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Oro-Facial Metastases from Renal Cell Carcinoma: A Systemic Review of the Literature with Focus on the Clear Cell Variant

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26 February 2024

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26 February 2024

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Abstract
Background: Metastatic tumors to the oro-facial tissues are rare, with an incidence ranging between 1% and 8% of all oral malignant tumors. Generally reported with a peak of incidence in the 5th–7th decades, but possibly occurring at any age, metastases may represent the first sign of an occult cancer or manifest in patient with an already known history of a primary carcinoma, mostly from the lungs, kidney, prostate, and colon-rectum in males, or uterus, breast, lung, and ovary in females. In the oro-facial tissues the sites mostly involved are the oral mucosa, gingiva/jawbones, tongue, and the salivary glands. Methods: A systemic Review of the literature on the oro-facial metastases from Renal Cell Carcinoma has been conducted by searching the most used databases, also focusing the attention on the Clear Cell histological variant, representing the most frequent one. Results: Among the 160 analyzed studies, 211 cases of oral metastases of renal cancer were found (148 in males, 70.1%; 63 in females, 29.8%), with an average age of 59.8 years. In almost 40% of cases, metastasis represented the first clinical manifestation of the primary tumor and 122 were histologically diagnosed as ccRCCs (57.8%). The tongue was involved in most of the cases (26% - 55 cases), followed by mandible (18.9% - 40 cases), gingiva (18.4% - 39 cases), maxilla (10.9% - 23 cases), parotid gland (10.4% - 22 cases), buccal mucosa (5.2% - 11 cases), lips (3.3% - 7 cases), hard palate (2.8% - 6 cases), soft palate, masticatory space and submandibular gland (0.9% - 2 cases), lymph nodes, tonsil and oral floor (0.4% - 1 case). Among the 122 ccRCCs (84 were males, 68.8 %; 38 females, 31.1%), with an average age of 60.8 years and representing in 33.6% the first clinical manifestation, the tongue remained the most involved site (25.4% - 31 cases), followed by the gingiva (17.2% - 21 cases), parotid gland (13,1% - 16 cases), mandibular bone (12.2% - 15 cases), maxillary bone (11.4% - 14 cases), buccal mucosa and lips (4.9% - 6 cases), hard palate (4% - 5 cases), submandibular gland and soft palate (1.6% - 2 cases), lymph nodes, tonsil, oral floor and masticatory space (0.8%. 1 case). The clinical presentation in soft tissues was represented by a fast-growing exophytic mass, sometimes accompanied by pain. Instead inn bone appeared as radiolucent lesions, with ill-defined borders and cortical erosion. Conclusions: Our data focus the attention on the incidence of Renal cancer Metastases in the oro-facial tissues. Their early identification surely represents a diagnostic challenge, especially when the clinical work-up is limited to the cervico-facial region. Nevertheless, early diagnosis and recently introduced adjuvant therapies may represent the key for better outcomes. Therefore, general guidelines about clinical and radiological identification of oro-facial potentially malignant lesions should be part of the cultural background of any dentists.
Keywords: 
Subject: Medicine and Pharmacology  -   Oncology and Oncogenics

1. Introduction

Metastatic dissemination of solid tumors may involve the Head and Neck, including the oral cavity, although infrequently and with an incidence between 1% and 8% of all oral malignant tumors (1–4) and a peak of incidence in the 5th–7th decades (2). Excluding the malignant tumors of the childhood, Oro-Facial Metastases (OFMs) may represent the first sign of an occult or still undiagnosed cancer or manifest during the clinical follow-up of a patient with an already diagnosed primary carcinoma (5–7). Metastases to the oro-facial tissues can involve soft and hard tissues or both synchronously, thus including the oral mucosa, jawbones, the salivary glands, the neck lymph nodes; the most frequent primary localization is represented by lung, kidney, prostate and colon-rectum in males, uterus, breast, lung and ovary in females (1,2,8,9), according to the overall incidence rate of each one among general population.
It is generally accepted that the metastatic diffusion shows a predilection for some specific sites in the oro-facial region, regardless the main tissue target of the primary tumor (e.g. bone for prostate cancer) and, additionally, it may be influenced by peculiar clinical conditions, mainly inflammatory conditions of the gingival-periodontal tissues or in edentulous individuals bearing removable prostheses. In such instances, the re-organization of the district blood flow related to the inflammation or induced by the pressure or trauma of the prosthesis, have been postulated to facilitate the metastatic growth (10). The jawbones and more specifically molar and premolar areas are frequently involved in view of their rich vascularization and high bone marrow content. In addition, metastases may develop in residual alveolus after tooth removal (post-extraction sites) probably as consequence of the increased blood flow related to the blood clot formation (1,2,8,10).
Renal cell carcinoma (RCC) is the most common form of kidney malignancy, accounting for more than 90% of all renal malignancies in the adult population. It occurs predominantly in males and, on average, around the age of 60 (11–17). Several risk factors have been claimed to favor RCC development, in particular an elevated body mass index (18), urinary stones in males (19), type 2 diabetes in females (20), chronic liver and kidney diseases (21) and long-term use of analgesics (22) in addition to environmental factors (23,24). On average, locoregional or distant metastases develop in one third of patients, and recurrence is observed in about 25% of cases with localized renal disease treated with nephrectomy. Metastases of RCC generally involve the lungs, regional lymph nodes, liver, bones, and brain (25). Localization to the oro-facial tissue has been seldom described in the literature. In this region, RCC metastases are relatively rare, with the tongue being predominantly involved, followed by the gingiva and maxillary bones (26,27).
RCC has several recognized histologic variants. In particular, clear cell RCC (ccRCC) (accounting for 70% of cases) (28,29), papillary RCC (pRCC) (10 to 15%), and chromophobe RCC (chRCC) (5%) are the most frequently encountered forms and represent 90% of RCCs (30). Among all, RCC, clear cell type, has a known propensity to metastasize, most commonly via direct invasion of the renal veins and vena cava, with subsequent hematogenous dissemination to the lungs; however, unusual metastatic sites or late metachronous metastases (>10 years) are not infrequent, and distant metastasis may be the first clinical presentation of the tumor (31). Metastatic ccRCC to the OFTs have been occasionally reported (1,2,28,32) and, in some instances, they may represent the initial manifestation of the disease (2,6,7,33), thus representing a true diagnostic dilemma both for clinicians (mainly for the rarity and the early diagnosis) and pathologist; in fact, due to the high glycogen and lipid content, the tumor cells of ccRCC display evident cytoplasmic vacuolization and clearing, mimicking other neoplasms of odontogenic or salivary gland origin that more commonly affect this area (2,28,29,32,34–36). Consequently, the oral localization of an occult ccRCC surely may represent a diagnostic challenge, especially when the clinical work up is still limited to the cervico-facial region (6,7,37–40).
The present study is proposed to systematically review case reports and case series of RCC's metastasis to the OFTs. Our primary aim was to perform a comprehensive review of all published cases of ccRCC metastases according to PRISMA guidelines for systemic review. (Graphic 1)
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Graphic 1. The PRISMA flow chart for reporting systematic reviews.
Graphic 1. The PRISMA flow chart for reporting systematic reviews.
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2. Materials and Methods

A systematic review of the literature was conducted intending to provide an overview of the available evidence in reliable databases. The terms “renal metastasis” or “renal metastases” or “clear cell renal cell carcinoma” AND “oral” o “Head and Neck” were alternatively used in searching, restricting their presence to the title of the article in the PubMed, Scopus, Web of Sciences and Google Scholar databases. The search was only limited to the studies on humans. All kind of papers were collected, thus including case report, case series, review of the literature, systematic review of the literature. After introducing the keywords in the databases, a total of 5865 results were obtained. First, the titles of the articles were read, and 540 articles were selected for reading the abstract as all papers reporting duplicate cases were deleted. Of these, 261 articles were chosen for full-text reading. 101 were removed because the lesion was not confirmed as metastasis at theanatomopathological examination or because the metastasis was outside the limits of the Head and Neck, because the gender and the age of the patients were not specified or because it was not proven whether the oral manifestation was the first sign of disease or not. Thus, 160 articles were chosen for inclusion in the present systematic review of the literature. The reading, selection, and analysis of the articles included in this systematic review were performed by a single clinician.

3. Results

In the 160 analyzed studies, 211 cases of oral metastases of renal cancer were found, of which 122 were histologically demonstrated to be ccRCCs (57.8%) at the final diagnosis. The tongue was involved by renal metastases in most of the cases (26% - 55 cases), followed by the mandibular bone (18.9% - 40 cases), gingiva (18.4% - 39 cases), maxillary bone (10.9% - 23 cases), parotid gland (10.4% - 22 cases), buccal mucosa (5.2% - 11 cases), lips (3.3% - 7 cases), hard palate (2.8% - 6 cases), soft palate, masticatory space and submandibular gland (0.9% - 2 cases), lymph nodes, tonsil and oral floor (0.4% - 1 case). Of the 211 total cases, 148 involved males (70.1%) and 63 females (29.8%). Average age was 59.8 years. Average male age was 61.8; average female age was 55.3 (Table 2). In almost 40% of cases, the development of an oral metastasis represented the first clinical manifestation of the primary tumor, which was previously unknown. Data have been globally collected in Table 1, listing Author/authors name, year of publication, site/sites, histological histotype, sex, age, occurrence as first sign of metastatic disease or not.
Focusing on the numbers of the most frequent histotype (ccRCC) we see that 122 cases of oral metastases of ccRCCs the tongue was involved in most cases (25.4% - 31 cases), followed by the gingiva (17.2% - 21 cases), parotid gland (13,1% - 16 cases), mandibular bone (12.2% - 15 cases), maxillary bone (11.4% - 14cases), buccal mucosa and lips (4.9% - 6 cases), hard palate (4% - 5 cases), submandibular gland and soft palate (1.6% - 2 cases) and lymph nodes, tonsil, oral floor and masticatory space (0.8%. 1 case). It is clear that soft tissues are more affected by ccRCC metastases than hard tissues.
Focusing on the numbers of the most frequent histotype (ccRCC) we found the tongue was involved in most cases (25.4% - 31 cases), followed by the gingiva (17.2% - 21 cases), parotid gland (13,1% - 16 cases), mandibular bone (12.2% - 15 cases), maxillary bone (11.4% - 14cases), buccal mucosa and lips (4.9% - 6 cases), hard palate (4% - 5 cases), submandibular gland and soft palate (1.6% - 2 cases) and lymph nodes, tonsil, oral floor and masticatory space (0.8%. 1 case). It is clear that soft tissues are more affected by ccRCC metastases than hard tissues. Of the 122 total cases, 84 are male (68.8 %) and 38 are female (31.1%). Average age is 60.8 years. Average male age is 61.7; average female age is 59. In almost 33.6% of cases, the development of an oral metastasis is the first clinical manifestation of the primary tumor. Clinical presentations vary depending on the affected tissue: at the level of soft tissues, metastases frequently present as fast-growing and exophytic masses, accompanied or not by pain; bone’s metastases radiologically appeared as radiolucent lesions, with ill-defined borders and cortical erosion. In addition, some of them also expanded into the adjacent soft tissues, thus causing submucosal swelling on the gingiva. (Table 3)

4. Discussion

Metastatic tumors from distant organs and tissues to the oro-facial tissues are not encountered frequently. According to the literature, metastatic tumors comprise about only 1% of all oro-facial malignancies. (114,158) Renal cell carcinoma (RCC) is the most common form of kidney malignancy, accounting for more than 90% of all renal malignancies in the adult population (11). Distant metastases from RCC are very common and usually multiple to different organs, with a decreasing incidence respectively to the lungs (50%–60%), bones and liver (30%–40%), and head and neck (12%–16%) (1,2). Among the latter, 50% of the metastases were detected in the thyroid, nose and paranasal sinuses, and pharynx (28,33,197). According to the recent review of Kase AM et al. (198) statistic data a 70% five-year survival for patient with regional disease which drastically decreased to 13% for those showing distant metastases. Such data highlights the importance of the early detection of metastatic lesions which can be difficult in absence of signs and/or symptoms in the whole organism with the exclusion of the oro-facial tissue which, conversely are relatively affordable due to the facility of clinical exploration and/or the frequent use of dental panoramic radiogram and/or CT for dental therapies over the life, at least in the occidental countries.
Generally, in the oral cavity, large and/or rapidly growing swellings in the tongue and periodontal tissue, as well unpredictable tooth mobility or gingiva-periodontal inflammation (including the peri-implant hard and soft tissues) surely represent clinical signs of possible malignancy (and consequently also of metastatic diffusion), when the most common lesions of benign nature (mainly odontogenic abscess, periodontal or perimplant abscess) have been excluded. The early detection by well addressed general dentists and their radiological evaluation always need the anatomopathological confirmation by hard or soft biopsy which represent the true key for the early and the differential diagnosis. In fact, data reported by Schütz V. et al. in a recent review on Stage T1N0M1 RCC, evaluate by comparison the long-term survival of 27 patients with ccRCC stage T1N0M1 in comparison to 18 patients without distant metastases also by using the immunohistochemistry staining for CD8+ tumor infiltrating lymphocytes; authors concluded, as expected, that, at the same T1N0 conditions, M1 patients showed a significantly worse median cancer specific survival of 2.8 years, in contrast to the M0 patients with a value of 17.7 years and, additionally, number of CD8+ TILs was substantially higher in stage M1 compared to M0 ccRCC patients, thus obviously suggesting a more aggressive tumor biology; but, interesting, they also described a survival rate much higher than average (over five years) in the 29.6% of their T1N0M1 patients (eight patients) and three of those survived over a decade thanks to an intensified and multimodal treatment including metastasis-directed therapy (199).
Therefore, along with the targeted therapies which significantly impact positively both in treatment and prognosis of metastatic RCC patients, the early diagnosis surely plays a key rule too, as reported also by The International Metastatic Renal Cell Carcinoma Database Consortium risk model listing it among the risk factor (diagnosis to systemic therapy< 1 year), together with Karnofsky performance status < 80%, corrected calcium > normal, hemoglobin < normal, neutrophil > normal, and platelet count > normal, which globally may help to prognosticate survival in such patients. To date, this model indicated a median OS of 43.2 months in 0 risk factors group, 22.5 months in the 1–2 risk factors group, and 7.8 months in the poor risk group exhibiting 3 or more risk factors (200).
This model continues to be used widely today in clinical practice and as a predictive tool for responses to new combinations of immunotherapies. VEGFR axis has proven to be a key therapeutic target in metastatic RCC leading to improved outcomes in these risk categories. As translational work advanced, it was demonstrated that RCC has a unique immunogenicity that would forever change the treatment landscape (Figure 2).
RCC is the third most common malignancy to metastasize to the head and neck region, after lung and breast carcinomas. Oro-facial metastasis is the presenting complaint in 7.5% of patients with RCC (50). Distant metastases to the oro-facial tissues may involve the jaws, especially the mandible, or the soft tissues, mostly gingiva and frequently the tongue as emerging from the current review with a prevalence of 26 % (Graphic 2).
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Graphic 2. showing the prevalence of lesions by site of involvement 
Graphic 2. showing the prevalence of lesions by site of involvement 
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The correct diagnosis of metastatic lesions of the oral cavity represents a challenge for the clinician, especially when the patient has no history of malignant diseases. This literature review shows that in 36.4% of cases (77 of 211 patients affected by oral metastases) the development of an oral metastasis is the first clinical manifestation of the primary tumor.
The gingival lesions are more complex to diagnose a because of the presence of several benign conditions that may be potentially included among the differential diagnoses (e.g., pyogenic granuloma, peripheral giant cell granuloma, and ossifying fibroma, Fibrous Hyperplasia), thus frequently leading to a diagnostic delay. However, clinical signs, such as rapid enlargement or invasion of the underlying bone, may support the diagnosis by excluding an inflammatory origin of the lesion (27). Among the reactive lesions of the gingiva, the Fibrous Hyperplasia is surely very common accounting for up to 40% of mucosal pathology in large series reported and occurring in a wide age range (201).
Also vascular epulis, differently called pyogenic granuloma, is a frequently occurring gingival lesion, usually presenting as a soft bright red swellings also with focal ulceration providing a grey/yellow appearance, usually related to trauma or chronic irritation and mostly sex hormones level alterations (e.g. puberty, pregnancy, use of oral contraceptive drugs or hormone replacement therapy); its clinical presentation along with the easily provoked bleeding after trauma broadens the spectrum of the differential diagnosis thus including malignant lesions (such as metastasis) as well systemic causes of vascular expansion of the gingiva such as leukemia and granulomatosis with polyangiitis.
The most common Peripheral Odontogenic Tumors frequently involving the gingiva, peripheral odontogenic fibroma and peripheral ameloblastoma are the most frequent (PA) occurring most commonly; their occurrence in young-adults, the slow growth, and the clinical presentation mostly as gingival swelling with intact overlying mucosa surely represent important criteria for the differential diagnosis from malignancy; some suspicion may arise with peripheral ameloblastoma which can have a variable clinical presentation showing a granular or erythematous surface (202).
Among malignancies with gingival localization, the verrucous carcinoma surely represent the most frequent, although its clinical presentation usually as white plaque or verrucous lesion helps clinicians in diagnosing it; nevertheless, the occurrence of most aggressive squamous cell carcinoma in the periodontal tissue should be consider too mainly when occurring with granular or erythematous aspect often associated to periodontal and bone invasion and the related clinical (bleeding, teeth mobility, pain) and radiological signs (enlargement of the periodontal space, radio-transparencies). Additionally, the AIDS-related type of Kaposi’s Sarcoma may show gingival manifestation generally with reddish appearance (thus mimicking mainly hemangioma, pyogenic granuloma and giant cell epulis especially when nodular in appearance) but also ulcerated when of larger dimension leading to a differential diagnosis obviously including other malignancies. Lastly, the head and neck represent the second most common extra-nodal site for lymphoma occurrence (11–33%), especially diffuse large B-cell non-Hodgkin lymphoma, with the most common sites affected being the gingiva, mandible, palate, maxilla and tongue (203, 204).
Additionally, the gingiva is frequently affected in patients with acute myeloid leukemia (205). Although Lymphoma and leukemia have a non-specific clinical presentation in the periodontal tissue, often present with swelling and reddening of the gingival tissues (mimicking gingivitis, periodontitis of different stages and hyperplastic gingivitis of different etiology when generalized and pyogenic granuloma or giant cell epulis when swellings are localized) while advanced cases may show sign of malignancy as accompanied by alveolar bone loss and tooth mobility; in such cases patients have frequently a well-recognized history of generalized/systemic disease but when still undiagnosed surely represent a challenging situation for the clinicians with the differential diagnosis is likely to include several non-neoplastic and neoplastic conditions depending on the extent of disease at presentation.
Also the intraosseous presentation of metastasis in the jaws is extremely variable and consequently the early diagnosis of jawbone metastasis both as first sign diffuse neoplastic or not disease is more difficult than their counterpart of the soft tissues; the frequent association with decayed or unvital teeth or residual root fragments, periodontitis, peri-implant inflammatory conditions, the possible periapical localization, the un-specificity of the clinical symptoms (pain, anesthesia, paresthesia, swelling, teeth mobility, gingival bleeding, etc.) and the highly variable combination of them, the un-specificity of the radiological signs (as usually appearing as radiolucent area with ill-defined borders but also as a radiopaque or mixed radiopaque-radiolucent lesion mostly when of prostatic origin) make the spectrum of the potential differential diagnosis extremely wide (206).
Metastasis occurrence in the major salivary glands and especially in the parotid gland (as the most frequent site of inflammatory and neoplastic salivary gland lesions) also represents a true diagnostic dilemma mainly because the majority of patients manifest the metastasis first and undergo parotid surgery before the primary tumor diagnosis and staging; also, a further complication is the constant increasing of their overall incidence along with the un-specific characteristics on the radiological examination, generally MRI and US (207).
Probably, the tongue involvement by metastatic disease represents the most challenging situation to differently diagnose, first for the rarity generally reported in literature but mainly for the variability of the clinical presentation as they typically remain asymptomatic, but alternatively could present as painful hard masses with or without superficial ulceration due to biting trauma; as so, the differential diagnosis is very challenging and the histological examination of sample tissue should be performed soon to define the tumor and its origin. Also, tongue lesions frequently required treatment as may interfere with vital function (swallowing, biting, breathing, drinking) which generally is a total or partial surgical excision combined to adjuvant radiotherapy for local and general disease control (208). Of note is the data about ccRCC occurrence in the tongue among patients list in the current review as its incidence represents the 25.4% - 31 cases.
The clinical suspicion always needs to be supported by histology and immunohistochemistry to discriminate renal metastases from other lesions characterized by the histologic presence of clear cells. When occurring in major salivary glands, the differential diagnosis of clear cell neoplasms includes mucoepidermoid carcinoma (MEC) and other salivary gland tumors, such as epithelial-myoepithelial carcinoma, oncocytomas, hyalinizing clear cell carcinoma (HCCC) and acinic cell carcinoma (ACC). All these tumors may display a clear cell component (28,29,35). The differential diagnosis of jawbone metastases also includes some histological types of odontogenic tumors, which may also display clear cells, such as clear cell ameloblastoma (CCA), calcifying epithelial odontogenic tumor (CEOT) and clear cell odontogenic carcinoma (CCOC) (8,10,29). In particular, immunohistochemistry is extremely important to perform differential diagnosis with clear cell salivary and odontogenic neoplasms (144). ccRCC consistently express positivity for CD10, cytokeratins AE1/AE3, Epithelial Membrane Antigen (EMA), PAX-8, Renal Cell Carcinoma Antigen (RCCAg) and vimentin. Conversely, ccRCC do not express cytokeratin 7, calretinin, CD117, muscle markers (smooth muscle actin, calponin, myosin) and Glial Fibrillary Acidic Protein (GFAP). Comparatively, all salivary gland tumors show immunoreactivity for cytokeratin 7, cytokeratins AE1/AE3 and EMA, with fainter and less diffuse positivity for cytokeratin 7 in epithelial-myoepithelial carcinoma (EMEC), hyalinizing clear cell carcinoma (HCCC) and myoepithelioma, for cytokeratins AE1/AE3 in myoepithelioma, and for EMA in HCCC and myoepithelioma. Muscle markers (smooth muscle actin, calponin, myosin) may be expressed in adenoid cystic carcinoma, EMEC, myoepithelioma and pleomorphic adenoma. CD117 is usually expressed in a strong and diffuse manner in adenoid cystic carcinoma and EMEC and, with a lower extension, in mucoepidermoid carcinoma and pleomorphic adenoma. GFAP is diffusely expressed in pleomorphic adenoma and only focally observable in EMEC and myoepithelioma. Calretinin may be occasionally expressed in a minority of acinic cell carcinomas, usually in few tumor cells. As regards odontogenic tumors, cytokeratins AE1/AE3, cytokeratin 7 and EMA are observable in odontogenic carcinoma, while cytokeratins AE1/AE3 and calretinin in ameloblastoma. However, CD10, PAX8 and RCCAg are consistently negative in all salivary glands and odontogenic tumors showing clear cell features, allowing certain differential diagnosis with ccRCC metastasis (192). Furthermore, though for speculative purposes only, clear cell sarcoma of the kidney should be considered in the differential diagnosis, at least in pediatric patients, being the second most common malignant tumor in children. This tumor may be easily ruled out by immunohistochemistry, because is negative for cytokeratins, EMA and CD10 (121,127). Consequently, it is important to highlight that the final diagnosis, together with the exclusion of all the possible differential diagnosis, is only made with certainty after histopathological examination. Hence, the biopsy is always mandatory, and role of the anatomical pathologist is vital in the clinical work up of patients with oral metastases from ccRCC.
From the literature over the past 100 years, we identified that the age at diagnosis ranged from 18 to 89 years. Metastases are more common in men than women (148 versus 63 cases, respectively), mirroring the male predominance of RCC more generally. The majority of RCC are clear cell type. Oral metastases from renal cell carcinoma can involve soft tissues and jawbones almost equally. The most affected sites are tongue and mandibular bone (Graphic 1, Table 2). The mass or nodule was the most common clinical manifestation, while pain was the most prevalent symptom. In cases where bone was affected by metastasis, a radiolucent image was the most reported. Any mass present in the oral cavity should be biopsied and analyzed carefully, as metastatic lesions may resemble clinically benign lesions.

5. Conclusions

The current review of the literature confirms the well-recognized data about the low incidence of metastases in the oro-facial tissues and that the occurrence is mostly related to an advanced stage of disease. We found that in almost the 40% of cases the oro-facial tissues, metastases represented the first clinical manifestation of a still unknown clear cell renal cell carcinoma; this data is higher than the overall general incidence for all metastases to the head and neck presenting as first manifestation of an occult malignancy, generally accounting for about 20–35%. Hence, this tumor seems to predilect oro-facial-tissues more than others. Moreover, metastases to the head and neck from clear cell renal cell carcinoma can occur at any age and the prognosis is generally poor.
All collected data highlight the importance of early diagnosis, especially for metastasis from clear cell renal cell carcinoma in absence of an already known primary tumor (metastases as first sign of disease), despite the evident difficulties of their identification both by clinical examination and conventional (first grade) radiological investigations. The early clinical identification, with consequent histological definition and TNM staging, along with targeted therapies, may be vital in order to guarantee better outcomes for patients presenting with metastatic clear cell renal cell carcinoma.

Author Contributions

Conceptualization, S.C.; methodology, V.G., A.L.F.; validation, C.C., G.F.; resources, M.F., D.D.V, G.I.; data curation, V.G., A.D.A., A.M.; writing—original draft preparation, S.C., V.G.; writing—review and editing, S.C., M.F.; supervision, S.C. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Data collected in the current study have been downloaded by the following databases: PubMed, Scopus, Web of Sciences and Google Scholar.

Conflicts of Interest

The authors declare no conflicts of interest.

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Table 1. METASTASES OF RENAL CARCINOMA TO THE ORAL CAVITY: REVIEW OF LITERATURE.
Table 1. METASTASES OF RENAL CARCINOMA TO THE ORAL CAVITY: REVIEW OF LITERATURE.
AUTHORS Years Site Histotype Gender Age First sign of Disease
Ray et al (41) 2013 Tongue RCC M 65 Yes
Kalinin et al (42) 2023 Tongue ccRCC F 58 yes
Nishii et al (43) 2020 Maxillary bone ccRCC M 89 No
Zhang et al (44) 2020 Mandibular bone RCC F 56 Yes
Jung et al (45) 2023 Mandibular bone RCC F 22 Yes
Stojanovic et al (46) 2020 Gingiva RCC M 53 Yes
Li et al (47) 2001 Parotid RCC M 63 No
Kundu et al (48) 2001 Parotid ccRCC M 61 Yes
Park and Hlivko (49) 2002 Parotid ccRCC F 83 No
Pritchyk et al (50) 2002 Lip
Maxillary bone
Tongue		 RCC
RCC
RCC		 M
F
M		 70
53
60		 Yes
Göğüş et al (51) 2004 Parotid ccRCC F 59 No
Torres-Carranza et al (52) 2006 Tongue ccRCC F 49 No
Newton et al (53) 2007 Parotid ccRCC F 74 No
Yoshitomi et al (54) 2011 Tongue ccRCC M 47 Yes
Morvan et al (55) 2011 Tongue ccRCC F 48 No
Balliram et al (56) 2012 Tongue pRCC M 72 Yes
Serouya et al (57) 2012 Submandibular gland ccRCC M 60 No
Wadasadawala et al (58) 2011 Tongue RCC M 48 No
Deeb et al (59) 2012 Parotid RCC M 82 No
Özkiriş et al (60) 2011 Cervical lymph nodes ccRCC F 56 No
Ghazali et al (61) 2012 Tongue ccRCC F 64 No
Lau et al (62) 2012 Parotid ccRCC F 79 No
Mazeron et al (63) 2013 Tongue ccRCC M 66 Yes
Yanlan et al (64) 2013 Parotid ccRCC F 44 Yes
Udager and Rungta (65) 2014 Parotid ccRCC M 64 No
Abbaszadeh-Bidokhty et al (66) 2014 Tongue ccRCC M 80 No
Kotak and Merrick (67) 2014 Lip ccRCC M 64 No
Suojanen et al (68) 2014 Lip ccRCC M 71 No
Kudva et al (69) 2016 Buccal mucosa ccRCC F 36 Yes
Georgy et al (70) 2017 Gingiva ccRCC M 63 Yes
Nifosì et al (71) 2017 Gingiva ccRCC M 58 No
Raiss et al (6) 2017 Tongue RCC M 55 Yes
Vasilyeva et al (72) 2018 Gingiva RCC F 78 Yes
McNattin and Dean (73) 1931 Tongue Tubular Adenocarcinoma M 58 Yes
Altinel et al (74) 2010 Tongue ccRCC M 67 Yes
Syryło et al (75) 2010 Lip ccRCC M 59 Yes
Gil-Julio et al (76) 2012 Buccal mucosa ccRCC M 65 No
Shirazian and Bahrami (77) 2016 Gingiva ccRCC M 45 Yes
Schrag and Jordan (78) 1945 Tongue RCC M 34 No
Carmen and Korbitz (79) 1970 Tongue ccRCC M 77 No
Friedlander et al (80) 1978 Tongue RCC M 84 No
Fitzgerald et al (81) 1982 Gingiva and Tongue RCC M 63 No
Inai et al (82) 1987 Tongue RCC M 42 No
Ishikawa et al (83) 1991 Tongue RCC F 58 No
Okabe et al (84) 1992 Tongue ccRCC M 58 No
Shibayama et al (85) 1993 Tongue RCC M 41 No
Ziyada et al (86) 1994 Tongue ccRCC M 59 Yes
Airoldi et al (87) 1995 Tongue RCC M 51 No
Aguirre et al (88) 1996 Tongue ccRCC F 82 Yes
Konya et al (89) 1997 Tongue RCC M 59 Yes
Tomita et al (90) 1998 Tongue ccRCC M 50 No
Navarro et al (91) 2000 Tongue ccRCC M 62 No
Mekni et al (92) 2002 Tongue ccRCC M 63 No
Kyan and Kato (93) 2004 Tongue ccRCC M 66 No
Huang et al (94) 2006 Tongue
Parotid		 RCC
ccRCC		 F
F		 76
56		 No
No
Cochrane et al (95) 2006 Tongue RCC M 41 No
Del Rosario Regalado et al (96) 2007 Tongue RCC M 81 No
Longo et al (97) 2008 Tongue RCC M 68 No
Kella et al (98) 2009 Tongue ccRCC F 67 Yes
Friedmann and Osborn (99) 1965 Maxillary bone RCC M 63 No
Trinca and Willis (100) 1936 Tongue RCC M 57 Yes
Branch and Norton (101) 1928 Gingiva ccRCC F 64 Yes
Salman and Langel (102) 1954 Gingiva RCC F 62 No
Persson and Wallenius (103) 1961 Gingiva ccRCC F 60 No
Cranin et al (104) 1966 Gingiva RCC M 72 No
Buchner and Begleiter (105) 1980 Gingiva ccRCC M 46 No
Nishimura et al (106) 1982 Mandibular bone
Gingiva
Mandibular bone
Mandibular bone		 RCC
RCC
Transitionalcell cR
RCC		 F
M
M
F		 61
72
61
36		 yes
yes
no
yes
Fay and Weir (107) 1983 Gingiva ccRCC F 18 No
Zohar et al (108) 1985 Gingiva ccRCC F 54 Yes
Tsianos et al (109) 1987 Gingiva RCC M 78 No
Müller-Mattheis et al (110) 1989 Gingiva RCC F 47 No
Hagen et al (111) 1989 Gingiva RCC F 46 No
Corsi et al (35) 1994 Lip ccRCC M 44 No
Salman and Darlington (112) 1944 Hard palate ccRCC F 54 No
Mallet (113) 1961 Mandibular bone ccRCC F 72 Yes
Meyer and Shklar (114) 1965 Parotid
Maxillary bone
Mandibular bone
Mandibular bone		 RCC
RCC
Reticulumcell sarc.
RCC		 M
F
M
M
 48
73
43
57		 No
No
No
No
Godby et al (115) 1967 Gingiva ccRCC M 45 No
Milobsky et al (116) 1975 Maxillary bone RCC F 66 Yes
Nagayama and Oka (117) 1979 Mandibular bone
Hard palate		 ccRCC
ccRCC		 F
F		 61
43		 yes
Susan et al (118) 1979 Hard palate
Hard palate		 ccRCC
ccRCC		 M
M		 53
62		 yes
yes
Matsumoto and Yanagihara (119) 1982 Maxillary bone
Maxillary bone		 ccRCC
ccRCC		 M
M		 73
48		 yes
yes
Pick et al (120) 1986 Mandibular bone ccRCC M 71 Yes
Florine et al (121) 1988 Mandibular bone Clear cell sarcoma M 15 m. No
Zachariades et al (122) 1989 Mandibular bone RCC M 78 No
Jones and al (123) 1990 Mandibular bone
Mandibular bone		 ccRCC
ccRCC		 F
F		 62
52		 yes
yes
Fandella et al (124) 1992 Maxillary bone ccRCC M 62 Yes
Lee et al (125) 1998 Maxillary bone RCC M 76 Yes
Guyot et al (126) 1999 Mandibular bone RCC M 83 No
Toranzo-Fernandez et al (127) 2000 Mandibular bone Clear cell sarcoma M 8 Yes
Honig (128) 2000 Maxillary bone RCC M 46 No
Shetty et al (129) 2001 Mandibulr bone RCC M 62 Yes
Heinroth et al (130) 2006 Maxillary bone ccRCC F 53 yes
Ðanić et al (26) 2018 Tongue RCC M 51 yes
Madison and Frierson (131) 1988 Tongue
Tongue		 ccRCC
ccRCC		 M
M		 29
63		 No
No
Kishore et al (132) 2018 Lip ccRCC M 54 No
Abro et al (133) 2019 Tongue RCC M 54 No
Netto et al (134) 2019 Gingiva RCC M 68 Yes
Walsh et al (135) 2022 Tongue ccRCC M 63 No
Mrena et al (136) 2008 Parotid
Parotid
Parotid		 ccRCC
RCC
RCC		 F
F
F		 58
76
62		 Yes
No
No
Aljawad et al (137) 2023 Parotid ccRCC M 65 No
Migliorelli et al (138) 2023 Maxillary bone ccRCC F 54 Yes
Maschino et al (139) 2013 Maxillary bone
Maxillary bone
Parotid
Tongue		 ccRCC
ccRCC
ccRCC
RCC		 M
F
M
M		 73
84
78
66		 No
No
No
No
Wallace et al (140) 2022 Soft palate ccRCC M 50 No
Ludwig et al (141) 2020 Mandibular bone ccRCC M 78 Yes
Melnick et al (142) 1989 Parotid ccRCC M 72 Yes
Borghi et al (143) 1995 Parotid ccRCC M 68 No
Seijas et al (144) 2005 Parotid ccRCC M 67 Yes
Goel et al (145) 2003 Tongue ccRCC M 62 Yes
Lenkeit et al (146) 2020 Tongue RCC M 71 No
Ruiz-Oslé et al (147) 2017 Parotid
Mandibular bone
Gingiva
Masticatory space		 RCC
RCC
RCC
RCC		 M
M
M
F		 72
55
62
52		 yes
yes
yes
no
Doykos (148) 1969 Mandibular bone Wilm’s Tumor F 9 Yes
Schwab and Lee (149) 2012 Maxillary bone ccRCC M 63 No
Erkilic et al (150) 2017 Gingiva Collecting duct adenocarcinoma F 54 Yes
Lee and Lee (151) 2017 Mandibular bone RCC M 62 No
Guimarães et al (152) 2016 Gingiva ccRCC F 31 No
Owosho et al (153) 2016 Mandibular bone
Mandibular bone
Gingiva
Buccal mucosa
Buccal mucosa
Gingiva
Buccal mucosa		 RCCRCCRCCRCCRCCRCCRCC F
F
F
M
M
M
M		 61
63
18
75
70
59
66		 No
No
No
No
No
No
No
Nisi et al (154) 2020 Tongue
Buccal mucosa		 ccRCC
ccRCC		 M
M		 61
71		 yes
yes
Lang et al (155) 2003 Tongue ccRCC M 45 No
Bucín et al (156) 1982 Gingiva RCC M 65 No
Marioni et al (157) 2004 Tongue ccRCC F 87 No
Van der Wall et al (158) 2003 Soft palate
Maxillary bone
Mandibular bone
Buccal mucosa		 ccRCC
ccRCC
ccRCC
ccRCC		 F
F
M
M		 62
64
48
67		 No
No
No
No
Fukuda et al (159) 2002 Mandibular bone RCC M 76 No
Makos and Psomaderis (27) 2009 Gingiva ccRCC M 63 No
Dehner (160) 1973 Mandibular bone Wilm’s Tumor F 6 No
Morii (161) 1975 Buccal mucosa ccRCC M 63 No
Sidhu (162) 1982 Mandibular bone RCC F 32 Yes
Sánchez Aniceto et al (163) 1990 Mandibular bone RCC M 54 Yes
Maestre-Rodríguez et al (164) 2009 Gingiva ccRCC M 52 Yes
Will et al (165) 2008 Floor of mouth ccRCC M 63 no
Nesbitt et al (166) 2019 Gingiva Sarcomatoid RCC M 59 Yes
Patel et al (167) 2020 Gingiva ccRCC F 59 yes
Narea-Matamala et al (168) 2008 Gingiva RCC M 74 yes
Massaccesi et al (169) 2009 Tonsil ccRCC M 76 yes
Shinozaki et al (170) 2009 Mandibular bone ccRCC F 76 No
Ohmura et al (171) 1981 Mandibular bone ccRCC M 53 No
Nakano et al (172) 2013 Gingiva ccRCC M 72 No
Ficarra et al (173) 1996 Wharton’s duct ccRCC M 73 No
Tunio et al (174) 2012 Tongue ccRCC M 35 No
Milner et al (175) 2014 Hard palate ccRCC M 67 Yes
Santana et al (176) 2000 Gingiva ccRCC M 63 Yes
Kizaekka et al (177) 2019 Tongue ccRCC M 77 No
Paraskevopoulos et al (178) 2021 Mandibular bone ccRCC M 72 Yes
Morita et al (179) 2018 Buccal mucosa ccRCC M 75 No
Prol et al (180) 2019 Mandibular bone
Gingiva
Gingiva
Mandibular bone
Masticatory space		 ccRCC
ccRCC
ccRCC
chRCC
ccRCC		 M
M
F
M
M		 55
62
52
56
65		 No
No
No
No
No
Shimono et al (181) 2021 Mandibular bone
Maxillary bone
Tongue		 RCCRCCRCC M
M
M		 62
89
63		 Yes
No
no
Ali and Mohamed (182) 2016 Gingiva ccRCC M 60 Yes
Selvi et al (183) 2016 Gingiva ccRCC M 51 No
Jatti et al (184) 2015 Lip ccRCC M 60 No
Sikka et al (185) 2013 Gingiva ccRCC M 73 Yes
Ganini et al (186) 2012 Tongue ccRCC M 70 No
Lutcavage et al (187) 1984 Hard palate RCC M 55 No
Azam et al (188) 2008 Tongue ccRCC M 78 Yes
Basely et al (189) 2009 Tongue ccRCC F 46 No
Ahmadnia et al (190) 2013 Mandibular bone ccRCC M 57 Yes
Ord et al (191) 1990 Maxillary bone
Maxillary bone		 RCC
RCC		 M
M		 58
73
yes
Capodiferro et al (192) 2020 Gingiva
Tongue
Mandibular bone
Mandibular bone
Parotid
Parotid
Mandibular bone		 ccRCC
ccRCC
ccRCC
ccRCC
ccRCC
ccRCC
ccRCC		 F
M
M
M
M
F
M		 69
56
45
63
55
55
60		 No
No
No
No
No
No
No
Andabak Rogulj et al (193) 2018 Maxillary bone
Maxillary bone
Mandibular bone
Maxillary bone
Mandibular bone
 ccRCC
ccRCC
RCC
RCC
RCC		 M
M
F
M
F
 65
58
64
61
68		 No
No
No
No
No
Derakhshan et al (194) 2018 Maxillary boneMaxillary bone ccRCCccRCC M
M
 54
51		 yes
yes
Altuntaş et al (195) 2014 Tongue pRCC M 70 No
Amiruddin and Yunus (196) 2013 Tongue ccRCC M 66 No
Table 2. DATA ANALYSIS OF ORO-FACIAL METASTASES OF RENAL CELL CARCINOMA.
Table 2. DATA ANALYSIS OF ORO-FACIAL METASTASES OF RENAL CELL CARCINOMA.
SITE CASES
tongue 55 26%
mandibular bone 40 18.9%
gingiva 39 18.4%
maxillary bone 23 10.9%
parotid gland 22 10.4%
buccal mucosa 11 5.2%
lips 7 3.3%
hard palate 6 2.8%
soft palate 2 0.9%
masticatory space 2 0.9%
submandibular gland 2 0.9%
lymph nodes 1 0.4%
tonsil 1 0.4%
oral floor 1 0.4%
GENDER CASES
male 148 70.1%
female 63 29.85%
Table 3. METASTASES OF CLEAR CELL RENAL CELL CARCINOMA TO THE ORO-FACIAL TISSUES AND CLINICAL RADIOLOGICAL PRESENTATION.
Table 3. METASTASES OF CLEAR CELL RENAL CELL CARCINOMA TO THE ORO-FACIAL TISSUES AND CLINICAL RADIOLOGICAL PRESENTATION.
Authors Site Gender Age First sign of Disease Clinical presentation Radiological aspect
Kalinin et al (42) Tongue F 58 yes Painless nodule -
Nishii et al (43) Maxillary bone M 89 No Swelling of the left maxillary ginguva Osteolytic area
Kundu et al (48) Parotid M 61 Yes Facial weakness and post-auricular pain -
Park and Hlivko (49) Parotid F 83 No infra-auricular swelling -
Göğüş et al (51) Parotid F 59 No pre-auricular swelling -
Torres-Carranza et al (52) Tongue F 49 No Pedunculated painless mass -
Newton et al (53) Parotid F 74 No Pre- auricular swelling -
Yoshitomi et al (54) Tongue M 47 Yes mass -
Morvan et al (55) Tongue F 48 No Painful mass -
Serouya et al (57) Submandibular gland M 60 No Submandibular mass -
Özkiriş et al (60) Cervical lymph nodes F 56 No Multiple mass in neck region -
Ghazali et al (61) Tongue F 64 No Painless mass -
Lau et al (62) Parotid F 79 No Parotid mass -
Mazeron et al (63) Tongue M 66 Yes Exophytic mass -
Yanlan et al (64) Parotid F 44 Yes Painless mass in parotid region -
Udager and Rungta (65) Parotid M 64 No Painless mass in parotid region -
Abbaszadeh-Bidokhty et al (66) Tongue M 80 No Swelling -
Kotak and Merrick (67) Lip M 64 No Asymptomatic swelling -
Suojanen et al (68) Lip M 71 No Spontaneously bleeding mass -
Kudva et al (69) Buccal mucosa F 36 Yes Painful ulcer Bone erosion
Georgy et al (70) Gingiva M 63 Yes Gingival nodule -
Nifosì et al (71) Gingiva M 58 No small painful reddish indurated swelling -
Altinel et al (74) Tongue M 67 Yes Tongue mass -
Syryło et al (75) Lip M 59 Yes Upper lip nodule -
Gil-Julio et al (76) Buccal mucosa M 65 No Discomfort in left cheek -
Shirazian and Bahrami (77) Gingiva M 45 Yes red-purple rubbery, sessile exophytic lesion with smooth surface Saucer shape resorption of the crestal bone
Carmen and Korbitz (79) Tongue M 77 No Painful mass -
Okabe et al (84) Tongue M 58 No Painless mass -
Ziyada et al (86) Tongue M 59 Yes Tongue mass -
Aguirre et al (88) Tongue F 82 Yes swelling -
Tomita et al (90) Tongue M 50 No Hemorragic mass -
Navarro et al (91) Tongue M 62 No Exophytic lesion -
Mekni et al (92) Tongue M 63 No NA -
Kyan and Kato (93) Tongue M 66 No Tongue mass -
Huang et al (94) Parotid F 56 No Bilateral enlarging mass in parotid region -
Kella et al (98) Tongue F 67 Yes NA -
Branch and Norton (101) Gingiva F 64 Yes Epulis-like mass -
Persson and Wallenius (103) Gingiva F 60 No Rapidly growing swelling -
Buchner and Begleiter (105) Gingiva M 46 No Rapidly growing mass -
Fay and Weir (107) Gingiva F 18 No Soft, fluctuant mass Demarcated radiolucency
Zohar et al (108) Gingiva F 54 Yes Soft, friable red mass -
Corsi et al (35) Lip M 44 No NA -
Salman and Darlington (112) Hard palate F 54 No Ulcerated nodule NA
Mallet (113) Mandibular bone F 72 Yes Pain and swelling Osteolytic area
Godby et al (115) Gingiva M 45 No Gingival mass Bone resorption
Nagayama and Oka (117) Mandibular bone
Hard palate		 F
F		 61
43		 yes
 Swelling
Palate’s perforation		 Osteolytic area
NA
Susan et al (118) Hard palate
Hard palate		 M
M		 53
62		 yes
yes		 Swelling
Pedunculated lesion		 NA
NA
Matsumoto and Yanagihara (119) Maxillary bone
Maxillary bone		 M
M		 73
48		 yes
yes
Cheek’s swelling
epistaxis		 Osteolytic area
NA
Pick et al (120) Mandibular bone M 71 Yes Swelling mixed radiolucent and radiopaque lesion
Jones and al (123) Mandibular bone
Mandibular bone		 F
F		 62
52		 yes
yes		 Swelling
Swelling		 osteolytic area
osteolytic area
Fandella et al (124) Maxillary bone M 62 Yes epistaxis NA
Heinroth et al (130) Maxillary bone F 53 yes Painful swelling opacity in the maxillary sinus
Madison and Frierson (131) Tongue
Tongue		 M
M		 29
63		 No
No		 NA
NA		 -
-
Kishore et al (132) Lip M 54 No swelling -
Walsh et al (135) Tongue M 63 No Pedunculated lesion -
Mrena et al (136) Parotid
 F
 58
 Yes
 Non-tender nodule -
Aljawad et al (137) Parotid M 65 No Non-tender mass -
Migliorelli et al (138) Maxillary bone F 54 Yes Facial pain Bone erosion
Maschino et al (139) Maxillary bone
Maxillary bone
Parotid
 M
F
M
 73
84
78
 No
No
No
 Exophytic mass
Pain, discomfort
Rapid growth mass		 Osteolytic lesion
NA
Wallace et al (140) Soft palate M 50 No Globular lesion -
Ludwig et al (141) Mandibular bone M 78 Yes Painful swelling and paresthesia NA
Melnick et al (142) Parotid M 72 Yes Parotid mass -
Borghi et al (143) Parotid M 68 No Painless swelling -
Seijas et al (144) Parotid M 67 Yes Painless mass -
Goel et al (145) Tongue M 62 Yes Swelling -
Schwab and Lee (149) Maxillary bone M 63 No Bilateral, friable masses with a foul odor NA
Guimarães et al (152) Gingiva F 31 No Painful growth Enlargement of the periodontal ligament
Nisi et al (154) Tongue
Buccal mucosa		 M
M		 61
71		 yes
yes		 Swelling
Large mass		 -
-
Lang et al (155) Tongue M 45 No Pedunculated mass -
Marioni et al (157) Tongue F 87 No Exophytic, ulcerated mass -
Van der Wall et al (158) Soft palate
Maxillary bone
Mandibular bone
Buccal mucosa		 F
F
M
M		 62
64
48
67		 No
No
No
No		 NA
NA
NA
NA		 -
-
-
-
Makos and Psomaderis (27) Gingiva M 63 No Epulis-like mass -
Morii (161) Buccal mucosa M 63 No NA -
Maestre-Rodríguez et al (164) Gingiva M 52 Yes Granulomatous gingival lesion -
Will et al (165) Floor of mouth M 63 no Indurated mass -
Patel et al (167) Gingiva F 59 yes pink-red, oval, ulcerated lesion with a white pseudomembranous surface -
Massaccesi et al (169) Tonsil M 76 yes dysphagia -
Shinozaki et al (170) Mandibular bone F 76 No swelling Multilocular bone destruction
Ohmura et al (171) Mandibular bone M 53 No NA NA
Nakano et al (172) Gingiva M 72 No swelling -
Ficarra et al (173) Wharton’s duct M 73 No Movable mass in the floor of the mouth -
Tunio et al (174) Tongue M 35 No Painless swelling -
Milner et al (175) Hard palate M 67 Yes Irregularly shaped lump none
Santana et al (176) Gingiva M 63 Yes Double lobe nodule Radiolucent lesion
Kizaekka et al (177) Tongue M 77 No Pedunculated lesion -
Paraskevopoulos et al (178) Mandibular bone M 72 Yes NA -
Morita et al (179) Buccal mucosa M 75 No Swelling and facial asymmetry -
Prol et al (180) Mandibular bone
Gingiva
Gingiva
Masticatory space		 M
M
F
M		 55
62
52
65		 No
No
No
No		 Mass
Mass
NA
Mass		 NA
-
-
NA
Ali and Mohamed (182) Gingiva M 60 Yes Gingival mass Erosive bone changes
Selvi et al (183) Gingiva M 51 No Rapidly progressive, painless exophytic lesion Destruction of the alveolar bone
Jatti et al (184) Lip M 60 No Ulcerated nodule -
Sikka et al (185) Gingiva M 73 Yes Multiple painless swelling -
Ganini et al (186) Tongue M 70 No Ulcerated lesion -
Azam et al (188) Tongue M 78 Yes Pedunculated lesion, difficulty in swallowing solid -
Basely et al (189) Tongue F 46 No Swelling on the left side of the neck -
Ahmadnia et al (190) Mandibular bone M 57 Yes Swelling, trismus Radiolucent lesion
Capodiferro et al (192) Gingiva
Tongue
Mandibular bone
Mandibular bone
Parotid
Parotid
Mandibular bone		 F
M
M
M
M
F
M		 69
56
45
63
55
55
60		 No
No
No
No
No
No
No		 Large fungating mass
Large fungating mass
-
-
growing mass
growing mass
-		 Bone rarefaction
-
Osteolytic area
Osteolytic area
-
-
Osteolytic area
Andabak Rogulj et al (193) Maxillary bone
Maxillary bone
 M
M
 65
58
 No
No
 Mobility of tooth
Exophytic lesion		 NA
NA
Derakhshan et al (194) Maxillary boneMaxillary bone M
M
 54
51		 yes
yes		 Pain and swelling
Polypoid mass		 intraosseous radiolucency
Amiruddin and Yunus (196) Tongue M 66 No Painless mass -
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