Primary Cutaneous CD30+ Anaplastic Large T Cell Lymphoma in a Patient Treated with Cyclosporine for Actinic Reticuloid.

Actinic reticuloid (AR)-a subtype of chronic actinic dermatitis-clinically and histopathologically shows lymphoma-like features. We report a male patient initially diagnosed with erythrodermic cutaneous T cell lymphoma (CTCL) who developed severe broadband photosensitivity. Clinical evaluation, histopathology, and phototesting were consistent with AR. The patient was treated with cyclosporine 150-300 mg/d. Under this therapy, he developed several times primary cutaneous anaplastic large cell lymphomas (C-ALCL) which in part tended to regress spontaneously under cyclosporine reduction. The association between cyclosporine treatment and development of C-ALCL and other CD30+ lymphoproliferative disorders has previously been reported in patients with atopic dermatitis, psoriasis, and transplant patients. In conclusion, the present case highlights the difficulties arising in the distinction between AR and CTCL and shows that long-term cyclosporine treatment may cause C-ALCL development in AR as well.

Evaluation of two histological classifications for actinic keratoses - PRO classification scored highest inter-rater reliability.

BACKGROUND: Actinic keratoses (AKs) can histologically be classified by the extent of atypical keratinocytes throughout the epidermis or their pattern of basal proliferation. Currently, no data on the inter-rater reliability of both scores is available. OBJECTIVE: To evaluate the inter-rater reliability of the two classification schemes; histological grade (AK I-III) and basal proliferation (PRO I-III). METHODS: Histological images of 54 AKs were classified by 21 independent dermatopathologists with regard to basal proliferation (PRO I-III), histological grade (AK I-III) and assumed risk of progression into invasive carcinoma. RESULTS: Overall, of the 54 AKs 16.7% (9/54) were classified as AK I, 66.7% (36/54) as AK II, and 16.7% (9/54) as AK III. With regards to basal growth pattern, 25.9% (14/54) were classified as PRO I, 42.6% (23/54) as PRO II, and 31.5% (17/54) as PRO III. We observed a highly significant inter-rater reliability for PRO-grading (P < 0.001) which was higher than for AK-grading (Kendall's W coefficient: AK = 0.488 vs. PRO = 0.793). We found substantial agreement for assumed progression risk for AKs with worsening basal proliferation (k = 0.759) compared to moderate agreement (k = 0.563) for different AK-gradings. CONCLUSIONS: Histological classification of basal growth pattern (PRO) showed higher inter-rater reliability compared to the established classification of atypical keratinocytes throughout epidermal layers. Moreover, experienced dermatopathologists considered basal proliferation to be more important in terms of progression risk than upwards directed growth patterns. It should be considered to classify AKs according to their basal proliferation pattern (PRO I-III).

Extended surgical safety margins and ulceration are associated with an improved prognosis in pleomorphic dermal sarcomas.

BACKGROUND: Pleomorphic dermal sarcomas (PDS) are frequent UV-induced sarcomas of the skin of intermediate grade malignant potential. Despite the fact that PDS have a noteworthy potential to recur (up to 28%) as well as to metastasize (up to 20%), there are no specific clinical guidelines with respect to follow-up these patients. Moreover, little is known about clinical, histological or molecular prognostic factors in PDS. OBJECTIVE: The aim of the present study was to identify risk factors to predict relapse in a large multicentre sample cohort of PDS which could aid to optimize personalized treatment recommendations regarding surgical safety margins and adjuvant radiotherapy. METHODS: Patients with a diagnosis of PDS were selected from nine European institutions based on the histopathologic criteria described by Fletcher. Clinicopathologic and follow-up data were collected and statistically analysed calculating univariate hazard ratios with 95% confidence intervals by use of the Cox proportional-hazards model and a significance level of P < 0.05. Patients with an incomplete excision of the tumour were excluded. RESULTS: Univariate Cox regression analysis of possible prognostic factors for progression-free survival (PFS) performed in 92 patients revealed that an excision margin of <2 cm is significantly associated with relapse of PDS [hazard ratio 4.478 (95% CI 1.536-13.055), P = 0.006]. Ulceration of the tumour was associated with a significantly better prognosis [0.396 (0.174-0.904), P = 0.028] whereas adjuvant radiotherapy did not reach statistical significance to improve prognosis in patients with PDS [0.775 (0.231-2.593), P = 0.679]. Gender, age, immunosuppression, intratumoural necrosis, tumour location, vertical thickness or horizontal diameter did not significantly influence PFS in PDS. CONCLUSION: We identified surgical safety margins of <2 cm and absence of ulceration as risk factors for relapse in patients with PDS. These findings may be implemented into both the primary treatment as well as the further monitoring of patients with PDS.

Melanocytic soluble adenylyl cyclase protein expression around lentigo maligna and in contralateral control skin.

Recurrence rates of both lentigo maligna (LM) and lentigo maligna melanoma (LMM) following conventional surgery are usually relatively high. We aimed to assess the frequencies of melanocytes in tumour-free margins around LM/LMM using soluble adenylyl cyclase (sAC) immunohistochemistry, and to compare these with those of matched healthy contralateral skin. Using the primary mouse-anti-human sAC antibody R21, we evaluated pan-nuclear melanocytic R21 immunostaining, and found that it was significantly (P < 0.001) higher in peritumoural melanocytes (median 20%; range 0-100%) than in contralateral healthy skin (mean 0%; range 0-20%). Accordingly, there was no correlation between peritumoural and contralateral R21 immunoreactivity (r = 0.12; P = 0.18). In conclusion, melanocytic R21 immunoreactivity in melanocytes is higher in tumour-free margins around LM/LMM than in site-matched contralateral skin. This observation may indicate that the biology of 'healthy'-appearing melanocytes around LM/LMM might be different from that of truly benign melanocytes.

Compression and venous ulcers.

Compression therapy is considered to be the most important conservative treatment of venous leg ulcers. Until a few years ago, compression bandages were regarded as first-line therapy of venous leg ulcers. However, to date medical compression stockings are the first choice of treatment. With respect to compression therapy of venous leg ulcers the following statements are widely accepted: 1. Compression improves the healing of ulcers when compared with no compression; 2. Multicomponent compression systems are more effective than single-component compression systems; 3. High compression is more effective than lower compression; 4. Medical compression stockings are more effective than compression with short stretch bandages. Healed venous leg ulcers show a high relapse rate without ongoing treatment. The use of medical stockings significantly reduces the amount of recurrent ulcers. Furthermore, the relapse rate of venous leg ulcers can be significantly reduced by a combination of compression therapy and surgery of varicose veins compared with compression therapy alone.

Does chemosensitivity-assay-directed therapy have an influence on the prognosis of patients with malignant melanoma stage IV? A retrospective study of 14 patients with malignant melanoma stage IV.

OBJECTIVE: To evaluate the efficacy of chemosensitivity-testing directed chemotherapy in comparison with empirically chosen therapy regimens in patients with malignant melanoma stage IV. PATIENTS AND METHODS: Retrospective study including 14 patients with histologically confirmed malignant melanoma and diagnosis of stage IV disease by routine diagnostic procedures. Patients in group A (n = 7) were treated according to their individual chemosensitivity testing results, whereas patients in group B (n = 7) received empirically chosen treatment regimens. Chemosensitivity testing was performed using a nonclonogenic ATP-TCA assay. For statistical analysis the Kaplan-Meier method was used to calculate survival curves. The log-rank test was performed to compare the overall survival according to treatment group, LDH level in serum and AJCC-category. To compare the distribution of sex, LDH level in serum and AJCC-category between the treatment groups, the Fisher exact test was used. RESULTS: The median overall survival of group A exceeded the median overall survival of group B by 8 versus 3 months, respectively with a median overall survival of 5 months for the whole study population. LDH level in serum at study entry showed a strong correlation with overall survival, with normal LDH levels leading to a statistically significant longer survival (p = 0.006 for the log-rank test, respectively). Moreover, stage AJCC M1a/b yielded to a better prognosis compared with stage AJCC M1c (log-rank test p = 0.066; not statistically significant). CONCLUSION: Chemosensitivity-assay directed therapy might be a useful tool in determining the optimized chemotherapeutic drug or drug combination in the individual patient and might contribute to a better prognosis in patients with metastatic melanoma stage IV.