Cohen R J, McNeal J E, Edgar S G, Robertson T, Dawkins H J
Urological Research Centre, Perth, Western Australia.
Hum Pathol. 1998 Dec;29(12):1488-94. doi: 10.1016/s0046-8177(98)90020-x.
Cytoplasmic clarity is a histological feature of normal prostatic secretory cells, but in this study, tissue fixation in strong (>2.5%) glutaraldehyde dramatically altered cytological staining. Secretory cytoplasm appeared red and granular on routine stains because of myriad intensely staining eosinophilic granules (PSG). Immunostaining for prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) showed their exclusive localization to the PSG. Electron microscopy confirmed these findings and also showed that after fixation in many agents, including formaldehyde, PSG appeared empty, accounting for the artefactual "clear cell" appearance on light microscopy. PSG were most densely concentrated apically in a bud-shaped luminal compartment in which cytokeratin was selectively absent. Normal exocrine secretion was visualized as detachment of apocrine buds or their in situ disintegration. Distinctively in dysplasia and almost all carcinomas, PSG were rare to absent, and proteases were free in the cytoplasm, often concentrated beneath the apical membrane. The apocrine compartment was absent, with no observed secretory mechanism. Tumor cells had dark amphiphilic cytoplasm after all fixatives. This provided a reliable method of distinguishing malignant from benign glands in tissues fixed in strong glutaraldehyde. Clear cell carcinomas, whose cytoplasm mimicked routinely fixed normal secretory cells, surprisingly had almost no PSG. Instead, their "granules" were lipid-filled vacuoles reflecting a secretory pathway not seen in normal cells, dysplasia, or the common "dark cell" carcinomas. These observations may define two distinctive biological pathways of prostate cancer evolution and may facilitate diagnostic decisions on needle biopsy samples.
胞质透明是正常前列腺分泌细胞的一种组织学特征，但在本研究中，用强（>2.5%）戊二醛进行组织固定显著改变了细胞学染色。由于大量强嗜酸性颗粒（PSG），分泌性胞质在常规染色上呈红色且颗粒状。前列腺特异性抗原（PSA）和前列腺酸性磷酸酶（PAP）的免疫染色显示它们仅定位于PSG。电子显微镜证实了这些发现，还显示在包括甲醛在内的多种固定剂固定后，PSG呈现为空泡状，这解释了光镜下人为造成的“透明细胞”外观。PSG最密集地集中在顶端呈芽状的管腔隔室中，其中细胞角蛋白选择性缺失。正常外分泌分泌表现为顶浆分泌芽的脱离或其原位崩解。在发育异常和几乎所有癌中，显著的是PSG很少或缺如，蛋白酶在胞质中游离，常集中在顶端膜下方。顶浆分泌隔室不存在，未观察到分泌机制。在所有固定剂处理后，肿瘤细胞具有深色的双嗜性胞质。这提供了一种在强戊二醛固定的组织中区分恶性和良性腺体的可靠方法。透明细胞癌的胞质模仿常规固定的正常分泌细胞，令人惊讶的是几乎没有PSG。相反，它们的“颗粒”是充满脂质的空泡，反映了一种在正常细胞、发育异常或常见的“暗细胞”癌中未见的分泌途径。这些观察结果可能定义了前列腺癌演变的两种独特生物学途径，并可能有助于对针吸活检样本做出诊断决策。
