Role of Nkx2.2 immunohistochemistry in distinguishing Ewing sarcoma from neuroendocrine neoplasms at different sites

Ewing sarcoma is a high grade round cell sarcoma that exhibits considerable histomorphological overlap with other round cell tumors, especially neuroendocrine neoplasms. In the present study, we compared the immunohistochemical expression of Nkx2.2 in cases of Ewing's sarcoma, neuroendocrine neoplasms at different sites, and a small subset of other mesenchymal and nonmesenchymal tumors in order to assess its utility in their distinction.

This descriptive retrospective study lasted for 14 months and investigated 60 cases, with 17 cases of Ewing sarcoma, 34 cases of neuroendocrine neoplasms and nine cases of other tumors. Hematoxylin and eosin and Nkx2.2 immunohistochemistry-stained slides of previously diagnosed cases were retrieved and reviewed.

Nkx2.2 exhibited sensitivity of 88.2% and specificity of 53.4% in the diagnosis of Ewing's sarcoma. Nkx2.2 expression was also present in neuroendocrine neoplasms (especially those of gastrointestinal and pancreatic origins) with 52.9% sensitivity and 34.6% specificity. Other neuroendocrine neoplasms that were positive for Nkx2.2 included those of prostate, female genital tract, and larynx origins. Among other tumors, pleomorphic sarcoma and melanoma exhibited Nkx2.2 positivity. Most cases (83.3%, 5/6) of lung neuroendocrine neoplasms were negative for Nkx2.2.

Nkx2.2 exhibited high sensitivity in diagnosing Ewing's sarcoma and certain neuroendocrine neoplasms (especially those of gastrointestinal and pancreatic origins), but its lower specificity and varied expression across other tumor types highlight the need for a cautious and context-specific approach when used in clinical practice.