An Unusual Gingival (Peripheral) Tumor with Features of Keratoameloblastoma with Cytologic Atypia or Possible Malignant Transformation Exhibiting ARID1A Mutation.

BACKGROUND: Keratoameloblastoma is a poorly characterized and rarely reported odontogenic neoplasm that can exhibit overlapping histopathologic features with conventional ameloblastoma and keratocystic odontogenic tumor (KCOT), with an ambiguous relationship to the so-called solid KCOT. METHODS: A peripheral maxillary tumor causing bone saucerization in a 54-year-old male is described and investigated with immunohistochemistry and Next-Generation Sequencing (NGS). RESULTS: Microscopically, the tumor comprised of a predominantly plexiform proliferation of odontogenic epithelium with central keratinization and evidence of surface origin. Peripheral cells exhibited nuclear palisading with variable reverse polarization, while stellate reticulum-like areas were observed internally. A few follicles and a few foci in the lining of cystic spaces revealed increased cellularity with cells exhibiting small but conspicuous nucleoli, focal nuclear hyperchromatism, and a few mitoses mostly seen in the peripheral outer cell layer. Nuclear staining for ki-67 was increased in those areas when compared with the other cystic, follicular, and plexiform areas. These features were interpreted as cytologic atypia suggesting also the possibility of a malignant process. Immunohistochemically, the tumor was positive for CK19 and negative for BRAF VE1, calretinin, and CD56. Ber-Ep4 was only focally positive. By sequencing, an ARID1A c.6527_6538delAG frameshift mutation (VAF: 5.8%), classified as likely oncogenic, and an FBXW7 c.1627 A > G missense mutation (VAF: 8.0%), classified as a variant of uncertain significance, were detected. Two mutations, probably germline (VAF ~ 50%), were recorded for RNF43 and FBXW7. No pathogenic variants were identified in PTCH1, BRAF, NRAS, HRAS, KRAS, FGFR2, or SMO genes. CONCLUSION: The significance of an ARID1A variant in keratoameloblastoma is uncertain since this variant has not been reported in ameloblastoma or KCOT, to date. Alternatively, it may characterize malignant transformation in the present case since ARID1A mutations have been encountered in various cancers. Sequencing of additional cases is necessary to determine whether this may represent a recurrent genomic event.

Macro and microscopic study of a rare case of Papilliferous Keratoameloblastoma using a stereo zoom microscope.

Papilliferous keratoameloblastoma is an extremely rare variant of ameloblastoma, a benign odontogenic tumor, with only seven cases reported in the English language literature. This variant presents with the metaplastic transformation of stellate reticulum-like cells to the extent of forming papillary structures exhibiting superficial keratinization of varying thickness. This paper describes the pathognomonic macroscopic features of this tumor observed during gross examination under the stereo zoom microscope that differentiate it from the other odontogenic tumors which have not been explored in the previously documented cases. Also, in this paper, a detailed comparison of the macroscopic features observed under the stereo zoom microscope during gross examination with the microscopic features of the histologic section has been described proving to be useful in the histological differential diagnosis of the keratinizing variants of ameloblastoma.

Keratoameloblastoma: A Report of Seven New Cases and Review of Literature.

BACKGROUND: Keratoameloblastoma (KA) is an uncommon and controversial variant of ameloblastoma exhibiting central keratinisation. Due to their rarity, there is limited information in the literature on their clinical, radiologic and histologic features. This study adds seven additional cases of KA to the literature, and reviews the current published literature on this rare entity. METHODS: KAs were retrospectively reviewed over a 20-year period from three Oral and Maxillofacial Pathology Laboratories. Included cases were examined and the diagnosis confirmed under conventional microscopy. Immunohistochemistry with the use of a monoclonal antibody against calretinin was performed on included cases. The clinical, radiologic and histologic features of the seven new cases of KA were analysed and compared to existing cases in the literature. RESULTS: KAs presented at a mean age of 40 years with a nearly equal gender distribution and a mandibular predilection (65%). The majority (92%) of cases presented with localised swelling with associated pain in 32% of cases. Mixed density or internal calcifications were noted in 40% of cases. All tumours presented with bony expansion, with cortical destruction noted in 62% of cases. Histologically, all tumours consisted of solid and cystic follicles with surface parakeratinisation and lamellated accumulations of central keratin. In areas the cystic follicles had an epithelial lining suggestive of an OKC. There were focal luminal areas of loosely arranged polygonal cells reminiscent of the stellate reticulum. The basal cells consisted of columnar cells with evidence of palisading and prominent subnuclear vacuolisation. Of the cases treated via tumour resection, 27% presented with tumour recurrence. CONCLUSION: This case series reports seven additional cases of KA, taking the total to 26 reported cases. The identification of subtle histologic features, including focal stellate reticulum-like central areas, subnuclear vacuolisation and lamellated-type central keratinisation, are key in diagnosing KA. The radiologic features will often indicate signs of aggressiveness such as cortical destruction, differentiating KA from OKC. All cases were completely negative for calretinin IHC, limiting its use in distinguishing KA from OKC. Further large series are needed to expand the current understanding of this rare variant of ameloblastoma.

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.

Papilliferous keratoameloblastoma - A rare entity: A case report with a review of literature.

Ameloblastoma is the most common odontogenic tumor which presents with a variety of histopathological patterns. Among all, papilliferous keratoameloblastoma (PKA) is a very rare type which is characterized by multiple epithelial cysts of varying size, which are lined by non-keratinized papilliferous epithelium which is filled with necrotic desquamated epithelial cells. In this study, we reported PKA with characteristic ameloblastic features in a 65-year-old male patient who presented with a swelling in the right mandibular body region. This is the seventh case of PKA to be reported in the English literature till date. Present case showed multicystic areas in incision biopsy which lead to misdiagnosis as calcifying odontogenic cyst with adenomatoid odontogenic tumor, but in excision biopsy which turned out to be papilliferous keratoameloblastoma, further in this paper we had discussed all the areas which lead to misdiagnosis of calcifying odontogenic cyst with adenomatoid odontogenic tumor. In outlook, more cases will put an insight to the behavioral aspects of this rare histological type of ameloblastoma.

Peripheral keratoameloblastoma: A novel case report.

Keratoameloblastoma is an exceptionally rare subtype of ameloblastoma that has been reported <20 times previously in the literature. All present as intraosseous lesions. We report an unusual case of keratoameloblastoma localized in the palate without involving palatal bone, thus presenting as a peripheral lesion. To the best knowledge of the authors, no case of peripheral keratoameloblastoma has been reported in the English literature till now, probably rendering this case to be the first one. Therefore, the purpose of this article is to present a rare and the first case of peripheral keratoameloblastoma with histopathological features of this tumor.

Papilliferous Keratoameloblastoma: A Rare Case Report.

Ameloblastoma is true odontogenic tumor of epithelial origin, which is described as locally aggressive with varying chances of recurrence. It is believed to derive from enamel organ, remnants of dental lamina, lining of odontogenic cysts, or basal cells of oral epithelium. Radiologically, it may present as unilocular or multilocular radiolucency commonly. Although conventional ameloblastoma presents typical histological features as described by Vickers and Gorlin, few unusual variants have been reported with different histological patterns. However, the clinical and biological behavior of these lesser known variants has not been established yet due to the scarcity of cases reported. Here, we report an extremely rare case of papilliferous ameloblastoma in a young male patient with 2-year follow-up and presenting with unusual histological presentation than conventional ameloblastoma.

Ceratoameloblastoma: uma lesão muito rara com recidiva incomum / Keratoameloblastoma: a very rare lesion with an unusual recurrence

A denominação ceratoameloblastoma tem sido utilizada para descrever um grupo histológico heterogêneo de variantes do ameloblastoma, que tem em comum a formação de ceratina pelo epitélio ameloblastomatoso. Até o momento, vinte casos foram previamente reportados na literautra, dos quais cinco exibem um componente papilifero. Nós relatamos um novo caso de um tumor recidivado que se enquadra no espectro do keratoameloblastoma, o qual apresentava uma lesão expansiva, sólida, com calcificações internas, na fossa infratemporal direita, seis anos após uma hemimandibulectomia ipsilateral, de uma mulher branca de 46 anos. Ilhas de células colunares que lembram ameloblastoma ao redor de uma área central com células estreladas, algumas das quais completamente preenchidas por ceratina e outras exibindo células basais colunares a cuboidais com núcleo hipercromático, foram observadas na avaliação histológica do espécime. Nós revisamos o padrão clínico, histopatológico e radiográfico dos casos previamente publicados de ceratoameloblastoma, além do tratamento e acompanhamento realizado. Embora um pequeno número de casos tenha sido reportado, o comportamento biológico agressivo e altas taxas de recorrência sugerem que um manejo mais agressivo deve ser realizado. Ressecção com margens de segurança e análise histopatológica dessas margens são altamente recomendadas. (AU)

The denomination keratoameloblastoma has been used to describe a histologically heterogeneous group of ameloblastoma variants which have in common the formation of keratin by the ameloblastomatous epithelium. Up to now twenty cases of keratoameloblastoma have been previously reported in the literature, of which five exhibited a papilliferous component. Here we report a new case of a relapsed tumor that fits the spectrum of keratoameloblastoma which presented as an expansile, solid lesion with internal calcification in the right infratemporal fossa six years after ipsilateral hemimandibulectomy of a 46- year-old white female. Islands of columnar cells resembling ameloblasts surrounding a central area with starry cells, some of them completely filled with keratin and others also showing columnar to cuboidal basal cells with hypercromatic nuclei were observed in the histological evaluation of the specimen. The clinical, histopathologic and radiographic features of keratoameloblastoma are reviewed so as treatment and follow up. Although only few cases have been reported, the biological aggressive behavior and the high recurrence suggest that a more aggressive approach should be performed. A resection with sufficient safety margins and histopathological analysis of surgical margins are highly recommended. (AU)

Keratoameloblastoma: Report of a rare variant with review of literature.

Ameloblastoma has intrigued clinicians as well as pathologists due to its diverse clinical behavior and histomorphologic presentations. Keratoameloblastoma is a rare histologic sub type, characterized by extensive keratin formation within ameloblastic epithelium, with only a handful number of cases described in the literature. Here, we report a case of this uncommon sub type of ameloblastoma in a young female patient presenting as an extensive lesion in mandibular ramus area. The radiological and fine needle aspiration findings suggested of a keratinizing cystic lesion and incisional biopsy showed features of ameloblastoma. Patient underwent segmental mandibulectomy and histological examination of excisional specimen revealed features of ameloblastoma with abundant keratinization leading to a diagnosis of keratoameloblastoma. The diagnostic pitfalls related with the lesion have been discussed along with a short review of the literature.

Keratoameloblastoma of the maxilla: a case report

A keratoameloblastoma is a histologically variant of the ameloblastoma group, which varies in size and contains keratin material in the fibrous connective tissue among cystic lesions. A keratoameloblastoma is a rare disease with only 13 cases reported in the literature since Pindborg's first report in 1970. A 41-year-old man visited, complaining of pus discharged from the right maxilla. He had been diagnosed with an odontogenic keratocyst and was treated with cyst enucleation in the past. The clinical and radiology examination found evidence of recurrence and finally diagnosed him with keratoameloblastoma after enucleation and biopsy. This report discusses the clinical, radiological and histological characteristics of keratoameloblastoma and its treatment. In addition, we report another case of keratoameloblastoma that had transformed from an odontogenic keratocyst.

Keratoameloblastoma of the mandible.

Keratoameloblastoma is a very rare ameloblastoma variant defined by extensive squamous metaplasia and keratinization. There are 13 previously reported cases in the literature, with a male predilection of 3:1. A 38-year-old male presented with a painless mandibular swelling which had been progressively increasing in size for 18 months. The incisional biopsy was misdiagnosed as basaloid squamous carcinoma. Owing to financial constraints, the patient had mandibular resection a decade after first noticing the growth, during which the clinical course was essentially benign, thus casting doubt on the initial diagnosis. The final histological diagnosis for both the incisional and resection biopsy specimens was keratoameloblastoma.