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Keywords:

  • fine-needle aspiration biopsy;
  • palpable mass;
  • cytopathology;
  • community hospital

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

BACKGROUND

Fine-needle aspiration biopsy (FNAB) is a reliable, rapid, minimally invasive alternative to surgical biopsy when it is performed by physician specialists for the diagnosis of palpable masses. FNAB may be under-utilized in community hospitals in the U.S. because physicians without specialty training commonly provide the service, resulting in less reliable results.

METHODS

Records were reviewed retrospectively from 730 consecutive FNAB cases that were performed and interpreted by expert cytopathologists practicing in an outpatient community hospital setting between 2000 and 2004. Data concerning patient demographics, referring physician specialty type, body sites, diagnoses, specimen adequacy, accuracy of diagnosis, and follow-up were examined and analyzed.

RESULTS

FNAB was diagnostic in 93% of patients and was 95% accurate. There were 5 false-negative results and no false-positive results for the diagnosis of malignancy. The overall sensitivity of FNAB was 93%, and the specificity was 100%. Using either histology or clinical follow-up, the positive predictive value was 100%, and the negative predictive value was 99%.

CONCLUSIONS

Highly reliable results can be obtained when patients are referred to specialty-trained cytopathologists practicing in the community for FNAB of palpable mass lesions. Clinicians are encouraged to seek out and support specialized FNAB services in their own communities. Cancer 2006. © 2006 American Cancer Society.

Fine-needle aspiration biopsy (FNAB) is a rapid, accurate, minimally invasive, and cost-effective method for the diagnosis of palpable mass lesions.1–4 In Europe and Asia and in academic centers within the U.S., FNAB often is the first procedure of choice for the diagnosis of palpation-guided, superficial mass lesions. In these centers, FNAB is performed by trained physician specialists, either cytopathologists or clinicians working closely with the cytopathology team, resulting in highly accurate diagnoses.1–4 When untrained personnel perform FNAB, the results may not be reliable.1–4

In 2000, we established a community hospital-based FNAB clinic with the objective of providing expert FNAB services for clinicians practicing in the community. In this article, we report the reliability of FNAB for the diagnosis of palpable mass lesions on different body sites in 730 consecutive cases over a 4-year period.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

The FNAB Clinic Setting

The Fine-Needle Aspiration Biopsy Clinic is a specialty outpatient service offered by our 217-bed community hospital and is housed within the Pathology Department. We accept patients the same day that they present to their physician to minimize patient apprehension and to expedite patient care. The patient is registered as a hospital outpatient, the FNAB procedure is explained, and informed written consent is obtained. The patient completes a history form with an emphasis on prior or current malignancy. A patient chart is initiated and maintained in the Cytology Section of the Pathology Department.

Procedure

After a limited physical examination, the FNAB procedure was performed in the usual manner by a single cytopathologist (B.D.F.). Initially, from 1 to 3 aspirates were taken using needles that ranged from 25 gauge to 23 gauge. Conventional smears were prepared from each aspirate. Representative smears were stained by rapid Romanovsky-type stain and were evaluated microscopically for adequacy and preliminary diagnosis.

If sufficient diagnostic material was obtained, then the procedure was terminated, and the patient was discharged. If the immediate microscopic evaluation demonstrated a lesion for which ancillary studies were needed, then additional material was obtained immediately to fulfill those specimen requirements (such as immunostains, flow cytometry, and microbiologic cultures). If the immediate evaluation did not show diagnostic material, then repeat aspirates were performed until adequate material was obtained or until it was determined that the nature of the lesion was not going to yield diagnostic material. Occasionally, after performing the physical examination, the targeted area either could not be palpated or clinically was insignificant. In such a scenario, the cytopathologist, with the consent of the patient and referring clinician, sometimes elected not to perform the FNAB. In these instances, the patient was asked to return for periodic clinical follow-up with the referring clinician.

Cytopathologist-Clinician Interactions

For urgent cases, the clinician was notified directly after the procedure. All routine examinations were reported to the clinician within 24 hours. The cytopathologist also functioned as a consultant for the referring clinician, recommending additional studies or follow-up as needed. The case was sometimes discussed by telephone with the clinician and/or through clinically helpful written recommendations that were included in the FNAB report.

Data Analysis

FNAB data abstraction and entry

After approval was obtained from the hospital Institutional Review Board Committee, all FNAB charts from the study period (November 1, 2000 to October 31, 2004) were reviewed retrospectively, and the relevant information from each patient was abstracted and recorded in a computerized form (Access; MicroSoft Corp., Redmond, WA). The abstracted information included referring clinician type, patient age, gender, FNAB site (breast, lymph node, soft tissue, thyroid, and salivary gland), relevant history and clinical findings, FNAB result, and whether the FNAB diagnosis represented new or recurrent disease. (Note that “soft tissue” refers to all masses that are not identified as lymph node, thyroid gland, salivary gland, or breast.)

Categorization of the FNAB results

For data analysis, first, all aspirates were deemed either diagnostic or nondiagnostic (Fig. 1). An aspirate was considered diagnostic if it provided a concordant clinical-cytologic diagnosis of the lesion type. In some cases, the smear alone provided sufficient information to make the diagnosis; in other cases, the cellular material alone was nonspecific, but the cytopathologist was able to reach a concordant clinical-cytologic diagnosis by taking into account the combined cytologic and clinical findings. An example of the latter would be an aspirate that showed fibroadipose tissue in a patient with the clinical impression of lipoma. All diagnostic specimens were classified further as either “benign” or “malignant.”

thumbnail image

Figure 1. This flow chart shows anticipated patient management for patients who undergo fine-needle aspiration biopsy (FNAB). aSurgery is included as part of the therapeutic regime only; the FNAB already has established the diagnosis preoperatively. Such benign lesions generally are removed because of expected growth or the potential for malignant transformation. bThis category excludes congenital/developmental cysts. cSurgery is included as part of the therapeutic regime only; FNAB already has established the diagnosis preoperatively. dAdditional studies would be anticipated for diagnosis, most commonly additional tissue sampling (repeat FNAB, core biopsy, or open surgical biopsy).

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All nondiagnostic results were classified as either “inconclusive” or “inadequate.” Results were categorized as “inconclusive” when the smear showed adequate cellular material but the material was not diagnostic. (These were “atypical” and “suspicious” results in which the difficulty in achieving a diagnosis usually was because of overlapping cytologic features between benign and low-grade malignant entities). Results were categorized as “inadequate” when the cellular material was insufficient for evaluation. Based on the FNAB results, the diagnoses within each category (benign, malignant, inconclusive, and inadequate) were divided into 1 of the following anticipated patient management scenarios: surgery anticipated, no surgery anticipated, or additional studies anticipated.

Follow-up

Using follow-up data, the anticipated clinical management for each patient was compared with the actual clinical management and recorded in the data base. Follow-up information was sought by reviewing all of the subsequent information in each patient's electronic medical record from our institution and contacting referring clinicians by telephone or mail. In addition, a list was submitted to the California Cancer Registry in May 2005 of all patients in the study. The California Cancer Registry is California's statewide population-based cancer surveillance system and collects information about all cancers diagnosed in California, except nonmelanoma skin cancers and carcinoma-in-situ of the cervix. The latter step was taken to assure that there were no unknown false-negative FNAB results for the malignant category. (According to the California Cancer Registry, the completeness of the data for 2004 could not be guaranteed.) Patients were considered lost to follow-up when additional evaluation subsequent to the FNAB would be expected but no such information could be found.

Cytologic-histologic correlation was recorded for patients who underwent documented surgical excision of the index mass subsequent to FNAB, and the reasons for any discrepant results were examined. The FNAB slides from all patients with discrepant results were reviewed by 2 of the authors and were determined to be major (missed malignancy) or minor (missed benign process) and due to either sampling error or interpretive error.

Analysis of the accuracy of FNAB

An accurate FNAB result was defined as one that correctly identified the mass as malignant or benign and also provided the correct diagnostic subtype. For this calculation, all diagnostic FNAB results from patients who underwent a subsequent surgical biopsy were compared for diagnostic concordance using the histology results as the “gold standard.” In addition, the FNAB results were analyzed for the ability to recognize malignancy by using the statistical parameters of “absolute” sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), as defined by Trott.5 “Absolute” sensitivity5 is defined as the number of unequivocally diagnosed cancers expressed as a proportion of the overall number of cancers aspirated, that is, the ability to identify malignancy correctly by FNAB when cancer is present. Specificity5 is defined as the number of benign lesions diagnosed correctly expressed as a proportion of the overall number of benign lesions aspirated, that is, the ability to render a benign diagnosis when malignancy is absent. The PPV5 indicates the degree of confidence with which a clinician can regard a positive FNAB result and is calculated as the number of true malignancies divided by all lesions diagnosed as malignant by FNAB. For example, a PPV of 1.0 (100%) means that every time a malignant diagnosis is rendered by FNAB, the patient has malignant disease. The NPV5 is defined as the number of true-negative results expressed as a proportion of all negative results, including those that are diagnosed subsequently as malignant.5 It indicates the degree of confidence with which a clinician can regard a negative FNAB result. For example, an NPV of 0.99 means that 99% of the time, the clinician can be certain that a negative FNAB diagnosis means that the patient's mass is not cancerous.

Because histologic diagnoses generally are accepted as the “gold standard” with which FNAB is compared, the sensitivity, specificity, and PPV for detecting malignancy were calculated by using the results from patients who had both a diagnostic FNAB result and a histologic tissue diagnosis. However, the NPV was calculated by using all benign FNAB results whether or not subsequent histology tissue was taken. This is because, for many benign lesions, a histologic tissue diagnosis is not expected subsequent to FNAB; here, the FNAB, in conjunction with conservative clinical follow-up, commonly functions as the definitive diagnostic endpoint. Excluding such results would falsely decrease the NPV, because it would be biased toward patients who underwent surgery based on a clinical suspicion of malignancy, despite the negative FNAB results.6 Nondiagnostic FNAB categories were omitted from the analysis.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

Physician Referrals

The referrals came from 88 health care providers practicing in the local community: 40% of referrals were from primary care practitioners, 27% of referrals were from otolaryngologists, 11% of referrals were from oncologists, 10% of referrals were from general surgeons, 6% of referrals were from endocrinologists, and 5% of referrals were from gynecologists. Self-referral and radiologist referrals comprised the remaining patients (1%).

Patient Study Group

In total, 730 patients were referred for FNAB during the study period. Sixty-one patients were excluded because of the lack of a suitable palpable lesion for aspiration. The remaining 669 patients formed the study group. In total, 730 aspirates were obtained from these patients; 38 patients had >1 site aspirated at the initial presentation, and 16 patients were referred back to the clinic for a follow-up aspirate or an aspirate of a different site. The ages of patients ranged from 2 years to 92 years (average age, 47 years). The majority of the FNAB procedures were performed on female patients (497 females; 74% of the study group).

Distribution of FNAB Diagnoses According to Body Site

The distribution of FNAB results by site (Table 1) indicates that the most common site aspirated was breast (187 cases), followed by lymph node (174 cases), soft tissue (168 cases), thyroid (145 cases), and salivary gland (56 cases). The majority of aspirates were benign for each individual body site (161 of 187 breast aspirates, 105 of 174 lymph node aspirates, 117 of 168 soft tissue aspirates, 119 of 145 thyroid aspirates, and 51 of 56 salivary gland aspirates). The most common benign lesions were goiterous thyroid nodule (19%) and reactive lymph nodes (19%) followed by fibrocystic breast changes (16%), soft tissue lipoma (10%), and pleomorphic adenoma of the salivary gland (3%). With the exception of pleomorphic adenoma (which requires surgery), conservative observation of these other common benign conditions is accepted patient management. Carcinoma was the most common malignant lesion for each site, with 100% of breast malignancies, 67% of lymph node malignancies, 61% of soft tissue malignancies, and 100% of thyroid and salivary gland malignancies representing carcinomas.

Table 1. Fine-Needle Aspiration Biopsy Results by Site for All Lesions
BreastNo.Lymph NodeNo.Soft TissueNo.ThyroidNo.Salavary GlandNo.
  1. FA indicates fibroadenoma; EIC, epidermal inclusion cyst; diff, differentiated; HL, Hodgkin lymphoma.

Benign:n = 553 (76%)         
 Fibrocystic90Reactive hyperplasia105Lipoma53Goiterous nodule106Pleomorphic adenoma15
 FA27  Inflammatory22Hashimoto thyroiditis10Hyperplasia/Sialodenitis13
 Gynecomastia13  EIC14Thyroglossal duct cyst2Sialoadenitis10
 Lipoma10  Tumor-like lesion8Parathyroid cyst1Warthin tumor7
 Inflammatory10  Cyst5  Cyst2
 Fat necrosis4  Nerve sheath tumor4  Duct ectasia1
 EIC4  Fat necrosis3  Lipoma1
 Other3  Axillary breast2  Traumatic neuroma1
    Accessory tragus1  Dermoid cyst1
    Dermoid cyst1    
    Hernia1    
    Radiation changes1    
    Rannula1    
    Granular cell tumor1    
Malignant:n = 122 (17%)         
 Carcinoma21Metastatic carcinoma37Metastatic carcinoma20Papillary carcinoma9Carcinoma3
  Lymphoma17Lymphoma6Carcinoma, well diff1  
  Metastatic melanoma1Sarcoma4    
    Metastatic melanoma3    
Inconclusive:n = 38 (5%)         
 Fibroepithelial lesion1Atypical lymphoid proliferation5Cystic lesion2Follicular lesion14Neoplasm, benign or low-grade malignant1
 Proliferative breast lesion, favor benign2Hemorrhagic cystic lesion1Tumor-like lesion2  Neoplasm, favor pleomorphic adenoma1
 Proliferative breast lesion1Suspicious for lymphoma3Suspicious for HL1    
 Suspicious for malignancy1Suspicious for carcinoma1Atypical lipoma1    
    Spindle cell lesion1    
Inadequate:n = 17 (2%)0 4 11 2 0

Nondiagnostic Results

Seven percent of FNAB results were “nondiagnostic.” Of these, 5% were “inconclusive,” and 2% were “inadequate.”

Distribution of Malignant FNAB Diagnoses: New (First-Time) and Recurrent Disease

The aspirates from malignant lesions were separated according to whether they represented new disease or recurrent disease (Table 2). FNAB established a first-time diagnosis of malignancy in 66% of lesions, and recurrence was assessed in 34% of lesions. Metastatic malignancy was the most commonly diagnosed malignancy, representing 50% of all malignant diagnoses.

Table 2. Malignant Fine-Needle Aspiration Biopsy Results for New or Recurrent Disease (n = 122)
FNAB Results (No. of Cases)No. with New Disease (%)No. with Recurrent Disease (%)
  1. FNAB indicates fine-needle aspiration biopsy.

Breast  
 Carcinoma (21)20 (95)1 (5)
Lymph node  
 Metastatic carcinoma (37)25 (45)12 (22)
 Lymphoma (17)8 (15)9 (16)
 Metastatic melanoma (1)0 (0)1 (2)
Soft tissue  
 Metastatic carcinoma (20)9 (27)11 (33)
 Lymphoma (6)2 (6)4 (12)
 Sarcoma (4)3 (9)1 (3)
 Metastatic melanoma (3)2 (6)1 (3)
Thyroid  
 Carcinoma (10)10 (100)0 (0)
Salivary gland  
 Carcinoma (3)2 (67)1 (33)
Total all sites/all types (122)81 (66)41 (34)

Follow-Up

Follow-up ranged from 7 months to 55 months (mean, 27 months; median, 31 months). For all sites combined, the clinicians followed the FNAB recommendations 88% of the time (range, 75-94%, depending on the site). In total, 140 patients had histologic confirmation of their FNAB results. These results are summarized in Table 3. Ninety-nine of 140 patients had FNAB results indicating that surgery would be appropriate, and an additional 41 patients underwent surgery because of clinical considerations despite FNAB results that indicated no need for surgery. Twenty-eight patients who had “nondiagnostic” FNAB results underwent a surgical procedure. In 46 patients, either no surgery was done despite an FNAB indication for surgery or no information was available. In 3 patients, a repeat FNAB was done because of a previous nondiagnostic FNAB result; in each patient, the repeat FNAB result was benign, and the patient was followed conservatively.

Table 3. Summary of 140 Fine-Needle Aspiration Biopsy Results with Histology Diagnoses
FNAB Results (No. of Cases)Histology DiagnosisConcordant?
  • FNAB indicates fine-needle aspiration biopsy.

  • *

    Extranodal subcutaneous soft tissue.

  • Deep soft tissue.

Breast (n = 31)  
Benign (n = 11)  
 Abscess (1)Abscess (1)Yes
 Fibrocystic (1)Fibrocystic (1)Yes
 Fat necrosis (1)Fat necrosis (1)Yes
 Fibroadenoma (1)Fibroadenoma (1)Yes
 Fibroadenoma (1)Adenocarcinoma (1)No
 Fibrosis (1)Fibrosis (1)Yes
 Granulomatous mastitis (1)Granulomatous mastitis (1)Yes
 Gynecomastia (2)Gynecomastia (2)Yes
 Muscle (1)Gynecomastia (1)No
 Silicone granulomatosis (1)Silicone granulomatosis (1)Yes
Malignant (n= 16)  
 Adenocarcinoma (16)Adenocarcinoma (16)Yes
Inconclusive (n = 4)  
 Fibroepithelial lesion (1)Fibroadenoma (1) 
 Proliferative breast lesion, favor benign (1)Adenosis tumor (1) 
 Proliferative breast lesion (1)Ductal carcinoma in situ (1) 
 Suspicious for carcinoma (1)Adenocarcinoma (1) 
Lymph node (n= 35)  
 Benign (n = 3)  
  Reactive lymphadenopathy (1)Reactive lymphadenopathy (1)Yes
  Reactive lymphadenopathy (2)Malignant lymphoma (2)No
 Malignant (n = 24)  
  Malignant lymphoma (5)Malignant lymphoma (5)Yes
  Metastatic carcinoma (19)Metastatic carcinoma (19)Yes
 Inconclusive (n = 8)  
 Atypical lymphoid proliferation (3)Malignant lymphoma (3) 
  Hemorrhagic cystic lesion (1)Intranodal hemangioma (1) 
  Suspicious for lymphoma (3)Malignant lymphoma (3) 
  Suspicious for carcinoma (1)Metastatic squamous cell carcinoma (1) 
Salivary gland (n= 16)  
 Benign (n = 12)  
  Duct ectasia (1)Chronic sialoadenitis (1)Yes
  Pleomorphic adenoma (10)Pleomorphic adenoma (10)Yes
  Warthin tumor (1)Warthin tumor (1)Yes
 Malignant (n = 2)  
  Carcinoma (2)Adenoid cystic carcinoma (1), squamous cell carcinoma (1)Yes
 Inconclusive (n = 2)  
  Neoplasm, benign or low-grade malignant (1)Salivary gland carcinoma, not otherwise specified (1) 
  Neoplasm, favor pleomorphic adenoma (1)Pleomorphic adenoma (1) 
Soft tissue (n = 29)  
 Benign (n = 12)  
  Benign axillary breast tissue (1)Benign axillary breast tissue(1)Yes
  Cystic lesion suggestive of inguinal hydrocoele (1)Inguinal hernia(1)Yes
  Epidermal inclusion cyst (1)Epidermal inclusion cyst (1)Yes
  Lipoma (3)Lipoma (3)Yes
  Granular cell tumor (1)Granular cell tumor (1)Yes
  Nerve sheath tumor (2)Nerve sheath tumor (2)Yes
  Nodular fascitis (1)Nodular fascitis (1)Yes
  Benign, favor ranula (1)Ranula (1)Yes
  Tumor-like lesion, favor nodular fascitis or dermatofibroma (1)Nodular fascitis (1)Yes
 Malignant (n = 13)  
  Malignant lymphoma (2)*Malignant lymphoma (2)Yes
  Metastatic melanoma (1)*Metastatic melanoma (1)Yes
  Malignant melanoma or clear cell sarcoma (1)Metastatic melanoma (1)Yes
  Metastatic carcinoma (7)*Metastatic carcinoma (7)Yes
  Sarcoma (2)*Malignant hemangioendothelioma (1), malignant fibrous histiocytoma (1)Yes
 Inconclusive (n = 4)  
  Suspicious or Hodgkin lymphoma (1)Inflammatory proliferation (1) 
  Atypical lipoma (1)Lipoma (1) 
  Cystic lesion (1)Branchial cleft cyst (1) 
  Spindle cell lesion (1)Intramuscular lipoma (1) 
Thyroid (n = 29)  
 Benign (n = 9)  
  Thyroglossal duct cyst (2)Thyroglassal duct cyst (2)Yes
  Goiterous nodule (5)Goiterous nodule (5)Yes
  Goiterous nodule (2)Papillary carcinoma (2)No
 Malignant (n = 10)  
  Papillary carcinoma (9)Papillary carcinoma (9)Yes
  Carcinoma, well differentiated (1)Follicular variant of a papillary carcinoma (1)Yes
 Inconclusive (n = 10)  
  Follicular lesion (10)Goiter (4), follicular adenoma (2), papillary carcinoma (4) 

Five hundred forty-one patients (74%) were spared surgery as a result of the FNAB. Of these, 90% of patients had benign lesions and received conservative clinical follow-up, and 10% of patients had a diagnosis of a medically managed malignancy. An additional 99 patients (13%) required surgery, but they were spared an additional diagnostic procedure (core biopsy or open biopsy with or without frozen section) that commonly is required to establish a tissue diagnosis prior to the definitive surgery, because FNAB substituted for this diagnostic procedure.

Cytologic-Histologic Concordance and Accuracy of the FNAB Results

Of 140 patients who underwent FNAB and also had histology results available, 112 had “diagnostic” FNAB results; and 106 of those 112 patients (95%) had concordant FNAB-histologic results (Table 3). There were 6 patients who had discrepant FNAB-histologic results. One of these was minor and clinically insignificant: It was diagnosed as “muscle” by FNAB but was identified on histology as gynecomastia. The remaining 5 cases involved missed diagnoses of malignancy because of either FNAB sampling error or interpretative error, and are detailed below.

The sensitivity, specificity, and PPV of FNAB for the detection of malignancy are shown in Table 4. FNAB had an overall sensitivity of 93% (range, 83-94%), a specificity of 100%, and a PPV of 100%. The sensitivity for thyroid lesions was the lowest in this series (83%); this low sensitivity was attributed to sampling errors in large, multinodular goiters. The overall NPV was 99% (Table 5).

Table 4. Sensitivity, Specificity, and Positive Predictive Value of Fine-Needle Aspiration Biopsy for Detecting Malignancy
FNAB DiagnosisHistopathologic Diagnosis (No. of Cases)Sensitivity (%)Specificity (%)PPV (%)
MalignantBenign
Breast  94100100
 Malignant160   
 Benign110   
Lymph node  92100100
 Malignant240   
 Benign21   
Soft tissue  100100100
 Malignant130   
 Benign012   
Thyroid  83100100
 Malignant100   
 Benign27   
Salivary gland  100100100
 Malignant20   
 Benign012   
Total all sites  93100100
 Malignant650   
 Benign542   
Table 5. The Negative Predictive Value of Fine-Needle Aspiration Biopsy Using Histology or Clinical Follow-Up Data*
FNAB ResultsConfirmed by Histology (n = 47)Clinical Follow-Up Only (n = 506)NPV (%)
  • NPV indicates negative predictive value; FNAB, fine-needle aspiration biopsy.

  • *

    The mean and median clinical follow-up was 27 months and 31 months, respectively (range, 7-55 months).

Breast  99
 True negative10150 
 False negative1  
Lymph node   
 True negative110298
 False negative2  
Soft tissue  100
 True negative12105 
 False negative0  
Thyroid  98
 True negative7110 
 False negative2  
Salivary gland  100
 True negative1239 
 False negative0  
All sites  99
 True negative42506 
 False negative5  

False-Negative Results

We had 5 false-negative instances of missed malignancy (Table 6): Patient 1 had a delay in her diagnosis of breast cancer because of the under-call of an “atypical” lesion as benign and nonadherence to the triple-test method of evaluation; Patients 2 and 3 had papillary carcinomas that occurred in multinodular goiter of thyroid; and Patients 4 and 5 were middle-aged men who had lymphoma with lymphadenopathy. Descriptions of these 5 patients are provided in Table 6.

Table 6. Description of 5 Patients with False-Negative Fine-Needle Aspiration Biopsy Results
Patient No.Age (Years)GenderSiteClinical PresentationOriginal FNAB diagnosisAdditional Studies Performed or RecommendedFollow-UpReview FNAB DiagnosisType of ErrorImpact on Patient Care
  • FNAB indicates fine-needle aspiration biopsy; CCR, California Cancer Registry.

  • *

    The “triple test” is 1 of 3 diagnostic tools used in evaluating palpable breast masses. The other 2 arms of the triple test are imaging assessment and clinical breast examination. Use of the triple test assessment serves to minimize the number of cancers that would be missed because of the inherent false-negative rate when FNAB or core-biopsy results are used as the sole diagnostic method. Patients with benign triplets are instructed to return to their clinician for follow-up clinical breast examination in 3 to 6 months. Patients with mixed triplets are reevaluated (see National Institutes of Health Consensus Development Conference, 19977).

  • Breast carcinomas that are diagnosed within 36 months of a negative needle aspirate taken from the same area of the breast conventionally are considered false negatives (see Trott, 19965).

  • Although there is no additional information as to the histology correlate of this case, based on the retrospective review of the cytology, we believe we sampled a small low-grade in situ or invasive carcinoma within or next to a dominant benign lesion.

  • §

    The tumor size in both of these patients is are unknown. Patient 4 died from unrelated causes (myocardial infarction) prior to thyroidectomy. Although the tumor size in Patient 5 is unknown, the patient received radioactive iodine after surgery; thus, it is clear that the tumor must have been of sufficient size to be clinically significant.

143FemaleBreastLeft-sided breast mass clinically benign; last mammogram 3 years priorBenignDiagnostic imaging studies ordered by the family physician as part of the triple-test evaluation,* but patient failed to follow through or return to clinician for follow-up clinical breast examination as instructedAccording to the CCR data base, 22 months later, the patient was diagnosed with carcinoma in the same breast; no additional follow-up was availableAtypicalInterpretativeMajor error leading to a delay in diagnosis and possible adverse patient outcome
273MThyroidLarge goiter of several years.BenignRoutine follow-upSeveral months after thyroid FNAB, patient returned with cervical neck mass; FNAB of neck mass showed metastatic papillary carcinomaBenignSampling§Major error, no adverse patient outcome
341MThyroidLarge goiter noted by patient.BenignRoutine follow-upSeveral months after FNAB, the thyroid was excised; surgical excision showed goiter with papillary carcinomaBenignSampling§Major error, no adverse patient outcome
449MLymph node10-month history of mildly enlarged right cervical lymph nodes; asymptomaticBenignFlow cytometry performed on FNAB sample failed to show monoclonal cell population Patient instructed to return to clinic for follow-up if the processes did not resolve.Patient returned 11 months later with increasing right cervical lymphadenopathy; FNAB diagnosis of “atypical” made; lymph node excised; histology revealed low-grade follicular center cell lymphoma; tissue from index lymph node sent to another flow cytometry laboratory, negative result reportedAtypicalInterpretative§Major error leading to a delayed diagnosis, no adverse impact on patient care (treatment: patient observation)
550MLymph nodeGeneral lymphadenopathy and viral-like flu symptoms for 1 monthBenignExcision recommended if process did not resolvePatient admitted to hospital and lymph node excised; angioimmunoblastic T-cell lymphoma was diagnosed with the combination of clinical setting, histology, and T-cell gene-rearrangement studiesBenignInterpretative error attributed to limitations of FNAB in diagnosing T cell lymphomasMajor error, no adverse patient outcome; correct diagnosis made days after initial presentation

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

To our knowledge, this is the first systemic study of superficial FNAB conducted at a community hospital. Our study confirmed that, when FNAB is performed and interpreted by trained cytopathologists in the community setting, it is a reliable, rapid, and clinically useful procedure for the diagnosis of superficial masses. Our community hospital-based FNAB clinic had a 95% accuracy rate, which is comparable to the average accuracy rate of 94% over a 10-year period at Massachusetts General Hospital's pathology-run FNAB service.8 1n a study of 1043 consecutive FNAB specimens of the breast, Ljung and colleagues2 reported that physicians who received formal training in sampling technique missed 2% of cancers, whereas physicians without formal training missed 25% of tumors. This is in agreement with others,1, 3, 4 who have noted that training and expertise in the areas of both sampling and interpretation are essential to the success of the FNAB procedure.

Despite the potential usefulness of FNAB, community-based cytopathology FNAB clinic services are scarce and underdeveloped in the United States. Historically, there has been a shortage of trained cytopathologists practicing in the community; however, since the establishment of a formal, 1-year Cytopathology Fellowship Program by the Accreditation Council for Graduate Medical Education in 1992, the number of graduating cytopathologists is rising. The academic year 2001 to 2002 saw the total number of filled cytology fellowship positions at 92; this number has increased steadily so that, for the academic year 2005 to 2006, there are 131 cytopathology fellows.9 Increased numbers of specialty-trained cytopathologists are likely to increase their availability to community-based practices.

The limitations of FNAB include a low percentage of false-negative results. Of 675 diagnostic FNAB results in the current series, 0.7% (5 lesions) represented false-negative results of missed malignancy. The false-negative rate is not unique to FNAB; false-negative results also are seen with histology. Ballo and Sneige10 examined 124 patients who presented at The University of Texas M.D. Anderson Cancer Center for evaluation of a palpable breast mass and reported that the false-negative rate for detecting a malignant neoplasm was lower for FNAB than for core-needle biopsy (2.5% vs. 10%). Histology also can yield incorrect results because of observer variability. 1n a multiinstitutional review, Raab et al.11 reported a mean 6.7% frequency of discrepancies discovered through second review of histologic specimens. Although the majority of discrepancies in their study had no effect on patient care, 5.3% had a moderate or marked effect on patient care.11

We analyzed our 5 false-negative results to understand the limitations of FNAB. The accuracy of FNAB for palpable breast masses, which represented 1 of our 5 missed diagnoses, can be improved by using the triple-test method. Lau et al.6 reported on the Massachusetts General Hospital experience, in which 450 palpable breast aspirates were performed by experienced cytopathologists or fellows over a 4-year period. Those authors6 observed a 14% false-negative FNAB rate for the diagnosis of malignancy in their series; the use of the triple-test reduced their false-negative rate to <1%.6 From that report, we learn that adherence to the triple-test approach is crucial to keep missed breast malignancies to a minimum. Clinicians should have a reminder system to track the completion of each part of the triple-test for each patient.

Two of our missed diagnoses were thyroid malignancies arising in large, multinodular goiters. This is not surprising, because clinically unsuspected papillary carcinomas are present in at least 10% of large, multinodular goiters; therefore, false-negative FNAB results are not uncommon in this situation.12 Palpable-guided FNAB is highly accurate for solitary thyroid nodules and remains the recommended initial diagnostic test for the evaluation of all palpable thyroid nodules.13 However, it is not as accurate for multinodular goiters because of the multiplicity of nodules and the impracticality of sampling all of the nodules. It has been demonstrated that ultrasound guidance is useful, because it allows for directed sampling toward nodules that may not be palpable but, nevertheless, may represent carcinoma.14 Hence, we advise clinicians of an increased likelihood of sampling error with multinodular goiters to let them decide whether ultrasound-guided FNAB is indicated.

The role of FNAB in diagnosing lymphoma remains controversial. Two of our 5 misdiagnoses involved lymphomas: 1 low-grade B-cell lymphoma and 1 peripheral T-cell lymphoma. These highlight a known problem of FNAB: namely, a limited ability to discern between some lymphomas and reactive lymphadenopathy. Flow cytometry and immunocytochemical marker studies can be extremely helpful in the diagnosis of low-grade B-cell lymphomas and also may be somewhat helpful in diagnosing certain T-cell lymphomas.15 1n our patient with missed low-grade B-cell lymphoma, it is noteworthy that flow cytometry marker studies failed to detect low-grade B-cell lymphoma in both the FNAB specimen and the excised tissue. This is very rare but can occur because of partial lymph node involvement.15 Because of these 2 examples, we rely less heavily on ancillary lymphoma marker results and remind our clinicians to excise any lymph node after a short period of close clinical follow-up in any patient with clinically suspicious, persistent lymphadenopathy. Moreover, even when FNAB identifies lymphoma, it can be difficult to subclassify the type of lymphoma necessary for optimum oncologic treatment. In a recent publication,16 the authors concluded that the use of FNAB for diagnosing lymphoma may even misguide treatment.16 For these reasons, we have changed our approach to the diagnosis of new lymphomas. Now, when we observe an aspirate with a lymphoid proliferation that is worrisome for lymphoma, the procedure is stopped, and the referring clinician is notified and asked to decide whether surgical excision or ancillary marker studies on the FNAB material is preferred.

Despite the shortcomings of FNAB for the diagnosis of lymphomas, it remains the best initial diagnostic test for the triage of lymph nodes, because most enlarged lymph nodes at the primary care level are benign.17 In our series, >50% of the lymph nodes were benign; and, once they were diagnosed, the patients received safe medical management. Our overall malignancy rate of 28% lymph node and soft tissue FNAB results are similar to those of Abele and Miller,18 who reported a 24% malignancy rate in their 5552 patients who underwent lymph node and soft tissue FNAB. Similar to other reported series,19, 20 lymphoma comprised a minority of lymph node malignancies, representing 39% of all lymph node malignancies in our series.

FNAB is excellent for the detection of nonhematologic malignancies that involve lymph nodes, with an overall reported sensitivity rate of >95% for metastatic malignancies.20 Like others,21 we found that FNAB of lymph nodes and soft tissue was especially useful in nonhematologic metastatic malignancies that originated from unknown primary sites. In fact, this was the most common malignant FNAB result for our lymph node and soft tissue patients and comprised 70% of all new lymph node and soft tissue malignancies in our series.

In conclusion, the current data demonstrate the clinical utility of community-based FNAB clinic services. In many cases, this technique replaces surgical biopsy and can be used to triage patients for conservative treatment or surgery. Our experience suggests that FNAB services performed and interpreted by expert cytopathologists who practice in the community setting offers similar accuracy and convenience to services that are provided at major medical centers.

Acknowledgements

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

We thank Daniele M. Washburn, MBA and Barbara J. Edelman, CTR from the Henry Mayo Newhall Memorial Hospital; Dennis Deapen, DrPH, and Ann Hamilton, PhD, from the Los Angeles Cancer Surveillance Program; and Andrea Gwosdow, PhD, for editing this article.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES
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