Jerrold L. Abraham

Silicone granulomas: Report of three cases and review of the literature

Since silicone is rapidly becoming one of the most commonly used biomaterials in modern medicine, pathologists will be observing increasing numbers of cases of silicone-related disease. Although numerous case reports have established that silicone elicits a characteristic response in tissues, the varying tissue reactions to silicone gels, liquids, and elastomers (rubber) have not been emphasized. Three cases are reported, and the literature is reviewed to illustrate the varying features of tissue reaction to silicone in its different forms. The first case is an example of silicone lymphadenopathy in an inguinal lymph node. This case demonstrates exuberant foreign body granuloma formation in response to particles of silicone elastomer. The second case involves a patient who had facial subcutaneous liquid silicone injections, and the third case is that of a woman in whom breast carcinoma developed 13 years after mammary augmentation with liquid silicone injections. These two cases illustrate the characteristic reaction to silicone liquid, with numerous cystic spaces and vacuoles in the soft tissues but minimal or no foreign body giant cell reaction. Scanning electron microscopy and energy dispersive x-ray analysis were performed in the first two cases, confirming the presence of silicon. Silicone migration and the clinical significance of various silicone-induced lesions are discussed.

Dermal inorganic gadolinium concentrations: evidence for in vivo transmetallation and long-term persistence in nephrogenic systemic fibrosis.

Background  Gadolinium (Gd)‐based magnetic resonance contrast agents (GBMCA), including gadodiamide, have been identified as the probable causative agents of the serious disease, nephrogenic systemic fibrosis (NSF).

Desquamative interstitial pneumonia in an aluminum welder.

Chronic interstitial pneumonia of predominantly desquamative pattern in an electric arc welder is described. Large amounts of finely divided particulate matter (0.02 to 0.2 μ m particle diameter) were detected in the lung, particularly in alveolar macrophages and focal perivascular collections of interstitial macrophages. Phagocytosis of the particles by type 1 alveolar epithelial cells was also observed. Electron microprobe analysis showed that the particulate matter contained abundant aluminum.

Gadolinium‐Induced Nephrogenic Systemic Fibrosis Is Associated with Insoluble Gd Deposits in Tissues: In Vivo Transmetallation Confirmed by Microanalysis

Background: Nephrogenic systemic fibrosis (NSF) is an extremely debilitating systemic fibrosing disorder affecting renal failure patients. The association of NSF with gadolinium (Gd) containing magnetic resonance contrast agents was noted in 2006. Gd deposition in skin biopsies was demonstrated shortly thereafter.

Multiorgan gadolinium (Gd) deposition and fibrosis in a patient with nephrogenic systemic fibrosis—an autopsy-based review

BACKGROUND Nephrogenic systemic fibrosis (NSF) is a systemic disorder of patients with severe renal insufficiency who have received gadolinium (Gd)-based magnetic resonance contrast agents (GBCAs). The causative association with Gd exposure was strengthened by the demonstration of Gd in various tissues of NSF patients, predominantly at the bulk chemical level. The distribution of Gd at the histologic level of organs other than skin has not been reported previously. METHODS We analysed tissues from an autopsy case with verified advanced NSF by light microscopy and scanning electron microscopy/energy-dispersive X-ray spectroscopy. Furthermore, we reviewed published literature to compare the histological and histochemical findings in NSF patients and chronic renal failure (CRF) patients without NSF. RESULTS Insoluble Gd-phosphate deposits were detected in the skin, liver, lungs, intestinal wall (ileum), kidney, lymph node, skeletal muscle, dura mater and cerebellum of the NSF autopsy case, primarily in vascular walls. Some, but not all, Gd deposits were seen in fibrotic areas. Literature review highlighted that non-specific tissue fibrosis and calcification are frequent findings in tissues of patients with CRF with and without NSF. CONCLUSIONS Vascular and extracellular Gd deposits are found in multiple organs of NSF patients, associated with calcification, and often in fibrotic areas. Gd deposits are not seen in patients with CRF unexposed to GBCAs but rarely may be seen in GBCA-exposed patients without clinical signs of NSF. Apart from diagnostic findings in skin, fibrosis of muscle and dura may be more prominent in NSF patients. Our findings should stimulate further investigation of mechanisms of fibrosis and pathologic calcification.

Synchrotron X‐ray analyses demonstrate phosphate‐bound gadolinium in skin in nephrogenic systemic fibrosis

Background  Nephrogenic systemic fibrosis (NSF) is an incurable, debilitating disease found exclusively in patients with decreased kidney function and comprises a fibrosing disorder of the skin and systemic tissues. The disease is associated with exposure to gadolinium (Gd)‐based contrast agents (GBCA) used in magnetic resonance imaging (MRI). Tissue samples from many patients with NSF contain micron‐sized insoluble Gd‐containing deposits. However, the precise composition and chemical nature of these particles is unclear.

Gadolinium released from MR contrast agents is deposited in brain tumors: in situ demonstration using scanning electron microscopy with energy dispersive X-ray spectroscopy

Background: Gadolinium (Gd)-containing MRI contrast agents (GdCA) are widely used in studies of brain tumors, and a number of reports suggest that under certain conditions, such as renal failure, Gd may be released from GdCA into patients tissues. Whether this may happen in abnormal tissues in the absence of renal failure has not been studied. Purpose: To test the hypothesis that the local retention of GdCA resulting from brain tumor-associated alterations in the blood–brain barrier (BBB) may result in the deposition of Gd released from the GdCA, depending on stability. Material and Methods: In this retrospective study, 30 selected brain tumor biopsies from 28 patients (taken before and after an institutional switch from a less stable to an intermediate stable GdCA) were searched for Gd-containing deposits using scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDS). Relevant histories and laboratory results were obtained through institutional electronic records. Associations between the presence of deposits and other variables were tested for statistical significance using the two-tailed Fishers exact test. Results: Insoluble deposits containing Gd associated with phosphorus and calcium were found in seven biopsies from five patients. These deposits were found in patients with estimated GFRs above 53 ml/min, and were detected more often in those receiving GdCA before the switch from a less stable to an intermediate stable GdCA (P = 0.04), and may be more frequent in patients receiving more than one contrast-enhanced MR scan (P = 0.15). Conclusion: Gd-containing deposits are present in brain tumors following contrast-enhanced MR scans in patients without severe renal disease. Further studies are needed to assess the clinical importance of the deposits we observed and to determine whether they are also found in other conditions that alter the integrity of the BBB.

Indicators of airborne fungal concentrations in urban homes: Understanding the conditions that affect indoor fungal exposures

Indoor fungal exposure can compromise respiratory health. Low-income urban areas are of concern because of high asthma and allergy rates and housing disrepair. Understanding the conditions that affect indoor fungal exposures is important for assessing health risks and for developing mitigation strategies. We examined the types and concentrations of airborne fungi inside and outside of homes in low-income areas of Syracuse, NY as well as the effect of snow cover on fungal levels. At 103 homes, air samples for viable fungi were collected, occupants were interviewed and homes were inspected for visible mold, musty odors, water problems and other factors. Multivariable logistic regression was used to relate high fungal levels to home conditions. Predominant indoor fungi included Cladosporium, Penicillium, Aspergillus, Alternaria and hyaline unknowns. Basidiomycetes and an uncommon genus Acrodontium were also found frequently due to analysis methods developed for this project. With snow cover, outdoor total fungal levels were depressed and indoor concentrations were three times higher than outdoor on average with a maximum of 29 times higher. Visible mold was related to elevated levels of Penicillium (OR 4.11 95% CI 1.37-14.0) and bacteria (OR 3.79 95% CI 1.41-11.2). Musty, moldy odors were associated with elevated concentrations of total fungi (OR 3.48 95% CI 1.13-11.6) and basidiomycetes. Cockroaches, an indicator of moisture, were associated with elevated levels of Penicillium (OR 3.66 95% CI 1.16-13.1) and Aspergillus (OR 4.36 95% CI 1.60-13.4). Increasing relative humidity was associated with higher concentrations of Penicillium, yeasts and basidiomycetes. Visible mold, musty odors, indoor humidity and cockroaches are modifiable factors that were important determinants of indoor fungal exposures. Indoor air investigators should interpret indoor:outdoor fungal ratios cautiously when snow cover is present.

Lanthanum deposition in a dialysis patient

Lanthanum carbonate (LaCO(3)) is an oral phosphate binder widely used in end-stage renal disease (ESRD). Preclinical animal studies reported the highest La concentrations outside the gut to be in mesenteric lymph nodes. We observed previously unreported La deposition visible by light microscopy and confirmed by scanning electron microscopy with energy dispersive x-ray spectroscopy in a mesenteric lymph node at autopsy of a 38-year-old female ESRD patient 3 years following LaCO(3) administration. Although LaCO(3) is generally thought to be minimally absorbed, this demonstration suggests the need for further investigation of the extent and potential effects of such absorption.

An Official American Thoracic Society Statement: Diagnosis and Management of Beryllium Sensitivity and Chronic Beryllium Disease

RATIONALE Beryllium continues to have a wide range of industrial applications. Exposure to beryllium can lead to sensitization (BeS) and chronic beryllium disease (CBD). OBJECTIVES The purpose of this statement is to increase awareness and knowledge about beryllium exposure, BeS, and CBD. METHODS Evidence was identified by a search of MEDLINE. The committee then summarized the evidence, drew conclusions, and described their approach to diagnosis and management. MAIN RESULTS The beryllium lymphocyte proliferation test is the cornerstone of both medical surveillance and the diagnosis of BeS and CBD. A confirmed abnormal beryllium lymphocyte proliferation test without evidence of lung disease is diagnostic of BeS. BeS with evidence of a granulomatous inflammatory response in the lung is diagnostic of CBD. The determinants of progression from BeS to CBD are uncertain, but higher exposures and the presence of a genetic variant in the HLA-DP β chain appear to increase the risk. Periodic evaluation of affected individuals can detect disease progression (from BeS to CBD, or from mild CBD to more severe CBD). Corticosteroid therapy is typically administered when a patient with CBD exhibits evidence of significant lung function abnormality or decline. CONCLUSIONS Medical surveillance in workplaces that use beryllium-containing materials can identify individuals with BeS and at-risk groups of workers, which can help prioritize efforts to reduce inhalational and dermal exposures.