Epithelioid sarcoma masquerading as Peyronie\'s disease

EPITHELIOID SARCOMA MASQUERADING AS PEYRONIE’S DISEASE STEPHEN W. MOORE, MD,* JAMES E. WHEELER, MD,+AND LAWRENCE G. HEFTER, MD?

A 23-year-old man presented with a firm plaque-like penile mass with pain and deviation on erection, suggesting Peyronie’s disease. Biopsy was erroneously interpreted as confirmatory. Irradiation was the one mode of therapy which gave temporary subjective relief. Extension of the mass and focal gangrene led to rebiopsy 6 years later. Epithelioid sarcoma was present microscopically, and was also found on re-examination of the original biopsy. Partial penectomy was performed, but pulmonary metastasis had already occurred. He was treated with chemotherapy and radiotherapy and is now alive with disease 2 years later. The diagnosis of possible penile sarcoma, although rare, must be considered in patients with symptoms suggesting Peyronie’s disease, especially if the lesion continues to enlarge. Cancer 35 :1706-1 7 10, 1975.

W

E REPORT HERE A CASE OF EPITHELIOID

sarcoma of the penis initially misdiagnosed both clinically a n d on biopsy as Peyronie’s disease, with local recurrence followed by pulmonary metastasis. Peyronie’s disease is an uncommon disorder usually developing in middle life with the formation of one or more fibrous plaques or nodules on the shaft of the penis, commonly associated with curvature and pain on erection.’WhiIe these lesions may persist and even enlarge over several years, surgical intervention is not recommended by many authors, as recurrences are common a n d may actually be larger a n d more symptomatic than the original lesion. According to Frank and Scott,‘ no case of malignant degeneration has ever been described. O n review of the literature pertaining to sarcoma of the penis, no case has been diagnosed as epithelioid sarcoma, although

From the Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia, PA, and the Department of Pathology, T h e Fairfax Hospital, Falls Churrh, VA. Supported in part by a Clinical Fellowship from the Ameriran Cancer Society. * Senior Resident i n Pathology, University of Pennsylvania, and Clinical Fellow. American Cancer Society. ’ Assistant Professor, llepartment of Pathology, Universit y of Pennsylvania. Pathologist, T h e Fairfax Hospital. Address for reprints: Dr. Stephen W. .\loore, Sacred Heart Hospital, 9th and Wilson Sts., Chester, PA 19013 T h e authors express their appreciation to bliss Claudette Rarbetta for assistance in typing the manuscript. Received for publication M a y 17, 1974.

a case designated as fascia1 sarcoma in a recent review by Dehner and Smith3 may well represent such a case

CASEREPORT A 23-year-old Caucasian graduate student was referred to the Hospital of the LJniversity of Pennsylvania in November, 1965, complaining of a mass of 5 weeks’ duration involving the glans penis, causing pain a n d leftward deviation on erection. There was no other history or symptoms of genitourinary disease. O n examination, a nontender plaque-like firm mass was noted at the distal penis, seeming to encircle all but the right lateral margin just proximal to the glans. Within this was a 5-mm firm nodule. T h e remainder of the physical examination was negative; chest roentgenogram a n d routine laboratory studies were normal. Biopsy was performed. H e was discharged in 5 days on potassium para-aminobenzoate. Despite this, local and systemic steroids, a n d xylocaine injections, the lesion a n d associated symptomatology persisted. T w o 5-week courses of surface irradiation, each totaling 1000 rads using a 100-kV unit, brought about a transient decrease in pain though not in mass. In December, 1969, hesitancy a n d urgency developed; a voiding cineurethrogram demonstrated external compression of the urethra. Dilatation brought symptomatic relief. In November, 1971, the entire glans became darkened; the patient was readmitted. A hard plaque was noted to extend circumferentially around the entire length of the shaft of the penis. T h e glans was diffusely hyperemic, with a gangrenous-appearing focus.

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T h e dorsum of the penis was opened and several plaques were removed. Following the report of sarcoma, a partial penectomy was done. A chest roentgenogram at this time showed a 1.5-cm nodule in the right upper lobe not present before; laminagrams revealed several smaller nodules as well in the right upper lobe. A month later, when the patient was readmitted for continuation of reconstructive surgery, these nodules had enlarged on roentgenogram. In another month, when plastic surgery was completed, a n additional nodule was noted on roentgenoyam in the left lower lobe. T h e patient returned to his home in Virginia where, during evaluation for chemotherapy, open biopsies of the upper a n d lower lobes of the right lung were performed, and the diagnosis of metastatic e ithelioid sarcoma made. Chemotherapy a n 2 radiotherapy were instituted. A year a n d a half later the patient is alive and his metastatic disease stationary. He has had no local recurrence or clinical evidence of new metastatic disease elsewhere.

Pathology Tissue submitted for histologic examination from the initial biopsy in 1965 consisted of eight pieces of irregular dense fibrous tissue measuring Up to 1.5 c m in greatest dimensions. O n

FIG. I . Original biopsy showing benlqn-appearing fibrous area ( X I 3CJ).

FIG.2. Original biopsy showing focus of spindle and plump acidophilic cells (X210).

microscopic examination there were dense acellular bands of collagenous tissue, with interspersed cellular spindle cell foci resembling fibromatosis. Occasional hyalinized foci suggested osteoid (Fig. 1); there was focal calcification. Other areas contained cords a n d nests of plump cells having acidophilic cytoplasm and round, ovoid, or bean-shaped vesicular nuclei with fine chromatin (Fig. 2). Occasional mitoses a n d mild nuclear atypism were present in these foci. In a few areas the cells formed small nodules, some with central fibrosis. T h e histologic findings were interpreted as consistent with Peyronie’s disease. T h e repeat biopsy in 1971 was followed a week later by partial penectomy. This specimen measured 8 cm in length and 3 cm in diameter, with a distal biopsy site about which extensive firm fibrous induration was seen. T h e proximal margin appeared grossly unremarkable. Microscopic findings were identical for the two specimens. Present within fibrous tissue were cellular nodules of varying size, the larger ones with central necrosis or fibrosis (Fig. 3 ) . T h e cells were epithelial-like, with abundant acidophilic cytoplasm (Fig. 4). Considerable nuclear pleomorphism was evident, and mitoses were easily found. In some fields these nodules blended imperceptibly into the surrounding

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FIG. 3, Penectomy specimen showing granuloma-like tumor nodule with focal central necrosis (X130).

FIG. 4. Penectomy specimen showing epithelioid tumor cells (X260).

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fibrous tissue; in others, the nodules were more sharply demarcated. Numerous foci of perineural invasion were seen (Fig. 5); cellular tumor extended into the sinuses of the corpus cavernosum (Fig. 6). No mucicarminophilic material was identified in tumor cells, and a reticulum network was seen around both individual tumor cells and nests. No squamous features were identified, and in none of the numerous sections taken was an origin from skin of the shaft or mucosa of the glans present. The surgical margin was not involved. Pathologic diagnosis was epithelioid sarcoma of the penis. At this time, the original biopsy was reviewed. Atypical hypercellular nodules which had not been appreciated originally were recognized as sarcomatous. In retrospect. epithelioid features of the sarcoma were present at this time. Although focal benign-appearing fibrous areas were consistent with Peyronie’s disease, the overall appearance was not. Lung biopsy in April, 1972, yielded several small wedges of peripheral lung and pleura each about 1.5 cm in diameter. Within these were numerous 0.2-0.7 cm nodules, consisting histologically of a loose, fibrous proliferation, containing small, irregular nests of rather large, irregularly-outlined cells, having abundant acidophilic and hyperchromatic

FIG 5. Penectomy specimen showing perineural invasion by tumor ( X 130).

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pleomorphic nuclei (Fig 7). Giant a n d multinucleated cells were common. These nodules were present about small vessels or bronchi and were rimmed by hyperplastic alveolar lining cells. Mucicarmine, P T A H , and PAS stains were negative. T h e lesions were thought to represent metastases from the sarcoma of the penis .

DWXJSSION Epithelioid sarcoma was first described by Enzingera in 1970, based on his series of 62 cases. It occurs mainly in young adults with a male preponderance. It usually affects tendons, aponeuroses, a n d superficial tissue of the extremities. A slowly-growing mass, typically present for years, recurs after biopsy (85% of cases followed by Enzinger) and yields metastases in a significant number (30%),confirming its malignant character. Histologically, spindle and epithelioid polygonal cells with acidophilic cytoplasm form granuloma-like nodules within dense fibrous connective tissue. These nodules often show central necrosis or fibrosis. Cellular features of malignancy should serve to avoid a mistaken benign diagnosis. Since Enzinger’s publication, several other s e r i e ~ ~ -have ’ ~ ~ ’sup~

FIG.6 Penectomy specimen showing tumor invading :)us cavernasurn (X80).

COT-

FIG.7. Lung biopsy showing pulmonary metastasis with reactive hyperplasia of alveolar lining cells ( X 130).

ported his observations. T h e authors of two studies on the fine structure have reached differing conclusions as t o the histogenesis. A possible synovial origin is postulated by Gabbiani and coworkers,7 whereas Fisher a n d Horvat5 favor a fibroblastic origin. I n their light microscopic study, Soule and Enriquez” advance a unifying concept of common histiocytic origin for the four entities studied: atypical fibrous histiocytoma, malignant fibrous histiocytoma, malignant histiocytoma, a n d epithelioid sarcoma. Although sites of origin other than extremities have now been reported, no case arising in the penis has been previously noted. I n their review of soft tissue tumors of the penis, Dehner a n d Smith3 illustrate a 7-cm tumor of the ventral penile shaft in a 35-year-old Negro, which was present 12 years prior to resection. They term it “fascia1 sarcoma” though the photomicrograph suggests epithelioid sarcoma. No followup is given. Though accumulated series contain over 1500 cases of Peyronie’s d i ~ e a s e , its ’ ~ etiology, natural history, and histology are still not well understood. Biopsy is seldom done because the lesion is readily diagnosed clinically, and surgery appears less effective than nonoperative

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1710 methods of management. Smith’s studies” provide a good description of the histology. In two series totaling 79 cases of Peyronie’s d i s e a ~ e ~ followed .’~ up to 16 years, no lesion became larger once diagnosed. None of these patients developed sarcoma of the penis. In a review of the English literature concerning sarcomas of the penis, no case could be found in which a sarcoma arose in a previously diagnosed Peyronie’s disease. However, two cases raise such possibility because of their long clinical course. Ashley a n d Edwards’ describe a man who had a small lump on the glans, present for 12 years when excised. Histology was not recorded. I t recurred years later a n d 28 years following the initial removal a re-excision was diagnosed histologically as leiomyosarcoma. T h e long course of the mass suggests Peyronie’s disease, but the other clinical features are lacking. A second possible association involving Peyronie’s disease and sarcoma is presented by Hutcheson and Whitaker.8First noted at age 53, a penile mass was initially biopsied 5 years later, revealing a benign fibrous lesion. Three years later biopsy of a local recurrence showed a mixture of low-grade leiomyosarcoma with fibromatosis. Because of a massive enlarging recurrence 3 years later, penectomy was done,

showing a mitotically quite active leiomyosarcoma. Five years following this a perineal recurrence was excised. Though a n evolution from a benign fibrous lesion is suggested, clinical features of Peyronie’s disease were lacking. In our case, pain a n d deviation on erection, association with a plaque-like encircling mass of the shaft of the penis were present, all features typical of Peyronie’s disease. Portions of the initial biopsy were consistent with this, but foci of intense cellularity, composed of spindle a n d plump epithelial-like cells along with occasional mitoses a n d nuclear atypism should have led the pathologist to the diagnosis of sarcoma. As epithelioid sarcoma had not been described yet, a diagnosis of sarcoma of undetermined type might have been reasonable. Thus, though our case clinically mimicked Peyronie’s disease, biopsy showed sarcoma. Unlike Peyronie’s disease, the lesion continued to enlarge a n d subsequently proved its malignant character with pulmonary metastases. T w o years later the patient’s metastases remain stationary after chemotherapy a n d radiotherapy. This case emphasizes that both urologist and pathologist must be alert to the rare occasion when a slowly growing sarcoma produces clinical features of Peyronie’s disease.

ADDENDUhI Since acceptance of this article for publication, the patient has died. T h e immediate cause of death was respiratory failure. At autopsy he was found to have a right hemothorax with marked atelectasis of the right lung and massive left-sided pulmonary edema. hletastatic tumor involved lungs, pleura, kidneys, a pelvic lymph node, and skin of the neck and scalp ( 1 1 nodules). This pattern oldissemination. with frequent metastases to lung and scalp, was noted by Enzinger.‘

REFERENCES 1. Ashley, D. J . B., and Edwards, E. C : Sarcoma ol’the penis. Br. J . Surg. 45:170-179, 1955. 2. BystrBm, J.,Johansson, B., Edsmyr, F., Korlof, B., and Nylkn, B . : Induratio penis plastica. Scand. J . L’rol. Nephrol. 6:l-5, 1972. 3. Dehner, L. P.. and Smith, B. H . : Soft tissue tumors of the penis. Cuncer 25:1431-1447, 1970. 4. Enzinger, F. M . : Epithelioid sarcoma. Cancer 26: 1020- 104 I , 1970. i. Fisher, E. K., and Horvat, B.: The fibrocytic derivation of the so-called epithelioid sarcoma. Cancer 30:1074-1081, 1972. 6. Frank, 1. N . , and Winfield, LV. S.: T h e ultrasonic treatrnent of Peyronie’s disease. J . Urd. 106:883-887, I97 I , 7. Gabbiani, G., Fu, Y. S., Kaye, G. I . , Lattes, R., and light and electron hlajno, G.: Epithelioid sarcoma-A microscopic study suggesting synovial origin. Cancer

30:486-499, 1972. 8. Hutcheson, J . B., Whitaker, M. H., and Fronstin, M. H.: Leiomyosarcoma of the penis-Case report and review of literature. J . L’rd 101:874-875, 1969. 9. hlcRoberts, J . W.: Peyronie’s disease. Sure. Gjnecol. Obsfet. 129:1291-1294, 1969. 10. Santiago, H., Feinerman, L. ti., and Lattes. K . : Epithelioid sarcoma-A clinical a n d pathologic study of nine cases. Hum Pu/ho/. 3:133-147, 1972. 11. Smith, B. H.: Peyronie’s disease. A m . J . Cltn. Pathol. 45:670-678, 1966. 12. Soule, E. H . , and Enriquez, P.: Atypical fibrous histiocytoma, malignant fibrous histiocytoma, malignant histiocytoma, and epithelioid sarcoma. Cancer 30:128-143, 1972. 13. Williams, J . L., a n d Thomas, G. G.: T h e natural history of Peyronie’s disease. 1.Urol. 103:75-76, 1970.