Epithelial Tumors Research Articles

A Curious Case of Pancreatoblastoma in an Older Age Woman

Abstract Introduction/Objective Pancreatoblastoma is a malignant epithelial neoplasm of the pancreas and displays multiple lines of differentiation with acinar differentiation as the predominant pattern. The squamoid nests are considered a defining component of pancreatoblastoma. Pancreatoblastoma is seen most often in children, however, rare cases in adults have been described in the literature. In children, most pancreatoblastomas are indolent and curable, however, the prognosis is worse in adults due to the presence of frequent metastasis. Methods/Case Report We report an interesting case of pancreatoblastoma in a 65-year-old woman with no pertinent medical history who presented with abdominal discomfort. MRI abdomen showed an 11.3 cm mass with central necrosis within the head of the pancreas. Fine-needle aspiration (FNA) of the mass showed monotonous cells with neuroendocrine differentiation and FNA was signed out as a low-grade neuroendocrine tumor (NET). The patient underwent a Whipple resection for a presumed NET. On gross examination, a 14 cm large solid, fleshy, lobulated, partially encapsulated mass was noted in the head of the pancreas. H&E slides on low power showed the tumor composed of highly cellular lobules separated by fibrous bands. Within the lobules, the neoplastic cells predominantly had an acinar differentiation with focal trabecular or solid areas. Dispersed within the tumor were squamoid nests composed of plump to spindle-shaped cells with abundant eosinophilic cytoplasm arranged in whorls. Immunohistochemical stains demonstrated squamoid nests being positive for CK5/6 and had a nuclear-staining pattern with beta-catenin. The remaining tumor was positive for trypsin, chymotrypsin, BCL-10, synaptophysin (focal), chromogranin (focal), and INSM-1 (patchy). On MSK-Impact (next- generation sequencing), a mutation in CTNNB1 was detected. Results (if a Case Study enter NA) NA Conclusion In adults, it is important to consider pancreatoblastoma in the differential diagnoses of solid pancreatic tumors while being cautious not to confuse it with neuroendocrine tumor or acinar cell carcinoma. The presence of squamoid nests is critical for its diagnosis. Making a diagnosis of pancreatoblastoma through FNA or pancreatic biopsy can be exceptionally challenging in cases lacking squamoid nests.

Gastric Epithelial Neoplasm of Fundic-Gland Mucosa Lineage: Showed the Same Genetic Lineage and Ki67 May Help in Their Identification

Abstract Introduction/Objective Gastric epithelial neoplasm of the fundic-gland mucosa lineages (GEN-FGMLs) are rare form of gastric tumors that encompasses oxyntic gland adenoma (OGA), gastric adenocarcinoma of the fundic-gland type (GA-FG), and gastric adenocarcinoma of the fundic-gland mucosa type (GA-FGM). There is no consensus on the clinicopathologica and molecular characteristics of GEN-FGMLs, and misdiagnosis is common because of similarities in symptoms. Methods/Case Report The NGS and immunohistochemical staining were performed on 37 cases diagnosed with GEN-FGMLs with a thorough histological evaluation. Gene alternations were analysed and compared across histological subtypes. we used an artificial intelligence approach for the recognition of the Ki67 immunohistochemistry stained. Results (if a Case Study enter NA) The patient’s ages ranged from 42 to 79 years, with a median age of 60. 17 were male and 20 were female. Morphologically, 19 OGAs, 16 GA-FGs, and two GA-FGMs were identified. Histopathological similarities exist between GEN-FGMLs. The tumors demonstrated well-formed glands, expanding with dense growth patterns comprising pale, blue-grey columnar cells with mild nuclear atypia. The normal gastric pit epithelium covered the entire surface of the OGA and GA-FG, but the dysplasia pit epithelium covered the GA-FGM. Compared with OGA, GA-FG and GA-FGM were more prominent in the macroscopic view (p<0.05) and had larger sizes (p<0.0001). Additionally, GA-FG and GA-FGM exhibited higher Ki67 indices than OGA (p<0.0001). The heterogeneity of mutational signatures, somatic mutations, and copy number variations was revealed across histological subtypes. The top five mutational signatures in OGA were ROS1, CTNNA1, GNAS, BRCA2, and ZFHX3. The top five mutational signatures in GA-FG and GA-FGM were GNAS, MLL3, BRAF, MSH3, and EGFR. GNAS were both found in OGA, GA-FG and GA-FGM. Compared with well-differencent gastric adenocarcinoma, The top five mutational signatures in GEN-FGMLs were GNAS, BRAF, ROS1, MLL3, and MSH3. Recurrently mutated key signaling pathways across tumor types in GEN-FGML were Wnt signaling pathways. Conclusion GEN-FGMLs are a group of well-differentiated gastric tumors with favourable biological behaviours. Compared with OGA, GA-FG and GA-FGM have larger sizes and higher Ki67 proliferation indices, indicating that they play a critical role in the identification of GEN-FGML. GEN-FGMLs showed the same genetic lineage, the Wnt signalling pathway plays a role in the development and progression of GEN-FGMLs.

Concordance in the estimation of tumor percentage in non-small cell lung cancer using digital pathology

The incorporation of digital pathology in clinical practice will require the training of pathologists in digital skills. Our study aimed to assess the reliability among pathologists in determining tumor percentage in whole slide images (WSI) of non-small cell lung cancer (NSCLC) using digital image analysis, and study how the results correlate with the molecular findings. Pathologists from nine centers were trained to quantify epithelial tumor cells, tumor-associated stromal cells, and non-neoplastic cells from NSCLC WSI using QuPath. Then, we conducted two consecutive ring trials. In the first trial, analyzing four WSI, reliability between pathologists in the assessment of tumor cell percentage was poor (intraclass correlation coefficient (ICC) 0.09). After performing the first ring trial pathologists received feedback. The second trial, comprising 10 WSI with paired next-generation sequencing results, also showed poor reliability (ICC 0.24). Cases near the recommended 20% visual threshold for molecular techniques exhibited higher values with digital analysis. In the second ring trial reliability slightly improved and human errors were reduced from 5.6% to 1.25%. Most discrepancies arose from subjective tasks, such as the annotation process, suggesting potential improvement with future artificial intelligence solutions.

METTL14-mediated m6A modification upregulated SOCS3 expression alleviates thyroid cancer progression by regulating the JAK2/STAT3 pathway

Thyroid cancer (TC) is the most common malignant tumor of the head and neck. As a common epigenetic modification in mRNAs, N6-methyladenosine (m6A) modification plays critical roles in biological process of cancers. However, m6A methyltransferase methyltransferase-like 14 (METTL14)-mediated m6A modification and its potential regulatory mechanisms in TC are not fully elucidated. In our study, we observed that METTL14 was decreased in TC tissues and cells. And upregulation of METTL14 induced apoptotic cell death and hampered cell proliferation, epithelial mesenchymal transition (EMT) and tumor growth in vitro and in vivo. Mechanistically, METTL14 increased the expression of suppressor of cytokine signaling 3 (SOCS3) through m6A methylation modification, and knockdown of SOCS3 reversed the inhibitory effect of overexpressing METTL14 on TC tumorigenesis. In addition, METTL14-mediated m6A modification of SOCS3 inactivated the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway, and in the METTL14-overexpressing TC cells, silencing SOCS3-induced upregulation of cell proliferation, EMT and suppression of apoptosis was reversed by JAK2/STAT3 inhibitor AG490 and WP1066. Together, we indicated that METTL14/m6A/SOCS3/ JAK2/STAT3 axis play an important role in the progression of TC.

Clinicopathological Characteristics of Colorectal Cancer in the Anatomical Pathology Laboratory of Dr. M. Djamil Padang 2017-2020

Colorectal cancer is a malignant epithelial tumor originating from colorectal mucosa. Clinicopathology factors including age, gender, location, histopathological type, differentiation, depth of invasion, lymph node metastasis, and lymphovascular invasion are known affect the prognosis. This study aims to determine the clinicopathological characteristics of colorectal cancer at Anatomical Pathology Laboratory RSUP. Dr. M. Djamil Padang in 2017-2020 This study was descriptive observational with total sampling technique from medical records. Samples included all colorectal cancer patients in 2017-2020 who were fulfilled inclusion criteria, with total 251 samples. The results showed that the most patiens were female (52.2%), the age group were > 50 years (66.1%), mostly located in the rectosigmoid (71.7%). Most of the histopathological types were adenocarcinoma (79.7%), with low grade differentiation (88.8%). More than a half of tumor invasion was at T3 (58.2%). Mainly metastatic status to lymph nodes was Nx (54.2%) and lymphovascular invasion were positive in 60% samples that included the lymphovascular invasion examination. The conclusion of this study is most of colorectal cancer in Anatomical Pathology Laboratory RSUP. Dr. M. Djamil Padang in 2017-2020 are in advanced stage, Early detection needs to be done so that colorectal cancer can be diagnosed at an early stage.

Clear Cell Adenocarcinoma of the Urinary Tract Primary to the Renal Pelvis: A Multi-institutional Clinicopathologic and Molecular Study of Five Patients.

Clear cell adenocarcinoma (CCA) of the urinary tract is a rare malignancy and tumors involving the renal pelvis are notably sparse in the literature, with only 5 other patients reported. We present 5 patients, 4 women, and 1 man, with CCA of the renal pelvis. The age at presentation ranged from 29 to 81 years. The tumor size ranged from 4.5 to 8.0 cm. Tumors exhibited shared morphologic and immunohistochemical features with CCA of the female genital tract and those originating in the bladder and urethra, including cells with large nuclei, prominent nucleoli, nuclear hobnailing, and scant clear cytoplasm. Common immunohistochemical findings included reactivity for PAX8, CK7, HNF1β, and Napsin-A. One of the tumors arose in the background of a mixed epithelial and stromal tumor. Another tumor occurred in a renal allograft and tumor cells were positive for the BK virus, demonstrated by SV40 immunohistochemistry. All tumors were negative for TFE3 and TFEB rearrangement and lacked TERT alterations. Follow-up was limited with no recurrence in 4 patients at a maximum of 20 months follow-up and 1 patient died of an unrelated cause at 25 months of follow-up. Next-generation sequencing analysis of all 5 CCAs revealed mutations within genes implicated in DNA damage repair and chromatin remodeling pathways, including ATM, BRCA1, BRCA2, ARID1A, DICER1, SMAD4, NOTCH1, and MYC amplification. These molecular findings underscore the dysregulation of fundamental cellular processes essential for genomic integrity maintenance.

Assessing the Tumor Immune Landscape Across Multiple Spatial Scales to Differentiate Immunotherapy Response in Metastatic Non-Small Cell Lung Cancer

Although immune checkpoint inhibitor-based therapy has shown promising results in non-small cell lung cancer patients with high programmed death-ligand 1 expression, not all patients respond to therapy. The tumor microenvironment (TME) is complex and heterogeneous, making it challenging to understand the key agents and features that influence response to therapies. In this study, we leverage multiplex fluorescent immunohistochemistry to quantitatively assess interactions between tumor and immune cells in an effort to identify patterns occurring at multiple spatial levels of the TME. To do so, we introduce several computational methods novel to a data set of 1,269 multiplex fluorescent immunohistochemistry images from a cohort of 52 patients with metastatic non-small cell lung cancer. With the spatial G-cross function, we quantify the degree of cell interaction at an entire image level, where we see significantly increased activity of cytotoxic T cells and helper T cells with epithelial tumor cells in responders to immune checkpoint inhibitor-based (P = .022 and P < .001, respectively) and decreased activity of T-regulatory cells with epithelial tumor cells compared with nonresponders (P = .010). By leveraging spatial overlap methods, we define tumor subregions (which we call the tumor “periphery,” “edge.” and “center”) and discover more localized immune-immune interactions influencing positive response, including those between cytotoxic T cells and helper T cells with antigen presenting cells in these subregions specifically. Finally, we trained an interpretable deep learning model that identified key cellular regions of interest that most influenced response classification (area under the curve = 0.71 ± 0.02). Assessing spatial interactions within these subregions further revealed new insights that were not significant at the whole image level, particularly the elevated association of antigen presenting cells and T-regulatory cells with one another in responder groups (P = .024). Altogether, we demonstrate that elucidating patterns of cell composition and interplay across multiple levels of spatial analyses can improve our understanding of the TME and better differentiate patient responses to immunotherapy.

Therapeutic vulnerabilities and pan-cancer landscape of BRAF class III mutations in epithelial solid tumors

BackgroundKinase-impaired class III BRAF mutations have recently received attention as a possible prognostic factor and therapeutic target. Class III BRAF variants differ from class I and class II mutations in terms of mechanism of pathway activation and therapeutic vulnerabilities. Genomic landscape analyses of tumors in large real-world cohorts represent a great opportunity to further characterize tumor-related molecular events and treatment vulnerabilities, however, such data is not yet available for tumors with BRAF class III mutations.MethodsWe investigated the pan-cancer genomic landscape of BRAF class III mutations in 376,302 patients. Patients had comprehensive genomic profiling either by FoundationOne® or FoundationOne®CDx from formalin-fixed, paraffin embedded tissue biopsies. 2 patient cases that harbored BRAF class III mutations who demonstrated dramatic response to anti-EGFR treatment were presented.ResultsBRAF class III mutations are likely to co-occur with RAF1, NRAS and HRAS alterations, while concomitant KRAS alterations were rare. Moreover, we found that alterations that predict resistance to anti-EGFR agents were significantly less common in tumors harboring BRAF class III mutations, which is of great importance as anti-EGFR therapies are a potential targeted treatment option in these tumors.DiscussionOur findings suggest a heterogenous interplay of oncogenic alterations in BRAF class III mutated tumors and have important implications for the molecular mechanisms of carcinogenesis while revealing potential therapeutic vulnerabilities.HighlightsTumors harboring BRAF class III (BRAF vIII) mutations comprise a novel subset with distinct genomic heterogeneity.BRAF vIII mutations may sensitize tumors to anti-EGFR treatments.BRAF vIII alterations show significantly less co-occurrence with alterations that predict resistance to anti-EGFR agents.Rare tumors with limited therapy options should be screened for BRAF vIII mutations as they may benefit from anti-EGFR agents.

Aberrant Expression of Pneumocytic Markers (TTF-1 and Napsin-A) in Biliary Duct and Gallbladder Adenocarcinomas; A Potential Diagnostic Pitfall.

Cholangiocarcinomas and gallbladder carcinomas are epithelial tumours with biliary differentiation. On histology and immunohistochemistry, they resemble adenocarcinomas and possess overlapping immunohistochemical profiles. Diagnosing these tumours is best done using appropriate imaging and clinical features with compatible immunohistochemistry. Immuno-staining for thyroid transcription factor-1 (TTF-1) and novel aspartic proteinase of pepsin A (Napsin-A) is believed to be specific for primary pulmonary adenocarcinomas. We herein report uncommon instances of strong and diffuse expression of these markers in two examples of adenocarcinomas arising from the bile duct and gallbladder. A review of the literature and a summary of similar studies relating to aberrant TTF-1 and Napsin-A expression in biliary tract adenocarcinomas are presented.

Data mining of PubChem bioassay records reveals diverse OXPHOS inhibitory chemotypes as potential therapeutic agents against ovarian cancer

Focused screening on target-prioritized compound sets can be an efficient alternative to high throughput screening (HTS). For most biomolecular targets, compound prioritization models depend on prior screening data or a target structure. For phenotypic or multi-protein pathway targets, it may not be clear which public assay records provide relevant data. The question also arises as to whether data collected from disparate assays might be usefully consolidated. Here, we report on the development and application of a data mining pipeline to examine these issues. To illustrate, we focus on identifying inhibitors of oxidative phosphorylation, a druggable metabolic process in epithelial ovarian tumors. The pipeline compiled 8415 available OXPHOS-related bioassays in the PubChem data repository involving 312,093 unique compound records. Application of PubChem assay activity annotations, PAINS (Pan Assay Interference Compounds), and Lipinski-like bioavailability filters yields 1852 putative OXPHOS-active compounds that fall into 464 clusters. These chemotypes are diverse but have relatively high hydrophobicity and molecular weight but lower complexity and drug-likeness. These chemotypes show a high abundance of bicyclic ring systems and oxygen containing functional groups including ketones, allylic oxides (alpha/beta unsaturated carbonyls), hydroxyl groups, and ethers. In contrast, amide and primary amine functional groups have a notably lower than random prevalence. UMAP representation of the chemical space shows strong divergence in the regions occupied by OXPHOS-inactive and -active compounds. Of the six compounds selected for biological testing, 4 showed statistically significant inhibition of electron transport in bioenergetics assays. Two of these four compounds, lacidipine and esbiothrin, increased in intracellular oxygen radicals (a major hallmark of most OXPHOS inhibitors) and decreased the viability of two ovarian cancer cell lines, ID8 and OVCAR5. Finally, data from the pipeline were used to train random forest and support vector classifiers that effectively prioritized OXPHOS inhibitory compounds within a held-out test set (ROCAUC 0.962 and 0.927, respectively) and on another set containing 44 documented OXPHOS inhibitors outside of the training set (ROCAUC 0.900 and 0.823). This prototype pipeline is extensible and could be adapted for focus screening on other phenotypic targets for which sufficient public data are available.Scientific contributionHere, we describe and apply an assay data mining pipeline to compile, process, filter, and mine public bioassay data. We believe the procedure may be more broadly applied to guide compound selection in early-stage hit finding on novel multi-protein mechanistic or phenotypic targets. To demonstrate the utility of our approach, we apply a data mining strategy on a large set of public assay data to find drug-like molecules that inhibit oxidative phosphorylation (OXPHOS) as candidates for ovarian cancer therapies.Graphical

Transgenic overexpression of the miR-200b/200a/429 cluster prevents mammary tumor initiation in Neu/Erbb2 transgenic mice.

Although significant progress in the treatment of breast cancer has been achieved, toxic therapies would not be required if breast cancer could be prevented from developing in the first place. While breast cancer prevention is difficult to study in humans due to long disease latency and stochastic cancer development, transgenic mouse models with 100% incidence and defined mammary tumor onset, provide excellent models for tumor prevention studies. In this study, we used Neu/Erbb2 transgenic mice (MTB-TAN) as a model of human HER2+ breast cancer to investigate whether a family of microRNAs, known as the miR-200 family, can prevent mammary tumor development. Overexpression of Neu induced palpable mammary tumors in 100% of the mice within 38 days of Neu overexpression. When the miR-200b/200a/429 cluster was co-overexpressed with Neu in the same mammary epithelial cells (MTB-TANba429 mice), the miR-200b/200a/429 cluster prevented Neu from inducing mammary epithelial hyperplasia and mammary tumor development. RNA sequencing revealed alterations in the extracellular matrix of the mammary gland and a decrease in stromal cells including myoepithelial cells in Neu transgenic mice. Immunohistochemistry for smooth muscle actin confirmed that mammary epithelial cells in control and MTB-TANba429 mice were surrounded by a layer of myoepithelial cells and these myoepithelial cells were lost in MTB-TAN mice with hyperplasia. Thus, we have shown for the first time that elevated expression of miR-200 family members in mammary epithelial cells can completely prevent mammary tumor development in Neu transgenic mice possibly through regulating myoepithelial cells.

7187 Non-islet Cell Tumor Hypoglycemia in a Patient With Metastatic Renal Cell Carcinoma

Abstract Disclosure: G.W. Bao: None. A.Y. Yin: None. We report a rare case of non-islet cell tumor hypoglycemia (NICTH) in a patient with metastatic renal cell carcinoma. NICTH is a paraneoplastic syndrome due to increased production of an incompletely processed form of insulin-like growth factor 2 (“big IGF-2”). It requires a high-level of suspicion for diagnosis and is challenging to manage. Our patient is a 69 year old gentleman with a history of deceased donor renal transplant in 1994 and 2008. He was diagnosed with renal cell carcinoma (RCC) metastatic to bone, lymph nodes, and lungs, which was initially treated with cabozantinib, later switched to lenvatinib and everolimus due to disease progression. On admission, he presented with anasarca and weakness. He had recurrent fasting hypoglycemia associated with confusion and lethargy. The lowest serum glucose was 28 mg/dL. He was also diagnosed with primary hypothyroidism (TSH 25.1 uIU/mL and free T4 0.31 ng/dL), suspected to be due to tyrosine kinase inhibitor therapy. Levothyroxine was initiated. Cosyntropin stimulation resulted in a post-stimulation cortisol of 7 ug/dL, although this was felt not to be reliably diagnostic of adrenal insufficiency in the setting of profound hypoalbuminemia. IGF-1 and IGF-2 were 16 ng/mL and 388 ng/mL, respectively; IGF-2: IGF-1 ratio was 24.3. He was treated with intravenous dextrose and prednisone 30mg daily with stabilization of glucoses for a few days. On hospital day 19, he acutely decompensated and passed away shortly after being transitioned to comfort-focused care. Non-diabetic hypoglycemia is relatively uncommon, and may be seen in patients with liver disease, sepsis, adrenal insufficiency, and malignancy. We report a case of NICTH in a patient with metastatic RCC, which is a particularly rare cause of hypoglycemia. NICTH is due to tumor production of “big IGF-2”, a precursor of IGF-2, which mimics the effects of insulin and causes fasting hypoglycemia. NICTH is more commonly associated with mesenchymal and epithelial tumors such as fibromas, fibrosarcomas, and hepatocellular carcinomas. NICTH due to RCC appears to be a much more rare entity, with as few as four cases reported in the literature. Laboratory findings of NICTH include low insulin, pro-insulin, C-peptide, and β-hydroxybutyrate during hypoglycemia. An IGF-2: IGF-1 ratio &amp;gt;10 is considered virtually diagnostic. Surgical excision is curative, although often delayed or not feasible, and patients frequently require intravenous dextrose. High-dose steroids (ie, prednisone 30-60mg daily) can be used, which promotes “big IGF-2” clearance. NICTH is likely under-recognized in patients with advanced malignancies. This diagnosis should be considered in those with refractory hypoglycemia, although management is challenging if tumor control cannot be achieved. Presentation: 6/1/2024

9182 Metastatic Extra-Gastrointestinal Stromal Tumor Presenting As Hypoglycemia

Abstract Disclosure: O. faour: None. D. John: None. S.K. Suryanarayanan: None. A.A. Rizvi: None. Introduction: Non islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome seen in association with solid abdominal tumors of mesenchymal and epithelial origin. We report a case of metastatic extra-gastrointestinal stromal tumor (E-GIST) presenting with severe hypoglycemia as its initial manifestation. CASE DESCRIPTION: A 46-year-old patient was found to have a blood glucose of &amp;lt;45 mg/dl during a routine clinic visit with her primary care physician. Although she was asymptomatic, she was sent to the emergency room (ER) for further evaluation. She had a history of prediabetes managed by lifestyle modification. She has been experiencing multiple episodes of hypoglycemia previously which fulfilled the Whipple’s triad in the preceding months. These hypoglycemic episodes included loss of unconsciousness, falls in the shower with head injury, and several hospital visits. Serum glucose in the ER was 14 mg/dl and hypoglycemia persisted despite continuous dextrose solution. Physical examination was notable for a distended, non-tender abdomen and cervical lymphadenopathy. CT scan showed a 15 cm mass in the liver, multiple large masses in the mesentery, and a 11 cm lesion in the left pelvis. There were enlarged lymph nodes in the abdomen, chest, and neck. Serum chemistries drawn when the patient was hypoglycemic revealed potassium level of 2.7 mg/dl (3.5-5.5) an insulin level of &amp;lt;1.0 mIU/L (5-25), C-peptide &amp;lt;0.1 ng/mL (0.5-2), cortisol 13.8 mcg/dL (5-25), and insulin-like growth factor-2 (IGF-2) was 270 ng/mL (38-267). The IGF-2/IGF-1 molar ratio was 3.4 (normal &amp;lt;3:1). The sulfonylurea drug screen came back negative. Upper and lower endoscopies were unrevealing. Biopsy of the liver lesion showed cytology and immunohistochemical findings consistent with a epithelioid metastatic extra-gastrointestinal stromal tumor. A provisional diagnosis of NICTH was made. The patient responded well to intravenous glucose, oral carbohydrate intake and high-dose corticosteroids. She was subsequently started on therapy with the tyrosine kinase inhibitor (TKI) imatinib. Discussion: Paraneoplastic hypoglycemia is often seen in association with metastatic epithelial and mesenchymal tumors. IGF-2 and incompletely processed pro-IGF-2 activates autocrine, paracrine, and endocrine pathways that lead to tumor growth, fasting hypoglycemia, rarely of acromegalic features. Treatment with octreotide, diazoxide, and glucagon is generally ineffective, while glucocorticoid use and surgical intervention are helpful in ameliorating the hypoglycemia. Tumor-directed therapy with TKIs, primarily imatinib, appears promising in achieving remission. Our case is a clinical reminder that hypoglycemia secondary to NICTH can be the predominant presenting feature in patients with underlying E-GIST. Presentation: 6/3/2024

6590 Androgen Derived Hepatocellular Adenoma And Reinitiation Of Gender Affirming Hormone Therapy

Abstract Disclosure: A.L. McKenna: None. Y. Huang: None. L. Yang: None. N. Loo: None. C. Ritchie: None. A. Metcalfe: None. R. Nakhleh: None. M. Krishna: None. S. Thota-Kammili: None. J. Eleazer: None. A.Y. Chang: None. Hepatocellular adenomas (HCA) are uncommon, benign epithelial tumors of the liver. Risk factors include exogenous estrogen or androgen use, and genetic and metabolic syndromes. Management of HCA is delineated by sex assigned at birth; Observation is recommended in an HCA less than 5 cm in an individual assigned female at birth, while resection of an HCA in an individual assigned male at birth is recommended no matter the size due to risk of malignant transformation. What is not known is whether risk is different for individuals with gender incongruence on gender affirming hormone therapy (GAHT). There is limited data on the risk of HCA in this population. One case report of a transgender man who continued GAHT after diagnosis of an HCA though no follow-up information was available. We present follow-up on a transgender man assigned female at birth with multiple hemorrhagic HCA that was re-initiated on GAHT after stabilization of adenomas off GAHT. Unlike prior cases, the molecular profile showed ß-catenin negative, estrogen and androgen receptors positive. This is the first case report to our knowledge reporting detailed follow-up after restarting masculinizing GAHT after diagnosis of HCA. A 24-year-old transgender man presented to the emergency department with right upper quadrant pain. Initial labs were notable for ALT of 239 units per liter (U/L) and AST 165 U/L. Magnetic resonance imaging (MRI) of the abdomen and liver elastogram revealed multiple bilobar hepatic masses, the largest measuring 9.9 cm concerning for hemorrhagic HCA which was subsequently confirmed on liver biopsy. Immunostains were positive for estrogen and androgen receptors. The patient had no history of alcohol or illicit drug use, tattoos, or family history of liver disease. The patient had been treated with 100 mg of intramuscular testosterone cypionate weekly for the past six years for gender incongruence locally. No testosterone concentrations were available from prior to or during acute presentation. Discontinuation of hormone therapy was recommended along with conservative management with frequent MRI. Over the next 19 months, monitoring revealed improvement/resolution of the auto infarcting adenomas with the last MRI noting two stable HCA measuring 2.1 cm and 0.8 cm without new or enlarging liver lesions. Due to gender dysphoria off GAHT, reinitiation of hormone therapy with low dose AndroGel 1.62% topically was prescribed at 18 months after presentation. The patient has been monitored with labs monthly and plans to obtain MRI abdomen every three months. To date, the patient has tolerated reinitiation of therapy. This case demonstrates that patients on masculinizing GAHT who develop HCA can be conservatively managed and monitored based on pathology and that testosterone does not necessarily explain sex differences in the presentation/malignant transformation of HCA cisgender men as opposed to cisgender women. Presentation: 6/3/2024

8036 A Rare Case of Cushing’s Syndrome Caused by a Pulmonary Carcinoid Tumor

Abstract Disclosure: A.C. Tep: None. F.M. Wolf: None. Introduction: The most common causes of ectopic ACTH (adrenocorticotropic hormone) syndrome include bronchial carcinoid tumors and other neuroendocrine tumors. Ectopic ACTH syndrome (EAS) can be difficult to diagnose. Differentiating Cushing’s disease and EAS is difficult, as ACTH-secreting tumors are often small and easily missed on imaging. Case Presentation: A 32-year-old male with a history of hypothyroidism presented with a 6-month history of facial rounding. He also noticed a dorsocervical fat pad, muscle weakness in the extremities, easy bruising, and elevated blood pressure progressing over the same period. A 24-hour urine free cortisol was elevated to 1797 mcg. Two salivary cortisol tests performed 1 hour after the patient’s usual bedtime had values of 4.4 ug/dl and &amp;gt; 1.000 ug/dl. Both the urine and salivary cortisol results were exceedingly high. ACTH was elevated (150 pg/ml). An MRI of the pituitary gland was normal without evidence of an adenoma. Frequently, ACTH-secreting pituitary adenomas are small enough that they are missed on MRI; however, given our patient’s rapid clinical presentation, additional imaging was performed to identify an ectopic source. A CT Chest/Abdomen/Pelvis showed a 1.2 cm nodule in the right middle lobe of the lung. The right middle lobe was resected, and pathology revealed a carcinoid tumor. His cortisol levels slowly decreased postoperatively and eventually normalized. At his one-month post-operative visit, his symptoms were all improving but not yet resolved. Discussion: This patient was found to have Cushing's syndrome due to ectopic ACTH production from a pulmonary carcinoid tumor. The patient demonstrated clinical improvement after resection of the tumor. Pulmonary carcinoid tumors are rare neuroendocrine epithelial tumors that account for 2-5% of all lung tumors. The annual incidence of these tumors is 2.3-2.8 cases per million people. Endogenous Cushing's syndrome is either ACTH-dependent or ACTH-independent. In ACTH-dependent Cushing's syndrome, the ACTH can either be from the pituitary or an ectopic source. Once ACTH-dependent disease is confirmed, a pituitary MRI is performed to evaluate for an ACTH-secreting pituitary adenoma; this is called Cushing’s disease. Some patients undergo inferior petrosal sinus sampling to confirm the source is central and to determine laterality before transsphenoidal resection of the adenoma. If the source of ACTH is not from the pituitary, obtaining a CT or MRI of the chest and abdomen locates tumors in most patients. At times a functional study, such as an octreotide or PET-DOTATE scan, is done to confirm the diagnosis before proceeding with surgical resection to avoid unnecessary removal of an incidental tumor. Ectopic ACTH production often causes a more rapid progression of Cushingoid features, which can be a clue to the diagnosis of this condition. Presentation: 6/1/2024

Giant serous cystadenomas encountered in clinical practice: A case series

Benign serous cystadenomas represent 16% of all ovarian epithelial neoplasms, and account for up to two-thirds of epithelial tumors of the ovary. They are commonly encountered after the 3rd decade of life and in the later decades, due to the slow growth nature over lifetime. These tumors may begin as small unilocular subcentimeter lesions, but may expand to fill the entire abdominal cavity. This may present with mass effect to surrounding tissues and organs, and lead to sequela of compartment syndrome of the peritoneal cavity. We present a case series of surgical evaluation and management of extremely enlarged serous cystadenomas of the ovary (&gt;30 cm) encountered in an atypical age presentation, with the first case involving a 19 year old who had a known 6 cm cyst four years prior, who presented to emergency room (ER) with gastrointestinal (GI) symptoms secondary to the tumors mass effect, imaging demonstrating a massive tumor, subsequently requiring surgical dissection. The second case demonstrates a 25 year old with known cyst (&gt;20 cm) two years prior who presented with even larger effect (close to 40 cm size) and worsening symptoms due to the tumors mass effect requiring removal. In both cases, patients presented to emergency room with acute symptoms, exploratory laparotomy was required for complete evacuation of lesion and for resolution of symptoms.

Calcifying epithelial odontogenic tumour with an atypical clinical presentation in a paediatric patient: A case report and literature review

AbstractAimWe report a rare case of a calcifying epithelial odontogenic tumour with atypical clinical presentation in an adolescent and present a literature review of this tumour in paediatric patients.Materials and MethodsA 12‐year‐old female patient presented with a painless swelling of the left mandible, with a history of 6 months. Clinical examination revealed a sessile mass with a reddish‐pink colour and firm consistency. Tomographic images showed a hypodense, unilocular lesion involving unerupted tooth #34, with a hyperdense focus in contact with the tooth crown disrupting the buccal cortex.ResultsEnucleation, curettage and peripheral osteotomy of the lesion were performed, and the impacted tooth was removed, followed by the application of autologous leucocyte and platelet‐rich fibrin matrices to the region. The patient evolved favourably with good clinical healing and evidence of new bone formation.ConclusionsDespite its aggressive potential, the conservative approach for CEOT in paediatric patients proved to be effective. Our review found reports of recurrence up to 13 years after surgery. Therefore, long‐term clinical and radiographical follow‐up is indicated.

PDOC-01 THERAPEUTIC DIFFICULTY IN THE MANAGEMENT OF A RECURRENT CRANIOPHARYNGIOMA IN A CHILD: REVIEW OF THE LITERATURE AND CASE REPORT

Abstract BACKGROUND Craniopharyngiomas are rare, benign epithelial tumors of embryonic origin in children that develop along the craniopharyngeal duct from Rathke’s pouch. The optimal treatment algorithm remains challenging. We report a child case of recurrent craniopharyngioma with therapeutic challenges. CASE PRESENTATION 12-year-old patient, followed for a multi-operated type 2 craniopharyngioma (December 2017, November 2018, and April 2022), stroke on left sylvian stenosis with right hemiplegia in 2020 during proton therapy (52 Gray), thrombolysed with good recovery after rehabilitation, sequellar panhypopituitarism. He was seen in consultation for visual field deterioration. Clinical examination showed a conscious, coherent, obese patient with a deteriorating visual field. Ophthalmological examination showed visual acuity 10/10 with slight temporal visual field amputation on the left and monocular blindness on the right due to probable optic atrophy sequelae of the craniopharyngioma. Magnetic resonance imaging revealed progression of the residual multicystic lesion in the sellar and left temporal regions, entering the sylvian valley and severely compressing the optic pathways. The tumor was removed under general anesthetic in a supine position, with release of the optic nerve, the carotid artery, and its division, and the left 3rd cranial nerve. The postoperative course is straightforward. CONCLUSION Morbidity and the assessment of sequelae are now at the forefront of the management of craniopharyngiomas. The current therapeutic approach should be reconsidered, in terms of the indications for surgery and the surgical protocol. This patient’s case is a typical example of the therapeutic difficulties involved in the management of craniopharyngiomas.

First-in-human clinical outcomes with NG-350A, an anti-CD40 expressing tumor-selective vector designed to remodel immunosuppressive tumor microenvironments

BackgroundTumor-selective oncolytic viral vectors are promising anticancer therapeutics; however, challenges with dosing and potency in advanced/metastatic cancers have limited efficacy and usage. NG-350A is a next-generation blood-stable adenoviral vector engineered...

Molecular Markers in the World Health Organization Classification of Head and Neck Tumors, Fifth Edition.

The past decade has seen exponential advancements in molecular markers and the genetics of tumors, recognizing the limitations of conventional histopathology for grading, classification, and prognostication. Such advances have resulted in changes to classification systems, for example, with the incorporation of objective molecular and genetic information into the 2021 World Health Organization (WHO) classification of central nervous system tumors. The fifth edition of the WHO classification of head and neck tumors (HN5) (beta online version, 2022) also introduced major changes based on molecular markers, including additions, deletions, and reclassifications of entities, with the idea of being more objective and standardized. These changes are highly relevant to therapy decisions, prognosis, and clinical research and for patients with resistant diseases to explore options in clinical trials. The HN5, for the first time, included a radiologist as a member of the writing team to incorporate pertinent imaging findings into the classification. It is important for the radiologist, as an integral part of the multidisciplinary team, to be up to date about these changes for a better understanding of tumor biology, to integrate this into their clinical practice, and to provide more value in their interpretations. The authors provide a basic understanding of pathology and genetics for the radiologist, highlighting the molecular changes in epithelial (including squamous cell) and nonepithelial tumors of the head and neck. The authors also highlight newly recognized and reclassified tumor entities and provide a brief discussion on the genetic tumor syndromes. ©RSNA, 2024 Supplemental material is available for this article. See the invited commentary by Junn and Baugnon in this issue.