Use of calretinin in the differential diagnosis of unicystic ameloblastomas

AIMS: Calretinin, a 29-kDa calcium-binding protein is expressed widely in normal human tissues and tumours including both unicystic and solid and multicystic ameloblastomas. The histological distinction between unicystic ameloblastomas and certain non-neoplastic odontogenic cysts can be problematic. The objective of this study was to determine whether calretinin was expressed in the lining epithelium of odontogenic keratocysts, residual and dentigerous cysts and to determine whether this calcium-binding protein could be used to distinguish these cysts from the unicystic ameloblastoma. METHODS AND RESULTS: The lining epithelium in 22 cases of odontogenic keratocyst, 26 cases of residual cyst and 20 cases of dentigerous cyst were examined for the expression of calretinin. No positive epithelial staining was observed in any of these cystic lesions. In comparison, however, 81.5% of cases of unicystic ameloblastoma showed a coarse dark brown staining of the more superficial epithelial cell layers. Scattered positive stromal and epithelial cells were present; these were interpreted as mast cells. CONCLUSIONS: Calretinin appears to be a specific immunohistochemical marker for neoplastic ameloblastic epithelium and we suggest that it may be an important diagnostic aid in the differential diagnosis of cystic odontogenic lesions and ameloblastic tumours.     

Comprehensive keratin profiling reveals different histopathogenesis of keratocystic odontogenic tumor and orthokeratinized odontogenic cyst

Keratocystic odontogenic tumor is a cystic lesion that behaves more aggressively than other jaw cysts. One of its characteristic histologic features is a parakeratinized uniform layer of lining epithelium. A jaw cyst lined with orthokeratinized epithelium is called an orthokeratinized odontogenic cyst. These keratinized jaw cysts are thought to be separate entities, although their histopathogenesis has not been fully assessed. To better understand these lesions, we performed comprehensive immunohistochemical profiling of the keratin expression of each. Orthokeratinized odontogenic cysts expressed keratin 1, keratin 2, keratin 10, and loricrin, suggesting differentiation toward normal epidermis. Keratocystic odontogenic tumors expressed keratin 4, keratin 13, keratin 17, and keratin 19, which is a unique expression pattern reminiscent of a mucosal squamous epithelium and an epithelial appendage. In neonatal rat tooth germ, cells strongly positive for keratin 17 and keratin 19 were observed, specifically in the dental lamina, implying the origin of keratocystic odontogenic tumor. GLI2, a downstream effector of hedgehog signaling, was significantly expressed in keratocystic odontogenic tumor and basal cell carcinoma, accompanied with robust expression of keratin 17, mammalian target of rapamycin, and BCL2. The expression of these GLI2- or keratin 17-related factors was not significantly observed in orthokeratinized odontogenic cysts. These findings provide evidence to support the viewpoint that keratocystic odontogenic tumor and orthokeratinized odontogenic cyst are separate entities, and furthermore suggest their characteristic histology, pathogenesis, and biological behaviors.     

Autofluorescent granular cells in odontogenic cysts

Three odontogenic cysts, two of dentigerous and one of dental type, are reported in which large numbers of cells containing autofluorescent granules were present, in both the capsule and cyst lining. Histochemical and electron microscopical studies suggest that the granules are composed of lipofuscin. Examination of 30 examples each of dental cysts, dentigerous cysts and odontogenic keratocysts indicated that the prevalence of occasional cells of similar appearance was about 40%, 50% and 17% respectively. The pathogenesis of these cells is discussed.     

Odontogenic classification of craniopharyngiomas: a clinicopathological study of 54 cases

Based on the striking histological similarity of craniopharyngiomas and some odontogenic tumours, we reclassified a series of 54 craniopharyngiomas (52 adamantinomatous and two papillary variants) according to the WHO classification of odontogenic tumours. Twenty-seven tumours (50%) corresponded histologically to calcifying odontogenic cyst, 13 tumours (24%) to ameloblastoma, and eight (15%) tumours showed features of both calcifying odontogenic cyst and ameloblastoma either within the same specimen or in specimens derived from different resections. Rare tumours included three cases resembling calcifying epithelial odontogenic tumour and one case resembling adenomatoid odontogenic tumour. No odontogenic counterpart could be established for papillary craniopharyngiomas. The two major subtypes, i.e. craniopharyngioma corresponding to calcifying odontogenic cyst and craniopharyngioma corresponding to ameloblastoma, did not differ in their basic clinical features. Our data confirm and extend the close histological resemblance between adamantinomatous craniopharyngioma and odontogenic tumours and cysts. Furthermore, although calcifying odontogenic cyst and ameloblastoma arising in the jaw differ in clinical presentation and outcome, our study did not reveal clinical differences for the corresponding subtypes of craniopharyngioma.     

Zur Pathogenese der calcifizierenden odontogenen Cyste (Gorlin-Cyste)

Summary Four new cases of calcifying odontogenic cyst (COC) were studied by light- and electronmicroscope. The ages of the patients were between 20 and 68 years. Three cysts were located in the maxilla, the other was in the mandible. The history of two patients was followed up for five and ten years respectively. The longer the history the bigger were the cysts. All cysts showed histologically identical alterations of the epithelium with 1) a pronounced cylindrical basal cell layer, 2) cells resembling stellate reticulum, and 3) ghost cells.So called dysplastic dentin was laid down in the connective tissue only in the two cases with a long history. Ultrastructurally the odontogenic epithelium of all cysts showed keratinization similar to the epidermis. Two types of keratinization are known to occur in the epidermis, soft keratinization with keratohyalin granules in ortho- and parakeratosis, and hard keratinization without keratohyalin granules in nails (horn). Both types of keratinization occur in odontogenic epithelium. The COC is an example of hard keratinization. Ghost cells form prekeratin which in turn becomes horn and is found in areas of confluent ghost cells and in the so called dysplastic dentin.We conclude that the alteration of odontogenic epithelium in COC and in special odontogenic tumors is a secondary phenomenon resembling ortho- and parakeratosis.

Mit Unterstützung durch die Deutsche Forschungsgemeinschaft     

Odontogenic cysts: an update

The classification of odontogenic cysts has been widely debated and there has been much debate and controversy about the true nature of some of the lesions. Although cysts are common in the jaws, most are radicular cysts of inflammatory origin or simple dentigerous cysts. Others are less frequently encountered and may present diagnostic difficulties because of their varied features. The previous WHO classification, in 2005, redesignated a number of these lesions as true neoplasms, but this was controversial and was not based on sound evidence. For the latest WHO classification (2017), an international consensus group reappraised these lesions and agreed a terminology and new classification. This brief review presents this new classification, and explains the reasoning behind the agreed terminology.     

Odontogenic ghost cell tumor: A case report with cytologic findings

Odontogenic ghost cell tumor is a rare, neoplastic form of calcifying odontogenic cyst (Gorlin cyst) whose cytologic features have not been previously reported. We present a case of odontogenic ghost cell tumor diagnosed by fine-needle aspiration biopsy (FNAB). The aspirate was characterized by (1) tissue fragments with basaloid epithelial cells, (2) “ghost” cells, (3) scattered multinucleated giant cells, (4) rare, eosinophilic, densely hyalinized “dentinoid” material in close association with the basaloid cells, and (5) calcific debris. The aspirate was diagnosed as “consistent with odontogenic ghost cell tumor.” The cytologic features of odontogenic ghost cell tumor, as described, closely parallel the major histologic findings in this rare tumor. The differential diagnoses include other odontogenic tumors, squamous cell carcinoma, basaloid cell tumors of the salivary gland, and pilomatrixoma. Diagn. Cytopathol. 1998;18:199–203. © 1998 Wiley-Liss, Inc.     

Central mucoepidermoid carcinoma arising from glandular odontogenic cyst confirmed by analysis of MAML2 rearrangement: A case report

Central mucoepidermoid carcinoma (MEC) poses a diagnostic challenge because of its rarity and histological overlap with glandular odontogenic cyst (GOC). In MEC of both salivary glands and jaws, MAML2 arrangement has been well known as the specific gene alteration. We report a case of central MEC arising from GOC diagnosed by MAML2 fusion gene. A 57‐year‐old male presented a multilocular cystic lesion in left molar region of the mandible. Histopathologically, multiple cysts lined by thin cuboidal or non‐keratinized squamous epithelium with small duct‐like structures, mucous cells and ciliated cells were present. It was diagnosed as GOC. The recurrent lesion after nine years showed the proliferation of many cystic and solid nests composed of epidermoid, mucous and intermediated cells. Nested PCR revealed CRTC3‐MAML2 fusion gene in the recurrent lesion, but not in the primary one. Similarly, MAML‐2 rearrangement by FISH analysis was positive in the recurrent lesion, while negative for the primary one, thus confirming the diagnosis of central MEC arising from GOC. Analysis of MAML2 rearrangement can be used as a supportive evidence to distinguish central MEC from GOC.     

Study of the biologic behavior of odontogenic keratocyst and orthokeratinaized odontogenic cyst using TGF-alpha and P53 markers

Odontogenic keratocyst (OKC) is an aggressive cyst, and its recurrence rate is higher than that of other odontogenic cysts. Orthokeratinized odontogenic cyst (OOC) is less aggressive than OKC, but bears the probability of carcinomatous changes. In this study, we evaluated the expression and intensity of P53 and TGF-alpha in order to compare the biologic behavior or probable carcinomatous changes of these two cysts.     

Latent form of multiple dermoid cysts in the jaw bone

Dermoid cysts of the jaw are exceedingly rare, and only six such cases have been documented. The present paper reports a case with multiple microcysts showing histological characteristics of dermoid cyst in the surgically resected mandibular bone. These cysts were located near the inferior border of the mandibular bone, and histologically composed of an inner thin layer of squamous epithelium with marked hyperorthokeratinization and an outer layer of fibrous tissue containing numerous mature sebaceous glands. In addition, a hair follicle-like epithelial sphere was seen in part. The present microcysts suggest that it arises de novo, and one possible cause of jaw cysts could be sequestration of the stomadeal ectoderm that may have been trapped deep in the surface and embedded in the developing mandibular bone during embryogenesis. It may not be possible that such cysts developed from the odontogenic epithelial remnant undergoing dermoid metaplasia.     

Pathogenesis of Rushton bodies: A novel hypothesis

Rushton bodies (RBs) are one of the characteristic features seen in the epithelial lining of odontogenic cysts mainly radicular, dentigerous and odontogenic keratocyst. It has two different histo-morphological appearances; granular and homogeneous. Although widely investigated, the exact pathogenesis and histogenesis of RBs is still an enigma. Many hypotheses were made in the literature but none has explained conceivably the two histo-morphological appearances of RBs and their association with inflammation. In the present paper the various pathogenesis for the formation of RBs proposed till date are discussed along with proposal for a novel hypothesis. The given hypothesis is mainly related to inflammation and its effect on pore size of basement membrane of odontogenic cystic epithelium. It explains RBs association with inflammation as well as existence of two histo-morphological appearances. The proposed hypothesis also justifies the RB’s presence inside the lining epithelium of odontogenic cyst despite its hematogenous origin. Future studies are advocated for isolating RBs using laser capture microdissection and subsequent biochemical, histochemical and electron microscopic analysis to substantiate the proposed hypothesis.     

Clinical management of primary odontogenic sarcoma in the mandible: a case report after WHO nomination

Ameloblastic fibro-odontosarcoma(AFOS)now designated as odontogenic sarcoma is an extremely rare odontogenic tumor,which histologically presents as a biphasic neoplasm with a malignant mesenchymal component plus ameloblastic epithelium.Here we report a 27-year-old Chinese female with the complaint of a painful swelling for half a month in the right mandible.A segmental mandibulectomy,with an immediate mandibular reconstruction using a free vascularized osteocutaneous fibular flap was performed using surgical guide models.Histological analysis revealed a primary odontogenic sarcoma.The postoperative period was uneventful,and no clinical indication of recurrence or metastasis was observed during the 3-year follow-up.No adjuvant therapy was proposed.This is the first odontogenic sarcoma case reported in China after the new World Health Organization classification of odontogenic lesions.     

Calcifying Odontogenic Cysts Associated with Odontomas: Confocal Laser Scanning Microscopy Analysis of 13 Cases

The so-called calcifying odontogenic cyst (COC) represents a heterogeneous group of lesions that exhibit a variety of clinico-pathologic features. It is an uncommon lesion and represents less than 2% of all odontogenic cysts and tumors. Recently, these lesions have been reclassified as calcifying cystic odontogenic tumors (CCOT), according to the new World Health Organization (WHO) classification. CCOT are frequently found in association with, or containing areas histologically identical to, various types of odontogenic tumors, such as complex/compound odontomas. This work analyzed clinical and histological data deriving from 13 patients affected by CCOT associated with odontomas. Moreover, a confocal laser scanning microscope (CLSM) analysis was undertaken to further a better understanding of the nature of this peculiar lesion.     

Immunocytochemical expression of growth factors by odontogenic jaw cysts.

AIM: To determine the immunocytochemical pattern of expression of transforming growth factor (TGF) alpha, epidermal growth factor (EGF), and TGF beta in the three most common types of odontogenic jaw cyst. METHODS: Growth factor expression was detected in paraffin wax sections of odontogenic cysts (27 odontogenic keratocysts, 10 dentigerous cysts, and 10 radicular cysts) using a streptavidin-biotin peroxidase technique with monoclonal antibodies directed against TGF alpha (clone 213-4.4) and TGF beta (clone TB21) and a polyclonal antibody directed against EGF (Z-12). RESULTS: The epithelial linings of all cysts showed reactivity for TGF alpha which was mainly localised to basal and suprabasal layers. Odontogenic keratocyst linings expressed higher levels of TGF alpha than those of dentigerous and radicular cysts, with 89% (24/27) of odontogenic keratocysts exhibiting a strong positive reaction compared with 50% (five of 10) of dentigerous and radicular cysts, respectively. EGF reactivity was similar in all cyst groups, weaker than that for TGF alpha and predominantly suprabasal. TGF alpha and EGF were also detected in endothelial cells, fibroblasts and inflammatory cells within the cyst walls. The most intense TGF beta staining in odontogenic cysts was extracellular within the fibrous tissue capsules, irrespective of cyst type. CONCLUSIONS: These results, together with previous studies of EGF receptor, indicate differential expression of TGF alpha, EGF and their common receptor between the different types of odontogenic cyst, suggesting that these growth factors (via autocrine or paracrine, or both, pathways) may be involved in their pathogenesis.     

Fine-needle aspiration diagnosis of enterogenous cyst of the orbit: A case report

Enterogenous cyst is a benign lesion derived from misplaced endodermal epithelium. We report the aspiration cytology findings of an orbital cyst from a 32-year-old woman. The smears contain benign-appearing cuboidal glandular cells with focal mucinous features. Carcinoembryonic antigen level in the cyst fluid was markedly elevated. These findings are consistent with recurrence of the enterogenous cyst initially diagnosed 7 years earlier. Diagn. Cytopathol. 16:450–453, 1997. © 1997 Wiley-Liss, Inc.     

Calcifying odontogenic cyst immunohistochemical detection of keratin and involucrin in cyst wall

Summary Calcifying odontogenic cysts (COC) were immunohistochemically described using different keratin proteins and involucrin as well as histopathology. The cystic lining epithelium was composed of calcifying, keratinizing, squamous, and columnar epithelial cells, and included calcified masses of irregular shape and various size as well as ghost cells. Calcifying epithelium gave negative or only trace staining for keratins detected with low molecular keratin (PKK1), but were regularly positive with high molecular keratin (KL1) and polyclonal antibody for keratin (TK). They were occasionally positive for involucrin. The cells located in the periphery of the calcified masses had a particular abundance of high molecular weight and total keratins (KL1 and TK). Calcified bodies and ghost cells were devoid of any immunoreactivity. Squamous epithelium was relatively similar to that of normal squamous cell epithelium in the oral mucosa. It were most commonly found in columnar cystic epithelial cells which displayed intense staining with all immunoreagents. It is postulated that such epithelial cells may have a strong potentiality to transform into ghost cells or to undergo metaplasia. They may develop altered synthesis of homogenous acellular materials and finally become transformed into calcifying epithelium containing dystrophic calcified masses.     

Expression of cytokeratins in the epithelium of canine odontogenic tumours

Odontogenic tumours are considered to be relatively rare; however, several histologically distinct types have been identified in dogs. The more common canine odontogenic tumours are peripheral odontogenic fibroma and canine acanthomatous ameloblastoma. The expression of cytokeratins (CKs) has been established for the human dental germ and odontogenic tumours. The aim of the present study was to describe the immunohistochemical expression of a panel of CKs in the epithelium of the canine dental germ, normal gingiva and odontogenic tumours arising in this species. Samples from 20 odontogenic tumours, 12 tooth germs and three normal gingival tissues were obtained. Each sample was stained with haematoxylin and eosin and subjected to immunohistochemistry for CK expression. The typical expression pattern of CKs in the odontogenic epithelium and gingiva of dogs was CK14 and CK5/6. CKs 7, 8, 18 and 20 were generally absent from the canine dental germ, gingiva and odontogenic tumours. Dogs and man therefore exhibit similar CK expression in the odontogenic epithelium.     

Cytological findings of odontogenic myxofibroma: A diagnostic dilemma

Odontogenic myxofibroma represents a rare slow‐growing benign neoplasm, which usually occurs in the second and third decades of life and rarely in children or adults over 50 years of age. Myxomas in general represent from 2.3% to 17.7% of all odontogenic tumors, and myxofibromas represent a small number of all myxomas. Limited evidence is present in literature regarding the cytological diagnosis of odontogenic myxoma/myxofibroma. We hereby report the cytomorphological features of a histologically confirmed case of odontogenic myxofibroma and the pitfalls of the cytological diagnosis. A painless jaw swelling in a young boy was aspirated. Scanty mucoid material was obtained. Cytology Smears were moderately cellular and showed a population comprising predominantly of singly scattered plump to fusiform cells with bipolar cytoplasmic processes showing mild to moderate atypia embedded within dense myxoid matrix and another population of cells arranged in clusters. Case was interpreted as low grade mesenchymal tumor. Subsequent biopsy confirmed it as odontogenic myxofibroma arising in a odontogenic keratocyst. Precise interpretation of intraosseous jaw lesions FNAC may not always be possible, but an attempt should be made to broadly classify the lesion as an inflammatory lesion, cystic lesion, giant cell lesion, fibro‐osseous lesion or as an odontogenic tumor. If dual population of odontogenic epithelium and mesenchymal cells embedded in myxoid matrix are identified in such aspirates, a possibility of myxoid odontogenic tumor may be suggested. Triple correlation of cytological, clinical and radiological findings can guide the surgeon for taking appropriate therapeutic decisions. Diagn. Cytopathol. 2016;44:329–333. © 2016 Wiley Periodicals, Inc.     

Evaluation of osteopontin and CD44v6 expression in odontogenic cystic lesions by immunohistochemistry

Odontogenic cysts are common lesions with different biological behavior. Odontogenic keratocysts (OKCs) and calcifying odontogenic cysts (COCs) with ameloblastoma-like epithelium are more aggressive than dentigerous cysts (DCs) and radicular cysts (RCs). Therefore, they were included in the list of odontogenic tumors by WHO. Osteopontin (OPN) is a calcium-binding glycoprotein present in many normal tissues. It plays a role in the migration and invasion of transformed epithelial cells. Binding of OPN to its receptor CD44v6 can enhance cell motility and migration. The purpose of this study was to compare the expression of these markers between odontogenic cysts of varying biological behavior. We examined OPN and CD44v6 expression in tissue sections of 14OKCs, 14COCs, 14RCs and 14DCs by immunohistochemistry. OPN and CD44v6 immunostaining was observed in all lining epithelial cells of the studied lesions with different degrees. The highest level of OPN and CD44v6 expression was found in OKCs, followed by COCs, RCs and DCs. Comparison of both markers among four groups revealed significant differences (P<0.001). Our findings suggest that higher level of OPN and CD44v6 expression in epithelial cells of some lesions such as OKC and COC can explain the local aggressive behavior of them.