Search Results (128)

Background/Objectives: Appendiceal cancer (AC) is a rare and understudied malignancy with limited genomic data available to guide clinical interventions. Historically treated as a subtype of colorectal cancer, AC is now recognized as a distinct disease with unique histologic subtypes and molecular features. This review aims to consolidate current genomic data across AC subtypes and explore the clinical relevance of recurrent mutations. Methods: A systematic literature review was performed in accordance with general Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines. Using search engines such as PubMed and Web of Science, we selected studies based on relevance to AC genomics using search terms such as “appendix cancer”, “appendiceal cancer”, “pseudomyxoma peritonei”, “sequencing”, “mutation”, and “genotype”. Results: AC comprises five major histologic subtypes—appendiceal neuroendocrine neoplasms (ANENs), mucinous appendiceal neoplasms (MANs), goblet cell adenocarcinomas (GCAs), colonic-type adenocarcinomas (CTAs) and signet ring cell adenocarcinomas (SRCs)—each with unique clinical behaviors and mutational profiles. Low-grade tumors, such as ANENs and MANs, frequently harbor KRAS and GNAS mutations, while high-grade subtypes, such as CTAs and SRCs, are enriched for TP53, APC, and SMAD gene alterations. GCA tumors exhibit a distinct mutational spectrum involving chromatin remodeling genes such as ARID1A and KMT2D. Compared to colorectal cancer, AC demonstrates lower frequencies of APC and TP53 mutations and a higher prevalence of GNAS mutations, consistent with a pathological divergence from CRC. Conclusions: The genomic heterogeneity of AC is commensurate with its histological complexity and has important implications for diagnosis, prognosis and treatment. While certain actionable mutations are present in a subset of tumors, large-scale genomic characterization efforts and development of subtype-specific models will be essential for advancing precision medicine in AC. Full article

Background: Collision tumors, especially in the ovary, are a rare phenomenon where two distinct types of tumors develop adjacent to each other within the same organ but remain separate histologically. We present a case of the first collision ovarian tumor in a 14-year-old girl consisting of a combined tumor and a mature teratoma. Case Report: A 14-year-old girl presented with abdominal swelling for the past three months, without other symptoms. Ultrasound (US) examination of the abdomen revealed a large cystic mass with multiple septa, filling the entire abdomen from the diaphragm to the pelvis. Magnetic resonance imaging (MRI) showed an intraperitoneal mass, inseparable from the right ovary, measuring 22 cm × 13 cm × 30 cm. Serum tumor markers were within normal limits. The tumor mass was completely extirpated along with the fallopian tube. Histological and immunohistochemical analysis determined that it was a mucinous cystadenocarcinoma, characterized by a transition pattern from benign and borderline components to an adenocarcinoma component with a smaller mature teratoma. Six-month follow-up revealed no recurrence or postoperative complications. Conclusions: As the first documented case, this case provides valuable insights into pediatric ovarian neoplasms, guiding future diagnostic and therapeutic approaches. Full article

Canine mammary tumors (CMTs) are among the most frequently diagnosed neoplasms in female dogs, with complex etiologies involving age, breed, body size, and reproductive status. This retrospective study analyzed 250 cases comprising 361 mammary tumors to evaluate demographic patterns, histopathological subtypes, and their topographical distribution. The majority of tumors (88.64%) were malignant, with complex carcinoma being the most common subtype (24%), followed by intraductal papillary carcinoma (14.95%). The mean age at diagnosis was 9.36 years, with 60.8% of cases occurring in dogs older than 8 years. Mixed-breed dogs were most frequently affected, followed by Bichon-type breeds and German Shepherds. Small-sized dogs (<10 kg) accounted for 43.5% of cases. Regarding the reproductive status, 35.6% of dogs were unspayed, while the remainder were either intact or had an undetermined status, reflecting regional spaying practices. A statistically significant association was identified between histological subtype and mammary gland location, revealing non-random, region-specific tumor distribution. Complex carcinomas were frequently located in the left canial abdominal mammary segment (L.A2), right canial abdominal mammary segment (R.A2), and left inguinal mammary segment (L.ING); mixed and tubular carcinomas were more prevalent in R.A2 and R.ING; and tubulopapillary carcinomas appeared predominantly in L.ING. While no significant overall association was found between tumor grade and gland location, grade III carcinomas showed a possible predilection for the left inguinal gland (L.INGH), indicating a regional tendency that warrants further investigation. These findings underscore the importance of anatomical factors in the development of CMTs and support the integration of gland-specific tumor patterns into diagnostic assessment and surgical decision-making. Full article

The aggressiveness of oral melanoma can be related to several mutations that occur during development. Based on the knowledge of the role of transcription factors of the SOX family in other neoplastic types, it is necessary to understand their behavior in oral melanomas. In this work, the expression of SOX2, SOX3, and SOX10 and its relationship with the proliferative index and histological aspects indicative of aggressiveness in canine oral melanomas were evaluated. Thirty tumors were histologically reviewed and the expression of Melan-A, SOX2, SOX3, SOX10, and Ki67 in these tumors were determined. All tumors presented histomorphological characteristics compatible with malignant tumors and immunopositivity for Melan-A. The expression of SOX2, SOX3, and SOX10 was observed in 7/30 (23.3%), 6/30 (20%), and 23/30 (76.6%) of the cases, respectively. Among the analyzed markers, the relationship between the loss of SOX3 expression in tumors with higher proliferative rates was highlighted. An inverse correlation was also observed between the expression cytoplasmic SOX10 and nuclear SOX10, suggesting a change in the location of this protein in oral melanomas. Among the SOX family proteins studied, the SOX3 protein plays a role in the regulation of cell proliferation in oral melanomas, and it is suggested that the SOX2 and SOX10 proteins are constitutively expressed in these neoplasms, without a determining role for aggressiveness. New studies of this gene transcription pathway may assist in possible prognostic and predictive determinations of the SOX3 protein in oral canine melanoma. Full article

An adult female Eurasian otter (Lutra lutra), introduced with another subject in the National Park of Gran Paradiso (Aosta Valley Region, Italy), was found dead. The necropsy found a mass involving mainly the gallbladder walls with other multicentric masses in the liver and pancreas. In addition to these, through the histological examination, other nodules were detected in the pancreas, with structure similar to gallbladder neoplasm. Histopathology diagnosed it as neoplasia composed of epithelioid cells, forming lobules of tubules and pseudoacini, with a very low mitotic count, discrete cellular pleomorphism, and prominent fibrous stroma. Neoplastic cells demonstrated positive immunoreactivity for cytokeratin and negative immunoreactivity for S100. Gross and histologic lesions and immunohistochemical findings were consistent with a primary gallbladder carcinoma (GBC) of metastatic type. GBC is a rare neoplasm in both humans and animals, sometimes associated with cholelithiasis and cholecystitis, with few reports in the veterinary literature especially in cattle, pigs, dogs and cats. To the best of our knowledge, this is the first report of GBC in a Eurasian otter. Full article

Background/Objectives: The 2019 WHO classification redefined high-grade gastrointestinal neuroendocrine neoplasms (GI NENs), encompassing not only poorly differentiated neuroendocrine carcinomas (NECs), but also well-differentiated grade 3 neuroendocrine tumors (NETs G3). Since both subtypes share a Ki-67 index > 20%, distinguishing them based solely on morphology is challenging. Prior studies have shown TP53 alterations in NECs but not in NETs. This study aimed to evaluate clinico-morphological parameters and the immunohistochemical (IHC) expression of p53 in high-grade GI NENs to identify relevant correlations. Methods: Tumors were stratified by Ki-67 index into two groups: >20–50% and >50%. p53 IHC expression was assessed as “wild-type” (1–20% positive tumor cells) or “non-wild-type” (absence or >20% positivity). Correlations were analyzed between Ki-67, p53 status, and various pathological features. Results: Significant correlations were found between the Ki-67 index and maximum tumor size, pT stage, lymphovascular invasion, perineural infiltration, and diagnostic classification. Similarly, p53 immunohistochemical status was significantly associated with lymphovascular invasion, lymph node metastasis, and tumor classification (NET G3 versus NEC, including NEC components of MiNENs). Conclusions: The findings support the value of Ki-67 and p53 as complementary biomarkers in the pathological evaluation of high-grade GI NENs. Their significant associations with key morphological parameters support their utility in differentiating NETs G3 from NECs, particularly in cases showing overlapping histological features. The immunohistochemical profile of p53 may serve as a useful diagnostic adjunct in routine practice. Full article

Background: Gastric neoplasms remain pathologies of the malignant spectrum with high incidence and prevalence, with their management requiring a precise histopathological characterization for optimal treatment planning. Methods: The present study is a retrospective analysis that included 67 histopathologically confirmed gastric neoplasia subjects and was performed at a single surgical center from January 2020 to December 2021. Demographics, tumor characteristics, surgical procedures, and oncologic outcomes were included, filtered, and subsequently analyzed using SPSS Statistics 29.0. Results: This study involved 67 patients (mean age 65.7 years, 56.7% men), with adenocarcinoma being the most common histologic type (91.0%) and most tumors being diagnosed directly as Stage III (40.3%). Lauren classification revealed the intestinal type as the most common (49.2%), followed by diffuse (36.1%) and mixed (14.8%). Poorly differentiated tumors (G3) accounted for 53.7% of cases. The surgical team performed curative resection in 75% (n = 50) of patients, achieving R0 margins in 88% of these cases. Subtotal gastrectomy with D2 lymphadenectomy yielded the highest curative success rate with 96.6% R0 resection. Statistically, we identified two significant correlations between age and tumor grade (rho = 0.28; p = 0.021) and between the number of lymph nodes examined and the number of lymph nodes invaded (rho = 0.65, p < 0.001). This study again revealed that adenocarcinomas showed higher rates of lymph node invasion than other tumor types (p = 0.017). Conclusions: The analysis of patients with gastric neoplasms is vital for appropriate therapeutic management. Even though the study period included a pandemic, the analysis remained a complex one with high-quality surgical outcomes, confirming the importance of maintaining oncologic standards during medical crises. Full article

Background and Clinical Significance: Brenner tumors are rare epithelial tumors that can occur in both males and females. They consist of ovarian transition cells surrounded by dense fibrous tissue and can be classified as benign, borderline, or malignant. While most commonly found in the ovary, extraovarian Brenner tumors (EOBTs) have been reported in the uterus, vagina, broad ligament, and omentum. Case Presentation: A 71-year-old postmenopausal woman presented with a polypous formation on the upper third of the posterior vaginal wall, which was found at a routine health check. Macroscopically, the lesion appeared as a solid, polypoid mass with a yellowish-gray cut surface, measuring approximately 25 × 20 mm. Histological examination revealed a polypoid formation covered by stratified squamous epithelium, with a dense fibrous stroma (Van Gieson [VG]+) and tubular structures lined by clear epithelial cells. Parenchymal cells showed low proliferative activity, with Ki-67 expression in less than 5% of cells, also Cytokeratin (CK) 7/+/p63:/+/ CK AE1/AE3: /+/ Estrogen Receptor (ER): /+/ and Progesterone Receptor (PR)/−/; CK20/-/; p53/−/, Wilms’ Tumor (WT)-1/−/; Prostate-Specific Acid Phosphatase (PSAP)/−/. The final diagnosis was an extraovarian Brenner tumor. The patient was monitored for two months post-excision, with no signs of recurrence. Conclusions: EOBTs are extremely rarely seen and vaginal involvement is far less common. Due to their rarity, these tumors may be confused with other benign or malignant vaginal lesions. In order to differentiate EOBTs from other neoplasms, histological analysis is crucial due to their characteristic transitional-type epithelium and large fibrous stroma. Further studies are required to understand the origin and clinical behavior of EOBTs. Long-term monitoring should be performed to look for any recurrence or malignant change, even though benign Brenner tumors usually have a good prognosis. Awareness of EOBTs and their possible locations is essential for accurate diagnosis and appropriate management. Full article

Background/Objectives: This study aimed to investigate oncologic and obstetrical outcomes of patients conservatively treated for atypical hyperplasia (AH), endometrial intraepithelial neoplasm (EIN), and early endometrial cancer (EC), as well as factors that influence these outcomes. Methods: This study included 87 women conservatively treated due to AH/EIN and well-differentiated endometrioid EC confined only to the endometrium during past 10 years. Therapy type, course, and duration were registered. The response totherapy after 12 months (remission vs. disease persisting or progressing) was considered as the oncologic outcome. All attempted and achieved pregnancies, along with conception method, gestational week, and delivery type, were recorded. The obstetrical outcomes were classified as adverse (miscarriage) or successful (healthy child). Results: All patients received LNG-IUD along with GnRHa and, if indicated, metformin. Complete remission was achieved in 74.7% of patients. The disease was persisting in 17.2% and progressing in 3.5% of patients, while recurrence was registered in 4.6% of patients. Radical surgery during follow-up was indicated in 15% of patients due to condition deterioration. Pregnancy was attempted by 29.9% of patients, out of which nine succeeded (34.6%). There were two early miscarriages, while the remaining seven pregnancies ended in a term delivery of a healthy child, mostly by planned cesarean section. The only predictor of long-term disease remission was malignancy-free control histological findings. Better therapy response and achieving remission in shorter time were predictors of good obstetrical outcome. Conclusions: This study proved the efficacy and safety of current protocols for AH/EIN/EC conservative treatment and indicated that adequate early (6-month) response totherapy has the most importance for long-term remission and pregnancy achievement. Full article

Background and Clinical Significance: Men who engage in anal fisting may experience full rectal and colon thickness injury resulting in an endoscopic emergency. The endoscopist does not routinely question patients about their sexual habits, nor are patients compliant with counseling during the endoscopy procedure as indicated by the infectious disease clinician. Case Presentation: A 47-years-old HIV- and monkeypox virus (MPXV)-negative Caucasian gay man underwent colonoscopy because of changes in bowel habits with anal discomfort and rectal bleeding. The first colonoscopy showed a vegetative annular neoformation of the anal canal. There was a concentric stenosis of the lumen. The endoscopist suspected the diagnosis of anal squamous cell carcinoma and a histopathology investigation was requested. Biopsy histology excluded a frank neoplasm or anal intraepithelial neoplasia (AIN). Then, the patient was referred to a multidisciplinary team. With adequate counseling, the patient disclosed his habitual anal fisting. Laboratory identification of L1–L3 Chlamydia trachomatis (CT) genovars was positive for CT L1, L2, real-time PCR for Neisseria gonorrhoeae (NG), and Mycoplasma hominis. Human Papillomavirus (HPV)-DNA detection identified HPV type 70, 68, and 61. We illustrate this case with plenty of histology and immunohistochemistry. We also review the differential diagnosis of AIN according to the 5th edition (2019) WHO Classification of Digestive System Tumours. Conclusions: Our patient emphasizes two important aspects of endoscopy and pathology: first, the significance of understanding patients’ sexual behaviors in diagnosing rectal and colon injuries, as well as the need for sexually transmitted infections (STI) screening especially for CT; and second, the effectiveness of a multidisciplinary communication model that encourages private discussions to alleviate patients’ fears and improve prevention efforts. Full article

Mixed-type carcinoma (MTC) accounts for 44% of mammary neoplasms in bitches and poses challenges in histological grading due to the heterogeneity of invasive areas. The present study aimed to measure and characterize invasive areas in the stroma of MTC and investigate the association of those parameters with lymph node status and survival. Forty cases were analyzed and divided into two groups: with metastasis and without metastasis. The size, perimeter, length, and number of invasive carcinomatous areas were measured. Cases with metastasis showed a higher number of foci (p = 0.003) and larger invasive areas (p = 0.006) compared to cases without metastasis. Bitches with invasive areas larger than 2 mm² had shorter survival times. No association was found between the perimeter or length of invasive areas, the expression of Ki67, ER, PR, COX-2, HER-2, and the immunophenotype. Thus, the number and size of invasive areas are associated with regional lymph node status, suggesting histomorphometry may serve as a valuable tool for evaluating the biological behavior of mixed-type carcinoma. Full article

Hybrid Peripheral Nerve Sheath Tumors (HPNSTs) are rare benign neoplasms that exhibit a combination of histological features from multiple types of benign peripheral nerve sheath tumors, including schwannomas, neurofibromas, and perineuriomas. These tumors present a diagnostic challenge due to their morphological and histological variability. In this article, we aim to summarize the key morphological, histological, and molecular characteristics of HPNSTs, providing insights into their diagnostic approaches. We review the different hybrid subtypes, including schwannoma–perineurioma, schwannoma–neurofibroma, and perineurioma–neurofibroma, emphasizing their clinical features, genetic associations, and the role of surgical excision as the gold-standard treatment. Full article

Background: Only a few published cases of primary adenocarcinoma of the upper urinary tract have been described in the literature. The aim of this systematic review was to collect all published cases of primary adenocarcinoma of the upper UT and identify prognostic factors and useful diagnostic modalities for their optimal treatment. Methods: Systematic research in the PubMed/Medline and Scopus databases concerning primary adenocarcinoma of the upper urinary tract was performed by two independent investigators. A total of 85 studies were included in the review. Results: In total, 84 patients were included, consisting of 54 males (64.29%) and 30 females (35.71%). Out of the available data, 24.71% reported a history of lithiasis, 16.47% episodes of pyelonephritis and 10.59% a history of hydronephrosis. Concerning histologic findings on excised tumors, 52.44% of neoplasms were mucinous, 19.51% tubulovilous, 18.29% papillary, 4.88% mixed mucinous–papillary and 4.88% poorly differentiated. Concerning anatomical origin, 62.34% of tumors were found in the renal pelvis, 22.08% in the ureter and 12.99% in both the renal pelvis and the ureter. Surgical treatment was the preferred therapeutic option and was performed in 96.39% of the included patients. In multivariable analysis, a statistically significant relationship was found between a clinical cure and ureter origin of the lesion (OR: 0.17, 95% CI: 0.00–0.22, p = 0.002), the presence of an abdominal mass (OR: 0.08, 95% CI: 0.01–0.63, p: 0.034) and a poorly differentiated histological type (OR: 0.02, 95% CI: 0.00–0.91). In multivariable time-to-event analysis, the male sex (HR: 0.12, 95% CI: 0.02–1.01, p: 0.019) and poorly differentiated histological type (HR: 91.06, 95% CI: 7.31–1134.32, p: 0.002) had statistically significant impacts on overall survival. Conclusions: Selection of the optimal surgical management, via either nephrectomy or nephroureterectomy, depends on the origin of the primary lesion and represents the mainstay of treatment. A suspicion from the urologist is needed for the identification and optimal treatment of these rare tumors. Full article

Background/Objectives: Thyroid cancer ranks among the most prevalent endocrine neoplasms, with a significant rise in incidence observed in recent decades, particularly in papillary thyroid carcinoma (PTC). This increase is largely attributed to the enhanced detection of subclinical cancers through advanced imaging techniques and fine-needle aspiration biopsies. The present study aims to externally validate a predictive model previously developed by our group, designed to assess the risk of a thyroid nodule being malignant. Methods: By utilizing clinical, analytical, ultrasound, and histological data from patients treated at the Puerto Real University Hospital, this study seeks to evaluate the performance of the predictive model in a distinct dataset and perform a decision curve analysis to ascertain its clinical utility. Results: A total of 455 patients with thyroid nodular pathology were studied. Benign nodular pathology was diagnosed in 357 patients (78.46%), while 98 patients (21.54%) presented with a malignant tumor. The most frequent histological type of malignant tumor was papillary cancer (71.4%), followed by follicular cancer (6.1%). Malignant nodules were predominantly solid (95.9%), hypoechogenic (72.4%), with irregular or microlobed borders (36.7%), and associated with suspicious lymph nodes (24.5%). The decision curve analysis confirmed the model’s accuracy and its potential impact on clinical decision-making. Conclusions: The external validation of our predictive model demonstrates its robustness and generalizability across different populations and clinical settings. The integration of advanced diagnostic tools, such as AI and ML models, improves the accuracy in distinguishing between benign and malignant nodules, thereby optimizing treatment strategies and minimizing invasive procedures. This approach not only facilitates the early detection of cancer but also helps to avoid unnecessary surgeries and biopsies, ultimately reducing patient morbidity and healthcare costs. Full article

Background: Intraductal papillary mucinous neoplasms (IPMNs) are pre-malignant pancreatic lesions that may progress to invasive pancreatic ductal adenocarcinoma (PDAC). IPMN-associated invasive carcinoma (iIPMN) has been associated with more favorable survival outcomes compared to non-iIPMN-derived PDAC. Here, we aim to investigate the genetic landscape of IPMNs to assess their relevance to oncologic outcomes. Methods: This retrospective study used a large single-institution prospectively maintained database. Patients who underwent curative-intent pancreatic resection between 2016 and 2022 with histologically confirmed diagnosis of IPMN were included. Demographic, pathologic, molecular, and oncologic outcome data were recorded. Kaplan–Meier survival analyses were performed. PDAC data from public genetic databases were used for mutational correlation analysis. p-value ≤ 0.05 was considered as significant. Results: A total of thirty-nine patients with resected IPMN with complete clinical and sequencing data were identified and included in the final cohort. The male-to-female distribution was 21:18, and the mean age was 70.1 ± 9.1 years. GNAS mutations occurred in 23.1% of patients, and 89.7% of patients had iIPMN. In iIPMN patients, GNAS mutation was strongly associated with improved disease-free survival: all GNAS-mutant patients survived to follow-up with significantly fewer recurrences than in GNAS wild-type (WT) patients (p = 0.013). Mutated GNAS closely co-occurred with wild-type KRAS (p < 0.001), and further analysis of large genomic PDAC datasets validated this finding (OR 3.47, p < 0.0001). Conclusions: Our study suggests prognostic value of mutational status in malignant resected IPMNs. WT GNAS, mutant P53, and mutant KRAS each correlate with recurrence and decreased survival. Further studies are required to validate these preliminary observations. Full article