Feline mammary tumors: Comparison of histological grading systems and Nottingham prognostic index in a 3-year survival study (Part II) Joana Rodrigues-Jesus, Ana Canadas-Sousa, Pedro Oliveira, Gonçalo N. Petrucci, Carla Marrinhas, Hélder Craveiro, Ana Dolores Ribeiro, Hugo Gregório, Flora Tinoco, Andrea Goulart, Helena Felga, Ramiro Pastorinho, Hugo Vilhena, Ana Catarina Figueira, Patrícia Dias-Pereira Veterinary Journal, 2026 Based on the longstanding Nottingham (EE) histological grading system – originally for grading of human breast carcinomas – a mitotic-modified (MMEE) and a revised (REE) grading systems were proposed to better accommodate feline mammary carcinoma (FMC) histopathological features. Additionally, a novel grading system (MGS) has also been proposed. This study aims to directly compare the EE grading with the proposed frameworks using the originally proposed mitotic count thresholds, and to evaluate their association with clinical outcomes. Additionally, we aim to calculate the veterinary Nottingham Prognostic Index (vet-NPI) and assess its prognostic value. Cohen’s kappa agreement analysis revealed poor, slight and fair agreement between EE grading and MMEE, REE and MGS grading systems, respectively. Although all histological grading frameworks were associated with overall survival in the univariate analysis, only the EE and REE systems remained significant prognostic factors after adjustment to other covariates. Furthermore, REE and MGS gradings were associated with tumor-specific survival, but the latter lost its significance on multivariate analysis. The MGS system was the only one that was significantly linked with disease-free interval in both univariate and multivariate analyses. While the inclusion of LVI and nuclear form represent good steps toward improving the prognostic value of histological grade, the mitotic count thresholds appeared inadequate for our cohort, raising concerns about its applicability across different settings. Our findings support the inclusion of the vet-NPI in routine diagnostic histopathology reports of FMC to improve TSS prognostic assessment when using the EE and MMEE grading systems. • The mitotic count score thresholds proposed in the latest grading systems for feline mammary carcinomas were inadequate for our case series • The revised Elston and Ellis framework showed consistent associations with overall and tumor-specific survival, whereas the novel Mills grading system was more relevant for disease-free interval • A higher veterinary-adapted Nottingham prognostic index was linked with unfavorable overall and tumor-specific survival • Further refinement and validation of existing grading criteria in independent cohorts is needed
Feline mammary tumors: Comparison of histological classifications and prognostic factors in a 3-year survival study (Part I) Joana Rodrigues-Jesus, Ana Canadas-Sousa, Pedro Oliveira, Gonçalo N. Petrucci, Carla Marrinhas, Hélder Craveiro, Ana Dolores Ribeiro, Hugo Gregório, Flora Tinoco, Andrea Goulart, Helena Felga, Ramiro Pastorinho, Hugo Vilhena, Ana Catarina Figueira, Patrícia Dias-Pereira Veterinary Journal, 2026 Feline malignant mammary tumors are frequently aggressive and associated with poor clinical outcomes. Over the years, the prognostic value of various clinical and pathological parameters has been investigated, though findings are not always consensual. Histologically, feline malignant mammary tumors are heterogenous tumors, and a recent revision of the 1999 World Health Organization (WHO) classification of canine and feline mammary tumors may provide a more accurate picture of their biological behavior. This study aimed to analyze and compare the 1999 WHO classification and the 2019 updated surgical pathology classification in the same case series. Additionally, we seek to evaluate the prognostic value of several clinicopathological features, including both histological classification systems. Our findings revealed that the 2019 revised surgical pathology classification allowed for a greater stratification of feline mammary tumors (FMT) compared to the 1999 WHO classification system. Notably, longer survival times were observed in queens with ductal-associated carcinomas. Other clinicopathological features were associated with unfavorable clinical outcomes, namely presence of multiple synchronous malignant mammary tumors, larger tumor size, higher clinical stage, infiltrative tumor growth and lymphovascular invasion ( p ≤ 0.05). Additionally, our findings suggest that the prognostic relevance of each parameter may vary according to the clinical endpoint, warranting careful consideration during clinical interpretation. The data presented in this study are available from the corresponding author upon reasonable request. • The 2019 histological classification of feline mammary tumors provided a more refined stratification compared to the 1999 classification. • Ductal-associated carcinomas appeared to be linked to more favorable clinical outcomes than other malignant mammary tumor subtypes. • Clinical stage, type of tumor growth and lymphovascular invasion showed significant associations with overall survival, tumor-specific survival and disease-free interval. • The prognostic value of other clinicopathological features seemed to vary depending on the clinical endpoint.
Canine Splenic Hemangiosarcoma: Biological Behavior, Clinical Challenges and Therapeutic Limitations Felisbina Pereira Queiroga, Ana Margarida Marques, Hugo Gregório, Gonçalo N. Petrucci Animals, 2026 Canine splenic hemangiosarcoma is a highly malignant vascular neoplasm and is among the most frequent and clinically relevant splenic tumors in dogs. Its biological behavior is characterized by rapid growth, marked invasiveness, and early metastatic dissemination, contributing to the poor prognosis commonly observed in affected animals. Clinically, splenic hemangiosarcoma often remains subclinical until acute presentation due to splenic rupture and hemoperitoneum, thereby substantially limiting opportunities for early diagnosis and timely therapeutic intervention. Despite advances in diagnostic imaging, surgical techniques, and the use of adjuvant chemotherapy, the impact of current therapeutic approaches on long-term survival remains limited. Splenectomy is primarily palliative for hemorrhage control, and adjuvant doxorubicin-based chemotherapy yields only modest improvements in median survival; alternative approaches (metronomic chemotherapy, immunotherapy, and targeted therapies) have not demonstrated consistent clinical benefit. This review summarizes the biological and pathophysiological features of canine splenic hemangiosarcoma, discusses the main clinical challenges associated with its diagnosis and staging, and critically reviews current therapeutic approaches and their limitations. By integrating biological behavior with clinical and therapeutic evidence, this article highlights the reasons why prognosis remains poor and underscores the need for more effective strategies to improve clinical outcomes in dogs with splenic hemangiosarcoma.
Characterisation of the Faecal Microbiota in Dogs with Mast Cell Tumours Compared with Healthy Dogs Catarina Aluai-Cunha, Diana Oliveira, Hugo Gregório, Gonçalo Petrucci, Alexandra Correia, Cláudia Serra, Andreia Santos Animals, 2025 Mast cell tumours (MCT) are the most common cutaneous neoplasms in dogs, with variable behaviours and patient survival time. Both indolent and aggressive forms have been described, but much remains to be explored regarding prognosis and therapy. Evidence has highlighted the influence of microbiota on multiple health and disease processes, including certain types of cancer in humans. However, knowledge remains scarce regarding microbiota biology and its interactions in both humans and canine cancer patients. This study aimed to characterise the faecal microbiota of dogs with MCT and compare it with that of healthy individuals. Twenty-eight dogs diagnosed with MCT and twenty-eight healthy dogs were enrolled in the study. Faecal samples were collected and analysed by Illumina sequencing of 16S rRNA genes. Alpha diversity was significantly lower in dogs with cancer, and the species diversity InvSimpson Indexwas reduced (p = 0.019). Principal coordinate analysis showed significant differences in the bacterial profile of the two groups: there was a significant lower abundance of the genera Alloprevotella, Holdemanella, Erysipelotrichaceae_UCG-003, and Anaerobiospirillum and, conversely, a significant increase in the genera Escherichia-Shigella and Clostridium sensu stricto 1 in diseased dogs. At the phylum level, Bacteroidota was significantly reduced in diseased dogs (25% in controls vs. 19% in MCT dogs). In conclusion, sequencing analysis provided an overview of the bacterial profile and showed statistical differences in the microbial communities of dogs with MCT compared with healthy dogs, suggesting a link between the gut microbiota and MCT in this species.
Diagnostic and Prognostic Value of Blood Ratios in Canine Splenic Hemangiosarcoma: A Multicentric Observational Study Ana M. Marques, Gonçalo Petrucci, Hugo Gregório, Luís Lobo, Joaquim Henriques, Ana C. Figueira, Hugo Vilhena, Carla Marrinhas, Felisbina L. Queiroga Veterinary Sciences, 2025 Peripheral complete blood cell count (CBC) and blood ratios, including neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-red blood cell ratio (NRR), and platelet-to-lymphocyte ratio (PLR), have been used in the diagnosis and prognosis of several cancers; however, their relevance in canine splenic hemangiosarcoma (HSA) remains to be investigated. This study investigated whether CBC, NLR, NRR, and PLR could be diagnostic and prognostic biomarkers in dogs with splenic HSA. Analyzing medical records of 154 dogs undergoing splenectomy from 2018 to 2022, we found that dogs diagnosed with splenic HSA (n = 63) had significantly higher neutrophil counts (14.9 ± 9.7 vs. 12.6 ± 9.6; p < 0.001), increased NRR (3.7 ± 2.6 vs. 2.7 ± 3.7; p < 0.001), lower platelet counts (145 ± 111 vs. 270 ± 213; p < 0.001), and reduced PLR (139.4 ± 160.0 vs. 259.9 ± 278.0; p < 0.001) compared to dogs with other splenic lesions. This study also identified a higher risk of relapse and mortality associated with increased NRR (p < 0.001 and p = 0.012, respectively) and an inverse relationship with PLR (p = 0.015 and p = 0.033, respectively), whereas NLR showed no significant association. The multivariate survival analysis identified NRR as an independent prognostic factor for DFI [hazard ratio (1.837); 95% confidence interval (1.147–2.942); p = 0.011], while for OS, the association did not reach statistical significance [hazard ratio (1.510); 95% confidence interval (0.985–2.314); p = 0.059]. These findings highlight the potential of NRR and PLR as biomarkers for assessing diagnosis and prognosis in canine splenic HSA, advocating for further validation in the future.
Prognostic Insights in Feline Mammary Carcinomas: Clinicopathological Factors and the Proposal of a New Staging System Mónica Monteiro, Gonçalo Petrucci, Felisbina L. Queiroga Animals, 2025 Feline mammary carcinoma (FMC) is an aggressive neoplasm with a poor prognosis. Clinical staging is crucial for risk assessment, yet the current WHO system lacks granularity, particularly in Stage III. Aligning this system with human breast cancer staging has the potential to improve prognostic accuracy. Additionally, prognostic factors such as tumor size, ulceration, lymph node metastasis, and lymphovascular invasion require further evaluation. This study retrospectively analyzed 75 female cats with FMC to assess the prognostic impact of clinicopathological factors and evaluate a novel staging system (new staging) adapted from the AJCC Cancer Staging Manual. Survival analyses included disease-free interval (DFI), and overall survival (OS). Tumor size >3 cm (p < 0.001), ulceration (p = 0.010), lymphovascular invasion (p < 0.001), lymph node metastasis (p < 0.001), WHO and new staging (p < 0.001) were significantly associated with shorter survival. The new staging refined Stage III into IIIA (T3N0M0), IIIB (T4N0M0), and IIIC (AnyTN1M0), improved prognostic differentiation. Stage IIIC cases had the worst survival (p < 0.001). Multivariate survival analysis identified lymphovascular invasion (HR = 2.834, 95% CI: 1.546–5.195, p = 0.001), histological Grade II (HR = 5.013, 95% CI: 1.122–22.397, p = 0.035) and III (HR = 9.894, 95% CI: 2.195–44.594, p = 0.003) and skin ulceration (HR = 2.462, 95% CI: 1.256–4.825, p = 0.009). These findings support the prognostic relevance of key clinicopathological factors in FMC and highlight the advantages of a refined TNM-based staging system, which may enhance risk stratification and therapeutic decision-making in veterinary oncology.
Level of Necrosis in Feline Mammary Tumors: How to Quantify, Why and for What Purpose? Joana Rodrigues-Jesus, Ana Canadas-Sousa, Marta Santos, Pedro Oliveira, Ana Catarina Figueira, Carla Marrinhas, Gonçalo N. Petrucci, Hugo Gregório, Flora Tinoco, Andrea Goulart, Helena Felga, Hugo Vilhena, Patrícia Dias-Pereira Animals, 2024 Necrosis is a common finding in human and animal neoplasms. The percentage of tumor necrosis is included in tumor grading schemes in veterinary oncology; however, evaluation methods are often overlooked. Different studies have assessed the prognostic value of tumor necrosis in feline mammary tumors with contradictory results, which could be related to methodologic variability. In this study, a comprehensive evaluation of tumor necrosis in feline mammary tumors (FMTs) was conducted, by applying a semi-quantitative and a quantitative methodology for assessing necrosis. The interobserver agreement, the relationship with clinicopathological characteristics and the prognostic value of necrosis were analyzed in 154 FMT cases. Although subjectivity in the assessment of necrosis existed, an almost perfect agreement (weighted quadratic k = 0.851) between two observers was obtained. Furthermore, there was a significant positive correlation between the semi-quantitative and quantitative methods. Necrosis was more common and more extensive in malignant tumors than in their benign counterparts. Despite the non-significant results in the survival analysis, extensive necrosis was significantly associated with aggressive clinicopathological features, such as higher histological grade, high mitotic count and lymphovascular invasion. Our results support the potential relevance of necrosis in FMT.
Pain Management in Animals with Oncological Disease: Opioids as Influencers of Immune and Tumor Cellular Balance Ana Vidal Pinheiro, Gonçalo N. Petrucci, Amândio Dourado, Filipe Silva, Isabel Pires Cancers, 2024 Advancements in understanding pain physiopathology have historically challenged animals’ absence of pain senses. Studies have demonstrated that animals have comparable neural pain pathways, suggesting that cats and dogs likely experience pain similarly to humans. Understanding brain circuits for effective pain control has been crucial to adjusting pain management to the patient’s individual responses and current condition. The refinement of analgesic strategies is necessary to better cater to the patient’s demands. Cancer pain management searches to ascertain analgesic protocols that enhance patient well-being by minimizing or abolishing pain and reducing its impact on the immune system and cancer cells. Due to their ability to reduce nerve sensitivity, opioids are the mainstay for managing moderate and severe acute pain; however, despite their association with tumor progression, specific opioid agents have immune-protective properties and are considered safe alternatives to analgesia for cancer patients.
Distribution of Inflammatory Infiltrate in Feline Mammary Lesions: Relationship With Clinicopathological Features Joana Rodrigues‐Jesus, Ana Canadas‐Sousa, Pedro Oliveira, Ana Catarina Figueira, Carla Marrinhas, Gonçalo N. Petrucci, Hugo Gregório, Flora Tinoco, Andrea Goulart, Helena Felga, Hugo Vilhena, Patrícia Dias‐Pereira Veterinary and Comparative Oncology, 2024 Inflammation is a frequent finding in feline mammary neoplasms. Recent research suggests that the presence and location of tumour‐associated immune cells might play a significant role in the clinical outcome of feline mammary carcinomas. The present study aimed to characterise the overall inflammatory infiltrates in healthy, hyperplastic/dysplastic, benign and malignant lesions of the feline mammary gland, and to evaluate its association with clinicopathological features. Perilesional and intralesional inflammatory foci were evaluated in 307 lesions from 185 queens, and categorised according to its distribution and intensity. The presence, location and density of tertiary lymphoid structures were also assessed. A control group included 24 queens without mammary changes. The presence of intralesional and perilesional inflammatory infiltrate was observed in a majority of the lesions (80.8% and 90.2%, respectively), but differed according to the type of mammary lesion, being more remarkable in malignant neoplasms. Only scarce individual cells were observed in 28.1% of the normal mammary glands. Data analysis revealed statistically significant associations (p < 0.05) between the presence of a more prominent intralesional and perilesional inflammatory reaction and several clinicopathological features associated with worse prognosis, including clinical stage, tumour size, mitotic count, lymphovascular invasion and lymph node metastasis. Furthermore, tertiary lymphoid structures were significantly more frequent in tumours with an infiltrative growth and lymph node metastasis. According to our results, the inflammatory reaction present in different types of feline mammary lesions is associated with the development of more aggressive tumours.
