Antiperspirant-related zirconium and aluminum-containing granulomas; histopathology and in situ chemical analysis.

The potential adverse health effects of antiperspirant use are of interest to patients, primary care providers, dermatologists, and pathologists. In rare instances, antiperspirants containing aluminum-zirconium complexes have been associated with granulomatous dermatoses despite being deemed non-sensitizing in experiments. In this case study, we present a detailed examination of an axillary granuloma in a 28-year-old female who had been using an aluminum-zirconium-based antiperspirant for several years and presented with a left axillary nodule that was excised and analyzed using scanning electron microscopy with energy-dispersive x-ray analysis (SEM/EDXA). Histopathological examination revealed a foreign body-type reaction with amphophilic granular material within giant cells that corresponded to collocated zirconium and aluminum on SEM/EDXA elemental maps. Our case adds to the limited reports of axillary granulomas related to aluminum-zirconium complexes. It illustrates the histopathological appearance and in situ distribution of the aluminum-zirconium complexes, supporting the formation of foreign body-type granulomas. Additionally, our case study illustrates the potential role of these compounds in such reactions and aims to increase awareness among pathologists and clinicians.

Particle analysis of surgical lung biopsies from deployed and non-deployed US service members during the Global War on Terrorism.

The role that inhaled particulate matter plays in the development of post-deployment lung disease among US service members deployed to Southwest Asia during the Global War on Terrorism has been difficult to define. There is a persistent gap in data addressing the relationship between relatively short-term (months to a few years) exposures to high levels of particulate matter during deployment and the subsequent development of adverse pulmonary outcomes. Surgical lung biopsies from deployed service members and veterans (DSMs) and non-deployed service members and veterans (NDSMs) who develop lung diseases can be analyzed to potentially identify residual deployment-specific particles and develop associations with pulmonary pathological diagnoses. We examined 52 surgical lung biopsies from 25 DSMs and 27 NDSMs using field emission scanning electron microscopy (FE-SEM) with energy dispersive x-ray spectroscopy (EDS) to identify any between-group differences in the number and composition of retained inorganic particles, then compared the particle analysis results with the original histopathologic diagnoses. We recorded a higher number of total particles in biopsies from DSMs than from NDSMs, and this difference was mainly accounted for by geologic clays (illite, kaolinite), feldspars, quartz/silica, and titanium-rich silicate mixtures. Biopsies from DSMs deployed to other Southwest Asia regions (SWA-Other) had higher particle counts than those from DSMs primarily deployed to Iraq or Afghanistan, due mainly to illite. Distinct deployment-specific particles were not identified. Particles did not qualitatively associate with country of deployment. The individual diagnoses of the DSMs and NDSMs were not associated with elevated levels of total particles, metals, cerium oxide, or titanium dioxide particles. These results support the examination of particle-related lung disease in DSMs in the context of comparison groups, such as NDSMs, to assist in determining the strength of associations between specific pulmonary pathology diagnoses and deployment-specific inorganic particulate matter exposure.

Localized Cutaneous Argyria at the Site of a Prior Melanoma Excision Confirmed by Scanning Electron Microscopy With Energy Dispersive X-ray Analysis.

ABSTRACT: Localized cutaneous argyria is a rare condition caused by the accumulation of silver particles in the skin, leading to blue-gray discoloration. Argyria may mimic melanoma and lead to misdiagnosis. We present a patient with a history of melanoma that developed a blue-gray nodule at a prior melanoma graft. The diagnosis was confirmed using scanning electron microscopy and energy dispersive x-ray analysis. These techniques differentiate argyria from melanoma and can be performed on formalin-fixed, paraffin-embedded, tissue sections. Health care providers should be alert that argyria may mimic recurrent melanoma in patients unaware of silver exposure.

Cutaneous Gamna-Gandy bodies: An unusual case of dystrophic calcification.

Dystrophic calcification is a common histopathologic finding that can be concomitant with a plethora of diseases, ranging from self-limited infections to insidious malignancies. Gamna-Gandy bodies (GGBs) are a form of dystrophic calcification associated with chronic hemolysis and are typically observed in the spleen. In this report, we present the case of a 92-year-old man who presented with a 4-mm blue papule that was biopsied given the concern for a blue nevus. The subsequent histopathologic examination of the biopsy specimen showed a dermal organizing hematoma adjacent to pale-yellow to brown, refractile material within fibrotic collagen consistent with GGBs. Scanning electron microscopy with energy-dispersive x-ray analysis (SEM/EDXA) revealed that the structures were composed of carbon (39%), oxygen (32%), iron (16%), phosphorus (7%), calcium (5%), and sodium (1%). Fourier transform infrared spectroscopy identified amorphous calcium phosphate. GGBs have not been previously described in the skin and have been rarely characterized with SEM/EDXA in other sites.

Migrated Bulking Material (Solesta) Presenting as a Vaginal "Cyst": Histopathologic and Chemical Analytical Features.

Performing injections with a bulking agent consisting of nonanimal stabilized hyaluronic acid and dextranomer is a well-tolerated and efficacious treatment for mild to moderate fecal incontinence. Here, we discuss a case of a patient with a history of a bulking procedure for fecal incontinence who presented to the obstetrics/gynecology clinic for evaluation of a new vaginal "cyst," which was excised. Histopathologic examination revealed migrated bulking agent within the excised specimen.

Exenatide-induced granulomatous panniculitis associated with poly(d,l-lactide-co-glycolide).

The extended-release formulation of exenatide for treatment of Type II diabetes mellitus is encapsulated in microspheres composed of poly(d,l-lactide-co-glycolide) (PLGA) and administered weekly. This medication has been reported to potentially cause injection-site reactions such as pruritus, transient nodules, and foreign body reaction. Here, we report a case of exenatide-induced granulomatous panniculitis. Our patient is a 63-year-old female with Type II diabetes presenting for concerns about painful nodules on her abdomen, developing approximately every week over the past year and migrating. Of note, the lesions appeared following exenatide injections in the same locations. Two deep-seated nodules of 1 cm were identified on examination. There were no overlying skin changes, and the lesions were tender to palpation. Punch biopsies of the two lesions were performed, which revealed a septal panniculitis containing amorphous material, along with a mixed inflammatory infiltrate. Gomori methenamine silver (GMS) and acid-fast bacilli (AFB) stains were negative for organisms. On infrared (IR) spectroscopy examination of the biopsy tissue, the spectral characteristics of (tissue) protein and PLGA were seen. Evaluation of the clinical and histopathologic findings, along with the IR spectroscopy match, determined that exenatide-induced panniculitis was the cause of the patient's nodules. This case highlights the importance of clinicians' awareness regarding injection-site reactions.

Pulmonary Pathology Diagnoses in the US Military During the Global War on Terrorism.

PURPOSE: To document and compare prevalences of pulmonary pathology diagnoses among US Service members deployed during the Global War on Terrorism and non-deployed US service members. Difficulties establishing associations between deployment-related exposures and pulmonary pathology reported among US military service members deployed during the Global War on Terrorism include retrospective estimations of exposures, documenting medical outcomes and lack of comparison groups. METHODS: Pulmonary diagnoses reported between 2002 and 2015 were identified from the records of the former Armed Forces Institute of Pathology and The Joint Pathology Center. Military service and deployment were confirmed by the Defense Manpower Data Center. Diagnoses were reviewed and coded due to variations in diagnostic terminology. Propensity matching and adjusted binomial modeling were applied to comparisons between the deployed and non-deployed to address possible confounding variables. RESULTS: 404 deployed and 2006 non-deployed service members were included. Demographic differences and the date of pathology report complicate unadjusted comparisons. The deployed had no significant increased prevalence of neoplastic conditions. Propensity matching identified a significant increased prevalence of organizing pneumonia in the non-deployed. An adjusted binomial model identified significant increased prevalences of small airways disease, constrictive bronchiolitis and hypersensitivity pneumonitis in the deployed. Both diagnoses were strongly associated with the date of pathology report. Small airways disease, constrictive bronchiolitis comprised 5% of deployed surgical lung biopsy diagnoses. CONCLUSION: This is the largest study of post-deployment pulmonary pathology diagnoses to date, and contains a comparison group. It provides context for studies of pulmonary outcomes among the deployed.

Particle Analysis by Scanning Electron Microscopy With Energy Dispersive X-Ray Analysis in Pulmonary Pathology Specimens From U.S. Military Service Members Deployed During the Global War on Terror 2002 to 2015.

INTRODUCTION: Between 2001 and 2015, 2.77 million U.S. military service members completed over 5 million deployments to Southwest Asia. There are concerns that deployment-related environmental exposures may be associated with adverse pulmonary health outcomes. Accurate pulmonary diagnosis often requires histopathological biopsy. These lung biopsies are amenable to chemical analysis of retained particulates using scanning electron microscopy with energy dispersive X-ray analysis (SEM/EDXA). METHOD: A retrospective review of SEM/EDXA data collected in conjunction with pathologic diagnostic consultations at the Joint Pathology Center from 2011 to 2016 was conducted. Sections adjacent to those obtained for pathologic diagnosis were prepared for SEM/EDXA particle analysis, which provides qualitative identification of elements present in each particle and semiquantitative estimations of elemental weight percent. The review includes comparison of the particle analysis data and diagnostic findings, the particle count for the standard field analyzed, and types of particles identified. RESULTS: Nonneoplastic lung biopsy specimens from 25 deployed and 7 nondeployed U.S. service members were analyzed as part of the Joint Pathology Center pathologic consultations. The major exogenous particle types identified in both groups include aluminum silicates, other silicates, silica, and titanium dioxide. Endogenous particle types identified include calcium salts and iron-containing particles consistent with hemosiderin. These particles are present in deployed and nondeployed service members and are particle types commonly identified in lung biopsy specimens from urban dwelling adults. Rare particles containing other elements such as cerium and iron alloys were identified in some cases. Possible sources of these materials include diesel fuel and occupational and other environmental exposures. CONCLUSION: Scanning electron microscopy with energy dispersive X-ray particle analysis of inhaled particulates retained in lung tissue from deployed service members identifies particles commonly present in inhaled dust. In this small case series, we were not able to detect particle profiles that were common and unique to deployed patients only.

Tophaceous pseudogout in a 12-year-old dog, with a review of applicable laboratory tests.

Pseudogout, also known as calcium pyrophosphate dihydrate (CPPD) deposition disease or chondrocalcinosis, is caused by crystalline deposits of CPPD within the extracellular matrix of articular hyaline cartilage and fibrocartilage, and within articular and periarticular connective tissue. Using a variety of laboratory techniques, we diagnosed pseudogout in the right hindlimb digit V of a 12-y-old Standard Poodle. Histologically, the joint, bone, tendon, and dermis were expanded and effaced by masses of mineralized, rhomboid crystals surrounded by macrophages, multinucleate giant cells, fibrous connective tissue, and chondroid and osseous matrix. Rhomboid crystals exhibiting weak-positive birefringence were identified under polarized light using a first-order red compensator filter. Scanning electron microscopy with energy-dispersive x-ray analysis (SEM-EDXA) revealed that the rhomboid crystals were composed of calcium, phosphorus, and oxygen. Fourier-transform infrared (FTIR) microspectroscopy confirmed the presence of calcium pyrophosphate. In dogs, tophaceous pseudogout, which was the variant of pseudogout in our case, occurs as a single, tumor-like periarticular mass that can be invasive and mimic neoplasia. Having ancillary confirmatory testing (SEM-EDXA and FTIR), particularly in unusual histologic scenarios, such as tophaceous pseudogout in dogs, is desirable for confirming the correct diagnosis, even though it is available only at certain reference centers. The pathogenesis of pseudogout is unknown.

Injection of oral medication into the skin confirmed by infrared spectroscopy.

"Skin popping" refers to the practice of injecting drugs, most commonly heroin, subcutaneously or into granulation tissue. Pharmaceutical tablets meant for oral consumption are modified into solutions for injection. Excipients-inactive substances that serve as vehicles for medication-are often not filtered out before injection and result in abscess formation, granulomatous inflammation, and scarring. Common excipients used in the production of pharmaceutical tablets include starch, microcrystalline cellulose, magnesium stearate, silica, and polyvinylpyrrolidone (PVP). Identification of these exogenous materials is valuable in confirming the diagnosis of skin popping, especially when patients may not be forthcoming about their drug use. We present a case of subcutaneous oral medication injection in which PVP and cellulose were identified by Fourier transform infrared spectroscopy. Considering the variable cutaneous manifestations of injection drug abuse, recognition of histopathologic and chemical characteristics of exogenous material from oral medications is helpful for diagnosis and intervention.

Histological Diagnoses of Military Personnel Undergoing Lung Biopsy After Deployment to Southwest Asia.

INTRODUCTION: The current understanding of associations between lung disease and military deployment to Southwest Asia, including Iraq and Afghanistan, is both controversial and limited. We sought to clarify the relation between military deployment and biopsy-proven lung disease. METHODS: Retrospective data were analyzed for military personnel with non-neoplastic lung biopsies evaluated at the Armed Forces Institute of Pathology or Joint Pathology Center (January 2005 to December 2012). RESULTS: Of 391 subjects, 137 (35.0%) had deployed to Southwest Asia prior to biopsy. Compared to non-deployed subjects, those deployed were younger (median age 37 vs. 51 years) with higher representation of African Americans (30.0 vs. 16.9%). Deployed patients were more likely diagnosed with non-necrotizing granulomas (OR 2.4). Non-deployed subjects had higher frequency of idiopathic interstitial pneumonias, particularly organizing pneumonia. Prevalence of small airways diseases including constrictive bronchiolitis was low. CONCLUSIONS: This study provides a broader understanding of diversity of biopsy-proven non-neoplastic lung disease as it relates to military deployment to Southwest Asia and importantly did not show an increased prevalence of small airway disease to include constrictive bronchiolitis.

Localized chrysiasis, aluminum salt deposition and dystrophic calcification a decade after gold injections.

Localized chrysiasis is rare and can occur in two settings: after localized or traumatic implantation of elemental gold or gold salts or after localized laser or light therapy in someone who has been previously exposed to systemic gold therapy. We report a unique case of localized chrysiasis with associated aluminum salt deposition and sclerosing lipogranulomas because of previous injections of aurothioglucose (Solganal®). The unique histopathologic findings seen in this case have not been previously reported.

Dystrophic calcification and accentuated localized Argyria after fractionated carbon dioxide laser therapy of hypertrophic scars.

IMPORTANCE: Fractionated, ultrapulsed carbon dioxide (CO2) laser therapy is a powerful tool for the treatment of scars. Common adverse effects of this therapeutic modality have been previously documented. We describe 2 unreported adverse effects of ultrapulsed CO2 laser treatment of mature scars in a patient previously treated with silver-impregnated dressings. OBSERVATIONS: A teenage survivor of toxic epidermal necrolysis presented with faint but diffuse dyschromia clinically and histologically consistent with localized argyria secondary to silver-impregnated dressings used years earlier. The patient was subsequently treated with fractionated CO2 for her scarring, but her hyperpigmentation worsened with each treatment. A subsequent biopsy specimen revealed a zone of dystrophic calcification with adjacent pseudo-ochronotic fibers that were not appreciated on biopsy specimens taken before CO2 laser treatment, suggesting unique complications not previously reported. CONCLUSIONS AND RELEVANCE: We present 2 unique complications secondary to ultrapulsed, fractionated CO2 laser treatment in a patient previously treated with silver-impregnated dressings: (1) the appearance of pseudo-ochronotic fibers in areas of worsening pigmentation and (2) evidence of dystrophic calcification limited to columns of fractionated laser ablation. Therefore, a history of argyria or treatment with silver-impregnated dressings should be considered before treatment with fractionated CO2 lasers.

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.

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 Masson's 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 material's light microscopic appearance.

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.