The anterior commissure of the human larynx revisited.

BACKGROUND: The anterior commissure (AC) of the human larynx is usually understood as an area of the glottis anteriorly situated between the two vocal folds inserting to the thyroid cartilage (TC). The pattern of spread of AC carcinoma could hypothesize that AC could include other structures of the ventral larynx as developmental anatomy could demonstrate. METHODS: Ten adult larynx specimens from donation program cadavers and 15 selected fetal specimens (from 11 to 34 weeks of amenorrhoea) were studied using microdissection and histological serial sections stained with hematoxylin-eosin and reticuline. RESULTS: In adult specimens, internal perichondrium of the TC was easily detached from the entire lateral lamina but not from an intermediate lamina superiorly marked by the superior thyroid notch. On this median band of TC is inserted the ventral connective tissue of the three levels of the larynx: the ventral part of the vocal folds with the anterior macula flava, the Broyle's epiglottic ligament, and the subglottic part of the conoid ligament. In young fetuses (11-12 weeks), intermediate lamina of TC joined at the glottic level but not at the supraglottic level; in fetuses at 22-25 weeks, a meshwork of bundles of connective fibers inserted to the intermediate lamina of TC. In fetuses at 33-34 weeks, organization is practically identical to adult specimens. CONCLUSION: According to the adult anatomical features and the organogenesis, the AC of the human larynx could be anatomically defined ventrally as being made up of the intermediate lamina of TC beneath the superior thyroid notch and dorsally the ventral insertions of vocal folds with macula flava, supraglottic Broyle's ligament, and subglottic conoid ligament leading to a "developmental" AC definition which could better explain specific spreading of AC carcinoma.

Switching of the Laryngeal Cavity From the Respiratory Diverticulum to the Vestibular Recess: A Study Using Serial Sagittal Sections of Human Embryos and Fetuses.

A cecum-like protrusion of the pharynx (the laryngeal cecum or vestibular recess [VR]) develops immediately anterior to the laryngeal part of the respiratory diverticulum. An expansion of the VR has been well described, whereas the fate of the diverticulum is still obscure, although its pharyngeal opening corresponds to the glottis. We observed sagittal sections of 10 embryos (five specimens at 5-6 weeks and another five at 7-8 weeks) and eight fetuses at 25-30 weeks. At 5-6 weeks, a lumen of the laryngeal part of the respiratory diverticulum appeared, and subsequently, the VR opened into the epithelial lamina. Because of this discrete separation, it seemed unlikely that the pharyngeal pouches contributed to the laryngeal epithelium. At 6-7 weeks, the VR exhibited a high boot-shaped lumen with canalization to the diverticular lumen at the level of the cricoid cartilage. Thus, in a midline area between the bilateral arytenoid cartilages, double laryngeal lumina were evident, separated by the thick midline epithelial lamina. At 25-30 weeks, the inferior part of the VR lumen had become enlarged because of the destruction of the epithelial lamina along the arytenoid and corniculate cartilages. In contrast, candidates for the initial diverticular lumen remained as epithelial slits in the anterosuperior side of the transverse arytenoid muscle. Therefore, the final anterior and lateral laryngeal walls seemed to originate from the VR with canalization, in contrast to the part of the posterior wall derived from the initial diverticular wall.

Embryological study of the glottic site and clinical implications.

The development of the glottic site, in particular of its ventral area, was studied to better understand the spreading pathways of T1, T2 cancer. Serial sections of larynges from human embryos, fetuses and adults were observed. A dorsal, a ventral and an intermediate compartment were found on the basis of their maturation schedule. A commissure muscle which develops in the anterior one third of the glottic site and wraps the connection system of vocal ligaments was recognized. The inferior paraglottic space, the compartment structures and the localization of superficial and deep blood vessels and of glands in the ventral compartment and the components of Broyles ligament were studied during ontogenesis. The compartments identified here have clinical and oncological relevance. Their detailed knowledge offers a prerequisite for planning and performing compartment conservative surgery in T1, T2 cancer, based on their spreading pathways.

Fetal airway wound repair: a new frontier.

PURPOSE: Fetal dermal repair is regenerative and scarless until middle to late gestation, when there is a transition to fibrotic repair. Fetal skeletal muscle and tendon undergo repair with fibrosis similar to the process in adults. This study addresses whether fetal mucosal healing is regenerative and scarless. METHODS: Anesthetized pregnant rabbits underwent laparotomy and controlled hysterotomy at 21 to 23 days' gestation (term is 31 days). A midline thyrotomy was made, followed by cricoidotomy and circumferential cauterization of the subglottic mucosa. A similar insult was applied to weanlings. The data were collected in 2 groups. One group was followed to term and killed at 4 weeks. A second group was killed after 6 days (30 days' gestation). The weanlings were killed at similar points. The larynges were harvested and processed for histological and morphometric analysis. RESULTS: Three litters were followed to term. Of these, 1 was not recovered; in the other two, 7 of 8 manipulated fetuses were found and 3 of 8 were viable. The fourth litter was harvested after 6 days; all 4 injured fetuses were recovered and viable. All animals in the fetal injury groups healed with complete regeneration of the airway mucosa. In contrast, weanlings injured post partum had mucosal inflammation, necrosis, and ulceration; squamous metaplasia and basal cell hyperplasia were also found. There were fibrosis, granulation tissue, and inflammation in the lamina propria; chondritis, cartilaginous necrosis, chondrolysis, and perichondritis were also found. CONCLUSIONS: Fetal airway mucosal healing is regenerative and, thus, scarless. This study provides further support for the thesis that skin and mucosa respond to injury similarly in both the developmental and postpartum stages, and that subglottic stenosis is reasonably thought of as the "hyperplastic scar" of the airway. These results have potential therapeutic applications for mucosal wound management.

Subglottic stenosis in infants and children.

Of 158 cases of subglottic stenosis 115 were congenital and 43 acquired. Current follow-up has been obtained in 146 (92%) which constitutes the determinate group. Although stridor was the most common presenting symptom of the congenital group, 34% presented with recurrent or prolonged episodes of croup. Tracheotomy was required in 47 of the 107 determinate cases (44%). Further management of the congenital cases was based on the experience that children outgrow this disorder; periodic dilatation may augment the natural process. Of those infants and children tracheotomized, all but five have been decannulated, and there was one death - a mortality rate of 2.1%. Acquired subglottic stenosis proved to be a more difficult management problem. Tracheotomy was necessary in 38 of the 39 determinate cases (97%). Repeated active dilatations for prolonged periods were usually required as well as endoscopic removal of granulation tissue. Of those infants and children tracheotomized, all but eight have been decannulated. There were nine deaths; five were due to unrelated underlying disease; four were attributable to complications of long-term tracheostomy. Thus, in the entire series, 85 infants and children required tracheotomy and five deaths may be attributable to long-term tracheostomy complications - a mortality rate of 5.9%.

Carcinoma of the anterior commissure of the larynx: I. Embryological and anatomic considerations.

In this study we attempt to define the organization of the anterior region of the adult larynx, on the basis of its development. For this purpose, we have studied the development of the anterior commissure region on serial sections of human larynges from embryos, fetuses, and adults. Our findings indicate that all the structures of this region derive from a single median mesenchymal band, first evident at 7 to 8 weeks of gestation, between the lateral laminae of the thyroid cartilage. This band of mesenchyme gives rise to all the structures along the midline of the thyroid cartilage and immediately beyond, including the intermediate lamina of the thyroid cartilage, the median process, and the connective tissue that connects the latter with the conoid ligament. We provide, for the first time, evidence that Broyles' ligament (commissural tendon) derives from the dorsal part of the median process and becomes intimately connected with the surrounding structures, including the insertion fibers of the vocal muscles, from early in development. On the basis of this finding we identify an independent anterior commissure region in the adult larynx, which comprises the intermediate lamina, Broyles' ligament, the connective tissue between the Broyles' and conoid ligaments, and the insertion fibers of the vocal muscles. The interpretation of all these structures as a unified region can explain the peculiar progression pathways and evolution of commissural and cordo-commissural tumors.

TNM glottic: role of the vocal muscle, arytenoid cartilage, and inferior paraglottic space in impaired vocal cord mobility (T2). An embryological and clinical study.

The TNM classification is unsatisfactory regarding the impaired mobility of the vocal cord and/or the arytenoid. The authors have studied the intrinsic laryngeal musculature, with particular attention to the medial thyroarytenoid muscle, the lateral thyroarytenoid muscle, and the inferior paraglottic space. The study was conducted on serial sections of 4 embryonal and 9 fetal larynges at different stages of development. The embryological observations showed that the lateral and medial thyroarytenoid muscles have different maturation times and probably different functions: phonatory and sphincteric. The authors have found that the inferior paraglottic space is situated between these 2 muscles. It would represent a path of diffusion for glottic cancer and play a central role in impaired vocal cord and/or arytenoid mobility, according to the degree of diffusion. Embryological observations have suggested the existence of laryngeal morphofunctional units belonging to the subsites of the glottic region and related to tumoral spreading.

Congenital glottic webs in children. A retrospective review of 51 patients.

This study is a retrospective review of congenital glottic webs in children. Its purpose is to clarify the controversial aspects of this lesion and to offer a more definitive approach to its treatment. The study includes discussions of embryology and anatomy, a thorough literature review, and a detailed statistical analysis of patient data. Fifty-one pediatric cases are reported, with symptoms and endoscopic findings described in detail. Treatment with dilatations, incisions (knife, scissors, laser), stenting, and external laryngeal surgery with keel insertion are evaluated, and results of therapy, both before and after the development of laser surgery, are reported. Of the 51 patients, 22 required tracheotomy and all who completed therapy were ultimately decannulated. Vocal dysfunction was the most difficult symptom to treat, and perfection of the voice was attained only infrequently. However, the ultimate results of therapy, as noted in this series of patients, should counter the pessimistic viewpoints expressed in the literature.

Development of the rat larynx: a histological study.

OBJECTIVES/HYPOTHESIS: To evaluate and describe the cartilaginous and muscular development of the rat larynx. STUDY DESIGN: Histologic evaluation. METHODS: The larynges of Sprague Dawley rats of embryonic day (E) 13, 15, 17, 19, 21, postnatal day 0, 14, and adult of 250 gm were collected. Four larynges of each age were harvested, cut into 15-µm serial sections, stained with hematoxylin and eosin, and evaluated under light microscopy. Representative digital images were recorded and evaluated at the preglottic (supraglottic in humans), glottic, and postglottic (subglottic in humans) levels. RESULTS: Brachial arches were observed at E13. At E17, immature structures of the larynx, including skeletal muscle, cartilage, and the lumen were identifiable. Chondrification and muscle formation were clearly seen by E19. The muscular and cartilagenous components of the larynx were well established by E21. During the span between birth and adult maturation, the size of the larynx increased from a height of 1.10 mm to 2.90 mm, and from a width of 1.80 mm to 5.40 mm, and from a length of 1.38 mm to 4.77 mm in the stained section. Although developed at E21, the laryngeal structures continued to grow by approximately 30%. CONCLUSION: Rat laryngeal development parallels that in mice and humans. In the rat, at E17 immature structures of the larynx are identifiable, they are well developed at birth and grow by approximately 30% into adulthood. Understanding the chronology and morphology of the embryogenesis of the rat laryngeal musculature is essential and will allow for further evaluation of the embryologic innervation of these muscles.

Posterior commissure of the human larynx revisited.

The existence of the posterior commissure (PC) of the human larynx has been disputed (Hirano M, Sato K, et al. The posterior glottis. Trans Am Laryngol Assoc. 1986;107:70-75). "The term posterior commissure has no relevance to anatomical structure. The term commissure means a joining together. The bilateral vocal folds never join at their posterior ends. The posterior aspect of the glottis is a wall. The posterior lateral aspect of the posterior glottis is also the lateral wall of the posterior glottis" (Hirano M, Sato K, et al. The posterior glottis. Trans Am Laryngol Assoc. 1986;107:70-75). This study is intended to clarify the development of anatomical and morphological aspects of the PC in conjunction with a clinical classification of the larynx in sagittal view. This study uses human embryo and fetal laryngeal sections from the Carnegie Collection of Human Embryos (the world standard) and whole organ laryngeal sections from the Tucker Laryngeal Fetal Collection. Correlation of histologic and gross anatomical structure is made with the Hirano et al atlas, the Vidic Photographic Atlas of the Human Body, and the O'Rahilly Embryonic Atlas. Embryologic data clearly describe and illustrate the posterior union of the cricoid cartilage with formation of the PC. The anatomical functional aspects of the posterior lateral cricoid lamina as the supporting buttress of the articulating arytenoid cartilages are illustrated.

A few remarks on the morphogenesis of the larynx.

After having reviewed the principal theories regarding the development of the larynx the authors performed a study on the morphogenesis of the above structure using four horizontally- and sagitally-sectioned human embryos. The conclusion of a study of these sections is that the LC constitutes the primordium of the laryngeal vestibule. From its lateral margin, caudally (Stage 19, Carnegie System), the primitive ventricles begin to form, while in the final stages the EL extends caudally enclosing a small cephalic infraglottic area and therefore completely separating the IG from the LC. Such findings in our opinion would confirm a different embryological derivation of the laryngeal cavity above and below the glottis.

Pathophysiology of subglottic tracheal stenosis in childhood.

Two particularly problematic clinical entities are chosen from the many possible causes of the pathophysiology of subglottic tracheal stenoses in childhood: malformations of the "hard" and "soft" types of stenosis occurring typically as primary lesions; and stenoses caused by trauma (following intubation or faulty tracheostomy) as the most common secondary lesions. It is shown with reference to experimental investigations that subepithelial layers play the leading role in the origin of stenoses, in contrast to hitherto existing ideas based on clinical observations. Traumatic stenoses caused by unphysiological mechanical stressing show striking parallels to those in other age groups, suggesting the conclusion that a reaction of the mesenchymal tissue layers of the airway regions in question is a typical response to mechanical forces.

The posterior glottis.

The posterior glottis is an area of the larynx previously referred to by the terms 'posterior commissure' and 'interarytenoid'; these are poorly defined and a new definition of this unique area of the larynx is provided. Within the text is a series of experiments performed on nearly 300 larynges. The posterior glottis was examined in relation to the following: the embryology, the epithelium, mathematical dimensions, gross anatomy, microanatomical structures, submucosal spaces and the spread of carcinoma related to this area. Various significant findings were made. There exists a pharyngoglottic duct which divides the embryonic larynx into anterior (membranous) and posterior (cartilaginous) parts. The epithelium of the posterior glottis in neonates and non-smokers is respiratory in nature and the notion of a laryngeal respiratory function is reinforced by a mathematical analysis of the cross sectional areas of the larynx during inspiration. The presence of a posterior cricoarytenoid ligament which stabilizes the arytenoid is confirmed. The spread of carcinoma to the posterior glottis from the different primary laryngeal and pyriform fossa sites shows differing modes of invasion but in particular a direct extension and connection with the subglottis. The most significant conclusion from these studies is that the posterior glottis is so intimately related to the subglottis that it must be considered as part of the subglottis. The acceptance of this fact, however, requires a new definition of the larynx from that given by the American Joint Committee on Cancer Staging and that of U.I.C.C. The posterior glottis considered as part of the subglottis requires a review of our present understanding of the structure and function of the larynx and in particular the spread of cancer posteriorly.