Renal Medullary Carcinoma in kidney tumors

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.

Carcinoma of the Bellini collecting duct in kidney tumors

CDC is a rare tumor cells derived from renal collecting ducts of Bellini, and has less than 1% renal malignancies. Reported by Mancilla-Jimenez et al. in its report on papillary tumors, the examination renal tissue distant from the tumor to appear, in some cases, atypical hyperplastic changes of collecting tubules.

This raised the possibility that some papillary tumors arose from distal tubular pithelium. Fleming and Lewi ago describe the detailed features of the CDC as pathological entity based on several case reports.

Pathology
This tumor is characterized by a core location, with a size ranging from 2 to 12 cm, the appearance of firm white-gray and irregular infiltrative edge. Grows radially from the renal hilum to invade the renal cortex, renal cap Sule, and the renal sinus. Histologically, an irregular pattern of growth embedded in a desmoplastic tubulopapillary stroma. The tubules are lined with cells with eosinophilic cytoplasm nail scarce. The cells display high-grade nuclei with brisk mitotic activity, and prominent nucleoli. Sometimes sarcomatoid changes or mucin can be seen. Molecular events and cytogenetic changes that contribute are not well characterized, and a different pattern has yet emerged. The immunohistochemical profile is variable, with generally positive for phytoagglutinins and high molecular weight cytokeratin, with coexpression of vimentin and negative for CD10 and villi.


Clinical Presentation
It is a very aggressive tumor, usually presenting at an advanced stage, with gross hematuria, abdominal pain / back pain and a flank mass. At diagnosis, they often have metastatic disease in the lung, liver, lymph nodes, bone, or adrenal gland. It is more common in men (ratio of about 2: 1) with a wide range of age groups (13-83 years with an
average 55 years). Computed tomography (CT), this tumor appears as a central mass arising infiltrating the preservation of the renal contour and minimal contrast enhancement. Patients may have generalized inflammatory symptoms secondary to the release of cytokines of the tumor and the inflammatory reaction associated with the tumor.

Treatment and Prognosis
The diagnosis of CDC is usually done after the operation, and unlike other radiological RCC is difficult and there is a low preoperative suspicion in view of the rarity of the disease. The prognosis is generally very poor with most patients with distant metastases developing rapidly, with a median survival of 22 months.

The role of nephrectomy has been the subject of debate due to frequent metastasis to the presentation. Radical nephrectomy in the context of metastasis CDC appears to be useful only for palliation. Based on the pathological, immunohistochemical and cytogenetic
similarity with urothelial (CTP), compared with conventional carcinomas clear cell RCC, the preferred approach in treatment of metastatic disease with chemotherapy has been in place for immunotherapy.

In the largest series reported Dimopoulos et al. subsequently reported the MD Anderson Cancer Center experience involving 12 patients with CDC treated from 1980-90. Seven of eight patients with metastatic disease were treated with different combinations of chemotherapy with doxorubicin and cisplatin, methotrexate; vinblastine (MVAC) regimen is the most common. Only one patient achieved a minor response lasting 5 months. Six patients were treated with a combination of interleukin-2 and IFN-α with a response in a patient. Peyromaure et al. reported two complete responses with cisplatin and gemcitabine combination chemotherapy, which lasted 9 and 27 months.

Radiotherapy in this series appeared to have minimal benefit for local recurrence. Chao et al. a review noted that some patients with regional nodal disease without distant etastases have long-term disease-free survival with adjuvant therapy.

While the overall benefit of chemotherapy or immunotherapy appears to be minimal, there seems to be a select group of patients who will benefit of these approaches. Cisplatin-Gemcitabine has significant activity with a favorable toxicity profile in urothelial cancers and has caused some significant response in patients with CDC. Thus access to the system to some extent, since the preferred first-line chemotherapy simply because it is less toxic than MVAC regimen, and no other major series of chemotherapy for collecting duct tumors has apparently better results.