A Practical Approach to the Differential Diagnosis of Intracranial Tumors: Gross, Histology, and Immunoprofile-based Algorithm

Intracranial tumors are a diverse group of conditions, both benign and malignant, primary and metastatic and always require detailed medical information, radiological reports and deep knowledge of the histological hallmarks and immunohistochemical profile of different types of tumors and tumor-like processes. Despite it clinically often being possible to differentiate between primary and metastatic tumors, based on the tumor location and age of the patient, histological variants and rare tumor entries should always be considered in the histological differential diagnosis. A thorough diagnostic algorithm based on the location of the tumor and its histological features, together with some common pitfalls in immunohistochemical profiling, based on the 2016 revised World Health Organization (WHO) classification of tumors of the central nervous system should be implemented in all cases. Such an algorithm is especially valuable in cases where only small tumor fragments are sent for morphological evaluation, such as in deep parenchyma tumors. In these instances where only small fragments of the tumor are present for histology, some key features, corresponding to the WHO grade, may easily be missed or underreported. Furthermore, the histological verification of the tumor entry is the first, often overlooked, step in defining the presence or absence of WHO grade-specific mutations.