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Optical coherence tomography (OCT) is a new imaging method with promising results for several dermatological indications, including preoperative skin tumour characterization. While high-frequency ultrasound (HFUS) is frequently used for this purpose, overestimation of tumour thickness is a problem, due to subtumoral inflammatory infiltration that cannot be differentiated from tumour tissue. The aim of this single-centre study was to describe OCT features of basal cell carcinoma (BCC) and to determine vertical tumour thickness accurately, including a comparison with HFUS and histopathology. Tumour thickness values of 10 BCCs measured by OCT did not differ significantly from those measured by histopathology (median difference 0.12 mm). By contrast, the difference between HFUS and histopathology was greater (median difference 0.3 mm). A Pearson's correlation coefficient of 0.83 showed a stronger correlation of OCT in measuring tumour thickness compared with HFUS (0.59). Bland-Altman plots revealed a better agreement of OCT and histopathology concerning tumour thickness measurements. On the basis of this explorative study cohort, OCt was more exact than HFUS in preoperative tumour thickness estimation of BCCs compared with histopathological measurements.

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BACKGROUND: Accurate assessment of vertical tumor size is important for surgical treatment planning of melanocytic skin lesions. High-frequency ultrasound (HFUS) is frequently used for this purpose, but overestimation of tumor thickness is known as a problem especially in thin melanocytic lesions. Optical coherence tomography (OCT) as a new imaging technique might be a promising alternative. OBJECTIVE: To evaluate the ability of OCT to accurately determine the vertical tumor thickness of melanocytic skin lesions and to compare it with HFUS and histopathology in order to improve surgical planning. METHODS: In this single-center study, 26 melanocytic lesions were imaged by OCT and HFUS. Vertical lesion dimensions of both methods were compared with histopathological measurements. RESULTS: Bland-Altman plots for OCT and histopathology as well as for HFUS and histopathology revealed better agreement for OCT and histopathology concerning tumor thickness measurements. Tumor thickness values for the melanocytic lesions measured by OCT presented a median tumor thickness of 0.31 mm (range 0.10-0.77) compared to a median tumor thickness of 0.25 mm (range 0.06-1.5) measured by histopathology. The median tumor thickness of HFUS was 0.44 mm (range 0.23-1.1). A Spearman correlation procedure including the correlation coefficient (r) showed a stronger relationship between OCT and histopathology (r = 0.734) compared to HFUS and histopathology (r = 0.390). CONCLUSIONS: On the basis of this smaller study cohort, OCT seems to be more exact than HFUS as far as thickness determination of thin melanocytic skin lesions is concerned.

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The prevalence of squamous cell carcinoma of the lower lip (SCC-LL) is increasing worlwide. The expression of the enzyme indoleamine 2,3-dioxygenase (IDO) by antigen-presenting cells and/or tumor cells leads to tumor escape by inhibiting T cell-mediated rejection responses. The aim of this study was to determine the expression of IDO in SCC-LL. IDO-expression was analyzed in 47 SCC-LL, together with the expression of markers of T-cells (CD3), myeloid DCs (S100, CD11c), macrophages (CD68, CD11c), Langerhans cells (CD1a, Langerin (CD207)), plasmacytoid DCs (CD123), and regulatory T cells (Foxp3) by immunohistochemistry and immunofluorescence analysis. Twelve specimens out of 47 LL-SCCs contained cells that expressed IDO. IDO-positivity was strongly associated with the intensity of the cancer-associated infiltrate (P=0.0007). IDO-positive cells are located right along the border between the developing tumor and the inflammatory infiltrate. Immunofluorescence stainings showed that CD11c+S100+CD68- dendritic cells (DCs) express IDO in SCC-LL. IDO expression in LL-SCC may aid immune escape and chronic inflammation to promote cancer progression. Inhibition of IDO might be a therapeutic strategy to increase the anti-tumor immune response in SCC-LL.

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BACKGROUND: Sentinel lymph node biopsy (SLNB) has become the standard care for melanoma and is an important diagnostic procedure. It has been doubted whether lymphoscintigraphy detects the correct sentinel lymph node (SLN) when excision of the tumor and SLNB are not performed at the same time. This would imply that this sequential approach may have an increased risk of undetected micrometastases resulting in a worse outcome. OBJECTIVE: The purpose of the present study was to compare the outcome of melanoma patients having received excision of the tumor and SLNB either at the same time or consecutively. METHODS: A total of 854 patients with cutaneous melanoma were enrolled in this retrospective study between September 1996 and November 2007. Disease-free (DFS) and overall survivals (OS) were estimated using the Kaplan-Meier product limit method and were analyzed by the log rank test. RESULTS: No statistically significant difference was found regarding DFS, progression rates and OS in patients with primary tumor excision and SLNB at the same time compared with patients with excisional biopsy of primary tumor and SLNB at different times. CONCLUSION: These data suggest that excisional biopsy of the primary tumor does not prevent the correct SLN mapping in melanoma patients.

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An elevated tumour thickness is strongly associated with an increased risk of mortality in melanoma patients. In the last few decades, an overall decrease of the tumour thickness to prognostically more favourable levels has been observed in several countries. Nevertheless, it is not clear whether this positive time trend occurred uniformly in specific subgroups of melanoma patients. Therefore, we aimed to assess time trends of tumour thickness by age group, tumour site and melanoma subtype. The study population consisted of 6475 patients with histologically proven primary invasive cutaneous melanomas seen at the Department of Dermatology and Allergology at the Ludwig-Maximilian-University Munich between 1977 and 2000. Age-adjusted time trends were assessed using linear and logistic regression analysis. Overall, a positive time trend with a decreasing tumour thickness was observed during the observation period in most subgroups. However, no significant time trend was observed in patients with a melanoma on the feet or with a nodular or acrolentiginous melanoma. The almost constant high tumour thickness of these patients might be caused by underaddressing the specific traits of these melanomas in earlier prevention campaigns. An important goal for the upcoming years should consist of a positive time trend with a decreasing tumour thickness in these subgroups.

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Actinic keratoses frequently occur in sun-exposed areas of the skin and, today, a variety of therapeutic options are available, including topical application of 5-fluorouracil (5-FU). Usually, 5-FU ointment needs to be applied twice daily for 2-4 weeks to achieve a therapeutic skin reaction. Here, we report on an immediate inflammatory reaction after single application of topical 5-FU in a patient receiving systemic treatment with the multitargeted tyrosine kinase inhibitor nilotinib for chronic myeloid leukemia. This side effect of nilotinib is new and might be of clinical relevance. We, therefore, discuss possible modes of action including other reports about different tyrosine kinase inhibitors which led to regression of aggravation of actinic keratoses.

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As a noninvasive diagnostic method, real-time B-mode sonography belongs to the diagnostic standard procedures in various fields of clinical medicine, for example, internal medicine, gynecology, and otorhinolaryngology. During the past 3 decades, ultrasound technology has been extended to clinical dermatology. High-frequency ultrasound systems with 20- to 50-MHz probes are used for the assessment of tumoral and inflammatory processes of the skin, providing information about their axial and lateral extension. They are of special interest in preoperative situations and for the monitoring of skin conditions under therapy. In contrast to high-frequency ultrasound systems, the value of ultrasound technology with the use of 7.5- to 15-MHz probes generally is not accepted worldwide, although it can be used easily and without significant side effects. Promising results have been reported from specialized diagnostic centers, especially for the assessment of peripheral lymph nodes and soft-tissue tumors. Although it is unable to provide malignancy specific information, ultrasound is nonetheless helpful in the follow-up of patients undergoing, for example, chemotherapy or radiotherapy. The 3-dimensional size and outline of a tumor as well as its relation to surrounding structures like vessels can be described. Moreover, information about the tumor quality (solid, cyst, complex) and the inner structure of a tumor (hypoechoic, hyperechoic, homogenous, inhomogenous, calcification foci, necroses) can be provided. In addition to conventional B-mode-sonography, newer ultrasound techniques like native and signal-enhanced color Doppler sonography as well as ultrasound-guided fine needle aspiration cytology are reviewed.

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BACKGROUND: Ultrasound (sonography, B-mode sonography, ultrasonography) examination improves the sensitivity in more than 25% compared to the clinical palpation, especially after surgery on the regional lymph node area. OBJECTIVE: To evaluate the distribution of metastases during follow-up in the draining lymph node areas from the scar of primary to regional lymph nodes (head and neck, supraclavicular, axilla, infraclavicular, groin) in patients with cutaneous melanoma with or without sentinel lymph node biopsy (SLNB) or former elective or consecutive complete lymph node dissection in case of positive sentinel lymph node (CLND). cv: Prospective multicenter study of the Departments of Dermatology of the Universities of Homburg/Saar, Tubingen and Munich (Germany) in which the distribution of lymph node and subcutaneous metastases were mapped from the scar of primary to the lymphatic drainage region in 53 melanoma patients (23 women, 30 men; median age: 64 years; median tumor thickness: 1.99 mm) with known primary, visible lymph nodes or subcutaneous metastases proven by ultrasound and histopathology during the follow-up. RESULTS: Especially in the axilla, infraclavicular region and groin the metastases were not limited to the anatomic lymph node regions. In 5 patients (9.4%) (4 of them were in stage IV) lymph node metastases were not located in the corresponding lymph node area. 32 patients without former SLNB had a time range between melanoma excision and lymph node metastases of 31 months (median), 21 patients with SLNB had 18 months (p < 0.005). In 11 patients with positive SLNB the time range was 17 months, in 10 patients with negative SLNB 21 months (p < 0.005); in 32 patients with CLND the time range was 31 months and in 21 patients without CLND 18 months (p<0.005). In thinner melanomas lymph node metastases occurred later (p<0.05). CONCLUSIONS: After surgery of cutaneous melanoma, SLNB and CLND the lymphatic drainage can show significant changes which should be considered in clinical and ultrasound follow-up examinations. Especially for high-risk melanoma patients follow-up examinations should be performed at intervals of 3 months in the first years. Patients at stage IV should be examined in all regional lynph node areas clinically and by ultrasound.

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In recent years, ultrasound scanning has become an important diagnostic tool in dermatology. It is easy to use, completely safe, and provides important diagnostic information. There are 2 basic types of ultrasonography with dermatologic applications. The best established is 20-MHz scanning, which can be used to measure tumor thickness and/or skin thickness when treating inflammatory diseases such as scleroderma or psoriasis. Real-time sonography with 7.5- to 10-MHz probes has assumed an increasingly important role, since it is used to search for and image lymph nodes and subcutaneous tumors in a variety of clinical settings, including preoperative staging and follow-up of melanoma. Ultrasonography is capable of revealing the 3-dimensional size and outline of subcutaneous lesions, for example, lymph nodes, subcutaneous tumor masses or hematomas, and their relation to adjacent vessels. Moreover, information about the lesion quality (solid, cystic, and combined) and the inner structure (homogeneous, inhomogeneous, hypoechoic, hyperechoic, calcification foci, and necroses) can be obtained. All this information can be combined to help distinguish between benign and malignant lymphadenopathy and to determine the malignant potential of a subcutaneous lesion. In addition to conventional B-mode sonography, newer ultrasound techniques such as native and signal-enhanced color Doppler sonography can be used to assess peripheral lymph nodes.

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The purpose of the study was to evaluate whether signal-enhanced color Doppler sonography (CDS) is superior to native CDS in detection of characteristic vascularity patterns that are important for the differentiation between benign and malignant lymphadenopathy in patients with cutaneous melanomas. Twenty-two melanoma patients presenting with 24 structures suspicious for metastases in B-Mode sonography were examined using native and signal-enhanced CDS in a prospective two-center study. Presumptive sonographic diagnoses were compared with results of histopathological and follow-up examinations. Signal-enhanced CDS gave additional information about vascularization of lymph node metastases and reactive lymph nodes, which was indicative for the differential diagnosis in 12 of 24 examinations. For lymph node metastases, signal enhancement improved the visualization of accessory peripheral vessels in four of 10 examinations. Concerning reactive lymph nodes, hilar vessels in part with branching to the lymph node periphery could be better identified after application of the contrast enhancer in eight of 13 examinations. Signal-enhanced CDS is demonstrated as an important additional diagnostic tool for improved differentiation between malignant and reactive lymph nodes and may be of special value in preventing unnecessary lymphadenectomy in small reactive lymph nodes.

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Seasonal patterns in diagnosis were examined in 7836 patients with cutaneous melanoma (clinical stage I and II) documented at the Department of Dermatology and Allergology at Ludwig-Maximilian-University in Munich, Germany, between 1977 and 2000. Of these patients, 2362 were first given a diagnosis in the summer months (June-August) and 1757 were first given a diagnosis in the winter months (December-February). A summer-to-winter ratio was determined for sex, age, anatomic tumor site, histopathologic subtype, and tumor thickness. The summer-to-winter ratio was 1.34 (95% confidence interval: 1.27-1.43) for all patients, with a ratio of 1.22 (95% confidence interval: 1.12-1.33) for men and 1.47 (95% confidence interval: 1.35-1.60) for women. The frequency of diagnosis of cutaneous melanoma was seasonal for all age classes, for all anatomic tumor sites, for all histopathologic subtypes except acrolentiginous melanomas, and for melanomas with a tumor thickness <3.0 mm. Comparing subgroups of the above-mentioned clinical and histopathologic parameters, significant differences could be observed for sex and anatomic tumor site. On the basis of this data, possible explanations for the diagnostic summer peak may be a greater awareness as a result of clothing habits in summertime or because of incurred sunburns in patients with skin type I and II, and the influence of public-health campaigns usually performed at the beginning of summer.

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A single-point mutation in exon 15 of the BRAF gene has recently been reported in a high percentage in cultured melanoma cells and in 6 of 9 primary melanomas examined. To evaluate the impact of the T1796A BRAF mutation, we screened primary melanomas, various types of nevi and lesions where a melanoma developed in an underlying nevus. We could detect the mutation in 28 of 97 (29%) melanomas and in 39 of 187 (21%) nevi, including blue nevi (0/20) and Spitz nevi (0/69), which did not carry the mutation. In melanomas with an underlying nevus, either the mutation was present in both the laser-microdissected nevus cells and the laser-microdissected melanoma cells (3/14) or both lesions were negative for the BRAF mutation except one case. In conclusion, mutations in exon 15 of the BRAF gene are nonspecific for progression of a nevus to a melanoma. Other so far unknown cofactors seem to be of importance.

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OBJECTIVE: To evaluate whether administration of a D-galactose-based signal enhancer is useful in color Doppler sonography (CDS) for better detection of vascularity patterns, which may help to differentiate malignant from benign lymph nodes in patients with cutaneous melanomas. DESIGN: Comparison of B-mode sonography, native CDS, and signal-enhanced CDS. SETTING: Department of Dermatology and Allergology, Ludwig-Maximilians-University, Munich, Germany. PATIENTS: Twenty examinations in 19 patients (median age, 60 years; 10 men) who presented with echo-poor structures suggestive of lymphadenopathy in B-mode sonography during follow-up for cutaneous melanomas. INTERVENTIONS: Histopathologic and follow-up examinations; documentation by color prints. MAIN OUTCOME MEASURES: Frequency of detection and description of different lymph node vascularity patterns in signal-enhanced CDS. RESULTS: Signal-enhanced CDS revealed additional information about vascularization of lymph node metastases, reactive lymph nodes, hematomas, and seromas, which was helpful for the differential diagnosis in 15 of 20 examinations. For lymph node metastases, signal enhancement facilitated the detection of accessory peripheral vessels in most investigations. Concerning reactive lymph nodes, hilar vessels in part with branching to the lymph node periphery could be identified only after application of the contrast enhancer in most patients. Quantitative variables could not be measured in all cases and did not help to differentiate between malignant and reactive lymph nodes. CONCLUSIONS: Administration of a D-galactose-based signal enhancer for CDS in patients with cutaneous melanomas can help to differentiate malignant from reactive lymph nodes, hematomas, or seromas. However, these promising results require confirmation in a prospective multicenter study.

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