Case Report: Rare site for intraoral meningioma.

Extracranial meningioma is very rare with few cases reported, especially in the oral cavity. Its diagnosis is considered a challenge owing to the unusual site of occurrence.  We report, to the best of our knowledge, the first case of extra-cranial meningioma as a primary tumor in the hard palate with no detected intracranial extension. A 59-year-old Egyptian female patient presented with a 22-year history of a large painless swelling at the right side of the hard palate, which could not be seen on radiographs.  An incisional biopsy was taken and, after assessment with a panel of immunohistochemical markers, the lesion was diagnosed as extracranical grade I mengiothelial meningioma. The patient did not show up for surgical excision and follow-up was not performed because of the lose of contact with the patient. Intraoral meningioma is a rare tumor. Immuohistochemical markers are important for confirming this diagnosis. Copyright:

Introduction

Meningioma is a benign neoplasm of meningothelial cells [1]. Meningioma may develop as a direct extension of a primary intra-cranial meningioma or as a true primary extra-cranial meningioma [2].

Extra-cranial (ectopic) tumors are mostly seen in the head and neck region with no connection intra-cranially [3]. The most common extra-cranial site is the orbits. Meningioma arising in the oral cavity is extremely rare [4]. To the best of our knowledge, 19 cases have currently been reported in the oral cavity [2, 4– 20] and we are reporting the first case in the hard palate.

Case report

A 59-year-old female patient presented to the outpatient clinic in the Oral and Maxillofacial Surgery Department, Cairo University in January 2019 complaining of a large painless swelling in the hard palate ( Figure 1). The patient reported that the swelling had been present in her oral cavity for 22 years. The patient’s medical and familial histories were unremarkable. As well as there was not a history of exposure to radiation. Upon clinical examination on the day of admission, a large hard palatal swelling (3 cm × 3 cm) was evident on the right side of the hard palate. The swelling was covered by normal mucosa and showed a slight bluish tinge. A provisional diagnosis of a benign peripheral nerve neoplasm and a minor salivary gland benign neoplasm were made. CT scan was performed with no evidence of bone involvement.

Figure 1.

Preoperative clinical picture showing 3 × 3cm swelling in the hard palate.

An incisional biopsy of the lesion was performed. Hematoxylin and eosin stained sections revealed meningothelial cells arranged in lobules. The cells exhibited round to oval nuclei ( Figure 2). Psammoma bodies were also present ( Figure 3). No mitotic activity and no cellular atypia were found. Immunohistochemical staining for tumor-associated markers was performed to confirm the diagnosis of meningioma and to exclude other mimic tumors as metastiatic carcinomas, schwannoma, neurofibroma, paraganglioma and perineurioma. Cells were positively stained using primary antibodies for epithelial membrane antigen (EMA) and vimentin ( Figure 4a, b), but were not stained when using primary antibodies for S100, pancytokeratin, p63, chromogranin and renal cell carcinoma glycoprotein ( Figure 5a–e).

Figure 2.

Hematoxylin and eosin-stained sections showing epithelioid cells forming meningiothelial whorls (magnification, ×100).

Indistinct cell membranes with uniform nuclei and no mitotic figures (inset; magnification, ×200).

Figure 3.

Hematoxylin and eosin-stained sections showing syncytial cells (magnification, ×100).

Psammoma bodies seen between meningiothelial cells (inset), (×200).

Figure 4.

Meningioma tumor cells showing a positive cytoplasmic immunohistochemical reaction for ( a) epithelial membrane antigen and ( b) Vimentin (magnification, ×200).

Figure 5.

Meningioma tumor cells react negatively following immunohistochemical staining for ( a) renal cell carcinoma glycoprotein, ( b) S100, ( c) chromoginin, ( d) p63, ( e) PanCK (magnification, ×100).

No therapy was administered to the patient during her admission. Unfortunately, the patient did not show up for surgical excision and follow-up.

Discussion

Primary extra-cranial meningioma is an unusual tumor, especially in the oral cavity [4]. The first intraoral meningioma reported was by Brown et al. in 1976, which presented as a periapical radiolucency in the anterior maxillary region [5].

To the best of our knowledge, 19 cases of primary meningioma in the oral cavity have been reported. Of these, 13 were in female patients, which is also true of the present case. However, the age range was wide in the reported cases – between 10 and 77 years old [2, 4– 20]; in the present case, the patient was 59 years old. Regarding the reported cases of intraoral primary meningioma, 6 of the 18 were in the maxilla [2, 4– 6, 9, 16], 10 were in the mandible [7, 10– 15, 19, 20], 2 in the buccal mucosa [17, 18] and one in soft palate [8]. To the best of our knowledge, we report the first case in the hard palate.

The histopathological criteria of extracranial meningiomas are similar to those of their intracranial counterparts. All documented cases shared the same characteristics: whorls of spindle cells or epithelioid cell proliferation and psammoma bodies. In our case, diagnosis was challenging because of the tumor’s similarity with other tumor entities of peripheral nerve origin, as well as the uncommon location of the tumor. An immunohistochemical panel of tumor-associated markers was used to confirm the diagnosis and to avoid unnecessary aggressive treatment. Most of the 19 cases reported in the literature were diagnosis using immunohistochemical markers. All reported cases that used immunohistochemistry techniques to diagnose meningioma [4, 9– 11, 13, 14, 16, 17, 19, 20] observed that the tumor cells stained positive for monoclonal antibodies against EMA and vimentin, with no immunoreactivity for S-100 protein, which was similar to our findings. However, EMA and vimentin are not useful to differentiate between meningioma and perineuroma as they both express positivity for EMA and vimentin but perineuroma the cells are spindle and elongated however, in our case they are rounded and polyhederal (meningiothelial pattern).

Unfortunately, our patient did not show up for surgical excision and follow-up was not done because of the loss of contact with the patient. However, most of the documented cases were treated successfully without recurrence by surgical excision. Some of the studies, such as that by Rommel et al. [20], preferred only to follow-up with the patient rather than conduct surgical intervention. However, others preferred to perform aggressive treatment, such as as segmental mandibulectomy or segmental resection [7, 12]

In conclusion, meningioma is a rare intraoral benign neoplasm. Immunohistochemical markers are an important tool to achieve a final diagnosis, especially for the differentiation from histological mimic entities of peripheral nerve origin, such as perineurioma and neurothekeoma and to avoid unnecessary aggressive treatment. Vimentin and EMA are the two important markers to confirm extra-cranial meningioma diagnosis.

Data availability

All data underlying the results are available as part of the article and no additional source data are required.

Consent

Written informed consent for publication of their clinical details and clinical images was obtained from the patient.

Ectopic Meningiomas are seen less frequently in oral regions, so it can be considered as a case report. However, the lack of follow-up of the case reduces the power of the article.

Clinical data and radiographic findings can be given in more detail.

Differential diagnoses should be discussed in the discussion section.

Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?

Partly

Is the case presented with sufficient detail to be useful for other practitioners?

Yes

Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?

Partly

Is the background of the case’s history and progression described in sufficient detail?

Yes

Reviewer Expertise:

maxillofacial surgery

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

The requested changes were made.

Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?

Partly

Is the case presented with sufficient detail to be useful for other practitioners?

Partly

Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?

Partly

Is the background of the case’s history and progression described in sufficient detail?

Yes

Reviewer Expertise:

Neuropathology

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

The case report presents an extracranial meningioma of the hard palate. The patient’s gender is conformed to the tumor but there are (likely) no contributing or risk factors associated with its occurrence. The lesion is asymptomatic and incisional biopsy was examined routinely and certain microscopic features were suggestive of meningioma. The specimen was further stained with a panel of markers and was diagnosed as meningioma of the palate. Unfortunately the patient did not return for surgical removal.  The patient’s background can be improved if relevant findings are reported such as previous exposure to radiation as a potential risk for development of meningioma. This is one of the unfortunate incidents where patient is not committed to treatment.

Is the background of the case’s history and progression described in sufficient detail?

Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?

Although it seems that the patient is asymptomatic except for the size of the palatal swelling, absence of radiograph (even if non-indicative) and not mention neurofibromatosis-type2, undermine the reader’s understanding of the case.

The clinical picture is good and clear.

Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?

Discussion is fine although it would’ve been beneficial to cite the other reported palatal lesions by Kishore A (2000) and Sinha (2002), for example. [1] , [2]

The immunohistochemistry test panel discussion would be more useful for the non-pathology reader if there were brief comment on the value of such tests of uncommon oral lesions with perplexing presentations.

Consequently, a short list of lesions to be included in a general dentist’s record when similar cases are detected, would be useful.

Few editing or English language corrections would help. For example “follow-up was not done because of loose of contact” in which “loss not loose” is meant. The statement is repeated in abstract and discussion and significantly alters the meaning of the sentence.

Is the case presented with sufficient detail to be useful for other practitioners?

Extracranial meningioma are rare and intraoral lesions are even rarer. It is of high pathological interest of both specialist and general practitioner to get updated on occurrence, presentation and diagnostic methods of such tumors.

The case and the tumor presented are useful, relevant and with corrections, the report would be more impactful.

Conclusions must be more powerful and instructive for the practitioner to:

Expect the unexpected when similar lesions are encountered.

Suggest an effective strategy to ensure patient’s return when the outcomes are suspicious.

Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?

Partly

Is the case presented with sufficient detail to be useful for other practitioners?

Partly

Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?

Partly

Is the background of the case’s history and progression described in sufficient detail?

Partly

Reviewer Expertise:

Oral Pathology, Oral medicine, medical and Dental Education

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

Firstly, thank you doctor for your valuable comments. We added that data and answers that you commented to the new version of the manuscript. And I will answer them too here as a respond to your report.

1- There was no previous exposure to radiation as a potential risk for development of meningioma.This is one of the unfortunate incidents where patient is not committed to treatment.

2- CT scan was done and there was no bone involvement and  neurofibromatosis-type 2 was excluded because the lesion is single and been present in her oral cavity for 22 year.

3- Discussion is fine although it would’ve been beneficial to cite the other reported palatal lesions.

4- The immunohistochemistry test panel discussion was added

5- Benign salivary gland neoplasm add to the  list of lesions to be included in a general dentist’s record when similar cases are detected.

6-  English language corrections were done.

7- Conclusions  were also corrected to include the consequence of wrong diagnosed.

Thanks again for your comments which add a lot to our knowledge and for your time too

The case report is well written and presents an interesting case of ectopic meningioma. Some amendment is needed however.

Radiological findings should be included. The authors merely mention that the lesion was not seen by radiology. Please clarify the technique used and relevant findings.

The grade of meningioma was not given

The differential diagnosis of meningioma from mimics was not sufficiently addressed. Different entities in the differential diagnosis were mentioned at different parts of the article without discussing the differentiating points. And the performed stains would not help in differentiating meningioma from perineurioma, both are positive for EMA and vimentin.

Grammatical and spelling mistakes are noted here.

Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?

Partly

Is the case presented with sufficient detail to be useful for other practitioners?

Partly

Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?

Partly

Is the background of the case’s history and progression described in sufficient detail?

Yes

Reviewer Expertise:

Neuropathology.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

Thank you Dr. Eman for your valuable comments and for your time. We added that data and answers that you commented to the new version of the manuscript. And I will answer them  here too as a respond to your report.

1-  All the English language corrections were done.

2- CT scan was done and there was no bone involvement.

3- Meningioma grade I.

4- The list of differential diagnosis was done and discussed.

Table 1.

Clinicopathological and radiographic data of the documented cases of extracranial meningioma.

Study	Age, years	Gender	Site	Tumor size	Radiographic findings	Treatment	Follow-up
Brown et al. [5]	69	M	Maxilla	NA	ML RL	Not completed	8 years
Simpson and Sneddon [6]	63	F	Maxillary alveolus	4.5 × 2.7 × 2.7 cm	Well-defined mixed RL RO	Surgical excision.	Under review
Landini and Kitano [7]	48	F	Mandible	NA	Well-defined RL	Block resection	2 years
Reddi et al. [2]	26	F	Maxilla	3 cm	Ill-defined RL	Surgical excision	2 years
Kishore et al. [8]	44	F	Soft palate	3 × 2 cm	NS	Excisional Biopsy	4 years
Pfeifer et al. [9]	77	F	Maxilla (temporal fossa )	NA	Dense soft tissue mass	Surgical resection	NS
Jones and Freedman [10]	41	F	Mandible	4 × 2 cm	Well defined RL	Excisional biopsy	NS
Jones and Freedman [10]	74	F	Mandible	4 × 3 cm	Well-defined RL	Excisional biopsy	NS
Kubotaa et al. [11]	10	M	Mandible	NA	Well-defined RL	Enucleated	4 years
Mussak et al. [12]	62	M	Mandible	7 × 3 cm	Well-defined RL	Segmental mandibulectomy	NS
Lell et al. [13]	40	F	Mandible	NA	Well-defined RL	NS	NS
Mosquede-Taylor et al. [14]	53	F	Mandible	4 cm	Ill-defined mixed RO RL	Surgical excision	6 months
Rushing et al. [15]	NA		Mandible	NA
Simsek and Komerik [4]	51	F	Maxilla	2 × 2 cm	Ill-defined mixed RL-RO	Surgical excision	5 years
Pinting et al. [16]	59	M	Maxilla	NA	Well-defined RL	Surgical excision and radiotherapy	NS
Maeng et al. [17]	66	F	Buccal mucosa	2 cm	Heterogenously enhanced mass	Surgical excision	Year and half
Nair et al. [18]	60	F	Buccal mucosa	4 × 3 cm	Mass of heterogeneous density	Surgical resection	One year
Rege et al. [19]	35	M	Mandible	NA	Ill-defined ML RL	Partial resection	5 years
Rommel et al. [20]	20	F	Mandible	2 × 1.8 cm	Well defined RL	No surgical intervention.	One year

M, male; F, female; RL, radiolucent; RO, radioopaque; UL, unilocular; ML, multilocular; NA, not available; NS, not stated.