原发性松果体区乳头状瘤1例

　　作者：张绍曾 作者单位：美国纽约Roswell Park癌症研究中心病理科

　　【摘要】 患者，男性，31岁。因头痛数年，加重3个月而急诊捡查。MRI检查显示第三脑室.松果体区有囊实质性肿块，并导致梗阻性脑积水。患者接受了双侧脑室腹腔分流术并在MRI引导下进行一系列立体定向活检。光镜显示:肿瘤含有乳头区和弥散的细胞区，肿瘤与少量正常组织混杂(图1)。免疫组织化学研究:肿瘤对S100在胞浆和核中呈局灶性阳性，对Cam5.2和Vimentin呈弥漫性强阳性而对CK7呈局灶性阳性。加上其他10余种免疫组化标记呈阴性反应，最后病理诊断:原发性松果体区乳头状瘤(PTPR)。原发性松果体区乳头状瘤极为少见，须与松果体实质肿瘤、脉络丛肿瘤、乳头状室管膜瘤、乳头状脑膜瘤等其他原发性中枢神经系统乳头状瘤相鉴别。而与原发性胚胎细胞瘤(如胚胎癌和卵黄囊肿瘤)以及来自肺、甲状腺、肾的转移性乳头状瘤则比较容易鉴别。

　　【关键词】 松果体区乳头状瘤 原发性 免疫组织化学 病理诊断

　　A31-year-old man with a large posterior third ventricular mass and hydrocephalus

　　A31-year-old gentleman who has had a past medical history of head-aches for many years was brought to the emergency room several times by his mother during the past3months.He suffered from the symp-toms of hydrocephalus:sluggish，confusion，severe headache，gait

　　imbalance，rigidity etc.

　　MRI revealed a solid and cystic mass in the midline centered on the third ventricle.pineal region causing obstructive hydrocephalus.It is displacing the tectum downward and splaying the Sylvian aqueduct.On the diffusion images the mass is hypointense in its cystic area and hyperintense in the solid area.On the post contrast images，the solid area showed intensive enhancement.

　　The patient received bilateral ventriculoperitoneal shunt and under-went a series of MRI-guided stereotactic biopsies of the tumor.

　　Microscopically，the biopsy specimens showed cellular tumor frag-ments intermingled with normal brain parenchyma.The tumor contains papillary areas and diffuse cellular areas(Fig1).The epithelial layer is irregular and several cells thickwith surface cilia.The papillae con-tain small to medial sized blood vessels.The tumor cells are uniformly in size with well-defined cytoplasmic membrane.The cytoplasm is eosinophilic and focally clear.The nuclei are round to oval showing frequent intranuclear inclusions.Mitosis is rare and necrosis is not ob-served.

　　Immunohistochemistry stains showed that the tumor is focally posi-tive for S100in nuclei and cytoplasm.The tumor is strongly and dif- fusely positive for Cam5.2and Vimentin.The proliferative potential by Ki67labelling index is less than10%.The tumor is negative for mucin stain.The rest of immunohistochemical markers including cy-tokeratin AE1.3，EMA，CEA，Ber-EP4，synaptophysin，GFAP，CD10，RCC，thyroglobin，TTF-1，HMB45，and melan A are all neg-ative.

　　Pathologic Diagnoses:Papillary Tumor of the Pineal Region

　　Primary papillary tumors of the central nervous system are rare，in-cluding pineal parenchymal tumors，choroid plexus tumors，papillary ependymomas，papillary meningiomas，germ cell tumors such as em-bryonal carcinoma and yolk sac tumors.In the adult，it is also ex-tremely important to distinguish the metastatic papillary carcinomas from the primary CNS papillary neoplasm due to the rarity of the lat-ter. The present study illustrates a distinct subtype of CNS papillary tu-mor，namely papillary tumors of the pineal region(PTPR).Up to date，there are very limited numbers of cases published.Jouvet et al[1] has described six patients followed by an additional cased pub-lished by Shibahara[2] The tumor is currently thought to originate from the specialized ependymal cells which invade the human pineal gland from the subcommissural organ(SCO)in the first months of perinatal period.Ultrastructural features of PTPR show intermediate filaments in cytoplasm，abundant rough endoplasmic reticulum，zipper-like junc-tions at the apical pole of cells and surface microvilli.

　　For the purpose of differential diagnosis，this rare tumor needs to be distinguished from other papillary tumors of CNS，and metastatic pap-illary carcinoma.Because of the location，pineal parenchymal tumors with papillary features needs to be considered first.The positive reac-tivity of cytokeratin and vimentin，and negative reactivity to synapto-physin in our tumorwere not those expected for pineal parenchymal tu-mors.Although the immunoprofile is very similar to that of choroid plexus tumor，including reactivity to cytokeratin，S100，and vimen-tin，the histological appearance of PTPR is less papillary with more diffuse cellular proliferation，the latter is not seen in the choroids plexus papilloma.In addition，this tumor is much better differentiated than choroid plexus carcinoma，with no mitosis，necrosis and low Ki67proliferative index(<5%).To differentiate it from papillary ependymoma，the immunohistochemical stains are very helpful.PTPR has strongly and diffuse reactivity to narrow-spectrum cytokeratin，es-pecially low molecular weight CK such as CK7，and Cam5.2，and GFAP is negative in the tumor，whereas ependymoma frequently ex-press GFAP and only express Pan-Cytokeratin.The current tumor shows intranuclear inclusions，resembling papillary meningioma.How-ever，the latter diffusely express EMA that is not seen PTPR.It is not difficult to distinguish this tumor fromCNS germ cell tumors on the ba-sis of morphology and immunohistochemical phenotypes.Before to make a diagnosis of PTPR，it is very important to rule out metastatic papillary carcinomas including carcinomas from lung，thyroid and kid-ney.Again with a panel of immunohistochemical markers，the differ-entiation will be not difficult.

　　In summary，this case illustrates the histopathology of an extremely rare entity of CNS papillary tumor:PTPR.The clinical behavior is not

　　well understood due to the limited number of cases and a lack of longer

　　clinical follow-up.However，it is expected to be similar to ependy-moma or choroid plexus tumor to have an indolent process，although local recurrence may occur.(Fig1see inside back cover)

　　【参考文献】

　　1 Jouvet A，Fauchon F，Liberski P，et al.Papillary tumor of the pineal region.Am J Surg Pathol，2003，27(4):505-512.

　　2 Shibahara J，Todo T，Morita A，et al.Papillary neuroepithelial tumor of the pineal region.A case report.Acta Neuropathol，2004，108(4):337-