The principle of sentinel lymph node (SLN) biopsy is to identify a small number of lymph nodes that have the greatest risk of metastatic tumor involvement in a certain anatomical location. This enables more intensive pathological processing (ultrastaging) of a few selected lymph nodes instead of routine processing of a larger number of nodes, enabling the detection of small-sized metastases that may be missed by standard processing [1,2].

In gynecological cancers, SLN biopsy with ultrastaging increases nodal metastasis detection across various tumor types and stages [[2], [3], [4]]. Therefore, in most situations, SLN biopsy should not be regarded as an alternative but rather a preferred strategy as it was shown that additional lymph node removal does not improve staging accuracy and SLN biopsy alone yields similar survival with lower morbidity [[5], [6], [7], [8]]. In gynecological oncology, suitable tumor sites with evidence to support its use include the cervix, endometrium and vulva [[9], [10], [11]].

With the increasing use of SLN biopsy, more cases of low volume metastases, including micrometastases (MIC) and isolated tumor cells (ITCs), will be encountered [12]. Many studies have shown a worse prognosis in patients with MIC in cancers of various sites, and the presence of MIC is considered nodal positivity (N1) by the FIGO and TNM classifications [13]. However, the prognostic significance of ITCs remains controversial. Their presence is recorded as N0(i+) and guidelines mostly provide no or very weak recommendations with regard to patient management. This is the result of conflicting and weak data in the literature and leads to heterogeneous clinical management [14,15].

The aim of this paper is primarily to emphasize that the current classification of lymph node macrometastases (MAC), MIC and ITCs based on size cut-offs is neither evidence based nor clinically relevant. We also discuss that cases with ITCs are too rare and ITCs are too small to be reliably detected in all cases, and therefore it will remain challenging to fully assess their prognostic impact. Although this review discusses gynecological malignancies with a focus on cervical cancer, the same principles also apply to other sites. Acknowledging these limitations, the international guidelines should provide solutions for managing cases with ITCs in SLN.