Organ Serial Sections Research Articles

Growth and development of epiglottis and preepiglottic space of larynx as it acquires vocal tract.

The growth and development of the epiglottis and preepiglottic space (PES) of the human larynx as it acquires the vocal tract were investigated. Three newborns, one infant, four children (2, 7, 8, and 12 years old), and two adult normal larynges were investigated and compared using the whole organ serial section technique. The newborn PES occupied a small area just anterior to the epiglottis. It was composed of immature adipose tissue and areolar tissue. The epiglottis lay on a somewhat horizontal axis and is partially obscured behind the hyoid bone. The hyoid bone overlapped the thyroid cartilage, partially obscuring the superior thyroid notch. The newborn epiglottic cartilage was immature elastic cartilage, and the elastic fiber component was sparse. In the first 8 years of life, as the PES grew, the PES was located not only anterior to but also posterolateral and inferolateral to the epiglottic cartilage and thyroepiglottic ligament. Meanwhile, the epiglottic cartilage matured. In order to develop the vocal tract for speech production, it is reported that the human larynx descends as the child grows in the first 9 years of life. This study showed that the PES, occupying a small area just anterior to the epiglottis, grew and existed astride the epiglottis as the larynx descended and the vocal tract developed. Consequently, its distribution allows the epiglottis to more effectively play the role of retroflection during swallowing in order to prevent aspiration. The human speech faculty likely develops in conjunction with swallowing physiology.

Comparative Histoanatomy of the Epiglottis and Pre-epiglottic Space of the Chimpanzee Larynx

Understanding of the evolution of the larynx clarifies the physiology and functional histoanatomy of the present-day human organ. Comparative histoanatomy of the epiglottis and pre-epiglottic space of the chimpanzee larynx (a hominid, phyletic closest relative of humans) was investigated. Two normal adult chimpanzee larynges obtained from natural deaths were investigated. The whole organ serial section technique was employed. The histoanatomical structures of the chimpanzees' epiglottis and pre-epiglottic space were considerably similar to those of human adults. The chimpanzees' epiglottic cartilage was relatively thin and composed of elastic cartilage. These histologic findings of epiglottis indicate that the chimpanzee's epiglottis is flexible and plays the role of retroflection. The chimpanzees' larynges had a pre-epiglottic space composed of adipose tissue and loose connective tissue. Epiglottic cartilage was connected to the thyroid cartilage anteroinferiorly with an intervening thyroepiglottic ligament and to the hyoid bone anteriorly with an intervening hyoepiglottic ligament. These histoanatomical structures of the epiglottis and pre-epiglottic space reflect the fact that chimpanzees have a descended larynx and acquire the pharyngeal space of the vocal tract. The results of this study are consistent with the hypothesis that, in the process of evolution, the histoanatomical structures of the epiglottis and pre-epiglottic space change and allow the larynx to descend and lengthen the pharyngeal space of the vocal tract which facilitates speech production in humans. Moreover, the distribution of the human pre-epiglottic space likely allows the epiglottis to more effectively play the role of retroflection during swallowing in order to prevent aspiration.

Comparative Histoanatomy of the Epiglottis and Preepiglottic Space of the Lemur Larynx

An adequate understanding of the evolution of the larynx presumably clarify the physiology and functional histoanatomy of the present-day human organ. This study investigated the comparative histoanatomy of the epiglottis and preepiglottic space of the lemur larynx (a non-human primate without vocal tract). Two normal adult ring-tailed lemur larynges obtained from natural death were investigated. The whole organ serial section technique was employed. The histologic structures of the lemur epiglottis and preepiglottic space differed considerably from that of human adults. The lemur epiglottis was proportionally thick and vertical. It was connected to the thyroid cartilage anteroinferiorly without an intervening thyroepiglottic ligament and to the hyoid bone anteriorly with intervening large bundles of collagen fibers, indicating that the lemur epiglottis does not play the role of retroflection. The lemur larynges did not have a preepiglottic space. These findings also reflect the fact that lemurs do not have a descended larynx and do not acquire the pharyngeal space of the vocal tract. The lemur epiglottis was composed of fibrocartilage, adipose tissue and a small amount of elastic cartilage covered with mucosa (lamina propria and pseudostratified ciliated columnar epithelium). The histologic findings also indicate that the lemur epiglottis is not flexible and does not play the role of retroflection. The results of this study are consistent with the hypothesis that, in the process of evolution, the histologic structures of epiglottis and preepiglottic space likely change to make the larynx descend and lengthen the pharyngeal space of the vocal tract for speech production in humans. Moreover, the distribution of the human preepiglottic space likely allows the epiglottis to more effectively play the role of retroflection during swallowing in order to prevent aspiration.

Laryngeal spaces in the newborn larynx

ObjectivesDistributions of laryngeal spaces are important in understanding their functional significance. However, laryngeal spaces in the newborn larynx are enigmatic. MethodsFive normal human newborn larynges were investigated using whole organ serial section technique. ResultsThe chief newborn laryngeal spaces were the preepiglottic space, the paraglottic space and the cricoid area. They consisted of an areolar tissue area composed of brown adipose tissue (immature adipose tissue) and loose elastic and collagen fibers. The newborn preepiglottic space was immature and occupied a small area anterior to the epiglottis. The epiglottis lied on a somewhat horizontal axis and was partially obscured behind the hyoid bone. The hyoid bone overlapped the thyroid cartilage, partially obscuring the superior thyroid notch. The thyroid cartilage was present close to the hyoid bone and the thyrohyoid membrane ran between the superior surface of the thyroid lamina, and not the anteroinferior, but the posteroinferior surface of the hyoid bone. The preepiglottic space was located anterior, lateral and posterolateral to the thyroepiglottic ligament. However, the preepiglottic space was located anterior to the epiglottic cartilage. As seen in adults, the paraglottic space existed medial to the lamina of each bilateral thyroid cartilage. Each bilateral cricoid area was located along not only the superomedial but also the medial portion of the cricoid arch on both sides. ConclusionsAs the child grows, the preepiglottic space, occupying a small area anterior to the epiglottis, likely grows as the larynx descends and acquires the human adult vocal tract. From the functional histoanatomical point of view, the newborn laryngeal spaces appear to be favored for respiration and maintenance of a protective sphincter for the lower airway over phonation.

Three-dimensional reconstruction of laryngeal cancer with whole organ serial immunohistochemical sections

Three-dimensional (3D) image reconstruction of tumors based on serial histological sectioning is one of the most powerful methods for accurate high-resolution visualization of tumor structures. However, 3D histological reconstruction of whole tumor has not yet been achieved. We established a high-resolution 3D model of molecular marked whole laryngeal cancer by optimizing the currently available techniques. A series of 5,388 HE stained or immunohistochemically stained whole light microscopic images (200 ×) were acquired (15.61 TB).The data set of block-face images (96.2 GB) was also captured. Direct volume rendering of serial 6.25 × light microscopy images did not demonstrate the major characteristics of the laryngeal cancer as expected. Based on fusion of two datasets, the accurate boundary of laryngeal tumor bulk was visualized in an anatomically realistic context. In the regions of interest, micro tumor structure, budding, cell proliferation and tumor lymph vessels were well represented in 3D after segmentation, which highlighted the advantages of 3D reconstruction of light microscopy images. In conclusion, generating 3D digital histopathological images of a whole solid tumor based on current technology is feasible. However, data mining strategy should be developed for complete utilization of the large amount of data generated.

Cartilage invasion patterns in laryngeal cancer.

The cartilaginous invasion determines the T and is one of the most common sources of mistake in tumor staging. Also it is of great importance when planning any therapeutic alternative. In the latest revision of the TNM classification a clear distinction is made between infiltration of cartilage without going through it, considered a T3 recently and that would be a T4 according to the previous classification, and those going through the cartilage, classified as T4a. While this classification makes the difference in depth of infiltration, it does not emphasize the extent of invasion. This paper provides a detailed description of the laryngeal cartilage tumor infiltration by whole organ serial section in which the invasion is considered both horizontal (transcartilaginous) and vertical (extent of invasion) and establishing patterns of three-dimensional infiltration of the cartilage. This is a cross-sectional study of prevalence. 275 records of patients treated for laryngeal squamous cell carcinoma between 1995 and 2000 were reviewed. The pathological processing of laryngectomy surgical specimens was performed following the method of whole organ serial section described by G. F. Tucker. The following patterns of cartilaginous infiltration were defined: (1) transcartilaginous infiltration; (2a) partial focal infiltration of the cartilage: infiltration not going through the cartilage but occupying one third or less of its extent; (2b) partial extensive infiltration of the cartilage: infiltration occupying two thirds or more of its length and (3) no cartilage infiltration: tumor in contact with the cartilage (paraglottic space) but without affecting it. 161 patients met the inclusion criteria. The most frequent tumor location was supraglottic (58 cases) followed by glottic (47). 109 patients (67.7%) were treated with total laryngectomy. Partial surgical techniques were performed in the remaining cases. TNM tumor staging was performed according to the results of pathological study (pTNM). 72.06% (116) were classified as advanced laryngeal tumors (pT3 and pT4). 46% of patients showed some extent of laryngeal cartilage infiltration (thyroid, cricoid, arytenoids, epiglottis). The cartilage most frequently infiltrated was the thyroid in 48 patients (29.8%) and when it is affected, in most cases (66.7%), the infiltration is transcartilaginous. The next most common pattern is partial focal infiltration (27%). In the cricoid cartilage, the most common pattern of infiltration is focal partial infiltration (52.6%). Of the 19 cases with infiltration of the cricoid, there are 12 cases with extra laryngeal invasion through a cricothyroid membrane perforation. The study of laryngeal cancer by laryngeal whole serial section has been proved to be very useful in offering a high precision pTNM staging and a detailed description of the infiltration of cartilage. We have seen that when the thyroid cartilage is infiltrated the tumor often passes through the cartilage. However, there are cases where the tumor is extremely aggressive, being very widespread in cartilage thickness without actually crossing it. The isolated infiltration of the cricoid cartilage is exceptional.

Toward Routine Use of 3D Histopathology as a Research Tool

Three-dimensional (3D) reconstruction and examination of tissue at microscopic resolution have significant potential to enhance the study of both normal and disease processes, particularly those involving structural changes or those in which the spatial relationship of disease features is important. Although other methods exist for studying tissue in 3D, using conventional histopathological features has significant advantages because it allows for conventional histopathological staining and interpretation techniques. Until now, its use has not been routine in research because of the technical difficulty in constructing 3D tissue models. We describe a novel system for 3D histological reconstruction, integrating whole-slide imaging (virtual slides), image serving, registration, and visualization into one user-friendly package. It produces high-resolution 3D reconstructions with minimal user interaction and can be used in a histopathological laboratory without input from computing specialists. It uses a novel method for slice-to-slice image registration using automatic registration algorithms custom designed for both virtual slides and histopathological images. This system has been applied to >300 separate 3D volumes from eight different tissue types, using a total of 5500 virtual slides comprising 1.45 TB of primary image data. Qualitative and quantitative metrics for the accuracy of 3D reconstruction are provided, with measured registration accuracy approaching 120 μm for a 1-cm piece of tissue. Both 3D tissue volumes and generated 3D models are presented for four demonstrator cases.

Mapping of Ki-67 protein distribution on whole organ serial sections of the larynx

Conclusions. Immunostaining of whole organ serial sections of the larynx is feasible and will allow analysis of cellular alterations in the undisturbed anatomical context of whole organ serial sections of the larynx. Objectives. Whole organ serial sections of the larynx have to date been used for conventional macroscopic evaluation of laryngeal tissues. The aim of this study was to establish a protocol for immunohistochemistry of whole organ sections of the larynx. Materials and methods. Five laryngectomy specimens were obtained during surgery for advanced laryngeal carcinoma. Using a novel method for paraffin embedding, we chose the proliferation marker Ki-67 antigen as a model target for immunoreactivity on serial sections. Results. We were able to produce whole organ serial sections that could then be immunostained for Ki-67. A complete mapping of proliferating cells throughout the tumour, at the tumour front and in skip lesions was subsequently obtained.

Histopathologic Changes in Laryngeal Mucosa of Extremely Low-Birth Weight Infants after Endotracheal Intubation

Advances in medicine have improved the survival of infants with increasingly lower birth weights. The histopathologic changes of intubation-related laryngeal injury in extremely low-birth weight infants (less than 1,000 g) have not been well known. We examined histopathologic changes in infant larynges, including extremely low-birth weight infants, after endotracheal intubation. Forty-four infants, including 21 extremely low-birth weight infants, who had been intubated for periods ranging from 10 minutes to 138 days, were examined in a whole organ serial section study. As the duration of intubation increased, the ulceration was found to be larger and deeper. The injury at the subglottis and posterior glottis was greater than that at other portions. The perichondrium of the cartilage was exposed in many cases intubated longer than 8 days. Repaired epithelium that was composed of squamous epithelium was present in 6 of 7 larynges that had been intubated more than 20 days, indicating that not only injury but also the healing process occurred during long intubation. There were no obvious relationships between the degree of intubation injury and the birth weight of the infants. Prolonged intubation is better tolerated by infants than adults. The intubation-related laryngeal injuries of extremely low-birth weight infants were histopathologically the same as those of infants of other birth weights.

Histopathological grading of laryngectomy specimens

A material comprising 118 laryngectomy specimens, prepared by whole organ serial sectioning, was analyzed to determine the prognostic significance of histopathological tumor grading. No statistically significant association could be demonstrated between grading and a number of clinical and histopathological variables, including pathological staging, lymph node metastases or recurrence rate. The study supports the contention that the prognostic value of histopathological grading of laryngeal squamous cell carcinoma remains uncertain and unproven. Serial sections of the whole organ, processed by routine laboratory techniques, remain important for studying tumor extension but do not contribute to establishing histopathological grading as a significant prognostic parameter.

Morphology of the human thyroglossal tract: a histologic and macroscopic study in infants and children.

The anatomic development of thyroglossal tract remnants is not understood at present. For analysis of morphology and growth patterns of thyroglossal tract remnants, we used histologic whole organ serial sections to determine developmental changes through the first years of life. Larynges of 58 infants and children ages 1 month to 13 years were obtained in whole organ serial step-sections in an axial plane. The slides were stained with hematoxylin and eosin, Alcian blue, and periodic acid-Schiff stains. Altogether, 3,247 histologic slices were examined. The resulting data were then correlated with the age and sex of the specimens. We found, in 24 cases (41.3%), remnants of the thyroglossal tract or ectopic thyroid tissue. In 4 specimens (16.6%), a complete thyroglossal tract could be observed that presented a ventral path in relation to the hyoid bone with no contact with the perichondrium of the cartilage. Hormonal activity of ectopic thyroid tissue was proven in 20 cases (34.5%). Thyroid follicles were located in 2 cases (3.5%) in the hyoid bone. The thyroglossal ducts revealed a modest tendency for a left-sided pathway, whereas thyroid follicles were located more on the right paramedian side. Morphometric data on the development and structure of the thyroglossal tract and the thyroid follicles during infancy and childhood are presented. The study provides quantitative data of clinical interest that elucidate the anatomy of thyroglossal tract remnants. In addition, our investigation supports Sistrunk's operative approach for avoiding recurrences in the treatment of thyroglossal duct cysts.

Anatomy of the glottis and subglottis in the pediatric larynx

The morphological development of the human larynx during the first years of life has previously not been studied in detail and has mainly been described on a qualitative basis. This study seeks to provide detailed morphometric data on the regular anatomy of the vocal cords, the subglottic airway and the tracheal airway dimensions gained from plastinated whole organ serial sections of 43 infant larynges and to determine morphological changes with age. Such information may be useful for the understanding of pediatric airway disease or for laryngeal surgery in children. The larynges of 43 children aged 1 to 60 months were plastinated. Whole organ serial sections were obtained by cutting the resulting specimen with a diamond band saw. Morphometry of whole-organ sections was accomplished using a high resolution, computer-based image analyzer. The total length of the glottis, length of the cartilaginous and ligamentous glottis, subglottic cartilaginous cross-section, subglottic airway and tracheal airway were determined for each specimen. The subglottic airway increases considerably in size during the first 2 years of life (from 13 to 28 mm2 in the means). Further growth seems to follow a linear mode. The relative proportion of the mucosal lining of the subglottic airway decreases likewise. While it occupies approximately 50% of the subglottic cartilaginous cross-section during the first two years of age, its relative proportion decreases to some 30 to 40% between age three to five. Other than in adults, and comparable to most mammals, the cartilaginous glottis accounts for 60 to 75% of the vocal folds' length in children under two years of age. The anterior ligamentous part of the glottis outsizes its posterior cartilaginous portion during the third year of life. This study supplies detailed morphometric data on the growth and structure of the human larynx during the first years of life that have not been available to date. Previous studies on the anatomical configuration of the infant larynx have focused on the the perinatal larynx, the prepuberal and puberal larynx, and the development of collagen fibres in the developing larynx. The human larynx has undergone significant evolutionary adaptations. Among them are the descent of the larynx, the capability of vocal fold adjustment in length, tension and shape, and the prominent configuration of the membranous part of the vocal folds as opposed to the cartilaginous part. The infant larynx is not just a miniature of the adult organ. It shows differences in its position relative to the vertebrate column, in the composition of cartilages and soft tissues, and in environmental adaptation. The present study is the first to supply detailed morphometric data on the growth and structure of the human larynx during the first five years of life and on the morphological changes of the larynx during this period. From these data it seems that some of the adaption of the human larynx as opposed to other vertebrates are not fully developed at birth, but undergo postnatal maturation. The relative proportions of the cartilaginous and membranous parts of the vocal folds clearly demonstrate this maturation process: While the posterior "respiratory" glottis accounts for some sixty to 75% of the total glottic length in newborns, its relative proportion decreases throughout the first years of life and finally equals the proportions of the adult larynx. Other than in adults, and in accordance with the literature, no sexual dimorphism of the larynx could be detected in this series of infant larynges. Morphometric data on the growth and structure of the human vocal folds and the subglottic airway during childhood are presented. Plastinated whole organ serial sections were used in the study to show the infant laryngeal morphology. The study provides quantitative anatomical data of clinical interest that light up the anatomy of the pediatric airways.

喉頭腺様嚢胞癌で判明した四重癌例

Malignant tumors arising from laryngeal gland cells are extremely rare. No more than 1% of the epithelial malignancies of the larynx are nonsquamous carcinomas. Moreover, adenoid cystic carcinomas make up fewer than 0.25% of all malignancies of the larynx. In the Japanese literature, only 28 cases have been reported. We have encountered a case of laryngeal (supraglottic) adenoid cystic carcinoma.A 68-year-old woman complained of hoarseness and slight dyspnea of six months' duration. We suspected a thyroid carcinoma and laryngeal tumor. We performed fine needle aspiration for the thyroid mass, and findings suggested papillary carcinoma. Laryngoscopic examination revealed a smooth mass involving the right false vocal cord and epiglottis. The pathology report indicated adenoid cystic carcinoma. The patient underwent total laryngectomy, subtotal thyroidectomy, right neck dissection, and reconstruction with LDMC. We examined the resected specimens histologically by whole organ serial sectioning and discussed the evaluation, treatment, clinical course and prognosis of adenoid cystic carcinoma of the larynx. The overall 10-year survival rate is worse than the overall 5-year survival rate. Therefore, we must observe cases of adenoid cystic carcinoma for over 10 years.

Morphology of the human larynx during the first five years of life studied on whole organ serial sections.

The morphologic development of the human larynx during the first years of life is poorly understood to date. This study used plastinated whole organ serial sections to determine the growth and structure of the infant larynx. The larynges of 43 children 1 to 60 months old were plastinated. Whole organ serial sections were obtained by cutting the resulting specimen with a diamond band saw. The slices were then submitted to computer-assisted morphometric investigation. We found that the subglottic airway rapidly increases in size during the first 2 years of life. Further growth follows a linear mode. The relative proportion of the mucosal lining decreases likewise. In contrast to that in adults, and comparable to that in most mammals, the cartilaginous glottis accounts for 60% to 75% of the vocal folds' length at <2 years. No sexual dimorphism of the larynx exists during childhood. This study supplies detailed morphometric data on the growth and structure of the human larynx during the first years of life. It is the first to use plastinated whole organ serial sections for morphology of the pediatric larynx. Therefore, this study provides quantitative anatomic data of clinical interest that have not been available to date.

Clinicopathological analysis of elective neck dissection for N0 neck of early oral tongue carcinoma

Background: The study aims at evaluation of the efficacy of elective neck dissection as a staging and therapeutic procedure for N0 neck of early carcinoma of the oral tongue by whole organ serial sectioning. Methods: There were 50 stage I and II patients. The neck dissection specimens were whole organ sectioned in 3-mm intervals for the evaluation of nodal metastasis. Results: There were 18 (36%) patients with subclinical nodal metastasis. The total number of metastatic nodes were 31 (1%) among all 2,826 nodes being examined. The metastatic foci had a median size of 3 mm and occupied a median of 6% of the cross sectional area of the involved nodes. The ipsilateral level II nodes were the commonest (26%) site of metastasis. Metastatic nodes were present in 34% patients who had negative preoperative radiological assessment and in 20% patients who had negative intraoperative frozen section sampling of neck nodes. Patients with subclinical nodal metastasis had a high incidence of regional recurrence (62%) and low survival (27%) when postoperative radiotherapy was not given after elective neck dissection. Conclusions: Ipsilateral level I,II,III neck dissection is an adequate diagnostic procedure for staging of the N0 neck of early oral tongue carcinoma. Its diagnostic role cannot be replaced by the available pre-operative radiological screening and intra-operative frozen section sampling. However, elective selective neck dissection is an effective but not adequate therapeutic procedure, and post-operative adjuvant radiotherapy and chemotherapy have to be considered for all pathologically positive necks.

Glottic-supraglottic barrier: fact or fantasy?

An anatomic structure that might act as a barrier between the glottic and supraglottic areas has never been demonstrated in whole organ serial section studies. Nevertheless, most squamous cell carcinomas arising on the supraglottic mucosa remain confined above the ventricle, and this fact is reflected in the high rate of local control obtained by surgeons performing horizontal supraglottic laryngectomy: 80.6% to 98%. Whole organ sections of laryngectomy specimens suggest that a tumor situated above and below the glottic level may have arrived there not by crossing the ventricle, but by encircling it. In so doing, part of the tumor is visible posterior to the ventricle or on the arytenoid cartilage-a finding that contraindicates conventional supraglottic laryngectomy, with or without limited mobility of the true vocal cord.

Sheet plastination of the larynx for whole-organ histology.

Whole organ serial sections of the larynx are recognized to improve the assessment of laryngeal pathology. The human larynx with its complex anatomy of different types of tissue with their marked differences in hardness complicate the cutting process. The methods established are either very costly, time consuming and prone to artefacts, or sections are too thick for a histological work-up. Prior decalcification causes major shrinkage, thus morphometry is not feasible. We describe a technique of sheet plastination to produce whole-organ sections which allows a full-scale histological investigation without prior decalcification. Deep-frozen larynges are cut into 4-micron-thick sections using an ordinary slicing machine. Slices are dehydrated in acetone and plastinated in Biodur E50/E7/ AE10/E700. These specimens are cut into sections of about 80 microns thickness using a diamond-wire saw. An ultra-milling device reduces the section thickness down to about 10 microns. Surface staining of different kinds like Richardson, methylene blue or Paragon yields sufficient contrast for exact diagnosis. Deplastination and consecutive paraffin-like staining is possible, but results are not yet fully satisfying. Histological sheet plastination produces almost artefact- and shrinkage-free whole-organ sections in a period of about 1 week. The technique is useful for studies of micromorphometry or tumor spread. Theoretically, application of immunohistochemical staining methods seems to be possible. This might lead to mapping the proliferation activity of laryngeal cancer as it is presented on whole-organ sections.

Fragmented, Distorted Cricoid Cartilage: An Acquired Abnormality

This paper reports the identification of the fragmented, distorted cricoid cartilage. The laryngeal findings in four patients with this acquired abnormality are presented. The postmortem whole organ serial section of their larynges is described and illustrated with horizontal sections from the Laryngeal Development Laboratory in Chicago. The histopathologic sequence, pathogenesis, and clinical relevance are elucidated.

喉頭内多発癌症例

Among 126 patients with laryngeal cancer treated between September 1986 and August 1993 at Nara Medical University, we encountered six patients with multicentric cancer of the larynx. We statistically investigated the role of tobacco and alcohol consumption to determine the causal factors in these cases. We chose as controls 60 patients with laryngeal cancer who had received total laryngectomy without irradiation therapy from among the 126 patients with laryngeal cancer. We confirmed that these multicentric intralaryngeal lesions were noncontinuous by examining whole organ serial sections. Tobacco consumption was highly related to the risk of multicentric cancer in the larynx (p<0.01), while alcohol consumption was not related to the risk of such lesions.Therefore, we conclude that synchronous secondary intralaryngeal lesions must not be overlooked and that the incidence of nonsynchronous secondary cancer of the larynx must be considered during follow-ups, when heavy-smokers are treated for laryngeal cancer by partial laryngectomy or irradiation therapy.

Location of the Preepiglottic Space and its Relationship to the Paraglottic Space

An investigation was carried out to determine the location of the preepiglottic space (PES) and its relationship to the paraglottic space (PGS). Excised human adult larynges served as materials for this study. The distribution of the PES of the larynx was determined histologically in 3 whole organ serial sections: sagittal, horizontal, and coronal. The results are summarized as follows. 1) The PES exists not only anterior, but also posterolateral and inferolateral to the epiglottis. 2) Its posterior end is located in the vicinity of the anteroposterior midpoint of the thyroid lamina. 3) The PES is adjacent to the PGS posteroinferiorly and is separated by fibrous tissue (the thyroglottic ligament). Posterosuperiorly, the 2 spaces are not clearly delineated from each other.