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Malignant Hemangio-Endothelioma of the Urethra: A Case Report
THE JOURNAL OF UROLOGY
Vol. 73, No. 4, April 1955 Printed in U.S.A.
MALIGNANT HEMANGIO-ENDOTHELIOMA OF THE URETHRA: A CASE REPORT DEAN C. VARNEY Frain the Cleveland Veterans Hospital, Cleveland, Ohio
Primary malignant tumors of the urethra are rare. Except for a few sarcomas, the majority of reported cases have been squamous cell and transitional cell carcinomas. However, Rolnick, in 1940, collected from the literature a group of 50 cases of sarcoma of the penis in which were included 12 instances of malignant endothelioma. In 1946, Coppridge et al. reviewed these latter cases of malignant endothelioma and presented an additional one of their own. The recent report of Cornwall and Whitaker in 1953 brings the known recorded total to 14. In all of these cases the tumor originated in the corpora and invaded the urethra only secondarily. This paper describes the first known case of malignant endothelioma presenting as a tumor of the urethra. A discussion of the classification and histopathology of this rare neoplasm is presented. CASE REPORT
A 54 year old white man was admitted on November 26, 1953 with a 3 day history of painless hematuria. He denied any past history of urethral stricture, infection or instrumentation. Physical examination revealed a tender, firm nodule, I cm. in diameter, in the floor of the anterior urethra approximately 6 cm. proximal to the urethral meatus. The admission urine exhibited microscopic hematuria. Otherwise the routine hematologic studies and x-rays were normal. An initial urethrogram revealed a nonopaque filling defect in the anterior urethra (fig. 1). On December 1, 1953, urethroscopy disclosed a hemorrhagic, cystic tumor arising from the anterior urethral floor. This was excised with the resectoscope loop and its base fulgurated. The pathologist's report was simple capillary hemangioma. The patient experienced an uncomplicated postoperative course and was discharged from the hospital on December 4, 1953. He returned on February 1, 1954 complaining of intermittent urethral bleeding of 3 weeks' duration and an aching discomfort in the left hip. Examination revealed a discrete, tender nodule, 0.5 cm. in diameter, at the approximate site of the original tumor. Cystoscopy was performed on February 5, 1954 and a discrete nodule was observed arising from the right wall of the anterior urethra approximately 6 cm. proximal to the external urethral meatus. This was resected and the base thoroughly fulgurated. M.icroscopic examination of the surgical specimen showed irregular spaces lined by relatively large, irregular, polygonal to umbrella-shaped cells which possessed a moderate amount of amphoteric cytoplasm, moderately distinct Accepted for publication October 15, 1954. 691
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DEAN C. VARNEY
Fm. 1. Urethrogram showing filling defect in distal portion of the anterior urethra.
,cytoplasmic borders and large vesicular to hyperchromatic basophilic nuclei. A few round eosinophilic nucleoli were seen. No mitotic figures were noted. Many ·Of the spaces contained erythrocytes. The ramifying and interlacing septae between these spaces consisted of fibroblasts and smooth muscle cells. Comparison with the first biopsy specimen was made and the original tumor was noted to possess septae of uniform thickness and only a suggestion of papilliform processes. The second biopsy showed more pleomorphism of the living cells, and within some ·of the septae there were sheets and masses of the lining cells (fig. 2). The pathological diagnosis was hemangioendotheliosarcoma of the urethra (Dr. ·William Morningstar). At this point radical amputation of the penis was considered. As the patient ,continued to complain of pain in the region of the left hip, making walking uncomfortable, a film of the pelvis was obtained on March 9, 1954. A circular area ·of destruction was noted involving the superior ramus of the left ischium and invading the hip joint (fig. 3, A). A previous film of the pelvis made at the time ·Of the original admission had been interpreted as being negative (fig. 3, B). Biopsy of the bony lesion was performed on March 15, 1954. The cortex of the ischium was destroyed over its posterior surface and there was invasion of the soft tissues adjacent to this area. Microscopic sections revealed similar structures and cells as noted in the urethral biopsies. In the bone there was a moderate desmoplastic reaction and osseous proliferation about the periphery of the tumor mass. Also, the solid collections of tumor cells were larger, with a degree of pleomorphism comparable to the second urethral biopsy (fig. 4). A skeletal survey was negative for other metastatic foci. The patient was started on irradiation therapy to the left ischium on March 22, 1954. A total tumor dose of 3500 r was given, interrupted only by the discovery and drainage -of a left gluteal abscess on April 15, 1954. On September 1, 1954 the patient was walking and free of pain. He had no uri-
Fm. 2. A, photomicrograph of removed tumor displaying numerous well-defined vascular spaces surrounded by an anaplastic stroma. B, selected focus in same specimen depicting anastomosing capillaries lined by swollen endothelial cells.
Fm. 3. A, plain film of the pelvis exhibiting an osteolytic lesion destroying superior ramus of left ischium. B, admission film of pelvis which was interpreted as normal.
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DEAN C. VARNEY
Fm. 4. Photomicrograph of biopsy taken from left ischium showing a marked similarity to figure 2, A.
nary symptoms, and the penis was grossly normal. U rethroscopy repeated on two occasions revealed no evidence of recurrent urethral tumor. Cysto-urethroscopy on January 4, 1955 disclosed a normal urethra. X-ray films of the area of metastasis exhibited definite sclerosis. A skeletal survey was negative and the patient asymptomatic. DISCUSSION
The general state of confusion that exists today in regard to the descriptive terminology and pathological classification of malignant tumors of blood vessel origin is quite remarkable. The only agreement appears to be one of disagreement. There are a few authorities that doubt the origin of malignant tumors from endothelium. However, gradually a body of knowledge has been accumulated that lends itself to classification. Stout has pioneered in the microscopic study and pathological grouping of the angiosarcomas and has proposed the following classification: 1) Malignant hemangio-endothelioma (synonyms: angiofibrosarcoma; hemangioblastoma; hemangio-endothelioblastoma; hemangio-endotheliosarcoma). This tumor apparently arises from vascular endothelium and is characterized microscopically by congeries of atypical capillaries ,vith a marked tendency to frequent anastomosis, and lined by swollen, anaplastic endothelioblasts that partially fill the lumens. In addition, the tumor cells are confined within a delicate reticulin sheath surrounding each vessel which serves to distingiush it from that group referred to as2) Malignant hemangiopericytoma (synomyms: angiosarcoma; hemangio-endothelioma; hemangiopericytic sarcoma; perithelial ang10sarcoma; penthelioma). In this tumor the blood vessels are lined by normal endothelium and the tumor cells are clustered outside of but closely applied to the reticulin sheath. The
MALIGNANT TUMOR OF URETHRA
695
dominant cell is the pericyte and is readily observed in its benign form, the glomus tumor. 3) Kaposi's sarcoma (synonyms: angiosarcoma multiplex; multiple idiopathic hemorrhagic sarcoma; sarcoma cutaneum telangiectaticum multiplex, etc.). The microscopic picture is one of interlacing groups of capillaries associated with growth of spindle-shaped cells and connective tissue fibers suggestive of fibrosarcoma. 4) Lymphangiosarcoma. This is a malignant tumor thought to arise from lymphatic endothelium. Of prime concern to the urologist is the malignant hemangio-endothelioma which, in Stout's opinion, embraces those malignant endotheliomas arising from the vascular endothelium within the corpora cavernosa and heretofore reported as presenting as a penile tumor. The tumor in our case, as can best be determined, arose from blood vessel endothelium in the corpora spongiosum and grew into the penile urethra with resultant ulceration and hematuria. It qualifies as a hemangio-endotheliosarcoma or under the classification proposed by Stout, a malignant hemangio-endothelioma. To the best of our knowledge it represents the first such tumor presenting in the urethra. Kaposi's sarcoma has been described originating on the glans penis and must be considered in the differential diagnosis of hemangiosarcomas of the penis. Benign angiomas of the glans penis and anterior urethra have been reported. However, in none of these cases did progression to a malignant state occur. This factor brings up several interesting points concerning the pathogenesis of malignant hemangio-endotheliomas. The first concerns the hypothesis of trauma and secondary production of granulation tissue with its rich capillary network and subsequent progression and development of a malignant hemangio-endothelioma. This has given rise to the term, granulation tissue sarcoma. It is very possible that our case can be explained on this basis as it was first considered a simple capillary hemangioma and following electrofulguration developed malignant changes with progression to hemangiosarcoma. :McCarthy and Pack, reporting on a series of 20 cases of angiosarcoma occurring in various sites, included three instances of angiosarcoma developing from benign angioma previously controlled by irradiation therapy with apparent cure, in l case, extending as long as 15 years. Secondly, we are concerned with the proposed entity of benign metastasizing hemangioma in which the original tumor is a benign hemangioma with subsequent appearance in distant areas as hemangioma or malignant hemangio-endothelioma. A number of such cases have been reported and, in one or two instances, apparently confirmed. However, the majority are thought to be originally malignant and the entity, as such, is rather dubious. Microscopically, angiosarcoma may be confused with chorio-epithelioma and the metastatic lesions of clear cell carcinoma with the latter tumor, perhaps, accounting for a certain number of erroneously diagnosed cases of angiosarcoma of bone. The proper therapy in these cases is based upon the location and gross extent
696
DEAN C. VARNEY
of the tumor. Metastases usually occur via the blood stream. However, lymphatic spread is not uncommon and, although relatively slow, may on occasion be extremely rapid, as demonstrated by our case in which marked metastatic destruction of bone occurred 3 months following previously negative radiographic findings. The treatment of choice is therefore radical excision or amputation with irradiation and radium therapy reserved for advanced or inoperable cases. The reported average survival period of malignant hemangio-endothelioma varies from 1 to 2,l,f years, compared to 8 years for Kaposi's sarcoma. SUMMARY AND CONCLUSIONS
A case of malignant hemangio-endothelioma, apparently ansmg from the corpus spongiosum, but presenting as and exhibiting the clinical characteristics of a urethral tumor, is described as the first of its type recorded. The pathological classification and micrm:copic description of that group of malignant tumors of blood and lymph vessel origin, termed the ang10sarcomas, are presented.
626 E. Santa Clara St., San Jose 12, Calif. REFERENCES CoPPRIDGE, W.W., PUTMAN, G. H. AND MrALE, J.B.: Endothelioma of the penis. J. Urol., 56: 112-117, 1946. CORNWALL, W. D. AND WHITAKER, L.: Endothelioma of the penis: A case report. J. Urol., 69: 307-308, 1953. FouLDS, G. S. AND FLETT, R.H.: Endothelioma of the corpora cavernosa. J. Urol., 40: 826-835, 1938. GRAVES, R. C. AND Gurss, L. W.: Tumors of the urethra. J. Urol., 46: 925-947, 1941. LANE, J. W.: Hemangioma of the glans penis. U.S. Armed Forces Med. J., 4: 139-140, 1953. McCARTHY, W. D. AND PACK, G. T.: Malignant blood vessel tumors. Surg., Gynec. & Obst., 91: 465-482, 1950. McCREA, L. E.: Angioma of the male urethra. Urol. & Cutan. Rev., 52: 204, 1948. lVIoRTENSEN' HENRY AND MURPHY, LEONARD: Angiomatous malformations of the glans penis. J. Urol., 64: 396--399, 1950. PEACHMAN, C. K.: Angioma of the glans penis. J. Urol., 57: 884-887, 1947. PHILLIPS, C.H. AND DouGLAS, M. D.: Tumors of the urethra. Am. J. Obst. & Gynec., 27: 99-104, 1934. RABSON, M. S.: Angioma of corpus cavernosum penis. J. Urol., 45: 111-117, 1941. ROBINSON, J. M. AND CASTLEMAN, B.: Benign metastasizing hemangioma. Ann. Surg., 104: 436-445, 1936. RoLNICK, H. C.: The Practice of Urology. Philadelphia: J. B. Lippincott Co., 1949, vol. 1, p. 205. STOUT, A. P.: Hemangio-endothelioma: A tumor of blood vessels featuring vascular endothelial cells. Ann. Surg., 118: 445-464, 1943. STOUT, A. P.: Tumors of the Soft Tissues, Atlas of Tumor Pathology. Washington, D. C., Armed Forces Inst. Path., Sec. II, fascicle 5: 99-103, 1953.
Vol. 73, No. 4, April 1955 Printed in U.S.A.
MALIGNANT HEMANGIO-ENDOTHELIOMA OF THE URETHRA: A CASE REPORT DEAN C. VARNEY Frain the Cleveland Veterans Hospital, Cleveland, Ohio
Primary malignant tumors of the urethra are rare. Except for a few sarcomas, the majority of reported cases have been squamous cell and transitional cell carcinomas. However, Rolnick, in 1940, collected from the literature a group of 50 cases of sarcoma of the penis in which were included 12 instances of malignant endothelioma. In 1946, Coppridge et al. reviewed these latter cases of malignant endothelioma and presented an additional one of their own. The recent report of Cornwall and Whitaker in 1953 brings the known recorded total to 14. In all of these cases the tumor originated in the corpora and invaded the urethra only secondarily. This paper describes the first known case of malignant endothelioma presenting as a tumor of the urethra. A discussion of the classification and histopathology of this rare neoplasm is presented. CASE REPORT
A 54 year old white man was admitted on November 26, 1953 with a 3 day history of painless hematuria. He denied any past history of urethral stricture, infection or instrumentation. Physical examination revealed a tender, firm nodule, I cm. in diameter, in the floor of the anterior urethra approximately 6 cm. proximal to the urethral meatus. The admission urine exhibited microscopic hematuria. Otherwise the routine hematologic studies and x-rays were normal. An initial urethrogram revealed a nonopaque filling defect in the anterior urethra (fig. 1). On December 1, 1953, urethroscopy disclosed a hemorrhagic, cystic tumor arising from the anterior urethral floor. This was excised with the resectoscope loop and its base fulgurated. The pathologist's report was simple capillary hemangioma. The patient experienced an uncomplicated postoperative course and was discharged from the hospital on December 4, 1953. He returned on February 1, 1954 complaining of intermittent urethral bleeding of 3 weeks' duration and an aching discomfort in the left hip. Examination revealed a discrete, tender nodule, 0.5 cm. in diameter, at the approximate site of the original tumor. Cystoscopy was performed on February 5, 1954 and a discrete nodule was observed arising from the right wall of the anterior urethra approximately 6 cm. proximal to the external urethral meatus. This was resected and the base thoroughly fulgurated. M.icroscopic examination of the surgical specimen showed irregular spaces lined by relatively large, irregular, polygonal to umbrella-shaped cells which possessed a moderate amount of amphoteric cytoplasm, moderately distinct Accepted for publication October 15, 1954. 691
t692
DEAN C. VARNEY
Fm. 1. Urethrogram showing filling defect in distal portion of the anterior urethra.
,cytoplasmic borders and large vesicular to hyperchromatic basophilic nuclei. A few round eosinophilic nucleoli were seen. No mitotic figures were noted. Many ·Of the spaces contained erythrocytes. The ramifying and interlacing septae between these spaces consisted of fibroblasts and smooth muscle cells. Comparison with the first biopsy specimen was made and the original tumor was noted to possess septae of uniform thickness and only a suggestion of papilliform processes. The second biopsy showed more pleomorphism of the living cells, and within some ·of the septae there were sheets and masses of the lining cells (fig. 2). The pathological diagnosis was hemangioendotheliosarcoma of the urethra (Dr. ·William Morningstar). At this point radical amputation of the penis was considered. As the patient ,continued to complain of pain in the region of the left hip, making walking uncomfortable, a film of the pelvis was obtained on March 9, 1954. A circular area ·of destruction was noted involving the superior ramus of the left ischium and invading the hip joint (fig. 3, A). A previous film of the pelvis made at the time ·Of the original admission had been interpreted as being negative (fig. 3, B). Biopsy of the bony lesion was performed on March 15, 1954. The cortex of the ischium was destroyed over its posterior surface and there was invasion of the soft tissues adjacent to this area. Microscopic sections revealed similar structures and cells as noted in the urethral biopsies. In the bone there was a moderate desmoplastic reaction and osseous proliferation about the periphery of the tumor mass. Also, the solid collections of tumor cells were larger, with a degree of pleomorphism comparable to the second urethral biopsy (fig. 4). A skeletal survey was negative for other metastatic foci. The patient was started on irradiation therapy to the left ischium on March 22, 1954. A total tumor dose of 3500 r was given, interrupted only by the discovery and drainage -of a left gluteal abscess on April 15, 1954. On September 1, 1954 the patient was walking and free of pain. He had no uri-
Fm. 2. A, photomicrograph of removed tumor displaying numerous well-defined vascular spaces surrounded by an anaplastic stroma. B, selected focus in same specimen depicting anastomosing capillaries lined by swollen endothelial cells.
Fm. 3. A, plain film of the pelvis exhibiting an osteolytic lesion destroying superior ramus of left ischium. B, admission film of pelvis which was interpreted as normal.
693
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DEAN C. VARNEY
Fm. 4. Photomicrograph of biopsy taken from left ischium showing a marked similarity to figure 2, A.
nary symptoms, and the penis was grossly normal. U rethroscopy repeated on two occasions revealed no evidence of recurrent urethral tumor. Cysto-urethroscopy on January 4, 1955 disclosed a normal urethra. X-ray films of the area of metastasis exhibited definite sclerosis. A skeletal survey was negative and the patient asymptomatic. DISCUSSION
The general state of confusion that exists today in regard to the descriptive terminology and pathological classification of malignant tumors of blood vessel origin is quite remarkable. The only agreement appears to be one of disagreement. There are a few authorities that doubt the origin of malignant tumors from endothelium. However, gradually a body of knowledge has been accumulated that lends itself to classification. Stout has pioneered in the microscopic study and pathological grouping of the angiosarcomas and has proposed the following classification: 1) Malignant hemangio-endothelioma (synonyms: angiofibrosarcoma; hemangioblastoma; hemangio-endothelioblastoma; hemangio-endotheliosarcoma). This tumor apparently arises from vascular endothelium and is characterized microscopically by congeries of atypical capillaries ,vith a marked tendency to frequent anastomosis, and lined by swollen, anaplastic endothelioblasts that partially fill the lumens. In addition, the tumor cells are confined within a delicate reticulin sheath surrounding each vessel which serves to distingiush it from that group referred to as2) Malignant hemangiopericytoma (synomyms: angiosarcoma; hemangio-endothelioma; hemangiopericytic sarcoma; perithelial ang10sarcoma; penthelioma). In this tumor the blood vessels are lined by normal endothelium and the tumor cells are clustered outside of but closely applied to the reticulin sheath. The
MALIGNANT TUMOR OF URETHRA
695
dominant cell is the pericyte and is readily observed in its benign form, the glomus tumor. 3) Kaposi's sarcoma (synonyms: angiosarcoma multiplex; multiple idiopathic hemorrhagic sarcoma; sarcoma cutaneum telangiectaticum multiplex, etc.). The microscopic picture is one of interlacing groups of capillaries associated with growth of spindle-shaped cells and connective tissue fibers suggestive of fibrosarcoma. 4) Lymphangiosarcoma. This is a malignant tumor thought to arise from lymphatic endothelium. Of prime concern to the urologist is the malignant hemangio-endothelioma which, in Stout's opinion, embraces those malignant endotheliomas arising from the vascular endothelium within the corpora cavernosa and heretofore reported as presenting as a penile tumor. The tumor in our case, as can best be determined, arose from blood vessel endothelium in the corpora spongiosum and grew into the penile urethra with resultant ulceration and hematuria. It qualifies as a hemangio-endotheliosarcoma or under the classification proposed by Stout, a malignant hemangio-endothelioma. To the best of our knowledge it represents the first such tumor presenting in the urethra. Kaposi's sarcoma has been described originating on the glans penis and must be considered in the differential diagnosis of hemangiosarcomas of the penis. Benign angiomas of the glans penis and anterior urethra have been reported. However, in none of these cases did progression to a malignant state occur. This factor brings up several interesting points concerning the pathogenesis of malignant hemangio-endotheliomas. The first concerns the hypothesis of trauma and secondary production of granulation tissue with its rich capillary network and subsequent progression and development of a malignant hemangio-endothelioma. This has given rise to the term, granulation tissue sarcoma. It is very possible that our case can be explained on this basis as it was first considered a simple capillary hemangioma and following electrofulguration developed malignant changes with progression to hemangiosarcoma. :McCarthy and Pack, reporting on a series of 20 cases of angiosarcoma occurring in various sites, included three instances of angiosarcoma developing from benign angioma previously controlled by irradiation therapy with apparent cure, in l case, extending as long as 15 years. Secondly, we are concerned with the proposed entity of benign metastasizing hemangioma in which the original tumor is a benign hemangioma with subsequent appearance in distant areas as hemangioma or malignant hemangio-endothelioma. A number of such cases have been reported and, in one or two instances, apparently confirmed. However, the majority are thought to be originally malignant and the entity, as such, is rather dubious. Microscopically, angiosarcoma may be confused with chorio-epithelioma and the metastatic lesions of clear cell carcinoma with the latter tumor, perhaps, accounting for a certain number of erroneously diagnosed cases of angiosarcoma of bone. The proper therapy in these cases is based upon the location and gross extent
696
DEAN C. VARNEY
of the tumor. Metastases usually occur via the blood stream. However, lymphatic spread is not uncommon and, although relatively slow, may on occasion be extremely rapid, as demonstrated by our case in which marked metastatic destruction of bone occurred 3 months following previously negative radiographic findings. The treatment of choice is therefore radical excision or amputation with irradiation and radium therapy reserved for advanced or inoperable cases. The reported average survival period of malignant hemangio-endothelioma varies from 1 to 2,l,f years, compared to 8 years for Kaposi's sarcoma. SUMMARY AND CONCLUSIONS
A case of malignant hemangio-endothelioma, apparently ansmg from the corpus spongiosum, but presenting as and exhibiting the clinical characteristics of a urethral tumor, is described as the first of its type recorded. The pathological classification and micrm:copic description of that group of malignant tumors of blood and lymph vessel origin, termed the ang10sarcomas, are presented.
626 E. Santa Clara St., San Jose 12, Calif. REFERENCES CoPPRIDGE, W.W., PUTMAN, G. H. AND MrALE, J.B.: Endothelioma of the penis. J. Urol., 56: 112-117, 1946. CORNWALL, W. D. AND WHITAKER, L.: Endothelioma of the penis: A case report. J. Urol., 69: 307-308, 1953. FouLDS, G. S. AND FLETT, R.H.: Endothelioma of the corpora cavernosa. J. Urol., 40: 826-835, 1938. GRAVES, R. C. AND Gurss, L. W.: Tumors of the urethra. J. Urol., 46: 925-947, 1941. LANE, J. W.: Hemangioma of the glans penis. U.S. Armed Forces Med. J., 4: 139-140, 1953. McCARTHY, W. D. AND PACK, G. T.: Malignant blood vessel tumors. Surg., Gynec. & Obst., 91: 465-482, 1950. McCREA, L. E.: Angioma of the male urethra. Urol. & Cutan. Rev., 52: 204, 1948. lVIoRTENSEN' HENRY AND MURPHY, LEONARD: Angiomatous malformations of the glans penis. J. Urol., 64: 396--399, 1950. PEACHMAN, C. K.: Angioma of the glans penis. J. Urol., 57: 884-887, 1947. PHILLIPS, C.H. AND DouGLAS, M. D.: Tumors of the urethra. Am. J. Obst. & Gynec., 27: 99-104, 1934. RABSON, M. S.: Angioma of corpus cavernosum penis. J. Urol., 45: 111-117, 1941. ROBINSON, J. M. AND CASTLEMAN, B.: Benign metastasizing hemangioma. Ann. Surg., 104: 436-445, 1936. RoLNICK, H. C.: The Practice of Urology. Philadelphia: J. B. Lippincott Co., 1949, vol. 1, p. 205. STOUT, A. P.: Hemangio-endothelioma: A tumor of blood vessels featuring vascular endothelial cells. Ann. Surg., 118: 445-464, 1943. STOUT, A. P.: Tumors of the Soft Tissues, Atlas of Tumor Pathology. Washington, D. C., Armed Forces Inst. Path., Sec. II, fascicle 5: 99-103, 1953.