Cytologic features of metastatic papillary thyroid carcinoma in cervical lymph nodes

OBJECTIVE: To elucidate the cytologic characteristics of metastatic papillary thyroid carcinoma (PTC) in cervical lymph nodes and the differences in cervical lymph nodes from those of stage I (intrathyroidal) PTC. STUDY DESIGN: Forty-seven cases of papillary thyroid carcinoma with cervical lymph node metastasis (group A) and 38 cases of intrathyroidal papillary carcinoma (group B) were included in this study. Preoperative fine needle aspiration cytology (FNAC) examination was performed on enlarged cervical lymph nodes (47 cases, group A) and enlarged thyroid nodules (13 cases, group A, and 38 cases, group B). All the cases were surgically excised and pathologically verified. The cytologic smears were reviewed and analyzed. RESULTS: The cytologic characteristics of metastatic PTC in cervical lymph nodes displayed a higher frequency of foamy macrophages (51.1% vs. 26.3%) and a lower frequency of distinct cell borders (38.3% vs. 71.1%) than those of stage I PTC. Metastatic PTC in cervical lymph nodes also had a higher frequency of cystic degeneration (44.7% vs. 5.3%) than intrathyroidal lesions. In 1 of the 47 cases with lymph node metastasis, the aspirate contained macrophages but no tumor cells. CONCLUSION: FNAC was useful in the diagnosis of metastatic PTC in cervical lymph nodes. However, because cystic degeneration appeared frequently, FNAC combined with thyroid ultrasonography to find the primary lesion is necessary in this situation.     

Indications for surgery of thyroid cancer based on bioptate molecular examination

INTRODUCTION: In differentiated thyroid cancer (DTC) the differentiation between reactive and metastatic lymph nodes is difficult at the early stages of metastasis. The aim of the study was to assess the results of fine needle aspiration (FNA) samples examination by the use of RT-PCR for Tg mRNA. The special attention was directed to the evaluation of specificity of TgRNA estimation. MATERIAL AND METHODS: The group consisted of 193 DTC patients with suspicion of lymph node recurrence and at least one positive RT-PCR result. Thyroglobulin RT-PCR was conducted in residual material left after preparation of cytological smears from FNA specimens. Primer spanning exons 3-5 were used with 39 cycles of PCR. RNA isolation control and cDNA amplification were carried out using GAPDH starters. 308 lymph node biopsies were included. RESULTS: 246 positive results for Tg RNA were observed in the analyzed group, 71.1% confirmed by FNA. Among other 71 results, in which cytological examination did not correspond unequivocally to molecular findings, in 34 metastases were confirmed both by cytological and clinical examination. There were 11 patients operated due to the positive serial molecular examination only. In 10 (91%) of them DTC metastases were confirmed. So, the positive predictive value of the molecular result ranged between 75-89% and the negative one was 100%. CONCLUSIONS: In DTC patients RT-PCR Tg mRNA is helpful in qualification of suspicious lymph nodes to surgery in DTC patients. At the negative cytological finding, the positive molecular result constitutes an indication for early surgery.     

Lymph node metastases of papillary thyroid cancer in immunohistochemical and molecular examination--preliminary report

BACKGROUND: Total thyroidectomy with lymphadenectomy is the most typical operation in a case of papillary thyroid cancer. Range of lymph node resection still remains a matter of controversy. In some publications treatment of lymph node metastases doesn't affect survival, so only selective lymph node resection is the extended enough operation. The others remark that, local relapse- the worst prognostic factor, appears the most often in the lymph nodes, so they suggest more aggressive treatment. To solve that problem we try to find more sensitive methods to examine lymph nodes. AIM: To compare the results of detection lymph node metastases of papillary thyroid cancer by immunohistochemistry with the results of RT- PCR for thyroglobulin (Tg) mRNA. MATERIAL AND METHODS: Each of one hundred eighty four cervical lymph nodes obtained from 24 patients, operated in our Department was divided into 2 halves: one was used for conventional histopathology and immunohistochemistry, the other part was investigated by RT- PCR for Tg mRNA. Immunohistochemical staining for Tg was performed on formalin-fixed, paraffin-embedded sections with anti-Tg antibodies. RESULTS: According to routine, histopathological examination 8 (33.5%) patients had involved lymph nodes. One hundred correspondence of the results of immunohistochemistry and histopathology was observed. We obtained different results of examination of the lymph nodes in 6 (25%) patients. In four patients (16.7%) RT-PCR was more sensitive in detection of positive lymph nodes, in two patients (8.3%) it revealed less metastasized lymph nodes than immunohistochemistry. The remaining 18 patients didn't have any differences, fourteen (58.3%) of them had the negative lymph nodes and four (16.7%) had positive, the same lymph nodes in all examinations. Finally, according to RT-PCR 10 (41.7%) of the patients had metastasized lymph nodes. COCLUSION: Tg RT-PCR is a sensitive method of detection of papillary thyroid cancer cells and may help to detect the metastases of papillary thyroid cancer in regional lymph nodes.     

Cystic Lymph Nodes in the Lateral Neck As Indicators of Metastatic Papillary Thyroid Cancer

ObjectiveTo determine whether radiographic findings portend to metastatic disease in patients with papillary thyroid carcinoma (PTC) and whether cystic lymph node metastasis can be recognized by preoperative, ultrasound-guided fine-needle aspiration (FNA).MethodsWe performed a retrospective review of patients with cystic lymph nodes in the lateral neck identified on preoperative ultrasonography between March 1996 and December 2009. Factors examined included demographic information; stage; cytologic and final pathologic findings; and imaging characteristics including location, size, and presence of vascularity and calcifications. Time of cystic node identification in relationship to initial diagnosis was also recorded.ResultsThirty patients had cystic lymph nodes in the lateral neck on cervical ultrasonography during the study period. Among this group, 28 (93%) had PTC, 1 (3%) had papillary serous carcinoma of the ovary, and 1 (3%) had poorly differentiated thyroid cancer. Median age at initial cancer diagnosis was 41 years (range, 16-64 years). Twenty-one patients (70%) were women, and median lymph node size was 1.8 cm (range, 0.6-4.8 cm). Twenty-three patients (77%) had a solitary cystic lymph node, and the remainder had more than 1 cystic lymph node. Cystic lymph nodes were identified at initial presentation in 11 patients (37%), while cystic lymph nodes were discovered in 19 patients (63%) after the initial operation. FNA was performed on the cystic lymph nodes of 23 patients (77%). Cytologic findings were positive for metastatic disease in 18 of 23 patients (78%). Among the 5 of 23 patients with negative cytologic findings, thyroglobulin aspirate was obtained in 1 patient, confirming metastatic PTC. Final pathologic review after surgical resection of cystic lymph nodes with negative cytologic findings from FNA was consistent with metastatic disease in 4 of 5 patients (80%).ConclusionsIn patients with PTC, the presence of a cystic lymph node by ultrasonographic examination is highly suggestive of locally metastatic disease. Confirmation of metastatic PTC may sometimes be achieved with thyroglobulin aspirate from cystic lymph nodes when cytologic findings are negative. Clinicians should strongly consider surgical lymph node resection of cystic lymph nodes regardless of the preoperative cytologic findings by FNA. (Endocr Pract. 2011;17:240-244)     

Initial axillary staging of breast cancer using ultrasound‐guided fine needle aspiration: a liquid‐based cytology study

A. Schiettecatte, C. Bourgain, C. Breucq, N. Buls, V. De Wilde and J. de Mey
Initial axillary staging of breast cancer using ultrasound‐guided fine needle aspiration: a liquid‐based cytology study Objective: To evaluate the preoperative detection of axillary metastasis combining ultrasound (US)‐guided fine needle aspiration cytology (FNAC) and liquid‐based cytology (Surepath^®) to reduce sentinel node procedures. Methods: In total, 148 patients with clinically negative lymph nodes and no preoperative therapy were included. All patients underwent preoperative ultrasound of the axilla with FNAC if suspicious lymph nodes were found. Complete axillary lymph node dissection was performed at primary surgery when FNAC was positive. All other patients underwent a sentinel node procedure. Results: US‐guided FNAC of the axilla revealed metastasis in 34 (23.0%) of the 148 patients. These 34 patients were 53.1% of all patients (n = 64) with proven axillary lymph node involvement. In 66 patients (44.6%), both ultrasound and histopathology were negative. Overall sensitivity of US‐guided FNAC was 50.0%, specificity 100%, positive predictive value 100% and negative predictive value 70.2%. In T1 tumours, all patients referred for sentinel node procedure were node‐negative. The correlation between malignant FNAC and histopathology was 100%. US‐guided liquid‐based FNAC in patients with no clinically positive lymph nodes reduced the necessity for a sentinel node procedure by 23.0%. Conclusions: We advocate that US‐guided fine needle aspiration (FNA) combined with liquid‐based cytology of axillary lymph nodes should be included in the preoperative staging of breast cancer.     

Fine needle aspiration biopsy of neuroendocrine breast carcinoma metastatic to the thyroid. A case report

BACKGROUND: Tumors showing neuroendocrine differentiation arise in a wide range of organs, and metastatic neuroendocrine tumors may be difficult to differentiate from primary tumors. This report describes an unusual case of metastatic breast carcinoma with neuroendocrine differentiation that presented as a solitary thyroid nodule. The diagnosis was made by fine needle aspiration biopsy (FNAB). CASE: A 52-year-old woman presented with a thyroid nodule and bilateral enlarged supraclavicular fossa lymph nodes. FNAB revealed a neuroendocrine carcinoma. Further questioning revealed that the patient had had a breast carcinoma resected eight years previously. The diagnosis of metastatic neuroendocrine breast carcinoma was established by immunocytochemistry. The patient received antiestrogen therapy but subsequently developed skeletal metastases. CONCLUSION: Neuroendocrine carcinomas from various sites show similar cytologic features. In this case, a diagnosis of breast carcinoma metastatic to the thyroid was suggested by the clinical history and confirmed by FNAB with immunocytochemistry.     

Fine needle aspiration of follicular variant of papillary thyroid carcinoma presenting with pleural effusion: a case report

BACKGROUND: Malignant pleural effusion in association with mesothelioma, bronchogenic carcinoma and breast carcinoma is common, although less frequently reported with other malignancies. We report a follicular variant of papillary thyroid carcinoma (FVPTC), diagnosed on fine needle aspiration cytology (FNAC) of thyroid and lymph nodes and subsequently proved to have metastasized to the pleural cavity. CASE: A 46-year-old man presented with history of breathlessness, thyroid swelling, pleural effusion and bilateral cervical lymphadenopathy. FNAC of the thyroid swelling and the lymph nodes showed features of FVPTC with cervical lymph node metastasis. Pleural fluid examination led to suspicion of pleural involvement by metastatic deposit, confirmed by subsequent pleural biopsy. CONCLUSION: Thyroid malignancies presenting with pleural effusion are rare. In this case, although pleural fluid cytology suggested involvement of pleura, a definitive diagnosis could be rendered only on pleural biopsy. An ancillary aid, such as immunocytochemistry, could have helped establish pleural involvement on routine pleural fluid cytology alone. This case emphasizes the possible existence of rare cases of FVPTC that may be associated with a dismal prognosis. In our case, initial diagnosis of FVPTC could be made only on correlating FNA features of thyroid aspirate with those of lymph node aspirate.     

Diagnostic value of needle aspiration cytology in the assessment of palpable axillary lymph nodes. A study of 336 cases

OBJECTIVE: To evaluate the diagnostic value of needle aspiration cytology (NAC) in the assessment of palpable axillary lymph nodes and determine whether ancillary procedures can be useful in enhancing the diagnosis. STUDY DESIGN: The material was analyzed in 336 cases with enlarged axillary lymph nodes in which NAC were performed by the conventional method. In all cases cytologic examination was done on site after staining the smears with the Papanicolaou method. In addition, air-dried smears, fixed smears, filter preparations from needle washings and cell blocks were studied. The NAC diagnosis was supported by examining cell blocks, which showed the reliability of histologic architecture; further support was obtained with tissue biopsy and/or comparison with the primary tumor in some of the cases. RESULTS: Twelve cases were diagnosed as inflammatory lesions, and 64 were unsatisfactory due to scanty/acellular samples (despite 2-3 repeat samplings). However, in 6 of these, malignant tumors were later found on a biopsy done due to persistent and continued enlargement of an axillary lymph node or nodes. One hundred twenty-two cases were regarded as negative (normal cellular elements, n = 52; reactive elements, n = 70), and 4 cases were suspicious for malignancy. In 124 cases a variety of metastatic tumors were diagnosed (breast, n = 63; melanoma, n = 22; others, n = 39), and in 10 cases a diagnosis of lymphoma was made. CONCLUSION: NAC of palpable axillary lymph nodes as a first-line of investigation is a cost-effective procedure and is not only useful in the diagnosis of various lesions but can also help in deciding on management. Also, histologic architecture from cell blocks can be correlated with cytology, and such material can be used for histochemical and immunomarker studies.     

The diagnostic value of fine needle aspiration cytology (FNAC) in the assessment of palpable supraclavicular lymph nodes: a study of 218 cases

The aim of this study was to evaluate the diagnostic value of fine needle aspiration cytology (FNAC) in the assessment of palpable supraclavicular lymph nodes. The material was analysed in 218 cases with enlarged supraclavicular lymph nodes in which FNAC was performed by the conventional method. In all cases cytological examination was performed on-site after staining the smears by the Papanicolaou method. In addition, air-dried smears, fixed smears, filter preparations from needle washings and cell blocks were studied. The FNAC diagnosis was supported by examining cell blocks which added the reliability of histological architecture; further support was obtained by tissue biopsy and/or comparison with the primary tumour in some of the cases. Eleven cases were diagnosed as inflammatory lesions and 41 cases were unsatisfactory because of scanty/acellular samples (despite two to three repeat samplings). However, in five of these, malignant tumours were later found on biopsy, which was done for persistent enlargement of the supraclavicular lymph node(s). Fifty-three cases were diagnosed as negative for malignancy (normal cellular elements, n=15; reactive elements, n=38) and 12 cases were suspicious of malignancy. In 11 cases a diagnosis of lymphoma was made on histology and in 90 cases metastatic tumours were diagnosed. The overall sensitivity was 92.7%, specificity 98.5%, positive predictive value 97.3% and the negative predictive value was 94.8%. Based on our study we feel that FNAC of palpable supraclavicular lymph nodes as a first line of investigation is a cost-effective procedure and is not only useful in the diagnosis of various lesions but can also help in deciding on appropriate management. Furthermore, the histological architecture from cell blocks can be correlated with cytology, and such material can be used for appropriate histochemical and immunomarker studies, which can be useful in enhancing the diagnosis.     

The potential value of the demonstration of thyroglobulin by immunoperoxidase techniques in fine needle aspiration cytology

The peroxidase-antiperoxidase method for the demonstration of thyroglobulin was performed on 30 fine needle aspiration smears. All of the benign thyroid lesions plus the papillary and follicular carcinomas of the thyroid were positive for thyroglobulin. Two cases of metastatic thyroid carcinoma in lymph nodes were also positive. Medullary carcinoma of the thyroid and ten control smears from various other tissues were negative. This proves the sensitivity and the specificity of the method, which may be used in routine cytology and may add to the accuracy of diagnosing metastatic tumors suspected of being of thyroid origin. The intranuclear cytoplasmic vacuoles in papillary carcinoma of the thyroid were negative for thyroglobulin. This unexpected finding is demonstrated, and a possible explanation is offered.     

On-levothyroxine measurement of thyroglobulin is not a reliable test for the follow-up of patients at high risk for remnant/recurrent differentiated thyroid carcinoma

INTRODUCTION: At present the most widely accepted tool for follow-up management of differentiated thyroid cancer (DTC) patients is serum thyroglobulin (Tg) measurement. It is not uncommon for the serum Tg level to be measured while the patient is taking thyroid hormones (on-treatment Tg measurement). The purpose of the study was to evaluate the accuracy of on-treatment measurement of serum Tg in detecting remnant/recurrent or metastatic disease in high-risk DTC patients. MATERIAL AND METHODS: We retrospectively analysed the medical records of 26 high-risk DTC patients and compared the on-treatment and off-treatment Tg levels of these patients. All patients were anti-Tg negative. Using off-treatment measurement of Tg as the gold standard, the results of on-treatment measurement of Tg in the diagnosis of remnant/recurrent disease were analysed for sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV). RESULTS: The median serum Tg level under thyroid hormone suppressive therapy (on-treatment Tg) was 16.5 ng/ml and after withdrawal of thyroid hormone suppressive therapy (off-treatment Tg) was 95.0 ng/ml (P value = 0.001). In 6 patients (23%) the on-treatment Tg level missed the recurrence of the disease. Regarding the off-treatment Tg as the gold standard, the sensitivity, specificity, PPV and NPV of the on-treatment Tg measurement were 72.7%, 100%, 100%, and 40% respectively. CONCLUSION: Normal serum Tg level without TSH-stimulation (on-treatment) is not diagnostically reliable in the follow-up of DTC patients with a high probability of residual/recurrent or metastatic disease.     

Ultrasound-guided fine needle aspiration cytology in the diagnosis and management of thyroid nodules

OBJECTIVE: To examine the accuracy of fine needle aspiration cytology (FNAC) in the diagnosis of thyroid nodules and compare the inadequacy rates for ultrasound-guided and freehand FNAC. METHODS: A retrospective study of 434 patients with thyroid nodules who underwent diagnostic FNAC over a 2-year period. Cytological diagnoses have been compared with the histological assessment of resection specimens in 69 cases. RESULTS: The inadequacy rate was significantly lower from ultrasound guided FNAC (24/373 cases, 6.4%) than from freehand FNAC (8/61 cases, 13.1%) (P = 0.043). Seventy-six percentage of patients had a non-neoplastic cytological diagnosis and, after multidisciplinary review, the patients were reassured and assigned to clinical follow-up. Sixty-seven patients had a resection for cytological appearances consistent with non-neoplastic disease (n = 34), suspicious of follicular neoplasia (n = 23), or suspicious of malignancy (n = 10), and two patients had resections following inadequate cytology with ultrasound appearances suspicious of a neoplasm. The overall accuracy of FNAC analysis for malignancy was 97.0%, with sensitivity 83.3%, specificity 98.0%, positive predictive value 71.4% and negative predictive value 98.4%. The overall accuracy of FNAC analysis for the prediction of neoplasia was 97.5%, with sensitivity 80.5%, specificity 97.8%, positive predictive value 89.2% and negative predictive value 95.9%. Difficulties in cytological diagnosis were associated with lymphoid infiltrates and with degenerative changes in follicular adenomas. CONCLUSION: Ultrasound-guided FNAC has a significantly lower yield of inadequate aspirates than palpable FNAC. The ability of FNAC to predict neoplasia in 89% patients and to exclude neoplasia in 95.9% patients makes an important contribution to the multidisciplinary assessment of patients.     

Lymphocytic Thyroiditis is Associated with Increased Number of Benign Cervical Nodes and Fewer Central Neck Compartment Metastatic Lymph Nodes in Patients with Differentiated Thyroid Cancer

Objective: Whether or not autoimmune thyroid disease influences the progression of differentiated thyroid cancer (DTC) remains controversial. Findings of previous studies are influenced by lead time bias and/or procedure bias selection. These biases can be reduced by studying a single-institution patient population that underwent a similar extent of surgical resection.Methods: From a cohort of 660 patients with DTC who underwent thyroidectomy, we retrospectively studied 357 patients who underwent total thyroidectomy and central compartment node dissection (CCND) for DTC between 2003 and 2013.Results: Forty-one percent (140/345) of study patients had lymphocytic thyroiditis (LT), and 30% (91/301) had serum positive for thyroglobulin antibody (TgAb). LT was reported in 78% of the TgAb-positive cases. Sixty percent (213/357) of cases had metastatic thyroid carcinoma in 1 or more neck lymph nodes (55% [198/357] central compartment, and 22% [77/356] lateral compartment). Patients with LT had fewer metastatic cervical lymph nodes than those with no LT (2.7 ± 4.7 vs 3.5 ± 4.8, respectively, P = .0285). Patients with positive TgAb and thyroiditis had a larger number of benign cervical lymph nodes removed than those with negative TgAb or no LT. No significant difference was observed in age, tumor size, multifocality, extrathyroidal extension, vascular invasion, or frequency of cervical lymph node metastasis between TgAb-negative and -positive cases or between cases with and without LT.Conclusion: Lymphocytic thyroiditis is associated with fewer central neck compartment metastatic lymph nodes and a larger number of excised reactive benign cervical lymph nodes. Whether this association indicates a protective role of thyroid autoimmunity in lymph node spreading remains unclear.Abbreviations:CCND = central compartment node dissectionDTC = differentiated thyroid cancerHT = Hashimoto thyroiditisLT = lymphocytic thyroiditisTgAb = thyroglobulin antibodyTPO = thyroid peroxidase     

The utility of sentinel lymph node biopsy in head and neck melanoma in the pediatric population

Intraoperative lymph node mapping and sentinel lymph node biopsy have proven beneficial techniques in staging adult patients with melanoma of the head and neck, where there is great variability in lymphatic drainage. This technique has also been applied to pediatric patients with truncal cutaneous melanomas in an effort to determine nodal status without the morbidity associated with complete lymph node dissection. Nevertheless, the utility of sentinel lymph node biopsy in head and neck melanoma in the pediatric population has not been established. The objective of the authors' study was to determine the clinical utility of intraoperative lymph node mapping and sentinel lymph node biopsy of head and neck melanoma in the pediatric population. The authors reviewed the records of seven pediatric patients with head and neck melanoma or borderline melanocytic proliferations of unknown biologic potential who underwent intraoperative lymph node mapping and sentinel lymph node biopsy between 1998 and 2001. All sentinel lymph node specimens were examined by a melanoma dermatopathologist for the presence of metastatic melanoma. The mean operative time for each case was 3 hours, 8 minutes (range, 2 hours, 15 minutes to 3 hours, 50 minutes). All seven pediatric patients who underwent extirpation of a primary head and neck melanoma and preoperative lymphoscintigraphy had unique and identifiable basins of drainage to regional nodal groups. Four of seven patients had at least one positive sentinel lymph node. Overall, five of 19 sentinel nodes (26 percent) resected had evidence of metastatic melanoma. Of the patients with positive sentinel lymph nodes, two of the primary lesions were diagnosed as melanoma while two were initially considered atypical melanocytic proliferations of uncertain biologic potential with melanoma in the differential diagnosis. Sentinel lymph nodes in pediatric patients with melanoma of the head and neck can be successfully mapped and biopsied, as in adult patients. In addition, this procedure can provide critical diagnostic information for those pediatric patients with diagnostically challenging, controversial, or borderline melanocytic lesions.     

Fine needle aspiration cytodiagnosis of clinically suspected tuberculosis in tissue enlargements

A retrospective study of the use of fine needle aspiration (FNA) cytology to confirm a clinical suspicion of tuberculosis in tissue enlargements was performed, using 70 cases. The criteria required to make an FNA cytodiagnosis of tuberculosis were reassessed, and the sensitivity and predictive value of cytology for diagnosing such aspirates was determined. All but 2 of the 70 aspirates contained adequate cellularity. The adequate samples were diagnosed as 40 cases of caseating tuberculosis, 11 cases of noncaseating tuberculosis and 17 cases of acute necrotizing granulomatous inflammation suspicious for tuberculosis. Subsequent histologic study verified the cytologic diagnosis in 27 of 27 biopsied caseating lesions, 4 of 7 biopsied noncaseating cases and 5 of 8 necrotizing cases. The six cases with a false-positive cytodiagnosis of tuberculosis were histologically diagnosed as one Lennert's lymphoma, two reactive lymph nodes and three necrotizing metastatic carcinomas. The sensitivity of FNA cytology for the diagnosis of tuberculosis was 100%, with the predictive value of a positive result being 88%. The findings in this study emphasize that all criteria for the diagnosis of tuberculosis in FNA samples must be utilized and that particular caution should be exercised in making a diagnosis of acute necrotizing tuberculosis.     

The Diagnostic Value of Calcitonin Measurement in Wash-out Fluid from Fine-Needle Aspiration of Thyroid Nodules in the Diagnosis of Medullary Thyroid Cancer

ObjectiveThe diagnostic value of calcitonin measurement in fine-needle aspiration biopsy (FNAB) washout fluid (Ct-FNAB) for medullary thyroid cancer (MTC) remains to be determined. This prospective study aimed to assess the diagnostic value of Ct-FNAB in thyroid nodules in comparison with basal serum calcitonin (Ct), pentagas- trin-stimulated Ct (Pg-sCt), and cytology.MethodsAmong patients with goiter addressed with US-FNAB who had an initial clinical suggestion for thyroidectomy, 27 patients with thyroid nodule/s (n = 60) and normal, borderline, or increased Ct fulfilled the criteria for thyroidectomy. All 27 patients (enrolled according to exclusion/inclusion criteria) underwent ultrasonography (US), Ct, Pg-sCt, US-assisted FNAB of each patient’s nodule for both cytology, and Ct-FNAB before thyroidectomy.ResultsCt-FNAB always resulted in >1,000 pg/mL in MTC nodules at histology. For values between 36 and pg/mL, MTCs and nodular or micronodular C-cell hyperplasia (CCH) results overlapped. Most of the nodules without MTC and/or CCH had Ct-FNAB <17 pg/mL. Ct-FNAB diagnostic power was superior to and similar to other diagnostic procedures (Ct, Pg-sCt, and cytology) in identifying both MTC and CCH, and MTC alone, respectively.ConclusionThe diagnostic power of Ct-FNAB is valuable compared with other routine procedures. Ct-FNAB is highly reliable for the early detection and accurate localization of MTC in thyroid nodules, but it does not differentiate between MTC and CCH. Ct-FNAB is an extremely valuable diagnostic tool, especially considering that other diagnostic procedures do not provide a definitive diagnosis, and it can be included in the clinical work-up of thyroid nodules when MTC is suspected. (Endocr Pract. 2013;19:769-779)     

Lymphatic mapping and sentinel lymph node biopsy in patients with melanoma of the lower extremity

Lymphatic mapping and sentinel lymph node biopsy is a new technique used in the surgical treatment of patients with malignant melanoma. The purpose of this study was to evaluate the results of this approach for patients with melanoma of the lower extremity. Between May of 1994 and June of 1997 at the H. Lee Moffitt Cancer Center and Research Institute, 85 consecutive patients with clinical stage I and II melanoma of the lower extremity underwent lymphatic mapping and sentinel lymph node biopsy. These nodes were identified in all 85 patients by intraoperative lymphatic mapping with both radiolymphoscintigraphy and a vital blue dye injection. Eleven patients (12.9 percent) had histologically positive sentinel lymph nodes, and 10 patients underwent inguinal complete lymph node dissections. All 10 patients had no further histologically positive lymph nodes confirmed by subsequent complete dissection. Among 74 patients with histologically negative sentinel lymph nodes, only 2 patients (2.7 percent) developed inguinal nodal metastases during a mean follow-up period of 21.8 months (range, 13.5 to 58.3 months). The sensitivity of lymphatic mapping and sentinel lymph node biopsy in this series was 100 percent and the specificity was 97.3 percent. Therefore, we conclude that the use of lymphatic mapping and sentinel lymph node biopsy can accurately stage patients with melanoma of the lower extremity and provide a rational surgical approach for these patients.     

BRAF Mutation Analysis of Fine-Needle Aspiration Biopsies of Papillary Thyroid Carcinoma: Impact on Diagnosis and Prognosis

Objective: The BRAF V600E mutation has been associated with aggressive disease in papillary thyroid carcinoma (PTC). Molecular testing has been proposed as a useful adjunct to cytology in the diagnosis of malignancy and for tailoring clinical management. The aims of our study were to evaluate the BRAF mutational status using archived fine-needle aspiration biopsy (FNAB) material from patients with long-term follow-up and to correlate it with the original cytology diagnosis, clinicopathological stage at surgery, and prognosis. Study Design: FNAB material from 52 cases of PTC, with a mean follow-up of 8.4 years, was used in this study. DNA was extracted from archival cytology slides. Mutation analysis was performed by standard sequencing and locked nucleic acid-PCR/sequencing. Results: The BRAF V600E mutation was present in 46% of cases, but it was absent in all FNABs diagnosed originally as atypical and in 14 of 17 suspicious cases. Recurrence was significantly more frequent (p = 0.006) in cases with BRAF mutations and 54% of these cases presented with stage 2 or higher. Conclusion: The BRAF V600E mutation is associated with a higher pathological stage at surgery and a higher rate of recurrence. BRAF mutation analysis did not provide a significant increase in the accuracy of thyroid FNABs diagnosed as suspicious or atypical in our institution.     

ProGRP as a Novel Biomarker for the Differential Diagnosis of Medullary Thyroid Carcinoma in Patients with Thyroid Nodules

Objective: To investigate the release of progastrin-releasing peptide (ProGRP) in patients with thyroid nodules and the value of ProGRP in fine-needle aspirate washout fluid (FNA-ProGRP) in the differential diagnosis between medullary thyroid carcinoma (MTC) and non-MTC thyroid nodules.Methods: We investigated 2,446 healthy persons and 212 patients with 235 thyroid nodules. They were classified into healthy, nodular goiter, chronic thyroiditis, thyroid follicular neoplasm, papillary thyroid carcinoma, follicular thyroid carcinoma, and medullary thyroid carcinoma. The serum ProGRP and FNA-ProGRP were measured.Results: The serum ProGRP median concentration in MTC was 124.40 pg/mL, significantly higher than in other groups. The cutoff value of serum ProGRP was 68.30 pg/mL, leading to 53.85% sensitivity, 96.98% specificity, and 0.51 kappa value in MTC. The FNA-ProGRP median concentration in MTC nodules was 2,096.00 pg/mL, significantly higher than in other groups. A receiver operating characteristic analysis of MTC nodules and non-MTC nodules indicated that the cutoff value was 22.77 pg/mL, leading to 94.12% sensitivity, 98.27% specificity, and 0.85 kappa value.Conclusion: FNA-ProGRP measurement could be served as an ancillary method for the differential diagnosis between MTC and non-MTC thyroid nodules.Abbreviations: CEA = carcinoembryonic antigen; CT = calcitonin; FNAC = fine-needle aspiration cytology; FNA-CT = calcitonin in fine-needle aspirate washout fluid; FNA-ProGRP = ProGRP in fine-needle aspirate washout fluid; MTC = medullary thyroid carcinoma; ProGRP = progastrin-releasing peptide; SCLC = small-cell lung cancer; TM = tumor marker     

The endoscopic diagnosis of gastroesophageal malignancy. A cytologic review

Cytologic reports were compared to final diagnoses for 1,157 gastroesophageal samples from an eight-year period in order to evaluate the diagnostic accuracy of endoscopic cytology and to determine the significance of a "suspicious" cytologic report. In the subgroup of patients with adenocarcinoma evaluated by paired endoscopic biopsy and cytology, the relative and combined sensitivities of the sampling methods were studied. Cytologic examination was reported as positive or suspicious in 85% of 229 cases of malignancy. There were three false-positive diagnoses of squamous-cell carcinoma of the esophagus, representing 0.3% of all submitted samples. Suspicious cytologic reports were issued in 5% of all cases. The majority (63%) of patients with a suspicious cytologic report had a final diagnosis of malignancy, with gastric adenocarcinoma present in almost half of the cases. Adenocarcinoma was diagnosed in 168 of the patients. Combined endoscopic biopsy and cytology was more sensitive (96%) than biopsy alone (90%) in making the initial diagnosis. Cytology may be of particular value in the diagnosis of gastroesophageal malignancy when the lesions are small and superficial or where stricture precludes adequate biopsy. Regardless of the biopsy findings, patients with "suspicious" cytologic reports require careful reevaluation since a high percentage of those cases in our series were subsequently verified as having malignancy.