What clinicians are asking pathologists when dealing with lung neuroendocrine neoplasms?

Ki-67 labeling index of neuroendocrine tumors of the lung has a high level of correspondence between biopsy samples and surgical specimens when strict counting guidelines are applied

“…On surgical specimens of lung NET, some methodological studies on quantification of Ki-67 staining to generate a Ki-67 LI by manual or automated analysis systems have been performed [17,19,32,[39][40][41]. None, however, compared biopsies with corresponding surgical specimens, probably because in these tumors, the Ki-67 LI is not used for diagnosis or grading or as a prognostic factor [4,6,30], as morphology remains the favored approach [3]. However, when diagnosing lung NET, a distinction has to be made between low-to intermediate-and high-grade NET even when biopsies are small or crushed, to avoid errors in patient management and provide appropriate treatment adapted to the intrinsic aggressiveness of the disease which often cannot be done by morphology only [1,20,21,31,33,38].…”

“…However, when diagnosing lung NET, a distinction has to be made between low-to intermediate-and high-grade NET even when biopsies are small or crushed, to avoid errors in patient management and provide appropriate treatment adapted to the intrinsic aggressiveness of the disease which often cannot be done by morphology only [1,20,21,31,33,38]. TC or AC is treated with somatostatin analogs, m-TOR pathway inhibitors, and/or peptide receptor radionuclide therapy (PRRT) [1,4,[42][43][44][45], once imaging, symptoms, tumor burden, individual risks of evolving disease, and actionable targets have been accounted for [1,21]. Once SCC has been ruled out, metastatic NETs are treated with PRRT or alkylating-based chemotherapy, to avoid the side effects of platinum/ etoposide [42,45].…”

“…Neuroendocrine tumors (NETs) of the lung are a heterogeneous family of neoplasms comprising four histologic variants: typical carcinoid (TC), atypical carcinoid (AC), largecell neuroendocrine carcinoma (LCNEC), and small-cell carcinoma (SCC) [1][2][3][4][5][6]. Classification criteria include cytological and histological features, the occurrence and extent of necrosis, the number of mitoses per 2 mm2, and the immunohistochemical (IHC) expression of pan-NE markers [1][2][3].…”

“…The role of Ki-67 LI in lung NET has been the subject of several independent investigations, with potential diagnostic, prognostic, and grading implications (recently reviewed by [30]. Although differences in Ki-67 LI are reported between the four histological variants [3,30], its significance as diagnostic criterion is contested [3] as there is overlap between the histological categories and Ki-67 LI are not perfectly congruent with other defining criteria [4][5][6]30]. Currently, in lung NET, Ki-67 LI can only be used to distinguish between TC/AC from SCC on cytology and/or biopsy samples, notably when the volume of material is limited [3] and/or crush artifacts are present [31].…”

Insights into Novel Prognostic and Possible Predictive Biomarkers of Lung Neuroendocrine Tumors

“…the percentage of labeled nuclei after immunohistochemical staining, is an emerging biomarker in NETs (56). The role of Ki-67 LI in lung NET has been the subject of several independent investigations, with potential diagnostic, prognostic, and grading implications (57). However, differences in Ki-67 LI are reported between the four histological variants (57).…”