Ki-67 Immunoreactivity in the Differential Diagnosis of Pulmonary Neuroendocrine Neoplasms in Specimens With Extensive Crush Artifact

Abstract

The aim of the present study was to evaluate the usefulness of immunohistochemical markers in the differential diagnosis of pulmonary neuroendocrine tumors with particular emphasis on the preservation of immunoreactivity in areas showing crush artifacts. Specimens from 9 carcinoid tumors (CTs) and 13 small cell carcinomas (SCCs) with crush artifact were stained with antibodies to Ki-67, chromogranin A, synaptophysin, and cytokeratin. The immunoreactivity was well preserved in the crushed areas. Ki-67 was expressed in the crushed areas of all SCCs. Reactivity was diffuse or at least present in 25% of the crushed areas. In contrast, the immunoreactive areas in CTs never exceeded 10%. Immunoreactivity for Ki-67, synaptophysin, chromogranin A, and cytokeratin is well preserved in tissue with crush artifacts and can be interpreted reliably. The diagnosis of SCC should be questioned if fewer than 25% of cells show reactivity for Ki-67.

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

“…Ki-67 LI has a major value in distinguishing TC and AC from high-grade NET 71,73,74 , especially when small crushed biopsy samples or cytology are dealt with (with a practical cutoff point of 25% to operate this distinction) 12,13,71,73,74 , as well as in differentiating between lower and higher malignant NE tumors in resection specimens of TC and AC (with cut-off thresholds ranging from 4% to 5%) 13,37,54,[75][76][77][78] in keeping with pancreatic NE tumors 79,80 , albeit sometimes with a non-independent value upon multivariate analysis In particular, SCC and TC are so agreed-upon tumor entities in the lung to seem too reductive to simply call them G3 and G1 tumors, respectively. However, establishing a grading system in lung NET independent of histology could be clinically warranted in individual tumor patients for the personalized therapy requirements, in keeping with the lesson of GEP-NET.…”

Utility of the Quantitative Ki-67 Proliferation Index and CD56 Together in the Cytologic Diagnosis of Small Cell Lung Carcinoma and Other Lung Neuroendocrine Tumors

“…However, these markers may have variable expression in SCLC [18,19,20,21], and lack of expression of these two markers in SCLC is not uncommon. In addition, neuroendocrine expression in low-grade neuroendocrine neoplasms (typical carcinoid) and intermediate-grade neuroendocrine neoplasms (atypical carcinoid) and in LCNEC and some NSCLC is documented [18,20,21,22].…”

“…CD56 is considered to be a less specific and the most sensitive neuroendocrine marker to detect SCLC. Besides neuroendocrine differentiation, the high proliferation index marked by Ki-67 is a defining feature of SCLC [4,19,24,25]. To date, there is no study in the English literature (1) comparing CD56 with synaptophysin and chromogranin to distinguish SCLC from other neuroendocrine neoplasms, and (2) examining the diagnostic value of CD56 and quantitative Ki-67 together in SCLC and other pulmonary neuroendocrine neoplasms.…”

Immunochemistry and Lung Cancer: Application in Diagnosis, Prognosis and Targeted Therapy

“…Crush artefact is a known characteristic of small cell carcinomas, regardless of their origin [66]. In such cases, immunostaining with Ki-67 has helped discriminate between these two tumour groups, with small cell carcinomas showing more than 25% immunoreactivity in the crushed areas compared to less than 10% for carcinoid tumours [67]. TTF-1 has a sensitivity of about 75–80% in SCLC.…”