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Vol. 88. Issue S4.
Pages S205-S211 (November - December 2022)
Case report
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Primary oral leiomyosarcoma of the maxillary bone and sinus: case report and up-to-date review of literature
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Niccolò Lombardia,b,
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niccolo.lombardi@unimi.it

Corresponding author.
, Elena M. Varonia,b, Dimitri Rabbiosic, Marco Cucurulloc, Laura Moneghinid, Giovanni Lodia,b
a Università degli Studi di Milano, Dipartimento di Scienze Biomediche Chirurgiche e Odontoiatriche, Milan, Italy
b ASST Santi Paolo e Carlo, Odontostomatology II Unit, Milan, Italy
c ASST Santi Paolo e Carlo, Maxillofacial Surgery Unit, Milan, Italy
d ASST Santi Paolo e Carlo, Human Pathology Unit, Milan, Italy
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Introduction

Leiomyosarcoma (LMS) is a mesenchymal malignancy of smooth muscle, which accounts for 1%–4% of head and neck sarcomas.1,2 The involvement of the oral cavity is considered extremely rare.1 Due to the lack of smooth muscle tissue in the oral cavity, it has been suggested that LMS arise from smooth muscle cells of the blood vessel walls, circumvallate papillae of the tongue, neuromuscular bundles, myoepithelial cells or pluripotent undifferentiated mesenchymal cells.1,3,4

Clinically, sarcomas of the oral cavity show nonspecific signs and symptoms and can appear as primary tumors, radiation-associated tumors or metastatic tumors.1,4,5 Biopsy, histological examination and immunohistochemical staining are mandatory to achieve a definitive diagnosis.1,5

The aim of this study was to report a case of maxillary LMS and to perform a review of literature including papers describing LMS of the oral cavity.

Methods

An electronic search in PubMed (National Library of Medicine) was performed including the previous reported cases of primary oral leiomyosarcoma from the year 2000 to March 2021. The terms “oral leiomyosarcoma” (295 results), “leiomyosarcoma tongue” (28 results), “leiomyosarcoma maxilla” (23 results), “leiomyosarcoma mandible” (31 results) and “leiomyosarcoma buccal” (13 results) were used. Cases were considered as “oral” if they primarily arose in mandible, maxillary bone, gingiva, buccal mucosa, lips, palate, tongue, and floor of the mouth. Only the article in English language were included in the final analysis. We excluded the articles which did not report complete immunohistochemical data related to LMS diagnosis. We included only the cases of primary oral LMS which stated, within the abstract or the manuscript, the immunohistochemical positivity for Smooth Muscle Actin (SMA) or at least for two of these markers: muscle specific actin (HHF35), desmin, h-caldesmon.6 When the full-text was not available, we directly contacted the authors.

Case report and literature review

A 67-year-old man presented at the oral medicine department for oral growing-mass, which caused difficult in feeding and speaking. The patient reported the first occurrence of a small swelling on the premaxilla’s palatal side approximately three months before, but he did not seek medical care due to the COVID-19 pandemic lockdown. He reported sporadic bleeding episodes and progressive increasing of lesion’s dimensions up to our observation. The clinical history was negative for systemic diseases and drug intake.

At the clinical examination, the patient showed impairment in speaking, due to a large painless brownish-reddish mass, which appeared bilobular and firm at palpation. The lesion had a total longitudinal size of 6 cm, it was extended at the buccal side of the premaxilla, covering the hard palate, and incorporating the teeth (Fig. 1). Orthopantomography and CT revealed a wide area of osteolysis of the maxillary and palatal bones, which bilaterally involved the nasal fossa and the right maxillary sinus and caused the dental root resorption (Fig. 2). Putative clinical diagnosis included mesenchymal tumors, Kaposi’s Sarcoma, hematologic or bone malignancies.7–9 Multiple incisional biopsies led to the histopathological diagnosis of high-grade leiomyosarcoma. Immunohistochemical profile of the lesion was positive for smooth-muscle-actin and muscle-specific antigen (HHF-35), shows minor-degree expression for desmin and was negative for S-100 protein (Fig. 3). Positron emission tomography showed large enhancing maxillary lesion (SUVmax 15.8), and few areas, putatively inflammatory, localized at the esophagus and mediastinum (SUVmax 2.2) (Fig. 2). Because of the patient’s good systemic condition (ECOG Performance Status scale grade 1), two cycles of neo-adjuvant chemotherapy with ifosfamide, doxorubicin and mesna were performed, before surgery, with subsequent reduction of tumour’s size. Total maxillectomy (with free resection margins) followed by cervical lymphadenectomy and reconstruction with fibula-free flap was performed (Fig. 4). After surgical resection, the patient received three further cycles of doxorubicin and dacarbazine, as adjuvant chemotherapy. The patient is currently on follow-up and, eight-months after surgery, he does not show clinical or radiological signs of recurrence (Fig. 4).

Figure 1.

Clinical picture of a large growing mass of the upper maxilla extended on both buccal and palatal sides (A; B).

(0.37MB).
Figure 2.

Wide maxillary osteolytic lesion associated with dental root resorption and involvement of the right maxillary sinus: orthopantomography (a), axial CT (b), 3D reconstruction (c) and PET (d) images.

(0.36MB).
Figure 3.

Hematoxylin and eosin stains show, under the oral epithelium, a sarcomatous proliferation characterized by fascicles of medium/large size spindle cells with abundant eosinophilic cytoplasm and well-defined cell borders (A). The nuclei are spindle or oval with mild to marked atypia. Both typical and atypical mitotic activity is easily found together a mild lymphocytic infiltrate without necrosis. Immunochemistry shows diffuse expression of smooth muscle actin (B) and HHF35 (C), and desmin (D) at a minor degree.

(0.75MB).
Figure 4.

Total maxillectomy and reconstruction with fibula free flap: orthopantomography (A) and 3D-CT images (B); clinical picture at follow-up examination, 6-months after surgical treatment (C).

(0.42MB).

Table 1 listed the cases found according to this literature review. A total of 73 cases of oral primary LMS have been identified, 42 (57.5%) in women and 31 (42.5%) in men, with a median age of 48 years old. Oral LMS arose in 35 (48%) cases from the soft tissues and in 38 (52%) cases from the hard tissues (Table 2).

Table 1.

Reported cases of oral primary leiomyosarcomas in the last two decades, excluding three manuscripts for which the full text was not available and the immunohistochemical details were not provided in the abstract (modified from).3

Author(s)  Year of publication  Patient gender  Patient age (years)  Primary location 
Lombardi et al. (present case)  2021  67  Hard tissue, maxilla 
Correia Neto IJ et al.16  2021  72  Soft tissue, buccal mucosa 
Choi YS et al.11202062  Hard tissue, maxilla 
61  Hard tissue, mandible 
66  Hard tissue, maxilla 
48  Hard tissue, mandible 
36  Hard tissue, maxilla 
23  Hard tissue, mandible, and maxilla 
16  Hard tissue, mandible 
55  Hard tissue, mandible 
Bala M et al.17  2019  54  Hard tissue, mandible 
Agarwal M et al.18  2018  45  Soft tissue, tongue 
Sumida T et al.19  2018  29  Hard tissue, mandible 
Ko ME et al.5  2018  86  Soft tissue, buccal mucosa 
Viviano M et al.20  2017  22  Soft tissue, mandible 
Li RH et al.21  2017  54  Soft tissue, floor of the mouth 
Kenea TT et al.22  2017  12  Soft tissue, mandible 
Lewandowski B et al.23  2016  58  Hard tissue, mandible 
Suarez-Alen F et al.1  2014  66  Soft tissue, buccal mucosa 
Sandhu SV et al.24  2014  63  Hard tissue, maxilla 
Moghadam SA et al.25  2014  67  Hard tissue, mandible 
Nagpal DKJ et al.26  2013  35  Soft tissue, buccal mucosa 
Patel K et al.27  2013  23  Hard tissue, mandible 
Schutz A et al.28a2013  75  Soft tissue, lip 
  39  Hard tissue, mandible 
  25  Soft tissue, floor of the mouth 
Rege IC et al.29  2013  64  Hard tissue, mandible 
Taghipour Zahir S et al.30  2013  24  Hard tissue, maxilla 
Divyambika CV et al.31  2012  Soft tissue, buccal mucosa 
Ahn JH et al.32  2012  54  Soft tissue, tongue 
Riaz N et al.33  2011  65  Hard tissue, maxilla 
Chew IK et al.34  2009  36  Hard tissue, maxilla 
Santana MVM et al.35  2008  14  Soft tissue, hard palate 
Mendonça EF et al.36  2008  Soft tissue, gingiva 
Yadav R et al.37  2008  27  Soft tissue, buccal mucosa 
Crossman T et al.10  2008  46  Soft tissue, tongue 
Pinheiro J et al.38  2007  40  Hard tissue, mandible 
Ethunandan M et al.14200779  Soft tissue, tongue 
97  Soft tissue, tongue 
50  Hard tissue, maxilla 
51  Soft tissue, buccal mucosa 
Rodini CO et al.39200754  Soft tissue, mandible 
63  Hard tissue, maxilla 
Castaldi A 40  2006  52  Soft tissue, tongue 
Yang S‐W et al.41  2006  54  Soft tissue, tongue 
Vilos GA et al.12200526  Hard tissue, mandible 
48  Hard tissue, mandible 
30  Soft tissue, soft palate 
20  Hard tissue, maxilla 
Cheng C‐Y et al.42  2004  Soft tissue, mandible 
Prasad KC et al.432004  27  Hard tissue, maxilla 
  42  Hard tissue, maxilla 
Ikram M et al.44  2003  41  Hard tissue, maxilla 
Lo Muzio L et al.45  2002  31  Soft tissue, maxilla 
Montgomery E et al.46b2002  37  Hard tissue, maxilla 
  21  Soft tissue, tongue 
  34  Hard tissue, maxilla 
  42  Soft tissue, buccal mucosa 
Wada S et al.47  2002  71  Hard tissue, maxilla 
Nikitakis NG et al.48200235  Soft tissue, mandible 
51  Hard tissue, mandible 
Dios PD et al.49  2001  67  Soft tissue, soft palate 
Sumida T et al.50  2001  77  Hard tissue, maxilla 
Dry et al.51c2000  31  Hard tissue, maxilla 
  58  Hard tissue, maxilla 
  88  Soft tissue, floor of the mouth 
  28  Hard tissue, maxilla 
  74  Hard tissue, mandible 
  34  Soft tissue, palate 
  91  Soft tissue, lip 
  27  Soft tissue, mandible 
  N/A  Soft tissue, gingiva 
Lo Muzio L et al.52  2000  67  Soft tissue, tongue 
a

Case nº 4 was excluded (SMA, HHF35 and desmin unknown).

b

Cases nº 8, 11, 12 excluded (positive only for desmin; SMA and HHF35 unknown).

c

Case nº 6 was excluded (positive only for desmin; SMA and HHF35 not performed).

Table 2.

Distribution of the LMS reported cases considering the arising tissues.

Hard tissues (n = 38)Soft tissues (n = 35)
Maxillary bone  21  Tongue 
Mandible  15  Buccal Mucosa 
Maxilla and mandible1Mandibular soft tissues 
Palate (hard and soft) 
Mouth-floor 
Gingiva 
Lip 
Maxillary soft tissues 
Discussion

Leiomyosarcoma is a malignant tumor of smooth muscle derivation which account for 5%–10% of all soft tissue sarcomas.3,10 LMS frequently affects the retro-peritoneal region, the uterus and the gastrointestinal tract.1,11 Oral LMS are extremely rare, accounting for 0.64% of all LMS and for 5.7% of head and neck LMS.5,11 The jawbones appear the most frequently affected oral sites (70% of cases) followed by tongue, buccal mucosa, soft palate, upper lip and floor of the mouth,1,5,11,12 although a recent systematic review, which reported published case of intra-oral LMS up to 2017, found that soft tissues were more frequently involved than bone.3 Oral LMS can occur at any age, commonly in the 5–7th decades, with similar gender incidence rate (M:F, 11:9).3,11 Clinically, it appears as a growing mass, painless and firm, which infiltrate the surrounding tissues with no pathognomonic signs.1,3

Due to its rarity, oral LMS can be misdiagnosed with other common benign lesions before biopsy.11 Moreover, due to overlapping histological features between different types of head and neck sarcomas, this lesion could be also misclassified for other more common spindle cell tumors of the oral cavity.3,5,13 For this reason, histological examination associated with immunohistochemical confirmation is mandatory to obtain a definitive diagnosis of oral LMS.1,3,11,13

Surgical resection with tumour-free margins is widely accepted as the treatment of choice for oral LMS.1,3,5,11 In cases where the anatomical location of tumor does not allow radical surgical intervention, radiotherapy and administration of neoadjuvant/adjuvant chemotherapy may improve survival time and decrease or delay the recurrence rate.1,2,11 However, no standard of care is still available.2

The prognosis for oral LMS is poor, associated with a high rate of recurrence (42% for high-grade LMS within 2 years from surgery) and regional or distant metastasis.1,2,5 Unfavorable clinical course is related to several factors, such as delayed diagnosis, tumor size (larger than 4 cm), histopathological high-grade (poorly-differentiated), site (bone involvement and extension into paranasal sinuses), lymphatic or hematogenous dissemination, positive surgical margins.1–3,5 The estimated 5-years survival rate for primary oral LMS range from 55% to 61%.1,12,14 Periodic follow-up examinations are mandatory for an early diagnosis of any signs of recurrence.1,2,11

In the case presented above, the delayed diagnosis is associated with an increased size of the tumor and a subsequent more aggressive surgical intervention; it is not possible to establish how much the delayed diagnosis could have influenced the prognosis for the patient. However, on our experience during the first months of COVID pandemic, patients were often more scared of contracting COVID-infection in the hospital rather than their neoplastic disease.15

Conclusion

Even if extremely rare, LMS should be considered in the differential diagnosis of oral growing-mass. Early diagnosis and treatment are essential to reduce the risk of recurrence and guarantee better prognosis. Periodic follow-up examinations are mandatory to identify early any signs of recurrence.1,2,11 Due to the rarity of oral LMS further studies are necessary to better characterize this disease.

Institution’s ethics committee

Institution’s ethics committee approval is not required for the case report.

The study was conducted in compliance with the recognized international standards, including the principles of the Declaration of Helsinki.

Patient’s informed consent

Data and samples were collected under patient’s informed written consent, guaranteeing anonymity.

Funding

The authors received no specific funding for this work. No funds, grants, or other support were received.

Conflicts of interest

The authors declare no conflicts of interest.

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