粘表-腺样囊性癌-腺泡细胞癌-上皮肌上皮癌

1、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 carcinomaAcinic cell carcinomaAdenoid 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

2、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 cellMucous cellClear cellP63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 硬化型透明细胞透明细胞嗜酸性细胞嗜酸性细胞梭形细胞梭形细胞硬化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LGHGHG PASDLGIG黏液表皮样癌的过

3、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 瘤伴鳞化瘤伴鳞化多形性腺瘤多形性腺瘤多形性腺瘤多形性腺瘤坏死性涎腺化生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

4、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

5、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正常的腺泡和闰管CKSome peculiar features ofacinic cell carcinoma Self-destructive quality in some: ischemia and necrosis - Solitary or loculated cysts with papillae and hydropic clear cells Lipogranulomatous reaction I

6、nfarct after FNABUnderdiagnosis of acinic cell carcinoma Some acinic cell carcinomas are predominantly cystic - can be mistaken for benign salivary cystAcinic cell carcinoma: behavior Low grade, indolent malignancy Grading or histologic variant has no prognostic significance Recurrence 35% (may be d

7、elayed 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 invasion High stage disease Desmoplasia Significant cellular atypia Increased mitotic activity or MIB1 index (5

8、%: 62% unfavorable outcome) J Pathol 1994;173:13-21 Dedifferentiated acinic cell carcinomaAtypiaDedifferentiated acinic cell CAAcinic cell carcinoma:favorable prognostic factors Small size (90% for incomplete excision)Acinic cell carcinoma:essence of diagnosis Identification of acinic cell different

9、iation 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, differentiationADENOID CYSTIC CARCINOMA An infiltrative carcinoma having various features

10、of three growth patterns: glandular (cribriform), tubular or solid Two cell type: ductal-lining cells myoepithelial / basal type cells Usually a slow-growing tumor Bone invasion may occur without radiological evidenceAdenoid cystic carcinoma: pathology Gross: Invasive borders; solid appearance Tubul

11、es, cribriform structures, solid masses Variable amounts of hyalinized stroma (sometimes “drowning” the tumor) May have lattice-like pattern, and abundant stromal mucin/hyaline material Perineural invasion is characteristic (but not essential for diagnosis)Adenoid cystic carcinoma:cell types Ductal

12、epithelium Cuboidal Surrounds distinct small lumina (often with eosinophilic secretion) Eosinophilic cytoplasm; vesicular nuclei Can be difficult to appreciate Small basaloid cells (modified myoepithelium) Often predominant Hyperchromatic nuclei Indistinct cell borders Often associated with basement

13、 membrane material, hyaline material or stromal mucinPseudocysts / stromal inclusionsc-kitp63SMAAdenoid cystic carcinoma: genetics A distinctive chromosomal translocation recently recognized in adenoid cystic carcinoma: t(6;9)(q22-23;p23-24), resulting in MYB-NFIB fusion This is found in 50-86% of a

14、ll cases, but not in other salivary gland tumors In future, detection of the molecular alteration may aid in the diagnosis of this tumor typeAdenoid cystic carcinoma: grading(M.D. Anderson)Adenoid cystic carcinoma: behavior Local invasion May extend for long distance along nerves Usually slowly prog

15、ressive course (depending on grade) Frequent recurrence Metastasis 30-40% (LN, lungs, bone) Majority of patients eventually succumb to disease after prolonged clinical courseAdenoid cystic carcinoma:prognostic factors Size (better if 2 cm) Histologic grade / presence of solid component Stage of dise

16、ase Bone invasion (unfavorable) Completeness of excision Presence of dedifferentiation (worsened prognosis)p63Adenoid cystic carcinoma: checklist for diagnosis Invasive borders Two-cell type (ductal epithelium may be difficult to find) Variable amounts of basement membrane and hyaline material Cribr

17、iform structures often present Clear cells very rareProblems in diagnosis ofadenoid cystic carcinoma Morphologic overlap with other entities with dual- cell type architecture: Pleomorphic adenoma, basal cell adenoma Epithelial-myoepithelial carcinoma Basal cell adenocarcinoma Solid areas may not be

18、diagnostic: need to search for interspersed tubules Marked stromal hyalinization renders recognition difficultPleomorphic adenomaS100Basal cell adenomaCD43Adenoid cystic carcinoma: DiagnosisDont make a diagnosis of adenoid cystic carcinoma if there is no invasion!EPITHELIAL-MYOEPITHELIAL CARCINOMA C

19、alled “clear cell adenoma” in the past Definition: Variable proportions of two cell types which typically form ductal structures: inner layer of ductal cells and outer layer of clear (myoepithelial) cells Most common in parotidEpithelial-myoepithelial carcinoma: histology Usually multinodular or par

20、tly encapsulated Invades in broad fronts Ductal epithelium: pink cytoplasm; lumen may contain eosinophilic secretion; may form branching lumina Outer layer of myoepithelium has clear cytoplasm (Glycogen +; S100 protein +; Actin +; Myosin +; p63+); often associated with thick B.M. or hyaline material

21、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 tubules Variable amounts of hyalinized stroma Perineural and vas

22、cular invasion sometimes seen PASPASDCD117p63SMAEpithelial-myoepithelial carcinoma: behavior Low grade, indolent tumor May evolve to a myoepithelial carcinoma Recurrence 30-40% (can be repeated) Cervical LN metastasis 10-20% Distant metastasis 9% Tumor mortality 9%Epithelial-myoepithelial carcinoma:

23、 D.Dx. Adenoid cystic CA More permeative borders Abluminal cells much smaller (“basaloid”) Clear cells rare Frequent cribriform structures with basophilic mucin Branching lumens rare Pleomorphic adenoma non-invasive clear cells rare chondromyxoid matrix “melting” myoepithelium Clear cell carcinomaACC