PNETs are highly aggressive, usually lethal neoplasms. Although the morphological and immunohistochemical features of pulmonary PNET are not different from its counterparts of other origin, special diagnostic considerations of other tumors with small, blue, round cell morphology and primarily small cell carcinoma of the lung is necessary. Small cell carcinomas usually present at older ages, and usually with a history of smoking, yet they and PNET may exhibit similar histological features. Some PNETs may even show reactivity for cytokeratin and synaptophysin [
11,
12]. Hence, a wider range of immunohistochemical markers, including chromogranin and TTF-1 to support a diagnosis of small cell carcinoma, and CD99, vimentin, or FLI1 for PNET should be used for the differential diagnosis. Lung carcinoids share a similar morphology to PNET and form rosettes. However, the detection of chromogranin, synaphtopysin, and neuron specific enolase is necessary to confirm the diagnosis of lung carcinoid. In addition, differential diagnosis is necessary to distinguish PNET from metastasis of small cell carcinomas of other origin. Another important diagnostic consideration for both children and adult patients is pulmonary rhabdomyosarcoma, which is also a rare tumor and belongs to the group of small,-blue,-round-cell tumors. Muscle-specific markers such as desmin, myogenin, or myo-D1, characteristic of rhabdomyosarcoma, should be included in the immunohistochemical study [
10]. Lymphoblastic lymphoma and the leukemia group of tumors are also an important diagnostic consideration, as they can be positive for CD99 and negative for epithelial markers. Precursor B-cell lymphoblastic lymphoma is an especially important mimicker of PNET. Like PNET, the malignant cells are small and uniform and have a diffusely infiltrative growth pattern, and they can even form rosette-like structures. Immunohistochemically, precursor B-cell lymphoblastic lymphoma is positive for CD99, and often nonreactive or only focally positive for conventional lymphoma markers such as LCA, CD20, and CD3. Immunopositivity for CD45, CD43, and CD79a are useful for separating lymphoblastic lymphoma/leukemia from PNET [
14]. Finally, to confirm the diagnosis of PNET, it is crucial to detect pass break or amplification of
EWSR1[
15]. However, because of the rarity of primary pulmonary PNETs, it is also important to exclude the possibility of metastasis from a bone or soft tissue primary to the lung. Detailed examination by clinical and radiological means should be performed to rule out metastatic tumor from an extrapulmonary primary site.