Skip to main content

A novel combination of multiple primary carcinomas: Urinary bladder transitional cell carcinoma, prostate adenocarcinoma and small cell lung carcinoma- report of a case and review of the literature



The incidence of multiple primary malignant neoplasms increases with age and they are encountered more frequently nowadays than before, the phenomenon is still considered to be rare.

Case presentation

We report a case of a man in whom urinary bladder transitional cell carcinoma, metachronous prostate adenocarcinoma and small cell lung carcinoma were diagnosed within an eighteen-month period. The only known predisposing factor was that he was heavy smoker (90–100 packets per year). The literature on the phenomenon of multiple primary malignancies in a single patient is reviewed and the data is summarized.


It is important for the clinicians to keep in mind the possibility of a metachronous (successive) or a synchronous (simultaneous) malignancy in a cancer patient. It is worthy mentioning this case because clustering of three primary malignancies (synchronous and metachronous) is of rare occurrence in a single patient, and, to our knowledge, this is the first report this combination of three carcinomas appearing in the same patient.


The phenomenon of multiple primary malignant neoplasms in the same individual was described firstly by Billroth at the end of the 19th century [1]. Since then, several cases of double or even triple primary malignant neoplasms have been reported. It is believed that multiple primary malignant neoplasms now occur more frequently than before. Although, not uncommon, they occur more often in elderly patients, as the incidence of malignancies increases with age. The diagnosis of second primary neoplasms is rising as a result of prolonged survival of patients treated for previous malignancy with alkylating agents, topoisomerase II inhibitors, and/or radiotherapy[2]. A review of the recent literature indicates clearly that they appear more frequently in the upper digestive tract, respiratory system, head and neck region, or urogenital system; the reported incidence ranges from 2% to 10% [3].

In this report we present a patient who developed primary bladder carcinoma and metachronous prostate and small cell lung carcinoma (SCLC) within an eighteen-month period. This combination of multiple primary carcinomas, to our knowledge, has never been reported in the literature.

Case presentation

A 75-year old ex-smoker (90–100 packet per year) underwent a transurethral resection of urinary bladder papilloma in February 2002. The histology of resected specimen was papillary transitional cell carcinoma grade II (Figure 1A). The tumor cells were positive for cytokeratin 7 (Figure 1B) and negative for cytokeratin 20. There were no muscle fibers in the examined tissue. The ultrasound examination of the urogenital system revealed nodular hyperplasia of the prostate. The tumor clinical stage according to the American Cancer Committee U.I.C.C. (1992) was Ta. Patient's cancer relapsed at the end of the same year and he underwent a programmed transurethral resection of the tumor, which proved to be papillary transitional cell carcinoma grade I-II. No lamina propria or muscle invasion was detected. The patient was also treated with intracystic infusion of bacille Calmette-Guerin (BCG). Ten days later, because of urine retention, he underwent transurethral resection of the prostate. Multiple tissue fragments of total dimensions 4.5 × 3.5 × 2.2 cm were examined histologically. Seven out of the 10 examined slides revealed foci of partially mucinous (Figure 2A) adenocarcinoma of the prostate (the greatest measured focus was 8.5 mm in maximum diameter), Gleason grade II-III and Gleason score 5 (Figure 2A, B). Immunohistochemical study was performed and showed strong positivity for Prostate Specific antigen (PSA) (Figure 2C) whereas; no expression of carcinoembryonic antigen (CEA) was detected in tumor cells. These findings confirmed the diagnosis of primary prostate adenocarcinoma. The tumor's stage according to the 1997 TNM staging system of prostatic adenocarcinoma was T1b. Serum prostate specific antigen (PSA) levels were elevated (9 ng/mL) before surgery. No additional surgical treatment was given and at follow-up visits prostate specific antigen (PSA) levels measurement and intracystic injection of BCG was performed. In September of the same year, due to progressively worsening dyspnea a computed tomography was performed that revealed a mediastinal mass in conjunction to the right lung hilum and to the right main bronchus with maximum diameter of 9 cm. Bronchoscopy showed a large mass which invaded the right main bronchus mucosa and extended to the carina. Histology of the bronchial mucosal sample showed infiltration of lamina propria by malignant cells (Figure 3A). Their immunophenotype was: CD56 (+) (Figure 3B), Pan-Cytokeratin (paranuclear dot stain positivity) (Figure 3C) and Leukocyte Common Antigen negative. Combining the morphological and the immunohistochemical results, we concluded that the patient was suffering from small cell lung carcinoma (SCLC). The patient's stage was IIIB. Ten days after the diagnosis was confirmed, the patient underwent the first cycle of chemotherapy (Cisplatin and Vepesid), during which he died from cardiac arrest due to chemotherapy toxicity.

Figure 1

Microscopically, the extracted urinary bladder tissue particles proved to be pieces of papillary transitional cell carcinoma grade II [A) hematoxylin and eosin × 40] and immunohistochemically they expressed cytokeratin 7 [B) cytokeratin 7 × 100].

Figure 2

Histologically, in most of the prostate tissue fragments were recognized areas of, partially mucinous, adenocarcinoma of the prostate, grade II-III (A. hematoxylin and eosin × 40, B: hematoxylin and eosin × 100). The tumor cells were strongly positive for PSA (C: PSA × 40).

Figure 3

The bronchial mucosa showed extensive invasion from small blue round cells (A: hematoxylin and eosin × 100) that were positive for the neuroendocrine marker CD56 (B: × 200) and pan-cytokeratin (C: × 200).


We report a patient who developed three histologically distinct malignancies, i.e. primary bladder carcinoma and metachronous prostate and SCLC within an eighteen-month period. There are several predisposing or causal factors for each malignancy. For our patient there was only one common causal factor, the fact that he was a heavy smoker (90–100 packets per year). No other predisposing factor or a family history was found that might have contributed to the development of these three malignancies. The presence of bladder and prostate carcinomas in the same patient is not a rare event. Chun [3] reported that the rate of bladder carcinoma in patients with prostate carcinoma is eighteen times higher (p < 0,01) and the rate of prostate carcinoma in those with bladder carcinoma is nineteen times higher (p < 0,01) than expected. Although bladder and prostate carcinoma can coexist in the same individual frequently enough, the rare event is the appearance of a third malignancy. There is a case report by Rovinescu et al [4] referring to a patient with three primary malignancies. The first tumor was a clear cell carcinoma of the kidney, which was followed by a transitional cell carcinoma of the bladder and then by a distinct adenocarcinoma of the prostate. More recently, in 2003, Satoh et al [5] also reported the same combination of multiple primary malignancies in a patient. Our case is the first one of an individual having these two primary malignancies of the urogenital system and another tumor of the lower respiratory tract.

Table 1 summarizes the cases with three or more primary malignancies. As can be easily seen, although the appearance of three primary malignancies in one patient is not very common, should not be considered such a rare event.

Table 1 There are summarized the cases of triple or more malignancies, the first author, journal, year of publication and combination of neoplasms.

Additionally, studying the existing bibliography, we noticed that there is a little confusion regarding the terms used, such as synchronous, simultaneous and metachronous or successive neoplasms. All of these words have to do with the time that the neoplasms are discovered and have nothing to do with the time of their genesis. The word synchronous is a Greek one that should refer to neoplasms appearing in the same time. It is synonymous to the word simultaneous and they are interchangeable. Metachronous (meta- means after and -chronous is the time) is also a Greek word referring to a neoplasm that is discovered while there is already a known neoplasm in the same patient. The word successive could be used equally to metachronous.


Summarizing, it is important for the clinicians to keep in mind that the appearance of another tumor in a patient suffering from cancer could be either a metastasis or another malignancy and should always investigate the possibility of a metachronous (successive) or a synchronous (simultaneous) malignancy. Moreover, the combination of the three different neoplasms (bladder, prostate and SCLC) in one patient, to the best of our knowledge, has never been reported before.


  1. 1.

    Billroth T: [General surgical pathology and therapy. Guidance for students and physicians. Lecture]. Khirurgiia (Mosk). 1991, 136-143.

    Google Scholar 

  2. 2.

    Munker R, Hiller E, Melnyk A, Gutjahr P: Second malignancies: clinical relevance and basic research. Int J Oncol. 1996, 763-776.

    Google Scholar 

  3. 3.

    Chun TY: Coincidence of bladder and prostate cancer. J Urol. 1997, 157: 65-67. 10.1097/00005392-199701000-00018.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Rovinescu I, Rousseau E: [Considerations relating to multiple primary carcinomas of the urinary tract (author's transl)]. J Urol Nephrol (Paris). 1976, 82: 621-626.

    CAS  Google Scholar 

  5. 5.

    Satoh H, Momma T, Saito S, Hirose S: [A case of synchronous triple primary carcinomas of the kidney, bladder and prostate]. Hinyokika Kiyo. 2003, 49: 261-264.

    PubMed  Google Scholar 

  6. 6.

    Crail HW: Multiple primary malignancies arising in the rectum, brain, and thyroid. US Naval Med Bull. 1949, 49: 123-128.

    CAS  Google Scholar 

  7. 7.

    Hamoudi AB, Ertel I, Newton WAJ, Reiner CB, Clatworthy HWJ: Multiple neoplasms in an adolescent child associated with IGA deficiency. Cancer. 1974, 33: 1134-1144.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Ohsato K, Hashimoto H, Itoh H, et : Familial adenomatosis of the colon associated with brain tumor (Turcot's syndrome): report of a case and review of the literature (Japanese). STOMACH INTEST (Tokyo). 1975, 10: 1511-1517.

    Google Scholar 

  9. 9.

    Kawanami K, Ohno M, Matsuura K, et : Turcot's syndrome: report of an autopsy case. STOMACH INTEST (Tokyo). 1976, 11: 1075-1082.

    Google Scholar 

  10. 10.

    Itoh H, Ohsato K, Yao T, Iida M, Watanabe H: Turcot's syndrome and its mode of inheritance. Gut. 1979, 20: 414-419.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  11. 11.

    Mullen JL, Reichman J, Rosato EF: Multiple carcinomas following therapy for Hodgkin disease. J Surg Oncol. 1979, 11: 75-78.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Pinel J, de Romanet JB, Fontanel JP: [Multiple carcinomas of the upper digestive tract. 7 tumour sites in 9 years (author's transl)]. Ann Otolaryngol Chir Cervicofac. 1979, 96: 619-621.

    CAS  PubMed  Google Scholar 

  13. 13.

    Cohen C: Multiple cutaneous carcinomas and lymphomas of the skin. Arch Dermatol. 1980, 116: 687-689. 10.1001/archderm.116.6.687.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Friedman CD, McCarthy JR: Multiple primary malignant neoplasms. IMJ Illinois Medical Journal. 1982, 161: 115-116.

    CAS  PubMed  Google Scholar 

  15. 15.

    Li FP, Little JB, Bech-Hansen NT, Paterson MC, Arlett C, Garnick MB, Mayer RJ: Acute leukemia after radiotherapy in a patient with Turcot's syndrome. Impaired colony formation in skin fibroblast cultures after irradiation. Am J Med. 1983, 74: 343-348. 10.1016/0002-9343(83)90643-5.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Haibach H, Rosenholtz MJ: Synchronous thyroid, renal, and duodenal carcinomas. Arch Pathol Lab Med. 1984, 108: 272-274.

    CAS  PubMed  Google Scholar 

  17. 17.

    Alessi E, Brambilla L, Luporini G, Mosca L, Bevilacqua G: Multiple sebaceous tumors and carcinomas of the colon. Torre syndrome. Cancer. 1985, 55: 2566-2574.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Kobayashi T: Diagnosis and treatment of multiple primary neoplasm—brain tumors and cancer of other organs. Saishin Igaku. 1985, 40 : 1613-1620.

    Google Scholar 

  19. 19.

    Megighian D, Zorat PL: A rarely observed case of primary multiple carcinomas of the head and neck. Arch Otorhinolaryngol. 1985, 242: 7-12. 10.1007/BF00464399.

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Staren ED, Roberts J: Multiple primary cancers of the respiratory tract: a case of synchronous carcinoma of the larynx, carcinoma of the floor of the mouth, and dual primary bronchogenic carcinomas. J Surg Oncol. 1985, 29: 261-263.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Craig DM, Triedman LJ: Four primary malignant neoplasms in a single patient. J Surg Oncol. 1986, 32: 8-10.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Ogasawara K, Ogawa A, Shingai J, Kayama T, Wada T, Namiki T, Suzuki J: [Synchronous multiple primary malignant tumors accompanied by glioblastoma. Case report]. Neurol Med Chir (Tokyo). 1986, 26: 908-912.

    CAS  Article  Google Scholar 

  23. 23.

    Hayashi K, Ohtsuki Y, Sonobe H, Takahashi K, Wada S, Yoshida K: [An autopsy case of triple primary cancers consisting of glioblastoma multiforme of the pons, colon cancer and rectal carcinoid--a statistical analysis of cases of brain tumor combined with other primary cancers in Japan autopsy annuals]. Gan No Rinsho. 1987, 33: 1846-1853.

    CAS  PubMed  Google Scholar 

  24. 24.

    Kobayashi T, Takahashi T, Tanaka T, Tateishi T, Miura S: [Multiple primary neoplasm--glioblastoma combined with cancer of other organs]. No Shinkei Geka. 1987, 15: 1011-1017.

    CAS  PubMed  Google Scholar 

  25. 25.

    Ohi H, Kikuchi K, Futawatari K, Kowada M: A histologically-verified triple cancer--report of a rare case involving a primary brain tumor. Gan No Rinsho Japan Journal Of Cancer Clinics. 1988, 34: 1001-1005.

    CAS  PubMed  Google Scholar 

  26. 26.

    Baigrie RJ: Seven different primary cancers in a single patient. A case report and review of multiple primary malignant neoplasia. Eur J Surg Oncol. 1991, 17: 81-83.

    CAS  PubMed  Google Scholar 

  27. 27.

    Solan MJ: Multiple primary carcinomas as sequelae of treatment of pulmonary tuberculosis with repeated induced pneumothoraces. Case report and review of the literature. Am J Clin Oncol. 1991, 14: 49-51.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Melkert PW, Walboomers JM, Jiwa NM, Cuesta MA, Kenemans P, Meijer CJ: Multiple HPV 16-related squamous cell carcinomas of the vulva, vagina, anus, skin and cervix in a 31-year-old woman. Eur J Obstet Gynecol Reprod Biol. 1992, 46: 53-56. 10.1016/0028-2243(92)90280-C.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Marcos Sanchez F, Salvador Fernandez M, Juarez Ucelay F, Druet Ampuero J: [Carcinomas of the colon, kidney, and breast in the same patient. A new case of multiple primary malignant neoplasms]. An Med Interna. 1992, 9: 257-257.

    CAS  PubMed  Google Scholar 

  30. 30.

    Brugieres L, Gardes M, Moutou C, Chompret A, Meresse V, Martin A, Poisson N, Flamant F, Bonaiti-Pellie C, Lemerle J, Feunteun J: Screening for germ line p53 mutations in children with malignant tumors and a family history of cancer. Cancer Research. 1993, 53: 452-455.

    CAS  PubMed  Google Scholar 

  31. 31.

    Kikuchi T, Rempel SA, Rutz HP, de TN, Mulligan L, Cavenee WK, Jothy S, Leduy L, Van Meir EG: Turcot's syndrome of glioma and polyposis occurs in the absence of germ line mutations of exons 5 to 9 of the p53 gene. Cancer Res. 1993, 53: 957-961.

    CAS  PubMed  Google Scholar 

  32. 32.

    Shiseki M, Nishikawa R, Yamamoto H, Ochiai A, Sugimura H, Shitara N, Sameshima Y, Mizoguchi H, Sugimura T, Yokota J: Germ-line p53 mutation is uncommon in patients with triple primary cancers. Cancer Lett. 1993, 73: 51-57. 10.1016/0304-3835(93)90187-E.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Bumpers HL, Natesha RK, Barnwell SP, Hoover EL: Multiple and distinct primary cancers: a case report. J Natl Med Assoc. 1994, 86: 387-388.

    PubMed Central  CAS  PubMed  Google Scholar 

  34. 34.

    Nishihara K, Tsuneyoshi M, Shimura H, Yasunami Y: Three synchronous carcinomas of the papilla of Vater, common bile duct and pancreas. Pathol Int. 1994, 44: 325-332.

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Angeli-Besson C, Koeppel MC, Jacquet P, Andrac L, Sayag J: Multiple squamous-cell carcinomas of the scalp and chronic myeloid leukemia. Dermatology. 1995, 191: 321-322.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Hayashi T, Sagawa H, Kobuke K, Fujii K, Yokozaki H, Tahara E: Molecular-pathological analysis of a patient with three synchronous squamous cell carcinomas in the aerodigestive tract. Jpn J Clin Oncol. 1996, 26: 368-373.

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Nagane M, Shibui S, Nishikawa R, Oyama H, Nakanishi Y, Nomura K: Triple primary malignant neoplasms including a malignant brain tumor: report of two cases and review of the literature. Surg Neurol. 1996, 45: 219-229. 10.1016/0090-3019(95)00305-3.

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Potzsch C, Fetscher S, Mertelsmann R, Lubbert M: Acute myelomonocytic leukemia secondary to synchronous carcinomas of the breast and lung, and to metachronous renal cell carcinoma. J Cancer Res Clin Oncol. 1997, 123: 678-680. 10.1007/s004320050124.

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Shan L, Nakamura Y, Nakamura M, Zhang Z, Jing X, Hara T, Yokoi T, Kakudo K: Synchronous and metachronous multicentric squamous cell carcinomas in the upper aerodigestive tract. Pathol Int. 1997, 47: 68-72.

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Cribier B, Lipsker D, Grosshans E: Eccrine porocarcinoma, tricholemmal carcinoma and multiple squamous cell carcinomas in a single patient. Eur J Dermatol. 1999, 9: 483-486.

    CAS  PubMed  Google Scholar 

  41. 41.

    Ramsay HM, Fryer A, Strange RC, Smith AG: Multiple basal cell carcinomas in a patient with acute myeloid leukaemia and chronic lymphocytic leukaemia. Clin Exp Dermatol. 1999, 24: 281-282. 10.1046/j.1365-2230.1999.00480.x.

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    Schon MP, Reifenberger J, Von SS, Megahed M, Lang K, Gattermann N, Meckenstock G, Goerz G, Ruzicka T: Multiple basal cell carcinomas associated with hairy cell leukaemia. Br J Dermatol. 1999, 140: 150-153. 10.1046/j.1365-2133.1999.02626.x.

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Beswick SJ, Garrido MC, Fryer AA, Strange RC, Smith AG: Multiple basal cell carcinomas and malignant melanoma following radiotherapy for ankylosing spondylitis. Clin Exp Dermatol. 2000, 25: 381-383. 10.1046/j.1365-2230.2000.00668.x.

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Mukai M, Macuuchi H, Mukohyama S, Oida Y, Himeno S, Nishi T, Nakazaki H, Satoh S: Quintiple carcinomas with metachronous triple cancer of the esophagus, kidney, and colonic conduit following synchronous double cancer of the stomach and duodenum. Oncol Rep. 2001, 8: 111-114.

    CAS  PubMed  Google Scholar 

Download references


The permission was obtained from the next of kin of patient for publication of this case report.

Author information



Corresponding author

Correspondence to Anastassios V Koutsopoulos.

Additional information

Competing interests

The author(s) declare that they have no competing interests.

Authors' contributions

KAV wrote the original manuscript and performed histopathological evaluation of the lung lesion.

DKI participated in the writing of the original manuscript and prepared photomicrographs.

DG performed histopathological evaluation of the urinary bladder lesion.

GE performed histopathological evaluation of the prostate lesion.

FM performed bronchoscopy and patient's management.

SE prepared requested revisions of the manuscript.

Authors’ original submitted files for images

Below are the links to the authors’ original submitted files for images.

Authors’ original file for figure 1

Authors’ original file for figure 2

Authors’ original file for figure 3

Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and Permissions

About this article

Cite this article

Koutsopoulos, A.V., Dambaki, K.I., Datseris, G. et al. A novel combination of multiple primary carcinomas: Urinary bladder transitional cell carcinoma, prostate adenocarcinoma and small cell lung carcinoma- report of a case and review of the literature. World J Surg Onc 3, 51 (2005).

Download citation


  • Prostate Specific Antigen
  • Prostate Carcinoma
  • Transitional Cell Carcinoma
  • Transurethral Resection
  • Bladder Carcinoma