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Prostatic Melanosis with Involvement of Benign and Malignant Epithelium
0022-5347 /82/l?,84-0825$02.00 Vol. 128, October
THE JOURNAL OF UROLOGY
Copynght © 1982 by The Viiiiiarns & Wilkins Co.
Printed in U.S.A.
PROSTATIC MELANOSIS WITH INVOLVEMENT OF BENIGN AND MALIGNANT EPITHELIUM MANUEL AGUILAR, EOIN F. GAFFNEY
AND
DONALD P. FINNERTY*
From the Departments of Surgery and Pathology, Emory University School of JVledicine and Grady Memorial Hospital, Atlanta, Georgia
ABSTRACT
We report an unusual case of pro static melanosis. Grossly, the majority of prostatic chips contained areas of black discoloration. Microscopically, pigment was identified within the prostatic stroma, in benign prostatic ducts and within the cells of a well differentiated prostatic adenocarcinoma. The pigment was identified as melanin by histochemical methods and electron microscopy. The histogenesis of prostatic melanosis is discussed and it is proposed that the melanin pigment is derived from (aberrant) stromal melanocytes. Prostatic melanosis (prostatic blue nevus) is an uncommon lesion. Whether melanin originates in the stroma or in the epithelium is unsettled and has been a basis for speculation. Some investigators believe that melanin is produced by melanocytes in the stroma and is transferred to the glandular epithelium.1-6 Others propose that the melanin pigment in the glandular epithelium is a result of direct melanogenesis rather than transfer of pigment from melanocytes. 7 • 8 Recently, Rios and Wright reported a case of stromal and epithelial melanosis and also identified melanin in the epithelial component of a well differentiated prostatic adenocarcinoma. 6 Herein we describe another case of prostatic melanosis in which melanin also was identified histochemically and ultrastructurally in an otherwise typical prostatic adenocarcinoma. The histogenesis of prostatic melanosis is discussed and it is proposed that the melanin pigment is derived from stronial melanocytes.
containing melanosomes were clearly distinct from the stromal smooth muscle cells whose cytoplasm contained microfilaments with periodic condensations in their long axes. The nonneoplastic epithelial cells and the malignant epithelial cells contained stage IV melanosomes but no early stage melanosomes. DISCUSSION
Prostatic melanosis (prostatic blue nevus) is described macroscopically as dark brown india ink-like streaks or as solid black areas measuring 1 to 2 cm. in diameter. 1-3 • 9- 11 Microscopically, isolated brown pigmented elongated cells or aggregates of such cells are seen within the fibromuscular stroma. Histochemical stains and ultrastructural studies have suggested that these cells are melanocytes. The melanocytes are considered aberrant or ectopic and are of presumed neural crest origin. 12- 14 Goldman 7 and Tannenbaum 8 described cases in which the acinar epithelial cells contained abundant, finely granular brown pigment. However, in their cases no pigment was discerned within the stroma. They concluded that the epithelium was melanogenic. Gardner and Spitz reported a melanin-containing lesion of the prostate in which there was glandular and stromal melanosis. 4 They favored the view of transfer of pigment to glandular epithelium from surrounding stromal melanoblasts. Reported cases of prostatic melanosis are summarized in the table. In our case, as well as the case reported by Rios and Wright, 6 melanin also was identified within the cells of an otherwise typical well differentiated prostatic adenocarcinoma. The tumor cells in our case contained a striking amount of melanin by light microscopy and were found ultrastructurally to be filled with stage IV melanosomes that were basally located between the cell membrane and the nucleus. The pigmented cells in the stroma were compatible with melanocytes or melanophores. No stage I or II melanosomes (diagnostic of melanocytes and other melanogenic cells) were seen, which may have been a consequence of either suboptimal tissue processing or the small sample obtained for electron microscopy. In heavily pigmented malignant melanomas early stage melanosomes also may be difficult or impossible to find. It is our contention that the pigmented cells within the prostatic stroma in our case (and in other cases of prostatic melanosis) included melanocytes that migrated to the prostate at an early stage in embryogenesis. The melanin-containing benign and malignant epithelial cells probably acquired melanin by phagocytosis from incontinent stromal melanocytes, since they lacked morphological or ultrastructural features of melanin-producing cells. It is conceivable that in some cases of prostatic melanosis melanin in stromal melanocytes is present in insufficient quantities to be detected by routine histochemical methods. This may have prompted the suggestion (which
CASE REPORT
A 64-year-old man with a history of hesitancy presented with urge incontinence. Physical examination showed a moderately enlarged prostate that was smooth and firm, with the right lobe larger than the left lobe. An excretory urogram revealed mild hypertrophy with increased post-void residual. Transurethral resection of the prostate was done and most of the prostatic chips were black. On macroscopic examination the specimen consisted of multiple fragments of rubbery pinkish tissue, the largest fragment measuring 1 X 1 X 1.5 cm. with an aggregrate weight of 20 gm. It was striking that the majority of tissue fragments contained areas of black discoloration. Microscopic examination showed nodular and stromal hyperplasia, and dark brown-black pigment (which stained positively for melanin and was completely bleached by the melanin bleach) in spindle-shaped stromal cells and in benign ductal and acinar epithelium (part A of figure). In many cells the nuclei were obscured due to the abundance of pigment. Several foci of a well differentiated prostatic adenocarcinoma were identified and the adenocarcinoma cells were more densely pigmented than the nonneoplastic epithelium (part B of figure). Most of the pigment in the epithelium was basally located. Tissue from selected areas in 3 paraffin blocks was processed for electron microscopy. The melanin-containing stromal spindle cells seen by light microscopy had elongated nuclei and contained clusters of randomly oriented stage III and stage IV melanosomes in their cytoplasm (part C of figure). Although cell preservation was suboptimal, because the tissue had been processed initially for light microscopy, the cells Accepted for publication January 22 , 198 1. * Requests for reprints: Department of Surgery, Division of Urology, Grady Memorial Hospital, 80 Butler St., S. E., Atlanta, Georgia 30335. 825
826
AGUILAR, GAFFNEY AND FINNERTY
A, low power view of prostatic duct (center) and stroma shows extensive melanin pigment within stromal cells and, to a lesser extent, in epithelial cells. Fontana-Masson, reduced from XlOO. B, focal accumulation of melanin in well differentiated prostatic adenocarcinoma. H & E, reduced from X250. C, electron micrograph of part of stromal cell that contains numerous melanosomes (stages III and IV). Reduced from X44,000.
827
PROSTATIC MEI.,ANOSIS Jlffelanin in the prostate Microscopic Location of Melanin References
No. Cases
Simard and associates 11 Kovi and associates 10 Nigogosyan and associates 1 Jao and associates9 Block and associates2 Goldman' Langley and W eitzner:i Gardner and Spitz4 Guillan and Zelman5 Rios and Wright6 Present case
1 1 3 1 8
Gross
India ink-like pigment, scattered and solid areas Brown black areas 2 X 1.5 X 1.5 Diffusely gray with dark brown streaks Brownish discoloration No pigmented areas observed Pigment in medial, anterior and lateral lobes
13
Dense aggregates of black pigment Areas of black discoloration
we consider unlikely) that the epithelium is melanogenic. 7• 8 Prostatic melanosis is considered a benign proliferation and must be distinguished microscopically from malignant melanoma that has distinctive microscopic growth patterns and is composed of cytologically malignant melanocytes. Urologists and pathologists should be aware of this unusual lesion that grossly mimics malignant melanoma. Careful ultrastructural study of appropriately fixed tissue should confirm the hypothesis that prostatic melanosis is the urologic analogue of the dermal blue nevus and is derived from aberrant prostatic stromal melanocytes. REFERENCES
1. Nigogosyan, G., De La Pava, S., Pickren, J. W. and Woodruff, M. W.: Blue nevus of the prostate gland. Cancer, 16: 1097, 1963. 2. Block, N. L., Weber, D. and Schinella, R.: Blue nevi and other melanotic lesions of the prostate: report of 3 cases and review of the literature. J. Urol., 107: 85, 1972. 3. Langley, J. W. and Weitzner, S.: Blue nevus and melanosis of prostate. J. Urol., 112: 359, 1974. 4. Gardner, W. A., Jr. and Spitz, W. U.: Melanosis of the prostate gland. Amer. J. Clin. Path., 56: 762, 1971. 5. Guillan, R. A. and Zelman, S.: The incidence and probable origin of
Strama
Benign Epithelium
Carcinomatous Epithelium
+ + + + +
0 0 0 0 0
0
+ + + 0
0 0 0 0 0 0 0 0 0
+ +
+ +
+ + + + +
Electron Microscopic Studies
0
+ 0
+ 0 0 0 0 0 0
+
melanin in the prostate. J. Urol., 104: 151, 1970. 6. Rios, C. N. and Wright, J. R.: Melanosis of the prostate gland: report of a case with neoplastic epithelium involvement. J. Urol., 115: 616, 1976. 7. Goldman, R. L.: Melanogenic epithelium in the prostate gland. Amer. J. Clin. Path., 49: 75, 1967. 8. Tannenbaum, M.: Differential diagnosis in uropathology. III. Melanotic lesions of the prostate: blue nevus and prostatic epithelial melanosis. Urology, 4: 617, 1974. 9. Jao, W., Fretzin, D. F., Christ, M. L. and Prinz, L. M.: Blue nevus of the prostate gland. Arch. Path., 91: 187, 1971. 10. Kovi, J., Jackson, A. G. and Jackson, M. A.: Blue nevus of the prostate: ultrastructural study. Urology, 9: 576, 1977. 11. Simard, C., Rognon, L. M. and Pilorce, G.: Le probleme du naevus bleu prostatique. Ann. Anat. Path., 9: 469, 1964. 12. Dorris, F.: Differentiation of pigment cells in tissue culture of chick neural crest. Proc. Soc. Exp. Biol. Med., 34: 448, 1936. 13. Rawles, M. E.: Origin of melanophores and their role in development of colour patterns in vertebrates. Physiol. Rev., 28: 383, 1948. 14. Nakai, T. and Rappaport, H.: A study of the histogenesis of experimental melanotic tumors resembling cellular blue nevi: the evidence in support of their neurogenic origin. Amer. J. Path., 43: 175, 1963.
THE JOURNAL OF UROLOGY
Copynght © 1982 by The Viiiiiarns & Wilkins Co.
Printed in U.S.A.
PROSTATIC MELANOSIS WITH INVOLVEMENT OF BENIGN AND MALIGNANT EPITHELIUM MANUEL AGUILAR, EOIN F. GAFFNEY
AND
DONALD P. FINNERTY*
From the Departments of Surgery and Pathology, Emory University School of JVledicine and Grady Memorial Hospital, Atlanta, Georgia
ABSTRACT
We report an unusual case of pro static melanosis. Grossly, the majority of prostatic chips contained areas of black discoloration. Microscopically, pigment was identified within the prostatic stroma, in benign prostatic ducts and within the cells of a well differentiated prostatic adenocarcinoma. The pigment was identified as melanin by histochemical methods and electron microscopy. The histogenesis of prostatic melanosis is discussed and it is proposed that the melanin pigment is derived from (aberrant) stromal melanocytes. Prostatic melanosis (prostatic blue nevus) is an uncommon lesion. Whether melanin originates in the stroma or in the epithelium is unsettled and has been a basis for speculation. Some investigators believe that melanin is produced by melanocytes in the stroma and is transferred to the glandular epithelium.1-6 Others propose that the melanin pigment in the glandular epithelium is a result of direct melanogenesis rather than transfer of pigment from melanocytes. 7 • 8 Recently, Rios and Wright reported a case of stromal and epithelial melanosis and also identified melanin in the epithelial component of a well differentiated prostatic adenocarcinoma. 6 Herein we describe another case of prostatic melanosis in which melanin also was identified histochemically and ultrastructurally in an otherwise typical prostatic adenocarcinoma. The histogenesis of prostatic melanosis is discussed and it is proposed that the melanin pigment is derived from stronial melanocytes.
containing melanosomes were clearly distinct from the stromal smooth muscle cells whose cytoplasm contained microfilaments with periodic condensations in their long axes. The nonneoplastic epithelial cells and the malignant epithelial cells contained stage IV melanosomes but no early stage melanosomes. DISCUSSION
Prostatic melanosis (prostatic blue nevus) is described macroscopically as dark brown india ink-like streaks or as solid black areas measuring 1 to 2 cm. in diameter. 1-3 • 9- 11 Microscopically, isolated brown pigmented elongated cells or aggregates of such cells are seen within the fibromuscular stroma. Histochemical stains and ultrastructural studies have suggested that these cells are melanocytes. The melanocytes are considered aberrant or ectopic and are of presumed neural crest origin. 12- 14 Goldman 7 and Tannenbaum 8 described cases in which the acinar epithelial cells contained abundant, finely granular brown pigment. However, in their cases no pigment was discerned within the stroma. They concluded that the epithelium was melanogenic. Gardner and Spitz reported a melanin-containing lesion of the prostate in which there was glandular and stromal melanosis. 4 They favored the view of transfer of pigment to glandular epithelium from surrounding stromal melanoblasts. Reported cases of prostatic melanosis are summarized in the table. In our case, as well as the case reported by Rios and Wright, 6 melanin also was identified within the cells of an otherwise typical well differentiated prostatic adenocarcinoma. The tumor cells in our case contained a striking amount of melanin by light microscopy and were found ultrastructurally to be filled with stage IV melanosomes that were basally located between the cell membrane and the nucleus. The pigmented cells in the stroma were compatible with melanocytes or melanophores. No stage I or II melanosomes (diagnostic of melanocytes and other melanogenic cells) were seen, which may have been a consequence of either suboptimal tissue processing or the small sample obtained for electron microscopy. In heavily pigmented malignant melanomas early stage melanosomes also may be difficult or impossible to find. It is our contention that the pigmented cells within the prostatic stroma in our case (and in other cases of prostatic melanosis) included melanocytes that migrated to the prostate at an early stage in embryogenesis. The melanin-containing benign and malignant epithelial cells probably acquired melanin by phagocytosis from incontinent stromal melanocytes, since they lacked morphological or ultrastructural features of melanin-producing cells. It is conceivable that in some cases of prostatic melanosis melanin in stromal melanocytes is present in insufficient quantities to be detected by routine histochemical methods. This may have prompted the suggestion (which
CASE REPORT
A 64-year-old man with a history of hesitancy presented with urge incontinence. Physical examination showed a moderately enlarged prostate that was smooth and firm, with the right lobe larger than the left lobe. An excretory urogram revealed mild hypertrophy with increased post-void residual. Transurethral resection of the prostate was done and most of the prostatic chips were black. On macroscopic examination the specimen consisted of multiple fragments of rubbery pinkish tissue, the largest fragment measuring 1 X 1 X 1.5 cm. with an aggregrate weight of 20 gm. It was striking that the majority of tissue fragments contained areas of black discoloration. Microscopic examination showed nodular and stromal hyperplasia, and dark brown-black pigment (which stained positively for melanin and was completely bleached by the melanin bleach) in spindle-shaped stromal cells and in benign ductal and acinar epithelium (part A of figure). In many cells the nuclei were obscured due to the abundance of pigment. Several foci of a well differentiated prostatic adenocarcinoma were identified and the adenocarcinoma cells were more densely pigmented than the nonneoplastic epithelium (part B of figure). Most of the pigment in the epithelium was basally located. Tissue from selected areas in 3 paraffin blocks was processed for electron microscopy. The melanin-containing stromal spindle cells seen by light microscopy had elongated nuclei and contained clusters of randomly oriented stage III and stage IV melanosomes in their cytoplasm (part C of figure). Although cell preservation was suboptimal, because the tissue had been processed initially for light microscopy, the cells Accepted for publication January 22 , 198 1. * Requests for reprints: Department of Surgery, Division of Urology, Grady Memorial Hospital, 80 Butler St., S. E., Atlanta, Georgia 30335. 825
826
AGUILAR, GAFFNEY AND FINNERTY
A, low power view of prostatic duct (center) and stroma shows extensive melanin pigment within stromal cells and, to a lesser extent, in epithelial cells. Fontana-Masson, reduced from XlOO. B, focal accumulation of melanin in well differentiated prostatic adenocarcinoma. H & E, reduced from X250. C, electron micrograph of part of stromal cell that contains numerous melanosomes (stages III and IV). Reduced from X44,000.
827
PROSTATIC MEI.,ANOSIS Jlffelanin in the prostate Microscopic Location of Melanin References
No. Cases
Simard and associates 11 Kovi and associates 10 Nigogosyan and associates 1 Jao and associates9 Block and associates2 Goldman' Langley and W eitzner:i Gardner and Spitz4 Guillan and Zelman5 Rios and Wright6 Present case
1 1 3 1 8
Gross
India ink-like pigment, scattered and solid areas Brown black areas 2 X 1.5 X 1.5 Diffusely gray with dark brown streaks Brownish discoloration No pigmented areas observed Pigment in medial, anterior and lateral lobes
13
Dense aggregates of black pigment Areas of black discoloration
we consider unlikely) that the epithelium is melanogenic. 7• 8 Prostatic melanosis is considered a benign proliferation and must be distinguished microscopically from malignant melanoma that has distinctive microscopic growth patterns and is composed of cytologically malignant melanocytes. Urologists and pathologists should be aware of this unusual lesion that grossly mimics malignant melanoma. Careful ultrastructural study of appropriately fixed tissue should confirm the hypothesis that prostatic melanosis is the urologic analogue of the dermal blue nevus and is derived from aberrant prostatic stromal melanocytes. REFERENCES
1. Nigogosyan, G., De La Pava, S., Pickren, J. W. and Woodruff, M. W.: Blue nevus of the prostate gland. Cancer, 16: 1097, 1963. 2. Block, N. L., Weber, D. and Schinella, R.: Blue nevi and other melanotic lesions of the prostate: report of 3 cases and review of the literature. J. Urol., 107: 85, 1972. 3. Langley, J. W. and Weitzner, S.: Blue nevus and melanosis of prostate. J. Urol., 112: 359, 1974. 4. Gardner, W. A., Jr. and Spitz, W. U.: Melanosis of the prostate gland. Amer. J. Clin. Path., 56: 762, 1971. 5. Guillan, R. A. and Zelman, S.: The incidence and probable origin of
Strama
Benign Epithelium
Carcinomatous Epithelium
+ + + + +
0 0 0 0 0
0
+ + + 0
0 0 0 0 0 0 0 0 0
+ +
+ +
+ + + + +
Electron Microscopic Studies
0
+ 0
+ 0 0 0 0 0 0
+
melanin in the prostate. J. Urol., 104: 151, 1970. 6. Rios, C. N. and Wright, J. R.: Melanosis of the prostate gland: report of a case with neoplastic epithelium involvement. J. Urol., 115: 616, 1976. 7. Goldman, R. L.: Melanogenic epithelium in the prostate gland. Amer. J. Clin. Path., 49: 75, 1967. 8. Tannenbaum, M.: Differential diagnosis in uropathology. III. Melanotic lesions of the prostate: blue nevus and prostatic epithelial melanosis. Urology, 4: 617, 1974. 9. Jao, W., Fretzin, D. F., Christ, M. L. and Prinz, L. M.: Blue nevus of the prostate gland. Arch. Path., 91: 187, 1971. 10. Kovi, J., Jackson, A. G. and Jackson, M. A.: Blue nevus of the prostate: ultrastructural study. Urology, 9: 576, 1977. 11. Simard, C., Rognon, L. M. and Pilorce, G.: Le probleme du naevus bleu prostatique. Ann. Anat. Path., 9: 469, 1964. 12. Dorris, F.: Differentiation of pigment cells in tissue culture of chick neural crest. Proc. Soc. Exp. Biol. Med., 34: 448, 1936. 13. Rawles, M. E.: Origin of melanophores and their role in development of colour patterns in vertebrates. Physiol. Rev., 28: 383, 1948. 14. Nakai, T. and Rappaport, H.: A study of the histogenesis of experimental melanotic tumors resembling cellular blue nevi: the evidence in support of their neurogenic origin. Amer. J. Path., 43: 175, 1963.