Definition/General

Introduction:
-Male breast cancer is a rare disease, accounting for less than 1% of all breast cancers and less than 1% of all cancers in men
-The vast majority are invasive ductal carcinomas.
Origin:
-Similar to female breast cancer, it arises from the epithelial cells of the breast ducts
-The terminal duct-lobular units are rudimentary in males, so lobular carcinoma is very rare.
Classification:
-The histological types are similar to those in females, with invasive ductal carcinoma, no special type, being the most common (85-90%)
-DCIS is also seen
-Lobular carcinoma is extremely rare.
Epidemiology:
-The incidence increases with age, with a peak in the late 60s and 70s
-Risk factors include genetic predisposition (BRCA2 mutations), conditions causing hyperestrogenism (e.g., Klinefelter syndrome, liver disease), and radiation exposure.

Clinical Features

Presentation:
-Typically presents as a painless, subareolar mass
-Nipple retraction, skin ulceration, and bloody nipple discharge are more common than in females
-Due to the small amount of breast tissue, it can invade the skin and chest wall earlier.
Symptoms:
-A palpable lump is the most common symptom
-Pain, nipple changes, and skin changes can also occur
-Axillary lymphadenopathy is present in about 50% of cases at diagnosis.
Risk Factors:
-BRCA2 gene mutations are a significant risk factor
-Klinefelter syndrome (XXY)
-Family history of breast cancer
-Obesity
-Chronic liver disease
-Testicular conditions.
Screening:
-There are no routine screening recommendations for men
-Diagnosis is usually made after a man presents with symptoms
-A high index of suspicion is needed for any breast mass in a male.

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Gross Description

Appearance:
-Usually a firm, irregular mass located in the subareolar region
-The cut surface is gray-white and gritty
-Fixation to the skin or underlying muscle may be present.
Characteristics:
-The tumors are often centrally located
-Size is variable but they tend to be diagnosed at a slightly larger size than in females.
Size Location:
-Central/subareolar location is most common
-Size can range from small to large.
Multifocality: Multifocality is uncommon.

Microscopic Description

Histological Features:
-The histology is predominantly that of invasive ductal carcinoma, no special type
-The tumor cells form nests, cords, and glands infiltrating a desmoplastic stroma
-The features are similar to IDC in females.
Cellular Characteristics:
-The tumor cells are pleomorphic with high-grade nuclei and prominent nucleoli
-Mitotic figures are frequent.
Architectural Patterns:
-The patterns are similar to IDC in females, including solid, cribriform, and papillary patterns
-An associated DCIS component is common.
Grading Criteria:
-The Nottingham grading system is used, just as in female breast cancer
-Most male breast cancers are Grade 2 or 3.

Immunohistochemistry

Positive Markers:
-A very high percentage of male breast cancers are positive for Estrogen Receptor (ER) and Progesterone Receptor (PR) (>90%)
-Androgen Receptor (AR) is also frequently positive.
Negative Markers:
-HER2 overexpression is less common than in females (about 5-15%)
-Triple-negative breast cancer is rare in males.
Diagnostic Utility:
-IHC is essential for determining hormone receptor and HER2 status, which guides therapy
-Distinguishing from metastasis from other sites (e.g., prostate cancer with PSA) can be necessary.
Molecular Subtypes: The vast majority of male breast cancers are of the Luminal A or Luminal B subtypes.

Molecular/Genetic

Genetic Mutations:
-BRCA2 mutations are found in about 10-15% of cases
-BRCA1 mutations are less common
-PALB2 is another important susceptibility gene
-Somatic mutations in PIK3CA and TP53 are also found.
Molecular Markers: The genomic landscape is similar to that of ER-positive female breast cancer.
Prognostic Significance:
-The prognosis is generally similar to that of female breast cancer when matched for stage
-However, men are often diagnosed at a later stage, which contributes to a worse overall outcome
-Lymph node status is the most important prognostic factor.
Therapeutic Targets:
-Endocrine therapy (tamoxifen is the standard of care) is the mainstay of treatment due to high ER/PR positivity
-Chemotherapy and radiation are used based on stage and risk factors
-HER2-targeted therapy is used for HER2-positive cases.

Differential Diagnosis

Similar Entities:
-Gynecomastia
-Metastatic carcinoma (e.g., from prostate, lung)
-Benign breast lesions (rare in men).
Distinguishing Features:
-Gynecomastia shows ductal hyperplasia without atypia and a characteristic periductal stromal proliferation
-Metastatic tumors will have a different IHC profile (e.g., PSA positive for prostate cancer).
Diagnostic Challenges:
-The main challenge is the low index of suspicion for breast cancer in men, leading to delayed diagnosis
-Differentiating from gynecomastia with atypia can sometimes be difficult on small biopsies.
Rare Variants:
-Papillary carcinoma is a relatively more common special subtype in men compared to women
-Lobular, medullary, and mucinous carcinomas are very rare.

Sample Pathology Report

Template Format

Sample Pathology Report

Complete Report: This is an example of how the final pathology report should be structured for this condition.

Specimen Information

[specimen type], measuring [size] cm in greatest dimension

Diagnosis

[diagnosis name]

Classification

Classification: [classification system] [grade/type]

Histological Features

Shows [architectural pattern] with [nuclear features] and [mitotic activity]

Size and Extent

Size: [X] cm, extent: [local/regional/metastatic]

Margins

Margins are [involved/uninvolved] with closest margin [X] mm

Lymphovascular Invasion

Lymphovascular invasion: [present/absent]

Lymph Node Status

Lymph nodes: [X] positive out of [X] examined

Special Studies

IHC: [marker]: [result]

Molecular: [test]: [result]

[other study]: [result]

Final Diagnosis

Final diagnosis: [complete diagnosis]