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Nuclear morphological characterisation of lobular carcinoma variants: a morphometric study
Ayaka Katayama1, Shorouk Makhlouf2,3, Michael S Toss2,4
1Diagnostic Pathology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Histopathology
|December 10, 2024
Summary
This study refines the diagnosis of pleomorphic lobular carcinoma (pLC) in breast cancer by establishing objective nuclear measurement criteria. These quantitative features improve the accuracy and reproducibility of pLC identification.
Area of Science:
- Oncology
- Pathology
- Digital Pathology
Background:
- Lobular carcinoma (LC) of the breast presents diverse morphology and clinical behavior.
- The pleomorphic variant (pLC) is more aggressive than classic LC (cLC), but its diagnosis is subjective.
- Refining diagnostic criteria for pLC is crucial for accurate patient management.
Purpose of the Study:
- To objectively define cytonuclear features distinguishing pleomorphic lobular carcinoma (pLC) from other lobular carcinoma (LC) subtypes.
- To establish quantitative thresholds for pLC diagnosis using digital image analysis.
- To identify distinct cytomorphological characteristics within pLC variants.
Main Methods:
- Analysis of whole slide images from 59 lobular carcinoma (LC) cases (in situ and invasive).
- Quantitative scoring of nuclear size, variability, and perimeter using QuPath image analysis software.
- Comparative analysis with normal cells and invasive breast carcinoma of no special type (IBC-NST), alongside visual assessment of 90 pLC cases.
Main Results:
- Pleomorphic invasive lobular carcinoma (pILC) exhibited larger nuclear area, higher nuclear variability, and more cytoplasm than classic ILC (cILC).
- Established cut-off values for differentiating pILC included median nuclear area > 48.2 μm², IQR > 19.4; nuclear perimeter median > 25.2 μm, IQR > 5.3; and maximum diameter > 9.1 μm, IQR > 2.2.
- Maximum nuclear diameter was the most significant independent predictor of pILC (P < 0.001); two pILC subtypes (apocrine and non-apocrine) were identified based on visual assessment.
Conclusions:
- Objective nuclear measurements, complemented by cytoplasmic and architectural features, offer a robust diagnostic framework for LC subtypes.
- Implementing these quantitative criteria enhances diagnostic accuracy and reproducibility for pleomorphic lobular carcinoma.
- This approach facilitates more precise classification and management of lobular carcinoma variants.
