In 1976, Mancilla Jimenez et al. first reported that some papillary renal cell carcinoma originated from the collecting duct. Fleming and Lewi described 6 cases of CDC and presented diagnostic criteria to recognize it as a unique pathologicalsubtype of RCC. It was listed as one of the major subtypes of renal cell carcinoma in both the 2002 and 2006 WHO classifications. The key point of pathological diagnosis is the nail-like cells are covered on the inner surface of the papillary gland arranged on the tumor cells. The tumor interstitial inflammatory fibrosis and collagen secretion are obvious and the tumor tissue is dense. The pathological examination results of this group of cases basically conform to these characteristics (Figure 8 A-D).
A wide patient age range exists, with a mean age at diagnosis of 64 years and a 3:1 male predominance. Although it is similar to the series of reports[8,9], this demographic proﬁle also applies to renal cell carcinoma in general and is therefore not a useful discriminator. The clinical manifestations of the patient are not specific compared to any other renal cell carcinomas and may have gross hematuria and waist and abdomen pain, abdominal fullness, and sometimes palpable mass. 11 (84.6%) cases had gross hematuria, and 6 (46.2%) had low back pain or lumbar discomfort. One of the patients had no clinical manifestations of urinary disease with low fever and night sweats and admitted to hospital for suspected tuberculosis.
Site and Border
CDC has the following pathological features. The initial site of the tumor is in the renal medulla, which is grayish white or light yellow. The texture is more tough than the clear cell carcinoma. The renal interstitial is used as a scaffold for tumor cells to diffuse and infiltrate along the collecting duct to the renal pelvis and renal cortex. Therefore, most of the tumors occur in the medulla and infiltrate into the cortex and renal pelvis. There is no clear junction with normal kidney tissue. The borders are irregular and most of the kidney tumors have an outward expansive growth pattern from the center. Normal renal parenchyma is displaced and/or local kidney contour bulged and the formation of a pseudocapsule[17,19]. Jonathan RY et al. found that sarcomatoid RCCs and collecting duct carcinoma were both more likely than common RCC subtypes and benign RCC mimics to have an infiltrative spread pattern andan irregular contour. When used to discriminate sarcomatoid RCC and collecting duct carcinoma from other solid renal masses, an infiltrative spread pattern had a specificity of 93% (287/308) and sensitivity of 82% (9/11), while an irregular contour had specificity of 98% (303/308) and sensitivity of 64% (7/11).
According to the infiltration site of CDC, it can be divided into medulla type, cortex-medulla type and cortex-medullary-pelvis type. There was no simple medullary type of this group of patients. The masses were mostly located in the cortex-medulla type (6 cases, 46.2%) and the cortex-medullary-pelvis type (7 cases, 53.8%) . This feature is different from the common renal clear cell carcinoma derived from cortical renal tubules. The latter is centered on the renal cortex and invaded to the medulla or extrarenal. There is no uniformity and clear boundaries between uniformly strengthened normal kidney tissue and tumors centered on the cortex-medullary-pelvis. The tumor can rapidly grow toward the renal pelvis and cortex and destroy the renal pelvis and renal hilum structure, even severely involve the upper ureter. Thus, assessing for the presence of an infiltrative spread pattern and an irregular contour can provide a simple, noninvasive means of discriminating collecting duct carcinoma from other solid renal masses with a relatively high specificity, sensitivity, and negative predictive value.
Morphology and Size
The morphology of tumors is closely related to the biological behavior and growth pattern of tumors. Despite its medullary derivation, almost all tumors exhibit focal cortical extension, and perinephric extension is also common. It has been mentioned that the growth mode of CDC tumors is spread along the collecting duct with invasive growth and there is more fibrous tissue hyperplasia in tumor stroma[5,8]. Therefore, most of CDC are not as sharp as the other tumors in the kidney. The tumors have diffuse enlargement based on the kidney contour or a certain kidney segment without clear boundaries, capsules or pseudocapsule. This characteristic can be observed in 12 of the 13 cases (92.3%) in our group. There are also 2 cases of mass-type in this group. In one case, the inflammatory fibrous tissue proliferation of the tumor interstitial of CDC is not significant. The tumor outline is bounded by the tumor cell aggregation area. Therefore, we believe that the morphology of CDC tumors is related to the degree of tumor interstitial fibrous tissue hyperplasia. The more significant interstitial fibrosis is, the less clear the tumor outline and vice versa. According to the morphological characteristics of the tumor, it is helpful to distinguish it from other kidney tumors.
The diameter of the tumors ranged from 5.12 to 12.40 cm ( mean diameter, 8.48 ± 2.48cm ) , 4 cases were greater than 10 cm. In general, the size of CDC is often relatively large. A medullary origin can be difﬁcult to appreciate with large tumors. Fukuya et al. described the CT findings of small tumors, all measuring between 3 and 4.5cm. These lesions were all centered in the renal medulla, four of five protruded in the central sinus, and none showed exophytic growth but, rather, preserved the reniform contour in all cases.
CT density and MRI signal
The originating organ of CDC is water-rich kidney tissue. The tumor stroma has more fibrous tissue hyperplasia and collagenation. So when compared with normal tumor tissue adjacent to the tumor, the tumor parenchyma show relatively high density, which is the overall feature of this group of CDC tumors in plain scan CT. This is different from renal cell carcinoma origining from renal cortex. CDC has obvious interstitial reaction. The interstitial is dense or the collagen secretion is large. Most of which are inflammatory fibroblastic tissue hyperplasia and rich in fibrous tissue components. It is an important basis for pathological diagnosis and appear as low signal on magnetic resonance T2WI.
The MR examinations reported by Pickhardt et al. (4 cases in total) showed that the parenchymal components of all 4 tumors showed equal signals on T1WI. 1 case of tumor with multiple cystic components, each cyst showed a low to high T1 signal (including water, fat, bleeding and other signals). On T2WI, the parenchymal components of all 4 tumors were lower than normal renal parenchyma. There is no low signal on the edge of tumor indicating the presence of a pseudo-envelope observed on MRI. In this group, 1 case of MRI showed that the tumor parenchyma was low signal on T2W1. The cystic necrosis area was high and low mixed signal on T2WI, which was unclear with the surrounding normal renal parenchyma. There was no obvious ring-shaped low T2WI signal-like pseudo-envelope.
The incidence of calcification in CDC tumors is probably due to more fibrous tissue in the tumor stroma and calcium salts are easy to deposit in fibrous tissue. However, only 2 (15.4%) cases of this group of data found calcification. In contrast to conventional RCCs, calcification was also observed in only one case in Seong KY’s report. Because the CDC tumor is dense, the water content is less and there are more inflammatory fibrous tissue hyperplasia in the tumor interstitial. While the normal kidney tissue is rich in water (low T1WI, high T2WI signal). Therefore, the tumor parenchyma is equal, high signal on T1WI and low signal on T2WI. Kato et al. described the signal intensity of CDC at T2-weighted imaging as isointense or hypointense, which was thought to be due to haemosiderin deposition. Larger clear cell renal cell carcinomas tend to have a heterogeneous hyperintense signal on T2-weighted imaging, differentiating it from CDC.
Some liquid components can be seen as low-density areas in tumors. The shape is very irregular and the boundary is unclear. It is like the shape of a map or a lake, which is different from the necrotic morphology of common tumors. Combined with pathological results, we think these diffuse patchy low-density lesion should be based on the collagen denaturation zone. There is still a cystic lesion of cystic solid tumor in this group as a true cyst, which is a rare sign of CDC tumor. In the existing literature, only one of 17 cases of CDC reported by Perry is cystic CDC. The inner wall is covered with true epithelium, and its pathological mechanism remains to be further studied. When the essential components and cystic components coexist, careful analysis of the characteristics of the essential part is conducive to diagnosis and differential diagnosis.
The results of this group of patients show that the vast majority of CDC tumors are hypovascular. Most of the CDC tumors in the dynamic enhanced scan show relatively low density in the renal cortex and medulla. The parenchymal part of the mass is uneven lightly-moderately enhanced by marginal in cortical or medullary phase (intracapsular papillary can also be strengthened) and lower than the surrounding renal parenchyma. The medullary phase showed uneven and mild delayed enhancement. The degree of enhancement was still lower than that of the renal parenchyma, which is consistent with the results of another group of Chinese study. This enhancement type is different from the blood-rich clear cell renal cell carcinoma, renal medullary carcinoma, renal angiomyolipoma and renal angioma. Seong KY et al. also found that unlike in the case of the more common conventional RCC, contrast-enhanced CT scans of the CDCs usually demonstrated weak (69%) and heterogeneous enhancement (85%). This enhanced feature is still different from renal clear cell carcinoma, which is significantly enhanced in cortex phase, its density value quickly reaches its peak and decreases significantly during the medullary phase. This enhanced pattern of CDC tumors also contributes to the identification of renal clear cell carcinoma. Fujimoto et al. analyzed the enhancement pattern of renal cell carcinomas greater than 5cm in diameter on contrast-enhanced helical CT. They reported that strong enhancement equal to the renal cortex was noted only in conventional renal carcinoma (75%). Jeong KK et al. reported that conventional renal carcinoma showed stronger enhancement than nonconventional renal carcinomas in both the corticomedullary and excretory phases, and the tumors that enhanced more than approximately 84HU in the corticomedullary phase and 44HU in the excretory phase were likely to be conventional renal carcinoma, while our data showed only 23.5HU increased in cortical phase.
CTA can show that the renal artery participates in blood supply and the distal branches are destroyed. The filling defect can be seen in renal vein and inferior vena cava. The tumor thrombus has an expanded shape and the degree of enhancement is similar to the central necrotic area and the hypovascular area. No tumor blood vessels were observed in the vicinity of the tumor and the original renal blood vessels were not thickened or significantly displaced. These characteristics indicate that CDC tumor cells do not produce angiogenic factors, and the original renal artery branches are rarely destroyed by tumor cells. The fibrous tissue in the tumor stroma will also compress the intratumoral vessels, which is different from the renal tubular cell carcinoma. The renal tubular cell carcinoma has hyperplasia of vessels and in spherical shape with tumors.
Most common renal cell carcinomas have low FDG metabolism and are similar to normal renal parenchyma, 18F-FDG PET has certain limitations in the detection and diagnosis of common renal cancer. Due to renal collecting duct cancer is rare, there is not much literature on PET performance. Ye et al reported a case of collecting duct carcinoma with a maximum diameter of 4.6 cm in the right kidney. The SUVmax of PET was 7.0. Two patients in our group underwent PET/CT examination, and the primary lesions were highly metabolized, with SUVmax of 14.9 and 14.3, respectively. Moreover, one of the PET/CT images showed higher metabolism in lymph nodes, lungs, pleura and multiple bone metastases, which was consistent with HU and other studies. Compared with other common renal cancer pathological types (such as clear cell carcinoma), collecting duct carcinoma may be characterized by high invasiveness and poor prognosis, often showing high FDG uptake. 18F-FDG PET/CT has obvious advantages in the judgment of renal tumor metastases. Besne I and other studies have shown that the 5-year survival rate of distant metastasis of urinary tumors is 0%-20%. However, if the isolated metastases are resected, the 5-year survival rate can reach 25%-50%. Therefore, early detection of metastases is essential. Safaei et al reported that the sensitivity and specificity of PET for detecting renal cell carcinoma metastases were 87% and 100%, respectively. Majhail et al studied biopsy or surgical resection of 36 metastatic lesions in 24 patients with renal cell carcinoma. The results showed that the specificity and positive predictive value of 18F-FDG PET/CT for distant metastasis were 100%. But this group of the high-metabolism lymph nodes revealed by PET-CT showed no metastasis after surgical resection, which proved that the diagnosis of lymph node metastasis by PET-CT remains to be discussed.
Local invasion and distant metastasis
CDC cancer has high malignancy, strong invasiveness and early metastasis. This feature has become a consensus[5,7,10,15-16,18]. The incidence of extracranial metastasis of CDC tumor in this group further confirms the characteristics of early metastasis of CDC. The incidence of metastasis reached 69%. The rapid metastatic spread and aggressiveness of the CDC may be due to its central or perihilar location. The tumor has the characteristics of infiltration into the kidney and local lymph node metastasis and distant metastasis. Most patients have lymph nodes enlargement and distant organs metastasis. Among them, lymph node metastasis accounts for 80%, lung and adrenal metastasis accounts for 25%, and the liver metastasis accounted for 20%. The prognosis was extremely poor, the patients died within 2 years of onset. In this case, 9 (69.2%) cases of lymphatic metastasis, 2 (15.4%) cases of adrenal gland involvement, 1 (7.7%) case of inferior vena cava involvement, 3 (23.1%) cases of bilateral lung metastasis, 1 (7.7%) case of bilateral pleural metastasis, 1 (7.7%) case of brain metastasis, 1 (7.7%) case of bone metastases (including the right rib, pubis and left side scapula) is associated with its high degree of malignancy and its invasive biological characteristics.
There are some limitations to our study. The main limitation is that the number of CDCs was too small for the analysis of CT and histopathologic findings to be significant. Future study with a larger number of cases is necessary.