Diagnostic Pitfalls in Breast Cancer Pathology With an Emphasis on Core Needle Biopsy Specimens

Introduction

• Diagnostic pitfalls in breast cancer pathology are numerous and can have significant management implications.

• Ductal carcinoma in situ (DCIS) and invasive breast carcinomas present challenges in diagnosis, particularly with core needle biopsy (CNB) specimens.

• Awareness of these pitfalls can aid in creating differential diagnoses and improve accurate classifications and management.

Objective

• The purpose is to highlight diagnostic challenges and provide histologic clues and guidance on using immunohistochemistry for accurate diagnosis.

Ductal Carcinoma in Situ (DCIS)

Overview

• DCIS is characterized by malignant intraductal epithelial proliferation of varying nuclear grades (low, intermediate, high).

• Features range from architectural forms including solid, cribriform, micropapillary, and more.

• Wide variability in lesions can mimic DCIS, complicating diagnosis.

Key Diagnostic Pitfalls

1. Distinction Between UDH and Intermediate-Nuclear-Grade DCIS

   • Usual Ductal Hyperplasia (UDH) may mimic intermediate-grade DCIS; careful evaluation of morphology is essential.

   • Key features:

     • UDH shows polymorphous epithelial cells, often with distinct cytological characteristics.

     • Intermediate-grade DCIS is typically more uniform with less architectural organization.

2. DCIS vs. Lobular Carcinoma In Situ (LCIS)

   • High-grade DCIS may resemble the pleomorphic variant of LCIS or vice versa, making distinction crucial.

   • Classic LCIS lacks the architectural atypia seen in DCIS and is characterized by dyshesion due to E-cadherin loss.

   • Diagnostic clues include looking for microacini or rosette formations in DCIS.

3. Necrosis as a Diagnostic Feature

   • Necrosis can complicate diagnosis; while often associated with DCIS, can be present in UDH, leading to potential misclassification.

   • Immunostaining with estrogen receptor (ER) and CK5/6 can be helpful:

     • DCIS shows strong ER positivity and CK5/6 negativity.

     • UDH presents variable expression.

Indicators of DCIS vs. LCIS

• Immunohistochemical Clues:

  • ER positivity in DCIS with a mosaic staining pattern seen in UDH.

  • Clues to focus on when necrosis is evident.

  • Background atypical proliferations in breast tissue can assist in the differentiation of these lesions.

Managing Implications of Misdiagnosis

• A misdiagnosis of DCIS may result in unnecessary surgical interventions and treatments, whereas UDH may require no further management.

• Critical to differentiate accurately to prevent overtreatment or undertreatment of patients.

Cribriform Lesions and Other Mimics

• Collagenous spherulosis may mimic cribriform DCIS patterns.

• Adenoid cystic carcinoma shows similar patterns but features distinctive nuclear arrangements and fewer infiltrative characteristics.

• Papillary lesions can also overlap with DCIS; distinguishing features rely on the presence or absence of myoepithelial cells in the architecture.

Additional Diagnostic Considerations

1. Lymphovascular Invasion (LVI) vs. DCIS

   • The presence of tumor nests in lymphovascular spaces can mimic DCIS; recognizing distribution and utilizing myoepithelial cell markers can clarify diagnosis.

2. Papillary Carcinoma

   • Encapsulated papillary carcinomas and solid papillary carcinomas may often present indistinctly.

   • Need for careful differentiation using immunostains and morphologic characteristics.

3. Triple-Negative Breast Carcinomas (TNBC)

   • high-grade TNBC must differentiate from other high-grade carcinomas.

   • Considering clinical history and immunostaining helps avoid misclassification.

Conclusion

• Accurate recognition of diagnostic pitfalls in breast pathology, particularly from CNB, requires a strong understanding of morphologic features and the appropriate application of immunohistochemistry to aid in preventing misdiagnosis.

• Descriptive diagnoses with recommended excisions for definitive assessments are critical to ensure accurate patient management.