0022-534 7/90/1434-0824$02.00/0 Vol. 143, April

THE JOURNAL OF UROLOGY Copyright© 1990 by AMERICAN UROLOGICAL ASSOCIATION, INC.

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POSTOPERATIVE SPINDLE CELL NODULE OF THE PROSTATE AND BLADDER WEI-LI HUANG,* JAE Y. RO,t DAVID J. GRIGNON, DAVID SWANSON, NELSON G. ORDONEZ ALBERTO G. AYALA

AND

From the Departments of Pathology and Urology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

ABSTRACT

Postoperative spindle cell nodule of the prostate and bladder (a rare lesion often misinterpreted as sarcoma) is important to recognize. The nodule consists of a reactive proliferation of spindle cells occurring up to several months after a lower genitourinary tract procedure, such as transurethral resection or biopsy. We report on 5 patients with a spindle cell nodule after a prior operation on the prostate or bladder. Of these patients 2 initially were diagnosed as having leiomyosarcoma, including 1 who underwent radical cystoprostatectomy. Because of the potential for inappropriate treatment the clinician must be aware of this entity so that he might question the diagnosis and raise the possibility of a postoperative spindle cell nodule whenever sarcoma is diagnosed after recent surgical instrumentation for a nonmesenchymal lesion in the genitourinary tract. (J. Ural.,

143:824-826, 1990) Postoperative spindle cell nodule resembling sarcoma of the prostate and bladder is a recently described benign entity that is important for urologists and pathologists to recognize. The lesion originally was described in the pathology literature and only a handful of cases have been reported. Since postoperative spindle cell nodule has received scant attention in the urological literature, we attempt to familiarize clinicians with this entity. The lesion often is confused with sarcoma and patients consequently may undergo a radical operation for benign disease. We report 5 cases of postoperative spindle cell nodule and summarize the clinicopathological features of 7 cases previously reported in the literature. CASE REPORTS

Case 1. A 65-year-old man underwent transurethral resection of the prostate for outlet obstruction at another institution. He was referred to our cancer center with recurrent symptoms 1 month later, at which time transurethral resection was repeated. Well differentiated prostatic adenocarcinoma and leiomyosarcoma were diagnosed on the basis of the repeat surgical specimen. After receiving 50 Gy. preoperative radiation to the prostate, the patient underwent cystoprostatectomy and ileal conduit urinary diversion. Residual moderately differentiated adenocarcinoma was present and confined to the prostate. No leiomyosarcoma was present in the cystoprostatectomy specimen. The patient was free of disease after 8 years. Case 2. A 74-year-old man underwent transurethral resection of the prostate, which revealed 3 foci of well differentiated prostatic adenocarcinoma. Repeat transurethral resection 49 days later showed moderately differentiated adenocarcinoma in 1 of 60 chips and a focal spindle cell proliferation that was diagnosed as a postoperative spindle cell nodule. The patient was treated with 60 Gy. radiation to the prostate and was doing well after 8 months. Case 3. A 45-year-old man with gross hematuria underwent transurethral biopsy of a papillary tumor on the posterior bladder wall that revealed poorly differentiated transitional cell carcinoma. The patient underwent cystectomy and pelvic lymphadenectomy 33 days later, and the surgical specimen Accepted for publication October 27, 1989. * Current address: Methodist Hospital, 1701 N. Senate Blvd., P. 0. Box 1367, Indianapolis, Indiana 46206. t Requests for reprints: Department of Pathology, Box 85, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030.

revealed transmurally invasive transitional cell carcinoma and postoperative spindle cell nodule at the site of the previous biopsy. He was well at 4 years. Case 4. A 66-year-old man had undergone numerous transurethral resections of the bladder for recurrent transitional cell carcinoma, the last 8 weeks previously. A prostatic nodule was palpated and needle biopsy of the prostate revealed leiomyosarcoma. The patient underwent cystoprostatectomy and ileal diversion. Invasive intermediate grade transitional cell carcinoma was present in the bladder but the prostate contained no evidence of leiomyosarcoma. The patient was well at 1 year. Case 5. A 65-year-old man with a history of painless gross hematuria underwent several transurethral resections, all for intermediate grade transitional cell carcinoma. He also was treated with 4 courses of intravesical thiotepa. Cystoprostatectomy 1 month after the last transurethral resection revealed high grade papillary transitional cell carcinoma invasive into the muscularis propria and a postoperative spindle cell nodule at the verumontanum. The carcinoma extended to the prostatic urethra and the patient was scheduled to undergo urethrectomy but he did not return. He died of recurrent disease 1 year later at another institution. SUMMARY OF CLINICAL ASPECTS

Our 5 patients with a postoperative spindle cell nodule ranged from 45 to 74 years old (median age 65 years). Three nodules were in the prostate, 1 in the bladder and 1 in the prostatic urethra. All patients were men who had undergone transurethral resection of the prostate or bladder for primary disease 1 month to 8 weeks before the nodule developed. The primary diagnosis in 2 patients was prostatic adenocarcinoma and in the other 3 it was transitional cell carcinoma of the bladder. All 5 postoperative spindle cell nodules were discovered incidentally at operation (transurethral prostatectomy or cystoprostatectomy) or needle biopsy for the primary disease. One patient with prostatic adenocarcinoma (case 1) underwent cystoprostatectomy solely for presumptive leiomyosarcoma. He would not have received such radical treatment for the primary disease alone, thus, demonstrating the importance of recognizing a postoperative spindle cell nodule. No further problem or recurrent postoperative spindle cell nodule was noted in any patient.

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spindle cell nodules and for desmin (intermediate filaments present in myofibroblasts and smooth muscle cells) in 2, One case was tested for cytokeratin which was nonreactive (intermediate filament in epithelial cells). SUMMARY OF CASES IN THE LITERATURE

Case 1, misdiagnosed as leiomyosarcoma. A, note interlacing fascicles of spindle cells, scattered inflammatory cells and small blood vessels. H & E, reduced from XlOO. B, note occasional mitoses (arrows) at high magnification. Cells of postoperative spindle cell nodule are relatively uniform and nuclear features of malignancy are not present. H & E, reduced from X250. PATHOLOGICAL SUMMARY

No gross descriptions of the postoperative spindle cell nodules are available, since the lesions were seen only microscopically. The nodules in all 5 of our patients were poorly defined and ranged from approximately 5 to 9 mm. in greatest diameter. Microscopically, the postoperative spindle cell nodules were moderately to markedly cellular, and composed of spindle cells with tapering ends arranged in a fascicular pattern, and interspersed with small blood vessels and acute and chronic inflammatory cells (see figure). The nuclei of the spindle cells were rather uniform, not pleomorphic. The number of mitotic figures ranged from 5 to 10 per 10 high power fields. No atypical mitoses were noted. Nucleoli were indistinct. The stroma showed slight to moderate edema and no hyalinization was present. Ulceration of the overlying transitional epithelium was noted in 1 case in which the cystoprostatectomy specimen was available for examination. No residual postoperative spindle cell nodule was found in the 2 patients in whom cystoprostatectomy was performed for leiomyosarcoma and the primary disease. Immunohistochemical examination was performed in 3 cases. Spindle cells stained positively for vimentin (intermediate filament found in mesenchymal cells) in all 3 postoperative

Clinical findings. Seven patients with a postoperative spindle cell nodule of the prostate or bladder have been described in the literature. 1- 3 Patient age ranged from 29 to 79 years (median age 60 years). The nodules occurred 2 to 15 months (median 3 months) after transurethral resection for nodular prostatic hyperplasia or transitional cell carcinoma. Wick and associates did not state the primary diagnoses for their 2 patients. 3 Of the lesions 3 were in the prostatic urethra and 4 in the bladder. Of the patients reported on by Proppe and associates 1 had obstructive symptoms, 2 had hematuria and 1 was asymptomatic. 1 The cystoscopic appearance of the postoperative spindle cell nodule varied from an ulcer to an ill-defined heaped up tumor to a definite nodule. 4 All 4 postoperative spindle cell nodules of the prostate and bladder reported by Proppe and associates were diagnosed initially as sarcoma. One patient underwent radical prostatectomy and postoperative irradiation, and 1 underwent cystoprostatectomy. One postoperative spindle cell nodule recurred at 6 weeks and was resected locally; the patient was free of disease at 3 years. One patient received no further treatment and cystoscopic examination at 9 months was negative for recurrence. The patient reported on by Young and Scully was well at 3½ years without further treatment. 2 The 2 patients reported on by Wick and associates showed no evidence of a spindle cell nodule at 6 and 12 months after local resection. 3 Pathological findings. The postoperative spindle cell nodules reported in the literature were similar in histological appearance to those in our patients. Of those reported by Proppe and associates 2 had focal hyalinization. 1 The mitotic counts ranged from 1 to 25 per 10 high power fields and included no atypical mitoses. Neither Young and Scully2 nor Wick and associates 3 provided the mitotic count in their cases of postoperative spindle cell nodule. Immunoperoxidase staining was not uniformly performed. Wick and associates found that their 2 postoperative spindle cell nodules stained with cytokeratin (an epithelial marker) and with a battery of mesenchymal markers (vimentin, smooth muscle actin and desmin). 3 Cytokeratin staining was negative in the case of Young and Scully. 2 Electron microscopy performed in a few cases in the literature showed fibroblastic or myofibroblastic differentiation. 1 • 4 DISCUSSION

Postoperative spindle cell nodule is a benign fibroproliferative process histologically resembling sarcoma. It was not a recognized entity until Proppe and associates described their cases in 1984. 1 Postoperative spindle cell nodule is a reactive phenomenon that occurs in the bladder, prostate or prostatic urethra weeks to months after a cystoscopic procedure for another disease, such as benign prostatic hyperplasia, prostatic adenocarcinoma or transitional cell carcinoma. The lesion is rare, considering the high number of lower genitourinary tract procedures performed each year. The 7 patients described in the literature and our 5 ranged from 29 to 79 years old (median age 60 years) at presentation. Six patients were asymptomatic, 2 had hematuria and 1 had urinary obstructive symptoms. Postoperative spindle cell nodule may recur locally, necessitating local excision but there is no case of distant metastasis. Histologically, a postoperative spindle cell nodule consists of a proliferation of uniform spindle cells intermixed with a slight to moderate number of inflammatory cells. The number of mitoses varies greatly, from 1 to 25 per 10 high power fields. Thus, when a postoperative spindle cell nodule contains many mitotic figures it may be confused with sarcoma.

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The lesion is related clinically and pathologically to other inflammatory spindle cell proliferations of the lower genitourinary tract resulting from a previous operation, chronic inflammation or irritation in men and women. Postoperative spindle cell nodules are known to occur in women in the vagina or endocervix after an operation, such as episiotomy, endocervical curettage or hysterectomy, and often are misdiagnosed as sarcoma.1· 5 Roth described a similar appearing pseudosarcomatous proliferation (so-called inflammatory pseudotumor) in a 32year-old woman with a prolonged history of recurrent cystitis (the last episode had been 9 months previously). 6 Segmental resection for intractable bleeding from the 1.5 cm., friable, bladder-fundic lesion was performed and the patient has been free of disease. Many benign and malignant neoplasms may simulate a postoperative spindle cell nodule histologically but none has been related to a clinical history of an operation on the bladder or prostate. Other neoplasms also tend to occur more often with symptoms, such as hematuria and obstruction, because of the larger size in contrast to a postoperative spindle cell nodule, which usually is asymptomatic and discovered incidentally in a biopsy or surgical specimen. Postoperative spindle cell nodule is confused most often with a smooth muscle neoplasm. Differentiation among postoperative spindle cell nodule, leiomyoma and leiomyosarcoma can be extremely difficult, especially in a small biopsy specimen. Histologically, although the number of mitoses may help to distinguish between leiomyoma and leiomyosarcoma, this factor is not useful to differentiate leiomyosarcoma from postoperative spindle cell nodule, since the latter may have up to 25 mitoses per 10 high power fields. 7·8 Furthermore, well differentiated leiomyosarcomas, like postoperative spindle cell nodules, usually do not contain cytological atypia. Postoperative spindle cell nodules usually are unsuspected clinically because of the small size, whereas leiomyoma and leiomyosarcoma may be large and symptomatic at identification. The key to recognizing a postoperative spindle cell nodule is the history of operation on the bladder or prostate within the previous few months. Other benign spindle cell lesions besides leiomyoma may be confused with a postoperative spindle cell nodule, including nodular fasciitis-like proliferations of the bladder, fibromyxoid nodules of the prostate and phyllodes-like prostatic hyperplasia.9-14 Unlike postoperative spindle cell nodules, these entities arise de novo without a history of disease or a urological operation. They are benign and should not present a therapeutic problem. Malignant spindle cell tumors in addition to leiomyosarcoma include rhabdomyosarcoma, neurofibrosarcoma and fibrosarcoma. 3• 14· 15 Malignant fibrous histiocytoma also has been described.16· 17 These lesions are sufficiently pleomorphic cytologically that differentiation from postoperative spindle cell nodule is not a problem. Another differential diagnosis of postoperative spindle cell nodule is sarcomatoid carcinoma of the bladder, variously known in the literature as spindle cell carcinoma, pseudosarcoma and carcinosarcoma. 3 Sarcomatoid carcinoma is a rare variant of invasive transitional cell or squamous cell cancer, or adenocarcinoma associated with a spindled sarcoma-like component.18· 19 It may be noted at presentation or it may occur after treatment for the associated conventional carcinoma. Like a postoperative spindle cell nodule, sarcomatoid carcinoma of the bladder may stain immunohistochemically for cytokeratin and vimentin. Sarcomatoid carcinoma of the prostate also has been described, and these tumors stain positively with cytokeratin, prostate specific antigen and prostatic acid phosphatase in some but not all cases. 20 , 21 Differentiation of sarcomatoid carcinoma with an exclusively spindle cell component from a postoperative spindle cell nodule may be problematic because both are likely to occur after a history of instrumentation or a urological procedure. They also

appear to be similar histologically, except for greater nuclear pleomorphism and the presence of occasional giant cells in sarcomatoid carcinoma. Wick and associates reported that sarcomatoid carcinoma of the bladder stains positively for epithelial membrane antigen, unlike postoperative spindle cell nodule, and this fact may help to differentiate the 2 entities. 3 Therefore, a postoperative spindle cell nodule may mimic many other benign and malignant spindle cell lesions. One of our patients (case 1) underwent radical cystoprostatectomy for leiomyosarcoma before a postoperative spindle cell nodule was first described. Had the lesion been recognized as a postoperative spindle cell nodule he might still have a functional bladder to date. Close cooperation between the urologist and pathologist is essential to avoid unnecessarily radical treatment for this lesion. The urologist should raise the possibility of a postoperative spindle cell nodule when sarcoma is diagnosed in a patient who has undergone a previous operation for another disease. Thomas Brooks provided technical assistance. REFERENCES 1. Proppe, K. H., Scully, R. E. and Rosai, J.: Postoperative spindle

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cell nodules of genitourinary tract resembling sarcomas. A report of eight cases. Amer. J. Surg. Path., 8: 101, 1984. Young, R. H. and Scully, R. E.: Pseudosarcomatous lesions of the urinary bladder, prostate gland, and urethra. A report of three cases and review of the literature. Arch. Path. Lab. Med., 111: 354, 1987. Wick, M. R., Brown, B. A., Young, R. H. and Mills, S. E.: Spindlecell proliferations of the urinary tract. An immunohistochemical study. Amer. J. Surg. Path., 12: 379, 1988. Young, R.H.: Non-neoplastic epithelial abnormalities and tumorlike lesions. In: Pathology of the Urinary Bladder. Edited by R. H. Young. New York: Churchill-Livingstone, pp. 44-49, 1989. Kay, S. and Schneider, V.: Reactive spindle cell nodule of the endocervix simulating uterine sarcoma. Int. J. Gynec. Path., 4: 255, 1985. Roth, J. A.: Reactive pseudosarcomatous response in urinary bladder. Urology, 16: 635, 1980. Regan, J.B., Barrett, D. M. and Wold, L. E.: Giant leiomyoma of the prostate. Arch. Path. Lab. Med., 111: 381, 1987. Carmel, M., Masse, S. R., Lehoux, J. G. and Elhilali, M.: Leiomyosarcoma of prostate. Urology, 22: 190, 1983. Tetu, B., Ro, J. Y., Ayala, A. G., Srigley, J. R., Begin, L. R. and Bostwick, D. G.: Atypical spindle cell lesions of the prostate. Sem. Diagn. Path., 5: 284, 1988. Nochomovitz, L. E. and Orenstein, J. M.: Inflammatory pseudotumor of the urinary bladder: possible relationship to nodular fasciitis. Two case reports, cytologic observations, and ultrastructural observations. Amer. J. Surg. Path., 9: 366, 1985. Attah, E. B. and Nkposong, E. 0.: Phyllodes type of atypical prostatic hyperplasia. J. Urol., 115: 762, 1976. Manivel, C., Shenoy, B. V., Wick, M. R. and Dehner, L. P.: Cystosarcoma phyllodes of the prostate. A pathologic and immunohistochemical study. Arch. Path. Lab. Med., 110: 534, 1986. Hafiz, M. A., Taker, C. and Sutula, M.: An atypical fibromyxoid tumor of the prostate. Cancer, 54: 2500, 1984. Ro, J. Y.,Ayala, A.G., Ordonez, N. G., Swanson,D. A. andBabaian, R. J.: Pseudosarcomatous fibromyxoid tumor of the urinary bladder. Amer. J. Clin. Path., 86: 583, 1986. Smith, B. H. and Dehner, L. P.: Sarcoma of the prostate gland. Amer. J. Clin. Path., 58: 43, 1972. Bain, G. 0., Danyluk, J. M., Shnitka, T. K., Jewell, L. D. and Manickavel, V.: Malignant fibrous histiocytoma of prostate gland. Urology, 26: 89, 1985. Harrison, G. S.: Malignant fibrous histiocytoma of the bladder. Brit. J. Urol., 58: 457, 1986. Koss, L. G.: Tumors of the urinary bladder. In: Atlas of Tumor Pathology. Washington, D. C.: Armed Forces Institute of Pathology, 2nd series, fasc. 11, p. 52, 1975. Ro, J. Y., Ayala, A. G., Wishnow, K. I. and Ordonez, N. G.: Sarcomatoid bladder carcinoma: clinicopathologic and immunohistochemical study on 44 cases. Surg. Path., 1: 359, 1988. Ordonez, N. G., Ayala, A. G., von Eschenbach, A. C., Mackay, B. and Hanssen, G.: Immunoperoxidase localization of prostatic acid phosphatase in prostatic carcinoma with sarcomatoid changes. Urology, 19: 210, 1982. Shannon, R. L., Grignon, D. J., Ro, J. Y., Ordonez, N. G., Mackay, B. and Ayala, A.G.: Sarcomatoid carcinoma of the prostate. Lab. Invest., 60: 87A, abstract 515, 1989.

Postoperative spindle cell nodule of the prostate and bladder.

Postoperative spindle cell nodule of the prostate and bladder (a rare lesion often misinterpreted as sarcoma) is important to recognize. The nodule co...
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