ANATOMY, HISTOLOGY, 1 AND EMBRYOLOGY
An understanding of the anatomic divisions composed of the vomer. This bone extends from of the head and neck, as well as their associ- the region of the sphenoid sinus posteriorly and ated normal histologic features, is of consider- superiorly, to the anterior edge of the hard pal- able importance when approaching head and ate. Superior to the vomer, the septum is formed neck pathology. The large number of disease by the perpendicular plate of the ethmoid processes that involve the head and neck area bone. The most anterior portion of the septum is a reflection of the many specialized tissues is septal cartilage, which articulates with both that are present and at risk for specific diseases. the vomer and the ethmoidal plate. Many neoplasms show a sharp predilection for The supporting structure of the lateral border this specific anatomic location, almost never of the nasal cavity is complex. Portions of the occurring elsewhere. An understanding of the nasal, ethmoid, and sphenoid bones contrib- location of normal olfactory mucosa allows ute to its formation. The lateral nasal wall is visualization of the sites of olfactory neuro- distinguished from the smooth surface of the blastoma; the boundaries of the nasopharynx nasal septum by its “scroll-shaped” superior, and its distinction from the nasal cavity mark middle, and inferior turbinates. The small su- the interface of endodermally and ectodermally perior turbinate and larger middle turbinate are derived tissues, a critical watershed in neoplasm distribution. Angiofibromas and so-called lym- phoepitheliomas, for example, almost exclu- sively arise on the nasopharyngeal side of this line, whereas schneiderian papillomas, lobular capillary hemangiomas, and sinonasal intesti- nal-type adenocarcinomas almost entirely arise anterior to the line, in the nasal cavity. NASAL CAVITY
Anatomy Although usually referred to as a single struc- ture, the nasal cavity consists of paired midfacial nares divided into two more or less mirror images by the nasal septum and at its extreme anterior, the columella (figs.1 -1, 1-2). Midline asymmetry of the nasal septum is common, however, result- ing in considerable variation in the contours and volumes of the left and right chambers. Each cav- ity is bounded anteriorly by the external naris, marking its junction with the external world; posteriorly by the nasal choana, forming its junction with the nasopharynx; and medially by the smooth-surfaced nasal septum. Figure 1-1 Beneath the mucosa, the septum is formed SAGITTAL VIEW OF UPPER RESPIRATORY TRACT by one cartilaginous and two osseous support- A midline sagittal section shows the major structures of ing structures. Posteriorly and inferiorly, it is the nasal cavity, pharynx, and larynx.
Tumors of the Upper Aerodigestive Tract and Ear
Figure 1-2 CORONAL VIEW OF UPPER RESPIRATORY TRACT A coronal section through the head at the level of the molar teeth displays the anatomy of the nasal cavity, as well as the pharynx, larynx, and some of the paranasal sinuses.
formed from the ethmoid bone (19). The lower Histology turbinate is a separate bone (19). There are multiple openings along the lateral The most anterior portion of the nasal cav- wall of the nasal cavity, primarily to the adjacent ity, or nasal vestibule, is an inward extension paranasal sinuses. The frontal sinus ostium is of the skin of the external nose. It is lined by located in the frontal recess at the anterior of the keratinized squamous epithelium with associ- middle turbinate. The sphenoid sinus opening ated dermal adnexa, including hair follicles, is in the sphenoethmoid recess located behind sebaceous glands, and sweat glands. This in- the superior turbinate. The opening to the ward cutaneous extension averages 1 to 2 cm posterior ethmoid air cells is located under the in depth, at which point there is a gradual loss superior turbinate, with openings to the middle of adnexal structures and replacement of the and anterior cells located in the ethmoid bulla keratinized squamous epithelium by schneide- and hiatus semilunaris of the middle turbinate rian epithelium (19), denoted with this eponym (19). The primary maxillary antrum ostium is primarily to emphasize its ectodermal origin, also located in the hiatus semilunaris, and there as distinct from the endodermal origin of the may be an accessory ostium located posterior mucosa lining the pharynx and larynx. The to the primary maxillary ostium. schneiderian epithelium lines the nasal cav- The most superior portion of the nasal cavity ity and paranasal sinuses. With the exception consists of the cribriform plate with its special- of olfactory mucosa, schneiderian epithelium ized olfactory mucosa (fig. 1-3). This merges lacks any histologic distinction from the lin- with the remainder of the cavity roof, which ings of the pharynx and larynx. It is primarily slopes downward posteriorly to form the su- composed of a mixture of nonkeratinizing squa- perior portion of the choana. The floor of the mous cells, ciliated respiratory cells, scattered nasal cavity is formed by a combination of the mucus-containing goblet cells, and “intermedi- hard and soft palates. ate” cells. The mucosa varies in thickness from
Anatomy, Histology, and Embryology
Figure 1-3 NASAL CAVITY The olfactory mucosa is confined to the most superior portion of the nasal cavity (blue shading). It involves the superior portion of the superior turbinate, the cribriform plate, and the superior approximate ly one third of the nasal sep tum. In adults, the distribution becomes patchy, due to multi focal replacement by non olfactory mucosa. The olfactory cells send processes through the cribriform plate to connect with the olfactory bulb.
Figure 1-4 NASAL STROMA Prominent blood vessels below the nasal seromucinous glands resemble erectile tissue and should not be confused with a vascular neoplasm. (Fig. 1-5 from Stelow EB, Mills SE. Biopsy interpretation of the upper aerodigestive tract and ear. Lippincott, Williams & Wil kins, Philadelphia, 2008:4.)
more prominent pseudostratified columnar lamina with underling loose stroma containing cells overlying the portions of the middle and variably prominent seromucinous glands. Deep inferior turbinates in direct contact with airflow, to the glands is a prominent erectile type of vas- to thinner layers of cuboidal cells lining the cular tissue which should not be confused with recesses of the nasal cavity and the paranasal a vascular neoplasm (fig. 1-4). sinuses (19). Areas of squamous metaplasia are The olfactory mucosa is normally confined occasionally found, primarily on the anterior to the cribriform plate, medial surface of the surfaces of the middle and lower turbinates superior turbinate, and superior one third of the and the anterior portion of the nasal septum nasal septum. The total surface area in adults (36). Beneath the mucosal surface is thin basal is approximately 1.5 cm2. Over time, areas of
Tumors of the Upper Aerodigestive Tract and Ear
Figure 1-5 OLFACTORY MUCOSA Left: Specialized olfactory mucosa is composed of a mixture of olfactory cells (OC) with neuronal processes that penetrate the cribriform plate, sustentacular epithelial cells (SC), and regenerative basal cells (BC). The olfactory cells extend to the surface where they form olfactory vesicles (OV). Above: The stratified, specialized olfactory epithelium has underlying Bowman glands, nerve fibers, and bone of the cribriform plate. (Fig. 15-51 from Balogh K, Pantanowitz L. Mouth, nose, and paranasal sinuses. In: Mills SE, ed. Histology for pathologists, 3rd ed. Philadelphia: Lippincott, Williams & Wilkins; 2007:428.) olfactory mucosa may be partially replaced by in a protective mucus blanket. Proximally, the schneiderian epithelium, resulting in a patchy neuronal cells form thin cytoplasmic processes distribution that presumably accounts for the containing unmyelinated nerve fibers which generally diminishing sense of smell with advanc- penetrate the cribriform plate to synapse in ing age. Whether olfactory neurons can regenerate the olfactory bulb. Small basal cells just above in humans is unclear, but has been demonstrated the basement membrane differentiate to form in other mammals (21). Rarely, ectopic foci of replacement sustentacular cells and may also olfactory mucosa lower in the nasal cavity have form replacement neuronal cells. Just beneath been described. Several studies using an olfactory the olfactory mucosa is a group of simple serous marker protein have allowed for easy mapping glands, referred to as the glands of Bowman (fig. of the mucosal distribution (16,22,23). 1-5). The distinctive appearance of these glands The specialized olfactory mucosa is composed and, particularly, their lack of mucin, aid in of three cell types (fig. 1-5). Most common are distinguishing olfactory mucosa from normal epithelial sustentacular cells, tall columnar schneiderian epithelium. eosinophilic cells anchored to the basement Embryology membrane but extending upward to the surface where they form microvilli. Interdigitated be- The nasal cavity is of ectodermal origin. Dur- tween the sustentacular cells are the elongated ing the fourth week of embryologic develop- neuronal olfactory cells. At the surface, these ment, a proliferation of ectoderm beneath the cells form widened peripheral processes con- forebrain forms a hollow invagination known taining olfactory vesicles. These are embedded as the olfactory pit. Cells within this pit acquire
Anatomy, Histology, and Embryology
neural features and send dendritic processes through the region of the subsequent cribriform plate to form synapses with the developing forebrain. While this neuronal differentiation is proceeding, adjacent mesodermal tissues form the structure of the nasal cavity and paranasal sinuses. During the sixth week, the nasal pit deepens considerably, and is initially separated from the primitive oral cavity by the oronasal membrane (15). This ruptures, placing the primitive nasal cavity in continuity with the developing oral cavity. With the fusion of the primitive palate and the lateral palatine shelves of the secondary palate, the nasal and oral cavi- ties become separated during the eighth week of development (15). During this process, the definitive nasal choanae form, separating the nasal cavity from the nasopharynx, and the nasal septum grows downward to join the newly fused palate (15). PARANASAL SINUSES
Anatomy The paranasal sinuses are diverticula of the Figure 1-6 nasal cavity (11). The maxillary, frontal, and PARANASAL SINUSES sphenoid sinuses are large, paired structures The frontal sinuses are most anterior, the maxillary (fig. 1-6). The ethmoid sinuses consist of vary- sinuses are beneath the cheek, the ethmoid sinuses occupy the interorbital region, and the sphenoid sinuses are most ing numbers of closely apposed air-filled spaces posterior, just beneath the base of the brain known as ethmoid air cells. All of the sinuses are small or vestigial structures at birth that progressively enlarge during childhood and adolescence. The frontal sinuses reach full size ethmoid air cells form the ethmoidal bulla and after puberty; the maxillary sinuses do not reach open at varying spots along the middle turbi- full development until late adolescence with the nate. The posterior ethmoid air cells may be acquisition of full permanent dentition. Much absent, but if present, they open around the su- of the change in facial contour associated with perior turbinate. The posterior ethmoid air cells adolescent growth is due to enlargement of the are closely associated with the sphenoid sinus maxillary sinuses. and may bulge into the sinus. They may also be The frontal sinuses vary considerably in size, closely associated with the optic nerve, separated and the larger may cross the midline to impinge from it by only a thin lamina of bone. on its smaller contralateral twin. The ostium of The maxillary sinus, or antrum, lies behind the frontal sinus is located beneath the anterior the prominence of the cheek. Its lateral wall, roof, end of the middle turbinate. and floor are formed primarily from the maxil- The ethmoid air cells vary in number from ap- lary bone, and its medial wall is the lateral wall proximately 3 to 18 cells. The anterior ethmoid of the nasal cavity. Its opening is high up on the air cells are more numerous and closely related medial wall of the sinus into the infundibulum. to the frontal sinus. Occasionally, they bulge into An accessory maxillary ostium more posteriorly the frontal sinus (11). The anterior ethmoid air beneath the middle turbinate is common. cells open beneath the middle turbinate near The paired sphenoid sinuses lie close together the opening of the frontal sinus. The middle within the body of the sphenoid bone. They are
Tumors of the Upper Aerodigestive Tract and Ear
Histology just below the pituitary gland. On either side of the sinuses are a considerable number of vital At the vermillion border of the lips, the skin structures including the carotid arteries, cavern- of the outer lip junctions with the squamous ous sinus, and the ophthalmic and maxillary mucosa of the oral cavity. Most of the oral branches of the trigeminal nerve (11). There cavity is lined by nonkeratinizing squamous may also be a close association with the optic epithelium. Portions of the oral cavity directly canal if the sinuses extend forward and upward involved in chewing, including the hard palate into this region. and parts of the gingiva, are lined by squamous Of the large paranasal sinuses, only the fron- mucosa with varying degrees of orthokeratotic tal have gravity drainage in an erect posture and parakeratotic surface epithelium, thick- (11). Thus, under normal conditions, most ening the underlying rete ridges. Identical drainage from these sinuses is by ciliary action. histologic changes develop in areas of chronic Gravity drainage of the maxillary sinus is best irritation, most often associated with poorly achieved by lying on the side opposite the fitting dentures. affected sinus; the sphenoid sinuses are best The tongue is covered by specialized filiform, drained by lying face down. The openings of fungiform, and circumvallate papillae which are the ethmoid sinus are so variable that no posi- involved in chewing and taste. Scattered mela- tion allows complete drainage. nocytes are normally present in the squamous mucosa of the oral cavity. On hematoxylin and Histology eosin (H&E)-stained sections they are difficult The lining epithelium of the paranasal si- to spot, and appear as clear cells in the basal nuses is similar to that of the nasal cavity and epithelial layer. Their elongated cell processes consists predominantly of ciliated respiratory interdigitate between mucosal epithelial cells, cells with scattered mucinous cells. The mucosa and are much better appreciated with immuno- is typically only about half as thick as that lining histochemistry for S-100 protein. The lamina the nasal cavity, and many of the lining cells are propria of the oral cavity is filled with seromu- cuboidal, or even flattened, rather than colum- cinous glands. These are especially prominent nar. The loose, richly vascular submucosal tissue in the lamina propria of the hard palate. The seen in the nasal cavity is absent. Only a thin stroma around the teeth often contains epithe- layer of fibrous tissue separates the epithelial lial rests of apparent odontogenic origin. The lining from the underlying periosteum. Sero- large epithelial nests of the organ of Chievitz are mucinous glands are rare in the lamina propria present in the lamina propria from the region of of the sinuses, and, when present, are primarily the retromolar trigone. These rests are discussed located close to the sinus ostia (33). the chapter 15. ORAL CAVITY PHARYNX
Anatomy Anatomy The oral cavity, or mouth, is bounded exter- The pharynx has three functionally and nally by the internal mucosa of the cheeks and structurally diverse components: the nasophar- the vermillion border of the lips. It is formed, ynx, oropharynx, and hypopharynx (12). The superiorly, by the hard and soft palate, and, nasopharynx is that portion of the pharynx inferiorly, by the anterior two thirds of the located above the soft palate (fig.1 -1) (20). The tongue with the attached mucous membranes anterior edge of the nasopharynx is demarcated, of the floor of the mouth (fig.1 -1). The posterior and perforated, by the nasal choana. The roof boundary of the oral cavity, at its junction with and posterior wall of the nasopharynx form an the oropharynx, is called the fauces. This is arch lying just below the base of the skull. The defined superiorly by the posterior edge of the posterior wall extends downward to the point soft palate and uvula and laterally by the tonsillar where it is intersected by a horizontal line from pillars. The inferior margin corresponds to a line the soft palate, demarcating the superior border across the circumvallate papillae of the tongue. of the oropharynx. The anterior border of the
Anatomy, Histology, and Embryology
oropharynx is partially defined by the fauces at the posterior extreme of the oral cavity, and below this by the dorsum of the tongue. The inferior margin of the oropharynx is marked by the tip of the epiglottis. Below this lies the hy- popharynx, which spreads out laterally around the body of the larynx as the pyriform sinuses. The aryepiglottic folds mark the junction of the larynx and hypopharynx. Moving inferiorly, the hypopharynx rapidly narrows and ends at its junction with the esophagus. Because of their location and intrinsically dif- ficult surgical access, resection specimens from the nasopharynx and oropharynx are virtually never encountered. The pharynx has complex musculature and innervation, which is reviewed elsewhere (12,20). It is important for pathologists to be aware of the normal distribution of lym- phoid tissue in this region, as well as the location and histologic features of several landmarks. The pharyngeal tonsil, or adenoid, is a convoluted mass of lymphoid tissue located in the roof of the nasopharynx. Although prominent in chil- dren, it typically atrophies in adults (20). The palatine tonsils lie along the anterolateral border of the oropharynx. They vary markedly in size depending upon the state of reactivity. The ton- Figure 1-7 sillar surface is covered with a large number of epithelial-lined pits which penetrate the tonsil- NORMAL TONSIL lar lymphoid tissue to form the tonsillar crypts. The squamous mucosa overlying the lymphoid tissue The immobile base of the tongue in the anterior of Waldeyer ring forms crypt-like invaginations into the lymphoid stroma with considerable disruption of the oropharynx contains abundant lymphoid tissue epithelium by the lymphoid cells. and is termed the lingual tonsil. Along with the pharyngeal and palatine tonsils, this oblique wreath of normal pharyngeal lymphoid tissue alternating islands of squamous and respiratory constitutes Waldeyer ring. epithelia are present in the mid-region. As in the The pharyngeal recess, or fossa, of Rosenmül- larynx, the junction between these zones may ler is a mucosal-lined depression in the posterior be sharp or there may be an area of intermediate lateral wall of the nasopharynx. Just anterior to epithelium representing progressive maturation this recess is the eustachian tube opening, which of immature to mature squamous metaplasia. is partially surrounded by mucosa-covered carti- The disorganization and basaloid appearance of lage from the wall of the eustachian tube (20). these interface regions may lead to confusion with dysplasia or carcinoma in situ. Histology The epithelium covering the adenoid and pala- A slight majority of the nasopharynx is lined tine tonsils extends downward into the tonsillar by squamous epithelium, with about 40 percent crypts were it blurs into the underlying lymphoid covered by ciliated respiratory mucosa (1). The tissue (fig.1 -7). At this interface, the epithelial cells respiratory component preferentially lines the typically assume a more basaloid appearance with region of the choanae and the roof of the naso- uniform, vesicular nuclei (fig.1 -8). There also may pharynx. Squamous epithelium predominantly be areas of abrupt keratinization with keratin pearl covers the lower portions of the nasopharynx; formation. Invariably, microscopic sections
Tumors of the Upper Aerodigestive Tract and Ear
ing age (20). Microscopic remnants of Rathke pouch epithelium are present in the roof of the nasopharynx in almost all individuals (4,17,18). These nests of epithelial cells, referred to as the pharyngeal pituitary, measure 0.2 to 6.0 mm in size and are located in the deep mucosa or underlying periosteum (18,20). Usually, these cell nests appear undifferentiated, but occasionally they have dis- tinctly basophilic or eosinophilic cytoplasm. The pharyngeal bursa normally forms pos- terior to the Rathke pouch; remnants of this bursa are found in the roof of the nasopharynx in about 3 percent of individuals (10,32). Cysts occasionally develop in this bursa adjacent to but distinct from the adenoid (25). Cysts also develop from the median pharyngeal recess, a nasopharyngeal indentation closely associated with the adenoid. These cysts are located within the adenoid and are removed with it. The oropharynx and hypopharynx are lined by squamous epithelium. The mucosa is nonke- ratinizing, except in areas of chronic irritation, where it may be covered with a layer of ortho- keratinized or parakeratinized cells. The lamina propria of the oropharynx and hypopharynx normally contains scattered lymphoid aggre- gates and follicles, as well as large numbers of Figure 1-8 seromucinous glands. NORMAL TONSIL LARYNX Basal epithelial cells from a tonsillar crypt are inter mingled with the associated lymphoid component. The resultant image, at high magnification, can be confused Anatomy with carcinoma. The larynx is bordered superiorly by the tip of the epiglottis and the aryepiglottic folds (figs. from these regions show disorganized, isolated 1-9, 1-10). The inferior border, the junction with nests of basaloid squamous cells with abrupt the trachea, is formed by the inferior margin of keratinization. These features should not be the cricoid cartilage. The anterior border is the confused with carcinoma (20). lingual edge of the epiglottis, the thyroid carti- In addition to the larger pharyngeal, palatine, lage, the anterior arch of the cricoid cartilage, and lingual tonsils, less prominent aggregates of the thyrohyoid membrane, and the cricothy- lymphoid tissue may be present in the lamina roid membrane (20). Posteriorly, the larynx is propria throughout the nasopharynx. These bounded by the posterior portion of the cricoid should not be overinterpreted as chronic in- cartilage and the arytenoid region. The pyriform flammation. Aggregates of lymphoid follicles fossa is not part of the larynx, but represents an are particularly prominent in the rim of the outpouching of the hypopharynx located on each eustachian tube opening (Gerlach tonsil) (20). lateral border of the larynx (fig.1 -10). It serves as a Seromucinous glands and their associated conduit for food and water, rather than air (20). ducts are located throughout the lamina pro- The structural integrity of the larynx is de- pria of the nasopharynx. Mucin production is rived from its major cartilages (fig. 1-11): the prominent in these glands, and the glands may cricoid, thyroid, and paired arytenoid carti- undergo oncocytic metaplasia with increas- lages, all of which are of hyaline cartilage type.
Anatomy, Histology, and Embryology
Figure 1-9 REGIONS OF THE UPPER Figure 1-10 RESPIRATORY TRACT SINONASAL TRACT, ORAL CAVITY, AND LARYNX The boundaries of the nasal cavity, nasopharynx, The pyriform recesses, or sinuses, are lateral to the larynx oropharynx, and hypopharynx are delineated in this and part of the hypopharynx, forming a conduit from the sagittal view. oropharynx to the esophagus.
Figure 1-11 LARYNX The laryngeal cartilages, viewed anteriorly (left) and posteriorly (right). The lamina of the thyroid cartilage, cricoid arch, and hyothyroid membrane are the major anterior supporting structures. Posteriorly, the major structural support for the larynx is derived from the lamina of the cricoid cartilage. The location of the speech- critical arytenoid cartilages are clearly visualized.
Tumors of the Upper Aerodigestive Tract and Ear
level of the vocal cords located between the arytenoid cartilages. This area is sometimes referred to as the posterior commissure, but a true posterior commissure does not exist (9). The subglottic larynx extends inferiorly from the lower border of the true vocal cords to the region of the inferior border of the cricoid car- tilage and the first tracheal cartilage (29). Histology In newborns, the larynx is entirely lined by ciliated respiratory epithelium, with the excep- tion of the true vocal cords, which are covered by stratified squamous epithelium (fig. 1-13) (13). Patches of squamous epithelium begin to appear on the false vocal cords at about 6 months of age, but large areas of ciliated epithe- lium may remain (27,35). The anterior, or lin- Figure 1-12 gual, surface of the epiglottis is not functionally VOCAL CORDS part of the larynx and is invariably covered with This endoscopic view shows the epiglottis anteriorly, squamous epithelium. The posterior surface in and the vocal cords with their posterior attachments to adults is covered by stratified squamous mucosa the arytenoids. The false cords are just above and lateral to at its upper end, but this merges with ciliated re- the true cords. (Fig. 16.3 from Mills SE, ed. Histology for spiratory epithelium inferiorly. In nonsmoking pathologists, 3rd ed. Philadelphia: Lippincott, Williams & Wilkins; 2007:433.) adults, the supraglottic and infraglottic portions of the larynx are typically lined by irregular patches of squamous epithelium, alternating Ossification of the thyroid and cricoid cartilages, with ciliated respiratory epithelium. In smokers, complete with the formation of bone marrow the entire larynx, along with large portions of elements, begins in adulthood. Importantly, os- the remainder of the tracheobronchial tree, may sified cartilage lacks the resistance to the spread be lined by squamous epithelium. of cancer manifested by unaltered hyaline car- The ciliated respiratory epithelium of the tilage. The remaining major laryngeal cartilage, larynx varies markedly in thickness (20). It the epiglottic cartilage, is of elastic type and sometimes consists of a flattened basal cell layer never undergoes ossification. It contains numer- over which is a second, modest layer of ciliated ous fenestrations, however, which allow for easy respiratory cells with minor variation in nuclear invasion and penetration by carcinoma. positioning. Alternatively, the ciliated layer is Primarily from a surgical point of view, and sometimes thickened and the nuclei are promi- partially related to embryology (see below), nently pseudostratified. Mucous cells vary from the larynx is typically divided into three major rare to numerous. The junction between areas compartments (supraglottic, glottic, subglottic). of respiratory and squamous epithelium may be The supraglottic larynx begins superiorly at the abrupt, but often there is a 1- to 2-mm transi- tip of the epiglottis and extends downward to tional zone in which columnar cells are gradually the superior edge of the true vocal cord (30). replaced by somewhat disorganized immature Included in the supraglottic larynx are the epi- squamous or basaloid cells (fig. 1-14). This zone glottis, aryepiglottic folds, false vocal cords, and of immature squamous metaplasia is analogous to laryngeal ventricles. The glottic larynx includes the junctional changes frequently encountered in the vocal cords and the anterior commissure the uterine cervix. This pattern can be confused that bridges them at their anterior point of at- with dysplasia or carcinoma in situ, particularly tachment (fig.1 -12) (2,28). It also includes the when dealing with frozen sections or otherwise small portion of posterior mucosal wall at the suboptimal preparations. Closer attention to
10 Anatomy, Histology, and Embryology
Figure 1-13 TRUE AND FALSE CORDS Left: A depiction of a coronal section through one side of the larynx shows false vocal cord with abundant seromucinous glands, the laryngeal ventricle and sac cule, and the true vocal cord with the underlying vocalis muscle. (Slide 2 from Mills SE, Fechner RE. Pathology of the larynx. Chicago: ASCP Press; 1985:3.) Right: The histologic equiv alent. (Fig. 1-16 from Stelow EB, Mills SE. Biopsy interpretation of the upper aerodigestive tract and ear. Lippincott, Williams and Wilkins, Philadelphia, 2008:12.)
Figure 1-14 LARYNX The zone of transitional epi thelium between overtly squa mous mucosa and respiratory mucosa has a disorganized ap pearance and should not be confused with dysplasia. (Fig. 1-15 from Stelow EB, Mills SE. Biopsy interpretation of the upper aerodigestive tract and ear. Lippincott, Williams and Wilkins, Philadelphia, 2008:11.)
cytologic detail shows that, although disorga- tened squamous cells with smaller nuclei. The nized, the cells have uniform nuclei, with mitotic overall thickness of the squamous epithelium figures confined to the basal cell layer; residual is highly variable, ranging from 5 to 25 cells in ciliated cells may be present. thickness (20). Normally, a well-formed para- The mature squamous epithelium of the keratotic or orthokeratotic cell layer is lacking, larynx varies in thickness. It consists of a although these changes are commonly present mitotically active basal cell layer which oc- in biopsies from chronic smokers. casionally contains scattered, interdigitating Seromucinous glands are present throughout melanocytes (5,7), covered by progressively the larynx, with one exception. They connect maturing squamous cells. The most superficial to the overlying surface epithelium via ducts component consists of two to three small flat- lined by mixtures of squamous and columnar
11 Tumors of the Upper Aerodigestive Tract and Ear
Figure 1-15 TRUE VOCAL CORD The loose fibromyxoid tissue beneath the epithelium of the vocal cord is devoid of seromucinous glands. Figure 1-16 ARYTENOID CARTILAGE epithelia (24). The glands are particularly nu- Sections from the posterior portion of the vocal cords merous beneath the false vocal cords. They also may include the vocal process of the arytenoid cartilage. This should not be confused with chondroid metaplasia or are numerous in the epiglottis and often fill neoplasia. (Slide 7 from Mills SE, Fechner RE. Pathology of the fenestrations in the epiglottic cartilage. In the larynx. Chicago: ASCP; 1985:4.) tangential sections, squamous-lined ducts from these glands may appear as isolated squamous nests. Distinction from invasive carcinoma is when edema fluid is trapped in this space. The usually straightforward with sections of ad- poor vascular access of the vocal cords may also equate quality, but the situation becomes more account for the excellent prognosis associated difficult when dysplastic changes from the over- with carcinomas confined to the true cords, lying surface mucosa extend into these ducts. since the chance of spread to regional or distant Seromucinous glands are absent or sparse sites is minimal. beneath the mobile portion of the true vo- The vocal process of the arytenoid cartilage cal cord (figs. 1-13, 1-15). In this region, the deserves special mention because this structure lamina propria is composed of loose to dense may cause considerable consternation in bi- connective tissue filling the space between the opsies from the posterior portion of the vocal surface epithelium and the underlying vocal cord (fig. 1-16). The vocal process is a sharply ligament (Reinke space) (20). This area has demarcated nodule of elastic cartilage, often limited vascular and lymphatic access. The poor surrounded by a narrow, condensed, concentric lymphatic drainage probably contributes to the layer of fibrous tissue. Its elastic nature distin- development of vocal cord nodules and polyps guishes it from chondroid neoplasms, which
12 Anatomy, Histology, and Embryology
Figure 1-17 CHONDROID METAPLASIA Chondroid metaplasia forms small, somewhat ill-defined elastochondroid nodules. (Fig. 1-17 from Stelow EB, Mills SE. Biopsy interpretation of the upper aerodigestive tract and ear. Lippincott, Williams & Wilkins, Philadelphia, 2008:13.)
are composed of hyaline cartilage. Chondroid arch, which also gives rise to the trachea and metaplasia of the vocal cords is present in 1 to lungs. Thus, as Bocca et al. (3) demonstrated, the 2 percent of autopsies (8,14), usually affecting larynx has two embryologically distinct compo- the middle and posterior portions of the vocal nents that form superior and inferior “hemila- cords, near the vocal process. Microscopically, rynges” with distinct and largely independent chondroid metaplasia consists of small, some- lymphatic drainage. Modes of local and regional what ill-defined elastochondroid nodules (fig. spread are accordingly different for supraglottic 1-17). The surrounding stroma is often rich than glottic and subglottic neoplasms. in acid mucopolysaccharides (14). Chondroid The first portion of the larynx to form during metaplasia can occur elsewhere in the larynx, embryogenesis is the epiglottis, and this structure particularly in the false vocal cords. is well-formed by the fifth week of embryologic development (26,34). The beginning form of a Embryology larynx is recognizable in a 6-mm embryo and by The supraglottic portion of the larynx, along 60 to 70 days, at the 30-mm embryo stage, the with the oral cavity and oropharynx, is derived vocal cords begin to differentiate. The larynx from the third and fourth branchial arches is a complex structure and subject to varied (3,20). In contrast, the glottis and subglottic embryologic anomalies; over 30 malformations larynx are derived from the sixth branchial of the larynx have been described (6).
13 Tumors of the Upper Aerodigestive Tract and Ear
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