Komminoth P, Roth J, Schröder S, Saremaslani P, Heitz P U
Division of Cell and Molecular Pathology, University of Zürich, Switzerland.
Lab Invest. 1995 Apr;72(4):424-31.
The differential diagnosis of cortical versus medullary tumors of the adrenal gland may be a problem in diagnostic pathology. Conflicting results have been reported about the distribution of various immunohistochemical markers in the normal as well as neoplastic adrenal cortex and medulla.
Archival, formaldehyde-fixed, and paraffin-embedded material comprising 27 adrenocortical carcinomas (ACC, meeting Weiss' histologic criteria), 28 pheochromocytomas (PCC), and adjacent nontumorous tissue (13 glands) were analyzed by immunogold-silver staining for the expression of polysialic acid (poly Sia), cytokeratins (CK), synaptophysin (SYN), chromogranin A (CrgA), somatostatin (SOM), calcitonin (CT), and the "adrenocortical marker" D11. Further, SYN mRNA expression was studied by nonradioactive in situ hybridization using digoxigenin-labeled oligonucleotide probes.
In the normal adrenal gland, poly Sia was exclusively detected in the medulla and in cortical nerves. In ACCs, SYN immunoreactivity was present in 23 of 27 tumors (85%), D11 was present in 22 of 27 (81%), poly Sia was present focally in 8 of 27 (29%), and CK was present in 7 of 27 (25%). Synthesis of SYN in ACCS was demonstrated by mRNA in situ hybridization. Immunoreactivity for CrgA, SOM, or CT was not detectable. No difference of the marker profiles was seen in the nine clinically hormone-producing (three androgen, five corticosteroid, one mineralocorticoid) ACCs compared with the clinically silent tumors. In PCCs, all 28 tumors were immunoreactive for poly Sia and SYN; CrgA was detectable in 26 of 28 (93%), CT was detectable in 6 of 28 (21%), and SOM was detectable in 2 of 28 (7%) tumors. Staining for D11 or CK was undetectable. By immunohistochemistry, no distinction was possible between the 4 clinically malignant, the 6 multiple endocrine neoplasia type 2A-associated, and the 18 sporadic benign PCCs.
Poly Sia of the neural cell adhesion molecule is consistently detected in normal adrenal medullary cells as well as in PCCs, and is occasionally focally expressed in ACCs. CrgA, CK, and D11 are reliable markers to immunohistochemically distinguish ACC from PCC. Immunoreactivity for SYN and detection of its mRNA in the majority of ACCs indicates the existence of tumor cells sharing both cortical and medullary features. Such focal neuroendocrine differentiation in ACCs can lead to confusion with PCCs.
肾上腺皮质肿瘤与髓质肿瘤的鉴别诊断在诊断病理学中可能是个难题。关于各种免疫组化标志物在正常及肿瘤性肾上腺皮质和髓质中的分布，已有相互矛盾的报道。
采用免疫金银染色法分析存档的、经甲醛固定和石蜡包埋的材料，这些材料包括27例肾上腺皮质癌（ACC，符合Weiss组织学标准）、28例嗜铬细胞瘤（PCC）以及相邻的非肿瘤组织（13个腺体），检测多唾液酸（聚唾液酸，poly Sia）、细胞角蛋白（CK）、突触素（SYN）、嗜铬粒蛋白A（CrgA）、生长抑素（SOM）、降钙素（CT）和“肾上腺皮质标志物”D11的表达。此外，使用地高辛标记的寡核苷酸探针通过非放射性原位杂交研究SYN mRNA的表达。
在正常肾上腺中，聚唾液酸仅在髓质和皮质神经中检测到。在肾上腺皮质癌中，27例肿瘤中有23例（85%）存在SYN免疫反应性，27例中有22例（81%）存在D11，27例中有8例（29%）局部存在聚唾液酸，27例中有7例（25%）存在CK。通过mRNA原位杂交证实肾上腺皮质癌中存在SYN的合成。未检测到CrgA、SOM或CT的免疫反应性。与临床无激素分泌的肿瘤相比，9例临床有激素分泌（3例雄激素、5例皮质类固醇、1例盐皮质激素）的肾上腺皮质癌在标志物谱方面无差异。在嗜铬细胞瘤中，所有28例肿瘤对聚唾液酸和SYN均有免疫反应性；28例中有26例（93%）可检测到CrgA，28例中有6例（21%）可检测到CT，28例中有2例（7%）可检测到SOM。未检测到D11或CK的染色。通过免疫组化，无法区分4例临床恶性、6例2A型多发性内分泌肿瘤相关和18例散发性良性嗜铬细胞瘤。
神经细胞黏附分子的聚唾液酸在正常肾上腺髓质细胞以及嗜铬细胞瘤中始终可检测到，偶尔在肾上腺皮质癌中局部表达。CrgA、CK和D11是免疫组化区分肾上腺皮质癌与嗜铬细胞瘤的可靠标志物。大多数肾上腺皮质癌中SYN的免疫反应性及其mRNA的检测表明存在兼具皮质和髓质特征的肿瘤细胞。肾上腺皮质癌中的这种局灶性神经内分泌分化可能导致与嗜铬细胞瘤混淆。
