Studies of the natural history of genitourinary tumors. I: Primary cancer of ureter

STUDIES OF THE NATURAL HISTORY OF GENITOURINARY TUMORS. I: PRIMARY CANCER OF URETER AUTOPSY

STUDY WITH REVIEW

OF THE LITERATURE

JUDSON B. GILBERT, M.D. SCHENECTADY,

T

HE purpose of this study is to add an autopsy report of primary cancer of the ureter to the 40 previousIy published cases. Twenty of these reports show that no operative intervention was attempted and that the majority of the others had expIoratory operations onIy. From this data the naturaI history processes of this disease can be estimated. This study has been directed particuIarIy to the duration of symptoms previous to observation and the tota Iength of life foIIowing diagnosis or operation. Since onIy reports of unquestioned primary maIignant tumors have been accepted a composite study of the metastases and their extension has also been made. A fuI1 abstract of these accepted cases is not presented as recentIy severa compIete reviews have been pubIished. Points of unusua1 interest are recorded and the accepted cases are arranged aIphabeticaIIy and chronoIogicaIIy in the bibIiography. CASE

REPORT

M. S., a sixty-eight year oId, singIe, Russian laborer was admitted to BelIevue HospitaI, with a chief compIaint of pain in the epigastrium. The famiIy and past histories were irreIevant. For two years the patient compIained of duI1 epigastric pain which radiated downward over the entire abdomen, with indefinite relationship to meals. Vomiting after meals, diarrhea and bIoody stooIs, anorexia, a sIightIy productive cough and dyspnea had a11 persisted for one month. PrecordiaI pain had been present for three days. He compIained of nocturia five to six times for a month, and had Iost 60 pounds in weight. PhysicaI examination revealed an eIderIy, markedIy emaciated, dehydrated and dyspneic

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man. The abdomen was sIightIy distended. The Iiver and spleen were paIpabIe but not enlarged. The kidneys were not paIpated. There were enlarged inguinaI Iymph nodes. His blood pressure was g8 systolic and 84 diastolic. Laboratory Reports. Urinanalysis showed specific gravity I .OIO; aIkaIine reaction; trace of albumin; a few epitheIia1 ceIIs but no pus or red blood ceIIs were reported. Blood count: Ieucocytes 8200; poIymorphonucIears 78, Iymphocytes 20, and transitional ceIIs 2 per cent; erythrocytes 5,4go,ooo; hemogIobin 70 per cent. A provisiona diagnosis of carcinoma of the stomach was made. The patient died the foIlowing day before further studies could be accompIished. Autopsy. An emaciated white maIe measuring 5 feet, IO inches and weighing about 150 pounds. No abnorma1 changes referrabIe to nose, mouth, eyes or ears were found, nor edema, jaundice or enlargement of the superficial Iymph gIands. The distribution of the hair was normal. The external genitalia appeared norma but the genitourinary organs were of most interest and are described in detai1. The right kidney weighed 140 grams, appeared to be of norma size and was of reddish coIor. The capsuIe stripped easiIy Ieaving a smooth surface. There were no hemorrhages. On section, the norma markings of the kidney were easiIy distinguished. The right ureter appeared normal. The Ieft kidney was increased in size and appeared Iobulated. The kidney was bluish-red and on section consisted of numerous we11 separated cystic areas. The parenchyma of the kidney was reduced to a she11 and a greenish-yeIIow exudate was present in the peIvis of the kidney. The ureter and the peIvis were markedly dilated, the ureter being diIated in its entirety. About 8 cm. from its entrance into the bladder there was a thickening of the uretera waI1

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consisting of firm, white tissue, with encroachment upon the Iumen by this growth. The bIadder was of normaI size with a sIightIy

Cancer Iated nucIei resting in reIativeIy very Iarge amounts of smooth, bright pinkish staining cytopIasm. The whoIe represented the remains of ceIIs of the squamous type. The tumor is a diffuseIy growing epitheIioma. Incidence. The observation here reported is the onIy instance of proved primary uretera cancer in the 22,810 autopsy

FIG. I. Low power

of diffuseIy growing epitheIioma of the ureter, grade II.

thickened waI1. CIose to the bIadder neck the mucous membrane appeared hypertrophied and there was a region of bluish-bIack discoIoration covered by an area of thick, yellowish exudate. The prostate was increased in size and cut with increased resistance, but appeared norma on section. There was no evidence of locai extension or metastases in the other abdomina1 or thoracic organs. Summary of Anatomical Diagnosis. Carcinoma of the lower third of the left ureter with diIatation; hydronephrosis of the Ieft kidney; cystitis; prostatic hypertrophy; bronchopneumonia; arterioscIerosis of the aorta; fatty degeneration of the liver, and general emaciation. Microscopic examination of the primary uretera tumor showed a background of fibromuscuIar tissue scattered through which were innumerable isIands of tumor ceIIs. The Iatter, for the greater part, showed Iarge rounded or oval, rather richIy chromatic nucIei embedded in a scanty smooth pinkish staining cytopIasm. Among them were a few very Iarge flattened ceIIs with richIy chromatic, sometimes Iobu-

fiIes of BeIIevue HospitaI from 1904-1935. The cIinica1 fiIes of the uroIogica1 service of BeIIevue HospitaI show no records of this rare disease; Pack and Le Fevre in 1930 discIosed no cases observed at the MemoriaI HospitaI of New York, in their study of 16,565 maIignant tumors. Age Period. There were no chiIdren or young aduIts in this series. Zironi’s and Scott’s reports are the onIy records of the fourth decade, both patiitnts being thirtysix years of age. The oIdest case reported by Richter, was an eighty year oId woman. There were I I cases in the fifth, IO each in the sixth and the seventh and 6 cases in the eighth decades. The mean age for the entire series was fifty-eight years whiIe the average age was fifty-seven years. Sex and Color. There were 24 maIes and 17 femaIes in this series. RousseIot and Lamon reported the onIy tumor present in a Negro. Previous Duration of Symptoms Related In 7 cases this data to Ureteral Cancer. is either missing or indefinite; in the remaining 34 cases the average duration prior to diagnosis or operation was fifteen and one-haIf months. If the cases of IsraeI

and Loewenstein, where the history recorded symptoms for ten years, and the recent report of Cochems and Grauer with a duration of fifteen years are excIuded, then we find a period of seven months as the average duration prior to diagnosis or operation. IsraeI and Loewenstein in Igr I reported a right sided ureteroceIe coincident with cancer of the Ieft ureter; the presence of this ureteroceIe suggests urinary tract pathoIogy of probably Iong duration. A recent report of my own with combined biIatera1 ureteroceIe, ureteritis cystica, and

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primary cancer of the right ureter aIso gave a seven year history of urinary symptoms. Cochems and Grauer’s patient, a fifty-one year oId woman, compIained of aching pain across the right abdomen and the right Iumbar region for fifteen years. No hematuria was noted but the right kidney was paIpabIe. The primary cancer, Iocated in the middle third of the right ureter was found associated with IeucopIakia and a smal1 caLzulus. Here again the Iong duration of symptoms suggests the presence of previous benign uretera obstruction with subsequent hydronephrosis. Symptomatology. Pain was the principa1 symptom which brought the patient for examination, as recorded in 33 cases. In 6 cases the pain was predominantly in the back, and in the cases of Spiess, Schmitt

and GIas the provisiona diagnosis of “ sciatica ” was made. Hematuria was noted 21 times. VoIante’s patient had noted gross bIeeding eIeven years previously. In 28 instances a paIpabIe tumor mass was noted on examination, which usuaIIy proved to be a hydronephrotic kidney above the uretera obstruction. The primary uretera tumors per se were not b u Ik y in cross section, aIthough the entire ureter may be invoIved.

Cystoscopy and Roentgenographic Examination. Cystoscopic examination was performed 22 times and in 16 cases aided directIy in estabIishing the correct diagnosis. The roentgenogram assisted in the diagnosis of associated caIcuIi in 5 of 6 cases. Davy in 1884 found the caIcuIus at autopsy; however, he performed cystoscopy but was unabIe to obtain urine from the Ieft ureter which Iater proved to be the Seat of primary cancer. Sommer in 1932

confused by the presence of a caIcified ovary which existed on the same side as the primary tumor. Severe hemorrhage foIIowed manipuIation in Scott’s and Hunter’s cases which directIy aided in the correct diagnosis. Diagnosis. In 9 reports a correct clinica was

diagnosis was made before operation or autopsy. The diagnosis of malignancy was

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made in the foIIowing cases: UreteraI tumor, eight times; osteosarcoma of the peIvis, twice; kidney tumor, twice; bIadder tumor, twice; kidney peIvis tumor, once; and cancer of the stomach, once. The 2 cases of Hektoen and ButIer suspected of being primary sarcoma of the peIvis Iater proved to be tumors of the Iower third of the ureter, both on the right side, with secondary extension to the bony structures. Our own case was in extremis and the provisiona diagnosis of cancer of the stomach was made from the history of predominantIy gastrointestinal symptoms. This symptom compIex is commonIy confusing in the presence of obstruction to the upper urinary tract.

Operative Procedure. SurgicaI remova was not attempted in 20 instances, due either to inability to make a correct diagnosis or the extremeIy poor condition of the patient on admission. Nephrectomy onIy was done by Gerstein. Nephrectomy and ureterectomy was done five times, whiIe nephrectomy and spIenectomy was done by IsraeI. PartiaI low ureterectomy onIy was performed in Snyder and Wood’s case because the condition of the patient prohibited further procedures. Hunter performed partia1 ureterectomy without nephrectomy and successfuIIy removed the entire tumor. Subsequent death was due to a coIIoid carcinoma of the stomach six years Iater. ExpIoratory kidney operations were done six times. ExpIoratory Iaparotomy, cystotomy, bIadder cauterization and prostatectomy were performed once each. In 2 cases, bladder tumors were considered as extensions of the primary uretera cancer. In the Iight of newer interpretation these tumors shouId be considered as the extensive or diffuse simultaneous appearance of the same process and not a metastasis or impIantation. Pathology. Side InvoIved. The seat of the primary tumor was Iocated 17 times on the right and 24 times on the Ieft side The right ureter was invoIved twice in the upper third, 6 times in the middIe, and 16 times in the Iower third. The Ieft ureter

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showed Iesions twice in the upper third, twice in the middle and 13 times in the Iower third. The middIe and Iower thirds were invoIved in one extensive tumor twice on the right and once on the Ieft side. UreteraI anomaIies were not common. Jona reported a papiIlary tumor present in a diverticulum of the lower third of the Ieft ureter about 1.5 cm. in diameter. Local Extension and Metastases. In the z cases of Jona and in the case of AscoIi the tumor was Iimited entireIy to the ureter without IocaI extension or metastases. In 13 instances there were no IocaI extensions while in 20 cases there were IocaIized periuretera1 infiItrations. The bIadder was invoIved five times whiIe the semina1 vesicIe and the dorsa1 vertebras were each invoIved once. Metastases. There were no metastases present in I I autopsies. The retroperitoneal Iymph gIands were invoIved 12 times; the Iiver g times; the Iungs 8 times; the kidneys 5 times; whiIe spIeen and bones were affected 3 times each, (iIium once and vertebras twice) ; peritoneum, appendix, pararecta1 Iymph gIands, FaIIopian tubes, vagina, pancreas, adrenaIs, skin, the vena cava, and the ureter of the opposite side once each. It wiI1 be noted that in onIy 8 cases the metastases extended above the diaphragm. Microscopic Diagnosis. Various terms were used to describe the non-papiIIary flat tumors which occurred in 7 instances. The distinctIy squamous tumors numbered I 5, whiIe carcinoma and adenocarcinoma were recorded twice each. Carcinosarcoma was diagnosed once in Renner’s case. Fourteen tumors were described as papiIIary in structure. The tumors coincident with caIcuIi are of specia1 interest as their presence as a source of chronic irritation is beyond doubt. The association of caIcuIi and tumors was noted in 15.3 per cent of the series. Six such reports are given by Davy 1884, Zironi Igog, Paschkis 1910, Volante 1927, RousseIot and Lamon 1930, and Cochems and Grauer, 1935. In the reports of Davy and

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Paschkis the tumors were papiIIary whiIe the remaining 4 were Aat or squamous in structure. MacMiIIan and I found the cIoseIy reIated tumors of the renaI peIvis to be highly maIignant and associated with caIcuIi in 52 per cent of 57 cases. We fee1 that the earIy removal of impacted caIcuIi shouId be considered as a prophyIactic procedure. Associated Diseases and Double Primary Tumors. Cross found puImonary tubercuIosis present in the autopsy of his fortyeight year oId maIe patient. Microscopic evidence of syphiIis was observed in Renner’s seventy-one year old maIe patient. OckerbIad and HeIIwig stated their patient had been cured of an epitheIioma of the nose five years previous to operation, aIthough microscopic evidence was not definiteIy stated. In both Renner’s, and Cochems and Grauer’s reports associated spindIe ceI1 sarcoma of the bladder was noted, whiIe RousseIot and Lamon observed a dermoid cyst of the ovary and adenomyosis of the FaIIopian tubes in a forty-eight year oId Negress. Hunter’s patient, a male, forty-three years of age, Iived six years after operation for a papiIIary carcinoma of the right ureter, onIy to die of a perforated coIIoid carcinoma of the stomach. Scott’s second case died foIIowing an expIoratory abdominal operation with coIostomy about three and a half months after nephrectomy for hydronephrosis. Autopsy discIosed two primary cancers; one of the transverse colon and the other of the Iower third of the right ureter. These cases of muItipIe primary tumors clearly show the necessity for complete autopsy studies. Six cases or 15 per cent is unusuaIIy high in any series of autopsy statistics. Prognosis. There are 6 records with incompIete data in regard to the duration of previous symptoms. Of the 35 cases with compIete data, Ig or 54 per cent lived a tota of two to nine months. ExcIuding the 2 cases with Iong histories there were

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14 patients, or 40 per cent who Iived from one to three years. The tota Iength of Iife of the entire series from the onset of the first symptom to the time of death was twenty-one months. With the excIusion of the reports by IsraeI and Loewenstein (ten years) and Cochems and Grauer’s (fifteen years) the tota length of life was exactly one year. The surgica1 figures of Scott aIso showed a postoperative mortahty of 27 per cent, and the foIIow-up reveaIed that more than $0 per cent died within tweIve months. Scott’s questionnaire on surgica1 endresuhs reveaIed the fact that 2 and probabIy 3 patients had survived remova for primary uretera cancer more than five years after operation. Kraft in Igzz reported the resuIt of nephroureterectomy for muItipIe papiIIary epitheIioma in a fifty-two year oId woman. FoIIow-up in July, 1932, reveaIed the patient aIive eIeven years after operation. Crance and Knickerbocker in 1924 made a preoperative diagnosis of primary tumor of the Iower right ureter in a forty-three year old woman who had symptoms for one year. Ureteronephrectomy reveaIed an epitheIioma, and the patient was reported we11 eight years Iater. Stewart’s patient in 1926, a seventy-five year oId woman Iived four years after nephrectomy and ureterectomy for papiIIary cancer of the middIe right ureter. Death occurred from pneumonia and cardiac failure. WhiIe no autopsy was performed, the disease was probabIy arrested. The onIy addition to these successfu1 surgica1 resuIts is the report of Hunter in 1935. His forty-three year oId maIe patient survived ureterectomy for papiIIary carcinoma of the Iower third of the right ureter for six years and three months from the onset of the initia1 hematuria. Death was due to a coIIoid cancer of the stomach with metastases to the omentum. It shouId be noted that 3 of these 4 cases were papiIIary carcinomas and that in a11 reports the authors suspected the correct diagnosis preoperatively and foIIowed we11 pIanned surgica1 procedures.

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SUMMARY

The Iiterature of 40 autopsy cases of primary cancer of the ureter is reviewed to which is added the onIy report from the BeIIevue HospitaI fiIes of 22,810 protocoIs. There were 24 maIes and 17 femaIes. The peak of the age incidence is in the fifth decade with the average at fifty-seven years. AI1 patients except one were white. The average duration of symptoms previous to observation was fifteen and one-half months. Two reports of extremeIy Iong previous histories are given for ten and fifteen years, respectiveIy. Pain, hematuria, and paIpabIe tumor were the three most constant findings in the history and physica1 examination. Backache was the chief symptom in 6 cases. Cystoscopy and roentgenogram directIy aided in making a correct diagnosis 16 times, whiIe associated caIcuIi were found 6 times, or 13 per cent. The tumor was right sided 17 times and on the Ieft 24 times. The Iower third of the ureter on both sides was the seat of the tumor in 77 per cent of the series, in 2 cases being IocaIized entireIy to the ureter. In 13 reports there was no IocaI extensions but distant metastases were present, whiIe I I showed no metastases. The metastases were variously distributed to the abdomina1 viscera and bone, but onIy 8 times extended above the diaphragm. Twenty-seven primary tumors were ffat or non-papiIIary whiIe 14 were papiIIary. Six or 15 per cent showed doubIe primary tumors. Nineteen or 54 per cent of patients Iived from two to nine months from the onset of the first symptom, whiIe 14 or 40 per cent Iived from one to three years. One six year surviva1 is added to 3 previousIy reported surgica1 resuIts where apparent successful remova was accomplished. I wish to thank Dr. DougIas Symmers for his review of the autopsy materia1. REFERENCES* WIESING, P. .I. and BLIX, C. Primary cancer of the right ureter. Hygeia, 40: 468, 1878. *This is a compkte autopsies.

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DAVY, R. CIinicaI Iecture on excision of the Ieft kidney. Brit. Med. Jour., 2: 757-758, 1884. JONA, G. Beitrag zu den primaeren Tumoren des Ureters. Centralbl. f. allg. Patb. u. patb. Anat., 5:

341352, 1931; Abst.: Centralbl. f. allg. Patb. u. patb. Anat., 54: I78-179, 1932. RENNER, M. J. Primary maIignant tumors of the ureter. Surg., Gynec. and Obst., 52: 793-803,

659662, 1894. VOELKER, A. V. Primary carcinoma of the ureter. Tr. Patb. Sot. London, 46: 133-135, 1894-1895. HEKTOEN, L. Primary carcinoma of the ureter. J. A. M. A., 26: IIIf-1117, 1896. RUNDLE, H. Epithelioma of the ureter causing hydronephrosis. Tr. Patb. Sot. London, 47: 128-132, 1896. GERSTEIN, K. Ein FaII von primaerem Krebs der rechten Uretermuendung. KieI I.D. 1902, p. 17. MINICH, C. K. Carcinoma uretaris, fornicem vaginae perforans. Pest. Med.-Cbir. Presse., 38: 941, 1902; Orvosi betil. Budapest, 46: 403, Igo2. St. Thomas HospitaI. Carcinoma of the Ieft ureter. St. Tbomas Hosp. Report, 32: 96, 1904. ADLER, L. Beitrag zur Kenntnis der primaren Tumoren des Ureters. M0natsber.f. Urol., IO: 129-142, rgo5. VORPAHL, K. 0. F. Ueber ein primaeres Karzinom des Ureters. GreifswaId I. D. 1905, p. 31. RICHTER, J. Primaeres Karzinom des rechten Ureters. Ztscbr. f. UrOl., 3: 416-422, 1909. ZIRONI, G. Cancer primitive de I’uretere droit. Ann. d. mal. des org. gen.-urin., I: 81-101, Igog. PASCHKIS, R. Primaerer Tumor des Harnleiters. Wien. klin. Wcbnscbr., 23: 361-362, IgIo. LOEWENSTEIN, E. Ein Fall von primaerem Karzinom des Ureter. Freiburg I. D. Igx I, p. 29. BUTLER, F. A. A case of primary carcinoma of the ureter with “sciatica.” Clifton Med. Bull., 2: 48-51, 1914. SPIESS, P. Die primaer epithaIiaIen Tumoren des Nierenbeckens und des Ureters. Centralbl. f. allg. Patb. u. patb. Anat., 26: 553-618, 1915. SCHMIDT, E. G. Primary carcinoma of the ureter. Jour. Cancer Res., I: 461-478, 1916. KNACH. FaII von papiIIaerem Karzinom des Iinken Ureters. Deutscb. med. Wcbnscbr., 18: 982, IgI8. MEEKER, L. H. and MCCARTHY, J. F. Primary carcinoma of the ureter. Report of a case with review of the literature. J. A. M. A., 81: Io4-log, 1923. GLAS, R. Ein Beitrag zum primaeren und metastatischen Ureterkarzinom. Wien. med. Wcbnscbr., 39:

193’. NAVRATIL, E. Primaeres Ureterkarzinom. Zentralbl. f. Gyniikol., 56: I I 16-1120, 1932. SOMMER, R. Primaeres Ureterkarzinom mit metastatischem Verschluss des anderen Ureters. Ztscbr. f. Ural., 26: I-g, 1932. SAUER, H. VON. Zur KIink und PathoIgoie der primaeren Uretertumoren. Ztscbr. f. urol. Cbir., 34: 165-178, 1932 (Case No. I.) GILBERT, J. B. Primary carcinoma of the ureter. Case report and brief review of the literature. Surg. Clin. N. Amer., 13: 448-493, 1933. SNYDER, W. H. and WOOD, B. S. Primary carcinoma of the ureter with report of a case. Jour. Ural., 29:

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VOLANTE, F. Contributo aI10 studio dei carcinomi primitivi deII’uretere. Arch. ital. di urol., 4: 10513% ‘927. KLAGES, F. BeitrLge zum primaeren Ureterkarzinom. Ztscbr. f. Ural., 28: 413-428, 1929. ASCOLI, R. Su di un case di carcinoma primitivo dell’uretere studio iniziaIe. Arch. ital. di urol., 6: 611-623, Ig3o. OCKERBLAD, N. F. and HELWIG, F. C. Primary carcinoma of the ureter. Report of a case. Jour. Ural., 24: 451-459, ‘930. ROUSSELOT, L. M. and LAMON, J. D. Primary carcinoma of the ureter. Surg., Cynec. and Obst., 50: 17-28, 1930. CROSS, J. B. Carcinoma of the ureter. Jour. Med. Assn. Georgia, 20: 125-127, 1931. MARRIANI, G. Sopra un case di cancro primitivo deII’uretere. Atti d. R. Univ. dei jisioc. Siena., 5:

577-585, 1933. HARRAH, F. W. Primary carcinoma of the ureter, with report of two cases. Amer. Jour. Surg., 26: 550560, 1934. SCOTT, W. W. Primary carcinoma of the ureter. Surg., Gynec. and Obst., 58: 215-227, I934 (Case No. 2). COCHEMS, F. M. and GRAUER, T. P. Squamous cell carcinoma, IeukopIakia and concretions of a megaIo-ureter. Jour. Urol., 34: 106-1 IO, 1935. HUNTER, A. W. Primary tumor of the ureter; end resuIts in three cases. Jour. Urol., 33: 443-455, ‘935. MATHE, C. P. and DE LA PENA, E. Primary carcinoma of the ureter. California and West. Med., 42: 357-363.

1935.

ADDITIONAL

. REFERENCES

CRANCE, 0. M. and KNICKERBOCKER, H. J. Primary carcinoma of the ureter; report of a case. J. A. M. A., 82: 1g3o-1932, 1924. GILBERT, J. B. Primary cancer of the ureter associated with ureteritis cystica. Case report with specia1 reference to its etioIogy. Ural. and Cutan. Rev., 40: IgI-195, 1936. GILBERT, J. B. and MACMILLAN, S. F. Cancer of the kidney, squamous ceI1 carcinoma of the renaI peIvis with specia1 reference to etioIogy. Ann. SUrg., 100: 42*444, 1934. KRAFT, S. FaeIIe von primaerem und sekundaerem UreterpapiIIom. Ztscbr. f. urol. Cbir., 16: 385-392, 1922. MORSE, H. D. The etioIogy and pathoIogy of pyeIitis cystica ureteritis cystica, and cystitis cystica. Amer. Jour. Patb., 4: 33-49. 1928. PACK, G. T. and LE FEVRE, R. G. The age and sex distribution and incidence of neopIastic diseases at the MemoriaI Hospital, New York City. Jour. Cancer Res., 14: 167-294, 1930. PATCH, F. S. The genesis and deveIopment of Brun’s nests and their reIation to cystitis cystica, cystitis gIanduIaris, and primary adenocarcinoma of the bladder. Canahan Med. Assn. Jour., 33: 597-606, ‘935. STEWART, R. L. Primary tumors of the ureter. Brit. Jour. Surg., 13: 667-682, 1926.