Authors’ response to Shah’s letter concerning the editorial “The future of the TNM staging system in laryngeal cancer: time for a debate?”

Abstract

Sir, We thank Dr. Shah for his letter [1] regarding the editorial entitled “The future of the TNM staging system in laryngeal cancer: time for a debate?” We think that it would be both practical and useful to explore the possibility of inclusion in the UICC/AJCC staging system, a designation of both (1) the presence or absence of micrometastases, as well as (2) the presence of isolated tumor cells found in general circulation (blood, bone marrow, other distant sites). Cases with only micrometastases might, in such scheme, be identiWed by the addition of “(mi)” to the pN and/or pM category [e.g., pN1 (mi) or pM1 (mi)] [2]. Admittedly, one wishing to utilize such an “ultrastaging” system would be well advised to formally identify the precise pathologic methods of evaluation used to arrive at such a classiWcation. It is virtually certain that detection modes more sensitive than conventional light microscopic pathologic methods (as for example, immunocytochemistry and molecular biology) will be required to identify the otherwise elusive micrometastases and isolated neoplastic cells whose identiWcation is part of such a scheme of ultrastaging [3]. Ultrastaging techniques are today 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 [3–5]. However, the mere fact that it may be possible to carry out ultrastaging of head and neck cancer patients, does not automatically mean that such an elaborate staging will beneWt them. It is possible that detection of micrometastases within the lymph node which are overlooked when nodes are analyzed by conventional pathologic methods may be of great importance in determining the prognosis [6]. However, it appears as though not all isolated tumor cells which may be found in the lymph nodes or in general circulation (blood, bone marrow, other distant sites) are clinically signiWcant. Only a very small percentage of circulating tumor cells (0.05%) seem to be capable of surviving and establishing a metastatic focus [7]. As is the case in routine pathologic 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 identiWable distant metastases; too, 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 the bone marrow by individual metastatic carcinoma cells was demonstrated by the use of immunocytochemistry, relying on a monoclonal antibody raised against cytokeratin no. 19. In the clinical stage I patients, tumor cells were detected only in 23.3% of the patients, whereas in stage IV patients almost twice as many individuals (47.7%) presented with tumor cells in the bone marrow. Patients who were shown to possess these A. Ferlito (&) · A. Rinaldo Department of Surgical Sciences, ENT Clinic, University of Udine, Policlinico Universitario, Piazzale S. Maria della Misericordia, 33100 Udine, Italy e-mail: a.ferlito@uniud.it