Reclassification of neuroendocrine tumors improves the separation of carcinoids and the prediction of survival.

Department of Pathology, Herlev University Hospital, division Gentofte, Copenhagen, Denmark.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer (Impact Factor: 4.55). 01/2009; 3(12):1410-5. DOI: 10.1097/JTO.0b013e31818e0dd4
Source: PubMed

ABSTRACT The classification of neuroendocrine lung tumors has changed over the last decades. Reliable diagnoses are crucial for the quality of clinical databases. The purpose of this study is to determine to which extent the use of different diagnostic criteria of neuroendocrine lung tumors has influenced the classification of these tumors. The prognostic information of tumor, node, metastasis descriptors was also evaluated.
We retrieved 110 tumors from the period 1989 to 2007. All tumors were reclassified according to the World Health Organization classification of 2004. Tumor, node, metastasis descriptors were evaluated.
By reclassification, the diagnoses on 48 tumors (44%) were changed. More diagnoses were changed in the older part of the material. A significantly different survival was shown for all patients in relation to tumor size (p < 0.0001). An endobronchial component was seen in 54%, 31%, and 11% of typical carcinoid, atypical carcinoid, and large cell neuroendocrine carcinoma, respectively with no impact on survival (p = 0.90). For all included patients the survival was significantly worse for patients having metastasis to N1 nodes as compared with N0 (p = 0.03). However, the number of removed lymph nodes were insufficient for definitive determination of the prognostic impact of node metastases. Regarding the revised diagnoses, a significant difference in survival between typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma and small cell carcinoma was noted (p < 0.005).
Tumors must be rediagnosed before entering a central database. Tumor and node seem to be useful predictors of survival.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pulmonary carcinoids are neuroendocrine tumors histopathologically subclassified into typical (TC; no necrosis, <2 mitoses per 2 mm) and atypical (AC; necrosis or 2 to 10 mitoses per 2 mm). The reproducibility of lung carcinoid classification, however, has not been extensively studied and may be hampered by the presence of pyknotic apoptosis mimicking mitotic figures. Furthermore, prediction of prognosis based on histopathology varies, especially for ACs. We examined the presence of interobserver variation between 5 experienced pulmonary pathologists who reviewed 123 originally diagnosed pulmonary carcinoid cases. The tumors were subsequently redistributed over 3 groups: unanimously classified cases, consensus cases (4/5 pathologists rendered identical diagnosis), and disagreement cases (divergent diagnosis by ≥2 assessors). κ-values were calculated, and results were correlated with clinical follow-up and molecular data. When focusing on the 114/123 cases unanimously classified as pulmonary carcinoids, the interobserver agreement was only fair (κ=0.32). Of these 114 cases, 55% were unanimously classified, 25% reached consensus classification, and for 19% there was no consensus. ACs were significantly more often in the latter category (P=0.00038). The designation of TCs and ACs by ≥3 assessors was not associated with prognosis (P=0.11). However, when disagreement cases were allocated on the basis of Ki-67 proliferative index (<5%; ≥5%) or nuclear orthopedia homeobox immunostaining (+; -), correlation with prognosis improved significantly (P=0.00040 and 0.0024, respectively). In conclusion, there is a considerable interobserver variation in the histopathologic classification of lung carcinoids, in particular concerning ACs. Additional immunomarkers such as Ki-67 or orthopedia homeobox may improve classification and prediction of prognosis.
    American Journal of Surgical Pathology 07/2014; DOI:10.1097/PAS.0000000000000300 · 4.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: J.M. van der Zwan), (A. Trama), (R. Otter), (N. Larrañ aga), (A. Tavilla), (R. Marcos-Gragera), (A.P. Dei Tos), (E. Baudin), (G. Poston), (T. Links). l The RARECARE working group consists of: Austria: N. Zielonke (Austrian National Cancer Registry); Belgium: E. Van Eycken (Belgian Cancer Registry), H. Sundseth (European Cancer Patient Coalition); France: G. Hedelin (Bas-Rhin Cancer Registry), J. Faivre (Cô te d'Or Digestive Cancer Registry A v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e j c a n c e r . c o m (Varese Cancer Registry), A. Fiore (Veneto Cancer Registry), Abstract Because of the low incidence, and limited opportunities for large patient volume experiences, there are very few relevant studies of neuroendocrine tumours (NETs). A large population-based database (including cancer patients diagnosed from 1978 to 2002 and registered in 76 population-based cancer registries [CRs]), provided by the project 'surveil-lance of rare cancers in Europe' (RARECARE) is used to describe the basic indicators of inci-dence, prevalence and survival of NETs, giving a unique overview on the burden of NETs in Europe. NETs at all cancer sites, excluding lung, were analysed in this study. In total over 20,000 incident cases of NETs were analysed and a data quality check upon specific NETs was performed. The overall incidence rate for NETs was 25/1,000,000 and was highest in patients aged 65 years and older with well differentiated endocrine carcinomas (non-function-ing pancreatic and gastrointestinal) (40 per 1,000,000). We estimated that slightly more than 100,000 people were diagnosed with NETs and still alive in EU27 at the beginning of 2008. Overall, NETs had a 5 year relative survival of 50%; survival was low (12%) for poorly differ-entiated endocrine carcinoma, and relatively high (64%) for well differentiated carcinoma (not functioning of the pancreas and digestive organs). Within NETs, endocrine carcinoma of thy-roid gland had the best 5-year relative survival (82%). Because of the complexity and number of the different disciplines involved with NETs (as they arise in many organs), a multidisciplinary approach delivered in highly qualified reference cen-tres and an international network between those centres is recommended.
    European Journal of Cancer 07/2013; 49:2565-2578. DOI:10.1016/j.ejca.2013.02.029 · 4.82 Impact Factor
  • Current Problems in Surgery 12/2014; 51(12):478-520. DOI:10.1067/j.cpsurg.2014.11.004 · 1.42 Impact Factor