Pathological changes in oral epithelium and the expression of SARS-CoV-2 entry receptors, ACE2 and furin.

BACKGROUND: Expression of angiotensin-converting enzyme (ACE)-2 and co-factors like furin, play key-roles in entry of SARS-CoV-2 into host cells. Furin is also involved in oral carcinogenesis. We investigated their expression in oral pre-malignant/malignant epithelial pathologies to evaluate whether ACE2 and furin expression might increase susceptibility of patients with these lesions for SARS-CoV-2 infection. METHODS: Study included normal oral mucosa (N = 14), epithelial hyperplasia-mild dysplasia (N = 27), moderate-to-severe dysplasia (N = 24), squamous cell carcinoma (SCC, N = 34) and oral lichen planus (N = 51). Evaluation of ACE2/furin membranous/membranous-cytoplasmic immunohistochemical expression was divided by epithelial thirds (basal/middle/upper), on a 5-tier scale (0, 1-weak, 1.5 -weak-to-moderate, 2-moderate, 3-strong). Total score per case was the sum of all epithelial thirds, and the mean staining score per group was calculated. Real time-polymerase chain reaction was performed for ACE2-RNA. Statistical differences were analyzed by One-way ANOVA, significance at p<0.05. RESULTS: All oral mucosa samples were negative for ACE2 immuno-expression and its transcripts. Overall, furin expression was weakly present with total mean expression being higher in moderate-to-severe dysplasia and hyperplasia-mild dysplasia than in normal epithelium (p = 0.01, each) and SCC (p = 0.008, p = 0.009, respectively). CONCLUSIONS: Oral mucosa, normal or with epithelial pathologies lacked ACE2 expression. Furin was weak and mainly expressed in dysplastic lesions. Thus, patients with epithelial pathologies do not seem to be at higher risk for SARS-CoV-2 infection. Overall, results show that oral mucosae do not seem to be a major site of SARS-CoV-2 entry and these were discussed vis-à-vis a comprehensive analysis of the literature.

Unexpected Candidal Hyphae in Oral Mucosa Lesions-A Clinico-Pathological Study.

Background: Oral mucosal biopsies might harbor candidal hyphae (CH) in the absence of any clinical signs or symptoms. Aim: To assess oral mucosa biopsies for the frequency of unexpected CH and characterize their clinico-pathological features. Materials and Methods: All biopsy reports (2004−2019) were searched using CH/candida/candidiasis as key words. Cases with clinical diagnosis of oral candidiasis (OC) were excluded. Demographic data, health status, smoking habits, clinical features and diagnoses were collected. Statistical analysis included the chi-square test; significance was set at p < 0.05. Results: Of all the biopsies, 100 (1.05%) reported microscopical evidence of CH without typical clinical signs/symptoms of OC. Fifteen cases were from healthy, non-smoking patients. CH was common on buccal mucosa (38%) and lateral tongue (23%). The tip of tongue (OR = 54.5, 95% CI 9.02−329.4, p < 0.001) and lateral tongue (OR = 3.83, 95% CI 2.4−6.09, p < 0.001) were more likely to harbor CH-positive lesions. CH-positive lesions were diagnosed as epithelial hyperplasia (55%) and exophytic reactive lesions (30%). No correlation was found between CH and the grade of epithelial dysplasia. Conclusions: Microscopic evidence of CH embedded into oral epithelium without typical signs/symptoms of OC is rare, especially in healthy, non-smokers. Since CH was occasionally found in oral sites prone to local trauma and in association with reactive lesions, in absence of host co-morbidities, the contribution of local mechanical forces to CH embedment cannot be ruled out.

Conceptual changes in ameloblastoma: Suggested re-classification of a "veteran" tumor.

OBJECTIVES: The merging of ameloblastoma (AM) with mural unicystic ameloblastoma (UAM-M) was suggested by the 2017 WHO based on similar treatment needs. In an international multicenter study, we investigated the characteristics of their merged product (merged-AM) and raised the possibility of unifying AM and UAM (total-AM). MATERIALS AND METHODS: AM and UAM (luminal/intraluminal/mural), separate and combined, were analyzed for demographic/clinical/radiological features. ANOVA and chi-square tests were followed by univariate and multivariate analyses, and significance was set at p < .05. RESULTS: The patients' mean age was 39.6 ± 20.3 years in merged-AM (147 AM, 76 UAM-M), 45.1 ± 19.4 years in AM (p = .009). Merged-AM comprised 51.3% multilocular/48.7% unilocular tumors, AM comprised 72.5%/27.5%, respectively (p < .001). Merged-AM was associated with impacted teeth in 30.8%, AM in 18% (p = .023). The probability of merged-AM for multilocularity increased by 2.4% per year of age (95%CI 0.6-4.2, p = .009). Association with impacted teeth decreased by 7.9% per year of age (95%CI 1.9-14.39, p = .009). Merged-AM did not differ from total-AM (p > .05). CONCLUSIONS: Merged-AM partially differed from AM, but differences appeared to diminish in an age/time-wise manner. Merged-AM and total-AM were nearly indistinguishable. Therefore, AM and UAM may be considered a continuous spectrum of one type of tumor, further necessitating revision of the treatment approaches.

Expression of stem cell markers in stroma of odontogenic cysts and tumors.

BACKGROUND: The stroma of odontogenic cysts/tumors may confer them differential biological behavior. We aimed to investigate the immunoexpression of stem cell markers (Nanog, SOX2, Oct4, and CD34) in the stroma of odontogenic cysts and tumors. CD34 was investigated exclusively as a marker for stromal fibroblast/fibrocyte cells (CD34 + SFCs). CD34 + SFCs were also investigated ultrastructurally. METHODS: Ten cases each of primary odontogenic keratocyst (OKC), recurrent OKC, dentigerous cyst, ameloblastoma, unicystic ameloblastoma, odontogenic myxoma, and 7 syndromic OKC were included. Results were represented as the mean score (%) of positive cells/field for each marker for each study group. For CD34 + SFCs, results are presented as the mean number of cells/field for each type of lesion. Kruskal-Wallis and Spearman's correlation statistical tests were used; significance was set at P < .05. RESULTS: All markers except Oct4 were expressed by stromal cells in all lesions. Expression of SOX2 was significantly higher in tumors than in cysts (P < .05). CD34 + SFCs were more frequent in cysts than in tumors. Ultrastructurally, CD34 + SFCs were identified for the first time in odontogenic lesions and showed characteristic bipolar/dendritic morphology. CONCLUSION: Among examined stromal stem cell markers, only SOX2 distinguished tumors from cysts. CD34 + SFCs may also contribute to the biological behavior of odontogenic lesions.

Metaplastic changes in the epithelium of radicular cysts: A series of 711 cases.

BACKGROUND: This study was aimed to evaluate the prevalence of metaplastic changes in the epithelium of radicular cysts and to investigate how they relate to the clinical and radiographic characteristics of the cysts, based on a large series of radicular cysts. MATERIAL AND METHODS: Biopsies of cysts of endodontic origin that were examined at the Department of Oral Pathology between 2004 and 2011 have been re-evaluated for this study. Only cases that were re-confirmed with clinical and histological diagnoses of a radicular or residual radicular cyst were included. The included cases were evaluated for the prevalence of metaplastic changes in the form of mucous secreting cells (MSC) or ciliated cells (CC). The relations between the metaplastic changes and the cyst type (radicular or residual radicular), as well as demographic, clinical and radiographic parameters, were statistically evaluated using Fischer and chi-square tests. Significance was set at p<0.05. RESULTS: A total of 711 cysts were included: 677 were radicular cysts (95%) and 34 (5%) were residual radicular cysts. 23 cases had histopathological diagnoses other than radicular or residual radicular cysts and were excluded from the study. MSC were present in 47 (6.6%) cysts. MSC were significantly more common in residual radicular cysts than in radicular cysts [8 (23.5%) and 39 (5.8%), respectively; p<0.001]. MSC-containing cysts were commonly found in asymptomatic patients (10.5%, p<0.001), and usually presented with well-defined radiographic borders (7.2%, p<0.05). CC were present in 34 (4.8%) cysts, with a markedly high prevalence in the maxillary molar sextant (15%, p<0.001). CONCLUSIONS: In the epithelium of radicular and residual radicular cysts the presence of specific metaplastic changes may be related to cyst type, symptomatology, radiographic findings and tooth location. Key words:Radicular cyst, metaplasia, mucous secreting cells, ciliated cells.

Central Dentinogenic Ghost Cell Tumor: An Update on a Rare Aggressive Odontogenic Tumor.

PURPOSE: Dentinogenic ghost cell tumor (DGCT) is a very rare odontogenic lesion, with most knowledge based on single case reports. Therefore, a comprehensive analysis was performed of the clinical and radiologic features of reported cases of DGCT with an emphasis on treatment modalities. MATERIAL AND METHODS: This is a case series of DGCTs collected from the literature after a systematic search of Medline's PubMed and Google Scholar. Three additional cases were included from the authors' files. Demographic data of the patients, lesion site and size, and radiologic features were analyzed. Treatment approach and events of recurrence were recorded. RESULTS: Forty-five cases (42 from the literature) were included. The mean age of patients was 39.7 ± 19.3 years (range, 12 to 79 yr) and the male-to-female ratio was 1.8:1. The mandible-to-maxilla ratio was 1.14:1, with the posterior region of the jaws being the most commonly involved site. Radiographically, 78% lesions were unilocular, 67% were mixed radiolucent and radiopaque, and 68% had well-defined borders. The mean lesion size was 4.0 cm (range, 1.8 to 13.0 cm). The primary treatment for 21 patients was conservative surgery consisting of enucleation or curettage. Follow-up information for longer than 1 year (mean, 6.2 ± 8.3 yr; range, 1 to 31 yr) was known for 15 patients, of whom 11 (73%) had recurrences. The primary treatment in 19 patients was radical surgery consisting of marginal or segmental resection. Follow-up information for longer than 1 year (mean, 3.3 ± 2.6 yr; range, 1 to 10 yr) was known for 12 patients, of whom 4 (33%) had recurrences. CONCLUSIONS: This study highlighted the potentially aggressive biological behavior of DGCTs that demands extensive surgery and long follow-up. However, owing to the rarity of DGCT, more well-documented cases with long follow-up periods are needed to further define the optimal treatment modalities and prognosis.

Histopathological spectrum of bone lesions associated with dental implant failure: osteomyelitis and beyond.

Early or late post-implant placement complications are usually localized infectious/inflammatory processes and treated accordingly. If the healing process does not take place within a reasonable timeframe, the possibility of a pathologic process beyond localized infection/inflammation should be suspected. We describe a radiological/histopathological spectrum of bony lesions ranging from inflammatory to malignant lesions surrounding failed dental implants. Five cases of mandibular dental implant failure that clinically, radiologically and histopathologically appeared to be inflammatory processes are presented. The failure of the dental implants was immediate in two cases and late in the remaining three. The radiological features were essentially similar for all five, and they included radiolucent or mixed radiolucent-radiopaque lesions with poorly defined borders. Three lesions were limited to the area of the failed implant, while the other two extended to a large part of the mandible. The histopathological findings ranged from acute osteomyelitis and chronic osteomyelitis with features of a fibro-osseous-like lesion and occasional rimming of atypical osteoblasts to osteogenic sarcoma that was admixed with a component of osteomyelitis (diagnosis of the latter was achieved only after a series of biopsies). In-depth investigative procedures are imperative in order to establish an accurate diagnosis whenever the histopathological diagnosis is inconsistent with persisting clinical signs and symptoms in bone lesions associated with failed dental implants.

Ameloblastic fibroma: a stage in the development of a hamartomatous odontoma or a true neoplasm? Critical analysis of 162 previously reported cases plus 10 new cases.

OBJECTIVE: To analyze neoplastic and hamartomatous variants of ameloblastic fibromas (AFs). STUDY DESIGN: Analysis of 172 cases (162 previously reported, 10 new). RESULTS: AF emerged as a lesion primarily of children and adolescents (mean age, 14.9 years), with about 80% diagnosed when odontogenesis is completed (age, < 22 years). Around 28% of all AFs were small and asymptomatic, and 72% exhibited moderate-to-severe bone expansion. CONCLUSIONS: There are 2 variants of AF: neoplastic and hamartomatous. Lesions in patients aged >22 years are considered true neoplasms, while those in younger patients may be either true neoplasms or odontomas in early stages of development. Although the histopathology of hamartomatous and neoplastic variants of AF are indistinguishable, clinical and radiologic features can be of some help to distinguish between them. Asymptomatic small unilocular lesions with no or minimal bone expansion in young individuals are likely to be developing odontomas, and large, expansile lesions with extensive bone destruction are neoplasms.

Unicystic ameloblastoma in an infant: a management dilemma.

The authors describe the conservative management of a rare case of unicystic ameloblastoma (mural subtype) in a 10-month-old girl, the youngest patient reported thus far in the literature. Rather than subject the infant to further surgery, it was decided to monitor her closely and perform an additional operation in the event of recurrence, thus enabling uninterrupted mandibular growth and tooth development. The patient is now 3.5 years old and periodic follow-up is ongoing, with no evidence of recurrence.

Expression of the homeostasis-related markers, maspin, heat shock proteins 70 & 90, glutathione S-transferase, aquaporin 5 and NF-kB in young and old labial and palatal salivary glands.

Intraoral salivary glands undergo remarkable age-related morphologic changes. This study investigated the expression of a panel of molecular markers known for cellular homeostatic activity, dependent on age and location of the salivary glands. Samples taken from healthy subjects were classified according to age ("young" <45 years, n=51, and "old" ≥60 years, n=45) and location (lip, n=47 and palate, n=49). They were immunohistochemically stained for mammary serine protease inhibitor (maspin), heat shock protein (HSP)70, HSP90, glutathione S-transferase (GST), aquaporine5 (AQP5), and nuclear factor kappa-B (NF-κB) for assessment of their expression in acini and ducts, and in cytoplasmic and nuclear compartments. Results were expressed as the mean percentage of positively stained component per age group, gland location and type of cell and cellular compartment. Statistical analysis was performed by two-way ANOVA and crosstabs. The expression of maspin was lower in the old group in both the palatal and labial glands (acini and ducts, cytoplasm and nuclei) compared to the young group (p<0.05). In both age groups, when compared to labial glands, palatal glands exhibited higher expression of HSP70 (p<0.05) and lower expression of AQP5 (p<0.001) and NF-κB (p=0.018). Collectively, the low expression of factors capable of preserving cellular homeostasis (i.e., maspin and AQP5) vis-à-vis a high expression of factors that are also related to cell survival (i.e., HSPs) that was demonstrated in the old palatal glands may point to their high vulnerability to undergo selective phenotypic changes.

Clinical and radiological profile of ameloblastic fibro-odontoma: an update on an uncommon odontogenic tumor based on a critical analysis of 114 cases.

Ameloblastic fibro-odontoma is an uncommon benign tumor of the jaws that belongs to the group of mixed odontogenic tumors. The descriptions of its clinical and radiological features in the literature are not always accurate and sometimes even contradictory. The aim of the present study was to critically evaluate their clinical and radiological features as reported in the English-language literature. A total of 114 well-documented cases of ameloblastic fibro-odontomas (103 from publications and 11 of our own new cases) were analyzed. The patients' age ranged from 8 months to 26 years (mean 9.6). There were 74 (65 %) males, with a male-to-female ratio of 1.85:1 (P = 0.001). The mandible was involved in 74 (65 %) cases, and the mandible-to-maxilla ratio was 1.85:1 (P < 0.001). Nearly 80 % of the lesions were located in the posterior region of the jaws, and most (58 %) were in the posterior mandible. Radiographically, most of the lesions were unilocular and only a few (~10 %) were multilocular. Most lesions were mixed radiolucent-radiopaque, and only a few (~5 %) were radiolucent. Almost all lesions (~92 %) were associated with the crown of an unerupted tooth/teeth. This comprehensive analysis of a large number of patients with an uncommon lesion revealed that ameloblastic fibro-odontomas are significantly more common in males and in the mandible, and that multilocular lesions are uncommon. It also revealed that, based on their clinical and radiological features, some of them are probably true neoplasms while others appear to be developing odontomas (hamartomas).

Warty dyskeratoma/focal acantholytic dyskeratosis--an update on a rare oral lesion.

BACKGROUND: Warty dyskeratoma (WD) is an uncommon lesion of the skin that is considered to be associated with the pilosebaceous apparatus. Histologically similar lesions have been described in the oral region mainly by case reports and under the terms 'WD' or 'focal acantholytic dyskeratosis (FAD)'. Owing to the paucity of reports, many aspects of the oral lesions remain unclear. The purpose of this study is to report a new case in an extremely rare location, the buccal mucosa, and to present a comprehensive updated review and analysis of the literature. METHODS: We reviewed all cases of oral lesions that were diagnosed as WD and FAD and analyzed them according to their clinical and pathologic features. RESULTS: The search yielded only 41 cases. The lesions usually appeared as asymptomatic, solitary, white nodules, papules, or patches on bone-bound mucosa. They occasionally had a rough surface and depressed center. The lesions were most common in the fifth to seventh decades. Use of tobacco appeared to be the most prevalent predisposing factor. The histopathological differential diagnosis of the lesion included acantholytic squamous cell carcinoma, keratoacanthoma, and Darier's disease. CONCLUSION: Warty dyskeratoma/FAD are uncommon oral lesions which are not encountered in the daily practice of oral pathologists. The absence of an association of oral lesions with the pilosebaceous apparatus suggests that they are probably distinctly different from cutaneous ones. As such, we suggest the histologic term isolated FAD for oral lesions, rather than WD.

E-cadherin in oral SCC: an analysis of the confusing literature and new insights related to its immunohistochemical expression.

E-cadherin plays a crucial structural role in cell-cell contacts in epithelial tissues, and a functional role in signaling pathways that regulate cell proliferation, differentiation, and survival. Reduced immunoexpression of E-cadherin adhesions is largely considered as being equivalent to defective functionality and malignancy, and has been used as a prognostic parameter. A critical analysis of studies on E-cadherin immunoexpression in oral carcinomas revealed a wide range of both technical and interpretational aspects. This paper highlights biological characteristics of E-cadherin with respect to its expression in normal and neoplastic epithelial cells and to its interrelations with the tumor microenvironment that can have an impact on immunohistochemical results and their application in the clinical setting.

Classic neurothekeoma (nerve sheath myxoma) and cellular neurothekeoma of the oral mucosa: immunohistochemical profiles.

BACKGROUND: Classic neurothekeoma (nerve sheath myxoma) is regarded as being a true benign cutaneous tumor of nerve sheath origin. Cellular neurothekeoma was separated from the classic type by histogenesis, morphology and immunophenotype. Whether cellular neurothekeoma represents a continuum within the spectrum of classic neurothekeoma or is an independent entity is controversial. Only a small number of classic neurothekeomas of the oral mucosa have been reported and there are even fewer publications on cellular neurothekeoma. We analyzed a series of oral neurothekeomas (classic and cellular) with a panel of neural and other mesenchymal markers to enhance their diagnosis and classification. METHODS: One cellular and three classic neurothekeomas were submitted to a panel of immunohistochemical stains with antibodies against S100, S100A6, NSE, NKI/C3, PGP9.5, α-SMA, HHF-35, CD68 and vimentin. Two cases of neurofibroma (plexiform type), representing a true lesion of neural origin, served as control. RESULTS: The cellular neurothekeoma yielded a positive immunoreaction for S100A6 and NKI/C3 and a negative immunoreaction for S-100. The classic neurothekeomas demonstrated a positive reaction for S-100 and S100A6, but a negative one for NKI/C3. Other markers were non-contributory to distinguishing between these types of lesions. CONCLUSIONS: The small number of reported oral neurothekeomas (classic and cellular) could be due, in part, to the lack of recognition of their particular morphologic and immunohistochemical features. Our results indicate that testing for NKI/C3 immunoreactivity may be of value in distinguishing between cellular and classic neurothekeoma.

Relative frequency of localized reactive hyperplastic lesions of the gingiva: a retrospective study of 1675 cases from Israel.

BACKGROUND: The gingiva reacts to chronic irritation or trauma with localized reactive hyperplastic lesions (LRHL) that can be classified into four groups: focal fibrous hyperplasia (FFH), pyogenic granuloma (PG), peripheral ossifying fibroma (POF), and peripheral giant cell granuloma (PGCG). This study determined the frequency of LRHL in an oral pathology biopsy service and compared these data with reports from other countries. METHODS: The material included the biopsies of all consecutive LRHL of the gingiva stored in the departmental database (1989-2008). Lesions were analyzed according to their location and to the patients' age and gender. The findings were compared with those published in studies from other countries. RESULTS: There were 1675 LRHL that comprised 6.7% of the 25,106 accessed biopsies. FFH was the most common (31.8%), followed by PG (29.1%), POF (20.4%), and PGCG (18.7%). POF tended to affect younger patients than did FFH, PG, and PGCG. FFH, PG, and POF were more common in women, while PGCG showed no gender predilection. PG and POF were more common in the maxilla, PGCG more common in the mandible and FFH was distributed equally between the jaws. The anterior region of the maxilla was the most prevalent site for FFH, PG, and POF. CONCLUSION: The results of this study differ somewhat from those of other countries. There is a need for further investigation to answer the question whether the differences can be attributed to geographic or ethnic factors and/or to small sample sizes of the reported studies.

Pediatric localized reactive gingival lesions: a retrospective study from Israel.

PURPOSE: Chronic irritation of the gingiva causes localized reactive hyperplastic lesions (LRHLs), which are classified into: peripheral ossifying fibroma (POF); peripheral giant cell granuloma (PGCG); pyogenic granuloma (PG); and focal fibrous hyperplasia (FFH). The purpose of this study was to determine the frequency of localized reactive hyperplastic lesions in Israeli children and adolescents. METHODS: All consecutive archival LRHL biopsies of the gingiva between 1989 and 2008 were included. Lesions were analyzed according to location and patients' age and gender. Our findings were compared to pediatric and all-age data in publications from other countries. RESULTS: Of 233 gingival LRHL specimens, POFs were most common (33%), followed by PGs (25%), FFHs (23%) and PGCGs (20%). PGs and FFHs were more common in females, and PGCG were more common in males. POFs showed no gender predilection. PGCGs and FFHs were distributed almost equally between the maxilla and mandible, while POFs and PGs were more common in the maxilla. Comparing data to other countries was problematic because there were so few dedicated to the pediatric population and because of inconsistencies in data presentation. CONCLUSIONS: Pediatric dentists should be aware of gingival LRHLs, because they are not uncommon among children.

Is maspin immunolocalization a tool to differentiate central low-grade mucoepidermoid carcinoma from glandular odontogenic cyst?

Mucoepidermoid carcinoma (MEC) of the salivary glands has a low-grade variant (LGMEC), which may be found within the jawbones. LGMEC shares a number of histopathological similarities with glandular odontogenic cysts (GOC) of the jawbones. Maspin has been identified in several benign and malignant salivary gland neoplasms. We investigated the immunolocalization of maspin in LGMEC and GOC and evaluated its potential to distinguish between these two entities. Cases of LGMEC (n=6), GOC (n=8) and various odontogenic cysts with marked mucous metaplasia (OCMM, n=7), which served as controls, were immunohistochemically labeled for the binding of an antibody directed against maspin. Immunomorphometry was performed separately for maspin-immunopositive epithelial cells and epithelial-mucous cells in either their nuclear or cytoplasmic compartments. Results were presented as the volume fraction (Vv) of each element. The Vv of the maspin-immunopositive epithelial-mucous cytoplasm and nuclei was significantly higher in LGMEC than in GOC and OCMM (p<0.001 and p=0.026, respectively). In the epithelial cells, no significant differences were observed among the lesions (p>0.05). It is suggested that the high levels of maspin in the epithelial-mucous cells (in both cytoplasm and nuclei) in LGMEC may serve as a tool to distinguish it from GOC. This may be useful especially in equivocal cases and in small incisional biopsy samples.

Stromal myofibroblasts accompany modifications in the epithelial phenotype of tongue dysplastic and malignant lesions.

Stromal myofibroblasts (SMF) associated with various types of carcinomas are believed to emerge under the influence of the tumor cells. Recent studies have shown that SMF may originate from fibroblasts within the tumor stroma or even from carcinoma cells by the process of epithelial-mesenchymal transition. The aim of this study was to investigate the concomitant expression of epithelial membrane antigen and alpha-smooth muscle actin in cells at the tumor-connective tissue interface in human tongue carcinoma, as a possible reflection of epithelial-mesenchymal transition. Given its key role in this process, expression of transforming growth factor-beta in the malignant cells was assessed as well. Immunostaining with alpha-smooth muscle actin was performed on cases of hyperplasia (n = 16), mild dysplasia (n = 12), moderate-to-severe dysplasia (n = 11) and carcinoma (n = 22). Transforming growth factor-beta assessment and double immunostaining with epithelial membrane antigen and alpha-smooth muscle actin were performed only in cases of carcinoma. SMF were significantly associated with carcinomas, while their number in pre-malignant lesions (hyperplasia and dysplasia) was significantly lower (P < 0.001). Although SMF were found in all carcinomas, they were heterogeneous in their frequency and patterns of distribution. In addition, 95% of the carcinomas expressed transforming growth factor-beta and 41% exhibited cells positive for both epithelial membrane antigen and alpha-smooth muscle actin. SMF were almost exclusively associated with established carcinomas and not with pre-malignant lesions. Cells that co-expressed epithelial membrane antigen and alpha-smooth muscle actin can be a manifestation of epithelial-mesenchymal transition and, as such, may serve as a source for SMF in these tumors. These findings appear to be linked to the frequent expression of transforming growth factor-beta by the malignant cells.

Congenital granular cell epulis presents an immunohistochemical profile that distinguishes it from the granular cell tumor of the adult.

Congenital granular cell epulis (CGCE), a rare benign lesion arising from the mucosa of the alveolar ridges of the jaws in newborns, has a clinical course characterized by lack of further growth after birth. Histomorphologically, it resembles a granular cell tumor (GCT) of the adult. The histogenesis of this lesion is unclear. We submitted a series of five CGCEs to a large panel of antibodies in order to trace the origin of the constituent granular cells. The resultant immunohistochemical profile showed positivity of these cells to vimentin, NKI/C3, and PGP9.5. This does not confirm any particular cell type for the histogenetic origin of CGCE but may rather reflect a local metabolic or reactive change, providing supporting evidence that the lesion is of a non-neoplastic nature. In addition, the granular cells were non-reactive for S-100, NGFR/p75, and inhibin-alpha, which further contributes to the distinction between a CGCE and the adult GCT.

Granular cell tumor of the oral cavity: updated immunohistochemical profile.

BACKGROUND: Granular cell tumor (GCT) is a benign lesion that occurs at different body sites with preponderance to the oral cavity. It is generally believed to be of schwann cell/neural cell origin. We used a large panel of both traditional and recently developed antibodies in an attempt to trace the origin of GCTs on the basis of their immunoprofile. METHODS: The patients' demographic data and the cytological and architectural features of the lesions were analyzed in a large series of oral GCTs (n = 68). Forty-two lesions were also submitted to a panel of immunohistochemical stains with antibodies against S-100, CD-68 (KP-1 and PG-M1), vimentin, calretinin, NKI/C3, PGP9.5, p75/NGFR and inhibin-alpha. RESULTS: The tongue was the most common location of oral GCTs (81%). The granular cells demonstrated a wide array of cytological features in terms of cell shape and position of the nucleus. In addition, the lesions showed different architectural patterns, including 'infiltration' with satellite nodules. Interestingly, no recurrences were reported, even in lesions that were not completely excised. Granular cells were usually found to be strongly and diffusely positive for p75, vimentin, calretinin and NKI/C3, inhibin-alpha, PGP9.5, and S-100. CONCLUSIONS: Immunoreactivity of the granular cells to a broad panel of antibodies that characterize different tissues does not confirm any particular cell type for the histogenetic origin of GCTs. Furthermore, GCTs could be regarded as lesions that reflect a local metabolic or reactive change rather than a true neoplasm.