Uncertain Malignant Potential Research Articles

Reappraisal of bone and soft tissue cytopathology classification using the modified Milan system.

A standardized reporting system for bone and soft tissue tumor cytopathology has not yet been established. The objective of this study was to explore the potential utility of a classification modified from the Milan System for Salivary Gland Cytopathology and compared it with the upcoming World Health Organization (WHO) system for fine-needle aspiration of soft tissue lesions. The authors reviewed 285 cytology cases of bone/joint (n=173) and soft tissue (n=112) lesions, scoring each within diagnostic categories. The results were compared with histologic diagnoses and the risk of malignancy (ROM) for each category, and diagnostic reliability was analyzed. All 285 cases were successfully classified into one of the following categories: nondiagnostic (6.3%), non-neoplastic (11.9%), atypia of uncertain significance (11.9%), benign neoplasm (5.6%), bone and soft tissue neoplasm of uncertain malignant potential (25.3%), suspicious for malignancy (1.4%), and malignant (37.5%). The ROM was 44.4% (eight of /18 cases) in nondiagnostic, 0% (zero of 34 cases) in non-neoplastic, 32.4% (11 of 34 cases) in atypia of uncertain significance, 0% (zero of 16 cases) in benign neoplasm, 16.7% (12 of 72 cases) in bone and soft tissue neoplasm of uncertain malignant potential, 75.0% (three of four cases) in suspicious for malignancy, and 100% (107 of 107 cases) in malignant categories. Using the WHO system, the proportion and ROM of the benign category (non-neoplastic and benign neoplasm) was 17.5% and 0%, respectively. Among benign and malignant lesions, the diagnostic accuracy, sensitivity, and specificity for detecting malignancy were 99.4%, 100%, and 98.0%, respectively. The modified Milan system as well as the WHO system may be a useful cytopathologic classification tool for both bone and soft tissue lesions.

Sinonasal Leiomyoma: A Case Report and a Review of the Literature

Abstract Sinonasal leiomyoma is an exceptionally rare neoplasm arising from smooth muscle cells within the sinonasal tract. This abstract presents a case study of a 43-year-old male patient diagnosed with sinonasal leiomyoma, a distinctive and challenging entity in otolaryngology. The patient presented with a complex clinical history, including a 2-year interval between initial evaluation and definitive diagnosis. Initial histology suggested a smooth muscle tumour of uncertain malignant potential, highlighting the diagnostic intricacies associated with this condition. The radiological assessment revealed an extensive soft tissue mass with the involvement of multiple adjacent structures. The patient subsequently underwent surgical resection, leading to a revised histological diagnosis of leiomyoma. This case underscores the diagnostic challenges associated with sinonasal leiomyoma, emphasising the importance of comprehensive evaluation, including clinical history, radiological imaging, and histopathological examination. Long-term follow-up is essential for monitoring potential recurrences and optimising patient outcomes. By presenting this rare case, we aim to contribute to the limited body of literature on sinonasal leiomyoma and highlight the complexities surrounding its diagnosis and management in clinical practice.

Proteomics profile in encapsulated follicular patterned thyroid neoplasms

Diagnosing encapsulated follicular-patterned thyroid tumors like Invasive Encapsulated Follicular Variant of Papillary Thyroid Carcinoma (IEFVPTC), Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP), and Well-Differentiated Tumor of Uncertain Malignant Potential (WDT-UMP) remains challenging due to their morphological and molecular similarities. This study aimed to investigate the protein distinctions among these three thyroid tumors and discover biological tumorigenesis through proteomic analysis. We employed total shotgun proteome analysis allowing to discover the quantitative expression of over 1398 proteins from 12 normal thyroid tissues, 13 IEFVPTC, 11 NIFTP, and 10 WDT-UMP. Principal component analysis revealed a distinct separation of IEFVPTC and normal tissue samples, distinguishing them from the low-risk tumor group (NIFTP and WDT-UMP). IEFVPTC exhibited the highest number of differentially expressed proteins (DEPs) compared to the other tumors. No discriminatory proteins between NIFTP and WDT-UMP were identified. Moreover, DEPs in IEFVPTC were significantly associated with thyroid tumor progression pathways. Certain hub genes linked to the response of immune checkpoint inhibitor therapy, revealing the potential predictor of prognosis. In conclusion, the proteomic profile of IEFVPTC differs from that of low-risk tumors. These findings may provide valuable insights into tumor biology and offer a basis for developing novel therapeutic strategies for follicular-patterned thyroid neoplasms.

Stromal lymphocytes are associated with upgrade of B3 breast lesions

Various histopathological, clinical and imaging parameters have been evaluated to identify a subset of women diagnosed with lesions with uncertain malignant potential (B3 or BIRADS 3/4A lesions) who could safely be observed rather than being treated with surgical excision, with little impact on clinical practice. The primary reason for surgery is to rule out an upgrade to either ductal carcinoma in situ or invasive breast cancer, which occurs in up to 30% of patients. We hypothesised that the stromal immune microenvironment could indicate the presence of carcinoma associated with a ductal B3 lesion and that this could be detected in biopsies by counting lymphocytes as a predictive biomarker for upgrade. A higher number of lymphocytes in the surrounding specialised stroma was observed in upgraded ductal and papillary B3 lesions than non-upgraded (p < 0.01, negative binomial model, n = 307). We developed a model using lymphocytes combined with age and the type of lesion, which was predictive of upgrade with an area under the curve of 0.82 [95% confidence interval 0.77–0.87]. The model can identify some patients at risk of upgrade with high sensitivity, but with limited specificity. Assessing the tumour microenvironment including stromal lymphocytes may contribute to reducing unnecessary surgeries in the clinic, but additional predictive features are needed.

A clinical ultrasound algorithm to identify uterine sarcoma and smooth muscle tumors of uncertain malignant potential in patients with myometrial lesions: the MYometrial Lesion UltrasouNd And mRi study

BackgroundDifferential diagnosis between benign uterine smooth muscle tumors and malignant counterpart is challenging. We evaluated the accuracy of a clinical and ultrasound based algorithm in predicting mesenchimal uterine malignancies (MUMs), including smooth muscle tumors of uncertain malignant potential (STUMPs). MethodsWe report the twelve-months follow-up of an observational, prospective, single-centre study that included women with at least one myometrial lesion ≥3 cm on ultrasound examination. These patients were classified according to a three-class diagnostic algorithm, using symptoms and ultrasound features. “White” patients underwent annual telephone follow-up for 2 years, “Green” patients underwent a clinical and ultrasound follow-up at 6, 12 and 24 months and “Orange” patients underwent surgery. We further developed a risk class system to stratify the malignancy risk. Findings2,268 women were included andtarget lesion was classified as benign in 2,158 (95.1%), as other malignancies in 58 (2.6%) an as mesenchymal uterine malignancies in 52 (2.3%) patients. At multivariable analysis, age (OR 1.05 (95% CI 1.03-1.07), tumor diameter >8 cm (OR 5.92 (95% CI 2.87-12.24), irregular margins (OR 2.34 (95% CI 1.09-4.98), color score=4 (OR 2.73 (95% CI 1.28-5.82), were identified as independent risk factors for malignancies, whereas acoustic shadow resulted in an independent protective factor (OR 0.39 (95% CI 0.19-0.82). The model, which included age as a continuous variable and lesion diameter as a dichotomized variable (cut-off 81 mm), provided the best AUC (0.87 (95% CI 0.82-0.91)). A risk class system was developed, and patients were classified as low-risk (predictive model value <0.39%: 0/606 malignancies, risk 0%), intermediate risk (predictive model value 0.40%-2.2%: 9/1,093 malignancies, risk 0.8%), high risk (predictive model value ≥2.3%: 43/566 malignancies, risk 7.6%). ConclusionThe preoperative three-class diagnostic algorithm and risk class system can stratify women according to risk of malignancy. Our findings, if confirmed in a multicentre study, will permit differentiation between benign and MUMs allowing a personalized clinical approach. FundingNothing to declare.

Milan System Categorization and Reporting of Salivary Gland Tumors: A Literature Review

Abstract Salivary gland tumors (SGTs) are uncommon and represent about 6% of all head and neck tumors and 0.3% of all malignant tumors worldwide. The reporting system of SGTs before 2018 was individualized and may be problematic and confusing for some pathologists and clinicians. In 2018, the Milan Categorizing System for Salivary Gland Tumors (MSRSGC) was developed by an international consortium of experts and endorsed by the American Society of Cytopathology and the International Academy of Cytology; the aim was to standardize the reporting terminology to replace the conventional, descriptive interpretation for salivary gland fine needle aspirations for better communication between clinicians and between institutions. This review aims to stand on the extent of the MSRSGC in resolving the conflicts among pathologists and clinicians and highlight the problems that have been reported through studying the published literature. Since its development, the MSRSGC has provided to some extent a unified reporting system that elevated the communications among pathologists and clinicians. In addition, the MSRSGC has provided information about the risk of neoplasia (RON), risk of malignancy, and line of management for each category; however, most discussions have shown that some cases in the intermediate group are still indicating conflicts in its diagnosis and reporting, especially those of SGTs of uncertain malignant potential (SUMP) with distinct cellular features, such as basaloid, oncocytic, and squamoid features and a need to be recategorized individually, and the strength of the system in the category toward diagnostic feature of malignancy.

Uterine Tumor Resembling Ovarian Sex-Cord Tumor (UTROSCT): A Rare Polyphenotypic Neoplasm.

Uterine tumor resembling ovarian sex-cord tumor (UTROSCT) is a rare form of uterine mesenchymal neoplasm. Although UTROSCT generally exhibits benign behavior with a favorable prognosis, this neoplasm is nevertheless classified as being of uncertain malignant potential, given its low rate of recurrence and the fact that it rarely produces metastases (e.g., in the lymph nodes, epiploic appendix, omentum, small bowel, subcutaneous tissue, lungs). Its histogenesis is also uncertain. Typically, UTROSCT occurs in peri-menopausal or menopausal women, but it can sometimes be observed in young women. Usually, this neoplasm can be found in the uterine corpus as a nodular intramural lesion, while it is less frequently submucosal, subserosal, or polypoid/intracavitary. UTROSCT can cause abnormal bleeding, pelvic pain, enlarged uterus, and mass sensation, but sometimes it is found purely by chance. This neoplasm can be considered polyphenotypic on morphological, immunohistochemical, and genetic analyses. Generally, upon microscopic examination, UTROSCT shows a predominant pattern of the cords, nests, and trabeculae typical of sex-cord tumors of the ovary, while immunohistochemically it is characterized by a coexpression of epithelial, smooth muscle, and sex-cord markers. The aim of this review is to report clinical and pathological data and genetic alterations to establish their impact on the prognosis and management of patients affected by this rare entity.

Bronchial Basaloid Papillary Tumor of Uncertain Malignant Potential: A Case Report.

Bronchial papillomas are benign tumors, which can be divided into different subtypes based on the cellular features. So far, no bronchial papilloma with basaloid cell features has been reported. We report a bronchial basaloid papillary tumor in a 67-year-old woman. Tumor recurrence and malignant transformation were observed after a long-term follow-up. The clinical, histological, immunohistochemical, and genetic features were reappraised. The primary tumor was characterized by papillary growth pattern and basaloid neoplastic cells, only a small amount of neoplastic cells showed mature characteristics. The tumor originated from respiratory epithelium and had a low proliferation index by Ki-67. Keratin (KRT) 5/6 and KRT7 showed patchy or partial positivity. Myoepithelial markers were negative. P63 was diffusely positive, but it was negative in the small amount of tumor cells with mature characteristics. The common genetic alterations (EGFR, KRAS, BRAF V600E, HER2, and ALK) of lung cancers were not detected. However, tumor recurrence was observed in the mediastinum and esophagus 12 years after surgery. The recurrent tumor had a morphology overlapping with that of the primary tumor; however, it displayed significantly malignant characteristics. The recurrent tumor was not related to high-risk HPV. A high variant allele frequency was observed in tumor suppressor gene BRCA1, TP53, oncogene GNA11, and KIT, which were all missense mutations. Considering the bland features of the primary tumor and the fact of tumor recurrence and undisputed malignant transformation, the basaloid papillary tumor was considered a tumor with uncertain malignant potential.

Warthin-like Variant of Mucoepidermoid Carcinoma of the Parotid Gland

A 57-year-old woman with a 2-year history of a left infra-auricular mass with no associated symptoms presented with a 6.0 cm ´ 4.0 cm ´ 3.0 cm firm, non-tender, movable mass. No imaging was done. Fine needle aspiration biopsy (FNAB) revealed sheets of epithelial cells that had abundant dense grayish-blue cytoplasm in a mucinous background with abundant lymphocytes (Figure 1), suggestive of salivary gland neoplasm with oncocytic or oncocytoid features (Category IVB, Salivary Gland Neoplasm of Uncertain Malignant Potential).1 Total parotidectomy revealed a 4.3 X 3.2 X 3.0 cm deep lobe lesion with a tan-grey to dark brown, smooth and dull external surface. Cut sections showed a cream-white to pink, lobulated, heterogenous cut surfaces. Microscopically, the lesion was unencapsulated with poorly demarcated borders. The neoplastic cells were arranged in haphazard sheets and surrounded by abundant lymphocytes. The tumor cells had abundant eosinophilic and granular cytoplasm compatible with oncocytes with mild to moderate nuclear atypia. There were occasional cystic spaces that contained mucin though mucocytes were not readily apparent. (Figure 2) Necrosis, perineural and lymphovascular space invasion or anaplasia were not evident.

Abstract PO3-07-09: B3 breast lesions in Asian Centers: malignant upgrade rates and risk factors

Abstract Background Lesions of uncertain malignant potential in the breast (B3 lesions) are composed of a wide spectrum of pathologies with differing risks of breast cancer. With the widespread implementation of screening programs globally, the incidence of these lesions has increased substantially. Asian women tend to have smaller and denser breasts than Western women, making identifying and treating these lesions more challenging. Previous papers quote an upgrade of B3 lesions to malignancy such as ductal carcinoma in situ (DCIS) or cancer at rates of 9.9% to 35.1%. Malignant upgrade on final histology increases patient anxiety and healthcare costs as a second surgical intervention is often required for pathological clearance or lymph node staging. This study aimed to assess the malignant upgrade rate of B3 lesions in Asian women and to evaluate any key factors that may predict the risk of a malignant upgrade. Materials and Methods A retrospective multicentre international study was done on patients at Seoul National University Hospital (SNUH), South Korea, from April 2021 to 2023, and Tan Tock Seng Hospital (TTSH), Singapore, between March 2006 and 2023. Patients who were diagnosed with a B3 lesion on initial breast core needle biopsy and underwent surgical open excision were included in the study. Results A total of 1049 patients were diagnosed with B3 lesions, with 154 (14.7%) upgrading to malignancy. The most common malignancy was DCIS, 118 (76.6%), followed by invasive ductal carcinoma (IDC), 20 (13.0%) and papillary carcinoma, 4 (2.6%). Within the types of B3 lesions, the malignant upgrade rates were found: atypical ductal hyperplasia (ADH), 88/252 (35%); intraductal papilloma (IDP) with atypia, 16/55 (29%); lobular neoplasia (LN), 9/34 (26%); and radial scar (RS), 5/21 (24%). Most patients had both ultrasound and mammographic evaluation, and all lesions in the study were graded BIRADS 4A and above. Univariate analysis showed that age &amp;gt;50 (OR 2.30 [1.61-3.31], p&amp;lt; 0.001), BMI &amp;gt;23 (OR 2.21 [1.20-4.12], p=0.01), post-menopausal status (OR 2.43 [1.34-4.34], p&amp;lt; 0.001), lesion being identified on mammography (OR 3.00 [2.04-4.51], p&amp;lt; 0.001) and presence of microcalcifications on mammography (OR 0.63 [0.41-0.98], p=0.04) were risk factors for malignant upgrade. Conclusion Based on our analysis of Asian women, post-menopausal patients with microcalcifications on mammography and a B3 biopsy result should be treated with a higher degree of suspicion for underlying malignancy. Surgical excision with adequate margins should be routinely considered for B3 lesions such as ADH, IDP with atypia, LN and RS. Avoidance of surgery or vacuum-assisted removal can be considered for younger patients with only ultrasound findings and diagnosis of FEA and IDP. Table 1. Malignant upgrade after excision Table 2. Clinical characteristics of all patients according to malignant upgrade Table 3. Univariate and multivariate analysis for malignant upgrade Citation Format: Wei Wen Ang, Ji-Jung Jung. B3 breast lesions in Asian Centers: malignant upgrade rates and risk factors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-07-09.

Abstract PO2-28-11: How to improve margins in breast cancer surgery: a

Abstract Objective: Intraoperative specimen mammography (ISM) is a diffuse technique that allows surgeons to check specimens immediately after lumpectomy, instead of intraoperative frozen sections, definitely abandoned. in Italy and Europe, because it is regarded as too expensive and time-consuming examination. Although the specimen is slightly compressed, the radiological image can be distorted by tissue overlap, and this may affect the evaluation of tumor borders, resulting in extension of the lumpectomy. As ISM may be less precise due to inadequate compression, a vacuum effect was applied to the specimen to increase the precision of margin detection. Study design: This study was conducted at St. Anna Hospital Breast Unit, Turin, Italy. Women who underwent lumpectomy for cancer were eligible for inclusion. BCS resection was performed with a free margin, and the surgical specimen was imaged immediately by SSM and evaluated by an expert radiologist and surgeon.Inclusion criteria were: breast cancer detected by a screening test, and treatment with surgical lumpectomy. Both standard ISM (sISM) and vacuum ISM (vISM) were performed. A dedicated breast surgeon at the study institution performed both surgery and radiological scans, and their interpretation. A dedicated radiologist reviewed all of the images. ISM was performed by a digital specimen mammography system (Faxitron, Bioptics Inc., Tucson, AZ, USA) in the operating room. Specimen registration and ISM analysis took 3 min. sISM (two orthogonal projections) was performed. Specimens were sealed in plastic bags in the vacuum apparatus (TissueSAFE Milestone Medical, Sorisole, Italy); this process took a few seconds. 152 specimens obtained after lumpectomy from 1 April 2021 to 31 April 2022 were scanned. sISM (two orthogonal projections) was performed. Next, the specimen was placed in a vacuum bag, and vISM was performed. Additional tissue was removed if the surgeon considered that excision was inadequate. Finally, the specimen was sent for definitive histopathological analysis, which is the gold standard for the assessment of surgical margins. Intraoperative histological margin assessment was not performed. The sISM and vISM images and final histopathology reports were compared. A first experience on a limited number of patients to demonstrate feasibility of the technique, is reported in table 1 and 2. Results: For sISM, specificity was 43,85% [95 % confidence interval (CI) 35.96-51.73], sensitivity was 40.91% (95 % CI 33.09-48.73), positive predictive value (PPV) 10.98% (95 % CI 6.01-15.95) and negative predictive value (NPV) 81.43% (95 % CI 75.25-87.61). For vISM, specificity 92,31% (95 % CI 88,07-96.54), sensitivity 72.73% (95 % CI 65.65-79.81), PPV 61.54% (95 % CI 53.80-69.27) and NPV 95.24% (95 % CI 91.85-98.62). Conclusion: ISM is a valid, safe and quicker alternative to intraoperative histopathological study, but has been reported to be limited due to less compression than standard SSM. Consequently, ISM may result in a high percentage of false-positive results, meaning unnecessary wider resections that lead to increased operative times and worse aesthetic results. A vacuum effect was performed on the specimen to increase the precision of margin detection. vISM images seem to be easier to interpret than sISM images (Figs. 1–3) as they are characterized by a vacuum-created radiolucent rim that better defines the tumor margins. These data suggest that the vacuum technique is feasible, cost-saving and yields results that are similar to those from frozen sections but without the limitations, such as prolonged operating time, high variability in sensitivity due to pathologists abilities, risk of compromising the histology, and unreliability for small lumps and ductal carcinoma in situ. Keywords: Breast cancer; Intraoperative mammography; Lumpectomy; Specimen mammography; Vacuum intraoperative mammography. Table 1. Clinical Data IC, invasive cancer; DCIS ductal carcinoma in situ; ADH, atypical ductal hyperplasia; ILC, invasive lobular cancer; B3, lesions of uncertain malignant potential; IMPC, invasive micropapillary carcinoma; NST, no special type; sISM, standard intraoperative specimen mammography; vISM, vacuum intraoperative specimen mammography. ª Margin: 0, involved; 1, free Table 2. Figure 1 - 2 - 3 Standard intraoperative specimen mammography (left) and vacuum intraoperative specimen mammography (right). Citation Format: Maria Grazia Baù, Vincenzo Marra, Alessandra Surace, Donatella Tota, Maria Piera Mano, Aurelia Mondino, Alessandro Bottero, Elisabetta Robba. How to improve margins in breast cancer surgery: a [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-28-11.

Abstract PO4-18-09: SMALL: Open Surgery versus Minimally invasive vacuum-Assisted excision for smaLL screen-detected breast cancer – a UK phase III randomised multi-centre trial

Abstract Background: Mammographic screening programmes reduce breast cancer mortality but detect many small good-prognosis tumours which may not progress. Screen-detected cancers are currently treated with standard surgery and adjuvant therapies, with associated morbidities. There is a need to reduce overtreatment of good prognosis tumours and numerous studies are evaluating omission of radiotherapy in low-risk disease. However, there is little evidence to support surgical de-escalation, although percutaneous minimally invasive treatment approaches have been described. Vacuum-assisted excision (VAE) is in widespread use for management of lesions of uncertain malignant potential and benign lesions. SMALL (ISRCTN 12240119) is designed to determine the feasibility of using this approach to treat small invasive tumours detected within the UK NHS Breast Screening Programme. Methods: SMALL is a phase III multicentre randomised trial comparing standard surgery with VAE for screen-detected cancers. Main eligibility criteria are age ≥47 years, unifocal grade 1 tumours with maximum diameter 15mm, strongly ER/PR+ve and HER2-ve, with negative axillary staging. Patients are randomised 2:1 to VAE or surgery, with no axillary surgery in the VAE arm. Completeness of excision is assessed radiologically, and if excision is incomplete, patients undergo surgery. Adjuvant radiotherapy and endocrine therapy are mandated in the VAE arm but may be omitted following surgery. Co-primary end-points are: 1. Non-inferiority comparison of the requirement for a second procedure following excision 2. Single arm analysis of local recurrence (LR) at 5 years following VAE Recruitment of 800 patients will permit demonstration of 10% non-inferiority of VAE for requirement of a second procedure. This ensures sufficient patients for single arm analysis of LR rates, where expected LR free survival is 99% at 5 years, with an undesirable survival probability after VAE of 97%. To ensure that the trial as a whole only has 5% alpha, the significance level for each co-primary outcome is set at 2.5% with 90% power. The Data Monitoring Committee will monitor LR events to ensure these do not exceed 3% per year. Secondary outcome measures include time to ipsilateral recurrence, overall survival, complications, quality of life and health economic analysis. A novel feature of SMALL is the integration of a QuinteT Recruitment Intervention (QRI), which aims to optimise recruitment to the study. Recruitment challenges are identified by analysing recruiter/patient interviews and audio-recordings of trial discussions, and by review of trial screening logs, eligibility and recruitment data and study documentation. Solutions to address these are developed collaboratively, including individual/group recruiter feedback and recruitment tips documents. Results: SMALL opened in December 2019, but recruitment halted in 2020 for 5 months due to COVID-19. At 6th July 2023, 39 centres are open, with 300 patients randomised from 32 of these, with a randomisation rate of approximately 45%, and a per site recruitment rate of 0.4-0.5 patients/month. Despite the pandemic, SMALL achieved the internal pilot feasibility targets and continues to recruit to the main study, with estimated completion of recruitment in June 2025. Drawing from preliminary QRI findings and insights from patient representatives, a recruitment tips document has been circulated (on providing balanced information about treatments, encouraging recruiters to engage with patient preferences, and explaining randomisation). Individual recruiter feedback has commenced and wider feedback is being delivered across sites via recruitment training workshops. Conclusion: Despite pandemic-related challenges, SMALL has excellent recruitment to date and is expected to have a global impact on treatment of breast cancer within mammographic screening programmes. SMALL is funded by the UK NIHR HTA programme award 17/42/32 Citation Format: Stuart McIntosh, Charlotte Coles, David Dodwell, Kenneth Elder, Jessica Foster, Claire Gaunt, Amanda Kirkham, Iain Lyburn, Sangeetha Paramasivan, Jenna Morgan, Sarah Pinder, Shelley Potter, Tracy Roberts, Nisha Sharma, Hilary Stobart, Elizabeth Southgate, Sian Taylor-Phillips, Matthew Wallis, Daniel Rea. SMALL: Open Surgery versus Minimally invasive vacuum-Assisted excision for smaLL screen-detected breast cancer – a UK phase III randomised multi-centre trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-18-09.

Prostatic stromal tumor of uncertain malignant potential: a case report and literature review.

Prostatic stromal tumors, encompassing prostatic sarcoma and stromal tumors of uncertain malignant potential (STUMP), represent an exceedingly rare category of prostatic diseases, with a prevalence of less than 1%. We present a rare case involving a man in his early 40s diagnosed with STUMP. Despite presenting with normal prostate-specific antigen (PSA) concentrations, the patient experienced persistent dysuria and gross hematuria for >7 months, leading to an initial misdiagnosis of benign prostatic hyperplasia. Persistent symptoms prompted further investigation, with magnetic resonance imaging (MRI) revealing a suspicious lesion on the left side of the prostate, initially thought to be malignant. Transrectal prostatic biopsy subsequently confirmed the presence of mucinous liposarcoma, with no medical history of diabetes, coronary heart disease, or hypertension. The treatment approach comprised robot-assisted laparoscopic radical prostatectomy, culminating in a postoperative pathological definitive diagnosis of STUMP. This case underscores the indispensable role of early MRI in the diagnostic process, highlighting the necessity of detailed pathological examination for a conclusive diagnosis. Our report aims to illuminate the diagnostic challenges and potential treatment pathways for STUMP, emphasizing its consideration in the differential diagnosis of prostatic tumors to advance clinical outcomes in this rare but important condition.

Breaking New Ground: Unraveling Sinonasal Hemangiopericytoma Through a Rare Case Series on Endoscopic Excision and Postoperative Monitoring.

Hemangiopericytoma is a rare vascular neoplasm derived from pericytes, with uncertain malignant potential. It mainly occurs in the retroperitoneum and lower extremities, with a lower incidence in the head and neck region and nasal cavity. Diagnosis is aided by histopathological examination and immunohistochemistry. Surgical excision is the preferred treatment, with different approaches depending on tumour size. Endoscopic excision is suitable for small tumours, while larger ones may require external approaches. The recurrence rate is approximately 25%, emphasizing the importance of long-term follow-up. Our study aims to discuss a rare series of sinonasal hemangiopericytoma cases, their clinical presentation, and their management. In this study, we are discussing the prospective study of six cases of sinonasal hemangiopericytoma that were presented to a tertiary hospital, from June 2017 to June 2023, with complaints of nasal obstruction and bleeding episodes. They were assessed with a detailed history, blood investigations, radiological investigations, and diagnostic nasal examination, and underwent endoscopic surgical excision of the nasal mass, with the diagnosis confirmed by histopathological examination and immunohistochemistry. All cases were followed up for 1year postoperatively, except one case which missed follow-up after 6months and with no postoperative complications and recurrences. All six cases came with complaints of nasal obstruction and bleeding from the nasal cavity. All six cases underwent endoscopic surgical excision of the tumour and were followed for 1year in five cases; one case missed follow-up after 6months of postoperative follow-up, but no recurrence was noted in all the cases. For small-sized hemangiopericytoma tumours, endoscopic excision offers benefits such as improved visualization, easy resection, preservation of the normal anatomical structure, and maintenance of physiological function in the sinonasal cavities. With a recurrence rate of approximately 25%, surgical excision and long-term follow-up play essential roles in successful tumour management.

Uterine Smooth Muscle Tumors: An Overview.

Uterine smooth muscle tumors are a heterogeneous group of mesenchymal neoplasms with multiple histologic variants and distinct biological behaviors. Pathologic classification (benign, uncertain malignant potential, malignant) relies on the evaluation of mitotic index, necrosis, and degree of cytologic atypia, with different thresholds based on each subtype. Immunohistochemistry and other ancillary studies may be necessary to establish the diagnosis in a subset of cases, given the morphologic overlap with other mesenchymal neoplasms, including low-grade and high-grade endometrial stromal tumors, inflammatory myofibroblastic tumors, and PEComa. Recent advances in molecular diagnostics have refined the classification of smooth muscle tumors, but most cases are diagnosed purely on histologic grounds.

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.

Assessing the Accuracy of a Computer-Aided Detection System for Suspected Malignant Breast Lesions Using Magnetic Resonance Imaging

Background: Mammograms often reveal breast microcalcifications, necessitating invasive procedures to ascertain whether they are cancerous or benign. Objectives: Although many microcalcifications are linked to noncancerous conditions, this study sought to investigate the efficacy of a computer-aided detection (CAD) system using breast MRI in distinguishing between benign and malignant breast anomalies. Methods: This cross-sectional study included forty patients with mammographically suspicious microcalcifications who underwent stereotactically-guided biopsies at our institution over two years. Prior to the biopsy, these patients received a breast MRI within eight weeks. Surgical interventions were carried out for cases identified as malignant or of uncertain malignant potential. The study aimed to determine diagnostic benchmarks by comparing the breast imaging reporting and database system (BI-RADS) category assignments from initial mammography screenings and breast MRI reports to the pathology findings. Results: Histopathology reports showed that of the total cases, 23 were benign, and 17 were malignant. Breast MRI exhibited a sensitivity of 88.8%, specificity of 54.5%, a positive predictive value of 58.5%, and a negative predictive value of 94.1%. Further analysis using CAD demonstrated sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 50.0%, 59.0%, and 100%, respectively. Conclusions: Utilizing breast MRI with the support of CAD, radiologists could significantly enhance their capability to differentiate between benign and malignant mammographic microcalcifications. This innovative diagnostic approach has the potential to decrease the necessity for unnecessary breast biopsies.

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.