Fibrosarcoma |
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Plump, spindled tumor cells stream
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Quick Review for Patients
| The fibrosarcoma is a malignant proliferation of fibroblasts, the cells which normally produce the fibrous tissue throughout the body. It has a tendency to grow slowly at first and in the mouth can appear as a quite innocuous submucosal mass with is firm and normal colored and painless. It may be lobulated and occasionally will be ulcerated on the surface. This cancer metastasizes late in its growth and treatment is radical surgical removal, with only a third of patients surviving for 5 years or more. |
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Malignancies of fibroblasts are decidedly rare in the oral and oropharyngeal
region, but fibrosarcoma is, nevertheless, the most common mesenchymal
cancer of the region, representing more than half of all sarcomas.
Twenty-three percent of head and neck fibrosarcomas occur within the oral
cavity. Radiotherapy to the local site is known to increase the
risk of fibrosarcoma development but there are no other known etiologic factors.
On the perioral skin, occasional cases develop at the site of thermal damage or
of a pre-existing scar.
Clinical Features
Persons affected by oral/pharyngeal fibrosarcoma are usually 30-50 years of age, but there is a wide age range and many patients are less than 20 years of age. Fibrosarcoma has been diagnosed in the oral region of infants. There is no apparent gender predilection and any submucosal site may be involved, although the buccal mucosa and tongue account for three-fourths of oral lesions.
Fibrosarcoma most often presents as a clinically innocuous, lobulated, sessile, painless and nonhemorrhagic submucosal mass of normal coloration. It may, however, be a rapidly enlarging, hemorrhagic mass similar in clinical appearance to an ulcerated pyogenic granuloma, peripheral giant cell granuloma or peripheral ossifying fibroma. Even lesions which do not demonstrate surface ulceration or rapid growth may show destruction of underlying muscle and bone.
Pathology and Differential Diagnosis
The cut surface of a fibrosarcoma is dense and shows swirling or intertwining fibrous streams, usually with a whitish-gray color and sometimes with irregular hollow spaces indicative of past, localized necrosis (Figure 2). Fibrosarcoma is a lesion with a varied microscopic appearance. The low grade or well differentiated variant is usually somewhat circumscribed and comprised of such mature spindle cells that differentiation from benign fibrous hyperplasia and proliferation may be quite difficult. The presence of focal anaplasia and increased mitotic activity becomes paramount in such cases, and aggressive clinical behavior must be taken into account when making a histopathologic diagnosis. Fibrosarcoma of infancy and early childhood demonstrates smaller, more numerous and more primitive cells than the adult lesion.
Lesional cells are spindle-shaped with pale eosinophilic cytoplasm and spindled nuclei with tapered ends (Figure 3). Cells flow in interweaving fascicles or bundles, often producing a herring-bone pattern in focal areas. The lesion is typically quite cellular but moderate amounts of mature collagen may be produced, perhaps with areas of hyalinization. Scattered, histologically normal mitotic figures are seen in small numbers, but cells and nuclei are not pleomorphic.
Less well differentiated fibrosarcoma shows minimal collagen production and marked cellularity. Lesional cells exhibit larger, more hyperchromatic, more pleomorphic and more rounded nuclei, although the pleomorphism is seldom pronounced. Multinucleated giant cells are rarely seen. There seems to be an association between patient age at diagnosis and lesional differentiation, with less differentiated neoplasms occurring in the younger patients.
Focal areas of tumor necrosis may be seen in the poorly differentiated fibrosarcoma and myxoid areas, as well as occasional chronic inflammatory cells, may be seen in infantile fibrosarcoma. Stromal hemorrhage is not seen.
Fibrosarcoma of the oral region must be differentiated from a variety of other malignant and benign spindle cell proliferations. The most problematic malignancies in this regard include the malignant fibrous histiocytoma, malignant peripheral nerve sheath tumor (malignant schwannoma), dermatofibrosarcoma protuberans, leiomyosarcoma, and certain carcinomas such as desmoplastic (sarcomatoid) melanoma, spindle cell (sarcomatoid) carcinoma and myoepithelial carcinoma. The carcinomas are distinguished by focal transition areas with epithelioid or pigmented cells, perhaps requiring immunoperoxidase confirmation of their epithelial nature via positive reactivity for cytokeratins (using MNF116 and CAM 5.2) and S-100 protein. It is important to remember that fibrosarcoma, especially in adults, is extremely rare in the mouth and that the diagnosis is many times one of exclusion in a lesion which is negative to appropriate immunohistochemical markers.
Malignant fibrous histiocytoma can usually be differentiated from fibrosarcoma by the more pronounced pleomorphism of its cells and nuclei, and by the presence of a storiform or whorling stromal pattern rather than a herringbone pattern, and by immunoreactivity for Factor XIIIa or alpha-1-antichymotrypsin antibodies.
Leiomyosarcoma has the fascicular pattern and uniform cellularity of a low-grade fibrosarcoma, but nuclei have more blunted ends ("cigar-shaped") and fuchsinophilic fibers can be demonstrated by the Masson trichrome stain. Lesional cells are immunoreactive for a variety of antibodies, including vimentin, desmin, alpha-smooth muscle actin, muscle-specific actin, and S-100 protein.
Malignant peripheral nerve sheath tumors can usually be differentiated by their greater degree of pleomorphism and by the presence of wavy or comma-shaped bipolar nuclei with pointed ends or with one pointed and one blunted end (arrowhead nucleus). The stroma often demonstrates large whorls or nodules with a neural or myxoid appearance, and many tumors show alternating patterns of hypercellular, and perhaps herringboned fascicles with hypocellular myxoid zones. This tumor often contains cells which are immunoreactive for S-100 protein, NSE, cytokeratin, BCL2, and CD34, but negative cases do not eliminate it as a viable diagnosis so long as lesional cells are not reactive for vimentin, smooth muscle actin, desmin, or HMB45.
Another sarcoma which may mimic fibrosarcoma is the synovial sarcoma, especially the monophasic type. The examination of multiple microscopic sections may be needed in order to identify an area with the classic biphasic pattern. Lacking this, it should be understood that the spindle cell phase of the synovial sarcoma typically has significantly more collagen, has areas of myxoid stroma, and has an extremely uniform cellular pattern. Electron microscopy may be necessary to demonstrate the epithelioid cells of synovial sarcoma and immunohistochemistry may be helpful. The recently described sclerosing epithelioid fibrosarcoma may also present with numerous polygonal epithelioid cells but these grow in distinct nests and chords.
Spindle cell carcinoma is discussed elsewhere in this website, but it can be said here that it differs from fibrosarcoma in that it has a "separated bundle" growth pattern and the nuclei are large and open with a retained nucleolus, i.e. they remain similar to the nuclei of routine squamous cell carcinoma. There are no perinuclear vacuoles and some cells should appear epithelioid. Immunohistochemical markers of epithelial differentiation may be negative in spindle cell carcinoma, and the most likely markers to elicit positive reactivity include EMA, CK (AE1/3, CAM52), vimentin and muscle-specific actin (scattered cells only). Spindle cells in the myoepithelial carcinoma co-express S-100 protein, vimentin and CK of low molecular weight.
Fibromatosis may be histologically and clinically indistinguishable from well-differentiated fibrosarcoma. The spindle cells may be numerous but are uniformly bland. Stroma contains abundant mature collagen and there is a lack of herringbone change. Areas of fibromatosis may show increased cellularity and mitotic activity, but this is not seen uniformly throughout lesional tissues. Some authorities insist on the presence of areas with more than 5 mitotic figures per high power field for a diagnosis of fibrosarcoma.
Nodular fasciitis can be distinguished from well-differentiated fibrosarcoma by its rapid growth, superficial location and mixture of fibroblasts, myofibroblasts and chronic inflammatory cells, including occasional histiocyte-like cells demonstrating pleomorphism. The stroma is often myxoid with focal areas of mucoid change; the latter is a feature not seen in fibrosarcoma.
Treatment and Prognosis
Well-differentiated fibrosarcoma is treated by wide
local excision, while more poorly differentiated tumors require radical surgery,
including removal of potentially invaded muscle and bone. Fibrosarcoma seldom metastasizes except late in its clinical course, but when
this does occur the metastatic deposits are usually blood-born and carried to
distant sites, especially the lungs, liver and bones. Radiotherapy may be used
as salvage for recurrences. The five-year survival rate for this disease in
poor, ranging from 20-35%.
References (Chronologic Order)
Note: General references can be found by clicking on that topic to the left.
Ellis GL, Corio RL. Spindle cell carcinoma of the oral cavity. A clinicopathologic assessment of fifty-nine cases. Oral Surg Oral Med Oral Pathol 1980; 50:523-533.
Batsakis JG, Rice DH, Howard DR. The pathology of head and neck tumors: spindle cell lesions (sarcomatoid carcinomas, nodular fasciitis, and fibrosarcoma) of the aerodigestive tracts: part 14. Head Neck Surg 1982; 4:499-513.
Barnes L. Tumors and tumorlike lesions of the soft tissues. In: Barnes l. Surgical pathology of the head and neck. New York: Marcel Dekker, 1985:725-780.
Fletcher CD, McKee PH. Sarcomas–a clinicopathologic guide with particular reference to cutaneous manifestations: III: angiosarcoma, malignant hemangiopericytoma, fibrosarcoma and synovial sarcoma. Clin Exp Dermatol 1985; 10:332-349.
Oppenheimer RW, Friedman M. Fibrosarcoma of the maxillary sinus. Ear Nose Throat J 1988; 67:193-198.
Slootweg PJ, Roholl PJ, Muller H, et al. Spindle-cell carcinoma of the oral cavity and larynx. Immunohistochemical aspects. J Cranio-Maxillofac Surg 1989; 17:234-236.
Mark RJ, Sercarz JA, Tran L, et al. Fibrosarcoma of the head and neck. The UCLA experience. Arch Otolaryngol Head Neck Surg 1991; 117:396-401.
Meis-Kindblom JM, Kindblom LG, Enzinger FM. Sclerosing epithelioid fibrosarcoma – a variant of fibrosarcoma simulating carcinoma. Am J Surg Pathol 1995; 19:979-993.
Brooks JSJ. Soft tissue lesions of the oral and maxillofacial region. Proceedings, Annual meeting of the American Academy of Oral & Maxillofacial Pathology; Dallas, Texas, May, 1998.
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Figure 1: [return to text] |
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Figure 2: Cut surface shows a streaming, whitish-tan stroma with focus of necrosis represented by the irregular hollow space toward the left. [return to text] |
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Figure 3: High-grade fibrosarcoma.
Spindle-shaped lesional cells have blunt-ended nuclei and here are
surrounded by minimal fibrous stroma. Many mitotic figures are
seen.
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