An institutional review board exemption and a waiver of the requirement for written informed consent from the patients to perform the present retrospective study were obtained from the First Affiliated Hospital of Fujian Medical University (Fuzhou, China). A search in the pathology records and the picture archiving and communication system of the hospital identified 6 patients with RMC, who were hospitalized at the First Affiliated Hospital of Fujian Medical University between 2003 and 2014. Details of the patients, including age, gender, ethnicity and clinical symptoms, were recorded, in addition to characteristics of the tumor, including size, location (right or left), surgery or biopsy confirmation, and presence of metastasis, necrosis and/or hemorrhage, pyelocaliectasis, vascular invasion and SC trait.

All examinations were performed on multi-slice CT (MSCT) scanners (Aquilion 16 and Aquilion ONE; Toshiba Medical Systems Corporation, Otawara-shi, Japan), using the following abdominal scanning parameters: i) Detector collimation, 16.0×0.5 mm (n=4) or 320.0×0.5 mm (n=2); ii) gantry rotation time, 0.35–0.50 sec; iii) pitch, 1.0–1.4; iv) tube voltage, 120 kV; and v) abdominal reference tube current, 60–120 mA. All images were reconstructed from the contrast-enhanced MSCT scans with a slice thickness of 0.75–1.00 mm and reconstruction increments of 0.5 mm.

For contrast-enhanced CT scanning, an 80–100-ml bolus of iopromide (300 mg/ml; Bayer HealthCare Pharmaceuticals, Berlin, Germany) was administered at a rate of 4–6 ml/sec via injection into an antecubital vein, followed by injection of 40 ml saline solution. The enhanced CT scans were initiated at 20–25 sec following injection for the arterial (cortical) phase; after 65–75 sec for the cortico-medullary (medullary) phase; and after 270–300 sec for the excretory (delayed) phase. In all cases where an initial non-contrast CT scan was available, the degree and pattern of enhancement of the tumor were determined in the nephrographic phase.

Evaluation of gross specimens was conducted to assess their shape; presence of necrotic components; formation of fibrous capsule; and invasion into the renal pelvis, calyx, ureter, renal vein or inferior vena cava. Light microscopy was used to evaluate pathological specimens, using an XP-201 polarizing microscope (Nanjing Jiangnan Novel Optics Co., Ltd., Nanjing, China), and an immunohistochemical analysis was also conducted. The tissue was obtained from the surgical resection or biopsy specimens in six cases. All tumors were fixed in neutral buffered formalin and all were paraffin embedded. Four-micron-thick sections of paraffin-embedded materials were cut, deparaffinized in xylene and rehydrated in descending dilution of ethanol. The sections were subjected to heat-induced epitope antigen retrieval using an electric pressue cooker set at 120°C for 5 min. For CAM5.2, enzyme treatment (IP enzyme [ventana,Tucson,AZ,USA]) was used in addition to the heat-induced epitope antigen retrieval. The tissue was pretreated with 3% hydrogen peroxidase for 10 min to block endogenous peroxidase activity. The sections were incubated in 10% normal goat serum in PBS for 10 min to block non-specific binding. The sections were washed three times for 5 min with TBS between incubation steps. The sections were incubated with the primary antibodies listed in Table II for 60 min. The sections were then washed as before and incubated with the secondary antibody, RealTM EnVision (K5007; Dako Denmark) for 30 min. Real TM DAB+Chromogen (Dako Denmark) was used as a chromogen for antigen localization. Slides were exposed to diaminobenzidine for 5 min. After immunostaining, the sections were counterstained with hematoxylin, coverslipped and sealed. PBS was used as a negative control for the primary antibody for each group. All renal tumors were confirmed to be RMC based upon the histological examination and immunohistochemical findings (1,13).

The imaging characteristics of the tumors were retrospectively evaluated by two genitourinary radiologists in consensus. The following parameters were evaluated in the tumors: Location; size; presence of calcification, cystic or necrotic components; and attenuation on unenhanced CT scan. The degree of enhancement of the tumors on enhanced CT was assessed during the aforementioned 3 phases, and the results were expressed in Hounsfield units (HUs). The presence of a capsule, hydronephrosis, perinephric stranding, vascular and renal tissue invasion, and metastases to retroperitoneal lymph node or other locations, was also documented.

On non-contrast enhanced CT, tumors were considered ‘isodense’ if their density in HU was equal to that of the renal parenchyma; ‘high’ if >30 HU; ‘mildly high’ if >10 HU; and ‘low’ if<10 HU, compared with the contralateral normal renal parenchyma. The tumors were considered to be solid or cystic masses based on the predominance. Tumor location was categorized as medullary, cortical or exophytic based on the association of the tumor with the renal parenchyma, and perinephric or renal sinus fat. Thus, a medullary tumor, in which a component extended into the renal pelvis, was considered to possess a medullary location. Similarly, any tumor that was limited to the confines of the renal contour was considered to have a cortical location; and an exophytic location was assigned to any tumor extending beyond the renal contour. The absence or presence of a tumor boundary was assessed on the delayed phase of CT as a poorly or clearly defined margin.

The attenuation of the tumor and the normal renal medulla and cortex of the contralateral kidney were measured during the 3 enhanced phases of CT. Intratumoral calcifications and cystic components were excluded from the measured tumor area, which was situated at the center of the mass and was defined as the region of interest (ROI). In each phase, each 10-mm area within the ROI was measured 4 times, and the mean value was calculated. The pattern of enhancement of the tumor was defined as heterogeneous or homogeneous, and its degree of enhancement was based on the HU attenuation of the tumor, renal cortex and medulla.

Statistical analyses were performed with SPSS statistical software, version 3.0 (SPSS Inc., Chicago, USA). The numerical data were presented as the mean ± standard deviation. One-way analysis of variance was used to compare the evaluated characteristics. P<0.05 was considered to indicate a statistically significant difference.

The present study included 6 patients with RMC (3 females and 3 males), whose clinical data are presented in Table I. The mean age of the patients at the time of diagnosis was 50.5 years (range, 22–72 years). Tumors were located in the right kidney in 3 cases, and the left kidney in the remaining 3 cases. The diameter of the tumors ranged from 2.90 to 10.50 cm (mean diameter, 7.48±3.25 cm), and tumor shape was observed to be oval in 4 cases, and irregular in 2. Of the 6 patients, 2 presented with retroperitoneal lymph node metastasis, and 3 with hydronephrosis. According to hemoglobin analyses, SC hemoglobinopathy was present in only 1 case, whereas the presence of SC trait was unknown for the remaining 5 cases, prior to detection of the tumor. There was no bias towards any particular location of the tumors or gender of the patients among the 6 cases included in the study.

All RMCs were located in the medulla and invaded the renal pelvis. The tumors extended to the renal cortex in 4 cases, and to the perirenal tissue in 1 case.

In all 6 cases, the tumor mass was predominantly solid and heterogeneous, and presented cystic or necrotic components. Punctate calcifications were detected in 1 case. A poorly defined margin of the RMC was observed in 4 cases on the delayed phase of CT, whereas the margin of the remaining 2 cases appeared well-defined. No fibrous capsule was present in any of the 6 cases. In 1 case, the tumor had spread into the retroperitoneal soft tissue, invaded the left renal artery, and developed regional lymph node metastasis.

The CT attenuation of the RMC was equal to that of the normal renal cortex and medulla (42.3±2.7 vs. 40.7±3.6 and 41.2±3.9 HU, respectively; P>0.05). On unenhanced CT, the attenuation of the solid part of the RMC was isodense, equal to that of the normal renal parenchyma, in all 6 cases (Fig. 1).

On dynamic contrast-enhanced CT scan, the attenuation of RMC was markedly lower than that of the normal renal cortex and medulla during all enhanced phases (P<0.05, n=6; Table III and Fig. 2).

All 6 patients with RMC underwent surgery. In 4 cases, the masses were oval, and in 2 cases, the masses were irregular in shape and exhibited regional lymph node metastasis. The tumor masses were firm or rubbery with white-to-grey color, and occupied the medulla (Fig. 3). All 6 tumors had invaded into the renal pelvis or calyx.

Despite the total nephrectomy performed, the patients presented a poor outcome. Consequently, chemotherapy and/or immunotherapy was administered post-surgically in 5 cases: One case received sunitinib at a dose of 50 mg/day, administered in one 6-week cycle of daily oral therapy for 4 weeks, followed by 2 weeks off. After the cycle, abdominal CT images revealed an enlargement of the previously observed retroperitoneal lymph nodes. The patient was then treated with two 7-week cycles of high-dose-intensity MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin), which was initially described by Sternberg et al (14,15). Doses of 30 mg/m² methotrexate and 3.0 mg/m² vinblastine were administered by intravenous infusion on days 1 and 15. Doses of 30 mg/m² doxorubicin and 70 mg/m² cisplatin were administered by intravenous infusion on days 2 and 16 of 28-day cycles. The other cases were treated with 1–3 cycles of high-dose-intensity MVAC. By contrast, 1 case diagnosed with increasing metastatic burden did not receive adjuvant therapy. The clinical condition of the patients rapidly deteriorated following diagnosis of RMC. The median survival time of the 6 cases from the time of diagnosis was 11 weeks.

All 6 tumors displayed similar microscopic characteristics, including a cribriform architecture and stromal desmoplasia (Fig. 4). The reticular pattern of growth consisted of tumor cell aggregates forming spaces of different sizes. An adenoid-cystic pattern of growth was further identified in 5 tumors. Necrosis was noted in all cases. Immunohistochemical studies confirmed homogeneous expression of low molecular weight cytokeratin CAM 5.2, and co-expression of vimentin and epithelial membrane antigen in all tumors.