Endodermal sinus tumor. 1. Undifferentiated germ cell tumor. 1 those patients who had histologic or clinical follow-up, was. 97%. The corresponding specificity ...
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Clinical Medicine The Use of Fine-Needle Aspiration Biopsy in Children MICHAEL B. COHEN, MD, New York; KENT BOTTLES, MD; ARTHUR R. ABLIN, MD; and THEODORE R. MILLER, MD, San Francisco
Fine-needle aspiration biopsy has become increasingly popular for evaluating both palpable and nonpalpable masses. Judging from the current body of literature, this procedure is underused by American pediatricians. We report a series of 84 pediatric patients-younger than 16 years-who underwent 92 fine-needle aspiration biopsies to evaluate a large variety of masses. The results of 51 (55%) were benign, and 33 (36%) biopsies revealed malignancy. In two cases (2%) the findings were suggestive of malignancy, and in six cases (7%), insufficient material was rendered for diagnosis. Either histologic or clinical follow-up or both were available for 85 procedures. Based on these cases, the sensitivity was 97% and the specificity was 95%, indicating that fine-needle aspiration biopsy is a good method for screening and observing patients for various malignant tumors in a variety of organs. (Cohen MB, Bottles K, Ablin AR, et al: The use of fine-needle aspiration biopsy in children. West J Med 1989 Jun; 150:665-667)
Although used successfully in Europe for 35 years, fine-
needle aspiration biopsy (FNAB) has only recently been gaining interest in the United States.' The procedure uses 22- to 25-gauge needles for the biopsy of palpable and nonpalpable masses without anesthesia. Advantages attributed to FNAB include a rapidity of diagnosis, minimal morbidity and mortality, low cost, and a high degree of accuracy. In a recent survey of private practice clinicians in San Francisco who treat adult patients, 83% (307/369) anticipated that FNAB would be used more frequently in the future. 2 Until recently, the application of FNAB to the pediatric population has largely been ignored in the American FNAB and pediatric literature. Previous reports in this country have studied its use in only small series of pediatric patients.34 In this report, we present the largest United States series of pediatric FNABs; this study includes 92 FNABs from pediatric patients seen at the University of California, San Francisco (UCSF), and the San Francisco General Hospital (SFGH) medical centers.
Patients and Methods Between 1982 and 1985, the UCSF and SFGH FNAB services did more than 7,000 procedures. All reports of FNABs from patients younger than 16 years of age were obtained from the files of the UCSF Cytology Registry and the teaching files of SFGH. In all, pathology reports, slides, and selected medical records of 84 study subjects (43 male, 41 female) were reviewed, and FNAB reports obtained from them. Five patients had two procedures, and one had four biopsies. The mean age of the patients was 5.8 years; the youngest patient was 9 months. The FNABs were done as previously described.5 7 All FNABs were done by an attending cytopathologist or by an
invasive radiologist in cooperation with the FNAB service. Briefly, the needle, attached to a syringe mounted onto a syringe holder, was introduced through alcohol-wiped skin into the mass. One hand fixed the mass between two fingers while the other hand manipulated the needle back and forth within the mass with full suction exerted on the syringe. The procedure was terminated by releasing the suction before removing the needle from the mass. While an assistant applied pressure to the puncture site, the aspirator prepared air-dried slides for May-Grunwald-Giemsa staining and alcohol-fixed slides for Papanicolaou staining. For nonpalpable masses, computed tomographic scans or ultrasonography were used to precisely localize the biopsy site, and a fast stain was done by the attending cytopathologist to ensure the adequacy of the specimen. Some of the patients required sedation for the biopsy of nonpalpable masses. Sensitivity and specificity were calculated according to the definitions of Galen and Gambino.8 Several of the patients described in this study have been previously report-
ed.9'l0 Results The fine-needle aspiration biopsies revealed 51 benign lesions (55%) and 33 malignant neoplasms (36%). Of the remaining eight cases, six (7 %) had insufficient material for diagnosis and in two (2 %), the results were suggestive of malignancy. Table 1 lists the anatomic sites at which biopsies were done. Five sites accounted for 75 % of all specimens: lymph nodes, extremities, head and neck region, abdomen, and orbit. Table 2 lists the malignant diagnoses. Of the 33 malignant cases, 31 had previous, concurrent, or subsequent surgical biopsies in the same area as the FNAB; there were no
From the Department of Pathology, Columbia University College of Physicians and Surgeons, New York (Dr Cohen), and the Departments of Pathology (Drs Bottles and Miller) and Pediatrics (Dr Ablin), University of California, San Francisco, School of Medicine. Reprint requests to Theodore R. Miller, MD, Department of Pathology, HSW-501, Box 0506, School of Medicine, University of California, San Francisco, CA 94143.
FINE-NEEDLE ASPIRATION BIOPSY
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FINE-NEEDLE
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ABBREVIATIONS USED IN TEXT FNAB = fine-needle aspiration biopsy SFGH = San Francisco General Hospital [Medical Center] UCSF = University of California, San Francisco
false-positive FNAB results in these cases. The other two cases were treated without histologic confirmation or comparison with previous histologic material. The FNAB diagnoses ofthese two cases were lymphoma and neuroblastoma. The malignant nature and type of neoplasm of these two FNAB diagnoses were based on the light-microscopic appearance, enzyme histochemistry, immunohistochemistry, electron microscopy, and clinical course. Of the 51 patients with benign findings, 13 underwent a surgical biopsy in the same area as the FNAB, and no malignant lesions were found. An additional 27 cases had a follow-up of one to four years' duration, and no malignancy developed at the FNAB site. Follow-up on the remaining 11 cases was not available. Six cases had insufficient material for diagnosis. On only one of these was a surgical biopsy done, and it showed histiocytosis X involving the skin. The other five patients have been observed clinically for one to four years and show no evidence of disease. Both patients with suggestive findings underwent a surgical biopsy, and the results were histologically benign. The sensitivity of our series, including only TABLE 1.-Biopsy Site of Fine-Needle Aspiration Biopsy Cases, No. node ............ 23 Lymph Extremities ............. 13 Head and neck ........... 12 Abdomen .............. 11 9 Orbit ............... Salivary gland .......... 7 Thorax ............... 6 Back .3 Central nervous system ..... 3 2 Skin ............... Pharynx ............... 2 Thyroid ................1 Total ............... 92
Site
TABLE 2.-Malignant Diagnoses by Fine-Needle Aspiration Biopsy* Diagnosis
Cases, No.
9 5 4 Neuroblastoma. 3 Retinoblastoma. Wilms' tumor. 2 Undifferentiated small-cell tumor. 2 1 Astrocytoma .........1 Medulloblastoma. .I Adenocarcinoma 1 Ewing's sarcoma. 1 Undifferentiated sarcoma. 1 Histiocytosis X. 1 Endodermal sinus tumor. Undifferentiated germ cell tumor. 1 *32/33 cases were correctly identified by fine-needle aspiration biopsy; there was 1I
Rhabdomyosarcoma. Lymphoma/leukemia.
false-negative case, a retinoblastoma.
ASPIRATION
BIOPSY
those patients who had histologic or clinical follow-up, was 97%. The corresponding specificity was 95%. There were no complications.
Discussion Despite increased interest in this country, FNAB has been used predominantly to diagnose neoplasms in adults. The adult FNAB literature has established that it is a safe diagnostic procedure. A literature review by Livraghi and coworkers of 11,700 abdominal FNABs revealed 1 death due to pancreatitis (0.008%) and 6 patients with major complications (0.05%). l Similar results have been obtained from about 17,000 prostatic FNABs done in Sweden, wherein there were 11 major complications and 1 death.12 Fears of tumor seeding along the need-le tract and of decreased survival rates as a result of a hematogenous spread of tumor cells have been allayed by studies that showed similar survival rates for patients with FNAB-diagnosed breast or kidney cancer and for control groups diagnosed by open surgical biopsies. 13 14 Although scattered reports from other countries of pediatric FNAB use exist, I `I only in the past few years have any American pediatric series been published. In 1983 Schaller and colleagues reported on 32 infants and children who underwent FNAB of suspected malignant neoplasms.3 Of the 32 FNABs, 19 revealed malignancy, and there were no complications or false-positive or false-negative results. In 1984 Taylor and Nunez reported 64 FNABs from 56 pediatric patients in which there were 19 malignant diagnoses, a sensitivity of 76%, and a specificity of 100% .I Our present study confirms the conclusions reached by investigators in other adult and pediatric series. We found that FNAB can be useful in diagnosing suspected malignant tumors; the sensitivity and specificity rates of FNAB in our series were 97% and 95 %, respectively; no complications occurred in our patients. The cells and tissue clusters obtained by FNAB can be analyzed by a number of contemporary diagnostic methods. Enzyme and immunohistochemical tests of plastic-embedded sections from FNABs are useful in the differential diagnosis of small round-cell tumors of childhood. For example, a diffuse staining with acid phosphatase was observed in 6/6 neuroblastomas.9 Such staining has not been seen in leukemias, lymphomas, or rhabdomyosarcomas. Other researchers are investigating the use of electron microscopy, computer-based image analysis, and measurements of DNA synthesis. 1I18-20 When fully developed, these techniques may allow us to more precisely identify tumors by FNAB and to more accurately predict a tumor's biologic behavior. Although FNAB is predominantly used to evaluate suspected malignant lesions, it can also successfully diagnose inflammatory masses. In the present study, the FNAB specimen of a benign lesion of a child's neck mass revealed granulomas and acid-fast bacilli, thus establishing the diagnosis of mycobacterial infection. Even when a causative organism could not be seen on the FNAB smear, a culture of a portion of the aspirated specimen was often successful in identifying the cause of inflammatory masses in adults.21 In an article on the management of lymphadenitis in children, FNAB was advocated as a diagnostic and therapeutic procedure for all children with fluctuant lymph nodes.22 In 1933 Stewart observed that "diagnosis by aspiration is as reliable as the combined intelligence of the clinician and
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the pathologist makes it."23 This statement is still true today, and it applies to the use of FNAB in children. Close cooperation between clinician, radiologist, and pathologist is essential if the FNAB is to be accurate. We have found that errors in any of the four steps of FNAB-biopsy, smear, interpretation, and communication of results-can adversely affect the accuracy of the procedure. Some studies have emphasized that the diagnostic accuracy of FNAB appears to be highest in centers where the biopsies, smears, and interpretation of findings are done by the same person. t For this reason, we have established a centralized pathology-based FNAB service staffed by experienced attending cytopathologists who do and interpret the FNABs. When interpreting pediatric FNABs, it is also imperative that the cytopathologist know the clinical history, age, sex, radiologic findings, the exact size of the lesion, and the chemotherapeutic and radiotherapeutic histories of the patient. Communication with the child's physician is essential to understand the differential diagnosis and the selection of appropriate diagnostic studies. Implications Fine-needle aspiration biopsy is an increasingly popular method for evaluating a variety of masses and can readily be applied to pediatric patients. It is a safe procedure with no or minimal morbidity and mortality, and fears about tumor spread have not been supported by the literature. 1.11-14 Other advantages include its relatively low cost, its accuracy, and the rapidity with which a diagnosis can be rendered. Fineneedle aspiration biopsy need not replace the open surgical biopsy, but it can be a valuable tool for screening both palpable and nonpalpable masses, to follow up patients with a history of malignancy, and as a means of doing a biopsy on patients who are at an increased risk from surgical procedures. For its diagnostic potential to be realized, however, pediatricians must understand the strengths and weaknesses of this test and its technical difficulties. REFERENCES
Bottles K, Miller TR, Cohen MB, et al: Fine needle aspiration biopsy: Has its time come? Am J Med 1986; 81:525-531 1.
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2. Bottles K, Cohen MB, Sachs ST: Clinician perceptions of fine needle aspiration cytology. Diagn Cytopathol 1985; 1:249-254 3. Schaller RT, Schaller JF, Buschmann C, et al: The usefulness of percutaneous fine-needle aspiration biopsy in infants and children. J Pediatr Surg 1983; 18:398-405 4. Taylor SR, Nunez C: Fine-needle aspiration biopsy in a pediatric population-Report of64 consecutive cases. Cancer 1984; 54:1449-1453 5. Frable WJ: Thin-needle aspiration biopsy-A personal experience with 469 cases. Am J Clin Pathol 1976; 65:168-182 6. Linsk JA, Franzen S: Introduction, Clinical Aspiration Cytology. Philadelphia, JB Lippincott, 1983, pp 6-8 7. Abele JS, Miller TR, King EB, et al: Smearing techniques for the concentration of particles from fine needle aspiration biopsies. Diagn Cytopathol 1985; 1:59-65 8. Galen RS, Gambino SR: Beyond Normality: The Predictive Value and Efficiency of Medical Diagnoses. New York, John Wiley & Sons, 1975, pp 10-40 9. Miller TR, Bottles K, Abele JH, et al: Neuroblastoma diagnosed by fine needle aspiration biopsy. Acta Cytol 1985; 29:461-468 10. Char DH, Miller TR: Fine needle biopsy in retinoblastoma. Am J Ophthalmol 1984; 97:686-690 11. Livraghi T, Damascelli B, Lombardi C, et al: Risk in fine-needle abdominal biopsy. JCU 1983; 11:77-81 12. Zajicek J: Prostate gland and seminal vesicles, Aspiration Biopsy Cytology, Part 2, Cytology of Infradiaphragmatic Organs. New York, S. Karger, 1979, pp 127-166 13. Berg JW, Robbins GF: Late look at the safety of aspiration biopsy. Cancer 1962; 15:826-827 14. Schreeb T von, Arner 0, Skovsted G, et al: Renal adenocarcinoma-Is there a risk of spreading tumour cells in diagnostic puncture? Scand J Urol Nephrol 1967; 1:270-276 15. Jereb NM, Us-Krasovec M, Jereb M: Thin needle biopsy of solid tumors in children. Med Pediatr Oncol 1978; 4:213-220 16. Valeri V, Valeri FV, Rego SFM, et al: Stereotaxic fine needle aspiration biopsy ofabdominal masses in childhood (Abstr). Acta Cytol 1981; 25:54 17. Woyke S, Gajewski P: Fine needle puncture in the diagnosis of tumors in children. Paediatr Grenzgeb 1980; 19:239-242 18. Akhtar M, Ali MA, Sabbah RS, et al: Fine needle aspiration diagnosis of round cell malignant tumors of childhood: A combined light and electron microscopic approach. Cancer 1985; 55:1805-1817 19. Akhtar M, Ali MA, Sabbah RS, et al: Aspiration cytology of Ewing's sarcoma: Light and electron microscopic correlations. Cancer 1985; 56:2051-2060 20. Akhtar M, Ali MA, Sabbah RS, et al: Aspiration cytology of neuroblastoma: Light and electron microscopic correlations. Cancer 1986; 57:797-803 21. Bottles K, Miller TR, Jeffrey RB, et al: Aspiration cytology characterization of inflammatory masses. West J Med 1986; 144:695-699 22. Fleisher G, Grosflam J, Selbst S, et al: Management of lymphadenitis in childhood: The role of percutaneous needle aspiration. Ann Emerg Med 1984; 13:908-911 23. Stewart FW: The diagnosis of tumors by aspiration. Am J Pathol 1933; 9:801-815
