Development and growth of median structures in the human tongue: A histological study using human fetuses and adult cadavers.

Glossectomy is a surgical procedure performed to remove all or part of the tongue in patients with cancer. The removal of a significant part of the tongue has a marked effect on speech and swallowing function, as patients may lose not only the tongue muscles but also the median lingual septum (MLS). Therefore, to achieve successful tongue regeneration, it is necessary to investigate the developmental processes of not only the tongue muscles but also the MLS. This study was conducted to clarify the mutual development of the tongue muscles and the MLS in human fetuses. Serial or semi-serial histological sections from 37 embryos and fetuses (aged 5-39 weeks) as well as nine adults were analyzed. The MLS appeared at Carnegie stage 15 (CS15), and until 12 weeks of gestation, abundant fibers of the intrinsic transverse muscle crossed the septum in the entire tongue. However, in near-term fetuses and adults, the contralaterally extending muscles were restricted to the deepest layer just above the genioglossus muscle. This finding indicates that the crossing transverse muscle showed the highest density at mid-term. A thorough understanding of both the MLS and the tongue muscles is necessary for successful tongue regeneration.

Development and growth of auricular cartilage and muscles: A study using human fetuses.

OBJECTIVES: The auricle is a key target in pediatric plastic surgery and is considered to develop from a ring- or funnel-like arrangement of six hillocks in the embryo. However, there has been no report showing the morphologies of the auricular muscle and cartilage after midterm in humans. METHODS: We examined histological sections of 20 near-term human fetuses (29-40 weeks) and those from 7 midterm fetuses (15-16 weeks). RESULTS: At midterm, the auricular cartilage was a single wavy plate with the helicis major muscle (HMM). The superior and posterior auricular muscles (SAM, PAM) were inserted into the middle parts, and the anterior auricular muscle (AAM) was inserted into the lowest part of the cartilage plate, while the tragus and antitragus were not clearly identified. In near-term fetuses, the cartilage plate varied in size and shape between specimens. The scapha and antihelix were separated from the cartilage plate with major or minor involvement of the HMM from the initial mass along the helix. The SAM inserted to the crus helix or the developing scapha, while the insertion sites of the AAM and PAM into the helix were stable. The tragus-antitragus cartilages were well-developed and they sandwiched a deep notch of skin below the helix tail. The antitragicus muscle was more evident than the tragicus muscle. An unnamed muscle was evident along the external acoustic meatus. The other intrinsic muscles, including the transverse and oblique muscles, might develop from the HMM after birth. CONCLUSIONS: Development of the auricle was advanced after midterm. However, a single wavy plate-like cartilage was maintained until late-stage. Near term, the antihelix and scapha developed from the plate-like core of the auricle and the tragus and antitragus were added in the antero-inferior side of the cartilage plate. Establishment of muscle arrangements was markedly delayed compared to cartilage development. Altogether, the classical concept of an initial funnel-like arrangement of cartilage anlagen might have been biased by studies of adult morphology.

Is the ultimobranchial body a reality or myth: a study using serial sections of human embryos.

Reported morphologies of the ultimobranchial body had varied between researchers: a cluster of mitotic cells, a duct-like structure and a rosette-like cell mass. To clarify the true morphology, we studied tilted horizontal sections of 20 human embryos (crown-rump length 5-18 mm; 4-6 weeks). The sections displayed a ladder-like arrangement of the second to fourth endodermal pouches and, in 5 early embryos we found the fifth pouch attached to the fifth ectodermal groove near the fourth pharyngeal arch artery. The bilateral fifth pharyngeal pouches protruded anterolaterally to form a U-shaped lumen surrounding the arytenoid swelling. The third to fifth pouches were each characterized by a pedal-shaped inferior end. We identified several types of cell clusters as candidates for the ultimobranchial body, but morphologically most of them were, to various degrees, likely to correspond to the blind end of the lower pouch when cut tangentially. Because of the topographical relation to the common carotid artery, a cyst-like structure with a cell cluster seemed to be the most likely candidate of the ultimobranchial body (a common anlage of the thymus and parathyroid). However, we were not able to deny a possibility that a certain plane cutting the pouch end incidentally provided such a cyst-like structure in sections. At any stage, the ultimobranchial body might not appear as a definite structure that is discriminated from others with routine staining. A concept of the ultimobranchial body might be biased by comparative anatomy that shows the ultimobranchial gland in adult birds and reptiles.

Pyramidal lobe of the thyroid gland and the thyroglossal duct remnant: a study using human fetal sections.

To investigate developmental changes in the thyroglossal duct, we observed serial sagittal sections of eight embryos (crown-rump length (CRL) 6-12 mm; approximately 5-6 weeks of gestation) as well as serial horizontal or cross-sections of 70 embryos and fetuses (CRL 15-110 mm; 6-15 weeks). In the sagittal sections, the thyroglossal duct was identified as a small sheet or mass of relatively large cells with vacuolization anterior, superior or inferior to the fourth pharyngeal arch artery. However, we found no continuous duct-like structure that reached the thyroid gland. Thus, previous classical schemes might have overestimated the continuity of the duct. Among cross-sections of 70 specimens, we found the thyroglossal duct remnant in only two specimens (CRL 15 mm and 100 mm), in contrast to the pyramidal lobe, which was seen in one-third of the specimens. The duct remnant ran downward along the lateral edge of the hyoid body to reach the anterior aspect of the thyroid cartilage. However, the connection between the pyramidal lobe and the duct remnant was interrupted by the anterior cervical muscles. Therefore, it was unlikely that the thyroglossal duct remnant would more frequently be evident in fetuses than in adults. The highly tortuous course of the duct along the lingual aspect of the hyoid body, which has been reported previously, appeared to become established near term. Descent of the thyroid gland was not evident after the CRL 20 mm stage (6 weeks): the gland appeared to retain its position at the level of the third-sixth cervical vertebrae.

Site- and stage-dependent differences in vascular density of the human fetal brain.

BACKGROUND AND PURPOSE: Less information is available about site-dependent differences in fetal intrabrain angiogenesis. Quantitative evaluation is especially limited, with the measured area limited to the cerebral gray and white matters and the periventricular germinal matrix. PATIENTS AND METHODS: We measured vascular density (number of vessels per square millimeter) and percent vascular area (percentage of areas occupied by vessels) of CD34-positive microvessels in 14 human fetal brains, including 4 fetuses at 14-16 weeks of gestation, 5 at 25-28 weeks, and 5 at 35-37 weeks. Site-dependent differences were examined among the cerebral cortex, thalamus, internal capsule, corpus callosum, ganglionic eminence, midbrain, and cerebellar cortex and nuclei. RESULTS: The parameters examined tended to be high in the cerebral germinal matrix, thalamus, midbrain, and cerebellum. Significant site-dependent differences were observed: lower vascular densities were observed in the internal capsule and corpus callosum than in other parts of the brain (p < 0.05) and a larger percent area was observed in the cerebellar nuclei than in other areas. Vascular density was higher during the early than late stage because of the larger numbers of CD34-positive islands of cells in the early stage, although there were several exceptions. Percent area was not stage dependent but was almost constant at many sites. CONCLUSION: Consequently, except for developing nuclei, the prenatal development of intrabrain vessels after 15 weeks may proceed without any significant changes in density.

Origin of the torus mandibularis: an embryological hypothesis.

Torus mandibularis, a well-known protuberance in the dental field, has been defined as a hyperostosis in the lingual aspect of the body of the mandible above the mylohyoid line. However, the origin of the torus mandibularis has not yet been clarified. The aim of this study was to provide a better understanding on the origin of the torus in view of the specific development of Meckel's cartilage at the site corresponding to the adult torus. A total of 40 mid-term human fetuses at 7-16 weeks of gestation were examined. The 10-13 weeks stage corresponded to the critical period in which Meckel's cartilage with endochondral ossification underwent a bending at the beginning of the intramandibular course. At the level of mental foramen, which was located between the deciduous canine and the first deciduous molar germs, the medial lamina of the mandible protruded medially to reach Meckel's cartilage. Thus, the medial lamina covered the posterior and superior aspect of the bending Meckel's cartilage just above the attachment of the developing mylohyoid muscle (i.e., in the oral cavity). We considered a bony prominence, which composed the protruding medial lamina and the bending Meckel's cartilage as the fetal origin of the torus mandibularis. A new theory is proposed for the origin of the torus mandibularis based on the existence of an anlage formed during the development of the mandible, variable in morphology and size, but always constant.

Transsphenoidal meningocele: an anatomical study using human fetuses including report of a case.

An asymptomatic transsphenoidal meningoencephalocele was discovered incidentally by fiber laryngoscopic examination in a 62-year-old man suffering from hoarseness due to dysplasia of the vocal cord epithelium. To provide a better understanding of the pathogenesis of this anomaly, we performed histologic observations of paraffin-embedded specimens of 42 human fetal heads at 12-16 weeks of gestation. At these stages, ossification had started in the clivus but the sphenoid sinus was not developed. In contrast to the very low incidence of the intra- or trans-sphenoidal remnant of Rathke's pouch after birth, we found (1) the typical mid-line cleft of the sphenoid body in two specimens (2/42 or 4.8 %) and (2) a duct-like, sellar inferior protrusion ending in the sphenoid body in 12 specimens (12/42 or 28.6 %). The cyst-like structure in the protrusion (two specimens) seemed to be composed of obstructed veins. The intra- and trans-sphenoidal anomalies were observed more frequently in specimens without ossification of the sphenoid body than in those with ossification. However, irrespective of ossification, a cyst-like remnant of the most upper part of Rathke's pouch was always seen between the anterior and posterior lobes of the developing pituitary gland. In addition, the bursa pharyngea was seen in four specimens and we confirmed that the notochord was attached to the bursa in each case. The consistent remnant of the intrasellar Rathke's pouch appeared to explain the high incidence of Rathke's cleft cyst in adults. The relatively high incidence of intrasphenoidal anomalies in fetuses (14/42) suggested that the intra- or trans-sphenoidal remnant of Rathke's pouch was physiologically closed by ossification of the sphenoid body.

Rathke's pouch remnant and its regression process in the prenatal period.

OBJECTS: During ontogeny, part of Rathke's pouch, a physiologically superior pouching of the stomodeal ectoderm, may remain, forming the usual anomaly known as Rathke's cleft cyst. More rarely, however, the entire pouch (i.e., the craniopharyngeal canal) remains, resulting in transsphenoidal meningoencephalocele. This study is aimed to provide a better understanding of the pathogenesis. MATERIALS AND METHODS: We histologically evaluated the inferior protrusion of the putative hypophysial fossa in 35 embryonic and fetal heads, respectively (15 at 5-8 weeks and 20 at 12-16 weeks of gestation). RESULTS: In 3 of the 35 specimens, we observed a complete cleft originating from the adenohypophysis, passing through the sphenoid and connecting with the pharyngeal epithelium or pharyngobasilar fascia. In another 18 specimens, we observed a duct-like structure protruding from the fossa and ending in the sphenoid. The sellar protrusion contained vein-like structures and debris of red blood cells. The protrusion was located on the anterior or anterosuperior side of the notochord. No ossification center was observed around the sellar region of the embryos. Although ossification occurred in 12 of the 20 fetuses, nine of the latter showed no evidence of cleft or protrusion, indicating that the incidence of Rathke's pouch remnant was lower in the fetuses (11/20) than in the embryos (11/15). CONCLUSION: Rathke's pouch may be closed by ossification of the sphenoid, but increased cell proliferation and/or large amounts of degenerated veins may provide a structure resistant to the mechanical pressure caused by ossification.

Glandular odontogenic cyst: two high-risk cases treated with conservative approaches.

BACKGROUND: The glandular odontogenic cyst is a rare jawbone cyst that is considered to be an independent entity, although its histopathological characteristics may lead to an incorrect diagnosis as a low-grade mucoepidermoid carcinoma. The treatment of glandular odontogenic cysts is controversial. CASE REPORT: We present two high-risk cases treated with conservative approaches, one by enucleation and curettage and the other by marsupialisation. This report also presents a review of the clinical and pathological aspects of glandular odontogenic cysts, and considers their development. No evidence of disease was observed after 3 years of follow-up in the two cases presented. CONCLUSIONS: When possible, treatment plans for these lesions should be customised for each case, taking into account the data available in the literature and patient preferences. For high-risk cases, that are treated with conservative approaches, such as the two cases presented here, strict and regular controls and rigorous radiological follow-up evaluations are mandatory.

Fetal intrahepatic gallbladder and topographical anatomy of the liver hilar region and hepatocystic triangle.

The fetal gallbladder (GB) is embedded in a deep fossa surrounded by the liver parenchyma. Using 15 specimens with intrahepatic GB (crown-rump length 45-92 mm; approximately 9-13 weeks of gestation), we assessed the fetal topographical anatomy of the hepatocystic triangle and the porta hepatis. The cystic duct displayed a long upward course (0.9-4.5 mm along the supero-inferior axis) from the GB, along the duodenum, to the common bile duct in the hepatoduodenal ligament, via an independent mesentery separated from liver parenchyma by a recess of the peritoneal cavity. Notably, the course varied in length among specimens, not among stages. At the porta hepatis, we were able to distinguish the supraportal course of the posterior right hepatic duct overriding a portal vein branch to segment 8 (6/15) from the other, infraportal course (9/15). In the latter type, the portal vein bifurcation was superior to the cystic duct course. Two margins of the hepatocyctic triangle were very long in fetuses because of the inferiorly located intrahepatic GB. Thus, the triangle seems to be difficult to identify in prenatal ultrasound. During changes in location after 9 weeks, the GB fundus remains attached to the liver because the cystic artery was often embedded in the liver parenchyma. A failure in the embedding and re-exposure process of the GB may result in anomalous peritoneal folds around the GB.

Muller's muscle, no longer vestigial in endoscopic surgery.

BACKGROUND: As a thin filmy covering overlaying the inferior orbital fissure (IOF), Muller's muscle was considered a vestigial structure in humans, and for this reason, its anatomical significance was neglected. Because of increasing interest in endonasal approaches to the skull base that encompasses this region, we re-examined this structure's role as an anatomical landmark from an endoscopic perspective. METHODS: In 10 cadaveric specimens, microanatomical dissections were performed (n = 5); endoscopic dissections were performed (n = 5) via approaches of the middle turbinate or inferior turbinate, and via the Caldwell-Luc approach through the maxillary sinus. Histological examinations were performed in 20 human fetuses (Embryology Institute, Universidad Complutense de Madrid, Madrid, Spain). RESULTS: In cadaveric dissections, Muller's muscle was demonstrated in all specimens, serving as a bridge-like structure that spanned the entire IOF and separated the orbit from the temporal, infratemporal, and pterygopalatine fossas. Depending on which endoscopic corridor was used, a different aspect of the IOF and Muller's muscle was identified. In our endoscopic and microscopic observations, Muller's muscle was extensive, not only spanning the IOF but also extending posteriorly to reach the superior orbital fissure (SOF) and anterior confluence of the cavernous sinus. Histological analysis identified many anastomotic connections between the ophthalmic venous system and pterygoid plexus that may explain how infection or tumor spreads between these regions. CONCLUSIONS: Muller's muscle serves as an anatomical landmark in the IOF and facilitates anatomical orientation in this region for endoscopic skull base approaches. Its recognition during endoscopic approaches allows for a better three-dimensional understanding of this anterior cranial base region.

Fetal development of the human epiglottis revisited: appearance of GFAP-positive mesenchymal cells and fibrous connections with other laryngeal and lingual structures.

The fetal anatomy of the human epiglottis has not yet been fully described. We investigated the histology (paraffin-embedding) of 18 mid-term fetuses at 7-25 weeks of gestation (three fetuses each at 7, 9, 12, 15, 20 and 25 weeks). A mesenchymal condensation of the epiglottic cartilage appears posterior and somewhat superior to the hyoid body at 9 weeks, but at 12 and 15 weeks, the root or inferior part descends to the level of the thyroid cartilage. The covering epithelium stains much darker with hematoxylin than other pharyngeal epithelia. After 20 weeks, the epiglottis again protrudes superiorly beyond the hyoid body. In contrast to other laryngeal cartilage anlagen, the mesenchymal condensation of the epiglottis begins to express glial fibrillary acidic protein (GFAP) at 15 weeks. At the same stage, mucosal glands begin invading into the epiglottic mesenchyme. The developing cartilage becomes penetrated and fragmented by abundant mucosal glands up until 25 weeks. The thyro-epiglottic ligament seems to develop from the GFAP-positive mesenchymal condensation, whereas the hyo-epiglottic ligament is likely to originate from the fasciae of lingual muscles. Epithelial-mesenchymal interaction is strongly suggested in the development of the epiglottic cartilage and concomitant glands.