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Pathology of Anilin Tumors of the Bladder
ANILIN TUMORS OF BLADDER
137
that practically all cases could be detected by their method, they did admit, however, that the cystoscopic examination was undoubtedly safer. Apparently their only reason for not adopting this method is the fact that they feel the workmen would definitely object and it might cause serious labor difficulties within the plant. We are definitely of the opinion that should we rely upon the urine tests, many early tumors would be missed. Gross of Elberfeld and Simon of Ludwigshafen are decidedly opposed to biopsy of any bladder tumors and they emphatically state that it will lead to multiple implants and recurrences. They make their diagnosis mainly upon the appearance of the growth and in doubtful cases by observation after fulguration, claiming that all simple tumors respond favorably to fulguration, malignant tumors do not. SUMMARY
1. Bladder tumors occur more frequently among dye workers
than among non-dye workers and in our experience they occur to the extent of per cent. 2. The combined experiences of the dye industries of Germany, Switzerland, England and America, indicate that probably anilin, alpha and beta naphthylamine and benzidine are the etiological compounds. 3. Bladder tumors may appear any time after two years exposure and removal from the dye operation does not eliminate the possibility of future developments which may occur at any time. 4. The adoption of a completely closed and properly ventilated process, together with careful medical supervision and protection will eliminate the hazard, but these methods will require many years of active enforcement and must continue as long as the compounds are made.
PATHOLOGY OF ANILIN TUMORS OF THE BLADDER DOUGLAS M. GAY Wilmington, Delaware
The pathological anatomy of bladder tumors occurring in dye workers is not essentially different from that of the tumors of unknown origin.
138
SYMPOSIUM
The tumors are single or multiple, papillary or sessile, infiltrating or not infiltrating, ulcerating or not ulcerating, or there may be any combination or sequence of these characteristics. An analysis of 124 of the approximately 200 cases reported from various German sources (table 1) indicates that the incidence of carcinoma is about twice that of papilloma. The occurrence of non-epithelial neoplasms is very rare. As shown in table 2, papillomas are more frequently single and carcinomas are more TABLE 1 Diagnosis of 124 anilin tumors of the bladder (collected series f rom various German sources) Papilloma . ... . . . . . .. . . . .. . . . ... . . . . . .... .. ... . . . . . . . . ... .. .. . ....... . . .. . .. 41 Carcinoma.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 Papilloma and carcinoma. . . ... .... . .... . . . . . . .. . . . .. .. . . .. . . .... . . . . .. .. . .. 3 Papilloma and (later) carcinoma . . . . . . . . . .. .. .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Sarcoma. . ... .. ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Sarcoma and carcinoma.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
TABLE 2 Number and location of anilin tumors of bladder (collected series from vari ous German sources) PAPILLOMA
Number: Single .. . . .... . ....... . .. . . .... . ............ . . ..... . Multiple . . .. . . . . . . . .. . ... . . . . ... . . . .. _. ... . . . . . . . . . . Location: Trigone .. .. . .. . .... . .. . . . .. . ... .. . . . . . .. . . . .. . . ... . Elsewhere . ... . . . . . ... . .. . . ... . . . . . . . . .... . . . .. . . . . .
CARCINOMA
10 3
3
14 3
23
6
13
frequently multiple in the reported cases. Thirty-seven tumors were located on the trigone and 16 were found elsewhere in the bladder. In this series tumors elsewhere than on the trigone appeared to be more malignant than those situated at the bladder base. Simon (14) reporting a series of 85 cases claims a better outcome in the anilin group than in those bladder tumors of unknown etiology (table 3). This however is more apparent than real. The anilin patient is younger and a better surgical risk. Although the tumor may invade the tissues of the pelvic cavity,
139
ANILIN TUMORS OF BLADDER
metastases are extremely rare. There are many records of submucous hemorrhages, localized areas of hyperemia or cystitis which later developed tumors. Simon (15) believes that slight hyperemia is a precancerous lesion but this view is not held by Oppenheimer (4), although he admits that bladder irritation and tumor may be caused by the same injurious agent. Janssen (16) adds cystitis cystica and glandularis as precancerous lesions, stating that the transition from these conditions to mucous and glandular cancer has been demonstrated histologically many times. In the routine cystoscopic examination of the dye workers in our care numerous instances of local hyperemia, especially on the trigone, have been observed but there has been no opportunity TABLE 3 Per cent survival of patients with bladder tumors after three and five years Series of 85 cases reported by Simon
TUMORS
TUMORS OF UNKNOWN ETIOLOGY
per cent
per cent
ANILIN
Three-year survival. ................................ . Five-year survival.. ................................. .
54
21
48
10.5
for microscopic study. The suggestion is made that this is a more or less transitory capillary dilatation rather than hemorrhage, because the hyperemia has been observed to disappear and blood pigment is rarely present in the tumors microscopically examined. However, permanent telangiectases are often observed by cystoscope. Table 4 outlines the data on 17 of our series of anilin tumors of the bladder that have been examined microscopically. Seven were papillomas, grade I. The remaining 10 carcinomas were divided as follows: 4 papillary carcinomas, grade II; 1 carcinoma, grade III; 1 carcinoma, grade IV; 3 papilloma and carcinoma coexisting and 1 was diagnosed carcinoma but not graded. The multiple tumors were all carcinomas. Seven of the single tumors were papillomas and 3 were carcinomas. The tumors were pre-· ceded by no symptoms in 8 instances. THE JOURNAL OF UROLOGY, VOL. XXXI, NO.
2
TABLE 4 Anilin tumors of the bladder (Wilmington series)
~
H'>-
0 CASE NUM-
AGE
BER
YEARS IN DYE
FIRST
WORKS
SYMPTOMS
15
None None Hematuria; frequency None None None Hematuria Hematuria
------
TIME ELAP3ING BEFORE BIOPSY
GROSS PAPILLARY
Number
Location
MICROSCOPIC
Diagnosis
Grade
years
2 3 4
45 49 50
5 6 7 12 14
50 57 58 38 52
15
41
10
12 11
18 18 9 5 14
16
45
14
19
36
6
20 21
39 51
14 13
22 23
60 44
13
24 25
32 31
10 12
* Not graded.
15
Single 3 years
10 months 3½ years
' Single
Single
Single Single Single Multiple Multiple
Trigone Trigone Trigone
Papilloma Papilloma Papillary carcinoma
I I II
Trigone Trigone Trigone Trigone Trigone and anterior wall Lateral wall {
Papilloma Papilloma Papilloma Papillary carcinoma Papillary carcinoma
I I I II II
'ti
Right papilloma Left papillary carcinoma Anterior posterior and { Papilloma right wall Papillary carcinoma Posterior and right walls Carcinoma
I II I II III IV II
Single Single
Trigone Anterior, posterior and right walls Left wall Left wall
Single Single
Trigone Trigone
Multiple
Frequency; hematuria None
7 months
Burning on voiding Hematuria Burning; hematuria Hematuria Hematuria; burning None None
6 years
Multiple
4 months 13 months
Multiple Multiple
6 months 16 months
Multiple
~
Carcinoma Papillary carcinoma Carcinoma Papilloma invaded by carcinoma Papilloma Papilloma
*
I III I I
0
~
§
141
ANILIN TUMORS OF BLADDER
Case 22 is the one fatality of the series. The post-mortem examination showed a recto-vesical fistula and extensive pelvic cellulitis. There was no gross or microscopic evidence of tumor outside of the trigone. The following are presented as illustrative of the variety of structure of anilin tumors of the bladder as we have found them.
Fm.
1.
PAPILLOMA,
GRADE
I,
oF BLADDER.
ARRANGED IN ANASTOMOSING STRANDS
TRANSITIONAL EPITHELIUM
ON A DELICATE CONNECTIVE
TISSUE AND VASCULAR FRAMEWORK (CASE
3)
Case 3 with no history or symptoms suggesting bladder pathology was found on cystoscopic examination to have a small tumor on the trigone. The bladder mucosa was moderately congested. The biopsy (fig. 1) shows' a papilloma, grade I, composed of transitional epithelium arranged in anastomosing strands on a delicate connective tissue and vascular framework.
142
SYMPOSIUM
Case 2 was entirely free of bladder symptoms and examination by means of the cystoscope one year before showed no evidence of bladder pathology. The single neoplasm removed from the trigone is papillary in structure with lymphocytic infiltration of the stroma.
FIG. 2.
VASCULAR CHANGES AT BASE OF
p APILLOMA
OF BLADDER (CASE
5)
Case 7 presented a single papillary tumor, more compact in structure than the preceding, located on the trigone. The patient was symptomatically well. Case 6 likewise had no symptoms. The single papillary tumor removed from the trigone shows marked proliferation of the blood vessels. In case 5, presenting no symptoms, a single papillary tumor was
ANILIN TUMORS OF BLADDER
143
found just the right ureter. The submucosal blood ves~ sels are numerous, irregular, dilated, occasionally thrombosed and have the appearance of varices (fig. 2). The single papilloma, removed from above the right ureter of another patient, presenting no symptoms, shows a striking dilatation of some of the villi (fig. 3).
FIG. 3.
CYSTIC DILATATION OF
VILLI;
PAPILLOMA, GRADE
I,
OF BLADDER (CASE
25)
Case 14 is interest in that multiple tumors on the base and anterior wall of bladder were successfully treated transurethral electrocoagulation. After a three year period of freedom from further symptoms a papillary carcinoma, grade II, appeared above the right ureter. This and the numerous other instances of multiple bladder tumors sugge'3t that the fundamental pathol-
144
SYMPOSIUM
ogy is an affection of the entire viscus although the visible change may be local. Case 19 suffered from burning on voiding for six years before he sought medical aid and is unique because he has never has hematuria. Biopsy specimens removed at two and three month
FIG. 4.
CARCINOMA, GRADE III,
OF BLADDER.
SOLID MASSES OF IRREGULAR
TUMOR CELLS IN DISORDERLY ARRANGEMEN'"r (CASE
19)
intervals from the multiple lesions on the posterior and right lateral walls have consistently shown a grade III carcinoma characterized by solid masses of irregular epithelial cells in disorderly arrangement (fig. 4). Case 20 represents microscopically the most malignant tumor of the series and is designated as carcinoma, grade IV. The
ANILIN TUMORS OF BLADDER
145
patient sought relief from hematuria and was found to have multiple papillary infiltrating tumors around the bladder orifice. Microscopic examination shows a mass of irregular cells so rapidly growing that they are outrunning their blood supply. Well preserved cells are seen only near the blood vessels. The more distant cells are necrotic (fig. 5). Other portions of the same tumor are composed of a loose arrangement of slightly elongated cells suggesting sarcoma.
FIG. 5.
GRADE
IV,
OF BLADDER.
SOLID ;\fASSES OF RAPIDLY
GROWIKG Tm,IOR CELLS (CASE
20)
Transition from this type of cell to those which are epithelial can traced (fig. 6). The next 2 cases illustrate the simultaneous occurrence of tumors of different grades at different sites. Case 15, giving a history of urinary frequency as the first symptom, was treated expectantly until a massive hematuria occurred four months later. At that time papillary tumors were found on the lateral walls. The tumor from the right is composed
146
SYMPOSIUM
layers of fairly well differentiated transitional epithelium supported by a central core of fibroblasts and capillary blood vessels. The tumor from the left is also papillary and shows in addition, irregular large vesicular cells invading the stroma (fig. 7). Case 16 gave no history or symptoms referable to the bladder and was found normal by cystoscopic examination one year before. The tumor on the posterior wall is a typical papilloma,
Fm.
6.
CARCINOMA, GRADE IV, oF BLADDER.
FIGURE
5,
SAME TuMoR ILLUSTRATED IN
SHOWING VARIATION IN APPEARANCE (CASE
OF TUMOR CELLS
20)
while those on the anterior wall in the midline, and right lateral wall are distinctly more irregular in structure and show a few groups of tumor cells breaking through the base membrane, invading the stroma. Case 23 illustrates a papilloma invaded by a carcinoma. The material at hand was removed fifteen months after the initial symptom of hematuria and represents a single papillary tumor on the left wall of the bladder. The papillae, covered with
ANILIN TUMORS OF BLADDER
147
orderly transitional epithelium are invaded from the base by a carcinoma, grade IIL The photomicrograph (fig. 8) is of a villus in cross-section showing the central mass of irregular carcinoma cells in contrast to the more faintly staining superficial epithelium. A subsequent biopsy shows in addition the edematous character
FIG. 7. p APILLARY
CARCINOMA, GRADE
II,
OF BLADDER SLIGHTLY IRREGULAR
VESICULAR TUMOR CELLS BENEATH INTACT SURFACE EPITHELIUM (CASE
15)
of the villi. We point to this case in support of the theory that the primary epithelial change in bladder tumor occurs in the basal layer of the epithelium. Whether the injurious agent exerts its first effect on the submucous blood vessels or directly on the epithelium cannot be proved with the material at hand; but we do hold to the hypothe-
148
SYMPOSIUM
sis that anilin tumors are caused by an agent, to which the tissues of the bladder are specifically vulnerable. Although the greatest changes are in the region of the trigone, the multiplicity and subsequent origin of tumors in different sites leads us to believe that
FIG. 8.
CROSS-SECTION OF A VILLUS, PAPILLOMA, GRADE I, OF BLADDER INVADED BY A CARCINOMA, GRADE III (CASE
23)
the injury involves the entire bladder, probably due to the circulation of a cancerogenic agent in the blood.
INCIDENCE, SYMPTOMS AND SIGNS, RESULTS OF SURVEY LANG W. ANDERSON Wilmington, Delaware
Rehn, of Frankfort Germany (1), was the first to discover 3 cases of bladder tumors among 45 workmen engaged in the preparation of fuchsin and believed this condition was caused by a chronic irritation of the bladder mucosa due to the absorption of certain chemical compounds into the system for a period of many
137
that practically all cases could be detected by their method, they did admit, however, that the cystoscopic examination was undoubtedly safer. Apparently their only reason for not adopting this method is the fact that they feel the workmen would definitely object and it might cause serious labor difficulties within the plant. We are definitely of the opinion that should we rely upon the urine tests, many early tumors would be missed. Gross of Elberfeld and Simon of Ludwigshafen are decidedly opposed to biopsy of any bladder tumors and they emphatically state that it will lead to multiple implants and recurrences. They make their diagnosis mainly upon the appearance of the growth and in doubtful cases by observation after fulguration, claiming that all simple tumors respond favorably to fulguration, malignant tumors do not. SUMMARY
1. Bladder tumors occur more frequently among dye workers
than among non-dye workers and in our experience they occur to the extent of per cent. 2. The combined experiences of the dye industries of Germany, Switzerland, England and America, indicate that probably anilin, alpha and beta naphthylamine and benzidine are the etiological compounds. 3. Bladder tumors may appear any time after two years exposure and removal from the dye operation does not eliminate the possibility of future developments which may occur at any time. 4. The adoption of a completely closed and properly ventilated process, together with careful medical supervision and protection will eliminate the hazard, but these methods will require many years of active enforcement and must continue as long as the compounds are made.
PATHOLOGY OF ANILIN TUMORS OF THE BLADDER DOUGLAS M. GAY Wilmington, Delaware
The pathological anatomy of bladder tumors occurring in dye workers is not essentially different from that of the tumors of unknown origin.
138
SYMPOSIUM
The tumors are single or multiple, papillary or sessile, infiltrating or not infiltrating, ulcerating or not ulcerating, or there may be any combination or sequence of these characteristics. An analysis of 124 of the approximately 200 cases reported from various German sources (table 1) indicates that the incidence of carcinoma is about twice that of papilloma. The occurrence of non-epithelial neoplasms is very rare. As shown in table 2, papillomas are more frequently single and carcinomas are more TABLE 1 Diagnosis of 124 anilin tumors of the bladder (collected series f rom various German sources) Papilloma . ... . . . . . .. . . . .. . . . ... . . . . . .... .. ... . . . . . . . . ... .. .. . ....... . . .. . .. 41 Carcinoma.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 Papilloma and carcinoma. . . ... .... . .... . . . . . . .. . . . .. .. . . .. . . .... . . . . .. .. . .. 3 Papilloma and (later) carcinoma . . . . . . . . . .. .. .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Sarcoma. . ... .. ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Sarcoma and carcinoma.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
TABLE 2 Number and location of anilin tumors of bladder (collected series from vari ous German sources) PAPILLOMA
Number: Single .. . . .... . ....... . .. . . .... . ............ . . ..... . Multiple . . .. . . . . . . . .. . ... . . . . ... . . . .. _. ... . . . . . . . . . . Location: Trigone .. .. . .. . .... . .. . . . .. . ... .. . . . . . .. . . . .. . . ... . Elsewhere . ... . . . . . ... . .. . . ... . . . . . . . . .... . . . .. . . . . .
CARCINOMA
10 3
3
14 3
23
6
13
frequently multiple in the reported cases. Thirty-seven tumors were located on the trigone and 16 were found elsewhere in the bladder. In this series tumors elsewhere than on the trigone appeared to be more malignant than those situated at the bladder base. Simon (14) reporting a series of 85 cases claims a better outcome in the anilin group than in those bladder tumors of unknown etiology (table 3). This however is more apparent than real. The anilin patient is younger and a better surgical risk. Although the tumor may invade the tissues of the pelvic cavity,
139
ANILIN TUMORS OF BLADDER
metastases are extremely rare. There are many records of submucous hemorrhages, localized areas of hyperemia or cystitis which later developed tumors. Simon (15) believes that slight hyperemia is a precancerous lesion but this view is not held by Oppenheimer (4), although he admits that bladder irritation and tumor may be caused by the same injurious agent. Janssen (16) adds cystitis cystica and glandularis as precancerous lesions, stating that the transition from these conditions to mucous and glandular cancer has been demonstrated histologically many times. In the routine cystoscopic examination of the dye workers in our care numerous instances of local hyperemia, especially on the trigone, have been observed but there has been no opportunity TABLE 3 Per cent survival of patients with bladder tumors after three and five years Series of 85 cases reported by Simon
TUMORS
TUMORS OF UNKNOWN ETIOLOGY
per cent
per cent
ANILIN
Three-year survival. ................................ . Five-year survival.. ................................. .
54
21
48
10.5
for microscopic study. The suggestion is made that this is a more or less transitory capillary dilatation rather than hemorrhage, because the hyperemia has been observed to disappear and blood pigment is rarely present in the tumors microscopically examined. However, permanent telangiectases are often observed by cystoscope. Table 4 outlines the data on 17 of our series of anilin tumors of the bladder that have been examined microscopically. Seven were papillomas, grade I. The remaining 10 carcinomas were divided as follows: 4 papillary carcinomas, grade II; 1 carcinoma, grade III; 1 carcinoma, grade IV; 3 papilloma and carcinoma coexisting and 1 was diagnosed carcinoma but not graded. The multiple tumors were all carcinomas. Seven of the single tumors were papillomas and 3 were carcinomas. The tumors were pre-· ceded by no symptoms in 8 instances. THE JOURNAL OF UROLOGY, VOL. XXXI, NO.
2
TABLE 4 Anilin tumors of the bladder (Wilmington series)
~
H'>-
0 CASE NUM-
AGE
BER
YEARS IN DYE
FIRST
WORKS
SYMPTOMS
15
None None Hematuria; frequency None None None Hematuria Hematuria
------
TIME ELAP3ING BEFORE BIOPSY
GROSS PAPILLARY
Number
Location
MICROSCOPIC
Diagnosis
Grade
years
2 3 4
45 49 50
5 6 7 12 14
50 57 58 38 52
15
41
10
12 11
18 18 9 5 14
16
45
14
19
36
6
20 21
39 51
14 13
22 23
60 44
13
24 25
32 31
10 12
* Not graded.
15
Single 3 years
10 months 3½ years
' Single
Single
Single Single Single Multiple Multiple
Trigone Trigone Trigone
Papilloma Papilloma Papillary carcinoma
I I II
Trigone Trigone Trigone Trigone Trigone and anterior wall Lateral wall {
Papilloma Papilloma Papilloma Papillary carcinoma Papillary carcinoma
I I I II II
'ti
Right papilloma Left papillary carcinoma Anterior posterior and { Papilloma right wall Papillary carcinoma Posterior and right walls Carcinoma
I II I II III IV II
Single Single
Trigone Anterior, posterior and right walls Left wall Left wall
Single Single
Trigone Trigone
Multiple
Frequency; hematuria None
7 months
Burning on voiding Hematuria Burning; hematuria Hematuria Hematuria; burning None None
6 years
Multiple
4 months 13 months
Multiple Multiple
6 months 16 months
Multiple
~
Carcinoma Papillary carcinoma Carcinoma Papilloma invaded by carcinoma Papilloma Papilloma
*
I III I I
0
~
§
141
ANILIN TUMORS OF BLADDER
Case 22 is the one fatality of the series. The post-mortem examination showed a recto-vesical fistula and extensive pelvic cellulitis. There was no gross or microscopic evidence of tumor outside of the trigone. The following are presented as illustrative of the variety of structure of anilin tumors of the bladder as we have found them.
Fm.
1.
PAPILLOMA,
GRADE
I,
oF BLADDER.
ARRANGED IN ANASTOMOSING STRANDS
TRANSITIONAL EPITHELIUM
ON A DELICATE CONNECTIVE
TISSUE AND VASCULAR FRAMEWORK (CASE
3)
Case 3 with no history or symptoms suggesting bladder pathology was found on cystoscopic examination to have a small tumor on the trigone. The bladder mucosa was moderately congested. The biopsy (fig. 1) shows' a papilloma, grade I, composed of transitional epithelium arranged in anastomosing strands on a delicate connective tissue and vascular framework.
142
SYMPOSIUM
Case 2 was entirely free of bladder symptoms and examination by means of the cystoscope one year before showed no evidence of bladder pathology. The single neoplasm removed from the trigone is papillary in structure with lymphocytic infiltration of the stroma.
FIG. 2.
VASCULAR CHANGES AT BASE OF
p APILLOMA
OF BLADDER (CASE
5)
Case 7 presented a single papillary tumor, more compact in structure than the preceding, located on the trigone. The patient was symptomatically well. Case 6 likewise had no symptoms. The single papillary tumor removed from the trigone shows marked proliferation of the blood vessels. In case 5, presenting no symptoms, a single papillary tumor was
ANILIN TUMORS OF BLADDER
143
found just the right ureter. The submucosal blood ves~ sels are numerous, irregular, dilated, occasionally thrombosed and have the appearance of varices (fig. 2). The single papilloma, removed from above the right ureter of another patient, presenting no symptoms, shows a striking dilatation of some of the villi (fig. 3).
FIG. 3.
CYSTIC DILATATION OF
VILLI;
PAPILLOMA, GRADE
I,
OF BLADDER (CASE
25)
Case 14 is interest in that multiple tumors on the base and anterior wall of bladder were successfully treated transurethral electrocoagulation. After a three year period of freedom from further symptoms a papillary carcinoma, grade II, appeared above the right ureter. This and the numerous other instances of multiple bladder tumors sugge'3t that the fundamental pathol-
144
SYMPOSIUM
ogy is an affection of the entire viscus although the visible change may be local. Case 19 suffered from burning on voiding for six years before he sought medical aid and is unique because he has never has hematuria. Biopsy specimens removed at two and three month
FIG. 4.
CARCINOMA, GRADE III,
OF BLADDER.
SOLID MASSES OF IRREGULAR
TUMOR CELLS IN DISORDERLY ARRANGEMEN'"r (CASE
19)
intervals from the multiple lesions on the posterior and right lateral walls have consistently shown a grade III carcinoma characterized by solid masses of irregular epithelial cells in disorderly arrangement (fig. 4). Case 20 represents microscopically the most malignant tumor of the series and is designated as carcinoma, grade IV. The
ANILIN TUMORS OF BLADDER
145
patient sought relief from hematuria and was found to have multiple papillary infiltrating tumors around the bladder orifice. Microscopic examination shows a mass of irregular cells so rapidly growing that they are outrunning their blood supply. Well preserved cells are seen only near the blood vessels. The more distant cells are necrotic (fig. 5). Other portions of the same tumor are composed of a loose arrangement of slightly elongated cells suggesting sarcoma.
FIG. 5.
GRADE
IV,
OF BLADDER.
SOLID ;\fASSES OF RAPIDLY
GROWIKG Tm,IOR CELLS (CASE
20)
Transition from this type of cell to those which are epithelial can traced (fig. 6). The next 2 cases illustrate the simultaneous occurrence of tumors of different grades at different sites. Case 15, giving a history of urinary frequency as the first symptom, was treated expectantly until a massive hematuria occurred four months later. At that time papillary tumors were found on the lateral walls. The tumor from the right is composed
146
SYMPOSIUM
layers of fairly well differentiated transitional epithelium supported by a central core of fibroblasts and capillary blood vessels. The tumor from the left is also papillary and shows in addition, irregular large vesicular cells invading the stroma (fig. 7). Case 16 gave no history or symptoms referable to the bladder and was found normal by cystoscopic examination one year before. The tumor on the posterior wall is a typical papilloma,
Fm.
6.
CARCINOMA, GRADE IV, oF BLADDER.
FIGURE
5,
SAME TuMoR ILLUSTRATED IN
SHOWING VARIATION IN APPEARANCE (CASE
OF TUMOR CELLS
20)
while those on the anterior wall in the midline, and right lateral wall are distinctly more irregular in structure and show a few groups of tumor cells breaking through the base membrane, invading the stroma. Case 23 illustrates a papilloma invaded by a carcinoma. The material at hand was removed fifteen months after the initial symptom of hematuria and represents a single papillary tumor on the left wall of the bladder. The papillae, covered with
ANILIN TUMORS OF BLADDER
147
orderly transitional epithelium are invaded from the base by a carcinoma, grade IIL The photomicrograph (fig. 8) is of a villus in cross-section showing the central mass of irregular carcinoma cells in contrast to the more faintly staining superficial epithelium. A subsequent biopsy shows in addition the edematous character
FIG. 7. p APILLARY
CARCINOMA, GRADE
II,
OF BLADDER SLIGHTLY IRREGULAR
VESICULAR TUMOR CELLS BENEATH INTACT SURFACE EPITHELIUM (CASE
15)
of the villi. We point to this case in support of the theory that the primary epithelial change in bladder tumor occurs in the basal layer of the epithelium. Whether the injurious agent exerts its first effect on the submucous blood vessels or directly on the epithelium cannot be proved with the material at hand; but we do hold to the hypothe-
148
SYMPOSIUM
sis that anilin tumors are caused by an agent, to which the tissues of the bladder are specifically vulnerable. Although the greatest changes are in the region of the trigone, the multiplicity and subsequent origin of tumors in different sites leads us to believe that
FIG. 8.
CROSS-SECTION OF A VILLUS, PAPILLOMA, GRADE I, OF BLADDER INVADED BY A CARCINOMA, GRADE III (CASE
23)
the injury involves the entire bladder, probably due to the circulation of a cancerogenic agent in the blood.
INCIDENCE, SYMPTOMS AND SIGNS, RESULTS OF SURVEY LANG W. ANDERSON Wilmington, Delaware
Rehn, of Frankfort Germany (1), was the first to discover 3 cases of bladder tumors among 45 workmen engaged in the preparation of fuchsin and believed this condition was caused by a chronic irritation of the bladder mucosa due to the absorption of certain chemical compounds into the system for a period of many