Ganesan Santhi, Felo Joseph, Saldana Mario, Kalasinsky Victor F, Lewin-Smith Michael R, Tomashefski Joseph F
Department of Pathology, MetroHealth Medical Center and Case Western Reserve University School of Medicine, Cleveland, Ohio 44109-1998, USA.
Mod Pathol. 2003 Apr;16(4):286-92. doi: 10.1097/01.MP.0000062653.65441.DA.
Crospovidone is an insoluble polymer of N-vinyl-2-pyrrolidone that is used as a disintegrant in pharmaceutical tablets. It can potentially embolize to the lung when aqueous tablet suspensions are injected intravenously. In this report, we identified embolized crospovidone in autopsy-derived lung tissue from three adult IV drug users, 1 man and 2 women, whose ages respectively were 27, 38, and 40 years. Suspected crospovidone was compared with pharmaceutical-grade crospovidone by means of histochemical stains, transmission electron microscopy, and infrared spectroscopy. Similar particles were also observed by light microscopy in a 4-mg tablet of hydromorphone, a preparation prescribed to two of the patients. Two patients had sickle cell disease and were taking methadone and/or hydromorphone for pain management; the third was receiving parenteral hyperalimentation after small bowel resection. Crospovidone appeared as deeply basophilic, coral-like particles within pulmonary arteries and in extravascular foreign-body granulomas. Intrapulmonary crospovidone stained similarly to the pure substance, including intense staining with mucicarmine, Congo red, and Masson trichrome. With Movat pentachrome stain, both intravascular and purified crospovidone appeared orange-yellow, whereas most interstitial particles associated with giant cells stained blue-green. Alcian blue failed to stain intravascular or purified crospovidone but strongly decorated some phagocytized particles. Ultrastructurally, both purified powder and tissue deposits of crospovidone appeared as irregular, electron dense, laminated, and finely granular material. Intrapulmonary crospovidone was associated with inflammatory cells and exhibited degenerative changes. By infrared spectroscopy, crospovidone in tissue had the same spectral characteristics as pharmaceutical grade crospovidone and the library reference, polyvinylpyrrolidone (PVP). We conclude that crospovidone contributes to pulmonary vascular injury in some persons who illicitly inject pharmaceutical tablets. It is readily identifiable histologically and distinguishable from other tablet constituents, such as cornstarch, talc, and microcrystalline cellulose. The variable staining with Alcian blue and Movat suggests that crospovidone is altered in vivo by the inflammatory response.
交联聚维酮是N-乙烯基-2-吡咯烷酮的一种不溶性聚合物，用作药物片剂的崩解剂。当静脉注射水性片剂混悬液时，它有可能栓塞到肺部。在本报告中，我们在3名成年静脉吸毒者（1名男性和2名女性，年龄分别为27岁、38岁和40岁）尸检获得的肺组织中发现了栓塞的交联聚维酮。通过组织化学染色、透射电子显微镜和红外光谱，将疑似交联聚维酮与药用级交联聚维酮进行了比较。在给其中两名患者开具的4毫克氢吗啡酮片剂中，通过光学显微镜也观察到了类似的颗粒。两名患者患有镰状细胞病，正在服用美沙酮和/或氢吗啡酮进行疼痛管理；第三名患者在小肠切除术后接受肠外营养。交联聚维酮表现为肺动脉内和血管外异物肉芽肿内的深嗜碱性、珊瑚状颗粒。肺内交联聚维酮的染色与纯物质相似，包括黏液卡红、刚果红和马松三色染色呈强阳性。用莫瓦特五色染色法，血管内和纯化的交联聚维酮均呈橙黄色，而与巨细胞相关的大多数间质颗粒染成蓝绿色。阿尔辛蓝未能对血管内或纯化的交联聚维酮染色，但强烈地标记了一些吞噬颗粒。在超微结构上，纯化的粉末和交联聚维酮的组织沉积物均表现为不规则、电子致密、分层且细颗粒状的物质。肺内交联聚维酮与炎症细胞相关，并表现出退行性变化。通过红外光谱，组织中的交联聚维酮具有与药用级交联聚维酮和库参考物质聚乙烯吡咯烷酮（PVP）相同的光谱特征。我们得出结论，交联聚维酮在一些非法注射药物片剂的人中会导致肺血管损伤。它在组织学上很容易识别，并且可以与其他片剂成分如玉米淀粉、滑石粉和微晶纤维素区分开来。阿尔辛蓝和莫瓦特染色的差异表明交联聚维酮在体内因炎症反应而发生改变。
