Is It Time to Develop an ‘Ultrastaging System’ for Use in Patients With Head and Neck Malignancies?

INTRODUCTION The principal challenge faced by the head and neck oncologist in practice today has changed little over the past several decades, namely, that challenge continues to be, as it always has been, to find a consistently successful means of managing and eradicating not just primary neoplastic lesion, but both recurrent and metastatic disease as well. Despite the fact that head and neck cancers have been the focus of a variety of intensive investigative programs in centers across the world, the regrettable truth at present remains, that clinicians’ ability to cure many of their cancer patients, remains an elusive thing indeed. Most would agree that a comprehensive multidisciplinary approach to the evaluation of patients with head and neck cancers is absolutely essential for accurate classification, staging, and prediction of patient outcomes. Pierre Denoix in France developed the tumor, node, metastases (TNM) system for classification of malignant tumors between 1943 and 1952. Two of the most recent staging classification systems are the scheme crafted by the International Union Against Cancer (UICC) and that of the American Joint Committee on Cancer (AJCC). When the most recent revisions of these two staging classification systems were published in 1997, they had grown virtually identical to one another. Recently Hermanek et al. proposed that the staging system of the UICC/AJCC be modified again to include a designation of both the presence and absence of micrometastases, as well as the presence of isolated tumor cells found in general circulation (blood, bone marrow, other distant sites). Cases with only micrometastases might, in such a scheme, be identified by the addition of “(mi)” to the pN and/or pM category (e.g., pN1 [mi] or pM1 [mi]) (see Table I). As a practical matter, one wanting to use such an “ultrastaging” system would be well advised to formally identify the precise pathological methods of evaluation used to arrive at the classification. It is virtually certain that more sensitive detection modes (for example, immunocytochemistry and molecular biology) than conventional light microscopic pathological methods will be required to detect the otherwise elusive micrometastases and isolated neoplastic cells whose identification is part of such a scheme of ultrastaging. Ultrastaging techniques are presently more expensive than the traditional hematoxylin and eosin staining, but they clearly will increase the chances of detection of micrometastases; as such, such techniques are continuously expanding in their availability, playing (in the minds of many investigators) an increasingly important role in clinical practice. However, the mere fact that it may be possible to carry out ultrastaging of patients with head and neck cancer does not automatically mean that such an elaborate staging will benefit them. It is possible that detection of micrometastases within the lymph node, which are overlooked when nodes are analyzed by conventional pathological methods, may be of great importance in determining the prognosis. However, it appears as though not all isolated tumor cells that may be found in the lymph nodes or in general circulation (blood, bone marrow, other distant sites) are clinically significant. Only a small percentage of circulating tumor cells (0.05%) seem to be capable of surviving and establishing a metastatic focus. As is the case in routine pathological analysis, the clinical metastatic work-up also regularly overlooks (or, in other words, underestimates) the incidence of micrometastases. As well, it is now known that isolated tumor cells may be detected in the bone marrow of patients who bear no clinically identifiable distant metastases; as well, such isolated tumor cells may sometimes be found in regional lymph nodes in which no metastases have been found by conventional stains. In one series, individual disseminated carcinoma cells were detected in bone marrow aspirates in 41 of 108 patients (37%) with squamous cell cancer of the head and neck region. This contamination of From the Department of Otolaryngology—Head and Neck Surgery (A.F., A.R.), University of Udine, Udine, Italy; and the Department of Pathology (K.O.D.), University of Michigan, Ann Arbor, Michigan. Send Correspondence to Alfio Ferlito, MD, Professor and Chairman, Department of Otolaryngology—Head and Neck Surgery, University of Udine, Policlinico Città di Udine, Viale Venezia, 410, 33100 Udine, Italy.