June 2024 Medical Image of the Month: A 76-year-old Man Presenting with Acute Hoarseness

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

1. 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.
2. Reiter R, Hoffmann TK, Pickhard A, Brosch S. Hoarseness-causes and treatments. Dtsch Arztebl Int. 2015 May 8;112(19):329-37. [CrossRef] [PubMed]
3. Feierabend RH, Shahram MN. Hoarseness in adults. Am Fam Physician. 2009 Aug 15;80(4):363-70. [PubMed]
4. 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

May 2024 Medical Image of the Month: Hereditary Hemorrhagic Telangiectasia in a Patient on Veno-Arterial Extra-Corporeal Membrane Oxygenation

Figure 1.  Preoperative nasopharyngoscopic direct visualization of telangiectasia of the nasal turbinate.

Figure 2.  Noncontrast head CT on postoperative day 3 demonstrates extensive multifocal areas of low attenuation consistent with early signs of infarction involving much of the cerebral hemispheres, most prominently involving the left parietal lobe.

A 54-year-old man with a complex cardiac history, including Tetralogy of Fallot requiring Blalock-Taussig shunt in infancy, infundibular patch repair at age 7, and bioprosthetic tricuspid valve replacement at age 52, had ongoing frequent hospitalizations with decompensated right ventricular heart failure secondary to native pulmonary valve mixed stenosis plus regurgitation and left pulmonary artery stenosis. His case was further complicated by his history of hereditary hemorrhagic telangiectasia (HHT) with recurrent epistaxis and recent GI bleeds with multiple angiodysplastic lesions throughout the stomach, duodenum, and descending colon which were previously treated with argon plasma coagulation.

The patient was admitted to our hospital in NYHA class IV heart failure receiving a continuous dopamine infusion and aggressive diuresis. Upon admission, a right heart catheterization demonstrated severe pulmonary valve regurgitation, left pulmonary artery stenosis, and systemic hypoxemia suggestive of an intrapulmonary shunt. Admission transthoracic echocardiogram demonstrated normal left ventricular ejection fraction of 55-60%, a severely enlarged right ventricle, moderately reduced right ventricular systolic function, severe pulmonary valve regurgitation, and moderate pulmonary valve stenosis.

A multidisciplinary team including congenital cardiology, pulmonary hypertension, interventional pediatric cardiology, and congenital cardiovascular surgery was consulted and after extensive discussions the patient consented to surgical intervention. Prior to his operative date, he underwent cauterization of his bilateral nasal cavity telangiectasias by Otolaryngology (Figure 1). On hospital day sixteen, he underwent a fourth time redo median sternotomy, pulmonary valve replacement with St. Jude Epic 27-mm porcine bioprosthesis, and repair of left pulmonary artery stenosis. Intraoperative transesophageal echocardiogram at the end of the surgical case demonstrated severe right ventricular dilation, severe right ventricular systolic dysfunction, normal pulmonary valve prosthesis, and left ventricular ejection fraction of 55%. The case was technically challenging requiring a cardiopulmonary bypass time of 178 minutes, and massive transfusion (including twelve units packed red blood cells, two packs of platelets, 4 units fresh frozen plasma, and 10 units cryoprecipitate) for a total estimated blood loss of 3.9 L.

Postoperatively, he had persistent right ventricular systolic dysfunction and diffuse mediastinal hemorrhage. By postoperative day two, a repeat transesophageal echocardiogram revealed worsening right ventricular dilation and severe right ventricle systolic dysfunction. The multidisciplinary care team recommended central venoarterial extracorporeal membrane oxygenation (VA ECMO) support for both worsening hypoxemia and continuing severe right ventricular failure.  The aorta was cannulated with a 22 French Bio-Medicus cannula (Medtronic, Minneapolis, USA) and the right atrium cannulated with a 36 French venous cannula (Medtronic, Minneapolis, USA), and full ECMO support was initiated using a Cardiohelp console with a HLS 7.0 oxygenator (Getinge, Goteborg, Sweden) reaching ECMO blood flows of 6 L/minute (an indexed ECMO blood flow of 2.6 L/minute/m²).

On POD 3, bronchoscopy was performed and revealed diffuse thin bloody secretions in the distal airways without a focal source, which was cleared with suction but quickly reaccumulated. Due to the pulmonary hemorrhage and recent mediastinal hemorrhage, systemic anticoagulation was not started at that time. Due to a lack of awakening during a sedation vacation, computed tomography (CT) imaging of his head was obtained and demonstrated a large ischemic stroke affecting the majority of the left MCA territory and part of the right parietal lobe (Figure 2).

HHT (also known as Osler-Weber-Rendu disease) is an autosomal dominant genetic disease with various vascular manifestations (1). In addition to the more common mucocutaneous and gastrointestinal tract telangiectasias, some patients with HHT also have pulmonary arteriovenous malformations (AVMs) with right-to-left shunt that can cause hypoxemia with resultant polycythemia. Cerebral AVMs present a risk of intracranial hemorrhage, ischemia, and hydrocephalus, which correlate with the size of the vascular defect. Given the presence of AVMs and hemorrhagic complications related to telangiectasias, the use of extracorporeal membrane oxygenation (ECMO) in patients with HHT is a potentially high-risk situation.

This case highlights the risks of ECMO in patients with HHT. The causes of this patient’s hemorrhagic and thrombotic events were most likely multifactorial, including contributions from a dilutional and consumptive coagulopathy after cardiopulmonary bypass and hemorrhage, initiation of ECMO, kidney failure, and his underlying HHT. The timing and precise cause of our patient’s cerebral infarction are unclear. However, patients with HHT and clinically significant intrapulmonary AVMs may have an increased risk of paradoxical thromboembolic stroke (2). The international HHT expert guidelines assert that even though HHT is a hemorrhagic disorder, it provides no protection against thrombosis (3). In addition, patients with HHT may  levels of von Willebrand factor and factor VIII, which would potentially increase their risk of thrombosis (4). This case exemplifies the substantial risks of hemorrhagic and thrombotic complications associated with ECMO for patients with HHT. Further study is needed to help determine whether HHT should be considered a contraindication to ECMO.

Theodore O. Loftsgard, APRN, CNP^1,2; Kari A. Wilson, APRN, CNP^1,2; John K. Bohman, MD^2,3

¹Department of Cardiovascular Surgery, Mayo Clinic, Rochester, MN

²Critical Care Independent Multidisciplinary Program, Mayo Clinic, Rochester, MN

³Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN

References

1. Faughnan ME, Palda VA, Garcia-Tsao G, et al. International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia. J Med Genet. 2011 Feb;48(2):73-87. [CrossRef] [PubMed]
2. Dittus C, Streiff M, Ansell J. Bleeding and clotting in hereditary hemorrhagic telangiectasia. World J Clin Cases. 2015 Apr 16;3(4):330-7. [CrossRef] [PubMed]
3. Faughnan ME, Mager JJ, Hetts SW, et al. Second International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia. Ann Intern Med. 2020 Dec 15;173(12):989-1001. [CrossRef] [PubMed]
4. Shovlin CL, Sulaiman NL, Govani FS, Jackson JE, Begbie ME. Elevated factor VIII in hereditary haemorrhagic telangiectasia (HHT): association with venous thromboembolism. Thromb Haemost. 2007 Nov;98(5):1031-9. [PubMed]

Cite as: Loftsgard TO, Wilson KA, Bohman JK. May 2024 Medical Image of the Month: Hereditary Hemorrhagic Telangiectasia in a Patient on Veno-Arterial Extra-Corporeal Membrane Oxygenation. Southwest J Pulm Crit Care Sleep. 2024;28:68-70. doi: https://doi.org/10.13175/swjpccs015-24 PDF