Immunohistochemistry in the Diagnosis and Classification of Breast Tumors

Overview of Immunohistochemistry in Breast Pathology

• Immunohistochemistry (IHC) is a key technique in diagnosing and classifying breast lesions.

• Aims to summarize commonly used and newly established IHC stains for breast lesions.

• Focuses on the roles of IHC in identifying invasive and non-invasive lesions, as well as benign and malignant spindle cell lesions.

• Understanding the strengths and limitations of IHC markers is crucial for effective clinical practice.

Histologic Classification of Breast Carcinomas

Ductal Carcinomas

• Ductal Carcinoma In Situ (DCIS): Managed surgically with the goal of complete excision.

• Invasive Ductal Carcinoma (IDC): Histologically characterized by cohesive cell arrangements and defined borders.

• IHC supports the diagnosis by differentiating DCIS from invasive forms.

Lobular Carcinomas

• Lobular Carcinoma In Situ (LCIS): Often managed conservatively unless concerning features are present.

• Invasive Lobular Carcinoma (ILC): Exhibits different molecular traits than IDC, less sensitive to chemotherapy, and a tendency for multifocality.

• Histologically shows small, discohesive cells and lacks defined tubules/papillae.

• Key marker for lobular carcinoma: Loss of E-cadherin expression (CDH1 gene).

  • E-cadherin contributes to cell-cell adhesion, hence its loss is significant for diagnosis.

Common IHC Stains in Ductal vs. Lobular Carcinomas

• E-cadherin: Typically positive in ductal carcinomas, negative in lobular carcinomas.

• p120 Catenin: Shows cytoplasmic expression in lobular carcinoma, while remaining membrane-bound in ductal types.

• β-Catenin: Loss in lobular carcinoma and may misinterpret ductal carcinoma if its expression is reduced.

Classification of Spindle Cell Lesions

Benign Reactive Spindle Cell Tumor-like Lesions

• Reactive Spindle Cell Nodule: Develops post-operatively, characterized by spindle-shaped cells with minimal mitotic activity.

• Nodular Fasciitis (NF): Rapidly growing, benign, self-limiting lesion that may appear in various forms.

• Inflammatory Pseudotumor: Reactive lesion due to trauma or inflammatory stimulus, shows spindled myofibroblasts.

• Pseudoangiomatous Stromal Hyperplasia (PASH): Characterized by myofibroblast proliferation resulting in pseudovascular spaces.

Benign Spindle Cell Neoplasms

• Myofibroblastoma: Benign, slow-growing tumor in mammary stroma, characterized by bland spindle cells.

• Others: Leiomyoma, spindle cell lipoma, and solitary fibrous tumors can occur in the breast with histologic similarities to soft tissue counterparts.

Low-Grade Locally Aggressive or Malignant Spindle Cell Neoplasms

Desmoid Fibromatosis

• Locally aggressive, non-metastatic with high recurrence potential, can mimic carcinoma on imaging.

Malignant Phyllodes Tumor

• Often difficult to distinguish from metaplastic carcinoma due to overlapping features; IHC aids in diagnosis.

High-Grade Malignant Spindle Cell Neoplasms

Metaplastic Spindle Cell Carcinoma (SpCC)

• Can present as large, firm masses with mixed features of carcinoma; requires broad-spectrum IHC for accurate diagnosis.

Metastatic Neoplasms

• Rare and can resemble primary breast tumors; key markers for metastatic origins include CD31, D2-40, and others.

Evaluation of Invasion in Breast Cancer

• Invasion distinguished by the breach of the myoepithelial layer; IHC staining of myoepithelial markers assist in differentiating benign and malignant lesions, particularly in sclerosing lesions.

Diagnostic Markers for Breast Carcinoma

• IHC markers such as GCDFP-15, mammaglobin, GATA3, SOX10, and TRPS1 are critical in differentiating breast carcinomas from other neoplasms.

• GATA3 is recognized for its high sensitivity and utility in identifying breast cancer origins.

Highlights of New Markers

• TRPS1: Highly sensitive and specific for various breast cancers, particularly useful in diagnosing triple-negative breast cancer.

• SOX17: Identified as a potential discriminator between breast and ovarian carcinomas based on expression patterns.

Conclusion

• IHC is essential in breast pathology for diagnosis and classification, but H&E staining remains the primary diagnostic tool.

• Marker selection and understanding their sensitivity and specificity are paramount for accurate clinical evaluations.