- Email: [email protected]
Cutaneous metastases from prostatic carcinoma
CUTANEOUS
METASTASES
FROM PROSTATIC CARCINOMA NAEEM MICHAEL JOSEPH
PERVAIZ,
M.D.
J. FELLNER, E. DAVIS,
M.D.
M.D.
From the Departments of Urology and Dermatology, Medical College Flower and Fifth Avenue Hospitals, New York, New York
New York
ABSTRACT - A case of prostatic adenocarcinoma associated with extensive cutaneous metastases and malignant acanthosis nigricans is reported. Pertinent literature is reviewed. The pathogenesis of the possible mechanism of the development of cutaneous metastases in this as well as other related cases is discussed.
A sixty-five-year-old male was admitted to New York Medical College, Flower and Fifth Avenue Hospitals on November 28, 1972, in acute urinary retention. Digital examination of the rectum at that time revealed a relatively hard, non-nodular, right prostatic lobe. An excretory urogram and cystoscopy confirmed the diagnosis of enlarged, obstructing prostate gland and the patient underwent a transurethral prostatectomy on December 6, 1972. Microscopic examination of the resected prostatic tissue displayed infiltrating, poorly differentiated adenocarcinoma of the prostate gland. An extensive metastatic workup including a skeletal survey, bone scan, bone marrow biopsy, and liver scan was carried out and failed to reveal any evidence of metastatic disease. Bilateral pedal lymphangiogram, however, exhibited filling defects in paravesical and iliac lymph nodes consistent with replacement’ by extrinsic cell mass. A laparotomy and bilateral pelvic lymph node exploration was performed on December 27, 1972, to stage the disease process with the idea of proceeding with radical prostatectomy, if indicated. There was no evidence of any gross metastases to the liver or any other visceral organs at the time of but frozen section microscopy of surgery, pelvic lymph nodes revealed neoplastic foci consistent with metastatic adenocarcinoma. Having thus confirmed the diagnosis of Stage D
UROLOGY
/ APRIL 1978 / VOLUME
XI
NUMBER4
adenocarcinoma of prostate gland, the procedure was terminated. Postoperatively the patient was given a full course of radiotherapy consisting of 6,500 rads to the prostatic bed and pelvic lymph nodes and 5,450 rads to the periaortic nodes. It is noteworthy that the patient’s serum acid phosphatase level remained below 1.5 King-Armstrong units throughout his hospitalization. The patient was closely followed over the next three years and did fairly well on a regimen of oral stilbestrol (1 mg. per day) and mild analgesics for symptomatic relief of pain. The disease process during this period of time remained well under control as determined by yearly excretory urograms, skeletal surveys, and repeated estimation of serum acid phosphatase levels. In August, 1975, the patient was rehospitalized with the chief complaints of bone pain, suprapubic discomfort, and severe dysuria. He was also found to be in congestive heart failure thus necessitating discontinuation of estrogen therapy. A follow-up excretory urogram revealed moderate hydronephrosis on the right side due to partial ureterovesical junction obstruction as compared with the previous study. A lobulated, somewhat irregular mass projecting above the floor of the urinary bladder was also visualized and was thought to be due to the regrowth of prostatic tissue. A subsequent
403
FIGURE 1. Hyperpigmentation and (A) velvety appearance of penile skin exhibiting changes consistent with acanthosis nigricans. (B) Reddish brown nodular lesions with superficial ulcerations and encrustation illustrating cutaneous metastases from prostatic carcinoma. Note greater abundance of nodules in right inguinal region compared with left. (C) Closeregion. (D) up of metastasis in suprapubic of skin biopsy specimen Photomicrograph demonstrating adenocarcinoma of prostate in irregular deposits in dermis.
cystoscopic examination revealed complete fixation of prostatic urethra and vesical neck regions within rock-hard neoplastic tissue. The trigone exhibited diffuse nodularity and neither ureteric orifice could be recognized. The patient’s blood urea nitrogen and serum creatinine values were 24 mg. and 1.6 mg. per 100 ml., respectively, during this hospitalization, but skeletal survey and serum acid phosphatase levels were once again within normal limits. Bilateral orchiectomy was performed, and the patient was discharged only to be readmitted a week later with massive lymphedema of the entire right lower extremity. The left lower extremity and the penoscrotal regions were also involved in the process of lymphedema but to a lesser extent, the circumference of right thigh being 12 cm. greater than that of the left. Conservative measures, such as bed rest and elevation of right lower extremity, resulted in some improvement, and he was ambulatory at the time of his discharge from the hospital. Three months later in December, 1975, a striking observation was made when the patient presented with multiple, hard, nodular skin lesions in the lower part of the abdomen and both groins (Fig. 1). The skin in the penile region and both groins was noted to be dark and velvety in texture. This was subsequently diagnosed as malignant acanthosis nigricans by the consultant dermatologist. The cutaneous nodules were reddish brown in color, nontender, ranged from 0.5 to 2.5 cm. in diameter, and were more abundant in the right inguinal
404
region as compared with the left. Microscopic examination of two separate biopsy specimens from these cutaneous lesions revealed infiltrating, poorly differentiated adenocarcinoma, similar to that of the prostate gland as determined by its comparison to previously obtained sections of the prostatic tissue (Fig. 1D). The patient was placed on extensive cytotoxic therapy consisting of 5-fluorouracil, methotrexate, Oncovin, cyclophosphamide (Cytoxan), and prednisone in an effort to slow down the dissemination of neoplastic processes, but his condition continued to deteriorate. The patient was hospitalized again in June, 1976, when he presented with the signs and symptoms of distal colonic obstruction. His urine at this time was noted to be foul smelling and fecaloid. A barium enema study done under fluoroscopic control revealed a colovesical fistula. The entire rectosigmoid was extremely narrow and nodular. These findings were suggestive of diffuse carcinomatous infiltration of the pelvic viscera thus necessitating the performance of a transverse colostomy under local anesthesia on June 28, 1976. He was transferred to Calvary Hospital in the Bronx on July 13, 1976, for terminal care where he died five days later. No autopsy was performed. Comment Cutaneous malignancies
UROLOGY
lesions resulting are not common.
from internal In a series of
/ APRIL 1978 / VOLUME
XI
NUMBER
4
2,031 autopsies of patients with various types of carcinoma, Gates’ found cutaneous metastases in 58 cases; an incidence of 2.8 per cent. The recorded statistics of this occurrence in cases with documented internal organ involvement vary from 2.7 to 4.4 per cent. Carcinoma of the prostate gland rarely metastasizes to the skin. Gates’ noted only 1 case of prostatic carcinoma associated with cutaneous lesions in the series of autopsies he presented in 1937. Since then Ronchese,’ Barenghi,3 Huggins Arnheim,5 Comar,6 Bluefarb, Wallk, and Gecht,’ and Thivolet et aL8 have published histories of patients with cutaneous metastases resulting from carcinoma of the prostate, bringing the total number of cases reported in the literature to 15 over the last four decades. Brownstein and Helwig9 reported 5 cases of prostatic cancer in a study of 482 male patients with cutaneous metastases, an incidence of approximately 1 per cent. Recently, Razvi, Firfer, and Berkson’O reported a case of transitional cell carcinoma of the prostate gland which presented as rapidly growing cutaneous lesions on the nose and both sides of the anterior abdominal wall. These cutaneous metastases may sometimes resemble angiomas or may simulate “turban tumors” clinically, as described by Ronchese.’ Some of these lesions have been noted to have a zosteriform distribution following the course of the nerves.’ We believe that extensive radiotherapy resulted in fibrosis and eventually lymphatic obstruction in this case. The cutaneous metastases were noted three months after the development of the lymphedema in the penoscrotal region and both lower extremities. Moreover, the lesions were noted to be more abundant in the right inguinal region and the proximal part of the right thigh which happened to be the extremity most extensively involved in the process of lymphatic obstruction. These facts have led us to believe that the blockade of lymphatics might have played a significant role in the development of these cutaneous metastases, the lymphatic obstruction resulting in retrograde regurgitation of tumor emboli
UROLOGY
/
APRIL
1978
/
VOLUME
XI
NUMBER
4
along the cutaneous lymph channels with eventual deposition of neoplastic cells in the dermis. Another unusual but noteworthy feature of our patient was the association of the cancer with acanthosis nigricans. Malignant acanthosis nigricans is the classic example of a dermatosis causally related to an internal tumor. It is usually seen with gastrointestinal tumors of adenocarcinomatous character, mostly stomach (64 per cent), but has been reported to occur with prostatic cancer. After the two disorders are diagnosed, they run a parallel course, that is, they both increase in severity; or if the cancer is removed, the dermatosis may regress or temporarily disappear. It is recommended that if the diagnosis of malignant acanthosis nigricans has been established even without signs of a tumor in the patient, the search for a malignant tumor must be relentlessly undertaken l1 Fifth Avenue at 106 Street New York, New York 10029 (DR. DAVIS) References 1. Gates 0: Cutaneous metastases of malignant disease, Am. J. Cancer 30: 718 (1937). 2. Ronchese F: Metastases of the scalp simulating turban tumors, Arch. Dermat. Syph. 41: 639 (1946). 3. Barenghi I: Attulalita di Terapia Estrogenica, Lepetit, Nilan, Libreria Vulcania, 1946, cited by Comar.@ 4. Huggins C: Prostatic cancer treated by orchidectomy; 5 year results, J.A.M.A. 131: 576 (1946). 5. Amheim FK: Carcinoma of prostate: study of postmortem findings in 176 cases, J. Ural. 66: 599 (1948). 6. Comar OB: Metastasi cutanee de carcinoma prostatioo in adenomectomizzito, G. Ital. Chir. 11: 256 (1955). 7. Bluefarb SM. Wallk S. and Gecht M: Carcinoma of the prostate with zosteriform cutaneous lesions, Arch.. Dermatol. 76: 402 (1957). 8. Thivolet J, et al: Les metastases de la verge au tours du cancer prostatique. (A propos d’un cas de metastase isolee du gland.) Dermatologica (Basel) 130: 221 (1965). 9. Brownstein MH, and Helwig EB: Metastatic tumors of the skin, Cancer 29: 1298 (1972). 10. Razvi M, Firfer R, and Berkson B: Occult transitional cell carcinoma of the prostate presenting as skin metastases, J. Ural. 113: 734 (1975). 11. Curth HO: Cutaneous manifestations associated with malignant internal diseases, in Fitzpatrick TB, et al., Eds. : Dermatology in General Medicine, New York, McGraw Hill, Inc., 1971, pp. 1561-1564.
405
METASTASES
FROM PROSTATIC CARCINOMA NAEEM MICHAEL JOSEPH
PERVAIZ,
M.D.
J. FELLNER, E. DAVIS,
M.D.
M.D.
From the Departments of Urology and Dermatology, Medical College Flower and Fifth Avenue Hospitals, New York, New York
New York
ABSTRACT - A case of prostatic adenocarcinoma associated with extensive cutaneous metastases and malignant acanthosis nigricans is reported. Pertinent literature is reviewed. The pathogenesis of the possible mechanism of the development of cutaneous metastases in this as well as other related cases is discussed.
A sixty-five-year-old male was admitted to New York Medical College, Flower and Fifth Avenue Hospitals on November 28, 1972, in acute urinary retention. Digital examination of the rectum at that time revealed a relatively hard, non-nodular, right prostatic lobe. An excretory urogram and cystoscopy confirmed the diagnosis of enlarged, obstructing prostate gland and the patient underwent a transurethral prostatectomy on December 6, 1972. Microscopic examination of the resected prostatic tissue displayed infiltrating, poorly differentiated adenocarcinoma of the prostate gland. An extensive metastatic workup including a skeletal survey, bone scan, bone marrow biopsy, and liver scan was carried out and failed to reveal any evidence of metastatic disease. Bilateral pedal lymphangiogram, however, exhibited filling defects in paravesical and iliac lymph nodes consistent with replacement’ by extrinsic cell mass. A laparotomy and bilateral pelvic lymph node exploration was performed on December 27, 1972, to stage the disease process with the idea of proceeding with radical prostatectomy, if indicated. There was no evidence of any gross metastases to the liver or any other visceral organs at the time of but frozen section microscopy of surgery, pelvic lymph nodes revealed neoplastic foci consistent with metastatic adenocarcinoma. Having thus confirmed the diagnosis of Stage D
UROLOGY
/ APRIL 1978 / VOLUME
XI
NUMBER4
adenocarcinoma of prostate gland, the procedure was terminated. Postoperatively the patient was given a full course of radiotherapy consisting of 6,500 rads to the prostatic bed and pelvic lymph nodes and 5,450 rads to the periaortic nodes. It is noteworthy that the patient’s serum acid phosphatase level remained below 1.5 King-Armstrong units throughout his hospitalization. The patient was closely followed over the next three years and did fairly well on a regimen of oral stilbestrol (1 mg. per day) and mild analgesics for symptomatic relief of pain. The disease process during this period of time remained well under control as determined by yearly excretory urograms, skeletal surveys, and repeated estimation of serum acid phosphatase levels. In August, 1975, the patient was rehospitalized with the chief complaints of bone pain, suprapubic discomfort, and severe dysuria. He was also found to be in congestive heart failure thus necessitating discontinuation of estrogen therapy. A follow-up excretory urogram revealed moderate hydronephrosis on the right side due to partial ureterovesical junction obstruction as compared with the previous study. A lobulated, somewhat irregular mass projecting above the floor of the urinary bladder was also visualized and was thought to be due to the regrowth of prostatic tissue. A subsequent
403
FIGURE 1. Hyperpigmentation and (A) velvety appearance of penile skin exhibiting changes consistent with acanthosis nigricans. (B) Reddish brown nodular lesions with superficial ulcerations and encrustation illustrating cutaneous metastases from prostatic carcinoma. Note greater abundance of nodules in right inguinal region compared with left. (C) Closeregion. (D) up of metastasis in suprapubic of skin biopsy specimen Photomicrograph demonstrating adenocarcinoma of prostate in irregular deposits in dermis.
cystoscopic examination revealed complete fixation of prostatic urethra and vesical neck regions within rock-hard neoplastic tissue. The trigone exhibited diffuse nodularity and neither ureteric orifice could be recognized. The patient’s blood urea nitrogen and serum creatinine values were 24 mg. and 1.6 mg. per 100 ml., respectively, during this hospitalization, but skeletal survey and serum acid phosphatase levels were once again within normal limits. Bilateral orchiectomy was performed, and the patient was discharged only to be readmitted a week later with massive lymphedema of the entire right lower extremity. The left lower extremity and the penoscrotal regions were also involved in the process of lymphedema but to a lesser extent, the circumference of right thigh being 12 cm. greater than that of the left. Conservative measures, such as bed rest and elevation of right lower extremity, resulted in some improvement, and he was ambulatory at the time of his discharge from the hospital. Three months later in December, 1975, a striking observation was made when the patient presented with multiple, hard, nodular skin lesions in the lower part of the abdomen and both groins (Fig. 1). The skin in the penile region and both groins was noted to be dark and velvety in texture. This was subsequently diagnosed as malignant acanthosis nigricans by the consultant dermatologist. The cutaneous nodules were reddish brown in color, nontender, ranged from 0.5 to 2.5 cm. in diameter, and were more abundant in the right inguinal
404
region as compared with the left. Microscopic examination of two separate biopsy specimens from these cutaneous lesions revealed infiltrating, poorly differentiated adenocarcinoma, similar to that of the prostate gland as determined by its comparison to previously obtained sections of the prostatic tissue (Fig. 1D). The patient was placed on extensive cytotoxic therapy consisting of 5-fluorouracil, methotrexate, Oncovin, cyclophosphamide (Cytoxan), and prednisone in an effort to slow down the dissemination of neoplastic processes, but his condition continued to deteriorate. The patient was hospitalized again in June, 1976, when he presented with the signs and symptoms of distal colonic obstruction. His urine at this time was noted to be foul smelling and fecaloid. A barium enema study done under fluoroscopic control revealed a colovesical fistula. The entire rectosigmoid was extremely narrow and nodular. These findings were suggestive of diffuse carcinomatous infiltration of the pelvic viscera thus necessitating the performance of a transverse colostomy under local anesthesia on June 28, 1976. He was transferred to Calvary Hospital in the Bronx on July 13, 1976, for terminal care where he died five days later. No autopsy was performed. Comment Cutaneous malignancies
UROLOGY
lesions resulting are not common.
from internal In a series of
/ APRIL 1978 / VOLUME
XI
NUMBER
4
2,031 autopsies of patients with various types of carcinoma, Gates’ found cutaneous metastases in 58 cases; an incidence of 2.8 per cent. The recorded statistics of this occurrence in cases with documented internal organ involvement vary from 2.7 to 4.4 per cent. Carcinoma of the prostate gland rarely metastasizes to the skin. Gates’ noted only 1 case of prostatic carcinoma associated with cutaneous lesions in the series of autopsies he presented in 1937. Since then Ronchese,’ Barenghi,3 Huggins Arnheim,5 Comar,6 Bluefarb, Wallk, and Gecht,’ and Thivolet et aL8 have published histories of patients with cutaneous metastases resulting from carcinoma of the prostate, bringing the total number of cases reported in the literature to 15 over the last four decades. Brownstein and Helwig9 reported 5 cases of prostatic cancer in a study of 482 male patients with cutaneous metastases, an incidence of approximately 1 per cent. Recently, Razvi, Firfer, and Berkson’O reported a case of transitional cell carcinoma of the prostate gland which presented as rapidly growing cutaneous lesions on the nose and both sides of the anterior abdominal wall. These cutaneous metastases may sometimes resemble angiomas or may simulate “turban tumors” clinically, as described by Ronchese.’ Some of these lesions have been noted to have a zosteriform distribution following the course of the nerves.’ We believe that extensive radiotherapy resulted in fibrosis and eventually lymphatic obstruction in this case. The cutaneous metastases were noted three months after the development of the lymphedema in the penoscrotal region and both lower extremities. Moreover, the lesions were noted to be more abundant in the right inguinal region and the proximal part of the right thigh which happened to be the extremity most extensively involved in the process of lymphatic obstruction. These facts have led us to believe that the blockade of lymphatics might have played a significant role in the development of these cutaneous metastases, the lymphatic obstruction resulting in retrograde regurgitation of tumor emboli
UROLOGY
/
APRIL
1978
/
VOLUME
XI
NUMBER
4
along the cutaneous lymph channels with eventual deposition of neoplastic cells in the dermis. Another unusual but noteworthy feature of our patient was the association of the cancer with acanthosis nigricans. Malignant acanthosis nigricans is the classic example of a dermatosis causally related to an internal tumor. It is usually seen with gastrointestinal tumors of adenocarcinomatous character, mostly stomach (64 per cent), but has been reported to occur with prostatic cancer. After the two disorders are diagnosed, they run a parallel course, that is, they both increase in severity; or if the cancer is removed, the dermatosis may regress or temporarily disappear. It is recommended that if the diagnosis of malignant acanthosis nigricans has been established even without signs of a tumor in the patient, the search for a malignant tumor must be relentlessly undertaken l1 Fifth Avenue at 106 Street New York, New York 10029 (DR. DAVIS) References 1. Gates 0: Cutaneous metastases of malignant disease, Am. J. Cancer 30: 718 (1937). 2. Ronchese F: Metastases of the scalp simulating turban tumors, Arch. Dermat. Syph. 41: 639 (1946). 3. Barenghi I: Attulalita di Terapia Estrogenica, Lepetit, Nilan, Libreria Vulcania, 1946, cited by Comar.@ 4. Huggins C: Prostatic cancer treated by orchidectomy; 5 year results, J.A.M.A. 131: 576 (1946). 5. Amheim FK: Carcinoma of prostate: study of postmortem findings in 176 cases, J. Ural. 66: 599 (1948). 6. Comar OB: Metastasi cutanee de carcinoma prostatioo in adenomectomizzito, G. Ital. Chir. 11: 256 (1955). 7. Bluefarb SM. Wallk S. and Gecht M: Carcinoma of the prostate with zosteriform cutaneous lesions, Arch.. Dermatol. 76: 402 (1957). 8. Thivolet J, et al: Les metastases de la verge au tours du cancer prostatique. (A propos d’un cas de metastase isolee du gland.) Dermatologica (Basel) 130: 221 (1965). 9. Brownstein MH, and Helwig EB: Metastatic tumors of the skin, Cancer 29: 1298 (1972). 10. Razvi M, Firfer R, and Berkson B: Occult transitional cell carcinoma of the prostate presenting as skin metastases, J. Ural. 113: 734 (1975). 11. Curth HO: Cutaneous manifestations associated with malignant internal diseases, in Fitzpatrick TB, et al., Eds. : Dermatology in General Medicine, New York, McGraw Hill, Inc., 1971, pp. 1561-1564.
405