RCC. He has now completed his postsurgical recovery.

Notes

Cite this as: BMJ 2015;350:10.1136/bmj.h3

Footnotes

  • Competing interests: We have read and understood BMJ policy on declaration of interests and declare that we have no competing interests.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

  • Patient consent obtained.

References

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