Atypical Stromal Hyperplasia of the Prostate Gland EDWARD 'B. ATTAH, M.B., F.R.C.P. (C), AND MICHAEL E. A. POWELL, M.D., F.R.C.PATH.
ATYPICAL HYPERPLASIA of the prostate is infrequent. On the other hand, benign prostatic hyperplasia is common after middle age, and consists of nodular proliferation of the acini and the fibromuscular stroma. The histopathologic appearances vary according to the proportion of epithelial to stromal fibro-
From the Department of Pathology, University of Ibadan, and University College Hospital, Ibadan, Nigeria, and the Department of Pathology, Kingston Hospital, Kingston upon Thames, Surrey, England
muscular hyperplasia, size and composition of nodules, arrangement and height of epithelial cells, and accompanying inflammatory changes. In previously described cases of atypical hyperplasia of the prostate, the atypical changes have been in the epithelium. Such changes are described and illustrated by Evans. 3 Miller and Seljelid,5 on reviewing 3,636 surgical prostate specimens, found marked epithelial atypia in 100 and slight atypia in 307. There have been only three previous descriptions of atypical stromal hyperplasia so far as the authors are aware. The three cases presented here and the previously reported lesions referred to show various degrees of atypia in hyperplastic prostatic stroma, and illustrate a comparison with stromal and combined epithelial stromal changes in the female breast. Report of Three Cases
Received February 9, 1976; received revised manuscript May 11, 1976; accepted for publication May 27, 1976. Address reprint requests to Dr. Attah: Department of Pathology, University College Hospital, Ibadan, Nigeria. Supported by University of Ibadan Senate Research Grant UI/RGSC/71/441.
Case I. A 69-year-old man had a typical history of prostatism. He had an enlarged prostate, which was resected by the suprapubic approach. The prostate weighed 140 g and contained a well-defined large, firm, grey nodule. The nodule histologically consisted of fibromuscular tissue. Its appearance varied from area to area. There were loose hypocellular zones in which
FIG. 1 {upper , left). Case 1. Vasoformative zone with blood vessels of moderate size surrounded by moderately cellular fibromuscular proliferation. Hematoxylin and eosin. xl75. FIG. 2 (upper, right). Case 1. Focus of marked nuclear pleomorphism. Irregularly oriented, bizarre, hyperchromatic nuclei, many of which are vacuolated. No mitoticfiguresare present. Hematoxylin and eosin. xlOO. FIG. 3 (lower, left). Case 2. Compact cellular arrangement of smooth muscle cells, mostly in fascicles. In some foci are irregularities of nuclear orientation, shape and size, features consistent with leiomyoma with nuclear atypia. Hematoxylin and eosin. x 180. FIG. 4. (lower, right). Case 2. Bizarre smooth muscle nuclei displaying mitoticfigures,features indistinguishable from leiomyosarcoma. Hematoxylin and eosin. x700.
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Attah, Edward 'B., and Powell, Michael E. A.: Atypical stromal hyperplasia of the prostate gland. Am J Clin Pathol 67: 324-327, 1977. Hyperplastic lesions of the prostatic stroma with atypical changes are presented and discussed. One lesion was a leiomyoma with atypical organization and a limited area of nuclear pleomorphism without mitotic figures. One was a lesion which in many portions was histologically indistinguishable from leiomyosarcoma. It, however, had certain features probably connoting less sinister behavior, and at autopsy 16 months after resection there was no evidence of recurrence or metastasis. One lesion histologically resembled fibroadenoma of the female breast. These three lesions occurred in patients more than 50 years who had symptoms and signs of prostatism. Reference is made to two previously reported lesions reminiscent of cystosarcoma phyllodes of the female breast. All the lesions were located in the craniad prostate, which is estrogen-influenced. A parallel is drawn between these atypical changes in prostatic fibromuscular stroma and atypical changes in the connective tissue stroma of the female breast. (Key words: Atypical stromal hyperplasia; Atypical leiojnyoma; Leiomyosarcoma; Fibroadenoma; Cystosarcoma phyllodes; Craniad prostate; Estrogen.)
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FIG. 6 (right). Case 2. Sharp demarcation of tumor edge. Hematoxylin and eosin. x70.
the smooth muscle bundles were widely separated by edematous loose ground substance. Blood vessels were few in these regions. Figure 1 demonstrates an area of the tumor consisting of compact smooth muscle with vasoformative activity. In some areas, the lesion was much more compact, the muscle bundles coursing in fascicles and often in whorls. In one portion of this tumor, the nuclei showed marked pleomorphism and hyperchromasia, many nuclei containing several round and irregular vacuoles (Fig. 2). However, these changes were confined to a limited portion of the tumor, and there were no mitotic figures. Case 2. A 54-year-old man had had symptoms of prostatism for a year. The prostate was enlarged and a large prostatic filling defect representing middle lobe enlargement was demonstrated by intravenous pyelography. The bladder filled well but emptied poorly, leaving a large residue. Suprapubic prostatectomy was performed. The gland was diffusely enlarged and the histologic appearance was that of a smooth muscle tumor. There was some variation in cellularity from area to area, with different degrees of nuclear atypia and atypical arrangement. In some areas (Fig. 3), the
tumor consisted of a compact cellular arrangement of smooth muscle cells. The nuclei in these areas showed little pleomorphism. In some portions, the tumor was less cellular, but the nuclei manifested more marked atypia. Many nuclei were bizarre, and there were tumor giant cells. Marked mitotic activity with more marked nuclear pleomorphism was present in some areas (Fig. 4), giving a picture histologically indistinguishable from leiomyosarcoma. However, in some portions the atypical zones were separated by fascicles of hyperplastic smooth muscle with minimal or no atypia (Fig. 5). The edge of the tumor also was histologically well-defined (Fig. 6). The patient died 16 months after operation, and autopsy findings were severe coronary atherosclerosis with recent myocardial infarction and cerebral embolism. Case 3. A 56-year-old man had urinary retention and clinically benign prostatic enlargement. The prostatectomy specimen was an enlarged nodular prostate. Histologically there was growth of the fibromuscular stroma invaginating into the ducts and acini, producing slit-like spaces (Fig. 7). The proliferated stromal tissue was moderately cellular and the nuclei
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FIG. 5 (left). Case 2. Fascicle of smooth muscle cells and fibers showing minimal atypia coursing between two markedly pleomorphic zones. Hematoxylin and eosin. xl75.
ATYPICAL STROMAL HYPERPLASIA OF PROSTATE
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were inconspicuous, showing no atypicality. This change was universal in the prostate. The epithelium of the distorted ducts and acini showed slight to moderate hyperplasia, being crowded and heaped up in many areas. The cells were of the low columnar type and showed little nuclear atypia, and no mitotic activity or evidence of infiltrative growth. Epithelial alterations were not beyond those frequently seen in benign prostatic hyperplasia. The microscopic features resembled those of an intracanalicular fibroadenoma of the female breast. Discussion
FIG. 7. Case 3. Fibroadenoma. Proliferation of fibromuscular prostatic stroma with invagination and distortion of prostatic ducts and acini. Epithelial proliferation also is present, with crowding and focal pseudostratification. Hematoxylin and eosin. x64, reduced from x70.
phyllodes type of lesion previously reported by one of the authors1 occurred in a 31-year-old Nigerian who had no clinical prostatic enlargement. All the lesions presented and referred to here were located in the craniad prostate, which is estrogen-influenced. This lends weight to drawing a parallel between the atypical changes in the fibromuscular stroma of the prostate as seen in these lesions and atypical changes in the connective tissue stroma of the female breast as manifested in fibroadenomas and related lesions. These lesions are probably not sufficiently widely recognized. References 1. Attah E'B, Nkposong EO: Phyllodes type of atypical prostatic hyperplasia. J Urol 115:762-764, 1976 2. Cox R, Dawson LMP: A curious prostatic tumor; probably a true mixed tumor (cystadenoleiomyofibroma). J Urol 32: 306-311, 1960 3. Evans RW: Histological Appearances of Tumors. Second edition. Edinburgh and London, E. and S. Livingstone. 1968, p 1205 4. Gueft B, Walsh MA: Malignant prostatic cystosarcoma phyllodes. NY State J Med 75:226, 1975 5. Miller A, Seljelid R: Cellular atypia in the prostate. Scand J Urol Nephrol 5:17-21, 1971
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The lesion in Case 1 was interpreted as a leiomyoma with atypical arrangement and nuclear pleomorphism in some portions. It was regarded as benign pathologically, and clinically its behavior was benign. The area of nuclear pleomorphism was underscored by the absence of mitotic figures and the limitation of such alterations to a small region of an otherwise clearly benign lesion. In Case 2 the appearances of the tumor were in general indistinguishable from those of leiomyosarcoma. However, some features suggested less sinister behavior, namely, the presence in the middle of the tumor of fascicles with no atypia, and the distinct demarcation of the edges of the tumor. There was no evidence of recurrence of tumor or metastasis at autopsy 16 months after resection. The lesion in Case 3 was histologically reminiscent of fibroadenoma of the female breast. Cox and Dawson2 have described a prostatic tumor projecting into the bladder, histologically showing cystic spaces with intracystic epithelial covered papillary projections. Both epithelial and connective tissue elements were neoplastic, and they interpreted the tumor as akin to giant fibroadenoma of the breast. Another lesion that would complete this spectrum of stromal and mixed epithelial stromal atypia has been the subject of a separate report.1 This tumor bore a very close resemblance to cystosarcoma phyllodes of the female breast. The epithelial changes were disturbing but did not represent carcinoma. Although stromal alterations were so marked that the lesion was regarded as potentially malignant, there has been no recurrence three and a half years after resection. A similar lesion has recently been reported by Gueft and Walsh,4 their case being interpreted as malignant. The atypical leiomyoma, the lesion histologically suggestive of leiomyosarcoma with features indicating less sinister behavior, and the lesion histologically resembling intracanalicular fibroadenoma of the female breast occurred in men more than 50 years of age. These men are in the age group in which benign prostatic hyperplasia is common. Cox and Dawson's patient2 with cystic fibroadenoma was 41 years old. The
ATYPICAL HYPERPLASIA of the prostate is infrequent. On the other hand, benign prostatic hyperplasia is common after middle age, and consists of nodular proliferation of the acini and the fibromuscular stroma. The histopathologic appearances vary according to the proportion of epithelial to stromal fibro-
From the Department of Pathology, University of Ibadan, and University College Hospital, Ibadan, Nigeria, and the Department of Pathology, Kingston Hospital, Kingston upon Thames, Surrey, England
muscular hyperplasia, size and composition of nodules, arrangement and height of epithelial cells, and accompanying inflammatory changes. In previously described cases of atypical hyperplasia of the prostate, the atypical changes have been in the epithelium. Such changes are described and illustrated by Evans. 3 Miller and Seljelid,5 on reviewing 3,636 surgical prostate specimens, found marked epithelial atypia in 100 and slight atypia in 307. There have been only three previous descriptions of atypical stromal hyperplasia so far as the authors are aware. The three cases presented here and the previously reported lesions referred to show various degrees of atypia in hyperplastic prostatic stroma, and illustrate a comparison with stromal and combined epithelial stromal changes in the female breast. Report of Three Cases
Received February 9, 1976; received revised manuscript May 11, 1976; accepted for publication May 27, 1976. Address reprint requests to Dr. Attah: Department of Pathology, University College Hospital, Ibadan, Nigeria. Supported by University of Ibadan Senate Research Grant UI/RGSC/71/441.
Case I. A 69-year-old man had a typical history of prostatism. He had an enlarged prostate, which was resected by the suprapubic approach. The prostate weighed 140 g and contained a well-defined large, firm, grey nodule. The nodule histologically consisted of fibromuscular tissue. Its appearance varied from area to area. There were loose hypocellular zones in which
FIG. 1 {upper , left). Case 1. Vasoformative zone with blood vessels of moderate size surrounded by moderately cellular fibromuscular proliferation. Hematoxylin and eosin. xl75. FIG. 2 (upper, right). Case 1. Focus of marked nuclear pleomorphism. Irregularly oriented, bizarre, hyperchromatic nuclei, many of which are vacuolated. No mitoticfiguresare present. Hematoxylin and eosin. xlOO. FIG. 3 (lower, left). Case 2. Compact cellular arrangement of smooth muscle cells, mostly in fascicles. In some foci are irregularities of nuclear orientation, shape and size, features consistent with leiomyoma with nuclear atypia. Hematoxylin and eosin. x 180. FIG. 4. (lower, right). Case 2. Bizarre smooth muscle nuclei displaying mitoticfigures,features indistinguishable from leiomyosarcoma. Hematoxylin and eosin. x700.
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Attah, Edward 'B., and Powell, Michael E. A.: Atypical stromal hyperplasia of the prostate gland. Am J Clin Pathol 67: 324-327, 1977. Hyperplastic lesions of the prostatic stroma with atypical changes are presented and discussed. One lesion was a leiomyoma with atypical organization and a limited area of nuclear pleomorphism without mitotic figures. One was a lesion which in many portions was histologically indistinguishable from leiomyosarcoma. It, however, had certain features probably connoting less sinister behavior, and at autopsy 16 months after resection there was no evidence of recurrence or metastasis. One lesion histologically resembled fibroadenoma of the female breast. These three lesions occurred in patients more than 50 years who had symptoms and signs of prostatism. Reference is made to two previously reported lesions reminiscent of cystosarcoma phyllodes of the female breast. All the lesions were located in the craniad prostate, which is estrogen-influenced. A parallel is drawn between these atypical changes in prostatic fibromuscular stroma and atypical changes in the connective tissue stroma of the female breast. (Key words: Atypical stromal hyperplasia; Atypical leiojnyoma; Leiomyosarcoma; Fibroadenoma; Cystosarcoma phyllodes; Craniad prostate; Estrogen.)
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326
ATTAH AND POWELL
A.J.C.P. • April 1977
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FIG. 6 (right). Case 2. Sharp demarcation of tumor edge. Hematoxylin and eosin. x70.
the smooth muscle bundles were widely separated by edematous loose ground substance. Blood vessels were few in these regions. Figure 1 demonstrates an area of the tumor consisting of compact smooth muscle with vasoformative activity. In some areas, the lesion was much more compact, the muscle bundles coursing in fascicles and often in whorls. In one portion of this tumor, the nuclei showed marked pleomorphism and hyperchromasia, many nuclei containing several round and irregular vacuoles (Fig. 2). However, these changes were confined to a limited portion of the tumor, and there were no mitotic figures. Case 2. A 54-year-old man had had symptoms of prostatism for a year. The prostate was enlarged and a large prostatic filling defect representing middle lobe enlargement was demonstrated by intravenous pyelography. The bladder filled well but emptied poorly, leaving a large residue. Suprapubic prostatectomy was performed. The gland was diffusely enlarged and the histologic appearance was that of a smooth muscle tumor. There was some variation in cellularity from area to area, with different degrees of nuclear atypia and atypical arrangement. In some areas (Fig. 3), the
tumor consisted of a compact cellular arrangement of smooth muscle cells. The nuclei in these areas showed little pleomorphism. In some portions, the tumor was less cellular, but the nuclei manifested more marked atypia. Many nuclei were bizarre, and there were tumor giant cells. Marked mitotic activity with more marked nuclear pleomorphism was present in some areas (Fig. 4), giving a picture histologically indistinguishable from leiomyosarcoma. However, in some portions the atypical zones were separated by fascicles of hyperplastic smooth muscle with minimal or no atypia (Fig. 5). The edge of the tumor also was histologically well-defined (Fig. 6). The patient died 16 months after operation, and autopsy findings were severe coronary atherosclerosis with recent myocardial infarction and cerebral embolism. Case 3. A 56-year-old man had urinary retention and clinically benign prostatic enlargement. The prostatectomy specimen was an enlarged nodular prostate. Histologically there was growth of the fibromuscular stroma invaginating into the ducts and acini, producing slit-like spaces (Fig. 7). The proliferated stromal tissue was moderately cellular and the nuclei
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FIG. 5 (left). Case 2. Fascicle of smooth muscle cells and fibers showing minimal atypia coursing between two markedly pleomorphic zones. Hematoxylin and eosin. xl75.
ATYPICAL STROMAL HYPERPLASIA OF PROSTATE
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were inconspicuous, showing no atypicality. This change was universal in the prostate. The epithelium of the distorted ducts and acini showed slight to moderate hyperplasia, being crowded and heaped up in many areas. The cells were of the low columnar type and showed little nuclear atypia, and no mitotic activity or evidence of infiltrative growth. Epithelial alterations were not beyond those frequently seen in benign prostatic hyperplasia. The microscopic features resembled those of an intracanalicular fibroadenoma of the female breast. Discussion
FIG. 7. Case 3. Fibroadenoma. Proliferation of fibromuscular prostatic stroma with invagination and distortion of prostatic ducts and acini. Epithelial proliferation also is present, with crowding and focal pseudostratification. Hematoxylin and eosin. x64, reduced from x70.
phyllodes type of lesion previously reported by one of the authors1 occurred in a 31-year-old Nigerian who had no clinical prostatic enlargement. All the lesions presented and referred to here were located in the craniad prostate, which is estrogen-influenced. This lends weight to drawing a parallel between the atypical changes in the fibromuscular stroma of the prostate as seen in these lesions and atypical changes in the connective tissue stroma of the female breast as manifested in fibroadenomas and related lesions. These lesions are probably not sufficiently widely recognized. References 1. Attah E'B, Nkposong EO: Phyllodes type of atypical prostatic hyperplasia. J Urol 115:762-764, 1976 2. Cox R, Dawson LMP: A curious prostatic tumor; probably a true mixed tumor (cystadenoleiomyofibroma). J Urol 32: 306-311, 1960 3. Evans RW: Histological Appearances of Tumors. Second edition. Edinburgh and London, E. and S. Livingstone. 1968, p 1205 4. Gueft B, Walsh MA: Malignant prostatic cystosarcoma phyllodes. NY State J Med 75:226, 1975 5. Miller A, Seljelid R: Cellular atypia in the prostate. Scand J Urol Nephrol 5:17-21, 1971
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The lesion in Case 1 was interpreted as a leiomyoma with atypical arrangement and nuclear pleomorphism in some portions. It was regarded as benign pathologically, and clinically its behavior was benign. The area of nuclear pleomorphism was underscored by the absence of mitotic figures and the limitation of such alterations to a small region of an otherwise clearly benign lesion. In Case 2 the appearances of the tumor were in general indistinguishable from those of leiomyosarcoma. However, some features suggested less sinister behavior, namely, the presence in the middle of the tumor of fascicles with no atypia, and the distinct demarcation of the edges of the tumor. There was no evidence of recurrence of tumor or metastasis at autopsy 16 months after resection. The lesion in Case 3 was histologically reminiscent of fibroadenoma of the female breast. Cox and Dawson2 have described a prostatic tumor projecting into the bladder, histologically showing cystic spaces with intracystic epithelial covered papillary projections. Both epithelial and connective tissue elements were neoplastic, and they interpreted the tumor as akin to giant fibroadenoma of the breast. Another lesion that would complete this spectrum of stromal and mixed epithelial stromal atypia has been the subject of a separate report.1 This tumor bore a very close resemblance to cystosarcoma phyllodes of the female breast. The epithelial changes were disturbing but did not represent carcinoma. Although stromal alterations were so marked that the lesion was regarded as potentially malignant, there has been no recurrence three and a half years after resection. A similar lesion has recently been reported by Gueft and Walsh,4 their case being interpreted as malignant. The atypical leiomyoma, the lesion histologically suggestive of leiomyosarcoma with features indicating less sinister behavior, and the lesion histologically resembling intracanalicular fibroadenoma of the female breast occurred in men more than 50 years of age. These men are in the age group in which benign prostatic hyperplasia is common. Cox and Dawson's patient2 with cystic fibroadenoma was 41 years old. The
