Renal medullary carcinoma was first described by Davis et al. as a sickle cell nephropathy and termed so because of its predominantly medullary location. Prior to this report, many of these tumors were probably mistakenly classified as CDCs due to their histological resemblance to the latter. In a literature review of renal medullary carcinoma by Dimashkieh et al.,hemoglobinopathy was found in 53 of the 55 cases (50 patients had hemoglobin AS, two patients had hemoglobin SC, and one patient had hemoglobin SS disease).
Pathology
Renal medullary carcinoma is a centrally located tumor with an infiltrative growth pattern similar to that of CDC. It is believed to arise from the epithelium of the distal portion of the collecting duct. The right kidney is involved three times more commonly than the left kidney, and the mean tumor size ranges from 4–12 cm (mean of 7 cm).
Renal medullary carcinomas are widely infiltrative, and have variable areas of hemorrhage and necrosis. Histologically, a variety of growth patterns have been described with reticular growth pattern and compact adenoid cystic morphology being the common features. Most renal medullary carcinomas have areas of poorly differentiated cells with solid sheets of tumor cells. The tumor cells contain vesicular or clear nuclei with prominent nucleoli and amphophilic cytoplasm, which can have a squamoid or rhabdoid quality. The tumor cells are usually high grade and as with CDC, there is often marked desmoplasia and inflammation.
The immunohistochemical profile is similar to CDC but can be helpful in distinguishing renal medullary carcinoma from other poorly differentiated kidney tumors. The clinical scenario is the key to diagnosing this rare neoplasm.
Clinical Presentation
Renal medullary carcinoma is a highly aggressive tumor that occurs almost exclusively in young people (mean age 22 years), predominantly males (male to female ratio 2 : 1) with sickle cell disease or trait. The common presenting symptoms are gross hematuria, abdominal/flank pain, or weight loss. Metastatic disease in the lymph nodes or distant organs such as the brain can also be the initial evidence of the tumor. Of the patients with adequate staging information available from the two largest case series, 18% had stage III disease and 82% had stage IV disease on presentation.
Treatment and Prognosis
Renal medullary carcinomas are now widely regarded as a highly aggressive variant of RCC, with an almost uniformly fatal outcome. The mean survival after surgery has been about 4 months. Strouse et al. have reported that only one of the over 80 reported patients is alive at 2 years. This patient had a small tumor (<2 cm) confined to the kidney at the time of resection. Chemotherapy has been shown to increase survival beyond 4 months in anecdotal reports, but with no reported long-term survivors. In this review of chemotherapy, of the 15 patients assessable for response, there was one complete response, two partial responses, one minor response, one stable disease and ten patients had progressive disease.
The most common chemotherapy regimen used was MVAC. Radiation therapy in an adjuvant or palliative role was disappointing. Immunotherapy in a few patients also had disappointing results. In healthy patients
with systemic disease, treatment plans similar to those for urothelial cancers and CDC, with combination chemotherapy consisting of cisplatin-gemcitabine or the MVAC regimen) appears to be a reasonable choice, but is unsupported by specific data. We are unaware of any collaborative clinical trials addressing this issue.