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Background

This is enlargement of the male breast. It is the end result of hormonal imbalance with prolonged estrogen exposure. Occasionally there is a temporary physiologic change during puberty or old age. But in most cases, there is an underlying disease or medical condition.

Associations
Klinefelter's syndrome
Functioning testicular neoplasms (Leydig cell tumors, Sertoli cell tumors)
Cirrhosis of the liver
Alcohol
Marijuana
Heroin

A diagnosis of gynecomastia should prompt an investigation as to the source of hyperestrinism.

OUTLINE

Epidemiology  
Disease Associations  
Pathogenesis  
Laboratory/Radiologic/Other Diagnostic Testing  
Gross Appearance and Clinical Variants  
Histopathological Features and Variants  
Special Stains/Immunohistochemistry/Electron Microscopy  
Differential Diagnosis  
Prognosis and Treatment  
Commonly Used Terms  
Internet Links  


EPIDEMIOLOGY CHARACTERIZATION
INCIDENCE  

Breast masses in males: Multi-institutional experience on fine-needle aspiration.

Siddiqui MT, Zakowski MF, Ashfaq R, Ali SZ.

Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland.

Diagn Cytopathol 2002 Feb;26(2):87-91 Abstract quote

Male breast masses are uncommon pathologic findings. They are rarely aspirated, resulting in limited cytopathologic experience. The following study describes the cytopathology of male breast lesions from data collected for a period of 10 yr from three large institutions.

A total of 14,026 breast aspirations were performed of which 614 were from male patients. All cases were reviewed and correlated with the appropriate clinicopathologic follow-up. The FNA diagnoses were as follows: benign, 427 cases (gynecomastia 353, fat necrosis 21, miscellaneous 53); malignant, 32 cases (ductal carcinoma nos 15, metastatic tumors 17); and atypical/suspicious, 61 cases. Ninety-four cases were nondiagnostic due to scant cellularity. Male breast aspirates accounted for 4.3% of the total breast FNAs performed. The clinicopathologic follow-up in both the benign and malignant categories showed 100% correlation. The overall sensitivity was 95.3%, specificity was 100%, and diagnostic accuracy was 98%. A relatively high specimen unsatisfactory rate was seen (>15%).

The commonest cytopathologic diagnosis was gynecomastia, followed by ductal carcinoma. Florid duct atypia in gynecomastia may mimic adenocarcinoma, necessitating a higher threshold for cytopathologic interpretation for malignancy in males.

 

DISEASE ASSOCIATIONS CHARACTERIZATION
DRUGS  

Cytologic atypia in a 53-year-old man with finasteride-induced gynecomastia.

Zimmerman RL, Fogt F, Cronin D, Lynch R.

Departments of Pathology & Laboratory Medicine, Presbyterian Medical Center, University of Pennsylvania Health System, Philadelphia, PA 19104, USA.

Arch Pathol Lab Med 2000 Apr;124(4):625-7 Abstract quote

Finasteride has been associated with the development of gynecomastia. Although cytoplasmic vacuolization has been noted in prostatic epithelium in men taking this drug, we found no documentation of the cytologic changes in finasteride-associated gynecomastia. We present the case of a 53-year-old man who developed unilateral gynecomastia following finasteride therapy for alopecia. A fine-needle aspiration biopsy of the mass was diagnosed as adenocarcinoma on the basis of nuclear atypia and particularly because of cytoplasmic vacuolization. Subsequent excisional biopsy revealed benign gynecomastia with no evidence of malignant change. The ductal epithelium did exhibit cytoplasmic vacuolization similar to that described in the prostate following finasteride therapy. We believe this is the first reported case documenting the cytologic changes seen in gynecomastia secondary to finasteride therapy. Cytoplasmic vacuolization in this setting should not be considered evidence of malignancy in men with gynecomastia. As with gynecomastia in general, extreme caution should be used before rendering a cytologic diagnosis of malignancy.

Gynaecomastia and the herbal tonic "Dong Quai".

Goh SY, Loh KC.

Endocrine Unit, Department of General Medicine, Tan Tock Seng Hospital, Singapore.

Singapore Med J 2001 Mar;42(3):115-6 Abstract quote

We present a case of a man who developed gynaecomastia after ingestion of "Dong Quai" pills. "Dong Quai" is the Chinese name for the herb Angelica polymorpha var. sinensis which is widely used as a panacea for gynaecological problems, and it is also proclaimed as an invigorating tonic for both women and men.The pharmacological effects of "Dong Quai" are likely related to the phytoestrogen that it contains.

This report highlights the potential adverse effects associated with its consumption in the male, especially for the processed "Dong Quai" pills which may contain significantly higher levels of phytoestrogen than its original herbal product.

Gynecomastia in a case of hairy cell leukaemia--cladribine induced?

Abhyankar D, Saikia T, Advani S.

Department of Medical Oncology, Tata Memorial Hospital, Dr. Ernest Borges Road, Mumbai-400012, India.

Leuk Lymphoma 2001 Jun;42(1-2):243-6 Related Articles, Books, LinkOut Gynecomastia in a case of hairy cell leukaemia--cladribine induced? Abhyankar D, Saikia T, Advani S. Department of Medical Oncology, Tata Memorial Hospital, Dr. Ernest Borges Road, Mumbai-400012, India. Gynecomastia is benign enlargement of the male breast and is commonly drug induced. Various drugs are responsible and chemotherapeutic drugs can also cause gynecomastia. Cladribine is now widely used for the treatment of hairy cell leukaemia. We present a case report of development of unilateral gynecomastia in a case of hairy cell leukaemia treated with cladribine and question whether this was induced by the chemotherapy.

Gynecomastia with sulpiride.

Kaneda Y, Fujii A.

Department of Neuropsychiatry, The University of Tokushima School of Medicine, Tokushima, Japan, Department of Neuropsychiatry, Fujii Hospital, Japan.

J Clin Pharm Ther 2002 Feb;27(1):75-7 Abstract quote

Objective: Neuroleptic agents have been associated with gynecomastia, but evidence for a causal link is insufficient.

We describe a case of unilateral gynecomastia without galactorrhea in a 38-year-old man during sulpiride treatment for generalized anxiety disorder. The patient had been treated with sulpiride (100 mg/day) for about 5 months by a primary care physician. In this patient, no specific endocrine alterations were found, except for a marked increase in prolactin (PRL) level and slight decrease in testosterone (T)/estradiol (E2) ratio. Drug withdrawal led to a reduction of the lump. Sulpiride is a substituted benzamide with selective dopaminergic blocking activity.

From the marked increase in PRL level and the slight decrease in T/E2 ratio observed during sulpiride therapy, it is proposed that sulpiride may induce gynecomastia by inhibiting hypothalamic-pituitary function directly, and/or indirectly through hyperPRLemia.

ESTROGEN  

Prepubertal gynecomastia: indirect exposure to estrogen cream.

Felner EI, White PC.

Department of Pediatrics, Division of Endocrinology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Pediatrics 2000 Apr;105(4):E55 Abstract quote

OBJECTIVE: To describe the clinical course of 3 prepubertal boys who presented with gynecomastia resulting from indirect exposure to a custom-compounded preparation of estrogen cream used by each child's mother.

METHODOLOGY: Each child was initially referred to the Children's Medical Center of Dallas' Endocrinology Center and followed for over 1 year.

RESULTS: All 3 boys presented with gynecomastia and elevated estradiol levels. Two had accelerated growth and advanced bone ages. Within 4 months after each child's mother discontinued use of the topical estrogen preparation, each child's gynecomastia regressed and estradiol levels returned to normal.

CONCLUSION: Indirect exposure to excessive amounts of topical estrogen may cause gynecomastia, rapid changes in growth, and advanced bone age in prepubertal children. Because custom-compounded topical estrogen preparations are not regulated by the Food and Drug Administration and may contain high concentrations of estrogen, we recommend that women requiring estrogen use an alternate form of estrogen delivery if they are in frequent close contact with children.

HIV-1  

Incidence of gynecomastia in men infected with HIV and treated with highly active antiretroviral therapy.

Piroth L, Grappin M, Petit JM, Buisson M, Duong M, Chavanet P, Portier H.

Department of Infectious Diseases, University Hospital of Dijon, France

Scand J Infect Dis 2001;33(7):559-60 Abstract quote

A longitudinal study found that the incidence of gynecomastia in HIV-infected male patients treated with highly active antiretroviral therapy was 0.8/100 patient-years, with a prevalence of 2.8% in those treated for > or = 2 y.

Even though the physiopathology remains unclear, this study suggests that gynecomastia should be monitored in these patients.

HYPERPARATHYROIDISM  

Bilateral gynaecomastia as the primary complaint in hyperthyroidism.

Tan YK, Birch CR, Valerio D.

Department of Surgery, Grantham and District Hospital, Grantham, Lincolnshire NG31 8DG, UK.

J R Coll Surg Edinb 2001 Jun;46(3):176-7 Abstract quote

Association of gynaecomastia with hyperthyroidism is uncommon but has been well documented in the past. Gynaecomastia in a patient with hyperthyroidism rarely presents as a primary complaint. When this occurs, it may present a diagnostic challenge to the clinician.

We present the case of a patient who was referred initially to the breast clinic with bilateral gynaecomastia. Hyperthyroidism was subsequently confirmed and treated; gynaecomastia regressed with return to the euthyroid state.

SERTOLI-CELL TUMORS  

Feminizing Sertoli cell tumors associated with Peutz-Jeghers syndrome: an increasingly recognized cause of prepubertal gynecomastia.

Hertl MC, Wiebel J, Schafer H, Willig HP, Lambrecht W.

Department of Pediatric Surgery, University Hospital, Hamburg, Germany.

Plast Reconstr Surg 1998 Sep;102(4):1151-7 Abstract quote

Testicular sex cord tumors with annular tubules are an increasingly recognized cause of prepubertal gynecomastia typically accompanied by accelerated linear growth and advanced bone maturation. Serum estrogen levels may be elevated. Testicular ultrasound and biopsy are diagnostic, and mastectomy is indicated. Although these tumors can occur independently, causing gynecomastia in 10 percent of cases, they usually occur in patients with Peutz-Jeghers syndrome.

In any Peutz-Jeghers syndrome patient developing gynecomastia, a testicular tumor should be sought. Conversely, because a significant proportion of all reported prepubertal gynecomastia patients have Peutz-Jeghers syndrome with testicular tumors, this syndrome must be considered for all young boys in whom the cause of gynecomastia is not otherwise apparent. When Peutz-Jeghers syndrome is suspected, gastroscopy, colonoscopy, and testicular biopsies can be performed under one anesthetic at the time of mastectomy.

 

PATHOGENESIS CHARACTERIZATION
GENERAL  

Gynecomastia: pathomechanisms and treatment strategies.

Mathur R, Braunstein GD.

Cedars-Sinai Medical Center-UCLA School of Medicine, Los Angeles, Calif., USA.

Horm Res 1997;48(3):95-102 Abstract quote

Gynecomastia is common in adolescents and adults, and reflects an underlying imbalance in hormonal physiology in which there is an increase in estrogen action relative to androgen action at the breast tissue level. Most patients have persistent pubertal gynecomastia or breast glandular enlargement from medications, age-related reduction in testicular function, or idiopathic causes. Gynecomastia must be differentiated from pseudogynecomastia due to increased breast adipose tissue, as well as from breast carcinoma.

The evaluation of the causes of gynecomastia can be accomplished through history, physical examination and a few laboratory tests. Painful gynecomastia of recent onset may respond to antiestrogen therapy. Surgical removal is the mainstay for long-standing gynecomastia or glandular enlargement that is unresponsive to medical therapy.

CHROMOSOMAL ABNORMALITIES  

Chromosome banding analysis of gynecomastias and breast carcinomas in men.

Teixeira MR, Pandis N, Dietrich CU, Reed W, Andersen J, Qvist H, Heim S.

Department of Genetics, The Norwegian Radium Hospital and Institute for Cancer Research, Oslo.

Genes Chromosomes Cancer 1998 Sep;23(1):16-20 Abstract quote

Male breast cancer is 100 times less frequent than its female counterpart and accounts for less than 1% of all cancers in men. Although men with breast cancer also often have gynecomastia, it is still unknown whether gynecomastia per se predisposes the male breast to malignant disease.

We describe the cytogenetic analysis of three gynecomastias and four breast cancers in men. No chromosome abnormalities were detected in two cases of gynecomastia, with no other concomitant breast disease. The third gynecomastia sample, taken from a site where a breast carcinoma had previously been removed, had a t(2;11)(p24;p13) as the sole chromosome change; this is the first time that an abnormal karyotype has been described in gynecomastia. All four cancers had clonal chromosome abnormalities. Several cytogenetically unrelated clones were found in the breast tumor and in a metastasis from case 1. In the carcinoma of case 2, a single abnormal clone was found, characterized by loss of the Y chromosome, monosomy 17, and a deletion of the long arm of chromosome 18. In the carcinoma of case 3, a clone with loss of the Y chromosome as the sole change dominated, accompanied by the gain of an X chromosome in a subclone. In the lymph node metastasis examined from case 4, a single clone carrying trisomies for chromosomes 5 and 16 was detected.

Our findings, especially when collated with data on the six karyotypically abnormal breast carcinomas in men described previously, indicate that gain of the X chromosome, gain of chromosome 5, loss of the Y chromosome, loss of chromosome 17, and del(18)(q21) are nonrandom abnormalities in male breast carcinomas.

Clonal karyotypic abnormalities in gynecomastia.

Cornelio DA, Schmid-Braz AT, Cavalli LR, Lima RS, Ribeiro EM, Cavalli IJ.

Departamento de Genetica do Setor de Ciencias Biologicas, Universidade Federal do Parana, Curitiba, Parana, Brazil.

Cancer Genet Cytogenet 1999 Dec;115(2):128-33 Abstract quote

Gynecomastia is a benign condition that frequently occurs in the male breast gland; however, the cytogenetic data on this entity are very limited.

To our knowledge, three cases have been reported in the literature, and the only one with an abnormal karyotype had a concomitant breast carcinoma. In this study we report clonal chromosomal alterations in a gynecomastia sample without any signs of adjacent malignant tissue.

The nonrandom abnormalities observed were a deletion of 12p, monosomies of chromosomes 9, 17, 19, and 20, and the presence of a marker chromosome. Most of these alterations have been previously described in the literature in other breast lesions, including benign and malignant (male and female) tumors, indicating their recurrence and nonrandomness in abnormal processes of the mammary gland.

PEPSINOGEN C  

Expression of pepsinogen C in gynecomastias and male breast carcinomas.

Serra Diaz C, Vizoso F, Rodriguez JC, Merino AM, Gonzalez LO, Baltasar A, Perez-Vazquez MT, Medrano J.

Servicio de Cirugia General, Hospital Virgen de los Lirios, Poligono de Caramanxel s/n, 03804 Alcoy, Spain.

World J Surg 1999 May;23(5):439-45 Abstract quote

Pepsinogen C is a proteolytic enzyme involved in the digestion of proteins in the stomach; it is also synthesized by a significant percentage of female breast carcinomas. In addition, it has been demonstrated that pepsinogen C is one of the few proteins induced by androgens in breast carcinoma cells.

Here we evaluate the expression of pepsinogen C by immunoperoxidase staining in normal breast tissue from 3 male patients, 15 gynecomastia tissues, 2 male in situ breast carcinomas, and 68 male invasive breast carcinomas. Pepsinogen C immunostaining values were quantified in male breast tumors using the HSCORE system, which considers both the intensity and the percentage of cells staining at each intensity. The results indicated positive immunohistochemical staining for pepsinogen C in all gynecomastia tissues, the two in situ ductal carcinomas, and 52 of 68 invasive breast carcinomas (76.4%).

The three normal breast tissues analyzed showed negative staining for pepsinogen C, whereas invasive tumors showed clear differences among them with regard to the intensity and percentage of staining cells. In addition, pepsinogen C scores were significantly higher in well-differentiated (grade I, 188.7) and moderately differentiated (grade II, 145.8) tumors than in poorly differentiated (grade III, 98.5) tumors (p = 0. 032). Similarly, significant differences in pepsinogen C content were found between estrogen receptor (ER)-positive tumors and ER-negative tumors (158.5 vs. 44.3, respectively; p = 0.009). Patients with pepsinogen C-positive tumors reached longer relapse-free and overall survival periods than did those with tumors with negative staining, but no statistical differences were observed between survival curves calculated for these two groups of patients.

This results demonstrate expression of pepsinogen C by gynecomastias and by a high percentage of male breast carcinomas and may indicate an important role of pepsinogen C in the pathophysiology of male breast diseases.

 

LABORATORY/RADIOLOGIC/
OTHER TESTS

CHARACTERIZATION
RADIOLOGIC  
LABORATORY MARKERS  

Cost-effective management of gynecomastia.

Bowers SP, Pearlman NW, McIntyre RC Jr, Finlayson CA, Huerd S.

Department of Surgery, University of Colorado Health Sciences Center and Denver VA Medical Center, USA.

Am J Surg 1998 Dec;176(6):638-41 Abstract quote

BACKGROUND: Routine endocrine screening of idiopathic gynecomastia has been advocated, but may not be cost effective. We carried out a cost-benefit analysis of this approach.

METHODS: A retrospective study (1992 to 1997) of 87 adult males with symptomatic gynecomastia was performed.

RESULTS: Thirty-four (39%) patients had extrinsic causes; 53 (61%) were considered idiopathic. Forty-five idiopathic cases underwent endocrine testing: beta human chorionic gonadotropin alone, 16; and beta human chorionic gonadotropin, LH, estradiol, testosterone+/-testicular ultrasound, 29. One (2%) occult Leydig cell testicular tumor was detected. Forty-four patients had normal studies and remain well after local excision.

CONCLUSION: Routine endocrine evaluation of idiopathic gynecomastia is rarely productive; such testing is best done selectively.

 

GROSS APPEARANCE/
CLINICAL VARIANTS
CHARACTERIZATION
GENERAL  
VARIANTS  
FEMALE GYNECOMASTIA  

Gynecomastia-like changes of the female breast.

Kang Y, Wile M, Schinella R.

Department of Pathology, Monmouth Medical Center, 300 Second Ave., Long Branch, NJ 07740, USA.

Arch Pathol Lab Med 2001 Apr;125(4):506-9 Abstract quote

OBJECTIVES: Gynecomastia-like changes of the female breast are only sparsely reported and are not well defined in the literature to our knowledge. Our objectives were to determine the incidence, clinical presentation, mammographic findings, and the medical background of patients with these changes.

DESIGN: Two thousand seven hundred nine female breast surgical cases from 1995 to 1999 were searched by SNOMED. Three observers further reviewed all cases with gynecomastia-like changes. Strict criteria were developed and cases that fulfilled the criteria were analyzed further.

RESULTS: We found the incidence of female gynecomastia-like changes to be 0.15% (4/2709) of all female breast lesions, which represents an underestimation. Patients were usually young and had an average age of 32 years. The usual clinical presentation was a palpable mass with a size ranging from about 3.5 x 2 x 2 cm to 5 x 4 x 2.5 cm. Mammography showed either negative findings or a nonspecific density. Gross examination of these specimens revealed no distinct lesions. Histologically, the lesions consisted of ductal hyperplasia with periductal stromal fibrosis or edema. They were associated with fibrocystic changes in the adjacent breast. The patients had no significant medical history.

CONCLUSION: We propose that the gynecomastia-like change is a specific benign entity within the spectrum of benign fibrocystic changes and that it usually occurs in young patients.

 

HISTOLOGICAL TYPES CHARACTERIZATION
GENERAL Ducts are hyperplastic surrounded by a mildly cellular stroma with edema
VARIANTS  
CYTOLOGY  

Gynecomastia: cytologic features and diagnostic pitfalls in fine needle aspirates.

Amrikachi M, Green LK, Rone R, Ramzy I.

Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA.

Acta Cytol 2001 Nov-Dec;45(6):948-52 Abstract quote

OBJECTIVE: To illustrate some of the uncommon cytologic findings of gynecomastia, such as apocrine metaplasia, cellular atypia and foamy macrophages, that can be misinterpreted as evidence of malignancy.

STUDY DESIGN: The clinical data and fine needle aspiration (FNA) cytologic material from 100 men with the diagnosis of gynecomastia were retrospectively reviewed. The excisional biopsy slides were available for 16 cases. For comparison, FNA smears from five men with breast lesions other than gynecomastia were studied.

RESULTS: The patients ranged in age from 23 to 91 years. Cytologic findings were as follows: cohesive sheets of cells containing 20-1,000 cells (98%); scattered, single, bipolar cells (78%); spindle cells (68%); ductal epithelial atypia (26%); apocrine metaplasia (8%); and foamy histiocytes (12%). In nine cases the atypia was marked, and in two of them the possibility of malignancy could not be ruled out. Surgical follow-up on 16 patients, including the cases with marked atypia, showed gynecomastia. In one case, gynecomastia was associated with intraductal papilloma. No correlation between the underlying etiology and atypical cytologic features of gynecomastia was identified.

CONCLUSION: Apocrine metaplasia and epithelial atypia are common findings in gynecomastia. Attention to the cell patterns, the presence of sheets of ductal cells and absence of atypical single cells will point to the correct diagnosis.


Gynecomastia with marked cellular atypia associated with chemotherapy.

Jun Yang Y.

Department of Pathology, Weill Medical College of Cornell University, New York, NY.

Arch Pathol Lab Med 2002 May;126(5):613-4 Abstract quote

Gynecomastia is a common benign male breast disease, which may exhibit mild cellular atypia in cytology specimens. However, marked cytologic atypia can be seen in gynecomastia superimposed by chemotherapy.

The case described in this report demonstrated severe cytologic atypia of gynecomastia mimicking carcinoma in a patient treated with chemotherapy for acute leukemia. A distinct cytologic feature helpful in avoiding the diagnostic error is described, namely, atypical cells admixed with bland ductal cells and appearing at a different plane. The importance of applying strict diagnostic criteria in breast cytology and clinical correlation is also emphasized.

PSEUDOANGIOMATOUS HYPERPLASIA

Pseudoangiomatous hyperplasia of mammary stroma associated with gynaecomastia.

Milanezi MF, Saggioro FP, Zanati SG, Bazan R, Schmitt FC.

Department of Pathology, Botucatu School of Medicine, UNESP, Brazil.

J Clin Pathol 1998 Mar;51(3):204-6 Abstract quote

AIMS: To evaluate the prevalence of pseudoangiomatous hyperplasia of mammary stroma in gynaecomastia and its immunohistochemical profile in this setting.

METHODS: Eighty eight cases of gynaecomastia recovered from the files of the department of pathology, Botucatu School of Medicine from 1976 to 1996 were studied. In the cases associated with pseudoangiomatous hyperplasia of mammary stroma, immunoreactivity for cytokeratins (CAM 5.2), vimentin, CD34, factor VIII related antigen, and the oestrogen and progesterone receptors were studied.

RESULTS: Pseudoangiomatous hyperplasia of mammary stroma was found in 21 of 88 cases of gynaecomastia (23.8%). In all cases, the cells lining the spaces were positive for vimentin, whereas CAM 5.2 and factor VIII related antigen were consistently negative. Nineteen of the 21 cases showed immunoreactivity for CD34. Ductal epithelial cells were positive for both the oestrogen receptor and the progesterone receptor, whereas stromal cells were negative.

CONCLUSIONS: Pseudoangiomatous hyperplasia of mammary stroma was present in approximately one quarter of the cases of gynaecomastia. This immunohistochemical study confirms the mesenchymal origin of the stromal cells that line the pseudovascular spaces, as has been found in female cases of pseudoangiomatous hyperplasia of mammary stroma.

Gynecomastia in type-1 neurofibromatosis with features of pseudoangiomatous stromal hyperplasia with giant cells. Report of two cases.

Damiani S, Eusebi V.

Department of Oncology, Marcello Malpighi of the University of Bologna, Italy.

Virchows Arch 2001 May;438(5):513-6 Abstract quote

We describe the histological finding in two cases of gynecomastia in patients with von Recklinghausen's disease.

The histological and immunohistochemical features of the two cases were reviewed and compared with those of five cases of gynecomastia in men without clinical evidence of neurofibromatosis. In both patients bearing von Recklinghausen's disease, the breast stroma showed features consistent with pseudoangiomatous stromal hyperplasia (PASH). It was characterised by anastomosing empty spaces lined by spindle and multinucleated giant cells which were positive with CD34 and anti-vimentin antisera and negative with anti-FVIII and CD31 antisera. In two of five of the control cases without neurofibromatosis, the mammary stroma showed focal areas with features of PASH, but no multinucleated giant cells were present in any case. PASH with giant cells should be recognised as a feature of gynecomastia in von Recklinghausen's disease.

The presence of multinucleated giant cells is very unusual and, although more cases have to be studied, these cells seem to be a feature of PASH occurring in patients with von Recklinghausen's disease.

 

SPECIAL STAINS/IMMUNOPEROXIDASE/
OTHER
CHARACTERIZATION
SPECIAL STAINS  
IMMUNOPEROXIDASE  
ESTROGEN AND PROGESTERONE RECEPTORS  

Estrogen and progesterone receptors in gynecomastia.

Pensler JM, Silverman BL, Sanghavi J, Goolsby C, Speck G, Brizio-Molteni L, Molteni A.

Division of Plastic Surgery, Children's Memorial Hospital, Chicago, Ill., USA.

Plast Reconstr Surg 2000 Oct;106(5):1011-3 Abstract quote

The etiology of gynecomastia is unknown. There seems to be no increased incidence of malignancies in patients with idiopathic gynecomastia; however, patients with Klinefelter syndrome exhibit an increased incidence of malignancy.

The authors reviewed the results of 34 patients with gynecomastia diagnosed in adolescence who, following initial evaluation, had a mastectomy. The estrogen and progesterone receptors were analyzed in these patients. Three of the patients were diagnosed with Klinefelter syndrome. These three patients exhibited elevated amounts of estrogen and progesterone receptors. None of the patients who were not diagnosed with this syndrome demonstrated significant elevation of their estrogen or progesterone receptors. The presence of elevated estrogen and progesterone receptors in patients with Klinefelter syndrome provides a potential mechanism by which these patients may develop breast neoplasms.

The absence of elevated estrogen and progesterone receptors in patients with idiopathic gynecomastia may serve to clarify why these patients' disease rarely degenerates into malignancy.

PSA  

Immunohistochemical localization of prostate-specific antigen in ductal epithelium of male breast. Potential diagnostic pitfall in patients with gynecomastia.

Gatalica Z, Norris BA, Kovatich AJ.

Division of Surgical Pathology, John Sealy Hospital, University of Texas Medical Branch, Galveston 77555-0588, USA.

Appl Immunohistochem Mol Morphol 2000 Jun;8(2):158-61 Abstract quote

Enlargement of the male breast is frequently encountered in the course of adjuvant antiandrogen therapy for advanced prostate carcinoma. The clinical differential diagnosis in this setting includes hormonal imbalance-induced gynecomastia, primary breast carcinoma, and metastasis of prostatic carcinoma. Biopsy of the lesion with the identification of prostate-specific antigen (PSA) plays an important role in establishing the correct diagnosis. Recent studies showed that female mammary epithelium may be a significant source of PSA, but its expression in male breasts has not been sufficiently studied.

We found that normal and hyperplastic duct epithelium in gynecomastia exhibited focal, strong (+3) PSA immunoreactivity in 5 of 18 cases (28%). In contrast, no PSA reactivity was found in eight cases of male breast carcinoma. No reactivity was seen with antiprostatic acid phosphatase (PsAP) antibody, in either benign or malignant epithelium.

Frequent expression of PSA in gynecomastia may, in an appropriate clinical setting, cause confusion with metastatic prostatic carcinoma. The lack of immunoreactivity for PsAP in male breast epithelium indicates its usefulness in the differential diagnosis.

 

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES
DIABETIC MASTOPATHY  

Diabetic mastopathy in men: imaging findings in two patients.

Weinstein SP, Conant EF, Orel SG, Lawton TJ, Acs G.

Department of Radiology, University of Pennsylvania Medical Center, 3400 Spruce St, Philadelphia, PA 19104, USA.

Radiology 2001 Jun;219(3):797-9 Abstract quote

The classic imaging findings of diabetic mastopathy, an uncommon entity manifesting in patients with a history of long-standing insulin-dependent diabetes mellitus, have been reported in the literature in women but not, to the authors' knowledge, in men. Two men with diabetic mastopathy presented with palpable breast masses.

The clinical histories of the men in whom this condition was diagnosed were similar to those reported for women with the condition. The mammographic findings in both men, at presentation, were suggestive of gynecomastia.

GALACTOCELE  

Bilateral galactocele in a male infant: a rare cause of gynecomastia in childhood.

Cesur Y, Caksen H, Demirtas I, Kosem M, Uner A, Ozer R.

Department of Pediatrics, Faculty of Medicine, Yuzuncu Yil University, Van, Turkey.

J Pediatr Endocrinol Metab 2001 Jan;14(1):107-9 Abstract quote

A galactocele is a rare benign breast lesion usually occurring in females during or following lactation. These lesions are a rare cause of breast enlargement in infants and children.

In this article we present a 10 month-old boy who was admitted with a two-month history of bilateral progressive breast enlargement, and diagnosed as having galactocele.

Our purpose was to emphasize the importance of galactocele as a benign condition in the differential diagnosis of gynecomastia in childhood.

GRANULOCYTIC SARCOMA  

Acute myeloid leukemia relapsing as gynecomastia.

Au WY, Ma SK, Kwong YL, Lie AK, Shek WH, Chow WC, Liang R.

Department of Medicine, University Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong.

Leuk Lymphoma 1999 Dec;36(1-2):191-4 Abstract quote

Granulocytic sarcoma (GS) is an increasingly common relapse feature of acute myeloid leukemia (AML), late in the disease course or post bone marrow transplantation (BMT). Any solid organ can be affected, and there have been a number of reports of GS in breast tissue in female patients.

We present a unique case of GS in a male AML patient, presenting as painless gynecomastia immediately before BMT at advanced disease. Aberrant expression of CD56 was found in the relapsed GS tissue but not in the original AML clone. Twelve months after allogeneic BMT, leukemia relapsed again in the same breast, with normal marrow morphology and full donor chimerism. The lesion failed to respond to donor lymphocyte infusion, chemotherapy and radiotherapy, and disseminated to other subcutaneous tissues.

 

PROGNOSIS AND TREATMENT CHARACTERIZATION
PROGNOSTIC FACTORS  

Indications for and results of surgical therapy for male gynecomastia.

Colombo-Benkmann M, Buse B, Stern J, Herfarth C.

Department of Surgery, University of Heidelberg, Germany.

Am J Surg 1999 Jul;178(1):60-3 Abstract quote

BACKGROUND: The objective of our study was to analyze factors determining diagnostic versus cosmetic indication and postoperative results in the treatment of gynecomastia.

PATIENTS AND METHODS: Data from 100 patients and 141 breasts were analyzed retrospectively, and reevaluated by questionnaire (n = 81) and clinical examination (n = 33). Except for 2 patients, all underwent subcutaneous mastectomy through various incisions.

RESULTS: Diagnostic surgery was exclusively performed in unilateral, nodular gynecomastia being preferentially of grade I. Higher grade, bilateral gynecomastia led mainly to cosmetic surgery. Minor complications (skin retraction, hypertrophic scars, hypesthesia, skin redundancy) occurred in 53% of patients and significantly more often in grade III or II gynecomastia. Each incision was preferentially associated with specific sequelae. However, 86% of patients were satisfied with surgical results.

CONCLUSIONS: Laterality, consistency, grade, and age at onset of symptoms determine surgical indication. Despite the high number of sequelae due to preoperative grade and selected incision, most patients are satisfied with postoperative results.

TREATMENT  
DIHYDROTESTOSTERONE GEL  

Successful percutaneous dihydrotestosterone treatment of gynecomastia occurring during highly active antiretroviral therapy: four cases and a review of the literature.

Benveniste O, Simon A, Herson S.

Service de Medecine Interne, Groupe Hospitalier Pitie-Salpetriere, Paris, France.

Clin Infect Dis 2001 Sep 15;33(6):891-3 Abstract quote

Fourteen cases of gynecomastia occurring during highly active antiretroviral therapy (HAART) have been reported in the literature. To date, no specific therapeutic approach has been proposed, and gynecomastia has usually persisted.

We report 4 new cases of HAART-induced gynecomastia that were successfully treated with percutaneous dihydrotestosterone gel.

SUBCUTANEOUS MASTECTOMY  

Gynecomastia and the complete circumareolar approach in the surgical management of skin redundancy.

Persichetti P, Berloco M, Casadei RM, Marangi GF, Di Lella F, Nobili AM.

Department of Plastic and Reconstructive Surgery at Libera Universita-Campus Bio-Medico, Rome, Italy.

Plast Reconstr Surg 2001 Apr 1;107(4):948-54 Abstract quote

Gynecomastia is a benign enlargement of the male breast due to a physiological or pathological factor that interferes with the balance between estrogens and androgens in the serum. Gynecomastia itself requires no treatment unless the persistent enlargement of the male breast is a source of embarrassment and/or distress for the adolescent or adult man.

The indications for the surgical treatment of gynecomastia are founded on two main objectives: (1) the restoration of male chest shape and (2) diagnostic evaluation of suspected breast lesions.

The diagnostic evaluation begins with an adequate history and a thorough breast examination helped by laboratory tests and instrumental research. Several approaches for surgical treatment have been described in the literature. Some problems arise in patients who have significant enlargement and ptosis of the breast that will require skin reduction and in some patients requiring nipple-areola complex reduction. The authors believe that the complete circumareolar technique with purse-string suture creates the best aesthetic results, with fewer complications, in patients with moderate and severe ptotic glandular breast enlargements that have skin redundancy combined with areolar enlargement.

From 1995 through 1999, a total of 10 male patients with moderate to severe gynecomastia were treated surgically using a complete circumareolar approach. All patients achieved a good aesthetic contour of the chest. Only two patients required a revision of the circumareolar scar to correct postoperative enlargement.

Gynecomastia: complications of the subcutaneous mastectomy.

Steele SR, Martin MJ, Place RJ.

Department of Surgery, Madigan Army Medical Center, Fort Lewis, Washington 98431, USA.

Am Surg 2002 Feb;68(2):210-3 Abstract quote

Gynecomastia is a benign enlargement of the male breast secondary to gland proliferation. Subcutaneous mastectomy is performed for symptomatic patients and in those desiring cosmetic changes.

The aim of this study was to assess the risk factors and complications associated with the operation. We retrospectively examined the records of all patients undergoing a subcutaneous mastectomy for gynecomastia. Ninety-one patients were identified. We conducted telephone interviews with 52 patients and performed 65 subcutaneous mastectomies on those 52 patients.

Thirty of the 65 procedures (46%) developed complications. These included sensory changes, pain, seromas, scarring, breast asymmetry, hematomas, and wound infection. No preoperative risk factors were significant for postoperative complications. Eighteen of 22 cases with drains placed intraoperatively developed complications as compared with 12 of 43 cases without drains (P = 2.6 x 10(-7)). Specimens removed from the patients who had drains placed were significantly larger than those from patients who did not have drains placed (P = 1.5 x 10(-5)). However, specimen size was not an independent risk factor for development of a complication (P = 0.14).

We found a relatively high complication rate in subcutaneous mastectomy for gynecomastia. Most complications are minor with no long-term effect. Drain placement was the only risk factor associated with postoperative complications.

Rosai J. Ackerman's Surgical Pathology. Eight Edition. Mosby 1996.
Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.


Commonly Used Terms

Male Breast Disease


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