0022-534 7/79/1213-0303$02. 00/0 'j
Vol. 121, March Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright © 1979 by The Williams & Wilkins Co.
PROSTATIC ADENOCARCINOMA OF DUCTAL ORIGIN LAURENCE F. GREENE, GEORGE M. FARROW,* JOHN M. RAVITS
AND
FRED M. TOMERA
From the Mayo Clinic and Mayo Foundation, Rochester, Minnesota
ABSTRACT
Adenocarcinomas that arise from primary or secondary prostatic ducts have distinctive histopathologic features. The age of patients, symptoms, findings on digital rectal examination and determinations of serum acid and alkaline phosphatase are similar to those of patients with acinic carcinomas. Carcinomas of secondary ducts may be less responsive to endocrine manipulation and of greater malig-nancy than carcinomas of primary ducts. The course and survival of patients with ductal carcinomas treated conservatively are poor. Most adenocarcinomas of the prostate are of acinic origin and arise from peripheral tubular-alveolar secretory units within the posterior and posterolateral lobes. This is in contradistinction to adenocarcinomas of the breast, pancreas and salivary glands, which are mainly of ductal origin. Prostatic adenocarcinomas of ductal origin are rare and few reports of their histopathologic and clinical features are available. Nevertheless, such adenocarcinomas have distinctive histopathologic features that indicate their site of origin and should be recognized. In a previous report of adenocarcinomas of ductal origin from this institution 1 histologic sections of 4,286 consecutive adenocarcinomas of the prostate were studied. Approximately 94 per cent of the cases were the commonly encountered acinic adenocarcinomas, whereas purely ductal adenocarcinoma comprised approximately 1 per cent of the group. The remaining 5 per cent of the cases consisted of acinic adenocarcinomas with foci of ductal adenocarcinoma. Our previous report emphasized the histopathologic features of ductal adenocarcinomas. The purposes of this communication are to add data from 3 additional cases and to emphasize the clinical features of this malignant lesion. We also have attempted the difficult task of clinical staging of the disease retrospectively in relationship to survival of the patients. Included in the following data are 9 patients with adenocarcinoma of primary ducts and 49 patients with adenocarcinoma of secondary ducts. All patients in this series now qualify for 5-year survival statistics.
FIG. 1. Adenocarcinoma of primary prostatic ducts. Papillary neoplasm is within primary/rostatic ducts, directly beneath urethral mucosa. H & E, reduce from x80. Reprinted with permission of American Cancer Society. 1
HISTOPATHOLOGIC FINDINGS
Adenocarcinoma of primary prostatic ducts. These neoplasms were noted within large central periurethral prostatic duct spaces that were lined by a distinct basement membrane (fig. 1). Characteristically, the tumors exhibited papillary fronds supported by branching fibrous connective tissue cores and usually lined by a single layer of tall columnar epithelium. In some specimens invasion of the periductal stroma, prostatic tissue and secondary prostatic ducts was noted. Adenocarcinoma of secondary prostatic ducts. A typical feature of these neoplasms was multicentric involvement, characterized by areas in which the growth was confined within intermediate and small ducts. Small papillary projections were common and many of the lumina were filled with eosinophilic debris that imparted a comedo-like appearance (fig. 2). Invasion of prostatic tissue was noted in every specimen. Accepted for publication June 30, 1978. Read at annual meeting of American Urological Association, Washington, D. C., 21-25, 1978. * Requests for rP,rrn,ts· IVIayo Clinic, 200 First St. S. VI/.; Rochester, Minnesota 1
Fm. 2. Adenocarcinoma of secondary prostatic ducts. Epithelium forms small intraluminal projections. Note columnar cells with ample clear cytoplasm. H & E, reduced from x 100. CLINICAL FEATURES
304
GREENE AND ASSOCIATES
difference in average age, range of ages or distribution of ages between patients with carcinoma of primary ducts and those with carcinoma of secondary ducts. Likewise, the ages of patients in this study were similar to those of patients with acinic adenocarcinomas. Symptoms. Symptoms of urinary obstruction, hematuria, acute urinary retention and metastatic pain experienced by patients in this study were similar to those resulting from acinic adenocarcinomas. No significant difference was noted in frequency of symptoms between the patients with carcinoma of primary prostatic ducts and those with carcinoma of secondary prostatic ducts (table 2). Average duration of symptoms was 13 months in the former group and 27 months in the latter group. Findings on digital rectal examination. On digital rectal examination the prostate was suspected of being malignant in 50 patients and benign in the remaining 8 (table 3). Of interest is the fact that in 4 of the 9 patients with carcinoma of primary ducts the prostate was considered to be benign by this examination, whereas in only 4 of the 49 patients with carcinoma of secondary ducts the prostate was considered to be benign. Cystoscopic findings. Cystoscopic examination of patients with ductal carcinomas frequently demonstrated fixation and rigidity of the prostatic urethra, which commonly are noted with acinic adenocarcinomas; less frequently, carcinoma was not suspected by this examination. In 6 patients with carcinoma of primary ducts and in 3 patients with carcinoma of secondary ducts malignant-appearing polypoid or villous lesions were noted in the prostatic urethra. Acid and alkaline phosphatase determinations. Serum acid and alkaline phosphatase determinations tended to be increased if bony metastases were present and normal if such metastases could not be demonstrated (table 4). No significant difference in this pattern was noted between patients with carcinoma of primary ducts and those with carcinoma of secondary ducts.
sions the average survival was 59 months and 2 patients survived for 5 years. Thus, 3 of 9 patients in this group survived for 5 years or more after diagnosis. The average length of survival for patients with stage D lesions was 20 months; none of these patients survived for 5 years. Survival data in relationship to histologic grade, presence of metastasis and treatment are shown in table 6. Three of 5 patients with low grade (grade 1 or 2) lesions who were without metastasis at the time of diagnosis have survived for 5 years. One of these patients is the aforementioned patient who underwent radical retropubic prostatectomy and is well 67 months postoperatively. Patients with bony metastasis had lesions that were grade 2 or 3 and none survived for 5 years. Carcinoma of secondary ducts (49 patients). Each patient underwent transurethral prostatic resection. In addition, radical perineal prostatectomy, radical retropubic prostatectomy and suprapubic prostatectomy were done in 3 of these patients. Hormonal manipulation and radiation therapy also were used. Survival data in relationship to clinical staging and treatment are shown in table 7. The disease was stage C or D in most patients and only 14 of 49 patients survived for 5 years.
Carcinomas Malignancy Suspected Primary Ducts Yes: Localized Diffuse No TABLE
TABLE
1. Age distribution of patients Carcinomas
Age (yrs.) Primary Ducts 40-49 50-59 60-69 70-79 80-89 Av. yrs. (range)
Secondary Ducts
1 0 6 1 1 66.1 (41-80)
0
10 27 10 2 65.1 (50-81)
Secondary Ducts
1
9
4 4
36 4
4. Acid and alkaline phosphatase determinations Metastases Not Present
Values
TREATMENT AND RESULTS
Carcinoma of primary ducts (9 patients). Each patient underwent transurethral prostatic resection; in addition, retropubic prostatectomy was necessary in 1 patient. Hormonal manipulation, consisting of estrogen administration or orchiectomy or both, and radiation therapy also were used. Survival data in relationship to clinical staging and treatment are shown in table 5. One patient with a stage Bl lesion underwent radical retropubic prostatectomy and is well 67 months postoperatively. Among 5 patients with stage C le-
3. Findings on digital rectal examination
TABLE
Normal Increased Not measured
2
2
Alkaline Phosphatase 0
3 1
0
Carcinomas of secondary ducts 28 27 6
Normal Increased Not measured TABLE
Present
Acid PhosAlkaline Acid Phosphatase Phosphatase phatase Carcinomas ofprimary ducts 3 3 1 0 0 3
5
4
6
2 8
3
5
1
3
5. Carcinomas of primary ducts: survival data based on
clinical stage of disease Treatment
Clinical Stage
No. Pts.
A Bl B2 C D
0 1 0 5 3
Hormonal*
Survival
Radiation
4 3
Av. (mos.)
5-Yr.
67
1
59 20
2
3 2
* Orchiectomy or orally administered estrogen or both. TABLE
6. Carcinomas ofprimary ducts: survival data based on
histologic grade and metastasis TABLE
2. Symptoms Carcinomas
Obstruction Gross hematuria Acute retention Pain: Regional Metastatic bone Anorexia and weight loss Duration of symptoms: Av. mos. (range)
Survival
Treatment
Histologic Grade
No. Pts.
Primary Ducts
Secondary Ducts
7
43
1 2
3 1
9
3
6
4
2 3 0 0
1
6
1 0
5 2
1 2 3 4
0 2 2 0
12.7 (3-30)
26.8 (1 wk.-108)
Hormonal* Radiation Metastasis not present 1 2 2 1
Av. (mos.)
5-Yr.
84 59
2 1
33 6
0 0
Metastasis present 2 1
2 1
* Orchiectomy or orally administered estrogen or both.
DUCTAL PROSTATIC ADENOCARCINOMA TABLE
7. Carcinomas of secondary ducts: survival data based on clinical stage of disease Treatment
Clinical Stage
I.
r
Survival
No. Pts.
A
0 3 1 32 13
Bl B2
C D
Hormonal*
Radiation
Av. (mos.)
5-Yr.
2 1 30 13
0 1 13
36 84
5
31
0 1 11 2
57
* Orchiectomy or orally administered estrogen or both. TABLE
8. Carcinomas of secondary ducts: survival data based on histologic grade and metastasis Treatment
Histologic Grade
No. Pts.
1 2 3 4
1 17 14 4
1 2 3 4
0 2 9 2
Survival
Hormonal* Radiation Metastasis not present 14 13 4
Av. (mos.)
5-Yr.
180+ 61 66 30
1 8 4 0
18 34 17
0 1 0
8 4 1
Metastasis present 2 9 2
1 3 1
* Orchiectomy or orally administered estrogen or both.
Survival data in relationship to histologic grade, presence of metastasis and treatment are shown in table 8. Thirteen of 36 patients without metastasis survived for 5 years and 9 of these patients had low grade (grade 1 or 2) lesions. Patients with bony metastasis generally had grade 3 or 4 lesions and only 1 of 13 patients survived for 5 years.
DISCUSSION
The age, symptoms, findings on digital rectal examination and determinations of serum acid and alkaline phosphatase in patients with ductal adenocarcinomas are similar to those noted in patients with acinic adenocarcinomas. Metastases, when they occur, also are similar in both types of adenocarcinomas. The cystoscopic finding of malignant-appearing polypoid or villous lesions in the prostatic urethra may suggest the correct diagnosis. Ultimately, the diagnosis can be established only by the pathologist who is cognizant of the distinctive histopathologic features of this disease. It is difficult to elicit unchallengeable statistical data from this small group of patients. It seems unwise to compare data about results of treatment and survival for this small group with the voluminous data available for patients with acinic adenocarcinoma. 2 Nevertheless, certain impressions are gained from review of this small series of cases. The course and survival of patients with ductal carcinoma treated conservatively are discouraging and seem to be similar to those for patients with acinic adenocarcinoma treated in a similar manner. Carcinomas of secondary ducts, as a whole, may be less responsive to endocrine manipulation and of greater malignant potential than carcinomas of primary ducts. An awareness of this malignant lesion by the urologist and its recognition by the pathologist are necessary. Finally, earlier diagnosis and radical surgical treatment are the goals in management. REFERENCES
1. Dube, V. E., Farrow, G. M. and Greene, L. F.: Prostatic
adenocarcinoma of ductal origin. Cancer, 32: 402, 1973. 2. Varkarakis, M. J., Murphy, G. P., Nelson, C. M., Chehval, M., Moore, R. H. and Flocks, R. H.: Lymph node involvement in prostatic carcinoma. Urol. Clin. N. Amer., 2: 197, 1975.
Vol. 121, March Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright © 1979 by The Williams & Wilkins Co.
PROSTATIC ADENOCARCINOMA OF DUCTAL ORIGIN LAURENCE F. GREENE, GEORGE M. FARROW,* JOHN M. RAVITS
AND
FRED M. TOMERA
From the Mayo Clinic and Mayo Foundation, Rochester, Minnesota
ABSTRACT
Adenocarcinomas that arise from primary or secondary prostatic ducts have distinctive histopathologic features. The age of patients, symptoms, findings on digital rectal examination and determinations of serum acid and alkaline phosphatase are similar to those of patients with acinic carcinomas. Carcinomas of secondary ducts may be less responsive to endocrine manipulation and of greater malig-nancy than carcinomas of primary ducts. The course and survival of patients with ductal carcinomas treated conservatively are poor. Most adenocarcinomas of the prostate are of acinic origin and arise from peripheral tubular-alveolar secretory units within the posterior and posterolateral lobes. This is in contradistinction to adenocarcinomas of the breast, pancreas and salivary glands, which are mainly of ductal origin. Prostatic adenocarcinomas of ductal origin are rare and few reports of their histopathologic and clinical features are available. Nevertheless, such adenocarcinomas have distinctive histopathologic features that indicate their site of origin and should be recognized. In a previous report of adenocarcinomas of ductal origin from this institution 1 histologic sections of 4,286 consecutive adenocarcinomas of the prostate were studied. Approximately 94 per cent of the cases were the commonly encountered acinic adenocarcinomas, whereas purely ductal adenocarcinoma comprised approximately 1 per cent of the group. The remaining 5 per cent of the cases consisted of acinic adenocarcinomas with foci of ductal adenocarcinoma. Our previous report emphasized the histopathologic features of ductal adenocarcinomas. The purposes of this communication are to add data from 3 additional cases and to emphasize the clinical features of this malignant lesion. We also have attempted the difficult task of clinical staging of the disease retrospectively in relationship to survival of the patients. Included in the following data are 9 patients with adenocarcinoma of primary ducts and 49 patients with adenocarcinoma of secondary ducts. All patients in this series now qualify for 5-year survival statistics.
FIG. 1. Adenocarcinoma of primary prostatic ducts. Papillary neoplasm is within primary/rostatic ducts, directly beneath urethral mucosa. H & E, reduce from x80. Reprinted with permission of American Cancer Society. 1
HISTOPATHOLOGIC FINDINGS
Adenocarcinoma of primary prostatic ducts. These neoplasms were noted within large central periurethral prostatic duct spaces that were lined by a distinct basement membrane (fig. 1). Characteristically, the tumors exhibited papillary fronds supported by branching fibrous connective tissue cores and usually lined by a single layer of tall columnar epithelium. In some specimens invasion of the periductal stroma, prostatic tissue and secondary prostatic ducts was noted. Adenocarcinoma of secondary prostatic ducts. A typical feature of these neoplasms was multicentric involvement, characterized by areas in which the growth was confined within intermediate and small ducts. Small papillary projections were common and many of the lumina were filled with eosinophilic debris that imparted a comedo-like appearance (fig. 2). Invasion of prostatic tissue was noted in every specimen. Accepted for publication June 30, 1978. Read at annual meeting of American Urological Association, Washington, D. C., 21-25, 1978. * Requests for rP,rrn,ts· IVIayo Clinic, 200 First St. S. VI/.; Rochester, Minnesota 1
Fm. 2. Adenocarcinoma of secondary prostatic ducts. Epithelium forms small intraluminal projections. Note columnar cells with ample clear cytoplasm. H & E, reduced from x 100. CLINICAL FEATURES
304
GREENE AND ASSOCIATES
difference in average age, range of ages or distribution of ages between patients with carcinoma of primary ducts and those with carcinoma of secondary ducts. Likewise, the ages of patients in this study were similar to those of patients with acinic adenocarcinomas. Symptoms. Symptoms of urinary obstruction, hematuria, acute urinary retention and metastatic pain experienced by patients in this study were similar to those resulting from acinic adenocarcinomas. No significant difference was noted in frequency of symptoms between the patients with carcinoma of primary prostatic ducts and those with carcinoma of secondary prostatic ducts (table 2). Average duration of symptoms was 13 months in the former group and 27 months in the latter group. Findings on digital rectal examination. On digital rectal examination the prostate was suspected of being malignant in 50 patients and benign in the remaining 8 (table 3). Of interest is the fact that in 4 of the 9 patients with carcinoma of primary ducts the prostate was considered to be benign by this examination, whereas in only 4 of the 49 patients with carcinoma of secondary ducts the prostate was considered to be benign. Cystoscopic findings. Cystoscopic examination of patients with ductal carcinomas frequently demonstrated fixation and rigidity of the prostatic urethra, which commonly are noted with acinic adenocarcinomas; less frequently, carcinoma was not suspected by this examination. In 6 patients with carcinoma of primary ducts and in 3 patients with carcinoma of secondary ducts malignant-appearing polypoid or villous lesions were noted in the prostatic urethra. Acid and alkaline phosphatase determinations. Serum acid and alkaline phosphatase determinations tended to be increased if bony metastases were present and normal if such metastases could not be demonstrated (table 4). No significant difference in this pattern was noted between patients with carcinoma of primary ducts and those with carcinoma of secondary ducts.
sions the average survival was 59 months and 2 patients survived for 5 years. Thus, 3 of 9 patients in this group survived for 5 years or more after diagnosis. The average length of survival for patients with stage D lesions was 20 months; none of these patients survived for 5 years. Survival data in relationship to histologic grade, presence of metastasis and treatment are shown in table 6. Three of 5 patients with low grade (grade 1 or 2) lesions who were without metastasis at the time of diagnosis have survived for 5 years. One of these patients is the aforementioned patient who underwent radical retropubic prostatectomy and is well 67 months postoperatively. Patients with bony metastasis had lesions that were grade 2 or 3 and none survived for 5 years. Carcinoma of secondary ducts (49 patients). Each patient underwent transurethral prostatic resection. In addition, radical perineal prostatectomy, radical retropubic prostatectomy and suprapubic prostatectomy were done in 3 of these patients. Hormonal manipulation and radiation therapy also were used. Survival data in relationship to clinical staging and treatment are shown in table 7. The disease was stage C or D in most patients and only 14 of 49 patients survived for 5 years.
Carcinomas Malignancy Suspected Primary Ducts Yes: Localized Diffuse No TABLE
TABLE
1. Age distribution of patients Carcinomas
Age (yrs.) Primary Ducts 40-49 50-59 60-69 70-79 80-89 Av. yrs. (range)
Secondary Ducts
1 0 6 1 1 66.1 (41-80)
0
10 27 10 2 65.1 (50-81)
Secondary Ducts
1
9
4 4
36 4
4. Acid and alkaline phosphatase determinations Metastases Not Present
Values
TREATMENT AND RESULTS
Carcinoma of primary ducts (9 patients). Each patient underwent transurethral prostatic resection; in addition, retropubic prostatectomy was necessary in 1 patient. Hormonal manipulation, consisting of estrogen administration or orchiectomy or both, and radiation therapy also were used. Survival data in relationship to clinical staging and treatment are shown in table 5. One patient with a stage Bl lesion underwent radical retropubic prostatectomy and is well 67 months postoperatively. Among 5 patients with stage C le-
3. Findings on digital rectal examination
TABLE
Normal Increased Not measured
2
2
Alkaline Phosphatase 0
3 1
0
Carcinomas of secondary ducts 28 27 6
Normal Increased Not measured TABLE
Present
Acid PhosAlkaline Acid Phosphatase Phosphatase phatase Carcinomas ofprimary ducts 3 3 1 0 0 3
5
4
6
2 8
3
5
1
3
5. Carcinomas of primary ducts: survival data based on
clinical stage of disease Treatment
Clinical Stage
No. Pts.
A Bl B2 C D
0 1 0 5 3
Hormonal*
Survival
Radiation
4 3
Av. (mos.)
5-Yr.
67
1
59 20
2
3 2
* Orchiectomy or orally administered estrogen or both. TABLE
6. Carcinomas ofprimary ducts: survival data based on
histologic grade and metastasis TABLE
2. Symptoms Carcinomas
Obstruction Gross hematuria Acute retention Pain: Regional Metastatic bone Anorexia and weight loss Duration of symptoms: Av. mos. (range)
Survival
Treatment
Histologic Grade
No. Pts.
Primary Ducts
Secondary Ducts
7
43
1 2
3 1
9
3
6
4
2 3 0 0
1
6
1 0
5 2
1 2 3 4
0 2 2 0
12.7 (3-30)
26.8 (1 wk.-108)
Hormonal* Radiation Metastasis not present 1 2 2 1
Av. (mos.)
5-Yr.
84 59
2 1
33 6
0 0
Metastasis present 2 1
2 1
* Orchiectomy or orally administered estrogen or both.
DUCTAL PROSTATIC ADENOCARCINOMA TABLE
7. Carcinomas of secondary ducts: survival data based on clinical stage of disease Treatment
Clinical Stage
I.
r
Survival
No. Pts.
A
0 3 1 32 13
Bl B2
C D
Hormonal*
Radiation
Av. (mos.)
5-Yr.
2 1 30 13
0 1 13
36 84
5
31
0 1 11 2
57
* Orchiectomy or orally administered estrogen or both. TABLE
8. Carcinomas of secondary ducts: survival data based on histologic grade and metastasis Treatment
Histologic Grade
No. Pts.
1 2 3 4
1 17 14 4
1 2 3 4
0 2 9 2
Survival
Hormonal* Radiation Metastasis not present 14 13 4
Av. (mos.)
5-Yr.
180+ 61 66 30
1 8 4 0
18 34 17
0 1 0
8 4 1
Metastasis present 2 9 2
1 3 1
* Orchiectomy or orally administered estrogen or both.
Survival data in relationship to histologic grade, presence of metastasis and treatment are shown in table 8. Thirteen of 36 patients without metastasis survived for 5 years and 9 of these patients had low grade (grade 1 or 2) lesions. Patients with bony metastasis generally had grade 3 or 4 lesions and only 1 of 13 patients survived for 5 years.
DISCUSSION
The age, symptoms, findings on digital rectal examination and determinations of serum acid and alkaline phosphatase in patients with ductal adenocarcinomas are similar to those noted in patients with acinic adenocarcinomas. Metastases, when they occur, also are similar in both types of adenocarcinomas. The cystoscopic finding of malignant-appearing polypoid or villous lesions in the prostatic urethra may suggest the correct diagnosis. Ultimately, the diagnosis can be established only by the pathologist who is cognizant of the distinctive histopathologic features of this disease. It is difficult to elicit unchallengeable statistical data from this small group of patients. It seems unwise to compare data about results of treatment and survival for this small group with the voluminous data available for patients with acinic adenocarcinoma. 2 Nevertheless, certain impressions are gained from review of this small series of cases. The course and survival of patients with ductal carcinoma treated conservatively are discouraging and seem to be similar to those for patients with acinic adenocarcinoma treated in a similar manner. Carcinomas of secondary ducts, as a whole, may be less responsive to endocrine manipulation and of greater malignant potential than carcinomas of primary ducts. An awareness of this malignant lesion by the urologist and its recognition by the pathologist are necessary. Finally, earlier diagnosis and radical surgical treatment are the goals in management. REFERENCES
1. Dube, V. E., Farrow, G. M. and Greene, L. F.: Prostatic
adenocarcinoma of ductal origin. Cancer, 32: 402, 1973. 2. Varkarakis, M. J., Murphy, G. P., Nelson, C. M., Chehval, M., Moore, R. H. and Flocks, R. H.: Lymph node involvement in prostatic carcinoma. Urol. Clin. N. Amer., 2: 197, 1975.
