1. A Spontaneous Incidence of Non-Thymic Lymphocytic Lymphoma in SCID Mice
Vijaykanth G, Raghul J, Navin Rajesh B and Shridhar N
Department of Toxicology
Orchid Chemicals and Pharmaceuticals Limited, Sozhanganallur, Chennai
HISTOPATHOLOGY
Spleen effaced with Neoplastic cells and necrotic area (Fig 4).
Dissemination of Neoplastic cells in internal organs like liver, kidney, mesenteric lymph node and uterus (Fig 5-10).
Perivascular accumulation of neoplastic cells in the Lung (Fig 8) and complete replacement of normal architecture of ovary by neoplastic cells (Fig 9).
DESCRIPTION OF NEOPLASTIC CELLS
Round to oval (small lymphocyte like) uniform, non cohesive, prominent centrally located nucleoli, scanty cytoplasm with moderate mitotic index.
INTRODUCTION
Animal experiments remain essential to understand the fundamental mechanism underpinning malignancy and discover improved methods to prevent, diagnose and treat cancer.
Severe Combined Immuno Deficiency (SCID) mice provide an excellent in vivo model to study the molecular mechanisms of cancer and also the development of new anti tumor agents in drug discovery research.
Despite common usage, the availability of data on spontaneous background lesions in SCID mice is very minimal.
We concur to an earlier report (Peigen Huang et al., 2011), of a low incidence spontaneous non thymic lymphocytic lymphoma and add our findings, from a female SCID.
Fig 3 : Normal rudimentary SCID thymus
Fig 4 : Spleen - necrotic area with neoplastic cells (H&E 100X)
Fig 5 : Spleen - neoplastic cells with mitotic figures (H&E 400X)
Fig 6 : Kidney- inter tubular accumulation of neoplastic cells (H&E 400X)
Fig 7 : Liver- intercellular accumulation of neoplastic cells (H&E 400X)
Fig 8 : Lung- perivascular accumulation of neoplastic cells (H&E 400X)
Fig 10 : Infiltration of neoplastic cells in uterus (H&E 400X)
Fig 9 : Complete infiltration of neoplastic cells in ovary (H&E 400X)
DISCUSSION
MATERIALS & METHODS
SCID mice have a high incidence (approximately 10% to 20%) of spontaneous T-cell thymic lymphomas by 1 y of age (Huang et al 2011)
Custer et al (1985) reported as high as 15% thymic T cell lymphomas (41 of 269 SCID mice) and the tumor susceptible SCID–NOD strain had thymic lymphomas at a rate of 67% (Prochazka et al, 1992).
In a study elucidating the lymphomagenesis in SCID-NOD strain mice, there was incidence of non thymic lymphomas in 3/47cohorts but they were induced by tumor cell transplants (Chiu et al 2002).
Huang et al (2011) for the first time reported 4 spontaneous non thymic lymphomas among 1060 C.B-17/Icr-SCID retired breeders at average ages > 320 days in both sexes (506 males and 554 females).
We encountered a similar spontaneous non thymic lymphocytic lymphoma in a female breeder of approximately 150 days of age, an earlier incidence than reported by Huang et al (2011) and additionally, presence of neoplastic cells in ovaries and uterus.
Histomorphology as per ‘Guides for Toxicopathology’ was lymphocytic lymphoma with severe splenic enlargement and a rudimentary normal thymus that confirmed the non thymic origin (Firth et al, 1996).
Further immunophenotyping would help to decipher the origin of the tumor.
150 numbers of ICR TAC: ICR-PrKdc SCID mice from Taconic, UK were used to develop breeding nucleus.
Animals were reared inside the barrier facility in IVC cages, filled with autoclaved husk as bedding, fed ad libitum with gamma irradiated feed and sterilised RO water.
An unthrifty SCID female (>20 weeks old,), weighing 22.4 g , retired breeder with soiled anus received from our animal facility was euthanized and a routine necropsy was performed.
Routine histopathology of H&E stained 3-5 micron paraffin sections was carried out.
RESULTS
GROSS PATHOLOGY
Splenomegaly (relative weight-4.8%) with focal raised red areas (Fig. 1)
Hepatomegaly (relative weight-14%)
Pale colored Liver, Kidney , Uterus and Ovary (Fig 1)
Normal appearing rudimentary thymus (Fig 3).
CONCLUSION
This report of spontaneous non thymic lymphoma, concurred previous finding but had early incidence and utero-ovarian dissemination.
Fig 1 : SCID mice - Splenomegaly and pale colored internal organs
Fig 2 : Enlarged spleen with focal red raised areas
REFERENCES
1. Peigen Huang et al (2011). Spontaneous Nonthymic Tumors in SCID Mice,
Comparative Medicine, Vol 61, No 3,Pages 227–234.
2. Michal Prochazka et al (1992). The nonobese diabetic scid mouse: Model for spontaneous
thymomagenesis associated with immunodeficiency, Proc. Natl. Acad. Sci. Vol. 89, pp
3. Chiu et al (2002). Susceptibility to Lymphoid Neoplasia in Immunodeficient Strains of Nonobese
Diabetic Mice, Cancer research, 62, 5828–5834.
4. Custer RP, Bosma GC and Bosma MJ. (1985). Severe combined immunodeficiency (SCID) in
the mouse. Pathology, reconstitution, neoplasms.Am J Pathol 120:464–477
5. Frith et al (1996). Proliferative lesions of the Hematopoietic and Lymphatic systems in Rats.
Guides for Toxicologic Pathology.STP/ARP/AFIP.