OAT CELL CARCINOMA OF URINARY BLADDER C. A. D. R.
CHENG, M.CH., F.R.C.S. NICHOLSON, M.B.B.S. G. LOWE, M.D. S. KIRBY, M.D., F.R.C.S.
From the Departments of Urology and Histopathology, St. Bartholomew’s Hospital, West Smithfield, London, England ABSTRACT-Oat cell carcinoma of the urinary bladder is extremely uncommon. There have been 52 reported cases in world literature to date. On light microscopic, histochemical, and ultrastructural grounds, these tumors are similar to oat cell carcinoma of the bronchus and other extrapulmonary oat cell carcinomas. Furthermore, they may be grouped together as a clinical entity characterized by an aggressive clinical course with early and extensive metastases, and partial remission with certain chemotherapeutic agents. We report a case of primary small cell carcinoma of the urinary bladder in a forty-twoyear-old man and review previous reports with similar histology. The importance of establishing this diagnosis and the optimum forms of therapy are discussed. In 1926 Barnard’ first reported a case of oat cell carcinoma of the lung; since then the disease has been well documented and is believed to account for between one quarter to one third of all bronchogenic carcinomas.2 Histologically, the tumors consist of round cells about twice the size of a lymphocyte and are arranged in sheets, rosettes, or trabeculae which are intersected by thick strands of connective tissue.3 On electron microscopy, many cases have dense-core, membrane-bound granules (DCMG), similar to those seen in Kultschitzky cells in the gastrointestinal tract, and for this reason those tumors are considered to be part of the extensive family grouped under the acronym of APUD (amine precursor, uptake and decarboxylation) cells4 Clinically, bronchogenic oat cell carcinomas form a separate entity from other pulmonary tumors characterized by early age of onset, male predominance (85 % ), and early and widespread metastases. Combination chemotherapy offers the best chance of survival with complete response and prolonged survival seen in those with limited or extensive disease. Although the majority of oat cell carcinoma (OCC) occur in the bronchial tree, similar tumors have been reported in a wide variety of 504
extrapulmonary sites, and the histology of these is indistinguishable from that of bronchogenic OCC. These sites include the gastrointestinal tract, pancreas, thymus, larynx, pharynx and tongue, salivary glands, breasts, uterus, and skin.5 One of the rarest extrapulmonary sites is the urinary bladder and prostate. Of the former, only 52 cases have been described. Herein we report another case and review the literature on this subject. Case Report A forty-two-year-old man was investigated for hematuria of three months’ duration with associated urinary frequency. Physical examination revealed no abnormality. A chest x-ray film showed no abnormality. An intravenous urogram demonstrated normal upper tracts, and urine cytology was normal. Cystoscopy, however, revealed a polypoid tumor in the right lateral wall of the bladder. Biopsy showed transitional cell carcinoma with extensive areas of small cell carcinoma and smaller areas of adenocarcinoma and squamous cell carcinoma. Clinically this was a T3 (Stage C) tumor. There were no metastases detected by bone scan or
UROLOGY
i
JUNE
1992 /
VOLUME XXXIX,
NUMBER 6
FICUHE1. (A) Small cell anaplastic carcinoma indistinguishable from oat cell carcinoma of bronchus. (B) Area oj squamoid and spindle cell di.j erentiation. (C) In situ transitional cell carcinoma. (Hcmatoxylin and eosin, original magnifications x 100.) ultrasound and computerized tomography of the pelvis and liver. In view of the patient’s age, a nerve-sparing cystoprostatectomy was performed with primary reconstruction of an ileocolic bladder. Macroscopically, the tumor consisted of a round mass of 3 cm diameter infiltrating the full thickness of the bladder wall, but internal iliac lymph nodes were not involved. On light microscopy, a predominance of apparently undifferentiated, small, hyperchromatic cells that closely resembled oat cell carcinoma of bronchus were seen. The cells were arranged in diffuse sheets, with numerous areas of necrosis (Fig. IA). In addition, there were other histologic cell types, including moderately differentiated squamous cell carcinoma, adenocarcinema, transitional cell carcinoma, spindle cell carcinoma (Fig. lB), and flat in situ transitional cell carcinoma (Fig. 1C). Tumor cells showed focal positive staining with PGP 9.5 antibody for neurosecretory cells, and on electron microscopy a few of the small hyperchromatic tumor cells contained small numbers of membrane-bound dense core granules characteristic of neurosecretory cells (Fig. 2). A diagn’osis of primary oat cell carcinoma of the bladder was made. Postoperatively the patient was also started on a regimen of carboplatin (as he was reluctant IO receive alternative chemotherapy that
IJHOLOGY
JUNE: 1992
I
VOLUME
XXXIX.
NUMBER
FIGURE: 2. Electron micrograph of area of small cell carcinoma of bladder showing membranebound granules (original magnification x 112,000).
might cause hair loss). Initial progress was excellent and ten months later, he was well with full urinary continence day and night. He also was experiencing penile erection sufficient for sexual intercourse and has a normal response to papaverine. Urodynamics revealed a stable, large capacity (730 mL) neobladder with no ureteric reflux (Fig. 3). In the last month however, a follow-up CT scan has revealed recurrent tumor within the pelvis; this has been confirmed histologically. Despite further chemotherapy, he died eleven months after diagnosis. Necropsy was refused by his relatives .
ti
505
FIGURE 3.
Bladder at videourodynamics no ureteric reflux.
showing
Comment A total of 1.75 percent of tumors of the urinary bladder are undifferentiated histologically,22 and of these, one extremely rare variant is the oat cell carcinoma. As ultrastructural analysis is required to make this diagnosis, and since it has been described relatively recently, the true incidence is unknown. In 1981 Cramer, Aikawa, and Cebeli# described the first case of OCC in a bladder diverticulum; this patient was treated with local resection. Since then, cases with similar histology have been reported sporadically. To date, 52 cases have been reported in the world literature. Because of the similarities in light microscopy, histochemistry, ultrastructure, and immunocytochemistry between oat cell carcinoma of the bladder and oat cell carcinoma of the lung, OCC of the urinary bladder has come to be recognized as part of a widely distributed group of oat cell carcinoma that predominantly occurs in the bronchus but which may occur in many other sites. It has been suggested that these tumors develop from pre-existing APUD cells in the urinary tract. Certainly, agyrophillia, the ability to take up silver stains which is characteristic of APUD cells, has been demonstrated in the prostatic urethra and paraurethral glands of Littre,23 prostate,24 and bladder.25 An alternative theory of the origin of oat cell carcinoma is that they stem from multipotential epithelial reserve cells which are capable of differentiation into more than one cell line. This may explain the association of oat cell car-
506
cinoma with several other cell elements (squamous cell carcinoma, adenocarcinoma, and transitional cell carcinoma). This feature of mixed cell lines is seen also in oat cell carcinoma of the lung and other extrapulmonary sites.26 Review of the literature reveals a predominance of male patients with OCC of the bladder (4:l) and a wide age range (40-83 years). Hematuria is the most common presenting feature (83 %). The tumors tend to be large (2-10 cm diameter), polypoidal, and ulcerated. Microscopy shows a predominance of small cells often with an admixture of transitional cell dysplasia and carcinoma, adenocarcinoma, squamous cell carcinoma, and carcinoid tumor. Of the 52 patients, 11 (21%) were known to have metastases at diagnosis. Two of these were diagnosed at autopsy, and 4 more patients were dead by nine months and 1 by thirty months. In 32 patients subsequent metastases developed (64% or 32 of 50 patients, as 2 were diagnosed at autopsy). A total of 26 patients (50 %) died because of metastases, either present at diagnosis or subsequently, with the majority of deaths occurring within fifteen months from the time of diagnosis. The prognosis for those with initial or subsequent metastases of oat cell carcinoma is poor. Patients who received adjuvant chemotherapy appeared perhaps to fare better than those who received chemotherapy only after metastases had been detected. The latter group in turn did better than those who did not receive chemotherapy at all. However, chemotherapy did not prevent the development of metastases, and objective remission of definite secondary metastases were rare. We conclude that oat cell carcinoma of the urinary bladder is an important but under-recognized entity. It is aggressive, metastasizes early, and has a poor prognosis. Owing to the small number of reported cases, treatment at present is based on that of oat cell carcinoma of the lung. Chemotherapy seems to give the best hope for improving survival with or without surgery and radiotherapy. The diagnosis should be suspected when anaplastic carcinoma of the bladder is reported histologically. Electron microscopy should then be employed to look for neurosecretory granules in the cytoplasm of oat cells and distinguish these from anaplastic transitional cell carcinomas. Once the diagnosis is made, a full initial staging workup will distinguish patients with localized disease from those with extensive disease.
UROLOGY
/ JUNE1992
/ VOLUMEXXXIX,NUMBER6
Those with localized disease should receive adjuvant chemotherapy and the favored combination of chemotherapeutic agents seems to be vincristine, doxorubicin (Adriamycin), cisplatin, and etoposide. Although occult metastases are likely to be present initially, we believe that surgery in the absence of clinically obvious metastases and where the patient is fit may reduce the tumor volume and improve the responsiveness to chemotherapy. In addition, radiotherapy to the primary site may be of benefit.27 In patients with extensive disease, chemotherapy provides the main modality of treatment and surgery is clearly not appropriate, however, palliative radiotherapy may be helpful in the relief of bone pain and nerve compression. We conclude that the management of oat cell carcinoma of the bladder requires a multidisciplinary approach involving oncology, radiotherapy, and urology teams. We hope that as more cases are reported and longer term followup results become available, a clearer line of management will emerge.
three cases with ultrastructural analysis, Ultrastruct Path01 4: 197 (1983). 8. Kim CK, Lin JI. and Tseng CH: Small cell carcinoma of urinary bladder: ultrastructural study, Urology 24: 384 (1984). 9. Partenen S. and Asikainen U: Oat cell carcinoma of the urinary bladder with ectopic adrenocorticotropic hormone production, Human Pathol 16: 313 (1985). 10. Reyes CV. and Soneru I: Small cell carcinoma of the urinary bladder with hypercalcaemia, Cancer 56: 2530 (1985). 11. Abenoza I’, Manivel C, and Sibley RK: Adenocarcinoma with neuroendocrine differentiation of the urinary bladder: clinicopathologic, immunohistochemical and ultrastructural study, Arch Pathol Lab Med 110: 1062 (1986). 12. Lee JY-Y, Tang CK, and ‘Rodriguez F: Anaplastic carcinoma of urinary bladder with oat cell features, Urology 27: 474 (1986). 13. Ordoiiez NC, Khorsand J, Ayala AC, and Sneige N: Oat cell carcinoma of the urinary tract: an immunohistochemical and electron microscopic study, Cancer 58: 2519 (1986). 14. Paz RA, Ramos M, Ghioldi NS, and Sundblad AS: Carcinoma indiferenciado de pequenas celulas (oat cell): revision de 55 cases, incluidos 4 extrapulmonares, Medicina 46: 390 (1986). 15. Williams MR, Dunn M, and Ansell ID: Primary oat cell carcinoma of the urinary bladder, Br J Urol 58: 225 (1986). 16. Mills SE, et al: Small cell undifferentiated carcinoma of the urinary bladder: a light microscopic, immunocytochemical and ultrastructural study of 12 cases. Am J Surg Path01 11: 606 (1987). 17. Swanson PE, Brooks R, Pearse H, and Stenzel P: Small cell carcinoma of urinary bladder, Urology 32: 558 (1988). 18. Itoh K, et al: Small cell carcinoma of the urinary bladder: a case of remarkable remission with combined chemotherapy, Acta Ural Jpn 34: 1443 (1988). 19. Golomb J, et a/: Bladder neoplasms associated with augmentation cystoplasty: report of 2 cases and literature review, J Urol 142: 377 (1989). 20. Blomjous CEM, et al: Small cell carcinoma of the urinary bladder-a clinicopathologic, morphometric, immunohistochemical and ultrastructural study of 18 cases, Cancer 64: 1347 (1989). 21. Davis MP, et al: Successful management of small cell carcinoma of the bladder with cisplatin and etoposide, J Ural 142: Xl7 (1989). 22. Friedell GH, et al: Histopatholog) and classification of urinary bladder carcinoma, Urol Clin North Am 3: 53 (1976). 23. Feyrter F: Uber das urogenitale Helle-Zellen-system des Menschen, Mikrosk Anat Forsch 57: 324 (1951). 24. Kazzaz BA: Argentaffin and arkTrophilic cells in the prostate, J Pathol 112: 189 (1974). 25. Hofmann H: Gelbe (basalgekornte) Zellen in der schleimhaut einer ekstrophierten harnblase, Virchows Arch 309: 466 (1937). 26. Churg A, Johnston WH, and Stulbarg M: Small cell squamous and mixed small cell squamous-small cell anaplastic carcinomas of the lung, Am J Surg Pathol 4: 255 (1980). 27. Bunn PA Jr, et al: Chemotherapy alone or chemotherapy with chest radiation therapy in limited stage small cell lung cancer, Ann Intern Med 106: 655 (1987).
Department of Surgery The Chinese University of Hong Kong Shatin, New Territories Hong Kong (MR. CHENG) References 1. Barnard WC: The nature of the “oat-celled sarcoma” of the mediastinum, J Path01 Bacterial 29: 241 (1926). 2. Bensch KC. Corrin B, Pariente R, and Spencer H: Oat cell carcinoma of the lung: its origin and relationship to bronchial carcinoid. Cancer 22: 1163 (1968). 3. Azzopardi JC: Oat cell carcinoma of the bronchus, J Path01 Bacterial 78: 513 (1959). 4. Sidhu GS: The endodermal origin of digestive and respiratory tract APUD cells: histopathologic evidence and a review of the literature, Am J Path01 96: 5 (1979). 5. Ibrahim NBN, Briggs JC, and Corbishley CM: Extrapulmonary oat cell carcinomas Cancer 54: 1645 (1984). 6. Cramer SF. Aikawa M. and Cebelin M: Neurosecretorv granule:; in small cell invasive’carcinoma of the urinary bladder, Cancer 47: 724 (1981). 7. Davis BH, Ludwig ME, Cole SR, and Pastuszak WT: Small cell neuroendocrine carcinoma of the urinary bladder: report of
UROLOCY
JUNE
1992
i
VOLUME
XXXIX,
NUMBER
6
507
CHENG, M.CH., F.R.C.S. NICHOLSON, M.B.B.S. G. LOWE, M.D. S. KIRBY, M.D., F.R.C.S.
From the Departments of Urology and Histopathology, St. Bartholomew’s Hospital, West Smithfield, London, England ABSTRACT-Oat cell carcinoma of the urinary bladder is extremely uncommon. There have been 52 reported cases in world literature to date. On light microscopic, histochemical, and ultrastructural grounds, these tumors are similar to oat cell carcinoma of the bronchus and other extrapulmonary oat cell carcinomas. Furthermore, they may be grouped together as a clinical entity characterized by an aggressive clinical course with early and extensive metastases, and partial remission with certain chemotherapeutic agents. We report a case of primary small cell carcinoma of the urinary bladder in a forty-twoyear-old man and review previous reports with similar histology. The importance of establishing this diagnosis and the optimum forms of therapy are discussed. In 1926 Barnard’ first reported a case of oat cell carcinoma of the lung; since then the disease has been well documented and is believed to account for between one quarter to one third of all bronchogenic carcinomas.2 Histologically, the tumors consist of round cells about twice the size of a lymphocyte and are arranged in sheets, rosettes, or trabeculae which are intersected by thick strands of connective tissue.3 On electron microscopy, many cases have dense-core, membrane-bound granules (DCMG), similar to those seen in Kultschitzky cells in the gastrointestinal tract, and for this reason those tumors are considered to be part of the extensive family grouped under the acronym of APUD (amine precursor, uptake and decarboxylation) cells4 Clinically, bronchogenic oat cell carcinomas form a separate entity from other pulmonary tumors characterized by early age of onset, male predominance (85 % ), and early and widespread metastases. Combination chemotherapy offers the best chance of survival with complete response and prolonged survival seen in those with limited or extensive disease. Although the majority of oat cell carcinoma (OCC) occur in the bronchial tree, similar tumors have been reported in a wide variety of 504
extrapulmonary sites, and the histology of these is indistinguishable from that of bronchogenic OCC. These sites include the gastrointestinal tract, pancreas, thymus, larynx, pharynx and tongue, salivary glands, breasts, uterus, and skin.5 One of the rarest extrapulmonary sites is the urinary bladder and prostate. Of the former, only 52 cases have been described. Herein we report another case and review the literature on this subject. Case Report A forty-two-year-old man was investigated for hematuria of three months’ duration with associated urinary frequency. Physical examination revealed no abnormality. A chest x-ray film showed no abnormality. An intravenous urogram demonstrated normal upper tracts, and urine cytology was normal. Cystoscopy, however, revealed a polypoid tumor in the right lateral wall of the bladder. Biopsy showed transitional cell carcinoma with extensive areas of small cell carcinoma and smaller areas of adenocarcinoma and squamous cell carcinoma. Clinically this was a T3 (Stage C) tumor. There were no metastases detected by bone scan or
UROLOGY
i
JUNE
1992 /
VOLUME XXXIX,
NUMBER 6
FICUHE1. (A) Small cell anaplastic carcinoma indistinguishable from oat cell carcinoma of bronchus. (B) Area oj squamoid and spindle cell di.j erentiation. (C) In situ transitional cell carcinoma. (Hcmatoxylin and eosin, original magnifications x 100.) ultrasound and computerized tomography of the pelvis and liver. In view of the patient’s age, a nerve-sparing cystoprostatectomy was performed with primary reconstruction of an ileocolic bladder. Macroscopically, the tumor consisted of a round mass of 3 cm diameter infiltrating the full thickness of the bladder wall, but internal iliac lymph nodes were not involved. On light microscopy, a predominance of apparently undifferentiated, small, hyperchromatic cells that closely resembled oat cell carcinoma of bronchus were seen. The cells were arranged in diffuse sheets, with numerous areas of necrosis (Fig. IA). In addition, there were other histologic cell types, including moderately differentiated squamous cell carcinoma, adenocarcinema, transitional cell carcinoma, spindle cell carcinoma (Fig. lB), and flat in situ transitional cell carcinoma (Fig. 1C). Tumor cells showed focal positive staining with PGP 9.5 antibody for neurosecretory cells, and on electron microscopy a few of the small hyperchromatic tumor cells contained small numbers of membrane-bound dense core granules characteristic of neurosecretory cells (Fig. 2). A diagn’osis of primary oat cell carcinoma of the bladder was made. Postoperatively the patient was also started on a regimen of carboplatin (as he was reluctant IO receive alternative chemotherapy that
IJHOLOGY
JUNE: 1992
I
VOLUME
XXXIX.
NUMBER
FIGURE: 2. Electron micrograph of area of small cell carcinoma of bladder showing membranebound granules (original magnification x 112,000).
might cause hair loss). Initial progress was excellent and ten months later, he was well with full urinary continence day and night. He also was experiencing penile erection sufficient for sexual intercourse and has a normal response to papaverine. Urodynamics revealed a stable, large capacity (730 mL) neobladder with no ureteric reflux (Fig. 3). In the last month however, a follow-up CT scan has revealed recurrent tumor within the pelvis; this has been confirmed histologically. Despite further chemotherapy, he died eleven months after diagnosis. Necropsy was refused by his relatives .
ti
505
FIGURE 3.
Bladder at videourodynamics no ureteric reflux.
showing
Comment A total of 1.75 percent of tumors of the urinary bladder are undifferentiated histologically,22 and of these, one extremely rare variant is the oat cell carcinoma. As ultrastructural analysis is required to make this diagnosis, and since it has been described relatively recently, the true incidence is unknown. In 1981 Cramer, Aikawa, and Cebeli# described the first case of OCC in a bladder diverticulum; this patient was treated with local resection. Since then, cases with similar histology have been reported sporadically. To date, 52 cases have been reported in the world literature. Because of the similarities in light microscopy, histochemistry, ultrastructure, and immunocytochemistry between oat cell carcinoma of the bladder and oat cell carcinoma of the lung, OCC of the urinary bladder has come to be recognized as part of a widely distributed group of oat cell carcinoma that predominantly occurs in the bronchus but which may occur in many other sites. It has been suggested that these tumors develop from pre-existing APUD cells in the urinary tract. Certainly, agyrophillia, the ability to take up silver stains which is characteristic of APUD cells, has been demonstrated in the prostatic urethra and paraurethral glands of Littre,23 prostate,24 and bladder.25 An alternative theory of the origin of oat cell carcinoma is that they stem from multipotential epithelial reserve cells which are capable of differentiation into more than one cell line. This may explain the association of oat cell car-
506
cinoma with several other cell elements (squamous cell carcinoma, adenocarcinoma, and transitional cell carcinoma). This feature of mixed cell lines is seen also in oat cell carcinoma of the lung and other extrapulmonary sites.26 Review of the literature reveals a predominance of male patients with OCC of the bladder (4:l) and a wide age range (40-83 years). Hematuria is the most common presenting feature (83 %). The tumors tend to be large (2-10 cm diameter), polypoidal, and ulcerated. Microscopy shows a predominance of small cells often with an admixture of transitional cell dysplasia and carcinoma, adenocarcinoma, squamous cell carcinoma, and carcinoid tumor. Of the 52 patients, 11 (21%) were known to have metastases at diagnosis. Two of these were diagnosed at autopsy, and 4 more patients were dead by nine months and 1 by thirty months. In 32 patients subsequent metastases developed (64% or 32 of 50 patients, as 2 were diagnosed at autopsy). A total of 26 patients (50 %) died because of metastases, either present at diagnosis or subsequently, with the majority of deaths occurring within fifteen months from the time of diagnosis. The prognosis for those with initial or subsequent metastases of oat cell carcinoma is poor. Patients who received adjuvant chemotherapy appeared perhaps to fare better than those who received chemotherapy only after metastases had been detected. The latter group in turn did better than those who did not receive chemotherapy at all. However, chemotherapy did not prevent the development of metastases, and objective remission of definite secondary metastases were rare. We conclude that oat cell carcinoma of the urinary bladder is an important but under-recognized entity. It is aggressive, metastasizes early, and has a poor prognosis. Owing to the small number of reported cases, treatment at present is based on that of oat cell carcinoma of the lung. Chemotherapy seems to give the best hope for improving survival with or without surgery and radiotherapy. The diagnosis should be suspected when anaplastic carcinoma of the bladder is reported histologically. Electron microscopy should then be employed to look for neurosecretory granules in the cytoplasm of oat cells and distinguish these from anaplastic transitional cell carcinomas. Once the diagnosis is made, a full initial staging workup will distinguish patients with localized disease from those with extensive disease.
UROLOGY
/ JUNE1992
/ VOLUMEXXXIX,NUMBER6
Those with localized disease should receive adjuvant chemotherapy and the favored combination of chemotherapeutic agents seems to be vincristine, doxorubicin (Adriamycin), cisplatin, and etoposide. Although occult metastases are likely to be present initially, we believe that surgery in the absence of clinically obvious metastases and where the patient is fit may reduce the tumor volume and improve the responsiveness to chemotherapy. In addition, radiotherapy to the primary site may be of benefit.27 In patients with extensive disease, chemotherapy provides the main modality of treatment and surgery is clearly not appropriate, however, palliative radiotherapy may be helpful in the relief of bone pain and nerve compression. We conclude that the management of oat cell carcinoma of the bladder requires a multidisciplinary approach involving oncology, radiotherapy, and urology teams. We hope that as more cases are reported and longer term followup results become available, a clearer line of management will emerge.
three cases with ultrastructural analysis, Ultrastruct Path01 4: 197 (1983). 8. Kim CK, Lin JI. and Tseng CH: Small cell carcinoma of urinary bladder: ultrastructural study, Urology 24: 384 (1984). 9. Partenen S. and Asikainen U: Oat cell carcinoma of the urinary bladder with ectopic adrenocorticotropic hormone production, Human Pathol 16: 313 (1985). 10. Reyes CV. and Soneru I: Small cell carcinoma of the urinary bladder with hypercalcaemia, Cancer 56: 2530 (1985). 11. Abenoza I’, Manivel C, and Sibley RK: Adenocarcinoma with neuroendocrine differentiation of the urinary bladder: clinicopathologic, immunohistochemical and ultrastructural study, Arch Pathol Lab Med 110: 1062 (1986). 12. Lee JY-Y, Tang CK, and ‘Rodriguez F: Anaplastic carcinoma of urinary bladder with oat cell features, Urology 27: 474 (1986). 13. Ordoiiez NC, Khorsand J, Ayala AC, and Sneige N: Oat cell carcinoma of the urinary tract: an immunohistochemical and electron microscopic study, Cancer 58: 2519 (1986). 14. Paz RA, Ramos M, Ghioldi NS, and Sundblad AS: Carcinoma indiferenciado de pequenas celulas (oat cell): revision de 55 cases, incluidos 4 extrapulmonares, Medicina 46: 390 (1986). 15. Williams MR, Dunn M, and Ansell ID: Primary oat cell carcinoma of the urinary bladder, Br J Urol 58: 225 (1986). 16. Mills SE, et al: Small cell undifferentiated carcinoma of the urinary bladder: a light microscopic, immunocytochemical and ultrastructural study of 12 cases. Am J Surg Path01 11: 606 (1987). 17. Swanson PE, Brooks R, Pearse H, and Stenzel P: Small cell carcinoma of urinary bladder, Urology 32: 558 (1988). 18. Itoh K, et al: Small cell carcinoma of the urinary bladder: a case of remarkable remission with combined chemotherapy, Acta Ural Jpn 34: 1443 (1988). 19. Golomb J, et a/: Bladder neoplasms associated with augmentation cystoplasty: report of 2 cases and literature review, J Urol 142: 377 (1989). 20. Blomjous CEM, et al: Small cell carcinoma of the urinary bladder-a clinicopathologic, morphometric, immunohistochemical and ultrastructural study of 18 cases, Cancer 64: 1347 (1989). 21. Davis MP, et al: Successful management of small cell carcinoma of the bladder with cisplatin and etoposide, J Ural 142: Xl7 (1989). 22. Friedell GH, et al: Histopatholog) and classification of urinary bladder carcinoma, Urol Clin North Am 3: 53 (1976). 23. Feyrter F: Uber das urogenitale Helle-Zellen-system des Menschen, Mikrosk Anat Forsch 57: 324 (1951). 24. Kazzaz BA: Argentaffin and arkTrophilic cells in the prostate, J Pathol 112: 189 (1974). 25. Hofmann H: Gelbe (basalgekornte) Zellen in der schleimhaut einer ekstrophierten harnblase, Virchows Arch 309: 466 (1937). 26. Churg A, Johnston WH, and Stulbarg M: Small cell squamous and mixed small cell squamous-small cell anaplastic carcinomas of the lung, Am J Surg Pathol 4: 255 (1980). 27. Bunn PA Jr, et al: Chemotherapy alone or chemotherapy with chest radiation therapy in limited stage small cell lung cancer, Ann Intern Med 106: 655 (1987).
Department of Surgery The Chinese University of Hong Kong Shatin, New Territories Hong Kong (MR. CHENG) References 1. Barnard WC: The nature of the “oat-celled sarcoma” of the mediastinum, J Path01 Bacterial 29: 241 (1926). 2. Bensch KC. Corrin B, Pariente R, and Spencer H: Oat cell carcinoma of the lung: its origin and relationship to bronchial carcinoid. Cancer 22: 1163 (1968). 3. Azzopardi JC: Oat cell carcinoma of the bronchus, J Path01 Bacterial 78: 513 (1959). 4. Sidhu GS: The endodermal origin of digestive and respiratory tract APUD cells: histopathologic evidence and a review of the literature, Am J Path01 96: 5 (1979). 5. Ibrahim NBN, Briggs JC, and Corbishley CM: Extrapulmonary oat cell carcinomas Cancer 54: 1645 (1984). 6. Cramer SF. Aikawa M. and Cebelin M: Neurosecretorv granule:; in small cell invasive’carcinoma of the urinary bladder, Cancer 47: 724 (1981). 7. Davis BH, Ludwig ME, Cole SR, and Pastuszak WT: Small cell neuroendocrine carcinoma of the urinary bladder: report of
UROLOCY
JUNE
1992
i
VOLUME
XXXIX,
NUMBER
6
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