Expression of proteoglycans in two types of ameloblastoma: novel Immunohistochemical findings.

Alterations in cellular and extracellular matrix components play an important role during tumorigenesis; proteoglycans are included among these components. Ameloblastomas are odontogenic tumors distinguished as invasive and infiltrative neoplasms and are divided into different histological types, the most common of which are the unicystic ameloblastoma and the conventional ameloblastoma. The aim of this study was to identify the presence of two proteoglycans, perlecan and biglycan, in different types of ameloblastoma. Using immunohistochemistry, we determined the presence of both proteins in 28 unicystic ameloblastomas and 23 conventional ameloblastomas. We identified the cytoplasmic and nuclear presence of perlecan and the cytoplasmic presence of biglycan in both types of ameloblastoma. The mean values of immunoexpression were higher in the conventional type compared to the unicystic type. Neither the presence of biglycan in ameloblastomas nor the nuclear presence of perlecan in any odontogenic tumor has previously been reported. The differential immunoexpression of perlecan and biglycan in these types of ameloblastomas suggests their participation in the developmental process of these tumors.

Computed tomographic characteristics of odontogenic neoplasms in dogs.

Odontogenic neoplasms are locally invasive oral tumors in dogs. The purpose of this retrospective study was to describe CT characteristics for varying histopathologic types of canine odontogenic neoplasms. A board-certified veterinary radiologist who was unaware of histologic findings reviewed and scored imaging studies. A total of 29 dogs were included in the study. Twenty-three of these dogs had concurrent dental radiographs. The most common CT characteristics for all tumor types were a direct association with or in the region of multiple teeth in 96.4% (27/28), contrast enhancement in 96.3% (26/27), alveolar bone lysis in 93.1% (27/29), and mass-associated tooth displacement in 85.2% (23/27). Mass-associated cyst-like structures were identified in 53.6% (15/28) and were only present in tumors containing odontogenic epithelium. Canine acanthomatous ameloblastomas (n = 15) appeared as extra-osseous (10/15) or intra-osseous (5/15) masses. Intra-osseous canine acanthomatous ameloblastomas were more likely to have mass-associated cyst-like structures and were subjectively more aggressive when compared with extra-osseous canine acanthomatous ameloblastomas. Amyloid-producing odontogenic tumors (n = 3) had subjectively uniform CT imaging characteristics and consisted of round soft tissue and mineral attenuating masses with multiple associated cyst-like structures. Fibromatous epulides of periodontal ligament origin (n = 4) were contrast enhancing extra-osseous masses that were rarely referred for CT examinations and 25% (1/4) were not visible with CT. Other odontogenic tumors were less represented or had more variable CT imaging characteristics. Mass-associated tooth destruction was appreciated more often with dental radiographs and extra-oral tumor extension was identified more often with CT.

Expression of cell cycle and apoptosis-related proteins in ameloblastoma and keratocystic odontogenic tumor.

Tumors arising from epithelium of the odontogenic apparatus or from its derivatives or remnants exhibit considerable histologic variation and are classified into several benign and malignant entities. A high proliferative activity of the odontogenic epithelium in ameloblastoma (AM) and keratocystic odontogenic tumor (KCOT) has been demonstrated in some studies individually. However, very few previous studies have simultaneously evaluated cell proliferation and apoptotic indexes in AM and KCOT, comparing both lesions. The aim of this study was to assess and compare cell proliferation and apoptotic rates between these two tumors. Specimens of 15 solid AM and 15 KCOT were evaluated. The proliferation index (PI) was assessed by immunohistochemical detection of Ki-67 and the apoptotic index (AI) by methyl green-pyronin stain. KCOT presented a higher PI than AM (P < .05). No statistically significant difference was found in the AI between AM and KCOT. PI and AI were higher in the peripheral cells of AM and respectively in the suprabasal and superficial layers of KCOT. In conclusion, KCOT showed a higher cell proliferation than AM and the AI was similar between these tumors. These findings reinforce the classification of KCOT as an odontogenic tumor and should contribute to its aggressive clinical behavior.

Keratoameloblastoma, a very rare variant of ameloblastoma.

The keratoameloblastoma is a rare histologic variant of ameloblastoma. Fewer than 15 cases of keratoameloblastoma have been documented in the literature. We report a new case of keratoameloblastoma in a 21-year-old female patient with a unilocular radiolucent lesion between the roots of the right mandibular incisors. We describe the clinical, radiographic, and histopathologic features of this lesion along with a review on the characteristics of previous cases. We also discuss about classification and management of this lesion.

Metastatic malignant pilomatrixoma, acanthomatous ameloblastoma, and liver tumor in a dog with polyphagia, polyuria, polydipsia, and weight loss.

A 12-year-old, spayed female, Labrador dog was presented for evaluation of polyphagia, polyuria, polydipsia, weight loss of 2 months duration, and multiple cutaneous and subcutaneous masses. The dog was diagnosed with malignant pilomatrixoma with renal, lung, and lumbar metastases. This report describes an atypical presentation of malignant pilomatrixoma.

Pilomatrixoma malin avec métastases, améloblastome acanthomateux et tumeur hépatique chez une chienne avec polyphagie, polyurie, polydipsie et amaigrissement. Une chienne Labrador, âgée de 12 ans, était présentée pour l'évaluation d'une polyphagie, polyurie, polydipsie et d'un amaigrissement durant depuis 2 mois, ainsi que de multiples masses cutanées et sous-cutanées. Elle présentait un pilomatrixoma avec métastases aux reins, aux poumons et à une vertèbre lombaire. Ce rapport de cas décrit une présentation atypique de pilomatrixoma malin.(Traduit par les auteurs).

Vascularized mandibular anterior ameloblastoma - an entity still unresolved.

Vascularized ameloblastoma is a bewildering entity whose existence is questionable from its origin to nosology and its very characterization as a distinct variant of ameloblastoma. This uncertainty is largely because of a fewer number of documented cases and loss of long-term follow-up. The current paper describes two cases of ameloblastoma in the mandibular anterior region, which had features of so-called "hemangiomatous ameloblastoma" as it was originally described. Understanding its pathophysiology based on various views and clinical implications in terms of its biologic behavior are brought to light in this paper.

Differential expression of canonical and non-canonical Wnt ligands in ameloblastoma.

BACKGROUND: Canonical and non-canonical Wnt signaling pathways modulate diverse cellular processes during embryogenesis and post-natally. Their deregulations have been implicated in cancer development and progression. Wnt signaling is essential for odontogenesis. The ameloblastoma is an odontogenic epithelial neoplasm of enamel organ origin. Altered expressions of Wnts-1, -2, -5a, and -10a are detected in this tumor. The activity of other Wnt members remains unclarified. MATERIALS AND METHODS: Canonical (Wnts-1, -2, -3, -8a, -8b, -10a, and -10b), non-canonical (Wnts-4, -5a, -5b, -6, 7a, -7b, and -11), and indeterminate groups (Wnts-2b and -9b) were examined immunohistochemically in 72 cases of ameloblastoma (19 unicystic [UA], 35 solid/multicystic [SMA], eight desmoplastic [DA], and 10 recurrent [RA]). RESULTS: Canonical Wnt proteins (except Wnt-10b) were heterogeneously expressed in ameloblastoma. Their distribution patterns were distinctive with some overlap. Protein localization was mainly membranous and/or cytoplasmic. Overexpression of Wnt-1 in most subsets (UA = 19/19; SMA = 35/35; DA = 5/8; RA = 7/10) (P < 0.05), Wnt-3 in granular cell variant (n = 3/3), and Wnt-8b in DA (n = 8/8) was key observations. Wnts-8a and -10a demonstrated enhanced expression in tumoral buddings and acanthomatous areas. Non-canonical and indeterminate Wnts were absent except for limited Wnt-7b immunoreactivity in UA (n = 1/19) and SMA (n = 1/35). Stromal components expressed variable Wnt positivity. CONCLUSION: Differential expression of Wnt ligands in different ameloblastoma subtypes suggests that the canonical and non-canonical Wnt pathways are selectively activated or repressed depending on the tumor cell differentiation status. Canonical Wnt pathway is most likely the main transduction pathway while Wnt-1 might be the key signaling molecule involved in ameloblastoma tumorigenesis.

Clinicopathological Profile of 80 Cases of Unicystic Ameloblastoma Aided by a Histopathological Comparison Using Modified Philipsen-Reichart Classification and Marx-Stern Classification.

Unicystic ameloblastoma (UA) is an uncommon variant of ameloblastoma and behaves totally different from the solid multicystic variant of ameloblastoma (SMA); furthermore the histological subgroups of UA also show varied behavior regarding proliferation. The present multi-centric study was designed to present the clinicopathological features of unicystic ameloblastoma (UA) and to compare the two popular histological classifications systems. 80 satisfactory cases of UA were retrieved and evaluated for clinicopathological parameters from four teaching dental schools of North India. The cases were classified using modified Reichart and Philipsen system and Marx and Stern system followed by comparison of inter-observer variability. The results were analyzed using SPSS software. The mean age of occurrence was 30.79 ± 16.49 years. Males outnumbered females (M:F::1.67:1). The majority of cases occurred in the third decade irrespective of the gender. Most cases were found in body-angle-ramus region of the mandible. The modified Reichart and Philipsen classification yielded better interobserver agreement (kappa value 0.845). The modified Reichart and Philipsen classification yields better inter-rater agreement and is easy to reproduce amongst oral pathologists. Being simpler it may easily be understood by the operating surgeon for better treatment outcome.

Should the solid variant of odontogenic keratocyst and keratoameloblastoma be classified as the same entity? A clinicopathological analysis of nine cases and a review of the literature.

The solid variant of odontogenic keratocyst (SOKC) is an extremely rare odontogenic lesion, which remains poorly defined even in the 2017 World Health Organization odontogenic tumour classification. It is difficult to distinguish between SOKC and so called keratoameloblastoma (KAB), both rare lesions that have similarities in clinical, histological and biological characteristics. Here, we report clinicopathological data and results of molecular analysis of nine cases with a literature review. First, they were compared to previously reported cases of SOKC and/or KAB, and many overlaps were found in clinical and pathological characteristics. Second, we performed PCR analysis for BRAF V600E mutation. Although ameloblastoma-like epithelia were often encountered, none exhibited BRAF V600E mutation, which has been reported to occur frequently in ameloblastomas but not in odontogenic keratocysts (OKCs). One of two cases of SOKC in the present series from which fresh frozen tissue specimens were available was found to harbour PTCH1 mutations, indicating that these were more likely to be a subtype of OKC. Moreover, we also examined the differences between SOKC and primary intraosseous carcinoma (PIOC) with regard to the expression of cytokeratins (pan-CK, CK5/6, CK7, CK8/18, CK10, CK14 and CK19), p53 and Ki-67. The proportions of p53-and Ki-67-positive cells were significantly higher in PIOC than in SOKC. These findings suggest that immunostaining for p53 and Ki-67 would be useful to differentiate between SOKC and PIOC. We also conducted a review of SOKC and KAB cases reported in the English language literature.

A clinico-pathological comparison between mandibular and maxillary ameloblastomas in Sri Lanka.

BACKGROUND: The aim of this retrospective study was to analyse the relative prevalence and the clinico-pathological characteristics of mandibular and maxillary ameloblastomas in Sri Lanka. METHODS: Clinico-pathological features of a total of 286 cases of ameloblastomas were analysed. RESULTS: Out of the 286 cases, 87.8% (251/286) of ameloblastomas occurred in the mandible, while 10.8% (31/286) occurred in the maxilla indicating a ratio of 8:1. In the mandible, 54% (136/251), 40% (100/251) and 6% (15/251) of tumours and in the maxilla, 23% (7/31), 48% (15/31) and 29% (9/31) of tumours were solid/multicystic ameloblastomas (SMA), unicystic ameloblastomas (UA) and desmoplastic ameloblastomas (DA) respectively. No gender predilection was observed in mandibular or maxillary ameloblastomas. Most of the lesions were observed in 2nd to 5th decade of life (mean age 33.2 years). No differences between mandibular and maxillary ameloblastomas were observed with reference to overall cellularity and mitotic activity. Solid/multicystic and UAs showed a predilection to posterior region, while DAs were frequently found in the anterior region of both jaws. Twenty-one percentage (60/286) of ameloblastomas presented with recurrences, and 94% (34/36) of these recurrences were observed in cases treated conservatively. CONCLUSION: In conclusion, mandibular ameloblastomas were more prevalent than maxillary ameloblastomas, while no differences were observed in age or gender distribution between the mandibular and maxillary ameloblastomas. However, higher proportion of DAs and UAs was observed in the maxilla compared with some of the other studies. SMA should be treated with resection to prevent recurrences.

Immunohistochemical expression of p53 and murine double minute 2 protein in odontogenic keratocyst versus variants of ameloblastoma.

INTRODUCTION: Oncogenes and tumor suppressor genes play a major role in cancer formation, growth, and progression. One of the important findings in this area is that murine double minute 2 (MDM2) oncogene is a negative regulator of wild-type p53. In tumors, expressing wild-type p53, inhibition of MDM2 expression will stabilize p53 and allow it to perform its proapoptotic function, while simultaneously preventing MDM2 from exerting its p53-independent oncogenic effects. The intracellular levels of p53 are tightly regulated by MDM2, as it is a key player in autoregulatory feedback loop under nonstressed conditions. The p53-MDM2 relationship is vital not only for essential functions of the cell, but it also appears to be an integrated part of the complex cellular network which supports the importance of this affair and is a hallmark for its coexistence. SUBJECTS AND METHODS: This study was designed to identify immunohistochemically the expression of p53 and MDM2 gene using monoclonal antibody in 60 cases of formalin-fixed paraffin-embedded tissue blocks, of which 20 cases were of solid multicystic ameloblastoma (SMA), 20 cases were of odontogenic keratocyst (OKC), and 20 cases were of unicystic ameloblastoma (UA). RESULTS: Immunoexpression of p53 and MDM2 was highest in OKC followed by SMA and was minimum in UA. Further results showed positive correlation between both the molecules. CONCLUSION: The studied showed that the relationship has a significant role in cancer etiology and progression and therefore is an important topic for future research which should help in the development of new therapeutic agent against cancer.

Unicystic plexiform ameloblastoma: an insight for pediatric dentists.

Ameloblastomas have been categorized broadly into three biologic variants: cystic (unicystic), solid, and peripheral. The term plexiform unicystic ameloblastoma refers to a pattern of epithelial proliferation that has been described in cystic lesions of the jaws. Although the histology suggests that cystic ameloblastomas follow a biologically low-grade course, recent evidence suggests that they may often behave clinically as biologically aggressive tumors. This is supported by the high incidence of cortical perforation, tooth resorption, lesion size, bony destruction, and a high rate of recurrence after simple enucleation. This article tries to provide an insight for pediatric dentists regarding this biologically distinct entity. A literature review on the topic has been added along with a case report highlighting the state-of-the-art approach and management of such ameloblastomas, in pediatric patients.

Recurrence factors in pediatric ameloblastoma: Clinical features and a new classification system.

BACKGROUND: Ameloblastomas of jaw in the pediatric population are a rare clinical entity and have not been well addressed in the literatures. The present retrospective study analyzed the risk factors associated with recurrence of pediatric ameloblastomas. METHODS: Cases of primary pediatric ameloblastomas seen in a tertiary hospital between 2005 and 2015 were analyzed to identify the clinical factors associated with recurrence. RESULTS: There were a total of 104 cases of primary pediatric ameloblastomas. The overall mean maximum tumor diameter was 4.11 ± 1.339 cm. The receiver operating characteristic curve and the Youden Index showed an optimal cutoff point of 4.95 cm to accurately predict recurrence. Bone cortex/soft tissue invasion were associated with tumor recurrence (P < .001). CONCLUSIONS: The maximum tumor diameter, root resorption, and bone cortex/soft tissue invasion were risk factors for recurrence of pediatric ameloblastomas. The new classification system may serve as a predictor of recurrence in pediatric ameloblastomas.

Immunohistochemical detection of BH3-only proteins in ameloblastic tumors.

OBJECTIVE: To evaluate expression of BH3-only proteins in odontogenic tumors, expression of Bid, Bim, Bad, Noxa, and Puma was analyzed in ameloblastic tumors as well as in tooth germs. METHODS: Nine tooth germs, 37 ameloblastomas, and five malignant ameloblastic tumors were examined immunohistochemically with antibodies against Bid, Bim, Bad, Noxa, and Puma. RESULTS: Immunohistochemical reactivity for Bid, Bim, Bad, Noxa, and Puma was detected in the cytoplasm of cellular components in normal and neoplastic odontogenic tissues. Expression of these BH3-only proteins was evident in odontogenic epithelial cells near the basement membrane in tooth germs and ameloblastic tumors. Acanthomatous ameloblastomas showed no reactivity for Bid, Bim, Bad, Noxa, or Puma in keratinizing cells, whereas granular cells in granular cell ameloblastomas reacted with these BH3-only proteins. Basal and desmoplastic ameloblastomas and ameloblastic carcinomas showed immunoreactivity for the BH3-only proteins in most neoplastic cells. CONCLUSION: Expression of Bid, Bim, Bad, Noxa, and Puma in tooth germs and ameloblastic tumors suggests that the BH3-only proteins have a role in apoptotic cell death of normal and neoplastic odontogenic epithelium. Distinctive expression patterns of these BH3-only proteins in ameloblastoma variants suggest that the BH3-only proteins might be involved in tumor cell differentiation of ameloblastomas.

Expression of transforming growth factor beta1 in ameloblastomas.

The aim of the present study was to compare the expression of transforming growth factor (TGF) beta1 in ameloblastomas (AMs) with different risk of recurrence by immunohistochemistry. A total of 29 cases of AMs were evaluated. The tumors were divided into 2 groups: group A (10 cases) composed of unicystic and peripheral AMs, associated with a low risk of recurrence, and group B (19 cases) composed of solid AMs, associated with a high risk of recurrence. Statistical evaluation showed significant differences between groups A and B lesions, with higher values of positivity for TGF-beta1 in stromal cells in group B tumors (P = 0.0308). No statistically significant differences of immunoreactivity were found in vessels and odontogenic epithelium between the 2 groups. The increased TGF-beta1 expression in tumors with a high risk of recurrence could be explained with the fact that although TGF-beta acts as a potent tumor suppressor in the early stages of tumor progression, later it seems to enhance the invasive phenotype of the tumor.

Clinicopathologic features of ameloblastoma in Kenya: a 10-year audit.

This study describes the clinical and pathologic features of ameloblastomas seen in the 2 main craniofacial treatment centers in Kenya in the 10-year period between January 1995 and December 2005. A total of 184 patient records were analyzed for this study. Eighty-two (44.6%) of the patients were male, and 102 (55.4%) were female with an overall age range of 10 to 80 years (mean, 30.2 years; SD, 14.1 years). There was no significant difference in gender presentation of ameloblastomas, although females presented at a slightly older age. The mean age for males was 29.9 years, and for females, it was 30.5 years. Patients generally tended to seek medical advice late, with the mean duration at first presentation of 46.3 months for males and 44.4 months for females. Most of the ameloblastomas (n = 172; 93.5%) were located in the mandible, 11 (6.0%) were in the maxilla, and 1 (0.5%) was in the soft tissues. Presenting symptoms included swelling (n = 182; 98.9%), pain (n = 64; 36.0%), mobile teeth/history of extraction (n = 104; 57.5%), purulent discharge (n = 39; 21.7%) and paresthesia (n = 10; 5.6%). The posterior mandible was the most commonly affected site, whereas maxillary ameloblastomas tended to occur in anterior sites. One hundred fifty-three ameloblastomas (83.2%) were of the solid/multicystic subtype; 8 (5.3%) were unicystic; 1 (0.5%) was of extraosseous origin; 1 (0.5%) was desmoplastic; 9 (6.0%) were malignant, and 12 of the records had no histopathologic pattern specified.

[Malignant odontogenic tumors]. / Maligne odontogene Tumoren.

Malignant odontogenic tumors are extremely rare. As with benign odontogenic tumors, malignant epithelial odontogenic tumors or odontogenic carcinomas are distinguished from the even rarer mesenchymal ones, the odontogenic sarcomas. The existence of odontogenic carcinosarcomas is not yet acknowledged by the World Health Organization. Odontogenic carcinomas comprise ameloblastic carcinoma (AmCa), primary intraosseous carcinoma (PIOC), clear cell odontogenic carcinoma, odontogenic ghost cell carcinoma (OGCC), and the special case of metastasizing ameloblastoma. Odontogenic sarcomas consist of ameloblastic fibrosarcoma and ameloblastic fibrodentinosarcoma and fibroodontosarcoma. Whereas metastasizing ameloblastoma can be diagnosed only after having metastasized, all other malignant odontogenic tumors present with atypia, increased cellularity and mitoses, and invasion. Odontogenic sarcomas are regarded as low-grade tumors that rarely metastasize. Odontogenic carcinomas, however, especially AmCa, OGCC, and PIOC, are more aggressive, with a 5-year survival rate of about 70% for AmCa and OGCC and a 3-year survival rate of about 37% for PIOC. Radical surgery, eventually in combination with radiotherapy, is the treatment of choice.

[Benign epithelial odontogenic tumors]. / Benigne epitheliale odontogene Tumoren.

The group of benign epithelial odontogenic tumors consists of the four member types of the ameloblastoma family (solid/multicystic, extraosseous/peripheral, desmoplastic, unicystic), squamous odontogenic tumors, calcifying odontogenic tumors, adenomatoid odontogenic tumors, and keratocystic odontogenic tumors, the former "keratocysts" that were recently reclassified by the World Health Organization and are now regarded as tumors. The latter are by far the most frequent tumors in this group, followed by solid/multicystic ameloblastoma. Although the etiology of these lesions is still unknown, a close relationship to normal tooth development is obvious, which is partially imitated by some tumors. Despite some similarities to each other, at least in part, the biological behavior of these lesions is quite different, as are treatment modalities. The diagnosis is essentially based on localization (intraosseous vs. extraosseous/peripheral) and histology, whereupon the correlation of histological findings with radiographic morphology may be of additional diagnostic value. Because of the range of variation, immunohistochemical investigations are not helpful in diagnosing a particular case.

[Benign odontogenic ectomesenchymal tumors]. / Benigne odontogene ektomesenchymale Tumoren.

The group of odontogenic ectomesenchymal tumors consists of odontogenic fibroma (epithelium-rich and epithelium-poor types), odontogenic myxoma, and cementoblastoma. Whereas odontogenic fibromas and cementoblastomas are very rare lesions, odontogenic myxoma is the fourth common odontogenic tumor, preceded only by keratocystic odontogenic tumor, the odontomas, and ameloblastoma. The diagnosis of cementoblastoma rests on its connection to the root of a tooth. The differentiation of odontogenic fibroma and myxoma from other lesions, especially from normal structures such as dental follicles and papillae, may be challenging if the X-ray appearance (localized osteolysis containing a tooth) is not appreciated and subtle histological clues (remainders of inner enamel epithelium at the surface of the lesion, dentin fragments) are not properly recognized. While odontogenic fibromas have almost no tendency for recurrence and are treated by enucleation or local excision, cementoblastomas and especially odontogenic myxomas have a high percentage of recurrence if intralesional procedures are applied. Hence, complete resection with free margins is recommended--at least for larger odontogenic myxomas and, especially, lesions in the maxilla--to prevent further extension to the orbita or base of the skull.