An 8-month-old intact male domestic shorthair cat was referred to the Emergency Service of the Veterinary Teaching Hospital (VTH) of the Department of Veterinary Science of the University of Parma (Italy) from the Parma municipal multi-cat shelter, during the winter season (January 2023), for lethargy, anorexia, hypothermia, and hypoglycemia. At the VTH, upon cardiologic examination, an increase in heart rate, under normal blood pressure conditions, was detected. Signalment, clinical history, basal metabolic panel (BMP), ultrasound investigations, and cytological findings were all consistent with a diagnosis of feline infectious peritonitis (FIP). FIP was confirmed in the effusive abdominal fluid by a molecular genetic test (real-time PCR for feline coronavirus RNA). The molecular genetic investigation also detected an FCoV S gene single-nucleotide mutation: biotype M1058L. At necropsy, an effusive collection was recorded in the abdomen, thoracic cavity, and pericardium sac. White parenchymal nodules, of about 1 mm diameter, were found on the surface and deep in the lungs, liver, kidneys, and heart. Histopathology revealed the typical FIP pyogranulomatous vasculitis and IHC confirmed the presence of the FIP virus (FIPV) antigen. The most relevant histopathological finding was the myocarditis/myocardial necrosis associated with the presence of the S gene-mutated FCoV (M1058L biotype). This is the first case of myocarditis in a cat positive for the FCoV/FIP M1058L biotype. Further studies are necessary to support the mutated FCoV M1058L biotype, as an uncommon, but possible, causative pathogen of myocarditis in FCoV/FIP-positive cats. Studies including several FCoV/FIP M1058L-positive cases could allow us to make a correlation with heart gross pathology, histopathology, and immunolocalization of the FCoV/FIP M1058L biotype in the myocardium. The investigation will potentially allow us to determine the effective tropism of the FCoV/FIP M1058L biotype for myocardiocytes or whether myocardiocyte lesions are evident in the presence of concomitant causes related to the patient, its poor condition, or external environmental distress such as cold season, and whether the aforementioned concomitant events are correlated.

Cutaneous and subcutaneous mast cell tumors (MCTs) are common canine neoplasms characterized by variable biological behavior. Tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) can be effective prognostic markers in numerous human neoplasms and are increasingly investigated in dogs. The aim of this study was to characterize immune cells in canine MCTs and their relationship with histological location (cutaneous, subcutaneous) and histologic nodal metastatic status (HN0-3). Thirty-eight MCTs (26 cutaneous, 12 subcutaneous) from 33 dogs with known sentinel lymph node (SLN) metastatic status were immunolabeled for Iba1 (macrophages), CD20 (B cells), CD3 (T cells), and Foxp3 (regulatory T cells). Semiquantitative scoring of interstitial and perivascular CD3+, CD20+, and Foxp3+ cells and morphological evaluation of Iba1+ cells were performed. For each marker, the percent immunopositive area was evaluated by image analysis. All MCTs were diffusely infiltrated by Iba1+ cells and variably infiltrated by CD20+, CD3+, and rare Foxp3+ cells. Stellate/spindle Iba1+ cells were associated with HN2 and HN3 SLNs. Perivascular Foxp3+ cells, CD3+ cells, and percent CD3+ areas were increased in subcutaneous MCTs. Interstitial CD3+ cells were increased in cutaneous MCTs with HN0 SLNs. No differences in CD20+ cells were identified between cutaneous and subcutaneous MCTs and among SLN classes. MCTs were markedly infiltrated by TAMs and variably infiltrated by TILs. Stellate/spindle morphology of TAMs associated with HN2 and HN3 SLNs is suggestive of a pro-tumoral (M2) phenotype. Cutaneous and subcutaneous MCTs have different tumor-immune microenvironments, and T-cell infiltration might contribute to prevention of nodal metastatic spread of cutaneous MCTs.

Gastrointestinal graft-versus-host disease (GvHD) is a major cause of mortality and morbidity following allogeneic bone marrow transplantation (allo-BMT). Chemerin is a chemotactic protein that recruits leukocytes to inflamed tissues by interacting with ChemR23/CMKLR1, a chemotactic receptor expressed by leukocytes, including macrophages. During acute GvHD, chemerin plasma levels were strongly increased in allo-BM-transplanted mice. The role of the chemerin/CMKLR1 axis in GvHD was investigated using Cmklr1 -KO mice. WT mice transplanted with an allogeneic graft from Cmklr1 -KO donors (t-KO) had worse survival and more severe GvHD. Histological analysis demonstrated that the gastrointestinal tract was the organ mostly affected by GvHD in t-KO mice. The severe colitis of t-KO mice was characterized by massive neutrophil infiltration and tissue damage associated with bacterial translocation and exacerbated inflammation. Similarly, Cmklr1 -KO recipient mice showed increased intestinal pathology in both allogeneic transplant and dextran sulfate sodium–induced colitis. Notably, the adoptive transfer of WT monocytes into t-KO mice mitigated GvHD manifestations by decreasing gut inflammation and T cell activation. In patients, higher chemerin serum levels were predictive of GvHD development. Overall, these results suggest that CMKLR1/chemerin may be a protective pathway for the control of intestinal inflammation and tissue damage in GvHD.

Several studies evaluating Ki67 in canine cutaneous mast cell tumors (cMCTs) have reported its prognostic value when tumors of all histological grades are included. This study aims to evaluate whether the Ki67 index has a predictive value in a homogeneous cohort of G2/LG cMCTs with HN2 lymph nodes (LNs) and to describe the clinical outcome. The second goal was to explore the correlation between the Ki67 index and MC. The medical databases of three institutions were retrospectively searched for dogs undergoing surgical treatment for cMCT and LN extirpation, with a histological diagnosis of G2/LG with HN2 LNs. Information about histological margins, MC, Ki67 index, local recurrence, nodal relapse, distant metastasis, de novo cMCT occurrence and date and cause of death were included. A total of 39 cases were identified. None of these developed local and nodal relapse or metastatic distant disease. Median MC was 1 (0–2). Median Ki67 index was 3.5 (0.7–14.3). Ki67 and MC were not significantly correlated. At the end of the study, 32 (82%) dogs were alive, 7 (18%) dogs were dead from unrelated causes and 4 (10.2%) dogs were lost to follow-up. The median ST was not reached, and the mean was 893 days (104–2241 days). Considering the strict inclusion criteria, dogs affected by G2/LG with HN2 LNs treated with surgery alone may have a good oncologic outcome; the Ki67 index does not have prognostic impact.

Acute pancreatitis (AP) is a life-threatening condition, with a higher mortality rate in men than women and in which estrogens might play a protective role. This study aimed to investigate sex-dependent differences in a mouse model of caerulein-induced AP. Thirty-six C57BL/6J mice (19 females and 17 males) were treated intraperitoneally with phosphate-buffered saline or caerulein, and sacrificed 12 hours, 2 days, or 7 days after the last injection. Blood was collected for amylase, lipase, and glucose determination. Severity and extent of inflammation, apoptosis, and acinar to ductal metaplasia (ADM) in pancreatic tissue were scored histologically and total macrophages, major histocompatibility complex (MHC)-II+ cells, M2 macrophages, T and B cells, neutrophils, apoptosis, and ADM were marked immunohistochemically and quantified by digital image analysis. Serum amylase had a peak at 12 hours, without differences between the sexes. In females, pancreatitis reached a peak at 12 hours with a fast recovery while, in males, the peak was delayed to day 2 with residual apoptosis still present. Macrophages were the main inflammatory cell population, followed by T cells, B cells and neutrophils, without differences between sexes. In males, CD206+ cells and apoptosis were higher at both days 2 and 7, and cytokeratin-19+ (CK19+) ADM was higher at day 7 compared with females. The results of this study revealed a faster onset and resolution of caerulein-induced AP in female mice compared with male mice, supporting a sex-dependent modulation of acute pancreatitis.