Gerda Frentz

Malignant tumors in patients with psoriasis

BACKGROUND There is strong epidemiologic evidence that psoriasis treatments may cause nonmelanoma skin cancer and possibly other types of cancer. OBJECTIVE This study from Denmark reports the cancer incidence in 6910 patients with psoriasis discharged from the hospital from 1977 through 1987. METHODS Patients were identified in the National Hospital Discharge Register and information on cases of cancer was obtained through the files of the Danish Cancer Registry; observed figures were compared with those expected on the basis of cancer incidence rates for the national population. RESULTS A 2.5-fold increased risk was observed for nonmelanoma skin cancer in men and women, with no preponderance of any specific histologic subtype of cancer. In addition, excesses were seen of lung cancer in men (relative risk [RR] = 1.4) and women (RR = 1.6), of cancer of the larynx and pharynx in men (RR = 2.8 and 3.9), and of colon and kidney cancer in women (RR = 1.6 and 2.3). CONCLUSION The effect of cigarette smoking on the risk for noncutaneous cancer could not be assessed in this study; however, antipsoriatic treatment such as ionizing radiation and oral arsenicals must be considered as a possible cause of colon cancer, which has been observed in excess in two other studies of psoriatic patients.

Skin cancer as a cause of death in Denmark

Summary Denmark has a well‐established nation‐wide registration system for cancer incidence and mortality. In 1984, 2984 new cases of non‐melanoma skin cancer were notified to the Danish Cancer Registry and 40 deaths were attributed to this cause. An evaluation and validation of the death certificates indicate that the true number of deaths caused by non‐melanoma skin cancer was 18. Basal cell and squamous cell carcinoma accounted for three and 15 of the deaths, respectively. The estimated lethality is 4.3% for squamous cell carcinoma and 0.12% for basal cell carcinoma.

The nevoid basal cell carcinoma syndrome: Sensitivity to ultraviolet and x-ray irradiation

Demographic studies in patients with skin cancer have demonstrated the importance of exposure to ultraviolet and x-ray irradiation. This paper describes in vitro studies in peripheral lymphocytes from three patients with the nevoid basal cell carcinoma syndrome. Particular stress was placed on the following factors: (1) the distribution of the lymphocyte subsets, (2) the frequency of spontaneous sister chromatid exchange, (3) the effect of ultraviolet C (UVC) (254 nm) on deoxyribonucleic acid (DNA) synthesis, (4) the effect of UVC on the phytohemagglutinin-stimulated lymphocyte proliferation, and (5) the capacity to repair x-ray-induced DNA damage. Our data indicate that the distribution of the peripheral lymphocytes was normal, while the frequency of spontaneous sister chromatid exchange was high. The capacity of the lymphocytes to repair x-ray-induced DNA damage was low in all three patients. In two patients the UVC-induced DNA synthesis was reduced, while an increased UVC-induced inhibition of lymphocyte proliferation was observed. These cellular responses in vitro to ultraviolet and x-ray irradiation correspond to the clinical features of the nevoid basal cell carcinoma syndrome. A clearly defective in vitro cellular response to x-ray irradiation, reflecting the clinically evident x-ray sensitivity in the nevoid basal cell carcinoma syndrome, has not been reported previously.

Increased number of circulating suppressor T-Lymphocytes in Sun-induced multiple skin cancers

The distribution of peripheral lymphocyte subsets was studied in fifteen patients with multiple nonmel‐anoma skin cancers, selected according to history of ultraviolet (UV) or X‐ray exposure. The skin cancer was associated with previous heavy exposure to UV light in seven patients, and past exposure to x‐rays in eight patients. In the UV group, the helper T‐lymphocytes/suppressor T‐lymphocytes (Th/Ts) ratio was abnormally low (P < 0.01) compared with the ratios of the x‐ray and control groups. The low Th/Ts ratio was associated with an absolute increase in the number of Ts. This suggests that heavy sun exposure may cause a permanent increase in the number of Ts in certain persons. These extra T‐lymphocytes may in turn prevent immune rejection of transformed keratinocytes.

Grenz ray-induced nonmelanoma skin cancer

In 28 patients, nonmelanoma skin cancers developed in areas previously exposed to grenz rays. In 17 patients who did not have psoriasis, no other relevant carcinogenic exposure could be incriminated. Women were more often affected than men. Most of the tumors were basal cell cancers, and most of the patients had multiple tumors. No threshold dose could be established. The distribution of the latency time among patients without psoriasis was strictly normal (median 18 years). These observations suggest that usual therapeutic doses of grenz rays, as a single agent, are capable of causing skin cancer, but only in those persons who are abnormally sensitive to x-rays.

Eosinophilic pustular dermatosis: an early skin marker of infection with human immunodeficiency virus?

Two cases of eosinophilic pustular dermatosis are reported and both were associated with infection by human immunodeficiency virus (HIV‐1). We suggest that eosinophilic pustular dermatosis may occur as an early sign of infection with HIV.

Clonal heterogeneity in curetted human epidermal cancers and precancers analysed by flow cytometry and compared with histology.

DNA frequency distributions analysed by single nuclei flow cytometry were studied in sixty‐five curetted human epidermal tumours, i.e. five actinic keratoses (AK), seven Bowens diseases (BO), nine squamous cell carcinomas (SCC), forty‐three basal cell carcinomas (BCC) and one baso‐squamous carcinoma (BSC). Seventy‐five per cent (16/21) of the samples with squamous cell differentiation (AK, BO and SCC) showed features suggestive of more than one stem cell population, against 24% of the pure BCC samples (11/43).

DNA Flow cytometry of human epidermal tumours. Intra- and intertumour variability in ploidy and proliferative characteristics

SummaryTumour ploidy and proliferative characteristics can be estimated by flow cytometric measurements of the nuclear DNA content. This study considers the question whether human epidermal tumours are intrinsically homogeneous with regard to these properties, i.e. whether a single biopsy analysed by flow cytometry is representative of the entire tumour. Analyses of multiple biopsies from ten human epidermal tumours — two kerato-acanthomas (KA), two basal cell carcinomas (BCC), two basosquamous carcinomas (BSC), one Bowen’s disease (BO) and three squamous cell carcinomas (SCC) — indicated that both ploidy and proliferation characteristics were reproducible and specific for theperipheries of the different tumours regardless of the histopathologic diagnosis. The tumourcentres, however, may deviate considerably from the corresponding periphery. None of the ten tumour peripheries contained more than one cell clone, but six of the ten clones were aneuploid. Both the BO and the KA’s were hypodiploid, while one SCC, one BSC and one BCC were hyperdiploid as assessed in their peripheries. The remaining BSC was diploid in its periphery, while both a hypodiploid and a hypotetraploid cell clone were found in the corresponding centre.

DNA flow cytometry of human epidermis: interindividual and regional variations in normal skin.

Flow cytometrical measurements of individual nuclear DNA content in single nuclei suspensions prepared from normal skin of twenty leg ulcer patients aged 36–87 were used to study the variability in the fractions of cells with 2–4c DNA‐content (S‐fraction) and 40 DNA‐content (G2+ M‐fraction). No significant changes were found in these cell kinetic parameters in tower abdominal skin, as assessed by age and sex. However, the females, all being postmenopausal, exhibited wider variability in values than males, particularly in the G2+ M fraction.

X-ray and UV-radiation sensitivity of circulating lymphocytes in multiple epidermal cancer in relation to previous radiation exposure

The cellular sensitivity to X rays (200 kV, 16 mA) and UV radiation (254 nm) was examined in lymphocytes from three groups of patients with multiple epidermal malignant tumors, selected by their clinical history of carcinogenesis. Eight patients previously exposed to low energy ionizing radiation (less than or equal to 12 kV) had an increased cellular sensitivity to UV radiation as well as X rays compared with 24 age and sex matched controls. This indicates the existence of a cellular cross-sensitivity to UV radiation and ionizing radiation not previously established for human cells. In contrast six patients previously exposed to high energy ionizing radiation (between 25 and 170 kV) had normal cellular response to both UV radiation and X rays, indicating a different biologic effect of low and high energy ionizing radiation. In the third group of patients, previously exposed to therapeutic UV radiation/excess sunlight, the lymphocytes had a normal response to X rays, but an increased sensitivity to UV radiation. The possibility of evaluating the individual risk at radiation exposure is suggested.