Jaw metastases

Jaw metastases W. ~1. 11. vnn der Ku~rst nwd I. van der Wnnl, Amsterdam, The Netherlwlds DEPARTMENT

0F ORBI, SURGERY

AXD DEPARTMENT (PROF.

(PROF. DR. w. A. ix

OF ORAL PATHOLOGY,

DR. R. DONNER

INSTITUTE

AND PROF. DR. .J. OORT),

VAN DER KWAST), OF PATHOLOGY

TEACHING

HOSPITAL

OF TEIE FREE UNIVERSITY A general survey on metastasis is followed by a discussion of m&static spread to the mandible or maxilla of tumors locnlizcd clsemhwc in the body. This discussion is illustrated by five Case reports.

M

alignant tumors in the oral cavity are relatively rare. It has been reported that some 5 per cent of all malignant growth in the body are localized in the oral cavity.’ In the vast majority of oral malignancies the tumor is a primary one; secondary tumors (tumors of which the original localization is elsewhere in the body) are extremely rare. To warrant the use of the term metastasis, there should be histologic identity between the primary tumor and the growth suspected of being a metastasis; moreover, a distinct demarcation of healthy tissue should be demonstrable between the primary and the secondary tumors.2 TYPES OF METASTATK

SPREAD

A malignant tumor can spread in various ways. The most obvious way is that of permeation, i.e., direct extension of the tumor. This type of spread is not metastatic in the strict sense of the word. Embolic spread differs from permeation in that groups of tumor cells are transported through lymphatic vessels or blood vessels. It has so far been impossible to explain adequately why a sarcoma prefers hematogenous, and a carcinoma lymphogenous dissemination. Whereas lymphogenous spread involves a phased transfer from gland to gland, hematogenous spread consists of a phased transfer from organ to organ. Once the capillary filter in one organ is broken, dissemination to the next organ takes place. Hematogenous spread is based mainly on invasion into the venous lumen but it can also occur when lymph, “contaminated” with tumor cells, is effused into the bloodstream. 850

Jaw mnetastases 851

volunl~~ , .37 Number 6

Fig. 1. Orthopantomogrxm mandible

(Patient

shows rather

well-demnrcated

radioluceney

in the lower

left

1).

In addition to permeation or embolic spread, tumor cells can be disseminated by t~ansplantccthl. This may occur, for instance, when a tumor on one surface touches another surface: c.g., a carcinoma of the upper lip is transferred to the lower lip or a buccal carcinoma comes to involve the gingiva. Anglo-American literature has described this form as “kissing cancer.” FACTORS WHICH MAY PLAY A ROLE IN THE PRODUCTION OF HEMATOGENOUS AND LYMPHOGENOUS METASTASES An important property of cancer cells is their decreased mutual adhesiveness. A diminished calcium content of the tumor cells is believed to be an explanation of this phenomenon. Willis3 described several additional characteristics of the malignant cell, e.g., its ability to propagate progressively and to phagocytize adjacent healthy cells. Tumor cells are also believed to be capable of producing toxic or lytic substances with hyaluronidase-like properties. Moreover, malignant cells are reported to be capable of executing amcboid movements. Van Dongen” demonstrated that the risk of mctastatic spread increases as the size of the tumor increases. Roberts and associate9 demonstrated that, while no tumor cells circulated in the blood 11 days before an operation for ovarian carcinoma, palpation of the tumor raised the level to about 40 cells per milliliter of blood; the surgical procedure caused an increase to 120 cells per milliliter of blood. Experiments by PeytonG clearly revealed more metastases when local anesthesia had been used for a biopsy than with the use of general anesthesia, probably because of an increased tissue pressure. Tumor tissue, however, also can be transferred to the immediate vicinity as a result of accidental puncture by the needle.7 It is known that metastatic spread of most tumors is characterized by a

852

van der Kwast and vaz der Waal

Fig. (Patient

8. Mutinous adenocarcinoma : tumor cells 1). (Hematoxylin and eosin stain. Original

(a), mucous magnification,

secretion x130.)

(a),

bone

(0)

standard sequence : liveis-boric marrow-kidney. For some tumors, however, this sequence is different. Carcinomas of the breast, thyroid, and prostate are more likely to disseminate to the skeleton than to the liver; for these t,umors, the bone marrow is apparently a more attractive environment. The fact that the jaws arc part of the skeleton raises the question of the possible role of the mandible and maxilla as sites of metastases. METASTATIC SPREAD TO THE MANDIBLE AND MAXILLA Although diagnostic facilities have been greatly improved during this cent,ury, particularly in the field of radiology, metastases in the jaws have remained rare findings. In 1936 Geschickter and CopelandS wrote, “Although carcinoma metastasizing 60 bone is a relatively common condition, the upper and lower jaws are rarely involved.” Castigliano and Rominger” reported that 176 eases of jaw metastases were described between 1902 and 1953, in the following locations: thyroid, 47; mammary gland, 40; kidney, 19; lung, 13; prostate, 8; lip, 7; less common locations, 42. In 1965 Meyer and ShklaP reported on twenty-one patients with mctastatic jaw lesions. In seventeen cases the site of the secondary tumor was the mandible; in four cases it was the maxilla. Case reports have recently been published of some unusual metastatic tumors of the jaws.ll, I2 Some publications show that a metastatic tumor in the jaw may lead to identification of an otherwise asymptomatic primary tumor.10j l3 Moorman and Shafer’” reported on ten patients with carcinomas of various organs who were submitted to radiologic examinations of the jaws; in three, this examination revealed signs of tumor growth in the jaws. We do not know of any study which has corroborated the aforementioned assumption in a sufficiently large number of patients. Although some authors doubt whether metastases in the jaws are, in fact, very rare, the general view is that, as part of the skeleton, the jaws are seldom

Volume 37 Number 6

Fig. 5’. Extensive destruction ascending ramua (Patient 1).

Jaw metastases 853

of the left

mandihle,

reaching

from

the cuspid area to the

involved in the process of metastatic spread.l”, lfl This process preferably involves those skeletal structures that contain a large amount of red bone marrow. As the amount of red bone marrow increases, the flow rate of the circulating blood locally diminishes; this increases the risk of “sedimentation” of tumor cell emboli. In young persons red bone marrow is present in almost every part of the skeleton. With increasing age, the red bone marrow is replaced by fat in a number of skeletal structures, with the exception of the skull, sternum, ribs, clavicles, vertebrae, and the proximal se,ments of the limbs. Precisely these skeletal parts with a large amount of red bone marrow prove to be sites of predilection for metastatic tumors. As a,ge increases, red bone marrow gradually disappears from the jaws, only yellow bone marrow being left, as a rule.“-I9 This might explain why metastatic spread to the jaws is relatively uncommon. The fact that the marrow lacks a system of lymphatic vessels could be an argument in favor of mainly hematogenous metastatic spread to the skeleton. CASE REPORTS PATIENT

1

A 61-year-old woman noticed a gradually increasing swelling in the left mandible; she had been wearing full upper and lower dentures for 20 years. The swelling measured about 3 cm. in diameter and felt firm. The overlying mucosa showed normal features. There was hardly any extraoral asymmetry. Sensibility was undisturbed. No lymph nodes were palpable in the cervical region. The radiograph showed an ill-defined radioluceney with a trabecular pattern (Fig. 1). The patient had had a left-sided mastectomy 4 years earlier. This history, combined with the clinical and radiologic findings, was sufficient to warrant a suspicion of the microscopic features were those metastatic growth. A biopsy confirmed this suspicion; of .a mutinous adenocarcinoma and were identical to those of the primary tumor (Fig. 2). A detailed physical examination, made to rule out, other metastases, was negative. Radiotherapy was advised but the patient refused any type of treatment. After one year she could no longer wear the lower denture and numbness developed in the left mandibular nerve area.

Pig. 4. Large ulcerating There were no signs of metastases elsewhere. markedly (Fig. 3). The patient is still alive. PATIENT

mass on the palate The destruction

(Patient

4).

of the mandible

had progressed

2

A 54-year-old woman c>omplained of a swelling in the right mandible and paresthesia in the right half of the lower lip. Six months earlier all her teeth had been extracted. At that time the right. cheek had been swollen, which she ascribed to inflammation, but the swelling had persisted after the extraction. A mastectomy had been performed one year earlier because of carcinoma. Lntraoral examination revealed a swelling of the right mandible at the level of the third molar, extending on the buccal as well as on the lingual side. The mucosal lining was intact. A roentgenogram showed extensive destruction of the corpus and the mandibular ramus. Further investigation substantiated the suspicion that a metastasis of t,he mammary tumor was present in the right mandible. Treatment could be only palliative; the patient died six months after her visit to our department. PATIENT

3

A 57-year-old woman was referred to us because of pain radiating to the cheek and a swelling in the left lower jaw region. She had morn complete upper and lower dentures for 20 years. In view of her complaints, she had previously consulted a neurologist who had found no abnormalities. Five years before she had had a mastectomy for carcinoma. On physical examination, the submental lymph nodes were palpable and tender. Intraoral examination disclosed a tender swelling in the region of the lower incisors; the mucosal lining was intact and of normal color; its sensibility was undisturbed. A roentgenogram showed an ill-defined, symmetrical radiolucency beside the midline. An intraoral biopsy was performed in the mental area. The microscopic features of this specimen were identical to those of the primary tumor. The patient refused any form of treatment and died within a year. PATIENT

4

A 62.year-old woman was referred because of a bleeding tumor of the palate. Six months earlier this patient had consulted a general surgeon with complaints of a sense of pressure in the gastric region and poor passage of food of a few months’ duration. She had lost

Jaw metastases 855

Volume 37 Number 6

Fig.

5. Note the different

aspect of the lower second molar areas (Patient

5).

considerable weight during this period. Examination disclosed a large tumor arising from the right kidney; in addition, there were signs of pulmonary metastases. Operation included nephrectomy and extirpation of the tumor. In view of the pulmonary metsstases the prognosis was regarded as hopeless. On oral examination we found a large, lobular, ulcerating tumor of the palate (Fig. 4). In addition, numerous cutaneous metastases were palpable on the head and neck. The tumor on the palate was identified as a metastasis of t,ho renal t,umor. The patient died a few weeks after our first examination. PATIENT

5

An &year-old girl complained of an intraoral swelling in the lower right molar area. One year before, a medulloblastoma of the cerebellum, metastasized to the lumbar region, had been diagnosed. Treatment consisted of surgery, radiotherapy, and administration of a number of cytostatics. A ventriculoperitoneal shunt was made. The swelling in the oral cavity measured about 1.5 cm. It felt firm; the overlying mucosa did not show any abnormalities. A roentgenogram showed a partly formed second molar and distal bone destruction (Fig. 5). The patient was in a terminal stage of the disease. An diagnosis of jaw metastasis of a intraoral biopsy was taken post mortem; the tentative medulloblastoma was histologically confirmed (Fig. 6).

DISCUSSION The process of metastatic growth is only partially understood; there is no adequate answer to the question of why one type of tumor rapidly produces metastases whereas other tumors, even though very aggressive locally, rarely give rise to metastases. Nor is there any decisive answer as to why a given tumor type does not produce metastasis in one patient but does in another. The literature on malignant processes gives relatively little attention to the mechanism of metastatic growth. Understandably, it focuses on the aspects of primary tumor growth. Maxillary or mandibular metastases originating from tumors elsewhere in the body are relatively rare. In most cases the patient’s history is an important factor in establishing a tentative diagnosis. The definitive diagnosis can be made

Oral Burg. June, 1974

Fig. 6. Biopsy eosin stain. Original

of ja\v metastasis of x medullol~lxstomn magnification, x33.)

(Patient

5).

(Hematoxylin

and

only by microscopic examination of the lesion anal comparison with the histologic features of the primary t,umor. Naxillary or mandibular metastases are seldom diagnosed before the primary tumor is tliagnosed. A maxillary or mandibular metastasis poses therapeutic problems. The therapy instituted is dependent on a variety of factors, such as the radical extirpation of the primary tumor, possible metastases elsewhere, interval between primary tumor treatment and diagnosis of metastascs, type of tumor, and extent of metastatic growth. In many cases palliative treatment will prove to be the only justifiable one. In reviewin g our patients WC encounter a serious problem in the cast of Patient 1, a woman with a mandibular metastasis from a carcinoma of the breast. Physical examination did not reveal any evidence of local growth of the mammary carcinoma or of metastases elsewhere in the body. Moreover, the interval between the treatment of the primary tumor and the mandibular metastatic growth was comparatively long (4 years). Any attempt at curative operative therapy of this metastasis would involve considerable mutilation. Radiotherapy seemed to hold little promise, for the tumor in question was fairly well differentiated and partly embedded in bone. The final advice, after multidisciplinary consultation, was to submit the patient to palliative irradiation. The patient, however, refused any form of therapy. Understanilably, a curative approach to the metastases in Patient 2 was not even considered. The localization and extent of the metastases were such that

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neither surgery nor radiotherapy could be expected to offer a chance of success. Moreover, the interval between primary tumor treatment and the occurrence of the metastases was substantially shorter than in the case of Patient 1. The picture in Patient 3 was more or less identical to that in Patient 1, even so far as the history was concerned. However, the metastases proved to be larger and more aggressive, as indicated by such findings as anesthesia of the lower lip. This patient, too, was urlwilling to submit to any form of treatment. Patient 4 was cache&k when she came to our department, with multiple metastases throughout the body, including a large ulcerating metastasis on the palate. The only help WC c*oultl offer was to arrest. the hemorrhages from this tumor mass. Patient 5 finally developed a jaw metastasis of a medulloblastoma. She, too, was in a terminal stage of the disease. This case is quite comparable with the one reported by Eversole and associates. I2 The jaw metastasis may have been induced iatrogenically because of the ventriculoperitoneal shunt that was placed at the same side. REFERENCES

1. Sarnat, B. G., and &hour, I.: Oral and Facial Cancer, Chicago, 1957, Yeark Book Medical Publishers, Inc. 2. Clausen, F., and Poulsen, H.: Metastatic Carcinoma to the Jaws, Acta Path. Microbial. &and. 57: 361-374, 1963. 3. Willis, R. A.: The Spread of Tumours in the Human Body, London, 1952, Butterworth & Company, Ltd. 4. Van Dongen, J. A.: Haematogene metastasen, Amsterdam, 1961, Scheltema en Holkema. 5. Roberts, 8. S., Watne, A. L., McGrew, E. A., McGrath, R. G., Nanos, S., and Cole, W. H.: Cancer Cells in the Circulating Blood, Surg. Forum 8: 147-154, 1958. 6. Pevton, W. T.: Danger in the Use of Local Infiltration Anesthesia in Operations Upon M&e&t Tumors. A&. Surp. 111: 453-458. 1940. 7. VanODongen, 5. A., Jr., Hakpe, J. F., anh Van Slooten, E. A. : Betekenis, indicatie en techniek van proefexcisies. Ned. Tiidschrift Geneesk. 104: 1717-1722. 1960. 8. Geschiekter, c‘., and Copgland, M.Y Tumors of Bone, ed. 3, Philadelphia, 1949, J. B. Lippincott Company. 9. Castigliano. S. G.. and Rominper, Malignancv ..7 , C. J.: Me&static * of the Jaws, Am. J. Sure. 87: 436-5Oi, 1954. IO. Meyer, I., and Shklar, G.: Malignant Tumors Metastatie to Mouth and Jaws, ORAL SURG. 20: 350-362, 1965. 11. Yncabucei, J. E., Mainous, E. G., and Kramer, H. 5.: Hepatocellular Carcinoma Diagnosed Following Metastasis to the Mandible, ORAL SURD. 33: 888-893, 1972. 12. Eversole, L. R., Sabes, W. R., Brandebura, J., and Massey, G. B,: Medulloblastoma: Extraoral Metastasis to the Jaw; Report of Case, ORAL SURG. 34: 634-640, 1972. Tumors in the Jaws, ORAL 13. McDaniel, R. K., Luna, M. A., and Stimson, P. G.: Metastatic SURG.31: 380-386, 1971. 14. Moorman, W. C., and Shafer, W. G.: Metastatic Carcinoma of the Mandible, J. Oral Surg. 12: 205209, 1954. 15. Banerjee, S. C.: Metastasis to the Mandible, ORAL SURG.23: 71-77, 1967. J. E. A.: Metastatic Tumors of the Mandible, A., Costa, F. Q., and Miziara, 16. Burtelli,

ORAL SURG.30: 21, 1970. G. : Die Verletzungen 17. Perthes, 18. Box, H. K.: Red Bone Marrow 19. Sandherg, A. A., Moore, G. E., Tumor Cells in the Rone Marrow

und Krankheiten in Human Jaws, Gosswhite, B. A., and Rlood, Cancer

Reprint requests to: Prof. Dr. W. A. M. van der Kwast Department of Oral Surgery rnstitute of Pathology Teaching Hospital of the Frrc! Univcarsity Amstctrdnm, The Nethc~rlantls

der Kiefer, Stuttgart, 1907, Enke. Aust. Dent. 5. 6: 79-86, 1934. and Schuborn, J. R.: Frequency of 11: 1180-l 186, 195%