- Email: [email protected]
Bilateral atypical ductal hyperplasia, an incidental finding in gynaecomastia—Case report and literature review
ARTICLE IN PRESS The Breast (2005) 14, 317–321
THE
BREAST www.elsevier.com/locate/breast
CASE REPORT
Bilateral atypical ductal hyperplasia, an incidental finding in gynaecomastia—Case report and literature review Vani Prasada,, John M Kingb, William McLeayc, Wendy Raymondc, Rodney D. Cootera a
Waverley House Plastic Surgery Centre, 360, South Terrace, Adelaide SA 5000, Australia Drs King & Mower, Histopathology & Cytopathology, 117, Greenhill Rd, Unley, South Australia, Australia c Flinders Medical Centre, Bedford Park, South Australia SA 5042, Australia b
Received 21 September 2004; received in revised form 31 March 2005; accepted 13 April 2005
KEYWORDS Gynaecomastia; Atypical ductal hyperplasia; Bilateral
Summary Male breast cancer is a rare disease. Atypical ductal hyperplasia (ADH) in men is much rarer, and bilateral involvement is exceptional. A 20-year-old male presented with bilateral gynaecomastia who underwent subcutaneous mastectomies and histopathology revealed bilateral ADH. At 24 months, completion mastectomies were performed on both sides. The residual breast tissue revealed ADH similar to the initial specimen. ADH in women increases the risk of breast cancer by four to five times. To our knowledge, this is the first case report of bilateral ADH in a gynaecomastia specimen. & 2005 Elsevier Ltd. All rights reserved.
Introduction The term ‘‘gynaecomastia’’ has Greek origins and literally means ‘‘with breasts like a woman’’. Gynaecomastia is nearly always bilateral although clinically it often seems to appear like a unilateral lesion.1 Although an incidental finding of breast cancer in a patient with gynaecomastia has been reported,2 atypical ductal hyperplasia (ADH) in gynaecomastia is a rarity. In women, however, Corresponding author. Tel.: +61 8 8223 1330;
fax: +61 8 8223 1927. E-mail address: [email protected] (V. Prasad).
there are a number of case reports of occult breast cancer and ADH occurring in reduction mammaplasties.3,4 ADH in the female breast is a wellrecognised risk marker for subsequent development of breast cancer.
Case report A 20-year-old weight lifter presented with bilateral gynaecomastia, for surgical correction. Past medical history was essentially non-contributory, except for occasional use of recreational drugs
0960-9776/$ - see front matter & 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.breast.2005.04.010
ARTICLE IN PRESS 318 including marijuana. There was no history of use of anabolic steroids. His maternal grandmother had carcinoma of breast. The entire physical examination was normal except for bilateral gynaecomastia. Subcutaneous mastectomies were performed under local anaesthesia and intravenous sedation. The postoperative course was uneventful. The surgical specimens were sent for routine histopathological examination. Macroscopic examination showed fibro fatty breast tissue weighing 25 g on the right side and 10 g on the left side, but without any discrete lesion. Microscopic examination revealed glandular breast tissue within abundant fibrous stroma, in keeping with gynaecomastia. Many of the glandular structures on both sides showed cribriform hyperplasia with a rigid architecture as in Figs. 1A and B. Morphologically,
V. Prasad et al. this appearance was equivalent to ADH described in the female breast (Fig. 2). There was no evidence of intraductal or invasive malignancy. The slides were reviewed by a second independent pathologist who concurred with the original diagnosis. The patient was referred to two breast surgeons for opinions on further management. Their opinions were divided about the need for bilateral total mastectomies. Although referred for genetic testing, it was considered inappropriate due to lack of data on the risk of breast cancer following the identification of ADH in a gynaecomastia specimen. At 24 months after the initial surgery, bilateral completion mastectomies were performed. The residual tissue on both sides revealed ADH.
Discussion
Figure 1 (A) Right breast duct showing an atypical rigid cribriform epithelial proliferation with some but not all of the features of ductal carcinoma in situ (DCIS). Original magnification 100 . H&E stain. (B) Right breast duct showing an atypical rigid cribriform epithelial proliferation in keeping with atypical ductal hyperplasia. Original magnification 200 . H&E stain.
Male breast cancer represents 1% of all breast cancers and ADH is a very rare finding. ADH is a histological diagnosis and its actual incidence in an unbiased male population is difficult to ascertain. The only reports of male ADH were found in reviews on male breast cancer, familial male breast cancer and findings in human autopsy and surgical material. Bilateral ADH as an incidental finding after subcutaneous mastectomies for gynaecomastia has not been reported. Male ADH has not been as extensively studied, as it has in women. Page5,6 defined the term Atypical Hyperplasia in women to denote rare, worrisome lesions that have some, but not all, of the features of ductal carcinoma in situ. Tavassoli and Norris7 defined atypical intraductal hyperplasia in women as a lesion in which the proliferating epithelial cells display a cytological atypia similar to the cytologic features of one of the non-necrotic variants of intraductal carcinoma. Our case is the first to be reported in the literature with bilateral ADH in gynaecomastia specimens. Gynaecomastia is the most common benign condition of the male breast. The incidence of gynaecomastia in association with breast cancer varies from 0% to 40%. Nydick et al.8 found an incidence of 38.7% in adolescent boys. Crichlow9 in an extensive review found that only 17 of 625 patients with male breast cancer had gynaecomastia. Joshi et al.10 noted gynaecomastia in 37% of men with male breast cancer. In autopsy material from 100 consecutive, unselected cases, Andersen and Gram1 found that gynaecomastia was present in 55 cases. Out of the 55 cases, 7 cases had ADH in their gynaecomastia specimen. Andersen and Gram11 in another study demonstrated an incidence of 6.5% ADH in a surgical material of
ARTICLE IN PRESS
Bilateral atypical ductal hyperplasia, an incidental finding in gynaecomastia—Case report
Figure 2 Comparative microscopy of both breasts. H&E stain. A. Panoramic low-power view of ADH in gynaecomastia of right breast. Original magnification 20 . B. ADH in left breast ducts. Original magnification 40 .
319
ARTICLE IN PRESS 320 gynaecomastia. They concluded that the clinical significance of ADH must not be overestimated. But this perception was a reflection of the conclusion reached by Kramer and Rush12 on the basis of a similar investigation in the female breast. However, in the last 20 years there has been a change in the attitude of histopathologists and surgeons with regard to the importance of treating ADH, as it was found to increase the risk of breast cancer in women by four to five times. Bannayan and Hajdu13 conducted a clinicopathologic study on 351 cases of gynaecomastia and found that 15 of them had ADH. Cole and Qizilbash14 examined 233 cases of gynaecomastia and 32 cases of infiltrating cancer of male breast. In one of the 32 cases there was evidence of microscopic gynaecomastia and also showed atypical hyperplasia in association with infiltrating cancer. Turi et al.15 reported a 28-yearold male with invasive ductal carcinoma in the right breast and ADH and gynaecomastia in the left breast. Multiple drugs can induce gynaecomastia, including anabolic steroids and marijuana. The patient in this case report consumed marijuana occasionally. We cannot prove the pathogenesis in this case of gynaecomastia, but, having excluded many other diagnoses, we would like to propose that consumption of marijuana may have induced the gynaecomastia and possibly ADH, bilaterally. Many of these drugs alter the estrogen/androgen equilibrium by favouring increased synthesis of estrogen, or by depressing the synthesis of androgens. In 1972, Harman and Aliapoulios16 first reported the association of gynaecomastia in marijuana users. The same authors17 in 1974 conducted laboratory experiments on rats by injecting 9-tetrahydrocannabinol (THC) and observed that THC stimulated development of rat breast tissue. Kolodny et al.18 found that testosterone levels decreased in chronic marijuana users. Olusi19 observed that prolactin levels were significantly higher in patients with suspected cannabis-induced gynaecomastia. Olusi suggested Marijuana, like the phenothiazines may induce the production of prolactin that has been shown to produce gynaecomastia. In contrast to the above findings, Mendelson20,21 found no association between chronic marijuana use and plasma testosterone and prolactin levels. Pinedo et al.22 reported a case of atypical hyperplasia in gynaecomastia in a patient treated with cytotoxic therapy for lymphoma. There are several reports of ADH in patients being followed under familial male breast cancer. Everson et al.23 reported on familial breast cancer and found intraductal hyperplasia in tissue prophylactically removed from the contra lateral breast of
V. Prasad et al. a patient with breast cancer and from both breasts of his two sons. This finding suggests a tendency toward proliferation of ductal epithelium that may predispose to malignancy. Schwartz et al.24 reported familial breast cancer in a father and son. They found an atypical papillomatous lesion in the biopsy of the son’s right breast, which developed into a diffusely infiltrating, well-differentiated papillary carcinoma. In the literature on male breast cancer there is only scant reference to the specific morphology of ADH. Hittmair et al.25 in a morphologic study found ducts with atypical intraductal hyperplasia in 22 of the 84 cases of pure ductal carcinoma in situ and three of the 30 cases of ductal carcinoma in situ associated with invasive carcinoma. In a study of male breast cancer Joshi et al.10 found foci of atypical hyperplasia with direct progression to carcinoma in situ and invasive carcinoma in one case. Until now there is no study that addressed the question of risk of breast cancer following ADH in the male population. A diagnosis of ADH in a male patient presents a clinical conundrum. According to Page et al.6 the risk of carcinoma in women with ADH is four to five times that of age-matched women from the general population. We do not know if ADH increases the risk of breast cancer in men. Are men with gynaecomastia at increased risk of breast cancer? Since ADH is a risk marker for subsequent development of breast cancer in the female breast, could an analogous situation be anticipated in the male breast? Does ADH have implications for relatives of the patient of both sexes? Do these patients need bilateral total mastectomies? This case report underscores the clinical dilemma arising from a lack of conclusive guidelines for further management of ADH in men.
References 1. Anderson JA, Gram JB. Male breast at autopsy. Acta Pathol Microbiol Immunol Scand—Sect A, Pathology 1982;90: 191–7. 2. Fodor PB. Breast cancer in a patient with gynecomastia. Plast Reconstr Surg 1989;84:976–9. 3. Gottlieb JR, McKinney P, Walkinshaw MD, Sperling RL. Occult breast carcinoma in patients undergoing reduction mammaplasty. Aesthetic Plast Surg 1989;13:279–83. 4. Boice Jr. JD, Friis S, McLaughlin JK, et al. Cancer following breast reduction surgery in Denmark. Cancer Causes Control 1997;8:253–8. 5. Page DL. Atypical hyperplasia, narrowly and broadly defined. Hum Pathol 1991;22:631–2. 6. Page DL, DuPont WD, Rogers LW, Rados MS. Atypical hyperplastic lesions of the female breast. A long-term follow-up study. Cancer 1985;55:2698–708.
ARTICLE IN PRESS Bilateral atypical ductal hyperplasia, an incidental finding in gynaecomastia—Case report 7. Tavassoli FA, Norris HJ. A comparison of the results of longterm follow-up for atypical intraductal hyperplasia and intraductal hyperplasia of the breast. Cancer 1990;65: 518–29. 8. Nydick M. Gynecomastia in adolescent boys. J Am Med Assoc 1961;178:109–14. 9. Crichlow RW. Carcinoma of the male breast. Surg Gynecol Obstet 1972;134:1011–9. 10. Joshi MG, Lee AK, Loda M, et al. Male breast carcinoma: an evaluation of prognostic factors contributing to a poorer outcome. Cancer 1996;77:490–8. 11. Anderson JA, Gram JB. Male breast at autopsy. Acta Pathol Microbiol Immunol Scand—Sect A, Pathology 1982;90: 185–90. 12. Kramer WM, Rush Jr. BF. Mammary duct proliferation in the elderly. A histopathologic study. Cancer 1973;31:130–7. 13. Bannayan GA, Hajdu SI. Gynecomastia: clinicopathologic study of 351 cases. Am J Clin Pathol 1972;57:431–7. 14. Cole FM, Qizilbash AH. Carcinoma in situ of the male breast. J Clin Pathol 1979;32:1128–34. 15. Turi V, Lucev M, D’Abrosca F, Gerosa E. Cancer of the male breast with atypical ductal hyperplasia and contralateral gynecomastia (Italian). Minerva Chir 1990;45:203–5. 16. Harmon J, Aliapoulios MA. Gynecomastia in marihuana users. N Engl J Med 1972;287:936. 17. Harmon JW, Aliapoulios MA. Marijuana-induced gynecomastia: clinical and laboratory experience. Surg Forum 1974; 25:423–5.
321
18. Kolodny RC, Masters WH, Kolodner RM, Toro G. Depression of plasma testosterone levels after chronic intensive marihuana use. N Engl J Med 1974;290:872–4. 19. Olusi SO. Hyperprolactinaemia in patients with suspected cannabis-induced gynaecomastia. Lancet 1980; 1(8162):255. 20. Mendelson JH, Kuehnle J, Ellingboe J, Babor TF. Plasma testosterone levels before, during and after chronic marihuana smoking. N Engl J Med 1974;291: 1051–5. 21. Mendelson JH, Ellingboe J, Mello NK. Acute effects of natural and synthetic cannabis compounds on prolactin levels in human males. Pharmacol Biochem Behav 1984;20:103–6. 22. Pinedo F, Vargas J, de Agustin P, Garzon A, Perez-Barrios A, Ballestin C. Epithelial atypia in gynecomastia induced by chemotherapeutic drugs. A possible pitfall in fine needle aspiration biopsy. Acta Cytol 1991;35:229–33. 23. Everson RB, Li FP, Fraumeni Jr. JF. Familial male breast cancer. Lancet 1976;1(7949):9–12. 24. Schwartz RM, Newell Jr. RB, Hauch JF, Fairweather WH. A study of familial male breast carcinoma and a second report. Cancer 1980;46:2697–701. 25. Hittmair AP, Lininger RA, Tavassoli FA. Ductal carcinoma in situ (DCIS) in the male breast: a morphologic study of 84 cases of pure DCIS and 30 cases of DCIS associated with invasive carcinoma—a preliminary report. Cancer 1998; 83:2139–49.
THE
BREAST www.elsevier.com/locate/breast
CASE REPORT
Bilateral atypical ductal hyperplasia, an incidental finding in gynaecomastia—Case report and literature review Vani Prasada,, John M Kingb, William McLeayc, Wendy Raymondc, Rodney D. Cootera a
Waverley House Plastic Surgery Centre, 360, South Terrace, Adelaide SA 5000, Australia Drs King & Mower, Histopathology & Cytopathology, 117, Greenhill Rd, Unley, South Australia, Australia c Flinders Medical Centre, Bedford Park, South Australia SA 5042, Australia b
Received 21 September 2004; received in revised form 31 March 2005; accepted 13 April 2005
KEYWORDS Gynaecomastia; Atypical ductal hyperplasia; Bilateral
Summary Male breast cancer is a rare disease. Atypical ductal hyperplasia (ADH) in men is much rarer, and bilateral involvement is exceptional. A 20-year-old male presented with bilateral gynaecomastia who underwent subcutaneous mastectomies and histopathology revealed bilateral ADH. At 24 months, completion mastectomies were performed on both sides. The residual breast tissue revealed ADH similar to the initial specimen. ADH in women increases the risk of breast cancer by four to five times. To our knowledge, this is the first case report of bilateral ADH in a gynaecomastia specimen. & 2005 Elsevier Ltd. All rights reserved.
Introduction The term ‘‘gynaecomastia’’ has Greek origins and literally means ‘‘with breasts like a woman’’. Gynaecomastia is nearly always bilateral although clinically it often seems to appear like a unilateral lesion.1 Although an incidental finding of breast cancer in a patient with gynaecomastia has been reported,2 atypical ductal hyperplasia (ADH) in gynaecomastia is a rarity. In women, however, Corresponding author. Tel.: +61 8 8223 1330;
fax: +61 8 8223 1927. E-mail address: [email protected] (V. Prasad).
there are a number of case reports of occult breast cancer and ADH occurring in reduction mammaplasties.3,4 ADH in the female breast is a wellrecognised risk marker for subsequent development of breast cancer.
Case report A 20-year-old weight lifter presented with bilateral gynaecomastia, for surgical correction. Past medical history was essentially non-contributory, except for occasional use of recreational drugs
0960-9776/$ - see front matter & 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.breast.2005.04.010
ARTICLE IN PRESS 318 including marijuana. There was no history of use of anabolic steroids. His maternal grandmother had carcinoma of breast. The entire physical examination was normal except for bilateral gynaecomastia. Subcutaneous mastectomies were performed under local anaesthesia and intravenous sedation. The postoperative course was uneventful. The surgical specimens were sent for routine histopathological examination. Macroscopic examination showed fibro fatty breast tissue weighing 25 g on the right side and 10 g on the left side, but without any discrete lesion. Microscopic examination revealed glandular breast tissue within abundant fibrous stroma, in keeping with gynaecomastia. Many of the glandular structures on both sides showed cribriform hyperplasia with a rigid architecture as in Figs. 1A and B. Morphologically,
V. Prasad et al. this appearance was equivalent to ADH described in the female breast (Fig. 2). There was no evidence of intraductal or invasive malignancy. The slides were reviewed by a second independent pathologist who concurred with the original diagnosis. The patient was referred to two breast surgeons for opinions on further management. Their opinions were divided about the need for bilateral total mastectomies. Although referred for genetic testing, it was considered inappropriate due to lack of data on the risk of breast cancer following the identification of ADH in a gynaecomastia specimen. At 24 months after the initial surgery, bilateral completion mastectomies were performed. The residual tissue on both sides revealed ADH.
Discussion
Figure 1 (A) Right breast duct showing an atypical rigid cribriform epithelial proliferation with some but not all of the features of ductal carcinoma in situ (DCIS). Original magnification 100 . H&E stain. (B) Right breast duct showing an atypical rigid cribriform epithelial proliferation in keeping with atypical ductal hyperplasia. Original magnification 200 . H&E stain.
Male breast cancer represents 1% of all breast cancers and ADH is a very rare finding. ADH is a histological diagnosis and its actual incidence in an unbiased male population is difficult to ascertain. The only reports of male ADH were found in reviews on male breast cancer, familial male breast cancer and findings in human autopsy and surgical material. Bilateral ADH as an incidental finding after subcutaneous mastectomies for gynaecomastia has not been reported. Male ADH has not been as extensively studied, as it has in women. Page5,6 defined the term Atypical Hyperplasia in women to denote rare, worrisome lesions that have some, but not all, of the features of ductal carcinoma in situ. Tavassoli and Norris7 defined atypical intraductal hyperplasia in women as a lesion in which the proliferating epithelial cells display a cytological atypia similar to the cytologic features of one of the non-necrotic variants of intraductal carcinoma. Our case is the first to be reported in the literature with bilateral ADH in gynaecomastia specimens. Gynaecomastia is the most common benign condition of the male breast. The incidence of gynaecomastia in association with breast cancer varies from 0% to 40%. Nydick et al.8 found an incidence of 38.7% in adolescent boys. Crichlow9 in an extensive review found that only 17 of 625 patients with male breast cancer had gynaecomastia. Joshi et al.10 noted gynaecomastia in 37% of men with male breast cancer. In autopsy material from 100 consecutive, unselected cases, Andersen and Gram1 found that gynaecomastia was present in 55 cases. Out of the 55 cases, 7 cases had ADH in their gynaecomastia specimen. Andersen and Gram11 in another study demonstrated an incidence of 6.5% ADH in a surgical material of
ARTICLE IN PRESS
Bilateral atypical ductal hyperplasia, an incidental finding in gynaecomastia—Case report
Figure 2 Comparative microscopy of both breasts. H&E stain. A. Panoramic low-power view of ADH in gynaecomastia of right breast. Original magnification 20 . B. ADH in left breast ducts. Original magnification 40 .
319
ARTICLE IN PRESS 320 gynaecomastia. They concluded that the clinical significance of ADH must not be overestimated. But this perception was a reflection of the conclusion reached by Kramer and Rush12 on the basis of a similar investigation in the female breast. However, in the last 20 years there has been a change in the attitude of histopathologists and surgeons with regard to the importance of treating ADH, as it was found to increase the risk of breast cancer in women by four to five times. Bannayan and Hajdu13 conducted a clinicopathologic study on 351 cases of gynaecomastia and found that 15 of them had ADH. Cole and Qizilbash14 examined 233 cases of gynaecomastia and 32 cases of infiltrating cancer of male breast. In one of the 32 cases there was evidence of microscopic gynaecomastia and also showed atypical hyperplasia in association with infiltrating cancer. Turi et al.15 reported a 28-yearold male with invasive ductal carcinoma in the right breast and ADH and gynaecomastia in the left breast. Multiple drugs can induce gynaecomastia, including anabolic steroids and marijuana. The patient in this case report consumed marijuana occasionally. We cannot prove the pathogenesis in this case of gynaecomastia, but, having excluded many other diagnoses, we would like to propose that consumption of marijuana may have induced the gynaecomastia and possibly ADH, bilaterally. Many of these drugs alter the estrogen/androgen equilibrium by favouring increased synthesis of estrogen, or by depressing the synthesis of androgens. In 1972, Harman and Aliapoulios16 first reported the association of gynaecomastia in marijuana users. The same authors17 in 1974 conducted laboratory experiments on rats by injecting 9-tetrahydrocannabinol (THC) and observed that THC stimulated development of rat breast tissue. Kolodny et al.18 found that testosterone levels decreased in chronic marijuana users. Olusi19 observed that prolactin levels were significantly higher in patients with suspected cannabis-induced gynaecomastia. Olusi suggested Marijuana, like the phenothiazines may induce the production of prolactin that has been shown to produce gynaecomastia. In contrast to the above findings, Mendelson20,21 found no association between chronic marijuana use and plasma testosterone and prolactin levels. Pinedo et al.22 reported a case of atypical hyperplasia in gynaecomastia in a patient treated with cytotoxic therapy for lymphoma. There are several reports of ADH in patients being followed under familial male breast cancer. Everson et al.23 reported on familial breast cancer and found intraductal hyperplasia in tissue prophylactically removed from the contra lateral breast of
V. Prasad et al. a patient with breast cancer and from both breasts of his two sons. This finding suggests a tendency toward proliferation of ductal epithelium that may predispose to malignancy. Schwartz et al.24 reported familial breast cancer in a father and son. They found an atypical papillomatous lesion in the biopsy of the son’s right breast, which developed into a diffusely infiltrating, well-differentiated papillary carcinoma. In the literature on male breast cancer there is only scant reference to the specific morphology of ADH. Hittmair et al.25 in a morphologic study found ducts with atypical intraductal hyperplasia in 22 of the 84 cases of pure ductal carcinoma in situ and three of the 30 cases of ductal carcinoma in situ associated with invasive carcinoma. In a study of male breast cancer Joshi et al.10 found foci of atypical hyperplasia with direct progression to carcinoma in situ and invasive carcinoma in one case. Until now there is no study that addressed the question of risk of breast cancer following ADH in the male population. A diagnosis of ADH in a male patient presents a clinical conundrum. According to Page et al.6 the risk of carcinoma in women with ADH is four to five times that of age-matched women from the general population. We do not know if ADH increases the risk of breast cancer in men. Are men with gynaecomastia at increased risk of breast cancer? Since ADH is a risk marker for subsequent development of breast cancer in the female breast, could an analogous situation be anticipated in the male breast? Does ADH have implications for relatives of the patient of both sexes? Do these patients need bilateral total mastectomies? This case report underscores the clinical dilemma arising from a lack of conclusive guidelines for further management of ADH in men.
References 1. Anderson JA, Gram JB. Male breast at autopsy. Acta Pathol Microbiol Immunol Scand—Sect A, Pathology 1982;90: 191–7. 2. Fodor PB. Breast cancer in a patient with gynecomastia. Plast Reconstr Surg 1989;84:976–9. 3. Gottlieb JR, McKinney P, Walkinshaw MD, Sperling RL. Occult breast carcinoma in patients undergoing reduction mammaplasty. Aesthetic Plast Surg 1989;13:279–83. 4. Boice Jr. JD, Friis S, McLaughlin JK, et al. Cancer following breast reduction surgery in Denmark. Cancer Causes Control 1997;8:253–8. 5. Page DL. Atypical hyperplasia, narrowly and broadly defined. Hum Pathol 1991;22:631–2. 6. Page DL, DuPont WD, Rogers LW, Rados MS. Atypical hyperplastic lesions of the female breast. A long-term follow-up study. Cancer 1985;55:2698–708.
ARTICLE IN PRESS Bilateral atypical ductal hyperplasia, an incidental finding in gynaecomastia—Case report 7. Tavassoli FA, Norris HJ. A comparison of the results of longterm follow-up for atypical intraductal hyperplasia and intraductal hyperplasia of the breast. Cancer 1990;65: 518–29. 8. Nydick M. Gynecomastia in adolescent boys. J Am Med Assoc 1961;178:109–14. 9. Crichlow RW. Carcinoma of the male breast. Surg Gynecol Obstet 1972;134:1011–9. 10. Joshi MG, Lee AK, Loda M, et al. Male breast carcinoma: an evaluation of prognostic factors contributing to a poorer outcome. Cancer 1996;77:490–8. 11. Anderson JA, Gram JB. Male breast at autopsy. Acta Pathol Microbiol Immunol Scand—Sect A, Pathology 1982;90: 185–90. 12. Kramer WM, Rush Jr. BF. Mammary duct proliferation in the elderly. A histopathologic study. Cancer 1973;31:130–7. 13. Bannayan GA, Hajdu SI. Gynecomastia: clinicopathologic study of 351 cases. Am J Clin Pathol 1972;57:431–7. 14. Cole FM, Qizilbash AH. Carcinoma in situ of the male breast. J Clin Pathol 1979;32:1128–34. 15. Turi V, Lucev M, D’Abrosca F, Gerosa E. Cancer of the male breast with atypical ductal hyperplasia and contralateral gynecomastia (Italian). Minerva Chir 1990;45:203–5. 16. Harmon J, Aliapoulios MA. Gynecomastia in marihuana users. N Engl J Med 1972;287:936. 17. Harmon JW, Aliapoulios MA. Marijuana-induced gynecomastia: clinical and laboratory experience. Surg Forum 1974; 25:423–5.
321
18. Kolodny RC, Masters WH, Kolodner RM, Toro G. Depression of plasma testosterone levels after chronic intensive marihuana use. N Engl J Med 1974;290:872–4. 19. Olusi SO. Hyperprolactinaemia in patients with suspected cannabis-induced gynaecomastia. Lancet 1980; 1(8162):255. 20. Mendelson JH, Kuehnle J, Ellingboe J, Babor TF. Plasma testosterone levels before, during and after chronic marihuana smoking. N Engl J Med 1974;291: 1051–5. 21. Mendelson JH, Ellingboe J, Mello NK. Acute effects of natural and synthetic cannabis compounds on prolactin levels in human males. Pharmacol Biochem Behav 1984;20:103–6. 22. Pinedo F, Vargas J, de Agustin P, Garzon A, Perez-Barrios A, Ballestin C. Epithelial atypia in gynecomastia induced by chemotherapeutic drugs. A possible pitfall in fine needle aspiration biopsy. Acta Cytol 1991;35:229–33. 23. Everson RB, Li FP, Fraumeni Jr. JF. Familial male breast cancer. Lancet 1976;1(7949):9–12. 24. Schwartz RM, Newell Jr. RB, Hauch JF, Fairweather WH. A study of familial male breast carcinoma and a second report. Cancer 1980;46:2697–701. 25. Hittmair AP, Lininger RA, Tavassoli FA. Ductal carcinoma in situ (DCIS) in the male breast: a morphologic study of 84 cases of pure DCIS and 30 cases of DCIS associated with invasive carcinoma—a preliminary report. Cancer 1998; 83:2139–49.