ORIGINAL ARTICLE OBSERVER VARIATION IN THE HISTOPATHOLOGIC ASSESSMENT OF EXTRANODAL TUMOR SPREAD IN LYMPH NODE METASTASES IN THE NECK Michiel W. M. van den Brekel, MD, PhD, 1,2 Wouter L. Lodder, MD, 1 Herbert V. Stel, MD, PhD, 3 Elisabeth Bloemena, MD, PhD, 4 C. Rene ´ Leemans, MD, PhD, 5 Isaa ¨c van der Waal, DDS, PhD 6 1 Department of Head and Neck Surgery and Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. E-mail: m.vd.brekel@nki.nl 2 Department of Otorhinolaryngology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands 3 Department of Pathology, Tergooiziekenhuizen, Blaricum, Amsterdam, The Netherlands 4 Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands 5 Department of Otolaryngology – Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands 6 Department of Oral Maxillofacial Surgery/Pathology, VU University Medical Center, Amsterdam, The Netherlands Accepted 5 April 2011 Published online 24 August 2011 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/hed.21823 Abstract: Background. Extranodal spread (ENS) of tumors is widely used as a prognosticator for patients with head and neck cancer and is used as an indicator for postoperative treatment. However, the histopathologic agreement among pathologists on the assessment of the presence or absence of this criterion has never been studied. Methods. The interobserver and intraobserver agreement among 10 pathologists on the diagnosis of ENS in 41 tumor- positive lymph nodes was evaluated. Results. The kappa value of the interobserver agreement among pathologists varied between 0.14 and 0.75, the overall kappa value was 0.42 and 0.49 in the 2 scoring sessions. The intraobserver kappa value varied between 0.49 and 0.95. Conclusion. The intraobserver and interobserver agree- ment among pathologists in the assessment of the presence of ENS was low in metastatic lymph nodes in the neck. Because of the widely accepted prognostic significance and therapeutic consequences of ENS, there is a need for internationally accepted reproducible criterion for the histopathologic assess- ment of ENS in metastatic lymph nodes in the neck. V V C 2011 Wiley Periodicals, Inc. Head Neck 34: 840–845, 2012 Keywords: observer variation; head and neck cancer; extranodal tumor spread; histopathology; lymph nodes Apart from the number, level, and side of lymph node metastases, extranodal spread (ENS) is used as 1 of the most important prognosticators in patients with neck node metastases from squamous cell carci- nomas. 1–11 ENS is found to be a significant prognostic factor for local control, distant metastases–free sur- vival, and overall survival. 12–16 A meta-analysis by Dunne et al 17 showed a 5-year survival rate between 17% and 55.8% for neck metastases with ENS and 44.6% to 76% for patients with neck metastases with- out ENS. As a result, ENS is widely accepted to be a criterion for postoperative radiotherapy, boosting the area of ENS. With such regimen, several studies have shown ENS lost its significance in predicting regional failure 7,18,19 ; however, others did still find it to be an indicator of a poor prognosis. 20,21 Recently, several trials have shown postoperative concomitant chemoradiation renders a better survival in the presence of ENS than radiotherapy alone. 22,23 This extra modality, although proven to be beneficial, implies an enormous increase in treatment burden and morbidity, especially in combination with major surgery. It is, therefore, crucial to be critical on the indications of postoperative chemoradiation and search for the subgroup of patients that might benefit from this treatment. The basis of cancer diagnosis and pathological stag- ing remains to be histopathological assessment of a tis- sue biopsy and surgical resection specimen. In recent years, standard protocols for reporting head and neck cancer have been widely used and these improved the general level of pathological assessment. 24 In June 2005, the Royal College of Pathologists published the second edition of datasets for histopathology reports on head and neck carcinomas. 25 In this dataset, core data items to be included in the histopathology report are discussed. In 2009, the College of American Patholo- gists published their latest guidelines for ENS on head and neck carcinomas. 26 The reported incidence of microscopic ENS varies between 21% 15 and 85% 5 (Table 1) and the incidence of macroscopic ENS varies between 17% 4 and 54%. 5 Whether these different percentages reflect differences between patient populations studied or interobserver variation between pathologists on the interpretation of ENS has not been studied. In the literature, a Correspondence to: M. W. M. van den Brekel V V C 2011 Wiley Periodicals, Inc. 840 Histopathologic Assessment of Extranodal Tumor Spread HEAD & NECK—DOI 10.1002/hed June 2012