Gingival Leiomyosarcoma in a Young Woman Case report and literature review

Leiomyosarcoma (LMS) is a rare mesenchymal malignancy, of which 3–10% of cases occur in the head and neck region. We report a 22-year-old woman who was referred to the University Hospital of Siena, Italy, in 2016 with an ostensibly benign asymptomatic lump on the mandibular gingiva. The lesion grew rapidly, causing otalgia in the right ear. An excisional biopsy was performed and primary LMS was diagnosed histologically. Subsequently, the patient underwent radical re-excision of the perilesional mucosa, a partial bone resection and the extraction of four teeth. No recurrences or metastases were detectable at a 20-month follow-up. This report discusses the differential diagnosis of LMS with regards to other benign and malignant lesions and reviews the recent literature on primary and secondary oral LMS. Due to its innocuous clinical features—including its asymptomatic nature and presentation at a young age—this aggressive malignancy can go undetected; therefore, an early histopathological diagnosis is crucial.


C
onstituting 6-7% of all soft tissue sarcomas, leiomyosarcoma (LMS) is a malignant tumour of mesenchymal origin which occurs very rarely in the oral cavity, with only 3-10% of cases arising in the head and neck region. 1,2Oral LMS arises primarily in the bones and soft tissue and is reported predominantly among adult patients, without any significant gender predominance. 34][5] The sarcoma has an aggressive growth pattern and a high rate of recurrence due to its dissemination in the bloodstream. 5The presenting signs of oral LMS are generally nonspecific and the similarity of this entity to certain benign lesions typically delays its diagnosis.This report presents a case of oral LMS in a young patient which was rapidly diagnosed and resulted in a positive outcome.As the patient was disease-free following radical surgical excision, further surgery, chemotherapy or radiation therapy was avoided.

Case Report
A 22-year-old Caucasian woman was referred to the Department of Dentistry at the University Hospital of Siena, Italy, in 2016 with otalgia in the right ear and an asymptomatic swelling on the lower right lingual gingiva, which she had initially noticed approximately one month beforehand.The patient's medical history indicated that she was in good health and was not currently taking any medication.An examination of the antibiotics consisting of 1g of amoxicillin and clavulanic acid twice daily.
The excised mass was fixed in buffered formalin.A histopathological examination showed an unencapsulated tumour with pushing margins and an absence of infiltrative growth patterns.The lesion consisted of bundles of spindle cells intersecting at right angles, with well-defined brightly eosinophilic cytoplasm, cigar-shaped pleomorphic nuclei and occasional paranuclear vacuoles [Figure 3A].There were a few microfoci of coagulative necrosis and 13-15 10 mitoses in a high-power field at x400 magnification (corresponding to about 1 mm 2 ) [Figure 3B].Immunohistochemistry was performed on 3-μm-thick sections using the BenchMark ULTRA ® automated staining system (Ventana Medical Systems Inc., Roche Diagnostics, Monza, Italy).The ultraView Universal DAB Detection Kit ® (Ventana Medical Systems Inc.) was used with horseradish peroxidase multimer chromogen diaminobenzidine in order to stain positive structures brown.The neoplastic cells were positive for smooth muscle markers, including h-caldesmon (clone e89), HHF35, myosin, smooth muscle actin (clone 1A4) and smooth muscle myosin monoclonal antibody-1 [Figures 3C and D].The Ki-67 labelling index (clone MIB-1) was approximately 30-40%.All other tested antibodies were negative, including activin receptorlike kinase, cluster of differentiation (CD)34, c-Kit, desmin, DOG1, oestrogen receptors, pankeratin, progesterone receptors, skeletal muscle actin and S100 oral cavity revealed a hard, non-painful, reddish-pink, non-haemorrhagic gingival swelling around the first lower right molar (i.e.tooth number 46) [Figure 1A].The rest of the ear, nose and throat examination was normal.An orthopantomogram and periapical X-ray of tooth number 46 appeared normal [Figures 1B  and C].An excisional biopsy was subsequently performed under local anaesthesia, with the excised lesion measuring 1.5 x 1.2 cm [Figure 2].Following the surgery, the patient was prescribed a six-day course of

Discussion
Smooth muscle tumours rarely develop in the head and neck region; however, if present, they occur mainly in the walls of blood vessels, the erector pili musculature of the skin, the circumvallate papillae of the tongue and in the myoepithelial cells of the salivary glands. 7oft tissue LMS can be divided into retroperitoneal/ intra-abdominal, cutaneous/subcutaneous and vascular subgroups, with distinct clinical and biological differences despite their similar histology. 8The most common intraoral site for LMS appears to be the tongue, usually as a result of metastasis from a primary tumour in the uterus, gastrointestinal tract or retroperitoneum. 7,9Oral LMS may also involve the jaw bones, cheek, gingiva, floor of the mouth, mandible, soft or hard palate and lips.]8,10 Clinically, oral LMS is often confused with other benign and malignant lesions.With regards to the current patient, the clinical and macroscopic features of the case ostensibly mimicked a benign lesion.This was further compounded by the young age of the patient and the well-circumscribed growth of the swelling.Among benign tumours, the most problematic entity to exclude during the differential diagnosis is a leiomyoma, as well-differentiated LMS may show similar microscopic features, including a 'pushing' growth pattern; as a result, the absence of mitoses is the major differentiating factor. 10In the present case, mitoses were clearly observed, along with other features of malignancy including nuclear atypia and necrosis.Due to the insidious clinical presentation of LMS, histopathological analysis is critical to exclude other benign lesions such as fibromas, haemangiomas, neurofibromas, schwannomas and peripheral giant cell granulomas.The rapid growth of a lesion in a young patient and certain histological features may also suggest nodular fasciitis, although this is rare in the orofacial area and is usually characterised by selflimiting growth, mitotic activity and focal infiltration. 11icroscopically, a solitary fibrous tumour was also excluded in the current case as this entity is rarely reported in the oral cavity. 102][13][14][15][16][17] In particular, myofibroblastic sarcomas and rhabdomyosarcomas also affect younger individuals, proteins.The final diagnosis was of a well-differentiated grade I LMS. 6s a result of this diagnosis, further surgery was deemed necessary.Preoperatively, a contrast computed tomography (CT) scan showed thickening of the soft tissue adjacent to the inferior right hemimandibular surface, without bone or neck lymph node involvement.A metastatic work-up was negative, including CT imaging of the chest, abdomen and pelvis and a bone scan.A gynaecological examination and transvaginal ultrasound was also normal.However, an magnetic resonance imaging (MRI) scan showed increased mucosal impregnation near teeth number 46 and 47.Subsequently, under general anaesthesia an excision of the perilesional mucosa, a partial bone resection sparing the lingual and mandibular nerves and the extraction of teeth number 45-48 was performed [Figure 4A].Postoperatively, the patient was prescribed antibiotics (1 g of ceftriaxone per day) along with an anti-discolouration mouthwash containing 0.2% chlorhexidine and hyaluronic acid.
The patient was discharged two days later with no complications.Every three months, she attended follow-up appointments wherein MRI and chest and abdominal ultrasounds were performed.A wholebody CT scan was also undertaken six months after the surgery, with positron-emission tomography/CT performed at 12 months.At the time of writing, 20 months after the radical surgery, there were no signs of local recurrence or metastasis and the patient appeared healthy [Figure 4B].with the former showing local destructive growth. 13,16quamous cell carcinomas and their rarer spindle cell variants, sarcomatoid carcinomas, are the most frequent overall and spindle cell malignancies in the oral cavity, respectively. 10,11,17As such, all other malignant lesions with a spindle cell morphology were excluded in the present case due to their rare occurrence at this site.Moreover, the morphological features of the lesion-including the fascicles of spindle-shaped cells with abundant eosinophilic cytoplasm, bluntended cigar-shaped nuclei, high mitotic rate and pleomorphism-were consistent with a diagnosis of LMS; this was also supported by the immunohistochemical results of an extensive panel of antibodies. 8,18While metastasis from primary LMS arising in another site could not be excluded histologically, a high percentage of uterine LMS express oestrogen and/or progesterone receptors, which were negative in this case. 191][22] Currently, there are no standard criteria for therapy, although the complete excision of the tumour with wide surgical margins is recommended. 7,23,24The five-year survival rate among patients with primary oral LMS is 55%, with bone involvement and metastasis significantly associated with poorer prognosis. 24Lung and cervical lymph node metastases frequently occur, with the regional lymph nodes affected in >15% of oral LMS cases. 4Distant metastases, mostly in the lungs, occur in approximately 39% of patients with oral LMS; in addition, LMS lesions arising in the uterus, gastrointestinal tract and retroperitoneum sometimes metastasise to the lungs, brain, bone and oral cavity. 4,25As such, preoperative staging of the whole body is mandatory.In the present case, the regional lymph nodes were free and systemic tests did not reveal any metastasis; hence, no adjuvant therapy was given.However, regular follow-up is essential to rapidly detect recurrence.

Conclusion
Smooth muscle tumours of the oral cavity are exceedingly rare.A diagnosis of oral LMS should be established histologically and supported by immunohistochemical analysis using specific markers.In certain cases, such as the one presented here, early

Figure 1 :
Figure 1: A: Intraoral photograph of a 22-year-old woman with an asymptomatic gingival lesion.B: Preoperative orthopantomogram of the lesion showing no abnormalities.C: Preoperative periapical X-ray of the mandibular right molar which also appears normal.

Figure 3 :
Figure 3: A: Haematoxylin and eosin stain (H&E) at x100 magnification showing a leiomyosarcoma composed of perpendicularly oriented fascicles of spindle cells.B: H&E stain at x200 magnification showing deep eosinophilic cytoplasm and elongated blunt-ended nuclei with mitoses (arrows).C and D: Immunohistochemistry chromogen diaminobenzidine stains at x200 magnification showing diffuse cytoplasmic positivity for smooth muscle actin antibodies and h-caldesmon, respectively.

Figure 2 :
Figure 2: Intraoral photographs of a 22-year-old woman undergoing an excisional biopsy of an asymptomatic gingival lesion in which (A) the lesion was radically resected under local anaesthesia, leaving (B) the apparently healthy teeth, gingiva and alveolar bone intact.

Figure 4 :
Figure 4: Intraoral photographs of a 22-year-old woman (A) immediately after radical surgical bone resection and the extraction of teeth number 45-48 and (B) 20 months later with no evidence of recurrence of the leiomyosarcoma.