粘表-腺樣囊性癌-腺泡細(xì)胞癌-上皮肌上皮癌

1、粘液表皮樣癌、腺樣囊性癌，腺泡細(xì)胞癌和上皮-肌上皮癌陳國璋Mucoepidermoid carcinomaAcinic cell carcinomaAdenoid cystic carcinoma黏液表皮樣癌 癌細(xì)胞引人注目的特征：-鱗狀細(xì)胞-粘液細(xì)胞-不確定型細(xì)胞（中間細(xì)胞） 無痛性緩慢增長，實性腫塊黏液表皮樣癌大體觀 邊界不清的腫塊（可有囊性變） 質(zhì)地韌或硬 囊腫常見 囊腫內(nèi)可有黏液黏液表皮樣癌組織學(xué) 浸潤性 多個不規(guī)則腫瘤細(xì)胞巢 纖維性/促結(jié)締組織增生性間質(zhì)伴有炎癥細(xì)胞浸潤 上皮細(xì)胞巢實性或囊性（充滿分泌物） 粘液外滲黏液表皮樣癌的細(xì)胞類型1、粘液分泌細(xì)胞（柱狀或杯狀狀）2、表皮樣細(xì)胞

2、-多邊形，胞漿呈淡嗜酸性 -幾乎看不到細(xì)胞間橋或角化 -幾乎沒有明確鱗化！3、中間型細(xì)胞 細(xì)胞形態(tài)更小 鑲嵌狀排列在黏液細(xì)胞下 黏液表皮樣癌的細(xì)胞發(fā)生涎腺導(dǎo)管儲備細(xì)胞中間型細(xì)胞表皮樣細(xì)胞Squamous cellMucous cellClear cellP63免疫組化常常陽性！黏液表皮樣癌：變型 透明細(xì)胞（含有豐富的糖原） 嗜酸性細(xì)胞 梭形細(xì)胞生長 硬化型透明細(xì)胞透明細(xì)胞嗜酸性細(xì)胞嗜酸性細(xì)胞梭形細(xì)胞梭形細(xì)胞硬化硬化黏液表皮樣癌黏液進(jìn)入囊內(nèi)，形成微囊或大囊黏液滲出慢性炎癥反應(yīng)纖維化高級別腫瘤不突出高級別腫瘤不突出!黏液滲出粘液表皮樣癌：傳統(tǒng)的三層分級系統(tǒng)低級別低級別中級別中級別高級別高級別許多微

3、囊和大囊一些囊少數(shù)囊許多黏液細(xì)胞混合性細(xì)胞少量黏液細(xì)胞很少核分裂核分裂不常見很多核分裂溫和的細(xì)胞形態(tài)有一定的異型性細(xì)胞多形性LGHGHG PASDLGIG黏液表皮樣癌的過度診斷 Warthin 瘤鱗化和/或黏液上皮化生 (如果一個溫和的腫瘤有很多的鱗狀表現(xiàn)，它就不是一個黏液表皮樣癌) 囊腺瘤（非浸潤性和單型細(xì)胞） 壞死性涎腺化生Warthin 瘤伴鱗化瘤伴鱗化多形性腺瘤多形性腺瘤多形性腺瘤多形性腺瘤壞死性涎腺化生壞死性涎腺化生黏液表皮樣癌診斷不足 缺乏腫瘤細(xì)胞島和黏液外滲，誤診為黏液囊腫 溫和的細(xì)胞，誤診為良性腫瘤 囊性變占大部分的腫瘤（誤為囊腺瘤） 硬化和炎癥占主要部分 (誤診為炎癥性病變)

4、大涎腺不明原因的黏液池伴炎癥黏液表皮樣癌，除非被證實為其它黏液表皮樣癌診斷檢查表 浸潤性邊界 硬化性間質(zhì) (常見) 慢性炎癥細(xì)胞浸潤 (常見) 特征性上皮島/巢 如果有明顯的鱗狀上皮或角化，大概就不是黏液表皮樣癌了。腺泡細(xì)胞癌 定義：上皮性腫瘤顯示向細(xì)胞腺泡細(xì)胞分化 主要發(fā)生在腮腺 極少發(fā)生在小涎腺 慢性生長的腫瘤，有或無痛 可能是雙側(cè)性的（常見）腺泡細(xì)胞癌：病理 常常是局限性的，偶爾是多結(jié)性的或浸潤性的 實性或囊性 通常是混合生長模式 通?；旌霞?xì)胞形態(tài) (核分裂少見) 間質(zhì)通常不明顯 可能有突出的淋巴細(xì)胞聚集腺泡細(xì)胞癌：生長模式 微囊型* 腺泡群或簇 實性（常呈器官樣） 乳頭狀囊性（常富含空

5、泡、鞋釘、閏管及非特異性腺細(xì)胞） 濾泡（類似甲狀腺濾泡）腺泡細(xì)胞癌：細(xì)胞類型 腺泡細(xì)胞（偏位的暗的核，嗜堿性胞漿） 閏管樣細(xì)胞（小立方形細(xì)胞；中位核；粉紅色細(xì)胞質(zhì)）可占主導(dǎo)地位 空泡細(xì)胞（大小類似于腺泡細(xì)胞；單個或多個空泡） 非特異性腺細(xì)胞（通常是模糊的細(xì)胞邊界；中位核） 透明細(xì)胞(不常見，糖原陰性)沒有肌上皮/基底細(xì)胞，P63陰性正常的腺泡和閏管正常的腺泡和閏管CKSome peculiar features ofacinic cell carcinoma Self-destructive quality in some: ischemia and necrosis - Solitary o

6、r loculated cysts with papillae and hydropic clear cells Lipogranulomatous reaction Infarct 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

7、Grading or histologic variant has no prognostic significance Recurrence 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 invasion High stage diseas

8、e Desmoplasia Significant cellular atypia Increased mitotic activity or MIB1 index (5%: 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 excisi

9、on)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, diffe

10、rentiationADENOID CYSTIC CARCINOMA An infiltrative carcinoma having various features 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 eviden

11、ceAdenoid cystic carcinoma: pathology Gross: Invasive borders; solid appearance Tubules, 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 charac

12、teristic (but not essential for diagnosis)Adenoid cystic carcinoma:cell types Ductal 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 pre

13、dominant Hyperchromatic nuclei Indistinct cell borders Often associated with basement membrane material, hyaline material or stromal mucinPseudocysts / stromal inclusionsc-kitp63SMAAdenoid cystic carcinoma: genetics A distinctive chromosomal translocation recently recognized in adenoid cystic carcin

14、oma: t(6;9)(q22-23;p23-24), resulting in MYB-NFIB fusion This is found in 50-86% of all 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)Grade 1Grade 2Grade 3Tubul

15、ar and cribriform, with no solid areasPure cribriform or mixed but with 30% solid areas; necrosis common; more cellular atypiaUsually small and amendable to total surgical excision. Protracted course.Intermediate behaviorLarger tumors. Frequently recur (early). Often killing within 4 yrs.15-yr survi

16、val 39%26%5%Adenoid cystic carcinoma: behavior Local invasion May extend for long distance along nerves Usually slowly progressive course (depending on grade) Frequent recurrence Metastasis 30-40% (LN, lungs, bone) Majority of patients eventually succumb to disease after prolonged clinical courseAde

17、noid cystic carcinoma:prognostic factors Size (better if 2 cm) Histologic grade / presence of solid component Stage of disease Bone invasion (unfavorable) Completeness of excision Presence of dedifferentiation (worsened prognosis)p63Adenoid cystic carcinoma: checklist for diagnosis Invasive borders

18、Two-cell type (ductal epithelium may be difficult to find) Variable amounts of basement membrane and hyaline material Cribriform structures often present Clear cells very rareProblems in diagnosis ofadenoid cystic carcinoma Morphologic overlap with other entities with dual- cell type architecture: P

19、leomorphic adenoma, basal cell adenoma Epithelial-myoepithelial carcinoma Basal cell adenocarcinoma Solid areas may not be diagnostic: need to search for interspersed tubules Marked stromal hyalinization renders recognition difficultAdenoid cystic carcinomaBasal cell / pleomorphic adenomaBordersInfi

20、ltrativeCircumscribedCribriform patternVery commonRare (but can occur)Chondroid matrixAbsentCommon in pleomorphic adenomaSpindly stroma focallyAbsentDiagnostic of basal cell or pleomorphic adenoma“Melting” into stromaAbsent (but hyalinization may mimic “melting”)Diagnostic of pleomorphic adenomaPleo

21、morphic adenomaS100Basal cell adenomaAdenoid cystic carcinomaOther salivary tumorsCD43 / L60 clone(Woo, 2006)100%7% PLGA12% Monomorphic adenomaCD43 / MT1 clone(Seethala, 2004)48%0%CD43Adenoid cystic carcinoma: DiagnosisDont make a diagnosis of adenoid cystic carcinoma if there is no invasion!EPITHEL

22、IAL-MYOEPITHELIAL CARCINOMA Called “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: histolog

23、y Usually multinodular or partly 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 t

24、hick B.M. or hyaline materialEpithelial-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 hyalini

25、zed stroma Perineural and vascular 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: 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-i