粘表-腺样囊性癌-腺泡细胞癌-上皮肌上皮癌

,粘液表皮样癌、腺样囊性癌，腺泡细胞癌和上皮-肌上皮癌陈国璋,Mucoepidermoid carcinoma,Acinic cell carcinoma,Adenoid cystic carcinoma,黏液表皮样癌,癌细胞引人注目的特征：-鳞状细胞-粘液细胞-不确定型细胞（中间细胞）无痛性缓慢增长，实性肿块,黏液表皮样癌大体观,边界不清的肿块（可有囊性变）质地韧或硬囊肿常见囊肿内可有黏液,黏液表皮样癌组织学,浸润性多个不规则肿瘤细胞巢纤维性/促结缔组织增生性间质伴有炎症细胞浸润上皮细胞巢实性或囊性（充满分泌物）粘液外渗,黏液表皮样癌的细胞类型,1、粘液分泌细胞（柱状或杯状状）2、表皮样细胞 -多边形，胞浆呈淡嗜酸性 -几乎看不到细胞间桥或角化 -几乎没有明确鳞化！3、中间型细胞 细胞形态更小 镶嵌状排列在黏液细胞下,黏液表皮样癌的细胞发生,涎腺导管储备细胞,中间型细胞,表皮样细胞,Squamous cell,Mucous cell,Clear cell,P63免疫组化常常阳性！,黏液表皮样癌：变型,透明细胞（含有丰富的糖原）嗜酸性细胞梭形细胞生长硬化型,透明细胞,嗜酸性细胞,梭形细胞,硬化,黏液表皮样癌,黏液进入囊内，形成微囊或大囊,黏液渗出,慢性炎症反应,纤维化,高级别肿瘤不突出!,黏液渗出,粘液表皮样癌：传统的三层分级系统,LG,HG,HG,PASD,LG,IG,黏液表皮样癌的过度诊断,Warthin 瘤鳞化和/或黏液上皮化生(如果一个温和的肿瘤有很多的鳞状表现，它就不是一个黏液表皮样癌)囊腺瘤（非浸润性和单型细胞）坏死性涎腺化生,Warthin 瘤伴鳞化,多形性腺瘤,多形性腺瘤,坏死性涎腺化生,黏液表皮样癌诊断不足,缺乏肿瘤细胞岛和黏液外渗，误诊为黏液囊肿温和的细胞，误诊为良性肿瘤囊性变占大部分的肿瘤（误为囊腺瘤）硬化和炎症占主要部分 (误诊为炎症性病变),大涎腺不明原因的黏液池伴炎症,黏液表皮样癌，除非被证实为其它,黏液表皮样癌诊断检查表,浸润性边界硬化性间质 (常见)慢性炎症细胞浸润 (常见)特征性上皮岛/巢如果有明显的鳞状上皮或角化，大概就不是黏液表皮样癌了。,腺泡细胞癌,定义：上皮性肿瘤显示向细胞腺泡细胞分化主要发生在腮腺极少发生在小涎腺慢性生长的肿瘤，有或无痛可能是双侧性的（常见）,腺泡细胞癌：病理,常常是局限性的，偶尔是多结性的或浸润性的实性或囊性通常是混合生长模式通常混合细胞形态 (核分裂少见)间质通常不明显可能有突出的淋巴细胞聚集,腺泡细胞癌：生长模式,微囊型* 腺泡群或簇实性（常呈器官样）乳头状囊性（常富含空泡、鞋钉、闰管及非特异性腺细胞）滤泡（类似甲状腺滤泡）,腺泡细胞癌：细胞类型,腺泡细胞（偏位的暗的核，嗜碱性胞浆）闰管样细胞（小立方形细胞；中位核；粉红色细胞质）可占主导地位空泡细胞（大小类似于腺泡细胞；单个或多个空泡）非特异性腺细胞（通常是模糊的细胞边界；中位核）透明细胞(不常见，糖原阴性),没有肌上皮/基底细胞，P63阴性,正常的腺泡和闰管,CK,Some peculiar features ofacinic cell carcinoma,Self-destructive quality in some: ischemia and necrosis - Solitary or loculated cysts with papillae and hydropic clear cellsLipogranulomatous reactionInfarct after FNAB,Underdiagnosis of acinic cell carcinoma,Some acinic cell carcinomas are predominantly cystic - can be mistaken for benign salivary cyst,Acinic cell carcinoma: behavior,Low grade, indolent malignancyGrading or histologic variant has no prognostic significanceRecurrence 35% (may be delayed to 30 yr)Metastasis 16-19% (often delayed after many years)Lymph node Distant (lungs, bone)Survival: 5-yr 90%; 20-yr 56%,Acinic cell carcinoma:unfavorable prognostic factors,Gross invasionHigh stage diseaseDesmoplasiaSignificant cellular atypiaIncreased mitotic activity or MIB1 index (5%: 62% unfavorable outcome) J Pathol 1994;173:13-21Dedifferentiated acinic cell carcinoma,Atypia,Dedifferentiated acinic cell CA,Acinic cell carcinoma:favorable prognostic factors,Small size (90% for incomplete excision),Acinic cell carcinoma:essence of diagnosis,Identification of acinic cell differentiation in the tumor cells (which is often focal)Can be helped by:PAS-diastase stain (intracytoplasmic granules)Amylase immunohistochemistry (not readily available)Only luminal cell, but not abluminal cell, differentiation,ADENOID CYSTIC CARCINOMA,An infiltrative carcinoma having various features of three growth patterns: glandular (cribriform), tubular or solidTwo cell type:ductal-lining cellsmyoepithelial / basal type cellsUsually a slow-growing tumorBone invasion may occur without radiological evidence,Adenoid cystic carcinoma: pathology,Gross: Invasive borders; solid appearanceTubules, cribriform structures, solid massesVariable amounts of hyalinized stroma (sometimes “drowning” the tumor)May have lattice-like pattern, and abundant stromal mucin/hyaline materialPerineural invasion is characteristic (but not essential for diagnosis),Adenoid cystic carcinoma:cell types,Ductal epitheliumCuboidalSurrounds distinct small lumina (often with eosinophilic secretion)Eosinophilic cytoplasm; vesicular nucleiCan be difficult to appreciate,Small basaloid cells (modified myoepithelium)Often predominantHyperchromatic nucleiIndistinct cell bordersOften associated with basement membrane material, hyaline material or stromal mucin,Pseudocysts / stromal inclusions,c-kit,p63,SMA,Adenoid cystic carcinoma: genetics,A distinctive chromosomal translocation recently recognized in adenoid cystic carcinoma: t(6;9)(q22-23;p23-24), resulting in MYB-NFIB fusionThis is found in 50-86% of all cases, but not in other salivary gland tumorsIn future, detection of the molecular alteration may aid in the diagnosis of this tumor type,Adenoid cystic carcinoma: grading(M.D. Anderson),Adenoid cystic carcinoma: behavior,Local invasionMay extend for long distance along nervesUsually slowly progressive course (depending on grade)Frequent recurrenceMetastasis 30-40% (LN, lungs, bone)Majority of patients eventually succumb to disease after prolonged clinical course,Adenoid cystic carcinoma:prognostic factors,Size (better if 2 cm)Histologic grade / presence of solid componentStage of diseaseBone invasion (unfavorable)Completeness of excisionPresence of dedifferentiation (worsened prognosis),p63,Adenoid cystic carcinoma: checklist for diagnosis,Invasive bordersTwo-cell type (ductal epithelium may be difficult to find)Variable amounts of basement membrane and hyaline materialCribriform structures often presentClear cells very rare,Problems in diagnosis ofadenoid cystic carcinoma,Morphologic overlap with other entities with dual- cell type architecture:Pleomorphic adenoma, basal cell adenomaEpithelial-myoepithelial carcinomaBasal cell adenocarcinomaSolid areas may not be diagnostic: need to search for interspersed tubulesMarked stromal hyalinization renders recognition difficult,Pleomorphic adenoma,S100,Basal cell adenoma,CD43,Adenoid cystic carcinoma: Diagnosis,Dont make a diagnosis of adenoid cystic carcinoma if there is no invasion!,EPITHELIAL-MYOEPITHELIAL CARCINOMA,Called “clear cell adenoma” in the pastDefinition: Variable proportions of two cell types which typically form ductal structures: inner layer of ductal cells and outer layer of clear (myoepithelial) cellsMost common in parotid,Epithelial-myoepithelial carcinoma: histology,Usually multinodular or partly encapsulatedInvades in broad frontsDuctal epithelium: pink cytoplasm; lumen may contain eosinophilic secretion; may form branching luminaOuter layer of myoepithelium has clear cytoplasm (Glycogen +; S100 protein +; Actin +; Myosin +; p63+); often associated with thick B.M. or hyaline material,Epithelial-myoepithelial carcinoma: histology,Biphasic pattern may not be obvious in some cases: anastomosing islands and large sheets of clear cells (which can even become spindly, with fascicular growth), only occasional interspersed tubulesVariable amounts of hyalinized stromaPerineural and vascular invasion sometimes seen,PAS,PASD,CD117,p63,SMA,Epithelial-myoepithelial carcinoma: behavior,Low grade, indolent tumorMay evolve to a myoepithelial carcinomaRecurrence 30-40% (can be repeated)Cervical LN metastasis 10-20%Distant metastasis 9%Tumor mortality 9%,Epithelial-myoepithelial carcinoma: D.Dx.,Adenoid cystic CAMore permeative bordersAbluminal cells much smaller (“basaloid”)Clear cells rareFrequent cribriform structures with basophilic mucinBranching lumens rare,Pleomorphic adenomanon-invasiveclear cells rarechondromyxoid matrix“melting” myoepitheliumClear cell carcinoma,ACC,E