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Signet ring cell carcinoma of bladder
SIGNET RING CELL CARCINOMA
GARTH
E. AUSTIN,
M.D.
JUDITH
SAFFORD,
M.D.
From the Department of Pathology, University California, The Center for the Health Sciences, Los Angeles, California
OF BLADDER
of
ABSTRACT - The ninth reported cnse of primary signet ring cell carcinoma of the bladder is derepeatedly during its ecolution, scribed. This particular tumor, whose histology was exumined showed an interesting chunge in microscopic appeurance after irradiution. The emerging features of signet ring cell carcinomn of the bladder we discussed. ____~ _____ -
Adenocarcinoma of the urinary bladder accounts for as much as 2 per cent of bladder neoplasms, making it an entity with which most pathologists have some, albeit infrequent experience.’ However, of much rarer occurrence is the variant known as signet ring cell carcinoma, in which the majority of cells have a large cytoplasmic mucus-containing vacuole displacing the nucleus to a peripheral crescent. In fact, in the twenty years since Saphi? first described the entity, only 8 well-documented cases have appeared in the literature.2-7 This report documents the ninth pathologically proved case of this disease and discusses the emerging picture of this condition. Case Report A fifty-four-year-old Caucasian male was admitted to the hospital with a one-month history of fever, dysuria, and intermittent hematuria. Cystoscopy revealed a mass on the posterior wall of the bladder above the left ureteral orifice. A transurethral biopsy was performed which showed a poorly differentiated grade III papillary carcinoma with prominent glandular features interpreted as transitional cell carcinoma of bladder, Stage A (Fig. 1A). Transurethral resection of the tumor was performed, and the patient was followed by periodic cystoscopy. No recurrent tumor was noted at cystoscopy thirteen months after the initial resection, but two months later the patient presented to his
physician with acute urinary retention requiring Foley catheterization. Bladder biopsy perunformed at this time revealed an anaplastic, differentiated grade IV carcinoma showing features suggestive of glandular structures and occasional signet ring cells but lacking papillary configuration (Fig. 1B). The lesion, which was interpreted as consistent with transitional cell carcinoma grade IV, had infiltrated the submucosa and muscularis of the bladder. The patient was transferrred to UCLA hospital at this time where cystoscopy revealed a massive, solid tumor near the bladder neck, involving the trigone and base of the bladder. Search for metastases disclosed a single focus in the left iliac crest. The patient received radiation (2,000 rads) to the pelvis followed one month later by total cystectomyr and prostectomy with construction of an ileal loop urinary diversion. Microscopic examination of the excised bladder revealed a poorly differentiated adenocarcinoma, composed primarily of signet ring cells, many of which contained periodic acid, Schiff (PAS)-positive material (Fig. 1C). The tumor cells were infiltrating all layers of the bladder wall except the epithelium but including the perivesical fat; there was extension of the carcinoma to the right ductus deferens and the left and right seminal vesicles. An incidental finding detected in the surgical specimen was a microscopic focus of well-differentiated adenocarcinoma of the prostate, thought to be unrelated to the bladder neoplasm.
FIGLWS 1. 1.4) Initial biopsy: poorly diff~wntiatr~d pupillarly carcinoma with glandular f~~aturcs i hcmatoxylin x 400). (A 1 Second hiop~!y: anaplastic carcinoma showing f?aturc~.v suggestioc mnd twin, original magnijication (!f glnntlulur strwtwm and oc~casioncd signet ring ~11s (l~uriatoxylin and eosin, original triagnijit~ation X 400). 1C 1 C~ptccYorli!y specinwn: powly tliff crcn tia ted ade)locclrciiioinu comprised of sigwt ring c(dlscontaining P.AS-positir-c, matcricd jpwiorlic cdl-Sch@. x 100). (0) Biopsy of p&tontw/ rr~etc&mis: c~rigind mngnijicution filn-0dipo.w tivsfrf, rwntcliuing multiplr sigrwt ring ~11s (hcrrrcltosylin and cosin. original tnqgriifitwtio~r X 400).
Follomillg a two-month hospitalizatiol~ during which a repair of the left ureteroileal junction \\x rc~cluiwc!, the patient was discharged and \vas al)le to resume his normal activities. Three to four months post cystectom!~ the patient received a&litional radiation to the ~~hole pel\.is to the left iliac cwst (3,500 (2..500 ratls~ and rads). Siw inonths aft-cr cystectom!. hex ~~1s lwgun on immune rihonucleic acid therapy. (;ustroiiltt,stiiiul distress with niiilse’ii. and 0l)stipation necessitated his anorexia. one month lattlr. waclmissic,n to the hospital Laparotoni> re~~c~aled small-bowel obstruction wcond;~r~~ to irrdiation. The adhesions \vere I!-secl surgitrally, and aii ileotransversc c~olostom~\\ as pelforlntd; anterior pelvic peritoncsal hiops!. perforn~e’d at this time clisclosetl metastatic sigllc,t ring ~~~11carcinoma of the pelvic area (Fig. 111). Dt,spite the surgical intervention. gastrointcastinal distrc>ss cwltinuecl follo\ving clischargc an(l the patient gracluall~~ l~~~nc from hc~spit~il.
cwhectic. Ten months after cystt~ctoru\. he was rcaclmitted to the hospital Lvhere he received a single dose of c)-clophosphanlic~e i(:vtouan) therape’ for palliation. However. he died suddenl\~ on thy da\, after admissioll. At auto&y the pelvic a11d peritoncd cavities fhuntl to contain extensive fibroils atlhe\vtw sions w:hich were apparently responsil~lc fi)r the rcxwrrent gastrointestinal olxtnlctioil. Fibrous tissue (wntaining an abscess wvit) 1 filled the infclrior part of thy pelvis c’ncasirg the rec~tum. Histologic csamination re\~t~a‘letl anaplastic timior cells interspersed singl), ~tnd in grollps only a small pc~rwntagc throughout this tissue; of these ~11s retained a sign& riltg ~~11 morpliolog~~. No glandular or papillar! patterns \vc’w seen. The tumor did not invol\x$ thcl rec.tllln, antl no other sites of ~leoplastic~ in\wlvemcwt were identified grossly or i-lli~rc,sc,ol>icall~.. A sevc’rca l~roi~chopiieii~i~o~ii~t \\‘a~. t lit* apparent ~‘;lIls(’
of
deuth.
Comment In this patient biopsy was done on three separate occasions prior to cystectomy: the entire cystectomy specimen was examined, biopsy of the recurrent tumor was done at laparotomy, and a complete autopsy was performed. Thus, the present case provides the most complete documentation available of the development and progression of a treated signet ring cell carcinoma of the bladder. Comparison of this case with the 8 previously documented examples of the disease serves to illustrate the emerging features of this condition. Seven of the 9 patients were males. The age range at the time of diagnosis was thirty to sixty-two years; all except 2 of the patients were over fifty years. Two of the patients were black, the remainder Caucasian. Hematuria was a presenting complaint in all but 2 of the cases. Although some adenocarcinomas of the bladder are thought to arise in the urachus,1,8-‘0 it appears likely that none of the signet ring cell carcinomas so far reported was of urachal origin. Of the 9 tumors only that reported by Naeim, Schlezinger, and de la Maza’ appeared to arise on the anterior wall or dome of the bladder where carcinomas of urachal origin classically occur. Furthermore, that tumor was confined to the lamina propria of the bladder, which according to Mostofi, Thomson, and Dean” argues against urachal origin. On the other hand the presence of glandular structures in 7 of the tumors and transitional cell elements in a like number is compatible with the hypothesis that these tumors develop from the multipotential urothelium of the bladder. ‘sH The tumor described here underwent an apparent change in morphology after irradiation from an undifferentiated pattern to one consisting predominantly of signet ring cells. Naeim et ~1.~ reported an analogous change in their case following irradiation. Together, these observations strongly suggest that the signet ring cell variant is a relatively radioresistant form of bladder carcinoma. A high growth potential of this cell type is also indicated by the fact that in 3 of the previous cases with disseminated disease as well as in the present case, the metastases had a purely signet ring cell morphology even though the primary tumor contained glands and in 2 cases transitional cell elements as well. This tendency of signet ring cells to be more prominent in metastases than in the pri-
460
mary tumor appears to be a general characteristic of signet ring cell carcinomas no matter what their organ of origin.” A diffusely infiltrative pattern of growth and a tendency to metastasize early appear to be common features of signet ring cell carcinomas of the bladder as they are for other signet ring cell tumors.” Nonetheless, analysis of the 9 reported cases of this disease suggests that the over-all prognosis for this type of bladder carcinoma is not as bleak as was initially suggested. For example, one of the patients remained clinically free of tumor until his death from unknown causes thirty months after radiation and radical cystoprostatectomy. 7 Two other patients were clinically well (at last report) for several months after treatment, and the patient reported here survived for twenty-seven months from the time of onset of his symptoms. In those who died, urinary tract complications were the primary cause in 2 cases and disseminated metastases in 3 others. From the limited information yet available, radical resection coupled with local irradiation would appear to offer the best hope for cure in early cases.
Los Angeles, California 90024 (DR. AUSTIN)
References 1. Koss LG: Tumors of the Urinary Bladder, in Atlas of Tumor Pathology, Washington, D.C., Armed Forces Institute of Pathology, 1975, 2nd series, fax 11, p. 34. 2. Saphir 0: Signet-ring cell carcinoma of urinary bladder, Am. J. Pathol. 31: 223 (1955). 3. Payan HM, Mendoza C, Jr, Cabinum I>, and C&win IVH, Jr: Primary signet ring cell carcinoma of the urinary bladder, Arch. Surg. 92: 958 (1966). 4. Rosa+Uribe A, and Luna MA: Primary signet ring cell carcinoma of the urinary bladder. Report of two cases, Arch. Path& 88: 294 (1969). 5. Corwin SH, Tassy F, Malament M, and Grady HC: Signetring cell variant of mutinous adenocarcinoma of the hladdrr. J. Ural. 106: 697 (1971). 6. Naeim F, Schlezinger RM, and de la Maza LM Primary signet ring cell carcinoma of the bladder; report of a case and review of the literature, ibid. 108: 274 (1972). 7. DeTure FA, Dein R, Hackett RL. and Drylie DM: Primary signet ring cell carcinoma of bladder euemolifvine vesical enitheI hat m&potentiality, Urology 6: 240 (1975): ’ _’ 8. Mostofi FK. Thomson RV. and Dean AL. Ir: Mucous adenocarcinoma of the urinary bladder, Cancer 8: 74i (1955). 9. Rappoport AE, and Nixon CE: Adenocarciuoma of the urachus involving the urinary bladder, Arch. Pathol. 411: 388 11946). ’ 10.’ Wheeler JD, and Hill WT: Adenocarcinoma involving the urinary bladder, Cancer 7: 119 (1954). 11. Saphir 0: Signet-ring cell carcinoma, Mil. Surgeon 109: 360 (1951).
UROLOCY
/
OCTOBER
1978
i
VOLUME
XII,
NUMBER
4
GARTH
E. AUSTIN,
M.D.
JUDITH
SAFFORD,
M.D.
From the Department of Pathology, University California, The Center for the Health Sciences, Los Angeles, California
OF BLADDER
of
ABSTRACT - The ninth reported cnse of primary signet ring cell carcinoma of the bladder is derepeatedly during its ecolution, scribed. This particular tumor, whose histology was exumined showed an interesting chunge in microscopic appeurance after irradiution. The emerging features of signet ring cell carcinomn of the bladder we discussed. ____~ _____ -
Adenocarcinoma of the urinary bladder accounts for as much as 2 per cent of bladder neoplasms, making it an entity with which most pathologists have some, albeit infrequent experience.’ However, of much rarer occurrence is the variant known as signet ring cell carcinoma, in which the majority of cells have a large cytoplasmic mucus-containing vacuole displacing the nucleus to a peripheral crescent. In fact, in the twenty years since Saphi? first described the entity, only 8 well-documented cases have appeared in the literature.2-7 This report documents the ninth pathologically proved case of this disease and discusses the emerging picture of this condition. Case Report A fifty-four-year-old Caucasian male was admitted to the hospital with a one-month history of fever, dysuria, and intermittent hematuria. Cystoscopy revealed a mass on the posterior wall of the bladder above the left ureteral orifice. A transurethral biopsy was performed which showed a poorly differentiated grade III papillary carcinoma with prominent glandular features interpreted as transitional cell carcinoma of bladder, Stage A (Fig. 1A). Transurethral resection of the tumor was performed, and the patient was followed by periodic cystoscopy. No recurrent tumor was noted at cystoscopy thirteen months after the initial resection, but two months later the patient presented to his
physician with acute urinary retention requiring Foley catheterization. Bladder biopsy perunformed at this time revealed an anaplastic, differentiated grade IV carcinoma showing features suggestive of glandular structures and occasional signet ring cells but lacking papillary configuration (Fig. 1B). The lesion, which was interpreted as consistent with transitional cell carcinoma grade IV, had infiltrated the submucosa and muscularis of the bladder. The patient was transferrred to UCLA hospital at this time where cystoscopy revealed a massive, solid tumor near the bladder neck, involving the trigone and base of the bladder. Search for metastases disclosed a single focus in the left iliac crest. The patient received radiation (2,000 rads) to the pelvis followed one month later by total cystectomyr and prostectomy with construction of an ileal loop urinary diversion. Microscopic examination of the excised bladder revealed a poorly differentiated adenocarcinoma, composed primarily of signet ring cells, many of which contained periodic acid, Schiff (PAS)-positive material (Fig. 1C). The tumor cells were infiltrating all layers of the bladder wall except the epithelium but including the perivesical fat; there was extension of the carcinoma to the right ductus deferens and the left and right seminal vesicles. An incidental finding detected in the surgical specimen was a microscopic focus of well-differentiated adenocarcinoma of the prostate, thought to be unrelated to the bladder neoplasm.
FIGLWS 1. 1.4) Initial biopsy: poorly diff~wntiatr~d pupillarly carcinoma with glandular f~~aturcs i hcmatoxylin x 400). (A 1 Second hiop~!y: anaplastic carcinoma showing f?aturc~.v suggestioc mnd twin, original magnijication (!f glnntlulur strwtwm and oc~casioncd signet ring ~11s (l~uriatoxylin and eosin, original triagnijit~ation X 400). 1C 1 C~ptccYorli!y specinwn: powly tliff crcn tia ted ade)locclrciiioinu comprised of sigwt ring c(dlscontaining P.AS-positir-c, matcricd jpwiorlic cdl-Sch@. x 100). (0) Biopsy of p&tontw/ rr~etc&mis: c~rigind mngnijicution filn-0dipo.w tivsfrf, rwntcliuing multiplr sigrwt ring ~11s (hcrrrcltosylin and cosin. original tnqgriifitwtio~r X 400).
Follomillg a two-month hospitalizatiol~ during which a repair of the left ureteroileal junction \\x rc~cluiwc!, the patient was discharged and \vas al)le to resume his normal activities. Three to four months post cystectom!~ the patient received a&litional radiation to the ~~hole pel\.is to the left iliac cwst (3,500 (2..500 ratls~ and rads). Siw inonths aft-cr cystectom!. hex ~~1s lwgun on immune rihonucleic acid therapy. (;ustroiiltt,stiiiul distress with niiilse’ii. and 0l)stipation necessitated his anorexia. one month lattlr. waclmissic,n to the hospital Laparotoni> re~~c~aled small-bowel obstruction wcond;~r~~ to irrdiation. The adhesions \vere I!-secl surgitrally, and aii ileotransversc c~olostom~\\ as pelforlntd; anterior pelvic peritoncsal hiops!. perforn~e’d at this time clisclosetl metastatic sigllc,t ring ~~~11carcinoma of the pelvic area (Fig. 111). Dt,spite the surgical intervention. gastrointcastinal distrc>ss cwltinuecl follo\ving clischargc an(l the patient gracluall~~ l~~~nc from hc~spit~il.
cwhectic. Ten months after cystt~ctoru\. he was rcaclmitted to the hospital Lvhere he received a single dose of c)-clophosphanlic~e i(:vtouan) therape’ for palliation. However. he died suddenl\~ on thy da\, after admissioll. At auto&y the pelvic a11d peritoncd cavities fhuntl to contain extensive fibroils atlhe\vtw sions w:hich were apparently responsil~lc fi)r the rcxwrrent gastrointestinal olxtnlctioil. Fibrous tissue (wntaining an abscess wvit) 1 filled the infclrior part of thy pelvis c’ncasirg the rec~tum. Histologic csamination re\~t~a‘letl anaplastic timior cells interspersed singl), ~tnd in grollps only a small pc~rwntagc throughout this tissue; of these ~11s retained a sign& riltg ~~11 morpliolog~~. No glandular or papillar! patterns \vc’w seen. The tumor did not invol\x$ thcl rec.tllln, antl no other sites of ~leoplastic~ in\wlvemcwt were identified grossly or i-lli~rc,sc,ol>icall~.. A sevc’rca l~roi~chopiieii~i~o~ii~t \\‘a~. t lit* apparent ~‘;lIls(’
of
deuth.
Comment In this patient biopsy was done on three separate occasions prior to cystectomy: the entire cystectomy specimen was examined, biopsy of the recurrent tumor was done at laparotomy, and a complete autopsy was performed. Thus, the present case provides the most complete documentation available of the development and progression of a treated signet ring cell carcinoma of the bladder. Comparison of this case with the 8 previously documented examples of the disease serves to illustrate the emerging features of this condition. Seven of the 9 patients were males. The age range at the time of diagnosis was thirty to sixty-two years; all except 2 of the patients were over fifty years. Two of the patients were black, the remainder Caucasian. Hematuria was a presenting complaint in all but 2 of the cases. Although some adenocarcinomas of the bladder are thought to arise in the urachus,1,8-‘0 it appears likely that none of the signet ring cell carcinomas so far reported was of urachal origin. Of the 9 tumors only that reported by Naeim, Schlezinger, and de la Maza’ appeared to arise on the anterior wall or dome of the bladder where carcinomas of urachal origin classically occur. Furthermore, that tumor was confined to the lamina propria of the bladder, which according to Mostofi, Thomson, and Dean” argues against urachal origin. On the other hand the presence of glandular structures in 7 of the tumors and transitional cell elements in a like number is compatible with the hypothesis that these tumors develop from the multipotential urothelium of the bladder. ‘sH The tumor described here underwent an apparent change in morphology after irradiation from an undifferentiated pattern to one consisting predominantly of signet ring cells. Naeim et ~1.~ reported an analogous change in their case following irradiation. Together, these observations strongly suggest that the signet ring cell variant is a relatively radioresistant form of bladder carcinoma. A high growth potential of this cell type is also indicated by the fact that in 3 of the previous cases with disseminated disease as well as in the present case, the metastases had a purely signet ring cell morphology even though the primary tumor contained glands and in 2 cases transitional cell elements as well. This tendency of signet ring cells to be more prominent in metastases than in the pri-
460
mary tumor appears to be a general characteristic of signet ring cell carcinomas no matter what their organ of origin.” A diffusely infiltrative pattern of growth and a tendency to metastasize early appear to be common features of signet ring cell carcinomas of the bladder as they are for other signet ring cell tumors.” Nonetheless, analysis of the 9 reported cases of this disease suggests that the over-all prognosis for this type of bladder carcinoma is not as bleak as was initially suggested. For example, one of the patients remained clinically free of tumor until his death from unknown causes thirty months after radiation and radical cystoprostatectomy. 7 Two other patients were clinically well (at last report) for several months after treatment, and the patient reported here survived for twenty-seven months from the time of onset of his symptoms. In those who died, urinary tract complications were the primary cause in 2 cases and disseminated metastases in 3 others. From the limited information yet available, radical resection coupled with local irradiation would appear to offer the best hope for cure in early cases.
Los Angeles, California 90024 (DR. AUSTIN)
References 1. Koss LG: Tumors of the Urinary Bladder, in Atlas of Tumor Pathology, Washington, D.C., Armed Forces Institute of Pathology, 1975, 2nd series, fax 11, p. 34. 2. Saphir 0: Signet-ring cell carcinoma of urinary bladder, Am. J. Pathol. 31: 223 (1955). 3. Payan HM, Mendoza C, Jr, Cabinum I>, and C&win IVH, Jr: Primary signet ring cell carcinoma of the urinary bladder, Arch. Surg. 92: 958 (1966). 4. Rosa+Uribe A, and Luna MA: Primary signet ring cell carcinoma of the urinary bladder. Report of two cases, Arch. Path& 88: 294 (1969). 5. Corwin SH, Tassy F, Malament M, and Grady HC: Signetring cell variant of mutinous adenocarcinoma of the hladdrr. J. Ural. 106: 697 (1971). 6. Naeim F, Schlezinger RM, and de la Maza LM Primary signet ring cell carcinoma of the bladder; report of a case and review of the literature, ibid. 108: 274 (1972). 7. DeTure FA, Dein R, Hackett RL. and Drylie DM: Primary signet ring cell carcinoma of bladder euemolifvine vesical enitheI hat m&potentiality, Urology 6: 240 (1975): ’ _’ 8. Mostofi FK. Thomson RV. and Dean AL. Ir: Mucous adenocarcinoma of the urinary bladder, Cancer 8: 74i (1955). 9. Rappoport AE, and Nixon CE: Adenocarciuoma of the urachus involving the urinary bladder, Arch. Pathol. 411: 388 11946). ’ 10.’ Wheeler JD, and Hill WT: Adenocarcinoma involving the urinary bladder, Cancer 7: 119 (1954). 11. Saphir 0: Signet-ring cell carcinoma, Mil. Surgeon 109: 360 (1951).
UROLOCY
/
OCTOBER
1978
i
VOLUME
XII,
NUMBER
4