A comparison of paraganglioma, carcinoid tumor, and small-cell carcinoma of the larynx

Laryngeal paraganglioma, carcinoid tumor, and small-cell carcinoma are rare. Histologically they are similar to analogous tumors in other locations but may be difficult to identify in small biopsy specimens. We compared the light microscopic, histochemical, immunohistochemical, and electron microscopic features of two laryngeal paragangliomas, one carcinoid tumor, and six small-cell carcinomas. The paraganglioma chief cells stained with Grimelius stain and for chromogranin and neuron-specific enolase. The carcinoid tumor cells stained with Grimelius stain and for chromogranin, serotonin, neuron-specific enolase, and keratin. The small-cell carcinoma cells stained for keratin and neuron-specific enolase. The patients with paragangliomas and carcinoid tumor remain healthy through 20 months of follow-up. Four of the patients with small-cell carcinomas have died. Distinction between these tumors is warranted by differing histologic appearances, staining characteristics, and biologic behavior.     

Growth of Pakistani children in relation to the 1990 growth standards

This study was designed to compare the growth of Pakistani schoolchildren in the UK with the 1990 UK growth standards. Measurements of height, weight, and sitting height were performed on 785 Pakistani schoolchildren aged 5-14 years with the mean values for each age and sex being plotted on the UK growth standards. The results were expressed as SD scores relative to the 1990 reference data. The mean height for the boys was only 0.2 SD scores below the mean for the new growth standards with the mean height for the girls being 0.4 SD scores below the mean. The mean values for weight and body mass index were 0.3 and 0.5 SD scores less than the mean for boys and girls respectively. This study demonstrates that the growth of Pakistani schoolchildren in the UK is comparable to the 1990 UK growth standards with only minor differences. It is not safe to assume that short stature or low body weight in a Pakistani child is due to his or her ethnic background.     

Determination of malondialdehyde-induced DNA damage in human tissues using an immunoslot blot assay

Malondialdehyde (MDA) is a product of lipid peroxidation and prostaglandin biosynthesis. It is mutagenic and carcinogenic and the major adduct formed by reaction with DNA, a highly fluorescent pyrimidopurinone (M1-dG), has been detected in healthy human liver and leukocyte DNA. Analytical methods used so far for the detection of M1- dG have not been applied to a large number of individuals or variety of samples. Often, only a few microg of DNA from human tissues are available for analysis and a very sensitive assay is needed in order to detect background levels of M1-dG in very small amounts of DNA. In this paper, the development of an immunoslot blot (ISB) assay for the measurement of MI-dG in 1 microg of DNA is described. The limit of detection of the assay is 2.5 adducts per 10(8) bases. A series of human samples were analysed and levels of 5.6-9.5 (n = 8) and 3.1-64.3 (n = 42) of M1-dG per 10(8) normal bases were detected in white blood cell and gastric biopsy DNA, respectively. Results on four human samples were compared with those obtained using an HPLC/32P-post- labelling (HPLC/PPL) method previously developed and indicated a high correlation between M1-dG levels measured by the two assays. The advantages of ISB over other assays including HPLC/PPL, such as the possibility of analysing 1 microg DNA/sample and the fact that it is less time-consuming and laborious, means that it can be more easily used for routine analysis of a large number of samples in biomonitoring studies.      

Lipomatous metaplasia of superficial dermis

Lipomatous metaplasia is an uncommon phenomenon. After identifying the presence of a band of adipocytes in the superficial reticular dermis underlying two excisions for basal cell carcinoma, we prospectively reviewed all skin specimens accessioned in our laboratory over a 6‐month period and identified eight additional cases. In each example there was a band of adipocytes in the upper dermis, at the level of solar elastosis that was widely separated from the subcutaneous fat by a normal appearing reticular dermis. The cells were positive for S100 and negative for CD163. No connection between the superficial band of adipocytes and the subcutaneous or periappendageal fat was seen. The alterations were flat in configuration without polypoid changes. Eyerich et al. reported lipomatous metaplasia in the dermis of a patient with acute generalized exanthematic pustulosis and psoriasis, and postulated this to be a postinflammatory phenomenon. Fatty metaplasia occurs within a variety of cutaneous neoplasms including nevi, adnexal tumors and peripheral nerve sheath tumors. However, superficial dermal fatty metaplasia beneath cutaneous neoplasms is a newly described phenomenon and we suspect this process represents fatty metaplasia within solar elastosis and that it may occur more frequently than recognized.     

Tissue histiocyte reactivity with CD31 is comparable to CD68 and CD163 in common skin lesions

CD31 is a standard immunostain for evaluating vascular lesions of the skin, but CD31 reactivity for histiocytes is reported in only a small variety of pathological conditions. CD68 and CD163 are well recognized stains for cutaneous histiocytic lesions. We compared immunostaining of CD31 within that of CD68 and CD163 in five cases each of cutaneous lesions containing histiocytes: healing biopsy site, granuloma annulare, xanthogranuloma, ruptured follicular cyst and sarcoidosis. Reactivity was graded on a scale of 0–3 for brightness of immunostaining. Immunoreactivity was seen in histiocytes in all specimens for CD31, CD68 and CD163. The average intensity of staining was 1.7–2.5 for CD31, 2.6–3 for CD68 and 2.9–3 for CD163. The staining was somewhat less for CD31 because the reactivity is localized on the cell surfaces, whereas CD68 and CD163 react with cell surfaces and cytoplasm. We conclude that histiocytes in cutaneous lesions stain for CD31 and the staining is comparable to, but less intense, than that seen with CD68 and CD163. Caution is suggested in interpretation of CD31 staining in skin specimens, as CD31 shows reactivity with histiocytes as well as endothelial cells.     

Novel CARD9 mutation in a patient with chronic invasive dermatophyte infection (tinea profunda)

Caspase Recruitment Domain Family Member 9 (CARD9) is an adaptor molecule that drives antifungal activity of macrophages and neutrophils in the skin. Autosomal recessive loss-of-function mutations in CARD9 confer increased susceptibility to invasive disease with select fungi in non-immunosuppressed patients. We report on a patient with X-linked ichthyosis complicated by chronic cutaneous invasive dermatophyte infection. We identified a previously reported c.271T>C (p.Y91H) mutation and a novel intronic c.1269+18G>A mutation in CARD9 underlying recurrent deep dermatophytosis in this patient despite various antifungals for over three decades. Our case highlights susceptibility to invasive dermatophytosis related to autosomal recessive CARD9 deficiency and illustrates the range of CARD9 mutations to be pursued in immunocompetent patients with unexplained deep dermatophyte infections. Further studies are needed to define the best therapeutic regimen.     

Hemorrhagic tumor necrosis during a pilot trial of tumor necrosis factor-alpha and anti-GD3 ganglioside monoclonal antibody in patients with metastatic melanoma

Hemorrhagic tumor necrosis is an inflammatory event that leads to selective destruction of malignant tissues, with both potentially toxic and beneficial consequences. A pilot clinical trial was undertaken combining tumor necrosis factor-alpha (TNF-alpha) with the monoclonal antibody R24 (MoAb R24) against GD3 ganglioside in patients with metastatic melanoma. Patients received MoAb R24 to recruit leukocytes to the tumor followed by low doses of recombinant TNF-alpha to activate leukocytes. Eight patients were treated and seven patients had mild toxicity. One patient with extensive metastatic melanoma developed tumor lysis syndrome within hours after treatment with almost complete necrosis of bulky tumors in multiple visceral sites. To our knowledge, this is the first documented case of hemorrhagic tumor necrosis in a patient with metastatic cancer in multiple visceral sites.