Collecting-duct carcinoma was first described in 1949 and was recognized as a separate entity of renal cell carcinoma in 1986. Since then several case series have been reported, with these tumors now being recognized as an aggressive form of renal neoplasia.
Collecting-duct carcinomas comprise approximately 1% of renal epithelial malignancies and often present with advanced stage disease.
They have been described as occurring in a wide patient age range, but generally affect patients in the 4th to 7th decades (mean age 55 years), with a male predominance of approximately 2:1.
These tumors are frequently symptomatic, with typical presenting features being one or more of the classic renal tumor triad of hematuria, abdominal mass and intermittent flank/back pain, and also fatigue and weight loss.
The frequency of symptomatic presentation of these tumors reflects their rapid growth and early metastatic spread, with approximately one-third of patients being shown to have metastases at the time of diagnosis.
Evidence of a collecting-duct origin for these tumors is that when small, the primary tumor was usually confined to the renal medulla. Despite this these tumors are usually of large size when diagnosed and involve both the renal cortex and medulla.
Typically collecting-duct carcinomas are white to gray and have a firm consistency on sectioning. Tumor necrosis is typically present although hemorrhage is not usually seen macroscopically. These tumors may extend into the renal pelvis and on imaging studies may mimic pelvic urothelial carcinoma.
The microscopic features of collecting-duct carcinoma may be somewhat variable, however, the morphologic criteria for diagnosis are the presence of an infiltrative tubular or tubulopapillary pattern, associated with a desmoplastic stromal reaction.
The tumor cells typically exhibit a high grade of nuclear pleomorphism and nuclear atypia is seen in the epithelium of adjacent renal tubules. Mitotic figures are frequently present and histochemically both acid and neutral mucin may be seen.
In addition to the tubulopapillary architecture, these tumors may also contain compact papillary structures, solid sheet-like areas of tumor cells and microcysts. Occasionally foci of spindle cells are present, however, if this is more than a rare occurrence, the tumor should be considered to be a sarcomatoid carcinoma arising within a collecting-duct carcinoma.
There is usually an associated chronic active inflammatory cell infiltrate in and adjacent to the tumor, and in some cases a neutrophilic infiltrate can be quite pronounced. Tumor architecture may be recapitulated in extra-renal metastases.
Immunochemistry
The immunohistochemical expression of collecting-duct carcinoma reflects the origins of the tumor from the collecting duct of the distal nephron.
Tumors usually show positive reactions to lectins such as Ulex europeaus agglutinin-1 and peanut lectin, also e-cadherin, c-KIT, and both high and low molecular weight cytokeratins. Vimentin staining of tumor cytoplasm may also be present.
There is a variable expression of Leu M1 and EMA, whereas markers of proximal renal tubules (CD10, RCC antigen and AMACR) are almost always negative.
There are limited studies on the genetics of collecting-duct carcinoma and the results to date are inconclusive, with no consistent genetic abnormality being noted.
The karyotype of one tumor was reported as showing trisomy for chromosomes 4, 7, 8, 17 and 20 and loss of chromosomes 14, 18 and 22.
This compares with monosomy of chromosomes 1, 6, 14, 15 and 22 noted in three further cases.
Loss of chromosomes 4 and 18 was also found in two of these tumors, although in this latter series the diagnosis of some of the cases has been questioned. In further studies loss of heterozygosity of 8p and 13q has been reported.
Differential diagnosis
The differential diagnosis of collecting-duct carcinoma includes papillary renal cell carcinoma, renal medullary carcinoma, metastatic carcinoma and urothelial carcinoma with glandular differentiation.
Papillary renal cell carcinoma usually only poses a problem if it is of high grade, but usually lacks the desmoplasia and infiltrative pattern typical of collecting-duct carcinoma. Immunohistochemical staining can be useful in differentiating between these two tumor types with papillary renal cell carcinoma frequently showing positivity for CD10, AMACR and RCC antigen.
Medullary carcinoma may show a morphologic overlap with collecting-duct carcinoma, but usually exhibits reticular and solid patterns of growth. The constant association with sickle cell trait and young patient age at diagnosis are further indicators in favor of a diagnosis of medullary carcinoma.
Metastatic adenocarcinoma should always be considered in the differential diagnosis of these tumors, as there is usually a marked desmoplastic response to tumor associated with a brisk inflammatory cell infiltrate. A previous history of malignancy may be of diagnostic assistance and appropriate clinical and immunohistochemical investigations should be undertaken to further characterize tumors as metastatic rather than primary.
Upper tract urothelial carcinoma may cause some difficulty in differentiation from collecting-duct carcinoma, especially when glandular elements are identified within the tumor. In such cases, the presence of in situ urothelial carcinoma in adjacent calyces or within the renal pelvis argues against the diagnosis of collecting-duct carcinoma.
Immunohistochemical staining may also be useful in differentiating between these two tumors, with positive CK20 and low molecular weight cytokeratin indicative of urothelial carcinoma. Results of staining for markers of the distal nephron should be interpreted with caution as expression of cytokeratin AE1/AE3 and Ulex Europeaus agglutinin-1 has been reported in high-grade urothelial carcinoma arising from the renal papilla and exhibiting adjacent carcinoma in situ.
Recently immunoexpression of transmembrane enzyme complex carbonic anhydrase IX has been shown to differentiate urothelial carcinoma (diffuse to multifocal strong membrane staining in 90% of cases) from collecting-duct carcinoma (scanty, focal and weak membrane staining in 60% of cases).
Prognosis
Survival data from case reports and small case series indicates that these tumors have a poor prognosis. From these reports up to 40% of patients have metastatic spread of tumor at presentation and most patients die within 1–3 years of diagnosis. The largest case series to consider outcome to date was reported from Japan and consisted of 81 patients.
Regional lymph node metastases were present in 44% of the patients in this series at diagnosis, whereas 32% had distant metastases. The 1-, 3- and 10-year disease-specific survivals in this series were 69, 45 and 14%, respectively.
See also
- renal carcinomas
References
Uncommon and recently described renal carcinomas. Srigley JR, Delahunt B. Mod Pathol. 2009 Jun;22 Suppl 2:S2-S23. PMID: 19494850