Clinicopathologic Features, Diagnosis, and Characterization of the Immune Cell Population in Canine Choroid Plexus Tumors

Abstract

The World Health Organization characterizes human choroid plexus tumor (CPT) as papilloma (CPP), atypical CPP (ACPP), and carcinoma (CPC). CPCs can disseminate via cerebrospinal fluid and be mistaken for metastatic carcinoma, creating a diagnostic challenge. Kir7.1 immunohistochemistry (IHC) is a highly reliable tool for diagnostic confirmation of CPTs and their differentiation from metastatic carcinomas in human beings and dogs. This study describes the neuropathology, Kir7.1 staining profile, and the immune cell population within the tumor microenvironment in 11 CPTs in dogs. Archived tissue sections with a diagnosis of CPT were examined and immunolabelled with Kir7.1 for diagnostic confirmation. The number of Ki67-positive neoplastic cells was calculated in 2.4 mm 2 (equivalent to 10 FN22/40X fields), and a mean value was generated for each neoplasm. IHC for CD3, CD20, MAC387, and Iba1 was performed for immune cell characterization, and the number of stained cells for each antibody was counted in 2.4 mm 2 , generating individual cumulative values for each antibody. T -tests with Bonferroni correction evaluated IHC differences between tumor types, and Spearman's rank correlations evaluated relationships among IHC markers. Kir7.1 immunoreactivity was intense at the apical cell membrane in CPPs and ACPPs, and at the apical cell membrane and cytoplasm in CPCs. Ki67 immunoreactivity was detected in all cases. CD3+ and CD20+ lymphocytes trended together ( p = 0.005) and were present within and around all CPTs. Five cases had intravascular MAC387+ monocytes. Iba1 immunoreactivity was robust within and around all tumors. Statistical differences in immune cell markers were not found among tumor types. As previously reported, Kir7.1 is a reliable antibody for the diagnosis of canine CPTs. Although immune cells were present in all cases, no significant associations were found between the type of cells and tumor diagnosis. The characterization of the immune cells within CPTs could be useful in future studies involving immunotherapy.

Immunohistochemical evaluation of immune cell infiltration in canine gliomas

“…38,40,57 We found robust infiltration of tumors by Iba1þ microglia and macrophages, which has been documented in other studies of canine brain tumors including gliomas, meningiomas, and choroid plexus tumors. 1,6,12,63 Macrophages and microglia demonstrated a predominantly amoeboid phenotype in most gliomas, and this was particularly true in high grade oligodendrogliomas, with higher relative numbers of ramified and reactive microglial phenotypes in lower grade tumors and astrocytomas (Table 1). The changes in morphology of microglia from ramified through activated to amoeboid phenotypes are generally believed to correlate to a transition from a resting state to a more activated one in which the cells acquire more phagocytic properties.…”

Naturally-Occurring Invasive Urothelial Carcinoma in Dogs, a Unique Model to Drive Advances in Managing Muscle Invasive Bladder Cancer in Humans

“…Immune cells infiltrating the tumor can be visualized with IHC (163)(164)(165)(166). While all of the markers for various immune cells in humans are not available for dogs, CD3 IHC is a popular approach to assess tumor infiltrating lymphocytes (TILs) in canine cancer, including application to formalin fixed tissues (166). IHC protocols have also been described to detect regulatory T cells in canine tumors (167,168).…”

Spinal ectopic choroid plexus papilloma in a cat

“…12 Identification of atypical CPP in dogs is controversial and has been reported according to the mitotic index, cell density and multilayering of papillae. 13 , 14 The mitotic rate per high-power field, nuclear atypia, multilayered epithelium, high cell density, solid areas of cell growth, blurring of the papillary pattern and multifocal areas of necrosis are the criteria for distinguishing tumour types ( Table 1 ). 7 , 12 Tumour-associated glomeruloid microvascular proliferation, increased proliferative index and desmoplasia are significantly higher in CPC.…”

“… 13 , 15 Kir7.1 has been reported as an excellent specific immunomarker for CPTs in dogs and useful in differentiating from metastatic carcinoma. 14 , 20 …”