Andrew S Williams’s research while affiliated with Nova Scotia Health Authority and other places

Blunt thoracic aortic injury (BTAI) resulting from cardiopulmonary resuscitation (CPR) is rarely reported and most reports are of aortic rupture. Clinical reports have also documented aortic dissection and intramural hematomas with sequential imaging showing the development of these aortic injuries after the administration of CPR, suggesting that non-transmural aortic injury may also result from CPR. We report partial separation of an aortic intimal atheromatous plaque as a component injury in a case with multiple complications of manual CPR. A 74-year-old male presented to the emergency room (ER) with a 2-day history of chest pain. While in the ER, he suffered witnessed cardiac arrest and resuscitative attempts were pursued for 60 min prior to declaring death. At autopsy, there were numerous injuries attributable to CPR, including bilateral rib fractures, sternal fracture, retrosternal and mediastinal hemorrhage, epicardial ecchymoses, and ruptured pericardium. There was a perforated inferior wall myocardial infarct with a large left hemothorax. There was partial separation/laceration of an intimal atheromatous plaque on the anterior wall of the ascending aorta proximal to the origin of the brachiocephalic artery, forming a triangular flap, without associated intramedial dissection or hematoma. There was no thrombus formation, effectively excluding existence of the laceration prior to circulatory arrest. This aortic injury provides pathologic confirmation of non-transmural BTAI definitively sustained during manual CPR. Pathologists and clinicians alike should be cognizant of the possibility of BTAI resulting from CPR, which may manifest the full range of severity from intimal tear through aortic rupture.

ALK gene rearrangements are identified in 2–5 % of all non-small cell lung cancer and are more common in lifetime non-smokers with adenocarcinoma, but the prevalence of ALK rearrangements is not as well characterized in long-term ex-smokers (quit >10 years prior to diagnosis). Accurate and timely diagnosis of ALK-rearranged tumors is of clinical importance given the remarkable response to targeted inhibitors. ALK gene rearrangement may be detected by fluorescence in situ hybridization (FISH), and abnormal expression of ALK protein may be detected by immunohistochemistry (IHC), the latter of which is faster and less expensive. The aim of this study is to evaluate the prevalence of ALK rearrangement in non-smokers and long-term ex-smokers with lung adenocarcinoma and to assess the performance of IHC for the detection of ALK+ tumors when compared to FISH. Two hundred fifty-one cases of resected lung adenocarcinoma were retrospectively reviewed, including non-smokers (n = 79) or long-term ex-smokers (n = 172). ALK IHC and ALK FISH were performed on each case. Four cases demonstrated ALK rearrangement by FISH (4/251; 1.6 %). All cases were non-smokers (4/79; 5.1 %), and all were positive for ALK by IHC. No additional cases were considered positive by IHC, and only 26 (10.4 %) cases were considered equivocal using a conservative approach to interpretation, resulting in a sensitivity of 100 % and specificity of 89.5 %. ALK rearrangement was not observed in lung adenocarcinoma arising in long-term ex-smokers, whereas it is seen in up to 5.1 % of lifetime non-smokers. ALK IHC using the 5A4 antibody demonstrates high sensitivity, supporting its use as a screening test.

OCT4 and SALL4 are transcription factors within a complex network that functions to maintain pluripotency in primitive stem cells and germ cells. Nuclear expression of OCT4 is widely cited as sensitive and specific for primary and metastatic germ cell tumors and is commonly used in the diagnosis of central nervous system (CNS) germinomas. Studies have failed to systematically examine the expression of OCT4 or SALL4 in diffuse large B-cell lymphoma (DLBCL), although this entity enters the morphologic differential diagnosis of some germ cell tumors. A retrospective review was conducted on 145 consecutive cases of DLBCL and testicular lymphoma to evaluate the prevalence of OCT4 and SALL4 expression. Nuclear OCT4 expression was present in 2/11 (18%) testicular DLBCLs and 6/134 (4.5%) nontesticular DLBCLs. Most OCT4 cases demonstrated moderate to strong expression in >50% of neoplastic cells. Rare, weak nuclear SALL4 expression was detected in only 3 nontesticular DLBCLs. Within the extratesticular DLBCL group, 2/6 (33%) primary CNS DLBCLs expressed nuclear OCT4. In addition, OCT4 DLBCL showed an overall predilection toward non-germinal center B-cell phenotype (7/8; 88%) and had a higher than expected rate of CD5 coexpression (4/8, 50%). These results are cautionary against using OCT4 as a sole marker of germ cell differentiation in testicular and extratesticular sites, especially in the CNS. The apparent associations of OCT4 expression with primary CNS DLBCL, non-germinal center B-cell phenotype, and CD5 coexpression raise the question of whether OCT4 expression in DLBCL may reflect more aggressive biology.

Aortoenteric fistula (AEF) is an uncommon source of upper gastrointestinal (GI) tract hemorrhage, commonly occurring in persons with previous aortic surgery. Non-surgery related AEFs (primary AEFs) may occur in association with atherosclerotic lesions, infections, malignancies, or, rarely, result from penetrating/eroding foreign bodies. Given its rarity, primary AEF is not commonly considered in the pathologist's preliminary list of differential diagnoses at the commencement of an autopsy; however, the use of postmortem cross-sectional imaging may allow for the identification of primary AEF as a reasonable differential diagnoses prior to conventional autopsy. The current case outlines the forensic presentation, postmortem computed tomography (PMCT) features, and autopsy findings of a recent case of primary AEF resulting in lethal gastrointestinal hemorrhage. In such cases, PMCT features supporting primary AEF as the underlying cause of death include an atherosclerotic aneurysm abutting a segment of the GI tract with no definite soft tissue plane of separation, luminal GI contents of similar radiographic density to the aortic contents, lack of previous aortic surgery, and lack of a competing explanation for GI hemorrhage or a competing cause of death. Deaths from massive enteric hemorrhage without a medical history to suggest an underlying cause for the hemorrhage would fall under medicolegal jurisdiction and may, by examination of scene and circumstances alone, initially seem suspicious. This case demonstrates how PMCT could be used by a team of expert forensic radiologists and forensic pathologists to rapidly feedback vital information on the cause and manner of death to the criminal justice system.

Objectives: A variety of tissue-marking dye (TMD) colors can be used to indicate surgical pathology specimen margins; however, the ability of pathologists to differentiate between specific microscopic margin colors has not been assessed systematically. This study aimed to evaluate pathologists' accuracy in identifying TMD color and determine the least ambiguous combinations of colors for use in surgical pathology. Methods: Seven colors of TMD were obtained from three manufacturers and applied to excess formalin-fixed uterine tissue. Study blocks contained multiple tissue pieces, each marked with a different color from the same manufacturer. Slides were assessed by eight participants for color and color distinctness of each piece of tissue. Results: Black, green, red, and blue TMDs were accurately identified by most participants, but participants had difficulty identifying violet, orange, and yellow TMDs. Black, green, and blue TMDs were most commonly rated as "confidently discernable." Conclusions: Pathologists have difficulty identifying and distinguishing certain colors of TMDs. The combined use of certain colors of TMDs (yellow/orange/red, blue/violet, and red/violet) within the same specimen should be avoided to decrease the risk of inaccurately reporting specimen margins.

Pathology specimens often contain important margins that must be identified from specimen grossing through to microscopic examination. Commonly, unique colors of tissue marking dye (TMD) are applied to each margin, which facilitates both macroscopic and microscopic identification. Various techniques have been described, but color endurance and fidelity of TMDs through special tissue processing has not been addressed. To evaluate the performance of various TMDs through decalcification and immunohistochemistry (IHC) protocols. Methods: Samples of TMDs from two manufacturers and acrylic artists' inks were obtained in seven colors and applied to excess non-diagnostic surgical pathology tissue. Tissues were subjected to a decalcification protocol or directly processed in a routine fashion. The presence and color of TMD or ink was assessed on routine H&E sections and following IHC. Of the colors that reliably survived routine processing, loss of color and color change following decalcification and IHC protocols was seen with one manufacturer's product. TMD may lose or change its color through special tissue processing. This previously unreported artifact may lead to potentially serious errors in margin assessment and reporting. Laboratories should evaluate TMDs and inks through routine processing, decalcification, and IHC protocols to ensure color endurance and fidelity. This article is protected by copyright. All rights reserved.

Microsatellite instability (MSI) is a genetic feature of sporadic and familial cancers of multiple sites and is related to defective mismatch repair (MMR) protein function. Lynch syndrome (LS) is a familial form of MMR deficiency that may present with a spectrum of MSI positive cancers including gastrointestinal (GI) malignancies. The incidence of high level MSI (MSI-H) in colorectal carcinoma is well defined in both familial and sporadic cases and these tumours portend a better overall prognosis in colorectal carcinoma (CRC). There are certain morphological features that suggest MSI-H CRC and international guidelines have been established for the evaluation of MSI in CRC. The prevalence and morphological features of extracolonic GI MSI-H tumours are less well documented. Furthermore, it is unclear whether the guidelines for the assessment of MSI in CRC are appropriate for application to extracolonic GI malignancies. This review aims to summarise the recent literature on MSI in extracolonic LS-related GI tract malignancies with special attention to the assessment of the MMR system by evaluation of specific microsatellite markers and/or immunohistochemical evaluation of MMR protein expression. The reported prevalence of sporadic and LS-related MSI-H tumours along with their associated unique morphological patterns and related prognostic or therapeutic implications will be discussed.