Histological Origin Research Articles

Giant Mesenteric Cyst of The Large Bowel: Case Report

Introduction: Mesenteric cysts are rare, benign intra-abdominal cystic lesions that arise from the mesentery, the tissue fold attaching the intestines to the abdominal wall. They can develop from the duodenum to the rectum. Mesenteric cysts have various histological origins, with lymphangiomas being more common in children and mesothelial cysts in young to middle-aged women. While they can remain asymptomatic, they may also cause complications such as intestinal obstruction or perforation. Complete resection is the preferred treatment due to its lower recurrence rate. Case Presentation: A 48-year-old female with a medical history of systemic arterial hypertension, allergies, hysterectomy, appendectomy, cesarean section, right axillary lipoma resection, and a cyst in the left zygomatic region, presented in June 2021 with dull, constant pelvic pain. Over time, her symptoms progressed to include volume increase, fatigue upon sitting, constipation, and hand tremors. Imaging studies revealed a large cystic lesion extending from the left ovary. In January 2024, an abdominal ultrasound showed a complex ovarian cyst (O-RADS 4). Surgical exploration revealed a mesenteric cyst associated with the sigmoid colon, which was resected along with a distal segment of the descending and sigmoid colon, preserving the left colic artery. The patient recovered well postoperatively, with proper colostomy function. Discussion: Mesenteric cysts are benign tumors that can occur throughout the gastrointestinal tract, most commonly in the small bowel mesentery. Their clinical presentation can range from asymptomatic to acute abdominal pain secondary to complications such as intestinal obstruction or cyst rupture. Diagnostic imaging typically involves ultrasound, CT, and MRI. Surgical resection is the treatment of choice to prevent recurrence. The prognosis following complete cyst excision is favorable, with no reported recurrences. Conclusion: Mesenteric cysts present a diagnostic challenge due to their wide range of symptoms. The recommended treatment, as supported by literature, is complete resection to minimize recurrence. Our case followed this approach, and the patient showed a positive clinical outcome

Modern approaches for management patients with craniofacial tumors (literature review)

Despite a significant amount of information on approaches to managing patients with craniofacial tumors, the increasing number of modern high-tech technologies, there remain a number of controversial issues regarding the choice of treatment strategy that fully satisfies the requirements of objective assessment of effectiveness and the improvement of quality of life for patients suffering from oncological disease. Craniofacial approaches sufficiently adhere to oncological principles and allow for the removal of even extensive tumors which greatly improve immediate and long-term outcomes, reliably enhancing quality of life, which is the most important task in the surgery of malignant skull base tumors. As evident from the aforementioned modifications and classical approaches to reconstruction of defects following craniofacial resections, in order to summarize the vast amount of information on the advantages and disadvantages of corresponding methods, a multicenter independent prospective study is needed, during which data from different clinics would undergo critical analysis using modern evidence-based medicine methods. On the path to methodological comprehension of existing concepts and actions towards creating one’s own algorithms lies a multifactorial analysis of personal experience in management and undoubtedly the care of patients from a group with such an unfavorable prognosis for survival. An immediate observation that follows the realization of the practical significance of a surgical treatment algorithm common to all physicians and mid-level medical staff is that the most effective achievement of the above task lies in learning from one’s own mistakes during patient care. Very encouraging research results, in which attempts are made at mastering new materials, herald a future scientific breakthrough in craniofacial reconstruction. The use of bioprosthetics and synthetic analogs is particularly relevant for those patients for whom reconstruction using their own tissues is contraindicated for various reasons. This article demonstrates the most outstanding achievements in the treatment of patients with sinonasal tumors.Malignant tumors of the sinonasal region are rare and highly diverse in their histological origin neoplasms, accounting for an average of 0.2–1.1 % of all newly diagnosed tumors. Risk factors, to varying degrees pathogenetically linked to disease progression, include a mutation of the TP53 gene in 80 % of cases, prolonged exposure to industrial air pollutants, smoking, male gender, and age over 55 years in 85 % of cases, infection with human papillomavirus and Epstein–Barr virus. Despite a substantial amount of information on approaches to managing this patient population, the increasing number of modern technology-intensive methods has led to ongoing debates regarding the selection of a treatment strategy that fully meets the requirements for objectively assessing efficacy and improving the quality of life of patients suffering from oncological disease.Aim. To investigate modern approaches to treatment of patients with tumors of the craniocephalic location, identify factors of surgical treatment success and favorable long-term prognosis, develop a management algorithm for patients with sinonasal neoplasms, provide rationale for using various reconstruction techniques for postresection defects. Systemic approach to the analysis of effectiveness and expediency of modern approaches to treatment of patients with tumors of the craniocephalic region requires integration of several key concepts. Taking into account individual characteristics of the patient by an experienced surgical team can lead to good treatment results including increased survival rates.Development of algorithms for management of patients of this category and individualization of selection of reconstructive techniques are important problems in practical healthcare. Minimization of complications is one of the main goals of postoperative patient observation. The optimal approach to treatment even in this prospectless in the context of survival and social rehabilitation group of patients assumes greatest possible preservation of facial esthetic features and increased quality of life which can be achieved only with well-coordinated work of highly professional interdisciplinary team.

Using digital PCR to investigate the prevalence of KRAS variants in pituitary tumours.

Pituitary tumours (PT) are formed in the pituitary gland, a small gland situated at the base of the brain. These tumours can be categorized according to their histological origin and hormone production. In surgical series, non-functioning PT are the commonest subtype, followed by functioning somatotroph and corticotroph tumours. Different somatic alterations have been implicated in the pathogenesis of these tumours and the objective of our study was to expand our previous new finding of KRAS pathogenic genetic variants in pituitary tumours. We conducted a digital polymerase chain reaction (PCR) analysis on formalin-fixed paraffin-embedded tissue blocks belonging to 189 patients. The results showed that, from the 184 pituitary tumours with good quality samples, 13 tumours (7.1%) presented mutant KRAS. The median age of the mutated group was 47 years old (range 19-77) and most patients with mutant KRAS tumours were from the female gender (61.5%, 8/13) and non-functioning subtype. For the first-time, mutant KRAS in corticotroph and somatotroph tumours were detected, and the variants showed low allele frequencies. In conclusion, we demonstrated that pituitary tumours might have mutant KRAS, and these data were not previously described probably due to lack of sensitivity of previous technologies. By identifying these variants, even at minimal levels, we open doors to a deeper understanding of the tumour microenvironment, clonal evolution and potential therapeutic targets.

Analysis of real world FRα testing in ovarian, fallopian tube, and primary peritoneal cancers

BackgroundEpithelial ovarian cancer (EOC) remains a significant challenge in gynecologic oncology, particularly in the context of platinum-resistant disease. Mirvetuximab soravtansine (MIRV), was approved after trials revealed favorable response and survival outcomes. MIRV targets folate receptor alpha (FRα), a cell-surface receptor that is overexpressed in EOC and has been associated with aggressive disease phenotypes. MethodsThis retrospective study analyzed 425 patient samples tested for FRα using the VENTANA® FOLR1 RxDx immunohistochemical assay. The patient cohort included cases with high grade serous carcinoma predominantly, tested across various anatomical sites. Statistical analysis examined the correlation between FRα positivity and clinical parameters such as tumor site and histology. ResultsFRα was highly expressed in 36.3 % of the cases, with a significant association between FRα positivity and high grade serous ovarian histology. Tumor samples from the ovary, fallopian tube, adnexa, and dominant pelvic masses showed higher FRα positivity compared to metastatic sites (positive rates of 44.4 % vs 32.5 %, p = 0.02), highlighting the potential influence of tumor origin on expression of FRα. Time between sample collection and testing did not impact FRα expression, with sample testing spread over a median of 19.5 months post-collection. Eight patients had more than one specimen tested, of which 3 (37.5 %) had discordant results when a subsequent specimen was tested. ConclusionOur results highlight a need for standardized protocols for FRα testing to ensure accurate biomarker evaluation across varied clinical settings. The heterogeneity in FRα expression, influenced by tumor histology and anatomical origin, warrant further investigation to optimize therapeutic outcomes. Prior presentationPreliminary findings from this study were previously presented in poster format at the Society of Gynecologic Oncology 2024 Annual Metting. We confirm that the submission complies with the journal requirements.

Concurrent spinal schwannoma and meningioma without neurofibromatosis: case presentation and review of literature

BackgroundConcurrent multiple tumors developing in the spinal cord are rare, except for in genetic disorders, such as neurofibromatosis and von Hippel–Lindau disease. The presence of multiple histologically different spinal tumors in the absence of NF-2 is extremely rare. Schwannoma and meningioma can be explained partly by their common origin from the same mesenchymal cell, there is currently no explanation for the simultaneous existence of different spinal tumors other than simple coincidence.Case presentationAfter review of literature, there are thirteen such cases reported in the literature in addition to the present case. The current patient presents with lower limb weakness, and the patient radiology revealed intradural mass opposite the fourth lumbar vertebra with contrast enhancement and intradural extramedullary mass opposite the tenth dorsal vertebra with contrast enhancement in MRI spine. The coexistence of these tumors may be coincidental or might be due to a common histological origin of the Schwann cells and the meningocytes.ConclusionSchwannoma and meningioma have different radiological characteristics and require different managing procedures such as dural base coagulation in meningiomas and rootlet sacrifice in schwannomas.

Rare carcinoma of the ampulla of Vater with mixed histologies: A case report

The current case is about a 62-year-old female presented with persistent fever for 10 days and yellowing of the skin for 5 days at our outpatient clinic. Laboratory tests revealed elevated levels of total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase. Abdominal computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography revealed a mass in the ampulla of Vater, as well as dilatation of the intra- and extra-hepatic bile and pancreatic ducts. The patient underwent pancreaticoduodenectomy under general anesthesia. Post-operative pathological and immunohistochemical results confirmed a tumor located in the ampulla, measuring 1.5 × 1 × 1 cm. The main component of the tumor was a moderately differentiated pancreaticobiliary adenocarcinoma (ADC), combined with squamous cell carcinoma (SCC) as well as small cell neuroendocrine carcinoma (SCNEC). The cancer tissue infiltrated the entire intestinal wall, with no invasion of microvessels, lymphatic vessels, or nerves observed. Until 46 months later, there was no tumor recurrence or distant metastasis. We present an uncommon case of ADC of the ampulla of Vater combined with SCC and SCNEC. Carcinoma of the ampulla of Vater may have mixed histological components; therefore, in cases of ampullary carcinoma, appropriate specimen collection is necessary, and further studies with more focus on histological origins are required.

Treatment Considerations to Overcome the Barriers Associated with Skin Cancer Targeting

: Skin cancer is a prevalent and diverse group of malignancies affecting the skin, with three primary types: basal cell carcinoma, squamous cell carcinoma, and melanoma. Each subtype varies in terms of its histological origin, behavior, and potential for metastasis. Despite advances in treatment, skin cancer poses challenges due to biological barriers that hinder drug delivery, multidrug resistance mechanisms that limit treatment effectiveness, and the complex interplay of genetic alterations driving tumorigenesis. Current treatment strategies encompass a spectrum of approaches, including chemotherapies, immunotherapies, gene therapies, and innovative techniques such as photothermal therapy, iontophoretic therapy, electroporation therapy, microneedle array therapy, and nanotechnology- based treatments. The latter involves liposomes, niosomes, carbon nanotubes, dendrimers, hydrogels, and gold nanoparticles, all tailored to enhance drug delivery and therapeutic efficacy. Additionally, herbal drug-based therapy harnesses the potential of natural compounds to target various aspects of skin cancer progression. This review provides an overview of skin cancer types, challenges in treatment, and an extensive exploration of current therapeutic strategies, highlighting the everevolving landscape of innovative approaches that promise to transform how skin cancer is managed.

Changes in WHO classification of adrenal tumors and new ideas for multi-dimensional diagnosis and treatment

In 2022, WHO updated the classification and concept of adrenal cortical and medullary tumors. In terms of adrenal cortical tumors, the WHO classification further standardizes the nomenclature of nodular adrenal cortical disease and refines the pathological classification of primary aldosteronism. In terms of adrenal medullary tumors, the WHO classification unifies the concepts of pheochromocytoma and paraganglioma, and reclassifies various concepts, including paraganglioma-like neuroendocrine tumors. The new standards not only cover the clinical manifestations of the disease, but also include other multiple aspects such as the histological origin of the disease, immunohistochemical manifestations, physiological mechanisms of the disease, hereditary susceptibility and prognostic factors. This article intends to explore how to improve the diagnostic and therapeutic level of adrenal tumors.

New insights into acinic cell carcinoma of the breast: clinicopathology, origin of histology, molecular features, prognosis, and treatment.

Acinic cell carcinoma (AciCC) of the breast is a rare malignant epithelial neoplasm, with approximately 60 cases reported in the literature. It predominantly affects women and exhibits significant histological heterogeneity. The diagnosis of breast AciCC is primarily based on the presence of eosinophilic and/or basophilic granular cytoplasm and markers of serous acinar differentiation. Despite being considered a low-grade variant of conventional triple-negative breast cancer (TNBC), over 25% of patients with breast AciCC have adverse clinical outcomes. Additionally, in early research, microglandular adenosis (MGA) and atypical MGA were considered potential precursors for various breast cancers, including intraductal carcinoma, invasive ductal carcinoma, adenoid cystic carcinoma, metaplastic carcinoma, and AciCC. Similarly, some studies have proposed that breast AciCC should be considered a type of carcinoma developing in MGA with acinic cell differentiation rather than a distinct entity. Therefore, the pathogenesis of breast AciCC has not yet been clarified. Moreover, to the best of our knowledge, the literature has not summarized the latest prognosis and treatment of breast AciCC. In this review, we synthesized the current literature and the latest developments, aiming at exploring the clinicopathology, histological origin, molecular features, prognosis, and treatment of breast AciCC from a novel perspective.

Temporary halo fixation and radiotherapy as alternative to long-construct spondylodesis in patients with multiple unstable cervical metastases

Background and purposeCurrently no minimally invasive surgical treatment exists to provide immediate stability for unstable cervical/cervicothoracic metastases. Long-construct spondylodesis carries a high complication risk and has severe impact on residual range of motion. This study explores temporary halo fixation and radiotherapy as an alternative to long-construct cervical spondylodesis. Materials and methodsThis retrospective cohort study included twenty patients with multiple unstable cervical metastases treated between 2013–2023. All patients underwent halo fixation for an intended duration of three months to allow for safe reossification of lytic lesions following radiotherapy, with a dose fractionation scheme best suited to the histological origin of the tumor. ResultsImmobilization with halo fixation lasted a median 83 days (range, 41–132 days). Radiotherapy started on average 7 days after halo fixation (range, −35–118 days). The median pain score at baseline was 8, and was 0 at halo removal and at last follow-up. All patients had no or minor neurological deficits at baseline and did not develop new neurological deficits. At halo removal, 17/18 patients showed radiographic evidence of reossification. The majority of patients experienced minor limitations or had full range of motion of the neck at last follow-up. ConclusionPatients with multiple unstable cervical metastases treated with halo fixation and radiotherapy showed complete pain response or substantial pain reduction, reossification of the vertebrae and a, mostly, preserved range of motion. In selected neurologically intact patients, this treatment might be a patient-friendly alternative to fixation. Prospective evaluation of this treatment combination is needed.

Application of cell blocks to assist in precise cytological diagnosis of serous effusion

Objective: To investigate the importance of cell block and immunohistochemistry in the accurate diagnosis of serous effusion. Methods: A retrospective study was conducted on 3 124 cases of serous effusion from the Department of Pathology, Beijing Hospital from 2018 to 2022, include 2 213 cases of pleural effusion, 768 cases of peritoneal effusion, 143 cases of pericardial effusion. There were 1 699 males (54.4%) and 1 425 females (45.6%), average age 69 years old. Of which 1 292 cases were prepared with cell blocks and examined with immunohistochemical stain. Results: The percentage of malignant diagnosis increased from 64.9% (839/1 292) to 84.0% (1 086/1 292) after cell block preparation, and 1 086 cases were accurately diagnosed with histological type and/or origin of primary tumor. The undetermined diagnosis of suspected malignancy decreased from 13.3% (172/1 292) to 0.1% (1/1 292) and that of atypical hyperplasia from 18.8% (243/1 292) to 0.4% (5/1 292). The negative result for malignancy rate increased from 3.0% (38/1 292) to 15.5% (200/1 292). The differences highlighted above were statistically significant (Pearson's chi-squared test=12.739, P<0.01). Conclusion: Application of immunohistochemistry based on cell block can significantly improve malignant diagnosis in serous effusion, identify tumor origin and histological type as well as decrease the uncertain diagnosis.

Synchronous laryngeal cancer.

Multiple primary cancers are usually defined as primary malignant tumors of different histological origins in one person. Synchronous cancers are defined as two or more primary cancers diagnosed in the same patient at the same time or within six months after identifying the first tumor, and those cancers that develop at more than a six-month interval are termed as metachronous multiple primary cancers. Our study comprised of a patient with synchronous laryngeal cancer with double localizations. The case was solved through surgical excision of the tumors. Histopathological and immunohistochemistry examinations revealed synchronous laryngeal cancer. Laryngeal cancer should usually be managed through surgical resection, followed by oncological treatment.

Epidemiology, Pattern, and Survival of Multiple Primary Malignant Neoplasms in Southeast Iran: Results of Kerman Population-Based Cancer Registry 2014-2020.

Cancer survivors may experience a subsequent primary cancer that affects their survival and quality of life. This study aimed to investigate the epidemiology of multiple primary malignant neoplasms (MPMNs) in Kerman province, southeast Iran during 2014-2020. In this retrospective cohort study, all patients who had been diagnosed with primary cancers and registered with the Kerman Cancer Registry Program (KPBCR) during 2014-2020 were included. MPMNs were defined as primary malignant tumors arising in different sites and/or were of different histological or morphological origins. If the second malignancy was diagnosed within the first six months from the diagnosis of the first tumor it was considered synchronous, and if after six months it was defined as metachronous. Logistic regression was used to analyze the relationship between age, sex, and primary cancer site with incidence and survival of secondary in the entire population. Of 26,315 patients registered with a primary cancer diagnosis, 492 (1.86%) developed subsequent primary cancers. The most common type of secondary cancer was skin and mucosa (n=131, 26.63%) followed by urogenital (n=115, 23.37%), followed by, gastrointestinal (n=62, 14.45%), and breast neoplasms (n=57, 11.59%). Most patients had metachronous tumors (n=350, 71.13%). The primary cancer site (Skin and mucosa, urogenital, and breast) was significantly associated with developing subsequent cancer among cancer survivors. The overall 5-year survival of MPMNs cases was over 50%. Older age at diagnosis (HR= 1.02) and having synchronous tumors (HR=1.41) were negatively associated with the survival time of patients with MPMNs. Both patients and physicians should be taught about the importance of prevention and the provision of care and screening services among cancer survivors. Studying the epidemiology, susceptibility, and risk factors of MPMNs among cancer survivors will open windows to a better understanding of this phenomenon and policy making.

Radical cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal sarcomatosis: Results from a reference center and considerations based on current evidence

IntroductionPeritoneal sarcomatosis is a rare disease, with multiple histological origins and poor overall prognosis. The option of radical cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The results of a surgical team experienced in these procedures are analyzed and discussed based on the available evidence. MethodsStudy on a prospective database of patients with peritoneal sarcomatosis who underwent CRS and HIPEC, from 2016 to 2022, in a national reference center for sarcomas and peritoneal oncological surgery, who met the established inclusion/exclusion criteria. Results23 patients were included in the study, with a median age of 53 years (6−68). Recurrent/persistent clinical presentation predominated (78.3%). Visceral origin (including GIST and non-GIST peritoneal) accounted for 47.8% of patients, compared to 43.5% uterine and 8.7% retroperitoneal. The median PCI was 17 (3−36), with CC0 cytoreduction of 87%. Postoperative morbidity (Dindo Clavien III–IV) of 13%, with no postoperative mortality in the series. Overall survival and disease-free survival at 5 years were 64% and 34%, respectively. Histological grade was the most influential prognostic factor for survival. ConclusionsThe results of the series, with low morbidity, support the benefit of radical peritoneal oncological surgery in patients with peritoneal sarcomatosis after adequate selection, as long as it is performed in high-volume centers, experienced surgeons and expert multidisciplinary teams. However, the role of HIPEC remains to be demonstrated and pending future studies.

Cirugía citorreductora radical y quimioterapia intraperitoneal hipertérmica en el tratamiento de la sarcomatosis peritoneal: resultados de un centro referente y reflexiones sobre la evidencia actual

IntroductionPeritoneal sarcomatosis is a rare disease, with multiple histological origins and poor overall prognosis. The option of radical cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The results of a surgical team experienced in these procedures are analyzed and discussed based on the available evidence. MethodsStudy on a prospective database of patients with peritoneal sarcomatosis who underwent CRS and HIPEC, from 2016 to 2022, in a national reference center for sarcomas and peritoneal oncological surgery, who met the established inclusion/exclusion criteria. ResultsTwenty-three patients were included in the study, with a median age of 53 years (6-68). Recurrent/persistent clinical presentation predominated (78.3%). Visceral origin (including GIST and non-GIST peritoneal) accounted for 47.8% of patients, compared to 43.5% uterine and 8.7% retroperitoneal. The median PCI was 17 (3-36), with CC0 cytoreduction of 87%. Postoperative morbidity (Dindo Clavien III-IV) of 13%, with no postoperative mortality in the series. Overall survival and disease-free survival at 5 years were 64.6% and 34.5%, respectively. Histological grade was the most influential prognostic factor for survival. ConclusionsThe results of the series, with low morbidity, support the benefit of radical peritoneal oncological surgery in patients with peritoneal sarcomatosis after adequate selection, as long as it is performed in high-volume centers, experienced surgeons and expert multidisciplinary teams. However, the role of HIPEC remains to be demonstrated and pending future studies.

Ectodermal origin and tissue dedifferentiation in the podocyst production by the polyps of the Asian moon jelly (Aurelia coerulea).

The histological origin of podocysts in scyphozoans has long been undetermined, with uncertainty whether they arise from mesenchymal amoebocytes or stalk and pedal disc ectoderm in polyps. Histological investigation on the pedal disc was difficult due to the settlement of polyps on hard substrates. In this study, we investigated the histological characteristics of polyps during podocyst production in Asian moon jelly (Aurelia coerulea) with utilizing those attached on thin polystyrene substrates. Fine histological features of the pedal disc became possible after the substrates were decomposed during histological processing. Our findings unequivocally demonstrate that the cell mass of podocysts originates from the ectoderm of the pedal disc and the stalk without the involvement of amoebocytes in the mesoglea. Preceding the podocyst formation, the pedal disc undergoes enlargement facilitated by the elongated stalk ectodermal cells, which attach to a substrate. Subsequently, the pedal disc ectoderm give rise to the primary podocyst cells with accumulating nutrient granules in the cytoplasm and forming the cyst capsule cooperatively with the invaginated pedal disc ectoderm. Direct transformation from the ectodermal cells to podocyst cells suggests that podocyst formation involves tissue dedifferentiation. Throughout the period of podocyst production, the gastrodermis of polyps is physically separated from the ectoderm by the mesoglea and shows no histological changes, and no amoebocytes appear in the mesoglea. These histological properties are totally different from those in other modes of asexual reproduction, which incorporate the endoderm of polyps, suggesting the developmental and evolutionary differences between these asexual reproductions and podocyst production in Scyphozoa.

The [18F]F-FDG PET/CT Radiomics Classifier of Histologic Subtypes and Anatomical Disease Origins across Various Malignancies: A Proof-of-Principle Study.

We aimed to investigate whether [18F]F-FDG-PET/CT-derived radiomics can classify histologic subtypes and determine the anatomical origin of various malignancies. In this IRB-approved retrospective study, 391 patients (age = 66.7 ± 11.2) with pulmonary (n = 142), gastroesophageal (n = 128) and head and neck (n = 121) malignancies were included. Image segmentation and feature extraction were performed semi-automatically. Two models (all possible subset regression [APS] and recursive partitioning) were employed to predict histology (squamous cell carcinoma [SCC; n = 219] vs. adenocarcinoma [AC; n = 172]), the anatomical origin, and histology plus anatomical origin. The recursive partitioning algorithm outperformed APS to determine histology (sensitivity 0.90 vs. 0.73; specificity 0.77 vs. 0.65). The recursive partitioning algorithm also revealed good predictive ability regarding anatomical origin. Particularly, pulmonary malignancies were identified with high accuracy (sensitivity 0.93; specificity 0.98). Finally, a model for the synchronous prediction of histology and anatomical disease origin resulted in high accuracy in determining gastroesophageal AC (sensitivity 0.88; specificity 0.92), pulmonary AC (sensitivity 0.89; specificity 0.88) and head and neck SCC (sensitivity 0.91; specificity 0.92). Adding PET-features was associated with marginal incremental value for both the prediction of histology and origin in the APS model. Overall, our study demonstrated a good predictive ability to determine patients' histology and anatomical origin using [18F]F-FDG-PET/CT-derived radiomics features, mainly from CT.

Abstract 5897: Understanding and targeting fatty acid CoA ligase ACSL4 in human prostate cancer

Abstract Prostate cancer (PCa) is the most common non-cutaneous malignancy among men. Although localized prostate cancer is curable, recurrence of metastatic castration-resistant prostate cancer (mCRPC) is almost inevitable and is the major cause of death in human PCa. Recent findings from our lab and others demonstrate that RB1 loss drives lineage plasticity, metastasis, and lethality of prostate tumors initiated by PTEN loss. A downstream target upregulated by RB1 loss is acyl CoA synthetase long chain family member 4 (ACSL4), a fatty acid ligase with an essential role in utilization of long chain fatty acids. ACSL4 has been reported to be upregulated in cancers of various histological origins, including prostate cancer, and its high expression is correlated with aggressiveness of cancer. We hypothesize that ACSL4 is a critical downstream effector of RB1 loss-driven prostate tumorigenesis and pharmacological inhibition of ACSL4 could represent a novel therapeutic approach to the treatment of lethal RB1 deficient or ACSL4 overexpressing prostate cancer. Here we aim to develop novel ACSL4 inhibitors for preclinical studies. Through a structure based virtual screening that targeted ATP binding domains of ACSL4, we successfully identified 15 potential ACSL4 inhibitors. To validate the result, we performed an in vitro screening using various parental and isogenic human PCa cell lines, and found that 4 out of 15 compounds effectively inhibited PCa cell proliferation in a dose-response manner and their inhibitory effects positively correlated with cellular levels of ACSL4. Next, we will perform isotope-labeling enzyme activity assays to determine the specificity of the 4 candidate drugs, and PDPK analyses followed by characterizing their in vivo efficacies in preclinical studies, with a final goal to develop a well-validated ACSL4 inhibitor. Successful completion of this work will provide great insights into contributions of ACSL4 to prostate tumorigenesis as well as preclinical data of ACSL4 inhibitors to treat lethal prostate cancer. Citation Format: Jinjin Wu, Mu-En Wang, Ming Chen, Pyeong Hwa Jeong, Jiyong Hong, Lixin Wan. Understanding and targeting fatty acid CoA ligase ACSL4 in human prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5897.

PURE vs. mixed clear cell ovarian carcinomas: Is there any impact on survival?

ObjectiveOur primary aim in this study is to define the clinical characteristics of patients with clear-cell ovarian carcinoma and evaluate the prognostic factors affecting survival. Study designRecords of 85 patients, operated between 2000 and 2018, for an adnexal mass and whose final pathology reported clear cell ovarian carcinoma were reviewed. The study considered demographic data, clinical characteristics of the patients, as well as pure and mixed-type clear cell histology. The patients' follow-up time, disease-free and overall survival recorded. The primary outcomes were disease-free survival (DFS) and overall survival (OS). ResultsThe median age of the patients at diagnosis was 52. In 64.7 % of the cases, clear cell histology was pure, while the others (35.3 %) were mixed. Patients with ovarian endometriosis constituted 27.1 % of the whole population. The median OS for the entire population was 92 months (95 %CI:72–124). On univariate and multivariate analyses, advanced age was found to have a significant independent impact on OS and DFS (p < 0.05) and, was associated with a worse prognosis. Also, the multivariate analyses showed that the presence of endometriosis has a significant independent impact on OS (p < 0.05). When examining the relationship between the histological origin (mixed vs. pure) and 5-year survival, the mixed type showed longer OS and DFS rates (76.8 % vs. 69.8 %, 61.5 % vs. 53.8 %), the difference was not statistically significant (p > 0.05). ConclusionThis retrospective study showed that although mixed type histological origin was associated with higher OS and DFS rates compared to pure type in patients with CCOC, the difference was not statistically significant. Advanced age and the presence of endometriosis was found to have a significant independent effect on OS and DFS and was associated with a worse prognosis. Overall, this study provides useful insights into the clinical characteristics of patients with CCOC and identifies important prognostic factors affecting survival.

Metabolic heterogeneity in clear cell renal cell carcinoma revealed by single-cell RNA sequencing and spatial transcriptomics

BackgroundClear cell renal cell carcinoma is a prototypical tumor characterized by metabolic reprogramming, which extends beyond tumor cells to encompass diverse cell types within the tumor microenvironment. Nonetheless, current research on metabolic reprogramming in renal cell carcinoma mostly focuses on either tumor cells alone or conducts analyses of all cells within the tumor microenvironment as a mixture, thereby failing to precisely identify metabolic changes in different cell types within the tumor microenvironment.MethodsGathering 9 major single-cell RNA sequencing databases of clear cell renal cell carcinoma, encompassing 195 samples. Spatial transcriptomics data were selected to conduct metabolic activity analysis with spatial localization. Developing scMet program to convert RNA-seq data into scRNA-seq data for downstream analysis.ResultsDiverse cellular entities within the tumor microenvironment exhibit distinct infiltration preferences across varying histological grades and tissue origins. Higher-grade tumors manifest pronounced immunosuppressive traits. The identification of tumor cells in the RNA splicing state reveals an association between the enrichment of this particular cellular population and an unfavorable prognostic outcome. The energy metabolism of CD8+ T cells is pivotal not only for their cytotoxic effector functions but also as a marker of impending cellular exhaustion. Sphingolipid metabolism evinces a correlation with diverse macrophage-specific traits, particularly M2 polarization. The tumor epicenter is characterized by heightened metabolic activity, prominently marked by elevated tricarboxylic acid cycle and glycolysis while the pericapsular milieu showcases a conspicuous enrichment of attributes associated with vasculogenesis, inflammatory responses, and epithelial–mesenchymal transition. The scMet facilitates the transformation of RNA sequencing datasets sourced from TCGA into scRNA sequencing data, maintaining a substantial degree of correlation.ConclusionsThe tumor microenvironment of clear cell renal cell carcinoma demonstrates significant metabolic heterogeneity across various cell types and spatial dimensions. scMet exhibits a notable capability to transform RNA sequencing data into scRNA sequencing data with a high degree of correlation.