外科病理学实践:诊断过程的初学者指南 | 第13章 肾

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第13章 肾(Kidney)


The kidney is primarily composed of glomeruli, tubules, stroma, and vasculature. However, unlike in some other organs, the neoplasms of the kidney do not faithfully reflect or recapitulate their cells of origin. Therefore, recognizing a lesion is not so much a systematic process as a pattern recognition. However, there are certain features to notice in evaluating any kidney mass, as they will help narrow the differential diagnosis in tough cases:


  • Circumscription and/or encapsulation

  • 边界清楚和/或有包膜

  • Presence of stroma within the tumor

  • 肿瘤内存在间质

  • Vascular or capillary pattern

  • 血管或毛细血管模式

  • Architectural pattern (solid, acinar, trabecular, tubular, papillary, pseudopapillary, cystic)

  • 结构模式(实性、腺泡、小梁、管状、乳头状、假乳头状、囊性)

  • Cellular pleomorphism (monotonous to bizarre)

  • 细胞多形性(形态单一到奇异形)

  • Mitotic activity

  • 核分裂活性

  • Cytoplasm (clear to granular pink to densely eosinophilic; perinuclear halos)

  • 细胞质(透明至颗粒状粉红色至深嗜酸性;核周空晕)

  • Nuclear size and contour (note the shape and whether the membrane is smooth or wrinkled)

  • 核大小和轮廓(注意核形状,核膜是否光滑或起皱)

  • Nucleoli

  • 核仁

When studying the kidney grossly, many details crucial to staging are identified (or lost) at the bench. Key prognostic factors include the following:


  • Tumor extending through the kidney capsule and into the perirenal fat

  • 肿瘤穿透肾被膜延伸至肾周脂肪

  • Tumor invading adrenal gland (always note whether the adrenal is even present)

  • 肿瘤侵犯肾上腺(始终注意肾上腺是否存在)

  • Gross tumor in the renal vein, both at the margin and in the renal pelvis (always open the renal vein)

  • 肾静脉内肉眼可见肿瘤(始终打开肾静脉),以及切缘和肾盂肉眼可见肿瘤

  • Tumor growing through Gerota’s fascia (the very delicate membrane surrounding the peri-renal fat; this is actually fairly uncommon but indicates stage IV disease)

  • 肿瘤生长穿透Gerota筋膜(即肾筋膜;围绕肾周脂肪的非常菲薄的膜;这实际上相当少见,但表明为IV期疾病)

Other helpful gross features include the following:


  • Circumscription and presence of multiple lesions

  • 范围和存在多个病灶

  • If cystic, multilocular versus unilocular, the presence of mural nodules, relationship to pelvis

  • 如果是囊性,观察多房或单房,附壁结节,与肾盂的关系

  • If solid, the homogeneity and the color(s)—yellow gold, mahogany brown, areas of hemor-rhage, necrosis, fibrosis (gristle grey), or possible sarcomatoid foci (dense white)

  • 如果是实性,观察均质性和颜色(金黄色、红褐色)、出血、坏死、纤维化(软骨灰色)或可能的肉瘤样病灶(致密白色)

  • Site of origin (cortex vs. medulla or pelvis), if you can tell

  • 起源部位(皮质对比髓质或肾盂),如果你能辨别的话

Now that you have the key identifying features of your tumor, let us look at the differential diagnosis for tumors in the adult.


囊性病变(Cystic Lesions)

单纯性囊肿(Simple Cyst)

Simple cysts are a very common finding, even at autopsy. The simple cyst is essentially a dilated tubule and will have a low cuboidal or flattened pink epithelial lining (Figure 13.1). It is usually unilocular. If multilocular, the septa dividing the cysts should be unremarkable stroma with no epithelial islands or nodules. There should be no clear cells.


囊性肾瘤(Cystic Nephroma)

Cystic nephroma is an uncommon lesion, but file it away as “one of those ectopic-ovariantype-lesions in women.” This is a multilocular cyst with a background of ovarian-type stroma (fairly blue, cellular, spindly, and estrogen and progesterone receptor positive; Figure 13.2). The cyst lining is cuboidal to hobnailed. There should be no clear cells.


外科病理学实践:诊断过程的初学者指南 | 第13章 肾

Figure 13.1. Simple cyst. The cyst lining (arrowhead) consists of a thin layer of cuboidal cells. Below the cyst, dilated tubules filled with proteinaceous fluid are visible (arrow).


外科病理学实践:诊断过程的初学者指南 | 第13章 肾

Figure 13.2. Cystic nephroma. Like the simple cyst, this cyst is lined with bland epithelial cells (arrowhead). However, there is adjacent spindly stroma, similar to ovarian stroma (arrow). Kidney parenchyma is seen at right.


混合性上皮-间质肿瘤(Mixed Epithelial-Stromal Tumor)

The mixed epithelial-stromal tumors may be cystic, but are discussed with solid lesions, below.


肾细胞癌(Renal Cell Carcinoma)

Conventional (clear cell) renal cell carcinoma can present as a cyst in several ways. First, it can arise in the wall of a preexisting simple cyst. Second, it can undergo cystic degeneration of a solid tumor. Third, and most sneaky, it can occur purely as a cyst lining, usually in a multilocular cyst: this is called multilocular cystic renal cell carcinoma. The main indicator is the presence of clear cells in the cyst wall (Figure 13.3). The cyst walls may be denuded of epithelium, though, so careful sampling and hunting are essential.


外科病理学实践:诊断过程的初学者指南 | 第13章 肾

Figure 13.3. Multilocular cystic renal cell carcinoma. The cyst and fibrovascular septa (arrowhead) are lined by single clear cells with small dark nuclei (arrow); compare these cells to conventional renal cell carcinoma (see Figure 13.6).


有多种细胞群的病变(Lesions With Multiple Cell Populations)


The angiomyolipoma is, at first, a difficult lesion to recognize, because it looks like just a mishmash of normal soft tissue components. From the name, you know that it must have vessels, smooth muscle, and fat, but then so do most organs of the body. Also working against you is the fact that these lesions can have one or two components predominating, so all you see is a mass of plump spindly cells with a vessel here and there, and maybe a couple of fat cells. The key to recognizing an angiomyolipoma is knowing that you have a mass lesion and appreciating the unusual vessels that are the hallmark of this tumor. This tumor is benign. The usual histologic features include the following:


  • Large, tangled, tortuous, thick-walled, hyalinized vessels

  • 大的、缠结的、扭曲的、厚壁的、透明的血管

  • Smooth muscle cells (pink to clear and spindly) that seem to spin off of, or be continuous with, the vessel walls (Figure 13.4)

  • 平滑肌细胞(粉红色至透明和梭形),似乎从血管壁上脱落或与血管壁相连(图13.4)

外科病理学实践:诊断过程的初学者指南 | 第13章 肾

Figure 13.4. Angiomyolipoma. This example does not show the fatty component, but the prominent vessels (V) and smooth muscle components here are classic. In angiomyolipoma, the spindle cells seem to merge with, or spin off from, the thick-walled vessels (arrow).


  • Mature fat cells without atypia or lipoblasts

  • 成熟脂肪细胞,无异型性,无脂母细胞

  • Pushing borders but not encapsulated

  • 推挤性边界,但无包膜

  • HMB-45 and Melan-A positive (this tumor is in the perivascular epithelioid cell tumor family, all of which stain for melanoma markers)

  • HMB-45和Melan-A阳性(该肿瘤属于血管周围上皮样细胞肿瘤家族,均表达黑色素瘤标记物)

混合性上皮-间质肿瘤(Mixed Epithelial-Stromal Tumor)

The mixed epithelial-stromal tumor, although rare, is simple in concept: it is the renal version of an adenofibroma, or a fibroadenoma, or any other benign mixture of stromal and epithelial elements. Because it can be cystic, it is also included in the differential diagnosis of cystic lesions, discussed earlier. The histologic findings include a population of cytologically benign tubules of varying shapes and sizes set in a background of bland spindled stroma, which may consist of smooth muscle, fibroblasts, or myofibroblasts. This may also be in a spectrum with cystic nephroma (discussed earlier), because it also has estrogen receptor– and progesterone receptor–positive stroma.


实性肿瘤(Solid Neoplasms)

透明细胞(Clear Cells)

The presence of clear cells in a renal tumor immediately puts renal cell carcinoma at the top of the differential. For all practical purposes, there are no benign clear cell lesions. A 3-mm clear cell focus is still a clear cell carcinoma, albeit a fairly nonthreatening one. Renal cell carcinoma is now understood to have multiple variants, but the clear cell variety is often subtitled “conventional.” Note: Avoid the big, embarrassing, novice mistake number 1—mistaking the normal adrenal cortex for a clear cell tumor. The adrenal clear cell should have visible vacuoles that indent the nucleus, giving it a stellate outline (Figure 13.5).


外科病理学实践:诊断过程的初学者指南 | 第13章 肾

Figure 13.5. Normal adrenal cortex. Unlike clear cell carcinoma, the cells of the adrenal cortex have discrete cytoplasmic vacuoles that indent the nuclei, creating a stellate outline around the nucleus (arrow).


肾细胞癌,传统型或透明细胞型(Renal Cell Carcinoma, Conventional or Clear Cell Type)

Renal cell carcinoma is a common tumor that usually appears grossly as a granular, goldenyellowish-orange, well-circumscribed tumor, looking very much like normal adrenal tissue. It may get quite large and have areas of necrosis, hemorrhage, cystic degeneration, and fibrosis. All different-looking areas should be sampled, especially the firm solid white-to-grey areas, which could indicate sarcomatoid transformation.


Histologically, the tumor may be solid with an acinar pattern, pseudopapillary (which is an acinar pattern with centroacinar dropout), or cystic. Areas of sheeting, spindly, sarcomatoid growth will bump up the tumor to grade IV. Identifying features include the following:


  • A net-like array of delicate capillaries, dividing cells into packets (“acinar” pattern)

  • 纤细的毛细血管呈网状排列,将细胞分成小团簇(“腺泡”型)

  • Clear cytoplasm, at least focally if not diffusely (Figure 13.6)

  • 细胞质透明,如果不是弥漫的胞质透明,至少局部如此(图13.6)

外科病理学实践:诊断过程的初学者指南 | 第13章 肾

Figure 13.6. Clear cell renal cell carcinoma. The tumor is composed of packets of clear cells, divided by delicate fibrovascular septa (arrow). These septa are characteristic of renal cell carcinoma and are seen even in high-grade or metastatic tumors. The nuclei in this example are enlarged, but nucleoli are visible only at high power, consistent with Fuhrman grade II.

图13.6.透明细胞肾细胞癌。肿瘤由小团簇透明细胞包组成,被纤细的纤维血管间隔分隔(箭)。这些间隔是肾细胞癌的特征,甚至见于高级别或转移性肿瘤。本例中,核增大,但核仁仅在高倍可见,符合Fuhrman II级。

  • Delicate, distinct cell membranes

  • 纤细、清楚的细胞膜

  • Lack of desmoplasia (although sclerosis of burned-out tumor is common)

  • 缺乏促结缔组织增生(尽管燃烬的肿瘤继发硬化很常见)

Conventional renal cell carcinoma is graded cytologically according to Fuhrman grade. Lowgrade tumors have clear cytoplasm, polygonal cells, and round nuclei. Higher grade tumors get pink and pleomorphic. Grade criteria, with a 10× objective (Figure 13.7), are as follows:


外科病理学实践:诊断过程的初学者指南 | 第13章 肾

Figure 13.7. Fuhrman grades shown at 10×. (I) Nuclei are small and dense, resembling lymphocyte nuclei. (II) Nuclei are larger, but no nucleoli are visible at this power. (III) Nuclei are even larger, now with some visible nucleoli (arrowhead). (IV) Nuclei are frankly anaplastic (arrow) with large atypical mitoses (arrowhead). All images are taken at the same magnification.


  • Grade I: nuclei resemble lymphocytes, no nucleoli (rarely used)

  • I级:核类似淋巴核,无核仁(很少使用)

  • Grade II: nuclei still small and without nucleoli, but with open chromatin

  • II级:核仍然很小,没有核仁,但染色质开放

  • Grade III: easily recognizable nucleoli, larger nuclei

  • III级:易于识别的核仁,较大的核

  • Grade IV: pleomorphic and hyperchromatic nuclei with big nucleoli

  • Ⅳ级:核多形性、深染,大核仁

肾细胞癌,嫌色变异型(Renal Cell Carcinoma, Chromophobe Variant)

The chromophobe is a carcinoma that has some features of conventional renal cell carcinoma and some features of the oncocytoma. It is, overall, very pale pink under the microscope. It is not encapsulated, and it grows as a solid to papillary mass. Features include the following:


  • Distinct cell membranes that give the tumor a three-dimensional texture, like alligator skin (Figure 13.8)

  • 清楚的细胞膜,使肿瘤像三维结构,如鳄鱼皮(图13.8)

  • Cells of varying sizes and shapes

  • 不同大小和形状的细胞

  • Pink, granular, wispy cytoplasm, often with a perinuclear clearing

  • 粉红色,颗粒状,细腻的细胞质,常有核周透明

  • Nuclei that vary in size and shape and are crinkly, giving a koilocytic look (see Figure 13.8)

  • 核大小和形状不同,呈皱褶状,看似挖空细胞的核(见图13.8)

外科病理学实践:诊断过程的初学者指南 | 第13章 肾

Figure 13.8. Chromophobe carcinoma. (A) Low-power view of a chromophobe, showing packets of cells with clear-to-pink cytoplasm, perinuclear halos, and occasional binucleate cells (arrow). The cell membranes are distinct, giving the tumor a cobblestone or alligator-skin texture. (B) High-power view of a chromophobe carcinoma, eosinophilic variant. Although the granular pink cytoplasm resembles an oncocytoma (see Figure 13.9), the nuclei are distinctly koilocytic, with crinkly outlines and perinuclear halos (arrow). In addition, the crisp cellular membranes are preserved (arrowhead).


  • Cytoplasm positive for Hale’s colloidal iron

  • Hale胶体铁染色呈阳性的细胞质

  • Can transform to sarcomatoid morphology

  • 可转化为肉瘤样形态

The eosinophilic variant of chromophobe can look at low power like an oncocytoma, but the nuclei should still have a koilocytic flavor, unlike the very round and regular nuclei of the oncocytoma.


粉红色细胞(Pink Cells)

If the cells are not clear, your differential diagnosis includes the following:


  • Chromophobe (discussed above).

  • 嫌色细胞癌(上文讨论)。

  • High-grade conventional renal cell carcinoma (discussed above).

  • 高级别传统的肾细胞癌(如上所述)。

  • Oncocytoma: Oncocytoma is a benign tumor resembling oncocytes (or Hurthle cells) in other organs. Grossly, it is mahogany brown and well circumscribed but not encapsulated. There may be a stellate scar (a nonspecific sign of slow growth). The oncocytes are arranged in nests or cords of cells in a hypocellular stroma. The cells are round with dense pink cytoplasm and very regular, round nuclei (Figure 13.9). This regularity should strike you at low power, very different from a chromophobe. The oncocytoma is not graded. Features incompatible with this diagnosis include mitoses, papillary architecture, clear cells, and grossly identified vascular invasion.

  • 嗜酸细胞瘤:一种良性肿瘤,类似于其他器官中的嗜酸细胞(或Hurthle细胞,许特来细胞。译注:正确拼写u上面有两个小点)。大体呈红褐色,边界清楚,但无包膜。可能有星芒状瘢痕(生长缓慢的非特异性迹象)。肿瘤细胞在细胞稀少的间质中排列成巢或条索。细胞呈圆形,胞质深染,呈粉红色,核规则,呈圆形(图13.9)。这种规律在低倍就会让你震撼,与嫌色细胞癌非常不同。嗜酸细胞瘤不分级。不符合本诊断的特征包括核分裂、乳头状结构、透明细胞和肉眼识别的血管浸润。

外科病理学实践:诊断过程的初学者指南 | 第13章 肾

Figure 13.9. Oncocytoma. The nuclei are typically very round, uniform in size, and evenly spaced. Nucleoli may be seen, but there are no perinuclear halos. The cytoplasm is pink and granular, similar to oncocytic neoplasms elsewhere in the body.


  • Papillary renal cell carcinoma: Papillary renal cell carcinoma is a cellular tumor of pink-to-blue cells (low-nuclear-grade tumors tend to be blue at low power, and high-nuclear-grade tumors tend to be pink; this seems backward) that may be arranged in papillary formations (helpful), solid sheets, or trabecular cords. The classic image is that of a fibrovascular core packed with foamy macrophages and lined by cuboidal cells with round nuclei (Figure 13.10). This image is so pathognomonic that if you find it, you are basically done. You may also see psammoma bodies, hemosiderin-laden cells, and focal clear cells.

  • 乳头状肾细胞癌:由粉红色到蓝色的细胞组成的肿瘤(低核级别肿瘤在低倍镜下呈蓝色,而高核级别肿瘤呈粉红色;这似乎是反常的),可能排列成乳头状结构(有助于诊断)、实性片状或小梁状条索。经典图像为充满泡沫状巨噬细胞的纤维血管轴心,被覆圆核的立方细胞(图13.10)。这种图像如此具有病理诊断意义,如果你找到它,你基本上就确诊了。也可以看到砂粒体、含铁血黄素细胞和局灶性透明细胞。

外科病理学实践:诊断过程的初学者指南 | 第13章 肾

Figure 13.10. Papillary renal cell carcinoma. The tumor cells are eosinophilic, not clear, and range from cuboidal to columnar (arrowhead). This tumor may grow as solid sheets and tubules, but finding papillary structures with central cores packed with foamy histiocytes (arrow) is diagnostic. Although the tumor in this example is low grade cytologically, the cells have a relatively high nuclear/cytoplasmic ratio, and therefore this would be somewhat blue on low power.


°Papillary adenoma: By definition, a papillary adenoma is a papillary and non–clear cell neoplasm of low nuclear grade and less than 5 mm in diameter.


°Xp11: there are several translocation-defined renal cell carcinomas involving the TFE3 gene on Xp11. They occur in young adults. Histologically, they can be summed up as clear cell tumors with papillary architecture.


  • Collecting duct carcinoma: A collecting duct carcinoma is a high-grade tumor that arises in the medulla. It looks and acts much like an adenocarcinoma. The cytology is clearly malignant, there is a desmoplastic response, and it may stain for mucin and carcinoembryonic antigen. However, it is rare. Rarer still is the variant of collecting duct carcinoma found in sickle cell trait patients, the medullary carcinoma.

  • 集合管癌:发生在髓质的高级别肿瘤。形态学和生物学行为很像腺癌。细胞学明显恶性,有促结缔组织增生反应,黏液染色和CEA染色可能阳性。然而,此癌罕见。在镰状细胞特征的患者中发现的集合管癌变异型,即髓样癌,更为罕见。

蓝细胞(Blue Cells)

When the tumor looks blue, the differential diagnosis includes the following:


  • Metanephric adenoma (blue, indigo blue, lymph node blue): Metanephric adenoma is usually a 1x diagnosis. It is a circumscribed but nonencapsulated tumor of monotonous, small, tightly packed, dense blue cells (Figure 13.11). It has little or no cytoplasm. The patterns range from tiny tubules to serpiginous gland-like structures. If this looks like a Wilms’ tumor to you, you are an astute observer. The metanephric adenoma may be essentially a differentiated (mature) form of a pure epithelial Wilms’ tumor.

  • 后肾腺瘤(蓝色、靛蓝、淋巴结蓝色):后肾腺瘤通常为1x诊断(译注:1倍放大,即肉眼观察切片诊断)。它是一种边界清楚但无包膜的肿瘤,由形态单一、体积小、紧密堆积、致密分布的蓝色细胞构成(图13.11)。它几乎没有细胞质。结构模式从小管到蜿蜒的腺样结构不等。如果你觉得它像肾母细胞瘤,你的目光敏锐。后肾腺瘤实质上可能是一种分化(成熟)型纯上皮性肾母细胞瘤。

外科病理学实践:诊断过程的初学者指南 | 第13章 肾

Figure 13.11. Metanephric adenoma. This benign tumor is the bluest of them all because of the very high nuclear/cytoplasmic ratio of the cells. Here you can see tiny primitive blue tubules on the left, adjacent to normal kidney on the right.


  • Wilms’ tumor: Wilms’ tumors are unusual in adults. See the following discussion of the pediatric population.

  • 肾母细胞瘤:成人少见。参见以下关于儿科肾的讨论。

儿科肾简介(A Brief Introduction to the Pediatric Kidney)

The most common pediatric tumor is Wilms’ tumor, or nephroblastoma, one of the small round blue cell tumors of childhood.


术语的定义(Definition of Terms)

Nephrogenic rests: abnormally persistent foci of embryonal cells (small, round, and blue) that may develop into Wilms’ tumor, although most do not


Blastema: sheets of undifferentiated embryonal cells in a Wilms’ tumor, resembling small cell carcinoma


Anaplasia: unfavorable histology in a Wilms’ tumor, defined by large, hyperchromatic nuclei and abnormal mitotic figures (tripolar)


肾母细胞瘤(Wilms Tumor)

Wilms’ tumor is defined by triphasic histology, which means you should see three components (Figure 13.12): blastema (undifferentiated, very blue), stroma (generally less cellular, more pink), and epithelium (blue like blastema but organized into tubules). One component may predominate. Histology is defined as favorable or nonfavorable, based on the presence of anaplasia. Finding foci of anaplasia requires extensive sampling and eye-grinding hunting. A Wilms’ tumor may arrive at your bench post-chemotherapy. Chemotherapy changes include massive necrosis, fibrosis, histiocytic replacement, and maturation of the immature elements. One common finding is maturation to skeletal muscle cells.


外科病理学实践:诊断过程的初学者指南 | 第13章 肾

Figure 13.12. Wilms’ tumor. This small round blue cell tumor classically has three components: (1) epithelium, in which the cells form primitive tubules; (2) stroma, the mesenchymal component; and (3) blastema, the most primitive and undifferentiated component. Ratios may vary by tumor.


Wilms’ tumor, like renal cell carcinoma, can grossly resemble a multilocular cyst. This is called a cystic partially differentiated nephroblastoma. The three components are the same.


其他儿科肿瘤(Other Pediatric Tumors)

Congenital mesoblastic nephroma is a low-grade sarcoma that can resemble fibromatosis (classic type) or fibrosarcoma (cellular type). Metanephric stromal tumor is a spindle cell tumor that infiltrates and entraps native elements such as tubules and blood vessels. Other more aggressive tumors include clear cell sarcoma and rhabdoid tumor. Clear cell nomenclature, which is actually somewhat less than clear, is summarized in the following section.


关于透明细胞特征的概述(成人和儿童)(A Note on Clear Cell Features, in General (Adults and Children))

You know about clear cell renal cell carcinoma (classically positive for cytokeratins and epithelial membrane antigen [EMA]). Now you also know about the translocation tumors of the kidney, which are clear cells on a papillary core and which arise due to translocations of the TFE3 gene. This same gene can be translocated in the soft tissues, in which case you get alveolar soft part sarcoma(ASPS), which may or may not be clear-cell but does resemble renal cell carcinoma because of its delicate capillary network and alveolar architecture (hence the name). ASPS may be confused with the clear cell sarcoma(CCS) of soft tissue, otherwise known as melanoma of soft parts. Like alveolar soft part sarcoma, it has an alveolar pattern and clear cells; however, it stains for the melanoma markers (S100, Melan-A, and HMB45). This tumor should not be confused with the clear cell sarcoma of kidney, which is totally unrelated to the clear cell sarcoma of soft tissue and is negative for most markers, including S100, cytokeratin, and EMA. However, if you are in the kidney and you have a lesion that is staining for HMB45 and Melan-A, you are most likely looking at an angiomyolipoma, which is a benign tumor having nothing to do with melanocytes but which does stain for the melanoma markers. Is this clear?


内科肾,非肿瘤(Medical Kidney (Non-neoplastic))

The four main compartments of the nonneoplastic kidney are the glomeruli, the tubules, the interstitium, and the vessels. The compartments are differentially affected by systemic diseases, toxins, and so forth. When evaluating the biopsy, you are looking for the following:


  • In the glomeruli: the percentage of globally sclerosed glomeruli, hypercellularity (mesangial vs. endocapillary), inflammatory cells, the thickness of mesangial matrix, segmental sclerosis, hyalinosis, crescents, thrombi, and changes in the basement membrane of the capillary loops (especially by PAS and silver stains)

  • 肾小球:总体上硬化肾小球的百分比、细胞增多(系膜对比毛细血管内膜)、炎症细胞、系膜基质的厚度、节段性硬化、透明变性、新月体、血栓和毛细血管袢基底膜的改变(尤其是PAS和银染)

  • In the tubules: acute and chronic inflammation in the epithelium or lumen, injury (epithe-lial vacuolization, necrosis, or sloughing), cellular or hyaline casts, Tamm-Horsfall protein accumulation, atrophy (dropout)

  • 肾小管:上皮或管腔的急性和慢性炎症、损伤(上皮空泡化、坏死或脱落)、细胞管型或透明管型、Tamm-Horsfall蛋白积累、萎缩(脱落)

  • In the interstitium: inflammation, fibrosis (especially by trichrome stain), edema

  • 间质:炎症、纤维化(尤其是三色染色)、水肿

  • In the arteries and arterioles: intimal thickening, hyaline deposits, emboli, thrombotic micro-angiopathy (fibrin thrombi, red blood cell fragments in capillary walls, fibrinoid necrosis)

  • 动脉和小动脉:内膜增厚、透明物质沉积、栓塞、血栓性微血管病(纤维素血栓、毛细血管壁中的红细胞碎片、纤维素样坏死)

This chapter does not go into great detail on these nonneoplastic entities, except to put them into the very big picture.


急性和慢性损害模式(Acute and Chronic Damage Patterns)

肾炎表现(Nephritic Presentations)

Acute injury to the glomerulus (usually immune mediated) leads to a picture of acute glomerulonephritis (hematuria, proteinuria, oliguria, azotemia, edema, hypertension). Histologically, the glomerulus responds with increased cellularity, which includes mesangial cells, endothelial cells, and inflammatory cells. This is a proliferative  glomerulonephritis, and in this setting you will also see an interstitial response (edema and inflammation) and red cell casts in the tubules. Causes of this acute injury include postinfectious glomerulonephritis, IgA nephropathy, and lupus.


Severe acute injury causes an even more proliferative  response in the form of cellular crescents. These are collections of epithelial and inflammatory cells in Bowman’s space, hugging the glomerulus, and they are an indication of severe glomerular injury. You may also see necrosis of the glomeruli, fibrin deposition, and disruption of the basement membrane. Clinically, this appears as a rapidly progressive glomerulonephritis (which is the symptoms of glomerulonephritis plus acute renal failure) and causes include anti–glomerular basement membrane nephropathy (Goodpasture’s syndrome), vasculitis, and anything that can cause a proliferative  glomerulonephritis (see above).


Most of the above diseases are immune-complex mediated, so classification of the location and type of immune complex is key to subclassifying the disease. Immune complexes can be seen by electron microscopy as electron-dense areas, and their location with respect to the basement membrane is important. Immunofluorescence utilizes individual stains for IgG, IgM, IgA, and complement (C1q, C3), and their distribution also helps narrow the diagnosis. Most immune complex diseases have granular immunofluorescence staining, with the exception of anti–glomerular basement membrane disease, which has linear staining of the basement membrane.


肾病表现(Nephrotic Presentations)

Injury that is limited to the glomerular basement membrane or the podocytes can produce a much more subtle picture. Destruction of the foot processes of the podocytes, which line the basement membrane, or disruption of the basement membrane itself, can lead to a leaky glomerulus that just shows up as proteinuria. Severe proteinuria, and the subsequent edema, hypertension, and so forth, are called the nephrotic syndrome. Diseases in this category include minimal change disease, focal segmental glomerulosclerosis, membranous glomerulonephritis, and membranoproliferative  glomerulonephritis. Many other nonprimary renal diseases can also produce this picture, including diabetes, amyloid, lupus, drugs, and infections.


Of the four primary renal diseases listed earlier, two (minimal change and focal segmental glomerulosclerosis) are not immune complex mediated. They have little or no increase in cellularity and no immunofluorescence findings. You should see evidence of foot process damage by electron microscopy but no deposits. However, membranous and membranoproliferative  are immune mediated. Both show thickened and disrupted basement membranes, granular immunofluorescence staining, and ultrastructural deposits. Membranoproliferative  glomerulonephritis also has an inflammatory cellular component, so it has an added hypercellular (hyperproliferative ) picture as well as clinical evidence of inflammation (a nephritic picture in addition to the proteinuria).


Chronic injury to the kidney produces more of a sclerotic and scarring response, as in other organs. Chronically injured glomeruli become globally sclerotic and look like whorled amorphous pink blobs in the cortex. Chronically injured tubules become flattened, sparse, and dilated, surrounded by interstitial fibrosis and chronic inflammation. When these changes are extensive, you have end-stage kidney and chronic renal failure, and it can be impossible to figure out what the original injury was.


Most of the diagnoses listed earlier are patterns of injury. While they can be primary renal processes, they can also represent the kidney’s response to systemic diseases. Infection, drugs, and lupus are all examples of systemic diseases that can cause more than one type of kidney damage.


Diabetes and hypertension are common, and both are hard on the kidney. Diabetic nephropathy includes thickened basement membranes and increased mesangial matrix; it is not immune complex mediated. The hemodynamic alterations of diabetes also predispose the kidney to glomerulosclerosis, which may be nodular (the Kimmelstiel-Wilson bodies) or eventually global (end-stage kidney disease). Hypertension causes vascular changes in the kidney, including intimal fibrosis of arteries and hyaline deposits in arterioles.


Tubular diseases include acute interstitial nephritis and acute tubular necrosis. Acute interstitial nephritis is reversible damage secondary to drugs and is often associated with eosinophils. Acute tubular necrosis is acute and severe damage to the tubules causing acute renal failure. It may be caused by ischemia or a toxin.


Transplant rejection occurs in at least three forms: acute humoral, acute cellular, and chronic. Each form has specific criteria and an associated grading system. The features to look for include the following:


  • In humoral rejection: glomerulitis, tubular injury, margination of neutrophils, and C4d staining in the peritubular capillaries

  • 体液排斥反应:肾小球炎、肾小管损伤、中性粒细胞边集和管周毛细血管C4d染色

  • In acute cellular rejection: glomerulitis, interstitial inflammation, tubulitis, and intimal arteritis

  • 急性细胞排斥反应:肾小球炎、间质炎症、小管炎和动脉内膜炎

  • In chronic rejection: glomerulopathy (double contours in basement membrane), mesangial matrix increase, tubular atrophy, interstitial fibrosis, intimal thickening of arteries, and hyaline thickening of arterioles

  • 慢性排斥反应:肾小球疾病(基底膜双轮廓)、系膜基质增多、肾小管萎缩、间质纤维化、动脉内膜增厚和小动脉透明物质增厚

These types of rejection need to be separated from recurrence of the original disease process, preexisting donor disease (often vascular), and cyclosporine toxicity (tubular injury).



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


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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