Tumor Mass Research Articles

Guavira Fruit Pomace Promotes Immunomodulation and Reduction of Tumor Growth in Walker 256 Tumor-Bearing Rats

Background: Guavira fruit is widely used for juice extraction purposes, and this process generates large amounts of pomace (waste). Guavira pomace was dried and milled to produce guavira pomace flour (GPF), which is rich in antioxidants and dietary fibers (polysaccharides). These compounds are known for their immunomodulatory and antitumor effects. Objective: To investigate whether GPF intake promotes immunomodulation and reduces Walker 256 tumor growth in rats. Methods: GPF was provided to Wistar rats in two different models: 1) 15-day Model, according to which, Walker 256 tumor-bearing rats received GPF (63 mg/200 g b.w./day) simultaneously to tumor growth for 15 days; 2) 45-day Model, according to which, tumor-bearing rats received GPF for 30 days before tumor cell implantation, as well as during tumor growth - it totaled 45 days. After animals were euthanized, tumors were collected and weighed, and tumor cells were isolated for proliferation capacity determination ex vivo. Enzymatic/colorimetric methods were used to determine resident peritoneal macrophages’ functionality, whereas blood T and B lymphocytes were assayed for proliferation capacity, ex vivo, under stimuli. Results: The 15-day Model did not show tumor mass or cell proliferation reduction in the treated group. GPF stimulated macrophage response in tumor-bearing and non-tumor-bearing rats. However, there was a substantial reduction in tumor mass and tumor cell proliferation under the 45-day Model. Macrophage and lymphocyte response decreased; it suggested that GPF can directly act in the tumor. Conclusion: Based on these findings, GPF has immunomodulatory and antitumor actions, and ingestion time plays a key role in them.

Biological knee joint reconstruction using patella following giant cell tumor excision: a case report

A 20-year-old female patient presented to us with a large expansile swelling over right knee diagnosed clinically and confirmed histopathological and radiologically to be Giant Cell Tumor of upper end of Tibia involving both condyles with a breach in the posterior cortex. In this case report we tried to retain the joint function by biological reconstruction using the Patella after the wide excision of the tumor mass. A radical excision of the upper end of the Tibia was done. The Patella was used as an articular surface supported by ipsilateral Fibula and cortico-cancellous bone chips from the ipsilateral iliac crest as struts and complemented with synthetic bone graft pieces. Thus, the joint was reconstructed biologically. The case was followed for 1 year. The tumor was excised in toto, the knee joint was restored by the Patella and the bone graft struts. The results were discussed in detail.

Diagnostic incidence and pitfalls of rete testis hyperplasia and hyaline globules in a multi-institutional study of 348 testicular germ cell tumors.

The concept of rete hyperplasia with hyaline globules simulating testicular yolk sac tumor was first reported in a mostly retrospective review over 30 years ago. Nonetheless, we continue to encounter examples where this scenario resulted in misdiagnosis. Herein, we sought to investigate the incidence of rete hyperplasia/hyaline globules in germ cell tumors and their associated subtypes and hypothesize an etiology. A consecutive series of 348 germ cell tumor orchiectomies was evaluated for the presence of rete hyperplasia and hyaline globules, with clinicopathologic features recorded. The incidence of rete hyperplasia and/or hyaline globules in our cohort was 30%, with 56% of specimens with rete hyperplasia containing concomitant hyaline globules. Hyaline globules were more often identified in specimens with nonfocal rete hyperplasia (78%) vs focal rete hyperplasia (22%). Absence of a yolk sac tumor component was seen in over half (61%) of orchiectomies with concurrent rete hyperplasia/hyaline globules (n = 105), inclusive of tumors with "pure" subtypes (ie, pure seminoma, pure teratoma, or pure embryonal carcinoma). Of these 105 specimens, rete invasion was seen in only 48%; notably, Paneth cell-like metaplasia was identified in efferent ductules/epididymis in 13%. Rete hyperplasia and hyaline globules are not uncommon findings in the setting of germ cell tumors (including occurrences in various pure/mixed germ cell tumors) and can show striking overlap with yolk sac tumor. We hypothesize that these histologic pitfalls evolve secondary to testicular obstruction by the tumor mass. Recognition of and distinguishing this morphologic mimicry is fundamental to guide appropriate clinical management.

QSOX1 facilitates dormant esophageal cancer stem cells to evade immune elimination via PD-L1 upregulation and CD8 T cell exclusion

Dormant cancer stem cells (DCSCs) exhibit characteristics of chemotherapy resistance and immune escape, and they are a crucial source of tumor recurrence and metastasis. However, the underlying mechanisms remain unrevealed. We demonstrate that enriched Gzmk+ CD8+ T cells within the niche of esophageal DCSCs restrict the outgrowth of tumor mass. Nonetheless, DCSCs can escape immune elimination by enhancing PD-L1 signaling, thereby maintaining immune equilibrium. Quiescent fibroblast-derived quiescin sulfhydryl oxidase 1 (QSOX1) promotes the expression of PD-L1 and its own expression in DCSCs by elevating the level of reactive oxygen species. Additionally, high QSOX1 in the dormant tumor niche contributes to the exclusion of CD8+ T cells. Conversely, blocking QSOX1 with Ebselen in combination with anti-PD-1 and chemotherapy can effectively eradicate residual DCSCs by reducing PD-L1 expression and promoting CD8+ T cell infiltration. Clinically, high expression of QSOX1 predicts a poor response to anti-PD-1 treatment in patients with esophageal cancer. Thus, our findings reveal a mechanism whereby QSOX1 promotes PD-L1 upregulation and T cell exclusion, facilitating the immune escape of DCSCs, and QSOX1 inhibition, combined with immunotherapy and chemotherapy, represents a promising therapeutic approach for eliminating DCSCs and preventing recurrence.

Comparative mortality in pituitary adenomas subtypes: a tertiary referral center study.

Mortality in pituitary adenomas (PAs) has been extensively compared to general population. However, direct comparisons between PA subtypes are scarce. We aimed to compare mortality in various subtypes of PA (acromegaly, Cushing's disease (CD), macroprolactinomas and non-functioning pituitary macroadenomas (MacroNFPA)), within a single referral center. We retrospectively analyzed mortality and survival time in all 962 PAs admitted in our department between 2011 and 2023: acromegaly (n = 306), CD (n = 69), macroprolactinoma (n = 168) and MacroNFPA (n = 419). Median follow-up was 10.2 (5.2, 15.2) years. The overall survival probability was 90.9% and 78.1% after 10 and 20 years respectively with age at diagnosis as the only significant predictor. There were no significant differences in survival probability between various PA subtypes in the whole cohort. In patients over 45 years of age at diagnosis there was a significant difference in survival probability between the four groups (p = 0.01) in the first 15 years of follow-up. In head-to-head comparisons CD had a significantly higher mortality risk than patients with acromegaly (HR 3.38 [CI 95% 1.07 to 10.60]) even after adjusting for age and sex. Patients diagnosed with CD after 45 years of age have a significantly lower survival probability than other PA subtypes in the first 15 years of follow-up. All other PA subtypes had a similar survival probability after adjusting for age and sex. Due to advances in medical treatment of hormone secreting tumors, mortality in patients with PAs might increasingly depend more on tumor mass than on hormonal hypersecretion.

Myeloid Sarcoma: Novel Advances Regarding Molecular Pathogenesis, Presentation and Therapeutic Options

Myeloid sarcoma (MS), an extramedullary form of acute myeloid leukemia (AML) is a rare tumor mass of myeloid blasts. It can disseminate to any one or multiple anatomical sites, with (synchronous MS) or without (isolated MS) bone marrow (BM) involvement. The aim of this review is to describe the most recent advances in MS regarding diagnosis, molecular background, various clinical manifestations from several organs, and treatment approaches. Due to the lack of prospective, randomized clinical trials, therapeutic decisions are a challenge for the clinician. In the era of novel targeted AML treatments, a critical analysis of how to decide the best option for individual patients, also covering the possible central nervous system (CNS) prophylaxis is provided. For the majority of the patients, AML induction chemotherapy, followed by hematopoietic stem cell transplantation (HSCT) is generally recommended. This paper discusses the role of radiotherapy, the treatment of refractory and relapsed disease, along with the therapeutic approach of difficult-to-treat patients, due to specific problems related to different anatomical sites of MS.

Reconstruction of cancer marker analysis with holistic anatomical precision implicates heterogeneity development during breast tumor progression

Biomarkers are not only of significant importance for cancer diagnosis and selection of treatment plans but also recently increasingly used for the evaluation of malignancy development and tumor heterogeneity. Large-size tumors from clinical patients can be unique and valuable sources for the study of cancer progression, particularly to the extent of intratumoral heterogeneity. In the present study, we obtained a series of post-surgery puncture samples from a breast cancer patient with a 4 × 3.5 × 2 cm tumor in its original size. Immunohistochemistry for Ki-67, COX-2, and CA IX was performed and the expression levels within the breast cancer tumor mass were evaluated in the reconstructed 3D models. To further evaluate the intratumoral heterogeneity, we performed high throughput whole transcriptome sequencing of 12 samples from different spatial positions within the tumor tissue. Comparing the reconstructed 3D distribution of biomarkers with projected tumor growth models, asymmetric and heterogeneous expansion of tumor mass was found to be possibly influenced by factors such as blood supply, inflammation and/or hypoxia stimulations, as suggested from the correlation between the results of Ki-67 and CA IX or COX-2 staining. Furthermore, high-throughput RNA sequencing data provided additional information for profiling the intratumoral heterogeneity and expanded the understanding of cancer progression. Digital technology for medical imaging once properly integrated with molecular pathology examinations will become particularly helpful in dissecting out in-depth information for precision medicine. We prospect that this approach, facilitated by rapidly advancing artificial intelligence, could provide new insights for clinical decision-making in the future. Strategies for the continuous development from the present study for better performance and application were discussed.

First reported advanced pancreatic cancer with hyperprogression treated with PD-1 blockade combined with chemotherapy: a case report and literature review.

Pancreatic cancer is among the most immune-resistant tumor types due to its unique tumor microenvironment and low cancer immunogenicity. Single-agent immune modulators have thus far proven clinically ineffective. However, a growing body of evidence suggests that combination of these modulators with other strategies could unlock the potential of immunotherapy in pancreatic cancer. Herein, we describe the case of a 59-year-old male with metastatic pancreatic ductal adenocarcinoma, referred to our center to receive immunotherapy (serplulimab, a novel anti-PD-1 antibody) combined with chemotherapy (gemcitabine/nab-paclitaxel). During the initial three treatment cycles, the patient was assessed as having stable disease (SD) according to RECIST 1.1 criteria. However, following two additional cycles of combination therapy, the primary tumor mass increased from 4.9cm to 13.2cm, accompanied by the development of new lung lesions, ascites, and pelvic metastases. He succumbed to respiratory failure one month later. Retrospective analysis revealed that the patient had MDM4 amplification, identified as a high-risk factor for hyperprogressive disease (HPD). To our knowledge, this is the first reported case of HPD in pancreatic cancer with multiple metastases treated using combination therapy. We investigated the potential mechanisms and reviewed the latest literature on predictive factors for HPD. These findings suggest that while chemotherapy combined with immunotherapy may hold promise for treating pancreatic cancer, it is imperative to identify and closely monitor patients with high-risk factors for HPD when using immunotherapy.

Death Due to Embolic Renal Cell Carcinoma

Abstract Introduction/Objective While most pulmonary embolisms are composed of blood clot resulting from venous stasis, tumor embolism is rarely encountered. We describe an autopsy patient with an unexpected renal cell carcinoma (RCC) who expired after a massive tumor embolism to the pulmonary artery. Methods/Case Report A 56-year-old male presented with complaints of shortness of breath and was found to have a large right-sided pulmonary embolism with an incidental finding of a 9.0 cm right kidney mass on imaging. He was subsequently admitted for further management consisting of thrombo-aspiration. The procedure was largely unsuccessful and the patient’s respiratory status continued to decline and he subsequently expired. On autopsy, a 9.3 x 6.2 x 6.0 cm, yellow-tan, well-defined mass was discovered primarily in the lower pole of the right kidney with invasion into the hilar structures. The mass grossly appeared to be invading into the renal vein. Two large yellow-tan emboli were found to be causing significant obstruction of the inferior vena cava at the level of the right renal vein and in the right pulmonary artery. Microscopic evaluation revealed the kidney tumor to be consistent with renal cell carcinoma morphologically and immunohistochemically. Interestingly, all emboli discovered at autopsy are primarily composed of sheets of cells identical to the patient’s renal mass. It is therefore concluded that the patient’s kidney cancer invaded into the renal vein and embolized to the pulmonary artery, ultimately resulting in death. Results (if a Case Study enter NA) NA Conclusion Tumor embolism is a rare cause of death. Renal cell carcinoma is a relatively common neoplasm that has been described to present as a tumor thrombus in 13.3% of patients. Of these patients with RCC tumor thrombus, 1% embolize to the right atrium. Our case represents this rare phenomenon and demonstrates why it is crucial to confirm the contents of a pulmonary embolism, as not all are composed of blood components alone.

Non-homogenous intratumor ionizing radiation doses synergize with PD1 and CXCR2 blockade

The efficacy and side effects of radiotherapy (RT) depend on parameters like dose and the volume of irradiated tissue. RT induces modulations of the tumor immune microenvironment (TIME) that are dependent on the dose. Low dose RT (LDRT, i.e., single doses of 0.5–2 Gy) has been shown to promote immune infiltration into the tumor. Here we hypothesize that partial tumor irradiation combining the immunostimulatory/non-lethal properties of LDRT with cell killing/shrinkage properties of high dose RT (HDRT) within the same tumor mass could enhance anti-tumor responses when combined with immunomodulators. In models of colorectal and breast cancer in immunocompetent female mice, partial irradiation (PI) with millimetric precision to deliver LDRT (2 Gy) and HDRT (16 Gy) within the same tumor induces substantial tumor control when combined with anti-PD1. Using flow cytometry, cytokine profiling and single-cell RNA sequencing, we identify a crosstalk between the TIME of the differentially irradiated tumor volumes. PI reshapes tumor-infiltrating CD8+ T cells into more cytotoxic and interferon-activated phenotypes but also increases the infiltration of pro-tumor neutrophils driven by CXCR2. The combination of the CXCR2 antagonist SB225002 with PD1 blockade and PI improves tumor control and mouse survival. Our results suggest a strategy to reduce RT toxicity and improve the therapeutic index of RT and immune checkpoint combinations.

Fu-Zheng-Li-Fei Recipe (FZLFR) in the treatment of cancer cachexia: Exploration of the efficacy and molecular mechanism based on chemical characterization, experimental research and network pharmacology

Ethnopharmacological relevanceFZLFR was derived from a classic traditional Chinese medicine recipe, the Shiquan-Dabu decoction. FZLFR is commonly used in clinical practice to address muscle loss and associated cancer cachexia. However, the mechanism of by which FZLFR acts in cancer cachexia remains unclear. AimThis study aimed to assess the effects and explore the potential mechanism of action of FZLFR in treating cancer cachexia. MethodsCancer cachexia was induced by inoculating Lewis lung carcinoma cells into the right flank of male C57BL/6 mice. The efficacy of FZLFR was evaluated by comparing changes in body weight, tumor mass, food intake, survival time, weight, and cross-sectional area of the gastrocnemius and anterior tibial muscles. Moreover, inflammatory cytokines, such as TNF-α and IL-6, were detected by ELISA. The chemical components of FZLFR were analyzed using ultra-performance liquid chromatography-coupled with time-of-flight mass spectrometry. Network pharmacology analysis was performed to screen the core targets and potential pathways involved in FZLFR treatment of cancer cachexia. Molecular docking was used to analyze the binding ability of the core targets and key compounds. The expression levels of core targets and targets correlated with skeletal muscle atrophy were also assessed using western blotting. ResultsFZLFR enhanced the food intake and survival rate of mice with cancer cachexia. It also alleviated tumor-induced body weight loss, tumor growth, and muscle fiber atrophy in these mice. Additionally, it improved the weight and cross-sectional area of the gastrocnemius and anterior tibial muscles. FZLFR down-regulated the serum levels of TNF-α and IL-6. UPLC-ESI-Q-TOF-MS analysis identified 184 compounds in FZLFR. Network pharmacology analysis predicted that TNF signaling pathway, ErbB signaling pathway and VEGF signaling pathway might be essential in FZLFR action. Molecular docking showed that kaempferol, upafolin, apigenin, and luteolin might play key roles in FZLFR treatment. Moreover, FZLFR decreased MAFBx1, MURF1, NF-κB, TWEAK, MAPK8, and EGFR expression levels. FZLFR enhanced the expression of VEGFA and ESR1, as demonstrated by western blotting. ConclusionsFZLFR increased food intake and alleviated muscle atrophy in mice with cancer cachexia. The potential pharmacological mechanisms underlying its anticachexia effects include reducing inflammation, enhancing muscle vascular growth, inhibiting tumor angiogenesis, and modulating estrogen receptors.

Plasmonic semi shells derived from simultaneous in situ gold growth and anisotropic acid etching of ZIF-8 for photothermal ablation of metastatic breast tumor

Open nanoshells such as nanobowls or nanocups collectively described as ‘semi shells’ have unique plasmonic properties due to their lack of symmetry. So far, their fabrication was based on multistep and laborious methods such as solid state sputter coating or selective deposition/etching using sacrificial templates. In this work, we report a rapid one step colloidal synthetic protocol for PEGylated semi-shell (SS) fabrication by simultaneous facet specific anisotropic chemical etching of rhombic dodecahedral ZIF-8 and heterogenous nucleation & growth of gold. The SS possesses a strong localized surface plasmon resonance in the near-infrared region, which is retained after surface passivation with polyethylene glycol and subsequent cryopreservation for extended shelf-life. Freshly reconstituted PEGylated SS was found to be safe & non-toxic in healthy C57BL/6 mice post intravenous administration. The PEGylated SS displayed significant photothermal efficiency of ~37% with 808 nm laser irradiation. Preclinical assessment of intra-tumoral photothermal efficacy indicated complete remission of primary breast tumor mass with insignificant metastasis to vital organs in 4T1 FL2 tumor bearing CD1 nude mice. Further, PEGylated SS mediated photothermal therapy also yielded morbidity free survivael of 75% for up to 90 days, indicating their potential to significantly improve outcomes in advanced breast tumors.

Acromegalia em felinos

Acromegaly in felines occurs mainly due to a pituitary adenoma of somatotropic cells, and presents slow and progressive evolution, responsible for increasing the production and secretion of growth hormones (GH). This condition is common in senile or adult male domestic cats, neutered and with short hair. The pathophysiology is due to the excessive release of GH in the adenohypophysis region, whose synthesis is regulated by growth hormone-releasing hormone (GHRH) and somatostatin, responsible for stimulating or inhibiting the secretory axis, respectively. The anabolic action of GH is responsible for increasing the secretion of IGF-1, which is mainly responsible for the clinical signs of acromegaly, such as body growth and organomegaly. The catabolic effect refers to insulin resistance. Clinical signs may be associated with secondary diabetes mellitus (DM), weight gain, exacerbated growth of various tissues and neurological signs as the tumor mass grows. The diagnosis of the disease can be performed through laboratory, imaging and endocrine tests such as the specific immunoassay for GH and/or insulin-like growth factor 1 (IGF-1). Treatment is based on controlling the DM that develops secondary to it, as well as on attempts to reduce or even inhibit the excess release of GH. Treatment can be performed with somatostatin analogues and dopamine agonists. The use of stereotactic radiotherapy can also be recommended, with favorable results for tumor reduction, as well as the surgical technique of transsphenoidal hypophysectomy, which presents better results than other techniques but is a complex surgical procedure. This project aims to inform veterinarians of this endocrine disease and its main currently recognized diagnoses and treatments, emphasizing the need to establish a differential diagnosis for difficult-to-control DM.

Kinase library screening identifies IGF-1R as an oncogenic vulnerability in intrahepatic cholangiocarcinoma stem-like cells

BackgroundIntrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer of the peripheral bile ducts and is recognized by the abundance of cancer stem-like cells (CSCs) within the tumor mass. While CSC markers in iCCA are well-defined, the molecular vulnerabilities of this subpopulation remain elusive. MethodsThe 96-well, three dimensional (3D) tumorsphere culture was adapted from a well-established CSC model, validated for CSC markers through gene expression analysis. Kinase library screening was then conducted to reveal potential oncogenic vulnerable pathways. RNA interference was utilized to stably silence the candidate gene in three iCCA cell lines and its impact on iCCA cell proliferation and tumorsphere formation efficiency (TFE) was evaluated. ResultsKinase inhibitor library screening identified the top 50 kinase inhibitors crucial for tumorsphere viability, with 11 inhibitors targeting the IGF-1R/PI3K/AKT axis. Further dose-dependent analysis of the top ‘hit’ inhibitors confirmed IGF-1R as the candidate molecule. Upon stably silencing of IGF-1R, all three iCCA cell lines exhibited decreased AKT activation, impeded proliferation and reduced TFE, indicating a decline in CSC subpopulations. ConclusionsIGF-1R plays a critical role in maintaining iCCA-stem like cell populations. General significanceOur data highlight the potential utility of IGF-1R as a prognostic marker of iCCA and a therapeutic target for eliminating its CSC subpopulation.

7564 Adrenal Pheochromocytoma In A Clinically Inapparent Adrenal Mass

Abstract Disclosure: L. Medina Mora: None. S. Htoo: None. A. Sanchez Ruiz: None. M. Harshan: None. A. Busta: None. Introduction: Pheochromocytomas (PCC) are rare tumors that arise from the adrenal medulla, with an estimated annual incidence of 0.8 per 100,000 person-years. These tumors have been associated with significant morbidity and mortality and are considered among the most life-threatening endocrine diseases, particularly if left undiagnosed. Its symptoms can be related to the tumor's mass effect or catecholamine excess. As a result, they can mimic other conditions, often leading to delayed or incorrect diagnosis. A study conducted on 296 patients with PCC treated from 2005 to 2016 found that 61% were discovered incidentally through cross-sectional imaging (CSI). The widespread use of CSI in recent years has led to the identification of asymptomatic cases that would have otherwise gone undetected. In this case, we present a middle-aged female who was incidentally found to have a PCC. Case Report: A 59-year-old female with a history of hypertension, cerebrovascular accident, pulmonary hypertension, systolic heart failure, mitral valve replacement, and asthma presented to the clinic for evaluation of a right adrenal lesion measuring 4.2 x 3.5 cm found during an emergency room visit during the evaluation of chest pain. She had no known family history of brain or endocrine disorders. Her lab results showed elevated plasma metanephrine and normetanephrine to 578.4 (reference range: 0-88) and 459.9 (reference: 0-244), respectively. Additionally, her 24-hour urine metanephrine was elevated to 984 mcg (normal range: 36-209), and Chromogranin A was 164.3 (reference range: 0-101). The rest of her labs, including cortisol, renin, aldosterone, and DHEA-S were unremarkable. A CT with and without contrast revealed a 3.0 x 3.5 x 5.1 cm solid non-calcified right adrenal mass measuring 39 Hounsfield units (HU). In addition, it measured 53 HU in the venous phase and 61 HU in the 15-minute delayed phase (relative washout of <1%; absolute washout of <7%). The patient was treated with alpha-blockers and underwent a robotic-assisted right adrenalectomy. The pathology was significant for a 5.4 cm well-differentiated PCC. The tumor had extended into but not beyond the adrenal capsule. The postoperative course of the patient was uncomplicated. Discussion: After a PCC is detected, the most effective treatment option is to surgically remove it. This procedure necessitates a combination of alpha and beta-blockade to regulate blood pressure and prevent a hypertensive crisis. Despite the success of surgery, there is still uncertainty about the optimal follow-up after the procedure, which often leads to many patients being lost during the process. Furthermore, even a decade after the initial surgery, there remains a substantial likelihood of illness reoccurrence or metastasis, making the situation even more complex. Therefore, it is crucial to adhere to a lifelong follow-up plan that includes annual biochemical testing. Presentation: 6/2/2024

8659 Aldosterone-Secreting Adrenocortical Carcinoma: A Rare Cause Of Primary Hyperaldosteronism Associated With Dismal Outcome

Abstract Disclosure: S. Beeby: None. C.H. Huzita: None. F.Q. Aratani: None. L.S. Motomia: None. F. Coelho: None. M. Polo: None. C.R. Victor: None. A.O. Hoff: None. J. Chambo: None. V. Srougi: None. F. Ledesma: None. A. Latronico: None. M.Q. Almeida: None. B.B. Mendonca: None. M.C. Fragoso: None. Background: Adrenocortical carcinoma (ACC) is a rare and one of the most aggressive solid tumors, with an incidence of 1-2 cases per million. In adults, hormonal excess is usually manifested by ACTH-independent Cushing's syndrome or mixed endocrine syndrome due to cortisol and androgen production. Isolated aldosterone secretion is an extremely rare condition, with an estimated 2.5% of patients with ACC. We aimed to describe two patients with aldosterone-secreting ACC with poor outcomes. Case 1 - A 34-year-old male who was diagnosed with hypertension at 29 years of age, associated with hypokalemia needing intravenous potassium replacement therapy. Diagnosis of primary hyperaldosteronism was established with aldosterone levels of 72 ng/dL (RR < 23.1 ng/dL) and renin activity of 1.1 ng/mL/h (RR 0.3 to 5.8 ng/mL/h. An abdominal CT scan identified a tumor mass of 9.5 x 8.0 x 4.5 cm. He underwent a left adrenalectomy and histological and immunohistochemistry data suggested an adrenocortical carcinoma (modified Weiss score 5/7, Ki67 40%). Initial staging was ENSAT III and a Helsinki score of 48. There was transient improvement, however recent laboratory studies showed an increase in aldosterone (66,9 ng/dL) accompanied by new episodes of hypokalemia. CT scans on follow-up showed recurrence of disease, with the presence of nodules on the surgical site and abdominal wall. He received 3 lines of systemic chemotherapy and mitotane and underwent 2 other surgical procedures to treat the metastatic lesions. Currently, overall survival is 3 years. Case 2 - A 44-year-old female incidentally found a right adrenal mass (6.6 x 6.4 cm) on MRI during the investigation of elevated liver enzymes and abdominal pain. Laboratory studies showed hypokalemia, with potassium levels of 2 mEq/L (RR 3.5-5 mEq/L), aldosterone levels of 243 ng/dL (RR < 23.1 ng/dL), and renin of 12.2 uUI/mL (RR 4.4 - 46.1 uUI/mL). She underwent right adrenalectomy and histology and immunohistochemistry data showed a modified Weiss 7/7 and Ki67 of 80%. The patient had a germline pathogenic variant of TP53 (p.R337H). Initial staging was ENSAT III and a Helsinki score of 88. She received adjuvant mitotane and systemic chemotherapy. Even so, follow-up imaging showed hepatic metastatic disease, with an elevated aldosterone production surpassing 1000 ng/dL. The patient's overall survival was 2 years and she passed away during surgical procedure for resection of liver metastases. Discussion: ACC is a rare and aggressive tumor, and isolated aldosterone production by such tumors is extremely rare. We presented two cases with poor prognostic features and in which despite adjuvant mitotane and systemic chemotherapy there was disease progression. Due to the rarity of this condition, data on patient outcomes is limited, and further understanding of the molecular signature of these tumors could bring new insights on the tumorigenesis process. Presentation: 6/3/2024

8788 Implications of NTRK gene fusion in Papillary thyroid cancer

Abstract Disclosure: W. Medina-Torres: None. L. El Musa Penna: None. J. Segarra-Villafane: None. L.R. Sepulveda-Garcia: None. Z. Maisonet -Feliciano: None. I.C. Arroyo: None. M. Ramirez: None. M. Alvarado: None. L.A. Gonzalez-Rodriguez: None. V.J. Carlo: None. Thyroid cancer (TC) is the most common endocrine cancer. Papillary thyroid carcinoma (PTC) is the predominant contributor of this occurrence, comprising approximately 80% of all thyroid carcinomas. PTC has a good prognosis with a 5-year survival rate of more than 90% after resection. Nonetheless, factors such as tumor size, multifocality, nodal and distant metastases, characterize more aggressive cases including tall cell variant, columnar cell variant, and hobnail variant Aside from staging parameters, PTC behavior is mostly determined by morphologic variant. This is the case of 31 y/o female without known past medical history who was evaluated at endocrinology clinic due to a fine needle thyroid aspiration (FNA) positive for PTC, tall cell variant. Total thyroidectomy with central compartment dissection was performed. Pathology report presented a main tumoral mass of 3 cm but permeating multinodular pattern involving the entire gland with focal extrathyroidal extension, positive margins and six level VI positive lymph nodes. As per report, the tumor presented both papillary and follicular patterns of growth and other findings including oncocytic change, foci of clear cell change, low mitotic rate, and most notably "reverse polarization”. This pattern has the pathological features suggestive of the novel NTRK gene fusion mutation. The patient was treated with radioactive iodine (RAI) and one year post treatment there was evidence of elevated Thyroglobulin level at 904 ng/mLand thyroglobulin Ab at 2.48 IU/mL. A WBS +SPECT was done resulting in small uptake at left posterior thyroid bed and pulmonary intake. A chest CT revealed multiple bilateral sub centimeter nodules. Based on this result, a second course of RAI was given. Follow up neck ultrasound and chest CT presented persistent left level VI lymph nodes, increased amount of bilateral sub-centimeter pulmonary nodules and new thoracic(T11) lesion. FNA of left neck lymph nodes were positive for metastatic PTC for which left neck dissection was performed. Evaluation for actionable somatic mutations was requested based on resistance behavior, remarkable for TRIM33-NTRK1 chromosomal rearrangement. Patient was evaluated by Oncology service who started Larotrectinib treatment since it was approved for NTRK driven malignancies. Six-month post therapy patient achieved clinical and biochemical improvement. In the thyroid, NTRK-driven malignancies are rare and aggressive but treatable, in the evolving genomic era. As reviewed in the literature, NTRK fusion-positive TC exhibits distinctive clinicopathological features that could aid in identifying potential patients. Thus, in such patients who have PTC with non-classic pathologic patterns, specific molecular profile of the main tumor may have significant prognostic value that must be integrated into stratification system in order to provide target therapy on time. Presentation: 6/3/2024

8594 Pasireotide and Pasireotide Combined Treatment in Aggressive, Giant Pituitary Neuroendocrine Tumours

Abstract Disclosure: K. Ciszek: None. A. Bogusławska: None. M. Komisarz-Calik: None. J. Kunicki: None. A. Hubalewska-Dydejczyk: None. A. Gilis-Januszewska: None. Pasireotide is a second-generation somatostatin analogue that gained recognition as a treatment option for acromegaly and Cushing disease. Recently, there are single reports of pasireotide treatment in other subtype of pituitary neuroendocrine tumours (PitNETs).We present a case series of aggressive, giant PitNETs which were treated with pasireotide alone or as combined multimodal treatment. Case 1: A 59-year-old male presented in our Unit due to severe headaches and visual field deficits. The patient underwent transsphenoidal surgery (TSS) ten years ago. Histopathology results showed partially acidophilic adenoma (FSH- LH- GH- ACTH- PRL-). Control MRI showed tumour regrowth - 56x56x89mm and invasion of local structures. The patient was qualified for radiotherapy, to which he did not consent. Due to the progression of symptoms, temozolomide and pasireotide were introduced. After 5 months, significant improvement in headaches and vision was observed. In MRI stable pituitary mass was noted. Case 2: A 17-year-old male presented in our clinic due to daily severe headaches and peripheral vision loss who underwent two non-radical surgeries for dopamine-resistant giant prolactinoma. In control MRIs progressing mass 38x34x33mm invading local structures was observed. Due to resistance to dopamine agonists and worsening of the symptoms, pasireotide was introduced resulting in a decrease of headaches and improvement in vision. The tumour size remained stationary. Case 3: A 59-year-old male presented with severe headaches and life threatening tumour mass effect.In MRI a 48x48x33mm mass was observed. The patient underwent two non-radical TSS, 4 cycles of pasireotide, and cyberknife treatment. Histopathology showed gonadotroph PitNET. MRI showed tumour shrinkage to 45x46x29mm, with persistent severe headaches. The patient was re-qualified for pasireotide treatment. Case 4: A 33-year-old male reported to the Clinic due to severe headaches and vomiting. In MRI pituitary mass 33x39x55mm and a cerebral oedema were revealed. TSS with external ventricular drainage was performed -histopathology results showed densely granulated silent corticotroph adenoma subtype 1, Ki67<1%. After 3 months, MRI showed tumour progression to 39x40x30mm. Two emergency TSS followed by stereotactic radiotherapy were performed. Combined therapy with pasireotide, cabergoline and temozolomide was introduced. After 18 months, stabilization of the disease was observed with the complete disappearance of headaches. Conclusions: Our study demonstrates the clinical potential of pasireotide treatment in aggressive, giant PitNETs. The therapy alone, or in combination has a potential role in reducing the tumour size, and allows the stabilization of the disease. The analgesic and anti-inflammatory effect of pasireotide could potentially alleviate headaches in this subset of patients. Presentation: 6/2/2024

Sebaceous Adenoma in a Geriatric Poodle Dog: A Case Report

A 14-year-old black male Poodle was brought to the Animal Teaching Hospital, Udayana University by its owner with clinical signs of frequent licking of its left front paw. Upon examination, red bumps were observed on the left front leg, accompanied by small, round black spots scattered on the dorsal side of the body. Additionally, black nodules were present on the lower eyelids and hind limbs. Surgical intervention was undertaken to excise the tumor mass, with the animal under anesthesia induced by ketamine at 5 mg/kg BW intravenously. The reddish nodule was excised by performing an elliptical incision at the base of tumor. Postoperatively, the animal received an antibacterial injection comprising ceftriaxone and tazobactam at 25 mg/kg BW intramuscularly and antiseptic wound dressing for supportive care. Microscopic examination revealed neoplastic cells arranged into lobules of varying sizes and shapes within the tumor mass. These lobules consisted of differentiated sebocytes and basaloid cells. At the periphery of the neoplastic lobules, the basaloid cells displayed several layers and exhibited invasion with moderate anisocytosis. The mitotic index was no more than ten cells in one field of view. Based on these histopathological features, the tumor was confirmed to be a sebaceous adenoma. After a 10-month follow-up period, there were no signs of tumor recurrence observed.

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 (>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 (>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.