Anticerebellar Antibodies. Need for Vigorous Follow-up. JOHN E. GREENLEE, MD. H. ROBERT BRASHEAR, MD. Salt Lake City, Utah. KURT A. JAECKLE, MD.
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neuroleptic drug therapy, the most probable mechanism is presynaptic dopamine blockade."7 Tics can be induced by carbamazepine,22 tricyclic antidepressants,23 and central nervous system stimulants.'" We were, however, unable to find a report in which treatment with haloperidol exacerbated chronic motor tics. Our patient had two complications of neuroleptic drug use. He suffered an acute exacerbation of his chronic motor tic disorder and the occurrence of a new motor tic. We propose that the pathophysiologic mechanism for both conditions was mediated by presynaptic dopamine blockade. Symptoms of Tourette's disorder-tics, coprolalia, obsessive behaviors-have been found to worsen with haloperidol treatment.20 Given the ample evidence associating chronic motor tics with Tourette's syndrome, it is logical to expect similar reactions to treatment with haloperidol. Haloperidol, however, has been shown to prevent the worsening of tics induced by central nervous system stimulants. 4 In our case, treatment with haloperidol exacerbated a preexisting motor tic and induced a new tic. Given the possible complications associated with haloperidol treatment, there are several options available for the treatment of chronic motor tics and Tourette's syndrome (Table 1).24 For most patients who have an exacerbation of motor tics or the development of Tourette-like syndrome after neuroleptic drug therapy, these will resolve with the discontinuation ofthe drug.20 Treatment with an anticholinergic agent could be another available alternative. Physicians should know of the possible development of motor tics or exacerbation of preexisting motor tics during treatment with haloperidol. It is important to recognize them as neurologic rather than psychological manifestations2" so they may be appropriately managed. REFERENCES 1. Clementz GL, Lee RH, Barclay AM: Tic disorders of childhood. Am Fam Physician 1988; 38:163-170 2. Shapiro AK, Shapiro ES, Bruun RD, Sweet R, Wayne H, Solomon G: Gilles de la Tourette's syndrome: Summary of clinical experience with 250 patients and suggested nomenclature for tic syndromes, In Eldridge R, Fahn S (Eds): Advances in Neurology, Vol 14. New York, NY, Raven Press, 1976, pp 277-281 3. Committee on Nomenclature and Statistics: Diagnostic and Statistical Manual of Mental Disorders, Revised 3rd Edition. Washington, DC, American Psychiatric Association, 1987 4. Pauls DL, Towbin KE, Leckman JF, Zahner GEP, Cohen DJ: Gilles de la Tourette's syndrome and obsessive-compulsive disorder-Evidence supporting a genetic relationship. Arch Gen Psychiatry 1986; 43:1180-1182 5. Lang EL, Moldofsky H, Awad AG: Long latency between the onset of motor and vocal tics in Tourette's syndrome (Letter). Ann Neurol 1983; 14:693-694 6. Robertson MM, Gourdie A: Familial Tourette's syndrome in a large British pedigree-Associated psychopathology, severity, and potential for linkage analysis. Br J Psychiatry 1990; 156:515-521 7. Seignot MJN: Un cas de malade Gilles de la Tourette gueri par le R- 1625. Ann Med Psychol 1961; 119:578-579 8. Mueller J, Aminoff MJ: Tourette-like syndrome after long-term neuroleptic drug treatment. Br J Psychiatry 1982; 141:191-193 9. Lal S, AlAnsari E: Tourette-like syndrome following low dose short-term neuroleptic treatment. Can J Neurol Sci 1986; 13:125-128 10. Pauls DL, Leckman JF: The inheritance of Gilles de la Tourette's syndrome and associated behaviors-Evidence for autosomal dominant transmission. N Engl J Med 1986; 315:993-997 11. Comings DE, Comings BG: A controlled family history study of Tourette's syndrome-I: Attention-deficit hyperactivity disorder and learning disorders. J Clin Psychiatry 1990; 51:275-280 12. Devor EJ, Grandy DK, Civelli 0, et al: Genetic linkage is excluded for the D2dopamine receptor HD2G I and flanking loci on chromosome I lq22-q23 in Tourette syndrome. Hum Hered 1990; 40:105-108 13. Zausmer DM, Dewey ME: Tics and heredity-A study of the relatives of child tiqueurs. Br J Psychiatry 1987; 150:628-634 14. Price RA, Leckman JF, Pauls DL, Cohen DJ, Kidd KK: Gilles de la Tourette's syndrome: Tics and central nervous system stimulants in twins and nontwins. Neurology 1986; 36:232-237 15. Golden GS: The effect of central nervous system stimulants on Tourette syndrome. Ann Neurol 1977; 2:69-70
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16. Factor SA, Sanchez-Ramos JR, Weiner WJ: Cocaine and Tourette's syndrome. Ann Neurol 1988; 23:423-424 17. Gualtieri CT, Patterson DR: Neuroleptic-induced tics in two hyperactive children. Am J Psychiatry 1986; 143:1176-1177 18. Sandor P, Musisi S, Moldofsky H, Land A: Tourette syndrome: A follow-up study. J Clin Psychophannacol 1990; 10:197-199 19. Bruun RD: Subtle and underrecognized side effects of neuroleptic treatment in children with Tourette's disorder. Am J Psychiatry 1988; 145:621-624 20. Weiden P, Bruun R: Worsening of Tourette's disorder due to neurolepticinduced akathisia. Am J Psychiatry 1987; 144:504-505 21. Karagianis JL, Nagpurkar R: A case of Tourette syndrome developing during haloperidol treatment. Can J Psychiatry 1990; 35:228-232 22. Gualtieri CT, Evans RW: Carbamazepine-induced tics. Dev Med Child Neurol 1984; 26:546-548 23. Dekret JJ, Maany I, Ramsey TA, Mendels J: A case of oral dyskinesia associated with imipramine treatment. Am J Psychiatry 1977; 134:1297-1298 24. Van Woert MH: Gilles de la Tourette syndrome, In Chokroverty S (Ed): Movement Disorders. New York, NY, PMA Publishing, 1990, pp 309-317 25. Jankovic J, Fahn S: The phenomenology of tics. Movement Disorders 1986; 1:17-26
Pursuing an Occult Carcinoma in a Patient With Subacute Cerebellar Degeneration and Anticerebellar Antibodies Need for Vigorous Follow-up JOHN E. GREENLEE, MD H. ROBERT BRASHEAR, MD Salt Lake City, Utah KURT A. JAECKLE, MD
Charlottesville, Virginia ANDREW GELERIS, MD Covina, California KENNETH JORDAN, MD Loma Linda, California PARANEOPLASTIC CEREBELLAR degeneration is an uncommon complication of systemic malignancy. The disorder is characterized clinically by the rapid or subacute development of extreme ataxia, dysarthria, and nystagmus, producing a cerebellar deficit ofalmost unique severity.1"2 Pathologic findings in affected patients include extensive, often complete loss of Purkinje cells, with variable loss of granule cells." 2 The disorder has been associated with a number of malignant neoplasms, including adenocarcinomas of the ovary, fallopian tube, uterus, and breast, small-cell carcinoma of the lung, and Hodgkin's disease.1"2 Paraneoplastic cerebellar degeneration may develop as long as two or more years before the detection of a malignant tumor, during its course, or at a time when the carcinoma is thought to be in remission. 1-4 (Greenlee JE, Brashear HR, Jaeckle KA, Geleris A, Jordan K: Pursuing an occult carcinoma in a patient with subacute cerebellar degeneration and anticerebellar antibodies-Need for vigorous follow-up. West J Med 1992
Feb; 156:199-202) From the Neurology Service, Veterans Affairs Medical Center. and Department of Neurology, University of Utah Medical Center, Salt Lake City; the Departments of Neurology and Behavioral Medicine and Psychiatry, University of Virginia Medical Center, Charlottesville; the Magan Medical Clinic, Covina, California; and the Department of Neurology, Loma Linda University School of Medicine, Loma Linda,
California. This work was supported by a Merit Review Award from the United States Department of Veterans Affairs. Reprint requests to John E. Greenlee, MD, Neurovirology Research Laboratory (I5 IB), Veterans Affairs Medical Center, 500 Foothill Dr, Salt Lake City, UT 84148.
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ABBREVIATIONS USED IN TEXT CSF = cerebrospinal fluid CT = computed tomography Ig = immunoglobulin PBS = phosphate-buffered saline
The cause of paraneoplastic cerebellar degeneration is unknown. In recent years, however, antibodies reactive with cerebellar and other neurons have been repeatedly shown in serum and cerebrospinal fluid (CSF) of affected persons.3-25
This antibody response is rarely, if ever, detected in the absence of neoplasia, and the presence of antineuronal antibodies in a patient with subacute cerebellar degeneration thus provides strong presumptive evidence of an underlying tumor.3-17 In some antibody-positive patients presenting with cerebellar degeneration, however, a meticulous search may initially fail to identify the associated malignant disease. The case reported here emphasizes the need for vigorous, prolonged follow-up in antibody-positive patients in whom the search for an occult neoplasm is initially unsuccessful. Report of a Case The patient, a 52-year-old woman, was in good health until November 1985, when she awoke with diplopia on right lateral gaze and noted mild difficulty walking. A neurologic examination done the next day showed a left inferior rectus weakness, mild nystagmus on left lateral gaze, and diplopia that was most pronounced on right lateral gaze. No other abnormalities were detected. Over the next two weeks, diplopia on left lateral gaze developed, and she had progressive unsteadiness of gait and difficulty writing. When the neurologic examination was repeated, she was found to have ataxia. The results of hematologic studies, blood chemistry values, and serum protein electrophoresis were normal. A lumbar puncture revealed 68 x 106 per liter leukocytes (0.98 lymphocytes), a protein level of 0.67 grams per liter (67 mg per dl), and a glucose value of 3.4 mmol per liter (61 mg per dl) (Table 1). Two oligoclonal bands were present, and the CSF immunoglobulin (Ig) G synthesis rate was increased to 19.8 mg per hour (normal < 3.5 mg per hour). Cytologic examination of CSF did not reveal malignant cells, and cryptococcal antigen was not detected. Visual-evoked response tests, computed tomography (CT), and magnetic resonance imaging of the head with gadolinium enhancement were normal. The results of subsequent CSF examinations are shown in Table 1. Cultures of CSF were negative for bacteria, acidfast bacilli, and fungi, as were serologic studies for Toxoplasma gondii, Mycoplasma pneumoniae, Coccidioides
immitis, and several viral agents including herpes simplex virus, Epstein-Barr virus, and human immunodeficiency virus. An extensive search for an occult carcinoma, including pelvic and abdominal ultrasonography, mammography, chest CT, bronchoscopy, upper gastrointestinal series, and barium enema, elicited no abnormalities. Over the next month, the patient's speech, gait, and coordination continued to deteriorate. A neurologic examination in January 1986 revealed skew deviation with diplopia and nystagmus in all directions of gaze. Speech was dysarthric. Strength was normal, but the patient had a prominent perpendicular tremor on finger-to-nose and heel-to-shin testing, as well as severe truncal ataxia. The patient was able to stand with support but was unable to walk. An electroencephalogram revealed mild left temporal slowing. Head CT was normal. A serum assay for anticerebellar antibodies produced type I ("anti-Yo") staining typical of that produced by serum from patients with paraneoplastic cerebellar degeneration associated with ovarian and breast carcinomas (Figure 1). The results of breast examinations and mammography were negative, however, and pelvic examination under anesthesia and laparoscopy disclosed a normal uterus, normal adnexa, and atrophic ovaries. Treatment with prednisone and azathioprine failed to halt the progression of the patient's cerebellar deficit, as did six courses of plasmapheresis. The patient subsequently underwent laparotomy and bilateral oophorectomy, without detection of malignancy. She remained neurologically stable over the next 21 months, with prominent nystagmus in all directions of gaze, severe dysarthria with scanning speech, and profound truncal and appendicular ataxia. No evidence of tumor was found during follow-up visits. On December 7, 1987, however, repeat mammography detected a 1.5-cm lesion in the upper outer quadrant of the right breast, and needle biopsy revealed an infiltrating mammary carcinoma. The patient was treated with mastectomy and local radiotherapy. The patient has remained neurologically stable, with persisting profound neurologic deficit.
Materials and Methods The assay for anticerebellar antibodies in serum and CSF was done as previously described.4 Serial twofold dilutions of serum beginning at a dilution of 1:20 and of CSF beginning with undiluted material, prepared in phosphate-buffered saline solution, were reacted with sections of autopsy human cerebellum for 60 minutes at 37°C. Sections were washed in phosphate-buffered saline solution, reacted with a 1:20 dilution of fluorescein isothiocyanate-conjugated rabbit anti-human IgG, washed, coverslipped, and examined using
TABLE 1.-Cerebrospina Fluid (CSFJ FindinR and Anticerebellar Antibody Titers During XOnsetandProgression of'Pbraneoplastic CerebellarDegeneration
Protein, grms/liter (m/dl) Date x 106/liter Lympytes (mg;U) ;0 f;: 1 1/7/85 .. 0.98 3.4 (61) 0.67 (67) 0.68 0.95 0.52 52 3.2t(58 0.47 0.15 (15) 3.8 (9) 0.16 1.00 ,. 1/07/86..... _. t. 3/10/8 .-222/9.-.-..........-Cels
Glucse, mmnol/liter
...........
...
N/A - not assayed Values feeto a frKtion of 1.
tA CSF speoimenwas not obtained.
AnticerebellorAntibodies Serum Titer CSF Titer
N/A
N/A
N/A
1:320 1:20
1:2,60 1:320bt 1:640
*ftllowing plasma exchange.
N/A N/A
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Figure 1.-Top, A section of normal human cerebellum overlaid with a 1:40 dilution of the patient's serum and stained using indirect immunofluorescence methods shows intense staining of Purkinje cells. The punctate extracellular fluorescence seen in this section is due to lipofuchsin (original magnification x 150). Bottom, A Purkinje cell labeled with the patient's serum at a dilution of 1:40 and stained using indirect immunofluorescence methods shows intense granular cytoplasmic staining of the cytoplasm with sparing of the cell nucleus (original magnification
x
625).
a Leitz Ortholux microscope with a 495-nm excitation filter and a K530 barrier filter. Controls consisted of matched sections of cerebellum reacted with known positive and negative serum. All studies were carried out with Institutional Review Board approval and with appropriate informed
consent.
Results A serum specimen obtained on January 7, 1986, and submitted for assay for anticerebellar antibodies produced
bright, coarsely granular cytoplasmic staining restricted to cerebellar Purkinje cells through a dilution of 1:2,560 (Figure 1 and Table 1). A CSF specimen obtained concurrently produced an identical pattern of immunofluorescence staining through a dilution of 1:20. Testing of a specimen of CSF from the patient's December 3, 1985, lumbar puncture was positive through a dilution of 1:320. A serum specimen obtained on March 10, 1986, after the patient's final plasma exchange, produced staining through a dilution of 1:320. A serum titer on February 22, 1989, after detection and treatment of the patient's tumor, was 1:640.
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Discussion Two major patterns of antibody response have been associated with paraneoplastic cerebellar degeneration. Serum from patients with paraneoplastic cerebellar degeneration accompanying adenocarcinomas of the ovary, uterine adnexa, uterus, or breast contains antibodies that recognize a cytoplasmic antigen restricted to cerebellar Purkinje cells, deep cerebellar nuclei, and certain brain-stem nuclei.3-5'810'15 Immunoblot studies have shown that this antibody response, called type I or anti-Yo, is directed against proteins with molecular weights of 37 and 62 kilodaltons (kd).3"8 Type I antibody response has not been associated with paraneoplastic syndromes other than cerebellar degeneration.3-5'810'115' In contrast, serum and CSF from patients with paraneoplastic neurologic syndromes associated with small-cell carcinoma of the lung contain antibodies that produce intense nuclear labeling and varying degrees of homogeneous cytoplasmic staining of virtually all neurons. 6.9.16 This antibody response has been called type II or "anti-Hu." Immunoblot studies have shown that type II antibodies recognize a group of proteins whose molecular weights range from 35 to 40 kd.9 Type II antibody has been associated with various paraneoplastic neurologic syndromes, including cerebellar degeneration, limbic encephalitis, brain-stem encephalitis, and dorsal sensory neuronopathy.6'9"6 An antibody producing a similar pattern of immunostaining ("anti-Ri") but reacting with 53 to 61 and 79 to 84 kd antigens has been described in patients in whom paraneoplastic opsoclonus develops in association with carcinoma of the breast.19'20 Antibodies producing other patterns of immunohistologic staining and recognizing other protein in immunoblots have been described in a minority of patients with paraneoplastic cerebellar degeneration.7"13"14'21 In each instance, the antibodies have been specific for neurons and have not labeled normal extraneural tissue. Type I antibodies have been shown to recognize cellular antigens within the patients' tumors, suggesting that the antibody response in paraneoplastic cerebellar degeneration and other paraneoplastic neurologic syndromes may be elicited by tumor antigens that are immunologically similar to neuronal proteins.22 Although antibodies have repeatedly been detected in the CSF of affected patients, a spontaneous fall in CSF antibody titers during disease progression, as occurred in this patient, has not been reported previously. Experience with antineuronal antibodies as markers for occult malignancy is still limited. Types I and II antibody responses are strongly associated with cancer, however. Gynecologic or breast cancers have been identified in all but three patients thus far reported in whom type I antibody has been detected.'7 One ofthese three patients was found to have a lymphoma, but it was not thought that a gynecologic tumor had been excluded.'7 The other two patients are still being observed.'7 Hetzel and co-workers have recently reported the cases of seven patients with progressive cerebellar deficits in whom the detection of a type I serum antibody response led to the diagnosis of ovarian adenocarcinoma.l5 Type II antibody, as confirmed by immunohistologic and immunoblot studies, has been reported almost exclusively in patients with small-cell carcinoma of the lung.3'6'8'9"6 These data suggest that anticerebellar antibodies should be sought as part of a thorough neurologic evaluation in any adult patient with a rapidly progressive cerebellar deficit.
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In the present study, a patient with subacute cerebellar degeneration was found to have serum and CSF antibodies that produced immunofluorescence staining of cytoplasmic antigens of cerebellar Purkinje cells, characteristic of type I antibody response. Because the results of a breast examination and mammography were unremarkable, extensive search was undertaken for a pelvic malignant neoplasm. Efforts to detect a tumor culminated, as the patient's clinical condition continued to worsen, in exploratory laparotomy and bilateral oophorectomy. Despite this exhaustive search, the associated tumor, a breast carcinoma, was not detected until more than two years after the onset of the patient's cerebellar deficit. Type I antibody is most frequently associated with gynecologic malignancy, and its reported use as a predictor of occult malignancy has been restricted to carcinoma of the ovary, uterus, and adnexa.15 An identical antibody response may occur in patients with carcinoma of the breast, however.3'5 Meticulous follow-up with careful search for an occult tumor should thus be continued in antibodypositive patients in whom a tumor is not found. The possibility of breast as opposed to ovarian, uterine, or adnexal adenocarcinoma should be kept in mind in any patient with type I antibody response. Repeat mammography, in addition to further careful gynecologic evaluation, should be considered in any patient in whom type I antibody is detected but a neoplasm not initially found, with repeat evaluations at threeto six-month intervals over the next year or two. REFERENCES 1. Brain L, Wilkinson M: Subacute cerebellar degeneration associated with neoplasms. Brain 1965; 88:465-478 2. Henson RA, Urich H: Cortical cerebellardegeneration, In Henson RA, Urich H (Eds): Cancer and the Nervous System: The Neurological Manifestations of Systemic Malignant Disease. Oxford, England, Blackwell Scientific Publications, 1982, pp 346367 3. Anderson NE, Rosenblum MK, Posner JB: Paraneoplastic cerebellar degeneration: Clinical-immunological correlations. Ann Neurol 1988; 24:559-567 4. Greenlee JE, Brashear HR: Antibodies to cerebellar Purkinje cells in patients with paraneoplastic cerebellar degeneration and ovarian carcinoma. Ann Neurol 1983; 14:609-613 5. Jaeckle KA, Graus F, Houghton A, Cardon-Cardo C, Nielsen SL, Posner JB: Autoimmune response of patients with paraneoplastic cerebellar degeneration to a Purkinje cell cytoplasmic protein antigen. Ann Neurol 1985; 18:592-600 6. Greenlee JE, Lipton HK: Anticerebellar antibodies in serum and cerebrospinal fluid of a patient with oat cell carcinoma of the lung and paraneoplastic cerebellar degeneration. Ann Neurol 1986; 19:82-85 7. Tanaka K, Yamazaki M, Sato S, Toyoshima I, Yamamoto A, Miyatake T: Antibodies to brain proteins in paraneoplastic cerebellar degeneration. Neurology 1986; 36:1169-1172 8. Greenlee JE, Brashear HR, Herndon RM: Immunoperoxidase labelling of rat brain sections with sera from patients with paraneoplastic cerebellar degeneration and systemic neoplasia. J Neuropathol Exp Neurol 1988; 47:561-571 9. Anderson NE, Rosenblum MK, Graus F, Wiley RG, Posner JB: Autoantibodies in paraneoplastic syndromes associated with small-cell lung cancer. Neurology 1988; 38: 1391-1398 10. Smith JL, Finley JC, Lennon VA: Autoantibodies in paraneoplastic cerebellar degeneration bind to cytoplasmic antigens of Purkinje cells in humans, rats and mice and are of multiple immunoglobulin classes. J Neuroimmunol 1988; 18:37-48 11. McLellan R, Currie JL, Royal W, Rosenshein NB: Ovarian carcinoma and paraneoplastic cerebellar degeneration. Obstet Gynecol 1988; 72:922-925 12. Anderson NE, Budde-Steffen C, Wiley RG, et al: A variant of the anti-Purkinje cell antibody in a patient with paraneoplastic cerebellardegeneration. Neurology 1988; 38:1018-1026 13. Tsukamoto T, Yamamoto H, Iwasaki Y, Yoshie 0, Terunuma H, Suzuki H: Antineural autoantibodies in patients with paraneoplastic cerebellar degeneration. Arch Neurol 1989; 46:1225-1229 14. Tomimoto H, Brengman JM, Yanigahara T: Paraneoplastic subacute cerebellar
degeneration with circulating antibody against neural and extraneural tissues (Abstr). Ann Neurol 1990; 28:247 15. Hetzel DJ, Stanhope CR, O'Neill BP, Lennon VA: Gynecological cancer in patients with subacute cerebellar degeneration predicted by anti-Purkinje cell antibodies and limited in metastatic volume. Mayo Clin Proc 1990; 65:1558-1563 16. Moll JWB, Henzen-Logmans SC, Splinter TAW, Van der Berg ME, Vecht CJ: Diagnostic value of anti-neuronal antibodies for paraneoplastic disorders of the nervous system. J Neurol Neurosurg Psychiatr 1990; 53:940-943 17. HammackJE, Kimmel DW, O'Neill BP, Lennon VA: Paraneoplastic cerebellar degeneration: A clinical comparison of patients with and without Purkinje cell cytoplasmic antibodies. Mayo Clin Proc 1990; 65:1423-1431
18. CunninghamJ, Graus F, Anderson N, PosnerJB: Partial characterization of the Purkinje cell antigens in paraneoplastic cerebellar degeneration. Neurology 1986; 36:1163-1168 19. Anderson NE, Budde-Steffen C, Rosenblum MK, et al: Opsoclonus, myo-
clonus, ataxia, and encephalopathy in adults with cancer: A distinct paraneoplastic syndrome. Medicine (Baltimore) 1988; 67:100-109 20. Luque A, Furneaux HM, Wray S, Schold C, et al: Anti-Ri: An autoantibody associated with paraneoplastic opsoclonus. Ann Neurol 1989; 26:178-179 21. Sakai K, Mitchell DJ, Tsukamoto T, Steinman L: Isolation of a complementary DNA clone encoding an autoantigen recognized by an antineuronal cell antibody from a patient with paraneoplastic cerebellar degeneration. Ann Neurol 1990; 28:692-698 22. Furneaux HM, Rosenblum MK, Dalmau J, et al: Selective expression of Purkinje-cell antigens in tumor tissue from patients with paraneoplastic cerebellar degeneration. N Engl J Med 1990; 322:1844-1851 23. Brashear HR, Greenlee JE, Jaeckle KA, Rose JW: Anticerebellar antibodies in neurologically normal patients with ovarian neoplasms. Neurology 1989; 39:16051609 24. Furneaux HF, Reich L, Posner JB: Autoantibody synthesis in the central nervous system of patients with paraneoplastic syndromes. Neurology 1990; 40:10851091 25. Graus F, Abos J, Roquer J, Mazzara R, Pereira A: Effect of plasmapheresis on
autoantibody 1990; 40:1621-1623
serum and CSF
levels in CNS
paraneoplastic syndromes. Neurology
The Papanicolaou Smear ALAN KING, MD KEVIN CLAY, MD EUGENE FELMAR, MD DARRYL G. HEUSTIS, MD ROBERT M. KARNS, MD PAMELA KRAHL, MD WILLIAM D. TENCH, MD Loma Linda, Califomia
EVIDENCE IS overwhelming that cytologic screening has been instrumental in effecting a reduction of both incidence and
mortality rates of invasive cervical carcinoma. 1-9 The death rate from cervical cancer has decreased by 50% to 70% since the Papanicolaou smear was introduced. Papanicolaou smears are convenient, painless, sensitive, cost-effective, quick, and widely accepted. They are an important part of good care of patients and can help avoid litigation for failure to diagnose cervical cancer. Limitations of Papanicolaou Smears
Papanicolaou smears are only a portion of a complete pelvic examination. Cervical cytology as a screening test has an incidence of both false-negative and false-positive results.10-25 These problems will vary with collection technique, the laboratory involved, and patient demographics. Because cervical cytology is a screening test, abnormal findings have to be confirmed histologically. Suspicious cervical lesions should be evaluated regardless of cytopathologic findings. A biopsy should be taken of gross lesions. Colposcopically directed biopsies are indicated for accurate localization of optimum biopsy sites if an (King A, Clay K, Felmar E, et al: The Papanicolaou smear. West J Med 1992 Feb; 156:202-204) From the Department of Gynecology and Obstetrics, Loma Linda University Medical Center, Loma Linda, California. This is a statement by the physician education subcommittee of the American Cancer Society California Division's ad hoc Committee on Cervical Cancer. The California Division of the American Cancer Society provided financial support for meetings of the subcommittee to develop this statement. The contents do not necessarily represent the policies of the Society. Reprint requests to Alan King, MD, Department of Gynecology and Obstetrics, Loma Linda University Medical Center, 11234 Anderson St, Room 3401, Loma Linda, CA 92354.
