Clinicopathological Characteristics of Cancer-Associated Venous Thromboembolism (CAT-VTE) from a Medicolegal Autopsy.

Objective: This study aimed to determine the clinicopathological characteristics of cancer-associated venous thromboembolism (CAT-VTE). Methods: A total of 47 cases of lethal pulmonary thromboembolism (PTE) with active cancer were investigated by autopsy records. Results: We studied 22 men and 25 women who were deceased at a mean age of 66±11 years. Nine (19%) patients had recently undergone cancer resection, 14 (30%) were undergoing clinical treatment for cancer, and 24 (51%) were autopsy-proven CAT-VTE. The colon (eight cases), lungs (seven cases), and ovaries (six cases) were frequent sites of a tumor. There were 29 (62%) cases of acute PTE and 18 (38%) of recurrent PTE. The embolic source was detected in 36/39 (92%) cases. Among them, 33 cases were leg deep vein thrombosis (DVT) and 31 were calf-type DVT. Three cases were isolated vena cava thrombi that were present near the tumor. Twenty-three (64%) cases were recurrent DVT. Conclusion: Most of the lethal CAT-VTE cases were induced by the same mechanism as non-CAT-VTE that originated from calf-type DVT with proximal propagation. However, the finding that patients had tumor-related vena cava thrombi suggested that prevention of CAT-VTE requires individualized treatment of patients according to their pathological condition. (This is secondary publication from Jpn J Phlebol 2020; 31(3): 123-129.).

Intracranial vertebral artery dissection resulting in fatal subarachnoid hemorrhage: clinical and histopathological investigations from a medicolegal perspective.

OBJECT: Subarachnoid hemorrhage (SAH) due to a ruptured intracranial vertebral artery (VA) dissection sometimes results in a sudden fatal outcome. The authors analyzed the relationship between clinical features and histopathological characteristics among fatal cases to establish valuable information for clinical diagnostics and prophylaxis. METHODS: This study included 58 medicolegal autopsy cases of ruptured intracranial VA dissection among 553 fatal nontraumatic cases of SAH that occurred between January 2000 and December 2007. Their clinical features were obtained from autopsy records. Histopathological investigations were performed on cross-sections obtained from all 4-mm segments of whole bilateral intracranial VAs and prepared with H & E and elastica van Gieson staining. RESULTS: The autopsy cases included 47 males and 11 females, showing a marked predilection for males. The mean age was 46.8 +/- 7.7 years, with 78% of the patients in their 40s or 50s. Hypertension was the most frequently encountered history; it was found in 36% of cases from clinical history and in 55% of cases based on autopsy findings. Prodromal symptoms related to intracranial VA dissections were detected in 43% of patients. Headache or neck pain lasting hours to weeks was a frequent complaint. Of patients with prodromal symptoms, 44% had consulted doctors; however, in none of these was SAH or intracranial VA dissection diagnosed at a preventable stage. Autopsy revealed fusiform aneurysms with medial dissecting hematomas. Apart from ruptured intracranial VA dissection, previous intracranial VA dissection was detected in 25 cases (43%); among them, 10 showed previous dissection of the bilateral intracranial VAs. The incidence of prodromal symptoms (60%) among the patients with previous intracranial VA dissection was significantly higher than that (30%) among cases without previous dissection (chi-square test; p = 0.023). Most previous intracranial VA dissections formed a single lumen resembling nonspecific atherosclerotic lesions, with the exception of 3 cases (12%) with a double lumen. CONCLUSIONS: Intracranial VA dissection resulting in fatal SAH frequently affects middle-aged men with untreated hypertension. Related to the high frequency of prodromal symptoms, latent previous intracranial VA dissection was histopathologically detected. Furthermore, intracranial VA dissection tends to induce multiple lesions affecting both intracranial VAs recurrently. This suggests the importance of an awareness of sustained whole intracranial VA vulnerability for the prevention of recurrence. The incidence of prodromal symptoms was significantly higher among patients with previous intracranial VA dissections. Thus, earlier diagnosis of intracranial VA dissections at the unruptured stage is desirable for prophylaxis against fatal SAH.

Ruptured Syphilitic Aneurysm: A Cause of Sudden Death in a Man with Human Immunodeficiency Coinfection.

Syphilis, a sexually transmitted infection caused by the bacterium Treponema palladium, is experiencing a worldwide resurgence. The risk of syphilis infection is particularly high in men who have sex with men (MSM), especially those who are human immunodeficiency virus (HIV)-positive. Untreated syphilis can lead to rare but severe late-stage complications, including syphilitic aortitis. Herein, we present an autopsy case of a ruptured thoracic aneurysm that resulted from an undetected case of syphilitic aortitis in an HIV-positive Japanese MSM with undiagnosed syphilis. Although no syphilitic skin lesions were observed on the body, anatomical changes consistent with a syphilitic etiology were present at the site of the rupture, including medial aortic scarring with "tree-bark"-like atherosclerotic plaque. In addition, heart blood was positive for T. palladium in a latex agglutination test. This case highlights for forensic pathologists the importance of recognizing syphilis as a possible underlying cause of sudden death among HIV-positive MSM.

An autopsy case of pulmonary artery intimal sarcoma: detailed observation of tumor and its related lesions in pulmonary arteries.

We report an autopsy-proven case of a 33-year-old man who died of intimal sarcoma of the pulmonary artery. A large mass (5×4 cm) occluded the main and bilateral pulmonary arteries. Tumor cell morphology was consistent with that of undifferentiated pleomorphic sarcoma. Comprehensive histological observation of 18 pulmonary arteries from proximal to distal revealed continuous extension of the tumor from the main to the subsegmental arteries along the intima, forming an arteriosclerosis-like intimal thickening. Distal small arteries were also affected by eccentric intimal thickening or recanalization. Lung parenchyma was not involved, although there were two wedge-shaped small pulmonary infarctions caused by tumorous obstruction of the associated arteries. Histological results indicated that the intimal sarcoma in the pulmonary artery, which appeared occlusive with growth limited to the proximal artery, had in fact already spread more peripherally than expected. Both the proximal lesions and the distal small arteries were affected by peripheral tumor emboli or by pulmonary hypertension induced by the proximal tumor. However, as seen in this case, most of the occlusive tumor was located locally and intraluminally, in the proximal artery, and removing the proximal tumor by pulmonary endarterectomy was considered effective for symptomatic improvement.

Abdominal Stab Wounds with Tension Pneumopericardium Confirmed by Autopsy and Postmortem Computed Tomography.

We present the first report of pneumopericardium observed by autopsy and on postmortem computed tomography (PMCT) images. The subject was a woman who died of self-inflicted stab wounds to the abdomen. The PMCT scan revealed air in the pericardial sac, a "flattened heart" sign, and retroperitoneal hemorrhage. Medicolegal autopsy revealed two abdominal stab wounds near the xiphoid process that had cut the apical pericardium and adjacent diaphragm and liver. Examination of the open thorax confirmed that the pericardial sac was distended with air. The wound extended to the abdominal aorta, causing retroperitoneal hemorrhage. PMCT images showed that the pneumopericardial volume was 133 mL. We believe that cardiac tamponade occurred resulting from the tension pneumopericardium; however, the effects were mitigated by hypovolemia secondary to the retroperitoneal hemorrhage as well as obstructive shock. Therefore, the cause of death appears to have been low-pressure cardiac tamponade.

Pulmonary thromboembolism: overview and update from medicolegal aspects.

Pulmonary thromboembolism (PTE) has recently been the focus of research, with special attention to its clinical and medicolegal aspects. Deep vein thrombosis (DVT) is an important embolic source of PTE. We review the epidemiology, autopsy findings, pathophysiology, and clinical issues related to PTE and DVT in Japan based on our autopsy cases at the Tokyo Medical Examiner's Office.

Non-traumatic rupture of the intracranial vertebral artery of a man found dead in a severe car accident - histopathological differentiation by step-serial sections.

A 58-year-old male with untreated hypertension was found dead in his car after a traffic accident on his way to the office. Emergency head CT showed diffuse subarachnoid hemorrhage at cerebral base. On autopsy examination, traumatic injuries were seen on his face and lower extremities. The skull was not fractured and there were no brain contusions except subscalp bleeding at the frontal head. The brain weighed 1510g and showed diffuse subarachnoid hemorrhage due to a rupture of the left vertebral artery (VA). Histopathological examination using serial step sections of every 0.1mm of the whole VA revealed multiple arterial dissections (AD) with fresh and old states at bilateral VA. Previous dissections at the basilar artery and internal carotid artery were also observed. The symptoms that he reported a week before the accident, left sided headache and shoulder pains, could have come from previous dissections. We concluded that the AD occurred while driving and was the cause of death, with the car accident then being caused by the stroke. Other specific histopathological findings were medial degeneration and serrate changes of the internal elastic lamina which resembled lesion of the segmental arterial mediolysis. These would suggest a pathogenesis of intracranial AD. Differential diagnosis of subarachnoid hemorrhage from the ruptured VA, distinguishing between idiopathic AD and traumatic trilaminar rupture, is still a difficult matter in forensic autopsy. However, this serial step sections procedure could be useful for the morphological differentiation.

Severe brainstem compression by an unruptured giant vertebral aneurysm--an autopsy case.

We describe an autopsy case of sudden unexpected death due to severe brainstem compression by an unruptured giant vertebral aneurysm. A 71-year-old male was found dead in his bedroom. The forensic autopsy revealed no severe trauma leading to his death. On internal examination, a giant intracranial aneurysm (3.4 x 2.6 x 2.7 cm) was observed on the trunk of the right vertebral artery. The aneurysm compressed the right side of the lower one-third of the pons and adjacent medulla oblongata. On sectioning, almost all of the aneurysm lumen was filled with a firm, clearly laminated organized thrombus. There was no evidence of subarachnoid hemorrhage. Histopathological analyses revealed congestion and hypoxic tissue changes in all organs examined. In microscopic sections of the giant vertebral aneurysm, thick fibrotic walls, intimal hyperplasia and organized thrombi in the lumen were found. Lots of intrathrombotic clefts with fresh erythrocytes were also observed. Moreover, Elastica van Gieson staining revealed fragmentation and disruption of the intimal elastic lamina in the aneurysmal wall. Collectively, we considered that some triggers in his daily life, including head rotation, might have caused the rapid onset of respiratory disturbance due to severe brainstem compression by a giant vertebral aneurysm.

[Significance of the soleal vein for the pathogenesis of deep vein thrombosis leading to acute massive pulmonary thromboembolism].

Prophylaxis of deep vein thrombosis (DVT) is a serious matter as the source of pulmonary thromboembolism (PTE) in hospitalized patients. Leg DVT is classified into three groups: iliac, femoral and calf types. Among them, calf type DVT is closely connected with PTE. Especially, soleal vein is the most frequent site of thrombi formation occurring with venous stagnation. Although most cases of soleal vein thrombosis are resolved soon without specific treatments: in around 20% of cases the thrombosis propagates to the proximal drainage vein as float thrombi e.g. from peroneal vein and posterior tibial vein to popliteal vein. Thereafter, the organization of thrombi leads to venous valve insufficiency, so-called postthrombotic syndrome. As a result, it worsens blood stagnation and induces recurrent thrombi formation. The broad prophylaxis of DVT in the soleal veins for inpatients is the most important point in the initial stage of hospitalization.

Pathophysiology of Venous Thromboembolism with Respect to the Anatomical Features of the Deep Veins of Lower Limbs: A Review.

Here the pathophysiology of venous thromboembolism is reviewed with respect to the anatomical features of the deep veins of lower limbs. A thrombus is less likely to form in the thigh veins compared with that in the calf veins; however, clinical symptoms are more likely to appear in the thigh veins owing to vascular occlusion. When a patient is bedridden, thrombosis is more likely to occur in the intramuscular vein, which mainly depends on muscular pumping and the venous valve, rather than in the three crural branches, which mainly depends on the pulsation of the accompanying artery. Thrombi are prone to be generated in the soleal vein compared with those in the gastrocnemius vein because of the vein and muscle structures. A soleal vein thrombosis grows toward the proximal veins along the drainage veins. To prevent a sudden pulmonary thromboembolism-related death in bedridden patients, preventing soleal vein thrombus formation and observing the thrombus proximal propagation via the drainage veins are clinically important. When deep vein thrombosis occurs, avoiding embolization and sequela caused by the thrombus organization is necessary.

Clinical Significance of the Soleal Vein and Related Drainage Veins, in Calf Vein Thrombosis in Autopsy Cases with Massive Pulmonary Thromboembolism.

OBJECTIVE: To clarify the histopathological characteristics of deep vein thrombosis (DVT) resulting in lethal pulmonary thromboembolism (PE). SUBJECTS AND METHODS: We investigated 100 autopsy cases of PE from limb DVT. The distribution and chronology of DVT in each deep venous segment were examined. Venous segments were classified into three groups: iliofemoral vein, popliteal vein and calf vein (CV). The CV was subdivided into two subgroups, drainage veins of the soleal vein (SV) and non drainage veins of SV. RESULTS: Eighty-nine patients had bilateral limb DVTs. CV was involved in all limbs with DVT with isolated calf DVTs were seen in 47% of patients. Fresh and organized thrombi were detected in 84% of patients. SV showed the highest incidence of DVTs in eight venous segments. The incidence of DVT gradually decreased according to the drainage route of the central SV. Proximal tips of fresh thrombi were mainly located in the popliteal vein and tibioperoneal trunk, occurring in these locations in 63% of limbs. CONCLUSIONS: SV is considered to be the primary site of DVT; the DVT then propagated to proximal veins through the drainage veins. Lethal thromboemboli would occur at proximal veins as a result of proximal propagation from calf DVTs.

Histopathological study of pulmonary arteries in 14 autopsy cases with massive pulmonary thromboembolism.

As the pathological features of acute massive pulmonary thromboembolism (PTE) remain unclear, early diagnosis is difficult. We examined 14 autopsy cases of sudden death by massive PTE. Eight cases were male and six female, with a mean age of 57+/-18 years. While none of the cases were diagnosed with PTE during their lifetime, 12 cases had predicting factors for thrombosis. Deep vein thrombosis was found at autopsy in 11 cases. Cross sections of each segmental pulmonary artery were dissected for histological examination. The distribution of fresh thrombi and organized thrombi in the pulmonary arteries was investigated. Results revealed that 13 cases contained both fresh and organized thrombi. More detailed examination indicated that as the organized thrombi were spread in all lobes, the distribution of thrombi extended from the proximal to peripheral arteries. Our findings indicated that most cases of fatal PTE had a subclinical recurrent history. Thus, proper diagnosis and treatment of prior emboli may be vital for the prophylaxis of sudden death by PTE.

Pathomorphological differentiation between traumatic rupture and nontraumatic arterial dissection of the intracranial vertebral artery.

We aimed to establish an objective indicator for differential diagnosis between traumatic rupture of the intracranial vertebral artery (TRIVA) and nontraumatic rupture from intracranial vertebral artery dissection (NIVAD). We investigated 19 intracranial vertebral artery (IVA) samples, including three from TRIVA, seven from NIVAD and nine non-IVA rupture cases using 0.2-mm serial histological sections through the IVA. The internal elastic lamina (IEL)-adventitia ratio for each slide was calculated as the ratio of the traced length of the adventitia to the length of the IEL as measured by digital photomicrography. NIVAD cases showed a significant peak in the IEL-adventitia ratio around the area of rupture, whereas TRIVA and non-rupture cases showed no specific increase or decrease in IEL-adventitia ratios throughout the IVAs. All NIVAD cases had a significantly higher average IEL-adventitia ratio across 10 slides at the site of the rupture lesion than at the site furthest from the rupture. In contrast, two out of three TRIVA cases showed no significant difference between the two points. The other TRIVA case showed a significantly lower IEL-adventitia ratio at the point nearest the rupture compared with that at the point farthest from the rupture. Other histological characteristics considered specific to either TRIVA or NIVAD were observed. Our results indicate that measuring and comparing IEL-adventitia ratios at ruptured and non-ruptured sites of the IVA could be a useful practical indicator for differential diagnosis between TRIVAs and NIVADs.

Pathomorphometry of ruptured intracranial vertebral arterial dissection: adventitial rupture, dilated lesion, intimal tear, and medial defect.

OBJECT: Subarachnoid hemorrhage (SAH) due to ruptured intracranial vertebral artery (VA) dissection is a life-threatening disease. Angiographic and symptomatic prognostic factors for rupture and rerupture have been investigated, but the pathological characteristics have not been fully investigated. The authors aimed to investigate these features by performing a pathomorphometic study of ruptured intracranial VA dissections. METHODS: This study included 50 administrative autopsy cases of fatal SAH due to ruptured intracranial VA dissection among 517 fatal nontraumatic cases of SAH occurring between March 2003 and May 2011. Pathomorphometry was performed using serial 5-µm histological cross-sections with elastica van Gieson staining from each 0.2-mm segment around the ruptured intracranial VA. The longitudinal lengths of 4 types of vascular lesions-adventitial ruptures, dilated lesions where the internal elastic lamina (IEL) was ruptured with adventitial extension, intimal tears where the IEL was ruptured, and medial defects-were calculated based on the numbers of the slides in which these lesions were continuously detected (minimum 2 adjoining slides). The distance from the vertebrobasilar junction to the center of adventitial rupture was also calculated in 37 cases. RESULTS: All cases showed one adventitial rupture with a mean length of about 1.9±1.1 mm. The center of the adventitial rupture was located 5.0-26.8 mm (mean 14.6±5.5 mm) from the intracranial VA bifurcation. Adventitial ruptures existed in the centers of dilated lesions, where the adventitia was highly extended. Other vascular lesions were serially observed surrounding the adventitial rupture. The mean lengths of dilated lesions, intimal tears, and medial defects were 9.4±4.8 mm, 13.2±6.3 mm, and 15.6±7.2 mm, respectively. The lengths between proximal lesions and distal lesions from the center of the adventitial rupture for both medial defects and intimal tears were significantly longer at proximal lesions than at distal ones (chi-square test, p<0.01). CONCLUSIONS: Every ruptured intracranial VA dissection has a single point of adventitial rupture where the adventitia was maximally extended, so dilation appears to be a valuable predictive factor for hemorrhagic intracranial VA dissections. The adventitial ruptures were as small as 2 mm in length, and clinically detectable dilated lesions were about 9 mm in length. However, vascular vulnerability caused by IEL ruptures and medial defects existed more widely across a length of VA of 1.3-1.5 cm. Comparatively broader protection of the intracranial VA than the clinically detected area of dissection might be desirable to prevent rebleeding. Broader protection of proximal lesions than distal lesions might be effective from the viewpoint of site distribution of vascular lesions and blood flow alteration to the pseudolumen caused by the dissecting hematoma. Medial defects are the most widely seen lesions among the 4 types of vascular lesions studied. Medial degenerative disease, known as segmental arterial mediolysis, is suspected in the pathogenesis of intracranial VA dissections.

Segmental arterial mediolysis of varying phases affecting both the intra-abdominal and intracranial vertebral arteries: an autopsy case report.

We report an autopsy case of segmental arterial mediolysis (SAM) of various phases occurring in both the intracranial vertebral artery (IVA) and intra-abdominal arteries. The patient was a 70-year-old male found dead in his house. The cause of death was massive intra-abdominal hemorrhage owing to a ruptured right gastroepiploic artery. Histopathological examination revealed that there was a broad arterial dissection as long as 20 cm in the right gastroepiploic artery associated with SAM in the injurious phase. In addition, SAM in the reparative phase was observed as organized arterial dissections in the left gastric artery. Furthermore, SAM in the reparative phase was detected as an arterial dissection in the right IVA undergoing an organizing process. These three lesions were considered to have developed at different times. SAM occurring in both the intra-abdominal and intracranial vertebral arteries is extremely rare. This coincidence may provide a clue to the relationship between SAM and spontaneous IVA dissection.

Differential diagnosis between traumatic and nontraumatic rupture of the intracranial vertebral artery in medicolegal autopsy.

We attempted to establish histopathological identification between traumatic rupture and nontraumatic arterial dissection of the intracranial vertebral artery (IVA) resulting in subarachnoid hemorrhage (SAH). Step-serial observations of ruptured IVAs among four traumatic and 44 nontraumatic SAH patients were investigated. We found that the most specific characteristic for differentiation was the shape of the ruptured adventitia. Extension of the adventitia was clearly observed in nontraumatic cases. In contrast, traumatic cases showed transmural ruptures. Other specific characteristics were also detected. For traumatic cases, small incomplete tears of intima and media were frequently found; they formed oblique tears without adventitial extension. Fragmentized internal elastic lamina was also observed in traumatic cases. In contrast, previous arterial dissections were frequently confirmed in nontraumatic cases. Medial degenerations or defects were detected in all nontraumatic cases. In these cases, the peripheral lesion of the rupture was appeared as intimal tears at recessed vascular wall caused by medial defects. This suggested a relationship between medial lesions and pathogenesis of arterial dissections. These additional features were found in both ruptured and non-ruptured intracranial arteries. We concluded that histopathological investigation is a reliable method for differential diagnosis between traumatic and nontraumatic rupture of the IVA resulting in fatal SAH. These morphological differentiations could be valuable for medicolegal diagnosis.

Fatal vascular injury as a result of operations: experience of two surgery-related autopsies.

We experienced two autopsy cases of unexpected death during surgical operation. Case 1 was a 60-year-old male. Salvage esophagectomy was performed from the right side of the thrax. After dissection of the lymph node, blood pressure decreased suddenly. Emergency thoracotomy was done for diffuse hemothorax in the left thoracic cavity. The patient died despite aggressive hemostasis. Autopsy findings revealed that the operator dissected the left subclavian artery instead of the lymph nodes. Case 2 was a 60-year-old male with advanced thyroid cancer with pelvic metastasis. Surgical removal of the sacrum was attempted for pain relief. The operation was interrupted because of massive hemorrhage from the iliac veins. After the operation, the patient's left leg quickly became necrotic. Despite the bypass grafting from the right to the left femoral artery, the patient died of reperfusion injury. Autopsy revealed ligation of the left common iliac artery along with the accompanying vein. The leg necrosis was thought to have resulted from the vascular ligation. In these two cases, the demonstration and elucidation of the causes of deaths were required with medicolegal autopsies. However, it proved difficult to visualize the operated vessels in detail. In autopsy investigations related to surgical operations, detailed information of the clinical course is valuable and should be provided by the operators themselves, as well as being obtained from clinical charts.

Significance of the soleal vein and its drainage veins in cases of massive pulmonary thromboembolism.

In this report, we review the anatomical features of the crural veins and the importance of the soleal vein and its drainage veins for thrombi formation and propagation. The result of our investigation of 120 legs of 60 autopsy cases with fatal pulmonary thromboembolism showed that the soleal vein was the most frequent site of deep vein thrombosis, both for fresh and for organized thrombi. Furthermore, the detection rate of thrombi, both fresh and organized, showed that the most common site was in the soleal vein and then decreased progressively according to the drainage route of the soleal vein. Anatomical characteristics and physiological mechanisms play a major role in the occurrence and propagation of venous thrombi. Thus, an understanding of these features is essential for effective prophylaxis of venous thromboembolism.