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.

Assessment of malignant potential for HPV types 16, 52, and 58 in the uterine cervix within a Korean cohort.

High-risk human papillomavirus (HR-HPV) is the primary carcinogen in uterine cervical carcinoma. While genotype-specific carcinogenic risks have been extensively studied in Western populations, data from Korean are sparse. This study evaluates the malignant potential of the three most prevalent HR-HPVs in Korea: HPV16, HPV52, and HPV58. We analyzed 230 patients who underwent cervical conization and had been tested for HPV within a year prior to the procedure, excluding those with multiple infections. This analysis was confined to patients with single HPV infections and assessed outcomes of CIN3+, which includes carcinoma in situ (CIN3) and invasive carcinoma. The incidence of invasive cervical cancer was 6.7% for HPV16, 1.7% for HPV52, and 2.0% for HPV58; however, these differences were not statistically significant (p = 0.187). The rate of CIN3+ for HPV16, HPV52, and HPV58 were 70.6%, 51.7%, and 58.8%, respectively. Despite the small sample size, which may limit the robustness of statistical analysis, the data suggest a higher observed risk with HPV16. These findings highlight the need for vigilant clinical management tailored to specific HPV genotypes and support the implementation of a nine-valent vaccine in Korea. Physicians should be aware of these genotype-specific risks when treating patients.

Pediatric urothelial cancer: a cross-sectional descriptive analysis of the National Cancer Database.

Background: Urothelial cancer is a rare pediatric malignancy; previous analyses suggest lower rates of recurrence and death as compared to adults. We analyzed pediatric bladder cancer information in a national database, hypothesizing that survival would be better in children than adults. Methods: We analyzed the 2004-2016 National Cancer Database (NCDB) for children and adolescents (0-18 years) with urothelial bladder cancer. Rhabdomyosarcoma patients were excluded. Assessed variables included TNM staging, pathology, tumor size, surgical procedures, and post-operative re-admissions. Overall survival was defined as months since diagnosis as of last follow-up. Results: Of 140 urothelial tumors reported to NCDB between 2004-2016, 75.7% (N=106) were stage 0 at diagnosis, 6.4% (N=9) were stage I, 2.9% (N=4) were stage II and 3.6% (N=5) were stage IV, while 11.4% cases (N=16) were unknown. From available mortality data (121 patients), no patients died after definitive surgical resection. Only 1 mortality was reported at 90 days, although cause of death was reportedly unknown. Three (2.5%) patients were lost to follow-up, and most (96.7%) were alive at 90 days. Conclusions: Short-term survival outcomes among children and adolescents with urothelial bladder tumors captured in NCDB are reassuring. Future investigations focused on long-term outcomes and appropriate surveillance in this rare patient cohort are imperative to better guide management options.

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.

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.

Clinicopathological characteristics and typing of multilocular cystic renal neoplasm of low malignant potential.

BACKGROUND: Up until now, no research has been reported on the association between the clinical growth rate of multilocular cystic renal neoplasm of low malignant potential (MCRNLMP) and computed tomography (CT) imaging characteristics. Our study sought to examine the correlation between them, with the objective of distinguishing unique features of MCRNLMP from renal cysts and exploring effective management strategies. AIM: To investigate optimal management strategies of MCRNLMP. METHODS: We retrospectively collected and analyzed data from 1520 patients, comprising 1444 with renal cysts and 76 with MCRNLMP, who underwent renal cyst decompression, radical nephrectomy, or nephron-sparing surgery for renal cystic disease between January 2013 and December 2021 at our institution. Detection of MCRNLMP utilized the Bosniak classification for imaging and the 2016 World Health Organization criteria for clinical pathology. RESULTS: Our meticulous exploration has revealed compelling findings on the occurrence of MCRNLMP. Precisely, it comprises 1.48% of all cases involving simple renal cysts, 5.26% of those with complex renal cysts, and a noteworthy 12.11% of renal tumors coexisting with renal cysts, indicating a statistically significant difference (P = 0.001). Moreover, MCRNLMP constituted a significant 22.37% of the patient population whose cysts demonstrated a rapid growth rate of ≥ 2.0 cm/year, whereas it only represented 0.66% among those with a growth rate below 2.0 cm/year. Of the 76 MCRNLMP cases studied, none of the nine patients who underwent subsequent nephron-sparing surgery or radical nephrectomy following renal cyst decompression experienced recurrence or metastasis. In the remaining 67 patients, who were actively monitored over a 3-year postoperative period, only one showed suspicious recurrence on CT scans. CONCLUSION: MCRNLMP can be tentatively identified and categorized into three types based on CT scanning and growth rate indicators. In treating MCRNLMP, partial nephrectomy is preferred, while radical nephrectomy should be minimized. After surgery, active monitoring is advisable to prevent unnecessary nephrectomy.

Hepatic perivascular epithelioid cell tumors: Benign, malignant, and uncertain malignant potential.

In 2013, the World Health Organization defined perivascular epithelioid cell tumor (PEComa) as "a mesenchymal tumor which shows a local association with vessel walls and usually expresses melanocyte and smooth muscle markers." This generic definition seems to better fit the PEComa family, which includes angiomyolipoma, clear cell sugar tumor of the lung, lymphangioleiomyomatosis, and a group of histologically and immunophenotypically similar tumors that include primary extrapulmonary sugar tumor and clear cell myomelanocytic tumor. Clear cell tumors with this immunophenotypic pattern have also had their malignant variants described. When localizing to the liver, preoperative radiological diagnosis has proven to be very difficult, and most patients have been diagnosed with hepatocellular carcinoma, focal nodular hyperplasia, hemangioma, or hepatic adenoma based on imaging findings. Examples of a malignant variant of the liver have been described. Finally, reports of malignant variants of these lesions have increased in recent years. Therefore, we support the use of the Folpe criteria, which in 2005 established the criteria for categorizing a PEComa as benign, malignant, or of uncertain malignant potential. Although they are not considered ideal, they currently seem to be the best approach and could be used for the categorization of liver tumors.

B3 Breast Lesions: Positive Predictive Value and Follow-Up on a Large Single-Institution Series.

INTRODUCTION: Lesions of uncertain malignant potential (B3) represent 10% of core needle biopsies (CNBs) or vacuum-assisted breast biopsies (VABBs). Traditionally, B3 lesions are operated on. This study investigated the association between B3 subtypes and malignancy to determine the best management. METHODS: Pre- and postoperative histological reports from 226 patients, who had undergone excisional surgery for B3 lesions, following CNB or VABB, were retrospectively analyzed. The correlation between the CNB/VABB diagnosis and the final pathology was investigated, along with the correlation between malignancy upgrade and the type of mammographic lesion. The positive predictive value (PPV) of malignancy of B3 lesions was calculated by simple logistic regression. Patients without cancer diagnosis underwent a 7-y follow-up. RESULTS: Pathology showed 171 (75.6%) benign and 55 (24.3%) malignant lesions. The PPV was 24.3% (P = 0.043), including 31 (13.7%) ductal carcinomas in situ and 24 (10.6%) invasive carcinomas. The most frequently upgraded lesions were atypical ductal hyperplasia, 34.2% (P = 0.004), followed by lobular intraepithelial neoplasia, 27.5% (P = 0.025). The median diameter of mammographic lesions was 1.5 [0.9-2.5] cm, while for surgical specimens, it was 5 [4-7] cm (P < 0.0001). Mammographic findings and histology showed a significant correlation (P = 0.038). After a 7-y follow-up, 15 (8.9%) patients developed carcinoma, and 7 patients (4%) developed a new B3 lesion. CONCLUSIONS: We can conclude that atypical ductal hyperplasia and lobular intraepithelial neoplasia still require surgery for a significant PPV. Other types that lacked significance or confidence intervals were too wide to draw any conclusion.

Preferred labels and language to discuss low-risk lesions that may be cancer precursors: A review.

OBJECTIVES: Patients diagnosed with low-risk lesions are confused about whether they have cancer, and experience similar anxiety to those with invasive cancer, which affects quality of life. Current labels for low-risk lesions were chosen by clinicians and lack meaning to patients. METHODS: We reviewed published research on preferred labels and language for low-risk lesions, and the rationale for those preferences. RESULTS: Of 6569 titles screened, we included 13 studies. Among healthy adults with cervix or prostate lesions, use of the term "cancer" rather than "nodule" or "lesion" resulted in greater anxiety, higher perceived disease severity, and selection of more invasive treatment. Physicians asked about removing "carcinoma" from thyroid lesion labels to reduce patient anxiety and discourage over-treatment did not support this change, instead preferring a term that included "neoplasm". CONCLUSIONS: This review revealed a startling paucity of research on preferences for low-risk lesion labels and language, and associated rationale. Future research is needed to understand how to improve communication about low-risk lesions. PRACTICE IMPLICATIONS: To reduce anxiety and improve the overall well-being of patients, it is crucial to gain a deeper understanding of how to improve patient-provider conversations regarding screen-detected lesions with a low risk of developing into invasive cancer.

Uterine smooth muscle tumors of uncertain malignant potential (STUMP): A case report.

INTRODUCTION: Uterine smooth muscle tumors of uncertain malignant potential (STUMP) are extremely rare, defined as a uterine smooth muscle tumors that cannot be diagnosed as benign or malignant and does not satisfy all the criteria for leiomyosarcoma or leiomyoma. CASE REPRESENTATION: A 48-year-old woman who presented with a history of heavy menstrual bleeding and pelvic pain. Physical examination revealed an enlarged uterus. Ultrasonography showed lobular and enlarged uterus containing multiples leiomyomas. A subtotal hysterectomy was performed. A Pathological analysis revealed a uterine mass diagnosed as a smooth muscle tumor of uncertain malignant. DISCUSSION: Uterine STUMPs are rare and are commonly diagnosed by histopathological evaluation following myomectomy or hysterectomy. The most common clinical manifestations of uterine STUMP are the same as leiomyomas. Prognosis for the patient is unclear and there is a risk of recurrence with the tumors. However, considering their potential risk of recurrence and metastasis, it is advisable to maintain six-monthly controls for 5 years and then annual controls for 5 years more. CONCLUSION: Due to the rarity of uterine STUMP, there are no specific guidelines for their treatment and control. The scientific literature needs to be constantly updated in order to identify masses suspected of malignancy before surgery and improve patient management and follow-up.

Alpha-methyl CoA racemase (AMACR) reactivity across the spectrum of clear cell renal cell neoplasms.

a-Methylacyl coenzyme A racemase (AMACR) is traditionally considered to be a marker of papillary renal cell carcinoma. However, AMACR expression can be seen in other renal tumors. The aim of this study was to investigate AMACR immunoreactivity within the spectrum of clear cell renal cell neoplasms. Fifty-three clear cell renal epithelial tumors were used in assembling the following four cohorts: low grade (LG) clear cell renal cell carcinoma (CCRCC), high grade (HG) CCRCC, CCRCC with cystic changes, and multilocular cystic renal neoplasm of low malignant potential (MCRNLMP). Representative blocks were stained for AMACR, using two different clones (SP52 and OV-TL12/30). There were at least some AMACR immunoreactivity in 77.8 % and 68.9 % of CCRCCs (using SP52 and OV-TL12/30 clone, respectively). Moderate to strong positivity, or positivity in more than one third of the tumor (even weak in intensity) was detected in 46.7 % of CCRCCs using SP52 and in 48.9 % of CCRCC using OV-TL12/30 clone. The highest AMACR reactivity was observed in HG CCRCC (60 % by SP52 and 66.7 % by OV-TL12/30). Strong and diffuse AMACR positivity was detected in 8.9 % of all CCRCCs. AMACR immunoreactivity in MCRNLMP was 37.5 % (SP52 clone) and 25 % (OV-TL12/30 clone). We demonstrated relatively high expression rate of AMACR in CCRCC, while very variable in intensity and distribution. This finding may have diagnostic implications especially in limited samples (i.e., core biopsies), as AMACR positivity does not exclude the diagnosis of CCRCC.

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.

Solid pseudopapillary neoplasm (SPN) of the pancreas: current understanding on its malignant potential and management.

Solid pseudopapillary neoplasms (SPN) of the pancreas are presently recognized as low-grade malignant tumors that are frequently observed in young females. This tumor has a low incidence and is associated with an excellent prognosis following surgical resection. Typical SPNs primarily affect the pancreas and tend to have moderate or asymptomatic manifestations. Based on retrospective research, it is anticipated that patients with SPN can achieve disease-free survival, even in cases when metastasis is detected during inspection. However, the incidence of malignant SPN has been consistently underestimated, as evidenced by recent research findings. Malignancy of SPN primarily encompasses invasion and infiltration, metastasis, and recurrence after R0 resection. Imaging technologies such as Ultrasound, Computed Tomography, Magnetic Resonance Imaging, and Position Emission Tomography are capable of preliminarily identifying malignant SPN, which is primarily based on its invasive clinical features. Research on risk factors of malignant SPN revealed that larger tumor size, Ki-67 index, and several other parameters had significant correlations with invasive tumor behavior. Pathologic features of malignant SPNs overlay other pancreatic tumors, nevertheless they can provide valuable assistance in the process of diagnosis. Several confirmed specific pathologic biomarkers are related to its cellular origin, characteristic gene mutation, and cell proliferation. Considering the invasiveness of malignant SPN, it is imperative to enhance the comprehensiveness of its therapy. Tumor resection remains a suggested course of action in line with typical SPN, and additional lymph node dissection is seen as reasonable. Compared to benign SPNs, malignant SPNs have worse prognosis, underscoring the necessity of early identification and treatment in comprehensive medical centers to get improved clinical outcomes.

Perivascular Epithelioid Cell Tumor with Uncertain Malignant Potential Arising in the Round Ligament.

A 12-year-old adolescent was diagnosed with a right-sided solid mass in the round ligament of the uterus. The chief complaints were abdominal pain and pelvic discomfort. She underwent laparoscopic tumor resection. Histological examination demonstrated a trabecular growth pattern of epithelioid cells with mitotic activity (3 per 50 HPF), which expressed melanocytic and myoid markers. Due to aforementioned findings, a final diagnosis of perivascular epithelioid cell tumor (PEComa) with uncertain malignant potential was made. To the best of our knowledge, this localization of PEComa is considered to be infrequent with only occasionally reported cases.

Prostatic stromal tumour of uncertain malignant potential in a dog.

An 11-year-old male Miniature Dachshund dog was presented with dyschezia. Computed tomography examination 35 days after the initial visit revealed a prostate mass (4.0 × 3.5 × 2.7 cm) and prostatectomy and orchiectomy were performed 13 days later. Grossly, the prostate was rubbery and the cut surface of the mass was swollen. The mass was whitish and demarcated from the surrounding tissues. Microscopically, the mass had a capsulate consisting of atypical spindloid stromal cells arranged in a phyllode pattern and also in a fasciculated pattern admixed with acinar ductal cells. Atypical stromal cells contained round-to-oval finely hyperchromatic nuclei that had distinct nuclei and abundant eosinophilic cytoplasm. Immunohistochemically, the atypical stromal cells were positive for vimentin, CD34, desmin, α-smooth muscle actin, progesterone receptor and androgen receptor but negative for cytokeratin AE1/AE3, p63, c-Kit, DOG-1 and SOX10. On the basis of these findings, the tumour was diagnosed as a prostatic stromal tumour of uncertain malignant potential.

Paraovarian tumor of borderline malignancy: A case report.

Paraovarian tumors of borderline malignancy (PTBM) are exceedingly rare, with only slightly over 60 cases reported worldwide. This report presents the case of a 22-year-old nulliparous patient who incidentally discovered a left paraovarian mass during a routine abdominal ultrasound. Subsequent MRI revealed a 2.5×2.1 cm cystic lesion located in close proximity to, but outside of, the left ovary, with no other pathological findings. A laparoscopic cystectomy was performed with meticulous care to prevent tumor spillage, and the patient experienced an uneventful recovery. Histopathological examination unveiled irregularly shaped tissue measuring 2.2×1.2×1 cm, characterized by fibrous tissue/wall with spindle cell stroma and an epithelium displaying features consistent with a serous borderline tumor. Our multidisciplinary team recommended diligent follow-up. This case contributes to the existing literature on PTBM and highlights the imperative for additional cases to enhance our comprehension of the optimal management of these exceedingly rare tumors.

Papillary urothelial neoplasm of low malignant potential with osseous metaplasia in a 19-year-old chronic smoker: A case report with review of literature.

Urothelial tumors characteristically occur in elderly persons, more commonly in males with typical complaints of hematuria. Although few studies attempted to describe clinic-pathological features of urothelial malignancies in young patients, due to heterogeneity in the inclusion of age groups under "young patients" no reliable conclusions can be derived. Herein, we are describing an interesting case of papillary urothelial neoplasm of low malignant potential with osseous metaplasia in a 19-year-old chronic smoker young patient presented with chief complaints of abdominal pain with a review of the literature.

Long-Term Follow-Up of High-Risk Breast Lesions at Vacuum-Assisted Biopsy without Subsequent Surgical Resection.

Introduction: B3-lesions of the breast are a heterogeneous group of neoplasms, associated with a higher risk of breast cancer. Recent studies show a low upgrade rate into malignancy after subsequent open surgical excision (OE) of most B3-lesions when proven by vacuum-assisted biopsy (VAB). However, there is a lack of long-term follow-up data after VAB of high-risk lesions. The primary aim of this study was to demonstrate whether follow-up of B3 lesions is a beneficial and reliable alternative to OE in terms of long-term outcome. The secondary aim was to identify patient and lesion characteristics of B3 lesions for which OE is still necessary. Methods: This retrospective multicenter study was conducted at 8 Swiss breast centers between 2010 and 2019. A total of 278 women (mean age: 53.5 ± 10.7 years) with 286 B3-lesions who had observation only and who had at least 24 months of follow-up were included. Any event during follow-up (ductal carcinoma in situ [DCIS], invasive cancer, new B3-lesion) was systematically recorded. Data from women who had an event during follow-up were compared with those who did not. The results for the different B3 lesions were analyzed using the t test and Fisher's exact test. A p value of <0.05 was considered statistically significant. Results: The median follow-up interval was 59 months (range: 24-143 months) with 52% (148/286) having a follow-up of more than 5 years. During follow-up, in 42 women, 44 suspicious lesions occurred, with 36.4% (16/44) being invasive cancer and 6.8% (3/44) being DCIS. Thus, 6.6% (19/286) of all women developed malignancy during follow-up after a median follow-up interval of 6.5 years (range: 31-119 months). The initial histology of the B3 lesion influenced the subsequent occurrence of a malignant lesion during follow-up (p < 0.038). The highest malignancy-developing rate was observed in atypical ductal hyperplasia (ADH) (24%, 19/79), while all other B3-lesions had malignant findings ipsi- and contralateral between 0% and 6%. The results were not influenced by the VAB method (Mx-, US-, magnetic resonance imaging-guided), the radiological characteristics of the lesion, or the age or menopausal status of the patient (p > 0.12). Conclusion: With a low risk of <6% of developing malignancy, VAB followed by long-term follow-up is a safe alternative to OE for most B3-lesions. A higher malignancy rate only occurred in ADH (24%). Based on our results, radiological follow-up should be bilateral, preferable using the technique of initial diagnosis. As we observed a late peak (6-7 years) of breast malignancies after B3-lesions, follow-up should be continued for a longer period (>10 years). Knowledge of these long-term outcome results will be helpful in making treatment decisions and determining the optimal radiological follow-up interval.

Development and validation of a preoperative risk nomogram prediction model for gastric gastrointestinal stromal tumors.

BACKGROUND AND STUDY AIMS: Gastrointestinal stromal tumors (GIST) carry a potential risk of malignancy, and the treatment of GIST varies for different risk levels. However, there is no systematic preoperative assessment protocol to predict the malignant potential of GIST. The aim of this study was to develop a reliable and clinically applicable preoperative nomogram prediction model to predict the malignant potential of gastric GIST. PATIENTS AND METHODS: Patients with a pathological diagnosis of gastric GIST from January 2015 to December 2021 were screened retrospectively. Univariate and multivariate logistic analyses were used to identify independent risk factors for gastric GIST with high malignancy potential. Based on these independent risk factors, a nomogram model predicting the malignant potential of gastric GIST was developed and the model was validated in the validation group. RESULTS: A total of 494 gastric GIST patients were included in this study and allocated to a development group (n = 345) and a validation group (n = 149). In the development group, multivariate logistic regression analysis revealed that tumor size, tumor ulceration, CT growth pattern and monocyte-to- lymphocyte ratio (MLR) were independent risk factors for gastric GIST with high malignancy potential. The AUC of the model were 0.932 (95% CI 0.890-0.974) and 0.922 (95% CI 0.868-0.977) in the development and validation groups, respectively. The best cutoff value for the development group was 0.184, and the sensitivity and specificity at this value were 0.895 and 0.875, respectively. The calibration curves indicated good agreement between predicted and actual observed outcomes, while the DCA indicated that the nomogram model had clinical application. CONCLUSIONS: Tumor size, tumor ulceration, CT growth pattern and MLR are independent risk factors for high malignancy potential gastric GIST, and a nomogram model developed based on these factors has a high ability to predict the malignant potential of gastric GIST.

MED15::TFE3 fusion renal cell carcinoma with extensive cystic change: A clinicopathologic and molecular genetic study of 2 cases, with an emphasis on differential diagnosis.

OBJECTIVES: TFE3-rearranged renal cell carcinomas (RCCs) harbor gene fusions between TFE3 and 1 of many partner genes. MED15::TFE3 fusion RCC is rare, often cystic, and easily misdiagnosed. METHODS: This study aimed to characterize 2 cases of MED15::TFE3 fusion RCC with extensive cystic change using fluorescence in situ hybridization and targeted RNA sequencing. RESULTS: Both patients were young adult women aged 29 and 35 years. Radiologically, both presented with a cystic Bosniak category II renal lesion. The cysts measured 9.3 cm and 4.8 cm in greatest dimension. Both patients underwent cyst enucleation, and neither had tumor recurrence or metastasis at 26 and 6 months of follow-up, respectively. Microscopically, both tumors were entirely cystic, with thick, fibrous cystic walls lined by small clusters of cells with clear to eosinophilic cytoplasm and uniform, round nuclei with inconspicuous nucleoli. There were also small aggregations of similar clear cells within the cystic walls. Foci of basement membrane-like material depositions were noted in 1 case; calcifications were observed in both cases. Both cases demonstrated nuclear positivity for PAX8 and TFE3 and cytoplasmic staining for Melan-A; HMB45, CAIX, and CK7 were negative. Fluorescence in situ hybridization revealed that both tumors were positive for TFE3 rearrangements. RNA sequencing identified MED15::TFE3 gene fusions in both cases. CONCLUSIONS: The main differential diagnosis of MED15::TFE3 fusion RCC includes multilocular cystic renal neoplasm of low malignant potential and atypical renal cysts. Molecular confirmation of TFE3 fusion is essential for establishing the correct diagnosis.