Breast malignant, males, children
Male tumors
Male breast carcinoma - general

Author: Carlos C. Diez Freire, M.D. (see Authors page)
Editor: Shahla Masood, M.D.

Revised: 9 May 2018, last major update April 2018

Copyright: (c) 2001-2018, PathologyOutlines.com, Inc.

PubMed Search: Male breast carcinoma[TI] full text[sb]
Cite this page: Freire, C.C.D. Male breast carcinoma - general. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/breastmalignantmalecarcinoma.html. Accessed May 27th, 2018.
Definition / general
  • Male breast cancer is uncommon, accounting for less than 1% of all male cancers and 0.1% of male cancer deaths
  • Tends to occur at an older age than in women
  • Increasing incidence in U.S.
Essential features
  • Most are ductal carcinoma in situ or invasive ductal carcinoma
  • Most are ER+ and associated with BRCA2 gene mutations (Ann Oncol 2013;24:viii75)
Terminology
  • Invasive ductal carcinoma, ductal carcinoma in situ
ICD-10 coding
Epidemiology
  • Average age of onset of DCIS is sixth decade; for invasive carcinoma is seventh decade, although highest incidence occurs after age 85
  • Incidence is lower in Japanese and higher in African Americans from West Africa and United States when compared to whites from United States
  • 2x increased risk among first degree relatives of male breast cancer patients
Sites
  • Tend to be located centrally in retroareolar position and also in upper outer quadrants
Etiology
  • Associated with increased serum estrogen: liver disease, obesity, exogenous therapy, antiandrogen therapy
  • Associated with decreased serum androgen: Klinefelter syndrome, testicular injury / atrophy, occupational exposure to high temperatures
  • Drugs, exogenous agents: digitalis, tricyclic antidepressants, marijuana, lavender oil, tea tree oil
  • Radiation
  • Pituitary gland dysfunction: hyperprolactinemia
  • Hereditary: BRCA2 mutation carriers, PTEN mutation (Cowden syndrome), CHEK2 mutation carriers
Clinical features
  • Invasive carcinoma:
    • Average age of presentation is 60 to 70 years, although can present in younger men and children
    • ~75% of patients present with a palpable mass
    • Can also present with nipple retraction, ulceration or nipple discharge (serous); may be nodular and cystic
    • Time lapse between symptoms and clinical consultation varies from 6 months to 1 year
    • Tends to present with larger size and at a higher stage in men than in women
    • Lymph node metastases are more common in men than women
    • Axillary nodal staging is done by sentinel lymph node biopsy
    • History of breast cancer does not significantly affect the age or stage at time of diagnosis or the prognosis (Cancer 1999;86:821)
    • Tumors tend to be larger and at a higher stage in men than in woman
Diagnosis
  • Clinical presentation, imaging findings and ultimately image guided biopsies of the lesion provide an accurate pathologic diagnosis
Radiology description
  • No guidelines recommending mammographic screening for men have been established, even with documented genetic predisposition
  • Mammographic findings in men with breast cancer reveal distinct lesions with invasive margins that contrast sharply with the surrounding fatty tissue
  • Microcalcifications have been found in 9 - 30% of male breast carcinomas studied
  • Ultrasound: round mass with calcifications and papillary components like those seen in cystic or encapsulated papillary carcinoma
    • Can be used to differentiate gynecomastia from carcinoma
  • Inflammatory carcinoma of the male breast produces diffuse enlargement and thickening of the skin that can be detected by MRI
Prognostic factors
  • Poor prognostic factors: lymphatic tumor emboli, tumor size over 2 cm, poor histologic differentiation, HER2 overexpression, p53 expression, amplification of CCND1 (11q13)
  • Men with a prior diagnosis of breast carcinoma have a 30x increased risk of invasive carcinoma in the contralateral breast, increasing to 110x if the original diagnosis was before age 50
  • Death rate is higher among nonwhite U.S. men and lower 
among Japanese men
  • Most investigators believe men and women with the same stage disease have similar prognosis, but some believe men have poorer prognosis
  • AR+ luminal type A male breast cancer (ER+ HER2-, tumor grade 1/2) has better overall survival at 5 years but not 10 years compared to female breast cancer (Breast Cancer Res Treat 2012;133:949)
Case reports
Treatment
  • Treatment recommendations for male breast cancer are based on guidelines established for female breast cancer
  • Most men are treated with mastectomy and axillary lymph node dissection
  • Radiation, hormonal therapy and chemotherapy are also used
  • Breast conservation therapy may be possible, especially in older patients
  • Tamoxifen has less mortality when compared to aromatase inhibitors in men with stage I - III ER+ carcinoma (Breast Cancer Res Treat 2013; 137:465)
Gross description
  • Male breast cancers are grossly identical to female breast cancers; cystic papillary carcinomas can be striking
Gross images

Images hosted on other servers:

Intracystic papillary carcinoma

Microscopic (histologic) description
  • In situ carcinoma with papillary architecture is the most common pattern; also cribriform, micropapillary and solid patterns
  • Most (~85%) male breast carcinoma is poorly differentiated infiltrating ductal carcinoma, followed by papillary carcinoma and other types similar to female breast cancer
  • Lobular carcinoma represents 2% of cases
Microscopic (histologic) images

Scroll to see all images:


Images hosted on PathOut server:

Contributed by Semir Vranić, M.D., Ph.D.

Man with adenoid cystic carcinoma


c-kit

CK14



AFIP images:

DCIS solid type after estrogen for prostate cancer

Invasive carcinoma with cribriform pattern

Intracystic papillary carcinoma

Cystic papillary carcinoma with invasion



Images hosted on other servers:

DCIS, various

DCIS and invasive carcinoma

Invasive ductal and solid papillary carcinomas

Intracystic papillary carcinoma

Gynecomastia with chemoradiation induced atypia


Intracystic papillary DCIS

Nodal metastases


HER2+

Androgen receptor+

PSA+

p53+

Luminal B tumor

Various types

Cytology description
  • Reliable but underused
  • Dispersed epithelial cells with atypical features and high N/C ratio
  • Cell clusters can be present in papillary tumors
  • Gynecomastia present with sparsely cellular aspirate with loosely cohesive sheets of cells
Positive stains
  • ER (85 - 90%), PR (85%), AR (90 - 95%), BCL2 (94%)
  • Tumor cells are ER+, PR+, AR+ and frequently HER2-
  • Most male carcinomas are luminal type A and luminal type B
  • Younger patients (under 45 years) tend to have HER2+ tumors (Cancer 2013;119:1611) and older patients (over 65 years) are most likely to have ER+, PR+ and AR+ tumors
Negative stains
Electron microscopy description
  • Ssimilar to findings in female breast carcinoma
Molecular / cytogenetics description
  • p53 mutations in exon 6 found in over 90% of male cases compared to 33% of females with p53 mutations in exon 5 and 6 (Neoplasma 1996;43:305)
  • Gene expression performed in 66 male breast cancer tumors revealed 2 unique subgroups (luminal M1 and M2) that were different in biologic features and outcome when compared to female breast cancers (Breast Cancer Res 2012;14:R31)
  • EGFR and CCND1 genes are amplified more in male than female breast cancers
  • High methylation status of MSH6, WT1, PAX5, PAX6, GATA5 and CDH13 correlates with more aggressive phenotype and poor survival
    • Male and female breast cancers share many of these methylated genes but many genes are less frequently methylated in males
  • Methylation of RASSF1A (downregulation of ER alpha and micro RNAs) is more common in male than female breast carcinomas
Differential diagnosis
Board review question #1
What is the most common type of male breast carcinoma?

  1. Invasive lobular carcinoma
  2. Invasive papillary carcinoma
  3. Mucinous carcinoma
  4. Poorly differentiated invasive ductal carcinoma
  5. Well differentiated invasive ductal carcinoma
Board review answer #1
D. Poorly differentiated invasive ductal carcinoma. Approximately 85% of male breast carcinomas are poorly differentiated infiltrating ductal carcinomas, followed by papillary carcinomas and other forms similar to those found in female breast cancer. Lobular carcinomas represent 2% of cases.