1084 CASE REPORT DUMOULIN ET AL Ann Thorac SurgPREDISPOSITION TO IDIOPATHIC SUBGLOTTIC STENOSIS 2013;95:1084–6

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2. Refaat MM, Hashash JG, Shalaby AA. Late perforation bycardiac implantable electronic device leads: clinical presenta-tion, diagnostic clues, and management. Clin Cardiol 2010;33:466–75.

3. Bohora S, Unnikrishnan M, Ajit Kumar VK, et al. Lefthemothorax: a presentation of a late ventricular perforationcaused by an active fixation pacing lead. Int J Cardiol2010;141:e43– 6.

4. Sanoussi A, El Nakadi B, Lardinois I, et al. Late right ventric-ular perforation after permanent pacemaker implantation:how far can the lead go? Pacing Clin Electrophysiol 2005;28:723–5.

5. Merla R, Reddy NK, Kunapuli S, et al. Late right ventricularperforation and hemothorax after transvenous defibrillatorlead implantation. Am J Med Sci 2007;334:209–11.

6. Hirschl DA, Jain VR, Spindola-Franco H, et al. Prevalenceand characterization of asymptomatic pacemaker and ICDlead perforation on CT. Pacing Clin Electrophysiol2007;30:28 –32.

Idiopathic Subglottic Stenosis: AFamilial PredispositionElaine Dumoulin, MD, FRCPC,David R. Stather, MD, FRCPC, Gary Gelfand, MD, MS,Bruno Maranda, MD, FRCPC,Paul MacEachern, MD, FRCPC, andAlain Tremblay, MDCM, FRCPC

Departments of Medicine and Genetics, University ofSherbrooke, Sherbrooke, Quebec; and Department ofMedicine and Division of Thoracic Surgery, University ofCalgary, Calgary, Alberta, Canada

Idiopathic subglottic stenosis is a narrowing of the tra-chea at the level of the cricoid cartilage of unknownetiology. It is a rare condition for which the real inci-dence has never been established owing to the difficultyof making the diagnosis. Although there is a femalepreponderance, no familial cases have been reported inthe literature. We describe two pairs of sisters as well asa mother and daughter presenting with idiopathic sub-glottic stenosis. All known causes of tracheal stenosiswere excluded, including prolonged intubation, surgery,autoimmune and inflammatory disorders, infection andgastroesophageal reflux disease. These are the first casesreported in the literature that suggest a genetic predispo-sition for idiopathic subglottic stenosis.

(Ann Thorac Surg 2013;95:1084–6)© 2013 by The Society of Thoracic Surgeons

Subglottic stenosis is an inflammatory cicatricial nar-rowing of the airway, usually at the level of the

cricoid cartilage. It can be related to trauma duringairway instrumentation, surgery, radiation, autoimmunedisorders such as Wegener’s granulomatosis, infectionsuch as tuberculosis or histoplasmosis, and congenital

Accepted for publication July 19, 2012.

Address correspondence to Dr Dumoulin, Department of Respiratorye

Medicine, CHUS, 3001, 12 Ave Nord, Sherbrooke, Quebec J1H 5N4,

Canada; e-mail: elaine.dumoulin@usherbrooke.ca.

© 2013 by The Society of Thoracic SurgeonsPublished by Elsevier Inc

abnormalities [1]. Approximately 5% of cases will remainidiopathic after all known causes have been ruled out [2].

Idiopathic subglottic stenosis has a female preponder-ance, usually affecting women between 30 and 50 years ofage [3]. Aside from cases of congenital subglottic stenosisin siblings at birth [4], there are no cases of adult familialsubglottic stenosis described in the literature. We de-scribe two pairs of sisters, as well as a mother and adaughter, who were treated for idiopathic subglotticstenosis between 1990 and 2011.

Case Reports

Family 1SISTER (CASE 1.1). A 33-year-old woman presented in 2005 withsymptoms of shortness of breath for 5 years after unsuc-cessful treatment for asthma with salbutamol. She hadundergone a tonsillectomy at age 6. She had no history ofgastroesophageal reflux disease (GERD), trauma, or pro-longed intubation and was a lifetime nonsmoker. Workupfor autoimmune disease was negative, including antinu-clear antibody (ANA), antineutrophil cytoplasmic antibody(ANCA), and sedimentation rate. Flexible bronchoscopyrevealed a simple weblike subglottic stenosis 1.5 cm belowthe vocal cords. She underwent rigid bronchoscopy withradial electrocautery incision, mechanical dilation, and mi-tomycin application. Biopsy of the subglottic stenosis re-vealed mild chronic inflammation and fibrosis. She had arecurrence at 6 years and underwent a successful dilation inNovember 2011.SISTER (CASE 1.2). A 41-year-old woman presented in 2005with symptoms of progressive stridor. She had a ton-sillectomy at age 4 and no other comorbidities. She wasa lifetime nonsmoker. Workup for autoimmune diseasewas negative, including ANA and ANCA. Flexiblebronchoscopy revealed the presence of a simple web-like subglottic stenosis 2 cm below the vocal cords. Sheunderwent rigid bronchoscopy with dilation shortlyafter the diagnosis was made. The stenosis recurred 3years later, and another rigid bronchoscopy with dila-tion was performed. After another recurrence the sameyear, she underwent a cricotracheal resection. Thepathology report of the resection specimen revealed abenign trachea with luminal narrowing, chronic in-flammation, and fibrosis; the tracheal cartilage waspartially ossified. She had no recurrence at 4-yearfollow-up after the resection.FAMILY HISTORY. The subjects’ mother had been previouslyintubated but had no history of tracheal stenosis onclinical evaluation. Two brothers were also previouslyintubated but have no history of tracheal stenosis.

Family 2SISTER (CASE 2.1). A 51-year-old woman presented in 2010with a 4-year history of shortness of breath and progres-sive stridor. She had undergone cholecystectomy, hyster-ectomy, and hemithyroidectomy 15, 10, and 2 yearsearlier, respectively. Her pulmonary symptoms were

present before her hemithyroidectomy, but no difficult

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1085Ann Thorac Surg CASE REPORT DUMOULIN ET AL2013;95:1084–6 PREDISPOSITION TO IDIOPATHIC SUBGLOTTIC STENOSIS

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intubation was reported. She was on no medication, hadno history of GERD, and was a lifetime nonsmoker. Shehad a negative workup for autoimmune disease, includ-ing ANA, ANCA, rheumatoid factor, and sedimentationrate. Flexible bronchoscopy revealed a simple weblikesubglottic stenosis 1.7 cm below the vocal cords. Sheunderwent rigid bronchoscopy with radial electrocauteryincision, mechanical dilation, and mitomycin application.Biopsy of the subglottic stenosis revealed fragments offibrous tissue with chronic inflammatory infiltrate andareas of benign smooth muscle. At 14 months, she had arecurrence and is scheduled for a repeat rigid bronchos-copy and dilation procedure.SISTER (CASE 2.2). A 41-year-old woman presented in 2008with a history of progressive shortness of breath for 5years. She had undergone a tonsillectomy at age 6. Shehad no other comorbidities and was a lifetime non-smoker. Workup for autoimmune diseases was negative.Bronchoscopy revealed a simple weblike subglottic ste-nosis 1.5 cm below the vocal cords. She underwent rigidbronchoscopy with laser, mechanical dilation, and dec-adron application over the laser incisions. Biopsy of thesubglottic stenosis revealed squamous mucosal liningwith subepithelial stroma, negative for dysplasia andneoplasia. She has had no recurrence after 4 years offollow-up.FAMILY HISTORY. Both mother and father were previouslyintubated but have no tracheal stenosis in their clinicalhistory. One brother was previously intubated for backsurgery, but does not have tracheal stenosis on clinicalhistory.

Family 3DAUGHTER (CASE 3.1). A 24-year-old previously healthywoman presented in 2011 with gradual onset dyspnea onexertion. She was previously misdiagnosed with asthmabut had no response to therapy. Her only medication wasan oral contraceptive pill. She was a lifetime nonsmokerand had no prior intubations. Workup for autoimmunedisease was negative, including ANCA. She had twosisters with mild exercise-induced asthma. Flexible bron-choscopy done as part of an asthma study revealed asimple weblike 7-mm subglottic stenosis, 1.5 cm belowthe vocal cords. She underwent rigid bronchoscopy withradial electrocautery incision, mechanical dilation, andmitomycin application. Biopsy of the subglottic stenosisrevealed fibrotic tissue with no granuloma, no malig-nancy, and no acute inflammation. She had no recur-rence at 12 months of follow-up.MOTHER (CASE 3.2). A 33-year-old previously healthy womanpresented in 1991 with a history of shortness of breath.She had a history of intubation 2 years earlier for a tuballigation. She was on no medication. She had no allergiesand was a lifetime nonsmoker. Workup and rheumato-logic evaluation were negative for autoimmune disease.She underwent rigid bronchoscopy with laser therapy.She has required repeated dilations since then, with aninterval between procedures ranging from 9 months to 3

years. There was no change in the recurrence rate with

the use of prophylactic trimethoprim-sulfamethoxazoleor prednisone. Many years after her diagnosis, she wastreated for GERD without any changes in her symptoms.Her last procedure was in December 2009.FAMILY HISTORY. The mother has 3 sisters with no history oftracheal stenosis. The daughter has 2 healthy sisters whowere never intubated and have no known tracheal ste-nosis, although they carry a diagnosis of mild asthma.

Comment

Idiopathic subglottic stenosis is a rare condition. Theexact incidence and pathophysiology is unknown. Re-ports exist suggesting GERD as a causative factor, with asingle case report documenting successful therapy of asubglottic stenosis after GERD therapy [5]. None of ourpatients described symptoms of GERD. Many authorshave also suggested a hormonal cause for this conditionas it is mainly seen in women. Previous studies havefailed to demonstrate the presence of estrogen receptorsin the tissue biopsies of patients with subglottic stenosis,and no clear association has been found [5]. Autoimmunediseases, such as Wegener’s granulomatosis, have beendescribed in the literature as being an underlying causeof idiopathic subglottic stenosis [1]. Both ANCA andANA titer studies were negative in our patients.

Postintubation trauma is one of the most commoncauses of tracheal stenosis, and is thought to be related toischemic damage and the mechanical effects induced byprolonged or traumatic intubation [6]. The clinical pre-sentation of postintubation tracheal stenosis is stridorand shortness of breath after a recent prolonged intuba-tion. It occurs most commonly in the first 3 to 6 weeksafter extubation after mechanical ventilation of 5 to 7days [7]. No case of permanent tracheal stenosis has everbeen reported in patients with intubation for less than 18hours [8]. Several of our cases had either remote child-hood history (cases 1.1, 1.2, and 2.2) or trivial history (case3.2) of intubation for minor surgery. One case (2.1) didhave a history of three previous surgeries with intuba-tion, including a hemithyroidectomy, but none was pro-longed or traumatic. The hemithyroidectomy lasted for 1hour and 30 minutes. A complete review of the extendedfamilies was also performed. Given the numerous casesof intubation among unaffected family members, theredoes not seem to be a link between postintubationstenosis and familial history in our cases.

Idiopathic tracheal stenosis is a condition that can bechallenging to treat. Its management includes an endo-scopic approach with mechanical dilation using rigidbronchoscopy or balloon dilation with flexible bronchos-copy, but the rate of recurrence has been reported ashigh as 87% at 5 years [3]. Cricotracheal resection, a muchmore invasive approach, is the alternative, with a recur-rence rate that varies between 10% and 40% at 8 years [6].

We describe two pairs of sisters, as well as a motherand a daughter, who presented with idiopathic subglotticstenosis. To our knowledge, these are the first cases of

familial subglottic stenosis reported in the literature. The

1086 CASE REPORT TAYLOR ET AL Ann Thorac SurgCARCINOID, LYMPHOMA, AND SJÖGREN SYNDROME 2013;95:1086–7

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only cases previously reported were congenital subglotticstenosis in young siblings at birth [4]. Our cases open thedoor to the hypothesis of a genetic predisposition to thedevelopment of idiopathic subglottic stenosis in adults.Recognition and understanding of genetic abnormalitiesassociated with this condition could shed some light intoits etiology and, it is hoped, lead to improved therapeuticoptions for this difficult to treat condition.

References

1. Courey MS. Airway obstruction. The problem and its causes.Otolaryngol Clin North Am 1995;28:673–84.

2. Perotin JM, Jeanfaivre T, Thibout J, et al. Endoscopic man-agement of idiopathic tracheal stenosis. Ann Thorac Surg2011;92:297–302.

3. Grillo HC, Mark EJ, Mathisen DJ, et al. Idiopathic laryngotra-cheal stenosis and its management. Ann Thorac Surg 1993;56:80–7.

4. Linna O, Hyrynkangas K, Kaukola T, et al. Congenital sub-glottic stenosis in two unrelated pairs of sibling. Acta Paediatr2004;93:565–7.

5. Valdez TA, Shapshay SM. Idiopathic subglottic stenosis re-visited. Ann Otol Rhino Laryngol 2002;111:690–5.

6. Heather C, Herrington BA, Weber SM, et al. Modern manage-ment of laryngotracheal stenosis. Laryngoscope 2006;116:1553–7.

7. Wain JC. Postintubation tracheal stenosis. Semin ThoracCardiovasc Surg 2009;21:284–9.

8. Yang KL. Tracheal stenosis after a brief intubation. AnesthesAnalges 1995;80;625–7.

A Rare Association of PulmonaryCarcinoid, Lymphoma, and SjögrenSyndromeWilliam St. J. Taylor, MB ChB,Paul Vaughan, MD, MRCS Ed, Simon Trotter, FRCPath,and Pala B. Rajesh, FRCS (CTh), FECTS

Departments of Thoracic Surgery and Cellular Pathology,Heartlands Hospital, Birmingham, United Kingdom

Pulmonary carcinoid and pulmonary lymphoma are bothrare cancers and are seldom seen together. Cases havebeen reported of their coexistence in the gastrointestinaltract, but our literature searches only found a single caseof their coexistence in the lung. We discuss our case aswell as the literature to try to find a connection andexplanation for this occurrence.

(Ann Thorac Surg 2013;95:1086–7)© 2013 by The Society of Thoracic Surgeons

Carcinoid tumors are slow-growing neuroendocrinetumors, usually found in the gastrointestinal tract

or in the lung [1]. They are associated with other malig-nant syndromes, especially in patients with the MEN1gene mutation. An association between carcinoid andother noncarcinoid malignancies has been reported in upto 22% of cases [2]. The coexistence of a carcinoid tumor

Accepted for publication June 25, 2012.

Address correspondence to Dr Taylor, 28 St Peters Rd, Harborne, Bir-

mingham B170AY, United Kingdom; e-mail: wstjtaylor@doctors.org.uk.

© 2013 by The Society of Thoracic SurgeonsPublished by Elsevier Inc

and a mucosa-associated lymphoid tissue (MALT) lym-phoma is extremely rare. There is a single case ofcoexistence in the gastrointestinal tract, in which anadenocarcinoid was found incidentally in the ileum andappendix after a laparotomy for gastric MALT lymphoma[3]. There is also a single case in the literature of bothcoexisting in the lung [4].

Mucosa-associated lymphoid tissue lymphoma are adistinctive subtype of non-Hodgkin lymphoma. Theytend to occur most commonly in the gastrointestinaltract, but can also occur in the lung. They are associatedwith chronic inflammatory disorders and autoimmunediseases, including Sjögren syndrome [5]. The risk ofdeveloping malignant non-Hodgkin lymphoma in pa-tients with Sjögren syndrome (characterized by dry eyesand dry mouth) is 44 times higher than that of the normalpopulation. A common subtype is MALT lymphomas ordiffuse large B-cell lymphoma [6].

A 67-year-old woman presented with nonresolvingpneumonia. Subsequent computed tomography scandemonstrated a pedunculated lesion in her right mainbronchus. Her only significant past medical history wasSjögren syndrome. Flexible bronchoscopy confirmed asmooth, rounded mass, biopsy of which showed carci-noid tumor.

Rigid bronchoscopy identified the lesion arising fromthe medial bronchial wall at the junction of the rightmain bronchus and bronchus intermedius opposite theupper lobe orifice.

Preoperatively a bronchotomy and resection, orsleeve right upper lobectomy was planned. Unfortu-nately intraoperatively it became evident that toachieve a complete resection, this was impossible. Shetherefore underwent a middle and lower bilobectomywith anastomosis of the right upper lobe bronchus tothe stump of the right main bronchus. Postoperativelyshe made an uneventful recovery.

Fig 1. Photomicrograph showing the carcinoid tumor (arrow, bron-chial cartilage) with a high-power view (inset) showing typical neu-

roendocrine histology.

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