Search Results (53)

Undifferentiated pleomorphic sarcoma (UPS) is an exceptionally rare mesenchymal neoplasm in the feline oral cavity, presenting significant diagnostic and therapeutic challenges. A 10-year and 10-month-old, castrated male Korean Shorthair cat presented with a progressively enlarging sublingual mass measuring 2.77 cm × 3.02 cm × 1.86 cm. Computed tomography revealed a well-circumscribed, non-osteolytic sublingual mass without detectable mandibular bone erosion or regional lymphadenopathy. Gross complete surgical excision was performed via a transoral approach without mandibulectomy. Histopathological examination revealed a highly pleomorphic, sheet-like proliferation of atypical spindle to epithelioid cells with prominent giant binucleated cells and a low mitotic count (3 per 10 high-power fields). To establish a diagnosis of exclusion, an extensive immunohistochemical (IHC) panel was performed. The neoplastic cells were strongly positive for vimentin and diffusely positive for S100, but immunonegative for pancytokeratin (PanCK), Melan-A, Iba-1, desmin, and α-smooth muscle actin (α-SMA). These exclusionary IHC findings did not support epithelial, histiocytic, or myogenic differentiation, though amelanotic melanoma cannot be completely excluded based on Melan-A negativity alone. Rather than confirming definitive neural differentiation, the diffuse S100 immunoreactivity supported a final diagnosis of an S100-positive UPS. The patient achieved rapid functional recovery, with owner-reported absence of clinical signs of local recurrence over a 90-day follow-up period. This report underscores the necessity of a broad exclusionary IHC panel to accurately diagnose feline oral UPS and highlights surgical resection as a viable local management option. Full article

Species of the genus Opuntia exhibit considerable variation in chromosome number and ploidy level, making cytogenetic information essential for studies on evolution, taxonomy, and genetic improvement. However, cytogenetic information on several species of this genus remains limited. Therefore, the objectives of this study were to determine chromosome numbers and ploidy levels in seven Opuntia species and to characterize the karyotype of Opuntia microdasys as a representative diploid species. A total of 69 accessions representing seven species were collected from wild and cultivated populations in southeastern Coahuila, Mexico. Somatic cells obtained from root apices developed from cladodes were used to analyze chromosome numbers. Cytological preparations included determination of mitotic activity, pretreatment with p-dichlorobenzene, enzymatic digestion with pectolyase and cellulase, and acetocarmine staining, followed by chromosome counting and karyotype analysis of O. microdasys. The highest mitotic activity was recorded between 10:00 and 11:00 h. Chromosome counts revealed diploid (2n = 22), tetraploid (2n = 44), hexaploid (2n = 66), and octoploid (2n = 88) cytotypes. Notably, O. engelmannii exhibited intraspecific cytotypic variation, with both hexaploid and octoploid populations. The karyotype of O. microdasys was highly symmetrical, with a karyotype formula of 10m + 1sm, small chromosomes, and low asymmetry indices (A1 = 0.15; A2 = 0.106). These findings reveal substantial ploidy diversity among the seven Opuntia species analyzed and provide cytogenetic information relevant to the characterization, management, and conservation of Opuntia genetic resources, including their potential use in ex situ conservation and botanical collections. Full article

14-3-3σ is a cell-cycle regulatory protein implicated in tumor development and progression, but its expression in canine primary pulmonary carcinomas (CPPC) has not been characterized. This study investigated 14-3-3σ immunohistochemical expression in primary pulmonary carcinomas and its relationship with histological grade, proliferative activity, mitotic count, and tumor volume. Ten CPPCs were examined and graded according to established criteria. Immunohistochemical expression of 14-3-3σ was evaluated using a semiquantitative scoring system, while Ki-67 labeling was assessed by calculating the labeling index. Nine of 10 tumors (90%) showed 14-3-3σ immunoreactivity, which was predominantly multifocal, heterogeneous, and cytoplasmic; nuclear immunoreactivity was observed, particularly in areas showing strong cytoplasmic staining. Exploratory correlation analyses did not identify statistically significant associations between the 14-3-3σ immunohistochemical score and histological grade, Ki-67 labeling index, mitotic count, or estimated tumor volume. The Ki-67 labeling index ranged from 20.4% to 89.5% (median, 35.6%). These findings provide preliminary descriptive data on 14-3-3σ immunoreactivity in CPPCs. Larger studies incorporating quantitative assessment and clinical follow-up are warranted to determine its clinicopathological and prognostic significance. Full article

Introduction: The liver is a central metabolic regulator responsible not only for energy storage and allocation but also for the production of essential egg proteins. In seasonal breeders such as brown trout, physiological demands increase during spawning, requiring strong metabolic and structural adaptations. Understanding the cellular mechanisms underlying these fluctuations is essential for clarifying how liver function is regulated during reproduction. Objective: The aim of this study was to investigate cellular mechanisms underlying liver remodelling during the reproductive cycle of male and female brown trout by examining proliferation and apoptosis markers at both molecular and protein levels during four distinct reproductive stages: spawning capable, regressing, regenerating, and developing. Methodology: Adult male and female brown trout were sampled at four reproductive stages. Liver gene expression of proliferating cell nuclear antigen (PCNA) and caspase-3 was analysed using qRT-PCR. At the protein level, liver tissue sections were immunolabelled with antibodies against PCNA and caspase-3. Caspase-3 staining intensity was quantified using ImageJ, while PCNA expression was assessed by counting positively stained nuclei. Results: PCNA gene expression was upregulated during the regressing stage, while PCNA-positive nuclei immunolabelling increased during the regressing and spawning-capable stages. Caspase-3 transcript levels showed no significant differences among stages, whereas immunostaining increased during regenerating and developing stages. Conclusions: Overall, the liver undergoes dynamic cellular remodelling throughout the reproductive cycle, balancing proliferation and apoptosis to meet reproductive demands. The results suggest that proliferation is more evident during regenerating stages, while apoptotic activity may be regulated post-transcriptionally. PCNA also indicates that proliferative activity may persist during spawning capable stages, reflecting ongoing mitotic readiness despite reduced overall proliferation. Full article

Background: Smooth muscle tumors of uncertain malignant potential (STUMPs) are rare uterine neoplasms occupying the diagnostic continuum between benign leiomyoma and overtly malignant leiomyosarcoma. Their preoperative identification remains beyond the capability of current imaging modalities, and the diagnosis is almost invariably established through postoperative histopathological examination. The natural history of STUMP is highly variable, with recurrence rates ranging from approximately 7–27% and a documented potential for malignant transformation, underscoring the need for accurate pathological classification and long-term surveillance. Case Presentation: A 40-year-old woman with a history of hypertension presented with a 5-month history of progressive lower abdominal distension, urinary frequency, and menorrhagia. Transabdominal ultrasonography identified a large uterine fundal mass measuring approximately 10.89 × 8.96 cm. Preoperative laboratory findings demonstrated microcytic anemia. She underwent laparo-endoscopic single-site supracervical hysterectomy with bilateral salpingectomy. Histopathological examination revealed spindle cells with bland to mildly atypical nuclei, a mitotic count of <10/10 high-power fields, and focal necrosis, consistent with a diagnosis of STUMP. The patient remained free of recurrence over a 2-year follow-up period. Conclusions: This case illustrates the diagnostic challenge posed by STUMP in the preoperative setting and highlights the critical importance of thorough histopathological evaluation of all uterine smooth muscle tumor specimens. Minimally invasive hysterectomy with in-bag morcellation represents a feasible surgical approach, and long-term oncological surveillance is warranted given the risk of late recurrence and malignant transformation. Clinicians should maintain a heightened index of suspicion for borderline smooth muscle tumors when evaluating large or symptomatic uterine masses in premenopausal women. Full article

Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) develops through inflammation-driven preneoplastic alterations characterized by epidermal hyperplasia, dysplasia, and increased proliferative activity. C-phycocyanin (C-PC) possesses antioxidant and anti-inflammatory properties; however, its topical potential to attenuate a tumour-promoting cutaneous microenvironment is limited by poor skin penetration. This study evaluated the effects of C-PC-loaded transfersomes in a 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse model of skin carcinogenesis. Methods: Male BALB/c mice were assigned to six groups (n = 10 per group). Carcinogenesis was initiated with a single topical application of DMBA, followed by twice-weekly TPA application for 16 weeks. C-PC-loaded transfersomes (1 mg/mL or 10 mg/mL) were applied topically. Histopathological assessment included epidermal thickness, rete ridge depth, mitotic activity, mast cell density, and semi-quantitative scoring of hyperplasia, dysplasia, and inflammation. Ki-67 immunohistochemistry was used to evaluate basal and suprabasal proliferation. Results: Carcinogen exposure induced marked epidermal thickening, severe dysplasia, increased mitotic activity, elevated Ki-67 expression, and pronounced dermal inflammation. Treatment with C-PC-loaded transfersomes significantly reduced epidermal thickness, rete ridge depth, mast cell density, mitotic counts, and suprabasal Ki-67 index. The 1 mg/mL concentration demonstrated the most consistent attenuation of dysplasia severity and inflammatory changes. No adverse histopathological alterations were observed in internal organs. Conclusions: These findings indicate that transfersome-mediated topical delivery of C-PC attenuates early inflammation-driven epidermal remodelling and tumour-promoting alterations in experimental skin carcinogenesis, supporting its potential as a topical preventive strategy. Full article

The use of digitized slides for histopathological diagnosis has become common in veterinary pathology, and the validation of diagnostic techniques that are extrapolated from the evaluation of glass slides is needed. The goal of this study is to evaluate the efficiency of counting mitotic figures in physical glass slides and digitized slides of cutaneous tumors of dogs and cats. The mitotic count was performed by three pathologists on glass and digitized slides of ninety skin tumors, including 30 squamous cell carcinomas in dogs and cats, 30 mast cell tumors and 30 soft tissue tumors in dogs. An additional assessment of cellular proliferation was performed with immunohistochemistry for Ki67. Spearman’s correlation for the mean count of mitotic figures between the three observers on physical and digitized slides demonstrated a strong positive correlation for squamous cell carcinomas and mesenchymal tumors and a moderate correlation for mast cell tumors. Inter-observer agreement was moderate between the two methods. In conclusion, the results found suggest that digitized slides can be used reliably for mitotic figure counting in cutaneous neoplasms in small animals, without compromising their classification or prediction of prognosis. Full article

Background: Although Ki-67 is not included among the grading criteria in the current WHO Classification of Tumours of the Central Nervous System (CNS), it provides valuable, albeit limited, prognostic information. Immunohistochemistry for Ki-67 can reveal uneven proliferation patterns and assist in the assessment of mitotic counts. Several studies indicate that meningiomas with a proliferation index > 4% show recurrence rates comparable to CNS WHO grade 2 (atypical) tumors, while tumors with an index > 20% are associated with mortality rates similar to CNS WHO grade 3 (anaplastic) meningiomas. Issues related to Ki-67 assessment include interobserver variability, the use of different cut-off values among pathologists, and the presence of a complex inflammatory tumour microenvironment, which may lead to an overestimation of the proliferative index (PI). Methods: In this study, we describe how Double Staining Immunohistochemistry (dIHC) with EMA/Ki-67 better highlights neoplastic meningothelial cells compared with single-stain evaluation. Furthermore, the application of Digital Pathology provides quantitative digital data that allow a more accurate assessment of proliferation. Results: Ki-67 expression varied by grade, with digital image analysis (dIHC) showing high agreement with manual assessments. dIHC improved accuracy in evaluating diagnostic and proliferative markers within tumor samples. Conclusions: dIHC combined with DP can support and standardize the evaluation of the proliferative index in meningiomas in routine diagnostic practice. Full article

Canine and feline fibrosarcomas are malignant tumors of mesenchymal origin showing histological, molecular, and clinical structures similar to their human equivalent. In human medicine, cellular myelocytomatosis (c-Myc) has already been proposed as a vital gene that regulates aggressive cell growth and is a predictive marker and possible therapeutic target in fibrosarcomas. The goal of this study was to evaluate c-Myc expression in canine and feline fibrosarcomas by gene and protein analyses and correlate its expression to the histological grading system of the examined cancers. Nineteen archival formalin-fixed and paraffin-embedded canine and feline sarcoma samples were recruited. Sixteen of them were determined to be canine and feline fibrosarcomas. The samples consisted of eight cutaneous samples, four eyelid samples, three oral mucosa samples, and one vulva sample. Histopathological examinations were performed to estimate histological type, differentiation, cellularity, and mitotic count. On each sample, immunohistochemical assessment and mRNA expression were performed using an anti-c-Myc antibody and a c-Myc primer. The differences in the immunoreactivity staining values and the relative folds of the c-Myc mRNAs were categorized using already recognized grading criteria and a statistical analysis was performed. Among all the tested canine and feline fibrosarcomas, 75% of the grade II fibrosarcoma cases and all of the grade III fibrosarcoma cases were positive for the c-Myc protein. Furthermore, the relative values of the c-Myc gene were up-regulated in grade III compare to grade I and II fibrosarcomas. The results demonstrated that c-Myc expression was significantly higher in grade III than in grade II and I (p ≤ 0.05) fibrosarcomas regarding protein and gene levels. In summary, this work provides evidence for the high expression of c-Myc in canine and feline fibrosarcomas and proposes a supposed relationship with poor prognoses as determined by grading systems. Full article

Background/Objectives: Neuroendocrine neoplasms (NENs) are uncommon neoplasms. Grading informs the prognosis and treatment decision of NENs and is determined by cell proliferation, which is measured by mitotic count and Ki-67 index. These measurements present challenges for pathologists as they suffer inter- and intra-observer variability and are cumbersome to quantify. To address these challenges, we developed a machine learning pipeline for identifying tumor areas, proliferating cells, and grading NENs. Methods: Our study includes 385 samples of gastroenteropancreatic NENs from across British Columbia with two stains (247 H&E and 138 Ki-67 images). Labels for these cases are at the patient-level, and there are 186 patients. We systematically investigated three settings for our study: H&E, H&E with Ki-67, and pathologist-reviewed and corrected cases. Results: Our H&E framework achieved a three-fold balanced accuracy of 77.5% in NEN grading. The H&E with Ki-67 framework yields a performance improvement to 83.0% on grading. We provide survival and multivariate analysis with a c-index of 0.65. Grade 1 NENs misclassified by the model were reviewed by a pathologist to assess reasons. Analysis of our AI-graded NENs for the subset of pathologist-assessed G1s demonstrated a significant (p-value = 0.007) survival difference amongst samples the algorithm assigned to a higher grade (n = 20; median survival 4.22 years) compared to concordant G1 samples (n = 60; median survival 10.13 years). Conclusions: Our model identifies NEN grades with high accuracy and identified some grade 1 tumors as prognostically unique, suggesting potential improvements to standard grading. Further studies are needed to determine if this discordant group is a different clinical entity. 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: CIC-rearranged sarcoma is a rare and aggressive type of undifferentiated round cell tumor characterized by CIC gene fusion, most commonly CIC::DUX4. This study presents a series of eleven cases, highlighting their clinicopathological features. Methods: Pathology records (2019 to 2024) were searched using “sarcoma with CIC”, identifying eleven cases, of which seven referred cases were initially misdiagnosed. Pathological and clinical analysis was conducted. Treatment was dictated upon multidisciplinary panel discussion based on tumor stage. Follow-up data (1–25 months) was available for all patients. Results: The cohort included six males and five females, with a median age of 43 years (range;14–53), with nine in soft tissue and two in bone. Tumor size ranged from 3.5 cm to 20.0 cm (mean: 9.8 cm). Most cases showed sheets of undifferentiated round- to oval-shaped cells. Two cases showed an Ewing-like pattern, and one case showed spindle cells in a fibrotic stroma transitioning to epithelioid cells. Necrosis was present in nine cases, and mitotic count ranged from 2 to 38/ 10HPFs (mean = 14.2). CD99 was positive in (10/11) cases and WT-1 in (6/9). NKX2.2, S100, and MDM2 were positive in rare cases. CIC::DUX4 fusion was detected in four cases. FISH for CIC gene rearrangement was positive in seven cases, two of them confirmed by methylation analysis. Metastasis at diagnosis was common (n = 8), primarily in the lungs, with later metastasis to the brain and bone. At time of final analysis, eight patients died within a median of 10 months (range: 1–19 months), while three were alive, two with stable disease (for a period of 6 and 25 months) and one with progression after 10 months. Significant correlation was seen between overall survival and the presence of metastasis at diagnosis (p value = 0.03). Conclusions: CIC-rearranged sarcomas are rare, high-grade tumors with predilection for soft tissue. Misdiagnosis is frequent, necessitating molecular confirmation. These tumors are treatment-resistant, often present with lung metastasis, and carry a poor prognosis, especially with initial metastasis. Full article

Inter-individual variations in drug responses are major concerns in cancer treatment in human and veterinary oncology. Consequently, preclinical models have been proposed to predict drug responses and determine optimal individualized therapy. We aimed to evaluate the clinical utility of in vitro drug sensitivity testing using a patient-derived cell culture model to select appropriate adjuvant therapies for dogs with solid tumors. We screened medical records of 126 dogs with suspected tumors, including 33 dogs with solid tumors (guided group, 16; empirical group, 17). Anticancer drugs used for adjuvant therapy were determined based on in vitro drug sensitivity testing (guided group) or histopathological examination (empirical group) results. Time to tumor progression (TTP) was compared between groups. The guided group had significantly longer TTP than the empirical group (949 vs. 109 days). Median TTPs were significantly longer in the guided group than in the empirical group for dogs with incomplete surgical margin (949 vs. 109 days), dogs with mitotic count < 20 per 10 high power fields (949 vs. 105 days), dogs with no evidence of metastatic disease at initial diagnosis (455 vs. 196 days), and dogs receiving tyrosine kinase inhibitors (949 vs. 109 days). Our study suggests that in vitro drug sensitivity testing may be a useful tool for optimizing adjuvant therapy in dogs with solid tumors. Full article

Background and Clinical Significance: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract but are exceedingly rare in the appendix, with only 20 cases reported in the literature. Due to their rarity, clinical behavior, histopathologic features, and management of appendiceal GISTs remain poorly understood. Case Presentation: We present the case of a 74-year-old man who underwent a right hemicolectomy for colonic adenocarcinoma, during which an incidental 1.2 cm appendiceal GIST was discovered. Histopathological examination revealed spindle cell morphology with abundant skeinoid fibers (SF), minimal mitotic activity (<1/50 HPF), and no nuclear atypia. Immunohistochemical staining confirmed positivity for CD117, DOG1, and CD34. The tumor was classified as low risk based on its size and mitotic count, and the patient remained recurrence-free at a 4-month follow-up. Conclusions: Our case expands the limited literature on appendiceal GISTs by demonstrating their histopathological and immunohistochemical features, favorable prognostic outcomes, and potential for incidental detection during surgeries for unrelated conditions. However, additional studies are needed to further elucidate their molecular characteristics and overall clinical behavior. Full article

Background/Objectives: To evaluate the prognostic impact of immunohistochemical ki-67 staining analysis regarding lymph node involvement and survival data (overall/progression-free survival) in squamous cell carcinoma of the vulva. Methods: A systematic literature search of English and German articles was conducted (PubMed, Embase, Scopus, Web of Science) from 1980 to December 2023, including the search terms “vulvar Neoplasms”, “vulvar cancer”, “vulvar carcinoma”, “vulvar tumor”, ”vulvar tumour”, “vulvar malignancy”, “vulvar malignant”, “ki-67”, “MIB-1”, “MIB1”, “proliferative index”, “proliferative activity”, “mitotic index”, and “mitotic count”. Study quality was assessed using a two-step “mixed-criteria” approach; to synthesize study results, a narrative summary is provided. Results: In total, 13 studies were included in this systematic literature review. In general, two distinct methods of staining interpretation could be retrieved: A “pattern-based” method, as well as a cell count-based method. Ten of the included studies examined the relationship between ki-67 and lymph node involvement, nine studies included survival data as a parameter of interest; and only five studies defined both groin lymph node metastasis and survival data as outcome variables. While nine out of ten studies found no statistically significant association between ki-67 staining and lymph node metastasis, five out of nine studies determined an association between ki-67 status and overall survival, especially when employing a “pattern-based” method of staining interpretation. Conclusions: The prognostic value of ki-67 staining in terms of survival data has been reported ambivalently and should be subject to future studies. Furthermore, we did not find convincing evidence of an association between ki-67 and lymph node involvement. Full article