Neuroendocrine tumors (NETs) account for about 0.5% of all newly diagnosed malignancies. 1 Pulmonary NETs are rare, accounting for 1 to 2% of all invasive lung malignancies and involve about 20 to 25% of primary lung malignancies. 2,3 Their prevalence has increased by an estimated 6% per year over the past 30 years. 2 Nonetheless, the time of diagnosis is frequently delayed because of nonspecific symptoms that may imitate other pulmonary conditions.
In the normal pleural space, there is a steady state in which there is a roughly equal rate of fluid formation and absorption. Any disequilibrium may produce a pleural effusion. Pleural fluids can be transudates or exudates. Transudates result from imbalances in hydrostatic and oncotic pressures in the pleural space. Exudates result primarily from pleural and/or lung inflammation or from impaired lymphatic drainage of the pleural space. Clinical manifestations include cough, wheezing, recurrent pneumonia, hemoptysis and pleural effusions. We present a case of a man who developed a large left pleural effusion with a pathology report suggesting a pulmonary NET as the etiology. Being aware of this rare entity may help improve prognosis by making an earlier diagnosis and starting treatment sooner.
Case Presentation
A 90-year-old man with a medical history of arterial hypertension, hyperlipidemia, type 2 diabetes mellitus, coronary artery disease, and vascular dementia presented to the emergency department with hypoactivity, poor appetite, productive cough, and shortness of breath. The patient was a former smoker (unknown pack-years) who quit smoking cigarettes 7 years prior. Vital signs showed sinus tachycardia and peripheral oxygen saturation of 90% at room air. The initial physical examination was remarkable for decreased breath sounds and crackles at the left lung base. Laboratory findings showed leukocytosis with neutrophilia and chronic normocytic anemia. Chest computed tomography (CT) showed a large left-sided pleural effusion occupying most of the left hemithorax with adjacent atelectatic lung, enlarged pretracheal, subcarinal, and left perihilar lymph nodes (Figure 1).
The patient was admitted to the internal medicine ward with the diagnosis of left pneumonic process and started on IV levofloxacin. However, despite 7 days of antibiotic therapy, the patient’s respiratory symptoms worsened. This clinical deterioration prompted pulmonary service consultation. Chest radiography demonstrated an enlarging left pleural effusion (Figure 2). A thoracentesis drained 1.2 L of serosanguineous pleural fluid. Pleural fluid analysis showed a cell count of 947/cm3 with 79% of lymphocytes, total protein 3.8 g/dL, lactic dehydrogenase (LDH) level 607 U/L, and glucose level 109 mg/dL. Serum total protein was 6.62 g/dL, LDH 666 U/L and glucose 92 mg/dL (Tables 1 and 2). Alanine transaminase (ALT) and aspartate aminotransferase (AST) were 11 U/L and 21 U/L, respectively. Using Light criteria, the pleural:serum protein ratio was 0.57, the pleural:serum LDH ratio was 0.91, and the pleural LDH was more than two-thirds of the serum LDH. These calculations were consistent with an exudative effusion. An infectious disease workup, including blood and pleural fluid cultures, was negative.
The pleural fluid concentrated cell block hematoxylin and eosin (H&E) staining showed chromatin, prominent nucleoli, and nuclear molding, which was compatible with high-grade lung NET (Figure 3). The cell block immunohistochemistry (IHC) was positive for synaptophysin, chromogranin A, and neuron specific enolase (NSE) also consistent with a high-grade pulmonary NET (Figure 4). The proliferation marker protein Ki-67 labeling index (LI) showed a proliferation index > 20% (Figure 5). The patient did not have decision-making capacity given vascular dementia. Multiple attempts to contact the next of kin or family members were unsuccessful. Risks vs benefits were evaluated, and given the patient’s advanced age and multiple comorbidities, a conservative management approach under palliative care was chosen. For this reason, further genomic studies were not done.