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肾上腺皮质肿瘤的诊断方法(三)

2019-12-23 09:06| 免费平特一肖资料大全者: admin| 查看: 104| 评论: 0|免费平特一肖资料大全原免费平特一肖资料大全: 慧海拾穗

摘要: 【肾上腺皮质肿瘤的形态学诊断】MICROSCOPIC EXAMINATION显微镜检查Traditionally, ACTs are thought to arise from the different zones of the adrenal cortex and, as such, they most often recapitulate the ce ...

【肾上腺皮质肿瘤的形态学诊断】

MICROSCOPIC EXAMINATION

显微镜检查

Traditionally, ACTs are thought to arise from the different zones of the adrenal cortex and, as such, they most often recapitulate the cellular morphology characteristic of different adrenocortical cells. For example, it is common for ACAs to be composed of corded/nested lipid-rich cells with abundant vacuolated clear cytoplasm and low nuclear/cytoplasmic ratio reminiscent of the ZF, in addition to more compact or eosinophilic cells reminiscent of the ZR layer.

传统上,ACTs被认为是由肾上腺皮质的不同区域产生的,因此,它们最常重演不同肾上腺皮质细胞的细胞形态特征。例如,ACAs通常由富含脂质的索状/巢状细胞组成,富含空泡状透明细胞质,核/质比值低,与束状带(ZF)相似,此外还有更致密或嗜酸性细胞,与网状带(ZR)相似。

Depending on the hormonal functionality of the ACT being evaluated, genotypic-phenotypic features of the tumor and specific changes within the nontumor cortex may be apparent. For example, ACAs producing aldosterone are likely to be the most heterogeneous group among ACAs. Depending on their underlying molecular biology, they can show combinations of different cell types, including lipid-rich (ZF-like) cells, lipid-poor compact (ZR-like) cells, smaller cells resembling ZG-like cells, and compact cells with overlapping features of ZG-like and ZR-like cells (Figs. 4 and 5). The native ZG is commonly hyperplastic, so-called paradoxical ZG layer hyperplasia (Fig. 6), and may show micronodular proliferations that are now recognized as aldosterone-producing cell clusters (APCCs) (Fig. 7), a new concept in primary aldosteronism. When treated with spironolactone, an antagonist of aldosterone, aldosterone producing ACAs, in addition to the background parenchyma, show characteristic eosinophilic concentric lamellated intracellular inclusions called spironolactone bodies (see Figs. 5 and 7; Fig. 8). It has been reported that spironolactone bodies are not seen when eplerenone is administered (aldosterone receptor antagonist).

根据所评估的ACT的激素功能,肿瘤的基因型表型特征和非肿瘤皮质内的特殊变化可能是明显的。例如,产生醛固酮的ACAs可能是ACAs中异质性最强的一类。根据其潜在的分子生物学,它们可以显示不同细胞类型的组合,包括富脂(ZF样)细胞、低脂致密(ZR样)细胞、类似ZG样细胞的较小细胞和具有ZG样和ZR样细胞重叠特征的致密细胞(图4和5)。原生ZG通常是增生性的,称为似是而非的的ZG层增生(图6),并且可以显示微结节增生,现在被认为是醛固酮产生的细胞团(APCCS)(图7),这是原发性醛固酮增多症的新概念。当用螺内酯(醛固酮拮抗剂)治疗时,除背景薄壁组织外,产生醛固酮的ACAs显示出典型的嗜酸性同心片状胞内包涵体,称为螺内酯小体(见图5、7和8)。据报道,使用依普利酮(醛固酮受体拮抗剂)时,未见螺内酯小体。

Fig. 4. Clear cell–rich adrenocortical adenoma in primary aldosteronism. Aldosterone-producing adenomas can show combinations of different cell types, including lipid-rich (zona fasciculata–like) cells, lipid-poor compact (zona reticularis–like) cells, smaller cells resembling zona glomerulosa–like cells, and compact cells with overlapping features of ZG-like and zona reticularis–like cells. Shown is a clear cell–rich adenoma that is more commonly seen in tumors with KCNJ5 mutations.

图4 原发性醛固酮增多症中富含透明细胞的肾上腺皮质腺瘤产生醛固酮的腺瘤可表现出不同细胞类型的组合,包括富脂(束状带)细胞、低脂致密(网状带样)细胞、类似球带样细胞的较小细胞和具有ZG样和网状带样细胞重叠特征的致密细胞。图示富含透明细胞的腺瘤,多见于KCNJ5突变的肿瘤。


Fig. 5. Spironolactone bodies in aldosteroneproducing adenoma. Some aldosterone-producing adenomas are enriched in cells lacking ZF-like clear cell pre dominance. These tumors tend to be more frequent in KCNJ5 wildtype adenomas. Shown is an aldosterone-producing adenoma treated with spironolactone. The tumor cells also show intracytoplasmic eosinophilic concentric lamellated inclusions called spironolactone bodies (arrow).

图5 醛固酮腺瘤中的螺内酯一些产生醛固酮的腺瘤富含缺乏ZF样细胞前显性的细胞。这些肿瘤在KCNJ5野生型腺瘤中更为常见。图为螺内酯治疗的醛固酮腺瘤。肿瘤细胞也显示胞内嗜酸性同心片状包涵体,称为螺内酯小体(箭头)。


Fig. 6. ZG layer hyperplasia is characterized by the presence of continuous and/or multilayered ZG layer. In some cases, aldosterone-producing cell clusters can be seen in association with ZG layer hyperplasia.

图6 ZG层增生以连续和/或多层ZG层的存在为特征。在一些病例中,醛固酮生成细胞簇与ZG层增生有关。


Fig. 7. APCCs are microscopic aldosteroneproducing cortical proliferations originating from the ZG layer and extending into the ZF layer. The identification of somatic alterations implicated in the calcium/calmodulin kinase pathway supports their clonal (neoplastic) nature. Shown is an APCC that contains spironolactone bodies. Arrows outline the APCC.

图7。APCC是微小的生成醛固酮皮质增生,起源于ZG层并延伸到ZF层。与钙/钙调素激酶途径相关的体细胞改变的鉴定支持了它们的克隆(肿瘤)性质。所示为含有螺内酯体的APCC。箭头勾勒出APCC。


Fig. 8. Luxol fast blue (LFB) histochemistry. Because of their high phospholipid content, spironolactone bodies can be distinguished from potential mimics using LFB.

图8  Luxol快速蓝(LFB)组织化学染色:由于螺内酯的磷脂含量很高,因此可以用LFB将其与可能相似的物质区分开来。

In adrenal Cushing syndrome, there is a spectrum of cortisol-producing proliferations from bilateral micronodules (<1 cm) and macronodules (>1 cm) with their distinct molecular alterations representing PPNAD and PBMAH, respectively. Conceptually, the bilateral micronodular or macronodular disease can be regarded as multifocal ACAs, given their clonal nature. ACCs have been described in the context of PPNAD. Morphologically, PPNAD is composed of bilateral cortical micronodules composed of pigmented compact cell–rich proliferations with variable degrees of cortical atrophy in the intervening cortex. Sometimes, isolated nonpigmented or weakly/variably pigmented micronodular proliferations can also occur in the setting of Cushing syndrome. Tumor nodules identified in PBMAH are composed of cortical proliferations composed mainly of lipid-rich cells and variable amounts of compact cells that represent multiple nodules mostly exceeding 1 cm and irregular enlargement of both adrenal glands. Conventional cortisol-secreting ACAs show various morphologic features ranging from pure clear cell tumors to mixed clear and compact cell ACTs. The autonomous neoplastic cortisol secretion from the adrenal gland shuts down the hypothalamic corticotropin-releasing hormone, resulting in resting corticotrophs via Crooke hyaline change in addition to a lack of ACTH mediated trophic changes in both adrenal glands. Consistently, the background adrenal cortex and/or internodular adrenal cortex become atrophic because of the absence of the ZR layer along with a thinned ZF layer (Fig. 9). Sex hormone–secreting ACTs, in contrast with ACTs secreting other hormones, usually tend to be enriched in compact eosinophilic cells normally seen in the ZF. Nonfunctional ACAs can also show morphologic heterogeneity.

在肾上腺库欣综合征中,双侧小结节(<1cm)和大结节(>1cm)有一系列皮质醇产生的增生,其明显的分子改变分别代表PPNAD和PBMAH。从概念上讲,双侧小结节性或大结节性疾病可视为多灶性ACAs,因为它们具有克隆性。ACCs是在PPNAD的背景下描述的。形态学上,PPNAD由两侧皮质小结节组成,小结节由富含色素的致密细胞增生组成,中间皮质有不同程度的萎缩。有时,在库欣综合征的背景下,孤立的非色素性或弱/多少不等色素性小结节增生也可能发生。在PBMAH中发现的肿瘤结节是由主要由富含脂质的细胞和不同数量的致密细胞组成的皮质增生组成,这些细胞代表多个结节,大多超过1cm,两个肾上腺不规则增大。传统的分泌皮质醇的ACAs表现出多种形态学特征,从纯透明细胞肿瘤到混合透明致密细胞ACTs不等。肾上腺自主分泌的肿瘤性皮质醇关闭了下丘脑促肾上腺皮质激素释放激素,除了缺乏ACTH介导的两个肾上腺的分泌变化外,还通过Crooke透明变导致剩余促肾上腺皮质激素。由于缺乏ZR层和变薄的ZF层,背景肾上腺皮质和/或结节间肾上腺皮质萎缩(图9)。分泌性激素的ACTs,与分泌其他激素的ACTs相比,富含致密嗜酸性细胞通常在正常ZF中可见。无功能ACAs也表现出形态学异质性。


Fig. 9. Nontumorous cortical atrophy. In the absence of exogenous cortisol administration, nontumorous cortical atrophy distinguishes cortisol-producing adrenocortical tumors from those that produce aldosterone.

图9 非肿瘤性皮质萎缩。在没有外源性皮质醇给药的情况下,非肿瘤性皮质萎缩将生成皮质醇的肾上腺皮质肿瘤与生成醛固酮的肿瘤区分开来。


Several morphologic changes can be observed in both ACAs and ACCs, including oncocytic and myxoid changes as well as myelolipomatous change. Tumors are designated as mixed oncocytic ACTs when the cortical neoplasm shows 50% to 90% oncocytic change, whereas the term pure oncocytic ACT is applied to those tumors that show greater than 90% oncocytic change. Some rare changes, especially myxoid changes, are more common in ACCs. Sarcomatoid areas can be seen in ACCs and, when identified, can cause confusion with other malignant tumors in the differential diagnosis, particularly primary or secondary (metastatic) sarcomas. Given the range of morphologic heterogeneity,  histologic variants of ACC are currently recognized: conventional (Fig. 10), oncocytic (Fig. 11), myxoid (Fig. 12), and sarcomatoid. ACCs can also show a combination of these variants (Fig. 13).

一些形态学改变在ACAs和ACCs中均可见,包括嗜酸细胞和黏液样变以及髓脂肪瘤样改变。当皮质肿瘤显示50%到90%的嗜酸细胞变时,肿瘤定义为混合嗜酸细胞ACTs,而纯嗜酸细胞ACTs术语适用于显示90%以上嗜酸细胞变的肿瘤。一些少见的改变,尤其是黏液样变,在ACCs中更常见。在ACCs中可以看到肉瘤样区域,当被发现时,在鉴别诊断上可能与其他恶性肿瘤混淆,特别是原发性或继发性(转移性)肉瘤。鉴于形态学异质性,ACC的组织学变异目前认识的有:经典型(图10)、嗜酸细胞型(图11)、黏液样型(图12)和肉瘤样型。ACCs还可以显示这些不同亚型的组合(图13)。


Fig. 10. Conventional adrenocortical carcinoma.

图10 经典型肾上腺皮质癌。


Fig. 11. Oncocytic adrenocortical carcinoma (arrows indicate mitotic figures).

图11 嗜酸细胞型肾上腺皮质癌(箭头示核分裂象)。


Fig. 12. Myxoid adrenocortical carcinoma.

12 黏液样型肾上腺皮质癌。


Fig. 13. Adrenocortical carcinoma with myxoid and oncocytic change.

图13 肾上腺皮质癌伴黏液样和嗜酸细胞变。


~~~未完待续~~~


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慧海拾穗,主治医师。

从事儿童病理诊断,对淋巴造血、软组织和泌尿生殖系统肿瘤有着浓厚的兴趣

座右铭:《为病寻理》就要爱病理 !


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