Frozen section diagnosis of ovarian epithelial tumours: a practical guide for pathologists

The most common indication for frozen section at our Centre (NGOC, Gateshead, UK) is for the diagnosis of ovarian masses. The other indications are to assess the nature of uterine masses, assess adequacy of resection margins in trachelectomy specimens and assessment of lymph nodes for metastases prior to extensive surgical procedures such as pelvic exenterations and laterally extended endopelvic resections. This article will focus on practical issues relating to ovarian epithelial tumours, the most frequent group of tumours submitted for frozen section diagnosis. It will provide guidance on the approach to common entities, diagnostic pitfalls, and strategies for dealing with less frequently encountered lesions. Emphasis will be placed on macroscopic examination, appropriate sampling, and the use of intraoperative cytology as an adjunct. The aim is to provide clinically useful frozen section diagnosis in order to reduce the number of diagnoses deferred to paraffin section and facilitate optimal intraoperative management decisions.     

Fine-needle aspiration of renal masses in adults: analysis of results and diagnostic problems in 108 cases.

Fine-needle aspiration (FNA) biopsy of the kidney has a traditionally well-defined role in the diagnosis and treatment of renal lesions. Recent improvements in renal imaging techniques have also brought renal FNA to the forefront, since small and asymptomatic renal masses are increasingly being detected. Before the physician institutes a treatment plan, such lesions usually require a definitive diagnosis that is best provided by FNA. To assess various aspects of renal FNA, including specimen adequacy, questionable cytologic patterns, and diagnostic pitfalls, we retrospectively evaluate our experience with 108 FNA biopsies performed for the evaluation of renal masses in adults. For each case, the smears were reviewed and correlated with tissue sections from cell blocks, surgical specimens, or autopsy material, when available. The cytologic diagnoses were confirmed by cell block (59 cases), nephrectomy or autopsy (35 cases), or clinical follow-up. Of the 108 FNA biopsy samples, 17 showed evidence of blood, soft tissue, necrotic material, glomeruli, or tubular cells and were classified as unsatisfactory. The following diagnostic categories were noted in the 91 satisfactory aspirates: renal abscess (four cases), benign cyst (30 cases), suspicious lesions (11 cases), and malignant lesions (46 cases). In four cases of renal abscess, FNA found abundant clusters of neutrophils. For the 30 cases interpreted on cytologic evidence as benign cysts, the diagnosis was confirmed in 28 cases; the two remaining cases were acquired cystic kidney and cystic renal-cell carcinoma, respectively. Among the 11 suspicious lesions, the final diagnoses were one benign simple cyst, one angiomyolipoma, two multilocular cystic nephromas, two adult polycystic kidneys, one acquired cystic kidney, three cystic papillary renal-cell carcinomas, and one solid renal-cell carcinoma. Cases classified as suspicious shared characteristic cytologic patterns that distinguished them from simple benign cysts and from classic renal-cell carcinoma. Among the 46 malignant lesions, as evidenced on cytologic examination, 27 were renal-cell carcinomas, five were transitional-cell carcinomas, four were lymphomas, one was a small-cell undifferentiated carcinoma, and nine were metastatic carcinomas. False-positive or false-negative cases were not encountered in this category. In conclusion, FNA is an excellent method to diagnose space-occupying lesions of the kidney. For cystic lesions, cytologic-radiographic correlation is needed to avoid misinterpretation. Our study defines a spectrum of suspicious patterns characteristic of a group of renal lesions that are distinct from both benign simple cyst and straightforward renal malignancy.     

Intraoperative consultation in gynecologic pathology

Intraoperative consultation is widely used in gynecologic surgical practice to make intraoperative diagnosis, primarily to aid the surgeon to plan the extent of surgery. This article reviews the indications, performance and interpretation, accuracy and diagnostic pitfalls in the three major areas of gynecologic malignancies where intraoperative consultations are most frequently requested: ovarian masses, endometrial carcinoma and carcinoma of the cervix. For ovarian masses intraoperative consultation is usually requested either for histologic confirmation of malignant or borderline primary ovarian tumors before proceeding with radical surgery, or to rule out malignancy at the time of surgery for presumed benign disease. The diagnosis of endometrial carcinoma is usually made preoperatively before definitive surgical treatment. Thus, intraoperative consultation is most often used to identify the subgroup of patients with features of high risk disease who have an increased risk of metastases and who will benefit from formal surgical staging. In cases of carcinoma of the cervix frozen section is most commonly used to estimate the extent of spread of known invasive carcinoma at the time of radical surgery. Despite its restrictions, frozen section diagnosis is an important and reliable tool in the clinical management of patients with ovarian, endometrial and cervical tumors. The specificity of the method in experienced hands is high, the sensitivity is sufficient. The diagnosis of borderline ovarian tumors may be troublesome however, mainly due to their heterogeneity in appearance, especially in the case of large tumors of mucinous histologic type. It is important for pathologists to have a clear idea of the role and limitations of frozen section diagnosis in gynecological surgery in order to play a meaningful and optimal role in the management of the gynecologic oncology patient.     

Intraoperative pathology consultation during urological surgery: Impact on final margin status and pitfalls of frozen section diagnosis

Despite recent improvements in diagnostic and surgical techniques in urological oncology, positive resection margin remains a significant concern for surgeons. Meanwhile, intraoperative pathology consultation with frozen section assessment (FSA), particularly for histological diagnosis of the lesions incidentally found or enlarged or sentinel lymph nodes, generally provides critical information which enables immediate decision making for optimal patient care. The intraoperative evaluation of surgical margins is also often requested, although there are some differences in its application between institutions and surgeons. Importantly, it remains to be determined whether intraoperative FSA indeed contributes to reducing the risk of final positive margins and thereby improving long-term patient outcomes. This review summarizes available data indicating the potential impact of FSA at the surgical margins during urological surgeries, including radical or partial cystectomy, partial nephrectomy, radical prostatectomy, penectomy, and orchiectomy. The accuracy and pitfalls of the intraoperative consultation/FSA diagnosis are also discussed.     

Interinstitutional comparison of frozen section consultation in small hospitals: a College of American Pathologists Q-Probes study of 18,532 frozen section consultation diagnoses in 233 small hospitals

OBJECTIVE: To study pathology intraoperative consultation practices and the accuracy of diagnoses made by frozen section. DESIGN: In 1994, participants in the College of American Pathologists Q-Probes laboratory quality improvement program each completed questionnaires and prospectively collected data on up to 20 frozen section procedures performed over a 5-month period. SETTING: Surgical pathology laboratories serving private and public hospitals with 300 or fewer occupied beds. PARTICIPANTS: Two hundred thirty-two North American institutions and one New Zealand institution. MAIN OUTCOME MEASURES: The discordance and deferral rates of frozen section diagnoses and the reasons for frozen section discordance relative to corresponding diagnoses made on permanent (paraffin) sections. Calculation of frozen section discordance rates excluded diagnoses of subtypes or grade of malignancy, biopsies on specimens in which there was no gross lesion (eg, mammographic specimens), thyroid follicular lesions, tissue taken only to determine adequacy for other studies (eg, estrogen-binding proteins), and frozen sections performed to evaluate margins of specimens oriented en face. RESULTS: Out of 18,532 frozen section diagnoses performed on 327,884 surgical cases, 859 (4.6%) diagnoses were deferred until permanent sections were available for review; 17,357 (98.2%) nondeferred diagnoses agreed with, and 316 (1.8%) disagreed with, those diagnoses rendered on permanent sections. The most common cause of discordance was underdiagnosis of neoplasia, usually due to block- or tissue-sampling errors. CONCLUSIONS: We recommend that laboratories routinely monitor frozen section discordance, cut additional sections deeper into the frozen block and/or sample additional tissue when the initial frozen section diagnosis is negative or nonproductive, reconcile all discordant frozen section diagnoses in the final report, and periodically assess the value of performing frozen section examinations.     

Unilateral malignant struma ovarii in a case of bilateral ovarian teratoma with raised CA-125 level: a rare case with treatment dilemmas

Struma ovarii are specialized form of mature ovarian teratoma comprised predominantly of thyroid tissue (>50%). Most of the struma ovarii are benign; rarely can they undergo malignant transformation. Elevated CA-125 levels with benign struma ovarii have been seen in only 5 cases in literature. The association of malignant struma ovarii and high CA-125 levels with pseudo-Meig syndrome has been reported in only 2 cases in English literature. We describe a case of a 46-year-old multigravida who presented with an abdominal mass and raised CA-125 levels. Radiological investigations revealed bilateral cystic adnexal masses with ossified elements on left side suggesting a teratoma. Intraoperative frozen section and final pathology revealed bilateral teratoma with follicular variant of papillary thyroid carcinoma arising in the left ovary. To the best of our knowledge, this is the first case of malignant struma ovarii in combination with bilateral teratoma. The dilemmas related to preoperative diagnoses with elevated CA-125 levels, mimicking an epithelial ovarian neoplasm; intraoperative frozen section consultation; management and follow-up issues in this rare malignancy are discussed.     

Accuracy of frozen section diagnosis: a retrospective analysis of 4785 cases

During a 1-year period 4785 intraoperative consultations were performed. The pathology reports were retrospectively reviewed to determine the accuracy of frozen section diagnosis in various tissue types. Skin for evaluation of section margins and axillary sentinel lymph nodes for evaluation of metastatic disease were most frequently sent for frozen section diagnosis. The number of discordant cases were 182, 178 were false negative and four were false positive. When frozen section diagnoses were compared with permanent section diagnoses, the overall diagnostic concordance was 95.1%. The number of deferred specimens was 57. The accuracy of frozen section diagnosis varied between tissue types, and axillary sentinel lymph nodes accounted for the greatest number of discordances. In conclusion, the frozen section diagnosis is a reliable method with varying concordance and deferral rates between tissue types. We suggest regular monitoring of the performance in frozen section diagnosis.     

Multilocular renal cyst: A diagnostic pitfall on fine-needle aspiration cytology: Case report

Benign renal lesions, apart from simple cysts, are rarely sampled by fine-needle aspiration biopsy (FNAB) and are potential diagnostic pitfalls. A complex renal mass in a 33-yr-old pregnant woman, presenting in the second trimester with haematuria, was aspirated twice, a week apart, under ultrasound guidance. The second FNAB yielded predominantly mesenchymal elements thought to represent an angiomyolipoma, but the mass was identified as a multilocular renal cyst (MLRC) on the nephrectomy specimen. Differential diagnoses of angiomyolipoma, MLRC, and renal cell carcinoma (RCC) are compared and discussed in relation to patient management. © 1995 Wiley-Liss, Inc.     

Pancreatic frozen section nightmares

Pancreatic resections have steadily increased over the past few decades and as a consequence so have the number of pancreatic specimens submitted for intraoperative frozen section consultation. Frozen section evaluation of the pancreas is generally performed for tumour confirmation and the assessment of margin status. An accurate and prompt diagnosis is therefore critical in guiding surgical management. However, pancreatic frozen sections are among the most challenging specimens submitted to the pathologist. While the main diagnostic dilemma is between adenocarcinoma and chronic pancreatitis, the spectrum of reactive changes, preinvasive neoplasms, neoadjuvant treatment effect and incidental lesions can further confound this assessment. The purpose of this review is to briefly discuss practical guidelines in specimen handling, common tissue artifacts, non-neoplastic and neoplastic frozen section histology, and challenging scenarios. In addition, it is our hope that this review will serve to facilitate better communication between the surgeon and pathologist to enhance patient care.     

Incidence and predictive factors of benign renal lesions in Korean patients with preoperative imaging diagnoses of renal cell carcinoma

The present study was performed to determine the incidence and predictive factors of benign renal lesions in Korean patients undergoing nephrectomy for presumed renal cell carcinoma on preoperative imaging. We analyzed the pathologic reports and medical records of 1,598 eligible patients with unilateral, nonmetastatic, and nonfamilial renal masses. Of the 1,598 renal masses, 114 (7.1%) were benign lesions, including angiomyolipoma in 47 (2.9%), oncocytoma in 23 (1.4%), and complicated cysts in 18 (1.1%) patients. On univariate analysis, the proportion of benign lesions was significantly higher in female patients, and in patients with smaller tumors, cystic renal masses, and without gross hematuria as a presenting symptom. When renal lesions were stratified by tumor size, the proportion of benign as opposed to malignant lesions decreased significantly as tumor size increased. On multivariate analysis, female gender, smaller tumor size, and cystic lesions were significantly associated with benign histological features. The findings in this large cohort of Korean patients show a lower incidence (7.1%) of benign renal lesions than those of previous Western reports. Female gender, cystic renal lesions, and smaller tumor size are independent predictors of benign histological features.     

Bronchial margins in lung cancer resection specimens: utility of frozen section and gross evaluation.

Pathology reports for all lobectomy and pneumonectomy specimens at UNC Hospitals between 1991 and 2000 (n=405) were reviewed for correlation between frozen section and final bronchial margin, gross distance between tumor and margin and tumor type. Frozen section was performed in 268 cases (66%). A total of 243 were true negatives (90.6 %), 16 (6.0%) were true positives, four (1.5%) were false positives and five (1.9%) were false negatives. The site of tumor in true-positive cases was mucosal (11), submucosal (three), lymphatics (one), peribronchial (one). The site of tumor in false-negative cases was submucosal (two), lymphatics (one), peribronchial (two). In 137 cases, no bronchial frozen section was performed; there was one case (0.7%) with positive margin. There was no correlation between final margin positivity and distance between gross tumor and margin. Tumor distance to margin in positive margin cases varied from grossly involved to 3 cm away. There were 72 cases in which wedge resection was performed before lobectomy in which no gross tumor remained in the lobectomy, and in all cases final bronchial margins were negative. In all, 373 of cases (92%) were nonsmall carcinomas. Of these, 10 (2.7%) had positive margins. Tumors other than nonsmall cell carcinoma accounted for a disproportionate number of positive margins. In all, 3/6 of adenoid cystic/mucoepidermoid carcinoma, 1/7 small cell carcinoma and 1/1 lymphoma cases had positive margins. In conclusion, frozen section evaluation of bronchial margins is helpful in central lung tumors. Mucosal tumor is preferentially identified in frozen section. Gross evaluation of margins is problematic, as intramucosal carcinoma or tumor in lymphatics may not be detected, but 3 cm was a 'safe' distance for gross tumor from margin. In lobectomies following wedge resection in which no gross tumor remained, all had negative margins. Salivary gland-type tumors have a high incidence of positive margins, and frozen section is particularly indicated in these tumors.     

What can we learn from the errors in the frozen section diagnosis of pulmonary carcinoid tumors? An evidence-based approach

The intraoperative diagnosis of pulmonary neuroendocrine tumors can be difficult. Frozen section diagnosis was requested on 87 neuroendocrine tumors including 58 typical carcinoids, 8 atypical carcinoids, 18 large cell neuroendocrine carcinomas, and 3 small cell carcinomas from 2405 patients that underwent frozen section diagnosis at Cedars-Sinai Medical Center from 2002 to 2007. The deferral and error rate for carcinoid tumors was 4.13% and 7.5%, respectively, and resulted in 4 unnecessary lobectomies and 2 second thoracotomies. The most common errors included misdiagnoses as lymphoma, squamous carcinoma or metastasis from breast carcinoma. Thirty one pathologic features were evaluated in the 66 carcinoid tumors and 10 frozen sections each of lymphoma, squamous cell carcinoma, and metastatic breast carcinoma. Seven pathologic features were significant by chi square test at P > .05. Positive likelihood ratios identified 11 pathologic features that were useful for the diagnosis of carcinoid tumor from other neoplasms. The applicability of the 11 pathologic features was tested with a group of pathologists, resulting in significant improvement in diagnostic accuracy as measured by pre and posttests. The value of evidence-based pathology and Bayesian statistics to evaluate complex differential diagnoses in pathology is discussed.     

Intraoperative diagnosis of breast lesions. Comparison of cytologic with frozen section technics

A retrospective double-blind examination of the cytologic smears and frozen section tissue slides from 140 lesions of the breast was performed in order to assess the diagnostic accuracy of each method. The cases with diagnostic errors were reevaluated to define the pitfalls encountered in the intraoperative diagnosis of breast lesions by both methods. Results with the cytologic technics are more variable than with frozen sections, but when read by experienced observers the smears are as accurate as frozen sections and have the additional advantages of rapidity, sparing of tissue for other studies, better correlation with fine-needle aspiration cytologic results, and more complete sampling of large or multiple specimens. The authors recommend that intraoperative cytologic examination be employed routinely in breast diagnosis, initially always in conjunction with frozen section examination but eventually in many cases as an alternative technic.     

Tissue imprints in surgical pathology: a rapid intraoperative diagnostic aid

We studied the intraoperative diagnostic value of imprint cytology in 230 samples obtained from surgical specimens submitted for frozen section diagnosis. A rapid hematoxylin-eosin stain was used. Intraoperative imprint cytology achieved an accuracy rate of 94.3%; for benign lesions the accuracy was 97.5%, and for malignant lesions it was 91%. Overall, the false-negative and suspicious-for-malignancy rates were 1.3% and 4.3%, respectively. No false-positive results were found. The diagnostic yield when intraoperative imprint cytology and frozen section were used together was 99%. It is apparent that imprint cytology is a quick and simple method with wide applicability in the histopathologic diagnosis of lesions from all organs. The value of the method is enhanced when it is used with frozen section diagnosis.     

Frozen section diagnosis of pancreatic lesions

BACKGROUND: The clinical and radiologic diagnosis of pancreatic cancer and the safety of pancreatic resections have improved. These improvements, together with the indication for resection in some cases of complicated chronic pancreatitis, have reduced the necessity for confirmed preoperative tissue diagnosis. We investigated the clinical use and accuracy of frozen section diagnosis for pancreatic lesions. DESIGN: We searched archival files for the years 1989-2000 for patients with pancreatic lesions who had received a diagnosis based on frozen section results. We compared the diagnosis of all frozen section slides with that of the permanent sections and reviewed the clinical follow-up notes. We evaluated histologic features useful in differentiating between malignant and benign pancreatic lesions. RESULTS: A total of 538 patients underwent surgical biopsy and/or resection for suspected pancreatic lesions. Frozen section was requested in 131 cases (284 frozen sections). Ninety cases had frozen section of the pancreatic lesions, 70 cases had frozen section of metastatic sites, and 29 cases had frozen section of surgical margins. Of the 90 cases in which frozen section of the pancreatic lesions was requested, malignancy was diagnosed in 44, a benign lesion was diagnosed in 37, and the diagnosis was atypical and deferred in 9. In total, 3 false-negative frozen sections and 1 false-positive frozen section were identified for respective rates of 1.2% and 0.3%. In all cases in which the frozen section diagnosis was deferred or was inconsistent with the operative impression, and the surgeon acted on his/her impression, the operative diagnoses were subsequently confirmed by additional permanent sections and/or clinical follow-up. The most useful histologic features for the diagnosis of pancreatic adenocarcinoma in frozen sections were variation in nuclear size of at least 4:1, disorganized duct distribution, incomplete duct lumen, and infiltrating single cells. CONCLUSIONS: Frozen sections are useful in conjunction with the impression at surgery for the management of patients with pancreatic lesions. Frozen sections of resection margins were 100% accurate; frozen sections of pancreatic lesions or metastatic sites were accurate in 98.3% of cases. We found an acceptable rate of deferred frozen section (6.6%). The experienced surgeon's impression of malignancy is reliable in cases in which frozen section is deferred or has negative findings.     

Use and abuse of frozen section in the diagnosis of follicular thyroid lesions

The role of intraoperative frozen section in certain organ systems such as the thyroid continues to be problematic. In many cases, diagnoses are deferred or nonhelpful—“follicular lesion.” In the modern era, the widespread use of preoperative aspiration biopsy has allowed for more careful selection of patients who undergo thyroid surgery. In many cases, the fine-needle-aspiration (FNA) biopsy diagnosis can be definitive or can guide the specific surgical procedure. The literature supports our approach, which is summarized as follows: Intraoperative consultation is not needed on the intrathyroidal nodule if a preoperative FNA was definitive for papillary carcinoma. Frozen section is of no value in the intraoperative diagnosis of lesions diagnosed on FNA as “follicular neoplasm” or “Hürthle cell neoplasm” because the characterization of these lesions requires detailed analysis of the tumor capsule for the demonstration of capsular and/or vascular invasion—an analysis that is not practical in the intraoperative setting. Finally, intraoperative consultation including frozen section and intraoperative cytologic examination is most useful in those cases that are diagnosed as suspicious for papillary carcinoma by FNA, because the assessment of nuclear features needed for the definitive diagnosis is possible with intraoperative techniques in a significant number of cases.     

Potential pitfalls in the frozen section evaluation of parenchymal margins in nephron-sparing surgery

With advances in radiographic imaging, there has been an increase in the incidental detection of small renal cell carcinomas, with a resultant increase in partial nephrectomies for these tumors. Partial nephrectomy often necessitates assessment of renal parenchymal margins by frozen section. To determine the most common problematic "lesions" encountered on renal parenchymal margins, we evaluated all diagnostically challenging frozen sections that had been referred to a genitourinary pathologist. Frozen sections with detached atypical cells and crushed tubules were the most common lesions that presented diagnostic uncertainty. We found that normal constituents of renal parenchyma, namely tubules and glomeruli, can be mistaken for neoplasia. Neoplastic tubules of low-grade renal cell carcinomas may be misinterpreted as thickly cut, crushed benign tubules, and the significance of tubulopapillary "adenomas" in frozen sections is unclear. The present report highlights diagnostic difficulties that pathologists may encounter on frozen sections of renal parenchymal margins.     

A retrospective analysis of the diagnostic accuracy and technical quality of frozen sections in detecting hepatobiliary lesions

IntroductionPathological consultation on intraoperative frozen sections plays a crucial role in the management of patients undergoing surgical therapy, and is also a key indicator for quality assurance in anatomical pathology. This study aimed to evaluate the diagnostic accuracy and technical quality of frozen sections in detecting hepatobiliary lesions with malignant potential.Patients and methodsA retrospective database review was performed for 1208 cases intraoperative pathology consultation who underwent hepatobiliary lesions resection at our institution from 2016 to 2020. The intraoperative consultation cases during a 5-year period were reviewed and analyzed, including the measurement of the diagnostic accuracy and turnaround time of frozen sections, the reasons for discrepancies, and the rates of discordance and deferral.ResultsIn this study, we confirmed that the overall accuracy, sensitivity and specificity were 95.3 %, 96.3 % and 96.6 %, respectively, in distinguishing benign from malignant lesions. The rates of deferred and discordant diagnoses were 2.57 % and 2.2 %, respectively. The overall frozen section turnaround time was 22.1 min. The most common cause of deferred and discordant was poor section quality, the lesion of bile duct margin on the frozen section, misinterpretation of difficult and complicated cases, etc.ConclusionsThis study confirms that the intraoperative frozen sections can serve as a rapid, accurate and robust method for the pathological diagnosis of suspected hepatobiliary lesions. However, it should be noted that some poor technical problems, pathological assessment of tumor margin and difficult cases are the most frequently causes of deferred and discordant interpretations.     

Utility of intraoperative consultation touch preparations

Although intraoperative touch preparations (TPs) often are performed in conjunction with frozen sections, the comfort level of using TPs in actual practice and the effect of TP quality and cytologic experience on diagnostic accuracy have not been measured. To investigate the utility of intraoperative TPs and to compare them with that of frozen sections, five pathologists of differing levels of cytologic experience retrospectively reviewed 122 intraoperative TPs and frozen sections. Accuracy rates for individual pathologists were calculated and the accuracy using TPs was compared to that of frozen sections. TP accuracy was correlated with TP quality and cytologic experience. The mean rates of correct, incorrect, and atypical TP diagnoses were 88.5%, 4.1%, and 7.4%, respectively. The mean rates of correct, incorrect, and deferred frozen section diagnoses were 86.1%, 2.5%, and 11.9%, respectively. For the four pathologists with cytologic experience, both TP and frozen section diagnostic accuracy rates were similar; however, the pathologist who lacked cytologic experience had lower TP diagnostic accuracy. All pathologists who had cytologic experience requested a frozen section for cases with an atypical or incorrect TP diagnosis. In cases with a correct TP diagnosis a frozen section was requested 46.3% of the time. TPs of greater technical quality were associated with higher diagnostic accuracy. In conclusion, the use of performing TP and frozen section are complementary and result in increased diagnostic accuracy. For some pathologists, TPs may replace frozen sections in over 50% of cases.     

Cystic change in metastatic lymph nodes: a common diagnostic pitfall in fine-needle aspiration cytology

Fine-needle aspiration cytology (FNAC) of cystic metastases is a challenging diagnostic category and has been investigated in a limited number of malignancies and sites. The present study retrospectively reviewed 1,211 FNAC of superficial masses, including lymph nodes (1,102 aspirates), benign cystic lesions (64 aspirates), and lymphocysts (45 aspirates) with the aim of determining the tumors that cause cystic change in metastases. Cytology results from 1,102 lymph node aspirations were suspicious or positive for malignancy in 541 specimens (49.1%), benign in 230 (20.9%), and unsatisfactory in 331 (30%). There were 28 malignant aspirates demonstrating cystic change (5.2%). The tumor type that most frequently caused cystic change was thyroid papillary carcinoma (42.8% of cases), followed by squamous cell carcinoma (primary in the head and neck region 30.8% and in the skin 24%), tumors of unknown origin (6.3%), serous papillary carcinoma of the ovary or endometrium (4.8%), and malignant melanoma (2.1%). Cystic change was observed most commonly in the head and neck region lymph nodes (60%). The most challenging lesions to assess using FNAC were metastatic lymph nodes showing cystic change, accounting for six of the 16 false-negative diagnoses and one false-positive diagnosis. The results of this study suggest that cystic change in metastatic lymph nodes occurs in certain types of tumors and is an important cause of diagnostic error. FNAC should be repeated in case of suspicious hypocellular cystic aspirations, especially in patients with known malignancy.