Mesenchymal chondrosarcoma: a case report

J Oral Maxillofac 45~72-75.

Surg

1967

Mesenchymal

Chondrosarcoma:

A Case Report RONALD R. HOLLINS, DMD, MD,* DANIEL D. LYDIATT, DDS, MD,t RODNEY S. MARKIN, MD, PHD,$ AND LEON F. DAVIS, DDS, MD5

Mesenchymal chondrosarcoma is a rare malignant cartilaginous tumor arising within bone or soft tissue. It was first described in 1959 by Lichtenstein and Bernstein, and represents a distinct variant of the more common chondrosarcoma.’ In both the skeletal and extraskeletal form, the mesenchymal chondrosarcoma has a predilection for the head and neck. In a thorough survey of the world literature, Christensen found 23 reported cases of mesenchymal chondrosarcoma of the jaws, nine occurring in the mandible.* Our review revealed two additional cases of this tumor occurring within the mandible.3,4 The case presented represents another aggressive, persistent form of mesenchymal chondrosarcoma of the mandible.

prior to this time. The mass had increased in size to involve the ventral tongue, mouth floor, mandible and cutaneous tissue in the submental region by the time of admission. The patient complained of dull, constant, throbbing pain; hemorrhage of the oral lesion; serosanguineous discharge from a submental fistula; and mandibular instability. Despite tolerance of a soft diet, a 15 lb weight loss had been experienced in the three months preceeding presentation. Physical examination revealed a pale, cachectic 27year-old man in moderate distress due to pain in the oral region. Vital signs were within normal limits. Gross distortion of the oral cavity and adjacent structures was present. An exophytic mass involving the ventral tongue, anterior floor of mouth, mandible and lower lip. measuring approximately 7 x 7 cm, was present (Fig. 1). The mass was soft, hemorrhagic, and malodorous due to central tumor necrosis. Discharge was noted from fistuli associated with two areas of exophytic growth in the submental region. No cervical lymphadenopathy or masses were present. The lungs were clear to auscultation and percussion. Cardiovascular examination revealed a grade I/VI systolic murmur along the left sternal border. The abdomen was unremarkable, with a liver span of 10 cm in the midclavicular line. No neurologic deficits were noted

Report of a Case A 27-year-old male Hispanic American was admitted to the Oncology Service at the University of Nebraska Medical Center for evaluation of a large oral tumor. Fifty-five months prior to admission, this patient entered the United States and was seen at an El Paso hospital for evaluation of a large exophytic mass in the mandibular midline measuring 4 x 4 cm. The mass was biopsied and a histologic diagnosis of Ewing’s sarcoma was made. At that time the patient received radiation therapy with a total dose of 7310 rads in 43 treatment fractions. Upon completion of therapy, he was reported to be clinically free of disease. No adjuvant treatment was administered. One year after the initial diagnosis, the patient sustained a fracture of the mandible in the symphyseal region requiring open reduction and fixation. There was no evidence of tumor noted at that time. Six months before hospitalization at our institution, a growth was noted in the tissue overlying the mandible. He had been reportedly free of disease for three years Received from the University of Nebraska Medical Center, Omaha, Nebraska. * Former Resident, Department of Oral and Maxillofacial Surgery. t Assistant Professor, Department of Oral Surgery. $ Assistant Professor, Department of Pathology. 5 Associate Professor, Department of Oral Surgery. Address correspondence and reprint requests to Dr. Hollins: Department of Oral and Maxillofacial Surgery, University of Nebraska Medical Center, 42nd and Dewey Avenue, Omaha, NE 68105. 0278-2391187 $0.00 + .25

FIGURE I. Photograph showing tumor involvement of anterior and left lateral mandible.

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HOLLINS E:T AL.

FIGURE 2 (I&). FIGURE 3 (ri,ght).

Chest radiograph revealing metastatic disease in the rig ht lower lobe and left lateral lower lobe. Facial radiograph showing multiple lytic lesions and d estruction of the anterior mandible.

other than a decreased perception of pinprick and light touch in the distribution of the mental nerves bilaterally. Laboratory evaluation revealed a decreased hemoglobin of 9.3 g%, with a hematocrit of 27.6%. The red cell indices were microcytic, with a mean corpuscular volume of 78.7 m3 and a mean corpuscular hemoglobin of 26.6 pg. The white blood cell count was 6000, with 26% band cells. Urinary analysis was significant for a large quantity of occult blood. The electrolytes were within normal limits. Total serum protein was decreased (5.3 g/dl). with an albumin level of 2.8 g/dl. Serum iron was low at 16 p+g/dl, as was the total iron binding capacity at 174 kg/ dl. Ferritin was normal at 21 ng/dl. Radiographs of the chest revealed multiple nodules in both bases consistent with metastatic disease (Fig. 2). An IVP was normal, as was a metastatic bone survey. An abdominal ultrasound examination showed the liver and spleen to be unremarkable, and failed to identify any abdominal masses. Radiographic evaluation of the mandible revealed extensive destruction of the symphyseal region (Fig. 3). Cystoscopy was unremarkable. An incisional biopsy was obtained under local anesthesia. Several large fragments of tissue were examined histologically. The squamous lined surface was ulcerated and covered with a purulent exudate. There were foci of necrosis scattered throughout the specimen. Sheets of small round cells with pleomorphic nuclei and scant cytoplasm surrounded by thin fibrous septa comprised the majority of the tumor. Collections of cells similar to those seen in hemangiopericytoma were also present. Small amounts of chondroid material with foci of calcification

were seen scattered throughout the tumor. Periodic acidSchiff stains with and without diastase were positive for glycogen (Fig. 4). Electron microscopy revealed sheets of uniform cells with tightly packed nuclei. Individual cells were surrounded by a matrix composed of reticulin and collagen in lacunae-like spaces. Primative intercellular junctions and intracellular glycogen were seen. Occasional mitochondria were also noted (Fig. 5). A diagnosis of Ewing’s sarcoma was made. Treatment of the anemia, presumed to be due to blood loss superimposed on anemia of chronic disease. was accomplished with the transfusion of three units of packed RBCs and supplemental iron. The patient was initiated on the Memorial Sloan-Kettering T-2 protocol consisting of dactinomycin, adriamycin, vincristine and cyclophosphamide. No additional radiation therapy was possible because the area had previously received a maximal dosage. The lesion was felt to be advanced beyond surgical resectability. After receiving the initial course of chemotherapy, the patient was discharged to continue treatment as an outpatient, Two months after initial presentation, he was readmitted for additional T-2 chemotherapy and surgical debulking of the tumor. Eight months into the T-2 regimen, progression of the disease was apparent, with increasing size of the oral lesion and lung metastasis. The therapy was altered to hydroxyurea. Ten months into treatment, the hydroxyurea was discontinued and CCNU was begun due to lack of tumor response. Seventeen months after institution of chemotherapy (72 months after initial diagnosis) the patient died.

MESENCHYMAL

CHRONDROSARCOMA

FIGURE 4. Top left. histologic section demonstrating uniform, poorly differentiated cells with scant cytoplasm and large nuclei. Small fibrous septa separate groups of cells. (Hematoxylin and eosin. Original magnification, X 200.) Top right. histologic section showing chondroid element. (Hematoxylin and eosin. Original magnification. x 200.1 FIGURE 5 (bottom). Electron micrograph of specimen showing closely packed cells with large uniform nuclei. Primitive intercellular junctions are present. (Uranyl-acetate. lead citrate. Original magnification, x 16,000.)

Further

histologic

review

revealed

the original

diag-

nosis to be incorrect. Consultation with pathologists considered to be experts in small cell tumors, confirmed the presumed diagnosis of mesenchymal chondrosarcoma made on tissue processed at our hospital. Discussion

Mesenchymal chondrosarcoma of the jaw has been reported in patients from 11 to 46 years of age.2 The average age was 22 years, with most cases occurring in the second and third decades. When all disease sites are considered, the tumor has a greater incidence in later years, occurring most frequently in the fourth, fifth, and sixth decades. There appears to be no sex predilection. Both skeletal and extraskeletal forms of mesenchymal chondrosarcoma exist. Over 30% of the reported cases have occurred in soft tissues.5 In both

osseous and soft tissue forms, the head and neck is a common site of occurrence. The ribs are also frequently affected, while occurrence in tubular bones is rare. A painless mass is frequently the presenting complaint. In the mandible. paresthesia may be present due to compression of the inferior alveolar nerve. Secondary infection may also be present. Radiographically, the intraosseous lesions appear as nonspecific radiolucencies. They may be well or poorly demarcated, but never display a sclerotic margin. Evidence of cortical destruction may be present. Approximately 50% of bony lesions display diffuse calcification, while in the soft tissue irregular stippled calcification is almost always present.6 Histologically. the mesenchymal chondrosarcoma consists of sheets of undifferentiated round

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or oval cells surrounded by variable amounts of chondroid material. The undifferentiated cells contain hyperchromatic nuclei with scant cytoplasm. There is a tendency for the undifferentiated cells to be arranged around slit-like spaces or capillaries, often leading to the incorrect diagnosis of hemangiopericytoma. Calcification is occasionally seen in the chondroid material. Both electron and light microscopy are needed to make a definitive diagnosis since many different cell types may share the same poorly differentiated cytologic characteristics. Their differences can usually be confirmed by electron microscopy. lmmunoperoxidase is also helpful in differentiating between mesenchymal, lymphoid, neural, and epithelial origin. The prognosis for mesenchymal chondrosarcoma is poor. The course is rapidly fatal for lesions occurring in the jaws. Christensen reported that of 10 cases followed for at least five years, seven patients died as a result of their disease.2 In Rosen’s series of 32 patients with tumors in various locations, the median survival was 37.9 months, range of one month to 44 years.6 The five-year survival rate was 42% and the IO-year survival was 28%. Local recurrence is common, with distant metastasis observed in the lungs. Radical surgical excision, where possible, is the treatment of choice. Radiation therapy has not proven to be efficacious as the primary mode of treatment but can provide good palliation.’ Some centers advocate preoperative irradiation prior to radical excision.6 Adjuvant chemotherapy has recently shown promise in the treatment of mesenchymal chondrosarcoma. Rosen has advocated the use of a two-year sequential protocol (T-6 protocol) including dactinomycin, cyclophosphamide, bleomycin, vincristine, adriamycin, BCNU and metho-

trexatee6 The protocol has been used previously with success in the treatment of Ewing’s sarcoma. Summary Mesenchymal chondrosarcoma is a rare tumor distinctly different from the more common chondrosarcoma. It shows a predilection for the head and neck in both osseous and extraosseous forms. The prognosis for cure is poor, with a high incidence of local recurrence as well as regional and distant metastasis. Treatment is based on radical surgical excision, although combination chemotherapy has recently shown promise. Additional experience with this tumor is required to define the most efficacious form of treatment. References 1. Lichtenstein L, Bernstein D: Unusual benign and malignant chondroid tumors of bone: a surgery of some mesenchymal cartilage tumors and malignant chondroblastic tumors, including a few multicentric ones, as well as many atypical benign chondroblastomas and chondromyxoid fibromas. Cancer 12: 1142. 1959 2. Christensen RE Jr: Mesenchymal chondrosarcoma of the jaws. Oral Surg 54:197, 1982 3. Osbon DB, Feinberg SE, Finkelstein MW, et al: Delayed mandibular reconstruction following removal of a mesenchymal chondrosarcoma. Oral Surg 59557. 1985 4. Badia DM, Asrestini F, Marinelli M, et al: Mesenchymal type of chrondosarcoma of the iaws. Minerva Stomatol _ ji:271. 1985 (Eng abstract) 5. Salvador AH. Beabout JW, Dahlin DC: Mesenchvmal chondrosarcoma-observations on 30 new cases. Cancer 28:605, 1971 6. Huvos AG, Rosen G, Dabska M, et al: Mesenchymal chondrosarcoma: a clinicopathologic analysis of 35 patients with emphasis on treatment. Cancer 51:1230. 1983 7. Million RR, Cassisi NJ: Management of Head and Neck Cancer: a multidisciplinary approach. Philadelphia. JB Lippincott. 1984, p 629