The gray zone in breast fine needle aspiration cytology. How to report on it?

OBJECTIVE: To study the "gray zone" in breast fine needle aspiration cytology in which an unequivocal diagnosis cannot be reached with fine needle aspiration cytology findings. STUDY DESIGN: This study compared cytology and histopathology of 72 breast lesions in which an initial cytologic diagnosis of atypia was given. RESULTS: There were 36 benign (50%) and 36 malignant (50%) histologic biopsy cases in the cytologic atypia group. Anisonucleosis, chromatin and nuclear membrane irregularity, and presence of myoepithelial cells were significantly different in benign and malignant cases. CONCLUSION: The gray zone in breast fine needle aspiration cytology is a broad spectrum that changes from proliferative fibrocystic disease to sclerosing adenosis to malignancy. Diagnosing gray zone pathology as atypical in fine needle aspiration cytology causes no delay in treatment as excisional biopsy is recommended for all equivocal cases.     

Optimal recovery of DNA for polymerase chain reaction-based assays from fine needle Aspirates. A comparison of four preparation types

OBJECTIVE: To assess the ideal preparation for molecular techniques applied to cytologic specimens using polymerase chain reaction (PCR) on different types of cytologic preparations with specimens obtained from fine needle aspiration biopsy (FNAB). STUDY DESIGN: Besides conventional cytologic examination, PCR was performed on 30 consecutive cases of FNAB to analyze the beta-actin gene in four types of cytologic preparations, including fresh samples, previously stained Papanicolaou and Diff-Quik routine smears and cell blocks. Cellularity and cytologic findings were correlated with PCR results. RESULTS: The beta-actin gene was successfully amplified from all cases studied. Cellularity of the samples correlated directly with PCR results except for one case of metastatic melanoma with intense pigment retention. All specimens showed equivalent results as compared to fresh samples. Generally cell blocks were less cellular and consequently less effective. CONCLUSION: All conventional cytologic preparations tested were suitable for PCR-based assays when cellularity was adequate. Alcohol-fixed and air-dried smears can be successfully used for PCR studies, providing rapid and simple specimens for molecular studies, which can add important information concerning diagnosis, prognosis and management.     

Molecular genetic analysis in the diagnosis of lymphoma in fine needle aspiration biopsies. I. Lymphomas versus benign lymphoproliferative disorders

The configurations of immunoglobulin genes, T-cell receptor (TCR) beta chain genes and bcl-2 genes were analyzed by Southern blotting in DNAs derived from 35 fine needle aspiration biopsies from various lymphoproliferative disorders. Only 1 of 16 benign lymphoproliferative disorders showed clonality: the lymph node of a patient with Wiskott-Aldrich immunodeficiency syndrome, in which clonal rearrangement of the TCR beta chain gene was detected. Clonality was demonstrated in all 14 non-Hodgkin's lymphomas (NHLs), 2 of 3 cases of Hodgkin's disease (HD) and 2 cases diagnosed as NHL or angioimmunoblastic lymphadenopathy (AILD). None of the aspirates exhibited rearrangement of the bcl-2 gene. The studies of diagnostically difficult cases proved that molecular genetic analysis of DNA, when appropriately combined with clinical data and light microscopic analysis of the lesions, can be helpful in distinguishing between: (1) a hyperplastic lymph node and NHL or AILD; (2) NHL and well-differentiated lymphocytes; and (3) a hyperplastic lymph node and HD.     

Testicular fine needle aspiration cytology in male infertility

OBJECTIVE: To compare the accuracy of testicular fine needle aspiration and biopsy for diagnostic and therapeutic purposes. STUDY DESIGN: A comparison of testicular fine needle aspiration and biopsy was performed on 34 infertile men over a 2-year period. RESULTS: Concordance of the 2 tests was evident in 88% of cases. In discordant cases fine needle aspiration yielded more than biopsy, considering the existence of secondary spermatocytes and spermatids. Charcot-Bottcher crystalloids were frequently seen in the cytoplasm of Sertoli cells in normal and abnormal spermatogenesis. CONCLUSION: Testicular fine needle aspiration is a simple and cost-effective method of evaluating testicular pathology in male factor infertility. It may yield more diagnostic and therapeutic material than does biopsy.     

甲状腺良、恶性结节的临床、超声及细胞学特征分析

目的:研究良、恶性甲状腺结节的相关临床因素、超声特征与甲状腺细针穿刺细胞学检查结果之间的关系。方法:收集2010年1月至2013年12月在上海市第一人民医院因甲状腺结节就诊,并进行超声引导下FNAB检查患者的临床资料,以FNAB细胞学诊断结果为诊断标准,分析和比较不同性质甲状腺结节患者的年龄、性别、甲状腺疾病家族史、临床症状、血清甲状腺激素、甲状腺自身抗体(TPOAb和TRAb)水平,超声检查所发现的结节数量、性状、前后径与横径比(AP/TR)、回声类型、钙化类型、边界状态、血流情况等因素,采用Logistic多因素回归,探讨这些临床和超声特征与甲状腺良、恶性结节之间的关系。结果:根据FNAB结果,1592例患者中,良性结节者1492例,恶性结节者77例,结果不确定者23例。以良性组作为对照,年龄40岁、TPOAb(+)是恶性甲状腺结节的独立危险因素(P0.05);出现钙化点、细小钙化斑、边界不规整的超声表现的恶性甲状腺的风险显著升高(P0.05)。结论:超声检查甲状腺结节出现钙化点、细小钙化斑或边界不规整等与FNAB诊断的甲状腺恶性结节之间存在明显的关联。     

Diagnosis of lymphoma by image-guided needle biopsies: fine needle aspiration biopsy, core biopsy or both?

OBJECTIVE: To determine whether or not concurrent core biopsy adds to results obtained from image-guided fine needle aspiration biopsy (FNAB) in cases of lymphoma. STUDY DESIGN: Twenty-eight FNABs of lymphomas with adjuvant flow cytometry (FC) and concurrent core biopsy were evaluated retrospectively. In each case, completeness of diagnosis by FNAB, including phenotyping and grading, where appropriate, was reviewed. The contribution of core biopsy to the diagnosis in cases where FNAB did not render a complete diagnosis was assessed. Prognostic information not available from the FNAB but obtained from the core biopsy was also evaluated. RESULTS: FNAB with adjuvant FC gave a complete diagnosis, including phenotype and grade, where applicable, in 23 of 28 cases (82%). Core biopsy added to the diagnosis in 3 cases. In 1 case, large B-cell lymphoma was diagnosed on core biopsy when FNAB was unsatisfactory. In the other 2 cases, grade of follicle center cell lymphoma was higher on core biopsy than on FNAB. The addition of the information obtained by core biopsy to that obtained by FNAB raised the diagnostic accuracy to 93%. Core biopsy was used to assess nodularity, which could not be determined on FNAB. Core biopsy was also used to assess prognostic markers by immunohistochemistry (Ki-67 and p53); they were not available with FC. This was done in 11 cases when requested by the oncologist. CONCLUSION: FNAB with adjuvant FC is a useful technique for diagnosing and subtyping lymphomas. However, diagnosis and subclassification are often insufficient. Core biopsy material provides opportunity for obtaining additional diagnostic and prognostic information that may not be easily derived from the FNAB. This allows optimal treatment planning in patients for whom excisional biopsy is contraindicated.     

Diagnosis of follicular lymphoma by fine needle aspiration biopsy.

This study evaluated the diagnostic accuracy of fine needle aspiration biopsy (FNAB) of follicular lymphoma (FL). Fourteen aspirates of lymph nodes in which follow-up surgical biopsy revealed FL were studied. Two aspirates were deemed unsatisfactory because of a paucity of cells. The remaining 12 cases received the following diagnoses: 4 positive for malignant lymphoma, 4 highly suspicious for malignant lymphoma and 4 false negatives. FNAB of FL can show a monomorphic or polymorphic cell population. The aspirates with a positive or suspicious diagnosis showed monomorphic cell populations. False-negative diagnoses were attributable to misleading sampling or preparation methods in most cases. We conclude that FNAB of FL is less accurate than FNAB of non-Hodgkin's malignant lymphoma (NHL) in general, but the accuracy rate is similar to that of FNAB of all low-grade NHL. The value of current approaches to the diagnosis of suspected lymphoma by FNAB is emphasized.     

Nodal presentation of nasal-type NK/T-cell lymphoma. Report of two cases with fine needle aspiration cytology findings

BACKGROUND: Epstein-Barr virus (EBV)-associated NK/T-cell lymphoma typically occurs in extranodal sites, such as nasal cavity, nasopharynx, gastrointestinal tract, skin, testis and salivary gland. Secondary lymph node involvement is rarely encountered until late in the disease course. The fine needle aspiration cytology of NK/T-cell lymphoma with a nodal presentation has not been described before. CASES: Two cases of nasal-type (extranasal) NK/T-cell lymphoma with a nodal presentation were seen at Pamela Youde Nethersole Eastern Hospital, Hong Kong. Both patients presented with submandibular lymph node enlargement but unremarkable peripheral blood and bone marrow findings. Fine needle aspiration cytology was available in both cases, showing a heterogeneous population of small to medium-sized lymphoid cells, follicular center cells, plasma cells, eosinophils and some histiocytes. The medium-sized lymphoid cells showed readily discernible nuclear atypia with an irregular nuclear outline. Cell block sections revealed occasional lymphoid cells with pleomorphic nuclei. Immunocytochemical study confirmed the presence of CD56-positive lymphoma cells. In situ hybridization for EBV-encoded RNA also revealed positive nuclear signals. Histologic examination of the surgical biopsies showed interfollicular expansion by malignant lymphoid cells. Immunoglobulin heavy chain gene and T-cell receptor gene rearrangement studies demonstrated a germline pattern, confirming the putative NK (natural killer cell), non-B and non-T lineage of the lymphoma cells. CONCLUSION: Nodal presentation of NK/T-cell lymphoma, though rare, is diagnosable on the basis of fine needle aspiration biopsy alone, especially in view of its distinctive immunophenotype and EBV association. Recognition of the subtle but definite cytologic atypia of malignant lymphoid cells and presence of an appropriate background (including more eosinophils than usual), together with proper application of ancillary techniques, is crucial to arriving at a correct diagnosis.     

Acral myxoinflammatory fibroblastic sarcoma in FNAB samples: can we distinguish it from other myxoid lesions?

We analysed cytomorphological characteristics of three fine needle aspiration biopsy (FNAB) samples of acral myxoinflammatory fibroblastic sarcoma (AMIFS) as well as the features of a number of other benign and malignant myxoid lesions. The analysis showed that FNAB samples from two cases of AMIFS had similar cytomorphology, containing all the characteristic features described in surgical biopsies: myxoid material, spindle cells with bipolar cytoplasmic extensions, epithelioid cells with globules of extra-cellular material, ganglion-like and lipoblast-like giant cells. Only the inflammatory component was scarce. The third sample did not contain features typical of AMIFS. Samples from other myxoid tumours resembled AMIFS to some extent, however, none of them contained all three tumour components characteristic of AMIFS. Cytomorphology of AMIFS may be characteristic enough to enable a definitive diagnosis from FNAB, provided all the distinctive features are sampled.     

Cytodiagnosis of lymphoid proliferations by fine needle aspiration biopsy. Adjunctive value of flow cytometry

OBJECTIVE: To determine the accuracy of fine needle aspiration biopsy (FNAB) complemented by flow cytometry (FC) for the diagnosis of reactive and neoplastic lymphoid proliferations and subclassification of malignant lymphomas. STUDY DESIGN: Forty-one FNABs of lymphoid lesions on which FC had been performed were evaluated retrospectively. All cases were correlated with histology or clinical follow-up. RESULTS: Twelve FNABs were diagnosed as reactive. Eleven of the 12 were confirmed as reactive on follow-up. One was a case of posttransplant lymphoproliferative disorder. Twenty-five FNABs diagnosed as lymphoma were confirmed by histology. In 22 of these 25 cases, there was 100% correlation between the subclassification given on FNAB with FC and that given on histology. Two of the remaining cases, which were correctly called follicular center cell lymphoma, showed discrepancies in grading. One case called Hodgkin's disease on FNAB was T-cell lymphoma on histology. Of four FNABs given an inconclusive diagnosis, two were lymphoma on follow-up, and two were reactive. CONCLUSION: FNAB examination, when it includes immunophenotyping by FC, is a useful technique for distinguishing reactive lymphoid proliferations from malignant lymphomas and for the subclassification of lymphomas.     

The role of fine needle aspiration biopsy in the diagnosis of melanoma

The role of fine needle aspiration biopsy (FNAB) is discussed in the follow up of patients with the diagnosis of malignant melanoma. The review is based on literary data and the author's own material. The primary role of FNAB is to confirm metastatic or recurrent melanoma lesions. US or CT guided FNAB is valuable in the diagnosis of visceral metastases. FNAB has limited role in the diagnosis of primary melanomas except in cases with unusual clinical presentation (e.g. oral mucosa). In spite of the well-known cytology the diagnosis can be difficult due to the inherent histological variation of malignant melanomas, especially in cases with unusual localisation and amelanotic tumor presentation when immunocytochemistry is needed. The known clinical history of melanoma is very helpful.     

Fine needle aspiration biopsy of vertebral and paravertebral lesions: retrospective study of 124 cases

OBJECTIVE: To evaluate the diagnostic value of image-guided fine needle aspiration biopsy (FNAB) in the diagnosis and management of vertebral and paravertebral lesions and to review similar studies in the literature. STUDY DESIGN: One hundred twenty-four FNAB cases (113 [corrected] patients) of vertebral and paravertebral lesions occurring over a 10-year period were retrieved from the archives of the University of Mississippi Medical Center for review and clinico-radiologic correlation. Thirty-four of the cases included a concurrent core needle biopsy sample, 15 cases had subsequent surgical specimens, while 32 cases had previously established malignancy. The age range was 11 days to 91 years (mean, 46 years), with 57 male patients and 56 female. RESULTS: One hundred five cases were vertebral lesions, and 19 cases were paravertebral lesions. FNAB diagnosis were malignant in 33.87% of cases, benign in 5.64%, suspicious in 4.03%, infectious/inflammatory and degenerative in 12.91%, unsatisfactory in 16.13% and negative in 27.42%. The overall sensitivity of the procedure was 89.3% and the specificity, 93.8%. The positive predictive value was 95.7% and negative predictive value, 85.2%. CONCLUSION: FNAB is an effective means of establishing a definitive diagnosis of vertebral and paravertebral lesions, allowing appropriate patient management. Cell blocks, core biopsies and ancillary studies are useful adjuncts in rendering the diagnosis.     

Diagnostic value of fine needle aspiration biopsy of palpable colonic masses.

OBJECTIVE: To assess the role of fine needle aspiration biopsy (FNAB) in patients with palpable colonic masses. STUDY DESIGN: FNAB was performed on 32 patients with palpable colonic masses before subjecting them to colonoscopic examination. Smears prepared from the material obtained by aspiration biopsy were examined. The results of aspiration biopsy were confirmed by histopathologic examination of the tissue obtained on colonoscopy or surgery or by a salutory response to antituberculous therapy in patients with tuberculosis of the colon. RESULTS: Twenty-nine patients had carcinoma of the colon, and three had ileocecal tuberculosis. Aspiration biopsy could correctly diagnose all the cases with malignancy and two of the three cases with colonic tuberculosis. Colonoscopy could not be performed on two patients with cancer of the colon. However, a barium enema examination revealed evidence of cecal malignancy in both patients. In the two patients diagnosed as having colonic tuberculosis by FNAB, colonoscopic biopsies revealed only nonspecific changes. There were no false positive results or complications of the procedure. CONCLUSION: FNAB is a simple, rapid and accurate method of diagnosing palpable colonic masses.     

Transcutaneous fine needle aspiration biopsy of the preepiglottic space

OBJECTIVE: To evaluate transcutaneous fine needle aspiration biopsy of the preepiglottic space for staging supraglottic squamous cell carcinoma. STUDY DESIGN: We studied 28 patients who underwent total or horizontal supraglottic laryngectomy as their main therapy modality due to supraglottic squamous cell carcinoma, followed in some cases by adjuvant radiation therapy. All the patients underwent transcutaneous fine needle aspiration. RESULTS: The cytopathologic examination of the material obtained by aspiration was compared to the histopathologic analysis of the laryngectomy specimens; the efficiency was 96.4%. The method did not cause any morbidity. CONCLUSION: Transcutaneous fine needle aspiration biopsy of the preepiglottic space is useful for preepiglottic space evaluation, with a high correlation with histopathologic results and no morbidity.     

Does Large Needle Aspiration Biopsy Add Pain to the Thyroid Nodule Evaluation?

Thyroid large needle aspiration biopsy is disregarded because it is thought to be associated with pain. This is in contrast with our 32 years long experience. We surveyed reports of pain in patients examined with fine needle aspiration biopsy (78, 87.2% women, mean age 59 years) or FNAB+large needle aspiration biopsy (48, 87.5% women, mean age 60 years). Each patient was questioned regarding a) no unpleasant sensation (score “0”); b) unpleasant sensation (“1”); c) mild pain (no analgesic used; “2”); or d) pain (analgesic used; “3”). The mean size of the needle used was for FNAB 22.3±0.7 or 20.8±1 gauge in the fine needle aspiration or fine needle aspiration plus large needle aspiration biopsy group, respectively (p<.0001). The number of percutaneous punctures was higher in the fine needle aspiration plus large needle aspiration biopsy group. However, the pain score in the fine needle aspiration biopsy or fine needle aspiration biopsy plus large needle aspiration biopsy group was not significantly different. Large needle aspiration biopsy after fine needle aspiration biopsy does not add any discomfort or pain and therefore in light of the demonstrable benefits, should be included in clinical algorithms for the evaluation of thyroid nodules.     

Fine needle aspiration biopsy for improving the diagnostic accuracy of cut needle biopsy of focal liver lesions

OBJECTIVE: To determine the value of fine needle aspiration biopsy (FNAB) in comparison to cut needle biopsy (CNB) for the diagnosis of malignancy of focal liver lesions. STUDY DESIGN: A retrospective analysis was conducted on 68 FNAB and 49 CNB procedures performed on 62 patients with focal liver lesions. RESULTS: Cytology permitted a diagnosis of the lesion in 78% of cases. When punctures with insufficient material were excluded (11), the diagnostic accuracy of FNAB was 93%. For the 49 patients who underwent both procedures, FNAB and CNB had the same diagnostic accuracy, 78%, when considered separately and of 88% when considered in combination. Sensitivity, specificity and positive predictive value were similar for the 2 techniques. The negative predictive value was 64% for FNAB and CNB used separately and reached 78% when the 2 techniques were combined. There were no complications during the execution of FNAB and CNB. CONCLUSION: FNAB is an effective and safe method for the diagnosis of focal hepatic lesions, with diagnostic accuracy similar to that of CNB. When the 2 techniques are combined, the accuracy of the diagnosis of malignancy of focal liver lesions increases.     

Combined hepatocellular-cholangiocarcinoma. Diagnostic challenge in hepatic fine needle aspiration biopsy

OBJECTIVE: To study the cytohistologic features of combined hepatocellular-cholangiocarcinoma (CHCC-CC) in fine needle aspiration biopsy (FNAB) material. STUDY DESIGN: Six hepatic FNAB cases with cell blocks (five) and hepatic resections (two) were analyzed cytohistologically and immunohistochemically. RESULTS: The six cases were diagnosed as CHCC-CC based on clinicopathologic correlation. Unequivocal hepatocellular carcinoma (HCC) cells corresponding to Edmondson and Steiner's grade 3 lesions were identified in the FNAB in three instances. Adenocarcinoma, represented by cohesive columnar cells with ovoid, basal nuclei displaying nuclear palisading, acini and/or papillary structures with variable intracytoplasmic intraacinar or brush border mucin production, was identified in all cases. Intermediate cells with hybrid/polymorphic cytologic features straddling malignant hepatocytes and glandular cells were identified in five instances. Tissue alpha-fetoprotein was negative. There was brush border and/or diffuse cytoplasmic p-carcinoembryonic antigen immunoreactivity in the glandular elements. CONCLUSION: FNAB diagnosis of CHCC-CC is possible if the clinical, cytohistologic and immunohistochemical findings support the presence of HCC and adenocarcinoma. Intermediate cells pose a great challenge to recognize and define: they tend to lose the classic cytologic features of malignant hepatocytes and acquire glandular characteristics. At the very least, there should be a high index of suspicion. These cases underscore the necessity for clinicopathologic correlation in enhancing the precision of FNAB diagnoses.     

FNAC of malignant lymphoma in an area with a high incidence of T-cell lymphoma. Correlation of accuracy of cytologic diagnosis with histologic subtype and immunophenotype

OBJECTIVE: To analyze the usefulness of fine needle aspiration cytology on malignant lymphoma in an area with a high incidence of T-cell lymphoma and to correlate the accuracy of cytologic diagnosis with histologic subtype and immunophenotype. STUDY DESIGN: We retrospectively studied the usefulness of fine needle aspiration cytology in the diagnosis of 49 cases of nodal and extranodal non-Hodgkin's lymphoma (NHL) and seven cases of Hodgkin's disease in a total of 56 patients in whom subsequent excisional biopsy revealed lymphoid malignancy. Slides showing the results of cytologic investigation were reviewed together with the information on which histologic diagnosis was based. On the basis of pathologic variables, such as prognostic groups based on the Working Formulation, so-called grade, cell size based on the modified Rappaport classification, and--in cases of NHL--immunophenotype, the accuracy of original and reviewed cytologic diagnoses was compared. RESULTS: Of the 49 cases of NHL, 8 (16.3%) were inadequate for cytologic diagnosis, and malignant lymphoma was diagnosed or suspected in 36 (73.5%), excluding inadequate specimens; the diagnostic accuracy for NHL was 87.8%. In high grade cases, malignant lymphoma was more easily diagnosed or suspected than in those that were low or intermediate grade. The rate of inadequate cases was highest in the "mixed small and large cell" category, and cases that were "false negative" were either composed entirely of small cells or contained a small cell component. Cytologic diagnosis or suspicion of malignant lymphoma was easily obtained in the "large cell" category, followed by mixed small and large cell and "small cell." Aspirates from non-B-cell type were more frequently acellular than those of B-cell type; with regard to diagnostic accuracy, however, there was no noticeable difference between the two immunophenotypes. CONCLUSION: In many cases in the mixed small and large cell category or where the immunophenotype was non-B, the aspirate was inadequate, and no definitive diagnosis was possible. Many of our cases of T-cell lymphoma were mixed small and large cell, and in Korea, where the incidence of extranodal and T-cell lymphoma is high, the usefulness of FNAC for the initial diagnosis of malignant lymphoma is limited. For a definitive diagnosis, biopsy is required.     

Transthoracic fine needle aspiration biopsy in pulmonary lesions. Updated results

An investigation was carried out on 271 patients who underwent transthoracic fine needle aspiration biopsy ( FNAB ) for suspected pulmonary lesions in a four-year period; 80% of them had a malignant tumor. The histologic control of the cytologic diagnoses made on the transthoracic FNAB was possible in over 50% of the cases. The sensitivity and predictive value for positive results were, respectively, 0.890 and 0.995, whereas the typing accuracy verified in 58 cases on the surgical specimen was 0.76. The comparison of the data obtained from the most recent case material with that of early observations confirmed the high sensitivity of transthoracic FNAB in the detection and characterization of malignant lesions in the lungs. The sensitivity was almost identical for primary tumors, 0.90, and metastatic disease, 0.88. Furthermore, over the years the data showed an improvement in the results due to the experience gained, the combined use of cytology and histology and the application of histochemical methods. More sophisticated methods, such as immunocytochemistry and electron microscopy, were essential to the final diagnosis in only a few cases.     

Fine needle aspiration biopsy of mixed medullary-follicular thyroid carcinoma. A report of two cases

BACKGROUND: Mixed differentiated thyroid carcinomas are rare tumors, difficult to recognize on fine needle aspiration biopsy (FNAB). Most cases are diagnosed only after histologic investigation. CASES: The cases entailed two cytologic samples and a thyroidectomy specimen. Two FNAB thyroidectomy specimens from a 60-year-old man presenting with a solitary thyroid nodule (case 1) were investigated. Both cytologic samples were referred as atypical, with a mixture of features indicating a proliferating follicular lesion but also containing some characteristics of medullary carcinoma. The serum calcitonin level was borderline. Surgery was recommended because of a suspicion of malignancy. The diagnosis of mixed medullary follicular carcinoma was established after a complex histologic investigation. The tumor was encapsulated, with partly microfollicular architecture. Immunohistochemistry was positive for both calcitonin and thyreoglobulin. Electron microscopy from the formol-paraffin block found neurosecretory granules in many cells. The patient was well one year after the operation. One FNAB and thyroidectomy specimen from a 47-year-old woman with long-treated lymphoplasmocellular thyroiditis (case 2) was investigated. The tumor in case 2 was diagnosed on FNAB as medullary carcinoma. Only after histologic and immunohistochemical investigation was mixed differentiation proven. CONCLUSION: Mixed differentiated thyroid tumors are a diagnostic challenge on fine needle aspiration. Irrespective of their rarity, they can be suspected if combined features are present. FNAB recognition of the medullary component in both cases was of crucial importance. Nevertheless, definitive diagnosis remains a histologic problem due to the necessity for topographic information.