The histopathological spectrum of acute generalized exanthematous pustulosis (AGEP) and its differentiation from generalized pustular psoriasis.

BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) represents a severe, acute, pustular skin reaction that is most often induced by drugs. AGEP can be difficult to differentiate from generalized pustular psoriasis (GPP) both clinically and histopathologically. We present a systematic description of the histopathological spectrum of AGEP and GPP with a focus on discriminating features. MATERIALS AND METHODS: A retrospective, descriptive, comparative histopathological study was completed utilizing step sections of 43 biopsies of 29 cases with a validated diagnosis of probable or definite AGEP and 24 biopsies of 19 cases with an established diagnosis of GPP. RESULTS: In AGEP, biopsies from erythema and pustules showed minor differences, whereas histopathology of the acute stage of GPP showed major differences compared to the chronic stage. Comparing AGEP and GPP, the presence of eosinophils, necrotic keratinocytes, a mixed interstitial and mid-dermal perivascular infiltrate and absence of tortuous or dilated blood vessels were in favor of AGEP. Moreover, chronic GPP was characterized by prominent epidermal psoriatic changes. The frequency of a psoriatic background of AGEP patients in our study was higher than that of psoriasis in the general population. However, histopathology of a subgroup of AGEP patients with a personal history of psoriasis revealed no significant differences from the other AGEP patients. CONCLUSIONS: The spectrum of histopathological features of both AGEP and GPP is presented. Despite considerable overlap, subtle consistent histopathological differences and the grade of severity of specific features can help in differentiation. We could neither substantiate earlier reports that follicular pustules exclude AGEP nor did we see vasculitis as a specific feature in AGEP. Our study also supports the concept that AGEP is a separate entity that is distinct from GPP.

Is disturbed clearance of apoptotic keratinocytes responsible for UVB-induced inflammatory skin lesions in systemic lupus erythematosus?

Apoptotic cells are thought to play an essential role in the pathogenesis of systemic lupus erythematosus (SLE). We hypothesise that delayed or altered clearance of apoptotic cells after UV irradiation will lead to inflammation in the skin of SLE patients. Fifteen SLE patients and 13 controls were irradiated with two minimal erythemal doses (MEDs) of ultraviolet B light (UVB). Subsequently, skin biopsies were analysed (immuno)histologically, over 10 days, for numbers of apoptotic cells, T cells, macrophages, and deposition of immunoglobulin and complement. Additionally, to compare results with cutaneous lesions of SLE patients, 20 biopsies of lupus erythematosus (LE) skin lesions were analysed morphologically for apoptotic cells and infiltrate. Clearance rate of apoptotic cells after irradiation did not differ between patients and controls. Influx of macrophages in dermal and epidermal layers was significantly increased in patients compared with controls. Five out of 15 patients developed a dermal infiltrate that was associated with increased epidermal influx of T cells and macrophages but not with numbers of apoptotic cells or epidermal deposition of immunoglobulins. Macrophages were ingesting multiple apoptotic bodies. Inflammatory lesions in these patients were localised near accumulations of apoptotic keratinocytes similar as was seen in the majority of LE skin lesions. In vivo clearance rate of apoptotic cells is comparable between SLE patients and controls. However, the presence of inflammatory lesions in the vicinity of apoptotic cells, as observed both in UVB-induced and in LE skin lesions in SLE patients, suggests that these lesions result from an inflammatory clearance of apoptotic cells.

Increased incidence of brain metastases in cutaneous head and neck melanoma.

The incidence of cutaneous melanoma is increasing, and 10-20% of these melanomas are located in the head and neck region. The incidence of brain metastases, risk factors and outcome were analysed for melanomas originating in the head and neck region. During the period 1965-2000, 324 patients [152 females (47%), 172 males (53%)] were treated for cutaneous melanoma of the head and neck. The patients were staged according to the 2002 American Joint Committee on Cancer (AJCC) melanoma staging system. A matched control analysis was performed in order to identify the risk factors for the occurrence of brain metastases. The analysis was performed using cross-tabulations, chi-squared test and the logistic regression method. Twenty six (8%) head and neck patients, compared with 5.2% of extremity/truncal patients, developed brain metastases (confidence interval, 0.058-0.108; P<0.05). The 26 head and neck patients (four Stage I, 10 Stage II and 12 Stage III) had a median age of 46 years (range, 16-79 years) and developed brain metastases after a median follow-up of 24 months (range, 4-75 months). The median Breslow thickness was 3.3 mm (range, 0.7-12 mm). The patients were treated with steroids, surgery, radiation, chemotherapy, or a combination of these. The median survival after the development of brain metastases was 2.4 months (range, 0.2-64.3 months), with a 1-year overall survival of 15%. Risk factors identified for the development of brain metastases from head and neck melanoma were a younger age, male gender, Breslow thickness greater than 4 mm and increased mitotic rate. The incidence of brain metastases is significantly higher in patients with cutaneous melanoma of the head and neck (8%) compared with those with extremity/truncal melanoma (5.2%). The prognosis is still extremely poor with current therapies.

Pregnancy and early-stage melanoma.

BACKGROUND: Cutaneous melanomas are aggressive tumors with an unpredictable biologic behavior. It has been suggested that women who present with melanoma during pregnancy have a worse prognosis due to more aggressive behavior of the melanoma. The objective of the current study was to evaluate the long-term effect of pregnancy on disease progression in women with Stage I-II melanoma. METHODS: From 1965 to 2001, 46 pregnant women were treated for a Stage I-II melanoma at the University Medical Center Groningen. These patients were compared with an age-matched and gender-matched control group (nonpregnant) of 368 women with Stage I-II melanoma. The patients were staged according to the 2002 American Joint Committee on Cancer TNM classification system for melanoma. The 10-year disease-free survival (DFS) and 10-year overall survival (OS) rates were calculated using logistic regression analysis. RESULTS: The median age of patients in the pregnant group was 30 years (range, 18-46 years), and the median age of patients in the nonpregnant group was 36 years (range, 17-45 years). The median follow-up was 109 months (range, 1-356 months). Pregnant patients presented more often with thicker melanomas (median, 2.0 mm vs. 1.7 mm; not statistically significant). No differences with regard to tumor location, histologic subtype, tumor ulceration, or vascular invasion were detected between the pregnant group and the nonpregnant group. There was no statistical difference in the 10-year DFS and 10-year OS rates between the two groups. The 10-year DFS rates for patients in the pregnant and nonpregnant groups, respectively, were 88% versus 86% for patients with Stage I melanoma and 67% versus 73% for patients with Stage II melanoma. The 10-year OS rates for patients in the pregnant and nonpregnant groups, respectively, were 94% versus 90% for patients with Stage I melanoma and 82% versus 81% for patients with Stage II melanoma. CONCLUSIONS: Pregnancy does not appear to have an adverse, long-term effect on survival in patients with clinically localized melanoma. Further studies should address whether pregnant patients present with thicker lesions and/or whether they have decreased DFS compared with nonpregnant women. The prognosis for women with melanoma during pregnancy, as it relates to survival, still is dependent on tumor thickness and ulceration.