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An Official Publication of the Indian Association of Oral and Maxillofacial Pathologists


 
  Table of Contents    
CASE REPORT  
Year : 2014  |  Volume : 18  |  Issue : 3  |  Page : 453-459
 

Primary leiomyosarcoma of the maxilla: An investigative loom-report of a challenging case and review of literature


1 Department of Oral and Maxillofacial Pathology, Genesis Institute of Dental Sciences and Research, Ferozepur, India
2 Department of Oral and Maxillofacial Surgery, Dashmesh Institute of Research and Dental Sciences, Faridkot, Punjab, India
3 Department of Oral and Maxillofacial Surgery, Oral Health Sciences Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India

Date of Submission11-Jun-2012
Date of Acceptance31-Dec-2014
Date of Web Publication13-Feb-2015

Correspondence Address:
Simarpreet Virk Sandhu
Professor and Head Department of Oral and Maxillofacial Pathology, Genesis Institute of Dental Sciences and Research, Ferozepur Moga Road, Ferozepur 152001, Punjab
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-029X.151350

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   Abstract 

Leiomyosarcoma (LMS) is a malignant neoplasm composed of cells showing distinct smooth muscle features. Majority of the tumors are located in the retroperitoneum, including the pelvis and the uterus but are rare in the oral and pharyngeal region. Intraorally, they are present as painless, lobulated, fixed masses of the submucosal tissues in middle-aged or older individuals. Lesions are usually slow growing and are less than 2 cm in diameter at the time of diagnosis. Here we report the clinico-pathological findings of a case of primary LMS of the maxilla in 63-year-old male patient with an emphasis on the judicious use of ancillary diagnostic modalities to arrive at a definitive diagnosis.


Keywords: Leiomyosarcoma, malignant spindle cell tumor, nuclear palisading, pleomorphic undifferentiated sarcoma, rhabdomyosarcoma, soft tissue sarcoma


How to cite this article:
Sandhu SV, Sodhi S P, Rai S, Bansal H. Primary leiomyosarcoma of the maxilla: An investigative loom-report of a challenging case and review of literature. J Oral Maxillofac Pathol 2014;18:453-9

How to cite this URL:
Sandhu SV, Sodhi S P, Rai S, Bansal H. Primary leiomyosarcoma of the maxilla: An investigative loom-report of a challenging case and review of literature. J Oral Maxillofac Pathol [serial online] 2014 [cited 2017 Dec 15];18:453-9. Available from: http://www.jomfp.in/text.asp?2014/18/3/453/151350



   Introduction Top


Leiomyosarcomas (LMSs) are relatively rare mesenchymal neoplasms composed of cells that exhibit smooth muscle differentiation. They account for 5-10% of soft tissue sarcomas. [1],[2] These adult soft tissue sarcomas are far out numbered by the more commonly occurring liposarcomas. Majority of these tumors are located in the retroperitoneum, including the pelvis and the uterus. LMS is a rare malignancy of the oral and pharyngeal region of unknown etiology. According to a review of smooth muscle tumors, only 0.06% occurred in the oral region. [1],[3] Although no definite causative factor has yet been identified, correlation has been established between LMS and exposure to radiations and chemicals and possibly trauma. Association of LMSs with hereditary (bilateral) retinoblastoma (Rb), which appears to result directly from mutations or deletions in the Rb 1 gene, suggests the role of chromosomal defects in the etiology of the tumor. [4]

These tumors arise from smooth muscle cells, especially those found in blood vessel walls and from undifferentiated mesenchymal cells. Often, the tumor completely obliterates its origin in the blood vessel walls. [2],[4]

The sex predilection of LMSs depends on the location of the tumor. Retroperitoneal and inferior vena cava LMSs are more common in women. On the other hand, the oral tumors do not display any significant gender predilection. LMSs present intraorally as painless, lobulated, fixed masses of the submucosal tissues in middle-aged or older individuals but are rarely found in children. [5],[6],[7] Oral lesions are usually less than 2 cm in diameter at diagnosis and are slow-growing, but secondary ulceration of the mucosal surface has been reported in a few cases. [2],[6]

Histological appearances differ according to the degree of differentiation but the presence of a focus of fascicles of elongated brightly eosinophilic spindle cells with vesicular, ovoid to cigar-shaped nuclei showing a strong positivity for smooth muscle actin (SMA) and/or desmin is a minimum requisite. [8] In well-differentiated lesions, there is fascicular streaming of spindled cells in a manner similar to that seen in a leiomyoma. About 10% of LMSs are anaplastic, which in the extreme cases may show pleomorphic undifferentiated sarcoma (PUS)/malignant fibrous histiocytoma (MFH) like pleomorphism. In these tumors, numerous pleomorphic giant cells with deeply eosinophilic cytoplasm are admixed with a set of more uniform-appearing spindle and round cells.

The purpose of this compilation is to present a case report of a primary LMS of maxilla in a 63-year-old male with a stress on comprehensive morphological analyses and careful interpretation of immunohistochemical markers to arrive at a correct diagnosis.


   Case report Top


A 63-year-old male patient reported to the out-patient department of the Dental School with a6-month history of progressive and continuous enlargement in the anterior maxilla.The growth was painless and non-tender and had loosened the upper front teeth. On examination, the growth was bosselated and arose from the anterior maxillary alveolus extending from right canine to left lateral incisor. There was a palatal extension in the antero-posterior direction. It was firm on palpation and demonstrated a patchy bluish discoloration. Based on the above findings, a clinical diagnosis of malignancy of maxilla was made. Computerized tomography scan showed an osteolytic lesion extending in the nasal chamber but not laterally in the maxillary sinuses. The axial section showed a diffuse soft tissue mass obliterating the anterior nasal chamber completely destroying the anatomy of the anterior palate and the nasal cartilaginous skeleton [Figure 1].
Figure 1: (a) Intraoral photograph showing bosselated growth in the anterior maxilla with patchy bluish discoloration extending from right canine to left lateral incisor with palatal extension in the anteroposterior
direction involving the midline. (b) Computed tomography (CT) axial section showing a diffuse soft tissue mass obliterating the anterior nasal chamber. The lesion is also seen extending in the anterior maxillary alveolus area completely destroying the anatomy of the anterior palate and the nasal cartilaginous skeleton


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Because of the non-specific clinical presentation, based on the age of the patient and location of the tumor, the differential diagnoses include a salivary gland tumor, a sarcoma and squamous cell carcinoma and incisional biopsy was planned under local anesthesia. Analysis of the biopsy specimen revealed a tumor mass composed of fascicles of interlacing spindle-shaped cells with abundant eosinophilic cytoplasm and moderately large nuclei exhibiting atypia. Based on the above features, a provisional diagnosis of a malignant spindle cell tumor was made. The differential diagnosis of spindle-shaped lesions included malignant lesions such as PUS, rhabdomyosarcoma (RMS), LMS, malignant peripheral nerve sheath tumor (MPNST) and fibrosarcoma.

Since the lesion showed aggressive clinical and radiological features suggestive of malignancy, resection of tumor with safe wide margins was planned under general anesthesia. The tumor was safely resected with approximately 1.5 cm of safe margin in the healthy tissue. A 2.4-mm titanium reconstruction plate was affixed in the residual maxilla to support a prosthesis in future. In order to rule out any primary or secondary foci of malignancy, a body scan was performed and the results were negative. The patient has been on regular follow-up for the last 2 years with no signs of recurrence. A tooth bearing obturator was delivered and the patient is presently satisfied with its appearance and function.


   Gross findings Top


The excised dentate hemimaxilla measuring 8 cm × 7.5 cm in dimension; reddish- brown in color and firm in consistency was received [Figure 2]. The cut surface of the tumor mass was solid, fibrous and yellowish-white in color with foci of hemorrhage and necrosis.
Figure 2: Gross appearance of the excised dentate hemimaxilla. The tumor mass measured 8 cm × 7.5 cm in dimensions and was creamish brown in color with color variegation ranging from brown to yellow and
was fi rm in consistency


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   Histopathological findings Top


Histopathologically, the tumor mass was composed of elongated spindle cells arranged in interlacing bundles in interweaving fascicles of varying size. The cells showed abundant eosinophilic cytoplasm and moderately large centrally located blunt ended nuclei with mild atypia. Cytoplasmic vacuolation was also seen. Hyperchromatism of nuclei was pronounced and numerous normal and abnormal mitotic figures were scattered throughout the lesion. Mitotic figures (MF) were abundant and ranged up to 22 MF/10 HPF (high power fields). Necrotic foci were scattered throughout the tumor. The stroma was composed of a delicate network of capillaries [Figure 3]. Numerous pleomorphic giant cells with deeply eosinophilic cytoplasm was intimately admixed with more typical cells. Pleomorphic areas imparting a pleomorphic appearance were abundant in the tumor hence a provisional diagnosis of pleomorphic sarcoma was made and the spectrum included tumors exhibiting prominent pleomorphism like PUS (storiform-pleomorphic MFH), pleomorphic liposarcoma, pleomorphic leiomyosarcoma and pleomorphic RMS [Figure 4]. The tumor was graded according to the French grading system as described by Coindre et al. [9] With this system, the differentiation grade of tumors, the number of MF/2 mm 2 and the amount of necrosis are scored. All tumors were divided into grade 1, grade 2 or grade 3 tumors. The mitotic index (number of MF/2 mm 2 ) was determined on hematoxylin and eosin (H and E) stained sections of the tumors; the areas with the highest rates of mitosis were selected.
Figure 3: Photomicrographs showing a) Low power view of a tumor mass with numerous engorged vascular channels (H&E stain, x40). (b) Tumor mass composed of fascicles of interlacing spindle-shaped cells with abundant eosinophilic cytoplasm and moderately large nuclei exhibiting atypia (H&E stain, x40). (c) Elongated cells with abundant cytoplasm exhibiting centrally placed blunt ended nuclei (H&E stain, x100). (d) Bizarre tumor cells with nuclear pleomorphism interspersed among regular spindle-shaped cells (H&E stain, x100)

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Figure 4: Photomicrographs showing pleomorphism in leiomyosarcoma. (a) Bizarre spindle cell exhibiting deeply eosinophilic cytoplasm with pleomorphic nuclei and nuclear vacuolization (H&E stain, ×400). (b) Cells exhibiting extreme degree of pleomorphism and occasional multinucleation resembling pleomorphic undifferentiated sarcoma/ malignant fi brous histiocytoma (H&E stain, ×400)

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The histopathological uncertainty prompted an immunohistochemical analysis. For immunohistochemical staining, the Strept Avidin Biotin (SAB) method was used with primary antibodies to vimentin, SMA, Muscle Specific Actin (HHF35), pancytokeratin, desmin, myogenin, h-caldesmon, CD31, CD34, S-100 protein,   human melanoma black (HMB) 45 and α 1 anti-chymotrypsin. The tumor cells showed a strong immunopositivity for vimentin with focal positivity for SMA and muscle HHF-35 [Figure 5]. The tumor cells were negative for pancytokeratin, Epithelial Membrane Antigen (EMA), desmin, myogenin, h-caldesmon, CD31, CD34, S-100 protein and HMB45 [Table 1].
Figure 5: Photomicrographs showing (a) Strong positive immunohistochemical reaction to antibodies against vimentin (IHC stain, ×100), (b) Focal expression of smooth muscle actin (SMA) in the tumour cells (IHC stain, ×100), (c) Focal reaction to muscle specifi c actin (HHF-35) by the tumor cells (IHC stain, ×400)

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Table 1: Immunohistochemical expression of the lesional cells

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Based on the above parameters, a diagnosis of Pleomorphic Leiomyosarcoma Grade 3/3 (Coindre Grading System) was made.


   Discussion Top


LMSs are malignant neoplasms composed of cells showing distinct smooth muscle features. [1] They comprise a heterogeneous group of neoplasms, each with unique clinical, histological and radiographic characteristics. [10]

LMS is listed as a "rare disease" by the Office of Rare Diseases (ORD) of the National Institute of Health (NIH). [11] It is rarer in the head and neck region and most commonly affects the nose and paranasal sinuses, skin, subcutaneous tissue and the cervical esophagus. [1] In the oral cavity, the maxillary sinus, mandible and maxilla appear to be the predilection sites for LMS, but other reported intraoral locations are the cheek, floor of the mouth, tongue, hard and soft palate, lips and gingiva. [1],[5] The rare occurrence of LMS in the oral cavity has been correlated to the scarcity of smooth muscle structures in this location, as compared with their abundance in other sites. LMSs occurring in the oral tissues in all probability arise from tunica media of blood vessels, arrectores pilorum, circumvallate papillae, myoepithelial cells and pluripotential undifferentiated mesenchymal cells. [1],[4]

The tumor lacks specific age or sex predilection. [3],[5] Oral and maxillofacial LMSs are rare and have no specific signs and symptoms, usually presenting as non-ulcerated painless masses. [6] As a result, some of these lesions are occasionally mistaken for the other common lesions affecting the oral cavity and correct diagnosis is made only after a judicious histologic examination. The clinical differential diagnosis for a palatal lesion includes benign and malignant salivary gland tumors (pleomorphic adenoma, mucoepidermoid carcinoma, adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma) and benign and malignant mesenchymal tumors. [5]

Because of lack of a distinct radiographic presentation, these tumors can simulate any expansive or destructive lesion of the jaw. [6] They can present as lytic lesions with ill-defined margins, periosteal elevation, calcification and cortical destruction. [12]

Microscopic diagnosis of the smooth muscle lesions is difficult due to the small biopsy sizes and the diversity of the lesions. [13] Morphological features in favor of smooth muscle differentiation include intersecting fascicles of spindle cells, eosinophilic cytoplasm, paranuclear vacuoles and blunt-ended nuclei. Para nuclear vacuole is seen at one end of the nucleus, causing a slight indentation, so the nucleus assumes a concave rather than a convex contour. Size, cellularity, atypia, necrosis and mitoses per HPF are indicators that help define the difference between a benign smooth muscle tumor and LMS. Of these indicators, mitoses per HPF is considered to be the most reliable. [1],[14]

In poorly differentiated LMS, lesional cells are less elongated, more fusiform or rounded, enlarged and pleomorphic. [5] Hyperchromatism of nuclei is often pronounced and numerous normal and abnormal mitotic figures are scattered throughout the lesion. Focal areas may contain giant cells with multiple, pleomorphic, even bizarre nuclei. [6],[8] The stroma is typically sparse, but cellular streaming is usually far less regular than in the low grade lesions, although the fascicles may be as uniform as those of well-differentiated lesions. [15] Hemorrhage, focal necrosis, increased vascularity and focal myxoid change are not uncommon features of poorly differentiated lesions. [1],[6],[12]

A score of 1 is currently assigned to sarcomas closely resembling normal adult tissue to such a degree as to be confused with benign tumors, such as a well-differentiated LMS. A score of 3 is given to embryonal and poorlydifferentiated sarcomas, sarcomas of doubtful histologic type, synovial sarcoma, primitive neuro-ectodermal tumor, osteosarcoma, pleomorphic RMS and pleomorphic liposarcoma. Other sarcomas of certain histologic type such as myxoid liposarcoma are scored 2. Mitotic count is obtained in 10 successive HPFs in most mitotic areas. This count is taken to establish the score: Score 1 for 0 to 9 mitoses; score 2 for 10 to 19 mitoses; and score 3 for more than 19 mitoses per 10 HPF. [9]

Our case represented Pleomorphic LMS Grade 3/3 (Coindre Grading System). It is a morphologic variant rather than a distinctive subtype and is usually associated with areas of undifferentiated pleomorphic sarcoma along with fields showing morphological, immunohistochemical or ultrastructural evidence of smooth muscle differentiation.

Although the present case displayed features of smooth muscle differentiation to some extent, the correct light-microscopic diagnosis was difficult, mainly because the tumor was pleomorphic, resembling a PUS (MFH).

The differential diagnosis of LMSs includes other sarcomas composed of fascicles of moderately differentiated spindle cells, such as fibrosarcoma and MPNST. Although the low-power appearance of all three can be similar, there is a greater tendency to see a close juxtaposition of longitudinally and transversely cut fascicles in a LMS. The cytological features play an important role in the differential diagnosis. Compared with the cells of LMS, those of a fibrosarcoma tend to be tapered and those of a MPNST are wavy, buckled and distinctly asymmetric. [1],[5],[6],[15],[16] Vimentin, SMA, desmin, h-caldesmon are positive in LMS but fibrosarcoma is diagnosed by exclusion as it is S-100 positive [Table 2]. Thus, careful scrutiny of cytological details in multiple sections, clinico-pathological correlation and immunohistochemistry (IHC) are mandatory for a definitive diagnosis.
Table 2: Tumor immunoreactivity reference chart[17]

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In pleomorphic LMS, the neoplastic cells have more bizarre features with numerous tumor giant cells, high mitotic activity and a prominent storiform pattern. The latter is sometimes so overwhelming that a diagnosis of PUS (MFH) is made on H and E. We encountered a similar problem in our initial diagnosis where the diffuse and prominent storiform arrangement of neoplastic spindle cells favored a diagnosis of PUS. Based on the IHC results a diagnosis of LMS was reached thus emphasizing its role in arriving at a final diagnosis in case of spindle cell tumors.

Originally the tumor was diagnosed as PUS (MFH) based on the whorled structural pattern and considerable cellular pleomorphism. The distinction between pleomorphic LMS and PUS (MFH) is probably the most difficult and controversial. Unless there are light microscopic areas that are diagnostic of smooth muscle differentiation, decision is based upon the immunoreactivity for various myogenic markers reflective of smooth muscle differentiation. [10] Significant amounts of actin or some degree of both actin and desmin immunoreactivity is required for the diagnosis of pleomorphic LMS. [1] Peripheral expression of actin immunoreactivity of myofibroblasts in PUS (MFH) contrasts with the diffuse actin immunoreactivity of smooth muscle cells in LMSs and careful evaluation is required to differentiate the two entities. PUS (MFH) are usually positive for α1-antichymotrypsin and vimentin and are negative for myoglobin and desmin. [1],[4]

In this case, discrimination of LMS from RMS was necessary. [15] The tumors that originate from muscle stain positive for desmin, HHF35 and vimentin; however, this case was positive for α-SMA and the diagnosis of RMS was ruled out. Immunohistochemical demonstration of muscle-specific actin and smooth-muscle-specific actin is a strong indicator for LMS. Also, desmin may be helpful in the diagnosis of LMS, since the intermediate filament desmin is present in both smooth muscle and striated muscle. Vimentin is considered a major component of the intermediate filaments of smooth muscle cells derived from vasculature. Spindle-shaped cells of LMS are usually negative for CKs [2],[8],[12],[13],[14],[16] [Table 2].

Intraoral LMSs are very aggressive tumors with high local recurrence and/or distant metastasis and the survival rate is very low. [4] Clinical data of reported cases of maxillary leiomyosarcoma is presented in [Table 3].
Table 3: Clinical data of the reported cases of maxilllary leiomyosarcoma (LMS)

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Generally, a complete surgical resection with tumor-free margins is recommended to control local recurrence and adjuvant radiotherapy or chemotherapy is considered to have little beneficial effect on decreasing recurrence of LMS or increasing survival time. [4] However, in some specific anatomic locations such as the vicinity of the infratemporal fossa, the maxillary sinus, the pterygoid plates and the mandibular condyle, it may be technically less feasible to achieve tumor-free margins because of difficult access, possibly resulting in residual microscopic disease leading to the local recurrence of the tumor and a poorer prognosis. [10],[16],[18] A few cases of metastatic LMS have been described in the oral cavity. [1] Distant metastases of intraoral LMS appear in up to 39% of cases. In oral LMS, metastasis to regional lymph nodes was relatively rare and the most common site of metastasis was the lungs. [19],[20][26][27][28][29]

LMS is a relatively rare tumor in the oral and maxillofacial region and has a poor prognosis as a result of high local recurrence. [4],[5] A thorough morphological analyses and careful interpretation of immunohistochemical markers is necessary to arrive at a correct diagnosis. [21] Accurate diagnosis, classification and multi-modality treatment approach is essential for favorable outcome. [22],[23],[24],[25]



 
   References Top

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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