Bethesda System Research Articles

8787 A Case of Indolent Medullary Thyroid Cancer with Sporadic HRAS Mutation and Prolonged Stability

Abstract Disclosure: M. Lozano: None. A. Pinero-Pilona: None. Background: Medullary thyroid cancer (MTC) is a rare neuroendocrine tumor that is derived from calcitonin-producing C-cells that accounts for the smallest portion (<5%) of thyroid cancer. Most of these cases are attributed to mutations in the RET oncogene. Of the remainder, approximately 70% of MTC cases without a RET mutation have been attributed to RAS gene mutations. We report a case of a patient who presented with a thyroid nodule present and stable for years and was found to have MTC with a HRAS mutation. Clinical Case: A 73-year-old Caucasian male with a history of metastatic squamous cell carcinoma (SCC) of the neck, orthostatic hypotension, pacemaker implantation, and coronary artery disease with prior stenting presented to the clinic for evaluation after an abnormal thyroid biopsy. His SCC was diagnosed 16 years ago and was treated with surgery and cetuximab. It was a poorly differentiated squamous cell carcinoma with 2 of 7 lymph nodes positive for malignancy. Fifteen years ago, as part of the evaluation for his SCC, the patient had CAT and PET scans that showed a small nodule with increased uptake in the right lower neck in the thyroid bed (2.7 SUVs) measuring about 1.4 cm in diameter. No further interventions were done back then, and the patient was unaware of the mass until his records were reviewed. The patient was more recently noted to have the incidental thyroid nodule 2 months prior to clinic evaluation after routine carotid ultrasound. The gland was described to be homogeneous; in the mid to inferior portion of the right lobe, there was a 1.2 cm TR5 nodule of which biopsy was recommended. Fine needle aspiration biopsy showed a follicular lesion of unknown significance Bethesda category 3 using AFIRMA GCS RNA molecular analysis. Subsequently, gene sequencing classification was performed and abnormal: results were positive for HRAS mutation. Sonography in the office showed a right-sided, slightly hypoechoic, taller-than-wide vascular nodule with well-preserved borders and intermediate risk of malignancy. No abnormal lymphadenopathy was observed regionally in the central or lateral neck. The patient then underwent total thyroidectomy with modified right level 3 dissection. The right mid-superior nodule was consistent with MTC without tumor necrosis and without lymphatic, perineural, or extrathyroidal extension, but there was angioinvasion of at least 3 vessels. Preoperative calcitonin was elevated at 71 pg/mL and the level was undetectable (<2 pg/mL) 8 weeks post operatively (n<=10 pg/mL). The patient was deemed cured based on these biochemical studies and is recovering uneventfully on supplemental levothyroxine. Conclusion: Given the predominant association of MTC with RET, it is worth noting this case of a sporadic HRAS mutation in a patient with prior SCC. This case illustrates an indolent MTC without aggressive behavior that stayed stable in size and without metastasis for 15 years. Presentation: 6/1/2024

7708 Navigating Thyroid Cancer With Differences in Thyroglobulin Assessment Techniques

Abstract Disclosure: M.S. Shah: None. S. Humayon: None. N.A. Mungo: None. This case report delves into the diagnostic journey of a patient with papillary thyroid carcinoma, emphasizing the importance of precise thyroglobulin measurement methods. The case highlights the differences between immunoassay and mass spectrometry in monitoring disease progression and treatment response.A 42-year-old female with a family history of thyroid-related issues, was found to have a thyroid nodule on physical exam. She underwent fine-needle aspiration (FNA) revealing papillary thyroid carcinoma, Bethesda category VI. Lymphatic invasion was present necessitating total thyroidectomy and lymph node dissection. Left level 3 and 4 lymph node excision showing 2 of 15 positive for metastatic papillary thyroid carcinoma without extranodal extension. Left superficial jugular lymph node excision showing 1 of 3 lymph node being positive for metastatic thyroid carcinoma without extranodal extension. RAI therapy and post-ablative scan showed focal moderate increased activity adjacent to the left hyoid bone. CT scan of the neck later showed stable appearance of the thyroidectomy bed with no new suspicious soft tissue mass. A small crescentic focus of enhancing soft tissue medial to the left common carotid artery is favored to represent residual thyroid tissue. Multiple small enhancing lymph node in the left neck at level llB and junction of levels ll and lll. Several of these are new or increased in size from prior examination and somewhat acidly enhanced. Although these are within normal limits by size criteria, recurrent diseases cannot be excluded. She underwent another surgical neck dissection with no cancer found. Given the negative findings, a shift from checking thyroglobulin (TG) from immunoassay to mass spectrometry was ideal.Patient was found to have persistent thyroglobulin elevation with Immunoassay, thyroglobulin level (60.5 ng/mL, n<35 ng/ml), without the presence of TG antibodies, whereas liquid chromatography-tandem mass spectrometry (LC-MS/MS) showing (<0.5 ng/mL), highlighting the methodological divergence. To date she has no imaging concerns and repeat testing from different labs similarly demonstrated undetectably Tg by LC-MS/MS and varying levels when tested by Immunoassay. Her levels by Immunoassay have trended down to her most recent level of (38 ng/ml).This case emphasizes the critical role of accurate thyroglobulin assessment in thyroid carcinoma follow-up. Immunoassay and mass spectrometry present divergent results, with LC-MS/MS proving more reliable in monitoring disease progression but more expensive and time consuming. Clinicians should consider the implications of methodological choices on patient management, particularly in cases of persistent elevation despite treatment. The potential discrepancies between these methods should be emphasized considering the impact on treatment decisions. Presentation: 6/1/2024

8390 It's not Cancer: Establishing the Diagnosis of Hyaline Trabecular Tumor

Abstract Disclosure: R.A. Zielinski: None. M. Khalifa: None. M. Dillon: None. M. Kaur: None. Background: Hyaline trabecular tumor (HTT) is a rare benign follicular thyroid neoplasm characterized by extensive intra-trabecular hyaline stromal material. Resemblances to other follicular neoplasms create difficulty in distinguishing HTT from its more nefarious counterparts such as medullary thyroid cancer (MTC) and papillary thyroid cancer (PTC).Clinical Case:Our patient is a 56-year-old female with Hashimoto’s thyroiditis diagnosed in her twenties who has been on different strengths of levothyroxine based on her fluctuating TSH. A thyroid ultrasound done to evaluate left-sided neck fullness on physical exam showed a solid, hypoechoic 2.3 cm x 1.4 x 0.9 cm left middle thyroid nodule without calcifications (TI-RADS 4) and benign-appearing lymph nodes, the largest of which was 1.5 cm at level 1B. Cytology from a thyroid FNA biopsy was suspicious for PTC, Bethesda category IV. A thyrosure genetic panel was negative for genetic mutations. FNA biopsy of the 1.5 cm lymph node was negative for malignancy. The patient was referred for thyroid lobectomy but instead elected to undergo total thyroidectomy with level VI lymph node dissection. Pathology revealed a 2.2 cm HTT in the left lobe, scattered psammoma bodies in adjacent soft tissue, and a 0.2 cm multifocal papillary microcarcinoma in the right lobe. The microcarcinoma had negative margins, no lymphatic or vascular invasion, and 7/7 benign level VI lymph nodes; staging it as pT1aN0. Immunohistochemistry staining was positive for TTF-1 and thyroglobulin and negative for calcitonin, chromogranin, and synaptophysin. Post-thyroidectomy she was started on Tirosint 175 mcg daily with good response. No I-131 treatment was pursued due to the microcarcinoma being categorized as low risk.Discussion and Conclusion: HTT is a benign neoplasm and management is usually conservative with surgical excision. The diagnosis of HTT by cytology alone is challenging due to the presence of nuclear clearing, grooves and intranuclear pseudo-inclusions that may be mistaken for PTC or MTC. Cell membrane immunoreactivity of MIB1 monoclonal to Ki67 and the molecular identification of the novel PAX8-GLIS1 or PAX8-GLIS3 fusions may aid in making the correct diagnosis.

7847 Radiomic Ultrasound Checkup of Thyroid Nodules Before Radiodiodine Therapy

Abstract Disclosure: A.A. Trukhin: Grant Recipient; Self; Russian Science Foundation (project N 22-15-00135). A.V. Manaev: Grant Recipient; Self; Russian Science Foundation (project N 22-15-00135). S.M. Zakharova: Grant Recipient; Self; Russian Science Foundation (project N 22-15-00135). M.S. Sheremeta: None. E.A. Troshina: Grant Recipient; Self; Russian Science Foundation (project N 22-15-00135). Background: Over 83 years radioiodine therapy (RIT) of autonomous thyroid nodules still have uncovered pages, according to its complexity and thyroid nodules variety. There are two main criteria to allow RIT – no malignancy and presence of iodine uptake, the last one could be checked by Tc-99m-pertachnetate or I-123, I-131 iodine scintigraphy. Case with thyroid nodules first undergo ultrasound (US) TI-RADS classification, then fine needle aspiration stratification according to the Bethesda system. Publications applied such algorithm shows 75-85% accuracy in malignancy determination, that in 15-25% can lead to improper RIT application. Aim: Method development for thyroid nodules ultrasound checkup before I-131 administration and I-131 24h uptake prognosis. Methods: Study includes 150 nodules (65 benign, 60 malignant, 25 autonomous benign thyroid nodules). Both US longitudinal and transversal thyroid nodule projections were obtained via GE Voluson E8 (36% benign cases / 27% malignant cases) and GE Logiq E (64% benign cases / 73% malignant cases) in cinematic loop regime. Autonomous thyroid nodules underwent I-131 pharmacokinetics examination with 24h uptake determination and RIT. Statistical textural features were obtained through spatial adjacency matrix. Results: Analysis of 16 statistical textural features shows weak correlation between 11 statistical textural features E (Energy), S (Entropy), LU (Local homogeneity), MP (Maximum probability), TR (Matrix trace), CORR (Correlation), IMC (information measure of correlation), DV (Difference variance), DE (Difference entropy), SE (Sum entropy), SA (Average value of the sum). ROC-analysis using 11 statistical textural features shows the best model for benign/malignance determination with AUC = 0.83, Se = 74%, Sp = 73%, PPV = 75%, NPV = 72%, Acc = 74%. I-131 pharmacokinetics examination shows strong correlation SA to I-131 24h uptake. Conclusions: The performed study demonstrates the possibility of using textural statistical features of ultrasound images as instrument for thyroid nodules ultrasound checkup before I-131 administration, for extra FNA prescription and prognosis the I-131 24h important in exact therapeutic I-131 activity calculation. Presentation: 6/2/2024

12351 Real World Performance of the Afirma Xpression Atlas in Bethesda V and Vi Thyroid Nodules: A Private Practice Experience

Abstract Disclosure: M.S. Tkach: None. E. Coughlin: None. A. Pinero-Pilona: None. Fine Needle Aspiration (FNA) is a cornerstone of the diagnosis of thyroid cancer. The Bethesda System for Reporting Thyroid Cytopathology (BS-TCP), developed in 2010, and genomic sequencing classifiers (GSC) now allow clinicians to objectively identify the risk of malignancy of thyroid nodules (“TN”) prior to surgical interventions. For further characterization, the Afirma Xpression Atlas (XA) was created and launched in May 2018, utilizing RNA sequencing to evaluate fusions and variants. As of 2023, the Afirma XA panel includes 905 genomic variants and 235 fusions from 593 genes. Post-validation studies for the Afirma XA have focused on large academic centers, but applicability or extrapolation to smaller endocrinology practices is less clear, potentially due to different patient population and thyroid cancer prevalence. This study was designed to analyze and measure the performance of the Afirma XA in BS-TCP V and VI TN classified as GSC suspicious for malignancy in a small endocrinology practice. We conducted a retrospective cohort analysis comparing all BS-TCP V and VI TN with their respective final surgical pathology results between June 2018 and December 2023. 76 TN meeting the criteria for BS-TCP V or VI classification were identified. We excluded any TN (12 total) for which pathology data was unavailable; reasons ranged from lack of patient follow-up to patient's death with no autopsy available. Forty-seven thyroid TN were therefore included, and the BS-TCP VI category was the predominant cytopathology discovered, representing 78.7% of the TN in this group. Afirma XA was able to identify genomic alterations in 78.7% of all included TN (thus 78.7% is its sensitivity). Sensitivity of XA was found to be 70% in BS-TCP V (n=10) and 81.1% in BS-TCP VI (n=37). 83% of the analyzed TN were from female patients and 17% were from male patients; there was no statistically significant difference between XA frequency in TN from male vs. female patients. 100% of all BS-TCP V and VI TN (n=47) as determined by the cytopathologist were associated with cancer on pathology; thus, the sensitivity of the cytopathology itself is 100%, and positive predictive value of XA in both groups was 100%. Age and nodule size were not significantly associated with XA presence or absence overall. XA was overwhelmingly comprised of BRAF :p:V600E c.1799T>A mutations: 70.2% of of XA findings showed this mutation (50% in V and 75.6% in VI). Our percentage of XA on BS-TCP V and VI nodules reflects similarity to prior large studies in academic centers. Based on this data, we conclude that XA is a valuable tool for high-risk TN classification and treatment guidance; it can both aid in surgical planning and determine options for potential pharmacotherapy. We conclude that in our study, the relation between XA and cytopathology in BS-TCP V and VI nodules correlates well with data from large academic center studies, even in a small private practice. Presentation: 6/3/2024

7812 Community Practice Setting Experience in Evaluation of Incidental Thyroid Nodules

Abstract Disclosure: N. Abate: None. H. Rhodes: None. M. Horlavadi: None. B. Adams-Huet: None. M. Chandalia: Advisory Board Member; Self; Boehringer Ingelheim. Speaker; Self; Boehringer Ingelheim, Eli Lilly & Company, Novo Nordisk. Background: There is a significant increase in detection of incidental thyroid nodules due to increase in routine screening ultrasounds at church, workplace, and health fairs, increase in routine ultrasound in primary care clinics and incidental finding of thyroid nodule during carotid artery ultrasound. These patients are then referred for thyroid nodule fine needle aspiration biopsy. Aim of this study was to evaluate real world data in frequency of thyroid cancer in patients referred for incidental thyroid nodule to a nonacademic Endocrinology clinic utilizing centralized collection of cytology and molecular analysis. Method: Medical records were reviewed for consecutive FNA of incidental thyroid nodule in an Endocrinology clinic in greater Houston from 2021 to 2023. FNA was performed in patients selected based on ACR TI-RADS classification. Patients with Bethesda score of 3 or more had molecular testing with Thyroseq performed. Patients with intermediate or high probability of cancer on Thyroseq as well as Patients with Bethesda 4 and 5 on cytopathology were referred for surgery. Surgical pathology was obtained in patients who underwent surgery. Data was tabulated and analyzed using SAS. Results: A total of 304 subjects, 267 Female and 37 males, age 57 ± 13, nodule size 2.69 ± 1.4 (mean ± SD), had thyroid nodule FNA between 2021 and 2023. Of these FNA, 23 (7.5%) sample collections were insufficient, 233 (77.3%) were benign (Bethesda 2), 46 (15%) were Atypia of undetermined significance or Suspicious for malignancy. Of those subjects with Bethesda 3 or higher, 36 patients had molecular testing by Thyroseq Method. Fifteen patients had intermediate and high risk finding on Thyroseq. Thirty-four subjects had surgery and 8 patients had malignancy on surgical pathology. One patient was identified as Medullary Thyroid cancer on Thyroseq, confirmed by surgery. Frequency of malignancy in incidentally detected thyroid nodule in the whole group was 2.6%, those with Bethesda 3 and more was 17.4% and those with Thyroseq intermediate or high risk was 27%. Conclusion: Availability of centralized cytopathology and reflex molecular testing to Community practice settings helps reducing unnecessary thyroid surgeries in patients with incidental thyroid nodules. Presentation: 6/1/2024

Macrofollicular subtype of papillary thyroid carcinoma: Ultrasonographic findings and clinical implications.

The macrofollicular subtype of papillary thyroid cancer (MFS-PTC) is a rare subtype often leading to a challenging diagnosis. To evaluate the ultrasonographic (US) features and clinical implication of MFS-PTC. Records of 14 patients histologically diagnosed with MFS-PTC at our institution over a period of 16 years were retrospectively reviewed. Preoperative US features, Bethesda categories determined by fine-needle aspiration (FNA) or core needle biopsy (CNB), and final pathology were assessed in all patients with MFS-PTC. Of the 14 MFS-PTC cases, most nodules were noted as smooth marginated, solid or predominantly solid isoechoic on US and were categorized as low suspicion in 12 cases and intermediate suspicion in 2 cases. The median tumor size was 1.2 cm (range, 0.6-5.6 cm). Of 11 cases that underwent FNA or CNB, 4 (36.4%) with Bethesda category II or III underwent the follow-up because of benign-looking appearance on US and benign results in subsequent CNBs. However, the patients underwent delayed surgery (31.3 months, range 12-41 months) because of serially increased tumor size. Seven patients diagnosed with Bethesda type IV, V, and VI subsequently underwent surgery. Gross extrathyroidal extension into subcutaneous fat tissue and lateral lymph node metastasis were noted in a patient who underwent follow-up. No distant metastases or recurrence was detected. MFS-PTC is representative of a benign sonographic appearance of PTC subtypes. Tumor growth on serial US images is the only suspicious finding for MFS-PTC because FNA or CNB is often false negative.

Effect of Clinicopathological Characteristics on the Outcomes of Topical 5-Aminolevulinic Acid Photodynamic Therapy in Patients with Cervical High-Grade Squamous Intraepithelial Lesions (HSIL/CIN2): A Retrospective Cohort Study.

Minimally-invasive 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is used for treating cervical high-grade squamous intraepithelial lesions (HSIL/CIN2). The purpose of this study was to analyze the factors affecting the efficacy of ALA-PDT in the treatment of cervical HSIL/CIN2 in order to guide physicians in making appropriate treatment decisions. A retrospective study including 69 female patients with pathologically diagnosed HSIL/CIN2 was conducted. Patients were given six doses of 20% ALA-PDT at 7-14-day intervals. Cytology, HPV testing, colposcopy, and pathology were performed before treatment and at 6-month follow-up after treatment to assess efficacy. The main outcome of this study was the regression of HSIL/CIN2 and the clearance of high-risk HPV (hrHPV) infection after ALA-PDT treatment. Clinicopathological characteristics were collected to analyze the factors affecting the effectiveness of ALA-PDT treatment for HSIL/CIN2. Between the successful and failed lesion regression group, there was a significant difference in sleeping disorders (p < 0.05). Between the successful and failed hrHPV clearance group, no statistically significant factors were found. With sensitivity values of 0.556 and 0.778, respectively, multivariate analysis showed that current smoking and sleeping disorders were independent prognostics of failure in lesion regression after ALA-PDT treatment. Smoking and sleep disorders were independent risk factors for failure in HSIL/CIN2 regression following ALA-PDT, suggesting the need for careful consideration of ALA-PDT for patients with these conditions.

Correlative evaluation of findings between ultrasonography, fine needle aspiration cytology and histopathology in cases of goitre

Background: Thyroid imaging reporting and data system (TIRADS) criteria is followed in ultrasonography (USG), based on the risk of malignancy depending on the presence of suspicious ultrasound features. Patients in the high-risk category of TIRADS undergo fine needle aspiration cytology (FNAC), with the Bethesda classification used to determine the risk of malignancy. There is dearth of data comparing sonographic classification of thyroid nodule and its cytological association with respect to final histopathological diagnosis in India. Methods: Prospective observational study on correlation of USG, FNAC and HPE of thyroid swellings conducted in department of otolaryngology at Jaipur national university institute for medical science and research centre, Jaipur, Rajasthan from June 2022 to April 2024 on 50 patients with palpable thyroid lump. Results: In the present study, USG has a sensitivity of 63.63%, specificity of 97.44%, a positive predictive value (PPV) of 87.5%, a negative predictive value (NPV) of 90.4% and an overall accuracy of 84.00%. FNAC shows a sensitivity of 72.7%, specificity of 89.7%, PPV of 66.7%, NPV of 92%, and an overall accuracy of 86%. Conclusions: Benign lesions on both FNAC and USG were almost in concurrence with HPE in our study. The results of FNAC for diagnosing malignancy in our study were almost at par with the results of HPE and outweighed the results of USG. Surgical management should be based on FNAC finding even if USG shows benign features. It should be essential part of armamentarium of evaluation of thyroid swelling. This combined approach provides a robust framework and enhances the accuracy for distinguishing between benign and malignant thyroid lesions, ultimately contributing to improved patient care and outcomes. However, the histopathological examination will remain the gold standard.

Risk-stratified management of cervical high-grade squamous intraepithelial lesion based on machine learning.

The concordance rate between conization and colposcopy-directed biopsy (CDB) proven cervical high-grade squamous intraepithelial lesion (HSIL) were 64-85%. We aimed to identify the risk factors associated with pathological upgrading or downgrading after conization in patients with cervical HSIL and to provide risk-stratified management based on a machine learning predictive model. This retrospective study included patients who visited the Obstetrics and Gynecology Hospital of Fudan University from January 1 to December 31, 2019, were diagnosed with cervical HSIL by CDB, and subsequently underwent conization. A wide variety of data were collected from the medical records, including demographic data, laboratory findings, colposcopy descriptions, and pathological results. The patients were categorized into three groups according to their postconization pathological results: low-grade squamous intraepithelial lesion (LSIL) or below (downgrading group), HSIL (HSIL group), and cervical cancer (upgrading group). Univariate and multivariate analyses were performed to identify the independent risk factors for pathological changes in patients with cervical HSIL. Machine learning prediction models were established, evaluated, and subsequently verified using external testing data. In total, 1585 patients were included, of whom 65 (4.1%) were upgraded to cervical cancer after conization, 1147 (72.4%) remained having HSIL, and 373 (23.5%) were downgraded to LSIL or below. Multivariate analysis showed a 2% decrease in the incidence of pathological downgrade for each additional year of age and a 1% increase in lesion size. Patients with cytology > LSIL (odds ratio [OR] = 0.33; 95% confidence interval [CI], 0.21-0.52), human papillomavirus (HPV) infection (OR = 0.33; 95% CI, 0.14-0.81), HPV 33 infection (OR = 0.37; 95% CI, 0.18-0.78), coarse punctate vessels on colposcopy examination (OR = 0.14; 95% CI, 0.06-0.32), HSIL lesions in the endocervical canal (OR = 0.48; 95% CI, 0.30-0.76), and HSIL impression (OR = 0.02; 95% CI, 0.01-0.03) were less likely to experience pathological downgrading after conization than their counterparts. The independent risk factors for pathological upgrading to cervical cancer after conization included the following: age (OR = 1.08; 95% CI, 1.04-1.12), HPV 16 infection (OR = 4.07; 95% CI, 1.70-9.78), the presence of coarse punctate vessels during colposcopy examination (OR = 2.21; 95% CI, 1.08-4.50), atypical vessels (OR = 6.87; 95% CI, 2.81-16.83), and HSIL lesions in the endocervical canal (OR = 2.91; 95% CI, 1.46-5.77). Among the six machine learning prediction models, the back propagation (BP) neural network model demonstrated the highest and most uniform predictive performance in the downgrading, HSIL, and upgrading groups, with areas under the curve (AUCs) of 0.90, 0.84, and 0.69; sensitivities of 0.74, 0.84, and 0.42; specificities of 0.90, 0.71, and 0.95; and accuracies of 0.74, 0.84, and 0.95, respectively. In the external testing set, the BP neural network model showed a higher predictive performance than the logistic regression model, with an overall AUC of 0.91. Therefore, a web-based prediction tool was developed in this study. BP neural network prediction model has excellent predictive performance and can be used for the risk stratification of patients with CDB-diagnosed HSIL.

Preliminary Evaluation of the Value of a Small-Molecule Probe Targeting DNMT1 in Detecting the Methylation of PAX1 in Cervical Cancer.

To investigate the screening value of a small-molecule probe to assess the methylation of PAX1 in cervical cancer. The diagnostic threshold of the grayscale values for cervical lesions was assessed by plotting the Receiver Operating Characteristic (ROC) curve of subjects. Grayscale values were significantly different among the four groups (p<0.05). Compared with the LSIL and cervicitis groups, a considerably higher grayscale value was found in the CA and high-grade squamous intraepithelial lesion (HSIL) groups (both p<0.05). The differential ROC curves of the grayscale values showed that the diagnostic Area Under Curve of the probe for cervicitis and low-grade squamous intraepithelial lesion (LSIL) was 0.8724 (95% CI=0.7762-0.9685, p<0.0001), for cervicitis and CA was 1.0000 (p<0.0001), for the LSIL and HSIL was 0.5484 (95% CI = 0.3826-0.7142, p=0.5755), and for the LSIL and CA was 0.7724 (95% CI = 0.6016-0.9432, p = 0.0138). The small molecular probe has certain application value in differentiating the type of cervical lesions and has better efficacy in distinguishing cervical inflammatory and precancerous lesions from carcinogenesis, but less efficacy in determining the type of precancerous lesions.

Prevalence of anal high-risk human papillomavirus (HR-HPV) types in people living with HIV and a history of cancer.

Referral tertiary care hospital for adult patients with cancer. We reviewed data of patients from the AIDS Cancer Clinic on antiretroviral therapy in chronic control who were consecutively referred for high-resolution anoscopy (HRA), where they underwent anal evaluation, collection of specimens for anal cytology and anal human papillomavirus (HPV) followed by HRA with directed biopsy if needed. A total of 155 patients were included; 149 (96.1%) were men, all of them men who have sex with men (MSM); the median age was 39 (IQR 32-47) years; 105 (67.7%) with Kaposi sarcoma, 40 (25.8%) with non-Hodgkin lymphoma and 10 (6.4%) with other neoplasms; only 7 (4.5%) had active cancer. The prevalence of HR-HPV infection was 89% (n=138) (95% CI 83-93) with at least one HR-HPV infection, and 62% (96) had coinfection with at least two types; the median HR-HPV types of coinfection were 3 (IQR 2-4). The number of patients infected with HPV 16 was 64 (41.3%, 95% CI 33.8-49.3), HPV 18 was 74 (47.7%, 95% CI 39.9-55.7) and with both 35 (22.6%). Some 59 patients (38%) had high-grade squamous intraepithelial lesions (HSIL) and 49 (31.6%) had low-grade squamous intraepithelial lesions (LSIL). The prevalence of HR-HPV and HSIL among patients aged ≤35 and >35 years was the same. In this cohort of PLWHIV with a history of malignancy we found a high prevalence of HR-HPV 16 and 18 and anal HSIL, even in persons aged ≤35 years. These data highlight the importance of anal cancer screening in PLWHIV and history of malignancy.

An unusual pattern of endometrial involvement: superficial spreading squamous cell carcinoma of the cervix.

Cervical squamous cell carcinoma (SCC) is the most common type of cervical carcinoma. Usually, the cancer metastasizes through lymphatic or hematogenous dissemination. However, it is uncommon for a superficial spreading of cervical cancer to reach the endometrium, fallopian tubes, and the ovaries. In the present study, we report 15 cases of superficial spreading SCC and discuss the possible mechanism involved. We collected 15 samples diagnosed by histopathology after surgery. Immunostaining, which included P16, P63, CD138, CD34, D2-40, and Ki-67, were performed for all samples. All patients were postmenopausal or perimenopausal women. The commonest clinical presentation was vaginal bleeding in 66.67%. All patients were infected with HPV 16. The endometrium was replaced by high-grade squamous intraepithelial lesion (HSIL), which involved the endometrial gland, even squeezing into the myometrium and forming SCC. Bilateral fallopian tubes and ovaries involvement was in 1/15. A total of 10/15 (66.67%) of the women had disease of stage 1B or less. All SCCs were moderately or poorly differentiated. Immunohistochemistry revealed that the tumor cells were positive for P63 and P16, with a high Ki-67 labeling index. There was CD138 positive expression in varying degrees, which was strongly and diffusely expressed in 6/15 (40.00%). Superficial spread of cervical cancer towards the endometrium is a rare but cognizable phenomenon, and a guideline for the management of these cases has not been established. Our present findings suggest that multiple factors may interact with each other simultaneously, contributing to this rare disease.

[Translated article] Retrospective Study of Risk Markers for Developing High-Grade Anal Intraepithelial Neoplasm in Men Who Have Sex With Men Living With HIV

BackgroundHigh-grade anal intraepithelial squamous lesion is significantly prevalent among men who have sex with men and are infected with the human immunodeficiency virus (HIV). This condition—the precursor to anal cancer—significantly increases the risk of developing it. Conversely, low-grade anal intraepithelial squamous typically follow a benign course and usually regress spontaneously. Materials and methodsTo describe a population of men who have sex with men living with HIV followed in a specialized anal cancer screening unit we conducted an observational, retrospective, and single-center study. ResultsNinety-four patients were analyzed, with a mean age of 39±9 years, and a 87% positivity rate for high-risk human papillomavirus (HR-HPV). At the initial visit, 47% presented with low-grade squamous intraepithelial lesions. The progression rate to high-grade squamous intraepithelial lesion was 37.2 per 100,000 patients/year. None of the patients developed anal cancer. Tobacco and alcohol consumption were associated with this progression. DiscussionIn this series, longer duration of HIV infection, tobacco and alcohol use and the presence of HR-HPV were significantly associated with the occurrence of high-grade intraepithelial lesions. A lower risk of progression was seen in patients with higher education. ConclusionIn men who have sex with men living with HIV, the association of factors such as smoking, alcohol, the presence of HR-HPV and an increased burden of human papillomavirus disease makes these patients more susceptible to develop high-grade anal squamous lesions.

Prevalence and Description of High-Grade Intraepithelial Lesions of Cervical Mucosa Cells in a Screening Programme for Cervical Cancer in Isère, France.

This study aims to analyse high-grade intraepithelial lesions (LIEHG) observed in a screening programme from 2010 to 2018 to more accurately describe them and formulate recommendations for best practices in the context of screening evolution following the introduction of an HPV test in primary cervical cancer screening in 2020. This study included 305,940 asymptomatic women aged 25-65 years. The eligible population was invited to undergo a screening cervico-uterine-smear every 3 years. If this smear was normal, the woman received a new invitation. In the case of a positive screen, the patient underwent further diagnostic procedures, such as colposcopy and biopsy to confirm the diagnosis. Only those diagnosed with LIEHG and above proceeded to treatment. The diagnoses associated with LIEHG were those related to the WHO Classification of tumours of the uterine cervix. Positive smears led to the diagnosis of 3230 LIEHG. The prevalence of LIEHG in the screened population was 0.4%. The LIEHG distribution varied significantly according to the age of the women. The probability of diagnosing LIEHG in young women was 12.2% at 25-29 years. This probability decreased by half after 50 years. We observed that the type of smear was significantly associated with LIEHG detection. The positive predictive value for diagnosing LIEHG was 70.3% for high-grade squamous intraepithelial lesion (HSIL) smears and 35.1% for atypical squamous cells cannot exclude HSIL (ASC-H) smears. In the study population, the prevalence of LIEHG was high in women under 35 years. Low-grade smears were correlated with the risk of LIEHG and should prompt screening facilities to allocate resources to ensure active follow-up of LSIL and ASC-US smears. Adherence to cytological screening recommendations was associated with a reduced risk of LIEHG in multivariate analysis.

Diagnostic Performance of European and American College of Radiology Thyroid Imaging Reporting and Data System Classification Systems in Thyroid Nodules Over 20 mm in Diameter

ObjectiveThe challenge of selecting thyroid nodules for fine needle aspiration (FNA) cytology has led to the development of the Thyroid Imaging Reporting and Data System, primarily in 2 formats: European Thyroid Imaging Reporting and Data System (EU-TIRADS) and American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS). Clinical observations suggest imperfect risk assessment for TIRADS 3 nodules ≥20 mm. This study aimed to evaluate the efficacy of TIRADS systems in distinguishing benign from malignant nodules in this subgroup. MethodsFrom May 2023 to March 2024, 1094 patients with thyroid nodules were referred for ultrasound at a University Hospital. Data on clinical, ultrasound, cytological, and histopathological parameters were collected. Nodules ≥20 mm were categorized by EU-TIRADS and ACR-TIRADS, and their predictive performance for malignancy was assessed through postthyroidectomy histopathology or FNA cytology (Bethesda classification). ResultsTwo hundred sixty-seven patients (mean age 60.3 ± 14.3 years; 46 men, 221 women) with 308 nodules were analyzed. Twenty-two malignancies and 286 benign nodules were recorded. Recalculating European Thyroid Imaging Reporting and Data System 3 performance using 25-mm and 30-mm thresholds (ACR-modified EU-TIRADS) avoided 24% and 41% of FNAs, respectively, while ACR-TIRADS would prevent 26.6% (P > .05). Two malignancies were missed. ConclusionEU-TIRADS and ACR-TIRADS show similar efficacy when using a 25 mm FNA threshold. Raising the cutoff for FNA in European Thyroid Imaging Reporting and Data System 3 nodules could reduce unnecessary procedures but may increase the risk of missed malignancies, impacting patient outcomes.

The sensitivity and specificity of fine needle aspiration cytology in detecting thyroid malignancy according to Bethesda system at a teaching hospital in Saudi Arabia

ABSTRACT Background: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) aims to standardize the terminology and morphologic criteria associated with thyroid fine-needle aspiration cytology (FNAC) results while also providing corresponding risk assessments for malignancy. contributing to more consistent and standardized reporting of thyroid nodules and aiding clinicians in making informed decisions. Since then, it has been undergoing revisions and updates to further improve its utility and accuracy. Materials and Methods: This is a retrospective study conducted at a tertiary care center. All patients with a history of thyroid gland swelling who had previously undergone FNA were included. The procedure included cytopathologists performing FNAC for all cases of midline neck swelling. Demographic and histopathology data were correlated with the cytological diagnosis. Results: We included 288 cases. Of those, 234 (81.3%) were female and 54 (18.8%) were male. The presentation age range was 18–91 years. The most reported category was benign, which constituted 30.9% of the cases followed by malignancy (27.1%). As for thyroid lesions, papillary carcinoma was the most prevalent (43.6%). The correlation on cyto-histopathology was presented in every diagnostic category, showing high heterogeneity in diagnostic specificity and sensitivity. The overall diagnostic specificity and sensitivity were 56.05% (95% confidence interval [CI]: 47.92–63.95%) and 80.92% (95% CI: 73.13–87.25%), respectively. Positive and negative predictive values were 60.57% and 77.88%, respectively. Conclusion: Our data suggests that the TBSRTC system promotes similar sensitivity and specificity to those reported elsewhere. It standardizes reporting and improves communication between cytopathologists and clinicians.

Nouveautés en pathologie thyroïdienne : classification OMS 2022, système Bethesda 2023, biologie moléculaire et testing moléculaire

WHO CLASSIFICATION 2022, BETHESDA SYSTEM 2023, MOLECULAR BIOLOGY AND MOLECULAR TESTING: Thyroid pathology has experienced significant advances with the publication of the 5th edition of the World Health Organization classification of endocrine tumors in 2022 and the third edition of the Bethesda system for thyroid cytopathology in 2023. At the same time, the availability of next-generation sequencing data coupled with numerous translational research projects have considerably increased our knowledge of the genomics and mechanics of thyroid cancers, enabling us to refine prognosis and propose new targeted therapies. In this review, we will take up the main new features of the WHO 2022 and Bethesda 2023 classifications, as well as molecular biology findings, with an emphasis on the practical implications for clinicians.

Risk Stratification of Thyroid Nodules Diagnosed as Bethesda Category III by Ultrasound, Size, and Cytology.

This study aimed to evaluate the performance of an integrated risk stratification system (RSS) based on ultrasound (US) RSSs, nodule size, and cytology subcategory for diagnosing malignancy in thyroid nodules initially identified as Bethesda category III on fine-needle aspiration. This retrospective study was conducted at two institutions and included consecutive patients with Bethesda category III nodules, and final diagnoses confirmed by repeat biopsy or surgery. A total of 320 Bethesda category III nodules (≥1 cm) from 309 patients (223 female and 86 male; mean age, 50.9 ± 12.0 years) were included. The malignancy risk of Bethesda category III nodules and predictors of malignancy were assessed according to US RSSs, nodule size, and cytology subcategory. The diagnostic performances of US-size cytology (USC) RSS and US RSS alone for malignancy were compared. The intermediate or high suspicion US category independently increased the malignancy risk in all US RSSs (P ≤ 0.001). Large nodule size (≥3 cm) independently increased the malignancy risk of low- or intermediate suspicion US category nodules. Additionally, the atypia of undetermined significance cytology subcategory independently increased the malignancy risk of low suspicion US category nodules in most US RSSs. The area under the receiver operating characteristic curve of the USC RSSs was greater than that of the US RSSs alone (P < 0.048). Malignancy was not found in the very low risk category of USC RSS. The diagnostic performance of USC RSS for malignancy was superior to that of US RSS alone in Bethesda category III nodules. Malignancy can be ruled out in the very low-risk category of USC RSS.

Molecular Markers in Follicular and Oncocytic Thyroid Carcinomas: Clinical Application of Molecular Genetic Testing.

Oncocytic thyroid carcinoma (OTC) was previously considered a variant of follicular thyroid carcinoma (FTC) but has recently been reclassified as a separate form of thyroid cancer. This study aimed to demonstrate that FTC and OTC are fundamentally distinct entities that can potentially be differentiated preoperatively through cytology and/or molecular testing. A retrospective chart review of patients diagnosed with FTC and OTC operated upon at two university health centers from January 2016 to September 2023 (n = 3219) was conducted. Molecular testing results were correlated with histopathologic diagnosis. Fifty patients met the inclusion criteria. FTC was identified in 27 (54.0%) patients, and OTC in 23 (46.0%) patients. Patients with OTC were older (61.8 years) than FTC patients (51.2 years) (p = 0.013). Moreover, aggressive tumors were found in 39.1% (9/23) of OTCs compared to 11.1% (3/27) of FTCs (p = 0.021). Amongst Bethesda category III and IV nodules, 17 out of 20 (85.0%) OTC cytology reports demonstrated an oncocytic subtype compared to only 5 out of 24 FTC cytology reports (20.8%) (p = 0.002). On molecular testing, the EIF1AX alteration was exclusively present in OTCs while the PAX8/PPARy and PTEN alterations were exclusively found in FTCs. Copy number alterations (CNAs) were found to be more prevalent in OTC (66.7%) compared to FTC (33.3%), and they were not indicative of tumor aggressiveness. Within the OTC group, all three patients who had a TP53 alteration were diagnosed with aggressive cancer. Lastly, the OTCs exhibited a higher frequency of multiple alterations on molecular testing (66.7%) compared to FTCs (33.3%). To our knowledge, this is the largest study to date comparing the clinical application of abnormalities found on molecular testing for FTC and OTC. It further demonstrates the distinct clinicopathological and molecular characteristics of OTC.