Malignant mesothelioma metastatic to the oral region and latest topics (Review)

  • Authors:
    • Yuichi Ohnishi
    • Tomoko Fujii
    • Tsukasa Sakamoto
    • Masahiro Watanabe
    • Tomokazu Motohashi
    • Hirohito Kubo
    • Masahiro Nakajima
  • View Affiliations

  • Published online on: September 7, 2020     https://doi.org/10.3892/mco.2020.2131
  • Article Number: 61
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Malignant mesothelioma (MM) is a rare neoplasm with poor prognosis that usually develops after exposure to asbestos, and is characterised by aggressive local invasion and metastatic spread. While metastasis to the oral cavity is very rare, a total of 23 cases of MM metastasising to the oral cavity were identifed. Among those, the tongue was the most common site of metastasis (39.1%), and frequently involved the epithelioid MM cell type. Recent studies have elucidated the mechanisms underlying the development of MM. Chronic inflammation has been implicated in promoting MM growth and was shown to play a key role by driving the release of high mobility group box protein 1 following asbestos deposition. Inherited heterozygous germline mutations in the deubiquitylase BRCA‑associated protein 1 were shown to increase the incidence of MM in some families. Infection by the simian virus 40 was also found to be associated with the occurrence of MM. Moreover, the increasing incidence rates of MM, together with its propensity to metastasise to the oral cavity, indicate that clinicians and pathologists should be highly aware of this disease. Furthermore, identification of novel serum biomarkers would enable better screening and treatment of MM, and improve the survival outcomes.

1. Introduction

Malignant mesothelioma (MM) is a rare tumor derived from the mesothelial cells lining the serosal surfaces of body cavities. There is currently no effective treatment for MM, and the majority of the patients succumb to the disease within 12-17 months post-diagnosis (1), as MM is resistant to most known treatment modalities (2). The majority of the MM variants have been reported to be associated with asbestos exposure (3,4). The incidence rates are higher among men compared with those among women (5:1), and most patients are aged 40-70 years at the time of diagnosis (5). Men exhibit a high association between the development of MM and exposure to asbestos, and they most commonly present with pleural MM. By contrast, MM in women is less likely to be associated with asbestos exposure (5). Similar to carcinoma, MM predominantly metastasises by direct invasion of adjacent tissue, in addition to lymphatic and haematogenous dissemination. Distant metastases are more common with the sarcomatous variant compared with other variants (6), whereas metastases to the oral cavity are rare. The aim of the present review was to assess the development of oral metastasis from MM and discuss the latest topics.

2. Clinical symptoms

MM affects the tissues surrounding the lungs, which are prone to inflammation caused by other agents, such as metallic ducts, gases, fumes and aerosols of biological agents; this may delay the correct diagnosis of MM by several months. Common symptoms include pain in the chest or lower back, shortness of breath, cough, difficulty swallowing, hoarseness, swelling of the face and arms, presence of lumps under the chest skin and unexplained weight loss. In the majority of the patients, the symptoms persist for at least a few months before diagnosis. The findings on chest X-ray, computed tomography (CT) and positron emission tomography (PET)-CT examination generally include pleural thickening, exudation and pleural masses. The early stages of pleural MM are associated with multiple tumor nodules on the serosal and parietal surface of the viscera, which may merge at a later stage (5).

3. Aetiology

Asbestos fibres initiate mitosis in mesothelial cells, inducing multiple chromosomal abnormalities, such as those of chromosome 22(7). To investigate the mechanism of inactivation of neurofibromatosis type 2 (NF2), a tumor suppressor gene implicated in MM, loss of heterozygosity analysis was performed with two microsatellite markers located in the vicinity of the NF2 locus on chromosome band 22q12(8). Of the 25 cell lines, 18 (72%) exhibited loss at one or both loci of NF2. All the cases exhibiting mutations and/or aberrant expression of NF2 displayed allelic loss, suggesting that inactivation of NF2 in MM occurs via a two-hit mechanism. Increased production of cytokines and growth factors and inactivation of tumor suppressor genes are associated with exposure to asbestos fibres.

It was previously suggested that alterations in the p53 and retinoblastoma (Rb) tumor suppressor pathways (9), and mutations in the NF2 and INK4a tumor suppressor genes, are closely associated with the pathogenesis of MM (10,11). Moreover, asbestos enhances the proliferation of mesothelial cells in culture via the production of tumor necrosis factor-α (TNF-α), and induces second messenger signalling via the nuclear transcription factor NF-κB (12). Asbestos-induced carcinogenesis is linked to chronic inflammation. The deposition of a sufficient number of asbestos fibres is accompanied by the release of pro-inflammatory molecules from macrophages and mesothelial cells, particularly high mobility group box protein 1 (HMGB-1) and TNF-α.

Other studies suggest that non-asbestos-related mechanisms may contribute to the development of MM. For example, simian virus 40 (SV40) has been shown to induce MM in experimental animals (13). Furthermore, treatment of other cancers with radiotherapy or exposure to erionite fibres have also been shown to promote the development of MM (14). However, how MM is initiated in individuals who have not been exposed to asbestos or received radiotherapy treatment for other cancers remains elusive (14). The findings mentioned above indicate that genetic predisposition, radiotherapy and viral infection are co-factors that can, either alone or in combination with asbestos and erionite, initiate the development of MM (15).

4. Pathology

MM arises following malignant transformation of the mesothelial cells that form the pleura and visceral peritoneum. MM may also develop, albeit rarely, from the mesothelial cells that line the pericardium and testicular sheath membrane. These mesothelial cells are undifferentiated and, hence, possess differentiation potential. Therefore, MM cells exhibit various morphologies, such as the epithelial-like, spindle-shaped cell (sarcomatoid or fibrotic MM) or biphasic variants (16), which are rare and may be misdiagnosed during routine pathological examination, such as synovial sarcoma and small-cell carcinoma. Histologically, epithelioid MM is less invasive compared with the spindle-shaped cell variants (16). The biphasic variants generally behave according to their main histological component, and fibrotic MM tends to be more malignant (16). Bueno et al (17) reported that recurrent gene fusions and splice alterations are frequent mechanisms underlying the inactivation of NF2, BRCA-associated protein 1 (BAP1) and the histone methyltransferase SET domain containing 2 (SETD2). Furthermore, with integrated analyses, Bueno et al identified alterations in the Hippo, mammalian target of rapamycin, histone methylation, RNA helicase and p53 signalling pathways in MM.

Despite identifying these alterations, patients with MM are often misdiagnosed. As reviewed by a thoracic pathologist in France, only 67% of the cases were initially diagnosed as MM (18). Additionally, the spindle-shaped cell variant is difficult to diagnose, although immunohistochemistry (IHC) may improve the diagnostic accuracy. Cellular proteins, such as calretinin and Wilms' tumor 1 (WT1), serve as positive markers for MM, along with thyroid transcription factor 1 (TTF-1), p63, epithelial glycoprotein 2 and carcinoembryonic antigen (CEA), which may help distinguish most other carcinomas from MM. WT1 is considered as a specific marker for MM, and tumor cells displaying nuclear staining for WT1 and calretinin, together with strong membranous staining for cytokeratin (CK) CAM5.2, have been characterised as MM cells (19,20).

5. Immunohistochemical characteristics

Studies suggest that the use of antibodies with appropriate negative and positive controls may improve the accuracy of MM diagnosis (21-28). Normal mesothelial cells express low molecular weight CKs and vimentin; hence, tumors expressing both types of intermediate filaments may have a mesothelial origin. The most sensitive antibodies for identifying pulmonary adenocarcinoma are MOC-31 and BG8 (both 93%), while the most specific are monoclonal antibodies against CEA (97%) and TTF-1 (100%). Furthermore, antibodies against CK5/6 (83%) and human bone marrow endothelial cells (HBME-1) (85%) are useful for the identification of epithelioid MM. However, none of these antibodies can differentiate between pulmonary adenocarcinoma and MM on their own. Therefore, the use of a combination of highly sensitive and specific antibodies is recommended (21).

All MM variants have been shown to express glucose transporter 1 (GLUT-1). GLUT-1 is absent during reactive mesothelial proliferation, which is associated with hyperplasia and neoplasia. Thus, GLUT-1 may allow distinguishing reactive mesothelial nodules from MM (22,23).

The majority of MMs exhibit positive staining for keratin markers (AE1/AE3, CK5/6, CK7, CK19 and CAM 5.3) (24), among which CK 5/6 is the most useful for the diagnosis of MM. Furthermore, MMs generally stain positive for epithelial membrane antigen and vimentin (25).

Calretinin is expressed in neuronal tissues, and often shows a helix-loop-helix domain structure expressed in the epithelioid MM variant (26). While both cytoplasmic and nuclear staining of calretinin may be observed, nuclear staining confirms MM (25). WT1 is expressed in normal mesothelial cells and shows nuclear positivity in most cases of epithelioid MM (20,23). Anti-HBME-1, an antibody that recognises normal and malignant epithelioid mesothelial cell antigens, may stain positive for another protein, mesothelin, in the microvilli (27,28). Antibodies against two or more epithelial markers generally allow identification of carcinomas, such as monoclonal and polyclonal anti-CEA, Ber-EP4, B72.3, CD15, MOC-31, TTF-1, BG8 and others, and two or more mesothelial markers, such as CK-5/6, calretinin, HBME-1, thrombomodulin, WT1, mesothelin, D2-40 and podoplanin, confirm the diagnosis of MM (25). CEA and TTF-1 serve as negative markers (23). Sarcomatoid MM stains positive for CK and vimentin, and few cases are positive for calretinin (25). Moreover, all types of MM are negative for neutral mucin on IHC.

Serum biomarkers are extensively used for the screening and identification of MM patients with known exposure to asbestos (28,29). Furthermore, measuring the serum levels of osteopontin and megakaryocyte potentiating factor may serve as a non-invasive method for assessing the response of patients to treatment (28).

6. Oral metastases from pleural MM

A comprehensive search for MMs that metastasise to the oral cavity was performed using the PubMed database and combinations of ‘mesothelioma’, ‘metastatic’ and ‘oral’ as the search terms. The reference lists of the related publications were also manually reviewed. The outcome of the literature search for cases of oral metastasis is summarised in Table I (30-50). A total of 23 cases of MM were metastatic to the oral cavity, and 11 cases were reported in different contexts on two occasions. Furthermore, 19 patients were men and the ratio of men to women was 4.8:1. The mean age at diagnosis was 61.7 years (range, 35-75 years). One patient (case 14) whose oral metastatic lesions were the first evidence of MM (43) was ultimately diagnosed with pleural MM. Furthermore, 9 of the 23 studies presented patients with tumor metastasis to the tongue (39.1%), most of which were of the epithelioid type. The epitheloid type is the most common variant of diffuse MM, and is also frequently observed in oral metastases. While these data may aid with diagnosis, it is necessary to differentiate MM from squamous cell carcinoma, which accounts for the majority of primary oral malignant lesions. A possible explanation for the frequent metastases to the tongue may be the rich capillary network, particularly where the fragmented basement membranes of proliferating capillaries allow easier penetration by malignant cells compared with mature blood vessels. Additionally, the tongue is well vascularised and it has been hypothesized that this may create favourable conditions for the establishment of the malignant cells (19). Moreover, Piattelli et al (32) suggested that the tongue may be the preferred site due to the abundant blood supply present in its posterior third. Thus, given the posterior location of the lesions, the symptoms may be vague and the lesions may be difficult to identify and palpate.

Table I

Details of reported cases of malignant mesothelioma metastastic to the oral region.

Table I

Details of reported cases of malignant mesothelioma metastastic to the oral region.

Case no.First authorSexAge at diagnosis (years)Oral siteHistopathology of metastasisImmunopathology (+)Immunopathology (-)(Refs.)
1KerpelM732x2-cm submucosal mass of ventral tongueEpithelioid with glandular areasCytokeratinVimentin, CEA, B72.3(30)
2KerpelM45Mass on lower gingiva with assosiated bone loss of the mandibleEpithelioid with glandular areasCytokeratin, focally vimentinLeu-M1, CEA, B72.3(30)
3SproatM48Mandibular alveolusSarcomatoidVimentin, focally cytokeratin (CAM5.2)CEA, EMA(31)
4PiattelliM52Lesion on lateral tongueEpithelioidVimentin, cytokeratinCEA, B72.3, Leu-M1(32)
5Garcia-ReijaM63Lower gingivaEpithelioid with glandular areasVimentinNot stated(33)
6CassarinoM640.8x0.7-cm ulcerated nodule of the upper lipEpithelioid with glandular areasCytokeratins (AE1/3,CK19), HBME-1CEA, BER-EP4, B72.3, Leu-M1(34)
7ZanconatiM71Ulcerated mass on dorsolateral tongueEpithelioidKeratins, EMA, vimentin, thrombomodulin, calretininNot stated(35)
8SoyuerF500.8-cm mass in the buccal mucosaNot statedCytokeratin cocktail, CEA, Leu-M1, B72.3, EMA, calretinin, vimentinNot stated(36)
9TerakadoM53Periapical radiolucency associated with mandibular third molarSarcomatoidVimentin, cytokeratin-AE1/3CD34, CK10, BER-EP4(37)
10ThoM702x1-cm lession on lateral tongueBiphasicCalretinin, mesothelin, CK5CEA, TTF-1, thrombomodulin(38)
11HigginsonM692.2x0.9-cm submucosal mass in floor of mouth with involvement of the tongueEpithelioidCalretinin, CK5/6, AE1/3, CD15BER-EP4, mucicarmine(39)
12HashitaniF590.5x0.5-cm nodule on dorsal tongueEpithelioid with glandular areasCK5/6, AE1/3, EMA, calretinin, HBME-1, mesothelin, TTF-1Not stated(40)
13KirkeM713-cm submucosal mass in floor of mouth with involvement of the tonguePoorly differentiated with squamoid cellsMNF116 keratin, EMA, CK5, calretininNot stated(41)
14MurrayF461x0.5-cm nodule on dorsal tongueEpithelioid with glandular areasCK7, CK19, AE1/3, CA125, EMACD31, CD34, Bcl2, GCDFP15, alpha actin, CK20, S100, CDX2, CEA, ER, TTF-1(42)
15SinonM650.8-cm submucosal mass in buccal mucosaEpithelioid with pseudoglandular areasCK5/6, CK7, CK19, CAM5.2, EMA, calretinin, WT1Not stated(43)
16BillèF68Mandibular alveolusSarcomatoidWT1, calretininClaudin-4, BER-EP-4(44)
17ArslanM59Retromolar trigone areaEpithelioidCalretininNot stated(45)
18OhnishiM623x2.5-cm mass in maxillary gingivaEpithelioidVimentin, focally cytokeratinCEA, EMA(46)
19MoserM751.5-cm mass in lower right molar gingivaEpithelioidCalretinin, CK5/6BER-EP4(47)
20SawakiM753.8x2-cm mass in upper gingivaEpithelioidVimentin, focally keratin AE1/3CEA, LCA, CD3, CD20, CD79, S-100, HMB-45(48)
21VazquezM663-cm mass in the anterior 2/3 of the tongueEpithelioidNot statedNot stated(49)
22ArslanM59Retromolar trigone areaEpithelioidCalretininNot stated(45)
23TanakaM660.5-cm mass in the left buccal gingiva of the maxillaEpithelioidCalretinin, thrombomodulin, CAM5.2MOC31, BER-EP4, TTF-1(50)

[i] CK, cytokeratin; EMA, epithelial membrane antigen; CEA, carcinoembryonic antigen; LCA, leukocyte common antigen; TTF-1, thyroid transcription factor 1; HMB-45, human melanoma black 45; WT1, Wilms' tumor 1; HBME-1, Hector Battifora mesothelial epitope-1; ER, estrogen receptor; BER-EP4, anti-human epithelial antigen; GCDFP15, gross cystic disease fluid protein-15.

The sarcomatoid variant of MM was identified in 3 cases, and was located at the mandibular region. Piattelli et al (32) reported that sarcomatous type tumors tend to metastasise haematogenously, similar to sarcoma, to the small intestine, axillary lymph nodes, mediastinal lymph nodes and mandible. Moreover, the haematopoietic areas in the mandible favour early deposition of tumor cells. Additionally, the bones with red marrow are common sites for metastatic adhesion, and red marrow is usually found in the posterior part of the mandible. Consistently, 3 of the cases of sarcomatoid MM presented herein involved the posterior part of the mandible. In such cases, it is difficult to distinguish inflammation and osteomyelitis from metastatic lesions. When a patient presents with a highly metastatic neoplasm in any organ, careful examination of the jaws should also be considered.

The diagnosis of primary MM is established based on the combination of clinical, imaging (CT, magnetic resonance imaging and PET-CT) and histopathological characteristics. The diagnosis of secondary MM in the oral region may be confirmed more readily in cases with a known history of primary MM. However, it may still be difficult to diagnose this disease, and it may be necessary to refer to the location and symptoms of the lesion, as described above. Additionally, both the primary and metastatic lesions of MM can be confirmed by immunostaining. The use of at least 2 positive (e.g., calretinin and WT1) and 2 negative MM markers (e.g., CEA and TTF1), along with a broad-spectrum CK as an initial screening panel, is recommended for confirmation (24,27). The results of immunostaining for all markers are summarised in Table I. The IHC markers used to distinguish between oral squamous cell carcinoma and MM are listed in Table II.

Table II

Summary of immunohistochemical markers useful for distinguishing between MM and OSCC.

Table II

Summary of immunohistochemical markers useful for distinguishing between MM and OSCC.

MarkerMMOSCC
CK20-+
CEA-+
Vimentin+-
Calretinin+-
HBME-1+-

[i] MM, malignant mesothelioma; OSCC, oral squamous cell carcinoma CK, cytokeratin; CEA, carcinoembryonic antigen; HBME-1, Hector Battifora mesothelial epitope-1.

The optimal method for treating tumors metastasising to the oral cavity has yet to be established. Moreover, considering the aggressive nature of MM and its poor prognosis, the treatment for metastasis must be determined based on holistic assessment of the invasiveness and residual functional disruption after surgery, length of survival and quality of life (QoL). Therefore, an accurate diagnosis is crucial for avoiding unnecessary aggressive surgery and preserving the QoL of the patients.

7. Asbestos and MM

Epidemiological and experimental studies that have primarily focused on asbestos fibre research over the past several decades, indicate a strong association between exposure to asbestos fibres and the occurrence of MM (3,51). Asbestos is a collective term referring to several types of mineral fibres that were used industrially in the 1970s (52). Several fibres have been shown to act as carcinogens, and their use has been largely unrestricted (53). The precise mechanism remains to be elucidated, although the role of chronic inflammation in promoting asbestos-induced carcinogenesis has been established (54). Two human MM cell lines were used to generate a SCID mouse xenograft model to assess the time-dependent patterns of inflammation and tumor formation (54). Inoculation of MM cells into the mice resulted in increased levels of interleukin (IL)-6, IL-8, basic fibroblast growth factor and vascular ndothelial growth factor. Furthermore, cytokine production was confirmed by an increase in neutrophil levels. These results indicate that the development of MM is dependent on inflammation and cytokine production. Furthermore, the exposure of human mesothelial (HM) cells, derived from pleural effusion of non-malignant patients, to asbestos induced necrotic cell death along with release of HMGB-1. This result suggests that asbestos-induced inflammation promotes mesothelial cell transformation (12,55). HMGB-1, a danger-associated molecular pattern (DAMP) molecule, which is normally present in the nucleus, mediates the initiation of asbestos-induced MM. HMGB-1 acts as a non-histone chromatin-binding protein that regulates nucleosome organisation and chromatin structure. As a DAMP, HMGB-1 is either released upon necrosis of HM cells, or secreted by immune cells or cancer cells, and initiates inflammation in response to asbestos. Moreover, asbestos persists in the body over a prolonged time period, initiating a chain reaction of chronic cell death and inflammation that promotes the development of MM (56). Thus, HMGB-1 acts as an important factor in the onset and maintenance of chronic inflammation causing MM cell proliferation. Additionally, high levels of HMGB-1 may be found in the serum of patients with MM and those exposed to asbestos. Furthermore, hyperacetylation of HMGB-1 is associated with its release by inflammatory cells. Comparative analysis suggests that the levels of HMGB-1 and fibrin-3 may allow distinguishing between patients with MM and those with other causes of pleural effusion. Taken together, these observations suggest that analysing acetylated HMGB-1 levels may enable selective identification of patients with MM and those exposed to asbestos (57).

8. BAP1 and MM

Erionite was shown to cause MM and death in >50% of the Turkish population exposed, strengthening the gene x environment hypothesis (58,59). Furthermore, certain American families were also found to be susceptible to MM, despite not being exposed to asbestos. The analysis suggested that these individuals carried germline mutations in BAP1, which also increased the risk of uveal melanoma or other carcinomas, such as renal cell carcinoma, basal cell carcinoma and lung adenocarcinoma, as well as that of MM, the risk of which increased further upon exposure to asbestos (60). These results may provide a basis for identifying individuals at higher risk of developing MM and improve diagnosis and treatment. Carriers of the BAP1 germline mutation exhibit early onset of characteristic benign melanocytic BAP1-mutated atypical intradermal tumors (61,62). Moreover, families with the BAP1 germline mutation present early in life with a novel cancer syndrome characterised by benign melanocytic skin tumors, and are at a higher risk of later developing MM, uveal melanoma, cutaneous melanoma, as well as other cancers (61). Furthermore, similar to other cancers, somatic mutations in BAP1 occur in >60% of sporadic MM cases, suggesting BAP1 to be one of the most commonly mutated genes in MM (63), regardless of the ethnic background or other clinical characteristics. IHC is considered to be an easily accessible and reliable method for detecting BAP1 status in MM biopsies.

Yoshikawa et al (64) have screened the genetic changes of chromosome 3p21 in 33 cases of MM using high-density array comparative genomic hybridisation (aCGH) and targeted next-generation sequencing (tNGS). The analysis identified recurrent biallelic genomic deletions in 46 genes on 3p21, where many deletions were distant and alternated with normal DNA segments as observed in chromothripsis, although independent deletion events may occur sequentially. Furthermore, mutations in BAP1, along with those in SETD2, PBRM1 and SMARCC1, were found to be frequent in MM. Moreover, that study provided the basis for the use of high-density aCGH and tNGS for precise estimation of the frequency and variety of inactivated genes in human cancers.

9. SV40 and MM

A study conducted in 1994 indicated that >60% of the MM samples carried SV40 DNA and expressed the SV40 large T (tumor) antigen. However, the percentage of positive samples ranged between 6 and 83%, which may be attributed to technical and geographical differences. For example, the presence of infectious SV40 in the polio vaccine administered to children in the former Soviet Union and other affected countries has been reported (65). However, according to the National Academy of Sciences Medical Research Institute, the evidence obtained were inadequate to firmly establish or exclude a causal association between the SV40-containing polio vaccine and cancer incidence. Furthermore, mechanical and animal experiments in HM cells support the role of SV40 and cofactors, such as asbestos fibres, to the pathogenesis of several cases of MM (66). Additionally, the lack of late viral gene expression may help SV40-transformed mesothelial cells to escape immune surveilance. Suppression of late viral gene products is considered to be an important step in viral carcinogenesis. Furthermore, when cells expressing p53 are infected with a DNA tumor virus, p53 binds to a viral tumor antigen (Tag). This Tag-p53 complex then binds to the insulin-like growth factor-1 (IGF-I) promoter with pRb and p300, and regulates transcription of the IGF-I gene to increase the expression of the IGF-1 receptor. The SV40 T antigen binds to and activates the IGF-1 receptor, thereby promoting tumor cell proliferation (67).

10. Conclusion

Based on the currently available information, the detailed mechanism underlying BAP1-induced carcinogenesis is expected to be elucidated in the near future. This may provide the opportunity to treat MM by inhibiting the components involved in the gene-environment interactions. A similar analysis of HMGB-1 or other biomarkers may allow stratification of asbestos-exposed patients at high risk and improve diagnosis and treatment. Moreover, genetic or biochemical tests for biomarker identification may also be of value in the treatment of MM patients with oral metastases. Our research group has focused on various aspects of MM, such as assessment of HMGB-1 and other biomarkers, identification of patients exposed to asbestos, and devising tests to identify patients with MM during the course of disease progression.

The predictions for occurrence of MM vary worldwide, with declining rates in France and the US, constant rates in Australia, and unclear in the UK (68,69). Furthermore, considering the latency period, precautionary measures to avoid exposure to asbestos may be effective in reducing the incidence of MM, particularly in the US (70). However, it is also predicted that the global incidence of MM may continue to increase, given the widespread exposure to asbestos in certain developing countries (71). Moreover, oral metastases from MM should also follow this trend and, although rare, may warrant differential diagnosis of the disease. Although a known previous diagnosis of MM may help oral cancer pathologists, precise diagnosis using histological and immunohistochemical analysis is recommended, in order to ensure avoiding unnecessary over treatment and improving the overall survival and QoL of the patients.

Acknowledgements

Not applicable.

Funding

No funding was received.

Availability of data and materials

Not applicable.

Authors' contributions

YO and TF designed the review. TS, MW, HK and TM were involved in the collection and collation of references. YO wrote, reviewed and edited the manuscript. MN critically revised the manuscript for intellectual content. All authors read and approved the final version of the manuscript.

Ethics approval and consent to participate

Not applicable.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

References

1 

Boutin C, Schlesser M, Frenay C and Astoul P: Malignant pleural mesothelioma. Eur Respir J. 12:972–981. 1988.PubMed/NCBI View Article : Google Scholar

2 

Sugarbaker DJ and Norberto JJ: Multimodality management of malignant pleural mesothelioma. Chest. 113 (Suppl 1):S61–S65. 1988.PubMed/NCBI View Article : Google Scholar

3 

Wagner JC, Sleggs CA and Marchand P: Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province. Br J Ind Med. 17:260–271. 1960.PubMed/NCBI View Article : Google Scholar

4 

Hanna L and Macbeth F: Mesothelioma. In: Practical Clinical Oncology. Hanna L, Crosby T and Macbeth F (eds). 1st edition. Cambridge University Press: Cambridge, New York, pp328-333, 978-0-521-61816-8, 2008.

5 

Galateau-Salle F, Brambilla E and Cagle PT: Clinical aspects of mesothelioma. In: Pathology of Malignant Mesothelioma. Galateau-Salle F (ed). Springer, London, pp31-39, 978-1-84628-012-2, 2006.

6 

Law MR, Hodson ME and Heard BE: Malignant mesothelioma of the pleura: Relation between histological type and clinical behaviour. Thorax. 37:810–815. 1982.PubMed/NCBI View Article : Google Scholar

7 

Hesterberg TW and Barrett JC: Induction by asbestos fibers of anaphase abnormalities: Mechanism for aneuploidy induction and possibly carcinogenesis. Carcinogenesis. 6:473–475. 1985.PubMed/NCBI View Article : Google Scholar

8 

Cheng JQ, Lee WC, Klein MA, Cheng GZ, Jhanwar SC and Testa JR: Frequent mutations of NF2 and allelic loss from chromosome band 22q12 in malignant mesothelioma: Evidence for a two-hit mechanism of NF2 inactivation. Genes Chromosomes Cancer. 24:238–242. 1999.PubMed/NCBI

9 

Cote RJ, Jhanwar SC, Novick S and Pellicer A: Genetic alterations of the p53 gene are a feature of malignant mesotheliomas. Cancer Res. 51:5410–5416. 1991.PubMed/NCBI

10 

Zucali PA, Ceresoli GL, De Vincenzo F, Simonelli M, Lorenzi E, Gianoncelli L and Santoro A: Advances in the biology of malignant pleural mesothelioma. Cancer Treat Rev. 37:543–58. 2011.PubMed/NCBI View Article : Google Scholar

11 

Papp T, Schipper H, Pemsel H, Bastrop R, Muller KM, Wiethege T, Weiss DG, Dopp E, Schiffmann D and Rahman Q: Mutational analysis of N-ras, p53, p16INK4a, p14ARF and CDK4 genes in primary human malignant mesotheliomas. Int J Oncol. 18:425–433. 2001.PubMed/NCBI View Article : Google Scholar

12 

Yang H, Bocchetta M, Kroczynska B, Elmishad AG, Chen Y, Liu Z, Bubici C, Mossman BT, Pass HI, Testa JR, et al: TNF-alpha inhibits asbestos induced cytotoxicity via a NF-kappaB-dependent pathway, a possible mechanism for asbestos-induced oncogenesis. Proc Natl Acad Sci USA. 103:10397–10402. 2006.PubMed/NCBI View Article : Google Scholar

13 

Cicala C, Pompetti F and Carbone M: SV40 induces mesotheliomas in hamsters. Am J Pathol. 142:1524–1534. 1993.PubMed/NCBI

14 

Jasani BI and Gibbs A: Mesothelioma not associated with asbestos exposure. Arch Pathol Lab Med. 136:262–7. 2012.PubMed/NCBI View Article : Google Scholar

15 

Cavazza A, Travis LB, Travis WD, Wolfe JT III, Foo ML, Gillespie DJ, Weidner N and Colby TV: Post-irradiation malignant mesothelioma. Cancer. 77:1379–1385. 1996.PubMed/NCBI View Article : Google Scholar

16 

Carbone M, Ly BH, Dodson RF, Pagano I, Morris PT, Dogan UA, Gazdar AF, Pass HI and Yang H: Malignant mesothelioma: Facts, myths, and hypotheses. J Cell Physiol. 227:44–58. 2012.PubMed/NCBI View Article : Google Scholar

17 

Bueno R, Stawiski EW, Goldstein LD, Durinck S, De Rienzo A, Modrusan Z, Gnad F, Nguyen TT, Jaiswal BS, Chirieac LR, et al: Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations. Nat Genet. 48:407–416. 2016.PubMed/NCBI View Article : Google Scholar

18 

Goldberg M, Imbernon E, Rolland P, Gilg Soit Ilg A, Savès M, de Quillacq A, Frenay C, Chamming's S, Arveux P, Boutin C, et al: The French National Mesothelioma Surveillance Program. Occup Environ Med. 63:390–395. 2006.PubMed/NCBI View Article : Google Scholar

19 

Carbone M, Shimizu D, Napolitano A, Tanji M, Pass H, Yang H and Pastorino S: Positive nuclear BAP1 immunostaining helps differentiate nonsmall cell lung carcinomas from malignant mesothelioma. Oncotarget. 7:59314–59321. 2016.PubMed/NCBI View Article : Google Scholar

20 

Guo Z, Carbone M, Zhang X, Su D, Sun W, Lou J, Gao Z, Shao D, Chen J, Zhang G, et al: Improving the Accuracy of Mesothelioma Diagnosis in China. J Thorac Oncol. 12:714–723. 2017.PubMed/NCBI View Article : Google Scholar

21 

King JE, Thatcher N, Pickering CAC and Hasleton PS: Sensitivity and specificity of immunohistochemical markers used in the diagnosis of epithelioid mesothelioma: A detailed systematic analysis using published data. Histopathology. 48:223–232. 2006.PubMed/NCBI View Article : Google Scholar

22 

Kato Y, Tsuta K, Seki K, Maeshima AM, Watanabe S, Suzuki K, Asamura H, Tsuchiya R and Matsuno Y: Immunohistochemical detection of GLUT1 can discriminate between reactive mesothelium and malignant mesothelioma. Mod Pathol. 20:215–220. 2007.PubMed/NCBI View Article : Google Scholar

23 

Brenner J, Sordillo PP, Magill GB and Golbey RB: Malignant mesothelioma of the pleura: review of 123 patients. Cancer. 49:2431–2435. 1982.PubMed/NCBI View Article : Google Scholar

24 

Husain AN, Colby TV, Ordóñez NG, Krausz T, Borczuk A, Cagle PT, Chirieac LR, Churg A, Galateau-Salle F, Gibbs AR, et al: Guidelines for pathologic diagnosis of malignant mesothelioma: A consensus statement from the International Mesothelioma Interest Group. Arch Pathol Lab Med. 133:1317–1331. 2009.PubMed/NCBI View Article : Google Scholar

25 

Galateau-Salle F, Brambilla E and Cagle PT: Classification and histologic features of epithelioid mesotheliomas. In: Pathology of Malignant Mesothelioma. Galateau-Salle F (ed). Springer, London, pp68-131, 978-1-84628-012-2, 2006.

26 

Doglioni C, Dei Tos AP, Laurino L, Iuzzolino P, Chiarelli C, Celio MR and Viale G: Calretenin: A novel immunocytochemical marker for mesothelioma. Am J Surg Pathol. 20:1037–1046. 1996.PubMed/NCBI View Article : Google Scholar

27 

Marchevsky AM: Application of immunohistochemistry to the diagnosis of malignant mesothelioma. Arch Pathol Lab Med. 132:397–401. 2008.PubMed/NCBI View Article : Google Scholar

28 

Pass HI and Carbone M: Current status of screening for malignant pleural mesothelioma. Semin Thorac Cardiovasc Surg. 21:97–104. 2009.PubMed/NCBI View Article : Google Scholar

29 

Ray M and Kindler HL: Malignant pleural mesothelioma: an update on biomarkers and treatment. Chest. 136:888–896. 2009.PubMed/NCBI View Article : Google Scholar

30 

Kerpel SM and Freedman PD: Metastatic mesothelioma of the oral cavity. Oral Surg Oral Med Oral Pathol. 76:746–751. 1993.PubMed/NCBI View Article : Google Scholar

31 

Sproat CP, Brown AE and Lindley RP: Oral metastasis in malignant pleural mesothelioma. Br J Oral Maxillofac Surg. 31:316–317. 1993.PubMed/NCBI View Article : Google Scholar

32 

Piattelli A, Fioroni M and Rubini C: Tongue metastasis from a malignant diffuse mesothelioma of the pleura: Report of a case. J Oral Maxillofac Surg. 57:861–863. 1999.PubMed/NCBI View Article : Google Scholar

33 

Garcia-Reija MF, Matilla JM, De Paz A, Sanchez-Cuellar A and Verrier A: Unusual metastasis to the mandibular alveolus of malignant pleural mesothelioma. Otolaryngol Head Neck Surg. 126:435–437. 2002.PubMed/NCBI View Article : Google Scholar

34 

Cassarino DS, Xue W and Shannon KJ: Widespread cutaneous and perioral metastases of mesothelioma. J Cutan Pathol. 30:582–585. 2003.PubMed/NCBI View Article : Google Scholar

35 

Zanconati F, Delconte A, Bonifacio-Gori D and Falconieri G: Metastatic pleural mesothelioma presenting with solitary involvement of the tongue: Report of a new case and review of the literature. Int J Surg Pathol. 11:51–55. 2003.PubMed/NCBI View Article : Google Scholar

36 

Soyuer I, Soyuer S, Canöz Ö, Coşkun S and Balkanli S, kun S and Balkanli S: Three patients with unusual metastases. Cytopathology. 15:58–62. 2004.

37 

Terakado N, Shintani S, Nakashiro K and Hamakawa H: Malignant pleural mesothelioma metastasis to the mandible. Int J Oral Maxillofac Surg. 33:789–800. 2004.PubMed/NCBI View Article : Google Scholar

38 

Tho LM and O'Rouke NP: Unusual metastases from malignant pleural mesothelioma. Clin Oncol (R Coll Radiol). 17(293)2005.PubMed/NCBI View Article : Google Scholar

39 

Higginson DS, Brahmer J, Tufano RP and Bajaj GK: Pleural mesothelioma metastatic to the tongue. J Clin Oncol. 25:2133–2135. 2007.PubMed/NCBI View Article : Google Scholar

40 

Hashitani S, Sakurai K, Takaoka K and Urade M: Metastatic malignant pleural mesothelioma of the tongue: Report of a case. Brit J Oral Maxillofac Surg. 47(247)2009.PubMed/NCBI View Article : Google Scholar

41 

Kirke D, Horwood K and Wallwork B: Floor of mouth and tongue metastasis from malignant pleural mesothelioma. ANZ J Surg. 80:556–558. 2010.PubMed/NCBI View Article : Google Scholar

42 

Murray LJ, Higham J, Suvarna SK, Craig GT, Bridgewater CH, Fisher PM and Thornhill MH: Oral presentation of malignant mesothelioma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 111:e21–e26. 2011.PubMed/NCBI View Article : Google Scholar

43 

Sinon SH, Rich AM, Hussaini HM, Yoon HS, Firth NA and Seymour GJ: Metastases to the oral region from pleural mesothelioma: Clinicopathologic review. Head Neck. 35:599–604. 2013.PubMed/NCBI View Article : Google Scholar

44 

Billè A, Platania M, Pelosi G, Padovano B, Quattrone P and Pastorino U: Gingival metastasis as first sign of multiorgan dissemination of epithelioid malignant mesothelioma. J Thorac Oncol. 9:1226–1229. 2014.PubMed/NCBI View Article : Google Scholar

45 

Arslan A, Ozcakir-Tomruk C, Deniz E and Akin O: A case report of metastasis of malignant mesothelioma to the retromolar trigone. World J Surg Oncol. 14(188)2016.PubMed/NCBI View Article : Google Scholar

46 

Ohnishi Y, Sugitatsu M, Watanabe M, Fujii T and Kakudo K: Metastasis of mesothelioma to the maxillary gingiva. Oncol Lett. 8:1214–1216. 2014.PubMed/NCBI View Article : Google Scholar

47 

Moser S, Beer M, Damerau G, Lubbers HT, Gratz KW and Kruse AL: A case report of metastasis of malignant mesothelioma to the oral gingiva. Head Neck Oncol. 3(21)2011.PubMed/NCBI View Article : Google Scholar

48 

Sawaki K, Okazaki F, Sato A, Najano M, Takagi S and Iida S: A case of malignant pleural mesothelioma with metastasis to the upper jaw. Japanese J Oral Maxillofac Surg. 61:168–172. 2015.

49 

Vazquez MV, Selvendran S, Cheluvappa R and McKay MJ: Peritoneal mesothelioma metastasis to the tongue-comparison with 8 pleural mesothelioma reports with tongue metastasis. Ann Med Surg (Lond). 5:101–105. 2016.

50 

Tanaka T, Nakamatsu K and Imamura T: Metastasis of malignant pleural mesothelioma to maxillary gingiva: A case report and literature review. J Oral Maxillofac Surg Med Pathol. 32:140–144. 2020.

51 

Spirtas R, Heineman EF, Bernstein L, Beebe GW, Keehn RJ, Stark A, Harlow BL and Benichou J: Malignant mesothelioma: attributable risk of asbestos exposure. Occup Environ Med. 51:804–811. 1994.PubMed/NCBI View Article : Google Scholar

52 

Baumann F, Ambrosi JP and Carbone M: Asbestos is not just asbestos: An unrecognised health hazard. Lancet Oncol. 14:576–578. 2013.PubMed/NCBI View Article : Google Scholar

53 

Carbone M, Baris YI, Bertino P, Brass B, Comertpay S, Dogan AU, Gaudino G, Jube S, Kanodia S, Partridge CR, et al: Erionite exposure in North Dakota and Turkish villages with mesothelioma. Proc Natl Acad Sci USA. 108:13618–13623. 2011.PubMed/NCBI View Article : Google Scholar

54 

Hillegass JM, Shukla A, Lathrop SA, MacPherson MB, Beuschel SL, Butnor KJ, Testa JR, Pass HI, Carbone M, Steele C and Mossman BT: Inflammation precedes the development of human malignant mesotheliomas in a SCID mouse xenograft model. Ann N Y Acad Sci. 1203:7–14. 2010.PubMed/NCBI View Article : Google Scholar

55 

Yang H, Rivera Z, Jube S, Nasu M, Bertino P, Goparaju C, Franzoso G, Lotze MT, Krausz T, Pass HI, et al: Programmed necrosis induced by asbestos in human mesothelial cells causes high mobility group box 1 protein release and resultant inflammation. Proc Natl Acad Sci USA. 107:12611–12616. 2010.PubMed/NCBI View Article : Google Scholar

56 

Carbone M and Yang H: Molecular pathways: Targeting mechanisms of asbestos and erionite carcinogenesis in mesothelioma. Clin Cancer Res. 18:598–604. 2012.PubMed/NCBI View Article : Google Scholar

57 

Napolitano A, Antoine DJ, Pellegrini L, Baumann F, Pagano I, Pastorino S, Goparaju CM, Prokrym K, Canino C, Pass HI, et al: HMGB1 and its hyperacetylated isoform are sensitive and specific serum biomarkers to detect asbestos exposure and to identify mesothelioma patients. Clin Cancer Res. 22:3087–3096. 2016.PubMed/NCBI View Article : Google Scholar

58 

Carbone M, Emri S, Dogan AU, Steele I, Tuncer M, Pass HI and Baris YI: A mesothelioma epidemic in Cappadocia: Scientific developments and unexpected social outcomes. Nat Rev Cancer. 7:147–154. 2007.PubMed/NCBI View Article : Google Scholar

59 

Dogan AU, Baris YI, Dogan M, Emri S, Steele I, Elmishad AG and Carbone M: Genetic predisposition to fiber carcinogenesis causes a mesothelioma epidemic in Turkey. Cancer Res. 66:5063–5068. 2006.PubMed/NCBI View Article : Google Scholar

60 

Testa JR, Cheung M, Pei J, Krausz T, Testa JR and Gaudino G: Germline BAP1 mutations predispose to malignant mesothelioma. Nat Genet. 43:1022–1025. 2011.PubMed/NCBI View Article : Google Scholar

61 

Carbone M, Yang H, Pass HI, Krausz T, Testa JR and Gaudino G: BAP1 and cancer. Nat Rev Cancer. 13:153–159. 2013.PubMed/NCBI View Article : Google Scholar

62 

Nasu M, Emi M, Pastorino S, Tanji M, Powers A, Luk H, Baumann F, Zhang YA, Gazdar A, Kanodia S, et al: High Incidence of Somatic BAP1 Alterations in Sporadic Malignant Mesothelioma. J Thorac Oncol. 10:565–576. 2015.PubMed/NCBI View Article : Google Scholar

63 

Mori T, Sumii M, Fujishima F, Ueno K, Emi M, Nagasaki M, Ishioka C and Chiba N: Somatic alteration and depleted nuclear expression of BAP1 in human esophageal squamous cell carcinoma. Cancer Sci. 106:1118–1129. 2015.PubMed/NCBI View Article : Google Scholar

64 

Yoshikawa Y, Emi M, Hashimoto-Tamaoki T, Ohmuraya M, Sato A, Tsujimura T, Hasegawa S, Nakano T, Nasu M, Pastorino S, et al: High density array-CGH with targeted NGS unmask multiple noncontiguous minute deletions on chromosome 3p21 in mesothelioma. Proc Natl Acad Sci USA. 113:13432–13437. 2016.PubMed/NCBI View Article : Google Scholar

65 

Cutrone R, Lednicky J, Dunn G, Rizzo P, Bocchetta M, Chumakov K, Minor P and Carbone M: Some oral poliovirus vaccines were contaminated with infectious SV40 after 1961. Cancer Res. 65:10273–10279. 2005.PubMed/NCBI View Article : Google Scholar

66 

Qi F, Carbone M, Yang H and Gaudino G: Simian virus 40 transformation, malignant mesothelioma and brain tumors. Expert Rev Respir Med. 5:683–697. 2011.PubMed/NCBI View Article : Google Scholar

67 

Bocchetta M, Eliasz S, De Marco MA, Rudzinski J, Zhang L and Carbone M: The SV40 large T antigen-p53 complexes bind and activate the insulin-like growth factor-I promoter stimulating cell growth. Cancer Res. 68:1022–1029. 2008.PubMed/NCBI View Article : Google Scholar

68 

Banaei A, Auvert B, Goldberg M, Gueguen A, Luce D and Goldberg S: Future trends in mortality of French men from mesothelioma. Occup Environ Med. 57:488–494. 2000.PubMed/NCBI View Article : Google Scholar

69 

Leigh J, Davidson P, Hendrie L and Berry D: Malignant mesothelioma in Australia, 1945-2000. Am J Ind Med. 41:188–201. 2002.PubMed/NCBI View Article : Google Scholar

70 

Price B: Analysis of current trends in United States mesothelioma incidence. Am J Epidemiol. 145:211–218. 1997.PubMed/NCBI View Article : Google Scholar

71 

Robinson BW and Lake RA: Advances in malignant mesothelioma. N Engl J Med. 353:1591–1603. 2005.PubMed/NCBI View Article : Google Scholar

Related Articles

Journal Cover

November-2020
Volume 13 Issue 5

Print ISSN: 2049-9450
Online ISSN:2049-9469

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Ohnishi Y, Fujii T, Sakamoto T, Watanabe M, Motohashi T, Kubo H and Nakajima M: Malignant mesothelioma metastatic to the oral region and latest topics (Review). Mol Clin Oncol 13: 61, 2020
APA
Ohnishi, Y., Fujii, T., Sakamoto, T., Watanabe, M., Motohashi, T., Kubo, H., & Nakajima, M. (2020). Malignant mesothelioma metastatic to the oral region and latest topics (Review). Molecular and Clinical Oncology, 13, 61. https://doi.org/10.3892/mco.2020.2131
MLA
Ohnishi, Y., Fujii, T., Sakamoto, T., Watanabe, M., Motohashi, T., Kubo, H., Nakajima, M."Malignant mesothelioma metastatic to the oral region and latest topics (Review)". Molecular and Clinical Oncology 13.5 (2020): 61.
Chicago
Ohnishi, Y., Fujii, T., Sakamoto, T., Watanabe, M., Motohashi, T., Kubo, H., Nakajima, M."Malignant mesothelioma metastatic to the oral region and latest topics (Review)". Molecular and Clinical Oncology 13, no. 5 (2020): 61. https://doi.org/10.3892/mco.2020.2131