Michael R. Lewin-Smith

Embolized Crospovidone (poly[ N -vinyl-2-pyrrolidone]) in the Lungs of Intravenous Drug Users

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.

Rapid onset of argyria induced by a silver‐containing dietary supplement

We describe a 53‐year‐old man in good general health who presented with an 8‐month history of progressive gray hyperpigmentation of the face. He denied using any prescription medications; however, he admitted to taking a herbal supplement. Clinically, the differential diagnosis included hemochromatosis, Wilsons disease and hyperpigmentation secondary to supplement use. Punch biopsies from the left forehead and preauricular region showed heavily sun‐damaged skin with a minimal inflammatory infiltrate. Closer inspection, however, revealed minute scattered black/brown particles distributed in the basement membrane zone of eccrine and sebaceous glands. Similar particles were also present in hair follicles, blood vessels and arrector pili muscles. The particles did not stain with Gomori methenamine silver, Fontana‐Masson or iron stains. Electron microscopy with energy‐dispersive x‐ray analysis showed numerous particles, less than 1 µm in greatest dimension, which showed peaks for silver and sulfur. This analytical result confirmed the impression of argyria. Further history revealed that the patient had indeed been taking a silver supplement for several months under the premise that it would boost his immune system. This case is unique in that the patients hyperpigmentation developed in a short period of time as compared with other reports in the medical literature.

Characterization of acrylic polyamide plastic embolization particles in vitro and in human tissue sections by light microscopy, infrared microspectroscopy and scanning electron microscopy with energy dispersive X-ray analysis

Vascular embolization is a well-established practice for the treatment of tumors and vascular lesions. Rounded beads (microspheres) of various materials (collagen, dextran and trisacryl-polymer-gelatin) were developed to solve problems encountered with earlier versions of embolic material. We performed histochemistry, Fourier transform infrared microspectroscopy and scanning electron microscopy with energy dispersive X-ray analysis on two uterine and one hepatic specimen with unidentified intravascular foreign material, and examined a reference embolization product for comparison. The hematoxylin and eosin stained tissue sections showed multiple foci with unidentified intravascular foreign material and fibrous obliteration of vessel lumens. Only one case had a clinical history of previous embolization but without specifying the material used. One case was submitted for identification of a ‘parasite’. The material stained positively with Sirius red and mucicarmine, variably with Massons trichrome stain and Movat pentachrome, and did not stain centrally with periodic acid Schiff with diastase. Infrared spectrophotometric analysis of the material from all three cases demonstrated the spectrum of acrylic polyamide plastic. A control sample of EmboGold™ exhibited infrared microspectroscopic spectra similar to the three tissue specimens. Analysis by scanning electron microscopy with energy dispersive X-ray analysis demonstrated some differences in elemental composition between the tissue sections and the selected reference material. To our knowledge, this is the first report of infrared spectrophotometric analysis with scanning electron microscopy with energy dispersive X-ray analysis of an acrylic polyamide plastic embolization product both in vitro and in human histologic tissue sections. In cases lacking appropriate clinical information, identification by these methods and/or a panel of special stains may assist pathologists unfamiliar with this materials light microscopic appearance.

Wound complications following the use of FiberWire in lower-extremity traumatic amputations. A case series.

With the development of new arthroscopic approaches over the last decade, one innovation that has facilitated this trend has been the introduction of high-tensile-strength sutures. These nonabsorbable sutures allow for the reliable and secure fixation of soft tissues, such as the glenoid labrum and rotator cuff, to bone by means of anchors1,2. Similarly, these sutures have gained great acceptance in open procedures, such as tendon repairs and suture fixation of fracture fragments3. FiberWire (Arthrex, Naples, Florida) is one of the first members of this family of sutures. Currently, it is one of the most commonly used high-tensile-strength sutures in orthopaedic surgery. FiberWire is composed of an ultra-high molecular weight polyethylene multifilament core surrounded by a braided polyester jacket4. A silicone coating has been added to the surface of the polyester jacket to improve the handling and knot-tying characteristics of the suture. Ticron (Tyco, Waltham, Massachusetts) is the only other high-tensile-strength suture sold in the United States that has an outer silicone coating. The remaining high-tensile-strength sutures all employ proprietary blends of polyethylene and polyester without the use of a silicone coating. Over a two and a half-year period, we performed or revised 193 lower-extremity amputations at our institution in our treatment of injured soldiers. Because of its strength and the excellent documented clinical experience with FiberWire, we used it to suture the myodesis in 178 (92%) of the 193 transtibial and transfemoral amputations. Recently, five patients with similar-appearing draining sinuses through previously well-healed incisions presented during follow-up visits for the lower-extremity amputations. In all five patients, FiberWire had been used to secure the myodesis. This clustering of similar complications suggested a common cause. Thus, a quality assurance review was initiated. The purpose of this case series is to present the results of …

Pathology of human immunodeficiency virus infection: Noninfectious conditions

Infection with the human immunodeficiency virus (HIV) and the subsequent derangement of host immunity place affected patients at risk for secondary infections. Some of the secondary pathogens occur with such frequency or are so rare in the non-immunosuppressed population that they have become part of the Centers for Disease Control and Prevention (CDC) classification for HIV/acquired immune deficiency syndrome (AIDS). Other infectious agents not yet included in the CDC definition are being reported in the HIV-infected population with increased frequency. General observations of the degree of immunosuppression associated with specific secondary infections have been useful in developing classification systems for HIV disease such as that of the CDC. However, the specific alterations in host immunity that promote infection with specific secondary pathogens are generally unknown. Geographic differences in the types and frequency of secondary infections also have been reported. Variation in strains of HIV, effect of malnutrition, lack of appropriate medical treatment, prevalence of virulent infectious diseases, and epidemiologic differences are possible contributing factors. Some infections that seemed likely to be closely associated with HIV infection have not occurred more frequently in HIV-infected patients. This review summarizes the histopathology of infectious conditions in the current CDC classification and highlights some conditions seen in HIV-infected individuals that are not currently HIV/AIDS-defining infections, yet may be seen by practicing pathologists.

Wound Fragments from Cutaneous Sites of U.S. Military Personnel Deployed in Operation Iraqi Freedom: Clinical Aspects and Pathologic Characterizations

BACKGROUND A wide variety of materials present in current military conflict zones may be implanted and retained as “foreign bodies” or fragments in wounds. Analysis of removed fragments can be valuable to the patient, for research purposes, and for the protection of future potential victims. OBJECTIVES The objectives were to evaluate the composition of retained fragments in wounds from combat injuries and correlate this information with the mechanism of injury. METHODS Wound fragments from 10 U.S. military personnel wounded while deployed in Iraq for Operation Iraqi Freedom were removed from their skin and were subjected to gross examination, light microscopy, and scanning electron microscopy/energy-dispersive X-ray analysis (SEM-EDXA), with specimen radiography and infrared spectroscopy if indicated. RESULTS A variety of exogenous substances, including iron, lead, antimony, copper, aluminum, and acrylonitrile-styrene plastic were detected. No (depleted) uranium was detected. There was a high degree of correlation between the composition of the fragment removed and the wounding event. CONCLUSIONS Wound fragments may take months to years to manifest. Their gross appearance can be misleading. Establishing the composition of retained materials in wounds may assist in the clinical care of the wounded, provide forensic information, and have broader value in wound analysis and research.

Deposition of calcium salts in a case of pulmonary zygomycosis: histopathologic and chemical findings☆

We report a case of pulmonary zygomycosis associated with unusual deposition of calcium salt crystals. The patient was a 75-year-old female who had onset of cough and shortness of breath. She was treated for community-acquired pneumonia but died despite intensive therapy. Postmortem examination revealed diffuse alveolar damage and multifocal necrotizing pneumonia associated with herpes simplex infection and invasive zygomycosis. Birefringent particles were seen associated with fungal elements in the lung parenchyma, within bronchial cartilage, and in blood vessel walls. By infrared spectroscopy, the birefringent particles in the pulmonary parenchyma and within bronchial cartilage had spectral characteristics of calcium oxalate dihydrate and calcium oxalate monohydrate, respectively. The birefringent crystals within vascular walls were identified as calcium carbonate. This case documents the chemical composition and location of 3 different calcium salt crystals in pulmonary zygomycosis. It also shows that among pulmonary fungal infections, calcium oxalate deposition is not restricted to aspergillosis.

The surgical pathology and cytopathology of US Persian Gulf War military veterans: Identification of diseases endemic to the theater of operations

BACKGROUND Tens of thousands of Persian Gulf War veterans (GWVs) have presented with medical symptoms since Operation Desert Shield and Operation Desert Storm. The Kuwait Registry at the Armed Forces Institute of Pathology was established to act as a repository for surgical pathology, cytopathology, and autopsy material from GWVs. OBJECTIVE To identify conditions known to be endemic to the theater of operations in our cohort of GWVs. METHODS The Kuwait Registry database was searched by computer for listed conditions endemic to the Persian Gulf region included in the registry through December 31, 1997. RESULTS Of the 2582 patients in this cohort, 1 patient with hepatitis B and 15 patients with hepatitis C were identified. Other known endemic conditions of the Persian Gulf region were not found. CONCLUSIONS Viral hepatitis (B and C), which is prevalent in the US population, was the only listed endemic condition identified in surgical pathology or cytopathology specimens in our cohort of GWVs.