<p>Supplementary data</p><p>Supplementary Figure 1. Reduction of the Tsc2 dose leads to exacerbated symptoms accompanied with lymphoadenopathy and splenomegaly in Pten+/- mice.</p><p>(A) B220 and CD3 staining of hyperplastic Pten+/- and Pten+/-Tsc2+/- lymph nodes on consecutive sections show indistinguishable patterns between the two different mutants (100x).</p><p>(B) Acute and chronic inflammation in the liver of a 6-month-old Pten+/-Tsc2+/- mouse. Arrows indicate polymorphonuclear cells (600x).</p><p>(C) H&E stained sections show exacerbated lymphoid infiltration in the kidney</p><p>(40x) and liver (100x) of a 6-month-old Pten+/-Tsc2+/- mouse compared with its</p><p>Pten+/- and Tsc2+/- littermates.</p><p>(D) H&E sections reveal severe extramedullary hematopoiesis in the spleen of a</p><p>6-month-old Pten+/-Tsc2+/- mouse compared with its littermates (40x). Note the normal spleen histology and well-defined white and red pulp in the spleen of the</p><p>Tsc2+/- mouse, while only mild red pulp expansion with mild focal extramedullary hematopoiesis is observed in the spleen of the Pten+/- mouse.</p><p>(E) Pelvic abscess with a necrotic center in a 6-month-old Pten+/-Tsc2+/- female mouse. The right panel (a magnified image of the boxed region in the left panel,</p><p>20x) represents the surrounding neutrophils, foamy histiocytes, and a fibrotic wall</p><p>(200x). Supplementary Figure 2. High-grade PIN and invasive carcinoma in AP, VP and DLP of an 8-month-old Pten+/-Tsc2+/- mouse, and in AP of a 5-month-old</p><p>Pten+/-Tsc2+/- mouse. Boxed regions and arrows indicate the area of invasion</p><p>(100x; 400x).</p><p>2</p>