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In recent decades, the fabrication of composite membranes using nanoparticles has played a vital role in membrane distillation (MD) technique. It could make available membranes with superior characteristics as excellent candidates for MD technique. The most well-known obstacles regarding the MD method are the low productivity and high cost. Thus, fabricating membranes with superior properties is a significant challenge. In the current study, a composite membrane has been fabricated using 0.25, 0.5, and 0.75 weight percent (wt.%) of graphene nanoparticles (GNPs) with polystyrene (PS) as a base polymer and characterized using SEM, FTIR, and contact angle. The characterization results prove the successful fabrication using electrospinning and the validity of the fabricated membranes to be applied to direct contact membrane distillation (DCMD). In addition, a DCMD experimental setup has been designed to examine the performance of the fabricated membranes and compare the performance of blank PS with composite PS/GNPs membranes. The results show that all fabricated membranes produced an approximately similar average flux of about 10 kg/m 2 h, while the highest GNPs wt.% showed the highest salt rejection. Accordingly, this composite membrane has been examined at different operating parameters and showed stable performance. Moreover, feed temperature and the rate of flow have a positive impact on the overall performance of the DCMD.

Membrane distillation is an active technique that provides pure water with very good rejection and could be applied to water of extremely high salinity. The low productivity of membrane distillation needs intensive efforts to be competitive with other desalination techniques. In this current study, a composite (PS/GNP) membrane, which is composed of polystyrene (PS) based and 0.25% weight percent graphene nanoplates (GNP) has been fabricated via electrospinning and compared with the blank PS membrane. SEM, FTIR, contact angle and porosity characterization have been performed, and the results show that the validity of the predefined conditions, and the contact angle of the composite membrane, which is found to be 91.68°, proved the hydrophobic nature of the composite membrane. A numerical simulation using Ansys 2020 software has been introduced to study the performance of the fabricated composite membrane when used in direct contact membrane distillation (DCMD). The numerical model has been validated with experimental work from the literature and showed an excellent match. The blank PS and composite PS/GNP membranes have been investigated and compared at different operating conditions, i.e., hot water supply temperature and system flow rate. The results show that the composite PS/GNP membrane outperforms the blank PS membrane at all studied operating conditions.

Objective: To comprehensively examine the prognostic significance of extranodal extension (ENE) in human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV-positive OPSCC)., Methods: Retrospective cohort of cases diagnosed with HPV-positive OPSCC from 2010 to 2015 in the National Cancer Database. Inclusion of all OPSCC HPV-positive cases with appropriate International Classification of Diseases-0-3 codes that received surgery with a neck dissection. Univariate and multivariable analyses were conducted. Hazard ratios (HR) for the independent effects of ENE and N stage on overall survival were estimated by Cox proportional hazards regression., Results: Cases that were ENE-negative had the highest 5-year survival (92.6%; 95% confidence interval [CI]: 90.5%-94.7%). ENE-positive cases had the lowest 5-year survival (84.0%; 95% CI: 80.7%-87.4%). After adjusting for confounding variables, ENE-positivity was associated with almost twice the hazard of death (HR = 1.90; 95% CI: 1.35-2.67) compared to ENE-negative cases. Nodal (N) category 1, ENE-positive status was associated with an increased risk of death (HR = 1.88; 95% CI: 1.26-2.80) compared with N1, ENE-negative status. Compared to N1/ENE-negative cases, N2/ENE-positive cases had the poorest survival (HR: 2.93; 95% CI: 1.94-4.43). Both microscopic and macroscopic ENE were associated with worse outcomes compared to node-positive/ENE-negative status., Conclusion: The implementation of the American Joint Committee on Cancer 8th edition staging system provides a much-improved framework to develop and discuss treatment plans for HPV-positive OPSCC. We feel that careful consideration should be given to the importance of ENE in patients with HPV-positive OPSCC., Level of Evidence: 4 Laryngoscope, 130:939-945, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Distant metastases are relatively common in breast cancer, but spread to the head and neck region is uncommon and can be diagnostically challenging. Pathology databases of two academic hospitals were searched for patients. The diagnoses were by morphologic comparison with the primary breast specimen (when available) or through the use of immunohistochemical stains characteristic of breast carcinoma (cytokeratin 7, mammaglobin, GCDFP15, and/or GATA3 positive-excluding new primary tumors at the respective head and neck sites). Of the 25 patients identified, only 22 (88.0 %) had a known history of breast carcinoma. Time from primary diagnosis to head and neck metastasis was highly variable, ranging from 1 to 33 years (mean = 10.9 years). The most common locations were neck lymph nodes (8 cases), orbital soft tissue (5), oral cavity (3), skull base (3), mastoid sinus (2), nasal cavity (1), palatine tonsil (1), and facial skin (1). Clinical presentations were highly variable, ranging from cranial nerve palsies without a mass lesion to oral cavity erythema and swelling to bone pain. Histologically, two cases showed mucosal (or skin)-based mass lesions with associated pagetoid spread in the adjacent epithelium, a feature normally associated with primary carcinomas. Three tumors were misdiagnosed pathologically as new head and neck primary tumors. This series demonstrates the extreme variability in clinical and pathologic features of breast cancer metastatic to the head and neck, including long time intervals to metastasis.

The BRAF mutation occurs commonly in papillary thyroid carcinoma (PTC). Previous investigations of its utility to predict recurrence-free survival (RFS) and disease-specific survival (DSS) have reported conflicting results and its role remains unclear. The purpose of this retrospective study was to determine the incidence of the BRAF mutation and analyze its relationship to clinicopathologic risk factors and long-term outcomes in the largest, single-institution American cohort to date. BRAF mutational status was determined in 508 PTC patients using RFLP analysis. The relationships between BRAF mutation status, patient and tumor characteristics, RFS, and DSS were analyzed. The BRAF mutation was present in 67% of patients. On multivariate analysis, presence of the mutation predicted only for capsular invasion (HR, 1.7; 95% CI, 1.1-2.6), cervical lymph node involvement (HR, 1.7; 95% CI, 1.1-2.7), and classic papillary histology (HR, 1.8; 95% CI 1.1-2.9). There was no significant relationship between the BRAF mutation and RFS or DSS, an observation that was consistent across univariate, multivariate, and Kaplan-Meier analyses. This is the most extensive study to date in the United States to demonstrate that BRAF mutation is of no predictive value for recurrence or survival in PTC. We found correlations of BRAF status and several clinicopathologic characteristics of high-risk disease, but limited evidence that the mutation correlates with more extensive or aggressive disease. This analysis suggests that BRAF is minimally prognostic in PTC. However, prevalence of the BRAF mutation is 70% in the general population, providing the opportunity for targeted therapy., (© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Sarcomatoid carcinomas are rare malignancies which represent poorly differentiated epithelial tumors that may be difficult to recognize as such. While some cases may have obvious epithelial areas, the sarcomatoid areas are poorly distinguishable from true sarcoma at the light microscopic level and, by immunohistochemistry, often show only limited staining for traditional epithelial markers such as cytokeratin or epithelial membrane antigen. This can be particularly problematic for diagnosis on small biopsy specimens. We sought to assess the diagnostic utility of several immunohistochemical markers of epithelial differentiation including p63, MOC-31, and thyroid transcription factor-1 on sarcomatoid carcinomas of the head and neck (19 cases; 'spindle cell carcinomas'), lung (19 cases), and urinary bladder (11 cases). These results were compared to immunohistochemistry for the traditional epithelial markers pan-cytokeratin and epithelial membrane antigen. Staining for p63 showed the greatest diagnostic utility, positive in 63, 50, and 36% of head and neck, lung, and urinary bladder sarcomatoid carcinomas, respectively. p63 stains were positive in many cases where immunohistochemistry was negative for both pan-cytokeratin and epithelial membrane antigen. All three alternative markers were quite specific for epithelial differentiation, each staining less than 10% of the control group of 73 various primary and metastatic sarcomas, melanomas, and benign spindle cell lesions. In conclusion, immunostaining beyond traditional pan-cytokeratin and epithelial membrane antigen may have diagnostic utility in this context., (Modern Pathology (2005) 18, 1471-1481. doi:10.1038/modpathol.3800451; published online 10 June 2005.)

The term juvenile ossifying fibroma is used in the literature in naming 2 microscopically distinct fibro-osseous lesions of the craniofacial skeleton. One is characterized by small uniform spherical ossicles resembling psammoma bodies (psammomatoid juvenile ossifying fibroma). The other is distinguished by trabeculae of fibrillary osteoid and woven bone (trabecular juvenile ossifying fibroma). Three new cases of each type are reported, and the literature is extensively reviewed for published cases of these 2 entities.Psammomatoid juvenile ossifying fibroma is reported more commonly than trabecular juvenile ossifying fibroma. It affects patients from a wider age range (3 months to 72 years) and an older mean age range (16-33 years) as compared with 2 to 12 years and 8(1/2) to 12 years, respectively, for trabecular juvenile ossifying fibroma. In both types there is a slight male predominance and the lesions are unencapsulated and tend to infiltrate adjacent bone. A significant difference between the 2 tumors is their site of occurrence. Although psammomatoid juvenile ossifying fibroma occurs predominantly in the sinonasal and orbital bones, trabecular juvenile ossifying fibroma predominantly affects the jaws. Aggressive growth occurs in some-but not all-cases of both types. Such behavior may be related to younger patient age and the concurrent development of aneurysmal bone cysts, which is seen more frequently in psammomatoid juvenile ossifying fibroma. This study demonstrates that not only histologic but also demographic and clinical differences between psammomatoid juvenile ossifying fibroma and trabecular juvenile ossifying fibroma warrant their classification as 2 distinct clinicopathologic entities.

Squamous papillomas of the lung are an uncommon feature of recurrent respiratory papillomatosis, occurring in fewer than 1% of cases. We describe a 23-year-old patient with pulmonary papillomas who developed a fatal squamous cell carcinoma of the lung. PCR-based human papillomavirus (HPV) typing showed the presence of HPV 11 DNA in both benign papillomas and invasive carcinoma. A review of the literature reveals four reports of malignant transformation of juvenile-onset recurrent respiratory papillomatosis in which HPV typing was performed. Similar clinical features are noted in all of the reports; specifically, each case has arisen in a young adult man with a history of papillomatosis since childhood. In each of the cases, HPV 11 was identified in association with the squamous cell carcinoma. Although HPV 11 is uncommonly associated with the development of invasive carcinoma at other sites, these findings suggest that it is correlated with malignant transformation in the setting of juvenile-onset recurrent respiratory papillomatosis.

Blastomycosis is a relatively uncommon fungal disease that most commonly affects the lungs. Other organs may be involved, usually secondary to dissemination of the organism. Laryngeal blastomycosis may occur in isolation from active pulmonary disease. The signs, symptoms, clinical features, and pathological findings of laryngeal blastomycosis mimic those of squamous cell carcinoma. Misdiagnosis may result in inappropriate treatment with potential morbidity. Proper understanding of the clinical presentation and familiarity with the histopathologic features of this disease are therefore imperative. In this paper, we report 2 cases of laryngeal blastomycosis, 1 of which was misdiagnosed as squamous cell carcinoma, clinically and microscopically, with consequent radiotherapy and laryngectomy. In the other case, a clinical diagnosis of glottic squamous cell carcinoma was rendered. However, blastomycosis was identified in a biopsy specimen. We also review cases of isolated laryngeal blastomycosis that have been reported in the English-language literature during the last 80 years. A number of those cases were misdiagnosed clinically and microscopically as squamous cell carcinoma.

Cementum is a calcified dental tissue that covers the roots of teeth and is part of the periodontium. Its function is to help anchor the teeth in their sockets within the alveolar bone of the jaws. Two benign mesenchymal odontogenic tumors are uniquely distinguished by elaboration of cementum or cementum-like material: cemento-ossifying fibroma and benign cementoblastoma (true cementoma). Cemento-ossifying fibroma, which is also termed periodontoma, is characterized by production of cementum and bone in a fibrous stroma. It is a painless, slow-growing tumor usually detected in the third and fourth decade of life and is more common in women. The mandible is its site of predilection. Benign cementoblastoma is intimately associated with the roots of teeth, most commonly mandibular molars. It affects young patients, usually under the age of 20 years. Pain is a common symptom in addition to bone expansion. Benign cementoblastoma bears considerable histologic resemblance to osteoblastoma.

Several regions of chromosome arm 8p are frequently deleted in a variety of human malignancies including those of the prostate, head and neck, lung, and colon, suggesting that there is more than one tumor suppressor gene on this chromosome arm. Both laryngeal and oral squamous cell carcinomas exhibit three distinct and nonoverlapping regions of deletion on 8p. We have further refined the localization of the putative suppressor in 8p23 by using eight microsatellite loci to create a high resolution deletion map of 150 squamous cell carcinomas of the larynx and oral cavity. These new data demonstrate that there are two distinct classes of deletion within this relatively small region of the chromosome and suggest two possible locations for the gene within the D8S264 to D8S1788 interval. We also determined that there is little difference between the allelic loss frequencies of microsatellites mapping near the telomeric ends of other chromosome arms and loci mapping to more centromere proximal regions of the same arm. These data suggest that the high allelic loss frequencies seen at 8p23 loci are not the result of a generalized instability of chromosome ends and are instead consistent with the activation of a specific suppressor gene.

Tubulopapillary hidradenoma is a benign sweat gland tumor that appears as a well-defined, superficially located dermal nodule. It combines ductal as well as apocrine and eccrine glandular differentiation. Microscopically, the tumor is composed of tubular structures that characteristically show intraluminal non-villous papillary projections and a peripheral myoepithelial cell layer. A tumor that is histologically and immunohistochemically identical to tubulopapillary hidradenoma occurred in the mandible of a 73-year-old man and resulted in considerable diagnostic difficulty. The neoplasm developed in a mandibular cyst and recurred 5 years after initial enucleation. This is the first report of a central (intraosseous) sweat gland adenoma of the mandible. The differential diagnosis and possible histogenesis are discussed.

Frequent allelic loss at a genetically polymorphic locus in tumors is an established marker for the presence of a tumor suppressor gene in the neighboring chromosomal region. This technique can be used to identify novel tumor suppressor genes and to monitor their status before the cloning of the gene itself. We have used the polymerase chain reaction and microsatellite loci on all 39 nonacrocentric autosomal chromosomal arms to identify sites of frequent allelic loss in squamous cell carcinomas of the supraglottic larynx. Our allelotype identified seven chromosomal arms (3p, 5q, 8p, 9p, 9q, 13q, and 17p) likely to contain tumor suppressor genes frequently inactivated during squamous tumorigenesis in the larynx. We tested for associations between allelic losses on these chromosomal arms and the clinical and histopathologic features of these tumors. There were no correlations with either T or N classifications. Allelic loss on chromosomal arm 13q is significantly associated with a number of histopathologic features characteristic of poorly differentiated or histologically aggressive tumors. Allelic loss on this arm also exhibits statistical trends toward association with early tumor recurrence and poor survival. The association with survival was substantiated by a multivariate Cox proportional hazards model.

Polymorphous low-grade adenocarcinoma is a recently recognized salivary gland carcinoma arising primarily within the oral cavity. Most of these tumors are readily diagnosed; occasionally, however, they may be confused histologically with cellular mixed tumors. The difficulty stems from the bland cytologic nature of cellular mixed tumors and their organizational diversity, together with the irregular pushing growth at their interface with adjacent soft tissues, on histologic examination. Because of this diagnostic problem, we evaluated the use of glial fibrillary acidic protein localization in the differential diagnosis of polymorphous low-grade adenocarcinoma and cellular mixed tumor. Twelve oral polymorphous low-grade adenocarcinomas (polymorphous low-grade adenocarcinoma) and twelve cellular mixed tumors were selected and stained for glial fibrillary acidic protein (glial fibrillary acidic protein) using a strept-avidin-biotin system and examined independently by each investigator. In addition, five tumors with limited material (three cellular mixed tumors and two polymorphous low-grade adenocarcinoma) from the consultation service of one author were evaluated using the same techniques. Two polymorphous low-grade adenocarcinoma stained positive in very focal areas and only in the epithelial component; staining did not occur in the stroma. Fourteen of fifteen mixed tumors focally to diffusely expressed glial fibrillary acidic protein. Only one tumor did not express glial fibrillary acidic protein. In mixed tumors with only focal staining, the most helpful differential diagnostic feature was positive staining of the mesenchyme-like cells adjacent to epithelial nests. We did not find this latter staining pattern in any of the polymorphous low-grade adenocarcinoma.

A case of primary intrathyroidal paraganglioma is reported, and the light microscopic and immunohistochemical findings are described. Primary paragangliomas of the thyroid region are extremely uncommon and are therefore often confused clinically and histopathologically with more common intrathyroidal mass lesions. The diagnostic difficulties are underscored by the present case, which was misdiagnosed twice, firstly as a medullary thyroid carcinoma and secondly as a follicular thyroid carcinoma. Immunohistochemistry may be very helpful in arriving at the correct diagnosis. The case was further complicated by a second neck mass contralateral to the original thyroid nodule, which was interpreted as consistent with metastasis. The second lesions was proved angiographically and histologically to be a carotid body paraganglioma.

Background: Loss of genetic heterogeneity (allelic loss or loss of heterozygosity) on chromosome arm 8p is frequent in squamous cell carcinomas of the head and neck and has been associated with poor prognosis. We have previously demonstrated that there are three minimal regions of allelic loss on this chromosome arm. The location of each region is marked by a microsatellite locus: D8S264 (8p23), D8S552 (8p23-p22), and D8S133 (8p21). These findings imply the existence of at least three putative tumor suppressor genes on this chromosome arm that may become inactivated during the progression of squamous cell carcinoma., Purpose: We used allelic loss data from these three loci to determine if inactivation of these putative suppressors is associated with poor prognosis for patients with squamous cell carcinoma of the supraglottic larynx. We also used multivariate statistics to compare the prognostic power of allelic loss at these genetic markers with that of demographic, clinical, and histopathologic parameters., Methods: We examined the D8S264, D8S552, and D8S133 microsatellites in tumors from a retrospective population of 59 patients. All patients had histologically confirmed squamous cell carcinoma of the supraglottic larynx and had been treated surgically. DNA was extracted from matched sets of normal and microdissected tumor tissue and used for polymerase chain reaction amplification of the microsatellite markers. Reaction products were separated by denaturing gel electrophoresis and visualized by autoradiography. Patient data were obtained from the original pathology report and from the tumor registry of the Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO. Histopathologic data were obtained by reviewing the portion of the resection specimen used for DNA extraction. Parameters whose association with reduced disease-free interval and reduced disease-specific survival was statistically significant were identified by use of the Kaplan-Meier method and the logrank statistic. Multivariate Cox proportional hazards models were used to identify independent predictors of poor prognosis. All statistical tests were two-sided., Results: In this patient population, allelic loss at the D8S264 locus was associated with both shorter disease-free interval (logrank P = .028) and reduced disease-specific survival (logrank P = .004). Allelic loss at the next most centromeric locus, D8S552, had a statistically significant association with only reduced disease-specific survival (logrank P = .034), whereas allelic loss at the most centromeric region, D8S133, showed no statistically significant association with reductions in either interval. Multivariate Cox models suggested that D8S264 was the only 8p marker of the three microsatellites with a statistically significant and independent association with shortened disease-free interval (relative risk [RR] = 3.38; P = .0107) and reduced disease-specific survival (RR = 3.41; P = .0105)., Conclusions: Allelic loss in the p23 region of chromosome 8 appears to be a statistically significant, independent predictor of poor prognosis in patients with supraglottic squamous cell carcinoma.

Background: Numerous clinical parameters have been suggested as predictors of outcome for patients with head and neck carcinoma treated with radiation therapy, but their applicability remains controversial. Inactivation of the p53 tumor suppressor results in radioresistance in experimental systems and might predict treatment failure in human patients. We have tested this hypothesis by comparing the predictive power of nuclear accumulation of p53 protein with that of clinical and histopathologic markers in patients with glottic carcinoma treated with primary radiotherapy., Methods: Clinical charts were reviewed for 165 patients with glottic squamous cell carcinoma treated with radiation therapy. One hundred and twenty-one patients with T1 or T2 classified tumors were determined to have received adequate treatment and to have adequate follow-up data for further study. Archival pretreatment tumor biopsies from a subpopulation of patients were examined for p53 protein by immunohistochemistry. The influence of clinical and histopathologic variables and p53 nuclear protein on tumor recurrence was studied by bivariate and multivariate analysis., Results: The recurrence rate was lowest for patients with moderately to poorly differentiated tumors (P < 0.05). This was the only significant predictor of outcome in this patient population. The presence of immunohistochemically detectable p53 antigen was not predictive of tumor recurrence in 70 patients for whom there was both p53 and sufficient follow-up data., Conclusions: Histologic differentiation was prognostic for tumor recurrence in this population of patients with glottic carcinoma treated with radiation therapy. In contrast, nuclear accumulation of p53 protein was not predictive of tumor response or recurrence in this population.

Primary epithelial neoplasms of the salivary gland in children are uncommon but are well recognized and occur principally in the major salivary glands. The purpose of this report is to document our experience with an adenocarcinoma of the buccal submucosa (one of several sites of minor salivary gland tissue) that metastasized to multiple bones as the initial sites of distant disease after a local recurrence. The clinical history, imaging studies, and microscopic sections including immunoperoxidase studies were evaluated from the primary tumor, local recurrence, and a metastatic lesion from the femur. The histopathologic features and immunohistochemical phenotype of the adenocarcinoma in the buccal submucosa supported its salivary gland origin. This case of adenocarcinoma of the intraoral buccal tissues independent of the parotid gland in a 12-year-old female is an unusual clinical presentation of a salivary gland neoplasm in childhood, and its ability to metastasize to distant skeletal sites is also remarkable in terms of a primary salivary gland carcinoma regardless of age at diagnosis.

The mutational inactivation of suppressor genes, a process required for cancer progression, generates new genetic subclones within a tumor. The allelic losses that frequently unmask these mutations serve not only as markers of the chromosomal locations of these genes but also as clonal fingerprints of the shifting relationships between these genetically heterogeneous cell populations. The rise of the metastasis-competent subclone to dominance within the primary tumor should be reflected in the similarity of the genetic fingerprints of the primary tumor and its resultant metastases. We have tested this hypothesis by comparing the patterns of allelic loss of individual primary laryngeal squamous cell carcinomas and their resultant cervical lymph node metastases at 16 different genetically polymorphic loci on 15 chromosome arms. Although primary tumors and metastases both frequently lose heterozygosity on the same chromosome arms (3p, 9p, 9q, 13q, and 17p), five of the 12 metastases differed from their primary tumors at one or two of the loci examined. Discordance between the two tumor cell populations from the same patient is suggestive of either subclone heterogeneity within the primary tumor at the time of establishment of the metastasis or further clonal evolution of both tumors after metastasis.

Eosinophilic ulcer of the oral mucosa (traumatic eosinophilic granuloma) mimics oral cancer clinically and is occasionally misdiagnosed as lymphoma on microscopic examination. Trauma is believed to play a role in its development, but its exact pathogenesis is not known. The demographic, clinical, and histologic features of 38 previously unreported cases of eosinophilic ulcer of the oral mucosa are reviewed. Nine representative cases were studied immunohistochemically. Microscopically, the lesions contained a polymorphic inflammatory infiltrate extending deep into the submucosa, underlying muscle, and salivary glands. Numerous eosinophils and large mononuclear cells with pale nuclei and frequent mitoses were seen in all lesions. Lymphocytes, histiocytes, plasma cells, granulocytes, and mast cells were also present. Immunohistochemical stains showed that the lymphocytic infiltrate was composed predominantly of T cells. T-cell-specific antigen-presenting cells were more numerous than the non-antigen-presenting cell type. The large cells with pale nuclei stained positively only for vimentin; the possible myofibroblastic nature of these cells is discussed. Although trauma might have an etiologic role, the pathogenesis of eosinophilic ulcer of the oral mucosa is probably T cell mediated.

The advantages of using a laser to cut a hole in the ossicular chain include increased precision, decreased likelihood of disarticulation, and elimination of noise-induced threshold shift associated with conventional drills. This study was designed to determine optimal energy settings and cooling technique to minimize tissue injury. Laser ablated holes were cut in rabbit femurs with different endostat fibers at power settings of 1.6 to 5.0 watts. Comparable burr holes were cut by a high-speed drill and the animals were sacrificed at different time intervals. Specimens were evaluated microscopically for tissue injury by the amount of cell necrosis of the surrounding osteocytes, bone marrow changes, and denaturation of bone matrix. Changes in healing were assessed by the production and ossification of the granulation tissue. Laser ablated holes created with 1.6 to 2.0 watts at 2 to 7 days demonstrated thermal damage comparable to conventionally drilled holes. At 14 to 28 days these holes demonstrated advanced healing and integrated lamellar bone. In contrast, higher power (> 3.5 watts) at 2 to 7 days demonstrated Significantly more osteocyte loss, marked bone marrow fibrosis, and bone matrix denaturation. At 14 to 28 days these holes showed evidence of delayed healing and osseous plugs not integrated with the surrounding bone.

The subepidermal calcified nodule, also known as cutaneous calculi, is a form of idiopathic calcinosis that affects children and is occasionally present at birth. It occurs usually in the facial skin and has no relationship to connective tissue disease or to any abnormality in calcium or phosphorus metabolism. The oral cavity is very rarely affected by calcinosis cutis of any type, and idiopathic calcinosis has not been previously reported in the oral mucosa. This is a report of two cases of calcified nodules that occurred in the gingiva of a 1-year-old girl and the tongue of a 5-year-old boy. The lesions showed clinical, histologic, and histochemical similarities to the subepidermal calcified nodule. The name oral mucosal calcified nodule is proposed for this form of calcinosis.

Peripheral ameloblastoma (PA) is a rare odontogenic tumor. Previously, only 39 cases of PA had been reported in the English literature. In this article 11 additional cases of PA are presented. Concordance with previous cases was evident with regard to race, clinical appearance, and site of predilection. However, differences were observed with regard to age, sex distribution, and predominant histologic pattern. The average age in the current cases is younger, there is no male bias, and the most common histologic pattern is plexiform rather than follicular or acanthomatous. Recurrence following simple excision is rare, but has been reported. Long-term postoperative follow-up is recommended.

The majority of primary intraosseous carcinomas of the jaws develop in preexisting odontogenic cysts. These tumors are usually well-differentiated keratinizing carcinomas with relatively good prognosis. Only two of 41 previously reported acceptable cases of primary intraosseous carcinomas from ex-odontogenic cysts were associated with cervical lymph node metastasis. Spindle cell carcinoma is an anaplastic dimorphic neoplasm with poor prognosis. It has a special predilection for the upper aerodigestive tract. This is to our knowledge the first report of spindle cell carcinoma developing in an odontogenic cyst. Cervical lymph node metastasis showing typical histologic features of spindle cell carcinoma was detected 8 months postoperatively. The prognostic implications of this finding are discussed in light of previously reported cases of intraosseous carcinoma arising in odontogenic cysts and of spindle cell carcinoma of the oral cavity.

The soft tissue profile adaptation to anterior maxillary intrusion was evaluated by comparing preoperative and 6-month postoperative cephalograms of ten adult patients. Holdaway's soft tissue analysis was the method utilized for profile evaluation. Lip protrusion and interlabial gap were decreased significantly and acceptable lip competency was provided postoperatively. Other factors also played a role in controlling the final soft tissue appearance.

Single crystal sapphire implants are commercially prepared ceramics of aluminum oxide. These endosseous implants have been placed in patients at Washington University since 1978. The course of patients has been followed closely with periodic clinical and radiographic evaluations. Sapphire is well tolerated by hard and soft tissue and provides excellent abutments for fixed partial dentures.

A case of calcifying odontogenic cyst is presented. An analysis of the previously reported cases indicates the variable clinical, radiographic and histopathologic features of the lesion.

A case of thromboangiitis obliterans (Buerger's disease) showing vascular lesions in the oral cavity is presented. To our knowledge, this is the first report of involvement of branches of the external carotid artery with this disease. The clinical, radiographic, plethysmographic, and histologic features of Buerger's disease are presented. Etiologic factors, pathogenesis, and treatment modalities are discussed.

The early manifestations of radiation injury in salivary glands were investigated in the rat. The animals received a single X-ray dose in the range of 200-2000 rad to their neck area. Glandular changes during the first 24 hours were studied by light and electron microscopy and by measuring serum amylase activity. The amount of cell necrosis was quantitated and expressed as necrosis index (NI), Parotid NI and serum amylase activity 24 hours following irradiation were directly proportional to the X-ray dose. The submandibular gland cells were radioresistant and so were the mucous cells of the sublingual gland. The major increase in parotid acinar cell necrosis occurred between 12 and 24 hours after irradiation. However, more than 100 per cent increase in serum amylase level was detected prior to the onset of any significant cell necrosis. As early as two hours following irradiation signs of cell membrane injury were demonstrable in the parotid by electron microscopy and consisted of intracellular oedema, sequestered degenerative cell membranes, and an accumulation of intramitochondrial particles. None of these changes was detectable in the submandibular gland. The implication of membrane injury in the lethal effects of radiation on parotid cells is discussed.

Cephalometric studies of eighteen cases of ankylosis of the temporomandibular joint, treated surgically, were undertaken. Arthroplasty tended to correct the characteristic facial deviation of patients with ankylosis and approximate the facial features of these patients to those of a normal person. These changes were found to occur in a larger percentage of the patients and to a greater magnitude 6 months postoperatively than 1 week following surgery. These findings support the concept that the mandible grows in response to functional stimulation and emphasize the importance of early surgical treatment of ankylosis of the temporomandibular joint.

Pellets of powdered DMBA were implanted in the parotid glands of inbred male Fischer rats, and all experimental animals in which the carcinogen was implanted for 8, 10, 12, and 14 weeks developed well-differentiated squamous-cell carcinomas. When the carcinogen was implanted for longer periods of time, tumors developed in a smaller percentage of the experimental animals. Also, the weight of the parotid glands continued to increase with time following implantation of DMBA, reaching its highest level after 10 weeks, and then gradually decreasing with time. Different possible explanations for the regression of the induced parotid tumors are offered.

A case of a cystic central mucoepidermoid tumor of the mandible is presented. The radiographic and histopathologic manifestations of the lesion bear some resemblance to the odontogenic cyst. Conservative treatment by simple enucleation resulted in 3 recurrences in a 7-year period. En block resection of such lesions is recommended.

The histopathologic features of 116 ameloblastomas were reviewed with special reference to the incidence of the recently described desmoplastic variant. The series included 110 intraosseous lesions and 6 extraosseous ameloblastomas. Ninety-six (88%) of the intraosseous tumors were found in the mandible, and 61% involved the molar-ascending ramus area. Fourteen examples of the desmoplastic variant were identified, representing 13% of the intraosseous tumors. The lesions showed distinctive histologic features characterized by an extensive collagenized stroma containing small islands of tumor epithelium with scant tendency to form cystic structures. This histologic variant has a marked tendency to involve the anterior portions of the jaws with 7 of the 14 examples being located in the maxilla. These desmoplastic lesions also showed unusual radiographic findings, often more suggestive of a benign fibro-osseous lesion than of ameloblastoma.

Cell death and necrosis are important reactions of liver cells to injury that play a role in a wide variety of human liver diseases. A review is given of the important facets known about the biochemical basis of toxic liver cell death. Liver cells can withstand a great many specific biochemical and morphologic changes without loss of viability. Disturbances in RNA and protein synthesis, mitochondrial function, or release of lysosomal enzymes do not play a primary causative role in cell death. Many previous studies have tended to implicate the plasma membrane and its presumed role in maintaining the proper Ca2+ balance as the primary site of the development of irreversible hepatocyte damage. These studies have generally faced a major difficulty in determining if the observed changes are the cause or an effect of cell death. Galactosamine-induced liver cell injury seems to offer a potentially analyzable model for the experimental analysis of liver cell necrosis. Our studies on the role of plasma membrane injury and associated increases in total cellular calcium are reviewed, and a tentative working hypothesis for the pathogenesis of galactosamine-induced liver cell necrosis is presented.