August 2008
PAP/NGC Programs Review

Susan D. Rollins, MD

The term “interventional cytopathologist” was coined in 1988 by Heinz Grohs. Unlike the traditional cytopathologist, the interventional cytopathologist doesn’t wait passively for biopsy samples to arrive in the lab. Instead, he or she is involved in all aspects of the fine-needle aspiration biopsy process, from patient history and physical examination to biopsy acquisition and final interpretation.

Until recently, the interventional cytopathologist was limited to performing FNA biopsies on palpable masses. Nonpalpable lesions were biopsied predominantly by radiologists under imaging guidance. Today, a new horizon for cytopathologists is emerging: the ability to perform ultrasound-guided FNA biopsies on nonpalpable lesions. This article describes our experience performing more than 10,000 ultrasound-guided FNA biopsies during the past 12 years.

The Outpatient Cytopathology Center, or OCC, established in 1991, is a freestanding fine-needle aspiration biopsy clinic in Johnson City, Tenn. Our laboratory is not affiliated with any of the area hospitals. Patients are referred to the OCC by primary care physicians, surgeons, obstetrician/ gynecologists, endocrinologists, and others. Patients typically have palpable masses or lesions documented previously on an imaging study. Initially, we perform a clinical assessment; then, if appropriate, we proceed with an FNA biopsy and interpretation.

We have been performing our own in-house ultrasound-guided FNAs since 1996. Before that, patients requiring ultrasound guidance were referred to the radiology department at local hospitals. Consequently, OCC cytopathologists lost direct control of the patient and were limited to offering immediate interpretation of aspiration biopsy samples obtained by the radiologist in the hospital. Circumstances changed in 1996, leading the OCC to offer in-house ultrasound-guided biopsies.

Learning to do ultrasound-guided aspirates opened the door to an incredible opportunity. Being able to perform ultrasound-guided FNAs in the clinic without having to refer and schedule the patient in the radiology department was a turning point for the practice. It was a convenience for patients and better for scheduling but, more important, the quality of aspiration biopsies performed at the OCC improved our ability to target specific areas of masses.

Over the years, we have expanded the use of ultrasound, the capabilities of which we have found to be indispensable to our practice. About 75 percent of all aspirations at the OCC are performed with ultrasound guidance, and there is an ultrasound machine in all examination rooms. Ultrasound can be used as an adjunct tool in several ways: visualizing needle placement in nonpalpable masses, determining depth and actual size of palpable masses, looking for solid areas within cystic masses, targeting areas of suspicious echotexture or calcifications, or avoiding structures such as implants or large vessels. However, ultrasound is never used in our practice as a diagnostic procedure. It is used only to guide FNA biopsy of a known lesion.

The cytopathologist takes a limited medical history and performs a focused physical examination on all patients referred to the OCC. Clinic notes and pertinent radiographic, surgical pathology, and laboratory study findings are reviewed. When needed, ultrasound, mammographic, and other films are reviewed also. This allows for a deeper understanding of the patient’s clinical picture and can give important clues for arriving at a correct diagnosis. Often, important information not covered by routine questions or specimen requisition slips is learned while talking to the patient. For example, the patient may spontaneously mention that there is a family history of a particular medical condition. On one occasion, while doing a soft tissue biopsy, the patient told me that he had von Recklinghausen’s disease (and wondered if it was pertinent!). Patients don’t always fill out completely the forms requesting medical history, and they do not always tell the referring clinician all history that may be significant for a particular lesion. The ability to talk with the patient and direct the questioning is of great benefit to the interventional cytopathologist. The pertinent information gleaned from the history and physical examination is documented in the final cytology report.

Patients are referred to our clinic with either palpable masses or nonpalpable masses found on imaging studies (such as ultrasound, CT, and MRI). For palpable masses, ultrasound may or may not be used, depending on circumstances to be discussed later. For nonpalpable masses previously seen on ultrasound, the cytopathologist examines the area of interest and correlates the ultrasound findings with the description of the mass (size, shape, echogenicity) in the prior report. The ultrasound is used to confirm the findings and guide the biopsy. For nonpalpable masses seen on imaging studies other than ultrasound, we attempt to identify the lesion on ultrasound and correlate the findings. If successful, we proceed with the ultrasound-guided biopsy, if clinically appropriate.

After collecting all of the clinical data, the cytopathologist may decide that an aspiration biopsy is not needed or may not be the procedure of choice. At the OCC, about seven percent of patients referred for a biopsy ultimately do not have a biopsy performed. A report is generated for the referring clinician explaining why the biopsy was not performed and providing recommendations for alternative medical followup, imaging studies, or referral for surgery.

We use a small B & W Digital Medison Ultrasound. The unit has provided satisfactory resolution of superficial tissues. A variety of manufacturers offer many other similar units.

Two issues are of particular importance regarding the ultrasound transducer head. Our transducer is variable frequency with a very small head size, measuring only 4.5 ∞ 1.5 cm. We have learned that having a very small head is helpful when performing aspiration biopsies of small organs and masses in tight spaces, such as thyroid or head and neck lymph nodes. By trial and error, we also found that the transducer head may be adversely affected by ethyl chloride. At the OCC, the skin is cleaned with alcohol and then sprayed with ethyl chloride for cutaneous analgesia. Unfortunately, we discovered that the ethyl chloride can etch the plastic on the transducer head and ruin it. Thus, if ethyl chloride is used such that the chemical may have contact with the transducer head, it is essential to determine before purchase whether the transducer head material is susceptible to ethyl chloride damage.

Special “echogenic” needles are marketed for ultrasound-guided biopsy. We have found these to be unnecessary. We use the same needles for ultrasound-guided FNAs as for the regular biopsies. We have found no need to purchase needles with special reflective properties. We also use a free-hand technique for guiding the needle and do not use a special needle guide that can be purchased with ultrasound units. When the needle is placed skillfully in a mass and the needle is in line with the ultrasound beam, the needle is easily seen.

FNA biopsy is a manual technique that requires training and practice. Ultrasound is no different. The ultrasound guidance is a technical skill that must be learned and practiced. I have the good fortune to be married to a radiologist who provided hands-on training and coaching during my apprentice years. Partners at the OCC have been trained in this manner also.

Certain essential skills, as well as tips and tricks, can improve results. We use a free-hand technique rather than a needle guide. The needle is inserted adjacent to the narrow end of the transducer, rather than the side, so that the entire needle tract can be visualized. The mass is placed so that it lies at the edge of the scanning field, rather than in the middle, thus decreasing the distance the needle must traverse before entering the target. Once the needle is correctly placed, a 10-mL syringe and Cameco syringe holder is attached and the aspiration biopsy is performed. For some masses, particularly in the thyroid gland, a needle-only technique may be used.

Choice of needle size depends on what is being aspirated. In general, we use a 27-gauge ∞ 1¼ needle for thyroid masses and a 25-gauge needle for all other locations. If thick viscous fluid needs to be aspirated and the lesion is not very vascular, a 22-gauge or 23-gauge needle may be needed.

Ultrasound provides visual guidance for biopsying selected masses. Also, correlating the ultrasound appearance of the area sampled with the cytologic features of the aspirated cells gives a distinct advantage in obtaining diagnostic material and providing a meaningful interpretation. Ultrasound is used in a variety of settings in our practice.

A mass may have a heterogenous appearance on ultrasound. With ultrasound guidance, specific areas with differing echogenicity can be sampled. Furthermore, ultrasound allows targeted sampling of solid areas in cystic/solid ­masses.

Visualizing a palpable mass with ultrasound can give information that is not readily apparent by palpation alone. Masses may lie deeper than they feel, or the palpated area may be only a small portion of the larger mass. Ultrasound may also reveal significant nearby masses that are not appreciated on physical examination. This extra information yielded by ultrasound may be indispensable in making a diagnosis. Occasionally, large masses are necrotic, and ultrasound helps guide and obtain viable cells from the edge of the mass for diagnosis.

On occasion, we will biopsy a palpable mass without ultrasound and diagnostic tissue is not obtained, or the material aspirated does not correlate with our clinical impression. When the mass is then visualized and biopsied with ultrasound, the previously nondiagnostic aspiration usually becomes diagnostic. For example, a patient may be referred for aspiration biopsy of a palpable “lymph node.” If the cytopathologist is thinking that the aspirated specimen is from a lymph node but sees other cells, such as oncocytes, he or she may become confused and think the mass is a metastatic tumor. However, if the aspirating physician can look at the mass with ultrasound and determine that the lesion aspirated actually is located in the parotid gland, the diagnosis of a Warthin’s tumor becomes easy.

In the thyroid gland, calcifications can be seen with ultrasound, and certain patterns are more suspicious for malignancy than others. Ultrasound allows specific targeting of suspicious calcifications. Such calcifications may not be associated with the largest mass and can thus be missed if doing a biopsy by palpation alone. Ultrasound features of thyroid lesions suggestive of malignancy include small intranodular punctate hyperechoic calcifications, lesions with irregular or microlobulated margins, and marked hypoechogenicity. In a multinodular thyroid gland, generally we will aspirate the dominant mass in each lobe, and if there are smaller masses with a suspicious appearance or different echotexture pattern, we can sample these as well. Not infrequently, we have found nondominant masses in the thyroid to harbor carcinoma.

Ultrasound can be used to look for additional pathology after the target lesion has been aspirated and an immediate interpretation of the smear performed. Examples include looking for a thyroid primary if a cervical lymph node shows metastatic papillary carcinoma and looking for axillary metastasis if breast carcinoma is found.

Masses within the thyroid, salivary glands, breast, lymph nodes, and soft tissue are usually easily visualized with ultrasound. Deep organs are not biopsied at the OCC because our ultrasound equipment is not designed for that.

Since ultrasound has expanded the expertise of our FNA practice, we have found the opportunity to use cells obtained by FNA for various ancillary test procedures. Flow cytometry is helpful in diagnosing non-Hodgkin lymphomas. Molecular tests, such as FISH, Southern blot analysis, and polymerase chain reaction, can sometimes help classify lymphomas. Sensitive thyroglobulin assays can help detect the presence of metastatic papillary thyroid carcinoma in lymph nodes. Immunocytochemistry for estrogen and progesterone receptors on smear preparations is available. Analysis for the BRAF mutation to help differentiate papillary thyroid carcinoma from hyperplasia is also possible. The list of ancillary tests that will use FNA as the specimen source will continue to increase.

References

1. American Association of Clinical Endocrinologists Medical Guidelines. Endocr Pract. 2006;12:1, 63–102.
2. Bentz JS. Molecular testing in cytopathology. Where are we, where do we go from here? CAP TODAY. February 2006; pp. 56–61.
3. Grohs HK. The interventional cytopathologist. A new clinician/pathologist hybrid. Am J Clin Pathol. 1988; 90: 351– 354.
4. Linsk JA. Aspiration cytology in Sweden: The Karolinska Group. Diagn Cytopathol. 1985;1:332–335.
5. Sigstad E, et al. The usefulness of detecting thyroglobulin in fine needle aspirates from patients with neck lesions using a sensitive thyroglobulin assay. Diagn Cytopathol. 2007;35:761–767.

Related Links

• For all of us, a place to ponder cytopathology’s future