Sudden death during prolonged religious fasting.

Sickle cell trait (SCT) is estimated to occur in 6% to 10% of Africans, and the United Kingdom (UK) prevalence rate has been estimated at 3.2%. Although sudden death in sickle cell disease is well known, its occurrence in SCT is rare and requires extremes of physiological stress. We present a case of a 29-year-old black woman who died suddenly during a period of religious fasting. Her medical history was unremarkable, and there was no family history of sickle cell disease. At postmortem, she was found to be dehydrated, and macroscopically, the main abnormal findings were congested lungs and a small spleen. Histological examination revealed extensive vascular congestion with red blood cell sickling in both lungs, the liver, and the spleen. Electrophoresis on a postmortem blood sample confirmed the clinical suspicion that the patient was a carrier of SCT. The case highlights a novel scenario of SCT associated sudden death. We discuss the potential pathophysiological mechanisms that may have led to the patient's demise. We also remind pathologists to consider this diagnosis as potentially contributing to the cause of death in apparently fit young people of ethnic origin during episodes of physiological stress.

Fatal overdose due to prescription fentanyl patches in a patient with sickle cell/beta-thalassemia and acute chest syndrome: A case report and review of the literature.

Introduced into clinical practice in the 1960s, the analgesic fentanyl is 100 times more potent than morphine. Various methods of administration exist including the transdermal Duragesic patch system, widely used in chronic pain and palliative care settings. Numerous, often imaginative methods of abuse of fentanyl patches have been reported; the majority of fatal fentanyl overdose cases resulting from deliberate abuse or suicide. We describe the accidental overdose of a young black male with sickle cell/beta-thalassemia who had been using the Duragesic system for almost 2 years.At autopsy the macroscopic findings were of nonspecific opiate overdose with congested heavy lungs. Histopathological examination revealed severe sickling of red blood cells in the lungs (acute chest syndrome). Toxicological examination revealed blood and urine fentanyl levels of 40 microg/L and 400 microg/L (10 fold and 100 fold higher than therapeutic levels). The mast cell tryptase was also significantly elevated at 76 microg/L, (Normal 2-14 microg/L). We discuss the relevance of these findings with regard to the cause of death, and stress the need to consider fentanyl when confronted with nonspecific signs of opiate overdose as it is not detected in routine toxicological drug screens.

DNA topoisomerase I and IIalpha expression in penile carcinomas: assessing potential tumour chemosensitivity.

OBJECTIVE: To examine the tissue expression of DNA topoisomerase I (Topo I) and IIalpha (Topo II), to pursue the possibility of future chemotherapy regimens for squamous cell carcinoma of the penis (SCCP), as high expression of Topo I might indicate sensitivity to the camptothecins, whereas high Topo II might indicate sensitivity to etoposide. PATIENTS AND METHODS: In all, 73 patients with SCCP were reviewed and then tissue samples microarrayed. These were then stained with immunohistochemistry for Topo I, Topo II and Ki-67. Tumour stage, grade and type were available. RESULTS: Topo II showed a strong positive correlation with the proliferation index as measured by Ki-67 (P < 0.001) but no correlation with Topo I. There were also strong correlations between tumour grade and Ki-67, and Topo II expression (both P < 0.001). Tumour type was also strongly correlated with Topo II and Ki-67 expression, with the highest expression in basaloid carcinomas and the lowest in verrucous carcinomas. However, Topo I expression was not correlated with any other tumour variable. CONCLUSION: The expression of Topo I is grade- and type-independent, and chemotherapy using the camptothecins is unlikely to be effective. The strong positivity of Topo II in high-grade and basaloid SCCPs suggests that treatment with etoposide or other Topo II 'poisons' might be a better target for future clinical trials.

Malignant clear cell hidradenoma of the vulva: report of a unique case and review of the literature.

Clear cell hidradenoma (CCH) is a rare tumor derived from eccrine sweat glands with a predilection for the head, face, and upper extremities. Its biologic behavior is unpredictable, although frank malignant transformation is reportedly rare (prevalence rate, 6.7% in a review). Malignant CCH (MCCH) exists only as case reports or very small series in the literature. We present a unique case of MCCH of the vulva with completely bland cytological features. A previously healthy 39-year-old woman underwent marsupialization of a presumed left-side vulval Bartholin gland cyst. Microscopy revealed a tumor with the features of CCH; no atypia, necrosis, or mitoses were observed. Ten months later, she developed enlarging left groin nodes, one of which contained a metastatic clear cell tumor. Radiological examination did not reveal any other primary source, and the diagnosis of MCCH was confirmed through an expert review. A reexcision of the vulval primary site, which contained residual tumor, was performed. The patient is currently free of any further recurrence 10 months after the excision of the lymph node metastasis. The case highlights the difficulty in predicting the behavior of CCH on the basis of histological examination alone. It also highlights the importance of considering MCCH in the differential diagnosis of a lymph node containing a metastatic clear cell tumor or an apparent metastatic clear cell lesion in the skin. We review the current literature on MCCH and discuss the problems in the differential diagnosis and treatment of this rare tumor.

Immunohistochemical analysis of negative inguinal lymph nodes in men with squamous cell carcinoma of the penis: are we missing micrometastases which could predict recurrence?

OBJECTIVE: To determine the presence or absence of micrometastases in lymph node dissection specimens of men with squamous cell carcinoma (SCC) of the penis using immunohistochemistry, and to correlate the results with clinical outcome. PATIENTS AND METHODS: In all, 13 men (mean age 55.8 years) with penile SCC, treated at St George's hospital between 2001 and 2005, were selected. All had prophylactic lymph node dissections; (12 bilateral and one unilateral). All lymph nodes were negative on standard haematoxylin and eosin (H&E) staining. Each block was stained for cytokeratins MNF 116 and LP34. In all, 217 lymph nodes were examined (mean 16.7 per patient). The median (range) follow-up was 23 (10-52) months. RESULTS: The mean tumour size and depth of invasion were 30.2 mm and 15.9 mm, respectively. There were eight T2 and four T3 tumours. Four tumours showed lymphovascular invasion. Information on tumour size and pathological grade was not available in one case. None of the patients have to date developed a local recurrence. A single lymph node was found to contain a micrometastasis, which was identified retrospectively on the original H&E slide. This measured 0.24 mm in maximum dimension. This patient had a T2G2 tumour with no vascular invasion; he has not progressed clinically in 10 months of follow-up. CONCLUSIONS: Anticytokeratin immunohistochemistry on H&E-negative inguinal dissection specimens in men with SCC of the penis can detect micrometastases that might be overlooked on routine stains. Their prognostic and therapeutic significance needs further study.