Clear Cell Carcinoma Research Articles

Integrated pan-cancer analysis and experimental verification of the roles of ZBED3 in kidney renal clear cell carcinoma

The present study investigated the Zinc finger BED-type containing 3 (ZBED3) mRNA expression levels, diagnostic and prognostic values, co-expressed and differentially expressed genes, immune infiltration, and functional enrichment analysis in patients with kidney renal clear cell carcinoma (KIRC) using various public databases such as The Cancer Genome Atlas, Genotype-Tissue Expression Project, LinkedOmics, Gene Set Enrichment Analysis databases, and the Xiantao academic tool. Through extensive data mining, our study revealed differential expression of ZBED3 in various tumor and paired normal tissues. Specifically, ZBED3 expression was found to be significantly decreased in KIRC, particularly in advanced pathologic stages and histologic grades, when compared to corresponding control tissues. Our analysis revealed that the overexpression of ZBED3 is associated with a favorable overall survival outcome in KIRC patients. Moreover, functional enrichment analysis identified key pathways related to inflammation response and DNA methylation of ZBED3 in KIRC. Additionally, our findings suggest that the upregulation of ZBED3 leads to the inhibition of cell proliferation by modulating cell-cycle progression in KIRC cell lines. Taken together, these results suggest that ZBED3 may serve as a promising biomarker and prognostic indicator for individuals diagnosed with KIRC.

HIF2A shows potential tumor promoting effect and could be poor prognostic factor in ovarian clear cell carcinoma

HIF2A shows potential tumor promoting effect and could be poor prognostic factor in ovarian clear cell carcinoma

An Overview of the Deubiquitinase USP53: A Promising Diagnostic Marker and Therapeutic Target

: Ubiquitination and deubiquitination are important mechanisms to maintain normal physiological activities, and their disorders or imbalances can lead to various diseases. As a subgroup of deubiquitinases (DUBs), the ubiquitin-specific peptidase (USP) family is closely related to many biological processes. USP53, one of the family members, is widely expressed in human tissues and participates in a variety of life activities, such as cell apoptosis, nerve transmission, and bone remodeling. Mutations in the USP53 gene can cause cholestasis and deafness and may also be a potential cause of schizophrenia. Knockout of USP53 can alleviate neuropathic pain induced by chronic constriction injury. Loss of USP53 up-regulates RANKL expression, promotes the cytogenesis and functional activity of osteoclasts, and triggers osteodestructive diseases. USP53 plays a tumor-suppressive role in lung cancer, renal clear cell carcinoma, colorectal cancer, liver cancer, and esophageal cancer but reduces the radiosensitivity of cervical cancer and esophageal cancer to induce radioresistance. Through the in-depth combination of literature and bioinformatics, this review suggested that USP53 may be a good potential biomarker or therapeutic target for diseases.

Clinical activity of tazemetostat, an EZH2 inhibitor, among patients with advanced endometrioid endometrial cancer and ovarian clear cell carcinoma with and without ARID1A mutations (NRG-GY014)

Clinical activity of tazemetostat, an EZH2 inhibitor, among patients with advanced endometrioid endometrial cancer and ovarian clear cell carcinoma with and without ARID1A mutations (NRG-GY014)

Efficacy of sintilimab plus bevacizumab in recurrent/persistent ovarian clear cell carcinoma (INOVA): A multicenter, single-arm, phase II trial

Efficacy of sintilimab plus bevacizumab in recurrent/persistent ovarian clear cell carcinoma (INOVA): A multicenter, single-arm, phase II trial

Targeting Mediator kinases CDK8/19 potentiates chemotherapeutic responses, reverses tumor growth, and prolongs survival from ovarian clear cell carcinoma

Targeting Mediator kinases CDK8/19 potentiates chemotherapeutic responses, reverses tumor growth, and prolongs survival from ovarian clear cell carcinoma

HIF2A shows potential tumor-promoting effect and could be a poor prognostic factor in ovarian clear cell carcinoma

HIF2A shows potential tumor-promoting effect and could be a poor prognostic factor in ovarian clear cell carcinoma

Adenomatoid Tumor Mimicking Peritoneal Carcinomatosis: A Case Report.

An adenomatoid tumor (AT) is a benign lesion, which is commonly located in the genital tract of both sexes. We present a case of a 66-yr-old woman with the unusual characteristics of an AT mimicking peritoneal carcinomatosis. The tumor was detected incidentally by ultrasound examination, and an ensuing imaging study raised suspicion of ovarian cancer with peritoneal carcinomatosis. From the pathologic diagnosis of frozen specimens, clear cell carcinoma was noted and the patient subsequently underwent cytoreductive surgery. An 8.5-cm-sized mass was observed on the uterine serosa, extending into the myometrium. In addition, multi-cystic nodular lesions were identified in the omentum, appendiceal and small bowel serosa, and the peritoneum. After histologic and extensive immunohistochemical examinations, the final diagnosis was AT. Recognition of the diverse presentations of AT is crucial for accurate diagnosis and appropriate treatment, as these tumors can involve multiple sites and mimic peritoneal carcinomatosis, potentially leading to a misdiagnosis of malignancy.

AI predictive modeling of survival outcomes for renal cancer patients undergoing targeted therapy.

Renal clear cell cancer (RCC) is a complex disease that is challenging to predict patient outcomes. Despite improvements with targeted therapy, personalized treatment planning is still needed. Artificial intelligence (AI) can help address this challenge by developing predictive models that accurately forecast patient survival periods. With AI-powered decision support, clinicians can provide patients with tailored treatment plans, enhancing treatment efficacy and quality of life. The study analyzed 267 patients with renal clear cell carcinoma, focusing on 26 who received targeted drug therapy. The data was refined by excluding 8 patients without enhanced CT scans. The research team categorized patients into two groups based on their expected lifespan: Group 1 (over 3 years) and Group 2 (under 3 years). The UPerNet algorithm was used to extract features from CT tumor markers, validating their effectiveness. These features were then used to develop an AI-based predictive model trained on the dataset. The developed AI model demonstrated remarkable accuracy, achieving a rate of 93.66% in Group 1 and 94.14% in Group 2. In conclusion, our study demonstrates the potential of AI technology in predicting the survival time of RCC patients undergoing targeted drug therapy. The established prediction model exhibits high predictive accuracy and stability, serving as a valuable tool for clinicians to facilitate the development of more personalized treatment plans for patients. This study highlights the importance of integrating AI technology in clinical decision-making, enabling patients to receive more effective and targeted treatment plans that enhance their overall quality of life.

NanoString nCounter-Based Assay for Detection of Fusion-Associated Salivary Gland Tumors.

Salivary gland tumors include numerous subtypes that vary from benign to highly aggressive, with many showing overlapping histopathological features that can make diagnosis challenging. Most subtypes express driver fusion genes that are tumor specific, and detection of such fusions is useful for differentiating amongst specific diagnoses, determining appropriate tumor grading, and guiding effective treatment. Currently, fusions can be detected by FISH, RT-PCR or through next-generation sequencing approaches, all of which are highly effective methodologies but can be costly or time consuming. We developed a rapid NanoString nCounter platform-based assay to detect salivary gland tumor fusions using a combination of fusion junction-specific probes and an approach through differential exon expression analysis. The assay includes 68 junction-specific probes and analysis of exon expression across 9 fusion-associated genes in a single multiplex assay. Out of 55 retrospective and 171 prospective cases assayed, we accurately detected the majority of cases of pleomorphic adenoma, adenoid cystic carcinoma, cribriform adenocarcinoma, clear cell carcinoma, secretory carcinoma and NUT-rearranged carcinoma, including cases of these tumor types arising in non-salivary gland sites, with the major drawback being an inability to detect MAML2-containing mucoepidermoid samples. With mucoepidermoid carcinoma excluded, the assay shows an overall sensitivity of 96.1% and specificity of 100%. We show that the majority of salivary gland tumor fusions can be effectively detected with a single rapid NanoString based assay, which can serve as a useful adjunctive tool for routine diagnostic head and neck pathology. The assay is low cost with a rapid turnaround time (30h total assay time per sample batch, with minimal technician input required) compared to alternate detection methods.

Gastric metastasis from renal cell carcinoma with submucosal invasion treated by surgical full-thickness resection: a case report

BackgroundMetastatic gastric tumors are rare and malignant melanoma, breast cancer, lung cancer, and esophageal cancer are common as primary lesions. On the other hand, renal cell carcinoma is easy to metastasize hematogenously to the whole body. However, metastasis to the stomach is rare and the detailed treatment of gastric metastasis is not mentioned. In this study, we report an uncommon case of gastric metastasis from renal cell carcinoma that underwent surgical full-thickness resection and reviewed the literature for treatment options.Case presentationThe patient was a female in her 60s and in January 2007, she underwent a transabdominal left nephrectomy for clear cell carcinoma of the left kidney. The pathological diagnosis was pT2N0M0 stage II. In October 2017, a total pancreatectomy with D2 dissection was performed for multiple pancreatic masses, in which the pathological diagnosis was pancreatic metastasis of renal cell cancer. In May 2019, an esophagogastroduodenoscopy for heartburn revealed redness and erosion in the greater curvature of the residual gastric body. The pathological diagnosis was gastric metastasis from renal cell carcinoma. No metastatic findings were observed and gastric wedge resection was performed. Pathological diagnosis of the resected specimen showed a 4-mm tumor, mainly within the mucosa and partly extended to the submucosal layer in 500 µm. The resected specimen had a clear resection margin.ConclusionsIn this study, we report a case in which a full-thickness resection was performed for gastric metastasis 12 years after renal cancer surgery and 2 years after pancreatic metastasis surgery. The patient survived 4 years and 8 months after gastric wedge resection. Although gastric metastasis often takes the form of submucosal tumors, it is necessary to select full-thickness resection for R0 resection, even in small and flat lesions.

Artificial Intelligence-Based Sentinel Lymph Node Metastasis Detection in Cervical Cancer

Background/objectives: Pathological ultrastaging, an essential part of sentinel lymph node (SLN) mapping, involves serial sectioning and immunohistochemical (IHC) staining in order to reliably detect clinically relevant metastases. However, ultrastaging is labor-intensive, time-consuming, and costly. Deep learning algorithms offer a potential solution by assisting pathologists in efficiently assessing serial sections for metastases, reducing workload and costs while enhancing accuracy. This proof-of-principle study evaluated the effectiveness of a deep learning algorithm for SLN metastasis detection in early-stage cervical cancer. Methods: We retrospectively analyzed whole slide images (WSIs) of hematoxylin and eosin (H&E)-stained SLNs from early-stage cervical cancer patients diagnosed with an SLN metastasis with either H&E or IHC. A CE-IVD certified commercially available deep learning algorithm, initially developed for detection of breast and colon cancer lymph node metastases, was employed off-label to assess its sensitivity in cervical cancer. Results: This study included 21 patients with early-stage cervical cancer, comprising 15 with squamous cell carcinoma, five with adenocarcinoma, and one with clear cell carcinoma. Among these patients, 10 had macrometastases and 11 had micrometastases in at least one SLN. The algorithm was applied to evaluate H&E WSIs of 47 SLN specimens, including 22 that were negative for metastasis, 13 with macrometastases, and 12 with micrometastases in the H&E slides. The algorithm detected all H&E macro- and micrometastases with 100% sensitivity. Conclusions: This proof-of-principle study demonstrated high sensitivity of a deep learning algorithm for detection of clinically relevant SLN metastasis in early-stage cervical cancer, despite being originally developed for adenocarcinomas of the breast and colon. Our findings highlight the potential of leveraging an existing algorithm for use in cervical cancer, warranting further prospective validation in a larger population.

Malignant transformation in mature cystic teratoma of ovary: Series of 4 cases

Mature cystic teratoma is the most common benign ovarian tumour of germ cell origin. Malignant transformation is rare in mature cystic teratoma. Here we present a series of 4 cases showing malignant transformation in the form of squamous cell carcinoma, follicular carcinoma, and clear cell carcinoma in mature cystic teratoma. Our case series suggest that there should be suspicion of malignant transformation in mature cystic teratoma when they are present in perimenopausal and postmenopausal females.

Targeting ZNF638 activates antiviral immune responses and potentiates immune checkpoint inhibition in glioblastoma.

Viral mimicry refers to the activation of innate anti-viral immune responses due to the induction of endogenous retroelement (RE) expression. Viral mimicry has been previously described to augment anti-tumor immune responses and sensitize solid tumors to immunotherapy including colorectal cancer, melanoma, and clear renal cell carcinoma. Here, we found that targeting a novel, master epigenetic regulator, Zinc Finger Protein 638 (ZNF638), induces viral mimicry in glioblastoma (GBM) preclinical models and potentiates immune checkpoint inhibition (ICI). ZNF638 recruits the HUSH complex, which precipitates repressive H3K9me3 marks on endogenous REs. In GBM, ZNF638 is associated with marked locoregional immunosuppressive transcriptional signatures, reduced endogenous RE expression and poor immune cell infiltration (CD8 + T-cells, dendritic cells). ZNF638 knockdown decreased H3K9-trimethylation, increased cytosolic dsRNA and activated intracellular dsRNA-signaling cascades (RIG-I, MDA5 and IRF3). Furthermore, ZNF638 knockdown upregulated antiviral immune programs and significantly increased PD-L1 immune checkpoint expression in patient-derived GBM neurospheres and diverse murine models. Importantly, targeting ZNF638 sensitized mice to ICI in syngeneic murine orthotopic models through innate interferon signaling. This response was recapitulated in recurrent GBM (rGBM) samples with radiographic responses to checkpoint inhibition with widely increased expression of dsRNA, PD-L1 and perivascular CD8 cell infiltration, suggesting dsRNA-signaling may mediate response to immunotherapy. Finally, we showed that low ZNF638 expression was a biomarker of clinical response to ICI and improved survival in rGBM patients and melanoma patients. Our findings suggest that ZNF638 could serve as a target to potentiate immunotherapy in gliomas.

Clear Cell Carcinoma Arising in Vaginal Endometriosis in a Patient 33 Years after Total Hysterectomy and Bilateral Salpingo-oophorectomy: A Case Report

Abstract Introduction/Objective Endometriosis, a common gynecological disorder characterized by ectopic endometrial tissue, is associated with an increased risk of extraovarian malignancies. Vaginal endometriosis is a rare condition, and the occurrence of vaginal malignancies arising from endometriosis is anticipated to be exceedingly rare. Here, we present a rare case of clear cell carcinoma arising in vaginal endometriosis, occurring three decades post-total hysterectomy and bilateral salpingo-oophorectomy. Methods/Case Report A 71-year-old female presented with abnormal Cologuard results, leading to a colonoscopy revealing a mass in the recto-sigmoid colon. She had undergone total hysterectomy and bilateral salpingo- oophorectomy for leiomyoma and endometriosis 33 years prior. Histopathological examination revealed clear cell carcinoma arising in vaginal endometriosis, with tumor extension through the colon wall to the colonic mucosal surface (Figure 1). Notably, the vaginal mucosal surface was negative for tumor. Immunohistochemistry staining demonstrated positivity for Pax8, CK7, AE1/3, racemase, and p16, while negtive for ER, PR, CDX2, CK20, CAIX, SatB2, RCC, WTI, Napsin, and calretinin (Figure 2). The staining for p53 was patchy (wild type, not mutated). Cancer-type relevant biomarkers reveal BRAF mutation (p.D594G), ARID1A mutation (p.M1564fs), PD-L1 mutation (Positive, CPS:80), and PIK3CA mutation (p.H1047L). The histologic and immunohistochemistry findings are consistent with clear cell carcinoma arising in a long-standing area of endometriosis (previous surgery in 1990). Results (if a Case Study enter NA) NA Conclusion Clear cell adenocarcinoma arising from endometriosis is exceptionally rare. Pathologists must consider the possibility of tumors arising from endometriosis when evaluating bowel or mesenteric neoplasms, even decades post-total hysterectomy and bilateral salpingo-oophorectomy. Immunohistochemistry plays a crucial role in the differential diagnosis between carcinoma arising from endometriosis and primary colonic carcinoma. Additionally, Sampson’s criteria are valuable for diagnosing malignant transformations in endometriosis. The identification of specific cancer-type relevant biomarkers, such as BRAF, ARID1A, PD-L1, and PIK3CA mutations, provides additional insights into the molecular characteristics of the tumor, which may have implications for prognosis and treatment selection.

Clear Cell Carcinoma Arising From Adenomyotic Cyst: A Case Report

Clear Cell Carcinoma Arising From Adenomyotic Cyst: A Case Report

The prognostic value and immunological role of calcium/calmodulin dependent protein kinase kinase 2 (CAMKK2) in pan-cancer study.

A thorough assessment of calcium/calmodulin dependent protein kinase kinase 2 (CAMKK2) in pan-cancer studies is currently absent. We integrate multi-omics and clinical data to conduct a molecular landscape of CAMKK2. Gene variation results revealed abnormal high frequency mutations of CAMKK2 in uterine corpus endometrial carcinoma, while expression level analysis demonstrated relatively high expression of CAMKK2 in prostate adenocarcinoma. The aberrant expression of CAMKK2 was found to be predictive of survival outcomes in several cancer types. Additionally, we identified potential regulators of CAMKK2 expression, including miRNAs such as miR.129.1.3p, as well as small-molecule drugs such as EPZ004777, which significantly correlated with CAMKK2 expression. Single-cell transcriptome analysis of kidney renal clear cell carcinoma further revealed a significantly higher expression of CAMKK2 in and monocyte and macrophage M1. Furthermore, in the kidney renal clear cell carcinoma IMvigor210 cohort, patients ongoing immunotherapy with higher CAMKK2 expression experienced a significantly longer median overall survival, but it was observed that in bladder urothelial carcinoma GSE176307 and skin cutaneous melanoma GSE78220 cohorts, CAMKK2 might significantly prolong overall survival. Briefly, CAMKK2 emerges as a promising molecular biomarker that holds potential implications for prognostic evaluation and predicting the effectiveness of immunotherapy across cancers.

Radiomics-based machine learning role in differential diagnosis between small renal oncocytoma and clear cells carcinoma on contrast-enhanced CT: A pilot study

PurposeTo investigate the potential role of radiomics-based machine learning in differentiating small renal oncocytoma (RO) from clear cells carcinoma (ccRCC) on contrast-enhanced CT (CECT). Material and methodsFifty-two patients with small renal masses who underwent CECT before surgery between January 2016 and December 2020 were retrospectively included in the study. At pathology examination 39 ccRCC and 13 RO were identified. All lesions were manually delineated unenhanced (B), arterial (A) and venous (V) phases. Radiomics features were extracted using three different fixed bin widths (bw) of 25 HU, 10 HU, and 5 HU from each phase (B, A, V), and with different combinations (B+A, B+V, B+A+V, A+V), leading to 21 different datasets. Montecarlo Cross Validation technique was used to quantify the estimator performance. The final model built using the hyperparameter selected with Optuna was trained again on the training set and the final performance evaluation was made on the test set. ResultsThe A+V bw 10 achieved the greater median (IQR) balanced accuracy considering all the models of 0.70 (0.64–0.75), while A bw 10 considering only the monophasic ones. The A bw 10 model achieved a median (IQR) sensitivity of 0.60 (0.40–0.60), specificity of 0.80 (0.73–0.87), AUC-ROC of 0.77 (0.66–0.84), accuracy of 0.75 (0.70–0.80), and a Phi Coefficient of 0.38 (0.20–0.47). None of the nine models with the lowest mean balanced accuracy values implemented features from A. ConclusionThe A bw 10 model was identified as the most efficient mono-phasic model in differentiating small RO from ccRCC.

8126 PTH-Independent, Calcitriol-Mediated Hypercalcemia In Renal Cell Carcinoma

Abstract Disclosure: G.K. Rai: None. A. De Rosairo: None. K. Madani: None. D. Sacoto: None. A.A. Franco-Akel, MD: None. R. Belokovskaya: None. Hypercalcemia of malignancy is a known complication of advanced cancer. It occurs through various mechanisms, one of which is via 1,25-dihydroxyvitamin D (calcitriol). Calcitriol-mediated hypercalcemia accounts for approximately 1% of cases of hypercalcemia in the setting of malignancy and is usually seen in lymphomatous solid tumors. We present a gentleman with clear cell renal cell carcinoma associated with hypercalcemia with normal levels of intact parathyroid hormone (PTH), PTH-related protein (PTHrP), and 25-hydroxyvitamin D but elevated calcitriol levels. A 48 year-old-male with no significant past medical history with complaints of fatigue, hematuria, and weight loss of 38 pounds in 3 months was following urology for an elective right-sided nephrectomy. MRI of the abdomen and pelvis found a 16.1 cm renal mass with necrotic areas, causing mass effects on the liver, pancreas, and IVC. Preoperative laboratory showed hypercalcemia of 13.7 mg/dL (corrected 13.9 mg/dL) with microcytic anemia (hemoglobin 8.8 g/dL, MCV 72 fl). Workup showed low iPTH (3 pg/dL), 25-hydroxyvitamin D (16.9 ng/dL), and phosphorus level (1.7mg/dL) with elevated calcitriol (94.3 pg/dL) and a normal PTHrP. CT chest showed multiple pulmonary nodules on bilateral lobes, with the largest nodule ∼ 4.5 mm. Hypercalcemia was managed with IV fluids, calcitonin 300 units Q12 for two days, Denosumab IV infusion, prednisone 60 mg for three days, and oral ergocalciferol 50,000 units weekly. Calcium levels normalized, after which the patient underwent nephrectomy. Pathology revealed renal cell carcinoma grade G4 with mixed features of clear cell carcinoma with sarcomatoid and rhabdoid features. We report an incidental finding of hypercalcemia in a patient with renal mass. The elevated calcitriol levels can be attributed to ectopic calcitriol production through the renal mass. Post nephrectomy calcium levels remained within normal range for consecutive weeks. With this, we concur that hypercalcemia most likely originated from the renal mass that had ectopic production of calcitriol. Dysregulated calcitriol production is a well-known complication of lymphomas and granulomatous disease but is seldom reported with solid tumors. Usually, the etiology for hypercalcemia in patients with renal cell carcinoma is the overproduction of PTHrP, which was not the case with our patient. The ultimate resolution of hypercalcemia of malignancy was attained by treating the underlying malignancy. Presentation: 6/1/2024

8126 PTH-independent, Calcitriol-mediated Hypercalcemia in Renal Cell Carcinoma

Abstract Disclosure: G.K. Rai: None. A. De Rosairo: None. K. Madani: None. D. Sacoto: None. A.A. Franco-Akel, MD: None. R. Belokovskaya: None. Hypercalcemia of malignancy is a known complication of advanced cancer. It occurs through various mechanisms, one of which is via 1,25-dihydroxyvitamin D (calcitriol). Calcitriol-mediated hypercalcemia accounts for approximately 1% of cases of hypercalcemia in the setting of malignancy and is usually seen in lymphomatous solid tumors. We present a gentleman with clear cell renal cell carcinoma associated with hypercalcemia with normal levels of intact parathyroid hormone (PTH), PTH-related protein (PTHrP), and 25-hydroxyvitamin D but elevated calcitriol levels. A 48 year-old-male with no significant past medical history with complaints of fatigue, hematuria, and weight loss of 38 pounds in 3 months was following urology for an elective right-sided nephrectomy. MRI of the abdomen and pelvis found a 16.1 cm renal mass with necrotic areas, causing mass effects on the liver, pancreas, and IVC. Preoperative laboratory showed hypercalcemia of 13.7 mg/dL (corrected 13.9 mg/dL) with microcytic anemia (hemoglobin 8.8 g/dL, MCV 72 fl). Workup showed low iPTH (3 pg/dL), 25-hydroxyvitamin D (16.9 ng/dL), and phosphorus level (1.7mg/dL) with elevated calcitriol (94.3 pg/dL) and a normal PTHrP. CT chest showed multiple pulmonary nodules on bilateral lobes, with the largest nodule ∼ 4.5 mm. Hypercalcemia was managed with IV fluids, calcitonin 300 units Q12 for two days, Denosumab IV infusion, prednisone 60 mg for three days, and oral ergocalciferol 50,000 units weekly. Calcium levels normalized, after which the patient underwent nephrectomy. Pathology revealed renal cell carcinoma grade G4 with mixed features of clear cell carcinoma with sarcomatoid and rhabdoid features. We report an incidental finding of hypercalcemia in a patient with renal mass. The elevated calcitriol levels can be attributed to ectopic calcitriol production through the renal mass. Post nephrectomy calcium levels remained within normal range for consecutive weeks. With this, we concur that hypercalcemia most likely originated from the renal mass that had ectopic production of calcitriol. Dysregulated calcitriol production is a well-known complication of lymphomas and granulomatous disease but is seldom reported with solid tumors. Usually, the etiology for hypercalcemia in patients with renal cell carcinoma is the overproduction of PTHrP, which was not the case with our patient. The ultimate resolution of hypercalcemia of malignancy was attained by treating the underlying malignancy. Presentation: 6/1/2024