Journial of Neuirology, Neurosurgery, anid Psychiatry, 1973, 36, 211-216

The numb chin in breast cancer'JOHN HORTON, EUGENE D. MEANS, T. J. CUNNINGHAM,

AND KENNETH B. OLSON

From the Departments of Medicine (Division of Oncology) and Neurology,Albany Medical College, Albany, New York 12208 U.S.A.

SUMMARY Numbness of the chin, an uncommon neurological symptom, was observed in 15patients with cancer. Thirteen had breast cancer. This symptom usually heralded progressive involve-ment of the cranial nerves or cerebrum and denoted a poor prognosis in patients with a short 'tumour-free interval'. The pathogenesis is commonly related to dural involvement of the Vth cranial nerve atthe base of the brain, although metastasis to the mandible might sometimes be implicated. Thereason for the peculiar predilection for the mandibular branch of the trigeminal nerve to be affectedby breast cancer is not known.

Unilateral facial numbness is an uncommonprimary symptom of neurological disease. It hasbeen reported in association with multiplesclerosis (McAlpine, Lumsden, and Acheson,1965), syphilis (Ornsteen, 1931), arachnoiditis(Hughes, 1958), sarcoidosis (Jefferson, 1957),connective tissue diseases (Ashworth and Tait,1971), and after exposure to toxic chemicals(Collard and Hargreaves, 1947; Mitchell andParsons-Smith, 1969). Trauma and dentalabnormalities (Collard and Hargreaves, 1947)have caused the symptom and the relationshipto space occupying lesions including primarynasopharyngeal cancer (New, 1922) and carotidaneurysm (Goldstein, Gibilisco, and Rushton,1963) is well recognized. A benign sensory tri-geminal neuropathy has also been described (Hill,1954).During the past five years we have seen 15

patients with a peculiar and distinctive symptomof numbness of the chin. Thirteen of thesepatients had breast cancer. The purpose of thisreport is to describe the clinical features of thesepatients, their progress, and the prognosticsignificance of this symptom.

PATIENTS

The patients included in this study were from a groupof 2,000 patients with cancer, including 300 patients1 Supported by Grant CA06594 of the National Cancer Institute ofthe United States Public Health Service and the Manning Foundation.

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with breast cancer, seen by members of the Divisionof Oncology at the Albany Medical College duringthe last five years. All patients volunteered the symp-tom spontaneously without special questioning. Thecommon complaint was of a unilateral sense ofnumbness occurring in the skin adjacent to the tipof the jaw. At times the area of numbness extendedas far as the angle of the jaw. Pain was almostalways absent but numbness of the subjacentmucous membrane occasionally occurred. Thesensory deficit was confirmed by clinical examina-tion. Studies performed on the patients usuallyincluded radiographs of the mandible and skull,lumbar puncture, electroencephalography, and,occasionally, Hg203 or Technetium brain scans.The clinical features, associated findings, and out-

come of the 15 patients are summarized in Table l.Thirteen patients (86%) had breast cancer and two(14%) lymphoma. All save one had metastaticdisease at the time of presentation. The numb chinwas the sole presenting neurological symptom ineight patients (530%). Other cranial nerves or themaxillary branch of the trigeminal nerve were in-volved in four patients (27%). Three patients (20%)had paraplegia, two (13%) proximal muscle weak-ness, and one had seizures.

Laboratory findings at the time of presentation ofthe neuropathy were of limited value. Radiographsof the skull showed evidence of metastatic involve-ment of the calvarium in seven patients. Carefulstudy, even in retrospect, failed to reveal definiteradiological evidence of bony defects in the region ofthe petrous temporal ridge. Figure 1 illustrates duralinvolvement of the base of the brain seen at necropsy

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John Horton, Eugene D. Means, T. J. Cunningham, and Kenneth B. Olson

of patient no. 3. No suggestion of this lesion wasseen radiographically. Specific radiological studies ofthe mandible were performed on eight patients,although a less adequate view was obtained of theremainder from skull radiographs. Only two patientsdemonstrated mandibular metastasis. Figure 2illustrates a radiograph of part of the mandible ofpatient no. 12. This shows extensive osteolysis.Lumbar puncture and electroencephalography wereusually not helpful and abnormalities of brain scansperformed reflected calvarial rather than intracerebraldisease.The clinical progression of the patients with

breast cancer was quite variable. Five patientsdeveloped further cranial nerve involvement, twodeveloped intracerebral metastasis, one had bothposterior pituitary and intracerebral metastases,and one had a combination of posterior pituitary,intracerebral, and cranial nerve involvement. Theneurological status remained unchanged in fourpatients but the survival of three of these patientswas less than two months. One of the two patientswith lymphoma had rapidly progressive cranialnerve dysfunction.

TABLE 2CORRELATION OF SURVIVAL OF PATIENTS WITH BREASTCANCER FROM TIME OF ONSET OF NUMBNESS OF CHIN WITHDURATION OF TIME BETWEEN INITIAL DIAGNOSIS OF BREASTCANCER AND ONSET OF FIRST EVIDENCE OF METASTATIC

DISEASE ('TUMOUR FREE INTERVAL')

'Tumour free Median Range Number ofinterval survival (months) patients

(yr) (months)

Over 10 48+* Both 48+ 25-10 14 - 11-4 5 2-24 7Less than 1 2 J-4 3

* + signifies still alive.

Survival of the patients with breast cancer rangedfrom two weeks to over four years. There was littlecorrelation between the type of progression of theneurological dysfunction and survival measured fromthe time of onset of mental numbness. A goodcorrelation existed between the duration of the so-called 'disease free interval' and subsequent survivalas shown in Table 2.

Treatment for the numb chin was not necessary asthe symptom itself was trivial. Most patients receivedradiation and/or chemotherapy to control progres-

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FIG. 1. Demonstratesinvolvement of the duramater at the base of thebrain ofpatient no. 3 bytumour metastasis.

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FIG. 2. Arrow points to an area ofosteolytic metastasis in the mandibleofpatient no. 12.

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Numb chin in breast cancer

sion of systemic metastatic disease. The numb chindisappeared only in one patient (no. 13) who had noevidence of metastases and had no antitumour treat-ment.

Dural involvement by tumour was demonstratedin six of the seven patients who had necropsies.Pathological studies of the mandible were not per-formed.

DISCUSSION

We observed unilateral numbness of the chin in400 of our patients with breast cancer. Except forthe two patients described who had lymphoma,the entity did not occur in patients with otherprimary sites of tumour. The incidence ofparenchymal brain metastasis is higher in lungthan in breast cancer at our institution (Horton,Baxter, Olson, and Eastern Cooperative Oncol-ogy Group, 1971) but none of the patients withlung cancer have complained of numbness ofthe chin. Rubinstein (1969) described six patientswith numbness of the chin of whom none hadbreast cancer but four had lymphoma or Hodg-kin's disease. The reason for the predilection inour series for breast cancer to cause this symptomis not clear. It parallels, however, our experiencewith metastases to the posterior pituitary gland(Houck, Olson, and Horton, 1970). There was apreponderance of involvement by breast cancerand, to a lesser degree, lymphoma and leukaemia.Our findings suggest that a single cause would

not satisfactorily explain the symptom in allpatients. In the patients who had tumour involv-ing the dura mater at necropsy there seems littledoubt that there was interference with the sen-sory pathway of the trigeminal nerve in theregion of the base of the skull where it is en-compassed by the dura mater. Direct tumourmetastasis to the nerve as described by Barron(Barron, Rowland, and Zimmerman, 1960) mayalso have played a role in two patients. The radio-logical evidence of metastatic disease in the man-dible in another two patients suggests that theremay have been interruption of function of themental nerve. Both patients, however, had duralmetastasis at necropsy. The pathogenesis in fourpatients with breast cancer whose neurologicaldeficit did not progress is not clear, since noneof the three who died came to necropsy. Theoutcome of one patient, who is still alive with noevidence of metastasis for four years after her

symptom developed, raises the possibility of thisbeing a neuropathy unrelated to direct involve-ment by tumour. It seems unlikely that sherepresents an example of benign sensory tri-geminal neuropathy, since the symptomatologyin this syndrome is usually short lived (Hill,1954).Four patients received drugs that can cause

peripheral neuropathy. Three received vincristine(Sandler, Tobin, and Henderson, 1969) and one1-acetyl, 2-picolinyl hydrazine (NSC 68626)(Olson, Horton, Pratt, Paladine, Cunningham,Sullivan, Hosley, and Treble, 1969). These drugstend to produce a symmetrical peripheral poly-neuropathy rather than a mononeuropathy andthey could not be implicated, since in each casethey were given after the symptom had appeared.Our experience that the mandibular branch of

the trigeminal nerve is peculiarly susceptible tothe effects of tumours parallels that of Rubinstein(1969). Of his patients with involvement of themandibular division the symptoms were mostpronounced on the chin and, like ours, there wasnever any dysfunction of the ophthalmic divisionor motor branch of the Vth nerve. None of thepatients had bilateral symptoms.The reason for this peculiar predilection for

involvement of the mandibular branch of thetrigeminal nerve is not clear. The commonlyencountered trigeminal sensory abnormality, ticdouloureux, characteristically also involves themandibular and/or the maxillary branch andrarely involves the ophthalmic division (Carney,1967). Benign sensory trigeminal neuropathy,too, follows this pattern. Mechanical factorshave been implicated in the genesis of trigeminalneuralgia (Lindsay, 1969) and may likewise playa part in our patients with numbness of the chin.It is possible that displacement or distortion ofthe trigeminal nerve or ganglion could haveresulted from radiologically undetected con-tiguous bony metastasis. Spread of tumour to thetrigeminal nerve from involved dura mater mayhave gone undetected, since necropsies were notperformed on some of these patients.

REFERENCES

Ashworth, B., and Tait, G. B. W. (1971). Trigeminal neuro-pathy in connective tissue disease. Neurology (Minneapolis),21, 609-614.

Barron, K. D., Rowland, L. P., and Zimmerman, H. M.

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(1960). Neuropathy with malignant tumor metastases.Journal of Nervous and Mental Diseases, 131, 10-31.

Carney, L. R. (1967). Considerations on the cause and treat-ment of trigeminal neuralgia. Neurology (Minneapolis), 17,1143-1151.

Collard, P. J., and Hargreaves, W. H. (1947). Neuropathyafter stilbamidine. Lancet, 2, 686-688.

Goldstein, N. P., Gibilisco, J. A., and Rushton, J. G. (1963).Trigeminal neuropathy and neuritis. Journal of theAmerican Medical Association, 184, 458-462.

Hill, T. R. (1954). Two cases of trig.minal neuropathy.Proceedings of the Royal Society of Medicine, 47, 914-915.

Horton, J., Baxter, D. H., Olson, K. B., and the EasternCooperative Oncology Group (1971). The management ofmetastases to the brain by irradiation and corticosteroids.American Journal of Roentgenology, Radium Therapy andNuclear Medicine, 111, 334-336.

Houck, W. A., Olson, K. B., and Horton, J. (1970). Clinicalfeatures of tumor metastasis to the pituitary. Cancer, 26,656-659.

Hughes, B. (1958). Chronic benign trigeminal paresis. Pro-ceedings of the Society of Medicine, 51, 529-531.

Jefferson, M. (1957). Sarcoidosis of the nervous system.Brain, 80, 540-556.

Lindsay, B. (1969). Trigeminal neuralgia: A new approach.Medical Journal of Australia, 1, 8-13.

McAlpine, D., Lumsden, C. E., and Acheson, E. D. (1965).Multiple Sclerosis, A Reappraisal, p. 121. Livingstone:Edinburgh.

Mitchell, A. B. S., and Parsons-Smith, B. G. (1969). Tri-chloroethylene neuropathy. British Medical Journal, 1,422-423.

New, G. B. (1922). Syndrome of malignant tumors of thenasopharynx. Journal of the American Medical Association,79, 10-14.

Olson, K. B., Horton, J., Pratt, K. L., Paladine, W. J., Jr.,Cunningham, T., Sullivan, J., Hosley, H., and Treble,D. H. (1969). 1-Acetyl-2-picolinoylhydrazine (NSC-68626) in the treatment of advanced cancer. CancerChemotherapy Reports, 53, 291-296.

Ornsteen, A. M. (1931). Isolated bilateral trigeminal nervedisease presumably syphilitic in origin. Journal of Nervousand Mental Disease, 74, 297-300.

Rubinstein, M. K. (1969). Cranial mononeuropathy as thefirst sign of intracranial metastases. Annals of InternalMedicine, 70, 49-54.

Sandler, S. G., Tobin, W., and Henderson, E. S. (1969).Vincristine-induced neuropathy. A clinical study of fiftyleukemic patients. Neurology (Minneapolis), 19, 367-374.

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