Long-Term Efficacy of Ethanol Ablation as Treatment of Metastatic Lymph Nodes From Papillary Thyroid Carcinoma.

CONTEXT: Ethanol ablation (EA) is considered an alternative to surgery for metastatic lymph nodes from papillary thyroid carcinoma (PTC) in selected patients. OBJECTIVE: The aim of this study was to evaluate the long-term efficacy and safety of this treatment. DESIGN AND SETTING: Adult patients with PTC who had received EA in lymph node metastasis at a tertiary referral center, and were included in a published study from 2011, were invited to participate in this follow-up study. METHODS: Radiologic and medical history were reviewed. Ultrasound examination of the neck was performed by radiologists, and clinical examination was performed by an endocrine surgeon. Response was reported according to predefined criteria for satisfactory EA treatment. Adverse events associated with EA were evaluated. Cause of death was reported for deceased patients. RESULTS: From the 2011 study, 51 of 63 patients were included. Forty-four patients were reexamined (67/109 lesions) and 7 patients were deceased. Median follow-up time from primary surgery was 14.5 years. Median follow-up from the latest performed EA in the 2011 study was 11.3 years. Local control was permanently achieved in most patients (80%). Recurrence within an ablated node was registered in 13 metastases in 10 patients. Seven of these patients also had recurrent disease elsewhere in the neck. No major side effects were reported. CONCLUSION: EA is a minimally invasive procedure with a low risk of complications. Our data suggest that EA is a safe and efficient treatment, providing excellent results for a large group of patients in the long term.

Subacute thyroiditis after vaccination against SARS-CoV-2. / Subakutt tyreoiditt etter vaksinering mot SARS-CoV-2.

BACKGROUND: Subacute thyroiditis is a clinical condition usually seen 1-2 weeks after a viral infection in the upper respiratory tract, and has also been reported following infection with COVID-19. Cases of subacute thyroiditis following a seasonal influenza vaccination have been described, and recent case reports have reported clinical symptoms and signs typical of subacute thyroiditis following vaccination with mRNA SARS-CoV-2 vaccine. CASE PRESENTATION: A young, healthy female underwent surgery with left-side lobectomy for papillary thyroid carcinoma. Hashimoto's thyroiditis was revealed as an additional histological finding. Six days prior to complementary thyroidectomy of the right lobe the patient received mRNA SARS-CoV-2 vaccine. The histological slides showed features consistent with extensive subacute thyroiditis throughout the entire lobe. INTERPRETATION: As no other aetiology could account for the subacute thyroiditis, the vaccination against COVID-19 is seen as a plausible source.

Survival and Surgical Complications in Anaplastic Thyroid Cancer Patients After Completed Multimodal Treatment.

BACKGROUND/AIM: This study aimed to examine survival and surgical complications in patients with anaplastic thyroid cancer (ATC) after multimodal treatment. PATIENTS AND METHODS: Since 2002, the recommended treatment strategy for ATC at our centre has been hyperfractionated accelerated radiotherapy (HART) with high doses to the neck (64 Gy), combined with weekly doxorubicin, and surgery after 4-8 weeks, if feasible. RESULTS: Between 2002 and 2014, 14 patients completed HART and thyroid surgery. Eight patients had preoperative HART, and six postoperative HART. Median survival was 20 months (range=4-110 months) in all patients, 51 months (range=4-110 months) and 18.5 months (range=9-56 months) in the preoperative and postoperative HART groups, respectively. Six patients survived for more than two years, and four patients survived for more than five years. Seven patients had postoperative complications. CONCLUSION: In this series of selected patients, an improved survival after aggressive, multimodal treatment was observed. Preoperative HART may promote survival although complications may be more frequent.

Thyroid nodules - investigation and follow-up. / Knuter i tyreoidea ­ utredning og oppfølging.

Thyroid nodules are common. As a result of increased use of diagnostic imaging, more nodules are detected as incidental findings. The great majority of them are benign and need no treatment. Systematic ultrasonography performed by a skilled doctor, possibly combined with cytology sampling, will to a large extent determine which nodules require follow-up.

Sarcoidosis with cryptococcal infection apparently engaging only immune-privileged body compartments: a case report.

BACKGROUND: Infection with the Cryptococcus neoformans yeast fungus is largely restricted to patients with HIV, sarcoidosis or immunosuppressive therapies. In sarcoidosis, there is intense local immune response in granuloma lesions, coupled with a paradoxical systemic anergy. An analysis of cryptococcal infection in sarcoidosis may therefore shed light on whether opportunistic pathogens preferentially engage immune-privileged tissues. CASE PRESENTATION: A 54-year-old man was admitted to our hospital after 2 months with palpitations and activity-related presyncope. A chest X-ray was normal, electrocardiography showed type-II atrioventricular-block, and there was a tentative diagnosis of myocarditis. Computed tomography reported minor hilar lymph glands and multiple nodular lesions in the lungs. Magnetic resonance imaging showed oedema and nodular structures in the heart, and fibrosis and granulomas were found in endomyocardial biopsies. The diagnosis was revised to cardiac sarcoidosis, and prednisone was initiated. In parallel, positron-emission tomography had revealed a marked uptake in the right thyroid lobe, a thyroid lobectomy was then performed, and the pathology showed a BRAF-positive papillary thyroid carcinoma. Four days postoperatively the patient developed symptoms suggestive of meningoencephalitis. Cerebrospinal fluid and blood cultures yielded growth of C. neoformans. Fungal staining of the thyroid specimen revealed cryptococcal elements in the carcinoma and in granulomas close to the tumour. Notably, there was no evidence of cryptococci in the heart sarcoid sections or in the normal thyroid parenchyma. The patient was successfully treated with antifungal agents and at the 2-year follow-up there was no evidence of thyroid cancer relapse. CONCLUSION: This sarcoidosis patient had a remarkable clinic with evidence of cryptococcal infection only in body compartments commonly regarded to be immune-privileged. The findings suggest that an opportunistic and environmentally abundant pathogen, when infecting an immunocompromised host, primarily engages immunodeficient locations such as the brain, a tumour microenvironment and some forms of granuloma.

The Role of Calcitonin in Predicting the Extent of Surgery in Medullary Thyroid Carcinoma: A Nationwide Population-Based Study in Norway.

BACKGROUND: Preoperative predictors for the need of prophylactic lymph node dissection in the lateral neck have been studied in patients with medullary thyroid carcinoma (MTC). OBJECTIVES: To evaluate the ability of serum calcitonin to predict the extent of surgery needed in the lateral neck. METHODS: This retrospective population-based cohort study includes data from 94 of 139 patients with MTC surgically treated in Norway from 2003 to 2016. Patients were identified in the 4 regional centers treating MTC and by the Cancer Registry of Norway, and grouped according to calcitonin levels. In 58 patients without distant metastases or disease progression to the next tumor level (NPNL), data were compared in prognostic groups (N0-NPNL), (N1a-NPNL), and (N1b-NPNL). RESULTS: At calcitonin levels ≤500, 501-1,000, and >1,000 pmol/L, metastatic lymph nodes in the lateral neck were found in 16, 50, and 71% of the patients, respectively. In the prognostic groups, 19% of N0-NPNL patients had calcitonin >500 pmol/L and 17% of N1b-NPNL patients had calcitonin ≤500 pmol/L. In multivariate analysis, factors predicting biochemical cure and calcitonin level ≤500 pmol/L were no metastatic lymph nodes in the lateral neck (p = 0.030) and tumor diameter ≤20 mm (p < 0.001), respectively. Factors related to metastatic lymph nodes in the lateral neck were extrathyroidal extension (p = 0.007) and no biochemical cure (p = 0.028). CONCLUSIONS: Basal calcitonin cannot predict the need for prophylactic lateral lymph node dissection in patients with MTC. Further prospective, randomized studies are warranted.

Trends in Diagnostics, Surgical Treatment, and Prognostic Factors for Outcomes in Medullary Thyroid Carcinoma in Norway: A Nationwide Population-Based Study.

BACKGROUND: Medullary thyroid carcinoma (MTC) is rare. Nationwide population-based studies are important to evaluate its clinical course. OBJECTIVES: To describe all patients with MTC in Norway during 1994-2016 and compare time-related trends in diagnostics and surgical treatment, including prognostic factors for biochemical cure and disease-specific survival (DSS). METHODS: This retrospective population-based cohort study includes data for 228 out of 237 patients (96%) with MTC; 201 patients were surgically treated. Patients were identified in the 4 regional centers treating MTC and by the Cancer Registry of Norway. Data were collected from patients' files. Trends were compared over 2 study periods. RESULTS: MTC accounted for 4.2% of thyroid carcinomas. During the study periods, the incidence increased from 0.18 to 0.25: 100,000 per year, preoperative diagnostics improved with increased use of calcitonin, ultrasound, and fine-needle cytology (p = 0.010, p < 0,001, and p = 0.001), patients were diagnosed at an earlier tumor stage (p = 0.004), and more patients were cured (p = 0.002). Via multivariate analysis of patients with metastatic lymph nodes, independent prognostic factors for cure were: a low ratio of metastatic and total number of dissected lymph nodes (p = 0.021) and no extrathyroidal extension (p = 0.030). Independent prognostic factors for DSS were: no distant metastasis, a younger age, and a low ratio of metastatic and dissected lymph nodes (p = 0.005, p = 0.020, p = 0.022). CONCLUSIONS: Preoperative diagnostics have improved over time with increased therapeutic control. A low ratio of metastatic and dissected lymph nodes predicts better outcomes in patients with metastatic lymph nodes.

Anaplastic thyroid cancer and hyperfractionated accelerated radiotherapy (HART) with and without surgery.

Anaplastic carcinoma of the thyroid gland (ATC) is one of the most aggressive cancers in humans. With insufficient treatment, the disease most often leads to death in suffocation. From 2002, our treatment strategy has been hyperfractionated accelerated radiotherapy (HART) with high doses (64 Gy) to the neck, followed by surgery 4-8 weeks later if feasible, with the aim to gain control in the neck. After a pathology review, 51 patients were diagnosed with ATC in the period 2002-2014 in the south-east of Norway. Thirty-one received HART, and we present a study of these patients, with death in suffocation as the primary endpoint and survival as the second. No patients treated with HART died in suffocation. Six had a tracheostomy during their course of disease, of whom four were dependent on a tracheal cannula when they died. The best median survival, 19 months, was obtained in the 13 patients where both radiotherapy and surgery were possible as primary treatments. Only surgery came out as a prognostic factor for survival in multivariate analysis. Patients surviving more than 2 years were characterised by having surgery with R0 resection and no or small residual foci of ATC in the specimens. Stage 4C patients survived 3 months only.

A Nationwide Study of Multiple Endocrine Neoplasia Type 2A in Norway: Predictive and Prognostic Factors for the Clinical Course of Medullary Thyroid Carcinoma.

BACKGROUND: Multiple endocrine neoplasia type 2A (MEN 2A) is an autosomal dominant syndrome caused by activating germline mutations in the RET (REarranged during Transfection) proto-oncogene. MEN 2A has a strong (>95%) and age-dependent (5-25 years) clinical penetrance of medullary thyroid carcinoma (MTC). Several major studies have analyzed the predictive and prognostic factors for MEN 2A to find indicators that predict the optimal timing of prophylactic thyroidectomy. The aims of this study were to describe all known RET positive MEN 2A patients diagnosed in Norway and to evaluate the clinical course of MTC, as well as its predictive and prognostic factors. METHODS: This nationwide retrospective cohort study included data for 65 (14 index and 51 screening patients) out of a total of 67 MEN 2A patients with the RET gene mutation who were diagnosed in Norway since 1974. Data were collected by reviewing patient files. The variables analyzed were genotype, phenotype, preoperative basal calcitonin, age at thyroid surgery, central lymph node dissection and nodal status at primary surgery, number of surgical procedures, and biochemical cure. Of the 65 patients, 60 had undergone thyroid surgery. The median follow-up period was 9.9 years. The patients were divided into pre-RET-and RET-era, which included patients who had thyroid surgery before January 1, 1994, and after, respectively. RESULTS: In index and screening patients, MTC was found, respectively, in 100% and 45% of cases, central lymph node dissection at primary surgery was done for 64% and 52% of patients, and the median total number of surgical procedures was two (range 1-6) and one (range 1-4). At primary surgery, all patients (n = 13) with lymph node metastases had preoperative basal calcitonin levels ≥68 pg/mL, and all patients (n = 17) without central lymph node dissection and preoperative basal calcitonin <40 pg/mL were biochemically cured. Multivariate analysis showed that preoperative basal calcitonin was a significant predictive factor for MTC superior to age at thyroid surgery when analyzing the entire period (p = 0.009) and the RET-era separately (p = 0.021). Prognostic factors for biochemical cure were preoperative basal calcitonin, central lymph node dissection, and nodal status at primary surgery (p = 0.037, p = 0.002, and p = 0.005) when analyzing the entire period, but only nodal status at primary surgery when the RET-era was considered separately (p = 0.006). CONCLUSIONS: Preoperative basal calcitonin alone can serve as an indicator for optimal timing and the extent of thyroid surgery for MEN 2A patients that could be considered safe. The results are consistent with previously reported data.

Survey of 548 oncogenic fusion transcripts in thyroid tumors supports the importance of the already established thyroid fusions genes.

Neoplasms frequently present structural chromosomal aberrations that can alter the level of expression of a protein or to the expression of an aberrant chimeric protein. In the thyroid, the PAX8-PPARG fusion is present in the neoplastic lesions that have a follicular architecture-follicular thyroid carcinoma (FTC) and follicular variant of papillary thyroid carcinoma (FVPTC), and less frequently in follicular thyroid adenoma (FTA), while the presence of RET/PTC fusions are largely restricted to papillary thyroid carcinoma (PTC). The ability to detect fusion genes is relevant for a correct diagnosis and for therapy. We have developed a new fusion gene microarray-based approach for simultaneous analysis of all known and predicted fusion gene variants. We did a comprehensive screen for 548 known and putative fusion genes in 27 samples of thyroid tumors and three positive controls-one thyroid cancer cell line (TPC-1) and two PTCs with known CCDC6-RET (alias RET/PTC1) fusion gene, using this microarray. Within the thyroid tumors tested, only well known, previously reported fusion genes in thyroid oncology were identified. Our results reinforce the pathogenic role played by RET/PTC1, RET/PTC3, and PAX8-PPARG fusion genes in thyroid tumorigenesis.

The new molecular markers DDIT3, STT3A, ARG2 and FAM129A are not useful in diagnosing thyroid follicular tumors.

Preoperative characterization of thyroid follicular lesions is challenging. Fine-needle aspiration specimens cannot differentiate follicular carcinomas from benign follicular neoplasias. Recently, promising markers have been detected using modern molecular techniques. We conducted a retrospective study to confirm the usefulness of immunohistochemical staining for the protein markers, DDIT3, STT3A (ITM1), ARG2 and FAM129A (C1orf24) in separating benign and malignant thyroid follicular lesions. Formalin-fixed, paraffin-embedded thyroid tissue from 30 in-house cases (15 follicular carcinomas and 15 follicular adenomas), as well as 8 follicular carcinomas and 21 follicular adenomas on tissue microarray slides were stained immunohistochemically for DDIT3, STT3A, ARG2 and FAM129A expression. Control tissue consisted of thyroid parenchyma adjacent to the tumors and 11 separate cases of normal thyroid parenchyma. All in-house cases of follicular adenomas, follicular carcinomas and adjacent normal thyroid tissue showed positive immunostaining with anti-DDIT3 and anti-STT3A. Anti-ARG2 and anti-FAM129A polyclonal antibodies showed positive staining in 20 and 60% of in-house follicular adenomas, and 40 and 87% of in-house follicular carcinomas, respectively. Monoclonal anti-FAM129A demonstrated positive staining in 13 and 33% of in-house follicular adenomas and follicular carcinomas, respectively. Polyclonal anti-DDIT3, -STT3A and -FAM129A antibodies showed positive staining in all tissue microarray slides of follicular carcinoma and in 76, 85 and 81% of the follicular adenomas, respectively. Monoclonal anti-STT3A stained 81% of the follicular adenoma cores. Anti-ARG2 stained positive in 13% of follicular carcinomas and 10% of follicular adenomas on the tissue microarray slides. In conclusion, DDIT3, STT3A, ARG2 and FAM129A immunohistochemistry does not appear to be useful in the diagnosis of thyroid follicular neoplasias, as they do not reliably distinguish follicular thyroid carcinoma from follicular thyroid adenoma.

Efficacy of ultrasound-guided percutaneous ethanol injection treatment in patients with a limited number of metastatic cervical lymph nodes from papillary thyroid carcinoma.

CONTEXT: Repeated neck explorations can be a difficult task in patients with recurrent metastatic cervical lymph nodes from papillary thyroid carcinoma (PTC). OBJECTIVE: The aim of this retrospective study has been to assess the efficacy of ultrasound (US)-guided percutaneous ethanol injection (PEI) as treatment of metastatic cervical lymph nodes from PTC. MATERIALS AND METHODS: Sixty-nine patients who previously had undergone thyroidectomy for PTC were selected for inclusion. However, three patients were later excluded due to lack of follow-up. Lymph node status was determined by US-guided fine-needle aspiration biopsy and/or by raised levels of thyroglobulin in washouts from the cytological needle. Guided by US, 0.1-1.0 ml of 99.5% ethanol was injected into the metastatic lymph nodes. RESULTS: Three patients (eight metastatic lymph nodes in total) were reassigned to surgery due to progression (multiple new metastases), leaving 63 patients and 109 neck lymph nodes to be included. Mean observation time was 38.4 months (range, 3-72). A total of 101 of the 109 (93%) metastatic lymph nodes responded to PEI treatment, 92 (84%) completely and nine incompletely. Two did not respond, and four progressed. Two lymph nodes previously considered successfully treated showed evidence of malignancy during follow-up. No significant side effects were reported. CONCLUSION: US-guided PEI treatment of metastatic lymph nodes seems to be an excellent alternative to surgery in patients with a limited number of neck metastases from PTC. This procedure should replace "berry picking" surgery.

Fine-needle aspiration cytology of the thyroid gland: comparative analysis of experience at three hospitals.

Fine-needle cytology is an effective and accurate diagnostic method for the assessment of thyroid lesions. The aim of the present study was to evaluate the role of thyroid cytology at a tertiary where cytopathologists with experience in thyroid cytology participate in the procedure and compare it with results in two community hospitals lacking pathology departments and on-site cytopathologists. A total of 1,770 specimens were diagnosed between 1998 and 2003. Of these, 425 were from the two local hospitals. The fraction of unsatisfactory specimens was 24% for submitted specimens and 9.5% for those taken in the presence of a cytopathologist. The percentage of malignant specimens was 4.1% at the tertiary center compared with 2.2% of submitted cases. These data highlight the need to centralize thyroid fine needle cytology to specialized centers with experienced cytopathologists.

Quantitative analysis of integrin expression in effusions using flow cytometric immunophenotyping.

We have previously shown that flow cytometric (FCM) immunophenotyping is a useful adjunct to morphology, in the diagnosis of serous effusions. The objective of the present study was to evaluate the possible application of FCM to quantitative analysis of adhesion molecule expression in this clinical setting. Fresh frozen cells from 67 effusions underwent quantitative analysis of alphaV, alpha6, beta1, and beta3 integrin subunit expression, using FCM. Specimens were diagnosed as carcinoma (n = 48), reactive (n = 12), or malignant mesothelioma (MM; n = 7) using morphology and, in selected cases, immunocytochemistry prior to FCM analysis. Antibodies against established epithelial, lymphoid, and mesothelial cell epitopes (Ber-EP4, anti-epithelial membrane antigen; (EMA), anti-CD45, anti-CD14, and anti-CD15) completed the panel. Results (percentage of cells expressing the antigen) were analyzed for relationship with the morphologic diagnosis. Frequent expression of the alphaV, alpha6, and beta1 subunits was seen in all diagnostic groups, with significantly higher expression of the alpha6 subunit in MM (P = 0.029, Kruskal-Wallis H test). The beta3 integrin subunit was not detected in any of the specimens. Ber-EP4 and CD15 expression was significantly higher in carcinomas compared with reactive effusions and MM (P < 0.001 and P = 0.001, Kruskal-Wallis H test), and EMA expression was higher in carcinomas and MM, compared with reactive specimens (P < 0.001, Kruskal-Wallis H test). In conclusion, FCM is an efficient tool for quantitative analysis of adhesion molecules in effusions. The high alpha6 integrin subunit expression in MM suggests involvement of this receptor in tumor attachment to laminin. The frequent expression of the alphaV and beta1 subunits support attachment to fibronectin and vitronectin as the major ECM ligands in body cavities.

Risk markers of oral cancer in clinically normal mucosa as an aid in smoking cessation counseling.

PURPOSE: Quitting smoking may prevent oral cancer. Behavioral intervention to quit smoking may be more efficient if persons are assigned an individual risk of cancer. PATIENTS AND METHODS: In this prospective study, we provided counseling and behavioral intervention toward smoking cessation, supplemented by genetic analyses in clinically normal oral mucosa of heavy smokers. Measurement of serum cotinine was used to assess changes in smoking habits. RESULTS: In cytologic scrapings from 275 heavy smokers with clinically normal mucosa, we found tetraploidy in four and aneuploidy in 19 persons (23 of 275; 8%). Twenty one (91%) of 23 persons with aneuploidy had quit or reduced their smoking habits at the 3-month follow-up, 20 (87%) of 23 persons had done so at 12 months, and 21 (91%) of 23 persons had done so at 24 months. Fifty-one (20%) of the 252 persons without genetic changes in their mucosa had quit or reduced their tobacco habits at the 3-month follow-up, 23 (9%) had done so at 12 months, and 17 (7%) had done so at 24 months (P < .001). After 24 months, normalization of DNA content to diploidy was observed in two of four persons with tetraploid (50%), and in 11 of 19 persons (58%) with aneuploid scrapings. One patient developed an oral carcinoma in the floor of the mouth: this patient had an aneuploid scraping obtained 43 months earlier and developed a leukoplakia 28 months before the carcinoma. CONCLUSION: Risk markers of oral cancer are present in clinically normal mucosa of heavy smokers, and such findings enhance the adherence to smoking cessation on counseling. Cytogenetic aberrations may normalize after quitting smoking.

The role of flow cytometric immunophenotyping in improving the diagnostic accuracy in referred fine-needle aspiration specimens.

Flow cytometric (FCM) immunophenotyping has an important role in the diagnostic work up of fine-needle aspiration (FNA) specimens obtained from lymphoid lesions. The objective of the present study was to evaluate the feasibility of this method with respect to referred FNA specimens. One hundred and two FNA specimens referred to our laboratory for FCM analysis during the last 3 years were studied. Specimens were sent, accompanied by cytological smears, from 11 distant hospitals by ordinary mail. The evaluation of potential B-cell monoclonality, the main diagnostic issue to be resolved using FCM, was possible in 86 of these 102 cases. The remaining 16 samples could not be analyzed or adequately interpreted because of sparse or necrotic material. A monoclonal B-cell population was found in 17/86 satisfactory cases, of which 16 were histologically confirmed. Eight cases contained cells positive for the epithelial marker Ber-EP4 and were diagnosed accordingly as carcinomas. FCM analysis of specimens obtained with a clinical question of Hodgkin lymphoma or T-cell lymphomas did not yield definitive data. The time lapse between sampling and analysis (12-84 hr) did not affect the results. This probably was due to the fact that all aspirates were taken in Roswell Park Memorial Institute (RPMI) cell medium, supplemented with 50% fetal calf serum. In conclusion, this retrospective study establishes that it is possible, in the majority of cases, to refer FNA material for FCM immunophenotyping by mail, and that results regarding B-cell clonality in the case of small-cell lymphomas are reliable also after a transportation period of 3-4 days. Carcinoma may be similarly diagnosed and a diagnosis of lymphoma may be excluded in reactive proliferations. Cases with only a few atypical cells or specimens from patients suspected of having Hodgkin lymphoma or T-cell lymphomas are not suitable for analysis by FCM.

Fine-needle aspiration cytology vs. core biopsy in the diagnosis of breast lesions.

Fine-needle aspiration cytology (FNAC) is an established, highly accurate method for diagnosing breast lesions. However, in recent years there has been increased use of core biopsy (CB) in this setting. The aim of this study was to evaluate the accuracy of FNAC and compare the quality assessment parameters of FNAC and CB in palpable and nonpalpable breast lesions. Data regarding FNAC, CB, and excision biopsy (EB) diagnoses were retrieved from the archives of our department. A total of 4,367 FNAC samples from the years 1999-2001 was reviewed. Of these, corresponding histology results were available for 1,275 lesions, of which 1,248 were primary breast epithelial lesions (788 EB, 199 CB, 261 EB+CB). All cases were analyzed for sensitivity and specificity of FNAC. Cases with both FNAC and CB were compared and quality assessment parameters were calculated using the methodology detailed in the National Health Service Breast Screening Program guidelines. High specificity and sensitivity, as calculated for satisfactory specimens, were achieved with the use of both FNAC and CB. False-positive and false-negative diagnoses were seen in 7/404 (1.7%) and 45/635 (7.1%) of biopsy-proven specimens sampled by FNAC. The corresponding values for CB were 0% and 5.7%, respectively. Inadequate sampling (15.1%) with use of FNAC was particularly seen in collagenous lesions and in submitted specimens sampled by physicians lacking experience with the FNAC procedure. FNAC is a valuable method, although moderately less sensitive than CB. CB is the preferred method for preoperative diagnosis when sampling FNAC provides scarce material and suspicion of a fibrotic and collagenous lesion such as lobular carcinoma and radial scar arises. FNAC is most accurate when experienced cytologists are available and when immediate assessment by professionals is performed for evaluation of material adequacy, so that additional aspirations can be done when needed.