Immunohistochemical Markers in Spindle Cell Neoplasms

Introduction to Diagnostic Markers

The European Respiratory Society recommends using EMA to identify epithelioid mesothelioma and distinguish it from adenocarcinoma when used in a panel 1.
The National Comprehensive Cancer Network suggests that broad-spectrum cytokeratins should be positive while S100, HMB45, and CD45 remain negative to confirm carcinomatous tumors 2.

The National Comprehensive Cancer Network states that p63 is highly specific for squamous differentiation, with 86% of poorly differentiated squamous cell carcinomas showing immunoreactivity 3, 4.
The American College of Chest Physicians recommends using p40 (ΔNp63 isoform) for squamous differentiation due to its 100% sensitivity and specificity 5.
The National Comprehensive Cancer Network notes that 70-95% of urothelial carcinomas express p63, while mesotheliomas are consistently negative 3, 4.

The College of American Pathologists states that S100 is the primary marker for melanocytic and neural differentiation, showing high sensitivity for melanoma and peripheral nerve sheath tumors 6.
The College of American Pathologists recommends using S100 positivity combined with SOX10 nuclear staining to indicate melanocytic origin 6.
The National Comprehensive Cancer Network notes that decreased S100 expression in neurofibromatosis type 1 suggests higher-grade lesions (MPNST) rather than benign neurofibroma 6.

The National Comprehensive Cancer Network states that CD34 positivity suggests fibroblastic, vascular, or specific spindle cell tumor origins, but has limited specificity 7.
The European Respiratory Society recommends using CD34 as a negative marker to confirm sarcomatoid mesothelioma 1.

The National Comprehensive Cancer Network recommends a sequential diagnostic approach, starting with a first-line screening panel of broad-spectrum cytokeratin, S100/SOX10, and CD45 6.
The American College of Chest Physicians suggests adding p63 (or preferably p40) to confirm squamous differentiation versus adenocarcinoma 5.
The College of American Pathologists recommends using a minimal, targeted panel rather than extensive immunohistochemistry to preserve tissue for molecular studies 8, 5.