Application of immunohistochemistry in clinical practice: a review.

BACKGROUND: Immunohistochemistry (IHC) has radically altered the practice of diagnostic histopathology. It is increasingly being applied for more accurate and precise diagnosis, theranostics and prognostics in the management of tumours. Unfortunately clinicians and pathologists in resource-constrained settings may not be exposed to its clinical utility. OBJECTIVES: To provide a review of the principles and utility of IHC in diagnosis as relevant to histopathological diagnosis in clinical practice. DATA SOURCES: A retrospective PubMed search was used to find most recent studies and reviews published on immunohistochemistry. Popular anatomical pathology textbooks and online resources were also searched. STUDY SELECTION: The searches for articles were limited to the MeSH terms "humans" and "English language". Emphasis was placed on recent review and original articles that are dealing directly with respective technical aspects and immunohistochemical stains of interest. DATA EXTRACTION: Both authors searched and reviewed related articles separately. DATA SYNTHESIS: The extracted information was compared so as to include the most updated information available. CONCLUSIONS: Immunihistochemistry has become an essential component of histopathology. Clinicians need to be conversant with developments in IHC in order to liaise appropriately with pathologists for the benefit of their patients. There is a need for urgent establishment of IHC practice within resource-constrained countries in order to meet current diagnostic standards in tumour pathology.

Fatal firearm wounds: a clinicopathologic study.

Firearm-related injuries are a leading cause of morbidity and mortality in South Africa. This retrospective autopsy study included all firearm-related fatalities seen at a central mortuary in Durban. These cases had initially been assessed by a clinician before death, from July 1998 to June 1999.A total of 322 cases of fatal gunshot wounds were reviewed. Medical records and postmortem findings were compared by data capture onto a spreadsheet. Twenty-eight cases were excluded because of surgical alteration of the wounds, making autopsy evaluation impossible. In 50.7% of cases, the number of wounds was correctly identified and in 55.1% the position was correctly identified. In only 36.1% of cases were the entry and exit wounds correctly identified. The total number of missed wounds was 504 (48.3% of cases). The majority of missed wounds were on the upper limbs (25%), with the anterior trunk (21.8%) and lower limbs (18.5%) making up the remainder. This study demonstrates that physicians in South Africa do not adequately document and interpret gunshot wounds, which may influence the treatment of the patient and have medicolegal consequences. Emphasis should be placed on undergraduate and postgraduate teaching for physicians to correctly identify, interpret, and document firearm wounds.

Lymphoproliferative disorders in Oxford renal transplant recipients.

BACKGROUND: Increased cancer incidence, particularly lymphoproliferative disease, is a complication of immunosuppression in organ transplantation. Non-Hodgkin's lymphomas (NHLs) occur frequently during the first year after transplantation, more so in North America than in Europe. METHODS: This study audited and correlated the demographic, clinical, pathological, and outcome features of post-transplant lymphoproliferative disorders (PTLDs) in a large centre in Oxford, and assessed whether the time of onset fitted more with the European or North American pattern. RESULTS: There were 1383 renal transplants in the study period and 27 patients developed lymphoma: 26 NHLs and one Hodgkin's disease (1.95%). Four of the patients never received cyclosporin. The mean time of diagnosis after transplant was 46 months. Most tumours (21/27) presented extranodally. Management included reduction of immunosuppression, surgical excision, antiviral treatment, radiotherapy, and chemotherapy. Three patients presented in the first post-transplant year-0.34% of cyclosporin managed patients-similar to the North American incidence, although the incidence of extranodal late PTLDs was also high (mean onset, 36 months v 15 months international mean). Post-transplant lymphomas were the most common malignancy associated with death in transplant patients. CONCLUSIONS: PTLDs occurred in 2% of renal transplant patients, presenting both in the first year in association with cyclosporin use, as in North America, but also in subsequent years, giving an overall presentation time later than the international mean. The disease usually presented extranodally, accounting for the wide range of symptoms and signs. Despite awareness and active management, the disease contributed to death in more that 50% of patients with PTLDs.

Mechanical airway obstruction caused by accidental aspiration of part of a ballpoint pen.

The authors present three cases of death in children aged 4, 9, and 10 years, respectively, that were first thought to be caused by herbal or other poisonings but at autopsy were found to be caused by airway obstruction from aspiration of ballpoint pen parts. Aspiration of a foreign body is a leading cause of accidental death in children, but the circumstances in these cases were unique. In the first case, a 4-year-old child died shortly after a visit to a traditional healer. The child's mother blamed him for the death and fatally assaulted him. The second case was a 9-year-old who died at school. Case 3 was a 10-year-old who collapsed while playing with a ballpoint pen in her mouth. In the latter two cases, the relatives alleged poisoning. At autopsy, there was no evidence of trauma, disease, or poisoning in all three cases. Ballpoint pen parts were present in the larynx, carina, and left main bronchus, respectively. Features of "asphyxial" death were present, and included subconjunctival hemorrhages, subendocardial hemorrhages, and congestion of the face and internal organs. These deaths are preventable by education of children, parents, and teachers. Ballpoint pen manufacturers should also modify the design of these pens to improve their safety.

Sudden death caused by myocardial tuberculosis: case report and review of the literature.

A 25-year-old fit man died suddenly while playing social soccer. Autopsy revealed an infiltrative lesion involving the left ventricle with overlying pericarditis. No other significant pathologic changes were observed. Histologic examination showed necrotizing granulomatous inflammation. No acid-fast bacilli were demonstrated in the pericardial fluid or on histologic examination. The presence of Mycobacterium tuberculosis DNA complex was confirmed by use of the ligase chain reaction technique. The differential diagnosis of myocardial tuberculosis includes sarcoidosis, rheumatic fever, rheumatoid arthritis, giant-cell-containing tumors, idiopathic (giant-cell) myocarditis, and bacterial infections such as tularemia and brucellosis. This case illustrates the protean manifestations of tuberculosis and highlights the use of molecular biologic techniques in arriving at a definitive diagnosis in cases of suspected tuberculosis.

Courting disaster? A survey of the autopsy service provided by district surgeons in Kwazulu-Natal.

AIM: To provide information on the overall quality of the autopsy service provided by district surgeons in KwaZulu-Natal (KZN) and in particular to identify factors which may have a negative impact on the judicial process. METHOD: Confidential questionnaires were sent to 73 district surgeons and 216 legal practitioners including prosecution advocates, regional court prosecutors, defence advocates and attorneys. One hundred and twenty (43%) replies (47 doctors and 73 lawyers) were suitable for analysis. RESULTS: District surgeons have no shortage of experience or maturity but their performance is hampered by the following: lack of appropriate training in forensic pathology; high case load; inadequate facilities and support staff; and lack of access to ancillary services. CONCLUSION: This study has shown that the standard of autopsy services by district surgeons varies considerably. Overall, there is evidence that inadequacies on the part of district surgeons have negative repercussions for the criminal justice system. Urgent attention should be given to implement training programmes for the district surgeons and to improve service conditions.

Histological evidence of hypertrophy and ischaemia in sigmoid volvulus among Africans.

OBJECTIVE: To document histological evidence of hypertrophy and ischaemia in sigmoid volvulus among Africans. DESIGN: Retrospective case series study of the histology of sigmoid volvulus over seven years with cadaveric controls. SETTING: King Edward VIII Teaching Hospital, University of Natal, Durban, South Africa. SUBJECTS: Fifty African patients with sigmoid volvulus and nine cadavers with normal sigmoid colon. RESULTS: There was hypertrophy of the submucosa, muscularis propria and nerve plexuses with features of ischaemia in the patients' specimens. Their veins were thrombosed and recanalized while mesentery and submucosa had fibrosis and vascular hyalinization. There was also hypertrophy and hyperplasia of Meissner's nerve plexus. In the autopsy study, normal African sigmoid specimen showed similar ischaemic features but specimens from the four Indian patients in the study did not have such abnormalities. CONCLUSION: We postulate that chronic ischaemia may account for postoperative anastomosis dehiscence in some cases where the resection margins involved the hypertrophic segment. The benefit of an extended resection with anastomosis being effected on the bowel with apparent normal thickness to avoid this possibility should be investigated.

Membranous fat necrosis due to subcutaneous elemental mercury injections.

Membranous fat necrosis (MFN) is a distinct abnormality in systemic and subcutaneous fatty tissue. Although ischemia and trauma have been implicated in its causation, the exact pathogenesis of MFN remains unknown. The deposition of metallic mercury in subcutaneous tissue due to accidental penetration or deliberate injection of mercury is unusual. Depending on the duration of the deposition, localized necrosis, suppuration, and granuloma formation have been described at mercury injection sites. We report subcutaneous MFN, a hitherto unrecognized histopathologic phenomenon at sites of mercury deposition, in a 21-year-old soccer player who had deliberate subcutaneous and intramuscular elemental mercury injections to improve his sporting performance.

Focal nodular hyperplasia of the liver coexisting with an adrenal pseudocyst.

A case of focal nodular hyperplasia (FNH) of the liver and an adrenal pseudocyst coexisting in the same patient is presented. The presentation was due to the large adrenal pseudocyst, which caused abdominal pain and swelling. At operation, the FNH was noted as an incidental finding. The aetiopathogenesis of both these lesions is thought to be the result of vascular malformation. FNH is associated with several other vascular malformations and lesions, and the association with an adrenal pseudocyst extends this concept. It also lends support to the theory that vascular abnormalities are important in the causation of these lesions.

TAL-1 protein expression in vascular lesions.

The distribution of TAL-1 protein, an important vascular promoter in mice, has been examined immunohistochemically in a range of human vascular lesions and normal tissues. Formalin-fixed, paraffin-embedded vascular lesions including granulation tissue, haemangiomas, Kaposi's sarcomas, spindle cell haemangioendotheliomas, and angiosarcomas, were examined using a monoclonal antibody to recombinant TAL-1. Endothelial cells in all lesions gave positive immunostaining of variable intensity. Granulation tissue and spindle cell areas of the vascular tumours gave the strongest staining (nuclear and cytoplasmic). The better-differentiated endothelial cells within the tumours and resident well-formed vessels were less positive and some cells were in fact negative. The malignant endothelial cells in angiosarcomas showed less intense positive staining than KS cells. This study has shown TAL-1 protein expression in a range of reactive, benign, and malignant vascular lesions. Protein expression appears to be stronger in the spindle cell areas, perhaps reflecting greater expression in less-differentiated endothelial cells.