Not All the Spindle Cell Tumors in Oral Cavity Are Sarcomatoid Squamous Cell Carcinoma

Introduction

Embryonal rhabdomyosarcoma (ERMS) is most common subtype of RMS arising from primitive embryonic skeletal-muscle cells. Hence, it can arise anywhere in the body, often in the sites where skeletal muscle is not usually found. RMS commonly occurs in the 1st decade of life in more than 50% of the cases. ERMS is extremely rare in adults. It commonly occurs in head and neck and genitourinary tract. Clinical manifestation varies depending upon mass effect and obstruction [1].

We reported a rare case of ERMS in a 48-year old male, presented as an ulcer over left buccal mucosa and rapidly progresses to a mass in left cheek, which was locally aggressive without distant metastasis. A detail histopathological examination with relevant IHC has to be performed in an atypical morphology at the odd site.

Case Report

A 48-year male beedi smoker was presented to the dentist in Jan 2016 with the complaint of pain at the angle of jaw, especially on opening the mouth and difficulty in opening the mouth since 2 months. Dentist advised him tooth extraction. After 10 days of tooth extraction, he indecently noted a mass in the left side of the cheek which was rapidly progressing in size. He had significantly lost 3 kg weight in ~ 1 month. However, there was no difficulty in swallowing and hearing. With these complaints, the patient was reffered to our institutes, where on oral examination, there was an ulceroproliferative lesion in left buccal mucosa. MRI showed a large lobulated enhancing altered signal intensity mass measured 7.4 × 5.9 × 4.4 cm was identified in left masticator space. It was involving left retromolar trigone, upper and lower gingivobuccal sulci, and adjoining buccal mucosa. Posteriory, it was involving left medial, lateral pterygoid muscles and extending along parapharangeal space reaching up to carotid space and abutting deep lobe of parotid gland. Superomedially, it was reaching upto left torus tubaris involving posterior maxillary alveolus in molar region; abutting lateral wall of left maxillary sinus with focal cortical breach, and mucosal thickening (Fig. 1). It was further extending superiorly into left infratemporal fossa upto the level of zygomatic process. Inferomedially, it was involving mandibular angle, adjoining ramus, and body of mandible in molar region. Anterolaterally, it was infiltrating the buccal fat with edematous changes reaching upto skin. An incisional biopsy from left buccal mucosa was performed showed an ulcerated mucosa with subepithelium exhibiting a tumor composed of round to oval to spindle cells arranged in diffuse sheets. The cells had scant cytoplasm, round to oval to spindled nuclei with coarse chromatin and inconspicuous nucleoli. Focal areas of necrosis were noted and the tumor cells showed brisk mitosis ~ 15–20/10HPF. Cambium layer was not seen. The tumor cells were immunopositive for SMA (focal cytoplasmic), desmin (diffuse cytoplasmic), vimentin, and myogenin (focal nuclear) while, negative for pancytokeratin, EMA, P40, S100. Based on histomorphological and immunohistochemical finding, we finally made the diagnosis of embryonal rhabdomyosarcoma (ERMS), left buccal mucosa. For the purpose of further clinical staging, bone marrow biopsy had done which was free of infiltration by the tumor. 99 m Tc-MDP whole body bones scan demonstrated no definite evidence of skeletal metastasis. Similarly, CECT chest, abdomen, and pelvis did not reveal any metastasis.

Fig. 1.

a–d Axial and coronal CT scan images showing ill-defined heterogeneously hypoenhancing mass with epicenter in the left retromolar trigone (RMT) region (white arrows). The mass is infiltrating the infratemporal fossa and masticator space (black arrows). There is infiltration of ipsilateral masseter and pterygoid muscle with erosion of ramus of the hemimandible and maxillary alveolar margin on the left side. Also noted is infiltration of left maxillary sinus

Discussion

Rhabdomyosarcoma (RMS) is a solid tumor, resulting from dysregulation of the skeletal myogenesis program. It was first described by Weber in 1854, and accounting for about 60% of pediatric soft tissue sarcoma (STS) [2]. International Classification of Rhabdomyosarcoma [ICR] has classified RMS into prognostically useful histologic categories. Embryonal, botryoid, and embryonal, spindle cell has superior prognosis. Embryonal, not otherwise specified (NOS) has intermediate prognosis while, alveolar and undifferentiated sarcoma has poor prognosis [3]. Embryonal rhabdomyosarcoma [ERMS] is the most common subtype. More than 80% of cases of ERMS in children occur before the age of 15 [4]. ERMS is rare in adults. Orbit is the most common site of involvement by ERMS in the head and neck region, followed by paranasal sinuses and the neck. Oral mucosa is the exceedingly rare site and when it occurs, it is more frequent in the soft palate [5, 6]. Left buccal mucosa was the site of presentation in our case, which was extremely rare as well the age of the patient, which was 48 years.

Clinical presentation of RMS is variable and depends upon the anatomical site, age, and the presence or absence of distant metastases. The lesion in head and neck region may cause impairment of vision, hearing, speech, swallowing, and respiratory symptoms. Our case indecently noted a nodule in the left side of the cheek 10 days after history of tooth extraction, which was rapidly progressed in size and caused limitation in opening of mouth and difficulty in chewing.

As such, there is no difference in the radiological appearance of RMS in children and adults. Radiological examination of the lesion is necessary to reveal the size, extension of the lesion, extent of bone destruction, post-therapy follow-up, and in diagnosing a possible recurrence of disease. It helps in precise pre-therapeutical staging of tumor, provides important prognostic information and hence, has an impact on the entire therapy management. Similarly in the present case, head and neck CT, PET-CT, and CT chest and abdomen guided our oncologist to make an important treatment decision regarding the case. About 45% of patient in due course develops distant metastasis with lung is the most common site, which was not seen in our patient [7].

Histologically, embryonal rhabdomyosarcoma is characterized by the presence of undifferentiated pattern less spindled cells and small round blue cell. Rhabdoid cells and strap cells if present, aid in the likelihood of ERMS [8]. The important differential in our case were spindle cell carcinoma and malignant peripheral nerve sheath (MPNST), amelanotic melanoma. Any ulceroproliferative lesion in oral cavity of an adult to elder patient, the first possible clinical diagnosis would be a carcinoma. Likewise, microscopically also, in any malignant spindle cell lesion in oral cavity, someone has to rule out the possibility of spindle cell carcinoma before making any exceptional diagnosis. Associated dysplastic overlying buccal mucosa favors spindle cell carcinoma. Pancytokeratin positivity in tumor cells supports the diagnosis of spindle cell carcinoma though overall only about 60% of cases may be positive [9]. In the present case, all the epithelial markers, i.e., pancytokeratin, EMA, and P40 were negative. S100 negativity in our case rules out the possibility of MPNST and amelanotic melanoma. Other exceptionally rare differentials could be Ewing’s sarcoma (ES) and Synovial sarcoma (SS) [10, 11]. Focal spindled morphology in our case helped us to keep aside from making a diagnosis of ES. Immunopositivity for desmin and myogenin excludes synovial sarcoma. In our case, the tumor cells are showing round to oval morphology along with spindle cell morphology which rules out spindle cell type of RMS.

Embryonal rhabdomyosarcoma is characterized by a consistent loss of heterozygosity (LOH) at chromosome 11p15.5 which may result in activation of a tumor suppressor gene or genes, including GOK. Some authors have reported trisomy 8 as a consistent finding in embryonal rhabdomyosarcomas. More recently, a number of studies found upregulation of genes involved in the hedgehog pathway, i.e., GLI1 and Ptch1 [8]. In the present case, no genetic testing was done.

Adult RMS are more aggressive, having overall worse survival rate and has a higher incidence of recurrence. Hence, best possible clinical outcome is achieved via a multimodal approach [12]. Effective surgical excision is challenging in cases of RMS of the head or neck region due to the involvement of other critical structures in these locations. As in the present case where the tumor was extending along parapharangeal space reaching up to carotid space and abutting deep lobe of parotid gland, made the effective surgical excision extremely challenging. RMS is a radiosensitive lesion but can result in radiation-induced secondary tumors [13]. In addition, multiagent chemotherapy, including vincristine, adriamycin, cyclophosphamide, and actinomycin D decreases micro metastases and malignant cell population, thus favoring long-term survival with fewer complications [14]. Current case similarly received VAC (vincristine, adriamycin, cyclophosphamide), followed by external beam radiotherapy after 9 weeks, and adjuvant chemotherapy of same regime, which did not showed any significant clinical response. However, in due course of time, patient lost the follow-up. Till the last visit to hospital, patient did not develop any distant metastasis.

Conclusion

Embryonal RMS of oral cavity in elderly patient is extremely rare. Spindle cell tumor in oral cavity with absence of dysplasia in overlying epithelium, immunonegativity for pancytokeratin, P40, and epithelial membrane antigen, should have to be investigated for sarcoma by using extended panel of immunohistochemistry (Fig. 2).

Fig. 2.

a (H&E × 100) and b (H&E × 400) show a spindle cell tumor arranged in a vague fascicular pattern. The tumor cells are having oval to elongated hyperchromatic nuclei with moderate nuclear atypia. There is brisk mitotic activity

The tumor cells are immunopositive for desmin (diffuse cytoplasmic) (c), myogenin (focal, nuclear) (d), vimentin (e) while immunonegative for pancytokeratin, epithelial membrane antigen (EMA), P40, and S100 (f)