Renal medullary carcinoma in a patient with sickle cell trait

A 29-year-old male patient of African descent presented to the Emergency Department with a short history (less than 2 days) of painless frank haematuria. This was associated with a 1-2 week history of right flank discomfort. He was otherwise well, with only a past medical history of sickle cell trait. 

Contrast-enhanced CT of the thorax, abdomen and pelvis (Figure 1a-c) revealed a heterogeneously enhancing mass involving the upper two-thirds of the right kidney, with invasion into the renal sinus. Tumour thrombus was evident within the ipsilateral renal vein and inferior vena cava. There was extensive retroperitoneal lymphadenopathy, posterior to the vena cava and surrounding the right renal artery. Lymphadenopathy extended to the upper mediastinum and multiple, bilateral pulmonary metastasis were evident. Aggressive osseous lesions were evident throughout the bony skeleton.

Whole-spine MRI (Figure 2) (performed due to lower back pain) demonstrated expansion of epidural fat with bizarre, irregular enhancement and crowding of the cauda equina. This was attributed to venous congestion, resulting from the large tumour thrombus filling the IVC. A ‘soft’ process of this kind would not exert significant mass effect on the cauda equina and this unusual appearance was important to distinguish from a malignant cauda equina compression / intrathecal leptomeningeal disease.

First documented in 1995 by Davis et al, renal medullary carcinoma (RMC) has been described as the ‘seventh sickle cell nephropathy’ [1]. It almost exclusively affects individuals with sickle cell trait. It is estimated that approximately 1 in 14 African Americans carry the sickle cell trait and of these, between 1- 20/40, 000 will develop RMC [2]. The typical age of patients is 11-39 years, with a male predominance of 3:1 [3].

The pathophysiology remains unclear.  It is supposed that in people with sickle cell trait, there is chronic hypoxia in the renal medulla, eventually resulting in transitional cell proliferation involving the terminal collecting ducts and papillary epithelium [1].

Clinical presentation is flank pain, haematuria as weight loss [3].

70% of cases affect the right kidney [2]. Imaging demonstrates an ill-defined, infiltrative and aggressive soft tissue mass arising from the renal medulla and invading the renal sinus. The tumour demonstrates heterogenous enhancement with central necrosis. The affected kidney becomes enlarged, sometimes with reniform preservation [4]. Caliectasis without pelviectasis is occasionally documented [5].

90% of patients present with metastasis [1]. Of these patients, 88% have stage IV disease [6]. Sites of metastasis are typically lymph nodes, liver, lungs, and bones. Brain involvement is uncommon [7].

In the thorax, pulmonary lymphangitic carcinomatosis can occur secondary to tumour growth in the pulmonary lymphatics. This results in smooth/nodular thickening of the pulmonary bronchovascular bundles, interstitium, and interlobular septa [6]. 

RMC is often described as the most aggressive kidney cancer’ with an average life expectancy following diagnosis of 15 weeks [3]. Limited data suggest that the use of upfront combined cytotoxic chemotherapy may increase survival to 13-months [8]. A multi-disciplinary team approach, including psychological support, is vital.

Although extremely rare, it may be possible as the reporting radiologist to anticipate this cell type if confronted with a CT of a young patient of African descent, with an aggressive-looking renal tumour particularly in those known to have sickle cell trait. Bloods may show anaemia with a disproportionately low MCV and mildly elevated bilirubin. This has significant clinical implications, as the suggestion of possible MRC should steer the MDT towards renal biopsy rather than diagnostic nephrectomy in this aggressive tumour type. It also introduces a level of urgency to the investigation and referral of this often rapidly progressive process [1].

The patient was deceased at the time of writing and consent could not be obtained.