title: CD44-expressing undifferentiated carcinoma with rhabdoid features of the pancreas: molecular analysis of aggressive invasion and metastasis.
abstract: Carcinoma with rhabdoid features is a rare malignant tumor with a poor prognosis whose molecular mechanism for aggressive behavior is unclear. We describe an undifferentiated pancreatic carcinoma with rhabdoid features that demonstrated extensive invasion and metastasis. Examination of a 63-year-old man with back pain disclosed a retroperitoneal tumor with multiple metastases. Lymph node biopsy revealed an undifferentiated carcinoma of unknown origin. Intensive chemotherapy was ineffective; the patient died 3 months after initial symptoms. Autopsy showed that the tumor displaced the retroperitoneal space: it diffusely invaded and destroyed the pancreas and duodenum. Histology demonstrated tumor cells with eccentric vesicular nuclei, large nucleoli, juxtanuclear eosinophilic inclusions, and poor cell adhesion. Immunohistochemistry showed that tumor cells expressed cytokeratin and vimentin, and electron microscopy confirmed a perinuclear mass of intermediate fibrils and lipid droplets, which indicated an undifferentiated carcinoma with rhabdoid features. Tumor tissue contained hyaluronan; tumor cells strongly expressed CD44, matrix metalloproteinase-9, hypoxia-inducible factor-1α, hyaluronan synthase 2, and acyl-CoA:cholesterol acyltransferase 1 and had a high Ki-67(+) ratio. Since hyaluronan is a ligand for CD44, formation of CD44-hyaluronan complex on the cell surface activates CD44 and this activation may explain why the tumor manifested aggressive invasion and metastasis throughout the clinical course.
authors.affiliation: Undergraduate student, The University of Tokushima School of Medicine, Tokushima, Japan; Department of Human Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Ohmoto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yoshitani
authors.forename: Kazuchika
authors.initials: K
authors.lastname: Nishitsuji
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Takayama
authors.forename: Yuto
authors.initials: Y
authors.lastname: Yanagisawa
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
authors.forename: Naomi
authors.initials: N
authors.lastname: Sakashita
mesh_terms: D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000473:pathology*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D018335:Rhabdoid Tumor / Q000378:metabolism / Q000473:pathology*
chemical_list: D018960:Hyaluronan Receptors
keywords: CD44; hyaluronan; hypoxia-inducible factor-1α (HIF-1α); matrix metalloproteinase-9 (MMP-9); pancreas; undifferentiated carcinoma with rhabdoid features