Pathol Int. 2015 Mar 9. doi: 10.1111/pin.12283. [Epub ahead of print]

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.
摘要 伴横纹肌特征的癌是一种预后极差的罕见恶性肿瘤，有关其侵袭性行为的分子机制仍然不甚清楚。作者报道1例伴有横纹肌特征的未分化胰腺癌，被证实有广泛的浸润和转移。一位63岁男性患者因背部疼痛入院检查发现腹膜后肿瘤并伴有多发转移。淋巴结活组织检查证实为未知起源的未分化癌，加强化疗无效，患者3个月后死亡。尸检发现肿瘤位于腹膜后间隙，弥漫侵犯并破坏胰腺和十二指肠。组织学瘤细胞偏心位泡状核，核仁明显，juxtanuclear嗜酸性包涵体，细胞粘附性差。免疫组化瘤细胞表达细胞角蛋白和vimentin，电镜下证实核周含大量中间丝和脂滴，提示为伴有横纹肌特征的未分化癌，肿瘤组织中含透明质酸，瘤细胞强表达CD44、基质金属酶蛋白-9、低氧诱导因子-1α、透明质酸合酶2和胆固醇酰基转移酶1（一种酰基-辅酶A），Ki-67增殖指数较高。透明质酸是CD44的一个配体，细胞表面形成的CD44-透明质酸复合物能够激活CD44，这种活化作用能够解释为什么该肿瘤具有很强的侵袭性累犯和转移的临床过程。