Atypical mature bone in the otosclerotic otic capsule as the differentiated zone of an invasive osseous neoplasm.

CONCLUSION: A large proportion of the mature otic capsule bone in cases of otosclerosis lies in plaques in direct contiguity with active otosclerosis and, because it shows significant structural defects, it should be regarded as part of the otosclerotic process. These appearances support our previously described suggestion that otosclerosis is an invasive osseous neoplasm, the mature atypical bone representing differentiation of earlier-formed invasive neoplastic osseous tissue. OBJECTIVES: We sought structural features in differentiated bone within the otic capsules of cases of otosclerosis that might indicate a relation to the underlying disease process. METHODS: Fifty temporal bones from 42 adult patients with otosclerosis were processed into stained histological sections and the appearance of the otic capsule was compared with that of the same tissue, processed in the same way, in 10 cases that did not show otosclerosis. RESULTS: In the cochlear otic capsules of otosclerotic temporal bones, when traced back along the otosclerotic plaque from the invasive front, atypical shapes and arrangements of osteons were seen, often with otospongiosis (severe dilatation of multiple Volkmann's canals), culminating in larger differentiated osteons with irregularities in structure. In the medial region of the otosclerotic cochlear otic capsule, at a similar position to that where giant normal osteons are present in the normal temporal bone, differentiated, giant abnormal osteons were seen. In the otosclerotic vestibular otic capsule there were changes similar to those of the otosclerotic cochlea (apart from the giant osteons) and many osteons composed of clusters of atypical osteoblast-like cells around highly atypical Volkmann's canals.

Origin and growth of otosclerosis.

CONCLUSION: The external layer of the otic capsule arises from periosteal osteoblasts, which produce large numbers of Volkmann's canals as well as lamellar bone. The main plaque of otosclerosis is a histologic replica of the external layer and seems to arise from similar cells in the periosteum and to follow a defined invasive course into the footplate of the stapes, the basal coil of the cochlea and the saccule. OBJECTIVES: To determine by histologic study of the developing otic capsule and temporal bones with otosclerosis the site, tissue of origin, and pathways of growth of the disease. METHODS: Step sections of 60 celloidin-embedded temporal bones from fetuses and 24 from patients aged between 1 and 52 years were examined in the study of the development of the otic capsule. Step sections of 65 temporal bones each with 2 or more deposits of otosclerosis were surveyed to obtain data on the site, tissue of origin, and pathways of its growth. RESULTS: The otic capsule differs from other bones in that the formation of the ultimate lamellar bone tissue is accompanied by very numerous intercommunicating channels. In the middle (cartilage origin) layer these are chondro-osseous canals and Volkmann's canals (like Haversian canals, but multidirectional). In the external (periosteal origin) layer these are Volkmann's canals only. In all, 63 of the 65 temporal bones with otosclerosis that were studied showed a prominent posterior otic capsule plaque. Evidence that this is derived from the periosteum of the external canal is as follows. (a) The otosclerotic tissue of the plaque--like all otosclerotic tissue--is composed of Volkmann's canals and lamellar bone only, as does external layer tissue. (b) All posterior plaques have an edge at the periosteum bordering the processus cochleariformis and tensor tympani muscle. The presumed invasive edge of the plaque on the opposite (cochlear) side shows a variable level of its front. (c) The tissue on the cochlear side of the plaque has a darkly stained appearance with large numbers of osteoblasts and poorly differentiated Volkmann's canals, suggesting that this is an invasive front. The otosclerosis becomes progressively better differentiated away from the darkly stained zone, indicating increasing maturation, which is greatest in the suggested origin of the plaque at the processus/tensor tympani muscle region because this would be the oldest region of the plaque. The pathway of the growth indicated by this study suggests a possible time sequence in the symptomatology of otosclerosis as it moves first to stapes footplate and then through the spiral ligament of cochlea to the saccule. An anterior plaque was seen in 42 of the 65 temporal bones with multiple sites of otosclerosis examined. These showed features similar to those listed above for the posterior plaque, with a base on the periosteum bordering the canal for the internal carotid artery, dark zonation at the invasive front near the cochlea, and increasing differentiation towards the base.

The intravestibular source of the vestibular aqueduct. III: Osseous pathology of Ménière's disease, clarified by a developmental study of the intraskeletal channels of the otic capsule.

CONCLUSION: Review of the histopathological changes in the vestibular arch in Ménière's disease, after a study of development of the otic capsule, indicated a severe apoptotic loss of osteoblasts with consequent denudation of these cells from and damage to the osseous canal structure of the arch. OBJECTIVE: To review previously reported histological findings in the inner layer of the vestibular aqueduct and its intravestibular source in Ménière's disease, using newer knowledge of otic capsule development. METHODS: Temporal bone histological sections from the vestibular arch region of eight patients with Ménière's disease were reviewed in our London-based material. RESULTS: Minute granules suggesting apoptotic bodies were found in the arch in the majority of cases, giving support for the concept of an apoptotic loss of osteoblasts. Explanation for the previously described appearance of proliferation of atypical channels and of small, finely outlined empty areas in the bone was provided by the observation of denudation of osteoblasts from Volkmann's canals and microcanals. These canals had been recently described in a developmental study of the otic capsule. Dislocation of dead microcanals into blood vessels of Volkmann's canals was seen in two of the cases.

The intravestibular source of the vestibular aqueduct. II: its structure and function clarified by a developmental study of the intra-skeletal channels of the otic capsule.

CONCLUSION: A developmental histologic study of the otic capsule indicates that it grows a system of lamellar bone with abundant interconnecting intraosseous channels. These include the 'cartilage canals' in the cartilage model, the chondro-osseous and Haversian-like (Volkmann's) canals in the ossified otic capsule, the fissula ante fenestram, which seems to function as a lifelong manufacturer of the latter two channels, and the inner layer (vestibular arch) of the vestibular aqueduct, which is a complex series of Volkmann's canals and microcanals. Chemical changes, possibly produced by breakdown of cells within the channels, may provide a homeostatic environment for the functions of hearing and balance that take place in the endolymphatic fluid. OBJECTIVES: We studied the development of the otic capsule to clarify the cellular appearances that we had previously described in the normal vestibular arch and the changes in that structure in Ménière's disease. METHODS: Step sections from 84 temporal bones, including those from fetuses, children and adults from a variety of ages were examined histologically. RESULTS: Cartilage canals, bringing blood vessels and mesenchymal cells from perichondrium to the depths of the cartilage model to mediate ossification, are found early in fetal life and disappear when ossification is complete at about 24 weeks. The otic capsule is formed of chondro-osseous canals, which are composed of trabeculae of mineralized cartilage lacunae containing mesenchymal cells that undergo ossification (globuli ossei); also Volkmann's canals (like Haversian canals in long bones but multidirectional), which are produced from osteoblasts. The lumina of the latter frequently link up with chondro-osseous canals. Lamellar bone forms the background of the otic capsule. The fissula ante fenestram is present from early in the cartilage model and then throughout life. It appears to mediate bone production and the new formation of chondro-osseous channels and Volkmann's canals. The internal layer of the vestibular aqueduct (vestibular arch) is seen in the cartilage model of the otic capsule (present in early fetal life) as a vascular layer of perichondrally derived connective tissue (not cartilage) surrounding the endolymphatic duct. When endochondral ossification starts, the bone from the adjoining cochlear and vestibular sides embrace this connective tissue layer to form the outer bony layer of the vestibular aqueduct. Osteoblasts then fill the inner layer with lamellar bone and macro- and mini-Volkmann's canals. At 1 year osteoblasts in the walls of macro-Volkmann's canals, proliferating thereafter throughout life, produce large numbers of microcanals. It is possible that slow breakdown of these osteoblasts and of similar cells in the canals of the otic capsule proper may contribute to the homeostasis of the endolymphatic duct and that of the rest of the membranous labyrinth, respectively.

Current review on squamous intraepithelial lesions of the larynx.

Squamous intraepithelial lesions (SILs) of the larynx, clinically usually defined as leukoplakia and chronic laryngitis, have remained the main controversial topic in laryngeal pathology for decades as regards classification, histological diagnosis and treatment. SILs are caused by smoking and alcohol abuse. There is also mounting evidence that gastroesophageal reflux is a potential aetiological factor. Human papillomavirus infection seems to play little if any role in laryngeal carcinogenesis. Histological classification of SILs is the central disputed aspect of these lesions. There are as yet no generally accepted criteria for histological grading of laryngeal SILs. Three currently used classifications of SILs are reviewed here: the dysplasia system, the Ljubljana classification and the binary system of squamous intraepithelial neoplasia. One of the most important issues of SILs is the risk of malignant transformation. Data in the literature are controversial because of inconsistent use of morphological criteria in different classifications. It is often difficult for clinicians to agree on the most appropriate therapeutic option for a particular grade of SIL that has been diagnosed. Transition from normal epithelium to SILs and squamous cell carcinoma is related to progressive accumulation of genetic changes leading to a clonal population of transformed epithelial cells. Despite extensive research into these genetic changes in laryngeal carcinogenesis, reliable genetic markers with diagnostic and prognostic value are still lacking.

Aggressive papillary tumor of the middle ear: a true entity or an endolymphatic sac neoplasm?

Aggressive papillary tumors of the middle ear are rare, and their true origin is not clear. We describe the clinical, radiologic, genetic, and histopathologic features of a papillary epithelial tumor filling the middle ear of a 68-year-old woman. Imaging revealed no evidence of petrous temporal bone apex involvement, nor did genetic studies demonstrate the von Hippel-Lindau mutation. A literature search revealed 24 previously reported cases of such a papillary epithelial tumor of the middle ear. All except 2 cases demonstrated apical petrous temporal bone invasion on imaging, and it has been suggested that they arose from a primary endolymphatic sac tumor, which has a similar papillary epithelial histology. Substantial numbers of cases of papillary epithelial tumors involving the middle ear are reported to be associated with von Hippel-Lindau disease, as are known cases of endolymphatic sac tumor. This is the third reported case of papillary epithelial tumor of the middle ear that does not show apical petrous temporal bone invasion on imaging, suggesting that such neoplasms do not always arise from a primary in the endolymphatic sac.

Recent technological developments: in situ histopathological interrogation of surgical tissues and resection margins.

OBJECTIVES: The tumour margin is an important surgical concept significantly affecting patient morbidity and mortality. We aimed in this prospective study to apply the microendoscope on tissue margins from patients undergoing surgery for oral cancer in vivo and ex vivo and compare it to the gold standard "paraffin wax", inter-observer agreement was measured; also to present the surgical pathologist with a practical guide to the every day use of the microendoscope both in the clinical and surgical fields. MATERIALS AND METHODS: Forty patients undergoing resection of oral squamous cell carcinoma were recruited. The surgical margin was first marked by the operator followed by microendoscopic assessment. Biopsies were taken from areas suggestive of close or positive margins after microendoscopic examination. These histological samples were later scrutinized formally and the resection margins revisited accordingly when necessary. RESULTS: Using the microendoscope we report our experience in the determination of surgical margins at operation and later comparison with frozen section and paraffin section margins "gold standard". We were able to obtain a sensitivity of 95% and a specificity of 90%. Inter-observer Kappa scores comparing the microendoscope with formal histological analysis of normal and abnormal mucosa were 0.85. CONCLUSION: The advantage of this technique is that a large area of mucosa can be sampled and any histomorphological changes can be visualized in real time allowing the operator to make important informed decisions with regards the intra-operative resection margin at the time of the surgery.

Origin of endolymphatic sac tumor.

Autopsy temporal bone sections showing a one mm papillary glandular neoplasm, confined to the left endolymphatic duct, are described. This is the second literature report confirming the post-mortem site of origin of the "endolymphatic sac tumor". The patient died after surgery for right vestibular schwannoma, but no features of von Hippel Lindau disease or neurofibromatosis 2 had been displayed clinically or at autopsy. A study of the epithelium of normal human mature endolymphatic ducts and sacs (EDSs) in archival temporal bone sections showed hyperplastic tubular outgrowths, usually situated in the intraosseous portion of the endolymphatic sac, in most cases. Such appearances imply that the epithelium of the EDS has the potential of producing a malignant papillary glandular neoplasm. Papillary ingrowths, some forming collagenous polypoid projections, and cysts were frequent among the epithelial cells. Psammoma bodies were present in the ducts and sacs of older patients. Appearances suggesting erosion of the bony interface of vestibular aqueduct with EDS could be ascribed to the entry and exit of blood vessels into and from the vestibular aqueduct. Care should be taken in the evaluation of surgical or autopsy material from EDSs not to overcall any of these normal features as malignant.

Immunohistochemical characterization of the epidermoid formation in the middle ear.

OBJECTIVE: To study the incidence, size, and origin of epidermoid formations after accurately characterizing them by cytokeratin immunohistochemical analysis. STUDY DESIGN: A strategy of screening sections for possible epidermoid formations in the entire eardrum area in paraffin-embedded, serially sectioned developing temporal bones was used. Unstained adjacent sections were subjected to immunohistochemical staining, to provide accurately identified epidermoid formations for a study of their appearance and size in relation to age. METHODS: The immunohistochemical expression patterns for epidermoid cytokeratins of several antibodies at different gestational ages were determined. Then, epithelial structures suspected as epidermoid formations were characterized as epidermoid with age-appropriate antibodies in 36 paraffin-embedded temporal bones from 19 cases with an age range of 6 gestational weeks to 15 months postpartum using a novel method of antigen retrieval by heating sections in a 70 degrees C water bath. RESULTS: Each of 22 temporal bones ranging in age from 16 weeks gestation to 8 months postpartum contained one or more, often numerous, epidermoid formations. Sizes of epidermoid formations increased significantly with increasing age. The formations were found anywhere in the annular lateral wall region of middle ear, but the majority were in the anterosuperior region. A further study of the interface between annular external canal epidermis and middle ear epithelium in a larger group suggested that epidermoid formations arise at approximately 16 gestational weeks from the external canal epidermis. CONCLUSION: The findings indicate that epidermoid tissue in the middle ear normally originates from external canal epidermis at approximately the 16th gestational week and grows before disappearing.