Primary Epithelial Tumors Research Articles

Low-grade Papillary Nasopharyngeal Adenocarcinoma: A Clinicopathologic Series of 35 Cases.

Low-grade nasopharyngeal papillary adenocarcinoma (LGNPPA) is a rare neoplasm originating from the surface mucosal epithelium in the nasopharynx. To clarify its clinicopathologic, immunohistochemical, and molecular features, we retrospectively enrolled 35 patients diagnosed with LGNPPA between May 2016 and March 2024. Our cohort consisted of 14 male and 21 female patients aged 11 to 71 years (median: 37y). The most common symptoms were rhinorrhea and nasal obstruction. Most tumors originated from the roof of the nasopharynx and were clinically staged as T1N0M0. None of the patients had a history of thyroid tumors. Microscopically, most of the LGNPPA were composed of irregular papillary structures covered with single-layer columnar or cuboidal epithelium. Eighteen cases (18/35, 51.4%) showed squamous epithelium coverage, and 9 cases (9/35, 25.7%) showed the characteristic transformation of squamous epithelium into neoplasm. Squamous differentiation and a significant spindle cell component were noted in 9 cases (9/35, 25.7%) and 26 cases (26/35, 74.3%), respectively. All cases were positive for thyroid transcription factor-1 protein, CK7, EMA, and Galectin-3 but negative for thyroglobulin, PAX8, and Napsin A. Ki-67 labeling was low and ranged from 2% to 5%. The Epstein-Barr virus or human papilloma virus infection and BRAF V600E mutation were not detected in any of the cases. All patients underwent endoscopic surgical resection, and 4 patients received radiotherapy followed by endoscopic surgery. Complete follow-up data were available for 33 patients. All patients had no recurrent or metastatic disease in the last follow-up (3 to 88mo). A definitive diagnosis depends on histopathology and immunohistochemistry studies. The optimal treatment for patients with LGNPPA is total excision. Given the extremely indolent biological behavior of LGNPPA, it may be more appropriate to classify it as a primary papillary epithelial tumor rather than an adenocarcinoma of the nasopharynx.

Diffuse Large B-cell Lymphoma (DLBCL) involving the Uterine Corpus presenting with Abnormal Uterine Bleeding: A Rare Case Report

Abstract Introduction/Objective Diffuse Large B-cell Lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma. Lymphomas affecting the female genital system are extremely rare, accounting for about 1% of extra-nodal lymphomas, with DLBCL being the most common type. We present a rare case of uterine lymphoma presenting with abnormal uterine bleeding. Methods/Case Report A 50-year-old female presented with abnormal uterine bleeding and fatigue for the past three weeks. Laboratory work-up showed hemoglobin level of 5.5 g/dL. Pelvic ultrasound revealed thickening of the endometrium and a 1.6 cm hypoechoic uterine lesion along with multiple enlarged bilateral adnexal lymph nodes. Histological examination of the endometrial biopsy demonstrated endometrial fragments with diffuse subepithelial proliferation of large, poorly differentiated cells with round nuclear contours, finely dispersed chromatin, relatively inconspicuous nucleoli and moderate amount of cytoplasm. Many scattered mitoses and apoptotic bodies were present. Primary set of immunohistochemical stains were performed to rule out primary uterine epithelial or mesenchymal tumors. The tumor cells were negative for pan-keratin, high and low molecular weight keratins and positive for CD45. Further work-up demonstrated CD20 positivity. It was diagnosed as DLBCL with a non-germinal center, double expressor phenotype and a high Ki-67 proliferation. Fluorescence in-situ hybridization studies were negative for MYC and BCL6 gene rearrangements and IGH-BCL2 translocation. Further radiological workup revealed diffuse lymphadenopathy with multiple pulmonary and renal nodules consistent with Stage IV DLBCL. She was treated with six cycles of R-CHOP regimen, and complete metabolic response was achieved. Results (if a Case Study enter NA) NA Conclusion Uterine lymphomas are very rare and on small biopsies may histologically mimic poorly differentiated uterine malignancies such as dedifferentiated/undifferentiated carcinomas. Adding lymphoma lineage markers to poorly differentiated tumors is recommended to avoid missing such a rare entity.

A Confirmed Extrarenal Birt-Hogg-Dubé-Associated Oncocytic Neoplasm.

Birt-Hogg-Dubé (BHD) syndrome is a rare inherited disease characterized by a variety of renal epithelial tumors and oncocytosis, with extrarenal manifestations primarily consisting of pulmonary cysts and cutaneous fibrofolliculomas. Here we report a unique case of a primary extrarenal BHD-associated oncocytic epithelial neoplasm which arose between the duodenum and head of the pancreas. The unusual morphology and immunoprofile of this lesion defied classification as any previously reported entity, despite an extensive diagnostic workup. The immunohistochemical and molecular features indicate the tumor was driven by FLCN loss, and thus a consequence of the underlying germline mutation with a somatic second hit. This tumor is the first reported example of an extrarenal BHD-associated oncocytic epithelial tumor driven by FLCN loss.

Correlation of PD-L1 expression with different clinico-pathological and immunohistochemical features of ovarian surface epithelial tumors.

Primary carcinoma of the ovary (OCs) are responsible for a significant number of deaths related to cancer, and have the highest rate of death related to cancers of the female reproductive organs. Programmed cell death 1 (PD1) protein, acts as an immune checkpoint, and has an important role in the down-regulation of the immune system by preventing the activation of T-cells, which will weaken the autoimmunity and increases self-tolerance. This study aimed at the evaluation of the immunohistochemical (IHC) expression of PD-L1 in various primary surface ovarian epithelial tumours and to test its correlation with different clinicopathological parameters together with the expression of a panel of P53, ER and PR. A set of 102 cases of primary ovarian surface epithelial neoplasms (benign, borderline and malignant) were collected to construct Tissue Microarray (TMA) using 3 tissue cores from each case. IHC for PD-L1, p53, PR and ER was performed. The expression of PD-L1 was evaluated in relation to some clinicopathological parameters and to the expression patterns of other markers. Expression of PD-L1 was detected in about 51% (n = 36) of malignant tumours. The malignant group significantly showed PD-L1 positivity compared to borderline and benign groups. The malignant tumours significantly showed PD-L1 and total p53 positivity in comparison to borderline group. Also, malignant tumours significantly showed higher combined positivity of PD-L1 and either PR or ER compared to borderline and benign lesions. No significant correlation was appreciated between PD-L1 expression and with any of the studied clinicopathological parameters. This study showed a significant PD-L1 expression in malignant primary surface epithelial tumours. Construction of a panel of IHC markers, including PD-L1, could have a potential value to define patients those would benefit from the addition of immunotherapy to the treatment plan.

Characterization of innate lymphoid cell subsets infiltrating melanoma and epithelial ovarian tumors

ABSTRACT The innate lymphoid cell (ILC) family is composed of heterogeneous innate effector and helper immune cells that preferentially reside in tissues where they promote tissue homeostasis. In cancer, they have been implicated in driving both pro- and anti-tumor responses. This apparent dichotomy highlights the need to better understand differences in the ILC composition and phenotype within different tumor types that could drive seemingly opposite anti-tumor responses. Here, we characterized the frequency and phenotype of various ILC subsets in melanoma metastases and primary epithelial ovarian tumors. We observed high PD-1 expression on ILC subsets isolated from epithelial ovarian tumor samples, while ILC populations in melanoma samples express higher levels of LAG-3. In addition, we found that the frequency of cytotoxic ILCs and NKp46+ILC3 in tumors positively correlates with monocytic cells and conventional type 2 dendritic cells, revealing potentially new interconnected immune cell subsets in the tumor microenvironment. Consequently, these observations may have direct relevance to tumor microenvironment composition and how ILC subset may influence anti-tumor immunity.

Abstract 6781: Maintaining the tumor microenvironment: Serum-free cell culture for an advanced 3D in vitro tissue model

Abstract Cancer research has made significant progress in recent years, especially in the field of immunotherapy that uses immune modulators. A significant portion of these novel therapeutic strategies focuses on manipulating the tumor microenvironment (TME). The TME is a complex structure that comprises various cellular elements, including cancer cells, immune cells, and structural components, such as secreted factors and extracellular matrix proteins. However, replicating the human TME in experimental murine models has proved challenging. Therefore, researchers have started to develop ex vivo cultivation protocols of tumor tissues, particularly precision-cut slices (PCS), that offer a three-dimensional representation of the TME. It is essential to select the best culture conditions to ensure the preservation of the TME that closely resembles the in vivo conditions. To further this research, a serum-free cell culture medium has been developed to propagate primary epithelial tumor cells originating from pancreatic, renal, and ovarian tissues. The optimized media formulation was successfully employed in the derivation and expansion of tumor cell lines, sourced from both primary and xenotransplanted tumors. An additional serum-free cell culture medium has been designed to cultivate primary lung cancer cells. Suitable culturing conditions have been introduced that maintain TME composition ex vivo cultured PCS prepared from fresh non-small cell lung carcinoma (NSCLC) tissue. Lung TumorMACS Medium and a serum-containing medium were compared, and it was found that the cellular composition of PCS cultivated in Lung TumorMACS was comparable to the original composition. At the same time, PCS cultivated in Lung TumorMACS showed a lower expression of stress genes, compared to the serum-containing alternative. Citation Format: Alina Siebenmorgen, Christian Wöhle, Katharina Lamfried, Lilian Martinez Carrera, Bianca Heller, Katharina Lupar, Giovanna Bergamini, Daniel Poeckel, Olaf Hardt, Benjamin Theek. Maintaining the tumor microenvironment: Serum-free cell culture for an advanced 3D in vitro tissue model [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 6781.

Genomic analysis of primary epithelial neoplasms of the seminal vesicle identifies a subset of mucinous cystic tumours driven by KRAS mutations.

Carcinomas of the seminal vesicle are exceedingly rare, with a limited number of cases described in the literature. Reported cases span a relatively wide morphological spectrum, and their genomic features remain unexplored. In this study, we interrogated five primary epithelial neoplasms of the seminal vesicle using a targeted DNA sequencing platform (OncoPanel, 447 genes). The tumours included one adenocarcinoma with intestinal phenotype presenting after external beam radiation (for prostatic adenocarcinoma), one carcinoma with Müllerian-type clear cell phenotype, two mucinous tumours resembling low-grade mucinous neoplasms of the appendix (LAMN) and one mucinous cystadenoma. The post-radiation mucinous adenocarcinoma had genomic findings consistent with bi-allelic inactivation of TP53, as well as multiple copy-number changes with regional and chromosomal arm-level copy-number losses. The Müllerian-type clear cell carcinoma exhibited a complex copy-number profile with numerous regional and arm-level copy-number changes, as well as focal amplification events, including copy-number gain of 8q and amplification of a region within 20q13. Both low-grade mucinous tumours resembling LAMN harboured hot-spot gain-of-function KRAS variants (p.G12V and p.G13D) as the only genomic alteration. No genomic alterations were detected inthe lesion diagnosed as mucinous cystadenoma. Our results suggest that primary low-grade mucinous neoplasms of the seminal vesicle may represent a distinct entity equivalent to appendiceal counterparts, driven by gain-of-function variants of RAS GTPases. The remaining tumours showed genomic features that closely resembled those of neoplasms with comparablephenotypes and/or biological characteristics arising in other sites, suggesting that they could be managed similarly, with special considerations related to their anatomical location.

Sinonasal (Schneiderian) Tumors in the Temporal Bone: Case Series and Systematic Review.

Neoplasms derived from the sinonasal epithelium are a rare finding in the temporal bone, and their origins are controversial. To review the characteristics of sinonasal epithelial (previously known as Schneiderian) tumors occurring in the temporal bone. This was a 2-center case series and systematic review of MEDLINE, EMBASE, and the Web of Science through May 2021. Patients with clinicopathologic evidence of temporal bone involvement by neoplasms of sinonasal epithelial origin were selected, with or without a history of prior primary sinonasal epithelial tumors. Clinical, radiologic, and pathologic data were extracted. The systematic review included 56 studies and our 8 unpublished cases, totaling 76 cases of papillomas or squamous cell carcinomas in the temporal bone. Of these, 51% occurred secondary to sinonasal tumors, and 49% occurred primarily. Secondary tumors were usually metachronous (77%), with a median delay of 1 year from sinonasal-to-temporal bone tumor diagnosis. Most cases were unilateral (90%); bilateral temporal bone involvement occurred only as secondary ("trilateral") tumors. Unilateral secondary tumors had ipsilateral (81%) or bilateral (19%) sinonasal counterparts. Secondary tumors were more likely to be malignant (OR, 6.7, P < .001). The review was based on case reports and small case series, which are subject to reporting bias. The observed tumor patterns support the hypothesis that the Eustachian tube facilitates the spread of sinonasal epithelium-derived neoplasms from the sinonasal cavity to the temporal bone. Transtubal spread of sinonasal epithelium-derived neoplasms should be considered among the rare causes of middle ear masses.

Morphologic, phenotypic, and genotypic similarities between primary tumors and corresponding 3D cell cultures grown in a repeatable system—preliminary results

BackgroundThree-dimensional (3D) cell cultures are the new frontier for reproducing the tumor micro-environment in vitro. The aims of the study were (1) to establish primary 3D cell cultures from canine spontaneous neoplasms and (2) to demonstrate the morphological, phenotypic and genotypic similarities between the primary canine neoplasms and the corresponding 3D cultures, through the expression of tumor differentiation markers.ResultsSeven primary tumors were collected, including 4 carcinomas and 3 soft tissue sarcomas. 3D cell cultures reproduced the morphological features of the primary tumors and showed an overlapping immunophenotype of the primary epithelial tumors. Immunohistochemistry demonstrated the growth of stromal cells and macrophages admixed with the neoplastic epithelial component, reproducing the tumor microenvironment. Mesenchymal 3D cultures reproduced the immunophenotype of the primary tumor completely in 2 out of 3 examined cases while a discordant expression was documented for a single marker in one case. No single nucleotide variants or small indel were detected in TP53 or MDM2 genes, both in primary tumors and in 3D cell cultures specimens. In one sample, MDM2 amplicons were preferentially increased in number compared to TP53 ones, indicating amplification of MDM2, detectable both in the primary tumor and in the corresponding cell culture specimen.ConclusionHere we demonstrate a good cell morphology, phenotype and genetic profile overlap between primary tumors and the corresponding 3D cultures grown in a repeatable system.

Histopathological spectrum of ovarian tumors in tertiary care centre of central India

Abstract Background: Ovarian tumors are common, ranking third in frequency after cervical and uterine cancer. According to the World Ovarian Cancer Coalition Atlas 2018, India has the second-highest incidence of ovarian carcinoma worldwide. In Chhattisgarh, ovarian malignancy accounts for 5.21% of all malignancies in females. Materials and Methods: The present descriptive observational cross-sectional study encompassed 108 cases of ovarian tumors. A histopathological examination was done, and data was compiled and analyzed. Observations and Results: Among the 108 ovarian tumors, 59.25% were noted in women aged 40–59 years. The primary presenting symptom was abdominal pain, reported by 57.40% of the cases. The majority of ovarian tumors were unilateral, the right side being more common. Primary ovarian tumors constituted 91.66%, while 8.33% were classified as secondary or metastatic ovarian tumors. Of 108 cases, 55.5% were malignant, 40.7% were benign, and 3.7% were borderline tumors. Surface epithelial tumors accounted for 73.14% of the cases; germ cell tumors constituted 9.25%, sex cord-stromal tumors were 7.4%, and mesenchymal tumors were 1.85%. Among surface epithelial tumors, serous cystadenocarcinoma was most common. Mature cystic teratoma was the most common germ cell tumor, and granulosa cell tumor was the most common sex cord-stromal tumor. Conclusion: Ovarian tumors were more commonly seen in the peri and postmenopausal age group. Primary malignant epithelial tumors were the most common type of ovarian tumor. The histopathological evaluation of ovarian tumors remains the gold standard for definitive diagnosis.

Characterization of alkaline phosphatase cytochemistry in canine neoplastic and non-neoplastic pulmonary mass aspirates.

Distinguishing primary and secondary pulmonary neoplasms can be challenging via cytology, and a rapid, inexpensive diagnostic tool to differentiate these neoplasms is unavailable. Alkaline phosphatase cytochemistry (ALP-CC) has been used to identify primary pulmonary carcinomas in human patients, and we hypothesized it could be applied to canine lung aspirates. We aimed to characterize ALP-CC expression in fine-needle aspirate (FNA) samples of canine pulmonary neoplastic and non-neoplastic tumors. A retrospective case search was conducted to identify cases with contemporaneous cytology and histopathology reports from pulmonary lesions, including neoplastic and non-neoplastic etiologies. Slides prepared from pulmonary aspirates were stained for ALP-CC activity, and the percentage of ALP-CC-positive primary pulmonary epithelial tumors was determined. To characterize the ALP-CC expression in non-neoplastic cellular constituents of pulmonary FNA samples, mesothelial cells were also evaluated. Forty-eight canine cases met the inclusion criteria. ALP-CC-positive cells were seen in both neoplastic and non-neoplastic lesions. In non-neoplastic lesions, pulmonary epithelial cells were ALP-CC positive. Eighty-nine percent of primary pulmonary epithelial neoplasms were ALP-CC positive, and no ALP-CC positivity was noted in mesothelial cells. ALP-CC-positive neoplastic cells were seen in a metastatic amelanotic melanoma. Primary pulmonary epithelial neoplasms are frequently ALP-CC positive, but such positivity is not restricted to this tumor type. Non-neoplastic pulmonary epithelial cells can be ALP-CC positive, whereas mesothelial cells are negative.

Craniopharyngioma-An update on metabolic and cognitive complications and new therapy.

Craniopharyngiomas (CPs) are rare primary brain epithelial tumors arising in the suprasellar region from remnants of Rathke's pouch. About 50% originate at the level of the third ventricle floor, including the hypothalamus (HT). CPs are characterized by a low proliferation rate and symptoms due to mass effect and local infiltration and are managed primarily with surgery and radiotherapy. Gross total removal of a CP will reduce the recurrence rate but increases the risk of HT damage. Today, subtotal resection is the goal and will reduce the risk of HT damage. There are two histological subtypes of CP-adamantinomatous (ACP) and papillary CP (PCP)-that differ in their genesis and age distribution. ACPs are driven by somatic mutations in CTNNB1 gene (encoding β-catenin), and PCPs frequently harbor somatic BRAF V600E mutations. There are also two phenotypes of outcome, the one with a rather good outcome without HT damage and the other with HT damage where recurrent operation with additional cranial radiotherapy results in HT obesity (HO), affecting psychosocial life and cognitive dysfunction. The group with HO suffers from metabolic syndrome, lower basal metabolic rate, and leptin and insulin resistances. There is currently no successful treatment for HO. The group with HT damage suffers from cognitive dysfunction with attention deficits, impaired episodic memory, and processing speed. Diffusion tensor imaging has shown significant microstructural white matter alteration in several areas important for cognition. Recently, complete or partial tumor response was shown to targeted therapy, with BRAF and Mekinist inhibitors for PCPs with BRAF V600E mutation.

Neuroendocrine Marker Expression in Primary Non-neuroendocrine Epithelial Tumors of the Ovary: A Study of 551 Cases.

Expression of neuroendocrine (NE) markers in primary ovarian non-NE epithelial tumors has rarely been evaluated. The aim of our study was to evaluate the expression of the most widely used NE markers in these neoplasms and to determine any prognostic significance of NE marker expression. The cohort consisted of 551 primary ovarian tumors, including serous borderline tumors, low-grade serous carcinomas, high-grade serous carcinomas (HGSC), clear cell carcinomas, endometroid carcinomas, mucinous borderline tumors, and mucinous carcinomas. Immunohistochemical analysis was performed using antibodies against INSM1, synaptophysin, chromogranin, and CD56 on tissue microarray. Positivity for INSM1, synaptophysin, chromogranin, and CD56 was most frequently observed in mucinous tumors (48.7%, 26.0%, 41.5%, and 100%, respectively). The positivity for these NE markers was mostly restricted to nonmucinous elements distributed throughout the tumor. The mucinous borderline tumor and mucinous carcinomas groups had similar proportions of positivity (mucinous borderline tumor: 53%, mucinous carcinomas: 39%). In the other tumor types, except for HGSC, there was only focal expression (5%-10%) or negativity for NE markers. HGSC showed high CD56 expression (in 26% of cases). Survival analysis was only performed for CD56 in HGSC as this was the only group with sufficient positive cases, and it showed no prognostic significance. Except for mucinous tumors, expression of NE markers in non-NE ovarian epithelial tumors is low. CD56 expression in HGSC occurs frequently but is without diagnostic or prognostic value.

P-118 Clinical significance of primary tumor sites and epithelial tumor markers in patients with unresectable/recurrent gastrointestinal neuroendocrine carcinoma treated with combined chemotherapy with irinotecan and cisplatin

P-118 Clinical significance of primary tumor sites and epithelial tumor markers in patients with unresectable/recurrent gastrointestinal neuroendocrine carcinoma treated with combined chemotherapy with irinotecan and cisplatin

Ileum neuroendocrine tumor: Case report and literature review

Ileal neuroendocrine tumors are rare primary epithelial neoplasm arising from enterochromaffin cells. A 65-year-old male presented with complaints of recurrent abdominal pain of 1 year duration. The pain was more aggravated in last 7 days associated with vomiting, loss of appetite and diarrhea. On radioimaging ultrasonography finding impression of small bowel mass lesion suggestive of ileac carcinoid tumor with ischemic bowel disease was given. Computerized tomograph abdomen pelvis showed a well-defined hypodense, round, hetergenous, enhancing mass measuring 2.6x1.6x1.2 cm., showing arterial enhancement in mesentery in close relation to ileum and metastatic lymph node mass- indicating likeness of neuroendocrine tumor. The surgical resection of ileum with mass and enlarged mesenteric nodes were done. On gross examination ileum specimen on cut open showed multiple, irregular mucosal thickenings with foci of ulceration. The submocosa showed single, circumscribed, round tumor measuring 3 x 2.5x1.5 cm. Cut section of tumor was yellowish, tan, well circumscribed and solid. The mesenteric lymph nodes were enlarged. The microscopic examination ileum showed a tumor composed of uniform, round cells having to oval nuclei with salt and pepper chromatin. Tumor cells were arranged in trabecular, nests, ribbons and in areas pseudo glandular pattern. Increased mitotic activity was noted (4/10 high power field). Mesenteric lymph nodes were involved by tumor. On histopathology reported as Well-differentiated neuroendocrine tumors (NET), G2, intermediate grade of ileum. The immunohistochemical stain were positive for synaptophysin, chromogranin A. The Ki-67 expression was &amp;#60;1%. Herewith we are presenting rare case of well-differentiated neuroendocrine tumor NET, G2, intermediate grade of ileum for its clinical, radio imaging ,pathological features and management.

Primary papillary epithelial tumor of the sella and posterior pituitary tumor show similar (epi)genetic features and constitute a single neuro-oncological entity.

"Primary papillary epithelial tumor of the sella (PPETS)" is a recently described rare tumor entity of the central nervous system (CNS) with stereotypic location in the sella. Comprehensive molecular investigations and epigenetic profiles of PPETS have not been performed to date. We report a comprehensive clinical, histopathologic, and molecular assessment of 5 PPETS cases in comparison with a cohort composed of 7 choroid plexus papilloma (CPP), 7 central neurocytoma (CN), 15 posterior pituitary tumor (PPT) including 4 pituicytoma, 6 granular cell tumors of the sellar region (GCT), and 5 spindle cell oncocytoma. All PPETS had good outcomes. Immunohistochemically, PPETS tumors showed positive staining with TTF1, EMA, AE1/AE3, MAP2, and Vimentin, but were negatively stained with Syn, GFAP, CgA, and S100, and sporadically stained with Ki-67. In unsupervised hierarchical clustering and t-distributed stochastic neighbor embedding analyses of DNA-methylation data, PPETS and PPT tumors formed a distinct cluster irrespective of their histologic types. However, PPETS tumors did not cluster together with CPP and CN samples. Similar findings were obtained when our samples were projected into the reference cohort of the brain tumor classifier. Substantial fractions of the PPETS and PPT tumors shared broadly similar chromosomal copy number alterations. No mutations were detected using targeted next-generation sequencing. Though more cases are needed to further elucidate the molecular pathogenesis of these tumors, our findings indicate that PPETS and PPT tumors may constitute a single neurooncological entity.

Abstract 56: Unlocking primary cell culture for more relevant in vitro models

Abstract Tumor cell lines are commonly used to investigate biological and translational questions. However, many cell lines have been cultured in serum-containing medium for decades, continuously accumulating genetic and epigenetic aberrations. Without a doubt, these cell lines have very little in common with the tumor they originate from, resulting in low biological and clinical relevance. Despite these drawbacks, cell lines are still the most frequent research tool when it comes to the use of ex vivo models. Yet, in light of higher consistency, reproducibility, and biological relevance, more and more researchers are paying attention to which cells and culture medium to use. Although primary cell cultures certainly reflect cellular and genetic heterogeneity of the original tumor, finding a suitable medium that supports their growth and maintains genetic heterogeneity remains challenging. To this end, we developed serum-free cell culture media to cultivate primary epithelial tumor cells of pancreatic, renal, and ovarian origin. Notably, generating in vitro models with high biological relevance was successful when using our media during the derivation and expansion of tumor cell lines from primary and xenotransplanted tumors. Here, we present another serum-free cell culture media supporting the in vitro growth of primary colon adenocarcinoma. Using this optimized medium, we had a 42% success rate in establishing a primary cell culture for a given tumor sample, higher than for any other media tested in our hands. Next to 2D cell culture, our formulation supports 3D tumoroid formation when cells are embedded in a basement membrane matrix. Furthermore, targeted sequencing of 486 tumor-associated genes revealed that more than 99% of the detected genetic variants in an early passage (p11) were also present after extended time in culture (p53). In summary, our new serum-free medium enables the efficient derivation and expansion of primary tumor and xenograft-derived colon adenocarcinoma cell cultures in 2D and 3D, yet retaining their genetic identity. Citation Format: Benjamin Theek, Anne Franke, David Agorku, Katharina Lamfried, Nojan Jelveh, Michael Linnebacher, Lilian Martinez Carrera, Olaf Hardt. Unlocking primary cell culture for more relevant in vitro models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 56.

Disparities in lung cancer short- and long-term outcomes after surgery: Analysis from the national cancer database

IntroductionSocial determinants of health are particularly important in lung cancer epidemiology. Previous studies have primarily associated social determinants with long-term outcomes, such as survival, but fail to include short-term outcomes after surgery. The National Cancer Database (NCDB) was used to draw associations between social factors of patients with lung cancer and short-term post-surgical outcomes, while comparing them to prognostic factors, including stage at diagnosis and survival. MethodsThe 2004–17 NCDB was queried for patients with primary epithelial tumor, squamous cell carcinoma, or adenocarcinoma of the lung treated with curative intent. Linear, binary logistic, Kaplan-Meier, and Cox proportional hazards regression models were utilized. ResultsOn logistic regression modeling, male gender, low income, lacking insurance, and facility in the central United States were associated with poor short-term outcomes (<0.05). Increased age, White race, and Black race were associated with increased length of hospital stay and mortality, but negatively correlated with readmission rates (<0.05). Medicare and Medicaid were associated with increased length of stay and mortality, respectively (<0.05). Similar patterns were observed for higher stage at diagnosis (<0.05). Hazard ratios were elevated with increased age, male gender, White race, lacking insurance, Medicaid, and facility in the central United States (<0.05). ConclusionMany social factors previously associated with poor prognosis after lung cancer diagnosis are also associated with poor short-term outcomes after surgery. This study implies that healthcare providers treating lung cancer should proceed with care while aware that patients with the discussed social factors are predisposed to complicated recoveries.

Grayscale ultrasound feature typing of metastatic ovarian tumors, particularly signet-ring cell carcinoma

To describe grayscale ultrasound (US) features of metastatic ovarian tumors (MOTs) based on origin of the primary tumor in a large sample size study. This retrospective cross-sectional single-center study included 112 patients with 190 histopathologically confirmed MOTs. Among the patients, 102 collectively had 144 masses, which were detected via US. The clinical data and static US images of MOTs were collected. The MOTs were mostly bilateral (78.9%) but had a lower rate of bilaterality when detected by US (55.6%). Breast cancer metastasis had the highest nondetection rate (69.6%), because its focal metastasis could only be recognized using histology or immunohistochemistry. The stomach was the most common origin of metastasis (45.3% and 50.7% detected via pathology and US, respectively). The US images were classified into three subtypes: multilocular solid (Type A), purely solid (Type B), and solid with several round or oval cysts (Type C). The MOTs that originated from the colon mostly belonged to Type A (65.1%) and closely mimicked primary epithelial ovarian tumor morphologically. The MOTs that originated from the stomach predominantly belonged to Types B (31.5%) and C (57.5%). Signet-ring cell carcinoma (SRCC) corresponded to Types B and C regardless of origin. The developed novel typing method provides more vivid images for classifying MOTs compared with existing typing methods. Given that no specific sonographic parameters have been established to distinguish MOTs from primary invasive ovarian tumors, these images may be helpful in diagnosing these masses.

Combined hepatocellular-cholangiocarcinoma: morpho-molecular updates and considerations

Combined Hepatocellular-Cholangiocarcinoma is a heterogenous primary malignant epithelial tumor of the liver with variable morphological and immunophenotypical features. Although the biology of this tumor has been described in the literature, changes in classification and its heterogeneity imply difficulties in collecting reliable homogenous groups to compare. The article aims to review available data on morphology and immunohistochemistry for practicing pathologists integrated with original data from our referral Center.