Discussion
NETs are a group of neoplasms that differ in site, amount of cell propagation, and clinical manifestations. 4 These tumors are rare with an estimated incidence of 25 to 50 per 100,000.4 The most commonly affected organ systems are the gastroenteropancreatic and the bronchopulmonary tracts, accounting for 60% and 25% of the tumors, respectively.4 The incidence is increasing over the past years in part because of novel diagnostic techniques.
The average age of diagnosis is between the fourth and sixth decades, affecting more women than men. 5 Smoking has been identified as a possible culprit for the development of these neoplasms; nonetheless, the association is still not clear. 4 For example, poorly differentiated pulmonary NETs have a strong association with smoking but not well-differentiated pulmonary NETs. 2
Patients typically present with cough, wheezing, hemoptysis, and recurrent pneumonias, which are in part a consequence of obstruction caused by the mass. 2 Sometimes, obstruction may yield persistent pleural effusions. Hemoptysis may be seen secondary to the vascularity of pulmonary NETs.
The diagnosis is often delayed because patients are frequently treated for infection before being diagnosed with the malignancy, such as in our case. Radiologic image findings include round opacities, central masses, and atelectasis. Pulmonary NETs are frequently found incidentally as solitary lung nodules. The CT scan is the most common diagnostic modality and can provide information about the borders of the tumor, the location and surrounding structures, including the presence of atelectasis. 5 Pulmonary NETs are usually centrally located in an accessible region for lung biopsy. In cases where the mass is not easily reachable, thoracentesis may provide the only available specimen.
The 2015 World Health Organization classification has identified 4 histologic types of pulmonary NETs, namely, typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC). 6 The low-grade pulmonary NET, the typical carcinoid, is slow growing and has lower rates of metastasis. The intermediate-grade NET, the atypical carcinoid, is more aggressive. The highgrade NETs, the LCNEC and the SCLC, are aggressive and spread quickly to other places. 6 Consequently, LCNEC and SCLC have higher mortalities with a 5-year survival, ranging from 13 to 57% and 5%, respectively. 7
Tumors may be histomorphologically classified by H&E staining. The main characteristics that differentiate the low- and high-grade NETs are the presence of necrosis and the mitotic rate. Both categories form neuropeptides and have dense granular cores when seen with an electron microscopy .6 The TC and AC have welldefined, organized histologic patterns, no necrosis, and scarce mitosis. On the other hand, the LCNEC and SCLC are poorly differentiated tumors with necrosis, atypia, and mitosis.6 LCNEC can be separated from SCLC and other tumors by IHC staining, whereas SCLC is primarily distinguished by morphology.
If the biopsy sample size is small, then IHC morphology and markers are helpful for subclassification. 8 IHC is used to discern between neuroendocrine (NE) vs non-NE. The evaluation of pleural fluid includes preparation of cell blocks. Cell block staining is deemed better for IHC because it mimics a small biopsy that enables superior stains. 9 The need for a pleural biopsy in cases where the cytology is negative depends on treatment aims, the kind of tumor, and the presence of metastasis. 10 In almost 80% of cases, pleural biopsy and cytology are the only specimens obtained for analysis.Therefore, identification of these markers is practical for diagnosis. 10 For this reason, pleural effusion samples are appropriate options to lung biopsy for molecular studies. 10
