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第22章肺（Lungs）

正常組織學（Normal Histology）

The lungs consist of principally four compartments: the large airways(bronchi), small airways and airspaces(bronchioles and alveoli), interstitium, and vessels. As in most organs, inflammatory processes tend to preferentially involve one or two compartments, so identifying the most affected area is key to the differential diagnosis. Normal histologic features include the following:

肺主要由四個部分組成：大氣道（支氣管）、小氣道和氣腔（細支氣管和肺泡）、間質和血管。與大多數(shù)器官一樣，炎癥過程往往優(yōu)先累及一個或兩個部分，因此確定最受影響的區(qū)域是鑒別診斷的關鍵。正常組織學特征包括：

Bronchi: The bronchi are lined with ciliated or columnar epithelium with scattered goblet cells. Goblet cell metaplasia is an indication of irritation, such as in bronchitis or asthma. Squamous cell metaplasia is common in smokers. Under the epithelium you should find seromucinous(salivary-type) glands, cartilage, smooth muscle, and branches of the bronchial arteries(Figure 22.1).

支氣管：支氣管內襯纖毛上皮或柱狀上皮，有散在的杯狀細胞。杯狀細胞化生提示受到刺激，如支氣管炎或哮喘。鱗狀細胞化生常見于吸煙者。在上皮下，你會發(fā)現(xiàn)漿粘液性（涎腺型）腺體、軟骨、平滑肌和支氣管動脈分支（圖22.1）。

Figure 22.1. Normal bronchus. The bronchus is lined by ciliated columnar epithelium(1), foci of goblet cells(2), cartilage(3), and smooth muscle(4). The small arteries seen here(5) are branches of the bronchial artery, which carries oxygenated blood from the left ventricle.

圖22.1 正常支氣管。支氣管由纖毛柱狀上皮（1）、小灶杯狀細胞（2）、軟骨（3）和平滑?。?）構成。這里所見的小動脈（5）是支氣管動脈的分支，它從左心室輸送含氧血液。

Bronchioles: Bronchioles should have a cuboidal epithelium without goblet cells(Figure 22.2). The Clara cells are probably secretory and reserve cells, but they are difficult to see. There is no cartilage.

細支氣管：細支氣管應有立方上皮，無杯狀細胞（圖22.2）。Clara細胞可能是分泌細胞和儲備細胞，但很難看到。沒有軟骨。

Figure 22.2. Bronchioles and alveoli. The small bronchiole(B) seen here is lined by a cuboidal epithelium and smooth muscle. The large adjacent arteriole(A) is a branch of the pulmonary artery. The veins or venules(V) run in septa. The alveolar walls(arrow) are normally lined with flat type I epithelium, of which only the nuclei are visible. Alveolar macrophages(arrowheads) are common.

圖22.2 細支氣管和肺泡。小細支氣管（B）有立方上皮和平滑肌排列。相鄰的小動脈（A）是肺動脈的分支。靜脈或小靜脈（V）位于肺泡隔中。肺泡壁（箭）通常被覆平坦的I型上皮，只看到核。常見肺泡巨噬細胞（箭頭）。

Alveoli: The alveoli are the terminal air sacs and therefore have extremely thin walls(see Figure 22.2); in atelectasis, a common biopsy artifact, it is difficult to pick out the collapsed airspaces. Normally they are lined by nearly invisible flat type I epithelium. The presence of a cuboidal epithelium indicates type II hyperplasia(surfactant and reserve cells, which are normally sparse), seen in chronic inflammation or repair. Alveolar macrophages are often scattered throughout but macrophages packing the alveoli is pathologic(see later discussion of desquamative interstitial pneumonia).

肺泡：肺泡是終末氣囊，因此非常薄壁（見圖22.2）；肺不張是一種常見的活檢假象，很難識別塌陷的氣腔。正常情況下，它們被覆幾乎看不見的扁平I型上皮。出現(xiàn)立方上皮提示II型增生（表面活性劑和儲備細胞，通常稀疏），見于慢性炎癥或修復。肺泡巨噬細胞通常散布于肺泡各處，但聚集在肺泡內的巨噬細胞是病理性的（見下文關于脫屑性間質性肺炎的討論）。

Vessels: Pulmonary arterioles run with bronchioles and have two elastic layers on Movats stain(train track appearance). Veins run in interlobular septa and have one irregular elastic lamina. Lymphatics run with arteries, veins, and in pleura.

血管：肺小動脈與細支氣管一起運行，在Movats染色上有兩層彈性層（火車軌道外觀）。靜脈在小葉間隔內運行，有不規(guī)則的彈性層。淋巴管與動脈、靜脈并行，胸膜也有淋巴管。

Movats stain is a standard supplemental stain for nonneoplastic lung. On this pentachrome stain, you will see elastic laminae highlighted as black fibers(useful for identifying pleural involvement by tumors as well), hyaluronic acid or mucin in aqua blue, mature collagen in yellow, smooth muscle in dull red, and fibrinoid necrosis(as in vessels) as bright red(Figure 22.3). This stain is very useful for identifying fibroblast foci in bronchiolitis obliterans–organizing pneumonia(discussed later) because they stand out as turquoise swirls on low power. Established interstitial fibrosis will be yellow.

Movats染色是非腫瘤性肺的標準補充染色。在這個五顏六色染色上，你會看到彈力層突出顯示為黑色纖維（也有助于識別腫瘤累及胸膜），透明質酸或粘蛋白呈水藍色，成熟膠原呈黃色，平滑肌呈暗紅色，纖維蛋白樣壞死（如血管）呈鮮紅色（圖22.3）。這種染色對于鑒別閉塞性細支氣管炎的成纖維細胞灶非常有用——機化性肺炎（稍后討論），因為它們在低倍鏡下呈青綠色漩渦狀突出。已確定的間質纖維化呈黃色。

Figure 22.3. Movats stain. The pulmonary arteries(A) have two elastic layers(arrowheads), while the veins(V) have one(arrow). The collagen lining the vessels is pale yellow-green in this stain.

圖22.3 Movats染色。肺動脈（A）有兩層彈性層（箭頭），而靜脈（V）有一層彈性層（箭）。血管內壁的膠原呈淡黃綠色。

非腫瘤性肺簡介（A Brief Introduction to Nonneoplastic Lung）

（譯注：這部分內容了解即可，作者前面說過初學者不要亂搞非腫瘤的東西）

In nonneoplastic lung, within each of the four compartments you are usually looking for something that does not belong. Examples of things that do not belong include heavy mononuclear cell infiltrates(lymphocytes and macrophages), neutrophils(other than in capillaries), eosinophils, granulomas, fibrosis and fibroblast foci, and substances such as amyloid, edema fluid, and asbestos. Table 22.1 lists differential diagnoses organized by what you see and in which compartment.

非腫瘤性肺，四個組成部分中的每一個，你通常都要尋找本來沒有的東西。多出來的東西，例如，嚴重的單個核炎癥細胞浸潤（淋巴細胞和巨噬細胞）、中性粒細胞（除外毛細血管內）、嗜酸性粒細胞、肉芽腫、纖維化和成纖維細胞灶，以及淀粉樣物、水腫液和石棉等物質。表22.1根據(jù)你看到什么和在哪個部分列出鑒別診斷。

Table 22.1. Differential diagnoses.

表22.1 鑒別診斷。

ABPFD, allergic bronchopulmonary fungal disease過敏性支氣管肺真菌病; ACIP, active chronic interstitial pneumonitis活動性慢性間質性肺炎; AIP, acute interstitial pneumonitis急性間質性肺炎; BCG, bronchocentric granulomatosis支氣管中心性肉芽腫; BOOP, bronchiolitis obliterans–organizing pneumonia閉塞性細支氣管炎-機化性肺炎; CEP, chronic eosinophilic pneumonia慢性嗜酸性肺炎; CIP, chronic interstitial pneumonia慢性間質性肺炎; DAD, diffuse alveolar damage彌漫性肺泡損傷; DIP, desquamative interstitial pneumonia脫屑性間質性肺炎; EAA, extrinsic allergic alveolitis(hypersensitivity pneumonitis)外源性過敏性肺泡炎（過敏性肺炎）; HM, hyaline membranes透明膜; LCH, Langerhans cell histiocytosis朗格漢斯細胞組織細胞增生癥; LIP, lymphocytic interstitial pneumonia淋巴細胞性間質性肺炎; NSIP, nonspecific interstitial pneumonia非特異性間質性肺炎; OB, obliterative bronchiolitis閉塞性細支氣管炎; PAP, pulmonary alveolar proteinosis肺泡蛋白沉積癥; PCP, Pneumocystis carinii pneumonia卡氏肺孢子蟲肺炎; RA, rheumatoid arthritis類風濕性關節(jié)炎; RB-ILD, respiratory bronchiolitis-interstitial lung disease呼吸性細支氣管炎-間質性肺病; SLE, systemic lupus erythematosus系統(tǒng)性紅斑狼瘡; TB, tuberculosis結核病; UIP, usual interstitial pneumonia普通間質性肺炎; WG, Wegener’s granulomatosis韋格納肉芽腫

對肺損傷的反應（Response to Injury in the Lung）

It is useful to think of the three phases of injury response in the lung: acute, subacute, and chronic. Acute injury, which may be from infection, trauma, toxins, drugs, or a transfusion reaction, manifests as diffuse alveolar damage. Clinically this pattern correlates with acute respiratory distress syndrome. Idiopathic diffuse alveolar damage, when no known precipitating factor can be identified, is called acute interstitial pneumonitis. The histologic picture is a nonspecific indication of injury and includes interstitial edema and hemorrhage, hyaline membrane formation, type II hyperplasia, and fibrin thrombi(Figure 22.4). There should be a uniform and diffuse appearance throughout the field of view(although it may be patchy grossly).

把肺損傷反應分為三個階段是有用的：急性、亞急性和慢性。急性損傷可能是由于感染、創(chuàng)傷、毒素、藥物或輸血反應，表現(xiàn)為彌漫性肺泡損傷。臨床上，這種模式與急性呼吸窘迫綜合征相關。特發(fā)性彌漫性肺泡損傷，當沒有已知的促發(fā)因素時，稱為急性間質性肺炎。組織學圖像是損傷的非特異性表現(xiàn)，包括間質水腫和出血、透明膜形成、II型增生和纖維素血栓（圖22.4）。在整個視野范圍內，應具有均勻且分散的外觀（盡管肉眼觀可能呈斑點狀）。

Figure 22.4. Diffuse alveolar damage. The alveolar spaces are full of fluid and blood(asterisk), which in some areas is beginning to coalesce into thick pink hyaline membranes(arrow). The interstitial spaces are thickened due to edema.

圖22.4 彌漫性肺泡損傷。肺泡腔充滿液體和血液（星號），在某些區(qū)域，這些液體和血液開始合并成厚的粉紅色透明膜（箭頭）。由于水腫，間質增厚。

When the initial injury begins to resolve, you see the organizing phase, which consists of new fibroblast foci forming in alveoli and bronchioles. These are the swirling nodules of stellate fibroblasts that appear myxoid on H&E stain and aqua on Movats stain(Figure 22.5). They are also the hallmark of bronchiolitis obliterans–organizing pneumonia(BOOP), the pattern of subacute injury response. It can be impossible to distinguish a primary BOOP from a resolving acute injury without the clinical context. It is also seen as a component of many other disease processes, but as a primary disease it is simply “idiopathic BOOP.” Obliterative bronchiolitis is a related lesion that is really only seen in transplant patients, and is a form of either rejection or graft-versus-host disease.

當最初的損傷開始消退時，你會看到機化階段，表現(xiàn)為肺泡和細支氣管中新生的成纖維細胞灶。成纖維細胞灶是星形成纖維細胞形成的漩渦狀結節(jié)，HE染色呈黏液樣，Movats染色呈藍綠色（圖22.5）。成纖維細胞灶也是閉塞性細支氣管炎的特征，稱為機化性肺炎（BOOP），屬于亞急性損傷反應模式。在沒有臨床背景的情況下，不可能區(qū)分原發(fā)性BOOP和消退期急性損傷。機化性肺炎也是許多其他疾病過程的一個組成部分，但作為一種原發(fā)性疾病，它只是“特發(fā)性BOOP”。閉塞性細支氣管炎是一種相關病變，僅見于移植患者，是排斥反應或移植物抗宿主病的一種形式。

Figure 22.5. Fibroblast foci.(A) By H&E stain, these myxoid swirls of new fibroblasts are pale and streamy(arrows).(B) On Movats stain, they are turquoise(arrow).

圖22.5 成纖維細胞灶。（A）HE染色，這些新生的成纖維細胞形成黏液樣漩渦，呈淡染的流水樣排列（箭）。（B）Movats染色呈藍綠色（箭頭）。

Chronic and repetitive injury to the lung is like a scab on the skin that gets repeatedly picked off; there are multiple cycles of damage and repair, and the end result is chronic inflammation and fibrosis. The final common pathway of many diseases, or end-stage lung, is called honeycomb lung. A specific pattern of chronic injury that may lead to honeycomb lung is usual interstitial pneumonia. Usual interstitial pneumonia is a nonspecific pattern; idiopathic pulmonary fibrosis is the name given to idiopathic usual interstitial pneumonia.

肺部的慢性和重復性損傷就像皮膚的結痂，被反復剝落；有損傷和修復的多個周期，最終結果是慢性炎癥和纖維化。許多疾病的最終共同途徑，或終末期肺，稱為蜂窩狀肺。一種可能導致蜂窩狀肺的特殊慢性損傷模式是普通間質性肺炎。普通間質性肺炎是一種非特異性模式；特發(fā)性普通間質性肺炎又稱為特發(fā)性肺纖維化。

Usual interstitial pneumonia should be temporally heterogenous, which means you should see evidence of all stages of injury(acute, subacute, and chronic). There is prominent interstitial fibrosis, which outlines large and angular distorted airspaces(Figure 22.6), but there should also be fibroblast foci. The airspaces are lined by plump, reactive, and scary looking type II pneumocytes. There is diffuse chronic inflammation, as well as pockets of acute inflammation.

普通間質性肺炎應該表現(xiàn)為暫時的異質性，這意味著你應該看到所有損傷階段（急性、亞急性和慢性）的證據(jù)。有明顯的間質纖維化，它勾勒出大而成角的扭曲的氣腔（圖22.6），但也應該有成纖維細胞灶。這些氣腔被覆著豐滿的、反應性、看起來嚇人的II型肺泡細胞。有彌漫性慢性炎癥，也有局部急性炎癥。

Figure 22.6. Usual interstitial pneumonia. The interstitial spaces are thickened and fibrotic(arrowhead), and there is abundant chronic inflammation(arrow). Inset: The scarred down, irregularly shaped, residual alveolar spaces are lined with type II pneumocytes, which protrude into the lumen and may have atypical nuclei.

圖22.6 普通間質性肺炎。間質增厚、纖維化（箭頭），有大量慢性炎癥（箭）。插圖：類似結痂的、形狀不規(guī)則的殘余肺泡腔襯覆II型肺泡細胞，這些細胞伸入管腔，可能有非典型核。

過敏性疾?。ˋllergic Disease）

There are two forms of allergic response in the lung: IgE-mediated disease and cell-mediated hypersensitivity reactions. Diseases in the first category include asthma, allergic bronchopulmonary fungal disease, bronchocentric granulomatosis(allergy to Aspergillus), and the eosinophilic pneumonias.

肺中有兩種形式的過敏反應：IgE介導的疾病和細胞介導的超敏反應。前者包括哮喘、過敏性支氣管肺真菌病、支氣管中心性肉芽腫（對曲霉菌過敏）和嗜酸性肺炎。

The prototypical cell-mediated hypersensitivity disease is extrinsic allergic alveolitis. It can have many causes and many appearances. This includes all the “(undesirable-job-here)’s lung” and “(exotic-pet-name) fancier’s lung” diseases(e.g., “formalin lung” and “l(fā)izard-lover’s lung”). Eosinophils do not feature prominently in extrinsic allergic alveolitis. The classic histologic triad includes(1) patchy chronic interstitial pneumonia, especially peribronchiolar;(2) poorly formed small nonnecrotizing granulomas; and(3) foci of BOOP.

后者典型疾病是外源性過敏性肺泡炎。它可能有許多原因和許多形態(tài)表現(xiàn)。包括所有的“不受歡迎的工作”的肺和“異國情調的寵物名”愛好者的肺“疾?。ɡ?，“福爾馬林肺”和“蜥蜴愛好者的肺”）。嗜酸性粒細胞在外源性過敏性肺泡炎中不是主要特征。典型的組織學三聯(lián)征包括：（1）斑片狀慢性間質性肺炎，尤其是細支氣管周圍；（2）不完好的非壞死性小肉芽腫；局灶BOOP。

吸煙者疾?。―iseases of Smokers）

Smokers get a spectrum of interstitial lung diseases, including desquamative interstitial pneumonitis(DIP), respiratory bronchiolitis, Langerhans cell histiocytosis, and probably usual interstitial pneumonia. They also get obstructive lung disease, which includes chronic bronchitis and emphysema. DIP is a disease process in which alveolar macrophages pack the alveoli; it is usually associated with smoking, but a DIP pattern may be seen in other processes as well.

吸煙者患有一系列間質性肺病，包括脫屑性間質性肺炎（DIP）、呼吸性細支氣管炎、朗格漢斯細胞組織細胞增生癥，可能還有普通間質性肺炎。他們還患有阻塞性肺病，包括慢性支氣管炎和肺氣腫。DIP是肺泡巨噬細胞充滿肺泡的疾病過程；它通常與吸煙有關，但其他疾病也可能會出現(xiàn)DIP模式。

Note that Langerhans cell histiocytosis, also called eosinophilic granuloma, does not have traditional granulomas and may not always have eosinophils. What it does have is collections of histiocytes, identified by their pale nuclei with folds and creases(or by immunostains). This disease may occur systemically in the pediatric population, but in adults(which are 50% of cases) it is an isolated pulmonary disease of smokers.

注意，朗格漢斯細胞組織細胞增生癥，也稱為嗜酸性肉芽腫，沒有傳統(tǒng)的肉芽腫，也可能不總是有嗜酸性粒細胞。它具有組織細胞聚積，組織細胞核淡染并有皺折和折痕，或通過免疫染色來識別。這種疾病可見于兒科患者的系統(tǒng)性疾病，但在成人（占50%）中，它是吸煙者的一種孤立性肺部疾病。

腫瘤性肺（Neoplastic Lung）

異型增生與原位癌（Dysplasia and Carcinoma In Situ）

The terms dysplasia and carcinoma in situ are not often used in pulmonary pathology. There are at least two types of epithelium that can be evaluated, the respiratory(columnar) and the squamous metaplastic. For the respiratory epithelium, the presence of cilia is a reassuring sign that all is well(Figure 22.7). However, chronically injured or irritated airspaces can get type II cell hyperplasia. On the slide, this appears as plump cuboidal to columnar eosinophilic cells, with enlarged nuclei, lining the airspaces. If this occurs as a prominent change within a small focus(less than 10 mm), it is analogous to dysplasia and is called atypical adenomatoid hyperplasia(Figure 22.8). Presumably these foci can go on to become bronchioloalveolar carcinoma, which is essentially adenocarcinoma in situ. Like dysplasia in other organs, these processes can be multifocal.

術語“異型增生”和“原位癌”在肺病理學中不常用。至少有兩種類型的上皮可以評估，呼吸上皮（柱狀上皮）和鱗狀上皮化生上皮。前者，存在纖毛是一個令人放心的跡象，表明一切正常（圖22.7）。然而，慢性損傷或受刺激的氣腔可導致II型細胞增生。在切片上，表現(xiàn)為肥碩的立方形到柱狀嗜酸性細胞，核增大，突入氣腔。如果這是一個小病灶（小于10mm）內的顯著改變，則類似于異型增生，稱為非典型腺瘤樣增生（AAH，圖22.8）。據(jù)推測，這些病灶可能會發(fā)展為細支氣管肺泡癌，實質上是原位腺癌。與其他器官異型增生一樣，這些過程可能是多灶性。

Figure 22.7. Reactive bronchial epithelium overlying a carcinoid tumor. Although the epithelium is very proliferative and has enlarged and crowded nuclei, the presence of cilia(arrows) indicates that these cells are benign.

圖22.7 覆蓋在類癌上方的反應性支氣管上皮。盡管上皮細胞增殖非?；钴S，核增大擁擠，但存在纖毛（箭頭所示）提示良性。

Figure 22.8. Atypical adenomatoid hyperplasia. In this tiny, limited focus, there is interstitial inflammation(arrow) and prominent type II hyperplasia(arrowhead). The adjacent alveolar walls are unremarkable.

圖22.8 非典型腺瘤樣增生。在這個微小的、有限的病灶中，有間質性炎癥（箭）和顯著的II型增生（箭頭）。相鄰的肺泡壁無特殊。

For squamous epithelia, although squamous dysplasia exists and is analogous to other organs, in practice it is not often caught on biopsy. Similarly, squamous carcinoma in situ exists in the bronchi just as in the larynx or oropharynx but is usually seen at the periphery of squamous cancers instead of as the sole finding in a biopsy specimen.

對于鱗狀上皮，雖然存在鱗狀上皮異型增生，類似于其他器官，但實際上在活檢中少見。類似地，鱗狀細胞原位癌與喉或口咽一樣存在于支氣管，但通常見于鱗癌周圍，而不是活檢標本中唯一發(fā)現(xiàn)。

癌（Carcinoma）

Most lung biopsies in the neoplastic category are performed because a mass lesion was detected on radiology. Dysplasia and carcinoma in situ generally are not mass forming, so once you have ruled out a granulomatous process(those can form nodules), you are trying to identify the neoplasm. The most common lesions are discussed below. However, keep in mind that in lung, most tumors are a mix of tumor types or variants(pluripotent stem cells?), so you must sample well, name the tumors for their major components, and ignore small foci of different morphologies. Non–small cell is sort of a wastebasket term used to mean adenocarcinoma or squamous cell carcinoma, which can be grouped like that because their clinical behavior is similar.

大多數(shù)腫瘤類別的肺活檢是因為影像學發(fā)現(xiàn)腫塊病變。異型增生和原位癌通常不形成腫塊，因此你一旦排除了肉芽腫疾?。赡苄纬山Y節(jié)），就要努力識別腫瘤。下面討論最常見的病變。然而，要記住，肺的大多數(shù)腫瘤是多種腫瘤類型或變異型（來自多能干細胞？）的混合，因此你必須仔細取材，根據(jù)主要成分命名腫瘤，并忽略不同形態(tài)的小病灶。非小細胞癌是一個垃圾桶術語，用來指腺癌或鱗狀細胞癌，因為它們的臨床行為相似，所以可以這樣分類。

Squamous carcinoma arises from squamous metaplasia, often in the major bronchi, and therefore is often central or hilar. The most recognizable form is the well to moderately differentiated keratinizing variety, with its pink, dense cytoplasm, keratin whorls, and distinct cell borders(Figure 22.9). It is graded on the typical well, moderately, or poorly differentiated scale. However, there are trickier variants, including the following:

鱗癌起源于鱗狀化生，常發(fā)生在主支氣管，因此常位于中央或肺門。最易辨認的形式是高-中分化的角化型，具有粉紅色、致密的細胞質、角蛋白旋渦和清晰的細胞邊界（圖22.9）。一般分為高、中或低分化。然而，還有一些更為棘手的變異型，包括：

Figure 22.9. Squamous cell carcinoma.(A) Moderately differentiated squamous cell carcinoma, with irregular nests of cells with highly pleomorphic nuclei and bright pink, dense cytoplasm(arrow). Keratin pearls may also be seen in more well-differentiated tumors.(B) Basaloid squamous cell carcinoma, with rounded nests of very blue tumor cells with high nuclear to cytoplasmic ratio and a high mitotic rate. Central necrosis(asterisk) is common.

圖22.9 鱗狀細胞癌。（A）中分化鱗狀細胞癌，細胞巢不規(guī)則，核高度多形性，胞質亮粉色、致密（箭）。角化珠也可見于分化較好的腫瘤。（B）基底樣鱗狀細胞癌，藍色腫瘤細胞圓形巢，高核質比和高核分裂率。常見中央壞死（星號）。

Nonkeratinizing
非角化
Basaloid: blue and palisading, with a dense syncytial look(see Figure 22.9)
基底樣：藍色和柵欄狀，緊密合胞體樣（見圖22.9）
Small cell: similar to small cell neuroendocrine, but with uglier nuclei and no neuroendo-crine staining
小細胞：類似小細胞神經(jīng)內分泌癌，但核更丑，無神經(jīng)內分泌染色
Spindle cell or sarcomatoid: densely cellular spindly pattern, resembling a sarcoma(Figure 22.10)
梭形細胞或肉瘤樣：細胞密集，梭形，類似肉瘤（圖22.10）

Figure 22.10. Sarcomatoid carcinoma. Sheets of spindled cells with large nuclei and prominent nucleoli are visible. Mitoses(arrow) are common. These cells should be positive for cytokeratin stains, confirming their epithelial origin.

圖22.10 肉瘤樣癌。成片的梭形細胞，核大，核仁顯著。核分裂（箭）常見。梭形細胞應表達CK，確認其上皮來源。

Clear cell(adenocarcinoma can also have clear cells)
透明細胞（腺癌也可以有透明細胞）
Intrabronchial papillary: architecture like a papilloma, but malignant
支氣管內乳頭狀：結構類似乳頭狀瘤，但惡性

Adenocarcinoma arises from multiple cell types and therefore can vary in morphology. Patterns include acinar, tubular, papillary, and solid, and they may be mucinous or nonmucinous. If you see gland formation or mucin production, it is almost certainly adenocarcinoma(Figure 22.11), and then you must decide if it is primary or metastatic.

腺癌起源于多種細胞類型，因此形態(tài)學可能有所不同。模式包括腺泡狀、管狀、乳頭狀和實性，細胞學可能是粘液性或非粘液性。如果你看到腺體形成或粘液產生，幾乎肯定是腺癌（圖22.11），然后你必須確定它是原發(fā)性還是轉移性。

Figure 22.11. Adenocarcinoma. In some areas this tumor is forming cribriform glandular spaces(arrow), and in others small malignant glands or single cells are seen embedded in a desmoplastic stroma(arrowhead), confirming invasion.

圖22.11 腺癌。在某些區(qū)域，腫瘤形成篩狀腺腔（箭），其他區(qū)域，小的惡性腺體或單個細胞埋陷在促結締組織增生的間質中（箭頭），證實了浸潤。

As described earlier, bronchioloalveolar carcinoma(BAC) is the in situ form of adenocarcinoma. BAC in pure form appears to have a better prognosis than other non–small cell cancers, but, surprisingly, it still behaves, and is managed like, a full-fledged carcinoma. BAC may be mucinous(probably arising from goblet cell metaplasia) or nonmucinous. Of the two, the nonmucinous type has a better prognosis and is more often solitary.

如前所述，細支氣管肺泡癌（BAC）是原位腺癌。純形BAC似乎比其他非小細胞癌的預后更好，但令人驚訝的是，它的生物學行為和治療方式仍然像一種成熟的癌。BAC可能是粘液性（可能由杯狀細胞化生引起）或非粘液性。在這兩種類型中，非粘液型預后較好，且多為單發(fā)。

BAC takes the form of columnar and usually eosinophilic cells growing along the bronchial and alveolar walls, outlining the structure of the airspaces(Figure 22.12). By definition, there must not be evidence of stromal invasion(irregularly shaped back-to-back glands, single cells, desmoplasia). BAC is often found at the periphery of invasive tumors, so this diagnosis should not be made on a biopsy specimen or frozen tissue or until the entire tumor has been sampled. This rule applies to most “improved-prognosis variant” tumors in pathology: you had better not label something as a good-prognosis tumor unless the entire lesion is of that type. A “BAC pattern” refers to a growth pattern of an invasive tumor that mimics BAC.

BAC呈柱狀細胞，通常嗜酸性，沿支氣管和肺泡壁生長，勾畫出氣腔的結構（圖22.12）。根據(jù)定義，不能有間質浸潤的證據(jù)（不規(guī)則形狀的背靠背腺體、單細胞、結締組織增生）。BAC通常發(fā)現(xiàn)于浸潤性腫瘤的邊緣，因此不應在活檢小標本或冷凍組織上進行診斷，除非對整個腫瘤進行取材。這條規(guī)則適用于病理學中大多數(shù)“預后改善的變異型”腫瘤：除非整個病變都是這種類型，否則最好不要稱為預后良好的腫瘤?！癇AC模式”是指假冒BAC的浸潤性腫瘤的生長模式。

Figure 22.12. Bronchoalveolar carcinoma. The malignant cells line the alveolar walls but do not invade the stroma.

圖22.12 細支氣管肺泡癌。惡性細胞襯覆肺泡壁上，但不侵入基質。

Large cell undifferentiated carcinoma arises when adenocarcinoma dedifferentiates into a very ugly tumor with no recognizable glandular features. It can also acquire pleomorphic or giant cell features. Another variety is the lymphoepithelioma-like carcinoma(scattered large malignant cells in a sea of lymphocytes). Neuroendocrine carcinoma can have large-cell morphology; this is discussed below.

大細胞未分化癌來自腺癌去分化，成為很丑的腫瘤，無法識別腺體特征。它還可以獲得多形性或巨細胞特征。另一種變異是淋巴上皮瘤樣癌（淋巴細胞海洋中散在大的惡性細胞）。神經(jīng)內分泌癌可以有大細胞形態(tài)；詳見下文。

神經(jīng)內分泌腫瘤（Neuroendocrine Tumors）

The neuroendocrine spectrum is broad and confusing in the lung. Rosai’s Surgical Pathology has a nice categorization of the tumor types, which includes the following:

肺的神經(jīng)內分泌譜系是廣泛而混亂的。Rosai外科病理學有很好的腫瘤分類，如下：

Carcinoid: A carcinoid is a well-differentiated(but not benign) neoplasm with classic neuroendocrine features, including epithelial-to-spindled architecture, regular round nuclei with fine chromatin, and no nucleoli(Figure 22.13). Despite the appearance, carcinoids can metastasize to lymph nodes.

類癌：低級別或高分化（但非良性）腫瘤，具有典型的神經(jīng)內分泌特征，包括上皮到梭形結構，規(guī)則的圓核，染色質細膩，無核仁（圖22.13）。盡管貌似溫良，類癌還是可以轉移到淋巴結。

Figure 22.13. Carcinoid. This high-power view of an intrabronchial carcinoid shows a nested and trabecular pattern of cells with oval nuclei and typical “neuroendocrine” chromatin, meaning finely textured and speckled, without nucleoli or prominent nuclear membranes.

圖22.13 類癌。支氣管內類癌的高倍，細胞呈巢狀和小梁狀排列，卵圓形核和典型的“神經(jīng)內分泌”染色質，即質地精細、點彩狀，無核仁或明顯核膜。

Atypical carcinoid: Atypical carcinoids are carcinoids with(1) increased mitoses, 2–10 per 10 high-power fields;(2) hyperchromatic nuclei; or(3) necrosis.
非典型類癌：與類癌相比：（1）核分裂增多，達到2-10個/10HPF；（2）核深染；或（3）壞死。
Small cell carcinoma: Small cell carcinoma is a high-grade neuroendocrine neoplasm with small cell morphology, including solid-to-trabecular-to-tubular patterns, hyperchromatic finely granular(denim-blue) nuclei, no nucleoli, syncytial appearance with nuclear molding, mitoses/apoptosis/necrosis, and streaming crush artifact(Figure 22.14). Small cell carcinoma may be found in combination with other carcinomas.
小細胞癌：高級別神經(jīng)內分泌腫瘤，細胞小，實性到小梁狀到管狀形態(tài)，深染細顆粒性（牛仔布藍）細胞核，無核仁，合胞體樣伴核鑲嵌，核分裂/凋亡/壞死和流水狀擠壓假象（圖22.14）。小細胞癌可與其他癌并發(fā)。

Figure 22.14. Small cell carcinoma. Sheets of nuclei appear molded together with interlocking shapes due to the near absence of cytoplasm. The chromatin, like low-grade neuroendocrine neoplasms, is uniform and lacks nucleoli. Necrosis and mitoses(arrow) are common.

Salivary neoplasms: The seromucinous glands around the bronchi can give rise to any of the 圖22.14 小細胞癌。由于幾乎沒有細胞質，成片的細胞核以交錯的形狀鑲嵌在一起。像低級別神經(jīng)內分泌腫瘤一樣，染色質均勻，無核仁。常見壞死和核分裂（箭）。

Large cell neuroendocrine: A large cell neuroendocrine tumor is a high-grade neuroendocrine neoplasm with some neuroendocrine features, either architectural or nuclear, and positive neuroendocrine immunostains. Note that the “l(fā)arge cell” refers to the presence of cytoplasm, not larger nuclei per se.
大細胞神經(jīng)內分泌腫瘤：高級別神經(jīng)內分泌腫瘤，具有某些神經(jīng)內分泌特征，包括結構或核，并且神經(jīng)內分泌免疫染色陽性。注意，“大細胞”是指存在細胞質，而不是核本身更大。
Non-small cell carcinoma with neuroendocrine features: Per Rosai, this lesion looks like non–small cell by any criteria, but you happen to accidentally demonstrate that it is chromogranin positive.
非小細胞癌伴神經(jīng)內分泌特征：根據(jù)Rosai的說法，這種病變用任何標準都符合非小細胞癌，但碰巧發(fā)現(xiàn)嗜鉻素陽性。

其他病變（不完整列舉）（Other Lesions(Incomplete Listing)）

Hamartoma: A hamartoma is a tumor-like mass composed of a disorganized mixture of the normal elements found in that organ. It is not clonal and therefore not really a neoplasm. In the lung, these are often masses of cartilage, fat, smooth muscle, and epithelium.
錯構瘤：腫瘤樣腫塊，由該器官中正常成分的無序混合物組成。它不是克隆性，因此不是真正的腫瘤。在肺中，這些腫瘤通常含有軟骨、脂肪、平滑肌和上皮。
Salivary neoplasms: The seromucinous glands around the bronchi can give rise to any of the traditional salivary gland neoplasms.
涎腺型腫瘤：來自支氣管周圍的漿粘液腺，可發(fā)生任何傳統(tǒng)類型的涎腺型腫瘤。
Carcinosarcoma: Carcinosarcoma is a truly biphasic malignant lesion, with a recognizable epithelial component(carcinoma) and a separate recognized form of sarcoma, such as osteosarcoma or chondrosarcoma. This is different from the sarcomatoid carcinoma, which is a pure carcinoma that has acquired spindle cell morphology.
癌肉瘤：是一種真正的雙相惡性病變，具有可識別的上皮成分（癌）和單獨的可識別的肉瘤形式，如骨肉瘤或軟骨肉瘤。這與肉瘤樣癌不同，肉瘤樣癌是一種獲得梭形細胞形態(tài)的純粹的癌。
Pulmonary blastoma: Pulmonary blastoma is a form of carcinosarcoma in adults in which the epithelial component resembles fetal lung and the stromal component may be composed of adult-type sarcomas or immature mesenchymal tissue.
肺母細胞瘤：是一種成人發(fā)生的癌肉瘤，其上皮成分類似于胎兒肺，間質成分可能是成人型肉瘤或未成熟間充質組織。
Pleuropulmonary blastoma: Pleuropulmonary blastoma is an embryonal-type sarcoma of infancy, intrathoracic but often extrapulmonary, which may have cartilage and rhabdomyoblastic elements but not a carcinoma component.
胸膜肺母細胞瘤：是一種嬰幼兒胚胎型肉瘤，位于胸腔內，但通常位于肺外，可能有軟骨和橫紋肌母細胞成分，但不是癌成分。

來源：

The Practice of Surgical Pathology：A Beginner’s Guide to the Diagnostic Process

外科病理學實踐：診斷過程的初學者指南

Diana Weedman Molavi, MD, PhD

Sinai Hospital, Baltimore, Maryland

ISBN: 978-0-387-74485-8 e-ISBN: 978-0-387-74486-5

Library of Congress Control Number: 2007932936

? 2008 Springer Science+Business Media, LLC

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