Cardiovasc lntervent Radiol t 1991) 14:55-62

CardioVascular andInterventional 9 Springer-Verlag New York Inc. 1991

Percutaneous Lymph Node Biopsy David D. Lawrence, I C. Humberto Carrasco. ~ Bruno Fornage, l Nour Sneige. z and Sidney Wallace ~ Departments of ~DiagnosticRadiology,Divisionof Diagnostic hnaging,and 'Cytology,Divi~,ionof Pathology,The Universityof Texas, MD. Anderson Cancer Centcr, Houston, Texas. USA

Abstract. Advances in imaging modalities for detecting lymphadenopathy, the ease, safety, and accuracy of the tools and techniques, and the addition of refined ancillary studies for cytologic analysis will continue to increase the acceptance and use of percutaneous lymph node biopsy (PLNB) by fine-needle aspiration (FNA), especially in lymphomas. Key words: Biopsy--Percutaneous lymph node-Fine-needle aspiration

Percutaneous lymph node biopsy (PLNB) is an important interventional method used in diagnosis and management of disease that arises in or spreads through the lymphatic system. The diagnosis and management of the patient with lymphadenopathy frequently entails PLNB by fine-needle aspiration (FNA) and cytologic analysis. Close cooperation and communication among the clinician, cytopathologist, and radiologist are essential to determine the exact nature of the problem to be solved and the imaging modality best suited to guide the biopsy procedure. At the University of Texas, M.D. Anderson Cancer Center (MDACC), in the Superficial Biopsy Clinic, lymph nodes, when palpable, are aspirated and evaluated by the cytopathologist. The aspiration biopsy of all other lymph nodes necessitates localization by fluoroscopy after lymphangiography (LAG), ultrasonography (US), computed tomography (CT), or magnetic resonance imaging (MRI). The choice is determined by the size and location of the suspected lymph node, the availability of the diagnostic modality for optimal visualization, the Address reprint requests to: David D. Lawrence, M.D., The University of Texas. M.D. Anderson Cancer Center. 1515 Holcombe Boulevard, Box 57, Hauston, TX 771)30, USA

experience and capability of the radiologist in the performance of the biopsy procedure, and the expertise of the cytopathologist to accurately define the nature of the specimen.

Technical Considerations Patient Preparation

Most biopsies are scheduled electively on an outpatient basis. Prothrombin time, partial thromboplastin time, and platelet count are necessary. Any correctable coagulopathies are remedied including platelet transfusions. Informed consent is obtained and the patient is reassured by a discussion of the steps required for the procedure. Anesthesia~Analgesia

Intravenous sedation and analgesia are helpful for most patients. Local anesthesia of the skin, subcutaneous, and deeper tissues is accomplished with 1% xylocaine. Needle-Syringe Biopsy Device

The recent literature describes or refers to a variety of needle types, tips and grips with suction, angulation, and automation that may enhance the biopsy technology, speed and accuracy of placement, and quality and quantity of biopsy sample, depending on the needs of the operator and the pathology services available [1-3]. At MDACC, 20-25 gauge Chiba needles (Cook Inc., Bloomington IL) are used for aspiration. Cutting needles (Surecut, Meadox Surgimed, Oakland, N J) are used for aspiration and tissue cores. Recently developed spring-loaded devices

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(Biopty gun, Bard, Covington GA.) using guillotine (Trucut, Baxter, Deerfield, [L) needles allow automated biopsy [4]. Success has been documented by most authors regardless of the devices employed. Recently there has been a renewed interest in using larger needles for tissue samples requiring histological study.

D.D. Lawrence et al.: P e r c u t a n e o u s t . y m p h Node Biops.v

Pathologic Evaluation Histologic and cytologic morphologic diagnoses are enhanced by immunocytochemical lymphocyte marker studies, nucleic acid (DNA) flow cytometry, cytogenetics, and molecular studies. These ancillary cytologic studies increase the objectivity of diagno-

D.D. Lawrence et al.: Percutuneous Lymph Node Biopsy

sis especially in lymphomatous diseases and are readily obtained by fine-needle aspiration (FNA). Tissue samples from each biopsy are immediately evaluated by the cytopathologist in the Department of Diagnostic Radiology for the content and adequacy of the specimen [5]. Microscopic and/or cell count analysis determine the number of passes I\3r additional material or special studies, tn general, two to four cellular aspirates will yield adequate material for most of the ancillary studies. For lymphoma, the Coulter Counter is used to determine the cell count. Two million cells per milliliter is considered adequate. Usually two slides are smeared carefully and air dried for Diff Quick (Harleco, Gibbstown, N J) staining. Two other slides are smeared and placed immediately in 95% alcohol solution for Papanicolaou staining The remaining contents of the syringe is expressed into a vial of RPMI 1640 medium (Gibco. Grand Island, NY) for ancillary studies and cell block for histology. Electron

Fig. I. Relapse of diffuse large cell lymphoma 4 yet~rs after initial diagnosis and treatment. Residual contrast in lymph node m left common iliac region changed in appearance. Repeat LAG and fluoroscopic-guided FNA biopsy of positive nodes was done with patient in the supine-oblique position via retroperitoneal approach. Adequate cytological material was obtained in two passes with a 22-gauge Chiba needle (A & B). Note the site of contrast aspiration from the iirst pass (arrow). Fig, 2. Recurrent right pericaval lymphadenopathy after right kidney resection for transitional cell carcinoma. A C T shows reruneat nodal mass in right prevertebral pericaval region at the level of the superior margin of the 2nd lumbar vertebral body. Position of arrow shows intended tract for FNA, B & C Bony landmarks were used at lluoroscopy for prone-oblique translumbur placement of a 22-gauge Chiba needle. There was positive cytology on the first pass. Fig. 3. Metastatic lymphadenopathy in porta hepatis. Several days after placement of biliary drainage tube for obstructive jaundice and decompression, a repeat limited cholangiogram was done (arrow). The point of obstruction adjacent to the drain was used for fluoroscopically guided FNA with a 22-gauge Chiba needle resulting in positive cytology. Fig. 4. t.eft anterior mediastinal nodal mass due to metastatic adenocarcinoma. An outside CT scan was used to document bony landmarks (left first parasternat intercostal space) and depth (6 cm) for 22-gauge Chiba needle placement by fluoroscopy farrow). Fig. 5. US-guided FNA ofa nonpalpable, metastatic lymph node adjacent to the carotid artery in u patient in excellent condition with a history of laryngeal cancer. Oblique scan of the neck shows the 0.8 • 0.5-cm node ~'arrows) and the fine needle larrowheuds) whose tip lies within the node. Fig. 6. US-guided FNA of retroperitoneal lymphadenoputhy. Transverse sonogram of the abdomen shows the bright needle tip (arrow) in the lymph node. A single pass provided an adequate specimen. Cytologic diagnosis was lymphoma. Note the hypoechoic lymphomatous involvement of ~he left lobe of the liver ~L) anteriorly.

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microscopy can be carriedout for undifferentiated neoplasms with one drop of aspirate placed in gluteraldehyde solution. The entire process can be repealed as many times as necessary with multiple passes depending on the clinical situation and the yield. After the biopsy, the patient is observed in the department for approximately I h prior to discharge.

Imaging Modalities

Fluoroscopy Lymph node abnormalities opacified by LAG are easily recognized and approached under fluoroscopic control. At MDACC, conventional uniplane, overhead, image-intensified fluoroscopy with a spot film device is used. Biplane or C-arm fluoroscopy would facilitate the procedure. The patient or the equipment is rotated so that the needle can be introduced into the lymph node in a line parallel to the central ray of the fluoroscopic beam. The depth of the lesion and the appropriate length of the needle is determined from fluoroscopy, radiographs, or prior scanning studies. The entry site on the skin is localized with a metal pointer and marked. The skin is prepared, draped, and anesthetized. The needle. usually a 22-gauge Chiba, is grasped at its hub with a sponge t\3rceps. The shaft of the needle is held by a hemostat close to the skin surface and directed into the lesion. As the lymph node is approached, more precise localization of the needle tip is necessary, accomplished by slight rotation of the patient. Bidirectional spot radiographs confirm the presence of the needle within the defect in the node. The opacified lymph node moves on entry anti with motion of the needle. A to-and-fro movement of 0.5-2 cm excursion of the needle-syringe is performed during manual aspiration with a 20 cc disposable syringe. The visualization of oil droplets in the cytologic preparation confirms nodal sampling. At times after aspiration, a new defect in the node will confirm the site of biopsy. For lilac and pelvic lymph nodes, a supine-oblique position with a retroperitoneal approach is desirable (Fig. 1) usually with a l0 or 15 cm needle. For higher retroperitoneal lymph nodes. with the patient supine, a direct transperitoneal approach is preferred. If these nodes.are not obscured by the spine, a prone-oblique position with a translumbar approach may be more ideal (Fig. 2). On occasion, when abnormal lymph nodes are seen on CT but not opacified by LAG, bony landmarks, clips, drains, or tubes adjacent to the lesion may be used for fluoroscopic localization (Figs. 2, 31. Information from CT, US, or MRI is often used to guide lymph node biopsy by fluoroscopy even if the lymph node is not opacified (Fig. 4). FNA b~

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fluoroscopic guidance is quick; safe, accurate, costeffective, readily accessible, and the method of choice if at all possible.

Ultrasound When adenopathy is detectable by this cross-sectional modality, full, continuous, real-time monitoring of the insertion of the biopsy needle is possible [1, 6-10]. At MDACC. conventional linear-array transducers and 20-22 gauge Chiba needles with free-hand biopsy technique are most often used with the highest MHz frequency possible to give the best depiction of both the target lymph node and the needle. Abnormal superficial lymph nodes, obscured from palpation by postoperative or postirradiation change, can readily be detected with high frequency (7.5 MHz) US [11-13]. FNA with short fine needles gives maximum safety in lymph nodes adjacent to carotid or femoral arteries (Fig. 5). For abdominal lymph nodes, various transducers are available for biopsy operating in the 2.25-3.5 MHz range; up to 5 MHz can be used in thin patients. The transducer is placed in a sterile bag containing alcohol which is also used as the couplant. Occasionally, 20-21 gauge Surecut needles can be used giving tissue cores as well as abundant cytological material. Various modifications of needles for improved US visualization have been proposed [14]. Usually, standard needles are well visualized, especially in the more hypoechoic background. Even though US is more operator dependent, the free-hand technique is the most useful and can be practiced on simple home-made phantoms. The position of the transducer is selected to provide the shortest and safest needle pathway to the target lymph node which is displayed along the midline of the scan. The needle is positioned adjacent to the midpoint of the probe and inserted obliquely toward the scan plane and the lesion and identified as soon as possible as a bright echo. Slight altering of the relative position of the probe and needle, as well as slight to-and-fro motion of the needle, confirm the position of the tip-echo. As a golden rule, if the needle is not visualized, it must be withdrawn, not further inserted. Any deviation of the needle can be repositioned. The entire procedure can be videotaped. When the needle tip has reached the center of the node, a hard copy image can be taken (Fig. 6). The actual to-and-fro FNA can be monitored with the needle tip in the lesion if a pistol grip (Cameco. Labonard, France), Vacutainer tube or an assistant with extension tubing are available to facilitate the aspiration. Slight reorientation of the needle in a fan-like manner within the lesion augments sample volume, which is

D.D. Lawrence et al.: Percutaneous Lymph Node Biopsy

an advantage over the "single-shot" cutting needles. Rarely are more than two passes necessary. Transvaginal and transrectal US are routinely used in evaluation of the pelvis. Endoluminal techniques are expected to expand the use of US guidance in biopsy of pelvic lymph nodes [15]. The US procedure is short, safe, accurate, and accessible. Because of limited resolution of US in depth, normal-sized abdominal lymph nodes are not visualized. Focal intranodal micrometastasis cannot be demonstrated sonographically. Biopsy of lymph node metastases smaller than 2 cm is better performed with CT guidance.

Computerized Tomography When lymphadenopathy causes enough nodal enlargement or inhomogeneity to be detected by CT, very accurate biopsy needle placement is possible at precise depths [16-19]. When using fine needles, straight axial transperitoneal, perivascular (Fig. 7) or transvascular (Fig. 8) placements are possible and are considered quite safe. As many passes as necessary are done and monitored with cytological evaluation. Larger needles have higher rates of complication which must be taken into consideration [20]. Angulated gantry technique may be useful in finding the safest path to the lesion; sometimes a coaxial needle system can be used. A 19-gauge thinwall outer needle tip is placed on the surface of the node, allowing multiple passes of an inner 22-gauge needle, with a slightly curved tip, into the lesion itself (Fig. 9). CT is more time consuming, less accessible, but very accurate and safe for small, deep. perivascular abnormalities.

MR1 This modality is highly sensitive in delineating adenopathy and margins of abnormal tissue. High nickel-stainless steel alloy, fine MR needles [21] (E-Z-EM, Westbury, NY) are available with grid techniques for precise needle localization. General experience with this modality is limited due to tow accessibility [see 22-241.

Results

Genitourinary The role of PLNB in genitourinary carcinoma has been reviewed extensively. Accuracy of detecting nodal metastases by FNA varies from 65 to 97.5%

D.D. Lawrence et al.: Perculaneous Lymph Node Biopsy

59

cancer staged by LAG and FNA [25], systematic PLNB of primary drainage nodes [26, 27] and higher suspicious nodes were performed and correlated with lymphadenectomy [28-31]. In bladder carcinoma, FNA had an accuracy rate of 93%. The overall accuracy was improved by 10%, and the falsenegative rate of 48% for LAG was reduced to 25%, if the medial group of the external iliac nodes (obturator nodes) were systematically punctured. For testicular carcinoma, FNA had an accuracy rate of 75%. including systematic puncture of the lateroaortic nodes [32, 33]. The accuracy rate for prostatic carcinoma was not evaluated because positive FNA results obviated radical surgery. Carcinoma of the cervix studied by FNA of positive nodes on LAG resulted in an overall accuracy rate of 68% [34]. Further analysis of data showed 77% accuracy in FNA detection of para-aortic adenopathy in this study. Another recent study [35] of Stage liB through IVA carcinoma of cervix examined by LAG, CT. US, and FNA of any positive results, and para-aortic lymphadenectomy confirmed that LAG was the most accurate modality (78.6%) for detecting disease in that area compared with C'F (34.4%) and US (18.5%).

Lymphoma At MDACC, the role of FNA in lymphomatous disease is expanding. The previously reported accuracy rate of 54% [36] is now in the 80% range. In a recent 2-year survey [37], 55 patients with FNA of 64 separate lymph nodes detected by LAG were analyzed. Fifty-four patients had subsequent excisional biopsy or were followed clinically and with radiographs; 39 patients with non-Hodgkins lymphoma had 47 different nodes evaluated by FNA with 78% accuracy; 16 patients with Hodgkin's lymphoma had 17 FNAs with an 86% accuracy rate. The overall accuracy rate of FNA for detection of lymphoma in 64 abnormal nodes was 80%.

Fig. 7. CT-guided FN A biopsy of interaortico-caval lymph node. A second pass of the 22-gauge Chiba needle gave positive cytological diagnosis of metastatic colon carcinoma. Fig. 8. A Lymphoma with residual retrocaval lymphadenopathy (arrow) B The CT-guided transcaval FNA biopsy with a 22-gauge Chiba needle showed lymphoma.

[2, 25] depending on the nature, location, and clinical stage of the type of carcinoma studied, as well as the imaging modality used to detect the metastasis and guide the PLNB. In a recent study on pelvic

Discussion

Metastatic lymphadenopathy from epithelial or glandular carcinomas of the head and neck, respiratory system, and gastrointestinal and genitourinary tract can generally be detected and studied with imagedirected FNA and cytologic microscopic diagnosis very safely and with a high degree of accuracy. If cytologic services are not available, histologic samples from larger coring or cutting needles may be necessary with attendant higher limitations of needle tract selection and complications. Metastatic lymph-

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D.D. Lawrence el al.: Percutaneous Lymph Node Biopsy Fig. 9. Recurrent Hodgkin's disease in the right external iliac

L.N. A Rapid change in the residual [,AG contrast in the high right external iliac lymph node (arrow). This became too fain! to be seen for adequate needle localization by flu~roscop~, alone. B A 19-gaugeSurecut needle was placed on the surface of the node with C'I"guidance. ('. Then a 22-gauge Chiha needle with a gently curved tip was passed in coaxial manner for multiple quadrant FNAs to oblain adequate c~,tological m~terials. "['he 19-gauge needle could be used for subsequent core biopsy, if necessary.

adenopathy from sarcomas, m e l a n o m a s , mesothetiomas, and other tumor transformations with "spindie'" cell characteristics may be difficult to identify cytologically. Again, larger coring needles and histologic diagnosis may be necessary for these lesions. False-negative results in P L N B remain a distinct possibility, and negative results do not always exclude the presence of malignancy. If adequate and accurate attempts give unsatisfactory cytologic or histologic material, then an excisional biopsy should be carried out depending on the clinical indication, eithcr as an exploratory or staging surgical procedure, or as part of a l y m p h a d e n e c t o m y in curative surgery. PL,NB in Hodgkin's l y m p h o m a and the non-Hodgkin's [ymphomas continues to pose a different problem in regard to c o m p l e t e reliance on F N A . Although cytologic diagnosis and subclassification can be established in a high percentage o f cases [38-41] excisional biopsy and histologic evaluation have been the mainstay oforimarv diagnosis in these diseases. Selection of therapy and determination of prognosis depend on accurate classification by histologic characteristics [42]. The diagnosis of H o d g k i n ' s disease is based on the presence of Reed-Sternberg cells in a background of small lymphocytes [43, 44]. l m m u n o p h e notyping is not yet specific for H o d g k i n ' s disease because lymphocyte populations fl'om normal, hyperplastic, or necrotic nodes and granulamotous or viral disorders can cause diagnostic problems [45-47]. Nonetheless, 86% a c c u r a c y was obtained with FNA in this group. In the non-Hodgkin's l y m p h o m a s , for many cases, adequate materials can be obtained by F N A , enabling a diagnosis and subclassification into the modified International Working Formulation for cytological classification. I m m u n o c y t o c h e m i c a l studies of lymphocyte surface markers [481, D N A flow cytometry [49], and cytogenetic [501 and molecular studies [51, 52] are acquiring more importance in subclassification, prognosis, and treatment. These ancillary cytological studies do not depend on histological characteristics and can easily be done on the F N A samples. They improve the accuracy and

D.D. l,awrence et al.: Percutaneous t,ymph Node Biop%v

61

5"~':v:",. (q; ..,;.~

i"

,~ A

Fig. 10. Malignant Bqymphoma, smallcelltypc. A lmmunoperoxidase staining for kappa light chain is positive in the majority of l,vmphoc)tes. Note dark staining granules in the cytoplasm of most cells. B Staining for lambda light chain is positive in less than 109& of cells. These findings together with the cytomorphologic features of the cell population establish the diagnosis. Original magnification x 1.000. {Black and white reproductions from color slides.)

objectivity in the evahtation of non-Hodgkin's lymphoma, especially the malignant B-cell lymphoma, which make up 80% of the lymphomas in the USA {53]. Immunocytochemical peroxidase stains easily and objectively identify and quantitatc the cell popuhttion in these lymphomas (Fig. 10), and also differentiation from reactive lymph nodes can be made [47, 54]. If results are questionable, then excisional biopsy is recommended. However. as ancillary cytoldgical studies gain more importance in the evaluation of non-Hodgkin's lymphoma so will the role of PLNB by FNA.

References I. Charboneau JW, Reading CC. Welch TJ (199111CT and sonographically guided needle biopsy: Current techniques and new innovations. AJR 154:1-10 2. Gothlin JH (1991)) Interventional radiology. Dondelinger RF. Rossi P. Kurdziel JC, Wallace Sleds). Thieme Medica{ Publishers, New York pp. 53-56 3. Biopsy Technology ~1991)1 Radiology: RSNA Index. p 313 4. Parker SH, Hopper KD, Yakes WF, Gibson MD, Ownbey J L, Carter TE (19891 Image-directed percutaneous biopsies with a biopsy gun. Radiology 171:663-669 5. Miller DA, Carrasco CH, Katz RL, Cramer FM, Wallace S. Charans:mgavej C (1986) Fine-needle aspiration biopsy: ['he role of immediate cytologic assessment. AJR 147:155-158

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,

".'~.

~,

.

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6. Goldberg BB. Cole-Beuglet C, Kurtz AB, Rubin CS (1980) Real-time aspiration biopsy transducer. J Clin Ultrasound 8:107-112 7. Otto R, Deyhle P t1980) Guided puncture under reahime sonographic control. Radiology 134:784-785 8. Fornage B, Touche D. Lemarie A. Deshayes JL, Simatos A, Faroux blJ (19841 Real-time ultrasound guidance of fineneedle puncturc-a,;piration of abdominal organs in patients with cancer. Report on 265 cases {in French}. J Radiol 65:533-544 9. ,luul N. Torp-Pederson S, Hohn HH (1984) Uhrasonically guided fine-needle aspiration biopsy of retroperitoneal mass lesions. Br .I Radiol 57:43-46 t0, Livraghi T (1982) A simple no-cost technique for real-time biopsy. J Clin Uhrasound 12:60-62 11. Bruneton JN, Normand F, Balt,-Maestro C, Kerboul P, Santmi N. Thyss A, Schneider M (1987) Lymphomatous superficial lymph nodes: US detection. Radiology, 165:233.-235 12. Baatenburg-de Jong RJ, Rongen RJ. Lameris JS, Harthoorn M. Verwoerd CD, Knegt P (1989) Metastatic neck disease. Palpation vs. ultrasound examination. Arch Otolaryngol Head Neck Surg 115:689-690 t3. Fornage BD, Lorigan JG (1989) Sonographic detection and line-needle aspiration biopsy of nonpalpable recurrent or metastatic melanoma in subcutaneous tissues. J Ultrasound .Med 8:421-424 14. Heckerm;mn R. Seidel K,I (1983) The sonographic appearance and contrast enhancement of puncture needles. J Clin Ultrasound 11:265-268 15. Quam JP, Reading CC, Charboneau JW (19891 Transrectat sonographically guided biopsy of a perirectal lymph node in recurrent rectal carcinoma {letter}. A JR 153:1101 16. Haaga JR, Alfidi RJ (1976) Precise biopsy localization by computed tomography. Radiology 118:603-607 17. Haaga JR (1979) New techniques t\-~r C'F-guided biopsies. AJR 133:633-641 18. Jaques PF. Staab E, Richey W, Photopulo:s G, Swanton M (19781 CT-assisted pelvic and abdominal aspiration biopsies in gynecological malignancy. Radiology 128:651-655 19. Ferrucci JT, Wittenberg J (1978) CT biopsy of abdominal tumors: Aids for lesion localization. Radiology 129:739-744 211. Welch TJ. Sheedy PF I1. Johnson CD, Johnson CM, Stephens DH (1987) CT-guided biopsy: Prospective analysis of 1,0tR'l procedures. Radiology 17 f:493-496 21. [,ulkin RB. Teresi [,M. Hanafee WN t1987) New needle for

62

22. 23.

24. 25.

26. 27. 28. 29.

30. 31. 32. 33. 34. 35.

36. 37. 38. 39.

D.D. Lav, rence et al.: Percutancous Lymph Node Biopsy MR-guided aspiration cytology of the head and neck, ,,\JR 149:380-382 Widder D.I (1988) Localization grid for blR-guided biopsy. (let ter) Radiology 166:58 I van Sonnenberg E, Hajek P, Gylys-Morm V, Varney RA, Baker L. Casola G, Christensen R, Mattrey RF (t988) A wiresheath system for MR-guided biopsy and drainage: Laboratory studies and experience in 10 patients. A JR 151:815-817 Duckwiler GR, Lutkin RB, Hanafee WN (1987) MR-directed needle biopsies. Radiol Clin North AM . . . . . . -.:-8 Chagnon S, Cochand-Priollet B, Gzaell M, .lacquenod P. Roger B, Boccon-Gibod L, Blery M (1989J Pelvic cancers: Staging of 139 cases with lymph0graphy and fine-needle aspiration biopsy. Radiology |73:103-106 Merlin C. Wajsman ZM, Baumgarlner G, Jennings E (1977) The clinical value of lymphangiography: Are the nodes surrounding the obturator nerves visualized? J Uro1177:762-764 Zoretic SN, Wajsman Z, Beckley SA, Pontes JE(1983) Filling of the obturator nodes in pedal tymphography: Fact or fiction? J Urol 129:533-535 Gothlin JH, Hoiem L (1981) Percutaneous fine needle biopsy of radiographically normal lymph nodes in the staging of prostatic carcinoma. Radiology 141:351-354 Wajsman Z. Gamaro M. Park J J, Beckely S, Pontes J E (1982) Transabdontinal fine needle aspiration of retmperitoncal lymph nodes in staging ofgeni~ourim:ry tract cancer {correlation with lymphography and I . ~ p h node dissection findings). J Urol 128:1238-1240 Kidd R, Correa RJ {1984) Fine needle aspiration biopsy of lymphangiographically normal lymph nodes: A negative view. A JR t42:1004-1006 Kidd R, Crane RD, Dail DH {1984) Lymphangiography and fine-needle aspiration biopsy: Ineffective for staging early prostate cancer. AJ R 141 : 1007- I012 Cook F, Lawrence D. Smith J. Gritta E 11965) Testicular carcinoma and lymphangiography. Radiology 84:420-427 Wallace S, Jing BS (1970) Lymphangiographic diagnosis of nodal metastases from tcsticular malignancies. JAMA 213:94-96 Edeiken-Monroe BS, Zornoza J (1982) Carcinoma of the cer',,ix: Percutaneous lymph node aspiration biopsy. A,IR 138:655-657 Heller P, Malfetano J, Bundy B (1989) Clinical-pathological study of carcinoma of cervix: Extended diagnostic evaluation for para-aortic node metastasts (reprintl. GOG study. Philadelphia Zornoza J (1981) Abdomen. In: Zornoza J (ed) Perctmlneous needle biopsy. Williams & Wilkins, Baltimore, pp 128-129 Carrasco CH, Richli WR, Lawrence D, Katz R, Wallace S (1990) Fine-needle as;piration biopsy in lymphoma. Radiol Clin North Am 28:879-883 Pontifex AH. Klimo P ( t 984) Application of aspiration biopsy cytology to lymphomas. Cancer 53:553-556 Qizilbash AH, Etavathil LJ. Chen V. Young JEM, Archibald SD (1985) Aspiration biopsy cytology of lymph nodes m malignant ]ymphomas. Diagn Cytopathol I : 18-22

40. Carter TR, Feldman PS, Innes DJ. Frierson HF 11987) The role of fine needle aspiration in lhe diagnosis of lymphoma (abstract). Acta Cylol 31:651-652 41. Sneige N, Dekmezian RH, Fanning CV. Manning JT, Ordonez NG. Katz RL 119901 Fine-needle aspiration ot inalignam lymphomas: A cytologic and immunocytochemical study. Acta Cytol 34:311-322 42. Metter GE, Nathwani BN, Burke JS, Winberg CI), Mann RB, Barcos M, Kjeldsberg CR. Whitcomb CC, Dixon DO. MiIler TP, et al. (1985) Morphological subclassification of follicular lymphoma: Variability of diagnoses among hematopathologists, a collaborative stud,,, between the repository center and pathology panel fi~r lymphoma clinical studies. J Clin Oncol 3:25-38 43. Kardos TF, Vin~on JH. Behm FG, Frable WJ, O'l)ov~d GJ f 1986) Hodgkin's disease: Diagnosis by fine-needle aspiration biopsy. Analysis of cytologic criteria from a selected series. Am J Clin Pathol 86:286-291 44. Dmitrovsky E. Martin SE, Krudy AG. Chu EW, Ja|'fe EN. Longo Dr,. Young RC !1986) Lymph node aspiration iu the management of Hodgkin's disease. J Clin Oncol 4:306--310 45. Frable WJ. Kardos TF ~'1988) Fine-needle asptratiorl biops?~. Applications in the diagnosis of lyn~phoprolifcrative diseases. Am .I Surg Pathol 12 (suppl I):62-72 46. Uu E, Horning S, Flynn S. Brown S. Warnke R, Sklar J (191'.16) Diagnosis of B-cell lympholna by analysis of immunoglobulin gene rearrangements in biopsy specimens obtained by fine needle aspiration. J Clin Oncol 4:278-283 47. Sncige N (1990~ I)iagnosis of lymphoma and reactive lymphoid hyperplasia by immunocytochemical analysi,, of fine-needle aspiration biopsy. Diagn Cyto[ 6:81-84 48. Martin SE, Zhang HZ. Magyarosy E, Jaffe ES, Hsu SM, Chu EW ( 1984'I Immunologic methods in cytology: Delinitive diagnosis of non-l-iodgkm's lymphomas using immunologic markers for "1- and B-cells, Am J Clin Pathot 82:666-673 49. Klemi PJ. Joensuu H (1988i Comparison of DNA ptoidy in routine fine-needle aspiration biopsy samples and paraffinembedded tissue samples. Anal Quant Cytol Histol 10:195-199 50. Cabanillas F, McLaughlin PC 1988) Ne',', melhodsofinvestigation for the characterization of lymphomas. In: Fuller I. led) Hodgkin's disease and non-Hodgkin'~, I,~nlphomas in adults and children. Raven Press, New York pp 102-114 51. Katz Rt,. Cabanillas F. Sneige N (1986)The value of fine needle aspiration in lymphoma for cytogenetic and molecular studies (abstractL Acta Cytot 30:574 52. Cossman J, Uppenkamp M, Sundeen J. Coupland R. Raffcld M (1988) Molecular genetics and the diagnosis of lymphoma. Arch Pathol Lab Med 112:117.-127 53. Harris NL (1987) Lymphoma 1987: An interim approach to diagnosis and classification. Pathol Annu 22:1-67 54. Levitt S, Cheng L, DuPuis MH, Layfield LJ (I985) Fine needle aspiration diagnosis of malignant lymphoma with confirmation by immunoperoxidase staining. Acta Cytol 29:895-902