BRCA1 and BRCA2 carriers with breast, ovarian and prostate cancer demonstrate a different pattern of metastatic disease compared with non-carriers: results from a rapid autopsy programme.

AIM: To catalogue and compare the pattern of metastatic disease in germline BRCA1/2 pathogenic mutation carriers and non-carriers with breast, ovarian and prostate cancer from a rapid autopsy programme. METHODS AND RESULTS: The number of metastases in the major body systems and the proportion of participants with metastases were documented in 50 participants (19 germline mutation carriers). Analysis was conducted on the participants' pattern of disease for the different cancers and mutation subgroups. The four commonly affected organ systems were the digestive (liver only) (82%), respiratory (76%), gastrointestinal (65%) and reticuloendothelial (42%). There were significant differences in the pattern of metastatic breast cancer in BRCA1/2 germline carriers compared with non-carriers. Breast cancer carriers had significantly fewer organ systems involved (median n = 3, range = 1-3) compared with non-carriers (median n = 9, range = 1-7) (P = 0.03). BRCA1/2 carriers with ovarian carcinomas had significantly more organ systems with metastatic carcinoma (median n = 10, range = 3-8) than non-carriers (median n = 5, range = 3-5) (P < 0.001). There were no significant differences in the number of involved systems in BRCA2 carriers compared with non-carriers with prostate cancer (P = 1.0). There was an absence of locoregional disease (6.5%) compared with distant disease (93.5%) among the three cancer subtypes (P < 0.001). The majority of metastatic deposits (97%) collected during the autopsy were identified by recent diagnostic imaging. CONCLUSION: Even though a major limitation of this study is that our numbers are small, especially in the breast cancer carrier group, the metastatic patterns of breast and ovarian cancers may be impacted by BRCA1/2 carrier status, suggesting that tumours derived from patients with these mutations use different mechanisms of dissemination. The findings may focus clinical diagnostic imaging for monitoring metastases where whole-body imaging resources are scant.

Suspension-associated dislocation of the jaw in hanging.

Hanging is a common type of death, and the role of the medical investigation of such deaths by a forensic pathologist not only requires the determination of the cause of death but providing information to assist in the determination of the manner of death. The forensic pathologist should be well versed in the spectrum of injuries known to be associated with neck compression, to document injuries known to be associated with hanging, but also to identify those that are inconsistent with self-inflicted hanging or that may suggest the involvement of a third party in the death. Comprehensive identification and correct interpretation of external and internal injury are crucial for the appropriate degree of police and coroner/medical examiner investigation. We present two cases of deaths believed to be caused by self-inflicted hanging that were observed to have unexpected unilateral dislocation of the temporomandibular joint identified on routine post-mortem computed tomography, without any evidence of involvement of a third party. This injury was unexplained and had not been previously observed at our Forensic Institute nor was it identified after a review of the published biomedical research literature. Issues regarding the cause of this abnormality, possible mechanisms, and the medicolegal significance of this finding will be discussed.

Marine mimicry is afoot.

It is a relatively common occurrence for forensic pathologists and anthropologists to be presented with what are believed to be human remains as part of their day-to-day practice. Despite this, the literature pertaining to such challenges is not extensive, and much knowledge of this is largely based on experience. As such, we present a case of what appeared to be a severed foot located on a beach, which examination revealed was a marine animal known as a sea squirt (ascidian). While marine scientists have been aware of such mimicry, to our knowledge, this has not been previously described in the forensic pathology literature. The external examination and post-mortem CT scan revealed the nonhuman nature of the remains, and an imminent police investigation was prevented, saving time and resources. Nonhuman remains may include animals and inorganic objects, and their discovery may invoke anxiety in the finder. A timely forensic pathology or anthropology examination will assist in alleviating such concern. Forensic pathologists and anthropologists should be prepared to face a variety of presented remains and objects.

Extensive subcutaneous needle fragment retention due to injecting drug use.

Deaths in those with a history of injecting drug use commonly come to the attention of forensic pathologists, and therefore, one must have knowledge of possible findings and hazards of performing autopsies in these cases. This case demonstrates the finding of extensive retained broken needles in the subcutis of the arms and femoral region in a man with a long history of injecting drug use. While few or single broken needles are not uncommonly encountered, the multiplicity of needles in this case is noteworthy. We have demonstrated the findings both radiologically with PMCT and by conventional autopsy.

Lethal hemorrhage from iliac vein rupture complicating inferior vena cava thrombosis demonstrated by post-mortem CT angiography.

Spontaneous iliac vein rupture is a rare cause of retroperitoneal hemorrhage that may present to the forensic pathologist. It has been reported in association with venous thrombosis, anatomical variants such as May-Thurner syndrome, and as a complication of a long-term indwelling IVC filter. It has a female predominance and most often occurs due to rupture of the left iliac vein. This is the first report of the use of post-mortem computed tomography (PMCT) and post-mortem computed tomography angiography (PMCTA) as an adjunct to a conventional autopsy to diagnose rupture of the left iliac vein causing retroperitoneal hemorrhage arising as a complication of an inferior vena cava (IVC) thrombus. We discuss the use of PMCTA as a useful tool in the diagnosis of vascular injury and how it can be used to assist the forensic pathologist. The use of PMCT with PMCTA is an invaluable adjunct to conventional autopsy to diagnose the site of vascular rupture.

Cutaneous squamous cell carcinoma associated with proliferation of osteoclast-like giant cells.

Proliferation of osteoclast-like giant cells in a cutaneous squamous cell carcinoma is a rare phenomenon and so far only four cases have been reported. In previous reports, osteoclast-like giant cells were admixed with sarcomatoid component of squamous cell carcinoma and it is therefore debatable if the osteoclast-like giant cells represent a reactive phenomenon or a part of the malignant tumour. A case of cutaneous squamous cell carcinoma associated with osteoclast-like giant cells is reported. However, sarcomatous component of squamous cell carcinoma was not identified in this case. Morphologically, the osteloclast-like giant cells appeared to be benign. The localization of the squamous cell carcinoma and the osteoclastic-like giant cells were separate from one another. Immunohistochemically, squamous cell carcinoma was positive for high molecular weight cytokeratin, cytokeratin-5 and p63, whereas the osteloclast-like giant cells were positive for histiocyte marker CD68 and vimentin and negative for epithelial markers supporting a reactive nature of osteoclast-like giant cells to the cutaneous malignancy.

Long QT molecular autopsy in sudden infant death syndrome.

OBJECTIVE: To describe experience of long QT (LQT) molecular autopsy in sudden infant death syndrome (SIDS). DESIGN: Descriptive audit from two distinct periods: (1) A prospective, population-based series between 2006 and 2008 ('unselected'). (2) Before and after 2006-2008, with testing guided by a cardiac genetic service ('selected'). LQT genes 1, 2, 3, 5, 6 and 7 were sequenced. Next of kin were offered cardiac evaluation. SETTING: New Zealand. PATIENTS: 102 SIDS cases. INTERVENTIONS: Nil. Main outcome measures Detection of genetic variants. RESULTS: Maori 49 (47%), and Pacific island 24 (23%), infants were over-represented. Risk factors were common; bed sharing was reported in 49%. Rare genetic variants were commoner within the selected than unselected populations (5 of 31 infants (16%) vs 3 of 71 infants (4%) p < 0.05). In the selected population two infants had variants of definite or probable pathogenicity (KCNQ1, E146K; KCNH2, R1047L), two had novel variants of possible pathogenicity in SCN5A (I795F, F1522Y) and one had R1193Q in SCN5A, of doubtful pathogenicity. R1193Q was also the only variant in the three cases from the unselected population and occurred as a second variant with R1047L. Engaging families proved challenging. Only 3 of 8 (38%) variant-positive cases and 18 of 94 (19%) of variant-negative families participated in cardiac/genetic screening. CONCLUSIONS: LQT molecular autopsy has a very low diagnostic yield among unselected SIDS cases where risk factors are common. Diagnostic yield can be higher with case selection. Engagement of the family prior to genetic testing is essential to counsel for the possible uncertainty of the results and to permit family genotype-phenotype cosegregation studies.