Criteria For Malignancy Research Articles

Cytological Diagnosis of Thyroid Follicular Lesion and Its Correlation with Histological Findings

Introduction: Follicular neoplasms represent a wide clinical spectrum of diseases, with tremendous overlap in clinicopathologic diagnosis, management, and prognosis. Suspicious sonographic features in conjunction with FNAC of thyroid nodules provide the most accurate preoperative diagnosis to guide therapy. Keeping the perception in mind, we summarize our experience with thyroid nodules that were defined as cellular follicular lesions by comparing the clinical, sonographic, and cytological features that were examined histologically to define the most reliable criteria of malignancy. Aim of the Study: The aim of the study was to find out the cytological diagnosis of thyroid follicular lesions and their correlation with histological findings. Methods: This cross-sectional observational study was conducted at the department of Otolaryngology, National institute of ENT, Tejgaon, Dhaka following approval of the protocol for the duration of 6 months. A total of 30 patients were included and they were subjected to details history taking, physical examination, and necessary investigations. We analyzed the data using SPSS version 23, and Chi-square test was used to analyze the significance level of P (<0.05). Results: A total of 30 consecutive patients with a follicular lesion on FNAC (5 men and 25 women) were included in this study. Their mean (SD) age was 46.7 (±13.0) years. Thyroid cancer was diagnosed on histopathology in 8 patients (27%). Papillary cancer was the most common cytologic finding in 6 patients [75%]) and 2 patients (25%) had a diagnosis of follicular cancer. Of the 6 patients with papillary cancer, 2 (33%) had a follicular variant of papillary cancer. The benign histologic diagnoses were follicular adenoma in 6 cases (27%), thyroiditis in 3 cases (13%), and nodular goiter in 13 (60%). The presence of a solitary nodule was not predictive of malignancy (p=0.57). Solid echo structure (p<0.02), presence of microcalcification (p<0.01), and hypoechoic nodules ...

Cytopathologie des séreuses : la classification internationale

The International System for Serous Fluid Cytopathology is a cytologic classification which purpose is to establish a consensus on diagnostic terminology. Five diagnostic categories are proposed associated to an increased rate of malignancy and specific cytological criteria. The categories are reported as: (I) Non-diagnostic (ND), the cells are insufficient for interpretation; (II) Negative for malignancy (NFM), only benign cells are present; (III) Atypia of undetermined significance (AUS), the cells present mild atypia more likely to be benign, but a malignant process cannot be definitively excluded; (IV) Suspicious for malignancy (SFM), the cells are present with atypia or in a number suspect of malignancy but with insufficient ancillary studies to give a positive malignant diagnosis; (V) Malignant (MAL), the cytological criteria are absolutely and definitively malignant. Malignant neoplasia can be primitive, it involves mesothelioma and serous lymphoma but most are secondary and correspond mainly to adenocarcinomas in adults and leukemia/lymphoma in children. The diagnostic should always be provided in the appropriate clinical context and be as definitive as possible. The ND, AUS and SFM are temporary or last intention categories. Immunocytochemistry in association with FISH or flow cytometry allow in most cases a conclusive diagnosis. These ancillary studies as well as ADN and ARN tests on effusion's fluids are particularly suited to give reliable theranostic results for personalized therapies.

Co-existence of Nodular Hyperplasia and Papillary Carcinoma Thyroid in a Case of Struma Ovarii: A Rare Occurrence

Struma ovarii is a monodermal ovarian teratoma. This is an ovarian germ cell tumour with more than 50% ovarian tissue. It is a rare tumour, accounting for only 3-5% of all ovarian teratomas. Malignant transformation occurs very rarely, only in about 0.3% cases. The authors report a case of struma ovarii with a malignant transformation to papillary carcinoma thyroid. Not much information is present in the literature about this rare entity. Due to the rarity of this condition, there is a lack of uniformity of histological criteria of malignancy and its management is not universally accepted by physicians. Here, the authors present a rare case of struma ovarii with malignant transformation to papillary carcinoma thyroid. A 62-year-old female presented with a left ovarian mass. On histopathological examination of the surgical specimen of hysterectomy it was found that the ovary had a neoplastic growth with morphological features of papillary carcinoma thyroid. The final diagnosis was struma ovarii with papillary thyroid carcinoma. Postoperative period was uneventful for the patient. However, follow-up was not done.

Contribution of combined use of different ultrasound modes to evaluate mediastinal lymph nodes.

To determine the contribution to diagnostic rates of the evaluation of the sonographic characteristics of lymph nodes with EBUS together with vascularity. In the present study, patients who underwent the Endobronchial ultrasound (EBUS) procedure were evaluated retrospectively. Patients were classified as benign or malignant by using the sonographic features of EBUS. EBUS-Transbronchial Needle Aspiration (TBNA) confirmed histopathologically with lymph node dissection or in cases where no disease progression was observed clinically or radiologically in at least 6 months of follow-up. Malignant lymph node diagnosis was based on histological examination. Evaluation was made of 165 patients comprising 122 (73.9%) males and 43 (26.1%) females with a mean age of 62.0 ± 10.7 years. Malignant disease was diagnosed in 89 (53.9%) cases and benign disease in 76 (46.1%) cases. The success level of the model was seen to be approximately 87%. The Nagelkerke R 2 value was calculated as 0.401. The probability of malignancy increased 3.86-fold (95% CI: 2.61-5.11) in lesions of diameter ≥20 mm compared to lesions <20 mm, 2.58-fold (95% CI: 1.48-3.68) in lesions not determined with central hilar structure (CHS) compared to those determined with CHS, 6.85-fold (95% CI: 4.67-9.03) in lymph nodes observed with necrosis compared to those without necrosis, and 1.51-fold (95% CI: 0.41-2.61) in lymph nodes with a vascular pattern (VP) score of 2-3 compared to those with a VP score of 0-1. Visualization of coagulation necrosis with EBUS-B mode and the determination of VP 2-3 in power Doppler mode were seen to be the most important criteria of malignancy.

Strategy for Accurate Diagnosis by Contrast-Enhanced Ultrasound of Focal Liver Lesions in Patients Not at High Risk for Hepatocellular Carcinoma: A Preliminary Study.

To develop an effective strategy for accurate diagnosis of focal liver lesions (FLLs) in patients with non-high risk for hepatocellular carcinoma (HCC). From January 2012 to December 2015, consecutive patients with non-high risk for HCC who underwent contrast-enhanced ultrasound (CEUS) were included in this retrospective double-reader study. All patients were stratified into 2 different risks (intermediate, low-risk) groups according to criteria based on clinical characteristics, known as clinical risk stratification criteria. For the intermediate-risk group, the CEUS criteria for identifying benign lesions and HCCs were constructed based on selected CEUS features. The diagnostic performance of the clinical risk stratification criteria, and CEUS criteria for identifying benign lesions and HCCs was evaluated. This study included 348 FLLs in 348 patients. The sensitivity and specificity of the clinical risk stratification criteria for malignancy was 97.8 and 69.8%. Patients were classified as intermediate risk if they were male, or older than 40 years of age, or HBcAb positive, or having positive tumor markers. Otherwise, patients were classified as low risk. Among the 348 patients, 327 were in the intermediate-risk group and 21 were in the low-risk group. In the intermediate-risk group, the CEUS criteria for identifying benign lesions were any of the following features: 1) hyper/isoenhancement in the arterial phase without washout, 2) nonenhancement in all phases, 3) peripheral discontinuous globular enhancement in the arterial phase, 4) centrifugal enhancement or peripheral enhancement followed by no central enhancement, or 5) enhanced septa. The accuracy, sensitivity, and specificity of the CEUS criteria for identifying benign lesions were 94.5, 83.0, and 99.6%, respectively. Arterial phase hyperenhancement followed by mild and late washout (>60 seconds) was more common in HCC patients than in non-HCC patients (P < .001). Using arterial phase hyperenhancement followed by mild and late washout as the CEUS criteria for identifying HCCs, the sensitivity and specificity were 52.6 and 95.3%, but unfortunately, the positive predictive value was only 82.0%. For the low-risk group, no further analysis was performed due to the small sample size. Initial clinical risk stratification followed by assessment of certain CEUS features appears to be a promising strategy for the accurate diagnosis of FLLs in patients not at high risk for HCC.

Novel, diagnostic, cytomorphometric profile of canine, classical haemangiopericytoma: including nuclear criteria of malignancy

Novel, diagnostic, cytomorphometric profile of canine, classical haemangiopericytoma: including nuclear criteria of malignancy

Combined utility of p16 and BRAF V600E in the evaluation of spitzoid tumors: Superiority to PRAME and correlation with FISH.

Spitzoid melanocytic neoplasms are diagnostically challenging; criteria for malignancy continue to evolve. The ability to predict chromosomal abnormalities with immunohistochemistry (IHC) could help select cases requiring chromosomal evaluation. Fluorescence in situ hybridization (FISH)-tested spitzoid neoplasms at our institution (2013-2021) were reviewed. p16, BRAF V600E, and preferentially expressed antigen in melanoma (PRAME) IHC results were correlated with FISH. A total of 174 cases (1.9F:1M, median age 28 years; range, 5 months-74 years) were included; final diagnoses: Spitz nevus (11%), atypical Spitz tumor (47%), spitzoid dysplastic nevus (9%), and spitzoid melanoma (32%). Sixty (34%) were FISH positive, most commonly with absolute 6p25 gain (RREB1> 2). Dermal mitotic count was the only clinicopathologic predictor of FISH. Among IHC-stained cases, p16 was lost in 55 of 134 cases (41%); loss correlated with FISH positive (p< 0.001, Fisher exact test). BRAF V600E (14/88, 16%) and PRAME (15/56, 27%) expression did not correlate with FISH alone (p= 0.242 and p= 0.359, respectively, Fisher exact test). When examined together, however, p16-retained/BRAF V600E-negative lesions had low FISH-positive rates (5/37, 14%; 4/37, 11% not counting isolated MYB loss); all other marker combinations had high rates (56%-75% of cases; p< 0.001). p16/BRAF V600E IHC predicts FISH results. "Low-risk" lesions (p16+ /BRAF V600E- ) uncommonly have meaningful FISH abnormalities (11%). PRAME may have limited utility in this setting.

Multiparametric Sonographic Imaging of Thyroid Lesions: Chances of B-Mode, Elastography and CEUS in Relation to Preoperative Histopathology.

Simple SummaryAs the incidence of thyroid lesions in Europe is rising, more and more people affected by thyroid pathologies seek treatment in a clinic. Every suspicious thyroid nodule needs to be confirmed as benign or malignant in order to be treated correctly. Unnecessary invasive diagnostics and thyroid surgery should be avoided. The aim of this retrospective study was to improve the distinction between benign and malignant nodules by using new high-performance multiparametric ultrasound examination techniques. By analyzing 122 thyroid nodules we created a score-based system combining B-mode, shear-wave elastography and contrast-enhanced ultrasound malignancy criteria. This system allows for a quite accurate detection of thyroid carcinomas with a sensitivity of 95% and specificity of 75.49%. Shear-wave elastography and contrast-enhanced ultrasound can detect unique malignancy features, which cannot be found in B-mode. Therefore, these criteria would present a relevant addition to the B-mode TI-RADS classification.Background: The aim was to improve preoperative diagnostics of solid non-cystic thyroid lesions by using new high-performance multiparametric ultrasound examination techniques. Methods: Multiparametric ultrasound consists of B-mode, shear-wave elastography and contrast enhanced ultrasound (CEUS) including Time-Intensity-Curve (TIC) analysis. A bolus of 1–2.4 mL Sulfur Hexafluorid microbubbles was injected for CEUS. Postoperative histopathology was the diagnostic gold standard. Results: 116 patients were included in this study. 102 benign thyroid nodules were diagnosed as well as 20 carcinomas. Suspicious B-mode findings like microcalcifications, a blurry edge and no homogeneous sonomorphological structure were detected in 60, 75 and 80% of all carcinomas but only in 13.7, 36.3 and 46.1% of all benign lesions. The average shear-wave elastography measurements of malignant lesions (4.6 m/s or 69.8 kPa centrally and 4.2 m/s or 60.1 kPa marginally) exceed the values of benign nodules. Suspicious CEUS findings like a not-homogeneous wash-in and a wash-out were detected almost twice as often in carcinomas. Conclusion: Multiparametric ultrasound offers new possibilities for the preoperative distinction between benign and malignant thyroid nodules. A score based system of B-mode, shear-wave and CEUS malignancy criteria shows promising results in the detection of thyroid carcinomas. It reaches a sensitivity of 95% and specificity of 75.49%.

Genistein anticancer efficacy during induced oral squamous cell carcinoma: an experimental study

BackgroundAbout 7 million people die from various types of cancer every year representing nearly 12.5% of deaths worldwide. This fact raises the demand to develop new, effective anticancer, onco-suppressive, and chemoprotective agents for the future fighting of cancers. Genistein exhibits pleiotropic functions in cancer, metabolism, and inflammation. It functions as an antineoplastic agent through its effect on the cell cycle, apoptotic processes, angiogenesis, invasion, and metastasis.Aim of the studyThe current study aimed to study the genistein onco-suppressive effects during 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters’ buccal pouch utilizing flow cytometry analysis (FMA), as a fast-diagnosing tool, in addition to the histopathology.Material and methodsThe buccal mucosa of adult male Syrian hamsters was painted with paraffin oil only (group 1), DMBA mixed in mineral oil (group 2), or orally administrated genistein along with painting DMBA (group 2B). The buccal mucosa was utilized for flow cytometric analysis and histopathological examination.ResultsGrossly, DMBA-induced carcinogenesis started at the 9th week. Progressive signs appeared in the following weeks reaching to large ulcerative oral masses and exophytic nodules at the 21st week. Histologically, invasive well-differentiated oral squamous cell carcinoma (OSCC) appeared in the underlying tissues from the 12th week, showing malignant criteria. Genistein had delayed clinicopathological change, which started 6 weeks later, than the DMBA-painted hamsters, as mild epithelial dysplastic changes. This became moderate during the last 6 weeks, without dysplastic changes. Flow cytometry revealed that DMBA led to considerable variation in DNA proliferation activity, aneuploid DNA pattern, in 47.22% of hamsters and significantly raised the S-phase fragment (SPF) values, which drastically reduced after genistein treatment.ConclusionTaken together, genistein could be employed as an onco-suppressive agent for carcinogenesis. Moreover, FMA could be used as an aiding fast tool for diagnosis of cancer.

1485O Percutaneous uterine needle biopsy with microscopic and array-CGH analyses in patients with suspicious myometrial tumors on MRI: A prospective study

Preoperative diagnosis of uterine tumors is of utmost importance to avoid inadvertent morcellation of leiomyosarcoma (LMS) and unnecessary hysterectomy in childbearing patients. There are no pathognomonic criteria for malignancy on Magnetic Resonance Imaging (MRI). The diagnosis of malignancy includes microscopic and genomic analyses with array-Comparative Genomic Hybridization (CGH). To date, no study has evaluated preoperative percutaneous uterine needle biopsy (PUB) with microscopic examination (M-PUB) and array-CGH analyses (MCGH-PUB).

Clinicopathologic features and biologic behavior of canine splenic nodules with stromal, histiocytic and lymphoid components.

The term fibrohistiocytic nodule has been discouraged in favor of specific pathologic entities, including complex nodular hyperplasia, splenic stromal sarcoma and histiocytic sarcoma. Nevertheless, the diagnosis of splenic lesions with mixed stromal, histiocytic and lymphoid components still remains a challenge due to lack of straightforward histologic criteria. Misestimation of the biologic behavior of these lesions may lead to detrimental consequences on the clinical management of patients. In this study, we retrospectively evaluated the clinicopathologic features and outcome of canine splenic nodular lesions with mixed components, to identify prognostic factors and histologic criteria of malignancy. Thirty-seven cases were included. Immunohistochemistry did not allow for further subclassification. Nine (24.3%) dogs died from disease-related causes after a median of 234 days (range, 48–1,247). One-, 2- and 3-year disease-specific survival rates were 80, 60, and 43%, respectively. When considering nodules with stromal cell atypia and at least one of mitotic count ≥9, presence of karyomegaly/multinucleated cells and lymphoid component <40%, half of these dogs died of disease-related causes with a median disease-specific survival time of 548 days (95% CI, 0-1216). In the remaining dogs, no disease-related death was reported (P < 0.001). Canine splenic nodular lesions with mixed stromal, histiocytic and lymphoid components and histologic criteria of malignancy may behave aggressively, leading to distant metastasis and death. In the absence of further criteria aiding their classification, and to better characterize their biologic behavior, we encourage the distinction of these complex splenic tumors from conventional sarcomas and histiocytic sarcomas.

Lambda light chain-induced monoclonal gammopathy of renal significance, manifesting with Fanconi Syndrome and osteomalacia

BackgroundMonoclonal gammopathy of renal significance (MGRS) encompasses a heterogeneous group of kidney diseases in which a monoclonal immunoglobulin secreted by a clone of B cells or plasma cells causes kidney damage without meeting the hematological criteria for malignancy. Among the various forms of involvement, MGRS can manifest as a proximal tubule disorder, such as Fanconi syndrome (FS), characterized by urinary loss of phosphate, glucose, amino acids, uric acid and bicarbonate. Few cases of MGRS have been described in the literature, manifesting as FS and monoclonal production of lambda light chains, almost all of which are secondary to the production of kappa light chains.Case presentationHere we report a clinical case of a 45-year-old Brazilian male, African descent, with proximal weakness of the lower limbs, whose initial assessment showed a urine summary with the presence of proteinuria and glycosuria without hyperglycemia, associated with mild worsening of renal function, hypouricemia, hypocalcemia and phosphaturia. Evolution was characterized by a MGRS manifesting as FS and osteomalacia.ConclusionThe diagnosis of MGRS is not always easy, it requires knowledge of the clinical characteristics, diagnostic criteria and prognosis of each case. Therefore, all possible efforts should be made for multidisciplinary diagnosis.

Monoclonal Gammopathy of Renal Significance: Histomorphological Spectrum at a Tertiary Care Center

Introduction: The term monoclonal gammopathy of renal significance (MGRS) has been described to include patients with renal manifestations associated with circulating monoclonal proteins with or without a clonal lymphoproliferation (B-cell or plasma cell) and not meeting diagnostic criteria for an overt hematological malignancy. A host of MGRS-associated lesions have been described that involve various renal compartments. Our study describes the histomorphological spectrum of MGRS cases at our center in the last 5 years and description as per the classification system of the International Kidney and Monoclonal Gammopathy Research Group (IKMG). Material and Methods: Retrospective analysis was carried out of all the renal biopsies with characteristic monoclonal immunoglobulin lesions for histopathological diagnosis between years 2015 and 2020 and reviewed by two independent pathologists. Results: Most patients in the study belonged to the fifth decade, with a median age of 50 years (mean 50.14 ± 10.43) range (24–68 years) with a male preponderance. Most patients presented with proteinuria as the sole manifestation (66.6%). Many of the patients (48%) had an M spike by serum protein electrophoresis or urinary protein electrophoresis with an abnormal serum free light chain assay (60.8%). AL amyloidosis was the most common diagnosis observed on histopathological evaluation (68.7%), followed by light chain deposition disease (10.4%). Conclusion: MGRS lesions are infrequently encountered in the practice of nephropathology and pose a diagnostic challenge due to the limitation of a congruent clinical or hematological picture. A thorough histological examination with immunofluorescence and electron microscopy often precipitates in the right diagnosis and prompts timely management.

Towards diagnostic criteria for malignant deep penetrating melanocytic tumors using single nucleotide polymorphism array and next-generation sequencing

AbstractCutaneous deep penetrating melanocytic neoplasms frequently simulate melanoma and might occasionally progress to metastatic melanoma. Distinguishing deep penetrating nevi (DPN) and deep penetrating melanocytomas (DPM) from malignant deep penetrating tumors (MDPT) is difficult based on histopathology alone, and diagnostic criteria for MDPT are currently lacking. Using a molecular workup, we aimed to provide readily available diagnostic tools for classification of deep penetrating tumors. We used clinical follow-up and Single Nucleotide Polymorphism (SNP) array for tumor classification of 20 deep penetrating neoplasms to identify associations with histopathological, immunohistochemistry, and NGS findings. Ten neoplasms were classified as MDPT, four as DPM, and six as DPN. Two MDPT showed metastases. The following parameters were statistically significantly associated with MDPT: severe nuclear atypia (risk ratio [RR] 2.9, p < 0.05), absence of a nevus component (RR 10.0, p = 0.04), positive PRAME expression (RR 9.0, p = 0.02), complete loss of p16 expression (RR 3.5, p = 0.003), TERT-p and APC mutations (RR 11.0, p = 0.01 and RR 2.7, p = 0.002, respectively), and ≥1 additional pathogenic mutation (RR 9.0, p = 0.02). Ki-67 expression ≥ 5% was not significantly associated with MDPTs, although it was <5% in all DPNs. Three MDPT did not show nuclear β-catenin expression despite having a CTNNB1 (n = 2) or an APC mutation (n = 1). Our findings suggest that complete loss of p16 and positive PRAME expression, a driver mutation in APC, ≥ 1 additional pathogenic mutation, especially in TERT-p, support an MDPT diagnosis in deep penetrating neoplasms. Besides severe nuclear atypia and possibly severe inflammation, we did not identify specific histopathological criteria for malignancy. Non-aberrant nuclear β-catenin expression might not exclude a deep penetrating signature in MDPT.

Giant luteinized follicular cyst of pregnancy

Functional cysts usually do not cause symptoms or require surgical intervention. We reported a 17-year-old primigravida, gestational age of 10 weeks and 2 days, and ultrasound showing anechoic cyst in the right parauterine region without septa, with a larger diameter of 13.5cm, 632ml, and Doppler color without peripheral vascularization. The patient was oligosymptomatic during gestation. At 37 weeks and 6 days, gestation was interrupted, when the cyst had 2600 ml by ultrasonography. Fetal extraction was performed by cesarean delivery, and a large adnexal cyst visualized on the right was removed. The histopathological analysis of the surgical specimen revealed a cystic lesion coated by luteinized cells with discrete hyperchromatic and slightly pleomorphic nuclei, with underlying fibrous stroma with sparse luteinized cells, characterizing a giant luteinized follicular cyst of pregnancy. The prevalence of ovarian masses in pregnancy is rare, usually not exceeding 5 cm in diameter, and disappearing spontaneously in the second trimester. The patient in the case report had a cyst of 632 ml, increasing in volume to 2600 ml at the time of delivery. Definitive preoperative diagnosis of ovarian masses is still difficult, and predictive criteria for malignancy include the use of tumor markers, ultrasound, and Doppler. The association of these tests should guide the clinician to define the best time for surgical intervention. The association of these tests should guide the clinician to define the best time for surgical intervention.

Radiologische Abklärung pulmonaler Rundherde

Pulmonary nodules are frequent and in most cases are benign. To avoid both unnecessary follow-up control and overlooked lung carcinomas, the further management should be risk-based. The risk of malignancy is primarily determined by the size of the nodule, but other radiological and non-radiological criteria may also be helpful in assessing the dignity. Recommendations for follow-up control of incidental nodules have been published by the Fleischner Society. For patients with a known malignancy or immunosuppression or in the context of a screening program, these criteria do not apply because of the different risk. In this article, the malignancy criteria of pulmonary nodules are explained, the recommendations of the Fleischner Society are presented, and a brief outlook on a possible lung cancer screening in Germany is given. The aim is to provide a practical guide for the radiological clarification of pulmonary nodules.

Gastroesophageal Glomus Tumors: Clinicopathologic and Molecular Genetic Analysis of 26 Cases With a Proposal for Malignancy Criteria.

Although criteria for malignancy have been established for glomus tumors of soft tissue, there are no accepted criteria for gastroesophageal glomus tumors, the behavior of which is considered to be unpredictable. Recently, both benign and aggressive gastroesophageal glomus tumors have been shown to harbor CARMN :: NOTCH2 fusions, but, as yet, there are no described genetic features that predict clinical behavior. Here, we evaluated 26 gastroesophageal glomus tumors to investigate histologic and genetic features that might predict malignant behavior. Seventeen patients (65%) were male. The median age at presentation was 54.5 years (range: 16 to 81 y). Primary sites were stomach (25 tumors) and distal esophagus (1). The median tumor size was 4.05 cm (range: 0.8 to 19.5 cm). Tumors were composed of lobules of rounded cells with sharp borders, palely eosinophilic to clear cytoplasm, and round nuclei. All tumors involved the muscularis propria, and 12 also involved the serosal surface. Mitoses ranged from &lt;1 to 53/10 HPF (median: 5/10 HPF). Sixteen tumors, including all 15 with mitoses ≥2/10 HPF, showed atypia (3 mild, 10 moderate, 3 severe), defined as spindle cell morphology, nuclear irregularity, nuclear size variability, enlarged nuclei, or coarse chromatin. Considering these histologic features and clinical behavior, tumors were classified as malignant (15 tumors) if they measured ≥5 cm or showed both atypia and mitoses ≥2/10 HPF, or benign (11 tumors) if these criteria were not met. Follow-up was available for 19 patients (73%; range: 1 to 15 y; median: 5.8 y), including 7 with benign tumors and 12 with malignant tumors. Two patients with malignant tumors had metastases at presentation, and 7 developed metastases subsequently. Follow-up was available for 8 of 9 patients with metastatic disease. Two were alive with disease at most recent follow-up. One underwent resection of a liver metastasis, with no subsequent metastases in 3 years of follow-up. Five patients died of metastatic disease. By immunohistochemistry, smooth muscle actin was diffusely positive in all evaluated tumors, and caldesmon and synaptophysin were positive in 94% and 73%, respectively. Sequencing identified NOTCH2 alterations in 4 benign tumors (80%) and 8 malignant tumors (80%), including CARMN :: NOTCH2 fusions in 2 benign and 5 malignant tumors. All 5 sequenced benign tumors lacked complex copy number alterations (CNAs), whereas all 10 sequenced malignant tumors showed complex CNAs, including recurrent loss of 9p21.3 (4/10, variably including CDKN2A / B and MTAP ) and ATRX inactivation (4/10). Complex CNAs were identified in all sequenced tumors that were ≥5 cm, exhibited both cytologic atypia and ≥2 mitoses/10 HPF, involved the serosa or metastasized. We propose that gastroesophageal glomus tumors ≥5 cm or with both atypia and mitoses ≥2/10 HPF should be considered malignant. Copy number analysis might be helpful in borderline cases.

Synchronous Clear Cell Renal Carcinoma And Bilateral Invasive Duct Carcinoma Breast- Rare association

Occurrence of multiple primary malignant tumors is very uncommon .Co occuring tumors can be synchronous or non synchronous.Tumors presenting within a period less than or equal to 6 months are called synchronous and if they occur after 6 months they are termed as metachronous. Synchronous malignancies are rarer than metachronous. For defining tumors as synchronous both the tumors should show criteria of malignancy, possibility of metastasis must have been ruled out and both the tumors should be pathologically distinct. Breast cancer is the commonest tumor to be associated with other malignancies such as colorectal, endometrial, ovarian carcinoma, yet occurrence of invasive ductal carcinoma with clear cell renal carcinoma is rare. We present a 70 year old female with synchronous Breast carcinoma and Renal clear cell carcinoma .

POS-025 COMPLEMENT MEDIATED MONOCLONAL GAMMOPATHY OF RENAL SIGNIFICANCE (MGRS)

Monoclonal gammopathy of renal significance (MGRS) is a condition in which a monoclonal immunoglobulin (MIg) causes kidney injury. The MIg is secreted by a B-cell or plasma cell clone but is not abundant enough to meet the diagnostic criteria of an overt hematological malignancy.

Use of modernized eligibility criteria in pancreatic cancer clinical trials.

6545 Background: In 2017, ASCO + Friends recommended modernized eligibility criteria to improve generalizability of clinical trial results. Traditional criteria contribute to disparities in trial participation, yet modernized criteria can equalize eligibility rates. We aimed to assess use of modernized eligibility criteria in pancreatic ductal adenocarcinoma (PDAC) clinical trials since the updated guidelines. Methods: Modernized eligibility criteria were obtained from ASCO + Friends guidelines. Clinicaltrials.gov was queried for “pancreas adenocarcinoma” trials from Jan. 1, 2018 onward and eligibility criteria were assessed for compliance with modernized criteria. Kruskal-Wallis and Fisher’s exact tests were used to determine differences in compliance based on disease stage(s), starting year, phase, and funder. Results: In total, 108 clinical trials were identified - 31.5% for resectable, 56.5% for unresectable, 12.0% for both resectable/unresectable disease. Most trials were phase 1 (24.1%), phase 1|2 (15.7%) or phase 2 (45.4%). Funding sources included industry (38.0%), NIH (22.2%) and other sources (39.8%). No trial was compliant with all modernized criteria. Only 34.7% of trials allowed patients with ECOG performance status of 2. HIV+ patients were not allowed in 56.5% of trials. Only 7 trials (6.5%) were compliant with assessing renal function whereas 64.8% appropriately used upper limit of normal cutoffs for labs. Among trials that excluded patients for CHF, 59.6% used a classification system for exclusion. Specific cardiac abnormalities were excluded in 60.2% of trials. Prior malignancy was allowed in 71.3% of trials if treated &gt; 2 years prior and concurrent malignancy, if stable, was allowed in 21.3% of trials. Prior PDAC treatment was allowed for 38.0% and required for 24.1% of trials. If prior treatment was allowed, 94% justified drug exclusions, 40.3% did not require a washout period, and 35.8% required recovery from prior adverse events. Stable/treated brain metastases were allowed in 33.8% of trials for unresectable cancer. Compliance with prior malignancy criteria improved from 2018-2019 to 2020-2022 (56.0% vs 84.5%, respectively; p = 0.001). Requirement of prior PDAC treatment was associated with disease stage (8.8% for resectable, 32.8% for unresectable, and 23.1% for both; p = 0.024), as was exclusion based on prior therapy (58.8% for resectable disease, 14.8% for unresectable, and 30.8% for both; p &lt; 0.0001). Earlier trial phase was associated with prior treatment allowance (p = 0.002), whereas later phase trials were less likely to allow prior treatment (p = 0.021). NIH-funded trials required prior treatment (37.5%) more than industry (29.3%) or other (11.6%) funded trials (p = 0.034). Conclusions: Modernized eligibility criteria are inadequately implemented in PDAC clinical trials. Efforts to improve their use are warranted to produce more generalizable results and advance inclusivity.