Carcinoma of the collecting ducts of Bellini and renal medullary carcinoma are rare aggressive neoplasms of putative distal nephron origin. First described in 1949, case reports and review articles constitute a major source of information on collecting duct carcinoma, whereas Davis and colleagues and the pediatric tumor registry have contributed the seminal works on renal medullary carcinoma. Here we present a detailed study of collecting duct carcinoma (n=39) and renal medullary carcinoma (n=13), characterizing these rare neoplasms and analyzing their interrelationship. Both collecting duct carcinoma and renal medullary carcinoma exhibited significant similarities, such as predilection for the right kidney, tumor mass with an epicenter in the renal medulla, and a mean size of 7 cm. Overall, both tumors exhibited a poorly differentiated adenocarcinoma histology with desmoplastic stromal response (100%), inflammatory infiltrate (100%), frequent perinephric extension (collecting duct carcinoma: 97%; renal medullary carcinoma: 83%), lymphovascular invasion (100%), intraluminal mucin (collecting duct carcinoma: 42%; renal medullary carcinoma: 73%), high nuclear grade (97%), overlapping immunoreactivity for Ulex europaeus agglutinin 1 (collecting duct carcinoma: 75%; renal medullary carcinoma:55%), CK7 (collecting duct carcinoma: 44%; renal medullary carcinoma: 71%), and high-molecular weight cytokeratin (collecting duct carcinoma: 26%; renal medullary carcinoma: 29%), and nonimmunoreactivity for Ksp-cadherin. Histologically, collecting duct carcinoma frequently had tubular, tubulopapillary, or irregular glandular architecture, whereas renal medullary carcinoma commonly demonstrated islands of anastomosing tubules and cords forming irregular microcystic spaces. Multiple metastases to the lymph nodes, lung, bone, and liver were observed in both categories at presentation (collecting duct carcinoma: 17%; renal medullary carcinoma: 36%). Only patients with organ-confined small tumors were disease free beyond the median survival time. Differential clinical features between collecting duct carcinoma and renal medullary carcinoma included proclivity for younger male individuals of African ancestry with hemoglobin abnormalities and a shorter median survival of 17 weeks (vs. 44 wk for collecting duct carcinoma) for renal medullary carcinoma. The markedly overlapping clinical features, histology, immunophenotype, metastasis patterns, and uniformly aggressive outcome in collecting duct and renal medullary carcinomas suggest that renal medullary carcinoma is a distinctive clinicopathologic subtype within the entity of collecting duct carcinoma. The extremely poor prognosis and ongoing clinical trials with specific therapeutic protocols argue for their accurate distinction from other renal cell carcinoma subtypes. © 2012 Lippincott Williams & Wilkins.36912651278Srigley, J.R., Moch, H., Carcinoma of the collecting ducts of Bellini (2004) Classification of Tumors Pathology & Genetics: Tumors of the Urinary System and Male Genital Organs, pp. 33-34. , Eble JN Sauter G Epstein JI et al eds World Health Organization Lyons: IARCAmin, M.B., Varma, V.D., Tickoo, S.K., Collecting duct carcinoma of the kidney (1997) Adv Anat Pathol, 4, pp. 85-94Fleming, S., Lewi, H.J.E., Collecting duct carcinoma of the kidney (1986) Histopathology, 10 (11), pp. 1131-1141Foot, N.C., Papanicolaou, G.N., Early renal cell carcinoma in situ: Detected by means of fixed urinary sediment (1949) J Am Med Assoc, 139, pp. 356-358Srigley, J.R., Eble, J.N., Collecting duct carcinoma of kidney (1998) Seminars in Diagnostic Pathology, 15 (1), pp. 54-67Avery, R.A., Harris, J.E., Davis Jr., C.J., Borgaonkar, D.S., Byrd, J.C., Weiss, R.B., Renal medullary carcinoma: Clinical and therapeutic aspects of a newly described tumor (1996) Cancer, 78 (1), pp. 128-132. , DOI 10.1002/(SICI)1097-0142(19960701)78:1<128::AID-CNCR18>3.0.CO;2- 1Milowsky, M.I., Rosmarin, A., Tickoo, S.K., Papanicolaou, N., Nanus, D.M., Active chemotherapy for collecting duct carcinoma of the kidney: A case report and review of the literature (2002) Cancer, 94 (1), pp. 111-116. , DOI 10.1002/cncr.10204Oudard, S., Banu, E., Vieillefond, A., Fournier, L., Priou, F., Medioni, J., Banu, A., Culine, S., Prospective Multicenter Phase II Study of Gemcitabine Plus Platinum Salt for Metastatic Collecting Duct Carcinoma: Results of a GETUG (Groupe d'Etudes des Tumeurs Uro-Génitales) Study (2007) Journal of Urology, 177 (5), pp. 1698-1702. , DOI 10.1016/j.juro.2007.01.063, PII S002253470700064XSrigley, J.R., Delahunt, B., Uncommon and recently described renal carcinomas (2009) Mod Pathol, 22 (SUPPL. 2), pp. S2-S23Staehler, M., Schoppler, G., Haseke, N., Carcinoma of the collecting ducts of Bellini of the kidney: Adjuvant chemotherapy followed by multikinase inhibition with sunitinib (2009) Clin Genitourin Cancer, 7, pp. 58-61Wu, Z.S., Lee, J.H., Kwon, J.A., Genetic alterations and chemosensitivity profile in newly established human renal collecting duct carcinoma cell lines (2009) BJU Int, 103, pp. 1721-1728Davis Jr., C.J., Mostofi, F.K., Sesterhenn, I.A., Renal medullary carcinoma. The seventh sickle cell nephropathy (1995) Am J Surg Pathol, 19, pp. 1-11Eble, J.N., Renal medullary carcinoma: A distinct entity emerges from the confusion of "collecting duct carcinoma (1996) Adv Anat Pathol, 3, pp. 233-238Albadine, R., Wang, W., Brownlee, N.A., Topoisomerase II alpha status in renal medullary carcinoma: Immuno-expression and gene copy alterations of a potential target of therapy (2009) J Urol, 182, pp. 735-740Rathmell, W.K., Monk, J.P., High-dose-intensity MVAC for advanced renal medullary carcinoma: Report of three cases and literature review (2008) Urology, 72, pp. 659-663Schaeffer, E.M., Guzzo, T.J., Furge, K.A., Renal medullary carcinoma: Molecular, pathological and clinical evidence for treatment with topoisomerase-inhibiting therapy (2009) BJU Int, 106, pp. 62-65Billis, A., Renal medullary carcinoma: Report of seven cases from Brazil (2007) Int Braz J Urol, 33, pp. 724-726Watanabe, I.C., Billis, A., Guimaraes, M.S., Alvarenga, M., De Matos, A.C., Cardinalli, I.A., Filippi, R.Z., Suzigan, S., Renal medullary carcinoma: Report of seven cases from Brazil (2007) Modern Pathology, 20 (9), pp. 914-920. , DOI 10.1038/modpathol.3800934, PII 3800934Davis Jr., C.J., Renal medullary carcinoma (2004) Classification of Tumors Pathology & Genetics: Tumors of the Urinary System and Male Genital Organs, pp. 35-36. , Eble JN Sauter G Epstein JI et al eds. World Health Organization Lyons: IARCAmin, M.B., Amin, M.B., Tamboli, P., Javidan, J., Stricker, H., Venturina, M.D.-P., Deshpande, A., Menon, M., Prognostic impact of histologic subtyping of adult renal epithelial neoplasms: An experience of 405 cases (2002) American Journal of Surgical Pathology, 26 (3), pp. 281-291. , DOI 10.1097/00000478-200203000-00001Downs, T.M., Schultzel, M., Shi, H., Renal cell carcinoma: Risk assessment and prognostic factors for newly diagnosed patients (2009) Crit Rev Oncol Hematol, 70, pp. 59-70Galfano, A., Novara, G., Iafrate, M., Cavalleri, S., Martignoni, G., Gardiman, M., D'Elia, C., Ficarra, V., Mathematical models for prognostic prediction in patients with renal cell carcinoma (2008) Urologia Internationalis, 80 (2), pp. 113-123. , DOI 10.1159/000112599Adsay, N.V., DeRoux, S.J., Sakr, W., Grignon, D., Cancer as a marker of genetic medical disease: An unusual case of medullary carcinoma of the kidney (1998) American Journal of Surgical Pathology, 22 (2), pp. 260-264. , DOI 10.1097/00000478-199802000-00017Baer, S.C., Ro, J.Y., Ordonez, N.G., Maiese, R.L., Loose, J.H., Grignon, D.G., Ayala, A.G., Sarcomatoid collecting duct carcinoma: A clinicopathologic and immunohistochemical study of five cases (1993) Human Pathology, 24 (9), pp. 1017-1022. , DOI 10.1016/0046-8177(93)90118-ZChao, D., Zisman, A., Pantuck, A.J., Gitlitz, B.J., Freedland, S.J., Said, J.W., Figlin, R.A., Belldegrun, A.S., Collecting duct renal cell carcinoma: Clinical study of a rare tumor (2002) Journal of Urology, 167 (1), pp. 71-74Dimopoulos, M.A., Logothetis, C.J., Markowitz, A., Amato, R., Sella, A., Ro, J., Collecting duct carcinoma of the kidney (1993) British Journal of Urology, 71 (4), pp. 388-391Hakimi, A.A., Koi, P.T., Milhoua, P.M., Blitman, N.M., Li, M., Hugec, V., Dutcher, J.P., Ghavamian, R., Renal medullary carcinoma: The bronx experience (2007) Urology, 70 (5), pp. 878-882. , DOI 10.1016/j.urology.2007.06.1124, PII S0090429507018092Kennedy, S.M., Merino, M.J., Linehan, W.M., Roberts, J.R., Robertson, C.N., Neumann, R.D., Collecting duct carcinoma of the kidney (1990) Human Pathology, 21 (4), pp. 449-456. , DOI 10.1016/0046-8177(90)90209-NMiyamoto, H., Kuwamitsu, O., Moriyama, M., Bellini duct carcinoma of the kidney (1992) Urol Int, 48, pp. 460-462O'Donnell, P.H., Jensen, A., Posadas, E.M., Renal medullary-like carcinoma in an adult without sickle cell hemoglobinopathy (2010) Nat Rev Urol, 7, pp. 110-114Peyromaure, M., Thiounn, N., Scotte, F., Vieillefond, A., Debre, B., Oudard, S., Collecting duct carcinoma of the kidney: A clinicopathological study of 9 cases (2003) Journal of Urology, 170 (4), pp. 1138-1140. , DOI 10.1097/01.ju.0000086616.40603.adSelby, D.M., Simon, C., Foley, J.P., Thompson, I.M., Baddour, R.T., Renal medullary carcinoma: Can early diagnosis lead to long-term survival? (2000) Journal of Urology, 163 (4), p. 1238Swartz, M.A., Karth, J., Schneider, D.T., Rodriguez, R., Beckwith, J.B., Perlman, E.J., Renal medullary carcinoma: Clinical, pathologic, immunohistochemical, and genetic analysis with pathogenetic implications (2002) Urology, 60 (6), pp. 1083-1089. , DOI 10.1016/S0090-4295(02)02154-4, PII S0090429502021544Weiss, L.M., Gelb, A.B., Medeiros, L.J., Adult renal epithelial neoplasms (1995) Am J Clin Pathol, 103, pp. 624-635Wesche, W.A., Wilimas, J., Khare, V., Parham, D.M., Renal medullary carcinoma: A potential sickle cell nephropathy of children and adolescents (1998) Pediatric Pathology and Laboratory Medicine, 18 (1), pp. 97-113. , DOI 10.1080/107710498174263Kausman, J.Y., Somers, G.R., Francis, D.M., Jones, C.L., Association of renal adenocarcinoma and BK virus nephropathy post transplantation (2004) Pediatric Nephrology, 19 (4), pp. 459-462. , DOI 10.1007/s00467-003-1407-7Kamranvar, S.A., Gruhne, B., Szeles, A., Masucci, M.G., Epstein-Barr virus promotes genomic instability in Burkitt's lymphoma (2007) Oncogene, 26 (35), pp. 5115-5123. , DOI 10.1038/sj.onc.1210324, PII 1210324Moscicki, A.B., HPV vaccines: Today and in the future (2008) J Adolesc Health, 43, pp. S26-S40O'Neil, J.D., Owen, T.J., Wood, V.H., Epstein-Barr virus-encoded EBNA1 modulates the AP-1 transcription factor pathway in nasopharyngeal carcinoma cells and enhances angiogenesis in vitro (2008) J Gen Virol, 89, pp. 2833-2842Emerson, L.L., Carney, H.M., Layfield, L.J., Collecting duct carcinoma arising in association with BK nephropathy post-transplantation in a pediatric patient A case report with immunohistochemical and in situ hybridization study (2008) Pediatr Transplant, 12, pp. 600-605Vats, A., BK virus and neoplasia: An emerging role (2008) Pediatr Transplant, 12, pp. 499-502Kalyanpur, A., Schwartz, D.S., Fields, J.M., Reyes-Mugica, M., Keller, I.S., Gosche, J., Renal medulla carcinoma in a white adolescent (1997) American Journal of Roentgenology, 169 (4), pp. 1037-1038Sathyamoorthy, K., Teo, A., Atallah, M., Renal medullary carcinoma in a patient with sickle-cell disease (2006) Nature Clinical Practice Urology, 3 (5), pp. 279-283. , DOI 10.1038/ncpuro0483, PII N0483Ataga, K.I., Orringer, E.P., Renal abnormalities in sickle cell disease (2000) American Journal of Hematology, 63 (4), pp. 205-211. , DOI 10.1002/(SICI)1096-8652(200004)63:4<205::AID-AJH8>3.0.CO;2-8Jiang, B.-H., Agani, F., Passaniti, A., Semenza, G.L., V-SRC induces expression of hypoxia-inducible factor 1 (HIF-1) and transcription of genes encoding vascular endothelial growth factor and enolase 1: Involvement of HIF-1 in tumor progression (1997) Cancer Research, 57 (23), pp. 5328-5335Kobayashi, N., Matsuzaki, O., Shirai, S., Collecting duct carcinoma of the kidney: An immunohistochemical evaluation of the use of antibodies for differential diagnosis (2008) Hum Pathol, 39, pp. 1350-1359Orsola, A., Trias, I., Raventos, C.X., Espanol, I., Cecchini, L., Orsola, I., Renal collecting (Bellini) duct carcinoma displays similar characteristics to upper tract urothelial cell carcinoma (2005) Urology, 65 (1), pp. 49-54. , DOI 10.1016/j.urology.2004.08.012, PII S0090429504009471Sibony, M., Vieillefond, A., Non clear cell renal cell carcinoma 2008 update in renal tumor pathology (2008) Ann Pathol, 28, pp. 381-401Esheba, G.E., Longacre, T.A., Atkins, K.A., Expression of the urothelial differentiation markers GATA3 and placental S100 (S100P) in female genital tract transitional cell proliferations (2009) Am J Surg Pathol, 33, pp. 347-353Higgins, J.P.T., Kaygusuz, G., Wang, L., Montgomery, K., Mason, V., Zhu, S.X., Marinelli, R.J., Brooks, J.D., Placental S100 (S100P) and GATA3: Markers for transitional epithelium and urothelial carcinoma discovered by complementary DNA microarray (2007) American Journal of Surgical Pathology, 31 (5), pp. 673-680. , DOI 10.1097/01.pas.0000213438.01278.5f, PII 0000047820070500000003Amin, M.B., Corless, C.L., Renshaw, A.A., Tickoo, S.K., Kubus, J., Schultz, D.S., Papillary (chromophil) renal cell carcinoma: Histomorphologic characteristics and evaluation of conventional pathologic prognostic parameters in 62 cases (1997) American Journal of Surgical Pathology, 21 (6), pp. 621-635. , DOI 10.1097/00000478-199706000-00001Amin, M.B., Maclennan, G.T., Gupta, R., Tubulocystic carcinoma of the kidney: Clinicopathologic analysis of 31 cases of a distinctive rare subtype of renal cell carcinoma (2009) Am J Surg Pathol, 33, pp. 384-392Albadine, R., Schultz, L., Illei, P., PAX8 (+)/p63 (-) immunostaining pattern in renal collecting duct carcinoma (CDC): A useful immunoprofile in the differential diagnosis of CDC versus urothelial carcinoma of upper urinary tract (2010) Am J Surg Pathol, 34, pp. 965-969Gupta, R., Balzer, B., Picken, M., Diagnostic implications of transcription factor Pax 2 protein and transmembrane enzyme complex carbonic anhydrase IX immunoreactivity in adult renal epithelial neoplasms (2009) Am J Surg Pathol, 33, pp. 241-247Gupta, R., Paner, G.P., Amin, M.B., Neoplasms of the upper urinary tract: A review with focus on urothelial carcinoma of the pelvicalyceal system and aspects related to its diagnosis and reporting (2008) Advances in Anatomic Pathology, 15 (3), pp. 127-139. , DOI 10.1097/PAP.0b013e31817145a9, PII 0012548020080500000001Cheng, J.X., Tretiakova, M., Gong, C., Mandal, S., Krausz, T., Taxy, J.B., Renal medullary carcinoma: Rhabdoid features and the absence of INI1 expression as markers of aggressive behavior (2008) Modern Pathology, 21 (6), pp. 647-652. , DOI 10.1038/modpathol.2008.44, PII MODPATHOL200844Elwood, H., Chaux, A., Schultz, L., Immunohistochemical analysis of SMARCB1/INI-1 expression in collecting duct carcinoma (2011) Urology, 78, pp. e471-e475Mejean, A., Roupret, M., Larousserie, F., Hopirtean, V., Thiounn, N., Dufour, B., Is there a place for radical nephrectomy in the presence of metastatic collecting duct (Bellini) carcinoma? (2003) Journal of Urology, 169 (4), pp. 1287-1290. , DOI 10.1097/01.ju.0000050221.51509.f5Wright, J.L., Risk, M.C., Hotaling, J., Effect of collecting duct histology on renal cell cancer outcome (2009) J Urol, 182, pp. 2595-2599Polascik, T.J., Cairns, P., Epstein, J.I., Fuzesi, L., Ro, J.Y., Marshall, F.F., Sidransky, D., Schoenberg, M., Distal nephron renal tumors: Microsatellite allelotype (1996) Cancer Research, 56 (8), pp. 1892-1895Schoenberg, M., Cairns, P., Brooks, J.D., Frequent loss of chromosome arms 8p and 13q in collecting duct carcinoma (CDC) of the kidney (1995) Genes Chromosomes Cancer, 12, pp. 76-80Fuzesi, L., Cober, M., Mittermayer, C., Collecting duct carcinoma: Cytogenetic characterization (1992) Histopathology, 21, pp. 155-160Selli, C., Amorosi, A., Vona, G., Sestini, R., Travaglini, F., Bartoletti, R., Orlando, C., Retrospective evaluation of c-erbB-2 oncogene amplification using competitive PCR in collecting duct carcinoma of the kidney (1997) Journal of Urology, 158 (1), pp. 245-247. , DOI 10.1097/00005392-199707000-00079Yang, X.J., Sugimura, J., Tretiakova, M.S., Furge, K., Zagaja, G., Sokoloff, M., Pins, M., Teh, B.T., Gene expression profiling of renal medullary carcinoma: Potential clinical relevance (2004) Cancer, 100 (5), pp. 976-985. , DOI 10.1002/cncr.20049Simpson, L., He, X., Pins, M., Huang, X., Campbell, S.C., Yang, X.J., Perlman, E.J., Bergan, R.C., Renal medullary carcinoma and ABL gene amplification (2005) Journal of Urology, 173 (6), pp. 1883-1888. , DOI 10.1097/01.ju.0000158448.56888.09Stahlschmidt, J., Cullinane, C., Roberts, P., Renal medullary carcinoma: Prolonged remission with chemotherapy, immunohistochemical characterisation and evidence of bcr/abl rearrangement (1999) Med Pediatr Oncol, 33, pp. 551-557