No Underlying Cause: A Case of a Fatal Neuroendocrine Lung Tumor

This case highlights a rare lung neuroendocrine malignancy in a 34 year old female. The patient had a rapid decline within 5 weeks and had very limited treatment options. The aim in presenting this case is to bring attention to the high mortality rate of such an aggressive lung tumor, and the need for early diagnosis and improved subtyping of the tumors, as well as improved treatment options in hopes of saving lives of patients who receive this diagnosis.


Introduction
This case highlights a rare lung neuroendocrine malignancy in a 34 year old female. The patient had a rapid decline within 5 weeks and had very limited treatment options. The aim in presenting this case is to bring attention to the high mortality rate of such an aggressive lung tumor, and the need for early diagnosis and improved subtyping of the tumors, as well as improved treatment options in hopes of saving lives of patients who receive this diagnosis.

Case Presentation
A 34 year old African American female presented to the emergency room accompanied by caregiver, in mild respiratory distress with a productive cough for the past 24 hours. Prior to examination, caregiver explained that the patient complained of a cough productive of sputum and diffi culty breathing over the course of one week. She had visited many outpatient clinics over a 2 month period and was give a course of Bactrim for presumptive pneumonia, which patient completed without any signs of resolution of her pneumonia. A course of Azithromycin was then given however her symptoms remained unresolved.
On physical examination, patient had a fever of 37.8 degrees Celsius (100.04 F), respiratory rate of 28 breaths per minute after administration of ipratropium-albuterol, and a heart rate of 112 bpm. She was admitted to telemetry for tachycardia and possible underlying pneumonia with pleural effusion.

Abstract
A 34 year old female with metastasizing neuroendocrine lung carcinoma with no underlying etiologies. Patient was diagnosed with stage 4 lung neuroendocrine cancer with treatment options limited due to intellectual disability and overall poor prognosis. The patient had a rapid decline over a 5 week period with decreased intake, decreased appetite, and overall azotemia and resulted in patient's death. Seventy-fi ve percent of neuroendocrine lung tumors are centrally located [2]. CT is followed by bronchoscopic biopsies for central lesions, or by transthoracic needle biopsy for peripheral lesions [2]. Biopsy analysis confi rms the diagnosis.
Using immunohistochemistry to identify cytoplasmic products such as chromogranin, neuron-specifi c enolase, and synaptophysin confi rm diagnosis of NEC, with 50 percent of lung neuroendocrine tumors staining positive for thyroid transcription factor 1 (TTF1) [5,6]. Presence or absence of necrosis, and number of mitoses per 2mm 2 of viable tumor sample helps to differentiate the subtype of lung NET [4]. TCs have <2 mitoses per 2mm 2 and no necrosis; ACs have 2-10 mitoses per 2mm 2 or necrosis; SCLC has >10 mitoses per 2mm 2 with cytological features of SCLC; and LCNECs have >10 mitoses per 2mm 2 with cytological features of LCNECs [4,7]. It must be noted that histopathological differences between subtypes can be very subtle, allowing room for notable differences in opinion between individual observers.
The preferred treatment option for patients with NETs is surgical resection as long as the patient has adequate pulmonary reserve. Patients may also undergo transbronchoscopic resection if lesions are low-grade and entirely endobronchial.
For patients with histologically aggressive-looking, Stage III, atypical NETs, platinum-based chemotherapy with or without radiation therapy may be considered as a viable alternative, however, there is no evidence to support this alternative [8]. There is also not enough research on whether radiation therapy improves outcomes post-operatively for atypical lung neuroendocrine tumor following surgical resection.

Conclusion
The guidelines for diagnosis and management of lung neuroendocrine tumors is not fully established. There is also a lack of known risk factors that aid in achieving an early diagnosis or implementing preventative measures. Our patient was initially suspected of having pneumonia based on her history of multiple upper respiratory tract infections. Two courses of antibiotics provided no resolution to her cough after two months. Based on CT scan impression, the next best step in management was to have a biopsy of the mass along with thoracocentesis. The main concern for this patient was her rapid decline. Treatment options for this patient were limited not only by her intellectual disability, late stage diagnosis, and size and metastasis of her tumor, but also due to the fact that her tumor could not be subtyped based on the current WHO 2015 recommendations for classifi cation of NETs. It was therefore in the best interest of the patient to provide comfort care.
Further research is needed to aid in categorizing a wider spectrum of neuroendocrine lung carcinomas whereby allowing a reduction in variability of opinions on histopathology, which is essential for subtyping these tumors and narrowing treatment regimens. There continues to be little evidence that chemotherapy and radiation are the best treatment options. It is recommended that further research be put into improving subtype classes and treatment options in order to improve quality of life of patients who receive this diagnosis.