1338
METASTATIC LEIOMYOSARCOMA
J Oral Maxillofac 48.1339-1340,
OF THE PALATE
Surg
1990
Metastatic
Leiomyosarcoma
of the Palate
STEVEN F. BOGART, DDS,* HARRY G. SACKS, DDS,t AND LINDA C. DEMARCO, MD*
Less than 1% of all cancers are soft-tissue sarcomas and, of these, only 2% to 8% are leiomyosarcomas. Leiomyosarcomas arise most commonly in the gastrointestinal and female genital tract*; other viscera, major arteries, veins, and the extremities are less frequent sites of origin. In general, softtissue sarcomas aggressively invade surrounding tissues and disseminate hematogenously, most frequently to the lung. Retroperitoneal and visceral soft-tissue sarcomas are more likely to metastasize than those in the extremities.’ In addition, leiomyosarcoma has a higher propensity to metastasize than do tibrosarcoma and liposarcoma. Metastasis to the oral cavity is an extremely rare event. This report presents a case of histologically proven metastatic leiomyosarcoma to the palatal soft tissues from a primary lesion in the lung. Report of a Case In July, 1987 a 58-year-old white woman presented to her family physician complaining of a persistent cough and hemoptysis. A radiograph of the chest at that time showed a lobulated mass in the upper right lobe. A thoracotomy with lobar resection was performed and the 4cm friable endobronchial tumor was diagnosed as a leiomyosarcoma. Metastatic workup showed no other systemic disease. In February 1988, the patient developed seizures that required Dilantin (Parke-Davis, Morris Plains, NJ) for control. Computed tomography scan showed bilateral intracerebral lesions. Whole brain radiation therapy with concurrent cisplatin chemotherapy was instituted. This was followed by Adriamycinldacarbazine (DTIC; Adria Labs, Dublin, OH) monthly for five cycles. In October 1988, a local recurrence was discovered in the pleural cavity and chest wall. The patient received radiation therapy and vincristine/DTIC chemotherapy.
* Chief Resident, Oral and Maxillofacial Surgery, Department of Dentistry, Metropolitan Hospital Center, New York. t Associate Attending, North Shore University Hospital, Manhassett, NY, and in private practice in Oral and Maxillofacial Surgery, New Hyde Park, NY. $ Instructor, Department of Medicine, Don Monti Division of Oncology, North Shore University Hospital, Manhassett, NY. Address correspondence and reprint requests to Dr Sacks: 2035 LakeviUe Rd, New Hyde Park, NY 10040. 0 1990 American Association of Oral and Maxillofacial
geons 0278-2391/90/4812-0017$3.00/0
Sur-
In November 1988, she developed a soft-tissue mass on the right thigh, in April 1989 a lesion on the left thigh and buttocks, and in May 1989 a lesion on the right scapula. Biopsies confirmed the diagnoses of leiomyosarcoma, and all were treated with radiation therapy. In June 1989, whole-brain radiation therapy was again administered to treat recurrent brain metastases in the right basal ganglia and left cerebellum. In June 1989, the patient was referred to the Oncology Department at North Shore University Hospital for systemic chemotherapy in an attempt to slow the progression of the disease. On admission, she complained of “easy bleeding of my gums” and difficulty swallowing. An oral and maxillofacial surgery consultation was requested. The patient stated that 1 week before admission she had seen her local dentist regarding bleeding gums. He had diagnosed Dilantin gingival hyperplasia and performed a deep curettage. Since that time, her gums had continued to slowly enlarge and bleed more frequently. Examination showed no focal neurologic deficits in cranial nerves II to XII. There was no facial swelling. A hemorrhagic crusting was noted on the lips. There was no submandibular or cervical lymphadenopathy. The facial surfaces of the maxillary right incisors were covered by a friable, exophytic, soft-tissue mass that appeared to be extruding from the interdental papillae (Fig 1). The mass also involved the entire right half of the palatal mucosa. A panoramic radiograph failed to show any osseous involvement. A presumptive diagnosis of metastatic leiomyosarcoma was made and an incisional biopsy and debulking procedure were performed under local anesthesia. Microscopic examination confirmed the diagnosis. Chemotherapy with isofamide was begun. Two weeks after the debulking procedure, the patient presented with the same complaints and examination showed that the intraoral oral lesion had recurred to its original size. The patient was treated with radiation therapy with an excellent response, although she developed a severe mucositis and candidal stomatitis. She was readmitted for a second cycle of ifosfamide and the chemotherapeutic regimen appeared to control further soft-tissue recurrence. However, in November 1989, she developed brain metastasis and she succumbed to her disease. HISTOPATHOLOGY Multiple soft-tissue specimens were prepared and stained with hematoxylin and eosin. The microscopic examination showed an infiltrating tumor with a storiform stroma consisting of poorly differentiated oval and spindle-shaped cells with hyperchromatic nuclei and eosinophiiic cytoplasm (Fig 2). Multinucleated giant cells and numerous atypical mitotic figures were also seen. The overlying mucosa was ulcerated and covered by numerous bacterial colonies. Immunoperoxidase studies were negative for cytokeratin and AEl/AE3 keratins. The cells
1339
BOGART ET AL
FIGURE I. View of friable, exophytic, soft-tissue mass covering the facial surfaces of the maxillary incisors.
showed weak but diffuse staining for muscle cell actin. The findings were consistent with a diagnosis of leiomyosarcoma. Discussion Metastasis of malignant disease can occur by either hematogenous or lymphatic routes. There is, however, a propensity for carcinomas to spread via the lymphatic system, while sarcomas favor the vascular route.3 Based on this observation, the reason for infrequent reports of metastatic spread of sarcomas to the oral cavity is unclear. Metastatic lesions comprise only 1% to 5% of all oral malignancies, with the mandible being the most frequently cited location (75%), followed by the
FIGURE 2. Photomlcrograph showing spindle and round cells, multiple giant cells, and atypical mitotic figures (hematoxylineosin, original magnification X 100).
maxilla and the intraoral soft tissues.4-6 Soft-tissue metastases most frequently involve in the tongue, gingiva, and floor of the mouth.5 Carcinomas account for the majority of these lesions; a review of the English language literature showed that sarcomas compromise less than 10% of all metastatic lesions to the oral cavity.‘.’ Meyer and Sklar6 reported 25 cases of metastasis to the oral cavity, of which only 3 proved to be sarcomas, and none of which were leiomyosarcomas. Clausen and Paulsen7 reported 97 cases of metastatic lesions, none of which were histologically consistent with a diagnosis of sarcoma. Of 41 cases reported by Nishimura,8 only one was diagnosed as a sarcoma. Hatziotis and Constantinidou’ were more specific in their report, limiting their study to metastatic lesions of the oral soft tissues. In an extensive review of the world literature between the years 1945 to 1970, they were able to list only 48 lesions, none of which were leiomyosarcomas. A diagnosis of metastatic disease requires the presence of a histologic similarity between the lesion in question and a defined primary tumor.4 The decision whether a lesion represents a metastatic lesion or a primary tumor may be difficult if the primary is occult. In cases where a malignancy is discovered in the oral cavity and the histologic type is rare in that location, an exhaustive search for an occult primary must be undertaken before instituting local therapy. In 5 of 25 cases reported by Meyer and Sklar,6 and 9 of 32 cases reported by McDaniel,” the intraoral metastatic lesion was the first sign of malignancy. According to Bhaskar,” in 33% of all cases, the oral lesion is the first indication of a primary malignancy elsewhere. The task of identifying the primary lesion, if one is not evident from the patient’s history, may not be difficult if the metastasis is well differentiated and resembles the tissue of origin. When the metastasis is anaplastic, it may be extremely difficult, if not impossible, to identify the primary site. Metastatic lesions of the oral cavity are most frequently associated with primary tumors in the breast, followed by the lung, kidney, prostate, and gastrointestinal tract.3-7,9 The Japanese literature, however, reports that the uterus is the most frequent primary site of origin, with no reported cases of metastatic lesions from the breasts.’ Noshimura’s report also implicated the lung and kidneys as frequent locations of primary tumor. The prognosis for patients with oral metastatic disease is poor, and most patients do not survive more than 2 years after the initial diagnosis of the intraoral lesion. In general, treatment of intraoral metastatic lesions is palliative or is included in the
1340 medical treatment of the primary lesion (ie, radiation or chemotherapy). Although resection of metastatic tumors is undertaken infrequently, debulking large intraoral tumors can be palliative. Leiomyosarcoma in soft tissue tends to be well circumscribed, smooth, and firm. Larger lesions may show focal necrosis and hemorrhage. Histologically, these lesions show elongated cells with blunt nuclei in interlacing cords. They tend to be extremely anaplastic.’ To be considered histologically malignant, the specimen should exhibit at least one mitotic figure per five high-power fields. ’ If the lesion exhibits a high degree of anaplasia, immunohistochemical studies may be required to make a diagnosis.” Leiomyosarcomas have not shown a good response to chemotherapeutic agents, although experimental protocols are currently being investigated.13 Radiation still appears to be the treatment of choice. References 1. Kissane JM (ed): Anderson’s Pathology (ed 9). St Louis, MO, Mosby, 1990, p 1861 (chapt 37)
METASTATIC LEIOMYOSARCOMA
OF THE PALATE
2. Torosian MH, Friedrich C, Gobold J, et al: Soft tissue sarcoma; Initial characteristics and prognostic factors in patients with and without metastatic disease. Semin Surg Oncol 4:13, 1988 3. Van der Kwast WAM, Van der Waal I: Jaw metastases. Oral Surg 37:850, 1974 4. Stypulkowska J, Bartkowski S. Panas et al: Metastatic tumors to the jaws and oral cavity. J Oral Surg 37:805, 1979 5. Oikarinen V, Calonius PEB, Sainio P: Metastatic tumours of the oral region. 1. An analysis of cases in the literature. Proc Finn Dent Sot 71:58, 1975 6. Meyer I, Sklar Cl: Metastatic tumors of the mouth and jaws. Oral Surg 20:350, 1965 7. Clausen F, Poulsen H: Metastatic carcinoma to the jaws. Acta Path01 Microbial Stand 57:361, 1963 8. Nisimura Y, Yakata H, Kawaski T, et al: Metastatic tumours of the mouth and jaws. A review of the Japanese literature. Int J Maxillofac Surg 10:253, 1982 9. Hatziotis JC, Constantinidou H, Papanayotou PH: Metastatic tumors of the oral soft tissues. Review of the literature and report of a case. Oral Surg 36:544. 1973 10. McDaniel RK, Luna MA, Stimson PG: Metastatic tumors in the jaws. Oral Surg 31:380. 1971 11. Bhaskar SN: Synopsis of Oral Pathology (ed 6). St Louis. MO, Mosby. 1981, pp 355-359 12. Stout AP, Hill WT: Leiomyosarcoma of the superficial soft tissue. Cancer 11:844. 1958 13. Chang A, Rosenberg S, Glatstein EJ, et al: Sarcomas of the soft tissue, in DeVita VT, Hellman S, Rosenberg S (eds): Cancer: Principles and Practice of Oncology (ed 3). Philadelphia, PA 1989, pp 13451398
METASTATIC LEIOMYOSARCOMA
J Oral Maxillofac 48.1339-1340,
OF THE PALATE
Surg
1990
Metastatic
Leiomyosarcoma
of the Palate
STEVEN F. BOGART, DDS,* HARRY G. SACKS, DDS,t AND LINDA C. DEMARCO, MD*
Less than 1% of all cancers are soft-tissue sarcomas and, of these, only 2% to 8% are leiomyosarcomas. Leiomyosarcomas arise most commonly in the gastrointestinal and female genital tract*; other viscera, major arteries, veins, and the extremities are less frequent sites of origin. In general, softtissue sarcomas aggressively invade surrounding tissues and disseminate hematogenously, most frequently to the lung. Retroperitoneal and visceral soft-tissue sarcomas are more likely to metastasize than those in the extremities.’ In addition, leiomyosarcoma has a higher propensity to metastasize than do tibrosarcoma and liposarcoma. Metastasis to the oral cavity is an extremely rare event. This report presents a case of histologically proven metastatic leiomyosarcoma to the palatal soft tissues from a primary lesion in the lung. Report of a Case In July, 1987 a 58-year-old white woman presented to her family physician complaining of a persistent cough and hemoptysis. A radiograph of the chest at that time showed a lobulated mass in the upper right lobe. A thoracotomy with lobar resection was performed and the 4cm friable endobronchial tumor was diagnosed as a leiomyosarcoma. Metastatic workup showed no other systemic disease. In February 1988, the patient developed seizures that required Dilantin (Parke-Davis, Morris Plains, NJ) for control. Computed tomography scan showed bilateral intracerebral lesions. Whole brain radiation therapy with concurrent cisplatin chemotherapy was instituted. This was followed by Adriamycinldacarbazine (DTIC; Adria Labs, Dublin, OH) monthly for five cycles. In October 1988, a local recurrence was discovered in the pleural cavity and chest wall. The patient received radiation therapy and vincristine/DTIC chemotherapy.
* Chief Resident, Oral and Maxillofacial Surgery, Department of Dentistry, Metropolitan Hospital Center, New York. t Associate Attending, North Shore University Hospital, Manhassett, NY, and in private practice in Oral and Maxillofacial Surgery, New Hyde Park, NY. $ Instructor, Department of Medicine, Don Monti Division of Oncology, North Shore University Hospital, Manhassett, NY. Address correspondence and reprint requests to Dr Sacks: 2035 LakeviUe Rd, New Hyde Park, NY 10040. 0 1990 American Association of Oral and Maxillofacial
geons 0278-2391/90/4812-0017$3.00/0
Sur-
In November 1988, she developed a soft-tissue mass on the right thigh, in April 1989 a lesion on the left thigh and buttocks, and in May 1989 a lesion on the right scapula. Biopsies confirmed the diagnoses of leiomyosarcoma, and all were treated with radiation therapy. In June 1989, whole-brain radiation therapy was again administered to treat recurrent brain metastases in the right basal ganglia and left cerebellum. In June 1989, the patient was referred to the Oncology Department at North Shore University Hospital for systemic chemotherapy in an attempt to slow the progression of the disease. On admission, she complained of “easy bleeding of my gums” and difficulty swallowing. An oral and maxillofacial surgery consultation was requested. The patient stated that 1 week before admission she had seen her local dentist regarding bleeding gums. He had diagnosed Dilantin gingival hyperplasia and performed a deep curettage. Since that time, her gums had continued to slowly enlarge and bleed more frequently. Examination showed no focal neurologic deficits in cranial nerves II to XII. There was no facial swelling. A hemorrhagic crusting was noted on the lips. There was no submandibular or cervical lymphadenopathy. The facial surfaces of the maxillary right incisors were covered by a friable, exophytic, soft-tissue mass that appeared to be extruding from the interdental papillae (Fig 1). The mass also involved the entire right half of the palatal mucosa. A panoramic radiograph failed to show any osseous involvement. A presumptive diagnosis of metastatic leiomyosarcoma was made and an incisional biopsy and debulking procedure were performed under local anesthesia. Microscopic examination confirmed the diagnosis. Chemotherapy with isofamide was begun. Two weeks after the debulking procedure, the patient presented with the same complaints and examination showed that the intraoral oral lesion had recurred to its original size. The patient was treated with radiation therapy with an excellent response, although she developed a severe mucositis and candidal stomatitis. She was readmitted for a second cycle of ifosfamide and the chemotherapeutic regimen appeared to control further soft-tissue recurrence. However, in November 1989, she developed brain metastasis and she succumbed to her disease. HISTOPATHOLOGY Multiple soft-tissue specimens were prepared and stained with hematoxylin and eosin. The microscopic examination showed an infiltrating tumor with a storiform stroma consisting of poorly differentiated oval and spindle-shaped cells with hyperchromatic nuclei and eosinophiiic cytoplasm (Fig 2). Multinucleated giant cells and numerous atypical mitotic figures were also seen. The overlying mucosa was ulcerated and covered by numerous bacterial colonies. Immunoperoxidase studies were negative for cytokeratin and AEl/AE3 keratins. The cells
1339
BOGART ET AL
FIGURE I. View of friable, exophytic, soft-tissue mass covering the facial surfaces of the maxillary incisors.
showed weak but diffuse staining for muscle cell actin. The findings were consistent with a diagnosis of leiomyosarcoma. Discussion Metastasis of malignant disease can occur by either hematogenous or lymphatic routes. There is, however, a propensity for carcinomas to spread via the lymphatic system, while sarcomas favor the vascular route.3 Based on this observation, the reason for infrequent reports of metastatic spread of sarcomas to the oral cavity is unclear. Metastatic lesions comprise only 1% to 5% of all oral malignancies, with the mandible being the most frequently cited location (75%), followed by the
FIGURE 2. Photomlcrograph showing spindle and round cells, multiple giant cells, and atypical mitotic figures (hematoxylineosin, original magnification X 100).
maxilla and the intraoral soft tissues.4-6 Soft-tissue metastases most frequently involve in the tongue, gingiva, and floor of the mouth.5 Carcinomas account for the majority of these lesions; a review of the English language literature showed that sarcomas compromise less than 10% of all metastatic lesions to the oral cavity.‘.’ Meyer and Sklar6 reported 25 cases of metastasis to the oral cavity, of which only 3 proved to be sarcomas, and none of which were leiomyosarcomas. Clausen and Paulsen7 reported 97 cases of metastatic lesions, none of which were histologically consistent with a diagnosis of sarcoma. Of 41 cases reported by Nishimura,8 only one was diagnosed as a sarcoma. Hatziotis and Constantinidou’ were more specific in their report, limiting their study to metastatic lesions of the oral soft tissues. In an extensive review of the world literature between the years 1945 to 1970, they were able to list only 48 lesions, none of which were leiomyosarcomas. A diagnosis of metastatic disease requires the presence of a histologic similarity between the lesion in question and a defined primary tumor.4 The decision whether a lesion represents a metastatic lesion or a primary tumor may be difficult if the primary is occult. In cases where a malignancy is discovered in the oral cavity and the histologic type is rare in that location, an exhaustive search for an occult primary must be undertaken before instituting local therapy. In 5 of 25 cases reported by Meyer and Sklar,6 and 9 of 32 cases reported by McDaniel,” the intraoral metastatic lesion was the first sign of malignancy. According to Bhaskar,” in 33% of all cases, the oral lesion is the first indication of a primary malignancy elsewhere. The task of identifying the primary lesion, if one is not evident from the patient’s history, may not be difficult if the metastasis is well differentiated and resembles the tissue of origin. When the metastasis is anaplastic, it may be extremely difficult, if not impossible, to identify the primary site. Metastatic lesions of the oral cavity are most frequently associated with primary tumors in the breast, followed by the lung, kidney, prostate, and gastrointestinal tract.3-7,9 The Japanese literature, however, reports that the uterus is the most frequent primary site of origin, with no reported cases of metastatic lesions from the breasts.’ Noshimura’s report also implicated the lung and kidneys as frequent locations of primary tumor. The prognosis for patients with oral metastatic disease is poor, and most patients do not survive more than 2 years after the initial diagnosis of the intraoral lesion. In general, treatment of intraoral metastatic lesions is palliative or is included in the
1340 medical treatment of the primary lesion (ie, radiation or chemotherapy). Although resection of metastatic tumors is undertaken infrequently, debulking large intraoral tumors can be palliative. Leiomyosarcoma in soft tissue tends to be well circumscribed, smooth, and firm. Larger lesions may show focal necrosis and hemorrhage. Histologically, these lesions show elongated cells with blunt nuclei in interlacing cords. They tend to be extremely anaplastic.’ To be considered histologically malignant, the specimen should exhibit at least one mitotic figure per five high-power fields. ’ If the lesion exhibits a high degree of anaplasia, immunohistochemical studies may be required to make a diagnosis.” Leiomyosarcomas have not shown a good response to chemotherapeutic agents, although experimental protocols are currently being investigated.13 Radiation still appears to be the treatment of choice. References 1. Kissane JM (ed): Anderson’s Pathology (ed 9). St Louis, MO, Mosby, 1990, p 1861 (chapt 37)
METASTATIC LEIOMYOSARCOMA
OF THE PALATE
2. Torosian MH, Friedrich C, Gobold J, et al: Soft tissue sarcoma; Initial characteristics and prognostic factors in patients with and without metastatic disease. Semin Surg Oncol 4:13, 1988 3. Van der Kwast WAM, Van der Waal I: Jaw metastases. Oral Surg 37:850, 1974 4. Stypulkowska J, Bartkowski S. Panas et al: Metastatic tumors to the jaws and oral cavity. J Oral Surg 37:805, 1979 5. Oikarinen V, Calonius PEB, Sainio P: Metastatic tumours of the oral region. 1. An analysis of cases in the literature. Proc Finn Dent Sot 71:58, 1975 6. Meyer I, Sklar Cl: Metastatic tumors of the mouth and jaws. Oral Surg 20:350, 1965 7. Clausen F, Poulsen H: Metastatic carcinoma to the jaws. Acta Path01 Microbial Stand 57:361, 1963 8. Nisimura Y, Yakata H, Kawaski T, et al: Metastatic tumours of the mouth and jaws. A review of the Japanese literature. Int J Maxillofac Surg 10:253, 1982 9. Hatziotis JC, Constantinidou H, Papanayotou PH: Metastatic tumors of the oral soft tissues. Review of the literature and report of a case. Oral Surg 36:544. 1973 10. McDaniel RK, Luna MA, Stimson PG: Metastatic tumors in the jaws. Oral Surg 31:380. 1971 11. Bhaskar SN: Synopsis of Oral Pathology (ed 6). St Louis. MO, Mosby. 1981, pp 355-359 12. Stout AP, Hill WT: Leiomyosarcoma of the superficial soft tissue. Cancer 11:844. 1958 13. Chang A, Rosenberg S, Glatstein EJ, et al: Sarcomas of the soft tissue, in DeVita VT, Hellman S, Rosenberg S (eds): Cancer: Principles and Practice of Oncology (ed 3). Philadelphia, PA 1989, pp 13451398
