Background
Collecting duct carcinoma (CDC) is a type of kidney cancer that originates in the duct of Bellini of the kidney and also known by several synonyms like Bellini duct carcinoma, medullary renal carcinoma, distal renal tubular carcinoma and distal nephron carcinoma[
1,
2]. CDC is an unusual variant of renal cell carcinoma and accounts for about 1% of all renal cell carcinomas. CDC is differentiated from other renal cell carcinomas by its characteristic location, typical histological appearance and poor prognosis[
1]. CDC metastasizes to regional lymph nodes in approximately 80% of cases, to the lung or adrenal gland in 25% and to the liver in 20%[
3]. Average survival time has been reported to be 22 months[
4]. Several treatments have been proposed but with limited efficacy, including radiation therapy, immunotherapy, chemotherapy, as well as combination therapy[
4‐
6].
Although many relevant studies have been reported[
7‐
9], it is necessary to gather more clinicopathological features of CDC to better diagnose and treat it. Therefore, we reported our experience with 5 CDC patients from August 2001 to September 2010 and explored their clinicopathological features and treatments in combination with literature review.
Discussions
CDC is located in the renal medulla and originates from the epithelial cells of Bellini collecting ducts[
1]. Because of its unique biological and pathologic characteristics that are different from the other renal cell carcinomas, it’s considered to be an independent histological type. Currently, WHO names it as Bellini duct carcinoma[
10].
CDC can occur at any age, and is more common in young adults. Men are more susceptible than women with the ratio of about 2:1. Tokuda et al.[
11] report that the average onset age is 58 years and male patients account for 71.6% of the cases. In present study, the average age was 54 years. Common clinical symptoms of CDC include painless gross hematuria, lumbar abdominal pain, waist and abdominal mass, fatigue, fever, and weight loss. It has a short and fast course. Normally, metastasis occurs in most of patients before treatment, including bone metastasis and lymph node metastasis[
11]. Three cases of lymph node metastasis and two cases of renal hilum fat metastasis were reported in the present study. Researchers have reported that CDC shows similar biological properties to those of urothelial cell carcinoma. Thus it is considered that they both originate from renal tubular and can occur simultaneously[
12].
Imaging examinations are the main methods for CDC diagnosis. The tumors are hypo-vascular with ill-defined border, and pose invasions to the renal cortex and renal sinus[
13,
14]. Hydrocalycosis often occurs because of the extruding from the tumors. Color ultrasound can reflect a hypoechoic, homogeneous or heterogeneous mass with irregular morphology and ill-defined bounder, as well as reduced blood flow signal. CT is able to detect the invasions of tumors into pelvis and renal cortex. Calcification and hemorrhage can also be seen in some cases. Mild to moderate uneven delayed enhancement can be detected in dynamic contrast-enhanced scan[
15]. MRI gives iso-intensity or hyper-intensity on T1WI and hypo-intensity on T2WI. The 5 cases in this study showed similar symptoms. CDC doesn’t have specific imaging features that distinguish it from other types of renal cell carcinoma such as renal medullary carcinoma, sarcomatoid renal cell carcinoma, and renal pelvis carcinoma, so its diagnosis requires pathological examination.
The pathological examination is the gold standard for diagnosis of CDC. As the tumors grow, they usually infiltrate into renal pelvis, renal cortex, and even renal hilum. CDC usually presents a tubulopapillary architecture, and tumor cells form hobnail pattern along the glandular tube. Poorly differentiated tumor cells show nest-shaped, rope-like, sarcomatoid or adenoid cystic morphology, with or without interstitial connective tissue reaction[
15‐
17].
Kidney cancer can be classified as multiple types based on the origin of tumor cell types, including renal cell carcinoma (RCC, the most common type), tubulocystic renal carcinoma[
18], renal solitary fibrous tumor[
19], renal pigmented paraganglioma[
20], and renal endocrine tumors[
21]. In addition to histological analyses, genetical and biochemical approaches are becoming more and more important for the differentiation and diagnosis of renal carcinomas. Genetical analyses include gene copy numbers, chromosomal imbalances, gene mutations and single nucleotide polymorphism (SNP) analysis[
18]. Many biomolecules, including epithelial-mesenchymal transition (EMT) markers such as N-cadherin[
22] and vimentin[
19] and human leucocyte molecules such as HLA-G and HLA-E[
23], are reported to be biomarkers for renal cancer. Immunohistochemical examination of these biomarkers is important for the determination of the origin and the diagnosis of CDC. Cancer cell have positive expressions of CK (AE1/AE3), CK7, CK19, EMA, vimentin, CK34BE12, PNA and ulex europeus agglutinin (UEA), and negative expression of CD10 and CK20. Combination of CK34BE12 and PNA is able to detect 90% of CDC[
24]. The results from pathological and immunohistochemical examinations are the important basis for the diagnosis of CDC and for differentiating it from other types of kidney cancer.
Radical nephrectomy is the major method to treat CDC. As the tumor cells spread in cortical collecting tubule, which results in poor prognosis, tumor enucleation and partial nephrectomy are not favorable. However, radiotherapy, chemotherapy and immunotherapy have limited efficacy on CDC[
12]. The postoperative survival time for the 2 cases of stage IV was 5 to 6 months, 18 months for the case of stage II, and 9 to 12 months for the 2 patients of stage III. Therefore, early detection and early surgery are the best way to prolong the renal collecting duct carcinoma survival time. Recently, there are a few reports on the effectiveness of targeted therapy with Sunitinib and sorafenib in treatment of CDC[
25‐
27]. However, there’s a study indicating no response of targeted therapy[
17]. Therefore, the efficacy of targeted therapy on CDC remains to be demonstrated.
Overall, our reports are beneficial supplements for better understanding the clinicopathological features of CDC. At the same time, the treatments and corresponding outcomes are valuable information for guiding future clinical practice.
Competing interests
The authors declare that they have no competing interests.
Authors’ contribution
XYW and JWH participated in the design, analyses and data interpretation and drafted the manuscript. RJZ, XSZ, TZY, DGD, LS, and ZHL helped to retrieve pathologic and clinical information and provide valuable insight during manuscript preparation. All authors reviewed and approved the final manuscript.