A comparative immunohistochemical study of malignant mesothelioma and renal cell carcinoma: the diagnostic utility of Leu-M1, Ber EP4, Tamm-Horsfall protein and thrombomodulin

Metastatic renal cell carcinoma has occasionally been reported to mimic malignant pleural mesothelioma. Morphologically, histochemically and immunohistochemically, similarities in the two tumours exist making their differentiation difficult, particularly in biopsy specimens. The aim of this study was to make a comparative immunohistochemical analysis of the two tumours by use of a panel of four antibodies (Leu M1; Ber EP4; thrombomodulin and Tamm-Horsfall protein). Their suitability in differentiating between the two tumours was assessed. We examined 20 cases of renal cell carcinoma and 20 cases of malignant pleural mesothelioma. On immunostaining with Leu M1, 14 of 20 renal cell carcinomas were positive, yielding 70% sensitivity and 95% specificity and one of 20 mesotheliomas. In comparison, Ber EP4 antibody stained only seven of 20 of the renal cell carcinomas. In addition, it was noted that four tubulopapillary pattern renal cell carcinomas stained positively with both anti-Leu M1 antibody and Ber EP4 antibody. Thrombomodulin immunostaining was present in 11 of 20 mesotheliomas (55% sensitivity and demonstrated 95% specificity) and one of 20 renal cell carcinomas. For epithelial mesotheliomas only, thromobomodulin staining was identified in 10 of 14 cases. In the differentiation of renal cell carcinoma from epithelial mesothelioma we recommend the use of Leu M1 and thrombomodulin as diagnostically useful markers. None of the antibodies used in this study was effective in distinguishing sarcomatoid renal cell carcinoma from sarcomatous mesothelioma. Tamm-Horsfall protein showed little diagnostic utility in differentiating the two tumours.     

Relating tooth‐ and blood‐lead levels in children residing near a zinc–lead smelter in India

International Journal of Paediatric Dentistry 2010; 20: 186–192 Background. Lead toxicity particularly affects children because of their increased capacity for absorption and retention. Blood‐lead (BPb) levels reflect recent exposure and are of limited value in predicting neurotoxicity, whereas in teeth, lead accumulates over a long period of time and provides an integrated record of lead exposure from intrauterine life until the teeth are shed. Aim. The present study aimed to relate tooth‐lead (TPb) and BPb levels in children residing near a zinc–lead smelter in India, and to evaluate the effectiveness of primary teeth as bioindicators of life‐long lead exposure. Design. The lead levels in primary teeth and blood of 100 children aged between 5 and 13 years, living in the proximity of a zinc–lead smelter were measured by atomic absorption spectrophotometry. The mean levels were tabulated based on village, age, sex and tooth type, and analysed statistically. Results. The mean BPb level was significantly influenced by proximity to the lead source, but not by age or sex. There was no consistent pattern of correlation between BPb and TPb levels. Conclusion. Primary teeth showed significantly high lead levels compared to blood; they reflect cumulative exposure to lead and prove to be better indicators of body lead burden.     

Immunohistochemically demonstrated metallothionein expression in malignant melanoma

Metallothioneins are ubiquitous proteins with a high affinity for heavy metal ions, e.g. zinc, copper and cadmium. Experimentally, metallothionein over-expression in cell lines derived from a variety of cancers has been associated with resistance to anticancer drugs and irradiation therapy. Using a monoclonal antibody (E9) to metallothionein we investigated immunoreactive expression in routinely fixed and paraffin-embedded tissue from 63 cases of malignant melanoma and 13 secondary deposits. Whereas a variety of cells in normal skin showed metallothionein expression, all forms of benign naevi studied were uniformly negative. In contrast 13/30 'thin' (≤1.5 mm; 0.7 ± 0.4). 25 29 'thick' malignant melanoma (> 1.5 mm; 5.5 ± 3.9) and 12/13 metastases were positive. Six patients with thin and 19 with thick melanoma with metallothionein expression died during a mean observation period of 6.4 ± 1.8 and 3.6 ± 2.5 years, respectively, their survival distribution function analyses giving statistically significant results for both the vertical tumour thickness ( P < 0.0001) and metallothionein expression ( P < 0.0001). These immunohistochemical results, based on routinely processed paraffin-embedded tissue, suggest that metallothionein expression in malignant melanoma is significantly associated with progressive disease and might therefore be a useful prognostic indicator.     

Parathyroid hyperplasia in tertiary hyperparathyroidism: a pathological and immunohistochemical reappraisal

Thirty-one parathyroid glands from 11 patients with tertiary hyperparathyroidism were examined histologically and immunohistochemically to characterize better the nature of the accompanying parathyroid hyperplasia. The parathyroids showed varying degrees of nodular and diffuse hyperplastic involvement as well as apparently normal background tissue. The nodules were usually multiple within any one gland and, together with diffuse hyperplastic tissue, showed a varied cyto-architectural pattern. All glands studied showed both cellular argyrophilia and parathyroid hormone immunoreactivity. The staining pattern for parathyroid hormone ranged from negative or weak to strong, and from patchy to diffuse in hyperplastic tissue from different glands and within the same gland, regardless of the cell type. Apparently normal areas usually showed only patchy weak to moderately strong parathyroid hormone positivity. From the data obtained the most striking feature of the parathyroid glands in tertiary hyperparathyroidism is their extreme variability, both morphological and functional, as indicated by parathyroid hormone immunoreactivity. Furthermore, the generally lesser degree of parathyroid hormone immunoreaction observed in apparently normal parathyroid tissue may reflect suppression of hormone synthesis, with accompanying morphological regression to normal of pre-existent diffuse hyperplasia by autonomous hyperfunctioning nodules associated with tertiary hyperparathyroidism.     

The effect of acetylsalicylic acid,phenylbutazone and indomethacin on the binding of 11-hydroxysteroids to plasma proteins in patients with rheumatoid arthritis

Plasma concentrations of total and unbound 11-hydroxysteroids in patients with rheumatoid arthritis have been determined using a fluorimetric method before and after administration of acetylsalicylic acid, phenylbutazone and indomethacin. Unbound 11-hydroxysteroids were measured in plasma ultrafiltrates obtained using the Toribara apparatus. Enhancement and quenching of fluorescence by acetylsalicylic acid, phenylbutazone, and indomethacin, and heparin used as an anticoagulant in the blood samples, have been shown to be absent. The results show that acetylsalicylic acid, phenylbutazone and indomethacin given in recommended therapeutic doses for periods of one week have no significant effect on plasma protein-binding of 11-hydroxysteroids.     

Twenty-three years of disease-free survival following cutaneous metastasis from a primary bladder transitional cell carcinoma

We present a case of cutaneous metastases from a primary bladder transitional cell carcinoma (TCC), with a prolonged survival of 23 years. Cutaneous metastases from primary bladder TCC are uncommon and, like all metastases, have a poor prognosis. The common modality of treatment of cutaneous metastases from a primary bladder cancer is wide local excision of the metastases followed by combination chemotherapy. Here, we present a case of a solitary cutaneous metastasis from a primary bladder TCC, which was treated with wide local excision and single agent chemotherapy. Twenty-three years on, the patient remains disease and recurrence free.