Description
Medullary carcinoma (MC) is a rare subtype of invasive ductal carcinoma (IDC) of the breast, accounting for 3-6% of all breast cancers and 10% of those in women under 35. It is characterised by the presence of five specific histologic features in ≥90% of the tumour: syncytial pattern (>75%), circumscribed pushing borders, marked lymphoplasmacytic infiltrate, high nuclear grade and mitotic count, and absence of gland formation. This type of carcinoma often exhibits triple-negative features (ER-, PR-, HER2-) and is associated with BRCA1 mutations. As with most special subtypes, survival is better than invasive ductal carcinoma of no special type (IDC NST). The term “medullary” is derived from the Latin word for marrow, reflecting its soft consistency compared to other breast carcinomas.
Pathogenesis
Medullary carcinoma arises from the epithelial cells lining the mammary ducts. It is characterised by the lack of a desmoplastic stroma, which contributes to its softer consistency. The pathogenesis involves mutations in the TP53 gene, commonly seen in basal-like cancers. The high prevalence of BRCA1 mutations in MC patients suggests a genetic predisposition, influencing tumour development and progression. The tumour’s immune microenvironment, rich in lymphoplasmacytic infiltrate, plays a significant role in its pathology and potentially its response to therapy.
Subtypes
- Typical Medullary Carcinoma: All five histologic features are present.
- Atypical Medullary Carcinoma: Lacks at least one of the five key features and is often classified as IDC, NOS with medullary features.
Epidemiology, Risk Factors & Associations
- Predominantly affects women aged 30-86 (mean age: 54).
- Rare in males.
- More common in Japanese and African American populations.
- Genetic Associations:
- BRCA1 mutations: Present in 25% of sporadic MC cases.
- BRCA1-associated cancers: 16% show medullary histology.
- Rare in BRCA2
- Family History: Significant in patients with BRCA1 mutations.
Clinical Features
- Enlarging, soft, and palpable breast mass.
- Axillary adenopathy, often reactive rather than metastatic.
- Typically presents as a circumscribed, oval, or lobulated mass without calcifications.
Complications
- Metastasis is less common than IDC NST; when present, involves fewer axillary nodes.
Pathological Features
Histopathology
- Macroscopic: Ovoid or lobulated, soft mass, median size 2-3 cm.
- Microscopic:
- Syncytial growth pattern – neoplastic cells are grouped in broad, cohesive sheets without distinct cell borders
- Pushing borders.
- Marked lymphoplasmacytic infiltrate.
- High nuclear grade with frequent mitoses.
- Absence of gland formation.
Serology
- Triple-negative phenotype (ER-, PR-, HER2-).
- Positive for basal markers CK5/6.
Biochemistry
- High mitotic rate and presence of TP53 mutations.
Radiological Features
General Features
- Mostly circumscribed, non-calcified mass on mammogram
- Upper outer quadrant most common
- Satellite masses and axillary adenopathy common (may be hyperplastic or neoplastic nodes)
- Rapid growth
Mammography
- Oval, round, or lobular mass with mostly circumscribed margins.
- Non-calcified; may have indistinct margins.
US
- Hypoechoic mass with posterior enhancement (pseudocystic appearance)
- Thick echogenic rim of peritumoral oedema
- Large lesions may show cystic areas due to necrosis
CT
- Not typically used for primary diagnosis but can assess extent and metastasis.
MRI
- T1: Rim-enhancing mass.
- T2: May show cystic components in necrotic areas.
- DWI/ADC: Useful in differentiating from other breast lesions.
Diagnosis
- Requires presence of all five histologic features.
- Core biopsy may suggest diagnosis; complete excision required for definitive diagnosis.
Differential Diagnosis
- Circumscribed Breast Cancer: IDC NST, mucinous carcinoma, encapsulated papillary carcinoma.
- Primary Breast Lymphoma: Mixed echogenicity on ultrasound.
- Fibroadenoma: Common in women under 35; circumscribed mass.
- Phyllodes Tumour: Hypoechoic mass with cystic spaces.
Management
- Referral to oncology and breast surgery.
- Standard treatment includes lumpectomy, radiation therapy, and chemotherapy based on size and nodal status.
- Genetic testing for BRCA1 mutations recommended.