Tumors Of Uncertain Malignant Potential Research Articles

Uterine Inflammatory Myofibroblastic Tumors: p16 as a Surrogate for CDKN2A Deletion and Predictor of Aggressive Behavior.

Uterine inflammatory myofibroblastic tumors (IMTs) are rare mesenchymal neoplasms of uncertain malignant potential. Aside from the recently described risk stratification score, which has not been validated by other studies, and rare reports of aberrant p16 expression in malignant tumors, there are no criteria to reliably predict behavior. Herein, we evaluated the clinicopathologic features and p16 expression patterns in 30 IMTs, with genomic profiling performed in a subset (13 malignant, 3 benign). Fifteen patients had malignant IMTs, defined by extrauterine disease at diagnosis (n=5) or recurrence (n=10; median: 24 mo). Patients ranged from 8 to 65 (median: 51) years and tumors from 6 to 22 (median: 12.5) cm. In primary tumors (n=13), infiltrative borders were noted in 10, moderate/severe cytologic atypia in 9, tumor cell necrosis in 7, and lymphovascular invasion in 6, while mitoses ranged from 0 to 21 (median: 7) per 10 high-power fields. In contrast, 15 patients with benign IMTs ranged from 28 to 65 (median: 44) years, with follow-up of 18 to 114 (median: 41) months. Tumors ranged from 1.9 to 8.5 (median: 5.5) cm, 2 demonstrated infiltrative borders, and 1 had moderate cytologic atypia. No other high-risk histologic features were observed. Application of the previously described clinicopathologic risk stratification score in all primary IMTs with complete data (n=18) classified 8 as high-risk (all malignant), 8 as intermediate-risk (3 malignant, 5 benign), and 2 as low-risk (benign). p16 was aberrant in all malignant IMTs, with <1% expression noted in 10, overexpression (>90%) in 4, and subclonal loss in 1; all benign tumors had patchy staining (20% to 80%; median 50%). Molecular analysis detected CDKN2A deletions in 8 of 9 tumors with <1% p16 expression, while the other harbored a TERT promoter mutation. TERT promoter mutations were also identified in 2 of 3 IMTs with p16 overexpression. Neither of these alterations was detected in the 3 sequenced benign IMTs. Thus, we recommend performing p16 on all uterine IMTs, which, combined with the risk stratification score, is a promising and cost-effective tool for predicting CDKN2A status and outcome in these patients. It may be particularly useful for tumors with incomplete information for risk stratification (ie, morcellated tumors) and for further stratifying intermediate-risk IMTs when sequencing is unavailable.

How the Milan System for Reporting Salivary Gland Cytopathology works in cytopathology practice: Meta-analysis of prospective studies and comparison with retrospective studies.

The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is widely accepted and endorsed by professional societies. Although several studies focusing on the MSRSGC have been published, few have been prospective studies. The objective of this study was to evaluate the effectiveness of the MSRSGC in cytopathology practice. A comprehensive literature search was conducted to identify all prospective studies on the MSRSGC. The risk of malignancy (ROM), risk of neoplasm, and diagnostic accuracy for each diagnostic category were calculated. Data were tabulated in Microsoft Excel, and analyses were performed with the Open Meta-Analyst program. Seven prospective and seven retrospective studies were identified. The total number of fine-needle aspirations (FNAs) was 1587 in the prospective studies and 1764 in the retrospective studies. The ROM values for the nondiagnostic, nonneoplastic, atypia of undetermined significance, benign neoplasm, salivary gland neoplasm of uncertain malignant potential, suspicious for malignancy, and malignant categories in prospective versus retrospective studies were 21.0% versus 26.6%, 9.4% versus 8.1%, 34.9% versus 39.6%, 2.4% versus 2.1%, 36.6% versus 31.2%, 86.0% versus 66.0%, and 97.0% versus 96.7%, respectively. Sensitivities, specificities, and diagnostic odds ratios were 83.1% (95% confidence interval [CI], 71.1%-90.8%) versus 89.1% (95% CI, 83.6%-92.9%), 98.4% (95% CI, 96.6%-99.3%) versus 94.9% (95% CI, 91.9%-96.9%), and 310.7 (95% CI, 121.2-796.6) versus 218.8 (95% CI, 107.3-438.1). This meta-analysis indicated that the MSRSGC works well in FNA cytopathology practice and improves diagnostic accuracy in all diagnostic categories. The ROMs of prospective studies were in concordance with the MSRSGC reference values.

Ultrasound and cytopathological characteristics of thyroid tumours of uncertain malignant potential - from diagnosis to treatment.

The latest World Health Organization (WHO) classification from 2022 distinguishes the division of low-risk thyroid neoplasms such as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), follicular tumour of uncertain malignant potential (FT-UMP), and well-differentiated tumour of uncertain malignant potential (WDT-UMP). The final diagnosis is made postoperatively according to histopathologic results. The aim of the study was the assessment of ultrasonographic and cytopathological features of borderline lesions to predict low-risk tumours preoperatively and plan the optimal treatment for that group of patients. A total of 35 patients (30 women; 5 men), aged 20-81 years with a mean age of 49 years, were enrolled in the study. The study evaluated 35 focal lesions of the thyroid gland, classified as low-risk neoplasms according to the WHO 2022 classification: FT-UMP (n = 21), NIFTP (n = 7), and WDT-UMP (n = 7). Ultrasonographic features of nodules including contrast-enhanced ultrasound (CEUS) and elastography were assessed by 2 specialists, and the risk of malignancy was evaluated according to EU-TIRADS-PL classification. Of the 35 focal thyroid lesions, most were categorised as low or intermediate risk of malignancy according to EU-TIRADS-PL, with dominant category 3 [n = 13 (37.2%)] and category 4 [n = 15 (42.8%)]. High-risk category 5 was assessed in 7 lesions (20%). In cytopathology nodules were categorised as follows (Bethesda System TBSRTC 2023): Bethesda II (n = 4), Bethesda III (n = 2), Bethesda IV (n = 25), Bethesda V (n = 3), and Bethesda VI (n = 1). In the CEUS study, contrasting patterns dominated compared to the surrounding parenchyma, such as enhancement equal to the parenchyma (66.6%) or intense (28.5%), heterogeneous (61.9%), centripetal (42.8%), or diffuse (57.1%) with fast (33.3%) or compared to parenchyma contrast wash-in (42.8%) and its fast (33.3%) or comparable to thyroid parenchyma wash-out (52.3%). The study indicates that lesions with uncertain malignant potential typically present features suggesting low to intermediate risk of malignancy based on EU-TIRADS-PL classification, with dominant cytopathologic Bethesda IV category. However, 20% of lesions were assessed tas EU-TIRADS-PL category 5. Low-risk tumours, including NIFTP, FT-UMP, and WDT-UMP, require careful observation and monitoring post surgical treatment due to their potential for recurrence and metastasis. The preoperatively prediction of borderline tumour may play an important role in proper treatment and follow-up.

Molecular analysis using SalvGlandDx improves risk of malignancy estimation and diagnosis of salivary gland cytopathology: An exploratory multicenter study.

Diagnosis of salivary gland neoplasms is challenging, especially on cytological specimens acquired by fine-needle aspiration. The recently implemented standardized Milan system for reporting salivary gland cytopathology provides an estimated risk of malignancy (ROM); yet, for two of the categories, the diagnosis of the lesion remains unclear. However, a precise diagnosis is desirable for optimal patient management, including planning of surgery and imaging procedures. Cytological specimens (n=106) were subjected to molecular analysis using the SalvGlandDx panel. The risk of malignancy was calculated for each detected alteration based on the diagnosis of the resection specimen. By taking into account the molecular alterations, their associated ROM, the clinical and cytological features, and the current literature, the Milan category was evaluated. Of n=63 technically valid cases, 76% revealed a molecular alteration. A total of 94% of these molecularly altered cases could be assigned to a different Milan category when additionally taking molecular results into account. In only 2% of the salivary gland neoplasms of uncertain malignant potential, in which a molecular alteration was detected, the classification remained salivary gland neoplasms of uncertain malignant potential. Molecular analysis of cytological specimens provides a benefit in classifying salivary gland neoplasms on fine-needle aspiration. It can improve the ROM estimation and thus help to assign cases of formerly unknown malignant potential to clearly benign or malignant categories.

Abstract 6273: GGCT expression is a useful marker for the diagnosis of follicular thyroid carcinoma

Abstract Background: Follicular thyroid carcinoma (FTC) and follicular adenoma (FA) have similar histological findings. FTC is distinct from FA based on the presence of capsular or vascular invasion in the tissues, but it is difficult to confirm the diagnosis in some cases. In this study, we aimed to establish useful molecular maker for differential diagnosis between FTC and FA. Methods: This study included FTC (n = 32), FA (n = 64), and follicular tumors of uncertain malignant potential (FT-UMP, n = 5). Invasive front tissue and tumor center tissue from 3 cases of FTC were collected using a laser microdissection system; RNA was extracted, followed by microarray analysis to examine molecules that were commonly highly expressed in the invasive front. Subsequently, immunohistochemical staining of gamma-glutamyl cyclotransferase (GGCT) was performed. For assessment of GGCT expression, the intensity of the nuclear staining was stratified using a four-tiered scale (0 to 3) and percentage of positive cells (0-100%) in the hotspot. Multiplying intensity score and percent of positive cells, an expression score ranging from 0 to 300 was calculated. The Ki-67 labeling index was examined in 20 cases of FTC, 25 cases of FA, and 4 cases of FT-UMP from the same cohort. We counted at least 2,000 tumor cells in the hot spot for the assessment of Ki-67 labeling index. Results: Microarray analysis revealed GGCT exhibited high expression levels at the invasive front of FTC. In immunohistochemical assessment, GGCT expression scores were significantly higher in FTC than in FA (118.5 ± 51.4 vs. 57.3 ± 34.7, p &amp;lt; 0.0001). The median Ki-67 labeling index were 3.9% (range 0.2 - 16.1) for FTC and 2.4% (range 0.3 - 7.0) for FA. FTC showed a higher Ki-67 index than FA (Wilcoxon rank sum test, p = 0.0444). With GGCT expression score, applying a cutoff value of 101.1, the distinction between FTC and FA resulted in a sensitivity of 68.8% and a specificity of 87.5% (AUC: 0.832). With Ki-67 labeling index, applying a cutoff value of 4.0%, the distinction between FTC and FA resulted in a sensitivity of 50.0% and a specificity of 80.0% (AUC: 0.677). The GGCT expression score was positively related with the Ki-67 labeling index in the FTC cases. (Spearman's ρ = 0.5293, p = 0.0164). There were no significant associations between GGCT expression scores and clinicopathological parameters, including age, gender, tumor diameter, pT stage, pN stage, pattern of capsular invasion, number of foci of vascular invasion, and the presence of distant metastasis. Conclusions: GGCT is a potential marker for differentiating FTC from FA. The GGCT expression of FTC may contribute to estimating the invasive activity and proliferative activity. Citation Format: Toshiyuki Mitsuhashi, Sachiko Ogasawara, Masamichi Nakayama, Reiichiro Kondo, Jun Akiba, Kenta Murotani, Takeharu Ono, Fumihiko Sato, Hirohito Umeno, Hirohisa Yano. GGCT expression is a useful marker for the diagnosis of follicular thyroid carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6273.

Solitary fibrous tumor of deep parotid gland preoperatively classified as salivary gland neoplasm of uncertain malignant potential by the Milan system for reporting salivary gland cytopathology: A common diagnosis for a rare entity.

Solitary fibrous tumor (SFT) is a rare fibroblastic tumor with spindle cell morphology, which is characterized by a prominent branching vasculature and a NAB2-STAT6 gene rearrangement. SFT may occur in any anatomical site and may involve salivary glands, including the parotid gland. We present a young female with a primary parotid SFT diagnosed as "neoplasm-Salivary gland neoplasm of uncertain malignant potential (SUMP)" per the Milan system for reporting salivary gland cytopathology by fine-needle aspiration (FNA) with surgical pathology follow-up. Cytomorphology of SFT is diverse and overlaps with more common entities causing a diagnostic challenge. Non-diagnostic FNA results are not uncommon. Thankfully, the majority of SFTs involving the salivary gland can be identified as "neoplasm" on FNA. The Neoplasm-SUMP subcategory is considered for the majority of cases, which would warrant a diagnostic excision with clear surgical margins, which is also curative in most cases. The Neoplasm-SUMP also perfectly encompasses the neoplastic behavior of SFT, which runs on a scale from indolent to malignant.

In silico annotation of follicular thyroid neoplasm associated metabolic pathways and involved biomarkers: An aid to diagnosis

The follicular thyroid neoplasm (FTN) is like an unsolved puzzle at some stage in preoperative diagnosis. Usually, for preliminary characterization of thyroid lesions, clinicians depend much on fine-needle aspiration cytology (FNAC). However, in the case of FTN, FNAC cannot distinguish between benign and malignant entities, as both are exhibiting predominant follicular architecture. Cytological/ architectural/ or cellular criteria alone is not enough to differentiate Follicular adenoma (FA), Follicular thyroid carcinoma (FTC), Follicular variant of papillary thyroid carcinoma (FVPTC) together with Non-Invasive Follicular variant of Papillary Thyroid Carcinoma (NIFTP), Encapsulated FVPTC (EFVPTC) and well-differentiated neoplasm of uncertain malignant potential. Thus, the genetic analysis can be used as a novel diagnostic approach that should be applied with the traditional method for easy diagnosis of follicular thyroid neoplasm, which reduces the risk of unnecessary surgeries. This present study tried to explore the current genetic assessment of FTN through review of the genetics of FTN studied from 2009 to 2019 which showed the characterization of differential gene expression in these follicular neoplasms some extent. Also, pathway analysis has potentially implemented to minimize the diagnosis dilemma. In addition to the previously identified pathways and associated target genes, some novel endocrine cancer-related pathways with putative target genes of FTN have been remoted from characterizing tumor with follicular pattern. The observed genes might be considered as diagnostic biomarker in the respective FTN associated metabolic pathways.

Uterine smooth muscle tumors of uncertain malignant potential: a retrospective evaluation of clinical pathology and immunohistochemistry features

BackgroundUterine smooth muscle tumor of uncertain malignant potential (STUMP) is a group of uterine smooth muscle tumors which cannot be classified as a subtype of leiomyoma or leiomyosarcoma. Diagnosis, prognosis, and treatment of these tumors are challenging due to recurrence, potential of malignancy, and metastasis.MethodsA retrospective cohort study was conducted in southern Iran during 2011 to 2020. We included records of 21 patients with STUMP and 24 patients with leiomyoma by simple randomized sampling in the tertiary health care centers in Shiraz, southern Iran. Slides were reviewed by an expert pathologist for examining mitosis, necrosis, and atypia, and also proper blocks were selected for immunohistochemistry (IHC) staining.ResultsFrom 45 participants, 21 (46.7%) and 24 (53.3%) patients were in the STUMP and normal leiomyoma groups, respectively. Odds ratio and 95% confidence interval (OR (95% C.I)) of pathologic size in the range of 5–10 cm was significantly higher in the STUMP group compared with normal leiomyoma. (CI: 7.22 (1.44–36.22)). Additionally, hyaline necrosis 0.05 (0.0-0.91), mild to moderate atypia 0.02 (0.0-0.4), moderate to severe atypia 0.01 (0.0-0.22), focal atypia 0.01 (0-0.26) and diffuse atypia 0.01 (0-0.26) were significantly fewer in normal leiomyoma compared to the STUMP group. Negative P16 0.01 (0.0007-0.24) and negative Bcl2 0.22 (0.06–0.81) were significantly higher in the normal leiomyoma group compared with the STUMP group. The cut-off points for predicting STUMP were 2.5% (sensitivity = 62% and specificity = 100%) and 45% (sensitivity = 43% and specificity = 96%) for P16 and bcl2, respectively.ConclusionThe category and management of STUMP continues to progress. The diagnosis for STUMP mainly depends on the histopathological manifestations. No single IHC marker such as P53, P16, and Bcl-2 has proved robust enough in separating STUMP from other leiomyoma variants; however, according to our study, we suggest combination use of P16 and Bcl-2 (cut off 2.5 and 45%, respectively) to distinguish equivocal cases of STUMP.

A Rare Case of Recurrent Vulvovaginal Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP)

Smooth muscle tumours are the most common mesenchymal tumors of the vulva and vagina, yet their infrequency is demonstrated by the prevalence of published reports as individual cases or small case series. This article reports a case of a 42-year-old woman who presented with apparently recurrent vulvovaginal leiomyoma and a past history of surgical excisions. Histopathology revealed Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP).

Should there be a paradigm shift for the evaluation of isthmic thyroid nodules?

Although the thyroid isthmus seems like a rudimentary structure that connects bilateral lobes, it is an undiscovered area that needs to be explored. Currently, the data is evolving that the increase in the risk of malignancy is higher in the isthmic nodules, and extrathyroidal extensions and lymph node metastases are more common in isthmic-derived malignant thyroid nodules. Therefore, we aimed to compare the malignancy rate of isthmic and lobar nodules, the ultrasonographic features of isthmic and lobar nodules, and presence of lymph node metastases, distant metastases, and extrathyroidal invasions in malignant isthmic nodules. In this retrospective study, we enrolled patients between the ages of 18-80years, who had thyroid nodule/nodules cytology and/or pathology results from January 2009 to November 2022. 9504 nodules were selected for the analysis of US findings, cytopathology results, and malignancy rates. A mean ± SD age of 55.3 ± 13.0years with a female to male ratio of [7618 (80.2%)/1886(19.8%)] were included in the study. 962 of the nodules were at isthmic localization; whereas 8542 nodules were at lobar localization. 1188 nodules were resulted as malignant from histopathological evaluation. Of the 1188 malignant nodules, 986 nodules were (83.0%) PTC, 114 nodules (9.6%) were FTC, 55 nodules were (4.6%) MTC, 16 nodules 1.3% were Hurtle cell carcinoma, 8 nodules (0.7%) were anaplastic thyroid carcinoma, and 9 nodules (0.8%) were thyroid tumors of uncertain malignant potential (TT-UMP). 156 of the malignant nodules (13.1%) were located in the isthmus, whereas the majority of the malignant nodules (n = 1032, 86.9%) were located at the lobar parts (right or left) of the thyroid. When the metastasis patterns of isthmic and lobar thyroid cancers were examined, no significant relationship was found between isthmic and lobar cancers in terms of capsule invasion (p = 0.435), muscle invasion (p = 0.294), and lymph node metastasis (p = 0.633). A significant relation was found between nodule localization (isthmus-upper-middle and lower lobes) and malignancy (p < 0.001). In our logistic regression analysis, isthmic and upper pole nodule localizations, age and TI-RADS were evaluated as independent risk factors for malignancy (p < 0.001 for all factors). We recommend nodule localization has to be considered an additional risk factor when performing a Fine Needle Aspiration Biopsy for the increased malignancy risk in this localization.

Role of fine-needle aspiration cytology in the evaluation of salivary gland lesion with utilization of Milan system for reporting

Background: Fine-needle aspiration cytology (FNAC) plays a role in the pre-operative diagnosis of salivary gland mass lesion. Salivary gland neoplasm accounts for 6% of all head and neck tumors. It is widely used safe and relatively non-traumatic procedure that can quickly provide important information. “The Milan system for reporting salivary gland cytopathology” (MSRSGC) was introduced, providing a guide for diagnosis and management according to the risk of malignancy (ROM) in different categories. Aims and Objectives: The objectives of the study are as follows: (1) To evaluate different types of salivary gland lesion in tertiary care center. (2) To see application of Milan system in the present scenario. Materials and Methods: A hospital-based and prospective study was conducted between March 2021 and September 2022 on all cases of salivary gland lesions who were referred for FNAC to the Department of Pathology at Netaji Subhash Chandra Bose Medical College Hospital in Jabalpur, Madhya Pradesh. In the present study, we categorize salivary gland cytopathology result as per Milan system (MSRSGC) and calculated diagnostic accuracy and ROM in each category of Milan system (MSRSGC). Results: Seventy seven cases distributed according to Milan category as follows: Non-diagnostic (ND) (2.59), non-neoplastic (NN) (29.33%), atypia of undetermined significance (AUS) (1.29%), 4a. Benign (29.87%), 4b. Salivary gland neoplasm of uncertain malignant potential (SUMP) (1.29%), suspicious of malignancy (SOM) (1.29%), and malignancy (10.38%). Out of 77 cases, histological follow-up was available in 27 cases and the ROM was calculated. The ROM for each category of the Milan system is as follows: ND (0%), NN (6.66%), AUS (100%), 4a. Benign (9.09%), 4b. SUMP (0%), SOM (100%), and Malignancy (100%). The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 77.7%, 100%, 100%, 92.59%, and 94.11%. Conclusion: FNAC of the salivary gland lesions is a safe, minimum invasive, and reliable diagnostic procedure. The Milan system of reporting is a risk stratification system which can improve the overall effectiveness of reporting.

The Milan system for reporting salivary gland cytopathology - Assessment of utility and the risk of malignancy.

Cytological diagnosis of salivary gland lesions furnishes several challenges to pathologists and clinicians owing to their diverse morphology and varying reporting terminology. The Milan system for reporting salivary gland cytopathology was proposed to overcome these defects. The aim of this study was to grade histopathologically diagnosed cases of salivary gland pathology using Milan system and to correlate Milan system with histopathological diagnosis. The study aims to assess the utility of the Milan system and the risk of malignancy in each category. This is a retrospective study of 4 years duration. All the cases of salivary gland pathology with fine-needle aspiration cytology findings from January 2015 to December 2018 were retrieved and classified according to the Milan system. Histopathology follow-up of these cases were reviewed from the archives, and risk of malignancy was calculated. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated using histopathological diagnosis as the gold standard. Cytology slides of 151 cases were reviewed, and the Milan system was applied. Histopathology follow-up was obtained in 94 cases (attrition rate = 37.74%). The percentage of cases in each category were as follows: nondiagnostic = 9.27%, nonneoplastic = 4.64%, atypia of undetermined significance = 3.97%, benign neoplasm = 23.84%, neoplasm of uncertain malignant potential = 8.61%, suspicious for malignancy = 11.92%, and malignant = 37.75%. Sensitivity, specificity, positive predictive value, and negative predictive value of the Milan system were 94.20%, 96.00%, 98.48%, and 85.71%, respectively. The Milan system has high sensitivity and specificity in comparison with histopathology. This system proves helpful to the pathologist as well as the clinician in achieving uniformity of reporting terminology by classifying salivary gland lesions into subcategories with prognostic relevance.

EphB3 protein is a potential ancillary diagnostic biomarker for thyroid cancers

ObjectiveTo investigate the expression of ephrin type B receptor 3 (EphB3) in thyroid tumors and its usage as an ancillary diagnostic biomarker for thyroid tumors. MethodsFormalin-fixed and paraffin-embedded (FFPE) tissue samples (78 cases) and FNAC samples (57 cases) were assessed with the EphB3 antibody using immunohistochemistry. PTC and other thyroid follicular tumors were compared regarding their EphB3 expression. Sanger sequencing was used to assess for the presence of a BRAF V600E mutation. ResultsEphB3 was positive in 81.8 % (27/33) of papillary thyroid carcinoma (PTC), 83.3 % (5/6) of medullary thyroid carcinoma (MTC), 25 % (1/4) of hyperplastic/adenomatoid nodule (HN), 14.3 % (1/7) of follicular adenoma (FA), and negative in follicular tumors of uncertain malignant potential (FT-UMP) (0/13), noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP) (0/7), thyroid follicular carcinoma (TFC) (0/4), Hashimoto's thyroiditis (0/4), and normal thyroid follicular tissues (0/33). In cellular blocks, EphB3 was positive in 87.1 % (20/23) of PTC, 75 % (3/4) of MTC, 20 % (2/10) of HN, and negative in atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) (0/20) and normal thyroid follicular cells (0/10). ConclusionEphB3 is expressed in the majority of PTC, but less so in benign follicular nodules. EphB3 expression in fine needle aspiration cytology (FNAC) specimens can be used as a diagnostic tool to differentiate thyroid cancer from other follicular lesions in its differential diagnosis, especially AUS/FLUS and PTC.

Beyond the three P's: adrenal involvement in MEN1.

Adrenal lesions (ALs) are often detected in patients with multiple endocrine neoplasia type 1 (MEN1). However, they are not well described in MEN1, making their clinical management unclear. This study examined the prevalence and outcomes of ALs found in MEN1. We performed a retrospective chart review of patients diagnosed with MEN1 from 1990 to 2021. ALs were diagnosed using abdominal or thoracic imaging and classified as being unilateral or bilateral, having single or multiple nodules, and as having diffuse enlargement or not. Measurable nodular lesions were analyzed for their size and growth over time. Patients' clinical and radiographic characteristics were collected. We identified 382 patients with MEN1, 89 (23.3%) of whom had ALs. The mean age at detection was 47 ± 11.9 years. We documented 101 measurable nodular lesions (mean size, 17.5 mm; range, 3-123 mm). Twenty-seven nodules (26.7%) were smaller than 1 cm. Watchful waiting was indicated in 79 (78.2%) patients, of whom 28 (35.4%) had growing lesions. Functional lesions were diagnosed in 6 (15.8%) of 38 that had functional work-up (diagnoses: pheochromocytoma (n = 2), adrenocorticotropic hormone-dependent hypercortisolism (n = 2), hyperandrogenism (n = 1), hyperaldosteronism (n = 1)); surgery was indicated for 5 (83.3%; n = 12 nodules), 2 of whom had bilateral, diffuse adrenal enlargement. Two patients were diagnosed with adrenocortical carcinoma and two with neoplasms of uncertain malignant potential. Radiographic or clinical progression of ALs is uncommon. Malignancy should be suspected on the basis of a lesion's growth rate and size. A baseline hormonal work-up is recommended, and no further biochemical work-up is suggested when the initial assessment shows nonfunctioning lesions.

Uterine smooth muscle tumors: a multicenter, retrospective, comparative study of clinical and ultrasound features

ObjectiveTo evaluate a wide range of clinical and ultrasound characteristics of different uterine smooth muscle tumors to identify features capable of discriminating between these types.MethodsThis was a retrospective, multicenter study...

Role of hypermethylated SLC5A8 in follicular thyroid cancer diagnosis and prognosis prediction

ObjectiveThyroid cancer is one of the most frequently reported endocrine system malignancies. It is difficult to distinguish follicular thyroid cancer (FTC) from follicular thyroid adenoma (FTA) during pathological diagnosis in patients without lymph nodes or distant metastases. Therefore, we conducted a retrospective study to investigate the significance of SLC5A8 methylation and expression in the diagnosis and prognosis of FTC.MethodsWe used 165 tissue samples, including FTC (n = 58), thyroid tumors of uncertain malignant potential (TT-UMP, n = 40), and FTA (n = 67), to explore the differences in SLC5A8 methylation and mRNA transcription in different pathological types. Survival analysis was conducted to evaluate the recurrence rate at a 5-year follow-up.ResultsThe SLC5A8 methylation positive rate was higher in patients with thyroglobulin ≥ 40 μg/l and Chol ≥ 5.17 mmol/l, and it was higher in patients with FTC (n = 42, 72.4%) than those with FTA (n = 27, 40.3%) and TT-UMP (n = 23, 57.5%). The relative concentration of SLC5A8 mRNA was lower in patients with FTC than in those with FTA (p < 0.05). At 5-year follow-ups, patients who were SLC5A8 methylation-positive had a higher recurrence rate than those who were methylation-negative.ConclusionsOur current study indicates that SLC5A8 gene methylation occurs more commonly in patients with FTC than in those with FTA. The differences in SLC5A8 methylation and expression among FTA, FTC, and TT-UMP provide an important basis for further exploration of epigenetic changes in the occurrence, development, and prognosis of thyroid cancer. Our findings need to be further validated in larger populations with long-term follow-up in the future.

Prognosis of Adrenal Oncocytic Neoplasms (AONs): Literature Review of 287 Cases and Presentation of the Oldest Patient.

The adrenocortical oncocytic neoplasms (AONs) are rare tumors of the adrenal gland, classified as oncocytoma (AO), oncocytic neoplasm of uncertain malignant potential (AONUMP) and oncocytic carcinoma (AOC). The aim of this study was to perform a review of the literature, in order to evaluate the prognosis of these rare cancers. We also reported the oldest patient with AON. A comprehensive literature review using as key words "adrenal oncocytoma", "adrenal oncocytic neoplasm", and "adrenal oncocytic carcinoma" was performed. We report the case of an 88-year-old woman receiving a left open adrenalectomy for an AON (15 × 10 × 8 cm). The considerable size and weight together with the presence of necrosis were indicative for a lesion with an uncertain potential for malignancy, according to Weiss modified criteria. After two years, the patient was free from any sign of recurrence. Only 287 AONs were detected in the scientific literature, exploring OVID, MEDLINE, PubMed and SCOPUS as dataset. These tumors are usually incidentalomas with an unpredictable malignant potential. Surgical resection remains the mainstay of treatment for AON. AO and AONUMP have an excellent prognosis and a low mortality rate, with only three cases of recurrence reported in the literature and one metastatic case four years after first adrenal surgery. In contrast, AOC carries a high risk of local relapses, distant metastasis, and a significantly higher mortality rate (30%). Surgical resection remains the primary treatment for adrenal oncocytic neoplasms.

FRI239 Oncocytic Adrenocortical Neoplasm Of Uncertain Malignant Potential

Abstract Disclosure: K. Barnett: None. A. Sandhu: None. F. Hasan: None. Introduction: Oncocytic adrenocortical neoplasms are a rare histological subtype of adrenal mass, characterized by their abundant eosinophilic cytoplasm. Like other adrenal masses, they can be functional, or hormone-producing, and present on a spectrum from benign to malignant. Case: Our patient is a 31 year old female with a past medical history of anxiety who presented to the ER for right upper quadrant abdominal pain. She described it as a colicky, aching pain, lasting for several minutes at a time. She could identify no known trigger. A CT abdomen with contrast showed cholelithiasis and a hypodense lesion on the right adrenal gland. Her primary care physician (PCP) ordered a follow-up MRI abdomen with contrast that showed an indeterminate, 2.9 cm x 2 cm mass on the right adrenal gland without evidence of microscopic fat. After consultation with an oncologist, her PCP then recommended a PET scan, which showed that the mass was mildly hypermetabolic. She presented to the endocrinology office for further evaluation shortly thereafter. Though her abdominal pain had subsided, she did endorse a 7 lb weight loss, attributed to decreased appetite from anxiety. Additional review of systems was grossly negative. Hormonal work-up, including DHEA, renin, AM cortisol, ACTH, aldosterone, and plasma metanephrines was normal. CT-guided biopsy was deferred in favor of a repeat CT abdomen with adrenal protocol, which showed the adrenal nodule measured 40 HU on unenhanced images, with an absolute contrast washout of 50%. As this was less than the 60% threshold typically utilized to indicate a lipid-poor adenoma, the nodule was deemed indeterminate. Given the concerning features of the mass: its lipid-poor nature on unenhanced CT, metabolic activity on PET scan, and washout that was below the threshold for an adenoma, adrenalectomy was recommended. She underwent a laparoscopic right adrenalectomy, with final pathology showing oncocytic adrenocortical neoplasm of uncertain malignant potential, based on Lin-Weiss-Bisceglia criteria. She was seen by oncology, and they recommended no adjuvant treatment at this time. A repeat CTAP abdomen with adrenal protocol is planned for 1 year after this procedure. Discussion: Given the rarity of oncocytic adrenocortical neoplasms, their classification into benign, uncertain malignant potential, or malignant using Lin-Weiss-Bisceglia criteria is essential to determining appropriate treatment and surveillance. A recent retrospective cohort study showed oncocytic neoplasms with uncertain malignant potential have favorable outcomes, however, patients require continued radiographic surveillance due to the risk of late recurrence. Reference: Shirali AS, et al. Differences in Clinicopathologic Behavior of Oncocytic Adrenocortical Neoplasms and Conventional Adrenocortical Carcinomas. Ann Surg Oncol. 2022;29(9):5555-5563. doi:10.1245/s10434-022-11626-w Presentation: Friday, June 16, 2023

A rare phenomenon, primary pulmonary smooth muscle tumor and its management

Smooth muscle tumors of uncertain malignant potential, the borderline tumors arising from the smooth muscle cells, usually grow slowly and do not fulfill the diagnostic criteria of leiomyosarcoma and its variants, but may behave in a malignant manner. A 15-year-old female patient with an endobronchial mass in the left main bronchus on thoracic computed tomography underwent thoracotomy and tracheobronchoplasty with a wide and safe margin. Histopathological evaluation revealed a smooth muscle tumor of uncertain malignant potential. There were no complications related to the operation during the hospital stay. At six months of surgery, there were no symptoms or signs suggesting any recurrence in her follow-up. In conclusion, In conclusion, pulmonary leiomyomas may rarely present as an endobronchial mass and may mimic asthma by causing respiratory symptoms developing as attacks due to displacement of the mass within the lumen.

Possibilities of immunocytochemical staining for HBME-1 expression in the «diagnostic search» of differentiated thyroid cancer. Own investigation

Objective — to investigate HBME-1 expression variants on cytological material classified as doubtful (III, IV, V), according to the Bethesda categories, to evaluate the value of the HBME-1 expression test on the corresponding histological material of nodular goiter, follicular tumor with an uncertain potential for malignancy for the differential diagnosis of thyroid carcinoma (ThC). Materials and methods. The analysis was performed on the data of 14 patients with thyroid nodular lesions and cytological Bethesda categories III, IV, and V (“gray zone“). The HBME-1 expression was determined by the results of immunocytochemical (ICC) and immunohistochemical (IHC) staining with the use of mouse monoclonal antibodies against human HBME-1 (1 : 500; cat № BSB 3459; «Bio SB» «Bioscince for the World» Santa Barbara USA). The HBME-1 expression grade was calculated as the sum of the score for staining intensity and cytoplasmic positive cells square, present in the IHC sample. HBME-1 positive result was considered with an IHC score &gt;6 point. Results. From 14 investigated patients, five were defined as HBME-1 positive. According to the postoperative histological conclusion for the group of HBME-1 positive patients, thyroid carcinoma was diagnosed in four subjects, including three cases of papillary ThC and one follicular ThC; in one patient follicular tumor of uncertain malignant potential (FT-UMP) was reported. Importantly, immunocytochemical and immunohistochemical HBME-1 reactions in the specimens of these patients were of the same intensity. Among 9 HBME-1 preoperative negative patients, none had malignancy according to the final histological study. Nodular goiter was diagnosed in six patients, and tumor of uncertain malignant potential (FT-UMP) was reported for three subjects. Histological specimens of all 9 patients were HBME-1 negative as well. The obtained results demonstrated an increase in cancer detection rates with increasing Bethesda category. Application of statistical software for biomedical research МedCalc revealed that positive predictive value (PPV) of the HBME-1 expression test was 80% (95% confidence interval CI 38.4—96.3%), and diagnostic efficiency was 92.9% (CI 66.1—99.8%). These results suggest the great potential of the test, however, due to the limited observations, the confidence intervals are too wide. Conclusions. HBME-1 can be used as an immuno­cytochemical marker for the differentiation of benign and malignant thyroid nodules, its use will help to reduce the number of unnecessary surgical removals of benign tumors, which will improve the quality of life of patients and reduce the burden on medical services.