Spontaneous neoplasms in laboratory mice are an important background finding that may influence the interpretation of studies on carcinogenesis. However, comprehensive pathological evaluations of spontaneous tumors throughout the natural lifespan of experimental animals remain limited. In this study, we observed and analyzed spontaneous tumor development in 74 wild-type C57BL/6JJcl mice that were maintained without exposure to carcinogenic stimuli until natural death. Spontaneous neoplasms were identified in 25 of the 74 mice (33.8%), with the most frequent tumor type being malignant lymphoma (20 cases), followed by liver histiocytic sarcoma (3 cases). Other rare tumors included lung adenocarcinoma, anal apocrine gland carcinoma, and anal squamous cell carcinoma (1 case each). One mouse developed both malignant lymphoma and a primary lung tumor that was histologically diagnosed as a papillary adenocarcinoma. Whole-exome sequencing of the neoplasms of this mouse revealed a Braf p.V637E mutation, whereas RNA sequencing indicated activation of the MAPK pathway in the lung tumor and the enrichment of genes in immune-related signaling pathways in the lymphoma. These findings suggest that spontaneous tumors arise through distinct molecular mechanisms, including mutation- and pathway-driven processes.

The most common genetic abnormality involved in human meningiomas, Neurofibromatosis type-2 (NF2) mutation, is associated with fibrous (grade 1), transitional (grade 1), and atypical (grade 2) meningiomas. The loss of Merlin, encoded by NF2, induces deregulation of Hippo pathway, resulting in nuclear translocation of YAP and TAZ (WWTR1) and promotes tumor cell proliferation. CD44 is regulated by Merlin and is involved in malignant transformation via deregulation of contact inhibition. Feline meningiomas are mostly fibrous and transitional, with histopathological features similar to those of human NF2 mutant meningiomas. In this study, we assessed the expression of Merlin, CD44, YAP, and WWTR1 and performed a genetic analysis of NF2 in feline meningiomas. The expression of these molecules was also evaluated in canine meningiomas, in which the loss of Merlin was not observed. Immunohistochemically, feline meningiomas were positive for Yap1 (15/18; 83.3%) and WWTR1 (18/18; 100%), but negative for Merlin and CD44. Canine meningiomas were positive for Merlin (41/48; 85.4%), CD44 (18/48; 37.5%), Yap1 (13/48; 27.1%), and WWTR1 (18/48; 37.5%). Therefore, the loss of Merlin and deregulation of Hippo pathway may be involved in tumorigenesis of feline meningiomas, but not in dogs. The non-expression of CD44 in feline meningiomas may be related to the differences in malignancy between feline and human meningiomas. Genetic examination revealed no pathogenic NF2 mutations in any of the 18 cases examined, suggesting that the loss of Merlin in feline meningiomas may be caused by chromosomal abnormalities, similar to some human NF2 mutant meningiomas.

Estrogen-induced pituitary proliferative lesions exhibit marked strain differences in rats; however, the molecular basis of this resistance remains unclear. This study compared estrogen-responsive Fischer 344 (F344) rats with resistant Brown Norway (BN) rats to identify candidate genes associated with resistance. Male F344 and BN rats received subcutaneous estradiol valerate (20 mg/kg) either as a single dose/as five injections over 9 weeks, with sampling performed one day after the final treatment; corn oil-treated animals served as controls. Macroscopic examination, pituitary weight measurement, and histopathology were conducted, followed by transcriptome analysis using RNA sequencing, and validation by quantitative polymerase chain reaction and immunohistochemistry. After 9 weeks of estradiol valerate treatment, F344 rats exhibited pronounced pituitary enlargement, accompanied by dark reddish discoloration with diffuse hyperplasia, characterized by hypertrophy of acidophilic cells, vascular congestion, and brown pigment deposition. In contrast, the BN rats showed only a slight increase in pituitary weight and no overt histological alterations. Transcriptome analysis identified 27 genes consistently regulated in BN rats after both single-dose and 9-week EV treatment but not significantly changed in F344 rats. Changes in the selected candidate genes were confirmed by quantitative polymerase chain reaction. Immunohistochemistry demonstrated increased RASA4 immunoreactivity and reduced GNB3 immunoreactivity in BN rats following treatment. These findings indicate that BN rats exhibit pituitary-specific resistance, potentially mediated by the strain-dependent transcriptional modulation of Ras-related pathways.

Primary neoplasms of the extrahepatic bile ducts are rare in dogs. This report describes a case in a 4-year-old male Beagle dog that exhibited elevated liver enzyme levels without any clinical signs. Grossly, a nodule was observed filling the lumen from the cystic duct to the common bile duct, causing biliary distension. Histopathologically, the neoplasm was characterized by papillary proliferation of epithelial cells with slight atypia, rare mitotic figures, and mucin production. Although these features do not fit the standard veterinary classification of cholangiocellular adenoma or carcinoma, they are highly consistent with those of human intraductal papillary neoplasms of the bile duct (IPNB). To the best of our knowledge, this is the first report of a canine IPNB-like neoplasm, suggesting that a canine equivalent to a human disease exists and warrants further investigation.

An extremely rare case of amelanotic melanoma was discovered in the deep soft tissue of the hind limb of a female Sprague-Dawley rat. A solitary, deeply seated mass was located between the metatarsal bone and the dermis. Histopathologically, the tumor cells had pale eosinophilic to clear cytoplasm, and the nests of the tumor cells were surrounded by an abundant extracellular matrix that was strongly positive for Type I collagen. Immunohistochemically, the tumor cells were positive for vimentin, S100, and PNL2. Transmission electron microscopy revealed structures consistent with those of premelanosomes. Trabecular and solid sheets or nested growth patterns within a fibrous matrix distinguish this tumor from typical rodent melanomas, which often arise in the dermal or head regions. These histological, immunohistochemical, and ultrastructural findings collectively supported the diagnosis of amelanotic melanoma over other soft-tissue neoplasms. This case highlights the rarity of melanoma in the deep soft tissues of albino rats and contributes to our understanding of melanoma diversity in laboratory rats.