Medullary Carcinoma

Key Facts

Terminology

Medullary carcinoma (MC)
- Rare subtype of invasive breast cancer with characteristic histologic features

Etiology/Pathogenesis

Many MCs downregulate BRCA1 either by promoter methylation (2/3) or mutation (1/4)
MC is member of basal-like group of breast carcinomas by gene expression profiling
- Typically negative for ER, PRP, and HER2
- Majority have TP53 mutations

Clinical Issues

MC, when strictly defined by morphologic criteria, has favorable prognosis
- Actuarial 10-year survival rates greater than 80% in some reports
Usually presents as palpable, often rapidly growing mass
Improved survival may be due to host immune response, syncytial growth pattern, &/or high mitotic rate leading to increased sensitivity to therapy

Top Differential Diagnoses

Atypical medullary carcinoma (AMC)
Carcinomas arising in women with BRCA1 mutations
- 13% have MC and 30-60% have carcinomas with medullary features
Intramammary nodal metastasis
Lymphoma

The diagnosis of medullary carcinoma requires that the carcinoma be well circumscribed

and associated with a prominent lymphoplasmacytic infiltrate

The carcinoma has a “syncytial growth” pattern with broad anastomosing sheets of tumor cells

with indistinct cell borders, pleomorphic high-grade nuclei, and frequent mitoses.

TERMINOLOGY

Abbreviations

Definitions

Rare histologic subtype of invasive breast cancer with characteristic histologic features
“Medullary” was applied to these carcinomas in 19th century based on their gross appearance
- “Medullary” refers to marrow of bones, signifying soft mass
- “Encephaloid” (resembling brain) was alternative term
- Lack of desmoplastic stroma resulting in soft consistency distinguishes MC from other carcinomas that are hard or scirrhous

ETIOLOGY/PATHOGENESIS

Molecular Pathology of MC

Syncytial growth pattern is critical for diagnosis and is linked to prognosis
- MC has increased expression of cell adhesion proteins including E-cadherin and β-catenin
- Tight cell adhesion may limit tumor cell dissemination via lymphatics correlating with fewer nodal and distant metastases
Many MC downregulate BRCA1
- Approximately 25% of apparent sporadic MC have BRCA1 mutations
- Approximately 2/3 of MCs without BRCA1 mutations have downregulation due to promoter methylation
- In turn, MC accounts for 13% of breast tumors arising in BRCA1 mutation carriers
  - 30-60% of carcinomas in BRCA1 mutation carriers have medullary features
  - Medullary features rare in women with BRCA2 mutations
Gene expression profiling
- MC is member of basal-like group of breast carcinomas
- MC has higher level of expression of CK5/6 and higher rates of gains and losses of DNA as compared to other basal-like carcinomas
- Most basal-like carcinomas have poor prognosis
  - MC is exception as it has more favorable prognosis compared to carcinomas of no special type when strict diagnostic criteria are applied

CLINICAL ISSUES

Epidemiology

Incidence
- MC represents 1-7% of all invasive breast cancers
  - Differences in incidence likely related to stringency of criteria used to make diagnosis
Age
- Average age at presentation: 45-52 years
  - Compared with 55 years for patients with IDC, not otherwise specified

Presentation

Most patients present with palpable mass
- May be soft and mobile and perceived as benign
- Often grows rapidly
Lymphadenopathy may be present
- Lymph nodes may be enlarged due to hyperplasia; metastases are uncommon

Treatment

Adjuvant therapy
- Some medical oncologists take more conservative approach for MC due to favorable prognosis
- However, favorable prognosis may not apply to large cancers or cancer in women with BRCA1 mutations
- Therefore, strict criteria should be used for diagnosis to avoid undertreating patients with poorly differentiated carcinoma of no special type

Prognosis

Tags: Diagnostic Pathology: Breast

Jul 6, 2016 | Posted by drzezo in PATHOLOGY & LABORATORY MEDICINE | Comments Off

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