In order to investigate the clinical pathology of severe acute respiratory syndrome (SARS), the autopsies of three patients who died from SARS in Nan Fang Hospital Guangdong, China were studied retrospectively. Routine haematoxylin and eosin (H&E) staining was used to study all of the tissues from the three cases. The lung tissue specimens were studied further with Macchiavello staining, viral inclusion body staining, reticulin staining, PAS staining, immunohistochemistry, ultrathin sectioning and staining, light microscopy, and transmission electron microscopy. The first symptom was hyperpyrexia in all three cases, followed by progressive dyspnoea and lung field shadowing. The pulmonary lesions included bilateral extensive consolidation, localized haemorrhage and necrosis, desquamative pulmonary alveolitis and bronchitis, proliferation and desquamation of alveolar epithelial cells, exudation of protein and monocytes, lymphocytes and plasma cells in alveoli, hyaline membrane formation, and viral inclusion bodies in alveolar epithelial cells. There was also massive necrosis of splenic lymphoid tissue and localized necrosis in lymph nodes. Systemic vasculitis included oedema, localized fibrinoid necrosis, and infiltration of monocytes, lymphocytes, and plasma cells into vessel walls in the heart, lung, liver, kidney, adrenal gland, and the stroma of striated muscles. Thrombosis was present in small veins. Systemic toxic changes included degeneration and necrosis of the parenchyma cells in the lung, liver, kidney, heart, and adrenal gland. Electron microscopy demonstrated clusters of viral particles, consistent with coronavirus, in lung tissue. SARS is a systemic disease that injures many organs. The lungs, immune organs, and systemic small vessels are the main targets of virus attack, so that extensive consolidation of the lung, diffuse alveolar damage with hyaline membrane formation, respiratory distress, and decreased immune function are the main causes of death.

Purpose: Nasopharyngeal carcinoma is highly prevalent in southern China and is often resistant to current treatment options. Experimental Design: Clinically relevant mouse models are necessary for further understanding and drug discovery in this disease. Two nasopharyngeal carcinoma cell lines, stably expressing green fluorescent protein (GFP), 5-8F-GFP and 6-10B-GFP, were established. The cells were orthotopically injected into the nasopharynx or ectopically into the subcutis of nude mice. Whole-body fluorescence imaging was used to monitor the growth of the primary tumor as well as angiogenesis and metastasis. Results: The metastatic behavior of 5-8F and 6-10B were distinct in the orthotopic model. Orthotopic implantation of highly metastatic 5-8F cells resulted in brain invasion, cervical lymph node metastases, and pulmonary metastases similar to what is often observed in patients. Cell line 6-10B was less metastatic, which occasionally resulted in pulmonary metastasis. GFP enabled imaging of micrometastasis. Neither 5-8F nor 6-10B were metastatic in the s.c. site. These results indicated that, in addition to the cancer cell type, the host microenvironment was critical for metastasis to occur consistent with the ''seed-and-soil'' hypothesis. 5-8F was highly sensitive to 5-fluorouracil (5-FU), whereas 6-10B was moderately sensitive. Conclusions: The imageable orthotopic model should play a critical role in elucidating the mechanisms involved in the growth, progression, metastasis, and angiogenesis of nasopharyngeal carcinoma and for evaluation of novel compounds with potential efficacy.Nasopharyngeal carcinoma (NPC) is endemic in a few welldefined populations, mostly in South China, Hong Kong, Taiwan, and Singapore. NPC was the fourth most common new malignancy in Hong Kong. NPC arises in the epithelial lining of the nasopharynx. NPC is classified into three histologic types: keratinizing squamous cell carcinoma (type I); and nonkeratinizing carcinoma, characterized as differentiated (type II) or undifferentiated (type III). Type III NPC comprises more than 95% of NPC in high-incidence areas, and most of the remaining 5% is type II NPC. In contrast, type I NPC is predominant in lowincidence regions and may have an etiology distinct from that of the other two histologic types (1). The etiology of NPC is poorly understood. Epstein-Barr virus (EBV) is associated with NPC, but its role is also not clear. The biology of NPC is also poorly understood, and treatment outcome is dismal. Better models could solve these two related problems of NPC.Previous models of NPC involved ectopic s.c. implantation of NPC human tumor tissue in immunodeficient mice (2-5). Such models differed significantly from the original donor tumors. For example, such tumors became encapsulated and did not metastasize. Also, the important early stages of tumor development were essentially hidden. Orthotopic models of many tumor types have been developed which metastasize in a similar manner as in patients (6). Fluorescent proteins such ...