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Malignant Tumor of a Diverticulum of the Urinary Bladder1
MALIGNANT TUMOR OF A DIVERTICULUM OF THE URINARY BLADDER 1 HAROLD L. STEWART
AND
GEORGE J. MUELLERSCHOEN
From the Laboratories of Pathology and the Urological Wards of Jefferson Medical College and Hospital
Cases of malignant tumors of a diverticulum of the urinary bladder are unusuaL Twenty-five cases have been reported to date. Kretschmer and Barber (1) collected and reviewed twentyone. Rathbun (3) reported a case; as did R. D. Gill (2), J. B. Hicks (3) and Hunt (4). Hunt believed that undoubted instances of primary carcinoma of a diverticulum of the bladder were rare. In 1929 he found only eleven undoubted instances of it. Judd and Scholl (5) reported ten cases but Hunt, after carefully reviewing them, believed that only one could be considered truly a cancer arising within the diverticulum. Preoperative diagnoses of this condition has been made in only a few instances, and then only when the tumor extended far enough into the bladder to be seen through a cystoscope. In Hicks' cases a diagnosis was made preoperatively of a concealed tumor of a diverticulum which turned out to be an epidermoid carcinoma. It was removed and the patient was well seventeen months later. Targett (6) reported a sarcoma. The case being reported is unusual in so many respects that none could be found to parallel it. J. F., white male, aged fifty-five years, was admitted to the Jefferson Hospital June 6, 1930. He was an express man. About six months previous he began losing weight, which in that time amounted to 32 pounds. During the same time he lost his appetite and strength and had to stop work. There had been no history of cancer, tuberculosis, diabetes, cardio-renal or mental diseases in his family. His general 1 A grant from the Martin Research Fund aided in this work. been filed in the Army Medical Muse um.
685
This case has
686
H. L. STEWART AND G. J. MUELLERSCHOEN
health had always been good. He had had the usual diseases of childhood, no operations, serious diseases nor injuries. He was married and had four children all normal. He denied gonorrheal and luetic infections. Until his present illness he had never had any symptoms referable to his genito-urinary tract. Six weeks prior to admission the patient developed symptoms of nocturia and hematuria. He consulted a physician, was x-rayed and cystoscoped and the diagnosis of stone in the bladder was made. He refused operation and went home. During this period of six weeks prior to admission he gradually lost ground. His symptoms became aggravated, his weight dropped, his fatigue increased, his appetite left him. He noticed an increase in sharp pains radiating down the inner side of both thighs to the ankle. These were accompanied by pain in the back and loss of sensation in his legs. It became increasingly difficult for him to start his urinary stream and when started it was feeble. He was constipated. Physical examination showed a cachetic elderly male weighing 110 pounds. The lower right cervical lymph nodes were enlarged, adherent to each other, to the skin over them and to the tissues beneath. They displaced the trachea to the left. The lungs were emphysematous. The heart was apparently normal. No masses were felt in the abdomen. There was tenderness over the right upper quadrant. The right arm _was paralyzed. Examination of the prostate showed it to be small and firm. He had a secondary anemia, hemoglobin 57 per cent, red blood cells 3,510,000. The white cells were normal. Wassermann and Kahn tests were negative. Blood sugar was 98, non-protein nitrogen 74.07 mgm., and creatinin 2.06 mgm. His blood pressure was 80/50. Temperature ran from 98° to 100°; pulse 100 to 110 and respirations 20 to 26. Examination of 1specimens of urine showed a fixed specific gravity 1.011 to 1.014 and the presence of albumin, pus and blood. The first cystoscopic study was made about May 15, 1929. The urinary bladder was filled with pus. On the left side of the bladder floor there was a raised area covered with bullous edema. Above was what appeared to be a large stone. The ureteral orifices were questionably located. One large opening on the left side was felt to be a possible diverticulum. An attempt to pass a catheter into this was not successful. X-ray examination showed the catheter coiled about th,e bladder behind a globular shadow which it was decided was a stone. The patient refused operation and left the hospital.
TUMOR OF DIVERTICULUM OF BLADDER
687
On June 6, 1930, he was cystoscoped in this hospital, but his general condition was so poor that not much time could be taken for fear the patient would die on the table. All that could be learned was that there was a marked cystitis. Nothing else was noted in this hurried examination. On account of his imminent death further cystoscopy was not advised.
FIG. L
URINARY BLADDER WITH DIVERTICULUM LAID OPE~
The carcinoma (on the right of photograph) is strictly confined to the diverticulum and covered with calcific material. The bladder is the seat of a suppurative inflammation.
On x-ray examination there was a generalized decrease in calcification of the pelvic bones, of the right femur at the lesser trocanter, and of the ischium. There was a nodule in the right lung. A calcified body in the pelvis the size of a small orange, was thought to be a cyst which had undergone calcification. The patient lost ground rapidly. He developed rales in his chest; THE JOURNAL OF UROLOGY, VOL. XXVII, KO.
6
688
H. L. STEWART AND G. J. MUELLERSCHOEN
expectorated and coughed considerably. On June 11, his temperature, pulse and respirations began to mount and he died at 9: 15 p.m., June 12. His temperature was 104°, pulse 160 and respirations 46. Autopsy showed a chronic suppurative inflammation of the urinary bladder (fig. 1). The inside of the bladder measured 9 by 9 cm., and was filled with cloudy urine containing flecks of pus and some free
FIG. 2. PHOTOMICROGRAPH. SPLEEN The small mass of dark cells is characteristic of tumor emboli.
X200
calcific material. Opening into the bladder, on its left wall, was a diverticulum. The diameter of its opening was 2 cm. It was practically spherical in contour and measured 5 cm. in diameter. It was almost completely filled by a rounded tumor mass measuring 4 cm. across, and springing from its outer wall. A friable fractured, easily dislodged crust of calcific material covered the free surface of the tumor
TUMOR OF DIVERTICULUM OF BLADDER
689
and diverticulum. On section the tumor was composed of grayish soft, friable, glistening tissue, which in some places, was hemorrhagic, in others necrotic and purulent. It infiltrated all the coats of the diverticulum. The ureteral and urethral orifices were normal. .· The tumor was confined within the diverticulum and did not involve the adjacent bladder.
FIG.
3.
PHOTOMICROGRAPH.
PRIMARY TUMOR OF DrvERTICULUM.
X160
Microscopically, this primary tumor growth (fig. 3) was composed of extremely cellular tissue. The cells varied considerably as to size and shape. They were hyperchromatic and undifferentiated. Many mitotic figures could be seen. The tumor cells were not accompanied by much fibrous stroma; it was quite vascular. Many areas of necrosis were found scattered throughout. The surface was necrotic and covered by calcific material. The outer wall of the diverticulum was diffusely infiltrated with the tumor.
690
H. L. STEWART AND G. J. 11/IUELLERSCHOEN
Metastasis was extensive. A button-like nodule, 2 cm. in diameter, was found on the inferior surface of the upper lobe of the right (fig. 4) A hilus lymph node on the same side was involved. In the liver a large nodule lay just beneath the right dome of the diaphragm. Histologically, in addition, numerous tumor emboli, too small to be observed grossly, were seen in the liver as well as in the spleen (fig. 2).
FrG.
4.
PHOTOMICROGRAPH
Lmrn
SHOWING METASTASIS.
Xl60
A large spherical metastatic tumor nodule was shelled out of the left adrenal. Several spherical nodules, 2 cm. in diameter, were found in the loose connective tissue at the inferior pole of the left kidney. A many nodules were found in the pancreas and the lymph nodes abouL it. In addition to t.he lymph nodes mentioned, those of the right lower cervical chain were cancerous, and the growth had infiltrated the skin and brachial plexus. The lymph nodes of the pelvis and
TUMOR OF DIVERTICULUM OF BLADDER
691
were cancerous. Many of the intercostal muscles were involved by metastatic tumor masses as well as all the musculature of the pelvis and the sacral plexus. There was a pathologic fracture of the fourth right rib on the.·anterior axillary line where it wzs infiltrated by a large tumor mass (fig. 5). Similar nodules were seen on the right second and sixth ribs, on the second, fourth, fifth and seventh left ribs, on the third, fourth andjfifth lumbar vertebrae; the lesser tuberosity of the right
Frn. 5. Rrn
SHOWI!',G METASTASIS.
X 160
femur and all the pelvic bones were extensively involved. Where the sigmoid passed over the prominence of the sacrum its wall was infiltrated by the tumor mass filling the pelvis. Histologically, the metastases corresponded to the main tumor mass in the diverticulum except that they were somewhat more anaplastie and more rapidly growing as evidenced by the number of mitotic figures. In addition, postmortem examination disclosed acute myocardial
692
H. L. STEWART AND G. J. MUELLERSCHOEN
degeneration, chronic fibrous endocarditis, arteriosclerosis of the aorta and coronary arteries, suppurative bronchopneumonia, pulmonary edema, chronic fibrous tuberculosis involving the upper lobes of both lungs, apparently inactive, chronic passive congestion of the liver, and calcification of a few lymph nodes about the pancreas. COMMENT
It is obvious that we are dealing with an exceedingly rapidlygrowing malignant tumor. The patient's first symptoms began in January and he was dead in June. The history of fatigue and loss of weight lasted only a few weeks when he developed pain in the thighs. This was followed rapidly by hematuria and metastasis to the right lower cervical lymph nodes. The very extensive and unusual metastases and the microscopic evidences of mitosis and anaplasia, all show this to be a very unusual diverticular tumor. The mistaken preoperative diagnoses of stone by one and calcified cyst by another roentgenologist is easily understood when the pathology is considered. The diverticulum had evidently been the seat of a chronic inflammation for a long period of time. Its interior had become calcified. Yet there appears to be no previous history of any symptoms referable to the genito-urinary tract. When the tumor appeared and began to grow rapidly this calcific material was pushed forward and began to fracture. Much of it remained attached to the exposed surface of the globular tumor mass giving the appearance both roentgenographically and through a cystoscope of a calcified cyst or stone. Some of it was broken off and appeared as loose fragments in the bladder causing urinary symptoms. There is no question in this case as to the origin of the tumor. It was attached to the outermost wall of the diverticulum. The margins of the sac adjacent to the bladder were not infiltrated nor was its opening or the bladder wall adjacent to it. While the cells forming the growth are undifferentiated, by the location of the lesion and the general morphology of the cell, its supportive stroma, its avascularity and well-formed vessels, it is considered to be epithelial in origin.
C
TUMOR OF DIV.ERTICULUM OF BLADDER
We are indebted to Dr, Baxter L. Crawford of this hospital Major Ash (7) of the Army Medical Museum for their study of the autopsy material in this case. CONCLUSIONS
L This is twenty-sixth case of a malignant tumor diverticulum to be reported. 2. A carcinoma of the diverticulum of the urinary bladder is reported. 3. No case in the literature shows such extensive metastases or such an anaplastic growth. 4. Preoperative diagnosis was not made, the baffling to which are explained. REFERENCES (1) KRETSCHMER, H. L., AND BARBER, K. E.: Jour. UroL, 1929, xxi, no. 1, 381. (2) GrLL, R. D .. Jour. UroL, November, 1930. (3) HrcKs, J.B.: Jour. Urol., August, 1930, xxiv, no. 2, 205. (4) HUNT, V. C.: Jour. Ural., 1929, xxi, J.-12. (5) JUDD, E. S., AND SCHOLL, A. J.: Surg., Gynecol.. and Obstet., 1924, xxxviii,
14--26. (6) TARGETT, J. H.: Brit. Med. Jour., 1893, ii, 218. (7) Personal communications.
AND
GEORGE J. MUELLERSCHOEN
From the Laboratories of Pathology and the Urological Wards of Jefferson Medical College and Hospital
Cases of malignant tumors of a diverticulum of the urinary bladder are unusuaL Twenty-five cases have been reported to date. Kretschmer and Barber (1) collected and reviewed twentyone. Rathbun (3) reported a case; as did R. D. Gill (2), J. B. Hicks (3) and Hunt (4). Hunt believed that undoubted instances of primary carcinoma of a diverticulum of the bladder were rare. In 1929 he found only eleven undoubted instances of it. Judd and Scholl (5) reported ten cases but Hunt, after carefully reviewing them, believed that only one could be considered truly a cancer arising within the diverticulum. Preoperative diagnoses of this condition has been made in only a few instances, and then only when the tumor extended far enough into the bladder to be seen through a cystoscope. In Hicks' cases a diagnosis was made preoperatively of a concealed tumor of a diverticulum which turned out to be an epidermoid carcinoma. It was removed and the patient was well seventeen months later. Targett (6) reported a sarcoma. The case being reported is unusual in so many respects that none could be found to parallel it. J. F., white male, aged fifty-five years, was admitted to the Jefferson Hospital June 6, 1930. He was an express man. About six months previous he began losing weight, which in that time amounted to 32 pounds. During the same time he lost his appetite and strength and had to stop work. There had been no history of cancer, tuberculosis, diabetes, cardio-renal or mental diseases in his family. His general 1 A grant from the Martin Research Fund aided in this work. been filed in the Army Medical Muse um.
685
This case has
686
H. L. STEWART AND G. J. MUELLERSCHOEN
health had always been good. He had had the usual diseases of childhood, no operations, serious diseases nor injuries. He was married and had four children all normal. He denied gonorrheal and luetic infections. Until his present illness he had never had any symptoms referable to his genito-urinary tract. Six weeks prior to admission the patient developed symptoms of nocturia and hematuria. He consulted a physician, was x-rayed and cystoscoped and the diagnosis of stone in the bladder was made. He refused operation and went home. During this period of six weeks prior to admission he gradually lost ground. His symptoms became aggravated, his weight dropped, his fatigue increased, his appetite left him. He noticed an increase in sharp pains radiating down the inner side of both thighs to the ankle. These were accompanied by pain in the back and loss of sensation in his legs. It became increasingly difficult for him to start his urinary stream and when started it was feeble. He was constipated. Physical examination showed a cachetic elderly male weighing 110 pounds. The lower right cervical lymph nodes were enlarged, adherent to each other, to the skin over them and to the tissues beneath. They displaced the trachea to the left. The lungs were emphysematous. The heart was apparently normal. No masses were felt in the abdomen. There was tenderness over the right upper quadrant. The right arm _was paralyzed. Examination of the prostate showed it to be small and firm. He had a secondary anemia, hemoglobin 57 per cent, red blood cells 3,510,000. The white cells were normal. Wassermann and Kahn tests were negative. Blood sugar was 98, non-protein nitrogen 74.07 mgm., and creatinin 2.06 mgm. His blood pressure was 80/50. Temperature ran from 98° to 100°; pulse 100 to 110 and respirations 20 to 26. Examination of 1specimens of urine showed a fixed specific gravity 1.011 to 1.014 and the presence of albumin, pus and blood. The first cystoscopic study was made about May 15, 1929. The urinary bladder was filled with pus. On the left side of the bladder floor there was a raised area covered with bullous edema. Above was what appeared to be a large stone. The ureteral orifices were questionably located. One large opening on the left side was felt to be a possible diverticulum. An attempt to pass a catheter into this was not successful. X-ray examination showed the catheter coiled about th,e bladder behind a globular shadow which it was decided was a stone. The patient refused operation and left the hospital.
TUMOR OF DIVERTICULUM OF BLADDER
687
On June 6, 1930, he was cystoscoped in this hospital, but his general condition was so poor that not much time could be taken for fear the patient would die on the table. All that could be learned was that there was a marked cystitis. Nothing else was noted in this hurried examination. On account of his imminent death further cystoscopy was not advised.
FIG. L
URINARY BLADDER WITH DIVERTICULUM LAID OPE~
The carcinoma (on the right of photograph) is strictly confined to the diverticulum and covered with calcific material. The bladder is the seat of a suppurative inflammation.
On x-ray examination there was a generalized decrease in calcification of the pelvic bones, of the right femur at the lesser trocanter, and of the ischium. There was a nodule in the right lung. A calcified body in the pelvis the size of a small orange, was thought to be a cyst which had undergone calcification. The patient lost ground rapidly. He developed rales in his chest; THE JOURNAL OF UROLOGY, VOL. XXVII, KO.
6
688
H. L. STEWART AND G. J. MUELLERSCHOEN
expectorated and coughed considerably. On June 11, his temperature, pulse and respirations began to mount and he died at 9: 15 p.m., June 12. His temperature was 104°, pulse 160 and respirations 46. Autopsy showed a chronic suppurative inflammation of the urinary bladder (fig. 1). The inside of the bladder measured 9 by 9 cm., and was filled with cloudy urine containing flecks of pus and some free
FIG. 2. PHOTOMICROGRAPH. SPLEEN The small mass of dark cells is characteristic of tumor emboli.
X200
calcific material. Opening into the bladder, on its left wall, was a diverticulum. The diameter of its opening was 2 cm. It was practically spherical in contour and measured 5 cm. in diameter. It was almost completely filled by a rounded tumor mass measuring 4 cm. across, and springing from its outer wall. A friable fractured, easily dislodged crust of calcific material covered the free surface of the tumor
TUMOR OF DIVERTICULUM OF BLADDER
689
and diverticulum. On section the tumor was composed of grayish soft, friable, glistening tissue, which in some places, was hemorrhagic, in others necrotic and purulent. It infiltrated all the coats of the diverticulum. The ureteral and urethral orifices were normal. .· The tumor was confined within the diverticulum and did not involve the adjacent bladder.
FIG.
3.
PHOTOMICROGRAPH.
PRIMARY TUMOR OF DrvERTICULUM.
X160
Microscopically, this primary tumor growth (fig. 3) was composed of extremely cellular tissue. The cells varied considerably as to size and shape. They were hyperchromatic and undifferentiated. Many mitotic figures could be seen. The tumor cells were not accompanied by much fibrous stroma; it was quite vascular. Many areas of necrosis were found scattered throughout. The surface was necrotic and covered by calcific material. The outer wall of the diverticulum was diffusely infiltrated with the tumor.
690
H. L. STEWART AND G. J. 11/IUELLERSCHOEN
Metastasis was extensive. A button-like nodule, 2 cm. in diameter, was found on the inferior surface of the upper lobe of the right (fig. 4) A hilus lymph node on the same side was involved. In the liver a large nodule lay just beneath the right dome of the diaphragm. Histologically, in addition, numerous tumor emboli, too small to be observed grossly, were seen in the liver as well as in the spleen (fig. 2).
FrG.
4.
PHOTOMICROGRAPH
Lmrn
SHOWING METASTASIS.
Xl60
A large spherical metastatic tumor nodule was shelled out of the left adrenal. Several spherical nodules, 2 cm. in diameter, were found in the loose connective tissue at the inferior pole of the left kidney. A many nodules were found in the pancreas and the lymph nodes abouL it. In addition to t.he lymph nodes mentioned, those of the right lower cervical chain were cancerous, and the growth had infiltrated the skin and brachial plexus. The lymph nodes of the pelvis and
TUMOR OF DIVERTICULUM OF BLADDER
691
were cancerous. Many of the intercostal muscles were involved by metastatic tumor masses as well as all the musculature of the pelvis and the sacral plexus. There was a pathologic fracture of the fourth right rib on the.·anterior axillary line where it wzs infiltrated by a large tumor mass (fig. 5). Similar nodules were seen on the right second and sixth ribs, on the second, fourth, fifth and seventh left ribs, on the third, fourth andjfifth lumbar vertebrae; the lesser tuberosity of the right
Frn. 5. Rrn
SHOWI!',G METASTASIS.
X 160
femur and all the pelvic bones were extensively involved. Where the sigmoid passed over the prominence of the sacrum its wall was infiltrated by the tumor mass filling the pelvis. Histologically, the metastases corresponded to the main tumor mass in the diverticulum except that they were somewhat more anaplastie and more rapidly growing as evidenced by the number of mitotic figures. In addition, postmortem examination disclosed acute myocardial
692
H. L. STEWART AND G. J. MUELLERSCHOEN
degeneration, chronic fibrous endocarditis, arteriosclerosis of the aorta and coronary arteries, suppurative bronchopneumonia, pulmonary edema, chronic fibrous tuberculosis involving the upper lobes of both lungs, apparently inactive, chronic passive congestion of the liver, and calcification of a few lymph nodes about the pancreas. COMMENT
It is obvious that we are dealing with an exceedingly rapidlygrowing malignant tumor. The patient's first symptoms began in January and he was dead in June. The history of fatigue and loss of weight lasted only a few weeks when he developed pain in the thighs. This was followed rapidly by hematuria and metastasis to the right lower cervical lymph nodes. The very extensive and unusual metastases and the microscopic evidences of mitosis and anaplasia, all show this to be a very unusual diverticular tumor. The mistaken preoperative diagnoses of stone by one and calcified cyst by another roentgenologist is easily understood when the pathology is considered. The diverticulum had evidently been the seat of a chronic inflammation for a long period of time. Its interior had become calcified. Yet there appears to be no previous history of any symptoms referable to the genito-urinary tract. When the tumor appeared and began to grow rapidly this calcific material was pushed forward and began to fracture. Much of it remained attached to the exposed surface of the globular tumor mass giving the appearance both roentgenographically and through a cystoscope of a calcified cyst or stone. Some of it was broken off and appeared as loose fragments in the bladder causing urinary symptoms. There is no question in this case as to the origin of the tumor. It was attached to the outermost wall of the diverticulum. The margins of the sac adjacent to the bladder were not infiltrated nor was its opening or the bladder wall adjacent to it. While the cells forming the growth are undifferentiated, by the location of the lesion and the general morphology of the cell, its supportive stroma, its avascularity and well-formed vessels, it is considered to be epithelial in origin.
C
TUMOR OF DIV.ERTICULUM OF BLADDER
We are indebted to Dr, Baxter L. Crawford of this hospital Major Ash (7) of the Army Medical Museum for their study of the autopsy material in this case. CONCLUSIONS
L This is twenty-sixth case of a malignant tumor diverticulum to be reported. 2. A carcinoma of the diverticulum of the urinary bladder is reported. 3. No case in the literature shows such extensive metastases or such an anaplastic growth. 4. Preoperative diagnosis was not made, the baffling to which are explained. REFERENCES (1) KRETSCHMER, H. L., AND BARBER, K. E.: Jour. UroL, 1929, xxi, no. 1, 381. (2) GrLL, R. D .. Jour. UroL, November, 1930. (3) HrcKs, J.B.: Jour. Urol., August, 1930, xxiv, no. 2, 205. (4) HUNT, V. C.: Jour. Ural., 1929, xxi, J.-12. (5) JUDD, E. S., AND SCHOLL, A. J.: Surg., Gynecol.. and Obstet., 1924, xxxviii,
14--26. (6) TARGETT, J. H.: Brit. Med. Jour., 1893, ii, 218. (7) Personal communications.