micrometastases

Micrometastases are small clusters of cancer cells that have detached from a primary tumor and spread to distant sites, yet are too small to be detected by conventional imaging or routine histopathology. In pathology, micrometastases typically refer to tumor deposits measuring between 0.2 and 2 millimeters. Submicrometastases are smaller than 0.2 mm, and isolated tumor cells are very small clusters below that threshold. Their detection often requires techniques such as ultrastaging and immunohistochemistry.

Detection and staging: In many cancers, micrometastases are identified during surgical staging, commonly in sentinel lymph nodes. Standard H&E sections may miss them, so serial sectioning and immunohistochemical staining for cytokeratins, or molecular assays, are used to improve sensitivity. The presence of micrometastases can alter nodal staging and signals systemic dissemination even when imaging is negative.

Clinical relevance and biology: The prognostic significance of micrometastases varies by cancer type. In breast cancer, sentinel-node micrometastases can be associated with higher recurrence risk and may influence adjuvant therapy decisions. Some micrometastases remain dormant for years, influenced by immune surveillance and the microenvironment; others may later grow. Not all micrometastases progress to overt metastases.

Challenges and management: Detection is limited by sampling and thresholds. Ultrastaging increases detection but can raise questions about clinical relevance and risk of overtreatment. Management decisions are individualized, balancing potential systemic therapy benefits against toxicity and patient preferences. Ongoing research aims to clarify when micrometastases warrant treatment and how best to monitor patients.