Figure 1. Anterior-posterior chest x-ray (A) showing moderate elevation of left hemidiaphragm (arrow) and an ill-defined nodular opacity in the left perihilar region (*) suspicious for a hilar mass. Axial image from a contrast enhanced chest CT (B) showing central left upper lobe mass extending into the hilum resulting in narrowing of the vascular and bronchial structures of the left upper lobe.
Figure 2. 400x magnification hematoxylin and eosin-stained endobronchial biopsy (A) demonstrating malignant cells with large hyperchromatic nuclei (circle) infiltrating through stromal tissue. Compare with the nuclear size of the nearby normal submucosal glands (arrows), 200x magnification image (B) demonstrating poorly differentiated carcinoma cells filling the subepithelial stroma. Normal ciliated mucosal cells are in the upper left of the image (arrowheads).
A 76-year-old man with a past medical history significant for coronary artery disease, diabetes mellitus, and 40-pack-year smoking history presented to the emergency department with 1 week of progressive hoarseness. Associated symptoms included a cough initially productive of green sputum that progressed to scant hemoptysis, as well as intermittent hiccups. Four days prior to presentation he sought treatment at a clinic in Mexico, where he was diagnosed with influenza and treated with Tamiflu and Moxifloxacin. His symptoms did not improve, prompting him to seek care at our hospital.
On interview, he denied fevers, chills, dysphagia, otalgia, odynophagia, dyspepsia, chest pain, dyspnea, or weight changes. His temperature was 36.3°C, heart rate 75 beats per minute, blood pressure 150/77 mmHg, respiratory rate 22 breaths per minute, and oxygen saturation 93% on room air. On physical examination, the patient was found to have a hoarse voice, with an otherwise normal oropharyngeal exam. Cardiopulmonary exam was notable for bowel sounds auscultated in the left lower lung fields. The remainder of the exam was unremarkable. Laboratory testing including CBC, CMP, and a respiratory pathogen PCR panel did not detect any viruses.
A chest X-ray was obtained (Figure 1A); imaging was significant for moderate elevation of left hemidiaphragm (A), an ill-defined nodular opacity in the left perihilar region, and suspicion for a hilar mass (B). Chest CT confirmed a large central left upper lobe hilar mass compressing regional vascular and bronchial structures (Figure 1B). The patient underwent Endobronchial ultrasound-guided fine needle aspiration (EBUS FNA) and endobronchial biopsy, which confirmed the diagnosis, recurrent laryngeal nerve injury secondary to left upper lobe non-small cell lung carcinoma (Figure 2).
Hoarseness can be caused by a diverse array of conditions, ranging from local inflammatory processes (e.g., laryngitis or benign vocal cord lesions), to more systemic, neurologic, or oncologic conditions. A systematic evaluation is therefore essential to create an appropriate differential and guide the diagnostic evaluation. This evaluation begins with a detailed history probing for any red flag symptoms: symptoms persisting greater than two weeks, dysphagia, odynophagia, weight loss, or hemoptysis, as was seen in the case above.
Recurrent laryngeal nerve injuries are a less common cause of hoarseness. An understanding of the anatomic course of the recurrent laryngeal nerve (RLN) aids in localizing pathology. The RLN branches off cranial nerve X, also known as the Vagus nerve, and supplies most of the laryngeal muscles. The left RLN extends inferiorly into the chest, and loops posteriorly under the aortic arch before returning superiorly through the neck. Similarly, the right RLN loops posteriorly around the right subclavian artery before traversing superiorly back through the neck. The majority of recurrent laryngeal nerve injuries are iatrogenic, secondary to thyroid or cardiothoracic surgery. However, in the absence of surgery, understanding the anatomy paired with further imaging can help localize the pathology.
The patient’s radiographic findings suggested an intrathoracic mass concerning for a primary lung malignancy. This mass was further characterized on chest CT, which confirmed a large central left upper lobe hilar mass compressing regional vascular and bronchial structures. In the setting of hoarseness, the malignancy was likely causing injury to the recurrent laryngeal nerve. Additionally, given the symptom of hiccups paired with image findings of an elevated hemidiaphragm, the phrenic nerve was also likely being compressed. A biopsy would then further identify the lung mass.
Bronchoscopy showed patent airways and extensive nodular mucosa and endobronchial tumor at the left upper lobe / lingula. Endobronchial biopsy of the left upper lobe revealed infiltrating malignant cells in the submucosal connective tissue. No keratin production or gland formation was seen. Further work-up with immunohistochemical preparations showed the tumor cells to be negative for TTF-1 and p40, markers indicative of pulmonary adenocarcinoma and squamous cell carcinoma, respectively. In light of these features, the most accurate diagnosis is non-small cell carcinoma, not otherwise specified (NOS).
The differential for dysphonia in an adult extends beyond the anatomic boundaries of the laryngopharynx, including an intrathoracic malignancy causing recurrent laryngeal nerve injury. Additionally, phrenic nerve palsy secondary to a mediastinal mass should be included in the differential for an elevated hemidiaphragm.
Alexandra Fuher MD1, Carrie B. Marshall MD2, William Aaron Manning MD3
1Department of Internal Medicine, University of Colorado Anschutz Medical Campus
2Department of Pathology, University of Colorado Anschutz Medical Campus
3Department of Pediatrics, University of Colorado Anschutz Medical Campus
References
- Culp JM, Patel G. Recurrent Laryngeal Nerve Injury. [Updated 2023 May 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560832.
- Reiter R, Hoffmann TK, Pickhard A, Brosch S. Hoarseness-causes and treatments. Dtsch Arztebl Int. 2015 May 8;112(19):329-37. [CrossRef] [PubMed]
- Feierabend RH, Shahram MN. Hoarseness in adults. Am Fam Physician. 2009 Aug 15;80(4):363-70. [PubMed]
- Travis WD, Brambilla E, Noguchi M, et al. Diagnosis of lung cancer in small biopsies and cytology: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. Arch Pathol Lab Med. 2013 May;137(5):668-84. [CrossRef] [PubMed]
Cite as: Fuher A, Marshall CB, Manning WA. June 2024 Medical Image of the Month: A 76-year-old Man Presenting with Acute Hoarseness. Southwest J Pulm Crit Care Sleep. 2024;28(6):78-80. doi:
https://doi.org/10.13175/swjpccs002-24 PDF
Tuesday, July 2, 2024 at 8:00AM 
Figure 1. Axial image from a CT scan (A) showing a spiculated left upper lobe nodule. An axial image from a more inferior slice, at the level of the left hilum (B), demonstrates prominent left hilar adenopathy filling the AP window/subaortic space (*).
Figure 2. Axial images from an FDG-PET CT obtained shortly after the initial chest CT demonstrates focal hypermetabolic activity associated with the left upper lobe nodule (A) and pre-aortic adenopathy (arrowhead). There is also hypermetabolism associated with the right (contralateral) vocal cord (B) (arrow).