Medullary Breast Carcinoma

👉 Introduction

• Medullary carcinoma is a very rare and distinct subgroup of breast carcinomas:
  • Accounting for less than 5% (some series 5% to 7%) of all invasive breast cancers
• This unique histologic subtype has very strict criteria for diagnosis, including:
  • Complete circumscription
  • Syncytial growth pattern of at least 75% of the tumor
  • Intermediate to high nuclear grade
  • An associated diffuse lymphocytic infiltrate
  • A lack of intraductal components or glandular differentiation

👉 Etiology

• It has been well established that both medullary carcinoma and invasive ductal carcinoma with medullary features are associated with:
  • Germline mutations in the BRCA1 gene

• Among BRCA1-associated breast cancers:
  • 7.8% to 19% are medullary carcinomas
  • 35% to 60% show the presence of medullary features:
    • This rate contrasts with the presence of only 2% medullary carcinomas:
    • • Among sporadic, non–BRCA-associated tumors

• Medullary carcinoma:
  • Has been shown to display the basal-like molecular subtype:
    • By gene expression profiling:
  • Which correlates with its immunophenotypic profile:
    • A high incidence of TP53 gene mutation also presents in these tumors

• Most cases are:
  • Aneuploid with a high S-phase fraction
• Array-based comparative genomic hybridization analysis:
  • Has demonstrated a recurrent pattern of chromosomal alterations in medullary carcinoma, including:
  • • 1q, 8q, 9p, 10p, and 16q gains
  • • 4p and X losses
  • • 1q, 8p, 10p, and 12p amplifications

👉 Epidemiology

• The patient’s age at presentation is younger than that for invasive ductal carcinoma NST:
  • With a mean age:
    • Ranging from 45 to 54 years

• Medullary carcinoma is unicentric in most of the patients:
  • Bilateral carcinomas:
    • Have an incidence ranging from 3% to 18%:

• • • • Bilateral tumors are common when a family history is present

• Typical medullary breast carcinoma:
  • Occurs more frequently in patients with mutations of:
    • The tumor suppressor gene BRCA-1

👉 Pathophysiology

• Medullary carcinoma:
  • Has been shown to contain an increased number of activated cytotoxic lymphocytes and most of the lymphoid infiltrate consists of T cells:
    • This feature reflects an active host response to the tumor and may account for its favorable prognosis

• Medullary carcinoma is well circumscribed and moderately firm
• The cut surface is fleshy and gray-tan and may appear lobular or nodular
• Foci of hemorrhage, necrosis, and even cystic degeneration are not unusual
• These tumors tend to be smaller than 3 cm:
  • With a median size of 2 cm to 3 cm

• The histologic criteria for medullary carcinoma:
  • Were first clearly defined by Ridolfi and associates in 1977, and since then, there have been several proposed modified classification schemes
• The diagnosis of medullary carcinoma in the majority of cases:
  • Is established based on H&E sections using histologic criteria without the need for ancillary studies
• Medullary carcinoma should meet all of the following five morphologic criteria as defined by the WHO:
  • Syncytial growth pattern in more than 75% of the tumor
  • No glandular or tubular structures, even as a minor component
  • Moderate to marked diffuse lymphoplasmacytic infiltrate in the stroma
  • Moderate to marked nuclear pleomorphism
  • Complete histologic circumscription
  • Mitoses are numerous, and atypical giant cells may be present;
    • The terms ”atypical medullary carcinoma” and ”carcinoma with medullary features” have been proposed for tumors that do not fulfill all these criteria

👉 History and Physical

• Most of the patients with medullary carcinoma present with a palpable mass:
  • Usually in the upper outer quadrant
• The tumor is often well-defined clinically and on imaging studies
• Some patients with this tumor type exhibit axillary lymphadenopathy at the time of presentation, suggesting the presence of metastatic disease