Undifferentiated pleomorphic sarcoma in the maxillary sinus: a case report

Abstract

Background

Undifferentiated pleomorphic sarcoma, previously called malignant fibrous histiocytoma, is a type of malignant mesenchymal tumor (sarcoma) of soft tissue and sometimes bone. It is uncommon in the oral cavity and very sporadic in the maxillary sinus. Microscopic diagnosis of this malignancy in the maxillary sinus can be very challenging, because there is a range of features that may overlap with other benign and malignant tumors.

Case presentation

In this paper, we report a case of undifferentiated pleomorphic sarcoma in the maxillary sinus of a 61-year-old Iranian man who was referred to the maxillofacial surgery ward due to pain and swelling of the upper jaw and visual problems in the right eye. In the initial incisional biopsy, peripheral giant cell granuloma was diagnosed in the hospital service. Yet, on request of the surgeon, during reviewing the slides in the oral pathology service of the School of Dentistry, and using an immunohistochemical method, undifferentiated pleomorphic sarcoma was diagnosed. In this paper, a case of undifferentiated pleomorphic sarcoma in the maxillary sinus is reported, with an emphasis on the management of its problems and diagnostic errors.

Conclusion

This study reviews the challenges and histopathological diagnostic errors of this uncommon tumor in this rare location. This lesion may be similar to other malignant tumors, and its correct diagnosis requires a detailed and complete examination.

Introduction

Undifferentiated pleomorphic sarcoma (UPS) is a high-grade malignancy of unknown etiology, often observed in soft tissue and sometimes in bone [1]. In most cases, it is clinically reported as a large and usually painless lump in the soft tissue [2]. It often occurs in late adulthood and between the ages of 50 and 70 years. Its prevalence is twice as common in men than in women [1,2,3,4]. The odds of incidence of UPS in the cervicocephalic region, involving the sinonasal canal and craniofacial bones, larynx, and cervical soft tissue, are low and entail 3–10% of cases. This malignancy rarely involves the maxillary sinus [1, 3, 5]. In this paper, a case of UPS in the maxillary sinus is reported, with an emphasis on the management of its problems and diagnostic errors [3]. The radical surgery of the patient was successfully performed and he was referred to the relevant specialists for additional radiotherapy and chemotherapy treatments.

Case presentation

A 61-year-old Iranian man with a complaint of slight pain and swelling in the upper jaw area on the right side that started 2 months ago. The medical, family, and psychosocial history was negative. The patient had no history of smoking or alcohol abuse, and there were no systemic problems in his medical history.

Clinical findings

A diffuse tender swelling of the right side of the upper jaw was identified. Owing to the enlargement of the lesion, an interference and disturbance was visible in closing the mouth and closing the right eye. In the intraoral examination, a soft tissue mass was observed that perforated anteroposterior the alveolar ridge of the right maxilla with an ulcerated surface. (Fig. 1 A, B).

Fig. 1

Clinical view of the patient. A Extraoral view. B Intraoral view

Diagnostic assessment

In panoramic radiograph of our patient, a destructive radiolucent lesion was observed in the right upper jaw that destroyed the sinus floor and the alveolar bone of that area (Fig. 2). In examining computed tomography (CT) scans and magnetic resonance imaging (MRI) radiographs, a lesion with unclear boundaries was visible that filled the maxillary sinus and destroyed the tuberosity of the maxilla and the lateral wall of the nose (Fig. 3 A, B).

Fig. 2

Panoramic radiograph view of the patient: radiolucent lytic lesion in the right upper jaw, destroying the sinus floor and alveolar bone of that area

Fig. 3

A Computed tomography view of coronal section, soft tissue window. B Axial section magnetic resonance imaging view of T2: a high signal lesion with unclear boundaries that filled the maxillary sinus, destroying the tuberosity of the maxilla and the lateral wall

Therapeutic intervention

The patient underwent an incisional biopsy in the maxillofacial surgery ward of the hospital and a diagnosis of peripheral giant cell granuloma was made. Nonetheless, owing to the inconsistency of this diagnosis with the clinical features, the patient was referred to the oral and maxillofacial pathology ward at the School of Dentistry for reexamination and review of the microscopic slides. The patient stated that within a few days after the incisional biopsy, the size of the swelling increased. In the extraoral examination, the patient appeared pale with no redness and swelling in the right side of the face. In the intraoral examination, a soft tissue mass was observed, which perforated anteroposterior the alveolar ridge of the right maxilla with an ulcerated surface. In this report, after confirming the diagnosis of UPS with the origin of the maxillary sinus, the patient underwent a hemimaxillectomy along with the removal of 5–15 mm of the apparently healthy margins around the lesion; after sending the biopsy to the frozen section, the margins around the tumor were negative.

Follow-up and outcomes

Almost a year after surgery the patient remains healthy with no recurrence of swelling or facial complaints.

Discussion

The term malignant fibrous histiocytoma (MFH) was first coined by Ozzello et al. [6] in 1963 and described by O’Brien and Stout [6] in 1964. Still, some papers have reported that the term MFH was first coined and proposed by Stout (1960) as pleomorphic sarcomata of soft tissue, which probably originate from histocytes that have the ability to be converted into fibroblasts [7]. Over the next two decades, the concept of MFH was confirmed and considered as the most common soft tissue tumor in adults. Nevertheless, recent clinicopathological and immunohistochemical studies showed that in most samples of this malignancy, tumoral fibroblasts do not originate from histocytes and were hence diagnosed as a subgroup of other pleomorphic sarcomas [7, 8]. Fletcher (1992) stated in a review study that out of 159 neoplasms diagnosed as MFH, only 13% could possibly be diagnosed as MFH. Most of these tumors were pleomorphic subtypes of other sarcomas, such as liposarcoma [9]. In 2002, the World Health Organization (WHO) no longer considered malignant fibrous histiocytoma as a distinct diagnostic category. Since then, this malignant neoplasm fell in a group called undifferentiated pleomorphic sarcoma [8,9,10]. Thus, since 2002, the term “undifferentiated pleomorphic sarcoma” replaced the old term MFH. In general, sarcomata comprise approximately 1% of adult tumors. Approximately 80% of these tumors originate from soft tissue and the remaining 20% originate from bone and cartilage [8]. Moreover, less than 10% of sarcomata are found in cases of the cervicocephalic region [2]. MFH, which was once the most common soft tissue neoplasm in adults, now accounts for only about 5% of soft tissue sarcomata in adults [11]. No definitive etiology has yet been identified for MFH, although a history of radiotherapy, bone fracture, osteonecrosis, trauma, and Paget’s disease has been reported for these patients [2, 3, 12]. Primary intraosseous MFH is usually detected in the metaphysis of long bones of the extremities, such as the femur and tibia. A review of studies showed only a few cases of primary malignant fibrous histiocytoma in the soft tissues of the oral cavity, and only 3–10% of cases were observed in the sinonasal region, larynx, soft tissue, and craniofacial bones [4, 13]. MFH usually occurs between the ages of 50 and 70 years, and is twice as prevalent in men than in women [2, 14]. In most cases, it has been observed clinically as a large painless lump in the soft tissue [2]. In the case reported in this study, the patient was a 61-year-old man who had been referred due to swelling and slight pain in the maxillary region. On the basis of some studies, the radiographic appearance of this lesion is usually an osteolytic lesion with an unclear margin and without a sclerotic margin [4]. In panoramic radiograph of our patient, a destructive radiolucent lesion was observed in the right upper jaw that destroyed the sinus floor and the alveolar bone of that area (Fig. 2). In examining CT scans and MRI radiographs, an ill-defined lesion was visible that filled the maxillary sinus and destroyed the tuberosity of the maxilla and the lateral wall of the nose (Fig. 3 A, B). On the basis of the clinical and radiographic views, differential diagnoses including carcinomas and adenocarcinomas originating from the maxillary sinus, including malignant tumors of the peripheral salivary glands, lymphoma, and melanoma, or sarcomata originating from bone, cartilage, nerve, or muscle in the area were proposed. Given the fullness of the maxillary sinus at the time of the patient’s visit and on the basis of the evidence of imaging and the short interval that had lapsed since the formation of the intraoral mass as the patient stated, there was a strong possibility that the lesion originated from the maxillary sinus, which was also confirmed by the surgical findings. The general histopathology of this lesion is often in the form of short clusters of spindle-shaped cells, usually arranged in a storiform pattern. Multinucleated giant cells, abnormal mitoses, necrotic areas, and scattered histocyte-like cells can be seen in the lesion context [12]. Histological subtypes for MFH include: storiform/pleomorphic, myxoid, giant cell, inflammatory, and angiomatoid. The most common type reported by scholars is the storiform/pleomorphic type, and the second most frequent type is the myxoid type, which has a better prognosis than other types [5]. Our patient underwent an incisional biopsy by a maxillofacial surgeon, and the sample was sent to the general pathologist for histopathology examination in the hospital. Owing to the observation of numerous giant cells in the connective tissue detected immediately in the superficial striated squamous epithelium, the diagnosis of peripheral giant cell granuloma was established (Fig. 4 A). However, the clear pleomorphism and abnormal mitotic forms in this sample were simply neglected (Fig. 4 B). Owing to the inconsistency of this diagnosis with the clinical features, the sample was again sent by the maxillofacial surgeon to the oral pathology ward of the School of Dentistry. In the detailed histopathological examination of the lesion, hypercellular proliferation of abnormal spindle-like fibroblastic cells with hyperchromic nuclei and abundant eosinophilic cytoplasm, along with some pleomorphic histiocytic-like cells with vesicular nuclei and foamy cytoplasm with storiform arrangement (Fig. 5 A, B), were observed in a fibrovascular stroma with extensive areas of hemorrhage and extravasated erythrocytes. In the context of the lesion, abnormal mitotic figures and multinucleated giant cells were abundantly visible. In addition, in the limited and superficial areas immediately under the covering epithelium, pseudo-osteoid deposits with a lace-like pattern were seen (Fig. 6). In this tumor type, storiform or woven growth patterns have been described as elongated cells or nuclei inside small bundles with a mat (or interwoven) pattern [15]. It should be noted that storiform design as an interwoven pattern is different from a wheel-shaped or whirlwind pattern. Owing to the different degrees of cellular pleomorphism, it is sometimes relatively difficult to diagnose UPS only through morphology as it may be confused with other lesions; therefore, immunohistochemical staining is necessary for the final diagnosis of the lesion [1]. In the present case, considering the possibility of pleomorphic sarcomata, immunohistochemical markers, cytokeratin, vimentin, CD68 antigen, S100 protein, and desmin were requested. Tumoral cells were diffusely positive for vimentin and focally positive for CD68 antigen (Figs. 7, 8), but other requested markers did not show any activity in the immunological lesion. Finally, these findings were consistent with the diagnosis of an undifferentiated pleomorphic sarcoma (or malignant fibrous histiocytoma), of storiform/pleomorphic giant-cell type, by excluding other possible diagnoses in an exclusive manner. Lawson et al. studied ten cases of malignant fibrous histiocytoma and found that all of them had vimentin expression. In addition, six cases showed desmin and neurofilament expression [16]. Yet, desmin is an interstitial muscle filament and its incidence is seen in smooth and striated muscle cells [1]; since the desired lesion was negative for the desmin marker, the possibility of smooth and striated muscle tumors was rejected. Owing to the negativity of the cytokeratin marker, the possibility of pleomorphic anaplastic carcinoma was ruled out. S100 markers were also negative in the present report, thus the possibility of melanoma and pleomorphic neoplasms of nerve and fat origin was excluded [12]. Another challenging diagnostic point in the present case was the observation of limited areas of pseudo-osteoid deposits with a lace-like pattern around the neoplastic cells immediately under the epithelium of the incisional biopsy (Fig. 6), suggesting the possibility of an extraskeletal osteosarcoma. It should be pointed out that some types of sarcomata can also form osteoids. Most of these sarcomata are seen in late adulthood and in the extremities, with a high histopathological grade that can be easily distinguished from osteosarcoma. Some benign soft tissue tumors that are hypercellular, mitotically active, and have steroid production increase the possibility of misdiagnosing an osteosarcoma, especially in a small biopsy, and it is important to differentiate these cases from each other [17]. In the present report, osteoid deposits were observed only in limited areas on the margin of the lesion immediately under the epithelium, but were not present in other parts of the lesion in incisional and excisional biopsy; therefore, the possibility of an extraskeletal osteosarcoma was rejected and the diagnosis of a UPS with reactive steroid production was confirmed. Basically, there are three types of treatment for malignant fibrous histiocytoma: surgery, radiotherapy, and chemotherapy. Sabesan et al. presented the treatment management of malignant fibrous histiocytoma of the head and neck as a challenge due to the anatomical and functional complexity of this area as well as the sporadic incidence of the lesion in this location. Furthermore, they suggested that the primary surgery for this tumor in the cervicocephalic region should be as radical as possible, and biopsy is necessary for diagnosis. Radiotherapy also diminishes the possibility of local recurrence and has become an integral part of treatment; nonetheless, the role of chemotherapy in the treatment of this tumor is not completely clear [17]. Yamaguchi et al. [18] reported that the rate of local recurrence in patients with adjuvant radiotherapy or chemotherapy combined with surgery was lower compared with patients who underwent surgery alone. However, the amount of metastasis did not show much disparity between them. They also stated that chemotherapy is useful for patients who have a high risk of lung metastasis. On the basis of the study conducted by Kearney et al. [19], the rate of recurrence in surgery related to this lesion was reported to be about 66% with a healthy margin of more than 3 cm around the tumor, and about 86% with a margin of less than 3 cm. In this report, after diagnosis was confirmed, the patient underwent hemimaxillectomy surgery along with the removal of 15 mm of the healthy margin around the lesion (Fig. 9). After sending the sample to be frozen, negative margins around the tumor were reported. The prognosis of this tumor is not good and its recurrence is common; there are usually metastases to the lungs, liver, and bones. Some researchers reported that 25–35% of patients with undifferentiated pleomorphic sarcoma in the cervicocephalic region are involved in metastasis [12]. Factors associated with a favorable prognosis in patients with malignant fibrous histiocytoma include: age less than 60 years, tumor size less than 5 cm, superficial lesion location, low-grade malignancy, myxoid histological subtype, and absence of metastatic disease [1, 20, 21]. Follow-up with lymph node examination in these patients should be performed every 3–6 months for 2 years and then at least once a year [21]. The overall survival rate after a 5-year follow-up of patients ranges from 30% to 74% [12]. Finally, the present case was referred to relevant specialists for additional chemotherapy and radiotherapy treatments. A year after surgery, the patient remains healthy with no recurrence of swelling or facial complaints (Fig. 10).

Fig. 4

A Presence of numerous giant cells in connective tissue. B Pleomorphic giant cells and mitosis

Fig. 5

Histopathological view of spindle-shaped cells with storiform design. A Image with 10× magnification. B Image with 40× magnification

Fig. 6

Areas of osteoid deposits with a lace-like design

Fig. 7

Immunohistochemical staining for tumoral cells with vimentin marker was diffusely positive (10× magnification)

Fig. 8

Immunohistochemical staining for tumoral cells with CD68 marker was focally positive (10× magnification)

Fig. 9

Picture during surgery of the patient

Fig. 10

Clinical appearance of the patient a year after surgery. A Extraoral view. B Intraoral view

Conclusion

UPS is an invasive mass with the ability to progress. It is very rare in the maxillary sinus region and can be associated with many diagnostic challenges. In terms of histopathology, this lesion may be similar to other malignant tumors, and its correct diagnosis requires a detailed and complete examination of the morphology and the use of immunohistochemical markers to exclude other pleomorphic sarcomata. Timely diagnosis and prompt referral have better results in the lifetime of patients.