Nuclear Features Of Papillary Carcinoma Research Articles

Cytomorphological comparison of ThinPrep and SurePath liquid-based cytology in thyroid fine-needle aspiration.

The two widely established systems for liquid-based cytology (LBC), ThinPrep and SurePath, employ different principles. The aim of this study was to compare the cytomorphology of thyroid lesions prepared by the two techniques. We retrospectively reviewed 44 thyroid FNA specimens prepared by LBC, including 20 ThinPrep and 22 SurePath. Cytologic diagnoses were made according to the Bethesda system and cytomorphologic parameters were evaluated. Acellular smears were significantly frequent in ThinPrep than SurePath (10% vs. 0%). Both techniques produced a clean background, well cell preservation, and not apparent cell shrinkage. ThinPrep showed significantly lower cellularity than SurePath (25% vs. 4.3%). ThinPrep produced considerable flattening and fragmented clusters, while SurePath contained larger clusters in a three-dimensional configuration. Colloid was significantly reduced in amount and fragmented in ThinPrep, and was easily observed in SurePath. In cases of Hashimoto's thyroiditis, ThinPrep produced much less leukocytes in background than SurePath. Aggregates of fibrin and leukocytes were frequently present in 10/16 cases (62.5%) processed by ThinPrep. Air-dry artifact at periphery of the ring was present in 6/16 cases (37.5%) processed by ThinPrep. The nuclear features of papillary carcinoma were similarly evident in both LBC preparations. SurePath seems to be superior to ThinPrep for diagnosing benign entities based on adequate representation of colloid and lymphocytes. The cell quality of both techniques in thyroid FNA was comparable, while each method introduces its own unique cytologic artifacts related to its methodology. We should recognize the cytomorphologic alterations to avoid misinterpretations.

Cribriform Morular Thyroid Carcinoma: A Rare Case and Associated Uncommon Features.

Cribriform morular thyroid carcinoma has been added under tumors of uncertain histogenesis. Its peculiar clinical, histomorphological pattern, and immunohistochemical profile have been proved different from papillary thyroid carcinoma. A 59-year-old female patient had a lesion in the left lobe of the thyroid. Fine needle aspiration cytology was reported as medullary thyroid carcinoma. The total thyroidectomy specimen showed a predominantly solid tumor of size 9.5 cm in the left lobe. Microscopy showed a mixed growth pattern with the dominant cribriform and solid morular area. Nuclear features of papillary carcinoma were not seen. Squamoid morules had nuclear clearing. Marked stromal hyalinization and calcification were noted. Extrathyroidal extension, lymphovascular invasion, and lymph node metastasis were not identified. Immunohistochemically the tumor cells were diffuse and strong nuclear positive for β-catenin, TTF1, PAX8, estrogen receptor, focal, and weak positivity for CD5. Synaptophysin, calcitonin, thyroglobulin, and CDX2 were negative. We report this rare cribriform morular thyroid carcinoma case with its associated uncommon histological and immunohistochemical features.

Diagnostic clues for hyalinizing trabecular tumor on fine needle aspiration cytology.

The hyalinizing trabecular tumor (HTT) is a rare benign neoplasm of the thyroid gland. This neoplasm has overlapping cytological features with Papillary Thyroid Carcinoma, Medullary Carcinoma and Follicular Neoplasm with Nuclear Features of Papillary Carcinoma. This can lead to misdiagnosis of malignancy in fine needle aspiration (FNA) cytology specimens with unnecessary total thyroidectomy. The aim of this study is to determine if there are some cytological features that could help us to suspect HTT on FNA specimens and avoid radical surgery. With this purpose we have collected 6 cases diagnosed of HTT in Hospital Clínico San Carlos of Madrid (Spain) in the last 10 years and reviewed the cytological specimens. We conclude that the presence of hyaline material in FNA specimens of HTT is a constant feature being a diagnostic clue. We must be cautious not to confuse it with dense colloid or amyloid material, the latter seen in Medullary Carcinoma. Papillary architecture and fibrovascular cores are not present in a HTT. Special stains as ki-67, calcitonin and Congo Red staining could help us in achieving the correct diagnosis. We feel the cytopathologists must be aware of the distinguishing features of this lesion, mainly the typical hyaline material to achieve a proper diagnosis and be able to reduce unnecessary aggressive management of these patients.

Lindsay tumour

The follicular tumours with nuclear features of papillary carcinoma are categorised as follicular variant of papillary thyroid carcinoma (FVPTC). They exhibit biologic and molecular properties that are different from conventional papillary thyroid cancer. Solid encapsulated follicular variant of papillary carcinoma of thyroid is termed as Lindsay tumour. Since they are encapsulated, they follow an indolent course. We present a case of Lindsay tumour in a 34-year-old female, who presented with swelling in the neck for six months. She had no other specific complaints. On local examination of her neck, there was a hemispherical swelling of size 6×5×2 cm, found in the midline which moves with deglutition. The swelling was firm in consistency and its surface was nodular. There were no palpable lymph nodes in the neck. The ultrasonogram of her neck revealed multinodular goitre. The fine needle aspiration cytology from neck swelling revealed colloid goitre with cystic degeneration. Her thyroid function tests were within normal limit. She was then, proceeded with total thyroidectomy. Her postoperative recovery was uneventful. Her histopathological report revealed an encapsulated follicular variant of papillary carcinoma of thyroid. She was then kept on half yearly follow-up with serum thyroglobulin. Therefore, this case provides an opportunity to review the encapsulated follicular variant of papillary carcinoma thyroid (Lindsay tumour) and its management.

Study of various nuclear features of papillary thyroid carcinoma in other thyroid lesions

Introduction: Papillary thyroid carcinoma is the only thyroid malignancy that is diagnosed on the basis of its nuclear characteristics, regardless of cytoplasmic features, growth patterns or immunohistochemistry. Although nuclear features have become hallmark for the diagnosis, they are neither constant nor specific. They can be seen in other tumours and non-tumours condition of thyroid. With the aim to know the frequency of various nuclear features of papillary thyroid carcinoma in other thyroid lesions and also to find out which of the various nuclear features are most diagnostic of papillary thyroid carcinoma, this study was done. Materials and Methods: The present study was conducted on Fine needle aspiration cytology of thyroid lesions where corresponding histopathological diagnosis was available, from 2010 to 2016. All cytology smears of were reviewed by two investigators who were blinded with respect to the final histopathological diagnosis. Results: 155 cases were included in the study; category 2 was the most common constituting 76%, followed by category 6 which was 35%. Frequency of various nuclear features of papillary carcinoma in other thyroid categories varied from 10% to 33%. Conclusion: Frequency of various nuclear features of papillary carcinoma in other thyroid categories varied from 10% to 33% and Intranuclear cytoplasmic inclusions are the most diagnostic nuclear features of papillary carcinoma. Keywords: Papillary thyroid carcinoma, Nuclear inclusions, Nuclear grooves, Fine granular chromatin.

Poorly differentiated thyroid carcinoma

Poorly differentiated thyroid carcinoma (PDTC) is an aggressive form of follicular cell derived thyroid carcinoma with a prognosis intermediate between the indolent well differentiated thyroid carcinomas and the rapidly growing often fatal anaplastic carcinoma. While all investigators agree on the presence of this entity, there is disagreement in regard to its definition. In 2006, a set of criteria based solely on mitotic index ≥5/10 high power fields and/or tumor necrosis was proposed by a group of researchers from Memorial Sloan Kettering Cancer Center (MSKCC criteria) in New York. A year later, alternative diagnostic criteria of PDTC, so called the Turin proposal, were advocated by an international consensus group. The Turin proposal requires three criteria: 1) solid/trabecular/insular growth pattern; 2) absence of nuclear features of papillary carcinoma; and 3) at least one of the following three features: mitotic index ≥3/10 high power fields (HPFs), necrosis, or convoluted nuclei. In this review, we summarize the histology, diagnostic criteria (Turin proposal and MSKCC criteria) with their pros and cons, the prognostic factors, and molecular profile of PDTC, aiming to provide a practical and compreshensive review of this challenging entity.

Prognostic Impact of the Turin Criteria in Poorly Differentiated Thyroid Carcinoma.

The Turin criteria including solid, trabecular, and/or insular architecture, lack of typical nuclear features of papillary carcinoma, and mitoses, necrosis, or convoluted nuclei were adopted in the recent 4th edition of the World Health Organization classification published in 2017. Between 2006 and 2017, 11,001 cases underwent initial surgery for primary malignant thyroid tumor derived from follicular cells. A total of 75 (0.7%) cases were diagnosed with PDTC according to the 2004 WHO classification. Based on the Turin criteria, 30 (40%) cases were re-classified as PDTC-Turin (+) and 45 (60%) cases were PDTC-Turin (-). Clinicopathological features and prognosis were compared between PDTC-Turin (+) and PDTC-Turin (-). Seventy-five patients (48 females and 27 males) had a median age at the time of surgery of 57years. Preoperative diagnosis was benign in 16 (21%), follicular tumor in 40 (53%), and malignant in 19 (25%). The 5-year cause-specific survival (CSS) and disease-free survival (DFS) rates were 97% and 44% for PDTC-Turin (+) and 100% and 88% for PDTC-Turin (-). On univariate analysis, CSS and DFS rates were significantly worse in the PDTC-Turin (+) than in the PDTC-Turin (-) (p = 0.0096, and p = 0.0016). Multivariate analysis showed that Turin criteria status, Ki-67 labeling index ≥ 10%, and age 55 ≥ years were the independent prognostic factors for recurrence. The prevalence of PDTC diagnosed with the Turin criteria was low, but it showed more aggressive behavior. The 2017 WHO classification reflects the prognosis more accurately than the 2004 WHO classification.

MON-552 Prognostic Impact of the Turin Criteria in Poorly Differentiated Thyroid Carcinoma

Background Poorly differentiated thyroid carcinoma (PDTC) is morphologically and behaviorally intermediate between differentiated carcinoma and anaplastic carcinoma. The Turin criteria including solid, trabecular, and/or insular architecture, lack of typical nuclear features of papillary carcinoma, and mitoses, necrosis, or convoluted nuclei were adopted in the recent 4th edition of the World Health Organization (WHO) classification published in 2017. Materials and Methods Between 2006 and 2017, 11,001 cases underwent initial surgery for primary malignant thyroid tumor derived from follicular cells. A total of 75 (0.7%) cases were diagnosed with PDTC according to the 3rd WHO classification. Based on the Turin criteria (4th WHO classification), 30 (40%) cases were re-classified as PDTC-Turin (+), and 45 (60%) cases were PDTC-Turin (-). Clinicopathological features and prognosis were compared between PDTC-Turin (+) and PDTC-Turin (-). Result The 75 patients (48 females, 27 males) had a median age at the time of surgery of 57 years. The 5-year cause-specific survival (CSS) and disease-free survival (DFS) rates were 96.4% and 38.6% for PDTC-Turin (+), and 100% and 88.4% for PDTC-Turin (-), respectively. On univariate analysis, CSS and DFS rates were significantly worse in the PDTC-Turin (+) cases than in the PDTC-Turin (-) cases (log-rank test, p=0.005, and p=0.0004). Multivariate analysis showed that Turin criteria status was an independent prognostic factor for recurrence. Conclusion The prevalence of PDTC diagnosed with the Turin criteria was low, but it showed more aggressive behavior. The 4th WHO classification reflects the prognosis more accurately than the 3rd WHO classification.

An International Interobserver Variability Reporting of the Nuclear Scoring Criteria to Diagnose Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: a Validation Study.

The aim of the study was to assess interobserver variation in reporting nuclear features of encapsulated follicular variant of papillary thyroid carcinoma, newly reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), based on a proposed standardized scoring system. An education module was individually reviewed as a pre-evaluation teaching guide of the specific features of classical papillary carcinoma, the specific inclusion and exclusion features for the diagnosis of NIFTP, and a catalog of the standardized scoring system of the nuclear features of papillary carcinoma used to reach this diagnosis. Participants subsequently reviewed 30 cases of thyroid lesions previously scored by members of the Endocrine Pathology Society Working Group for the Re-evaluation of the Encapsulated Follicular Variant of Papillary Thyroid Carcinoma. There was one uninvolved reference image to demonstrate fixation, processing, and cell size and one image from each case for scoring, with results recorded for each participant. The location of training (country and program), years as a practicing pathologist, and approximate number of thyroid gland surgical cases diagnosed per year were recorded. The degree of agreement between participants was assessed by kappa statistics, using the individual criteria and the average composite scores of the Working Group as a point of comparison. Using the Nuclear Standardized Scoring System, the interobserver agreement for final diagnosis score was generally excellent: unweighted and weighted kappa values between individual observers ranging from 0.242 to 0.930 (average 0.626). There was significant agreement between observers in reaching an interpretation of the presence or absence of nuclear features to diagnose NIFTP (score 0-1 versus score of 2-3), with California pathologists, 0.63 (median 0.66, SD 0.15); Japanese pathologists, 0.64 (median 0.66, SD 0.16); and UK pathologists, 0.60 (median 0.57, SD 014) compared to the expert panel, 0.70 (median 0.73, SD 0.19). The use of the nuclear scoring system to evaluate the nuclear features of papillary thyroid carcinoma as applied to reach the diagnosis of NIFTP shows a good to substantial interobserver agreement, suggesting that consensus can be reached in diagnosing the nuclear features required for this newly reclassified neoplasm.

Incidence and significance of true papillae in thyroid fine needle aspiration.

Whether true papillae without nuclear features of papillary carcinoma in thyroid fine needle aspirates should be diagnosed as atypia of undetermined significance (AUS) is unclear. The results of all thyroid FNAs performed from 2014-2016 with corresponding resections as well as aspirates from 2000-2016 with a diagnosis of follicular variant of papillary carcinoma or Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) were reviewed. Papillae with fibrovascular cores were identified in 17 of 149 consecutive cases (11%), 3 of which had nuclear features of papillary carcinoma and were papillary carcinoma at resection. All 14 cases of papillae without nuclear features of papillary carcinoma were benign. Of 29 papillary carcinomas, papillae were identified in 8 (28%) and "swirls" were identified in 3 (10%) additional cases, all in cases of papillary carcinoma, NOS. Papillae and swirls were not identified in any cases of NIFTP (13 cases) or follicular variants of papillary carcinoma (15 cases). True papillae are relatively common. Both papillae with nuclear atypia and swirls are highly specific for papillary carcinoma, NOS and are not seen in NIFTP. True papillae with fibrovascular cores but without cytologic features of papillary carcinoma are benign and should not be diagnosed as AUS. Diagn. Cytopathol. 2017;45:689-692. © 2017 Wiley Periodicals, Inc.

Preoperative diagnosis of follicular variant of papillary carcinoma of thyroid-A retrospective study

Background: Follicular variant of papillary carcinoma is the second common variant of papillary carcinoma. The diagnosis of follicular variant pre-operatively has been really very challenging and the incidence of false diagnosis is also very high. So, an attempt has been made to study the cytological as well as ultrasound findings of histologically proven cases of follicular variant of papillary carcinoma of thyroid. Materials and Methods: Sonographic findings and cytology findings of 20 histologically proven cases of Follicular variant of papillary carcinoma of thyroid are retrospectively reviewed. Results: Only 50% of cases were diagnosed as malignant on ultrasound and only 25% cases were diagnosed malignant on cytology. Conclusion: The sensitivity of diagnosis is more radiologically, so all the thyroid FNAC should be done under ultrasound guidance and also nuclear features of Papillary carcinoma should be more carefully looked into in all suspicious cases. With these initiatives, the accuracy of cytological diagnosis of FVPTC can be substantially increased. Key words: FNAC(Fine needle aspiration Cytology), FVPTC(Follicular variant of papillary carcinoma of thyroid)

Papillary carcinoma in struma ovarii: a case report

Introduction Struma ovarii is a form of teratoma composed predominantly of thyroid tissue, comprising 2.7% of all ovarian teratomas.1 Malignancy may occur in 5–10% of struma ovarii.2 There is controversy as to the best management and follow-up of these cases. We describe a rare case of a 45-year-old woman with struma ovarii showing features of papillary carcinoma. Case report The patient presented with 12 months of pelvic pain and heavy irregular vaginal bleeding. A pelvic ultrasound showed a small left-sided dermoid cyst. Laparoscopic salpingo-oophorectomy was performed. Sections of the ovarian cyst showed a mature teratoma. Thyroid tissue comprised approximately 50% of the specimen. The follicular cells displayed nuclear features of papillary carcinoma. This was present both in classical papillary form and as a follicular variant with prominent psammoma bodies. The patient was subsequently investigated to exclude a primary thyroid neoplasm. Thyroid function tests were normal. An ultrasound showed multiple benign thyroid nodules, one of which had minor non-specific uptake on PET scan. Subsequent FNA cytology was benign. Conclusion This patient had an incidental finding of papillary carcinoma in struma ovarii, independent of any thyroid pathology. This entity has a good prognosis in the absence of extra-ovarian spread. Struma ovarii is a form of teratoma composed predominantly of thyroid tissue, comprising 2.7% of all ovarian teratomas.1 Malignancy may occur in 5–10% of struma ovarii.2 There is controversy as to the best management and follow-up of these cases. We describe a rare case of a 45-year-old woman with struma ovarii showing features of papillary carcinoma. The patient presented with 12 months of pelvic pain and heavy irregular vaginal bleeding. A pelvic ultrasound showed a small left-sided dermoid cyst. Laparoscopic salpingo-oophorectomy was performed. Sections of the ovarian cyst showed a mature teratoma. Thyroid tissue comprised approximately 50% of the specimen. The follicular cells displayed nuclear features of papillary carcinoma. This was present both in classical papillary form and as a follicular variant with prominent psammoma bodies. The patient was subsequently investigated to exclude a primary thyroid neoplasm. Thyroid function tests were normal. An ultrasound showed multiple benign thyroid nodules, one of which had minor non-specific uptake on PET scan. Subsequent FNA cytology was benign. This patient had an incidental finding of papillary carcinoma in struma ovarii, independent of any thyroid pathology. This entity has a good prognosis in the absence of extra-ovarian spread.

Is Poorly Differentiated Thyroid Cancer Poorly Characterized?

Poorly differentiated thyroid cancer (PDTC) has remained a controversial diagnosis. Some clinicians refer to PDTC as thyroid cancers that do not trap radioiodine on radioiodine scans (either initially or during monitoring), and others believe that it is appropriate to refer to rapidly growing thyroid cancers that have apparently not responded to radioactive iodine therapy (1). However, in many instances it is difficult to determine whether radioiodine therapy has been partially effective. We and others had noted that “poorly differentiated thyroid carcinoma is a concept proposed to include carcinomas of follicular thyroid epithelium that retain sufficient differentiation to produce scattered small follicular structures and some thyroglobulin, but generally lack the usual morphologic characteristics of papillary and follicular carcinoma” (2–4). In separate reports, Sakamoto et al (3) in 1983 and Carcangiu et al (5) in 1984 initially pathologically described the discrete category of PDTC. However, these authors used different characteristics to define this entity, resulting in a long-standing dispute regarding the appropriate pathological definition of PDTC. The World Health Organization tumor classification attempted to better define this entity, but this also has been considered controversial (6, 7). Inaneffort toquell thecontroversy,agroupofestablished pathologists and investigators set forth what is referred to as the Turin proposal. This proposal set forth specific histological characteristics toattempt touniversallydefinePDTC(7). These criteria include: 1) the presence of a solid/trabecular/ insular pattern of growth; 2) the absence of the conventional nuclear features of papillary carcinoma; and 3) the presence of at least one of the following features: convoluted nuclei, mitotic activity 3 per 10 high-power fields, and tumor necrosis (7).However,PDTCremainsaclinicallyandpathologically inchoate disorder, and it is not known whether it represents a single clinical or molecular entity. Furthermore, the optimal clinical approach for monitoring and treatment modalities is unknown. Recent articles on the topic of PDTC have assessed and commented upon the diagnostic criteria and have reviewed this entity (8–13). These articles emphasize the variations in the diagnostic criteria and that PDTC is generally considered in the middle of the spectrum between well-differentiated thyroid cancer and undifferentiated or anaplastic thyroid cancer. Asioli et al (14) reported that poorly differentiated carcinoma had a prevalence (in pathological thyroid malignancies) of 1.8% (56 of 3128) in the Unites States (at Mayo Clinic)andof6.7%(96of1442) innorthernItaly (University of Turin). Thyroglobulin immunostaining was positive in 92% (95 of 103) of PDTC cases, and thyroid transcription factor 1 immunostaining was positive in each of 103 PDTC cases. The authors concluded, using univariate analysis, that PDTC was associated with a greater risk of death in patients age 45 or greater and for tumors of 4 cm or larger; multivariate analysis confirmed the age-related finding. The present study by Ibrahimpasic et al (15) from the well-respected Memorial Sloan Kettering group attempts to better define the prognosis of PDTC patients. They retrospectively analyzed 91 patients with PDTC treated at their institution between the years 1986 and 2009. Over a median of 50 months of monitoring, the 5-year overall survival was 62%, and disease-specific survival was 66%. The vast majority of disease-specific deaths were related to the presence of distant, metastatic disease (23 of 27 deaths; 85%). Locoregional control was higher at 81% than was distant control at 59%. Multivariate analysis showed that initial pT4a stage distant metastases (M1) were independently associated with poorer disease-specific survival,

Morphology predicts BRAF V600E mutation in papillary thyroid carcinoma: an interobserver reproducibility study

Papillary thyroid carcinomas (PTC) with BRAF (V600E) mutation are morphologically distinctive. They are typically classic or tall cell variants, show infiltrative borders, and are associated with desmoplasia/fibrosis, psammoma bodies, and well-developed nuclear features of papillary carcinoma. We hypothesize that morphologic features of PTC can help in the prediction of BRAF (V600E) mutation, and we evaluate the accuracy and the interobserver reproducibility of such prediction. Hematoxylin and eosin-stained sections from 50 PTCs comprising of 26 mutation-positive and 24 mutation-negative tumors were examined. BRAF (V600E) mutation was predicted correctly in 42/50 tumors (accuracy, 84 %) with 96 % sensitivity, 71 % specificity, and 78 % positive and 94 % negative predictive values (NPV). Subtle nuclear features of PTC (n = 10) had the highest (100 %) negative predictive value followed by well-circumscribed non-infiltrative tumor borders (17/22 mutation-negative tumors, 95 % NPV). The positive predictive value of infiltrative tumor borders (21/28 [75 %] mutation-positive), desmoplasia/fibrosis (23/31 [74 %] mutation-positive), and psammoma bodies (13/20 [65 %] mutation-positive) increased to 100 % when all three features were present (n = 8/8 mutation-positive). To assess interobserver reproducibility, two pathologists blinded to the mutational status evaluated 30 PTCs (15 mutation-positive and 15 mutation-negative) after self-training on 10 PTCs with known BRAF (V600E) mutational status (five mutation-positive and five mutation-negative). The prediction of the mutation was achieved with substantial agreement (κ value, 0.79) and accuracy (25/30, 83 %). This study demonstrates that BRAF (V600E) mutation in papillary thyroid carcinoma can be predicted on morphology with accuracy and with substantial interobserver agreement.

Diffuse sclerosing variant of papillary thyroid carcinoma: a study of fine needle aspiration cytology in 20 patients

A diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is a rare variant and reports describing the cytological findings are few. We studied 24 cytological samples from thyroid fine needle aspirates of 20 patients with DSV-PTC. The specimens were taken from 14 non-nodular lesions and 10 nodules. All aspirates taken from both non-nodular lesions and nodules had sufficient cellularity. The carcinoma cells frequently (70-100%) appeared as solid cell balls and hollow balls, and showed a hobnail pattern, squamous differentiation, septate cytoplasmic vacuoles and large unilocular vacuoles. Most of the carcinoma cells seem to be taken from the lumen of dilated lymph vessels. Ground glass nuclear chromatin, intranuclear cytoplasmic inclusions and grooved nuclei were infrequent (50% or less). In the background, a large number of lymphocytes and abundant psammoma bodies were almost always seen. Cytological findings of DSV-PTC are as follows: (1) solid cell balls and/or hollow balls containing lymphocytes; (2) hobnail cells; (3) septate cytoplasmic vacuoles; (4) large unilocular vacuoles; (5) squamous differentiation; (6) abundant psammoma bodies; (7) lymphocytic background; and (8) the absence or relative lack of characteristic nuclear features of papillary carcinoma. When DSV-PTC is suspected by ultrasound examination, the aspiration cytology from a non-nodular area of the thyroid can led us to the diagnosis of the variant.

39. A case of adenolipoma of thyroid gland

<h3>Introduction</h3> Adenolipoma of the thyroid gland is a thyroid adenoma containing mature fat tissue and is usually encapsulated. It is a rare benign neoplasm and usually biologically inactive. <h3>Case report</h3> A 52-year-old man presented a thyroid nodule which had been slowly increasing in size. Fine needle aspiration biopsy showed an atypical follicular pattern and right hemithyroidectomy was then performed. Grossly, a solid, well circumscribed nodule, 30x29x19mm, with a homogenous tan cut surface was present. Microscopically, the tumour showed a thin fibrous capsule with follicular epithelial cells arranged in a microfollicular pattern. Mature adipose tissue was seen in the tumour. No nuclear features of papillary carcinoma were seen. The follicular epithelial cells stained strongly with TTF-1. The diagnosis of adenolipoma was made. <h3>Discussion</h3> Adenolipoma of thyroid gland was first described by Schroder in 1984. It was reported to be seen in patients ranging from 23 to 75 years old and occurred equally in both sexes. Fine needle aspiration of the lesion may disclose follicular epithelial cells with admixed adipose tissue. Microscopically, it is typically enclosed within a fibrous capsule. The neoplastic follicles can show normofollicular, microfollicular and macrofollicular and occasionally, trabecular growth patterns. The tumour cells are cuboidal, columnar or polygonal and often have dark, round nuclei. Mitoses are rare. The stroma showed delicate capillaries. No capsular or vascular invasion is seen. The cells show staining with cytokeratin, thyroglobulin and TTF-1 but no staining with CK19, calcitonin or neuroendocrone markers. <h3>Conclusion</h3> Adenolipoma is a benign tumour and treatment is complete removal with surgery. The diagnosis should be supported by clinical, biochemical, radiological, cytological and histological findings.

Poorly Differentiated Thyroid Carcinomas

Poorly differentiated (PD) carcinomas of the thyroid are conceptually situated between well-differentiated (papillary or follicular) carcinomas and anaplastic thyroid carcinomas. Although the morphologic criteria for PD tumors are well defined, it is not clear how much of a PD area besides a well-differentiated component in a given tumor is required to allow such a diagnosis. We identified 42 patients suffering from thyroid carcinoma with an adverse clinical outcome. Fifty patients with follicular carcinoma were added as controls. We analyzed poorly differentiated areas by applying the Turin criteria of PD carcinomas. These criteria consisted of the presence of a solid/trabecular/insular growth pattern, lack of nuclear features of papillary carcinoma, and presence of 1 of the following features: (1) convoluted nuclei, (2) tumor necrosis, (3) 3 or more mitoses per 10 high-power fields. Using a cutoff value of 10% of PD areas per examined tumor surface, we identified a total of 35 PD carcinomas. Despite using a threshold of 10% of the tumor area as poorly differentiated, the survival data in a Kaplan-Meier analysis were significantly worse than those in the control group (P<0.001) and did not differ from tumors with a PD area >50%. In a multivariate analysis that included age, sex, tumor stage, and PD area >10% against survival data, the only consistent significant factor was PD differentiation (P<0.001). As even slight amounts of PD areas (≥ 10%) in a thyroid carcinoma affect the prognosis significantly, the presence of such areas may be worth reporting in thyroid carcinomas.

Poorly differentiated carcinoma of the thyroid: validation of the Turin proposal and analysis of IMP3 expression

The Turin Proposal algorithm defines poorly differentiated carcinoma on the basis of the presence of solid/trabecular/insular growth pattern, absence of conventional nuclear features of papillary carcinoma, and the presence of at least one of the following features: convoluted nuclei, mitotic activity ≥3/10 HPF, or tumor necrosis. IMP3 appears to have diagnostic and prognostic value in many solid tumors, including thyroid carcinomas. We examined a series of follicular-cell carcinomas with prominent solid patterns diagnosed at Mayo Clinic (56 cases) (Rochester, MN, USA) and at the University of Turin (96 cases) (Northern Italy) to validate the Turin consensus criteria defining poorly differentiated carcinoma of the thyroid and to evaluate the prevalence and prognostic behavior of this tumor. On this series, we analyzed the expression of conventional markers by immunohistochemistry and we investigated the expression of IMP3 by both immunohistochemistry and qRT-PCR. The prevalence of poorly differentiated carcinoma among the USA cases was 1.8% (56/3128) and that in the cases of Northern Italy was 6.7% (96/1442). Tumor characteristics were similar in the cases from the USA and from Italy except for extensive vascular invasion and a prevalent insular growth pattern (lower the former, higher the latter in the Italian series). In univariate analysis, the risk of death was higher for age ≥45, tumors ≥4 cm, and IMP3 positivity. Multivariate analysis showed that the risk of death from poorly differentiated carcinoma was higher for age ≥45. The Turin consensus criteria can reliably select poorly differentiated carcinomas. Tumors from the USA and from Italy showed similar overall survival, although the prevalence of poorly differentiated carcinoma was higher in Northern Italy. Expression of IMP3 appears to be an adverse prognostic factor for poorly differentiated thyroid carcinoma.

Is ionizing radiation responsible for the increasing incidence of thyroid cancer?

The dose of exposure to ionizing radiation appears to correlate with increased risk of thyroid microcarcinoma. Can ionizing radiation be a factor contributing to the increasing incidence of thyroid cancer around the world?

Interobserver and Intraobserver Variation Among Experts in the Diagnosis of Thyroid Follicular Lesions With Borderline Nuclear Features of Papillary Carcinoma

Distinguishing follicular variant of papillary carcinoma (FVPC) from follicular adenoma and follicular carcinoma can be difficult if nuclear features of papillary carcinoma are not well developed or only focally present. We assessed interobserver and intraobserver agreement among 6 thyroid experts by using 15 cases in which original pathologists suspected FVPC. There was unanimous expert agreement in diagnosing FVPC in only 2 cases (13%) and majority agreement in 6 cases (40%). Unanimous agreement on benign and malignant diagnoses was seen in 4 cases (27%) and majority agreement on malignancy in 8 cases (53%). Intraobserver agreement ranged from 17% to 100%. Histologic features considered most helpful in diagnosing FVPC were nuclear clearing, nuclear grooves, nuclear overlapping and crowding, nuclear membrane irregularity, and nuclear enlargement. This considerable interobserver and intraobserver variability in the diagnosis of FVPC seems to result from lack of agreement on the minimal criteria needed to diagnose FVPC, even among experts.