Evaluation of indeterminate thyroid cytology by second-opinion diagnosis or repeat fine-needle aspiration: which is the best approach?

OBJECTIVE: This study investigated a published series evaluating the role of second-opinion diagnosis (SOD) or repeat fine-needle aspiration cytology (RFNA) for indeterminate thyroid aspirates. STUDY DESIGN: Twenty-three studies were selected and the following parameters were analyzed: disagreement between SOD or RFNA and the original diagnosis (OD), reclassification of OD according to the Bethesda system for reporting thyroid cytopathology, the rate of definitive diagnosis and the diagnostic performance of SOD and RFNA. RESULTS: 7,154 thyroid FNAs were retrieved from 9 studies that investigated the role of SOD, including 1,048 (14.6%) cases originally reported as indeterminate. The 14 studies that analyzed the role of thyroid RFNA comprised 67,581 FNAs and included 7,246 (10.7%) indeterminate cases. A definitive diagnosis was achieved by SOD in 450 cases (42.9%) and RFNA in 1,645 cases (57.2%, p=0.0001). Based on cases with histological follow-up, SOD demonstrated significantly higher rates of positive predictive value and accuracy than RFNA (55.8 vs. 37.7%, p=0.0001; 67.4 vs. 56.0%, p=0.0034, respectively). CONCLUSIONS: Both SOD and RFNA demonstrated an improvement in the diagnosis of initially indeterminate thyroid FNAs. RFNA achieved a definitive diagnosis for the majority of indeterminate cases. Regarding histological follow-up, SOD was shown to be more accurate than RFNA.

The basal epithelial marker P-cadherin associates with breast cancer cell populations harboring a glycolytic and acid-resistant phenotype.

BACKGROUND: Cancer stem cells are hypoxia-resistant and present a preponderant glycolytic metabolism. These characteristics are also found in basal-like breast carcinomas (BLBC), which show increased expression of cancer stem cell markers.Recently, we demonstrated that P-cadherin, a biomarker of BLBC and a poor prognostic factor in this disease, mediates stem-like properties and resistance to radiation therapy. Thus, the aim of the present study was to evaluate if P-cadherin expression was associated to breast cancer cell populations with an adapted phenotype to hypoxia. METHODS: Immunohistochemistry was performed to address the expression of P-cadherin, hypoxic, glycolytic and acid-resistance biomarkers in primary human breast carcinomas. In vitro studies were performed using basal-like breast cancer cell lines. qRT-PCR, FACS analysis, western blotting and confocal microscopy were used to assess the expression of P-cadherin after HIF-1α stabilization, achieved by CoCl2 treatment. siRNA-mediated knockdown was used to silence the expression of several targets and qRT-PCR was employed to evaluate the effects of P-cadherin on HIF-1α signaling. P-cadherin high and low breast cancer cell populations were sorted by FACS and levels of GLUT1 and CAIX were assessed by FACS and western blotting. Mammosphere forming efficiency was used to determine the stem cell activity after specific siRNA-mediated knockdown, further confirmed by western blotting. RESULTS: We demonstrated that P-cadherin overexpression was significantly associated with the expression of HIF-1α, GLUT1, CAIX, MCT1 and CD147 in human breast carcinomas. In vitro, we showed that HIF-1α stabilization was accompanied by increased membrane expression of P-cadherin and that P-cadherin silencing led to a decrease of the mRNA levels of GLUT1 and CAIX. We also found that the cell fractions harboring high levels of P-cadherin were the same exhibiting more GLUT1 and CAIX expression. Finally, we showed that P-cadherin silencing significantly decreases the mammosphere forming efficiency in the same range as the silencing of HIF-1α, CAIX or GLUT1, validating that all these markers are being expressed by the same breast cancer stem cell population. CONCLUSIONS: Our results establish a link between aberrant P-cadherin expression and hypoxic, glycolytic and acid-resistant breast cancer cells, suggesting a possible role for this marker in cancer cell metabolism.

P-cadherin functional role is dependent on E-cadherin cellular context: a proof of concept using the breast cancer model.

P-cadherin overexpression is associated with worse breast cancer survival, being a poor prognostic marker as well as a putative therapeutic target for the aggressive triple-negative and basal-like carcinomas (TNBCs). Previously, we have shown that P-cadherin promotes breast cancer invasion of cells where membrane E-cadherin was maintained; however, it suppresses invasion in models without endogenous cadherins, like melanomas. Here, we investigated if P-cadherin expression would interfere with the normal adhesion complex and which were the cellular/molecular consequences, constituting, in this way, a new mechanism by which E-cadherin invasive-suppressor function was disrupted. Using breast TNBC models, we demonstrated, for the first time, that P-cadherin co-localizes with E-cadherin, promoting cell invasion due to the disruption caused in the interaction between E-cadherin and cytoplasmic catenins. P-cadherin also induces cell migration and survival, modifying the expression profile of cells expressing wild-type E-cadherin and contributing to alter their cellular behaviour. Additionally, E- and P-cadherin co-expressing cells significantly enhanced in vivo tumour growth, compared with cells expressing only E- or only P-cadherin. Finally, we still found that co-expression of both molecules was significantly correlated with high-grade breast carcinomas, biologically aggressive, and with poor patient survival, being a strong prognostic factor in this disease. Our results show a role for E- and P-cadherin co-expression in breast cancer progression and highlight the potential benefit of targeting P-cadherin in the aggressive tumours expressing high levels of this protein.

Liquid-based cytology in fine-needle aspiration of breast lesions: a review.

OBJECTIVE: Fine-needle aspiration (FNA) is a safe and cost-effective technique for the diagnosis of breast lesions, especially when correlated with clinical and imaging studies. However, the success of breast FNA is highly dependent on the adequate preparation of cytological conventional smears (CS). The liquid-based cytology (LBC) technique consists of an automated method for preparing thin-layer cytological samples from cell suspensions collected in alcohol-based preservative. LBC is designed to improve CS by avoiding limiting factors such as obscuring material, air-drying and smearing artifacts. STUDY DESIGN: We performed a review of the published literature about LBC applied to breast FNA. RESULTS: LBC preparations of breast aspirates demonstrated better cellular preservation, less cell overlapping and elimination of blood and excessive inflammation compared to CS. Conversely, alterations in architecture and cell morphology as well as loss of myoepithelial cells and stromal elements have been described in LBC specimens, requiring training before applying this technique for diagnosis. Studies have shown a similar accuracy between LBC and CS for the diagnosis of breast lesions. LBC also permits the use of residual material for ancillary tests, which is an important advantage compared to CS. CONCLUSIONS: LBC can be safely applied to breast FNA, showing a similar diagnostic accuracy to CS.

Analysis of nondiagnostic results in a large series of thyroid fine-needle aspiration cytology performed over 9 years in a single center.

OBJECTIVE: Thyroid fine-needle aspiration cytology (FNAC) is the most valuable, cost-effective and accurate method for the evaluation of patients with thyroid nodules. One of its limitations is that up to 20% of results are nondiagnostic or unsatisfactory. The aim of this study was to analyze the number of thyroid FNAC specimens with nondiagnostic results obtained on an outpatient basis and how many of these had to be repeated according to their results. STUDY DESIGN: This was a retrospective analysis of diagnostic reports of nondiagnostic thyroid FNAC specimens obtained between 1 January 2004 and 31 December 2012 which were retrieved by means of a computerized search. The FNAC results and the age and sex of the patients were collected. RESULTS: From a total of 15,292 thyroid FNAC specimens, 6.8% (n = 1,033) corresponded to nondiagnostic cases. Eligible diagnostic reports for analysis included 877 cases (106 were repetitions of previous nondiagnostic FNAC). After an initial nondiagnostic finding for 771 FNAC smears, 29.5% (n = 225) were repeated with the following results: 43.6% insufficient, 49.3% benign, 6.2% follicular neoplasm, 0.4% suspicious for malignancy and 0.4% malignant. Twenty-two patients underwent a second repeated FNAC. Here the findings were: 36.4% insufficient, 59.1% benign, 4.5% follicular neoplasm, 0.0% suspicious for malignancy and 0.0% malignant. CONCLUSIONS: There was a low rate of repeated FNAC among the group of nondiagnostic cases. With repeated FNAC, the rate of nondiagnostic cases and the number of results that potentially demand surgery diminish.

Detection of common and less frequent EGFR mutations in cytological samples of lung cancer.

OBJECTIVE: Lung cancer represents the leading cause of cancer death. EGFR mutations, detected in 10-40% of lung adenocarcinomas, are an essential key to therapeutic management. EGFR-activated mutations comprise mainly deletions in exon 19 and point mutations in exon 21. Although histology is the traditional method of detection, we investigated the role of cytology in EGFR mutations. STUDY DESIGN: A total of 774 lung cancers were studied for EGFR mutations (676 histological and 98 cytological samples), including 424 adenocarcinomas, 326 non-small cell lung carcinomas not otherwise specified, and 24 squamous cell carcinomas. RESULTS: We had a total of 164 (21.2%) cases of mutations. Common mutations were short in-frame deletions in exon 19 (53.7%) and single-nucleotide substitutions in exon 21 (34.1%); less frequent mutations included single-nucleotide substitutions in exon 18 (3.7%) and in-frame insertions/deletions in exon 20 (8.5%). Histologically, EGFR mutations in exons 19 and 21 occurred in 19.4% and in exons 18 and 20 in 2.2%, while the rates cytologically were 13.3% for exons 19 and 21 and 5.1% for exons 18 and 20. CONCLUSIONS: The sensitivity for the detection of EGFR mutations in cytological samples overlaps histology, so the use of cytological material constitutes an adequate approach for treatment selection in patients with locally advanced or metastatic lung cancer.

P-cadherin is coexpressed with CD44 and CD49f and mediates stem cell properties in basal-like breast cancer.

Although the luminal progenitor cell of the normal mammary gland hierarchy has been proposed as the cell-of-origin for basal-like breast cancers, finding the cancer stem cell (CSC) phenotype for this malignancy has proven a difficult task, mostly due to the lack of specific markers. Recently, basal-like sporadic and familial cases of breast cancer have been linked to BRCA1 gene inactivation, which enables the upregulation of the target-repressed CDH3/P-cadherin gene, an important biomarker of basal-like breast carcinomas. Previously, we demonstrated that P-cadherin overexpression can mediate aggressive behavior in these tumors. Thus, our aim was to test whether P-cadherin mediates stem cell properties in basal-like breast carcinomas. Using a series of breast cancer cell lines and primary tumors, we showed that P-cadherin was directly associated with the expression of the breast stem markers CD44, CD49f, and aldehyde dehydrogenase 1 in the basal subtype. Moreover, cell population enriched for P-cadherin expression comprised increased in vitro mammosphere-forming efficiency and capacity to grow colonies in three-dimensional cultures as well as greater tumorigenicity. Importantly, an association was found with stem-/progenitor-like phenotypes of the breast, including the luminal progenitor population, CD49f(+) CD24(+). Additionally, P-cadherin expression conferred resistance to x-ray-induced cell death, sustaining a role for this molecule in another stem cell property. In summary, we demonstrated, for the first time, that P-cadherin mediates stem cell properties, which could be explored in order to better define the CSC phenotype of basal-like breast tumors and the cell-of-origin of this malignancy.

Infiltration of a mixture of immune cells may be related to good prognosis in patients with differentiated thyroid carcinoma.

OBJECTIVE: Immune responses against differentiated thyroid carcinomas (DTC) have long been recognized. We aimed to investigate the role of immune cell infiltration in the progression of DTC. DESIGN: We studied 398 patients - 253 with papillary and 13 with follicular thyroid cancers, as well as 132 with nonmalignant tissues. PATIENTS AND MEASUREMENTS: Immune cell infiltration was identified using CD3, CD4, CD8, CD20, CD68 and FoxP3 immunohistochemical markers. In addition, we assessed colocalization of CD4 and IL-17 to identify Th17 lymphocytic infiltration and colocalization of CD33 and CD11b to identify infiltration of myeloid-derived suppressor cells (MDSC). RESULTS: Immune cells infiltrated malignant tissues more often than benign lesions. The presence of chronic lymphocytic thyroiditis (CLT) concurrent to DTC, CD68+, CD4+, CD8+, CD20+, FoxP3+ and Th17 lymphocytes but not MDSCs was associated with clinical and pathological features of lower tumour aggressiveness and a more favourable patient outcome. A log-rank test confirmed an association between concurrent CLT, tumour-associated macrophage infiltration, and CD8+ lymphocytes and an increased in disease-free survival, suggesting that evidence of these immune reactions is associated with a favourable prognosis. CONCLUSION: Our data suggest that the tumour or peri-tumoural microenvironment may act to modify the observed pattern of immune response. Immune cell infiltration and the presence of concurrent CLT helped characterize specific tumour histotypes associated with favourable prognostic features.

Prognostic value of NDRG1 and SPARC protein expression in breast cancer patients.

An increasing number of studies have shown altered expression of secreted protein acidic and rich in cysteine (SPARC) and N-myc down-regulated gene (NDRG1) in several malignancies, including breast carcinoma; however, the role of these potential biomarkers in tumor development and progression is controversial. In this study, NDRG1 and SPARC protein expression was evaluated by immunohistochemistry on tissue microarrays containing breast tumor specimens from patients with 10 years of follow-up. NDRG1 and SPARC protein expression was determined in 596 patients along with other prognostic markers, such as ER, PR, and HER2. The status of NDRG1 and SPARC protein expression was correlated with prognostic variables and patient clinical outcome. Immunostaining revealed that 272 of the 596 cases (45.6%) were positive for NDRG1 and 431 (72.3%) were positive for SPARC. Statistically significant differences were found between the presence of SPARC and NDRG1 protein expression and standard clinicopathological variables. Kaplan-Meier analysis showed that NDRG1 positivity was directly associated with shorter disease-free survival (DFS, P < 0.001) and overall survival (OS, P < 0.001). In contrast, patients expressing low levels of SPARC protein had worse DFS (P = 0.001) and OS (P = 0.001) compared to those expressing high levels. Combined analysis of the two markers indicated that DFS (P < 0.001) and OS rates (P < 0.001) were lowest for patients with NDRG1-positive and SPARC-negative tumors. Furthermore, NDRG1 over-expression and SPARC down-regulation correlated with poor prognosis in patients with luminal A or triple-negative subtype breast cancer. On multivariate analysis using a Cox proportional hazards model, NDRG1 and SPARC protein expression were independent prognostic factors for both DFS and OS of breast cancer patients. These data indicate that NDRG1 over-expression and SPARC down-regulation could play important roles in breast cancer progression and serve as useful biomarkers to better define breast cancer prognosis.

Anaplastic thyroid carcinoma: morphologic findings and PAX-8 expression in cytology specimens.

OBJECTIVE: To evaluate the morphologic findings most encountered in anaplastic thyroid carcinomas (ATCs) and evaluate for the expression of PAX-8. STUDY DESIGN: The cytology specimens from 21 cases of ATC were evaluated for the following several cytologic criteria: cell morphology, pleomorphism, presence or absence of multinucleated cells, colloid, neutrophilic infiltrate and well-differentiated component. Immunohistochemical studies for PAX-8 were performed on cell blocks in selected cases. RESULTS: The most common morphology present was epithelioid, followed by spindle, multinucleated giant cell and rhabdoid, with 75% demonstrating more than 1 cell morphology. Marked pleomorphism (81%), neutrophilic infiltrate (90%) and necrosis (63%) were frequent. No nuclear grooves, colloid or well-differentiated component was identified in any case. Immunocytochemical stains for PAX-8 were negative in 5 cases in which a cell block was available. CONCLUSION: ATC is a tumor with diverse morphologic characteristics, and more than 1 cell morphology is usually present. A neutrophilic infiltrate is a common finding and represents a clue to the correct diagnosis.

Screening anal dysplasia in HIV-infected patients: is there an agreement between anal pap smear and high-resolution anoscopy-guided biopsy?

PURPOSE: The purpose of this study was to analyze the agreement between anal Pap smear and high-resolution anoscopy-guided biopsy in diagnosing anal dysplasia in HIV-infected patients. METHODS: We conducted cross-sectional analysis of HIV-infected patients receiving anal dysplasia screening as part of routine care. Agreement between measures was estimated by weighted kappa statistics, using a three-tiered cytologic and histologic grading system (normal, low-grade dysplasia, and high-grade dysplasia). Estimates of sensitivity, specificity, and predictive values were calculated using a two-tiered cytologic and histologic grading system ("without dysplasia" and "with dysplasia of any grade"). Estimates were also calculated for the detection of high-grade dysplasia. RESULTS: During a one-year period, 222 patients underwent 330 anal Pap smears followed by high-resolution anoscopy-guided biopsies. There were 311 satisfactory Pap smears with concurrent biopsies. Considering histology the standard, the frequency of anal dysplasia was 46%. Kappa agreement between anal Pap smear and biopsy was 0.20. For detection of anal dysplasia of any grade, anal Pap smear showed sensitivity of 61%, specificity of 60%, positive predictive value of 56%, and negative predictive value of 64%. For high-grade dysplasia, anal Pap smear showed sensitivity of 16% and specificity of 97%. CONCLUSION: Anal Pap smears alone were not sensitive enough to rule out anal dysplasia. We recommend that high-resolution anoscopy-guided biopsy be incorporated as a complementary screening test for anal dysplasia in high-risk patients. Following baseline high-resolution anoscopy, these individuals could be followed with serial anal cytology to dictate the need for future high-resolution anoscopy-guided biopsies.

Isolated lymphadenitis due to Histoplasma capsulatum diagnosed by fine-needle aspiration biopsy and immunohistochemistry.

In the disseminated form of histoplasmosis, isolation and further identification of Histoplasma capsulatum can be performed by several methods, namely, bone marrow aspiration, blood culture, and liver biopsy. Lymph node disease usually is diagnosed by excisional biopsy. Although fungal stains can identify this fungus, detection of specific antigens by immunohistochemistry shows a higher specificity and sensitivity. This approach can use the cell block method when the material is not sent to fungal cultures or fresh staining.

Fine-needle aspiration biopsy of disseminated sporotrichosis: a case report.

In this report, we describe a case of disseminated sporotrichosis that was diagnosed by fine-needle aspiration biopsy (FNAB). The cytologic smears exhibited a large number of macrophages, few polymorphonuclear neutrophils and numerous round or oval, sometimes elongated, isolated and scattered yeast-like structures localized extracellularly or inside macrophages. These structures were clearly visualized by Giemsa and Papanicolaou methods. Cultures from skin biopsy material revealed fungal colonies which were subsequently identified as Sporothrix schenckii. The cytologic aspects, the correlation with histologic findings and the differential cytologic diagnosis were reviewed.

Fine needle aspiration biopsy in central giant cell lesion: a report of 3 cases.

BACKGROUND: Fine needle aspiration biopsy (FNAB) is a safe and efficient diagnostic method used in numerous lesions of the head and neck region. However, its use in central giant cell lesion (CGCL) is rarely seen. CASES: Three cases of CGCL were initially diagnosed with FNAB, emphasizing the cytologic and immunocytochemical features. CONCLUSION: FNAB, particularly when associated with clinical, radiographic and laboratory examinations, plays an important role in the preliminary diagnosis of CGCL.

Thyroid nodules: evaluation with power Doppler and duplex Doppler ultrasound.

This study purposes a new classification of thyroid nodules blood flow by power duplex Doppler ultrasound. A total of 177 nodules were studied with B-mode scanning, power Doppler, and spectral analysis. These data were compared with cytological results from ultrasound-guided fine-needle aspiration biopsy. Univariate and multivariate logistic regression analysis were performed. The power Doppler analysis of the nodules produced 5 vascular patterns: I, absence of signal blood flow; II, exclusively perinodular blood flow; III, perinodular >/= central blood flow; IV, central blood flow > perinodular blood flow; V, exclusively central blood flow. Statistical analysis revealed a significant relationship between these vascular patterns and cytological results. The spectral analysis demonstrated that the resistance index were higher in nodules with malignant versus other cytology ( P < 0.001). The results indicate that power duplex Doppler facilitates screening of thyroid nodules at high risk for malignancy with elevated sensitivity (92.3%) and specificity (88%).

Fine-needle aspiration biopsy of ectopic cervical spindle-cell thymoma: a case report.

In this report, we describe a case of ectopic cervical thymoma (medullary or type A thymoma, according to the WHO classification) located in the anterior cervical region (thyroid topography) that was submitted to ultrasound-guided fine-needle aspiration biopsy. The cytologic smears were moderately cellular to very cellular and were composed of numerous spindle-shaped cells placed predominantly in tissue fragments, with no specific arrangement. Isolated spindle-shaped cells were also present in a hemorrhagic background. The nuclei were elongated with finely granular chromatin and inconspicuous nucleoli. Mitosis, nuclear atypia, and necrosis were not detected. There was a scarce lymphoid population of small lymphocytes. The cytologic aspects, the correlation with histologic findings, and the differential cytologic diagnosis are reviewed.

The diagnostic and prognostic role of liquid-based cytology: are we ready to monitor therapy and resistance?

Here, we evaluate the diagnostic and prognostic role of liquid-based cytology (LBC) in different body lesions, including thyroid, lung, effusions and malignant breast lesions. LBC has gained consensus after being applied to both non-gynecologic and fine-needle aspiration cytology. Although some remain sceptical regarding the diagnostic efficacy of LBC, mainly when used alone, in recent years, good results have been obtained as long as it showed a high diagnostic accuracy. Here, we discuss the additional possibility of storing material for the application of ancillary techniques (immunocytochemistry-molecular analysis) with several diagnostic and prognostic advantages, which may pave the way for the challenging evaluation of both monitoring responses to treatment and resistance to targeted therapies in thyroid, lung, breast carcinoma or malignant effusions. Furthermore, it provides the use of several molecular spots as specific targets for personalized therapy.

Is thyroid gland only a "land" for primary malignancies? role of morphology and immunocytochemistry.

BACKGROUND: Thyroid Metastases (TM) represent a rare entity with an estimated variability ranging between 0 and 24%. Fine needle aspiration cytology (FNAC) might be useful in discriminating between primary and TM nodules especially when ancillary techniques (i.e., immunocytochemistry-ICC) are carried out. METHODS: We herein appraised a series of 20 TM on FNAC analyzed between 2000 and 2013. We included eight male and 12 female patients. The cytological cases were processed with both liquid based (LBC) and conventional cytology. RESULTS: We reported 2.2% TM out of 910 malignancies. Our TM cases resulted as: six lung (LG), five gastro-intestinal (GI), five breast (B), three larynx (LX), and one clear cell renal carcinoma (CCRC) metastases. All the patients had a previous known cancer history. Although the cytological features were likely to suspect a TM, the application of ICC panels was contributive in 100% cases. None of TMs resulted as a unique localization whereby two cases underwent total thyroidectomy (including one B and one CCRC) and 18 TM were treated with radio-chemotherapy approaches. CONCLUSIONS: FNAC empowered the diagnostic workup of patients with TM avoiding useless surgical approach. The low sensitivity of cytology might be reinforced by the application of ancillary techniques. In contrast with the reported predominant rate of kidney metastatic carcinomas, our findings underlined that intestinal cancer as well as lung and breast are the most common TM. TM are frequently multifocal and in a contest of a systemic disease so that a tailored therapy seems to be the best treatment.

Cytologic features of solitary fibrous tumor of the parotid gland. A case report.

BACKGROUND: Solitary fibrous tumor (SFT) is a rare neoplasm that most commonly involves the pleura but is increasingly recognized at other locations, including lung, liver, thyroid and parotid glands, with only a few reports describing its cytologic features. CASE: The fine needle aspiration biopsy (FNAB) features of an SFT located in the left parotid gland of a 34-year-old woman were compared to the histologic and immunohistochemical aspects of the lesion. CONCLUSION: This case confirms that SFT has distinct cytomorphologic features and that FNAB can be helpful in its diagnosis.

Cytologic findings of epithelioid angiosarcoma of the thyroid. A case report.

BACKGROUND: Angiosarcoma of the thyroid is a rare and aggressive tumor and occurs mainly in patients from central Europe, especially the alpine region. The fine needle aspiration findings of a keratin-positive epithelioid angiosarcoma of the thyroid occurring in a nonmountainous area in South America is described. CASE: A 65-year-old male from São Paulo, Brazil, presented with a mass in the anterior part of the neck with progressive enlargement for three months. The cytologic findings on the fine needle aspirate were a cellular smear composed of single cells and small clusters of neoplastic cells, oval and round. Cell borders were indistinct, and the cytoplasm was vacuolated. The nuclei were eccentrically located, with irregular nuclear membranes; single, prominent nucleoli; and a coarse chromatin pattern. Features suggestive of intracytoplasmic lumens were identified. Open surgical biopsy demonstrated a tumor infiltrating the thyroid gland and composed of large, round, atypical epithelioid cells lining vascular spaces. These neoplastic cells were immunoreactive for AE1:AE3, CK7, vimentin, CD31 and factor VIII. CONCLUSION: Epithelioid angiosarcoma should be considered in the differential diagnosis of epithelioid neoplasms of the thyroid. An immunohistochemical panel should include vascular markers even in the presence of immunoreactivity for epithelial markers.