Spontaneous nonthymic tumors in SCID mice

Abstract

SCID mice provide an excellent platform for cancer research. Because of their lack of immunity, SCID mice readily succumb to infectious pathogens and therefore must be maintained in an SPF, barrier-protected environment. Although SPF and barrier facilities prevent infection, SCID mice remain prone to premature death due in part to a high prevalence of spontaneous thymic lymphomas. However, little is known about spontaneous nonthymic tumors in SCID mice. We therefore analyzed the incidence of nonthymic tumor in our defined-flora C.B-17/Icr-SCID/Sed mice and examined their histopathologic characteristics. We necropsied 1060 retired SCID breeders (506 males, 554 females; average ages of 325 and 320 d, respectively) and found that 24 mice had developed nonthymic tumors, yielding an incidence of 2.26% (1.78% in males; 2.71% in females). The incidence of nonthymic tumors was substantially lower than that of thymic lymphomas in our retired SCID breeders (12.3% in males; 4.15% in females). Based on histopathology, 9 nonthymic tumors in male SCID mice consisted of 4 salivary gland myoepiteliomas, 2 rhabdomyosarcomas, and 3 cases of leukemia involving multiple organs. Female SCID mice had 15 nonthymic tumors consisting of 8 mammary adenocarcinomas, 4 salivary gland myoepitheliomas, and 1 case each of leukemia, rhabdomyosarcoma, and fibrosarcoma. In addition, we tested in vivo transplantability and characterized the growth behavior of several of these tumors. To our knowledge, this report is the first comprehensive description of spontaneous nonthymic tumors, including 8 myoepitheliomas and 3 rhabdomyosarcomas, from the same SCID mouse colony.

Figure 1.

Spontaneous myoepitheliomas of salivary gland in the SCID retired breeders: (A) A subcutaneous mass located in the ventral neck (arrow). (B) Histology of the myoepithelioma revealed a highly cellular, unencapsulated, expansile neoplasm (arrows) that invades into the adjacent salivary gland acinar tissues (SG). (C) Within the mass are cavities or pseudocysts (CY) filled with necrotic cellular debris or mucoil material. (D) The tumor is composed of large, pleomorphic, spindle-shaped cells (reminiscent of mesechymal cells) and clusters of polyhedral epithelioid cells with abundant cytoplasm. Mitoses are occasionally observed (arrows). Hematoxylin and eosin stain; bar, 100 μm.

Figure 2.

(A) Large mammary tumor along ventral thorax (T) in a SCID retired female breeder. The histology is of representative types of mammary gland adenocarcinomas with (B) well-differentiated acinar growth pattern, (C) solid and lobular epithelial growth pattern, and (D) papillary growth pattern. Note mitotic figures in the tumor tissue (C and D, arrows). Hematoxylin and eosin stain; bar, 100 μm.

Figure 3.

Spontaneous rhabdomyosarcomas in SCID retired breeder mice presenting as firm, gray to red, poorly circumscribed masses on the (A) foot (T) and (B) thigh muscles (arrow). (C, D) The histology of rhabdomyosarcoma is poorly differentiated and highly cellular neoplasm composed of pleomorphic and frequently multinucleated round to polygonal to muscle-like ‘strap’ cells. (C) The large multinucleated cells have a granulated or filamentous cytoplasm (arrows). (D) Cross-striations are evident within the large cells (arrow). Hematoxylin and eosin stain; bar, 100 μm.

Figure 4.

(A) High magnification of an area from Figure 3 D, showing the cross-striation within a large multinucleated tumor cell. (B, C, and D) Spontaneous lymphocytic leukemia involved the (B) liver, (C) kidney, and (D) lung (D) in SCID retired breeders. Tumor cells infiltrated the internal organs and displaced or replaced the normal tissue structures. Most tumor cells closely resemble small lymphocytes. Hematoxylin and eosin stain; bar, 100 μm.