Review of IgG4-related Hashimoto Thyroiditis With Best Practice Recommendations for Diagnosis and Reporting.

Found in virtually any organ system, immunoglobulin (Ig) G4-related disease (RD) is a recently recognized immune-mediated, systemic, a fibroinflammatory disease characterized histologically by storiform fibrosis, obliterative phlebitis, and lymphoplasmacytic infiltrate with IgG4-positive plasma cells (PCs). IgG4-related Hashimoto thyroiditis (IgG4-RHT), also called IgG4-related thyroiditis, shares many features with IgG4-RD but is distinct in several ways. A case of IgG4-RHT in a 51-year-old African American female is assembled together with a literature review which uncovered 82 cases of IgG4-RHT. The findings and criteria which the respective authors used to reach their diagnoses are analyzed. Findings common to all studies are lymphoplasmacytic infiltration and IgG4-positive staining, while most describe follicular atrophy (95.2%, 79/83). Stromal fibrosis involving >33% of thyroid architecture was reported in 74% (58/78) of cases. While few reports observed storiform fibrosis, all describe lack of obliterative phlebitis or systemic involvement. Discrepancies between reports exist in immunostaining thresholds, as well as grading systems for stromal fibrosis. Based on our review of the literature and experience, we propose a set of best practice recommendations for the diagnosis of IgG4-RHT. Our diagnostic criteria are (1) lack of extrathyroidal IgG4-RD, (2) the fibroinflammatory process should not extend beyond the thyroid capsule, (3) stromal fibrosis comprises at least 30% of the involved tissue, (4) >30% IgG4/IgG ratio, with absolute immunostaining cutoffs varying by the degree of stromal fibrosis: for >50% stromal fibrosis use >20 IgG4+PCs/HPF, for 30% to 50% fibrosis use >30 IgG4+PCs/HPF, (5) fibrosis infiltrates the interlobular/interfollicular space, (6) features of follicle injury, and (7) obliterative phlebitis is not required.

Determination of the Force Required to Produce Stab "Wounds" in Fruit Compared With Cadaveric Chest Tissue.

ABSTRACT: In laymen's terms, it can be difficult to communicate how much force is needed to create a stab wound into a person's chest. Previous work has determined the force to puncture the skin, rib cartilage, or bone but without putting the results in terms that are easy to understand.The purpose of this study was to determine the force needed to puncture 3 types of fruit using 3 different types of knives, namely, a steak knife, a butcher's knife, and a lock-blade knife, to help put these previous results in perspective.There was wide variation in the force required to insert a knife into different fruits, but no force for any knife at any location for all fruits exceeded 93.1 N. Results show that force needed to penetrate the skin and allow for an 8-cm blade penetration into the chest is similar to the force required to insert a steak knife for a 6-cm distance into a cantaloupe. In addition, the force needed to penetrate the cartilage is most similar to stabbing a watermelon to 6 cm with a butcher knife. However, the forces required to penetrate the bone are greater than those required to penetrate any fruit with any type of blade.

Death Due to Adrenal Crisis: Case Report and a Review of the Forensic Literature.

ABSTRACT: Adrenal crisis is a life-threatening manifestation of acute adrenal insufficiency. One of the most important underlying causes is Addison disease (primary adrenal insufficiency).A 42-year-old White woman with a medical history of Addison disease on chronic steroid therapy was admitted to the emergency department due to sustained episodes of cardiopulmonary arrest. Upon admission, she was hypotensive and hypoglycemic. Despite resuscitation attempts, she developed multiorgan failure and eventually died. At autopsy, no definitive adrenal gland tissue was grossly identified, but histology detected atrophy of adrenal glands with patchy chronic inflammation. Evidence of acute pneumonia was seen. The cause of death was determined to be complications of adrenal/Addisonian crisis.A review of the literature showed only a few autopsy studies regarding deaths due to adrenal crisis. Forensic pathologists should include adrenal crisis in their differential diagnosis. Adequate medical history and pertinent autopsy findings can corroborate deaths due to adrenal crisis, but exhaustive biochemical analyses are mandatory to support the diagnosis further.

Determination of Force Required to Produce Stab Wounds in Cadaveric Chest Tissues.

ABSTRACT: When investigating deaths due to stab wounds, a common question asked to the forensic pathologist concerns the force required to inflict a given wound.In this study, tests were performed on 6 human cadavers. A material testing machine was used to produce the stab wounds and to record the force required to penetrate skin, muscle, cartilage, and rib bone of the chest. Three different blades were used: a steak knife, a butcher knife, and a lock-blade knife. On each cadaver, chest injuries were produced at the following locations: (a) skin, intercostal soft tissues; (b) skin, muscle, and cartilage; and (c) skin, muscle, and bone. After the experiment, a chest dissection was performed to confirm the correct locations of the produced stab wounds.The force required to insert a knife into cartilage or bone was significantly greater than the force to insert it into a region only covered by skin. There was wide variation in the force required to insert a knife into different bodies, but no force for any knife at any location for all bodies was greater than 261 N.This study allowed us to obtain quantitative measures of the force required to penetrate human chest tissues, removing subjective factors.

Sudden death due to leukostasis in a subject with undiagnosed chronic lymphocytic leukemia.

Sudden death due to leukostasis and lymphocyte thrombi in patients with chronic hematologic malignancies is rare. Leukostasis is characterized by highly elevated leukemic cell count and decreased tissue perfusion symptoms, leading to severe complications and even death. Chronic lymphocytic leukemia (CLL) is a chronic lymphoproliferative disorder that shows a highly heterogeneous clinical course, ranging from indolent form to very aggressive disease. Due to its low metabolic and mitotic rate, there is a lower incidence of clinically significant leukostasis in patients with CLL. Two main theories have been proposed in the development of leukostasis: (1) increased blood viscosity due to large leukemic cell populations; (2) high metabolic activity and cytokine production by leukemic cells. Both mechanisms lead to local hypoxic damage.We present a case of a 70-year-old man who died suddenly in the absence of symptoms. Autopsy and histology examinations revealed findings consistent with CLL and diffuse leukostasis involving the major organs' vessels.In the presence of gross and/or microscopic findings suggesting a potential hematologic malignancy, undiagnosed or relapsing hematologic malignancies should be considered in the differential diagnosis of sudden deaths.

Death caused by a domestic pig attack.

The primary medico-legal investigation goal in deaths due to animal attacks is distinguishing between animal-related injuries and potential homicidal wounds. We report the case of a 49-year-old male found dead in his farm's pigsty, where a sow and her piglets were present. At the postmortem examination, numerous, severe blunt force injuries were observed on the body, with special regard to the upper extremities where massive injuries involving soft tissues, bones, and regional vessels, tendons, and nerves were present. The death resulted from severe bleeding from massive upper extremities injuries due to a domestic pig attack. Domestic pigs are usually placid but they can become aggressive if disturbed and attack humans producing severe injuries due to trampling, kicking and biting. Knowing the relevant anatomy, pattern of attack, and morphologies of wounds produced by particular animals can distinguish animal attacks from homicides, as well as attempt to identify the type of animal involved in an unwitnessed attack.

Head and Brain Postmortem Computed Tomography-Autopsy Correlation in Hospital Deaths.

The use of postmortem computed tomography (PMCT) to support autopsy pathology has increased in recent decades. To some extent, PMCT has also been contemplated as a potential alternative to conventional postmortem examination. The purpose of this study was to investigate the ability of PMCT to detect specific pathologic findings in the head and brain in natural hospital deaths.We examined postmortem CT images and autopsy data from 31 subjects who died at SUNY (State University of New York) Upstate University Hospital between 2013 and 2018. Each subject underwent a noncontrast PMCT and a traditional autopsy. A neuroradiologist analyzed PMCT images for head and brain abnormalities. The autopsies were performed by pathologists who were aware of the radiology results.In our series, PMCT was able to detect the majority of the significant space-occupying lesions, although it was not always reliable in ascertaining their nature. Postmortem computed tomography revealed findings usually challenging to detect at autopsy. Unfortunately, there were also situations in which PMCT was misleading, showing changes that were difficult to interpret, or that could be related to postmortem events. Therefore, we conclude PMCT should be used as an adjunct rather than a substitute to autopsy.

Atypical Enostoses-Series of Ten Cases and Literature Review.

Bone islands (BI; enostoses) may be solitary or occur in the setting of osteopoikilosis (multiple bone islands) and are sometimes associated with Gardner's Syndrome (osteopoikilosis and colonic polyposis). Characteristic features of bone islands are (1) absence of pain or local tenderness, (2) typical radio dense central appearance with peripheral radiating spicules (rose thorn), (3) Mean CT (computerized tomography) attenuation values above 885 Hounsfield units (HU) (4) absence of uptake on bone scan and (5) radiographic stability over time. However, when enostoses display atypical features of pain, unusual radiographic appearance, aberrant HU, increased radiotracer uptake, and/or enlargement, they can be difficult to differentiate from more sinister bony lesions such as osteoblastic metastasis, low grade central osteosarcoma, osteoid osteoma and osteoblastoma. In this retrospective case series, the demographic, clinical, radiographic, treatment and outcome for ten patients with eleven atypical bone islands (ABI) are presented, some showing associated pain (5), some with atypical radiographic appearance (3), some with increased activity on BS (4), some with documented enlargement over time (7), one with abnormal CT attenuation value, some in the setting of osteopoikilosis (2), one in the setting of Gardner's Syndrome and one osteoid osteoma simulating a bone island. This series represents the spectrum of presentations of ABI. Comprehensive review of the literature reveals that the previous largest series of ABI showing enlargement as the atypical feature was in younger patients with jaw BI. Hence, this represents one of the largest series reported of ABI of all types in adults.

Pneumosinus Dilatans frontalis: a case of incidental autopsy diagnosis.

Pneumosinus Dilatans Frontalis (PDF) is a rare pathologic condition characterized by expansion and hyper aeration of the frontal sinuses. This abnormality has been described in otolaryngology, ophthalmology, neurology, and radiology journals, while only a few autopsy studies are reported in the English literature. The etiology of this condition remains unclear, although multiple theories have been proposed. Clinically, PDF is often an asymptomatic condition, but it can lead to significant bone deformation with esthetic complaints, and even severe associated neurological deficits. In the following case report, a 20-year-old Caucasian male committed suicide by asphyxia due to plastic bag suffocation combined with a vitiated atmosphere as a consequence of helium inhalation. At postmortem an abnormal expansion of the frontal sinuses was detected, involving the frontal bone just above the orbits. The defect showed a multiloculated appearance in the sinus cavities. An incidental diagnosis of PDF was made. A description of the findings and a hypothesis of the clinical relevance of PDF in the reported case are presented.

Massive intracranial bleeding due to the rupture of a rare spontaneous pseudoaneurysm of the middle cerebral artery in a pediatric patient: case report with clinical, radiological, and pathologic findings.

Intracranial pseudoaneurysm (IPA) is a rare but likely underdiagnosed cause of intracranial hemorrhage, which accounts for just 1-6% of all intracranial aneurysms. Spontaneous IPAs are exceptionally rare, and their etiology and features are not well defined. Herein, we report a case of a pediatric patient who died from massive intracranial bleeding due to the rupture of a spontaneous IPA after undergoing multiple radiological studies and neurosurgical operations. At the postmortem examination of the brain, a giant size pseudoaneurysm of the right middle cerebral artery was observed. Microscopic examination demonstrated variable wall thickness and dense fibrosis focally in the vessel wall with disruption of the media structure together with a loss and fragmentation of the elastic laminae, loss of organization of smooth muscle cells in the media, and multifocal areas of hemorrhage throughout the vessel wall, as well as direct evidence of wall dissection. Since IPAs without any traumatic or infective history are extremely uncommon, further pathologic studies should be performed to clarify spontaneous pseudoaneurysm etiology.

Accuracy of MRI skeletal age estimation for subjects 12-19. Potential use for subjects of unknown age.

INTRODUCTION: In forensic practice, there is a growing need for accurate methods of age estimation, especially in the cases of young individuals of unknown age. Age can be estimated through somatic features that are universally considered associated with chronological age. Unfortunately, these features do not always coincide with the real chronological age: for these reasons that age determination is often very difficult. Our aim is to evaluate accuracy of skeletal age estimation using Tomei's MRI method in subjects between 12 and 19 years old for forensic purposes. MATERIAL AND METHODS: Two investigators analyzed MRI images of the left hand and wrist of 77 male and 74 female caucasian subjects, without chronic diseases or developmental disorders, whose age ranged from 12 to 19 years. Skeletal maturation was determined by two operators, who analyzed all MRI images separately, in blinded fashion to the chronological age. Inter-rater agreement was measured with Pearson (R (2)) coefficient. One of the examiners repeated the evaluation after 6 months, and intraobserver variation was analyzed. Bland-Altman plots were used to determine mean differences between skeletal and chronological age. RESULTS: Inter-rater agreement Pearson coefficient showed a good linear correlation, respectively, 0.98 and 0.97 in males and females. Bland-Altman analysis demonstrated that the differences between chronological and skeletal age are not significant. Spearman's correlation coefficient showed good correlation between skeletal and chronological age both in females (R (2) = 0.96) and in males (R (2) = 0.94). CONCLUSIONS: Our results show that MRI skeletal age is a reproducible method and has good correlation with chronological age.

A rare and lethal case of right common carotid pseudoaneurysm following whiplash trauma.

Whiplash trauma from a car crash is one of the most common causes of neck injury, resulting in pain and dysfunction. We report on an unusual case of post-whiplash pseudoaneurysm of the right common carotid artery, which led to acute massive hemorrhage and death days after the initial trauma. A post-mortem computed tomography angiography showed rupture of the pseudoaneurysm of the right common carotid artery with the contrast agent leaking out into the mouth. The subsequent autopsy confirmed a large hemorrhagic clot extending to the right side of the neck and mediastinum. A rupture of the right wall of the oropharynx was identified with massive bronchial hemoaspiration. The case demonstrates a rare but lethal clinical entity, and is important in providing a better understanding of the potentially fatal consequences of minor trauma, such as whiplash injury, and its physiopathological mechanisms. Thus, changing symptoms after a whiplash injury should be carefully evaluated since they can be related to the underlying severe consequences of a rapid hyperextension-hyperflexion of the neck, as in the reported case.

Intraductal papillary mucinous neoplasms of the pancreas: Cytologic-histologic correlation study and evaluation of the cytologic accuracy in identifying high-grade dysplasia/invasive adenocarcinoma.

Objective: Intraductal papillary mucinous neoplasms (IPMNs) may be associated with invasive adenocarcinoma, low-grade dysplasia (LGD), or high-grade dysplasia (HGD). We aimed to review the cytologic-histologic correlation of cases with a histologic diagnosis of IPMN. Material and Methods: A database search (January 2010-January 2021) was performed for resected IPMNs with preceding endoscopic ultrasound-guided fine-needle aspiration (FNA). Cytology slides were reviewed for the presence of benign, atypical, or malignant cells, and necrosis. Histologically, IPMNs were classified as benign (LGD) or malignant (HGD or adenocarcinoma). Results: There were 41 patients with IPMN; 24 malignant and 17 benign. Sixteen of the 24 malignant IPMNs were accurately classified as malignant on cytology. There were eight false negatives and one false positive. Cytology yielded a sensitivity of 67% and a specificity of 94%. Among the 16 true positives with FNA diagnosis of adenocarcinoma, seven were IPMNs with HGD, and nine had invasive adenocarcinomas on histology. Cellular morphology and absence or presence of necrosis did not help distinguish HGD from adenocarcinoma on cytology (P > 0.5). Sampling errors and interpretative errors resulted in false-negative cases. Cytology yielded diagnoses related to IPMN in 73% of cases (30/41) and lack of identification of mucinous cells/mucinous background resulted in interpretative errors (9). Conclusion: This study shows that there is a good correlation between cytopathology and surgical pathology diagnoses of IPMNs and that cytology is mostly able to recognize IPMN with HGD/adenocarcinoma. However, heterogeneity in areas of IPMN with HGD/adenocarcinoma may result in sampling errors yielding false-negative cases. Mucinous cells/background should raise the suspicion of IPMN on cytology, even when no neoplastic epithelium is present for the evaluation of dysplasia.

Five-year review (2014-2019) of paediatric accidental deaths in Cook County, Illinois (USA).

In the USA, intentional and accidental injuries are the most frequent causes of death in children. Many of these deaths could be avoided through preventive measures, and aetiological studies are needed to reduce fatalities. The leading causes of accidental death vary by age. We analysed all paediatric accidental deaths recorded by a busy urban Medical Examiner"s Office in Chicago, Illinois (USA). We searched the electronic database for accidental deaths in children aged under 10 between 1 August 2014 and 31 July 2019. 131 deaths were identified with a preponderance of males and African Americans. This is consistent with ratios of other deaths recorded for this age group (during the same period and area). The leading causes of death were asphyxia due to an unsafe sleeping environment (in subjects <1-year-old), and road traffic accidents/drowning (in subjects >1-year-old). Behaviours, risk factors and environments most likely to contribute to fatal injuries are discussed. Our study highlights the role of forensic pathologists and medico-legal death investigators who identify the causes and circumstances surrounding these deaths. The research results may help from an epidemiological perspective to implement age-specific preventive strategies.

Medico-legal scene investigation in the case of burned bodies - a systematic review.

A judicial on-site examination is essential for the correct analysis of a forensic case, particularly when there has been a fatal fire, as heat-related changes to bodies make identification by the forensic pathologist and other specialists difficult along with estimating the post-mortem interval and determining the precise cause and manner of death. We systematically reviewed all relevant articles dating from 2003 to 2022 in the PubMed database with a view to updating recommendations on how best to proceed. Our recommendations highlight the importance of a multidisciplinary team approach involving various forensic specialists.

Nonossifying Fibroma Involving Epiphysis of Long Bone-Case Report and Review of the Literature.

Nonossifying fibroma (NOF) is a common benign bone neoplasm and is usually observed in the first 2 decades of life. Most NOFs occur in the metaphysis of long bones of the lower extremities and migrate toward the diaphysis during skeletal maturation. Epiphyseal involvement by NOF has been rarely reported, with only one case found in the English literature. The authors report the second case of NOF involving the epiphysis of a long bone, the proximal tibia of a 21-year-old woman. Clinicians and pathologists should be aware of the rare possibility of epiphyseal involvement of long bones by this condition. Pathologists should select appropriate immunohistochemistry markers to rule out alternative diagnoses.

Genomic landscape of clinically advanced KRAS wild-type pancreatic ductal adenocarcinoma.

Introduction: KRAS mutation is a common occurrence in Pancreatic Ductal Adenocarcinoma (PDA) and is a driver mutation for disease development and progression. KRAS wild-type PDA may constitute a distinct molecular and clinical subtype. We used the Foundation one data to analyze the difference in Genomic Alterations (GAs) that occur in KRAS mutated and wild-type PDA. Methods: Comprehensive genomic profiling (CGP) data, tumor mutational burden (TMB), microsatellite instability (MSI) and PD-L1 by Immunohistochemistry (IHC) were analyzed. Results and discussion: Our cohort had 9444 cases of advanced PDA. 8723 (92.37%) patients had KRAS mutation. 721 (7.63%) patients were KRAS wild-type. Among potentially targetable mutations, GAs more common in KRAS wild-type included ERBB2 (mutated vs wild-type: 1.7% vs 6.8%, p <0.0001), BRAF (mutated vs wild-type: 0.5% vs 17.9%, p <0.0001), PIK3CA (mutated vs wild-type: 2.3% vs 6.5%, p <0.001), FGFR2 (mutated vs wild-type: 0.1% vs 4.4%, p <0.0001), ATM (mutated vs wild-type: 3.6% vs 6.8%, p <0.0001). On analyzing untargetable GAs, the KRAS mutated group had a significantly higher percentage of TP53 (mutated vs wild-type: 80.2% vs 47.6%, p <0.0001), CDKN2A (mutated vs wild-type: 56.2% vs 34.4%, p <0.0001), CDKN2B (mutated vs wild-type: 28.9% vs 23%, p =0.007), SMAD4 (mutated vs wild-type: 26.8% vs 15.7%, p <0.0001) and MTAP (mutated vs wild-type: 21.7% vs 18%, p =0.02). ARID1A (mutated vs wild-type: 7.7% vs 13.6%, p <0.0001 and RB1(mutated vs wild-type: 2% vs 4%, p =0.01) were more prevalent in the wild-type subgroup. Mean TMB was higher in the KRAS wild-type subgroup (mutated vs wild-type: 2.3 vs 3.6, p <0.0001). High TMB, defined as TMB > 10 mut/mB (mutated vs wild-type: 1% vs 6.3%, p <0.0001) and very-high TMB, defined as TMB >20 mut/mB (mutated vs wild-type: 0.5% vs 2.4%, p <0.0001) favored the wild-type. PD-L1 high expression was similar between the 2 groups (mutated vs wild-type: 5.7% vs 6%,). GA associated with immune checkpoint inhibitors (ICPIs) response including PBRM1 (mutated vs wild-type: 0.7% vs 3.2%, p <0.0001) and MDM2 (mutated vs wild-type: 1.3% vs 4.4%, p <0.0001) were more likely to be seen in KRAS wild-type PDA.

In vitro and in vivo degradation correlations for polyurethane foams with tunable degradation rates.

Polyurethane foams present a tunable biomaterial platform with potential for use in a range of regenerative medicine applications. Achieving a balance between scaffold degradation rates and tissue ingrowth is vital for successful wound healing, and significant in vivo testing is required to understand these processes. Vigorous in vitro testing can minimize the number of animals that are required to gather reliable data; however, it is difficult to accurately select in vitro degradation conditions that can effectively mimic in vivo results. To that end, we performed a comprehensive in vitro assessment of the degradation of porous shape memory polyurethane foams with tunable degradation rates using varying concentrations of hydrogen peroxide to identify the medium that closely mimics measured in vivo degradation rates. Material degradation was studied over 12 weeks in vitro in 1%, 2%, or 3% hydrogen peroxide and in vivo in subcutaneous pockets in Sprague Dawley rats. We found that the in vitro degradation conditions that best predicted in vivo degradation rates varied based on the number of mechanisms by which the polymer degraded and the polymer hydrophilicity. Namely, more hydrophilic materials that degrade by both hydrolysis and oxidation require lower concentrations of hydrogen peroxide (1%) to mimic in vivo rates, while more hydrophobic scaffolds that degrade by oxidation alone require higher concentrations of hydrogen peroxide (3%) to model in vivo degradation. This information can be used to rationally select in vitro degradation conditions that accurately identify in vivo degradation rates prior to characterization in an animal model.

Double Suicide Due to the Ingestion of Levamisole-Adulterated Cocaine: Case Report and Review of the Literature.

Suicide is a major public health issue and the risk of attempting and committing suicide increases with age. We present the case of an elderly couple who decided to commit suicide together by self-poisoning using levamisole-adulterated cocaine. The choice of committing a double suicide, the method selected (self-poisoning), the drug self-administered (cocaine), and the route of administration (ingestion) are events rarely encountered in the forensic pathology practice, especially not in combination. In this article, we will review the literature regarding the frequency and features of these methods of suicide. An overview of the effects and mechanism of action of levamisole is also provided, highlighting the importance of including this substance and its metabolites in the routine toxicological analyses for cocaine deaths.

Simon's sign: Case report and review of the literature.

Hanging is a common method of suicide and multiple autopsy findings can be observed at the postmortem examination. Simon's sign is a haemorrhage into the anterior aspect of the intervertebral discs of the lumbar region that can be observed in hangings and other traumatic causes of death. This finding is considered evidence of vitality. Several mechanisms have been proposed regarding bleeding development. In this paper, we present a case of hanging in which Simon's sign was observed at the autopsy. A review of the literature regarding Simon's bleeding has been performed, and a discussion of the potential mechanism is reported. Although Simon's sign may be observed in hangings, a careful evaluation of all the available data, including investigation, autopsy findings, and toxicology, is mandatory to avoid misinterpretation of death's cause and manner.