Follicular Variant Of Papillary Carcinoma Research Articles

Is Conservative Management of Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features (NIFTP) Possible in Children?

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a newly recognized entity with benign clinical characteristics. We aim to compare NIFTP with invasive encapsulated follicular variant papillary carcinoma (fvPTC) and to discuss the management. Records of patients with fvPTC and NIFTP between 2016 and 2022 were reviewed retrospectively. Two groups were compared according to demographics, surgical management, postoperative management, and long-term follow-up. Twenty patients were included in the study, with 10 in NIFTP group and 10 in fvPTC group. The mean age at operation was 14.10 ± 2.61 years. Demographics and preoperative nodule sizes (P = .912) were statistically similar between the 2 groups. Although lobectomy was more common in the NIFTP group, this difference was not statistically significant compared to the fvPTC group in terms of surgical treatment. Postoperatively, while no patient received radioactive iodine treatment(RAI) in NIFTP group, 6 patients in fvPTC group did (P = .011). Five patients in NIFTP group and 3 in the fvPTC group were followed up with lobectomy only, without any adverse events or recurrence, for 47.50 ± 19.25 and 30.10 ± 19.25 months, respectively. In conclusion, NIFTP appears to be an indolent disease in children. Therefore, observation with lobectomy is sufficient, and RAI is not necessary.

Diagnostic utility of RAS mutation testing for refining cytologically indeterminate thyroid nodules.

RAS mutations are prevalent in indeterminate thyroid nodules, but their association with malignancy risk and utility for diagnosis remains unclear. We performed a systematic review and meta-analysis to establish the clinical value of RAS mutation testing for cytologically indeterminate thyroid nodules. PubMed and Embase were systematically searched for relevant studies. Thirty studies comprising 13,328 nodules met the inclusion criteria. Random effects meta-analysis synthesized pooled estimates of RAS mutation rates, risk of malignancy with RAS positivity, and histologic subtype outcomes. The pooled mutation rate was 31 % (95 % CI 19-44 %) among 5,307 indeterminate nodules. NRAS mutations predominated at 67 % compared to HRAS (24 %) and KRAS (12 %). The malignancy rate with RAS mutations was 58 % (95 %CI=48-68 %). RAS positivity increased malignancy risk 1.7-fold (RR 1.68, 95 %CI=1.21-2.34, p=0.002), with significant between-study heterogeneity (I2=89 %). Excluding one outlier study increased the relative risk to 1.75 (95 %CI=1.54-1.98) and I2 to 14 %. Funnel plot asymmetry and Egger's test (p=0.03) indicated potential publication bias. Among RAS-positive malignant nodules, 38.6 % were follicular variant papillary carcinoma, 34.1 % classical variant, and 23.2 % follicular carcinoma. No statistically significant difference in the odds of harboring RAS mutation was found between subtypes. In conclusion, RAS mutation testing demonstrates clinical utility for refining the diagnosis of cytologically indeterminate thyroid nodules. Positivity confers a 1.7-fold increased malignancy risk, supporting use for personalized decision-making regarding surgery vs. monitoring. Follicular variant papillary carcinoma constitutes the most common RAS-positive malignant histological subtype. See also the graphical abstract(Fig. 1).

Correlation of FNAC with Histopathology in the Diagnosis of Differentiated Thyroid Carcinoma

Background: Fine-needle aspiration cytology (FNAC) is an important diagnostic tool for differentiating between neoplastic and non-neoplastic lesions of the thyroid. The current study was carried out to observe the comparison between preoperative fine needle aspiration cytology (FNAC) and postoperative Histopathology in the diagnosis of Differentiated Thyroid Carcinoma. Methods: This cross-sectional observational study was conducted in the department of Pathology, Rajshahi Medical College (RMC), Bangladesh from January 2019 to December 2020. Clinically suspected and diagnosed by FNAC, a total of forty patients of differentiated thyroid carcinoma attending outpatient and inpatient department of Otolaryngology, RMCH were enrolled in this study. Biopsy material was examined for histopathological diagnosis. Results: In this study, out of forty cases, 35 were papillary and 5 were follicular carcinoma. Mean age was 25.48+9.70 years and Male: Female was 1:6. Among 40 cases of FNAC findings, 33 cases (82.5%) were classic papillary carcinoma, 01(2.5%) case was follicular variant of papillary carcinoma, 5 cases were (12.5%) were follicular lesion and 01(2.5%) case was nodular goitre. Among 40 cases of histopathological findings, 32(80%) cases were classic papillary carcinoma, 03(7.5%) were follicular variant of papillary carcinoma and 5 cases were follicular carcinoma. In histopathological findings, none of them was nodular goitre. So, all FNAC findings were consistent with histopathological findings except nodular goitre which was diagnosed as classic papillary carcinoma in histopathology. Conclusion: FNAC is a safe and relatively accurate method for preoperative evaluation of thyroid malignancy before surgery. Therefore it is a reliable diagnostic test for evaluation of thyroid carcinoma. J Shaheed Suhrawardy Med Coll 2022; 14(1): 28-31

Malignant struma ovarii- Report of a rare case

Struma ovarii is a highly specialized form of mature ovarian teratoma in which the ovary contains >50% of thyroid tissue. It accounts for 1 – 3% of benign teratomas of the ovary. Malignant transformation is observed in 5-37% cases of struma ovarii. Peak age of incidence 4 - 5th decade with excellent prognosis. We report a rare form of malignant struma ovarii, composed of a follicular variant of papillary thyroid carcinoma with capsular invasion. A65-year-old hypertensive postmenopausal female presented with complaints of pain in abdomen, pelvic mass, frequent micturition, since 3 days. A pelvic sonogram showed an enlarged heterogenous right ovarian mass of sized 12 x 9 x 5 cm, with solid cystic lesion. Left ovary was unilocular and cystic of sized 5.5 x 4 x 3 cm. The uterus and cervix appeared to be normal. She underwent an exploratory laparotomy, and a total abdominal hysterectomy with bilateral salpingo-oophorectomy. Based on histopathological and radiological features an impression of follicular variant of papillary carcinoma of thyroid with capsular invasion was favoured. : The patient was successfully treated with total abdominal hysterectomy with bilateral salpingo-oopherectomy. There are no sign of recurrence and metastasis two months after surgery. Patient is under regular follow up. : Malignant struma ovarii is a medical rarity and very few studies have been reported.

Do large thyroid nodules (≥4 cm) without suspicious cytology need surgery?

Fine-needle aspiration biopsy (FNAB) is a good diagnostic tool for thyroid nodules; however, its high false-negative rate for giant nodules remains controversial. Many clinicians recommend surgical resection for nodules >4 cm owing to an increased risk of malignancy and an increased false-negative rate. This study aimed to examine the feasibility of this approach and investigate the incidence of malignancy in thyroid nodules >4 cm without suspicious cytology based on medical records in our center. This was a retrospective analysis of 453 patients that underwent preoperative FNAB for nodules measuring >4 cm between January 2017 and August 2022 at Severance Hospital, Seoul. Among the 453 patients, 140 nodules were benign and 119 were indeterminate. Among 259 patients, the final pathology results were divided into benign (149) and cancerous (110) groups, and the prevalence of malignancy was 38.9% in the benign group and 55.5% in the indeterminate group. Among the malignancies, follicular carcinoma and follicular variants of papillary carcinoma were observed in 83% of the cytologically benign group and 62.8% of the indeterminate group. Preoperative FNAB had high false-negative rates and low diagnostic accuracy in patients with thyroid nodules >4 cm without suspicious cytologic features; therefore, diagnostic surgery may be considered a treatment option.

Cytological Diagnosis of Follicular Patterned Lesion of Thyroid Nodule and its Follow-up Histopathology

The follicular patterned lesion of thyroid nodules is an exciting topic because it is not clear whether the lesion is benign or malignant. It comprises hyperplastic/adenomatoid nodules, follicular adenoma, follicular carcinoma and follicular variant of papillary carcinoma. The cytological diagnosis of atypia of undetermined significance/Follicular lesion of undetermined significance, follicular neoplasm/suspicious for follicular neoplasm and suspicious for malignancy remains controversial in terms of management. The study aimed to examine the extent of invasion of malignant lesions in follow-up histopathology diagnosed as undetermined lesions cytologically. A total of 256 cases were included in this study; among these, 199 cases were benign lesions, 15 cases were non-diagnostic and 42 cases were diagnosed either of uncertainty for malignancy with cellular atypia or malignancy. Subsequent follow-up resection and histopathology were done with 48 cases (18.75%), which comprises 1 non-diagnostic, 10 benign lesions, 21 atypia of undetermined significance/Follicular lesion of undetermined significance, 7 Follicular neoplasm/Suspicious for a follicular neoplasm, 5 suspicious for malignancy and 4 malignancies. Also, 6 Follicular variant of papillary thyroid carcinoma, 6 classic papillary carcinoma, 5 follicular carcinoma and 1 anaplastic carcinoma were diagnosed in follow-up resection histopathology of 48 cases. Thirty eight cases were of undetermined significance of malignancy with cytological features of the follicular lesion. Four Follicular variant of papillary thyroid carcinoma, 2 follicular carcinoma and 1 papillary carcinoma were diagnosed in 21 resected cases cytologically reported as Atypia of undetermined significance/Follicular lesion of undetermined significance with malignancy risk of 33.33%. Three malignancies in follicular neoplasm/suspicious for a follicular neoplasm with a risk of 42.85% and 4 malignancies in suspicious malignancy group with a risk of 80% were found. The average risk of malignancy of these three undetermined categories was reduced to 24.24% from 42.42% upon reclassification of the Follicular variant of papillary thyroid carcinoma. All the Follicular variants of papillary thyroid carcinoma diagnosed by histopathology were non-invasive regarding lymph node involvement and microvascular or capsular invasion. Mediscope 2023;10(2): 68-77

Comparative Study of FNAC and Histopathology in Diagnosis of Thyroid Swelling

Background: Neck swelling is a common clinical presentation in ENT practice and it carries significant morbidity and even mortality if not managed properly. Thyroid swelling being the most common type among them. We conducted a study to assess the role of FNAC in diagnosing the nature of thyroid swelling and comparing its result with histopathology finding. The aim and objectives of this study is to observe the correlation between preoperative Fine Needle Aspiration Cytology (FNAC) and post operative histopathology in the diagnosis of thyroid lesions.
 Materials and methods: A cross sectional study was done in the Department of Otolaryngology-Head & Neck Surgery and Department of Pathology, Chittagong Medical College, Chattogram from January 2018 to December 2020. Eighty (80) patients, both male and female of different age groups were included. The selected patients were subjected to clinical examination, routine hematological investigation, thyroid hormone test, USG, thyroid Scan, FNAC and histopathological examinations of the thyroidectomy specimens. Correlation between FNAC and histopathology reports were done in those patients.
 Results: In this study, age range of the patients were 11 years to 70 years. Out of 80 patients of thyroid swelling, the most of the patients 28(35%) were 31-40 years of age groups. out of 80 patients of thyroid swelling, 26(26.25%) were male and 59(73.75%) were female and male female ratio was1:2.81. On FNAC 64(80%) were non neoplastic and 16(20%) were neoplastic. Out of 64(80%) of non neoplastic lesions, 62(77.50%) were nodular goitre and 2(2.5%) were lymphocytic thyroiditis and out of 16(20%) neoplastic thyroid swelling, 2(2.50%) were follicular lesion, 12(15%) were papillary carcinoma, 1(1.25%) was follicular carcinoma and 1(1.25%) was suspicious for malignancy. On histopathology, out of 80 patients of thyroid swelling 60(75%) were non neoplastic and 20(25%) were neoplastic. out of 60(75%) non neoplastic, 59 (73.75%) were nodular, 1(1.25%) was Lymphocytic thyroiditis and out of 20(25%) neoplastic lesions, 3(3.75%) were follicular adenoma,13(16.25%) were papillary carcinoma,3(3.75%) were follicular variant of papillary carcinoma and 1(1.25%) was follicular carcinoma.
 Conclusion: It is concluded from the present study that female are more affected in our region. Non neoplastic lesions of the thyroid were more common (Nodular goitre being the commonest) than neoplastic lesions (Papillary carcinoma being the commonest). FNAC is essential diagnostic tool for thyroid swelling but final diagnosis to rule out thyroid cancer is surgical excision and histopathology.
 Chatt Maa Shi Hosp Med Coll J; Vol.22 (1); January 2023; Page 19-22

The Role of Cytomorphometric Image Analysis in the Diagnosis of Thyroid Nodules.

Introduction Fine needle aspiration cytology (FNAC) plays a vital role in the diagnosis of thyroid nodules. However, it is challenging due to the heterogeneity of thyroid nodules, overlapping cytomorphological features, and interobserver variability. Cytomorphometric analysis turns subjective observations into quantitative values. In this study, we performed cytomorphometric image analysis on cytological smears of thyroid nodules, classified according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Materials and methods A retrospective analysis of Papanicolaou (PAP) and Hematoxylin & Eosin (H&E) stained fine needle aspirate smears from 50 patients with thyroid nodules with available follow-up histopathology was performed for a period of two years (March 2021 - March 2023), after obtaining approval from the institutional human ethical committee (IHEC-LOP/2020/IM0355). The nodules were categorized according to TBSRTC and werethen subjected to cytomorphometric image analysis. Each nucleus was analyzed for 14 parameters, including aspect ratio, intensity, diameter, perimeter, roundness, area, fractal dimension, feret diameter, circularity, radii, fournier description, and chromatin texture parameters such as heterogeneity and clumpiness. The data obtained was analyzed through relevant statistical methods using SPSS version 23 (IBM Inc., Armonk, New York) and was compared by using the analysis of variance (ANOVA) test and post hoc test. Results Our results revealed that cytomorphometric image analysis not only distinguishes benign and malignant thyroid nodules but also can aid in categorizing thyroid nodules with predominant follicular patterns, such as follicular variant of papillary carcinoma, follicular adenoma and follicular carcinoma (p<0.001). Conclusions Morphometric analysis of cytological smears combined with cytomorphology has the potential to be an important tool in the diagnosis of thyroid nodules. It can improve diagnostic accuracy for better treatment and improved prognosis.

Expanding the Spectrum of BRAF Non-V600E Mutations in Thyroid Nodules: Evidence-Based Data from a Tertiary Referral Centre.

The BRAF p.V600E mutation represents the most specific marker for papillary thyroid carcinoma and is potentially related to aggressive behavior and persistent disease. BRAF alterations other than the p.V600E are less common in thyroid carcinoma and represent an alternative mechanism of BRAF activation with unclear clinical significance. The study aims to describe the frequency and clinicopathologic characteristics of BRAF non-V600E mutations in a large cohort (1654 samples) of thyroid lesions characterized by next-generation sequencing. BRAF mutations have been found in 20.3% (337/1654) of thyroid nodules, including classic (p.V600E) mutation in 19.2% (317/1654) of samples and non-V600E variants in 1.1% of cases (19/1654). BRAF non-V600E alterations include 5 cases harboring p.K601E, 2 harboring p.V600K substitutions, 2 with a p.K601G variant, and 10 cases with other BRAF non-V600E alterations. BRAF non-V600E mutations have been reported in one case of follicular adenoma, three cases of conventional papillary thyroid carcinoma, eight cases of follicular variant of papillary carcinomas, one case of columnar cell variant papillary thyroid carcinoma, one case of oncocytic follicular carcinoma, and two bone metastasis of follicular thyroid carcinoma. We confirm that BRAF non-V600E mutations are uncommon and typically found in indolent follicular-patterned tumors. Indeed, we show that BRAF non-V600E mutations can be found in tumors with metastatic potential. However, in both aggressive cases, the BRAF mutations were concomitant with other molecular alterations, such as TERT promoter mutation.

Role of GDF-15 as an Immunohistochemical Marker in Follicular Neoplasms and Lesions of Thyroid

Introduction: A pre-therapeutic distinction between benign and malignant thyroid nodules is critical for deciding the therapeutic strategy, wherein fine-needle aspiration cytology plays a major role. However, there are grey-zone categories in the Bethesda system for reporting thyroid cytopathology, which is currently, the universally accepted pattern for reporting thyroid FNAC. Several immunomarkers studied in these ‘indeterminate’ lesions have proven to be of limited value. Recent molecular studies have shown the growth differentiation factor-15 (GDF-15) gene to be a promising marker in various malignancies; though, there is sparse literature regarding its use as a surrogate immunohistochemical marker, especially in thyroid neoplasms. The present (pilot) study explores its possible utility in the pre-therapeutic distinction of follicular-patterned lesions and neoplasms of the thyroid by testing it initially on histopathologic sections. Objective: To assess the utility of GDF-15 as an immunohistochemical marker in distinguishing common follicular-patterned thyroid neoplasms and lesions. Materials and Methods: GDF-15 immunohistochemistry was performed on 75 surgical specimens of thyroid lesions, comprising 19 adenomatous nodules or follicular hyperplasias, 10 nodular goitres, 17 follicular thyroid adenomas, 8 follicular thyroid carcinomas, 12 follicular variant of papillary thyroid carcinomas, and 9 conventional papillary thyroid carcinomas. All these cases were histologically proven, and their immunohistochemical interpretation was performed using the immunoreactive scoring system. Pearson’s analysis was performed for the immunohistochemical correlation among the study groups. Results: The findings were inconsistent; 16 follicular-patterned malignancies (5 follicular carcinomas and 11 cases of follicular variant of papillary carcinoma) and seven conventional papillary thyroid carcinomas revealed both cytoplasmic and membranous expression of GDF-15. All benign lesions were negative except one follicular adenoma and three follicular hyperplasias, which exhibited patchy or focal GDF-15 positivity. However, three follicular carcinomas, one follicular variant of papillary carcinoma, and two conventional papillary carcinomas were found to be GDF-15-negative. Conclusion: Though there is a literature backup supporting the use of GDF-15 gene analysis in differentiating various follicular-patterned neoplasms, the GDF-15 protein, as an immunohistochemical marker failed to distinguish not only between benign and malignant follicular-patterned neoplasms but also between follicular carcinoma and follicular variant of papillary carcinoma.

What is the contribution of tumor capsule thickness and tumor nucleus diameter to differential diagnosis in encapsulated variant thyroid papillary carcinomas?

Objective: Capsule thickness and papillary carcinoma nuclear features are common diagnostic criteria for invasive follicular variant papillary thyroid carcinoma (IEFVPTC), non-invasive follicular thyroid neoplasm with papillary nuclear features (NIFT-P), and encapsulated papillary thyroid carcinoma (E-PTC). Our goal in this study is to evaluate these two histomorphological criteria using computerized image analysis systems and to determine whether they can serve as auxiliary criteria for distinguishing these diagnostic groups. Materials and methods: 10 patients were selected from IEFVPTC, NIFT-P, and E-PTC diagnostic groups. Slides containing the largest tumor diameter were scanned and digitized. Using computerized image analysis systems, tumor capsule thickness was measured from 4 areas of 4 equal quadrants, and the average tumor capsule thickness (TCT) was determined. Furthermore, from these 4 equal quadrants, the nucleus diameter of 10 clearly distinguishable cells was measured to determine the average tumor cell nucleus diameter (ND). Results: TCT and ND histomorphological criteria were statistically significant among the diagnostic groups. For IFVPTC diagnosis, both TCT and ND were found to be significant diagnostic tools. We demonstrated that ND can easily be used as a diagnostic tool for NIFT-P, whereas more caution is required for TCT. Conclusion: Differentiating papillary nuclear feature-containing follicular variant thyroid papillary carcinomas is challenging. In this study with a limited number of patients, we demonstrated that the TCT and ND criteria can, to some extent, contribute to differential diagnosis between diagnostic groups. Future studies with larger patient groups and more advanced computerized image analysis programs will yield more promising results.

Lodine-131 uptake in a patient with cholelithiasis on post-therapeutic scan

A 71-year-old male patient was diagnosed with papillary carcinoma follicular variant after bilateral total thyroidectomy and radioactive iodine treatment was applied. The post-therapeutic whole-body scan demonstrated a focal 131I uptake in the right lobe of the liver in the right upper quadrant of the abdomen. Single-photon emission computed tomography/computed tomography (SPECT/CT) was performed to determine the precise localization of 131I uptake. It was understood that the identified focal 131I activity was due to cholelithiasis. In the same period, free-floating gallstones in the lumen and the gallbladder neck were observed on the abdominal ultrasonography

Comparison between total thyroidectomy and hemithyroidectomy in TIR3B thyroid nodules management

PurposeThyroid nodules classified as TIR3B according to SIAPEC 2014 are considered a clinical challenge due to the risk to be malignant. This retrospective study aimed to compare the performances of total thyroidectomy (TT) and hemithyroidectomy (HT) in the surgical management of a consecutive cohort of patients affected by TIR3B thyroid nodule in terms of side effects and the rate of malignancy detected.MethodsFrom 2011 to 2019, 136 (111 women, 25 men; average age of 53.5 years) patients having a thyroid nodule with a cytological diagnosis of TIR3B who underwent TT or HT were retrospectively included.ResultsOut of 136 patients, 106 (78%) received TT, while the remaining 30 (22%) HT. The final diagnosis was malignant in 65 patients (48%), with follicular variant of papillary carcinoma as the most frequent. The diagnosis of malignancy was significantly more common in the TT group with 56 patients (53%) compared to the HT group with 9 cases (30%) (p = 0.001). Patients who underwent TT were significantly older, had larger nodules and the time between diagnosis and surgery was significantly longer compared to HT (p = 0.001; p0.003; p = 0.002). No main post-surgical complications were registered, except for one case of transient hypocalcemia in a patient who underwent TT.ConclusionsOur data showed a malignancy rate of TIR3B lesions higher than expected (48%). Both TT and HT seem to be effective approaches for the treatment of TIR3B nodules with a very low rate of post-surgical comorbidities. In the choice of surgical approach, it is crucial to consider the presence of risk factors (clinical and ultrasound characteristics), nodule size, patients’ opinion, and surgeon’s skills and experience.

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features; a single centre study

Introduction: Papillary carcinoma of the thyroid is the commonest cancer in the thyroid with an increasing incidence over the past few decades. A subset of papillary carcinomas was re-classified into “Non-invasive Follicular Thyroid Neoplasm with papillary-like nuclear features” (NIFTP) in late 2017, due to the excellent prognosis they exhibit. Identification of NIFTP is important because surgical management and follow up is similar to follicular adenoma, thus reducing the psychological burden to patient, eliminating unnecessary exposure to radiation and economic burden to the society. This study intended to assess the prevalence and the inter-observer consistency in identifying NIFTP in the study sample. Methods: This retrospective, descriptive, cross-sectional study included all thyroid specimens received at our department in 2017. Thyroid neoplasms with a potential for reclassification to NIFTP were reassessed according the WHO criteria by two investigators who were blinded to the previous and each other's diagnoses. Results: Out of the 256 thyroid specimens received, 74/256 (28.90%) considered to have potential to be reclassified as NIFTP which included 34 cancers. Only 5/74 (6.75%) satisfied the criteria for NIFTP. Three NIFTPs had been reported as papillary microcarcinoma and the other two as follicular variant of papillary carcinoma. Inter-observer consistency in re-classifying the 74 tumours was 94.6%, with a 100% consistency in diagnosing NIFTP. Following re-classification, the proportion of cancers in the study sample reduced to 56/256 (21.87%) from 61/256 (23.82%). The prevalence of NIFTP in the study sample was 1.95% (5/256). Conclusions: The prevalence of NIFTP in the study sample is comparable to the Asian population. The current study reports a high inter-observer consistency in recognizing NIFTP among potential lesions, most likely due to the strict adherence to WHO criteria.

Challenge in the Pathological Diagnosis of the Follicular- Patterned Thyroid Lesions.

Background:The follicular-patterned thyroid lesions (FPTLs) include hyperplastic nodules (HN), follicular adenoma (FA), non-invasive follicular neoplasm with papillary-like nuclear features (NIFTP), follicular carcinoma (FC), and the follicular variant of papillary carcinoma (FVPTC). Sometimes the pathologists cannot accurately separate these lesions from each others on a histological basis. Aims: To evaluate the utility of immunohistochemistry in the diagnosis of FPTLs. Materials and methods:Immunohistochemical analysis, incorporating 83 cases of histologically confirmed FPTLs out of which 20 carcinomas, 51 benign FPTLs (38 HN and 13 FA), and 12NIFTP were separated from each others using four immunostains (HBME-1, CK19, Galectin-3, and CD56). Results: We found statistically significantly more frequent expression of HBME-1, CK19, Galectin-3 proteins in carcinomas as compared to benign FPTLs (p = <0.01). HBME-1 and Galectin-3 were the most sensitive markers for the diagnosis of malignant FPTLs (75%). Galectin-3 was the most specific marker for the diagnosis of carcinoma (90.3%). Conclusions:The histomorphological features remain the cornerstone of the diagnosis of FPTN. Although HBME-1, Galectin-3, and CK19 immunostains have some diagnostic value in the separation of malignant from benign FPTLs, they are variably expressed in the benign and malignant FPTLs. No single immunostain has sufficient sensitivity and specificity and therefore their diagnostic use is controversial. Future studies are mandated to find more reliable markers that can separate between benign and malignant FPTLs.

Reporting Thyroid Cytology in a Globalized World

The Italian SIAPEC-AIT 2014 classification, the 2017 Bethesda System for Reporting Thyroid Cytology (TBSRTC), the 2016 UK Royal College of Pathologists (RCPath) thyroid reporting system, and the 2019 Japanese reporting system for thyroid aspiration cytology (JRSTAC2019) represent the most widely used reporting systems among clinicians and pathologists for the purpose of cytologically diagnosing, estimating the potential risk of malignancy (ROM), and defining the most appropriate treatment for a patient with a thyroid nodule. Although all the systems use overlapping diagnostic categories and morphologic criteria, they differ on the basis of the criteria for inclusion in the cytologic categories, which may, in turn, affect the ROM of a given category and the clinical management of the patient, particularly with regard to the “indeterminate” categories. The aim of this review is to analyze the main differences that emerge between the systems and to propose possible solutions for a comprehensive reporting system that integrates and harmonizes all the criteria of the Italian classification and the Bethesda system, also taking into account the impact that the new tumor entity NIFTP (non-invasive follicular tumor with papillary-like nuclear features) that has, in many instances, replaced the non-invasive form of the follicular variant of papillary carcinoma, has had on the modification of malignancy risks.

Long noncoding RNA landscapes specific to benign and malignant thyroid neoplasms of distinct histological subtypes

The main types of thyroid neoplasms, follicular adenoma (FA), follicular thyroid carcinoma (FTC), classical and follicular variants of papillary carcinoma (clPTC and fvPTC), and anaplastic thyroid carcinoma (ATC), differ in prognosis, progression rate and metastatic behaviour. Specific patterns of lncRNAs involved in the development of clinical and morphological features can be presumed. LncRNA landscapes within distinct benign and malignant histological variants of thyroid neoplasms were not investigated. The aim of the study was to discover long noncoding RNA landscapes common and specific to major benign and malignant histological subtypes of thyroid neoplasms. LncRNA expression in FA, FTC, fvPTC, clPTC and ATC was analysed with comprehensive microarray and RNA-Seq datasets. Putative biological functions were evaluated via enrichment analysis of coexpressed coding genes. In the results, lncRNAs common and specific to FTC, clPTC, fvPTC, and ATC were identified. The discovered lncRNAs are putatively involved in L1CAM interactions, namely, pre-mRNA processing (lncRNAs specific to FTC); PCP/CE and WNT pathways (lncRNAs specific to fvPTC); extracellular matrix organization (lncRNAs specific to clPTC); and the cell cycle (lncRNAs specific to ATC). Known oncogenic and suppressor lncRNAs (RMST, CRNDE, SLC26A4-AS1, NR2F1-AS1, and LINC00511) were aberrantly expressed in thyroid carcinomas. These findings enhance the understanding of lncRNAs in the development of subtype-specific features in thyroid cancer.

English

BACKGROUND Thyroid carcinoma is the most common endocrine malignancy. Galectin-3 has been implicated in malignant transformation and metastasis of cancer cells and it has received notable recognition for its usefulness as a diagnostic marker for thyroid cancer. We wanted to evaluate the expression of Galectin-3 on thyroid neoplasms, establish its diagnostic accuracy and also differentiate between benign and malignant thyroid lesions. METHODS A total of 54 thyroidectomy specimens were studied over a period of 3 years (2016 - 2019) which included 20 benign and 34 malignant thyroid neoplasms. Histopathologic evaluation of H &amp; E stained sections was done and immunohistochemistry (IHC) staining for Galectin-3 was performed for all neoplasms with the polymeric method using lyophilized mouse monoclonal antibody. (Path n Situ) and grading based on intensity of Galectin-3 expression were noted. RESULTS Galectin-3 expression was significantly higher (P &lt; 0.001) in malignant thyroid neoplasms in comparison to the benign neoplasms. Galectin-3 expression for malignant neoplasms showed sensitivity of 88.23 %, specificity of 95.0 %, positive predictive value (PPV) of 96.8 % and negative predictive value (NPV) of 82.6 %. Galectin-3 expression in Papillary thyroid carcinoma showed a sensitivity of 95.83 % and PPV of 88.2 %. While comparing the neoplasms showing follicular pattern, Galectin-3 expression was more in the malignant neoplasms (follicular carcinoma and follicular variant of papillary carcinoma thyroid) than benign neoplasms (follicular adenoma). CONCLUSIONS Galectin-3 is a useful marker in differentiating benign and malignant thyroid neoplasms. Galectin-3 is sensitive for Papillary thyroid carcinoma (PTC) and among the follicular patterned lesions, Galectin-3 is sensitive for follicular variant of papillary carcinoma and follicular carcinoma. Thus Galectin-3 protein expression evaluated using immunohistochemistry technique acts as an adjunctive ancillary technique in thyroid cancer diagnosis. KEYWORDS Galectin-3, Immunohistochemistry, Thyroid Carcinoma, Papillary Thyroid Carcinoma

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.

Not Your Typical “Lipoma”; An Unusual Case of Thyroid Cancer Presenting With a Skull Lesion

Abstract Background: Bone metastases from thyroid cancers tends to more commonly afflict the long bones, pelvis, ribs, vertebrae and sternum. Skull metastases are exceedingly rare being found in only ~2.5% of patients with thyroid cancer, more commonly in patients with Follicular thyroid carcinomas. We present an unusual case of thyroid cancer presenting with skull metastasis. Clinical Case: A 55 year- old male with a slowly growing skull lesion was referred to our center after an attempt to remove this scalp lesion was aborted as the lesion extended through a calvarial defect. This lesion was noted by the patient 1 year prior to presentation and was slowly growing in size. He opted for watchful monitoring as this was presumed to be a lipoma at the time. Imaging revealed a 6.4 x 4.6 x 6.3 cm lesion in the left parietal region with a large extra-axial and soft tissue components with intervening bone destruction as well as adjacent dural thickening. Differential for the lesion given the radiological appearance included meningioma, hemangiopericytoma, or an osseous/dural metastasis with an unclear primary malignancy. Excision of the extra-axial parietal lesion was consistent with metastatic thyroid carcinoma (follicular variant of papillary carcinoma). Further imaging revealed a multi nodular goiter with a prominent 6 cm left thyroid nodule. Patient had no obstructive symptoms. He underwent a total thyroidectomy with findings of a 6.8 cm minimally invasive follicular carcinoma with multifocal capsular invasion and a focus of vascular invasion. The right lobe revealed 1.5 cm classic PTC. Notably, margins were free of disease and cervical lymph nodes were negative for disease. Imaging revealed no other metastatic lesions. Patient received RAI after his total thyroidectomy and was started on suppressive doses of levothyroxine. He has been followed with annual MRI Brain, USG thyroid and Thyroglobulin levels and remains free of recurrence for the past 36 months. Conclusion: Thyroid cancer can present with skull metastasis without causing significant morbidity. This is a rare manifestation of disease and can be easily misdiagnosed. This case highlights the importance of keeping a broad differential when evaluating skull lesions.