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ORIGINAL ARTICLE
Year : 2023 | Volume
: 34
| Issue : 3 | Page : 131-135
Collecting duct carcinoma of the kidney: Clinicopathological profile and outcomes
Abhilash Cheriyan1, Rajiv Paul Mukha1, Shailaja Balakumar2, Nirmal Thampi John1, Santosh Kumar1
1 Department of Urology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
2 Department of General Pathology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
Correspondence Address:
Abhilash Cheriyan
Department of Urology, Christian Medical College and Hospital, Vellore - 632 004, Tamil Nadu
India
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/UROS.UROS_63_22
Purpose: Collecting duct carcinoma of the kidney (CDC) is an aggressive subtype of renal cell carcinoma with a dismal prognosis. The available knowledge concerning optimal management is still unclear. We report the largest single-institutional experience in the management of CDC. Materials and Methods: All the cases of CDC which were diagnosed at our center following a radical or partial nephrectomy in the past 15 years were included. Treatment details, radiological features, and histological features were reviewed. Descriptive statistics were used to show the clinicopathological profile and management of these patients, and Kaplan–Meier overall survival (OS) estimate was calculated. Results: Eighteen patients who were diagnosed and underwent the primary intervention at our center were included. The median age of patients was 40 years, with a male-to-female ratio of 5:1. Typical histopathological features included high-grade nuclear features, stromal desmoplasia, and tubular architecture. Surgery was the primary modality of treatment. Five (28%) patients who had metastases received adjuvant therapy, three received interferon-alpha therapy, and two received adjuvant chemotherapy with gemcitabine and cisplatin. The median follow-up was 19 months (range: 3–46 months). Kaplan–Meier OS estimate was 68% at 1 year and 48% at 3 years. Conclusion: CDC of the kidney often presents at an advanced stage, and has a poor prognosis. Survival remains poor despite surgery and adjuvant therapy.
Keywords: Bellini, collecting duct carcinoma, nonclear cell, renal cell carcinoma
Collecting duct carcinoma (CDC) of the kidney is a rare and aggressive subtype of renal cancer arising from the collecting duct epithelium of the kidney with an incidence of 0.4%–1.8% of all renal tumors. Most patients present at an advanced stage, and survival is poor.[1] Due to the disease's rarity, most data regarding these tumors come from retrospective case series and reports.
CDC's presentation is nonspecific and similar to other renal malignancies.[2] Distant metastases are usually present at the time of diagnosis in 20%–32% of cases[1],[2],[3] with lung and bone being the most common sites for metastases. Median survival is only approximately 1 year.[4] The role of systemic therapy has not yet been defined. This study presents the largest, single-institutional experience to date for managing these tumors and can, therefore, be added to the existing literature on this rare tumor.
Materials and MethodsA retrospective review of the hospital's electronic database was conducted to identify the cases of CDC of the kidney from among those patients who underwent either radical or partial nephrectomy between June 2005 and January 2020. This study was in accordance with the ethical standards of the institution and the 1964 Helsinki declaration and its later amendments. The study was approved by the Institutional Review Board and Ethical Committee of Christian Medical College and Hospital, Vellore, India, IRB Min 13737 dated January 27, 2021. A consent waiver was obtained from the Institutional Review Board as per the Indian Council of Medical Research (ICMR 2017 Guidelines National Ethical Guidelines for Biomedical and Health Research involving Human Participants, 2017). In addition, verbal consent was obtained from the patients who were contacted telephonically to gather survival data. A transcript of the verbal consent was approved by the Institutional Review Board and Ethical Committee. Eighteen cases of CDC diagnosed on biopsy during this period were included in the study.[5] Patients who did not follow-up at our center or who did not undergo surgery were excluded. Histopathological and radiological data were retrieved from the hospital's electronic database. All cases were diagnosed by a team of experienced pathologists, each with over 10 years of experience, according to the 2004 World Health Organization (WHO) classification.[6] Descriptive statistics were used to illustrate the clinicopathological profile and management of these patients. Kaplan–Meier survival curves were constructed to measure overall survival (OS) using IBM SPSS Statistics for Macintosh, Version 23.0. (Armonk, NY: IBM Corp). A telephonic follow-up was performed to collect missing survival data.
ResultsA total of 1924 patients had undergone nephrectomy for malignant renal tumors between June 2005 and January 2020. The incidence of CDC was 0.93% (n = 18) in this series. The patients' median age was 40 years with a male-to-female ratio of 5:1. Flank pain was the most common presenting symptom and was noted in 12 cases. Other symptoms included hematuria, weight loss, and fever. The left kidney was involved in 12 of the 18 cases.
All patients underwent a preoperative contrast-enhanced computed tomography (CECT) of the abdomen and pelvis. The median tumor size was 7 cm (range: 3–14 cm). Three patients had enlarged lymph nodes (cN1) on preoperative imaging. A tumor thrombus extended into the renal vein in two cases and into the inferior vena cava in one case. Five (28%) cases were metastatic at initial presentation with four metastasizing to the bone and one to the lungs. All five patients with metastasis on presentation underwent initial cytoreductive nephrectomy followed by adjuvant therapy. Baseline patient characteristics are summarized in [Table 1].
[Table 2] summarizes the radiological and histopathological features of the tumors. On CECT of the abdomen and pelvis [Figure 1], 14 (77%) of the tumors were nonenhancing, and the renal contour was maintained in 8 (38%) cases. On histopathological examination [Figure 2], all tumors showed a predominantly tubular architecture with stromal desmoplasia and high-grade nuclear atypia (Fuhrman grade 3–4). Two cases displayed sarcomatoid differentiation. An infiltrative growth pattern was seen in 17 out of 18 (94%) cases. Tumor immunohistochemistry was performed for six patients as illustrated in the [Supplementary Table 1] and [Figure 3]. The primary intervention was surgery in all patients. A total of 16 patients underwent radical nephrectomy, while two underwent partial nephrectomy. Three patients (3/18) were either pN1 or pN2. Three patients received adjuvant interferon-alpha therapy, while two received adjuvant chemotherapy with gemcitabine and cisplatin. Follow-up data were available for 14 patients with a median follow-up of 19 months (range: 3–48 months). One patient had a local recurrence but was subsequently lost to follow-up. The Kaplan–Meier survival estimate for OS [Figure 4] was 68% at 1 year and 48% at 3 years. Median OS for the entire cohort was 24 months (95% confidence interval (CI), 7.78–40.22). For those patients with metastatic disease, the median OS was 16 months (95% CI, 5.22–26.79). On stratifying patients according to age, younger patients (<40 years of age) had a median OS of 12 months (95% CI 3.0–46.00).
Figure 1: Axial section of a CECT abdomen showing a hypoenhancing, centrally located, endophytic tumor arising from the right kidney, CECT: Contrast-enhanced computed tomography
Figure 2: Photomicrograph showing, (a) Tubular architecture and stromal desmoplasia, (b) Hobnail cells (H and E, ×200)
Figure 3: Photomicrograph showing positive immunohistochemical staining with (a) HMWCK and (b) PAX8 (×400). HMWCK: High-molecular-weight cytokeratin, PAX8: Paired-box gene 8
Figure 4: Kaplan–Meier estimate for overall survival for patients who were metastatic and nonmetastatic at presentation Discussion CDC is a rare and aggressive tumor with a poor prognosis. While the incidence CDC in this series was similar to prior reports, most of the patients reported here were much younger (median age of 40 years) compared to other studies where the median age at diagnosis was 53–68 years.[1],[7],[8] Moreover, this study had a higher incidence of men (83%) compared to 63%–70% in prior reports. The median size of the tumor at presentation was 7 cm, which is similar to that reported by Tokuda et al. and Karakiewicz et al. (6 cm in both series).[2],[3] Pinto et al. in a multicenter series from 28 hospitals in Spain reported an incidence of metastatic disease at diagnosis of 32.6%.[8] In this study, 27% of the patients had a distant metastasis at their initial presentation. Although Karakiewicz et al. in a matched cohort analysis found a higher nodal involvement in CDC (49%) compared to an 8% incidence in conventional clear-cell renal cell carcinoma (RCC),[3] only 16.6% were pN+ in this cohort. Lymph node dissection is not routinely performed for RCC at this center. Nodes are sampled if there is suspicion of nodal involvement on imaging or during the operation.
Differential diagnoses on imaging include medullary carcinoma, papillary renal carcinoma, and urothelial carcinoma. On CECT, the majority of tumors are central in location. Pickhardt et al.[9] reported that the reniform contour was maintained in 41% of their cases. An infiltrative appearance was seen in the majority (66%) of those cases as opposed to expansile growth, and this can be confused with urothelial carcinoma which may have a similar appearance. CDC can have both a solid and cystic appearance. In another study that characterized the CT findings of CDC, of the 18 cases, 94% had a medullary location, 50% had a cystic component, 67% showed an infiltrative growth pattern, and the renal contour was maintained in 61%.[10] Most tumors are nonenhancing on CT.[2] This study showed similar findings.
The histopathological findings typical of CDC are high-grade nuclear atypia, hobnail cells, tubular architecture, and stromal desmoplasia which are seen in almost all cases.[11] Similar results were found in this study. The WHO's classification of tumors,[12] includes medullary involvement, typical histology of tubular architecture with a high nuclear grade and desmoplastic stroma, reactivity to antibodies against high-molecular-weight cytokeratin, Ulex europaeus agglutinin 1 (UEA-1), and the absence of urothelial carcinoma as the major criteria for the diagnosis of CDC.
Immunohistochemical (IHC) studies are useful in differentiating among CDC, urothelial, and papillary carcinomas since they can share similar imaging features.[13] Moreover, urothelial carcinoma and CDC have overlapping IHC features as well. UEA-1reactivity, positivity for E-cadherin, and c-KIT are effective in differentiating between CDC and papillary RCC. Papillary RCC has negative results for alpha-methylacyl-CoA racemase and CD10. Urothelial carcinoma has similar IHC features as CDC except that there is a higher rate of positivity for high-molecular-weight and low-molecular-weight cytokeratin. Therefore, a careful examination of routine stains is vital to differentiate the two. More recently, paired-box gene 8 (PAX8) and p63 have emerged as important IHC markers with CDC showing positivity for PAX8 in 90% of specimens, while p63 is positive in 97% of urothelial carcinoma cases. Therefore, PAX8+/p63 strongly favors CDC, while PAX8-/p63+ favors urothelial carcinoma.[14] However, specific IHC markers were not available until 2012 at our center, and therefore, were not performed in the majority of cases reported in this series.
Surgery is the primary mode of treatment.[3] It was the criterion for inclusion in this analysis. Adjuvant immunotherapy with interferons and several cases of chemotherapy with gemcitabine and carboplatin have been reported similar to this study. In a prospective multicenter phase II study from the GETUG group, 23 patients with metastatic CDC received gemcitabine and cisplatin as first-line chemotherapy.[15] A total of 87% had undergone radical nephrectomy in that cohort. That study showed an objective response rate of 26%, and concluded that platinum-based chemotherapy should be considered the standard regimen in metastatic CDC due to similarities in tumor biology with urothelial carcinoma. The role of targeted therapy has been investigated recently. Sheng et al., in a prospective, multicenter, phase II study, showed an objective response rate of 30% for the addition of sorafenib to platinum-based chemotherapy as first-line treatment for metastatic CDC.[16] Retrospective data have shown that interleukin-2, interferon-alpha, and interferon-gamma do not provide any meaningful response as adjuvant treatments.[17] The use of cabozantinib as first-line adjuvant therapy has also been explored.[18] Despite these efforts, survival remains poor.
One-year OS in studies reported from Japan, the USA, and Europe was 69%, 70%, and 86%, respectively. In this study, 1-year OS was 68%. Median survival was significantly poorer in those with metastasis at diagnosis as would be expected. The prognosis was significantly poorer in younger patients on stratification as <40 years and over 40 years of age at presentation. This study had a limited median follow-up of 19 months. Four of the 18 patients were lost to follow-up and could not be contacted.
Due to the rarity of the disease, prospective studies may not be feasible even in high-volume centers. A better understanding of the underlying tumor biology and multicenter studies to investigate the role of immunotherapy and targeted therapy may provide some insight for better management of this aggressive tumor.
ConclusionsIn this cohort, patients were much younger at the time of diagnosis when compared to other studies.[2],[3] CDC should be considered when a central, nonenhancing, and infiltrative mass on imaging is encountered. These tumors have characteristic histopathological features. Surgery is the mainstay of management; there are no effective adjuvant therapies; and unfortunately, prognosis remains dismal even in the current era, especially for younger patients.
Data Availability Statement
The datasets generated during and/or analyzed during the current study are available in the Mendeley repository from: https://data.mendeley.com/datasets/nwybh77rj8.
Acknowledgments
The authors would like to thank Department of Pathology of the hospital for capturing representative photomicrographs.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
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