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Author: Howard A Shaw, MD, Associate Professor of Obstetrics and Gynecology, University of Connecticut; Chairman/Director, Residency Program Director, Department of Obstetrics and Gynecology, St Francis Hospital and Medical Center

Howard A Shaw is a member of the following medical societies: American College of Forensic Examiners, American College of Obstetricians and Gynecologists, American College of Physician Executives, American Medical Association, American Society for Colposcopy and Cervical Pathology, American Urogynecologic Society, Association of American Medical Colleges, Association of Professors of Gynecology and Obstetrics, Central Association of Obstetricians and Gynecologists, Connecticut State Medical Society, International Urogynaecology Association, and Southern Medical Association

Coauthor(s): Samuel S Lentz, MD, Professor, Gynecologic Surgery and Oncology, Department of Obstetrics and Gynecology, Wake Forest University Health Sciences

Editors: Serdar H Ural, MD, Associate Professor of Obstetrics and Gynecology and Radiology, Director, Division of Maternal Fetal Medicine, Medical Director, Labor and Delivery Suite, Penn State University College of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Frederick B Gaupp, MD, Consulting Staff, Department of Family Practice, Hancock Medical Center; Michel E Rivlin, MD, Professor, Coordinator, Quality Assurance/Quality Improvement, Department of Obstetrics and Gynecology, University of Mississippi School of Medicine

Author and Editor Disclosure

Synonyms and related keywords: gynecologic needle biopsy, fine-needle aspiration, FNA, gynecology, gynecologic malignancies, gynecologic tumors, ovarian neoplasms, ovarian lesions, cervical cancer, metastatic disease, squamous cell carcinoma, SCC, metastatic ovarian adenocarcinoma, transvaginal biopsy, transrectal biopsy

Fine-needle aspiration (FNA) is an important diagnostic tool in gynecology. Its main role is in diagnosis of advanced and recurrent gynecologic malignancies. The technique uses a small-gauge needle to aspirate a lesion for cytologic analysis, sometimes with the aid of radiographic imaging techniques.

History of the Procedure

Ellis and Stuart first described the clinical use of FNA biopsy in the United States in the 1930s. In the 1960s, the procedure was popularized in Europe and Scandinavia as a diagnostic tool for the evaluation of ovarian neoplasms. Although use for this indication has not been considered appropriate in the United States, interest in using FNA for gynecologic tumors was renewed in the 1970s, mainly to evaluate cervical cancer. Since then, the uses of FNA have been refined and expanded in conjunction with modern-day diagnostic imaging to evaluate primary and recurrent gynecologic malignancies.

Problem

Use of FNA has been applied to several clinical situations in gynecologic oncology in which results affect treatment (eg, determination of the extent of disease at diagnosis, recurrence). Successful FNA eliminates the need for more extensive diagnostic procedures, such as laparotomy, and thereby reduces cost and morbidity.

Clinical

A typical clinical case in which FNA provides important information affecting treatment involves advanced cervical cancer, as in the following example case: A 36-year-old patient presented with a clinical stage IIIB squamous cell carcinoma of the cervix, which is typically treated with primary pelvic radiation. Pretreatment CT scan evaluation revealed para-aortic adenopathy, raising concern for metastatic disease. Outpatient CT scan–guided FNA confirmed para-aortic metastasis, and the radiation field was extended to include the para-aortic region.



The major indication for fine-needle aspiration (FNA) relates to diagnosis of either primary malignancy or metastatic disease. In addition, FNA may provide therapeutic benefit in some circumstances. As a diagnostic tool evaluating potentially malignant conditions, FNA is indicated for initial evaluation before treatment and for evaluation for recurrence after therapy.

Initial evaluation before treatment

In general, FNA may be indicated when imaging findings suggest nonfunctional complex ovarian cysts (low risk of malignant disease) and in patients in whom surgery is considered high risk. When performing transvaginal ultrasonographic-guided procedures, using a gynecologic lithotomy stirrups table, which allows for the flexibility in probe position necessary to direct the biopsy needle appropriately, is best.1

FNA can also be used to confirm diagnosis at the primary site (pelvic mass) and to determine the presence of metastasis (eg, lymphadenopathy, parenchymal lesions, ascites, pleural effusion).2

Evaluation for recurrence after therapy

Routine use of FNA for evaluation of a pelvic mass suspected to be ovarian in origin is generally contraindicated, particularly in cystic lesions, secondary to concerns of rupture and potential iatrogenic spread of an isolated malignancy. Also, concerns exist regarding false-negative results, and surgical excision of neoplastic lesions is usually necessary regardless of the histology.

However, certain clinical situations lend themselves to FNA evaluation of an ovarian lesion. These include metastatic lesions, such as breast or gastrointestinal malignancies, as well as rarer lesions such as lymphomas. In addition, for patients who are not deemed to be surgical candidates, such as those with extensive unresectable intra-abdominal malignancy, FNA may be used to establish a specific histologic diagnosis to direct initial chemotherapy treatment, possibly followed by an interval cytoreductive procedure.3

FNA can be used to evaluate possible metastasis either by direct aspiration of a palpable lesion (supraclavicular or groin node) or in conjunction with imaging modalities such as CT scanning.4 As illustrated in the previously mentioned case, findings can influence therapeutic decisions. Pulmonary or hepatic parenchymal lesions are amenable to FNA. Paracentesis in the clinical situation of ascites deserves consideration, although understanding its limitations is important.

In the initial evaluation of ovarian cancer, paracentesis provides little additional information, emphasizing the ultimate need for surgical exploration. In addition, the false-negative rate is high, approaching 50% in the face of advanced disease. Initial use of FNA is generally relegated to providing symptomatic relief of abdominal distention before surgery. Thoracentesis, on the other hand, may be important in establishing the disease stage of ovarian cancer and may be useful in improving pulmonary function preoperatively.

Posttherapy surveillance may incorporate FNA in the evaluation of lymphadenopathy, abdominal or pelvic masses, and abnormal fluid collections, thus eliminating the need for more extensive procedures. This application of FNA has been especially useful in patients with advanced cervical cancer when differentiating radiation effects from recurrent carcinoma is difficult.5 FNA may also prove useful in assessment of benign vaginal lesions such as cysts, leiomyomas, and endometriosis.6 Culdocentesis, which involves inserting a needle into the peritoneal cavity through the posterior cul-de-sac, once had a potential role in the evaluation of pelvic processes such as ectopic pregnancy and pelvic inflammatory disease. With the availability of laparoscopy and sensitive, readily available tests for serum human chorionic gonadotropin (HCG) levels, its use is now limited.



The safety of fine-needle aspiration (FNA) has been established and is related to small needle size (22-25 gauge), imaging guidance, and appreciation of the surrounding anatomical structures. The relevant anatomy depends on the site in question.

In the pelvis, percutaneous, transvaginal, and transrectal biopsies can be performed; thus, associated anatomical structures, particularly vessels and nerves, must be recognized.

Pelvic Anatomic Considerations

FNA ApproachVessels at RiskNerves at Risk
Percutaneous: anterior (groin)External iliac, femoralFemoral
Percutaneous: posteriorInternal iliac: posterior divisionSciatic
TransvaginalInternal iliac: anterior divisionObturator, pudendal
TransrectalInternal iliac: anterior divisionPudendal

Other common sites for FNA related to gynecologic malignancy include the supraclavicular and axillary areas, the retroperitoneum, the liver, and the lungs. CT scanning or ultrasonography is generally necessary for deep-seated biopsies to identify the lesion and important related anatomical structures.



Fine-needle aspiration (FNA) has few contraindications. Coagulopathy requires correction prior to the procedure because one of the rare major complications is hemorrhage. Anatomic restrictions must be observed, and guidance by ultrasound or CT scanning may be helpful. Patient tolerance may prohibit FNA being performed in the office setting using local anesthesia, and general or regional anesthesia may therefore be warranted.

As noted, initial evaluation of ovarian lesions with FNA is generally contraindicated, particularly in the perimenopausal or menopausal patient. Lesions in these age groups should be evaluated surgically. Concerns include diagnostic inaccuracy and rupture of malignant cystic lesions with potential spread. In young, carefully selected patients, FNA may be useful, as stated above.



Lab Studies

Generally, obtaining a coagulation profile is indicated prior to fine-needle aspiration (FNA) procedures, with the exception of a superficial biopsy.

Imaging Studies

Ultrasonography or other diagnostic imaging may provide additional information and may be used in conjunction with the FNA procedure. CT scan-guided FNA is a useful technique for biopsy of lesions that are not otherwise accessible.7 Also, intraoperative ultrasonography may be used to assist in directing FNA.

Diagnostic Procedures

  • FNA is generally defined as use of a 22-gauge (or smaller) needle. The needle may vary in length from a standard 1- to 1.5-inch needle to a 6-inch spinal needle, optimally with a clear hub. A 10-cc Luer-Lok syringe with finger holes is usually sufficient (see Media file 1). However, the pistol grip used with a 20-cc syringe can assist in obtaining adequate aspiration with one hand, while the other hand is used to stabilize the tissue (see Media files 2-3) Also, a needle guide can be used with a long needle to provide direction and prevent trauma to surrounding tissue. This is potentially useful with transvaginal or transrectal biopsies.
  • Specialty needles are sometimes used with image-guided FNA. A Chiba needle, as depicted in Media file 4, is used for deep-seated CT scan-guided biopsies. Images of this procedure are shown in Media files 5-6, in which a retroperitoneal mass is biopsied. With ultrasound-directed biopsies, a needle with enhanced sonographic visualization, such as the SonoVu US aspiration needle shown in Media file 7, can be used. Media file 8 depicts use of this method during a liver FNA biopsy.
  • FNA technique involves placement of the needle into the lesion in question and applying variable suction. A vigorous to-and-fro vertical motion is made to dislodge cells. The material should remain in the clear hub and suction should be released before withdrawing the needle to prevent aspiration into the syringe barrel. The number of passes is dictated by patient tolerance and sufficiency of the specimen. Having a pathologist present to examine the specimen microscopically helps determine adequacy.

    After the needle is withdrawn, it is removed from the syringe; air is then drawn into the syringe, and the needle is replaced. The aspirate is placed on a slide that is then smeared with an opposing slide. An air-dried Diff-Quik–stained slide is prepared to determine the adequacy of sampling, and the remaining slides are fixed with alcohol and subsequently stained with Papanicolaou or hematoxylin-eosin stain. Results are generally available within 24 hours. For superficial biopsies, gentle pressure is typically sufficient to establish hemostasis.

  • Preparations for pelvic biopsy are simple. Patients should empty the bladder unless a full bladder is needed for ultrasound enhancement. If transrectal sampling is to be performed, administering an enema is prudent prior to biopsy.
  • The FNA specimen is processed for cytologic analysis; the interpretation is based on the principles of exfoliative cytology. In specific circumstances, with abundant material, a cell block can be made, which allows immunohistochemical staining and flow cytometry.
  • The pathologist should be aware of the possible diagnosis. If recurrent malignancy is of concern, the primary tumor type should be provided to the pathologist, preferably with previous histologic material available for comparison. In addition, the pathologist should be informed of prior therapy (ie, radiation), the anatomic site of the FNA, and the technique used to obtain it (ie, transvaginal, transrectal). For example, a finding of squamous cells from a transrectal FNA of a pelvic lesion suggestive of recurrent squamous cell carcinoma of the cervix following radiation may be more worrisome than a transvaginal FNA in which contamination of the specimen by vaginal squamous cells may occur. Also, a finding of cells that are not usually present in a particular anatomic location (eg, squamous cells in a lymph node) may provide valuable information for the pathologist.
  • The specimen is first assessed for adequacy. A hypocellular specimen is often inadequate for interpretation. However, this result may be expected from aspiration of a postoperative lymphocyst, so communication with the pathologist is important. Adequate samples are generally interpreted as positive, suspicious, or negative. FNA specimens positive for malignancy are reliable, with a false-positive rate of less than 1%. Suspicious or negative results are more problematic; further assessment, including open biopsy, may be necessary after review with the pathologist.

Histologic Findings

Media file 9 depicts an FNA aspirate that is positive for recurrent squamous cell carcinoma. Note the large pleomorphic cells with a high nuclear/cytoplasmic ratio, "tadpole" shape, and glassy cytoplasm. Large syncytial groups may be seen, with intercellular bridges and associated keratin pearls. Media file 10 shows an FNA aspirate positive for metastatic ovarian adenocarcinoma. Here, cellular adherence is seen with a 3-dimensional configuration and high nuclear/cytoplasmic ratio. Pseudoglandular formation may also be observed.



Complications of fine-needle aspiration (FNA) are rare, with the incidence of major complications reportedly well below 1% and generally in the range of 0.05%. A review of the hazards associated with FNA in general reported a mortality rate of approximately .006%, or 1 death per 15,000 procedures.8 The most common cause of death was hemorrhage. Bleeding from CT scan-guided FNA of retroperitoneal adenopathy is reported as occurring in less than 1% of cases, despite the proximity to great vessels.7 Data specific for gynecologic malignancy indicate an overall complication rate of less than 1%.2 Another concern relates to needle-tract seeding of malignant cells. This risk is extremely low, with reported incidence of 0.009%.9



The positive predictive value of fine-needle aspiration (FNA) approaches 100%, with an extremely low false-positive rate (<1%). The false-negative rate is variable but approaches approximately 30%, with a negative predictive value of 50-75%. The specificity of the test is essentially 100%, while its sensitivity is about 65%. The overall accuracy of FNA in gynecologic malignancies is about 90%.10

Accuracy is affected by the specific location of the lesion and associated degree of hypocellularity. Deep lesions requiring imaging guidance reportedly have a lower rate of hypocellularity than superficial lesions. In addition, the accuracy of FNA in a field of prior radiation is reduced secondary to fibrosis and associated hypocellularity and to difficulty in distinguishing malignancy from radiation effect cytologically. Generally, negative FNA results warrant consideration of either a true-cut or open surgical biopsy, which increases the potential for morbidity and mortality.



Media file 1:  Aspiration needle and syringe.
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Media type:  Photo

Media file 2:  Pistol grip handle and syringe.
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Media file 3:  Pistol grip handle prepared for aspiration.
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Media file 4:  Chiba needle.
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Media file 5:  CT scan-guided fine-needle aspiration using Chiba needle.
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Media type:  CT

Media file 6:  Chiba needle penetrating a retroperitoneal lesion.
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Media type:  CT

Media file 7:  SonoVu US aspiration needle.
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Media type:  Photo

Media file 8:  Ultrasound-guided fine-needle aspiration of the liver using a SonoVu US aspiration needle.
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Media type:  Image

Media file 9:  Histopathology - Recurrent squamous cell carcinoma of the cervix.
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Media type:  Photo

Media file 10:  Histopathology - Recurrent ovarian carcinoma.
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Media type:  Photo



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Gynecologic Needle Biopsy excerpt

Article Last Updated: Jul 22, 2008