Somatic mutations in kinetochore gene KNSTRN are associated with basal proliferating actinic keratoses and cutaneous squamous cell carcinoma.

BACKGROUND: Mutations in kinetochore gene KNSTRN accelerate the development of cutaneous squamous cell carcinoma (SCC) and may correlate with different histological classifications of actinic keratosis (AKs). OBJECTIVE: To determine KNSTRN gene mutation frequency in healthy skin (HS), actinically damaged skin (ADS), in AKs with different histomorphological gradings and invasive SCCs. METHODS: All samples were histologically evaluated. AK lesions were additionally classified according to their upwards (AK I-III) and downwards (PRO I-III) directed growth pattern. Mutation analyses of all samples were performed using the Sanger method. RESULTS: With one exception, all detected mutations in KNSTRN gene showed an alanine-to-glutamate substitution at codon 40 (p.Ala40Glu). p.Ala40Glu mutation was found in 6.9% (2/29) of HS, in 16.1% (5/31) of ADS, in 18.3% (20/109) of AKs and in 30.0% (9/30) of invasive SCCs. Further stratification of AKs using the common AK classification of Röwert-Huber revealed the p.Ala40Glu mutation in 14.7% (5/43), 13.3% (4/30) and 24.4% (11/45) (AK I, II and III). In contrast, the new PRO classification showed a distribution of 3.6% (1/28) in PRO I, 21.7% (13/60) in PRO II and 28.6% (6/21) in PRO III. Mutation frequency in HS showed significant differences compared to AKs classified as PRO III and invasive SCCs (P < 0.05). In contrast, there were no statistically significant differences between HS and AKs when classified according to Röwert-Huber. CONCLUSIONS: Recurrent somatic mutation p.Ala40Glu in KNSTRN gene is associated with basal proliferating AKs in accordance with invasive SCCs. This supports the impact of basal proliferative pattern in terms of progression.

A randomized split-scalp study comparing calcipotriol-assisted methyl aminolaevulinate photodynamic therapy (MAL-PDT) with conventional MAL-PDT for the treatment of actinic keratosis.

BACKGROUND: Topical photodynamic therapy (PDT) is an approved treatment for actinic keratosis (AK). To enhance the efficacy of PDT for AKs, physical and chemical pretreatments have been suggested. OBJECTIVES: To compare the efficacy and safety of the combination of topical calcipotriol (CAL) before methyl aminolaevulinate (MAL)-PDT for AKs of the scalp vs. conventional MAL-PDT in a randomized controlled clinical trial. METHODS: Twenty patients with multiple AKs on the scalp were randomized to receive conventional MAL-PDT with previous curettage on one side of the scalp and CAL-assisted MAL-PDT once a day for 15 days before illumination on the other side. After 3 months, patients were evaluated for clearance of AKs, side-effects and histopathology before and after the procedure. Protoporphyrin IX (PpIX) fluorescence was measured before and after illumination on both sides. RESULTS: All 20 patients completed the study. Overall AK clearance rates were 92·1% and 82·0% for CAL-PDT and conventional PDT, respectively (P < 0·001). Grade 1 AKs showed similar response rates for both sides (P = 0·055). However, grade II AKs showed more improvement on the CAL-PDT side (90%) than on the MAL-PDT side (63%) (P < 0·001). Before illumination, PpIX fluorescence intensity was higher on the CAL-assisted side (P = 0·048). The treatment was more painful on the CAL-PDT side, although well tolerated. The mean visual analogue scale score was 5·4 ± 1·4 on the CAL-PDT side and 4·0 ± 0·69 on the conventional MAL-PDT side (P = 0·001). Side-effects such as erythema (P = 0·019), oedema (P = 0·002) and crusts (P < 0·001) were more pronounced on the CAL-assisted side. Histopathological analyses were obtained from five patients and both sides showed improved keratinocyte atypia following PDT, with slightly more improvement on the CAL-assisted side. CONCLUSIONS: CAL-assisted PDT proved to be safe and more effective than conventional MAL-PDT for the treatment of AKs on the scalp. CAL pretreatment increased PpIX accumulation within the skin and may have enhanced the efficacy in this first human trial.

Clinical, histopathological and immunohistochemical assessment of human skin field cancerization before and after photodynamic therapy.

BACKGROUND: The field cancerization concept in photodamaged patients suggests that the entire sun-exposed surface of the skin has an increased risk for the development of (pre)-malignant lesions, mainly epithelial tumours. Topical photodynamic therapy (PDT) is a noninvasive therapeutic method for multiple actinic keratosis (AK) with excellent outcome. OBJECTIVES: To evaluate the clinical, histological and immunohistochemical changes in human skin with field cancerization after multiple sessions of PDT with methyl-aminolaevulinate (MAL). METHODS: Twenty-six patients with photodamaged skin and multiple AK on the face received three consecutive sessions of MAL-PDT with red light (37 J cm(-2)), 1 month apart. Biopsies before and 3 months after the last treatment session were taken from normal-appearing skin on the field-cancerized area. Immunohistochemical stainings were performed for TP-53, procollagen-I, metalloproteinase-1 (MMP-1) and tenascin-C (Tn-C). RESULTS: All 26 patients completed the study. The global score for photodamage improved considerably in all patients (P < 0·001). The AK clearance rate was 89·5% at the end of the study. Two treatment sessions were as effective as three MAL-PDT sessions. A significant decrease in atypia grade and extent of keratinocyte atypia was observed histologically (P < 0·001). Also, a significant increase in collagen deposition (P = 0·001) and improvement of solar elastosis (P = 0·002) were noticed after PDT. However, immunohistochemistry showed only a trend for decreased TP-53 expression (not significant), increased procollagen-I and MMP-1 expressions (not significant) and an increased expression of Tn-C (P = 0·024). CONCLUSIONS: Clinical and histological improvement in field cancerization after multiple sessions of MAL-PDT is proven. The decrease in severity and extent of keratinocyte atypia associated with a decreased expression of TP-53 suggest a reduced carcinogenic potential of the sun-damaged area. The significant increase of new collagen deposition and the reduction of solar elastosis explain the clinical improvement of photodamaged skin.

Multiple fibroepithelial basal cell carcinoma of Pinkus associated with seborrheic keratosis in a nevoid distribution.

We describe a patient with multiple fibroepithelial basal-cell carcinoma (FEBCC) associated with seborrheic keratosis distributed in a neviform fashion on the left side of the body and clinically resembling skin tags.

Direct immunofluorescence in lupus erythematosus (LE).

One hundred and twenty-six patients with LE were studied. They were distributed as follows: 84 with DLE, 13 with SALE and 29 with SLE. Biopsies from the skin lesions were performed and submitted to DIF. Positive results were equal to 69, 61.5 and 72.4 percent of the DLE, SALE and SLE cases, respectively. These data are in accordance with the literature. IgM was the most frequently found immunoglobulin, followed by the association IgM + C3.

Articular inflammatory manifestations in patients with different forms of leprosy.

OBJECTIVE: To study the articular inflammatory manifestations of leprosy. METHODS: Sixty patients with leprosy from a public clinic in São Paulo, Brazil, participated in a study regarding their articular manifestations. The diagnosis and classification of leprosy were established by the clinical picture, skin smears, skin biopsy, and delayed hypersensitivity test to Mycobacterium leprae antigens (Mitsuda test). According to the Madrid and Ridley-Jopling classifications, 46 patients had lepromatous leprosy, 7 had borderline leprosy, 4 had tuberculoid leprosy, and 3 had indeterminate leprosy. History, general and articular examinations, and roentgenograms were employed and complemented in several cases by scintigraphic examinations with technetium methylene diphosphonate and computed tomographic studies. RESULTS: Three patients were excluded from study due to an association with a rheumatic disease. Among the 57 remaining patients, 44 had peripheral arthritis characterized by involvement of small joints (23/44), large joints (4/44), or both (17/44). The mean duration of arthritis was 11 years (range 1 mo to 51 yrs). Arthritis was detected in all subtypes of patients with leprosy. Supplementary radiological evaluation established the extent of inflammation and diagnosis of sacroiliitis. The diagnosis of sacroiliitis, based on the presence of sclerosis, erosions, and narrowing of the cartilage space in the sacroiliac joints, was established in 35 of 55 radiographs. Sacroiliitis varied from grade I to III, according to the Bennet and Wood classification, and was bilateral in most cases (30/35). There was no significant correlation between low back pain and the finding of sacroiliitis. CONCLUSION: Articular inflammatory manifestations may exist in patients with different forms of leprosy, and can follow a chronic course. In addition, sacroiliitis is a common, previously unrecognized manifestation in patients with leprosy.

Clinical aspects of epidermodysplasia verruciformis.

Thirteen patients with epidermodysplasia verruciformis (EV) were studied over a period of 7 years. EV is a rare genodermatosis characterized by a generalized infection with a specific group of human papilloma virus (HPV) and a propensity for developing skin malignant tumours in 30%-50% of patients. The diagnosis of EV was confirmed by histopathological and immunohistochemical findings. Three of our patients had the benign form of EV, which is characterized by monomorphous lesions and no malignant changes, whereas 10 had the malignant form, which is characterized by polymorphic lesions and development of cutaneous malignant tumours. All EV patients with the malignant form developed multiple skin tumours (77%). They started to appear at age 20, predominantly on the forehead (50%). Most were squamous cell carcinoma, extremely aggressive and invasive, which provoked metastasis and death in two patients.

Necrolytic migratory erythema associated with glucagonoma syndrome: a case report.

Necrolytic migratory erythema is a rare skin condition that consists of migrating areas of erythema with blisters that heal with hyperpigmentation. It usually occurs in patients with an alpha islet cell tumor of the pancreas-or glucagonoma-and when associated with glucose intolerance, anemia, hyperglucagonemia, and weight loss defines the glucagonoma syndrome. We describe a 52-year-old female patient with necrolytic migratory erythema associated with glucagonoma syndrome who had metastatic disease at presentation and passed away one week after her admission. The autopsy showed a tumor in the body of the pancreas, which was diagnosed as a neuroendocrine tumor and confirmed by immunohistochemistry. The diagnosis of necrolytic migratory erythema is a matter of great importance, since it might be an auxiliary tool for the early detection of glucagonoma.