Silicon Embolization Syndrome - A Diagnostic and Therapeutic Dilemma: A Case Series and Review of the Literature

In scientific literature, silicone embolization syndrome has been well described and multiple presentations have been delineated. The use of non-medical injections of silicone has become very popular with the public in general, in particular with certain groups that are highly focused on their physical image. Local effects including tissue necrosis, foreign body giant cell reaction, and community-acquired infection have been commonly recorded. Distal effects suggesting an embolic phenomenon can present as regional lymphadenopathy, granulomatous hepatitis, interstitial nephritis, and other acute systemic illnesses. But pulmonary and neurologic sequelae especially warrant emergency attention and can be fatal, if not identified immediately. Pulmonary manifestation can sometimes easily mimic bilateral pneumonia, especially if there is no suspicion for illicit silicone use, which was the case with our patients. The injected subcutaneous silicone migrated rapidly from the interstitial subcutaneous tissue into the general bloodstream resulting in systemic silicone embolization. An analysis of the presented case in conjunction with a review of the pertinent medical literature, including relevant case reports revealed the common clinicopathological manifestations of silicon embolism.

A Histopathologic Approach to Uterine Niche: What to Expect and to Report in Hysteroscopy-Resected Isthmocele Specimens

As one of the emerging complications of caesarean sections (CSs), pathologists will have an important role in handling samples of uterine niches. An isthmocele is a defect at the site of a previous CS scar resulting in a variety of symptoms and niche-related subfertility. There is a deficiency in the literature of the histopathologic features of hysteroscopy-resected isthmocele ridges. Our aim is to fill this gap to highlight what to expect to see and what important findings to report to guide gynecologists to the results of hysteroscopic isthmoplasty in relation to symptoms improvement, fertility restoration, and potential complications. We found 22 cases of hysteroscopy-resected isthmoceles by performing a retrospective review study. The majority of the women were symptomatic with secondary infertility. The resected isthmocele edges were lined by endocervical, endometrial, and isthmic mucosa either combined or isolated depending on each case. Isthmoceles could be classified depending on the predominant lining mucosa into endocervical-isthmoendocervical (low) and endometrial-isthmic (high-intermediate) niches. This could be correlated with certain symptoms. The edges showed variably thickened fibrous and fibromuscular stromal tissue with characteristic thick-walled blood vessels. Some cases showed miscellaneous findings such as hemosiderin pigments with foreign body giant cell reaction and placental implantation site tissue reflecting a previous history of surgical repair and scar pregnancy. Cauterization artifacts may impose interpretation challenges for pathologists. Utility of certain special stains helps delineate the nature of badly cauterized tissues. It is important to report certain histologic findings in isthmocele samples to correlate with clinical findings and guide gynecologists.

A multicenter retrospective study of heterogeneous tissue aggregates obstructing ventricular catheters explanted from patients with hydrocephalus

Background Implantation of ventricular catheters (VCs) to drain cerebrospinal fluid (CSF) is a standard approach to treat hydrocephalus. VCs fail frequently due to tissue obstructing the lumen via the drainage holes. Mechanisms driving obstruction are poorly understood. This study aimed to characterize the histological features of VC obstructions and identify links to clinical factors. Methods 343 VCs with relevant clinical data were collected from five centers. Each hole on the VCs was classified by degree of tissue obstruction after macroscopic analysis. A subgroup of 54 samples was analyzed using immunofluorescent labelling, histology and immunohistochemistry. Results 61.5% of the 343 VCs analyzed had tissue aggregates occluding at least one hole (n = 211) however the vast majority of the holes (70%) showed no tissue aggregates. Mean age at which patients with occluded VCs had their first surgeries (3.25 yrs) was lower than in patients with non-occluded VCs (5.29 yrs, p < 0.02). Mean length of time of implantation of occluded VCs, 33.22 months was greater than for non-occluded VCs, 23.8 months (p = 0.02). Patients with myelomeningocele had a greater probability of having an occluded VC (p = 0.0426). VCs with occlusions had greater numbers of macrophages and astrocytes in comparison to non-occluded VCs (p < 0.01). Microglia comprised only 2–6% of the VC-obstructing tissue aggregates. Histologic analysis showed choroid plexus occlusion in 24%, vascularized glial tissue occlusion in 24%, prevalent lymphocytic inflammation in 29%, and foreign body giant cell reactions in 5% and no ependyma. Conclusion Our data show that age of the first surgery and length of time a VC is implanted are factors that influence the degree of VC obstruction. The tissue aggregates obstructing VCs are composed predominantly of astrocytes and macrophages; microglia have a relatively small presence.

Cholesterol granuloma of the maxillary sinus: a forgotten entity

Aim of the study: Cholesterol granuloma is a histological entity which consists of granulation tissue in which a large quantity of cholesterol crystals provoke foreign body giant cell formation. Cholesterol granulomas are often found in the middle ear with rare presentation in the paranasal sinus. We would like to highlight the diagnostic challenges and the management of maxillary sinus cholesterol granuloma in a young woman presenting as a unilateral nasal mass. Case study: We report a young woman with cholesterol granuloma of maxillary sinus who initially presented with unilateral nasal obstruction. Rigid nasoendoscopy and imaging were suggestive of an antrochoanal polyp. Ipsilateral functional endoscopic sinus surgery was done successfully. Conclusion: Albeit rare, cholesterol granuloma ought to be considered a differential diagnosis in a sinonasal tumour. This case report highlights the rare presentation of maxillary sinus cholesterol granuloma which ought to be considered a differential diagnosis of a unilateral nasal mass.

Effects of Titanium Corrosion Products on In Vivo Biological Response: A Basis for the Understanding of Osseointegration Failures Mechanisms

Corrosion resistance is a key feature of titanium biocompatibility. However, Ti surfaces exposed to critical environments (such as, chronic infection and inflammation) can undergo corrosion processes in vivo, leading to an unfavorable biological response and clinical failure, which remains poorly explored. In this study, we characterized an experimental model to replicate the surface features of Ti corrosion process observed within in vivo failures, and the cellular, tissue and molecular events associated with corroded Ti surface implantation into subcutaneous and bone tissue of C57Bl/6 mice. Prior to in vivo implantation, commercially pure Ti Commercially pure titanium and Ti–6Al–4V alloy (Ti64) specimens were exposed to electrochemical polarization in 30% citric acid, while being polarized at 9 V against a saturated calomel electrode for 20 min. The electrochemical attack induced accelerated corrosion on both Ti-based specimens, producing structural and chemical changes on the surface, comparable to changes observed in failed implants. Then, microscopy and molecular parameters for healing and inflammation were investigated following control and corroded Ti implantation in subcutaneous (cpTi disks) and oral osseointegration (Ti64 screws) models at 3, 7, 14 and 21 days. The host response was comparatively evaluated between control and corroded Ti groups by microCT (bone), histology (H&amp;E, histomorphometry, immunostaining and picrosirius red), and real-time PCR array for inflammatory and healings markers. Corroded cpTi disks and Ti64 screws induced a strong foreign body response (FBR) from 3 to 21 days-post implantation, with unremitting chronic inflammatory reaction lasting up to 21 days in both subcutaneous and osseointegration models. In the subcutaneous model, FBR was accompanied by increased amount of blood vessels and their molecular markers, as well as increased TRAP+ foreign body giant cell count. In the osseointegration model, failures were identified by an osteolytic reaction/bone loss detected by microCT and histological analyses. The corroded devices were associated with a dominant M1-type response, while controls showed transient inflammation, an M2-type response, and suitable healing and osseointegration. In conclusion, corrosion of Ti-based biomaterials induced exacerbated inflammatory response in both connective tissue and bone, linked to the upregulation of fibrosis, pro-inflammatory and osteoclastic markers and resulted in unfavorable healing and osseointegration outcomes.

Suture thread: An unusual etiology of tracheal pseudotumor

A 66-year-old man ingested sodium hydroxide in a suicide attempt in June 2018. In emergency room, he presented burning of the tongue and uvula and supraglottic and vocal cords edema. Because of the risk of airway obstruction, the patient underwent endotracheal intubation and started invasive mechanical ventilation. Five days later, a surgical tracheostomy was performed due to a large laryngeal necrosis including extensive epligottis involvement. After prolonged mechanical ventilation through tracheostomy, the patient presented a favorable clinical course allowing ventilator weaning and decannulation 2 months after initial presentation. In February 2019, cervical Computed Tomography (CT) revealed a polypoid lesion occupying 25% of the tracheal lumen, with contrast uptake and suggestive of malignant etiology (Figure 1A-B). The patient was asymptomatic. Rigid bronchoscopy showed that the pseudotumoral tracheal lesion corresponded to granulation tissue around suture thread from the previous tracheostomy, which were successfully removed during the procedure (Figure 1C-E). Pathological examination showed granulation tissue with extensive inflammatory infiltrate and foreign-body giant cell reaction.

Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering

Tissue engineered vascular grafts hold promise for the creation of functional blood vessels from biodegradable scaffolds. Because the precise mechanisms regulating this process are still under investigation, inducible genetic mouse models are an important and widely used research tool. However, here we describe the importance of challenging the baseline assumption that tamoxifen is inert when used as a small molecule inducer in the context of cardiovascular tissue engineering. Employing a standard inferior vena cava vascular interposition graft model in C57BL/6 mice, we discovered differences in the immunologic response between control and tamoxifen-treated animals, including occlusion rate, macrophage infiltration and phenotype, the extent of foreign body giant cell development, and collagen deposition. Further, differences were noted between untreated males and females. Our findings demonstrate that the host-response to materials commonly used in cardiovascular tissue engineering is sex-specific and critically impacted by exposure to tamoxifen, necessitating careful model selection and interpretation of results.

Genetic variants of small airways and interstitial pulmonary disease in children

Genetic variants of small airways and interstitial pulmonary disease have not been comprehensively studied. This cluster of respiratory disorders usually manifests from early infancy (‘lung disease in utero’). In this study, 24 variants linked to these entities are described. The variants involved two genes associated with surfactant metabolism dysfunction (ABCA3 and CSF2RB), two with pulmonary fibrosis (MUC5B and SFTP), one with bronchiectasis (SCNN1B), and one with alpha-1-antitrypsin deficiency (SERPINA1). A nonsense variant, MUC5B:c.16861G > T, p.Glu5621*, was found in homozygous state in two siblings with severe respiratory disease from birth. One of the siblings also had heterozygous SFTPA1:c.675C > G, p.Asn225Lys, which resulted in a more severe respiratory disease. The sibling with only the homozygous MUC5B variant had lung biopsy, which showed alveolar simplification, interstitial fibrosis, intra-alveolar lipid-laden macrophages, and foci of foreign body giant cell reaction in distal airspaces. Two missense variants, MUC5B:c.14936 T > C, p.Ile4979Thr (rs201287218) and MUC5B:c.16738G > A, p.Gly5580Arg (rs776709402), were also found in compound heterozygous state in two siblings with severe respiratory disease from birth. Overall, the results emphasize the need for genetic studies for patients with complex respiratory problems. Identifying pathogenic variants, such as those presented here, assists in effective family counseling aimed at genetic prevention. In addition, results of genetic studies improve the clinical care and provide opportunities for participating in clinical trials, such as those involving molecularly-targeted therapies.

The Crushing Effects Of Opiate Abuse: Two Cases Illustrating The Morphologic Features Of Acute And Chronic Intravenous Administration Of Crushed Oral Opiates

Introduction/Objective Drug overdose related deaths in the US have shown a four-fold increase over the past two decades, increasing from 6.1 to 21.7 per 100,000, the increasing majority of which involve synthetic opioid use. With this continuing increase, it is important for pathologists to become aware of unusual gross and microscopic changes related to unconventional modes of drug abuse. A less recognized unconventional method for opiate abusers to ingest these substances exemplified by our two cases is by crushing oral tablets and inhaling or injecting the drug intravenously, subcutaneously or intramuscularly. Methods The two cases being presented show morphological features of acute and chronic opiate abuse by autopsy study. Case 1 was a 38-year old female, who underwent spinal fusion surgery 1 month prior, and was found unresponsive at home. Case 2 was a 37-year-old female with a history of Antiphospholipid Antibody Syndrome (APA) and upper limb DVTs who was found unresponsive one day after elective utero-vaginal prolapse surgery. Results At autopsy, Case 1 showed extensive embolization of polarizable foreign body material (possible “pill filler”) and fibrin in small and medium sized vessels without inflammatory reaction in the lungs bilaterally. The foreign material was also present in the small vessels of the heart associated with multifocal acute inflammation, hemorrhage, foreign body giant cell reaction and multiple myocardial infarcts (elevated troponin levels clinically). Blood and vitreous fluid were positive for oxycodone. At autopsy, Case 2 showed an extensive angiocentric miliary pattern of granulomatous reaction to polarizable foreign material, consistent with pill filler in the lungs bilaterally. This foreign material was also present within the lumens and walls of pulmonary vessels and in the skin of the legs. Chronic changes of hypertrophic cardiomyopathy, hepatic cirrhosis and congestive splenomegaly were evident. The blood oxycodone levels were ten times the normal limit. Conclusion These cases illustrate the importance of recognizing the clinical and morphological features of unorthodox acute and chronic opiate abuse. Lack of familiarity with their differing features can lead to a delay in diagnosis and institution of appropriate timely management and treatment.