Metastatic Squamous Cell Carcinoma of the Anus to the Lung Confirmed with Allelotyping

Histopathologic techniques are insufficient for distinguishing primary squamous cell carcinoma (SCC) from metastatic SCC, which is clinically important. A patient with SCC of the anus was found to also have SCC of the lung, and the question of metastatic versus synchronous primary diseases was raised. Immunohistochemical and hematoxylin and eosin (H&E) staining on sections of tissue could not discriminate between the two entities. Immunostain for p16 and chromogenic in situ hybridization for human papillomavirus (HPV) type 16 were positive in both tumors. Additionally, allelotyping for loss of heterozygosity displayed similar findings and confirmed the histopathological impression of anal SCC metastasis to the lung. The patient was treated with palliative chemotherapy instead of additional surgical treatment. When multiple tumors are present, determining metastatic versus synchronous primary tumors is necessary for appropriate treatment. Identification can be achieved using allelotyping for loss of heterozygosity. 1. Introduction Often clinical judgment has to be relied upon to differentiate between primary squamous cell carcinoma (SCC) of the lung and metastatic SCC of the anus. Hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining on biopsy cannot distinguish the two entities. This case report exemplifies a woman with SCC of the anus with confirmation of lung metastasis using human papillomavirus type 16 (HPV-16) chromogenic in situ hybridization (CISH) and allelotyping for loss of heterozygosity (LOH). To the best of our knowledge, this is the first case of anal SCC metastatic to the lung identified with p16 immunostaining, HPV type, and allelotyping in the literature. 2. Materials, Methods, and Results The patient is a 75-year-old woman diagnosed with a stage IV SCC of the anus. The patient reported hemorrhoidal problems which began to worsen in July 2003. A colonoscopy revealed the presence of grade 2 internal hemorrhoids, an anterior anal fistula, and a posterior anal papilloma. A fistulotomy and polypectomy were performed. The pathology report on the papilloma was unremarkable. She continued to have rectal bleeding and pain at the procedure site until a repeat colonoscopy was performed in March 2004, which revealed an anal fissure that was excised. At that time, the pathology report revealed an invasive poorly differentiated SCC with negative margins (Figure 1). Figure 1: Hematoxylin and eosin staining on anal fissure excision at 5x magnification (a) and 20x magnification (b). Immunohistochemical staining for p16 (c) and CISH for