Lymphomas and leukaemias involving the lung have in some cases been hard to distinguish from respiratory tract infection in Sprague-Dawley (SD) rats from long-term bioassays. In order to differentiate between tumours and immune cell infiltrates, updated pathological criteria and nomenclature were used and immunohistochemistry (IHC) was applied to haematopoietic and lymphoid tissue tumours (HLTs) in the original prenatal long-term Aspartame (APM) study performed by the Ramazzini Institute (RI). All 78 cases of HLTs from treated and control groups were re-examined based on light microscopic morphological characteristics and subjected to a panel of IHC markers including Ki67, CD3, PAX5, CD20, CD68, TdT, CD45, CD14 and CD33. The analysis confirmed the diagnoses of HLTs in 72 cases, identified 3 cases of preneoplastic lesions (lymphoid hyperplasia), and categorized 3 cases as inflammatory lesions. A statistically significant increase in total HLTs (p = 0.006), total lymphomas (p = 0.032) and total leukaemias (p = 0.031) in treated female rats was confirmed (high dose vs control), and a statistically significant linear trend for each HLT type was also observed. After the HLT cases re-evaluation, the results obtained are consistent with those reported in the previous RI publication and reinforce the hypothesis that APM has a leukaemogenic and lymphomatogenic effect.

在长期的生物测定中，在某些情况下，涉及肺的淋巴瘤和白血病难以与Sprague-Dawley（SD）大鼠的呼吸道感染区分开。为了区分肿瘤和免疫细胞浸润，在Ramazzini进行的原始产前长期阿斯巴甜（APM）研究中，使用了更新的病理学标准和术语，并将免疫组织化学（IHC）应用于造血和淋巴组织肿瘤（HLT）。研究所（RI）。根据光学显微镜的形态学特征对来自治疗组和对照组的所有78例HLT进行重新检查，并对其进行一系列IHC标记，包括Ki67，CD3，PAX5，CD20，CD68，TdT，CD45，CD14和CD33。该分析确认了72例HLT的诊断，3例肿瘤前病变（淋巴样增生），并归为炎症性病变3例。在治疗的雌性大鼠中，总HLT（p = 0.006），总淋巴瘤（p = 0.032）和总白血病（p = 0.031）的统计学显着性增加得到确认（高剂量vs对照），每种HLT的统计学趋势均呈统计学显着性类型也被观察到。在对HLT病例进行重新评估后，获得的结果与先前RI出版物中报道的结果一致，并强化了APM具有促白血病和促淋巴瘤作用的假说。