The very origins of the laboratory mouse were promulgated by an interest in the genetic basis of cancer, and this interest has accelerated with GEMs.
Many of the common inbred strains of mice were originally developed because of their propensity to develop tumors, such as mammary tumors in C3H/He mice, testicular teratomas in 129/Sv mice, multicentric lymphomas in BALB/c mice, and thymic lymphomas in AKR mice.
Perchance, some strains that were not selectively bred for cancer also happen to be prone to cancer, such as DBA mice with hepatocellular neoplasia. Others were bred for their predisposition to one type of tumor but unexpectedly develop a high prevalence of other types of tumors, such as A strain mice, which were selectively bred for mammary tumors but also develop pulmonary adenomas. Other strains were developed for their longevity and low tumor prevalence, such as B6 mice. Regardless, the genetic homozygosity of mice and the presence of retroviral elements in their genome make neoplasia a common cause of morbidity in many strains. This text covers only the major neoplastic disorders of common strains of mice and does not attempt to describe and document all types of spontaneous or induced neoplasia in laboratory mice. There are several excellent references for “wallpaper matching” naturally occurring mouse neoplasms with published images (see “General References on Diseases of Mice”).There are several features about the mouse that may reflect upon interpretation of neoplasia. Mouse tumors tend to grow by blunt expansion, rather than by invasive infiltration, but this does not mean that they do not display malignant properties. For example, most human pathologists would tend to deem spontaneous mouse mammary tumors as morphologically benign, yet nearly 60% metastasize to the lung. When tumors are metastatic in the mouse, the most common site of metastasis is the lung, which differs from other species, including humans. True metastasis must be differentiated from tumor embolization.
The pathologist can assist with this distinction by careful examination for the presence of endothelial cells surrounding the suspect metastatic masses within the lumina of blood vessels. These emboli may behave differentially from truly invasive metastases. Pulmonary adenomas, which are common in mice, are often misconstrued as metastases of other epithelial tumors. In addition, mouse epithelium of tubular organs, including neoplastic epithelium, is prone to herniation, which can be misconstrued as malignant behavior. This is especially common in hyperplastic epithelium of the colon, particularly when mice are infected with C. rodentium, Helicobacter spp., Cryptosporidium parvum, or when the mucosa is perturbed by rectal prolapse. These stimuli induce marked mucosal hyperplasia and dysplasia with frequent crypt herniation into underlying tissues. As the hyperplastic stimulus wanes within the herniated epithelium, mucinous differentiation tends to occur, with the formation of mucin-filled cysts, erosion of lining epithelium, crypt suppuration, crypt effacement, inflammation, and fibrosis. This process (colitis cystica) may be erroneously diagnosed as mucinous adenocarcinomas. Proof of neoplasia is autonomous growth and metastasis, which are seldom proven experimentally in these models.Genetic engineering, particularly the integration of onco-transgenes, has resulted in the expression of novel tumor phenotypes that do not occur as spontaneous tumors in mice. The failures of the mouse as a model of human cancer are increasingly being resolved by genomic manipulation. GEM neoplasms that mimic not only human tumor morphology but also human tumor biology are being increasingly studied. The raison d'etre of the laboratory mouse is to model human disease. Thus, nomenclature of mouse neoplasia continues to evolve in an effort to align mouse neoplasia with that of the human. Organ-site consensus reports have been published by the National Cancer Institute's Mouse Models of Human Cancer Consortium (MMHCC). These reports are intended to facilitate communication among pathologists about mouse models of human disease. These reports generally agree with, but somewhat modify, the World Health Organization (WHO) classification and nomenclature.