D4 Biopsy and histopathology

Topic

Biopsy and histopathological analysis constitute the gold standard for oncological diagnosis: no single imaging finding—whether computed tomography, magnetic resonance imaging, or positron emission tomography—nor any blood-based biomarker is sufficient on its own to initiate cancer treatment without histological confirmation of the tumor.

There are only two very specific exceptions to this requirement for histological confirmation: hepatocellular carcinoma in a patient with cirrhosis, where the lesion exceeds two centimeters and meets strict imaging criteria; and glioma presenting a characteristic appearance on MRI in a patient with an inoperable tumor. Apart from these two exceptions, histological confirmation remains indispensable.

Histopathology does more than simply confirm malignancy; it defines the tumor's histological subtype and grade of aggressiveness, determines whether the margins of the resected specimen are tumor-free, and provides the biological material necessary for a more detailed molecular diagnosis.

Fundamentally, the physics of a biopsy involves taking a spatial sample from a non-uniform system: tumors exhibit intratumoral heterogeneity—meaning distinct zones within the same tumor may possess different biological characteristics—so a biopsy taken from a single area may not accurately represent the tumor's biology as a whole.

To address this intratumoral heterogeneity, two strategies have been developed to capture the tumor's profile more effectively than a single biopsy: multi-region biopsy, which samples several distinct zones of the tumor rather than just one; and liquid biopsy, which detects genetic material in the patient's blood released by the tumor from all its regions simultaneously, independent of the specific site where the sample was taken. Thus, biopsy and histopathological examination remain the indispensable confirmation of an oncological diagnosis, even though the tumor itself—whose presence they confirm—is not, in reality, a uniform entity.

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