S Williams

Histopathological reporting of paediatric cutaneous vascular anomalies in relation to proposed multidisciplinary classification system

Background: The terminology applied to vascular anomalies has been variable in previously published literature making interpretation suboptimal. The International Society for the Study of Vascular Anomalies (ISSVA) has proposed a revised classification based on clinical features and histopathological findings. This classification is increasingly being accepted as clinically useful and a platform for future studies. Aims: To examine the extent to which the ISSVA classification can be practically applied to diagnostic histopathological specimens. Methods: Cutaneous vascular lesions received in a single paediatric pathology unit during a 2-year period (2004–5) were reviewed, including glucose transporter protein 1 (GLUT1) immunostaining where required, and lesions were reclassified according to the ISSVA classification. Results: 144 specimens were identified. Appropriate full clinical information was provided in only 17% of cases at submission. Infantile haemangiomas comprised 46% of cases, 18% of which were regressive type, initially inaccurately identified as vascular malformations before GLUT1 immunostaining. 30% of lymphatic malformations and all lymphovenous malformations were previously classified as vascular malformations, not otherwise specified. Conclusions: The ISSVA classification of vascular anomalies provides a useful framework for histopathologists to classify vascular anomalies. However, meaningful and appropriate use of such a system is dependent on the adequacy of clinical information provided and routine use of immunohistochemical markers.

Glomerular expression of monocyte chemoattractant protein-1 is predictive of poor renal prognosis in paediatric lupus nephritis

BACKGROUND Monocyte chemoattractant protein-1 (MCP-1) is upregulated and it recruits and activates inflammatory cells in murine lupus nephritis (LN). METHODS Clinical outcomes of children with LN were examined in relation to glomerular expression of MCP-1 and macrophage infiltration, as determined by immunohistochemical staining of renal biopsy sections with MCP-1 and CD68. Sections were analysed using a modified histological score (H-score; maximum of 300) based on both percentage of positively stained cells and intensity of staining. RESULTS Renal biopsies were examined from 34 children [27 (79%) female] aged 7.7-17.3 (median 13.7) years with 50% ISN/RPS Class IV LN. Renal dysfunction and proteinuria at follow-up of 2.2-15.4 (median 6.5) years were analysed with estimated glomerular filtration rates (eGFR) of 11.2-124.1 (median 93.6) ml/min/1.73 m(2) and urine albumin:creatinine ratios of 1-535 (median 63) mg/mmol. There was a correlation between glomerular expression of MCP-1 and CD68 (r = 0.98, P = 0.04; median modified H-score of 219.7 and 230.8, respectively). Patients with Class III and IV LN had increased glomerular expression of both MCP-1 and PGM1 compared to the other classes (P = 0.01) with Class IV-G LN patients having the most glomerular expression of MCP-1 (median of 227.3) and PGM1 (median of 237.5) and the worst renal prognosis (with proteinuria and reduced eGFR). CONCLUSIONS There is a correlation between glomerular expression of MCP-1 and PGM1 and worsening renal prognosis in paediatric LN. Larger prospective studies of paediatric LN are required to further evaluate MCP-1 and other markers of disease progression.

Risk of germ cell malignancy in children with XY intersex versus isolated cryptorchidism by immunohistochemistry.

The risk of subsequent development of testicular germ cell neoplasia is related to presence of underlying developmental defects such as cryptorchidism, in which the risk is around 0.5%, and XY intersex with abdominal testes, in which the risk may be as high as 20–25%. We examined the hypothesis that the increased risk of germ cell malignancy in intersex testes with Y chromosome was a direct consequence of an abnormal increase in number of PLAP/CD117+ immature germ cells into postnatal life. Archival cases of uncomplicated cryptorchidism (CO) and XY intersex (INT) were identified and anonymized, and a subgroup of aged-matched cases had sections immunostained with placental alkaline phosphatase (PLAP) and CD117. From a total of 89 intersex and 105 cryptorchid cases identified, a power calculation to detect a 20% difference in expression between groups (alpha = 0.05, power = 80%) determined that 18 intersex and 36 cryptorchid cases were required. Thus, 58 cases were examined, median age 3 (range birth–11) years, including 39 CO and 19 INT. The prevalence of any PLAP+ germ cells was 2/39 (5.1%) versus 3/19 (15.7%), respectively. (Z = 1.4, p = 0.17). In contrast, 94% of cases showed presence of any CD117+ germ cells, but the frequency of CD117+ cells was not significantly different between groups (t = 0.56, p = 0.58). CD117 and PLAP identify different populations of germ cells in pediatric testes. The extent of increased risk of malignancy in XY INT is not simply related to increased numbers of immature PLAP+/CD117+ germ cells present; additional factors play a pathogenic role.