HARADA ET AL
travel along the ciliary nerve of the ophthalmic division of the trigeminal nerve to the Gasserian ganglion. The efferent pathway is by the vagus nerve. Sinus bradycardia as well as cardiac arrest have been reported during eye surgery as manifestations of the OCR.’ Loewinger et al4 suggested a similar mechanism to occur with manipulation of facial bones whereby the afferent arc would be a maxillary division branch supplying sensory input to the involved bone, in this case the maxilla. The efferent pathway would again be via the vagus nerve. The present case would represent an extreme example of the trigeminovagal reflex (TVR) where sensory input from the manipulation of the free maxilla produced cardiac asystole. Preinduction IV atropine (0.01 mg/kg body weight for adults and 0.02 mg/kg body weight for children) has been proposed to prevent the occurrence of the OCR. In the present case, administration of atropine plus glycopyrrolate served to prevent the recurrence of the dysrhythmia. Glycopyrrolate was used because of its longer duration of action and greater protection against vagal-induced bradycardia as compared with atropine.6 The surgeon should be aware that the use of atropine is not 100% successful in preventing the TVR and there-
J Oral Maxillofac 47:1083-1087.
fore, should a dysrhythmia occur, the surgical procedure should promptly be stopped until a return to a normal sinus rhythm develops. Summary A case report of asystole occurring during downfracture of a maxilla in a Le Fort I osteotomy procedure is described. The case serves to illustrate an extreme example of the trigeminovagal reflex during manipulation of the maxilla. References 1. Kaufman L: Cardiac arythmias in dentistry. 2. 3. 4.
Lancet 1:287, 1965 (letter to the editor) Kaufman L: Unforeseen complications encountered during dental anesthesia: hoc R Sot Med 59:731, 1966 Robideux V: Oculocardiac reflex caused by midface disimpaction. Anesthesiology 491433, 1978 Loewinger J, Cohen M, Levi E: Bradycardia during elevation of a zygomatic arch fracture. J Oral Maxillofac Surg 45710, 1987 Alexander JP: Reflex disturbances of cardiac rhythm during ophthalmic surgery. Br J Ophthalmol 59:518, 1975 Dripps RD, Eckenhoff JE, Vandam LD: introduction to Anesthesia. The Principles of Safe Practice (ed 5). Philadelphia, Saunders, 1977, p 45
Ameloblastoma With Metastasis to the Lung and Associated Hypercalcemia K. HARADA, DDS, PHD,* S. SUDA, DDS, PHD,* T. KAYANO, DDS, PtiD,t H. NAGURA, DDS, PHD,* AND S. ENOMOTO, DDS, PHD*
Ameloblastoma is a slowly growing odontogenic epithelial tumor that is usually considered to be benign. Although this tumor is locally invasive and has a high tendency to recur, metastasis rarely occurs. This report describes an ameloblastoma of the Received from the Faculty of Dentistry, Tokyo Medical and Dental University, Tokyo. * Second Department of Oral and MaxiIIofacial Surgery. t Department of Oral Pathology, Faculty of Dentistry. Address correspondence to Dr Harada: The Second Depart-
ment of Oral and Maxillofacial Suraerv. Facultv of Dentistrv. Tokyo Medical and Dental University 5-45, Yushima, I-Chomk, Bunkyo-ku, Tokyo 113, Japan. 0 1989 American geons
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left mandible that metastasized to the left lung after repeated local recurrences. In addition, although there was no evidence of bone metastases, the pulmonary metastasis of the ameloblastoma was associated with hypercalcemia which resolved following lung resection. These findings suggest that the hypercalcemia occurred
1967, a 33-year-old Japanese man was referred to a local hospital complaining of swelling in the left molar region. This was diagnosed as ameloblastoma, and partial resection of the left mandible was performed. Two years later, local recurrence was observed, and he was referred to our University Hospital for treatment.
FIGURE 1. Cranial radiograph showing a soap-bubble-like bone defect in the left mandible (arrow). He was a normally developed and well-nourished man. There was a scar from the previous operation in the left submandibular region. Intraoral examination showed a purulent cavity 2 cm wide, 2 cm long, and 1.5 cm deep in the left molar region. Radiographic examination revealed a soap-bubble-like bone defect in the left body of the mandible (Fig 1). Following a needle biopsy, a histologic diagnosis of ameloblastoma was returned. In September 1969, segmental resection of the left mandible and reconstruction with an iliac bone graft were
FIGI JRE 2. CT scan (horizontal section) of the skull. Norte the tumor mass filling the left maxillary sinus and invading the left orbit.
AMELOBLASTOMA WITH METASTASIS TO THE LUNG
FIGURE 3. Chest radiograph showing a large lesion in the lower lobe of the left lung (arrow).
performed (first operation). In November 1975, a second recurrence of the tumor was observed and hemimandiblectomy was performed (second operation). The patient did well for several years after this operation and did not return to our hospital. However, in November 1981 he complained of a swelling in the left suborbital region. A computed tomography (CT) scan of the skull revealed a tumor filling the left maxillary sinus, invading the left orbit, and compressing the left globe (Fig 2). A needle biopsy was diagnosed as recurrent ameloblastoma. In March 1982, hemimaxillectomy and left orbital exonera-
HARADA ET AL
FIGI JRE 4. CT scan (horizontal section) of the chest _Note a large lesion in the left lung behind the heart (arrow).
tion were performed (third operation), and since then there has been no local recurrence. However, in October 1984 bloody sputum was observed, and a large lesion was found on the chest radiograph (Fig 3). A CT scan of the chest revealed a large lesion about 9 cm in diameter in the left lung behind the heart (Fig 4). Bronchoscopic examination revealed that a part of the tumor projected into a bronchus (Fig 5). The lesion was identified as metastatic ameloblastoma by transbronchial lung biopsy. The biochemical data at the time of admission are shown in Table 1. The serum calcium level was elevated to 12.8 mg/dL. The inorganic phosphate level was 2.2 mg/dL, slightly low, and the alkaline phosphatase level was elevated at 170 U/L. We suspected a bone metastatis of the tumor and performed a general bone scintigram, but no sign of bone metastasis was observed. Radiographs of the hands, skull, and jaws showed none of the changes characteristic of hyperparathyroidism, and the serum parathormone level was only 0.3 ng/mL, which is insufficient to cause the high serum calcium level. In December 1985, the pulmonary lesion
was resected. After this, the serum calcium level normalized (Table 1).
PATHOLOGYOF SURGICAL SPECIMENS The second surgical specimen, which was removed in November 1975, was solid and showed that tumor cells had infiltrated and resorbed the grafted iliac bone. The tumor consisted of dense alveolar structures with high cellularity (Fig 6). The peripheral cells lining the alveolar structures were stratified, with an atypical appearance and showing atypical nuclear division. These findings are not frequently observed in ameloblastomas and suggest that biologically and histologically this tumor showed malignancy with respect to its pattern of development. The first and third surgical specimens also had the same microscopic appearance. The histologic findings from the pulmonary specimen, which was removed in December 1985, were nearly identical to those of the jaw (Fig 7). Table 1. The Patient’s Biochemical Admission Data Before Lung Resection
Component Total protein (g/dL) Albumin (g/dL) BUN (mg/dL) Creatinine (mg/dL) Calcium (mg/dL) Phosphorus (mg/dL) LDH (U/L) GOT (U/L) GPT (U/L) Alkaline phosphatase PTH (ng/dL)*
FIGURE 5. Bronchoscopic photograph showing the tumor projecting into a bronchus (arrow).
After Lung Resection
11 0.9 12.8 2.2 120 13 17 170 0.3
14 0.9 8.9 184 14 10 127 -
* Serium PTH was quantitated with the antibody against Cterminal peptide of parathormone.
FIGURE 6. Photomicrograph of the second surgical specimen of the left mandible. The tumor consists of dense alveolar structure with high cellularity. (Hematoxylin and eosin. Original magnification, X52.)
Discussion It is well known that ameloblastoma is locally invasive and has a high recurrence rate. However, its metastasis to a distant organ is generally considered to be very rare. The route of metastasis of ameloblastoma to the lung has been generally thought to be by way of aspiration. Yonemoto et al’ presented a case of pulmonary metastasis that showed protuberances of the tumor on the bronchial mucous membrane of the upper bronchi and no evidence of endarteritis by tumor cells in the lung. On the other hand, metastasis by way of blood vessels has also been reported. Ito et al* described a tumor cell embolus to the pterygoid venous plexus from a recurrent tumor. Some cases of lymphatic metastasis have also been reported, but conclusive
TO THE LUNG
evidence is not always easily shown because it is difficult to exclude spread by continuity. In this case, the metastasis was in the lower lobe of the left lung, and a portion of the tumor was observed endobronchially. These findings suggest that a tumor fragment was aspirated. It is also quite possible that the route of metastasis was vascular because multiple small tumor foci were observed in the resected lung tissue. Additionally, there was no conclusive evidence of metastasis to the submandibular lymph nodes in the surgical specimens. A rare feature of this case is that the tumor was associated with hypercalcemia. Hypercalcemia is a common complication in many carcinomas and is usually associated with osteolytic bone metastasis. In this case, however, there was no evidence of bone metastasis or hyperparathyroidism, and the hypercalcemia resolved following resection of the pulmonary lesion, Situations such as this have been referred to as humoral hypercalcemia.3 The most frequent malignancy associated with humoral hypercalcemia is pulmonary cancer,3 and cases of humoral hypercalcemia caused by a so-called benign tumor like ameloblastoma is very rare. As far as we are aware, there is only one such case reported, involving a patient who presented with metastasizing ameloblastoma associated with renal calculi and hypercalcemia.4 The humoral hypercalcemia is thought to be the result of a certain osteolytic factor which is secreted by the tumor cells. It has been reported that the factor is a transforming growth factor5-’ or a parathyroid hormone-like substance.‘-” In certain kinds of lymphoma, an elevated serum concentration of 1,25dihydroxyvitamin D has been reported.‘*-l5 Recently it has been shown that multiple osteolytic factors are secreted
FIGURE 7. A, Middle-power photomicrograph of the pulmonary specimen. The findings were nearly identical to those of the jaw. The tumor consists of a dense alveolar structure with high cellularity. (Hematoxylin and eosin. Original magnification, x 130.) B, High-power photomicrograph. The peripheral cells lining the alveolus are stratified and show atypical nuclear division (arrowheads). Some necrotic regions are also seen (arrow). These findings are not frequently observed in ameloblastomas. (Hematoxylin and eosin. Original magnitication, x420.)
by the tumor cells. E-N In this case, too, it seems likely that the hypercalcemia was due to some osteolytic substance or substances secreted by the metastasized ameloblastoma. Further examination is needed in order to clarify the presence and nature of any osteolytic substances secreted by such ameloblastomas. Summary A case of ameloblastoma with metastasis to the lung is reported. A rare feature of this case was that the metastasized ameloblastoma was associated with hypercalcemia without osteolytic bone metastasis. References 1. Yonemoto H, Wakabayashi T, Kawano Y: An autopsy case of malignant adamantinoma with pulmonary metastasis. Shikoku Acta Med 15998, 1959 2. Ito K, Toeda K, Kaneda T: An autopsy case of the malignant ameloblastoma with pulmonary metastasis. J Jpn Stomato1 Sot 29:399, 1962 3. Mundy GR, Martin TJ: The hypercalcemia of malignancy: Pathogenesis and management. Metabolism 31: 1247, 1982 4. Seward GR, Beales SJ, Johnson NW, et al: A metastasising ameloblastoma associated with renal calculi and hypercalcemia. Cancer 36:2277, 1975 5. D’Souza SM, Ibbotson KJ, Smith DD, et al: Production of a macromolecular bone-resorbing factor by the hypercalcemic variant of the Walker rat carcinosarcoma. Endocrinology 115: 1746, 1984 6. Ibbotson KJ, D’Souza SM, Ng KW, et al: Tumor-derived growth factor increase bone resorption in a tumor associated with humoral hypercalcemia of malignancy. Science 221:1292, 1983 7. Ibbotson KJ, D’Souza SM, Smith DD, et al: EGF receptor
J Oral Maxillofac 47:1087-1089,
antiserum inhibits bone resorbing activity produced by a rat Leydig cell tumor associated with the humoral hypercalcemia of malignancy. Endocrinology 116:469, 1985 8. Burtis WJ, Wu T, Bunch C, et al: Identification of a novel 17,000-dalton parathyroid hormone-like adenylate cyclase-stimulating protein from a tumor associated with humoral hypercalcemia of malignancy. J Biol Chem 262:7151, 1987 9. Insogna KL, Stewart AF. Vignery AMC, et al: Biochemical and histomorphometric characterization of a rat model for humoral hypercalcemia of malignancy. Endocrinology 114:888. 1984 10. Rosol TJ, Capen CC, Minkin C: In vitro bone resorption activity produced by a hypercalcemic adenocarcinoma tumor line (CAC-81 in nude mice. Calcif Tissue Int 39:334. 1986 i ’ 11. Shigeno C, Yamamoto I, Dokoh S, et al: Co-purification of bone resorbing activity and adenylate cyclase stimulating activity from human tumors associated with the humoral hypercalcemia of malignancy. Acta Endocrinol 114: 18. 1987 12. Breslau NA, McGuire JL, Zerwekh JE, et al: Hypercalcemia associated with increased serum calcitoriol levels in three patients with lymphoma. Ann Intern Med 100: 1, 1984 13. Davies M, Hayes ME, Mawer EB, et al: Abnormal vitamin D metabolism in Hodgkin’s lymphoma. Lancet 1:1186. 1985 14. Mudde AH, Van den Berg H, Boshuis PG, et al: Ectopic production of 1,25-dihydroxyvitamin D by C-cell lymphoma as a cause of hypercalcemia. Cancer 59: 1543, 1987 15. Rosental N, Insogna KL, Godsall JW. et al: Elevations in circulating 1,25dihydroxyvitamin D in three patients with lymphoma-associated hypercalcemia. J Clin Endocrinol Metab 60:29, 1985 16. Docherty HM, Heath DA: The hypercalcemia of malignancy: Changing hypotheses. J Endocrinol 113:157, 1987 17. Insogna KL, Weir EC, Wu TL, et al: Co-purification of transforming growth factor B-like activity with PTH-like and bone-resorbing activities from a tumor associated with humoral hypercalcemia of malignancy. Endocrinology 120:2183, 1987 18. Mundy GR, Ibbotson KJ. D’Souza SM: Tumor products and the hypercalcemia of malignancy. J Clin Invest 76:391, 1985
Fibroma of the Mandible:
A Case With an Unusual Clinical Presentation GUIDO VALENTE,
MD,* MARIO MIGLIARIO, MDT SILVIO DIEGO BIANCHI, MD+- AND VITTORIO VERCELLINO, MDt
Received from the University of Turin, Italy. * Department of Biomedical Sciences and Human Oncology, Section of Pathology. t Institute of Odontostomatology I. $ Institute of Radiology. Address correspondence and reprint requests to Dr Valente: Department of Biomedical Sciences and Human Oncology, Section of Pathology, Via Santena 7, 10126 Torino, Italy. 0 1989 geons
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Desmoplastic tibroma of the bone is a rare benign tumor with a dense collagen matrix that resembles the desmoid of the soft tissues. Jaffe’ first described this lesion in 1958, reporting cases in the tibia, scapula, and femur. The metaphysis of the long bones is chiefly involved by the tumor,2 but cases have also been reported in the ilium, jawbones, and vertebra.3 The first case involving the jawbones was reported by Griffith and Irby in 1965.* A new case of nonodontogenic desmoplastic fibroma of the mandible