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  Table of Contents    
ORIGINAL ARTICLE  
Year : 2021  |  Volume : 64  |  Issue : 4  |  Page : 683-686
The Ring-and-Sling complex – Does it “Ring” true?


1 Department of Pathology, Seth GS Medical College, Mumbai, Maharashtra, India
2 Department of Cardiac Surgery, Boston Children's Hospital/Harvard Medical School, Boston, MA, USA

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Date of Submission10-Apr-2020
Date of Decision25-May-2020
Date of Acceptance30-May-2020
Date of Web Publication20-Oct-2021
 

   Abstract 


Background: The “Ring-and-Sling” complex (RSC) comprises congenital tracheal stenosis and an abnormal origin/course of the left pulmonary artery. Based on clinical and imaging studies, the luminal narrowing is assumed to be as a result of rings cartilage (forming an “O”). Aims: This is a postmortem based study of tracheal histology in infants after an autopsy encounter of a case of RSC. Subject and Methods: RSC was identified in an infant at autopsy. The tracheal histomorphology revealed the presence of cartilaginous plates (instead of rings) and fibro-elastotic proliferation at the site of trachealis muscle. These changes prompted a study on variations in the histology of the trachea (with no known anomaly) in 35 autopsied neonates and infants. The transverse sections of the trachea were taken at one or more levels (Level 1 – at the level of the thyroid, Level 2 – midway between the thyroid and the carina, and Level 3 – just above the carina. Statistical Analysis: Epi-info software (v1.4.3, CD, US). Results: On histology, 83 sections showed the trachealis muscle on the posterior aspect. A single semicircular cartilage was identified in only 17 of the 83 sections studied (20.5%, 6 in level 1, 9 in level 2 and 2 in level 3). In the remaining 66 sections (79.5%), the cartilage was disposed as multiple plates, ranging in number from 2 to 10. No significant association was found between semicircular cartilage rings and age, sex, gestational age, and level of section (P < 0.05). However, 14 cases with sectioning at all three levels were taken into account; all levels showed more cartilaginous plates compared to single rings, which were more common at level 1 (P > 0.05). Conclusions: The “ring” in RSC and normal infantile tracheas show cartilage plates with intermittent semicircular cartilage rings. These findings may have surgical implications for tracheal anomalies and bode favorable surgical outcomes.

Keywords: Congenital anomalies, Histology, Ring-and-Sling complex,Trachea

How to cite this article:
Ray M, Sathe P, Vaideeswar P, Marathe SP. The Ring-and-Sling complex – Does it “Ring” true?. Indian J Pathol Microbiol 2021;64:683-6

How to cite this URL:
Ray M, Sathe P, Vaideeswar P, Marathe SP. The Ring-and-Sling complex – Does it “Ring” true?. Indian J Pathol Microbiol [serial online] 2021 [cited 2021 Nov 27];64:683-6. Available from: https://www.ijpmonline.org/text.asp?2021/64/4/683/328556





   Introduction Top


The large airways of the respiratory tract are made up of the larynx, the trachea, and the two main bronchi, and congenital anomalies of these parts can be fatal to the newborn. When tracheo-esophageal fistulous connections are excluded, the prevalence of other congenital tracheal malformations ranges from 0.2 and 1 in 10,000 live births.[1] Often, these anomalies tend to involve the cartilaginous plates and are also associated with other thoracic and nonthoracic congenital abnormalities. The “Ring-and-Sling” complex (RSC) is one such association comprising congenital tracheal stenosis (CTS) and an abnormal origin/course of the left pulmonary artery.[2] The luminal narrowing is assumed to be as a result of complete continuous ring of cartilage (forming an “O”) as the cases reported in literature are based on clinical and/or imaging studies. However, on histological analysis of a case of the RSC and a subsequent study conducted on normal tracheal segments, we found that the tracheal cartilages are usually not oriented as either an intact “O” or a “C.”


   Subject and Methods Top


Case study

A 2-month-old female infant was admitted in our tertiary-care center with a 4-day history of fever, productive cough, and increased respiratory activity. There had also been suck-rest-suck cycle and forehead sweating. Similar symptoms had been present during the neonatal period. On examination, the baby had tachycardia (heart rate of 164 beats/minute), tachypnea (66 breaths/minute), a systolic murmur and bilateral crepitations. The clinical impression was pneumonia with septicemia. Her total leukocyte count was 16,300/cmm with an elevated absolute neutrophil count of 10,600/cumm. Blood cultures detected no growth. She was diagnosed as ventricular septal defect (VSD) with patent ductus arteriosus (PDA) on echocardiography. In view of impending respiratory failure (hypercapnia on arterial blood gas analysis), endotracheal intubation was attempted. Following its failure, tracheal narrowing was suspected. A tracheostomy was performed, and the child was mechanically ventilated with inotropic support. However, she developed worsening sepsis over the next 4 weeks and eventually succumbed.

A complete postmortem was performed. The heart and lungs [Figure 1]a and [Figure 1]b were preserved as a block and dissected. Apart from the subaortic perimembranous VSD and PDA, a left-sided superior vena cava and persistent foramen ovale were also identified. The aorta and pulmonary trunk (PT) had a normal relationship; the PT was larger than the aorta. In addition, left pulmonary artery (LPA) arose from the right pulmonary artery (RPA) at the right tracheal border and then turned leftwards to enter the left pulmonary hilum, coursing between the trachea and the esophagus – the sling (LPAS). The entire trachea was small in caliber and rigid, and the transverse section on gross examination revealed an “O” arrangement of the cartilage – the ring. However, on histopathology, samples from various levels of the trachea revealed a bronchial-like arrangement of the cartilaginous plates [Figure 2]a and [Figure 2]b with extensive fibroelastosis and increased submucosal glands, particularly in the region of the absent trachealis [Figure 2]c. No complete/intact rings were identified. The cause of death was related to bronchopneumonic consolidation.
Figure 1: (a) The trachea T is seen as a slender rigid tube; (b) The trachea T (reflected backwards) to show a retrotracheal course of the left pulmonary artery LPA. Left bronchus LB appears larger than the trachea (AA, ascending aorta; DTA, descending thoracic aorta; LAA, left atrial appendage; LCCA, left common carotid artery; LSA, left subclavian artery; LSVC, left superior vena cava; LV, left ventricle; PDA, patent ductus arteriosus; PT, Pulmonary trunk; RAA, right atrial appendage; RBCA, right brachiocephalic artery; RV, right ventricle)

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Figure 2: Section from the left posterolateral region of the trachea showing (a) H and E x 250 and (b) Elastic van Gieson x 250 – small cartilaginous islands with exceedingly thick peri-chondrial connective tissue; (c) The posterior tracheal wall (region of trachealis muscle) is occupied by very prominent fibro-elastotic tissue with increase in submucosal mucous glands (Elastic van Gieson x 250)

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These histopathological findings and paucity of literature on tracheal cartilages in normal as well as pathological states prompted us to conduct a study on variations in the histology of the trachea (with no known anomaly) in 35 consecutive autopsied neonates and infants. The heart-lung blocks were fixed in 10% buffered formal saline for a minimum of 24 h duration. Then, transverse sections of the trachea were taken at one or more levels (Level 1 – at the level of the thyroid, Level 2 – midway between the thyroid and the carina, and Level 3 – just above the carina. The tissues were processed and embedded in paraffin wax. Sections were cut at a thickness of 3–5 μm on a rotary microtome, stained with Harris' haematoxylin and eosin (H and E) stain and subjected to light microscopic examination for histological analysis. An excel sheet was prepared for the data collected. Statistical analysis was done on epi-info software (v1.4.3, CD, US). Descriptive analysis was done by calculating mean 2 percentages. Associations were tested using Chi-square test.


   Results Top


A total of 83 sections of the trachea (15 from level 1 and 34 each from levels 2 and 3) were evaluated from 35 deceased children (18 neonates, 17 infants with a male-to-female ratio of 1.06:1). Tracheal samples for histology were taken from all the 3 levels in 14 patients, from levels 2/3 in 19 patients, level 1/3 in one case, and level 2 in one other case.

On histology, all of the sections showed the trachealis muscle on the posterior aspect. A single semicircular cartilage was identified in only 17 of the 83 sections studied (20.5%, 6 in level 1, 9 in level 2, and 2 in level 3). In the remaining 66 sections (79.5%), the cartilage was disposed as multiple plates [Figure 3]a, ranging in number from 2 to 10 and was separated by mesenchymal tissue with or without mucinous glands. The maximum number was present at level 3. The plates were located on the anterior and lateral aspects, but some smaller cartilaginous islands were also observed behind the trachealis muscle [Figure 3]b in few sections. At various levels, there was some overlap between the plates (possibly their position at rest and during expiration), while few showed cartilaginous differentiation of intervening mesenchyme [Figure 3]c in-between the plates. No significant association was found between semicircular cartilage rings and age, sex, gestational age, and level of section (P < 0.05). However, when 14 cases with sectioning at all three levels were taken into account; all levels showed more cartilaginous plates compared to single rings, which were more common at level 1 (P > 0.05).
Figure 3: Normal tracheal sections showing (a) Multiple and (b) Overlapping, cartilaginous plates; (c) Cellular mesenchymal tissue (arrows) identified between cartilage (H and E x 250)

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   Discussion Top


The trachea is normally made up of up to 16 to 22 rings of cartilage that are connected to each other by the annular ligaments and attached dorsally to the trachealis muscle. The trachea develops from the laryngo-tracheal tube around the fourth week of life (embryo size 0.4 cm). The mesenchymal rudiments of the tracheal cartilages are seen by the eighth week (embryo size of 2.8–3.0 cm) with cranio-caudal extension over the next 2 weeks. Simultaneously, the mesenchyme between the cartilages give rise to fibroelastic tissue of the tracheal wall, and posteriorly, the trachealis muscle develops between the ends of the embryonic rings. All of the major microscopic features of the trachea are visible by the end of week 20.[3] In majority of the cases, abnormalities in this development give rise to either tracheomalacia or CTS.[1]

Ours is a case of RSC, identified at autopsy, in an infant with recurrent lower respiratory tract infections. The ring component refers to CTS produced by replacement of the usual horseshoe-shaped cartilage and the posterior membranous portion of the trachea by complete circular cartilaginous rings. This is a rare anomaly with an estimated incidence of 1 in 64500 births;[4] the actual incidence may not be known as in some instances, there might be early fatality. Dysregulation of smooth muscle orientation and degree of chondromatous differentiation are the pathogenetic mechanisms proposed to explain the stenosis.[5],[6] Since there are multitude of variations in the morphology and hence their consequent prognosis, the Great Ormond Street Hospital classification[7] is often used. It is based on the pattern of tracheobronchial arborisation, involvement of the trachea and/or bronchi, length of stenosis, and presence of lung agenesis. In the reported case, the branching of the trachea-bronchial tree and the caliber of the main bronchi were normal, but the entire trachea was uniformly narrowed – long segment stenosis.

On histology, the stenotic segment predictably showed absence of the trachealis muscle, but the cartilaginous plates were multiple, arranged in an “O”-shaped manner. Similarly, in the tracheal segments studied in 35 neonates and infants, we again found multiple plates arranged in a “C”-shaped fashion in 79.7% of the 83 tracheal sections studied. A thorough literature search revealed that there is a dearth of studies conducted on human tracheas in normal or diseased states. A quantitative study of the trachea conducted in 452 children described the age-related changes in the shape and length but had not focused on the cartilaginous disposition.[8] Though resections are often performed for congenital stenosis,[9] histopathogical aspects are hardly mentioned. In two case reports with CTS, Özer et al.[10] and Jabari et al.[11] have reported complete cartilaginous ring and multiple plates forming an almost complete ring (like our case) in a neonate and a child, respectively. The evidence of plates, normal semicircular rings, and abnormal circular rings at different levels of the trachea indicates that chondrogenesis and chondromatous maturation, modelling and remodelling occurs post birth, into infancy and may be well into adulthood. Hence, it is possible that complete rings may be present in adolescents or adults,[12] who have a late presentation or delayed diagnosis.

It is to be noted that the CTS is associated with cardiovascular and extra-cardiac malformations to the extent of 69% of the patients.[1] Among them, LPAS (the second component of the index case) is the most common association (48–57%), where the LPA originates from the posterior aspect of the RPA, passes between the trachea and esophagus before its entry into the left lung, thereby forming a sling around the airway. Another noteworthy fact is that the sling can occur independent of the ring with a prevalence of 59 per 1000000 children.[13] Characteristically, 70% of the patients with LPAS have a long segment tracheal narrowing, explained by synchronous airway and vascular maldevelopment.[14] Additionally, LPAS may also have other cardiac defects in 30% of the patients.[15] In our case, the entire trachea was narrowed and the heart showed the presence of intracardiac and extra-cardiac left-to-right shunts.

The clinical presentation of the RSC depends on the severity of stenosis. The symptoms can begin by the first year of life with features of airway obstruction such as noisy breathing and dyspnea, and later with recurrent respiratory tract infections and difficult intubations.[3] It is essential that the combination is identified early by appropriate preoperative imaging techniques because the tracheal stenosis and the anomalous artery are repaired simultaneously.[16]


   Conclusions Top


The “ring” in RSC is composed of a variable number of cartilage plates arranged in an “O” configuration, rather than a complete ring. Likewise, normal infantile tracheas also show cartilage plates with intermittent semicircular cartilage rings. These finding provide a clearer understanding of the true microscopic arrangement of tracheal cartilages and could possibly provide better surgical options for tracheal anomalies that bode favorable outcomes. A detailed study of the human adult tracheal histology is also warranted.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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Varela P, Torre M, Schweiger C, Nakamura H. Congenital tracheal malformations. Pediatr Surg Int 2018;34:701-13.  Back to cited text no. 1
    
2.
Berdon WE, Baker DH, Wung JT, Chrispin A, Kozlowski K, de Silva M, et al. Complete cartilage ring-ring tracheal stenosis associated with anomalous left pulmonary artery: The ring-sling complex. Radiology 1984;152:57-64.  Back to cited text no. 2
    
3.
Pansky B. Development of the lower respiratory system: Larynx and trachea. In: Pansky B, editor. Review of Medical Embryology. 1st ed. New York: MacMillan Publishing Co. Inc; 1982. p. 58.  Back to cited text no. 3
    
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Landry AM, Rutter MJ. Airway anomalies. Clin Perinatol 2018;45:597-607.  Back to cited text no. 4
    
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Sinner DI, Carey B, Zgherea D, Kaufman KM, Leesman L, Wood RE, et al. Complete tracheal ring deformity: A translational genomics approach to pathogenesis. Am J Respir Crit Care Med 2019;200;1267-81.  Back to cited text no. 6
    
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Speggiorin S, Torre M, Roebuck DJ, McLaren CA, Elliott MJ. A new morphologic classification of congenital tracheobronchial stenosis. Ann Thorac Surg 2012;93:958-61.  Back to cited text no. 7
    
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Wailoo MP, Emery JL. Normal growth and development of the trachea. Thorax 1982;37:584-7.  Back to cited text no. 8
    
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Backer CL, Holinger LD. A history of pediatric tracheal surgery. World J Pediatr Congenit Heart Surg 2010;1:344-63.  Back to cited text no. 9
    
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Özer EA, Cumurcu S, Bayol Ü, Özdemir SA, Ilhan Ö, Sütçüoğlu S. Congenital complete tracheal ring in a neonate: A case report. Turk Patoloji Derg 2017;33:259-61.  Back to cited text no. 10
    
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Jabari S, Hartmann A, Cesnjevar R. Congenital tracheal stenosis associated with left pulmonary artery sling accompanied by tracheal diverticula: A case report. J Pediatr Surg Case Rep 2016;16;28-31.  Back to cited text no. 11
    
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Sahoo DH, Karnal D, Gildea TR, Mehta AC. Complete tracheal ring. Respiration 2009;77:96.  Back to cited text no. 12
    
13.
Yu JM, Liao CP, Ge S, Weng ZC, Hsiung MC, Chang JK, et al. The prevalence and clinical impact of pulmonary artery sling on school-aged children: A large scale screening study. Pediatr Pulmonol 2008;43:656-61.  Back to cited text no. 13
    
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Fukushima N, Shimojima N, Ishitate M, Miyakawa T, Hirobe S, Miura M. Clinical and structural aspects of tracheal stenosis and a novel embryological hypothesis of left pulmonary artery sling. Pediatr Pulmonol 2020;55:747-53.  Back to cited text no. 14
    
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Hirsig LE, Sharma PG, Verma N, Rajderkar DA. Congenital pulmonary artery anomalies: A review and approach to classification. J Clin Imaging Sci 2018;8:29.  Back to cited text no. 15
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16.
Vinh VH, Khanh HQ, Quang NVD. Surgical reconstruction for congenital tracheal malformation and pulmonary artery sling. J Cardiothorac Surg 2019;14:49.  Back to cited text no. 16
    

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Correspondence Address:
Pradeep Vaideeswar
Department of Pathology (Cardiovascular and Thoracic Division), Seth GS Medical College, Parel, Mumbai - 400 012, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_363_20

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