Seven years of Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP): Rate of Acceptance and Variation of Diagnostic Approaches Across Different Continents.

CONTEXT: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced as a new entity replacing the diagnosis of noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC). Significant variability in the incidence of NIFTP diagnosed in different world regions has been reported. OBJECTIVE: To investigate the rate of adoption of NIFTP, change in practice patterns, and uniformity in applying diagnostic criteria among pathologists practicing in different regions. METHODS: Two surveys distributed to pathologists of the International Endocrine Pathology Discussion Group with multiple-choice questions on NIFTP adoption into pathology practice and whole slide images of 5 tumors to collect information on nuclear score and diagnosis. Forty-eight endocrine pathologists, including 24 from North America, 8 from Europe, and 16 from Asia/Oceania completed the first survey and 38 the second survey. RESULTS: A 94% adoption rate of NIFTP by the pathologists was found. Yet, the frequency of rendering NIFTP diagnosis was significantly higher in North America than in other regions (P = .009). While the highest concordance was found in diagnosing lesions with mildly or well-developed PTC-like nuclei, there was significant variability in nuclear scoring and diagnosing NIFTP for tumors with moderate nuclear changes (nuclear score 2) (case 2, P < .05). Pathologists practicing in North America and Europe showed a tendency for lower thresholds for PTC-like nuclei and NIFTP than those practicing in Asia/Oceania. CONCLUSION: Despite a high adoption rate of NIFTP across geographic regions, NIFTP is diagnosed more often by pathologists in North America. Significant differences remain in diagnosing intermediate PTC-like nuclei and respectively NIFTP, with more conservative nuclear scoring in Asia/Oceania, which may explain the geographic differences in NIFTP incidence.

The Effectiveness of Adjuvant PD-1 Inhibitors in Patients With Surgically Resected Stage III/IV Acral Melanoma.

Our aim was to assess the efficacy of adjuvant programmed cell death protein-1 (PD-1) inhibitors and compare the other adjuvant treatments in patients with surgically resected stage III or IV acral melanoma. This study is a multicenter, retrospective analysis. We included 114 patients with stage III or IV acral malignant melanoma who underwent surgery within the past 10 years. We analyzed the effect of adjuvant programmed cell death protein-1 inhibitors on disease-free survival (DFS). The mean follow-up was 40 months, during which 69 (59.5%) patients experienced recurrence. Among the participants, 64 (56.1%) received systemic adjuvant therapy. Specifically, 48.4% received anti-PD-1 therapy, 29.7% received interferon, 14.1% received tezozolomide, and 7.8% received B-Raf proto-oncogene/mitogen-activated protein kinase inhibitors. Patients who received adjuvant therapy had a median DFS of 24 (10.9-37.2) months, whereas those who did not receive adjuvant therapy had a median DFS of 15 (9.8-20.2) months. Multivariate analysis for DFS revealed that the receipt of adjuvant therapy and lymph node metastasis stage were independent significant parameters ( P = 0.021, P = 0.018, respectively). No statistically significant difference was observed for DFS between programmed cell death protein-1 inhibitor treatment and other adjuvant treatments. Regarding overall survival (OS), patients who received adjuvant treatment had a median OS of 71 (30.4-111.7) months, whereas those who did not receive adjuvant treatment had a median OS of 38 (16.7-59.3; P = 0.023) months. In addition, there were no significant differences in OS observed between various adjuvant treatment agents ( P = 0.122). In our study, we have shown that adjuvant therapy had a positive effect on both DFS and OS in patients with stages III-IV acral melanoma who underwent curative intent surgery. Notably, we found no significant differences between anti-PD-1 therapy and other adjuvant therapies.

TROP2: a potential marker in diagnosis of thyroid neoplasms.

BACKGROUND AND OBJECTIVES: The human trophoblast cell surface antigen (TROP-2), a transmembrane glycoprotein, has recently been investigated as a valuable marker of thyroid epithelial neoplasms. In this study, we aimed to demonstrate the diagnostic utility of TROP2 in thyroid neoplasms. METHODS: A total of 308 cases, including 170 cases of different PTC variants, 50 cases of benign and non-neoplastic lesions, and 86 cases of other neoplasms (NIFT-P, poorly differentiated thyroid carcinoma, anaplastic thyroid carcinoma, follicular thyroid carcinoma, Hürthle cell carcinoma, and medullary thyroid carcinoma), were included in this study. Only membranous staining with TROP2 was considered positive. RESULTS: In PTC, classical (n = 35), tall cell (n = 41), follicular (n = 39), solid (n = 19), hobnail (n = 10), Warthin-like (n = l0), columnar (n = 7), and oncocytic variant (n = 9) were 100%, 97.6%, 5.1%, 42.1%, 90%, 90%, 28.6%, and 33.3% positive, respectively. A negative reaction was observed in all 50 cases of benign and non-neoplastic lesions and also in surrounding normal thyroid tissue in all cases. Negative reactions were observed in 83 (n = 86) of other thyroid neoplasms including NIFT-P (n = 20), poorly differentiated thyroid carcinoma (n = 10), anaplastic thyroid carcinoma (n = 10), follicular thyroid carcinoma (n = 18), Hürthle cell carcinoma (n = 18), and medullary thyroid carcinoma (n = 10). Only focal positivity was observed in three Hürthle cell carcinoma cases. CONCLUSION: TROP2 was a helpful marker for differentiating PTC, especially in the classic, tall cell, hobnail, and Warthin-like variants, benign and non-neoplastic lesions, and other neoplasms of the thyroid.

Diagnostic utility of ThinPrep Imaging System® for detecting atypical glandular cells in cervical smear samples.

INTRODUCTION: The ThinPrep Imaging System® (TIS) is an automated system that has now been used for over 20 years in the primary screening of ThinPrep liquid-based cervical samples. Although there are a lot of publications about the diagnostic utility of this method in squamous cell lesions, which has advantages such as time-saving and standardization, there are only a few publications on this issue in glandular cell lesions in the literature. We aimed in this study to investigate the diagnostic utility of the system in the detection of premalignant and malignant glandular lesions in cervical smears. MATERIAL AND METHOD: Our study was conducted retrospectively, and a total of 126 cervical smear samples between 2010 and 2022 that have histological confirmation of endometrial adenocarcinoma (EAC), endocervical adenocarcinoma (ECAC), or adenocarcinoma in situ (AIS), were included. These samples were re-evaluated by manual and TIS by two experienced pathologists, and the results were compared in terms of sensitivity. RESULTS: We found out that 70 of the 126 smear samples have atypical glandular cells. We detect 48 cases (48/70) (sensitivity 68.5%) in manual examination, however TIS successfully determined 66 cases (66/70) (sensitivity 94.3%). In 4 cases (5.7%) TIS could not detect the atypical cells within the 22 areas. CONCLUSION: TIS is quite an effective method with a high sensitivity for detecting atypical glandular cells in cervical smears, like detecting squamous cell anomalies. Imposing this system in our laboratory and using them appropriately, save us time and help to ensure standardization. Additionally, it may be a good way to adopt artificial intelligence and digital pathology in today's world.

Diagnostic accuracy of Thinprep® in cervical lymph node aspiration: Assessment according to the Sydney system.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is a reliable technique that has been used for many years in lymphadenopathy diagnosis. Although conventional smear is the standard approach in FNAC, liquid-based cytology (LBC) is accepted as an alternative method. Reporting standardization is a significant gap in fine-needle aspiration cytology, leading to failure in pathologist-clinician dialog and interobserver variability. In 2020, an expert panel proposed the Sydney system for classifying and reporting lymph node aspiration cytology. This study aimed to evaluate the diagnostic accuracy of LBC in lymph node aspiration cytology under the guidance of the Sydney system. METHODS: Five hundred-four LBC samples were reevaluated and classified according to the Sydney system. Of these, n = 24 were categorized as L1-inadequate/non-diagnostic, n = 283 as L2-benign, n = 36 as L3- atypical cells of undetermined significance/atypical lymphoid cells of uncertain significance (AUS/ALUS), n = 48 as L4-suspicious, and n = 113 as L5-malignant. Four hundred-one samples were histopathologically confirmed. The diagnostic accuracy of LBC and the risk of malignancy for each Sydney category were calculated. RESULTS: The results were as follows: sensitivity 98.97%; specificity 98.60%; positive predictive value 94.80%; negative predictive value 99.29%; and overall diagnostic accuracy 98.75%. The ROM was 16.6% for L1, 0.7% for L2, 88.8% for L3, and 100% for L4 and L5. CONCLUSION: LBC is suitable for use in lymph node aspiration under the guidance of the Sydney system and has high diagnostic accuracy. Future comprehensive studies will increase the applicability of the Sydney system and minimize interobserver variability.

Primary Synovial Sarcoma of the Thyroid: Challenges in Cytologic Diagnosis and Review of the Literature.

BACKGROUND: Primary synovial sarcoma (SS) of the thyroid (PSST) is extremely rare. Its differential diagnosis from other neoplasms is essential since it has different management protocols and prognosis. CASE: A 26-year-old man with a 4.5-cm solid lobulated mass was seen at an outside hospital. Fine needle aspiration (FNA) was interpreted as a papillary carcinoma, and a total thyroidectomy was performed. The final histologic diagnosis was spindle epithelial tumor with thymus-like differentiation (SETTLE). No metastases were detected at that time, and the patient received radioactive iodine treatment. Two years post-surgery, he was seen at our hospital with a local recurrence, and FNA was considered as consistent with SETTLE. The mass was resected, and a left modified radical neck dissection was performed. The tumor revealed necrosis and a high mitotic index. Following histologic, immunohistochemical, and molecular studies, the tumor was classified as a PSST. The patient received chemotherapy and targeted immunotherapy, but he died 41 months after the initial presentation. CONCLUSION: The main diagnostic pitfall of PSST is SETTLE. The presence of mitotic figures and basal lamina material, negative staining for smooth muscle actin, and positive staining for transducer-like enhancer of split 1 antibody favor SS over SETTLE. SYT gene rearrangement is essential to establish the definitive diagnosis of PSST.

DNA Repair Gene (XPD, XRCC4, and XRCC1) Polymorphisms in Patients with Endometrial Hyperplasia: A Pilot Study.

BACKGROUND In this study, we aimed to evaluate the association between endometrial hyperplasia and DNA repair gene (XPD, XRCC4, and XRCC1) polymorphisms. MATERIAL AND METHODS There were 114 cases enrolled in the study in 4 groups: simple endometrial hyperplasia (SH) (Group 1), complex endometrial hyperplasia without atypia (CH) (Group 2), complex atypical endometrial hyperplasia (CAH) (Group 3), and normal endometrium (NE) (Group 4). Of these cases, 37 cases had SH, 36 cases had CH, 16 cases had CAH, and 25 cases had NE. To evaluate an association between atypia and DNA repair genes, we consider a group that included both SH and CH, the endometrial hyperplasia without atypia cases (Group 5). Genomic DNA was isolated from paraffin-embedded endometrial tissue collected from the Pathology Department of Gaziantep University Medical School. Polymerase chain reaction (PCR) and/or restriction fragment length polymorphism (RFLP) method was used for evaluating of XPD (-751), XRCC4 (-1394 and a variable number of tandem repeats in intron 3), and XRCC1 (-399) genes. RESULTS We observed a notable distinction in patients having endometrial hyperplasia without atypia (the SH+CH group) and the CAH group in terms of XPD (-751) gene polymorphisms. A notable contrast was observed in patients with endometrial hyperplasia without atypia (the SH+CH group) and the NE group in terms of XRCC4 (VNTR intron 3) polymorphisms (P=0.026, P=0.018, respectively). CONCLUSIONS It was evident the DNA repair gene XPD and XRCC4 polymorphisms had a role in the pathophysiology of endometrial hyperplasia.

Acute pancreatitis with eruptive xanthoma.

Eruptive xanthomas are benign skin lesions caused by localised deposition of lipids in the dermis. Xanthomas can present as early manifestations of systemic disorders, which are typically caused by elevated levels of serum triglycerides and uncontrolled diabetes. Early recognition and treatment of the underlying condition decreases morbidity and mortality. After treatment of the underlying metabolic disorders, lesions mostly disappear without leaving scars. We present a case with multiple yellowish, erythematous papules on the extremities suggestive of eruptive xanthomas admitted to our hospital with acute pancreatitis.

Metastasis of a Renal Collecting Duct Adenocarcinoma to the Oral Cavity After Tooth Extraction.

Metastatic tumors rarely occur in the oral cavity. The most common of the oral metastases are lung cancers in males, and breast and genital cancers in females. The most common primary tumor metastasis to the oral cavity is from the lung, kidney, liver, prostate, and colorectal cancers. The metastatic lesions are similar to oral lesions such as pyogenic granuloma, giant cell lesions, gingival polyps, hemangioma, peripheral fibroma, and adenoid squamous cell carcinoma. Therefore, the diagnosis of primary tumors is challenging. To our knowledge, this is the first reported case to feature metastasis of a renal collecting duct adenocarcinoma to the oral cavity after tooth extraction.

Association between Tumor Size and Bilateral Involvement in Papillary Thyroid Carcinoma.

Background. Tumor multifocality and bilaterality of papillary thyroid carcinoma (PTC) are important factors when selecting the most appropriate surgical procedure. The aim of this study was to assess the bilaterality rate in PTC and the relationship between the tumor size and bilaterality. Materials and Methods. Thyroidectomy specimens with a diagnosis of PTC were retrospectively reviewed in the Pathology Department of a tertiary care medical center. Specimens were divided into three groups according to the size of the primary and contralateral tumor foci. Tumors less than or equal to 1 cm in each lobe were included in group 1. Group 2 consisted of tumors greater than 1 cm in one lobe and less than 1 cm in the other lobe. Tumors greater than 1 cm in each lobe were included in group 3. Results. We identified 868 total thyroidectomy specimens with a diagnosis of PTC between 2001 and 2011. Of these cases, both thyroid lobes were involved in 262 cases (32%). There were 109 (42%), 121 (46%), and 32 cases (12%) in group 1, group 2, and group 3, respectively. Conclusion. Bilaterality is frequent in PTC and is not related to tumor size. Accordingly, the high frequency of bilateral disease in PTC should be kept in mind when determining the extent of the surgical procedure.

Histopathological features of bisphosphonates related osteonecrosis of the jaw in rats with and without vitamin d supplementation.

OBJECTIVE: Aim of this study was to investigate the effect of vitamin-D3 on the osteonecrosis of bone that was induced after tooth extraction was conducted on rats that were given zoledronic acid (Z.A). MATERIAL AND METHODS: Animals were divided into four groups. Two of the experimental groups were divided into two subgroups, third study group was not divided into subgroups, and control group was divided into three subgroups. Z.A was administered twice per week over the course of 7 weeks, dexamethasone was administered twice a week during the 5th-6th-7th weeks to all groups. Dental extraction was performed by drilling around the tooth at 7th week. In study-group-1; vitamin-D was administered twice per week during the 5th-6th-7th weeks. In study-group 2; vitamin-D was administered twice per week during the 8th-9th-10th weeks. In study-group-3; vitamin-D was administered twice per week during the 15th-16th-17th weeks. The animals were sacrificed at 10th-15th-17th weeks, and histologic samples were taken. RESULTS: Postoperative-15-group had a lower osteoblast number, which was statistically significant as compared to preoperative-15 and control-15-group. Control-10-group showed significantly lower osteoclast number in comparison to preoperative-10 and postoperative-10-group. Osteoclast number was significantly higher in the osteonecrosis-17-group as compared to control-17-group. Preoperative-10-group showed significantly higher inflammation in comparison to control-10-group. Postoperative-15-group had a lower histologic osteonecrosis, which was statistically significant as compared to the control-15-group. Macroscopic osteonecrosis was significantly higher in the control-17-group in comparison to the osteonecrosis-17-group. CONCLUSIONS: We concluded that there are some proofs for the treatment of BRONJ with systemic using of vitamin-D.

Expression Levels of miR-30a-5p in Papillary Thyroid Carcinoma: A Comparison Between Serum and Fine Needle Aspiration Biopsy Samples.

BACKGROUND: Fine needle aspiration biopsy (FNAB) is a useful tool in the diagnosis of thyroid nodules. However, some limitations exist as approximately 25% of the cases cannot be distinguished with this method. Therefore, identification of novel diagnostic markers is very important in improving the papillary thyroid carcinoma (PTC) diagnosis. microRNAs (miRNAs) are small regulatory RNA molecules that have been involved in a variety of biological processes, including tumorigenesis. Moreover, determination of miRNAs with prognostic, diagnostic, and therapeutic potential is of a great interest today. AIMS: In the present study, we evaluated the expression level of miR-30a-5p in serum and FNAB samples of PTC patients. METHODS: A total of 60 cases were included in the study, with the patients subdivided into four groups; benign, atypical cells of undetermined significance (ACUS), malignant group, including Hurthle cell PTC (HC-PTC), and malignant without Hurthle cell PTC (non-HC-PTC). Peripheral blood and FNAB samples of the cases were collected. The serum and FNAB expression levels of miR-30a-5p among the groups were compared. The miR-30a-5p expression level was determined using real-time polymerase chain reaction (RT-PCR). RESULTS: According to both pre- and postoperative pathological diagnosis, miR-30a-5p levels were significantly increased in both serum and FNAB samples of HC-PTC and non-HC-PTC groups compared to other groups. This increase was more evident in the non-HC-PTC group (p=0.0245 for FNAB, p=0.0166 for serum). CONCLUSIONS: The results of this study suggest that miR-30a-5p might be a novel diagnostic marker candidate in PTC. Further studies are required to investigate this possibility.

Evaluation of conventional imaging techniques on preoperative localization in primary hyperparathyroidism.

We aimed to evaluate the diagnostic and preoperative localization capacity of 99mTc methoxyisobutylnitrile (MIBI) parathyroid scintigraphy and ultrasonography (USG) in enlarged parathyroid glands in the primary hyperparathyroidism (pHPT) as well as the relationship between the success rate of these techniques and biochemical values. In this study, we retrospectively evaluated 39 patients with clinical and biological evidence of pHPT who referred to the university hospital for MIBI parathyroid scintigraphy. Patients were examined with USG and double-phase MIBI parathyroid scintigraphy for the detection of enlarged parathyroid glands. Preoperative serum intact parathyroid hormone (iPTH) levels, calcium (Ca), phosphate and alkaline phosphatase measurements were obtained. A total of 45 parathyroid lesions in 39 patients were reviewed. Thirty-four patients had a single adenoma and 5 patients with multi-gland disease had 11 abnormal parathyroid glands including three adenomas, whereas the remaining 8 glands showed hyperplasia. The overall sensitivities of MIBI parathyroid scintigraphy, USG and combined techniques were 85.3%, 72.5% and 90.4%, respectively; the positive predictive values (PPV) were 89.7%, 85.2% and 92.6%, respectively. The most successful approach for detection of enlarged parathyroid glands in hyperparathyroidism is the concurrent application of USG and MIBI parathyroid scintigraphy modalities. The concomitancy of thyroid diseases decreases the sensitivity of both MIBI parathyroid scintigraphy and USG in enlarged parathyroid glands.

Septin 7 immunoexpression in papillary thyroid carcinoma: a preliminary study.

Papillary thyroid carcinoma (PTC) is the most common type among thyroid cancers. The diagnosis of PTC may be challenging when follicular variant (FVPTC) of this disease is present due to the resemblance of nuclear properties of the classical type (CVPTC). However, making use of ancillary molecular markers in the diagnosis of PTC may help. In our study, we aimed to evaluate the SEPT7 protein expression in PTC. A total of 55 paraffin block tissue samples comprising encapsulated FVPTC (FVPTC(e), n=25), and CVPTC (n=15), and benign hyperfunctioning thyroid nodules (HypN, n=15) were used in this study. Nuclear, cytoplasmic, and overall (total) SEPT7 protein expression levels were determined by using immunohistochemistry. Nuclear, cytoplasmic, and overall SEPT7 expressions (p=0.02, p=0.001, p=0.002, respectively) were significantly lower in FVPTC(e) tissues when compared to HypN. In CVPTC group, nuclear expression was significantly lower (p=0.004) while overall and cytoplasmic expressions were not changed (p>0.05). In HypN group, highest nuclear (mean=2.73), cytoplasmic (mean=2.86), and overall (mean=2.86) expression scores were detected. Significantly lower SEPT7 expression in all expressional categories in FVPTC(e) group may be a sign of different molecular signature in this type of tissue.

MCM3 protein expression in follicular and classical variants of papillary thyroid carcinoma.

Minichromosome maintenance (MCM) proteins are needed as licensors in the DNA replication of eukaryotic cells and transcriptional control of MCM genes has critical role in the regulation of MCM functions. Different MCM protein family members are proposed as diagnostic or prognostic markers in various cancers due to their increased proliferative potential. Among MCM family members, minichromosome maintenance protein 3 (MCM3) expressions in both mRNA and protein levels were shown to be associated with papillary thyroid carcinoma (PTC). But, the usability of MCM3 in some histological variants of PTC might be controversial due to tissue specific molecular heterogeneities. In follicular variant of papillary thyroid carcinoma (FVPTC), a number of genes including MCM3 were shown to be differentially expressed which were specific to this kind of variant. Using immunohistochemistry method, MCM3 protein expression levels were compared in FVPTC, classic variant of papillary thyroid carcinoma (CVPTC), and multi-nodular goiter (MNG) tissues in a group of 32 cases. There was meaningful differences between MNG vs. FVPTC (p = 0.016) and MNG vs. CVPTC (p = 0.019) while there was no significant difference in the comparison FVPTC vs. CVPTC (p = 0.15). Four of the 5 CVPTC cases having surrounding tissue invasion had high expression values. For FVPTC and CVPTC, MCM3 protein expression results were parallel to our previous mRNA expression study while there was downregulation in protein expression despite the increased expression of MCM3 mRNA in MNG suggesting tissue-specific post-transcriptional events in benign thyroid neoplasms of which should be focused on. Moreover, the relatively lower MCM3 protein expression in FVPTC comparing to CVPTC could be due to a different tumorigenic pathway favored in this type of tissue.

Effect of dietary boron on 5-fluorouracil induced oral mucositis in rats.

OBJECTIVE: The aim of this study was to evaluate the effect of boron on 5-fluorouracil (5-FU)-induced oral mucositis in rats. MATERIALS AND METHODS: Sixty-four male Wistar albino rats were injected with 5-FU on days 1 and 3. The right cheek pouch mucosa was scratched with the tip of an 18-G needle, dragged twice in a linear movement, on days 3 and 5. The animals were randomly divided into two groups of 32: boron group (BG) and control group (CG). Rats in the CG did not receive any treatment, whereas the others were fed boron (3 mg·kg(-1)·day(-1)) by gavage. The animals were sacrificed on day 3 (n = 8), 6 (n = 8), 9 (n = 8), and 12 (n = 8), and the cheek pouch was removed for histopathological analysis. RESULTS: On day 3, both groups showed necrosis and active inflammation, but the inflammation was mild in CG and moderate in BG. On day 6, both BG and CG showed necrosis; in the CG, there was moderate inflammation, and in the BG, there was severe inflammation and granulation tissue around the necrotic area. On day 9, re-epithelization began in both groups, and there were no differences between groups. Re-epithelization was complete in both groups on day 12. CONCLUSION: We found no beneficial effect of boron in healing oral mucositis. Additional research is warranted to elucidate the pathogenic inflammatory mechanisms involved in mucositis and the prophylactic and therapeutic roles of antioxidants.

Late metastasis of an intracranial meningioma to the hard palate.

Meningiomas are benign neoplasms that arise from cellular elements of the meninges. Although meningiomas are usually considered as benign tumors, they have a potential to become aggressive and to metastasize to the extracranial structures. Distant metastasis most commonly occurs in lung, liver, and long bones. We present an extremely rare case of a delayed metastasis of a recurrent intracranial meningioma to the hard palate 19 years after the initial diagnosis. The patient underwent surgical excision without any complication and follow-up showed no recurrence.