Search Results (9)

Canine anal sac gland adenocarcinomas (ASACs) are locally aggressive and highly metastatic to regional lymph nodes. Tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) can be effective prognostic and predictive markers in numerous human neoplasms and are increasingly investigated in dogs. The aim of this study was to characterize immune cells in canine ASACs and their relationship with tumor size, histologic metastatic status, and tumor clinical stage. Thirty ASACs with known tumor size, metastatic status, and clinical stage were immunolabeled for Iba1 (macrophages), CD20 (B cells), CD3 (T cells), and Foxp3 (regulatory T cells). With image analysis, two areas of 1 mm² were analyzed for each case at the tumor core (TC) and invasive margin (IM) and immune cells were counted. Eighteen patients had metastasis at the time of diagnosis, of which fifteen were nodal only, and three were both distant and nodal. The median tumor size was 32.5 mm (range 11–70). The clinical stage was I in five cases, II in seven cases, III in fifteen cases, and IV in three cases. T cells and macrophages were the most abundant immune cells in all tumors. Tumor size did not influence the number or type of infiltrating immune cells. By contrast, significantly higher numbers of TC T lymphocytes were found in patients without metastasis, while significantly higher numbers of TC macrophages were found in dogs with metastasis. Immune cell infiltrate did not differ according to clinical stage. The results indicate that the tumor immune microenvironment, specifically TILs and TAMs, contribute to tumor behavior and may influence metastatic potential; in particular, high CD3 infiltration may prevent tumor progression, while increased macrophage infiltration could promote it. Full article

Apocrine gland anal sac adenocarcinoma (AGASACA) is a locally invasive tumor with a high potential for early metastasis. The most recent studies indicate that 23.4–83% of dogs have metastases to the iliosacral lymph nodes (LNs), and 2.1–31% have distant metastases to other organs at the time of first presentation. Usually, only one anal sac is affected, but bilateral involvement has been reported in 4–20% of dogs. About 16–53% of dogs present with paraneoplastic hypercalcemia. The most recent studies show an overall improvement in median survival time (MST) (15–28 months) for dogs with different stages of AGASACA treated with surgery and adjuvant therapy compared to those treated with chemotherapy alone (6.9 to 8.7 months). The highest MST (22–32 months) was reported when radiation therapy (RT) was selected as a sole or adjunctive treatment. Several studies have been published to identify the subset of tumors with more aggressive behavior and higher metastatic potential. The main negative prognostic factors are the size of the primary tumor, metastatic regional lymphadenopathy at first presentation, the size and the number of the metastatic lymph nodes, distant metastases at the time of diagnosis, and the histological characteristics of the primary tumor. In this critical review, the latest advancements in histological diagnosis, staging, treatment, and prognosis of AGASACA are described. The aim is to provide a full overview of this neoplasm, focusing on the latest advancements on prognostic variables and treatments. Full article

Apocrine gland anal sac adenocarcinoma is an aggressive neoplasm, and surgery remains the treatment of choice, although it is controversial in advanced cases. The prognostic factors are not well established. Human Epidermal Growth Factor Receptor 2 (HER2) is a membrane protein related to tumorigenesis, whereas Ki67 is a nuclear protein related to cell proliferation. Both are potential prognostic markers and therapeutic targets. This study aimed to evaluate the expression of HER2 and Ki67 markers in canine apocrine gland anal sac adenocarcinoma. The tumor samples were divided into four groups: largest tumor diameter less than 2.5 cm, largest tumor diameter greater than 2.5 cm, metastatic lymph nodes, and control group of non-neoplastic anal sacs. Each contained 10 samples. Immunohistochemistry was performed to verify the expression of HER2 and Ki67 markers. Positive HER2 staining was observed in 45% of the neoplastic cases and negative HER2 staining in 100% of the control group. The Ki67 expression had a median of 25% in all groups, except for the control group, which had a median of 8%. The HER2 and Ki67 expression was present in apocrine gland anal sac adenocarcinoma, making them potential therapeutic targets. However, it was not possible to determine the clinical value of either marker. Full article

This research aims to evaluate the outcomes of a radiotherapy protocol, consisting of five fractions of 4 Gy each, resulting in a total dose of 20 Gy for apocrine gland anal sac tumors and local lymph nodes in canines. This protocol was assessed as a palliative treatment for macroscopic tumors alone, or in combination with additional therapies under different scenarios. Medical records from fifty canine patients met the inclusion criteria and were divided into different treatment groups: radiotherapy alone (n = 22, 44%), radiotherapy with chemotherapy or targeted therapy with toceranib (n = 18, 36%), surgery with radiotherapy (n = 5, 10%), and surgery with radiotherapy and chemotherapy or targeted therapy with toceranib (n = 5, 10%). Patients who received radiotherapy alone had a median survival time of 384 days (95% CI 198–569) and 628 days (95% CI 579–676) for RT + additional therapies. The median time to progression for patients with radiotherapy alone was 337 days (95% CI 282–391 days), and 402 days (95% CI 286–517 days) for radiotherapy plus additional treatments. Acute side effects were mild, with the majority having diarrhea (61%), and only one patient developed grade III late effects VRTOG v2 classification; however, this happened 22 months after the first radiotherapy protocol after re-irradiation. The results demonstrate that radiotherapy alone under this protocol provided a comparable median time to progression vs. radiotherapy plus additional treatments while maintaining acceptable side effects. The combination of this protocol with other treatment modalities offers attractive results for local disease control and survival while maintaining acceptable toxicities. Overall, these findings contribute to the growing evidence supporting the role of radiotherapy in managing apocrine gland anal sac adenocarcinoma in dogs. Full article

Cancer is the leading cause of death in companion animals. The evaluation of locoregional lymph nodes, known as lymph node mapping, is a critical process in assessing the stage of various solid tumors, such as mast cell tumors (MCTs), anal gland anal sac adenocarcinoma, melanoma, and mammary gland adenocarcinoma. MCTs are among the most prevalent skin malignancies in dogs. Staging is used to describe the extent of neoplastic disease, provide a framework for rational treatment planning, and evaluate treatment results. The aim of this review is to present the current knowledge on sentinel lymph node (SLN) mapping in canine MCTs, its influence on treatment decisions and prognosis, as well as the advantages and limitations of different SLN techniques currently available in veterinary oncology. A search methodology was adopted using the PubMed, Scopus, and Google Scholar databases. Critical analyses of up-to-date research have shown that lymphoscintigraphy can achieve a lymph node detection rate of between 91 and 100%. This method is becoming increasingly recognized as the gold standard in both human and veterinary medicine. In addition, initial studies on a limited number of animals have shown that computed tomographic lymphography (CTL) is highly effective in the SLN mapping of MCTs, with detection rates between 90 and 100%. The first study on contrast-enhanced ultrasound (CEUS) also revealed that this advanced technique has up to a 95% detection rate in canine MCTs. These methods provide non-ionizing alternatives with high detection capabilities. Furthermore, combining computed tomography and near-infrared fluorescence (NIR/NIR-LND) lymphography is promising as each technique identifies different SLNs. Indirect lymphography with Lipiodol or Iohexol is technically feasible and may be also used to effectively detect SLNs. The integration of these mapping techniques into routine MCT staging is essential for enhancing the precision of MCT staging and potentially improving therapeutic outcomes. However, further clinical trials involving a larger number of animals are necessary to refine these procedures and fully evaluate the clinical benefits of each technique. Full article

Canine apocrine gland anal sac adenocarcinoma (AGASACA) is an aggressive canine tumor originating from the anal sac glands. Surgical resection, with or without adjuvant chemotherapy, represents the standard of care for this tumor, but the outcome is generally poor, particularly for tumors diagnosed at an advanced stage. For this reason, novel treatment options are warranted, and a few recent reports have suggested the activation of the immune checkpoint axis in canine AGASACA. In our study, we developed canine-specific monoclonal antibodies targeting PD-1 and PD-L1. A total of 41 AGASACAs with complete clinical and follow-up information were then analyzed by immunohistochemistry for the expression of the two checkpoint molecules (PD-L1 and PD-1) and the presence of tumor-infiltrating lymphocytes (CD3 and CD20), which were evaluated within the tumor bulk (intratumor) and in the surrounding stroma (peritumor). Seventeen AGASACAs (42%) expressed PD-L1 in a range between 5% and 95%. The intratumor lymphocytes were predominantly CD3+ T-cells and were positively correlated with the number of PD-1+ intratumor lymphocytes (ρ = 0.36; p = 0.02). The peritumor lymphocytes were a mixture of CD3+ and CD20+ cells with variable PD-1 expression (range 0–50%). PD-L1 expression negatively affected survival only in the subgroup of dogs treated with surgery alone (n = 14; 576 vs. 235 days). The presence of a heterogeneous lymphocytic infiltrate and the expression of PD-1 and PD-L1 molecules support the relevance of the immune microenvironment in canine AGASACAs and the potential value of immune checkpoints as promising therapeutic targets. Full article

The aim was to prospectively measure the shrinkage of primary apocrine gland anal sac adenocarcinoma (AGASACA) tumors after 24 and 48 h of formalin fixation. Dogs that were diagnosed with AGASACA pre-operatively by aspiration cytology were prospectively enrolled in the study. Tumor extirpation was performed in a closed technique. The tumor and associated tissues were examined on the back table away from the patient and the widest dimension of the tumor was measured using a sterile ruler (Medline^®; Northfield, IL, USA). This measurement was recorded in mm (t₀). The tissue was placed in 10% buffered formalin and stored at room temperature. Two further measurements were taken after 24 (t₂₄) and 48 (t₄₈) hours of formalin fixation. Once the 48 h measurement was taken, the tissue was submitted for histopathology. The percentage of shrinkage between time points was calculated by using the following equation: (1 − [time b/time a]) × 100. Overall, 23 dogs with 23 tumors were enrolled. The mean percentage of shrinkage after 24 and 48 h of formalin fixation was 4.8% and 7.2%, respectively. The median diameter of the tumors reduced by 1 mm over 48 h and was not significantly different at any time point. These data will aid clinicians in interpreting measurements of AGASACA tumors following formalin fixation and shows that minimal change in tumor size is expected following 48 h. Full article

Canine apocrine gland anal sac adenocarcinoma (AGASAC) is a malignant tumour with variable clinical progression. The objective of this study was to use robust multivariate models, based on models employed in human medical oncology, to establish clinical and histopathological risk factors of poor survival. Clinical data and imaging of 81 cases with AGASAC were reviewed. Tissue was available for histological review and immunohistochemistry in 49 cases. Tumour and lymph node size were determined using the response evaluation criteria in the solid tumours system (RECIST). Modelling revealed tumour size over 2 cm, lymph node size grouped in three tiers by the two thresholds 1.6 cm and 5 cm, surgical management, and radiotherapy were independent clinical variables associated with survival, irrespective of tumour stage. Tumour size over 1.3 cm and presence of distant metastasis were independent clinical variables associated with the first progression-free interval. The presence of the histopathological variables of tumour necrosis, a solid histological pattern, and vascular invasion in the primary tumour were independent risk factors of poor survival. Based upon these independent risk factors, scoring algorithms to predict survival in AGASAC patients are presented. Full article

Apocrine gland anal sac adenocarcinoma (AGASACA) is locally aggressive and highly metastatic to regional lymph nodes. The aim of this study was to evaluate the prognostic significance of Ki67 in surgically excised AGASACA. Prognostic impact of size, regional lymph nodes metastasis, hypercalcemia, histologic pattern, mitotic count, necrosis, inflammatory and lympho-vascular invasion, anisokaryosis and anisocytosis was also evaluated. Thirty-five dogs were included, twenty-four of which also had metastatic lymph nodes. When the entire population was evaluated, only metastatic disease spread to regional lymph nodes, and necrosis and inflammatory infiltration were correlated to prognosis. When only dogs with metastatic disease were evaluated, size, solid histologic pattern, presence of lymphatic and vascular invasion showed influence on prognosis. Ki67 index was not associated with survival time and disease free interval in any case. The results of this study showed that lymph nodes metastasis at diagnosis reduced disease free interval. Moreover, tumor size greater than 5.25 cm, presence of lymphatic and vascular invasion and a solid histologic pattern were associated with a shorter survival time in dogs with metastasis to regional lymph nodes. Ki67 expression was not significantly associated with prognosis, therefore it could not be considered as a prognostic factor in this tumor type, while the role of hypercalcemia remained unclear. Full article