Search

ObjectiveRecently, 60% discordancy was reported for distinction between typical carcinoid and atypical carcinoid in preoperative biopsy compared to the resection specimen. This study investigated the impact of biopsy surface size, obtained with flexible and rigid bronchoscopy, on diagnostic accuracy of typical and atypical carcinoid.MethodsBiopsy-resection paired specimens of patients referred for treatment to Amsterdam University Medical Centers were retrieved. Bronchial biopsies were obtained either by flexible or rigid biopsy. The definitive diagnosis was based on the resection specimen. Diagnosis according to the 2015 WHO classification, mitoses and necrosis in biopsy and resection specimen, were independently re-evaluated by two pathologists.ResultsAfter screening 298 patients, 64 biopsy-resection pairs with available tissue were included of which 34 (53%) were biopsied with flexible and 30 (47%) with rigid biopsy. In 35 (55%) patients, the tumor classification between the biopsy and resection specimen was concordant. The discordance in the remaining 29 cases (45%) was caused by misclassification of atypical as typical carcinoid in bronchoscopy specimens, predominantly in small flexible biopsies (59%, p=0.021). Of biopsies measuring 2, 79% were classified as discordant and 52% of the discordant biopsies measured 2.ConclusionHistological classification in central carcinoid tumors is discordant in 45% of the biopsies, with increasing diagnostic accuracy in larger biopsies. Distinguishing carcinoid tumor into typical or atypical carcinoid on biopsies 2 should be discouraged. A cumulative biopsy surface of at least 4 mm2 tumor is preferred to increase the diagnostic accuracy which helps in optimal treatment planning.

IntroductionThe extensive loss of lung parenchyma is a drawback of anatomical resection in bronchial carcinoids. Endobronchial therapy (EBT) has emerged as a safe and effective minimally invasive tissue sparing alternative for small intraluminal tumors. Currently, therapeutic decision making in patients with bronchial carcinoid is mainly based on tumor morphology and patient characteristics. The availability of more accurate biomarkers might help clinicians in selecting low-risk tumors for EBT. Therefore, we investigated radiological (tumor diameter), morphometric (mitotic index) and immunohistochemical (OTP, CD44, Ki-67, Rb and P16) markers as predictors of dissemination.Material and methodsPatients referred to Amsterdam University Medical Centers with available histology were included. Clinical and morphological characteristics relevant for classification such as tumor diameter, mitotic count (MAI) and prognostic immunohistochemical markers as Ki-67, P16, Rb, Orthopedia homebox (OTP) and CD44 were analyzed.ResultsIn a cohort of 171 patients, the vast majority were curatively treated with either EBT (n=61, 36%) or surgery (n=103, 60%). Seven (4%) patients presented with distant metastases at diagnosis. TC was diagnosed in 112 (65%) and AC in 59 (35%) patients. Nine (15%) patients treated with EBT had a local recurrence of disease during follow up and none developed lymph node or distant metastasis. Of all surgically treated patients, 13 (13%) had level 1 or 2 lymph node metastases. Additional 13 (13%) patients developed distant metastases, 11 (85%) were AC and 2 (15%) TC. Patients with tumor stage IA (tumor diameter ≤1cm) irrespective of tumor classification or immunohistochemical results did not develop distant metastases. Patients with typical carcinoid (2) stage ≥IB with Ki67 2), Ki-67 of ≥5% (p=p=5% or loss of CD44 metastasized occasionally (11%).ConclusionAdding tumor diameter, CD44 and Ki-67 to the widely used TC/AC classification, provides a multimodal biomarker that better stratifies patients in prognostically favorable and unfavorable categories than current standards. These findings enable risk stratification allowing a tailored treatment approach for patients with bronchial carcinoid.