COM March 2014 Diagnosis

Destructive Soft Tissue Lesion, Right Posterior Maxilla

Can you make the correct diagnosis?

This is a 65-year-old female referred by her dentist to the Department of Oral & Maxillofacial Surgery at the University of Washington for evaluation of a growing lesion in the right posterior maxilla.

1. Spindle Cell Carcinoma

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This lesion is radiographically ill-defined and is clinically destructive of soft tissue and bone, causing mobility of teeth. It is infiltrative, persistent, and mildly painful. All of these criteria point to a highly aggressive lesion that is more likely than not to be malignant in nature. For that reason, squamous cell carcinoma–of which spindle cell carcinoma is a variant–should be included on the differential diagnosis since it is by far the most common malignant neoplasm of the oral cavity, accounting for 90% of all oral malignancies. Neither the location nor the gender of this patient is typical of this condition; nor is the absence of tobacco use. The histology, however, is supportive of this diagnosis.

Spindle cell carcinoma (SpCC) is a rare variant of a poorly differentiated squamous cell carcinoma (SCC) of the head and neck area. It accounts for fewer than 1.3% of all the SCCs in this area. This neoplasm has a biphasic cellular morphology; one cell type is arranged in spindle-shaped cells streaming and crisscrossing each other that can be easily confused with a sarcoma. This confusion has given rise to the other names of this neoplasm, which is also known as “psuedosarcoma” or “sarcomatoid carcinoma.” Spindle cell carcinoma is more common in the larynx followed by the oral and nasal cavities. The clinical profile and etiology of SpCC is similar to that of conventional SCC: it is more common in adult males and strongly associated with tobacco use. Spindle cell carcinoma is more aggressive than the conventional oral and laryngeal SCC and is less responsive to radiotherapy. The average age of occurrence is around 51-58 with a range of 32-80 years of age. It is by far more common in males; one study reported on 18 patients, 17 of whom were males. The most common locations of occurrence in the mouth are the tongue, buccal mucosa, and lips. About 50%-70% of cases of SpCC present as fast-growing exophytic, polypoid, and ulcerated lesions, some presenting with a stalk. It is therefore important that SpCC be included on the differential diagnosis when dealing with a polypoid, exophytic lesion in the larynx and pharynx. Other SpCC are endophytic and destructive deeply, as is the case in this patient. The majority of these cases present in stages 3 and 4, resulting in a poor five-year survival rate. In one study 60% of patients with oral cavity SpCC died within one month to six years of diagnosis. Another study shows that sinonasal SpCC is more aggressive in behavior; 77% of patients died of the disease within 6 months to 2.5 years of diagnosis. Histologically, the diagnosis of this neoplasm can be challenging because of the biphasic cellular morphology. This neoplasm consists of streaming and crisscrossing spindle-shaped cells that resemble a sarcoma intermixed with sheets of more epithelial-looking cells. The spindle-shaped cells can be confusing for mesenchymal tissue when viewed only by hematoxylin and eosin stain. Immunohistochemistry staining for pancytokeratin, on the other hand, should be of assistance in differentiating between the two cell populations. However, occasionally these cells are also positive with smooth muscle actin, making it hard to make a definitive diagnosis. Surgery is usually the treatment of choice, similar to that of conventional oral SCC. The aforementioned study of eighteen patients had an overall one- and three-year survival rate of 37% and 28%. Tumors at stages 1 and 2 had 100% three-year survival rate while those at stages 3 and 4 had 9% one-year survival rate. Another study showed a 73% recurrence rate and 33% metastasis rate.

2. Chondrosarcoma

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As mentioned before, the clinical presentation of soft tissue and bony destruction with ill-defined radiographic margins and tooth mobility should make one think of a highly aggressive condition that is more likely than not to be malignant in nature. This could include a type of sarcoma. Given the age of the patient and the site of location in the maxilla, chondrosarcoma should be included on the differential diagnosis. The completely radiolucent nature of this lesion should not stop a clinician from including chondrosarcoma on the differential diagnosis, since occasionally they can be fully radiolucent in radiographic presentation. The histology, however, is not supportive of this diagnosis.

Chondrosarcoma is a malignant mesenchymal neoplasm of cartilage origin. It is uncommon, especially in the jaws. When it occurs in the jaws, it occurs more often in the maxilla, particularly in the incisor area. It can occur at any age but is most common in males in the sixth decade of life. This neoplasm has a low tendency for metastasis. In general, the prognosis is better than that of osteosarcoma, but it can vary depending on the stage of the disease. It commonly presents as an asymptomatic swelling with buccal and lingual expansion. Patients may experience unexplained paresthesia, headache, loosening and loss of teeth. Radiographically, it presents as an ill-defined radiolucency to mottled radiolucency with snowflake or punctate calcifications or diffuse radiopacity depending on the level of calcification. Sometimes, the teeth will show a widened periodontal ligament space. Histologically, it is characterized by immature and pleomorphic cartilage, but at times the cartilage is benign-looking. It is rare for the cartilage to calcify or differentiate and form bone. Therapy for chondrosarcoma ranges from wide local excision to radical resection with or without chemotherapy, depending on the stage of disease. The prognosis ranges from good to poor.

3. Malignant Lymphoma

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As mentioned before, the aggressive clinical presentation of persistence, ulceration, bone destruction and tooth mobility lends itself to a diagnosis of a highly aggressive lesion that is more likely than not malignant in nature. Given the location of occurrence and the age of the patient, malignant lymphoma (primary or secondary) should be included on the differential diagnosis. The histology, however, is not supportive of a diagnosis of malignant lymphoma.

Malignant lymphomas, both Hodgkin’s and non-Hodgkin’s, of the oral cavity are rare; they are especially rare in the jaws. They are less uncommon in the Waldeyers ring area, where 13% of all extranodal lymphomas occur. About 70% of Waldeyers ring lymphomas occur in the tonsils. Primary and secondary lymphomas of the oral cavity aside from the Waldeyers ring lesions are more common in the hard palate, maxillary sinus, maxilla and posterior mandible. Malignant lymphomas of the oral cavity are most commonly B-cell lymphomas, especially the diffuse large B-cell lymphoma type (DLBCL), which are aggressive in behavior and are slightly more common in males. They are more common in individuals around the fifth to ninth decade of age. Clinically, malignant lymphomas of the jaws present resembling a dental infection, usually with pain and swelling with or without surface ulceration. They can also present with tooth mobility, sinusitis, trismus, and/or a nonhealing extraction site. Sometimes, patients may also complain of otalgia, hearing loss and airway obstructions. In the jaw bone, the maxilla is more commonly affected than the mandible. Radiographically, this neoplasm is usually completely radiolucent but rare cases of radiolucency mixed with patchy bone formation are described. The margins are usually ill-defined with extensions that may be interpreted as multiple radiolucencies. As to the degree of destruction, it depends on the stage of the disease. The early stages of the disease may not be as clearly diagnostic. Radiation therapy and chemotherapy are the treatment of choice, sometimes combined, given the stage of the disease. Histologically, the neoplasm is made up of medium-to-large B-lymphocytes with large round-to-oval nuclei and multiple nucleoli present at the periphery. Neoplastic cells with large nuclei and centrally located prominent nucleoli are more consistent with the immunoblastic type. More aggressive neoplasms may also demonstrate the presence of many macrophages, high mitotic activity, necrosis and apoptosis. Surgery may be performed to relieve some of the clinical symptoms. The five-year survival rate ranges from 60% to 90% based on the stage of the disease. The lower the clinical stage, the better the prognosis.

4. Condition of the Maxillary Sinus (infection vs. malignant)

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Infection: Zygomycosis (Mucormycosis)

The destruction of bone and soft tissue, ill-defined radiographic findings, and tooth mobility are all more likely to be indicative of a malignant tumor; for that reason, most of the differential diagnosis in this case reflects that clinical impression. However, certain infections of the maxillary sinus, such as those in the zygomycosis family, can be just as aggressive and just as serious as any of the malignancies mentioned before. Zygomycosis is a less likely diagnosis in this case for multiple reasons, including the lack of a history of diabetes and of immune-compromised conditions that are essential for this condition to occur. The clinical presentation is also not typical since mucormycosis usually fills the sinus and destroys the palate, changing color to black because this fungus oxidizes as it breaks through the bone into the oral cavity. The histology in this case does not support a diagnosis of zygomycosis.

Zygomycosis is an opportunistic fungal infection most commonly described in uncontrolled insulin-dependent diabetics. The zygomycetes family of organisms includes Mucor, Rhizomucor, and Rhizopus. They are commonly found in decaying fruits and other such material and are common throughout the world. The disease is disseminated via inhalation of spores released in the air from the decaying material. The rhinocerebral form affects the maxillary sinuses, which can extend into the brain via the orbit. Zygomycosis can involve other areas. Zygomycosis is more common in individuals who have uncontrolled insulin-dependent diabetes and have ketoacidosis. This infection is also described in immunocompromised patients, including AIDS and transplant patients and patients receiving systemic corticosteroid therapy. It is very rare for this infection to affect otherwise healthy individuals. The clinical presentation of zygomycosis of the maxillary sinuses includes swelling of the palate or buccal vestibule, or both. In more advanced stages, the lesion ulcerates the palate, necrotizing the bone and causing black discoloration. The black discoloration is due to the organism oxidizing and changing color to black as it is released into the oral cavity. Zygomycosis can also present with nasal obstruction and nasal discharge, pain and visual disturbances. This is a serious disease that can affect cranial nerves and cause facial paralysis, blindness and seizures followed by death.

Malignant Neoplasms:

This can also be a malignant neoplasm arising from the maxillary sinus and breaking through the alveolar bone. It can be epithelial or mesenchymal in origin. However, the maxillary sinus is partially thickened or filled with the lesion which argues against the lesion originating from the sinus. If the origin of the tumor was from the maxillary sinus, it would be expected for that lesion to fill the sinus cavity.