Epithelial Tumors Research Articles

Patient-derived xenografts from circulating cancer stem cells as a preclinical model for personalized pancreatic cancer research

Patient-derived xenografts (PDXs) provide biologically relevant models and potential platforms for the development of treatment strategies for precision medicine in pancreatic cancer. Furthermore, circulating epithelial tumor cells (CETCs/CTCs) are released into the bloodstream by solid tumors and a rare subpopulation—circulating cancer stem cells (cCSCs) – is considered to be responsible for recurrence and plays a key role in metastasis. For the identification of cCSCs, an innovative in vitro assay to generate tumorspheres was established in this study. The number of tumorspheres and CETCs/CTCs was analyzed perioperatively in 25 pancreatic cancer patients. Additionally, an individual in vivo chorioallantoic membrane (CAM) culture system was used to generate PDXs from these tumorspheres. While overall correlations of CETCs/CTCs with clinicopathological parameters did not reach statistical significance, a significant difference in the number of tumorspheres was observed between patient subgroups with lower and higher UICC stages. This finding underscores their potential as biomarkers, providing valuable insights into clinical decision-making and tumor progression. The application of tumorspheres on the CAM successfully established PDXs within 7 days. These xenografts closely resembled the histological features of the primary tumor. Hence, this model represents a novel and fast option for individualized testing of new therapies for PDAC.

Mandibular Reconstruction With a Patient-Specific Implant Following Surgical Excision of an Acanthomatous Ameloblastoma in a Dog.

Canine acanthomatous ameloblastoma (CAA) is an invasive benign epithelial odontogenic tumour most commonly affecting the mandible of large breed dogs. To the author's knowledge, this report describes the first computer-aided design patient-specific implant (PSI) that has been placed for a critical sized bone defect in mandibular reconstruction of a dog in the UK. The aim was to restore mandibular stability using a regenerative approach combining a titanium locking plate and compression-resistant matrix infused with recombinant human bone morphogenetic protein-2 (rhBMP-2) to bridge the 85 mm mandibular defect created by a segmental mandibulectomy. A 7-year-old neutered crossbreed dog with a focal 60 × 45 × 30 mm3 mildly ulcerated mass on the left mandible was presented. Histopathology confirmed a CAA. A left segmental mandibulectomy was followed by a delayed (secondary) reconstructive surgery. The porous titanium scaffold was manufactured from the first computed tomography (CT) scan and was designed with a channel to be filled with a compression-resistant osteoconductive resorbable sponge material infused with an osteoinductive solution containing rhBMP-2. Follow-up CT scans were performed on the day of the second surgery, and 4 and 12 months after the second surgery. Filling the porous titanium scaffold with an osteoconductive strip mixed with rhBMP-2 promoted bone remodeling and stimulated partial osseous integration of the implant; however there was no evidence of complete osteosynthesis bridging the bone defect as initially expected. Twelve months after reconstruction, dorsal longitudinal implant exposure necessitated PSI explantation. This study reflects a recent surgical therapeutic approach that can be utilised to reconstruct mandibles. PSIs can help reduce the known postoperative complications inherent to large gap mandibulectomies. Therefore, their use has the potential to improve patient welfare by restoring mandibular and temporomandibular joint (TMJ) stability, preventing mandibular drift, improving prehension, and reducing the risk of secondary TMJ degenerative disease and pain. It is likely that some implant design refinement is required to achieve better success rates for these challenging cases.

First Clinical Experience of 68Ga-FAPI PET/CT in Tertiary Cancer Center: Identifying Pearls and Pitfalls.

Background/Objectives: Over the past four years, 68Ga-fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT) has been established at a tertiary cancer care facility in Jordan. This retrospective study aims to explore tracer uptake metrics across various epithelial neoplasms, identify diagnostic pitfalls associated with 68Ga-FAPI PET/CT, and evaluate the influence of 68Ga-FAPI PET/CT staging results on changes in therapeutic intent compared to gold standard molecular imaging modalities. Methods: A total of 48 patients with biopsy-confirmed solid tumors underwent 77 68Ga-FAPI PET/CT examinations for molecular imaging assessment, encompassing neoplasms originating from the gastrointestinal tract, head and neck, hepatobiliary system, pancreas, breast, and lung. Results: Notably, pancreaticobiliary tumors exhibited the highest tracer uptake, with mean maximum standardized uptake values (SUVmax) and tumor-to-background ratios (TBR) surpassing 10. A comparative sub-analysis of 68Ga-FAPI PET metrics in 20 treatment-naïve patients revealed a significant correlation between 68Ga-FAPI uptake metrics and tumor grade (Spearman's rho 0.83; p = 0.00001). Importantly, the results from 68Ga-FAPI PET/CT influenced treatment decisions in 35.5% of the cases, primarily resulting in an escalation of management plans. A total of 220 diagnostic challenges were identified across 88.3% of the scans, predominantly within the musculoskeletal system, attributed to degenerative changes (99 observations). Conclusions: This comprehensive analysis highlights the potential significance of 68Ga-FAPI PET/CT in oncological imaging and treatment strategy, while also emphasizing the necessity for meticulous interpretation to mitigate diagnostic challenges.

An Ultrasensitive Duplex Aptasensor Featuring the Target-Triggered Lanthanide Luminescence Antenna Effect for Wash-Free Detection of Epithelial Cancerous Exosomes.

Fluorescence sensing is widely used in in vitro detection due to its high sensitivity and rapid result delivery. However, detection systems based on nanomaterials involving complex and cumbersome purification steps can lead to sample loss and significantly reduce the accuracy of the results. To address this issue, we proposed a lanthanide-based aptasensor featuring the target-triggered antenna effect to significantly enhance the time-resolved luminescence (TRL) of chelated Tb3+ combined with a wash-free strategy. This sensor enabled highly sensitive detection of the epithelial cell adhesion molecule (EpCAM) on exosomes from epithelial tumors, eliminating the necessity for purification steps and thereby delivering more stable and reliable results. Specifically, using computer-aided design, a sequence capable of self-folding into a stable hairpin structure (Antenna-Hairpin-Tb) was obtained. After hybridization with an EpCAM-specific aptamer (AptEpCAM), a duplex aptasensor (Probe-Tb) was constructed for detection. When the targeted binding occurred between the AptEpCAM and exosomes, the Antenna-Hairpin-Tb dehybridized from the Probe-Tb and underwent self-folding, leading to a significant sensitized TRL signal due to the antenna effect-induced energy transfer from the antenna ligand to the chelated Tb3+. Over a broad range of exosome concentrations (spanning from 6.19 × 102 to 6.19 × 108 particles/mL), the emission intensity of chelated Tb3+ at 543 nm linearly increased with the exosome concentration (linear relationship: Y = 332.62 lg(Nexosomes) + 3690.5, R2 = 0.9956), achieving a theoretical detection limit as low as 17 particles/mL in the buffer. Furthermore, Probe-Tb enabled a swift and effective differentiation of all epithelial cancer serum samples from nonepithelial ones within just 30 min of a wash-free operation, achieving 100% sensitivity, 100% specificity, and 100% accuracy.

Mixed Epithelial and Stromal Tumor of the Kidney: Clinicopathologic Features and Surgical Outcomes in Four Patients

Mixed Epithelial and Stromal Tumor of the Kidney: Clinicopathologic Features and Surgical Outcomes in Four Patients

Incidence, characteristics, and comorbidities of a complete unselected Danish cohort of patients with thymic epithelial tumors.

We report the incidence, characteristics, and comorbidities of the complete unselected Danish cohort of patients with thymic epitheliums (TETs), which may serve as evidence for guiding treatment, surveillance, and counselling of TET patients. All patients diagnosed with TETs from January 1st, 2015, to December 31st, 2020, were identified using the Danish Pathology Data Registry. Data on patient characteristics, comorbidities, and tumor histology were collected from electronic medical records available for all patients. The cohort consisted of 283 patients with a mean age of 64 years (SD: 12). The crude rate was 8.2/1,000,000 TETs annually, thus higher than the age-standardized rates of 4.8/1,000,000 in the WHO World Standard Population and 6.1/1,000,000 in the European Standard Population. Thymomas were diagnosed in 240 patients (85%) (9% type A, 31% AB, 18% B1, 26% B2, 6% B3, 5% micronodular, 0.4% metaplastic, and 5% of unspecified subtype), thymic carcinomas in 39 patients (14%), and thymic neuroendocrine tumors in 4 patients (1.4%). Tumors in Tumour, Node, Metastasis (TNM) stage I were diagnosed in 181 patients (64%) and were mostly thymomas (72%). Prior to TET diagnosis, 91 (32%) patients presented with autoimmune disorders (19% myasthenia gravis) and 82 patients (29%) had at least one cancer diagnosis. We found a higher incidence of TETs in Denmark than in previous European population-based studies, while reporting a similar distribution of histological types and tumor stages. Furthermore, we found an increased prevalence of autoimmune disorders and cancers in the cohort before TET diagnosis compared to the general population.

Neoplastic premalignant pancreatobiliary lesions: current update on the spectrum of lesions and their imaging appearances.

Common pancreatobiliary epithelial malignancies such as pancreatic ductal adenocarcinoma, cholangiocarcinoma and gallbladder carcinoma have poor prognosis. A small but significant portion of these malignancies arise from mass-forming grossly and radiologically visible premalignant epithelial neoplasms in the pancreatobiliary tree. Several lesions, including a few recently described entities, fall under this category and predominantly include papillary epithelial lesions with or without mucin production. These include common lesions such as intraductal papillary mucinous lesions (IPMN) in pancreas and less common to rare lesions such intraductal papillary neoplasms of the bile ducts (IPNB), pancreatic and biliary intraductal oncocytic papillary neoplasms (IOPN) and intraductal tubulopapillary neoplasms (ITPN), intracholecystic neoplasms (ICN) in the gallbladder, intra-ampullary papillary-tubular neoplasms (IAPN) in the ampulla and mucinous cystic neoplasms in the pancreas, biliary tree and gallbladder. These lesions have an excellent prognosis before malignant transformation and even with malignant transformation, often fare better than the conventional malignant counterparts. These lesions have characteristic histologic, radiologic, and molecular characteristic features. Several of these neoplastic lesions are associated with field-effect phenomenon which means that in presence of even one of these lesions, the entire background ductal epithelium is at risk of developing synchronous or metachronous malignancies. Awareness of these lesions and their imaging appearances as well as utilization of relevant molecular diagnostics can help practicing radiologists and clinicians improve patient outcomes by detecting early and treating or surveilling such lesions before malignant transformation or before metastatic dissemination.

Viability and Radiosensitivity of Human Tumor Cells from Breast and Colon Are Influenced by Hypericum perforatum Extract HP01.

To enhance the treatment of tumors that are resistant to radio- and chemotherapy while minimizing the side effects of radiochemotherapy, researchers are continuously seeking new active compounds for use in combination with radiotherapy. Therefore, the aim of our study was to examine the cytotoxic and radiosensitizing effects of an extract from St. John's Wort (Hypericum perforatum), referred to as HP01, on human epithelial tumor cells in vitro. The growth of MCF-7 (breast carcinoma) and HT-29 (colon carcinoma) cells was examined under the influence of HP01. In combination with radiation, the effects of HP01 on cytotoxicity and long-term survival were assessed using a colony formation assay. The number of DNA double-strand breaks was analyzed using the γH2AX assay, while cell cycle distribution was examined via flow cytometry. A growth-inhibiting and cytotoxic effect was observed for both tumor cell lines starting at a concentration of 10 µg/mL HP01. Treatment with HP01 resulted in an inhibition of clonogenic survival of tumor cells after ionizing radiation (6 Gy). The number of DNA double-strand breaks (DSBs) in tumor cells increased with HP01 treatment, but the repair of radiation-induced DNA DSBs was not affected. Cell cycle analysis revealed that HP01, in addition to radiation, enhanced G2/M arrest in MCF-7 and HT-29 cells. Overall, HP01 not only showed a growth-inhibiting effect but also demonstrated a radiosensitizing effect on human tumor cells for the first time. We conclude that the HP01-induced G2/M accumulation of cells may be the main rationale for the drug-induced radiosensitivity. It is therefore a promising candidate for combined therapy in tumor diseases and warrants further investigation.

NAB2::STAT6 Rearranged Carcinoma of the Parotid Gland with Sebaceous Differentiation: A Case Report.

The NAB2::STAT6 fusion is predominantly associated with solitary fibrous tumors (SFTs) and is utilized in diagnosing SFTs through nuclear STAT6 protein overexpression. Recent studies expanded the phenotypic spectrum of NAB2::STAT6 rearranged neoplasms, including adamantinoma-like and teratocarcinosarcoma-like phenotypes. We report a case of a NAB2::STAT6 rearranged epithelial tumor exhibiting sebaceous differentiation in the parotid gland. Fine-needle aspiration (FNA), histopathology, immunohistochemistry, and molecular studies of this case were described. Fine-needle aspiration (FNA) revealed atypical basaloid cells, suggesting primary salivary gland carcinoma or metastasis. Histological examination showed basaloid-squamous cells with a monomorphic appearance containing foci of sebaceous differentiation, expressing pancytokeratin, p40, and androgen receptor, while CD34 staining was negative. Molecular studies identified a NAB2::STAT6 fusion, along with an AKT1 mutation. This case further expands the phenotypic spectrum of NAB2::STAT6 rearranged neoplasms and emphasizes comprehensive histopathological and molecular analysis in challenging head and neck tumors. It suggests STAT6 immunohistochemistry as a potential screening tool for head and neck tumors resembling sebaceous carcinoma, myoepithelial tumors, or GLI1-altered neoplasms.

Triple-Negative Breast Cancer Progression and Drug Resistance in the Context of Epithelial-Mesenchymal Transition.

Triple-negative breast cancer (TNBC) is one of the most difficult subtypes of breast cancer to treat due to its distinct clinical and molecular characteristics. Patients with TNBC face a high recurrence rate, an increased risk of metastasis, and lower overall survival compared to other breast cancer subtypes. Despite advancements in targeted therapies, traditional chemotherapy (primarily using platinum compounds and taxanes) continues to be the standard treatment for TNBC, often with limited long-term efficacy. TNBC tumors are heterogeneous, displaying a diverse mutation profile and considerable chromosomal instability, which complicates therapeutic interventions. The development of chemoresistance in TNBC is frequently associated with the process of epithelial-mesenchymal transition (EMT), during which epithelial tumor cells acquire a mesenchymal-like phenotype. This shift enhances metastatic potential, while simultaneously reducing the effectiveness of standard chemotherapeutics. It has also been suggested that EMT plays a central role in the development of cancer stem cells. Hence, there is growing interest in exploring small-molecule inhibitors that target the EMT process as a future strategy for overcoming resistance and improving outcomes for patients with TNBC. This review focuses on the progression and drug resistance of TNBC with an emphasis on the role of EMT in these processes. We present TNBC-specific and EMT-related molecular features, key EMT protein markers, and various signaling pathways involved. We also discuss other important mechanisms and factors related to chemoresistance in TNBC within the context of EMT, highlighting treatment advancements to improve patients' outcomes.

Exploring the debates surrounding keratoameloblastoma: An in-depth review of an emerging entity.

Ameloblastoma is a benign odontogenic epithelial tumor characterized by its aggressive behavior and a high likelihood of local recurrence if not fully excised. Ameloblastomas are a common type of slow-growing, true jaw tumor which may present as solid, multicystic or unicystic forms and originate from odontogenic epithelium and exhibit a variety of histological patterns. Keratoameloblastoma is considered to be a rare variant of ameloblastoma associated with more intense keratinization. Therefore, in this present review, authors report a case of keratoameloblastoma in a 14-year-old male and review giving a sneak-peek into this lesion with insight into the literature concerning its presentation, incidence, aetiology, clinical features, radiological appearance, histopathological findings and treatment options along with the current literature about this lesion.

Genotype-Phenotype Correlations in the Hyperparathyroidism-Jaw Tumor Syndrome.

Establishing genotype-phenotype correlations in disorders of hereditary endocrine neoplasia is important for clinical screening, genetic counseling, prognostication, surveillance, and surgical strategy, and may also provide clues about disease pathogenesis. Important genotype-phenotype correlations are recognized, for example, in pheochromocytoma/paraganglioma and multiple endocrine neoplasia type 2A. The presence of such correlations has been less clear in other familial endocrine disorders associated with primary hyperparathyroidism including multiple endocrine neoplasia type 1 (MEN1), and the hyperparathyroidism-jaw tumor syndrome (HPT-JT). Characteristic features of HPT-JT, apart from fibro-osseous jaw tumors and uterine lesions, include renal neoplasms, such as Wilms tumor and mixed epithelial and stromal tumor (MEST; "renal hamartomas"), and a high incidence of parathyroid cancer. Emerging evidence suggests two different genotype-phenotype correlations in HPT-JT based on the type of variant in the CDC73 tumor suppressor gene. Although multiple CDC73 genotypes can give rise to the Wilms tumor phenotype in HPT-JT, the development of MEST of the kidney specifically correlates with the presence of a start-loss variant affecting the initiator methionine codon of parafibromin, the protein product encoded by CDC73. Furthermore, the risk of parathyroid cancer in HPT-JT also appears to correlate with genotype: CDC73 frameshift indel, splice-site, and stopgain genotypes are associated with a greatly increased risk of parathyroid carcinoma compared to carriers of CDC73 missense and non-frameshift indel variants. The recognition of such genotype-phenotype correlations in HPT-JT may impact genetic counseling, patient care and disease surveillance.

Opportunities for predictive proteogenomic biomarkers of drug treatment sensitivity in epithelial ovarian cancer.

Genomic analysis has played a significant role in the identification of driver mutations that are linked to disease progression and response to drug treatment in ovarian cancer. A prominent example is the stratification of epithelial ovarian cancer (EOC) patients with homologous recombination deficiency (HRD) characterized by mutations in DNA damage repair genes such as BRCA1/2 for treatment with PARP inhibitors. However, recent studies have shown that some epithelial ovarian tumors respond to PARP inhibitors irrespective of their HRD or BRCA mutation status. An exclusive focus on the genome overlooks the significant insight that can be gained from other biological analytes, including proteins, which carry out cellular functions. Proteogenomics is the integration of genomics, transcriptomics, epigenomics and proteomics data. This review paper provides novel insight into the role of proteogenomics as an analytical approach to identify predictive biomarkers of drug treatment response in epithelial ovarian cancer. Proteogenomic analysis can facilitate the identification of predictive biomarkers of drug treatment response, consequently greatly improving the stratification of patients with EOC for treatment towards a goal of personalized medicine.

Cell-Based Therapies in GI Cancers: Current Landscape and Future Directions.

Cell-based therapies have become integral to the routine clinical management of hematologic malignancies. Tumor-infiltrating lymphocyte (TIL) therapy has demonstrated efficacy in immunogenic solid tumors, such as melanoma. However, in the GI field, evidence supporting the clinical success of cell-based therapies is still awaited. CLDN18.2, a key tight junction molecule in stomach epithelium, has emerged as a promising target for gastric cancer (GC) treatment. Because of its lineage-specific expression, significant efforts have been made to develop chimeric antigen receptor T-cell (CAR-T) therapies targeting CLDN18.2. These therapies have shown encouraging tumor shrinkage in patients with heavily pretreated GC. However, durable responses remain uncommon. CAR-T exhaustion driven by immune-suppressive cells in the tumor microenvironment, along with the heterogeneous expression of target molecules, poses significant challenges. In addition, managing on-target, off-tumor toxicities remains a critical issue in therapies targeting tissue-associated antigens. Next-generation CARs are expected to address these resistance mechanisms. Furthermore, adoptive macrophage and natural killer cell therapies hold promise for not only their efficacy but also for the ease off-the-shelf production. Advanced neoantigen prediction and identification of optimal T-cell activation targets could facilitate the clinical application of TIL and T-cell receptor-T therapies in GI cancers. Cell-based therapies might have the potential to transform the treatment landscape for GI cancers.

Immunophenotype of uterine tumor resembling ovarian sex cord tumor (UTROSCT): Case series and meta-analysis of the literature.

This study aimed to define the frequency of positivity of several immunohistochemical markers in uterine tumor resembling ovarian sex cord tumor (UTROSCT). All consecutive UTROSCT cases were retrieved from consultation files of one of the authors. Histological and immunohistochemical slides were reviewed. In addition, three electronic databases were searched from their inception to January 2024 for all studies assessing the immunophenotype of UTROSCT. Exclusion criteria were: sample size < 10 patients, overlapping patient data, reviews. Endometrial stromal tumors with sex cord-like areas (formerly called "type I UTROSCT") were excluded. Immunohistochemical markers assessed in ≥ 10 cases in at least 3 different series were included. For each marker, pooled positivity rate was calculated by using a random effect model; mean labeling index was calculated for Ki67. Thirty UTROSCT cases were retrieved Six studies were included, and 30 new cases were obtained, with a total of 181 UTROSCTs. Fourteen immunohistochemical markers were assessed. Pooled positivity rates were (in descending order): CD56 = 97 %, progesterone receptor = 91 %, estrogen receptor = 85.5 %, WT1 = 84 %, wide-spectrum cytokeratins = 78.7 %, CD99 = 77 %, desmin = 74.5 %, calretinin = 70.6 %, smooth muscle actin = 56.4 %, inhibin = 44.5 %, CD10 = 41 %, caldesmon = 21.9 %, Melan-A/MART-1 = 10.4 %. Mean Ki67 labeling index was 8.7 %. Immunophenotypically, UTROSCT is less consistent than ovarian sex cord tumors and overlaps with other mesenchymal and epithelial tumors; an integrated clinico-pathological and immunohistochemical evaluation appears necessary for a correct diagnosis.

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

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

Arenobufagin suppresses the progression of early-stage hepatocellular carcinoma by inhibiting EpCAM-mediated tumor stemness

Epithelial cell adhesion molecule (EpCAM) is a biomarker for epithelial cell-derived tumors. However, the specific role of EpCAM itself in early-stage hepatocellular carcinoma progression remains unclear, and small molecules targeting EpCAM have not yet been reported. Here, the protein expression profile of EpCAM in tumor-adjacent regions was found to be higher than that in tumor regions, and to be positively associated with the progression of early-stage liver cancer, as well as high frequency of recurrence, cirrhosis, lymph node metastasis, microvascular invasion and cancer stemness, in 68 patients with hepatocellular carcinoma (HCC). In vitro, EpCAM enhanced cancer cell stemness, as reflected by increased abilities of proliferation, self-renewal, migration and invasion, which was counteracted by arenobufagin. Furthermore, arenobufagin inhibited the viability of Hep3B and Huh7 cells with IC50 values of 36.4 nM and 123.4 nM after 72 h of treatment, respectively. Molecular docking data further indicated that arenobufagin binds EpCAM. Moreover, arenobufagin inhibited early progression of HCC through EpCAM in a zebrafish xenograft tumor model mimicking early-stage hepatocellular carcinoma without blood vessels in vivo. This study supports a tumor-promoting role of EpCAM in early-stage hepatocellular carcinoma by facilitating cancer stemness and suggests that arenobufagin might be promising candidate for EpCAM inhibition.

Advanced thymic epithelial tumour resection: vascular resection and reconstruction strategy

Advanced thymic epithelial tumour resection: vascular resection and reconstruction strategy

Diagnostic and prognostic relevance of inflammatory markers in surgically treated thymic epithelial tumors: An international multicenter study

Diagnostic and prognostic relevance of inflammatory markers in surgically treated thymic epithelial tumors: An international multicenter study

Low-grade Nasopharyngeal Papillary 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.