- Email: [email protected]
Blue nevus of the prostate: ultrastructural study
BLUE NEVUS OF THE PROSTATE: ULTRASTRUCTURAL STUDY* JOSEPH
KOVI, M.D.
AARON G. JACKSON, MARVIN A. JACKSON,
M.D. M.D.
From the Departments of Pathology and Surgery, Division of Urology, and the Cooperative Prostatic Research Group,! Howard University College of Medicine, Washington, D.C.
- A case of blue nevus of the prostate in a sixty-five-year-old black patient was studied by light and electron microscopy. In the melanocytes only fully melanized melanosomes were present; melanosomes in early stages of development were entirely absent. It was concluded that the fwmation of melanosomes within the melanocytes in blue nevus of the prostate is probably under genetic control.
ABSTRACT
The common blue nevus is a benign tumor composed of dendritic melanocytes and typically found on the skin.’ The presence of melanin pigment in the prostate was documented first in 1963.2 Since that time, altogether 13 authenticated cases of blue nevi involving the prostate have been reported. 2-7 Cognizance of this entity is important to the urologist because the pigmented lesion in the prostate grossly simulates a malignant melanoma involving the gland.’ Only in a single case was the melanocytic nature of the pigmented cells in the prostate demonstrated by electron microscopy. 4 This report is the second ultrastructural study of a blue nevus of the prostate gland.
*Supported in part by Grant CA-15448-01 from the National Cancer Institute under the aegis of the National Prostatic Cancer Project. tMembers of this group are Marvin A. Jackson, M.D., Chairman; B. S. Ahluwaha, Ph.D.; E. B. Attah, M.D., F.R.C.S. (Ibadan, Nigeria); Jay Herson, Ph.D.; Martin Y. Heshmat, M.D., D.P.H.; Aaron G. Jackson, M.D.; George W. Jones, M.D.; Surinder K. Kapoor, M.Sc.; Joseph Kovi, M.D.; A. 0. Lucas, M.D., F.R.C.P. (Ibadan, Nigeria); E. 0. Nkposong, M.D., F.R.C.S. (Ibadan, Nigeria); Emeka Olisa, M.D. ; and A. 0. Williams, M.D., F.R.C.P. (Ibadan, Nigeria).
576
Case Report A sixty-five-year-old black male was admitted to the urology service with prostatism manifested by slow stream, hesitancy eventuating in retention the night before admission. The patient had been diagnosed two years earlier as having bronchogenic carcinoma with metastases. Physical examination revealed a diffusely enlarged prostate gland of rubbery consistency. Cystoscopy showed bilobar obstruction of bladder neck. The patient subsequently underwent a transurethral prostatectomy. At the resection, a pigmented area was encountered on the right side of the gland, near the apical region. Pigmentation of the prostate occurred in both scattered and dense clusters, having the appearance as if india ink had been injected into the tissue. The pigmentation extended into the substance of the true prostate. The surgical specimen consisted of multiple fragments of prostatic tissue weighing in aggregate 25 Gm. Microscopic examination revealed varying degrees of hyperplasia of glandular and stromal elements in the prostate. The fibromuscular stroma was extensively infiltrated with fusiform, dendritic cells containing abundant coarse, brown pigment. The nuclei of these cells were often completely obscured
UROLOGY
/ MAY 1977 / VOLUME
IX, NUMBER 5
FIGURE 1. Prostate. (A) Di.use infiltration of the fibromuscular stroma with dendritic melanocytes. (Hematoxylin and eosin stain, original magnifiation x 200.) (B) Electron micrograph: several melanocytes packed with electron opaque melanosomes are noted adjacent to smooth muscle cells (SM) and collagen jibrils (original magnijkation x 6,900). (C) Under high magnifiation melanosomes appear as dense, ellipsoidal bodies without discernible internal structure, and without visible limiting membrane; only Stage IV melanosomes are present (original magnifiation X 24,000).
by the pigment granules (Fig. 1A). This pigment was negative for iron by the Prussian blue stain. The Fontana-Masson silver impregnation for melanin was, however, strongly positive. The pigment was easily bleached after treatment with potassium permanganate. Fragments of the formalin-fixed tissue were transferred into 3 per cent glutaraldehyde in 0.1 M phosphate buffer. The tissue blocks were postfixed in 3 per cent osmium tetroxide in 0.1 M phosphate buffer, and thereafter dehydrated in a graded series of ethyl alcohol, and embedded in Epon. For orientation purposes, 2pm. thick sections were prepared and stained with toluidine blue. The thin sections were examined in a Zeiss EM9S-2 electron microscope. Ultrastructurally, the pigment-containing cell exhibited a few distinctive features. The cell was bound by a smooth plasma membrane. The nucleus was elongated or slightly indented. The cystoplasm appeared literally loaded with huge, markedly electron-dense melanosomes (Fig. 1B). The melanosomes generally appeared as
UROLOGY
/ MAY 1977 / VOLUME
IX, NUMBER 5
ellipsoidal, or football-shaped bodies. No distinct limiting membrane could be discerned around them. The melanosomes measured 880 by 500 nm. in maximum diameter, with a range of 1,080 by 580 nm. to 630 by 380 nm. Only fully melanized, Stage IV melanosomes were present in the cytoplasm of the melanocytes, melanosomes at different stages of development, Stage I to III melanosomes were entirely absent (Fig. 1C). Comment Dendritic melanocytes within the fibromuscular stroma of the prostate (in blue nevus) were attributed to a probable migration from the neural crest.’ Malignant transformation of blue nevus in the prostate is highly unlikely, since malignant change has rarely, if ever, been reported in the common blue nevus of skin. The so-called malignant blue nevus usually arises from a cellular blue nevus in the skin.’ Although a dopa oxidase test was not performed in the present case, because the tissue had been already fixed in formalin, electron
microscopy gave unequivocal evidence of the malanosomal nature of the pigment granules. Melanin is an extremely dense polymer, virtually insoluble in almost all solvents, and resistant to chemical treatment (for example, formalin). 8 In the single case of blue nevus of the prostate in which an electron microscopic study has been performed, melanosomes in various stages of development were present in the melanocytes. The patient was a seventy-six-year-old white man.4 Only fully melanized, Stage IV melanosomes were found in the blue nevus of the black patient described in this case report. Considerable differences in human pigmentation on the ultrastructural level have been reported. Melanosomes in the Caucasoid skin are 600 to 700 nm. by 300 to 400 nm. in size, whereas in the Negroid skin these are 1,000 to 1,300 nm. by 500 to 600 nm. in diameter.g There are numerous Stage I to III melanosomes in the melanocytes of pale Caucasians. In the melanocytes of dark Caucasians and Negroes, the number of melanosomes in early stages is significantly less, while the number of fully melanized, Stage IV melanosomes is high. *,l” The variation of racial skin color may be accounted for by the interaction of three to four additive gene pairs.” A comparison of ultrastructure of dendritic melanocytes in the present and the previously reported similar case suggests that melanogenesis is under genetic control probably also in the blue nevus of the prostate.
578
Washington, D. C. 20059 (DR. KOVI) References 1. LEVER, W. F., and SCHAUMBURG-LEVER,G.: Histopathology of the Skin, 5th ed., Philadelphia, J. B. Lippincott Co., 1975, p. 646. 2. NIGOGOSYAN,G., DE LA PAVA, S., PICKREN, J. W., and WOODRUFF, M. W.: Blue nevus of the prostate gland, Cancer 16: 1097 (1963). 3. SIMARD,C., ROGNON,L. M., and PILORCE, 6.: Le probleme du naevus bleu prostatique, Ann. Anat. Pathol. (Paris) 9: 469 (1964). 4. JAO, W., FRETZIN, D. F., CHRIST, M. L., and PRINZ, L. M.: Blue nevus of the prostate gland, Arch. Pathol. 91: 187 (1971). 5. BLOCK, N. L., WEBER, D., and SCHINELLA, R.: Blue nevi and other melanotic lesions of the prostate, J. Urol. 10’7:85 (1972). 6. LANGLEY, J. W., and WEITZNER, S.: Blue nevus and melanosis of prostate, ibid. 112:359 (1974). 7. TANNENBAUM, M. : Differential diagnosis in uropathology. III. Melanotic lesions of prostate, Urology 4: 617 (1974). 8. FITZPATRICK, T. B., QUEVEDO, W. C., JR., SZAB~, G., and SEIJI, M.: Biology of the melanin pigmentary system, in Fitzpatrick, T. B., et al., Eds.: Dermatology in General Medicine, New York, McGraw-Hill, Inc., 1971, chap. 5, p. 117. 9. TODA, K., et al. : Skin color: its ultrastructure and its determining mechanism, in McGovern, V. J., and Russell, P., Eds.: Mechanisms in Pigmentation, Basel, S. Karger, 1973, p. 66. 10. SZAB~, G., GERALD, A. B., PATHAK, M. A., and FITZPATRICK, T. B.: Racial differences in human pigmentation on the ultrastructural level, J. Cell. Biol. 39: 132a (1968). Model estimates of the number of gene 11. STERN, C.: pairs involved in pigmentation variability of the NegroAmerican, Hum. Hered. 20: 165 (1970).
UROLOGY /
MAY 1977 /
VOLUME IX, NUMBER 5
KOVI, M.D.
AARON G. JACKSON, MARVIN A. JACKSON,
M.D. M.D.
From the Departments of Pathology and Surgery, Division of Urology, and the Cooperative Prostatic Research Group,! Howard University College of Medicine, Washington, D.C.
- A case of blue nevus of the prostate in a sixty-five-year-old black patient was studied by light and electron microscopy. In the melanocytes only fully melanized melanosomes were present; melanosomes in early stages of development were entirely absent. It was concluded that the fwmation of melanosomes within the melanocytes in blue nevus of the prostate is probably under genetic control.
ABSTRACT
The common blue nevus is a benign tumor composed of dendritic melanocytes and typically found on the skin.’ The presence of melanin pigment in the prostate was documented first in 1963.2 Since that time, altogether 13 authenticated cases of blue nevi involving the prostate have been reported. 2-7 Cognizance of this entity is important to the urologist because the pigmented lesion in the prostate grossly simulates a malignant melanoma involving the gland.’ Only in a single case was the melanocytic nature of the pigmented cells in the prostate demonstrated by electron microscopy. 4 This report is the second ultrastructural study of a blue nevus of the prostate gland.
*Supported in part by Grant CA-15448-01 from the National Cancer Institute under the aegis of the National Prostatic Cancer Project. tMembers of this group are Marvin A. Jackson, M.D., Chairman; B. S. Ahluwaha, Ph.D.; E. B. Attah, M.D., F.R.C.S. (Ibadan, Nigeria); Jay Herson, Ph.D.; Martin Y. Heshmat, M.D., D.P.H.; Aaron G. Jackson, M.D.; George W. Jones, M.D.; Surinder K. Kapoor, M.Sc.; Joseph Kovi, M.D.; A. 0. Lucas, M.D., F.R.C.P. (Ibadan, Nigeria); E. 0. Nkposong, M.D., F.R.C.S. (Ibadan, Nigeria); Emeka Olisa, M.D. ; and A. 0. Williams, M.D., F.R.C.P. (Ibadan, Nigeria).
576
Case Report A sixty-five-year-old black male was admitted to the urology service with prostatism manifested by slow stream, hesitancy eventuating in retention the night before admission. The patient had been diagnosed two years earlier as having bronchogenic carcinoma with metastases. Physical examination revealed a diffusely enlarged prostate gland of rubbery consistency. Cystoscopy showed bilobar obstruction of bladder neck. The patient subsequently underwent a transurethral prostatectomy. At the resection, a pigmented area was encountered on the right side of the gland, near the apical region. Pigmentation of the prostate occurred in both scattered and dense clusters, having the appearance as if india ink had been injected into the tissue. The pigmentation extended into the substance of the true prostate. The surgical specimen consisted of multiple fragments of prostatic tissue weighing in aggregate 25 Gm. Microscopic examination revealed varying degrees of hyperplasia of glandular and stromal elements in the prostate. The fibromuscular stroma was extensively infiltrated with fusiform, dendritic cells containing abundant coarse, brown pigment. The nuclei of these cells were often completely obscured
UROLOGY
/ MAY 1977 / VOLUME
IX, NUMBER 5
FIGURE 1. Prostate. (A) Di.use infiltration of the fibromuscular stroma with dendritic melanocytes. (Hematoxylin and eosin stain, original magnifiation x 200.) (B) Electron micrograph: several melanocytes packed with electron opaque melanosomes are noted adjacent to smooth muscle cells (SM) and collagen jibrils (original magnijkation x 6,900). (C) Under high magnifiation melanosomes appear as dense, ellipsoidal bodies without discernible internal structure, and without visible limiting membrane; only Stage IV melanosomes are present (original magnifiation X 24,000).
by the pigment granules (Fig. 1A). This pigment was negative for iron by the Prussian blue stain. The Fontana-Masson silver impregnation for melanin was, however, strongly positive. The pigment was easily bleached after treatment with potassium permanganate. Fragments of the formalin-fixed tissue were transferred into 3 per cent glutaraldehyde in 0.1 M phosphate buffer. The tissue blocks were postfixed in 3 per cent osmium tetroxide in 0.1 M phosphate buffer, and thereafter dehydrated in a graded series of ethyl alcohol, and embedded in Epon. For orientation purposes, 2pm. thick sections were prepared and stained with toluidine blue. The thin sections were examined in a Zeiss EM9S-2 electron microscope. Ultrastructurally, the pigment-containing cell exhibited a few distinctive features. The cell was bound by a smooth plasma membrane. The nucleus was elongated or slightly indented. The cystoplasm appeared literally loaded with huge, markedly electron-dense melanosomes (Fig. 1B). The melanosomes generally appeared as
UROLOGY
/ MAY 1977 / VOLUME
IX, NUMBER 5
ellipsoidal, or football-shaped bodies. No distinct limiting membrane could be discerned around them. The melanosomes measured 880 by 500 nm. in maximum diameter, with a range of 1,080 by 580 nm. to 630 by 380 nm. Only fully melanized, Stage IV melanosomes were present in the cytoplasm of the melanocytes, melanosomes at different stages of development, Stage I to III melanosomes were entirely absent (Fig. 1C). Comment Dendritic melanocytes within the fibromuscular stroma of the prostate (in blue nevus) were attributed to a probable migration from the neural crest.’ Malignant transformation of blue nevus in the prostate is highly unlikely, since malignant change has rarely, if ever, been reported in the common blue nevus of skin. The so-called malignant blue nevus usually arises from a cellular blue nevus in the skin.’ Although a dopa oxidase test was not performed in the present case, because the tissue had been already fixed in formalin, electron
microscopy gave unequivocal evidence of the malanosomal nature of the pigment granules. Melanin is an extremely dense polymer, virtually insoluble in almost all solvents, and resistant to chemical treatment (for example, formalin). 8 In the single case of blue nevus of the prostate in which an electron microscopic study has been performed, melanosomes in various stages of development were present in the melanocytes. The patient was a seventy-six-year-old white man.4 Only fully melanized, Stage IV melanosomes were found in the blue nevus of the black patient described in this case report. Considerable differences in human pigmentation on the ultrastructural level have been reported. Melanosomes in the Caucasoid skin are 600 to 700 nm. by 300 to 400 nm. in size, whereas in the Negroid skin these are 1,000 to 1,300 nm. by 500 to 600 nm. in diameter.g There are numerous Stage I to III melanosomes in the melanocytes of pale Caucasians. In the melanocytes of dark Caucasians and Negroes, the number of melanosomes in early stages is significantly less, while the number of fully melanized, Stage IV melanosomes is high. *,l” The variation of racial skin color may be accounted for by the interaction of three to four additive gene pairs.” A comparison of ultrastructure of dendritic melanocytes in the present and the previously reported similar case suggests that melanogenesis is under genetic control probably also in the blue nevus of the prostate.
578
Washington, D. C. 20059 (DR. KOVI) References 1. LEVER, W. F., and SCHAUMBURG-LEVER,G.: Histopathology of the Skin, 5th ed., Philadelphia, J. B. Lippincott Co., 1975, p. 646. 2. NIGOGOSYAN,G., DE LA PAVA, S., PICKREN, J. W., and WOODRUFF, M. W.: Blue nevus of the prostate gland, Cancer 16: 1097 (1963). 3. SIMARD,C., ROGNON,L. M., and PILORCE, 6.: Le probleme du naevus bleu prostatique, Ann. Anat. Pathol. (Paris) 9: 469 (1964). 4. JAO, W., FRETZIN, D. F., CHRIST, M. L., and PRINZ, L. M.: Blue nevus of the prostate gland, Arch. Pathol. 91: 187 (1971). 5. BLOCK, N. L., WEBER, D., and SCHINELLA, R.: Blue nevi and other melanotic lesions of the prostate, J. Urol. 10’7:85 (1972). 6. LANGLEY, J. W., and WEITZNER, S.: Blue nevus and melanosis of prostate, ibid. 112:359 (1974). 7. TANNENBAUM, M. : Differential diagnosis in uropathology. III. Melanotic lesions of prostate, Urology 4: 617 (1974). 8. FITZPATRICK, T. B., QUEVEDO, W. C., JR., SZAB~, G., and SEIJI, M.: Biology of the melanin pigmentary system, in Fitzpatrick, T. B., et al., Eds.: Dermatology in General Medicine, New York, McGraw-Hill, Inc., 1971, chap. 5, p. 117. 9. TODA, K., et al. : Skin color: its ultrastructure and its determining mechanism, in McGovern, V. J., and Russell, P., Eds.: Mechanisms in Pigmentation, Basel, S. Karger, 1973, p. 66. 10. SZAB~, G., GERALD, A. B., PATHAK, M. A., and FITZPATRICK, T. B.: Racial differences in human pigmentation on the ultrastructural level, J. Cell. Biol. 39: 132a (1968). Model estimates of the number of gene 11. STERN, C.: pairs involved in pigmentation variability of the NegroAmerican, Hum. Hered. 20: 165 (1970).
UROLOGY /
MAY 1977 /
VOLUME IX, NUMBER 5