Pathological diagnosis of pulmonary large cell neuroendocrine carcinoma by endobronchial ultrasound‐guided transbronchial needle aspiration

Abstract

BackgroundPulmonary large cell neuroendocrine carcinoma (LCNEC) is a relatively rare subtype of lung malignancy. According to revised 2015 World Health Organization (WHO) criteria for the pathological diagnosis of LCNEC, neuroendocrine markers must be examined by immunohistochemistry. In this study, we reevaluated endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) samples of patients previously diagnosed with LCNEC using the revised WHO criteria.MethodsClinical tissue samples that had been obtained by EBUS‐TBNA between January 2004 and December 2011, and that had been pathologically diagnosed as LCNEC according to the previous criteria, were reevaluated according to the revised WHO criteria.ResultsThe records of 471 lung cancer patients with mediastinal or hilar lymph node metastasis diagnosed by EBUS‐TBNA were analyzed. Thirteen patients were diagnosed with LCNEC; one of which was diagnosed based on cytology alone because the histological material was insufficient for a histological examination. Among the 12 cases in which a histological examination was performed, nine were diagnosed with possible LCNEC based on neuroendocrine marker positivity, while three were diagnosed with suspected LCNEC because they did not meet the immunostaining criteria. The patient who was cytologically diagnosed was found to have non‐small cell carcinoma with neuroendocrine morphology.ConclusionLCNEC could be pathologically diagnosed based on 2015 WHO criteria using EBUS‐TBNA samples.

Is the sum of positive neuroendocrine immunohistochemical stains useful for diagnosis of large cell neuroendocrine carcinoma (LCNEC) on biopsy specimens?

“…Previous studies that aimed to evaluate the LCNEC WHO 2015 criteria on biopsy specimens have shown high diagnostic specificity . Similarly, we provide evidence that the specificity for LCNEC on a biopsy specimen is acceptable (i.e.…”

“…H&E slides of both resection and biopsy specimens were examined for (i) cell type, presence of cytoplasm and tumour to lymphocyte ratio to assess NSCLC of SCLC features according to the WHO 2015 classification, (ii) the presence of neuroendocrine morphology, (iii) estimated mitotic activity in non-crushed fields [≤10, [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] or >30 mitoses/10 high-power field (HPF)], (iv) necrosis [none, 'dot-like' (=as occasionally seen in atypical carcinoids) or abundant (= more extensive than 'dot-like')]. If available, the MIB1 (Ki-67) staining was scored into <25% and >25%.…”

“…The diagnostic criteria for LCNEC include observation of abundant mitoses (>10 mitosis/2 mm 2 ), neuroendocrine morphology such as rosettes, trabecular growth pattern or palisading of cells and neuroendocrine differentiation usually identified by IHC markers. Although in recent practice LCNEC has been diagnosed more frequently on biopsy specimens, the diagnostic accuracy and precision for a diagnosis of LCNEC on a biopsy specimen is unknown and not well studied …”

“…Although in recent practice LCNEC has been diagnosed more frequently on biopsy specimens, 6 the diagnostic accuracy and precision for a diagnosis of LCNEC on a biopsy specimen is unknown and not well studied. [7][8][9][10][11] As described by national guidelines, one of the first-line treatment options for non-squamous NSCLC is cisplatinum-pemetrexed chemotherapy. 12 A patient with metastatic LCNEC disease that is not recognised as such, because neuroendocrine morphology is lacking in a biopsy specimen, may be diagnosed as nonsquamous NSCLC (i.e.…”

Management of Large Cell Neuroendocrine Carcinoma

“…Limited fine needle aspirate tissue especially from lung lesion is often not able to confirm the diagnosis. Despite the preference for larger samples endobronchial ultrasound-guided transbronchial needle aspiration has been shown to be effective in diagnosis of LCNEC (70). For pulmonary and gastrointestinal primary sites cross sectional imaging should be done for staging including CT of the chest, abdomen, and pelvis with intravenous contrast.…”