Post mortem computed tomography is highly sensitive for pyelonephritis. A radiologic-pathologic correlation series.

Pyelonephritis is a potentially lethal disease occasionally encountered in the forensic setting. Post mortem computed tomography (PMCT) is an important investigative tool for the forensic pathologist. In particular, it may be used to document and screen disease prior to traditional autopsy methods. While the sensitivity and specificity of computed tomography for pyelonephritis is well studied in the antemortem clinical setting, the test characteristics of PMCT are not yet described in the forensic pathology literature. A series of all cases of fatal pyelonephritis identified at the Ontario Forensic Pathology Service, over the course of 1 year was studied. Radiologic, clinical and pathologic findings were reviewed. A fulsome autopsy, including histopathologic examination, was considered the gold standard for sensitivity and specificity calculations. A control group consisting of 16 cases without pyelonephritis (ex: opiate toxicity) in which both PMCT and histologic data were available by way of comparison. Sixteen cases of pyelonephritis were identified. Post mortem computed tomographical signs of pyelonephritis included asymmetric renal enlargement, perinephric fat stranding, and ectopic renal air. The most (57%) individually sensitive of these findings was perinephric fat stranding but sensitivity increased to 100% if any of the three signs were present. The control group analysis revealed the specificity of air asymmetry (81%), asymmetric renal enlargement (81%), and fat stranding (69%). PMCT findings may rule in a diagnosis of pyelonephritis, and should prompt the pathologist to grossly and microscopically examine the kidneys.

Tattoo visualization using cross-polarized lighting and infrared photography.

Identification of the deceased is a critical responsibility of the death investigation system. If visual identification is inconclusive, tattoos can provide secondary identification but may be difficult to visualize at various stages of decomposition. We describe the case of a 35-year-old male found submerged underwater by police after swimming at a pier. The decedent was last seen earlier that day. Signs of immersion including sodden hands, feet, and clothing, wet sand on the torso and legs, and heavy edematous legs were observed. The post-mortem blood alcohol concentration was 427 mg/100 mL; signs of recent traumatic injury were not present. The immediate cause of death was drowning as a consequence of ethanol intoxication. When pulled from the water, the decedent's shoulder tattoo was not visible. Cross-polarized lighting and infrared photography visualized the tattoo to help confirm identity. These photographic methods were compared to hydrogen peroxide and optical coherence tomography techniques and described in detail to assist with future cases.

Fatal secondary aortoduodenal fistula diagnosed with postmortem computed tomography angiography.

Secondary aortoduodenal fistula (AEF), although less rare than its primary form, is an uncommon and frequently lethal cause of gastrointestinal (GI) bleeding. We report a case of fatal GI hemorrhage in a woman with a remote history of endovascular graft repair of an abdominal aortic aneurysm. Postmortem examination included computed tomography (PMCT) and CT angiography (PMCTA), which revealed air in the aorta, loss of the fat plane between the aorta and duodenum, and direct extravasation of contrast from the aorta into the duodenum. To our knowledge, this is the first published report of secondary AEF diagnosed by PMCT and confirmed with PMCTA. We propose a set of imaging criteria by which PMCTA can be used to supplant traditional anatomical dissection in the medicolegal investigation of deaths due to AEF.

Lymphatic endothelial cancerization in papillary thyroid carcinoma: hidden evidence of lymphatic invasion.

We hypothesize that cystic structures in metastatic papillary thyroid carcinoma (PTC) develop along the framework of lymphatic channels. To investigate this phenomenon, different categories of PTC were immunostained for D2-40 and TTF1. In this study, reactivity for D2-40 was considered as positive when there is membranous staining as often seen in lymphatic endothelial cells. Thirty cases of PTC with lymph node metastasis or with potential for lymphatic invasion and 20 cases metastatic PTC in lymph nodes were reviewed and found to show double/mosaic immunoreactivity for TTF1/D2-40 in 40-100% of cases. PTC metastasis in lymph nodes with cysts and some branching lymphatic-like channels lined by follicular cells with or without nuclear features of PTC were diffusely reactive to TTF1, and focally to D2-40. For primary and metastatic PTC, focal membranous D2-40 reactivity was also demonstrated in cysts or cleft linings. For25 thyroid neoplasms with no known potential for lymphatic invasion, there was no such immunoreactivity. The mosaic or double immunoreactivity for TTF1/D2-40 suggests lymphatic cancerization and possible endothelial mimicry of follicular cells. Mosaic/double immunoreactivity is helpful to detect the hidden pattern of lymphatic invasion masquerading as 'benign-appearing' follicles and supports our hypothesis of malignant cells developing along the lymphatic framework.

A novel software program for detection of potential air emboli during cardiac surgery.

BACKGROUND: Risks associated with air emboli introduced during cardiac surgery have been highlighted by reports of postoperative neuropsychological dysfunction, myocardial dysfunction, and mortality. Presently, there are no standard effective methods for quantifying potential emboli in the bloodstream during cardiac surgery. Our objective was to develop software that can automatically detect and quantify air bubbles within the ascending aorta and/or cardiac chambers during cardiac surgery in real time. FINDINGS: We created a software algorithm ("Detection of Emboli using Transesophageal Echocardiography for Counting, Total volume, and Size estimation", or DETECTS™) to identify and measure potential emboli present during cardiac surgery using two-dimensional ultrasound. An in vitro experiment was used to validate the accuracy of DETECTS™ at identifying and measuring air emboli. An experimental rig was built to correlate the ultrasound images to high definition camera images of air bubbles created in water by an automatic bubbler system. There was a correlation between true bubble size and the size reported by DETECTS™ in our in vitro experiment (r = 0.76). We also tested DETECTS™ using TEE images obtained during cardiac surgery, and provide visualization of the software interface. CONCLUSIONS: While monitoring the heart during cardiac surgery using existing ultrasound technology and DETECTS™, the operative team can obtain real-time data on the number and volume of potential air emboli. This system will potentially allow de-airing techniques to be evaluated and improved upon. This could lead to reduced air in the cardiac chambers after cardiopulmonary bypass, possibly reducing the risk of neurological dysfunction following cardiac surgery.

Nested and microcystic variants of urothelial carcinoma displaying immunohistochemical features of basal-like urothelial cells: an immunohistochemical and histopathogenetic study.

Nested/microcystic (NV/MV) urothelial carcinoma (UC) variants are associated with mild cytologic atypia and commonly present at high-stage disease. The histopathogenesis is investigated using urothelial basal cell markers. Archival 14 NV/MV and three inverted papilloma (IP) were immunostained for CD44, cytokeratin 5 (CK5), CK34bE12 and p63. Twenty consecutive cases of invasive high-grade UC including 14 superficial and 6 muscle-invasive UC cases were used as control. Immunostaining was scored as high for staining of full or more than 50% thickness of the epithelial nest or epithelium and low for lesser immunoreactivity and negative reactivity. All 14 NV/MV, 3 IP and 6 control cases showed a high score of immunoreactivity for CK5, CD44, CK34bE12 and focally for p63. The remaining control cases showed a high score of immunoreactivity for CK34bE12, while negative or low for CK5, CD44 and p63. In conclusion, immunoreactivity CK5 and CD44 commonly immunostained NV/MV and some invasive high grade UC. Other basal cell markers (CK34bE12 and p63) appear to be non specific or non sensitive. NV and MV and some UC likely represent a subset of UC displaying immunohistochemical features of urothelial basal cells. They had tendency of endophytic growth and early invasion despite the innocuous cytologic appearance.

Incidental endometrial carcinoma diagnosed at first trimester pregnancy loss: a case report.

BACKGROUND: All cases reported to date of endometrioid endometrial adenocarcinoma (EEA) associated with pregnancy have been treated surgically or medically. We describe a case of EEA in pregnancy that was managed expectantly, allowing for observation of the natural course of the disease. CASE: A 36-year-old woman, gravida 2 para 1, presented at eight weeks of pregnancy with heavy vaginal bleeding. Ultrasound assessment confirmed a missed abortion, and the patient underwent dilatation and curettage. Tissue pathology primarily suggested grade 1 EEA. The patient chose expectant management. Eight months later, she returned with vaginal bleeding. Hysterectomy was performed and the hysterectomy specimen showed FIGO grade 1 stage 1A EEA. CONCLUSION: Treating EEA associated with pregnancy is challenging. Our experience in the case described here suggests that expectant management should not be undertaken due to a high risk of recurrence.

Contexte : Tous les cas signalés à ce jour d'adénocarcinome endométrial endométrioïde (AEE) associé à la grossesse ont fait l'objet d'une prise en charge chirurgicale ou médicale. Nous décrivons un cas d'AEE pendant la grossesse ayant fait l'objet d'une prise en charge non interventionniste, ce qui a permis l'observation de l'évolution naturelle de la maladie. Cas : Une femme de 36 ans, gravida 2 para 1, nous a consultés à huit semaines de grossesse en raison de saignements vaginaux abondants. L'évaluation échographique a confirmé la présence d'une rétention fœtale et la patiente a subi une dilatation-curetage. L'analyse pathologique des tissus a d'abord indiqué qu'il s'agissait probablement d'un AEE de grade 1. La patiente a alors choisi une prise en charge non interventionniste. Huit mois plus tard, elle nous a consultés à nouveau en raison de ses saignements vaginaux. Une hystérectomie a été menée et le spécimen d'hystérectomie indiquait la présence d'un AEE de stade 1A grade 1 FIGO. Conclusion : La prise en charge de l'AEE associé à la grossesse est complexe. Notre expérience dans le cas décrit aux présentes semble indiquer qu'une prise en charge non interventionniste ne devrait pas être mise en œuvre, en raison d'un risque élevé de récurrence.

Earth, Air, Water, and Fire: Histopathology of Environmental Death.

Interpretation of deaths in hostile environments may be informed by postmortem microscopic examination of injured tissues. In context with their macroscopic correlates, the commonly observed histologic changes seen in environmental deaths are reviewed-these include exposure (i.e., hypothermia and hyperthermia), fire, electrocution, and water. Rarely observed pathognomonic findings are highlighted. While it may not yield specific findings, microscopic examination is one of the necessary steps of a thorough postmortem examination.

Noninvasive Papillary Basal-like Urothelial Carcinoma: A Subgroup of Urothelial Carcinomas With Immunohistochemical Features of Basal Urothelial Cells Associated With a High Rate of Recurrence and Progression.

BACKGROUND: We investigated the clinical and pathologic significance of a subgroup of noninvasive papillary urothelial carcinomas (UCs) expressing reactivity to urothelial basal cell markers. DESIGN: In total, 302 consecutive cases of noninvasive papillary UC were evaluated immunohistochemically with cytokeratin 5 (CK5)/CD44. Any UC that was reactive for greater than 25% thickness of the urothelium was designated as basal-like urothelial carcinoma (BUC); remaining UC cases were designated as non-BUC. The follow-up period was up to 3 years. Historical review of UC was extended for up to 3 retrospective years. RESULTS: Among 302 noninvasive UC, BUC was identified in 33 of 256 (12.9%) low-grade UC and 8 of 46 (17%) high-grade UC (P=0.041). Immunoreactivity for CD44 was similar to that of CK5, but displayed weaker and more diffuse staining. CK20 was reactive in 9 cases, primarily high-grade BUC. Other basal cell markers (34bE12, p63, bcl2, and EP4) were found to be neither sensitive nor specific in detecting UC with high CK5 expression. In comparison with non-BUC, BUC was associated with increased multifocality, larger tumor size, higher recurrence rate, and more frequent upgrading and stage progression. In the follow-up period of 3 years, distant metastasis occurred in 6 cases of which 5 were in the BUC subgroup. CONCLUSIONS: Our results showed that noninvasive papillary BUC represents a small subset associated with increased risk of tumor recurrence and progression. The aggressive behavior is likely associated with basal-like features of BUC, as seen in carcinomas with basal cell features in other body sites.

Novel technique of sampling the urinary bladder for urothelial carcinoma specimens.

Sampling of the urinary bladder (UB) in radical cystectomy specimens is usually performed by obtaining sections through the lesions taken in rather random planes. The technique is hindered by the difficulty in identifying the anatomical relationship of the tumor with the remaining urinary bladder. Fifty radical cystectomy specimens were bisected in the horizontal plane at the middle portion of the UB then fixed without tissue stretching in 10% buffered formalin for at least 24 hours. The UBs were serially sectioned in parallel horizontal planes from the UB neck to the dome into rings of 3 to 10 mm thickness. The sections were orderly arranged and photographed. At least one ring of tissue was entirely submitted along with areas of interest or representative areas. Our proposed technique of transverse sections results in a mild increase in the number of sections submitted for microscopic examination. The advantages of our methods are (a) consistency and ease of sampling that help the microscopic-macroscopic correlation, (b) suitability for gross examination and for determining depth of invasion and largest tumor diameter, (c) improved identification of satellite lesions, and (d) suitability for neoplastic mapping and suitability for reexamination. The technique was validated by comparing with results of current technique.

Invasive urothelial carcinoma exhibiting basal cell immunohistochemical markers: A variant of urothelial carcinoma associated with aggressive features.

We characterize invasive urothelial carcinoma (UC) exhibiting urothelial basal cell immunohistochemical markers. Consecutive invasive UCs were immunostained with CK20 and urothelial basal cell markers, cytokeratin 5 (CK5)/CD44. Immunostaining for CK5 and CD44 was scored as follows: positive for staining of more than 25% thickness of the epithelial nest or epithelium and low for lesser immunoreactivity. Invasive urothelial carcinoma (UC) exhibiting positive CK5/CD44 staining was designated as basal-like UC (BUC). In this study, of 251 invasive UC (pT1 in 57% and pT2-4 in 43%), BUC accounted for 40% of cases (accounting for most pT2-4 UC) and often presented as non-papillary UC without previous history of UC. In addition, BUC exhibited uniform nuclei with lesser degree of atypia than non BUC and decreased or negative cytokeratin 20 reactivity. Nested and microcystic variants of UC immunohistochemically stained as BUCs. Invasive non-BUCs were often papillary with marked cytologic atypia and pleomorphism, and accounted for most pT1 UC. The rates of perivesical invasion, lymph node and distant metastases were higher for BUC than non-BUC. All nine cases with absent/minimal residual in situ UC in 102 radical cystectomy specimens were from invasive non-BUC. BUC is distinguished from non-BUC due to this aggressive behavior, distinct immunohistochemical profile, and predominant non-papillary architecture. Our findings are consistent with recent studies identifying a subtype of muscle-invasive UC with molecular expression of basal cell and luminal cell molecular profiles. Our study further supports categorizing invasive UCs into these subtypes with different biological behaviors, possibly contributing to better therapeutic strategies.

Three-dimensional cell groups with disordered nuclei and cellular discohesion (3DDD) are associated with high sensitivity and specificity for cystoscopic urine cytopathological diagnosis of low-grade urothelial neoplasia.

Cystoscopic urine obtained before the resection of low-grade urothelial carcinoma (LGUC), with adequate cytological sampling of the tumor, frequently revealed the presence of three-dimensional cell groups with disordered nuclei and cellular discohesion (3DDD). 936 cystoscopic urine specimens were categorized into five groups: Group 1 (80 specimens) with biopsy-proven LGUC within 6 months of cytologic examination, Group 2 (23 specimens) with biopsy proven LGUC within 6 to 36 months of cytologic examination, Group 3 (527 specimens) with a history of LGUC but no tumor for a period of greater than 3 years, Group 4 (300 specimens) with no association with LGUC, and Group 5 (6 specimens) with urinary lithiasis. Specimens with scant cellularity accounted for 20% of those in Group 1. For 3DDD in detecting LGUC in adequate cystoscopic urine, the sensitivity was 70%, specificity was 94%. Two- or three-dimensional cell groups with ordered nuclei and/or cellular non-discohesion were often seen in specimens from Groups 4 or 5. The 3DDD was present in a significant number of cases with concurrent negative cystoscopic findings but also positive LGUC in ensuing follow-up. In these cases, 3DDD with or without tumor identified at concurrent cystoscopy were found to be morphologically similar. Furthermore, the presence of 3DDD in 8% of Group 3 likely represents urothelial dysplasia that is not cystoscopically detectable. The high specificity and sensitivity of 3DDD is demonstrated. These findings are consistent with the decreased cell adhesion and disordered nuclear arrangement of low grade urothelial neoplasia.