Monika-H. Schmid-Wendtner

Prognostic factors associated with sentinel lymph node positivity and effect of sentinel status on survival: an analysis of 1049 patients with cutaneous melanoma

Sentinel lymph node biopsy (SLNB) is a widely accepted staging procedure in patients with melanoma. However, it is unclear which factors predict the occurrence of micrometastasis and overall prognosis and whether SLNB should also be performed in patients with thin primary tumors. At our Department of Dermatology, University of Munich (Germany), 1049 consecutive melanoma patients were identified for SLNB between 1996 and 2007, and were followed-up to assess disease-free and overall survival. Of those, a total of 854 patients were analyzed prospectively. Patients with positive SLN were subjected to selective lymphadenectomy. The association of patient characteristics with SLN was assessed by multivariate logistic regression. Survival curves were performed using the Kaplan–Meier method. Cox proportional hazard regression with different adjustments was used to estimate the effect of SLN on survival. The detection rate of SLN was 97.24%, of which 24.9% were metastatic. Significant parameters upon SLN positivity were tumor thickness and nodular type of melanoma. The 5-year overall survival was 90.1 and 58.1% in SLN-negative and SLN-positive patients, respectively. Upon multivariate analysis tumor thickness and SLN status were significant factors influencing both disease-free survival and overall survival. In conclusion, our data confirm that SLNB is relevant as a diagnostic and staging procedure and that tumor thickness is of predictive importance. SLN status should be taken into account when designing clinical trials and informing patients about the probable course of their disease. Our data suggest that in case of a nodular melanoma subtype SLNB should also be considered at a tumor thickness below 1 mm.

Real-Time Tissue Elastography as Promising Diagnostic Tool for Diagnosis of Lymph Node Metastases in Patients with Malignant Melanoma: A Prospective Single-Center Experience

Background: Real-time tissue elastography is a new, noninvasive method in ultrasonography, differentiating tissues according to their stiffness. Earlier studies have highlighted this technique as a useful diagnostic tool for the detection of noncutaneous malignancies like breast, prostate and thyroid cancer based on the principle that tumor cells present a higher stiffness compared to the adjacent normal tissue. Objective: The purpose of our study was to investigate the value of real-time tissue elastography for the differentiation of benign and metastatic peripheral lymph nodes (LN) in patients with cutaneous melanoma by comparing this technique with conventional B-mode sonography combined with power Doppler sonography (PDS). Methods: In this prospective study, 36 melanoma patients (23 females and 13 males, mean age 62.7 ± 11.1 years) undergoing LN excision at the Department of Dermatology and Allergy, University of Bonn, were included between July 2011 and July 2012. Real-time tissue elastography was planned prior to surgery and histopathological examination. Elasticity images had been qualitatively scored for the proportion of stiff areas from pattern 1-5 (soft to stiff) on the basis of a newly defined system for LNs. Results: A total of 42 LNs have been removed in 36 patients. Of these 42 LNs, 21 carried melanoma cells and 21 were benign LNs. Significant differences in elastographic patterns were found between metastatic and nonmetastatic LNs. In real-time tissue elastography, 19 (90.5%) of 21 metastatic LNs showed a pattern of 3, 4 or 5. Of all benign LNs, 76.2% had a pattern of 1 or 2 in their elastogram. Sensitivity and specificity of B-mode sonography combined with PDS were 80.9 and 76.2%, respectively, 90.5 and 76.2% for elastography and 95.2 and 76.2% for the combined evaluation. Conclusion: An elastography pattern ≥3 was identified as an independent significant factor, predicting a metastatic LN involvement. The combination of elastography with conventional B-mode sonography has the potential to further improve the differentiation between benign and metastatic peripheral LNs in melanoma patients.

Dose-Dependent Development of Depressive Symptoms During Adjuvant Interferon-α Treatment of Patients With Malignant Melanoma

Background Adjuvant IFN- α treatment for patients with malignant melanoma is often complicated by depression. The influence of dosage, however, is unknown. Objective The authors sought to elucidate this dosage effect. Method Using the Zung Self-Rating Depression Scale and the German Bf-S Self-Rating (Affectivity) Scale, the authors prospectively compared the frequency and severity of IFN- α –induced depressive symptoms between a group of 29 patients receiving low-dose and 17 patients getting high-dose induction therapy for 4 weeks. Results Patients receiving high-dose induction treatment had significantly higher depression scores after 4 weeks, and significantly more patients in the high-dose group developed depression. Conclusion The authors concluded that frequency and severity of IFN- α –associated depression during melanoma treatment are dose-dependent.

High-Resolution Ultrasound Combined with Power Doppler Sonography Can Reduce the Number of Sentinel Lymph Node Biopsies in Cutaneous Melanoma

Background: Sentinel lymph node biopsy (SLNB) is a widely accepted procedure to accurately stage patients with cutaneous melanoma. Disadvantages of the SLNB procedure are the overall costs and potential side effects of the operation [J Dtsch Dermatol Ges 2009;7:318–327; J Am Dermatol 2010;62:737–748]. Objective: The purpose of our study was to evaluate whether high-resolution ultrasound combined with power Doppler sonography (PDS) is an appropriate tool for preoperative identification and characterization of sentinel lymph nodes (SLNs) in patients with cutaneous melanoma. Methods: In a prospective study eighty-one consecutive patients with cutaneous melanoma (33 females and 48 males) in whom dissection of SLNs was indicated underwent ultrasound examinations before and after the preoperative lymphoscintigraphy. Results: A total of 170 SLNs (mean 2.1 per patient) were removed and examined by histopathology. High resolution ultrasound combined with PDS correctly identified 2 of 9 positive SLNs. The sensitivity, specifity, positive predictive value, and negative predictive values of ultrasound were 22.2% (95% confidence interval (CI) = 2.8–60.0), 100% (95% CI = 97.7–100.0), 100.0% (95% CI = 15.8–100.0), and 95.8% (95% CI = 91.6–98.3), respectively. Conclusions: Although high-resolution ultrasound combined with PDS cannot substitute SLNB, this technique offers earlier diagnosis of lymph node involvement in a small subgroup of patients (with subcapsular location of metastases), and introduces the possibility to exclude those patients from SLN procedure and directly prepare them for complete lymph node dissection (CLND).

Complete remission of extensive cutaneous metastatic melanoma on the scalp under topical mono-immunotherapy with diphenylcyclopropenone

ejd.2013.2066 Auteur(s) : Torsten Hinz1 torsten.hinz@ukb.uni-bonn.de, Lin-Kristin Ehler1, Thomas Bieber1, Monika-H Schmid-Wendtner2 1 Department of Dermatology, Allergy University of Bonn Sigmund-Freud-Str 25 53105 Bonn Germany 2 Interdisciplinary Oncology Center (IOZ) Munich, Munich, Germany The management of disseminated cutaneous metastases without systemic spreading in melanoma patients is challenging and may lead to frustrating results. Various treatment regimens like radiotherapy, isolated [...]

Real time tissue elastography for diagnosis of cutaneous T-cell lymphoma

Ultrasonographic (US) elastography is a novel, noninvasive imaging technique that can be used to depict relative tissue stiffness in response to an applied force. It is based on the comparison of signals acquired before and after tissue displacement. In analogy to manual palpation, stiff tissues deform less and exhibit less strain than compliant tissues in response to the same force. Currently, US elastography is under validation for different types of tissues located near to the human skin surface, including breast, prostate, and thyroid structures [1,2]. We therefore hypothesized that US elastography might also be of diagnostic value in the assessment of subcutaneous skin tumors. A 45-year-old man presented to our outpatient clinic with a small number of irregular erythematous patches, 6–8 cm in diameter, located on the lower trunk and the legs. The primary histological examination revealed an acanthotic epidermis with mild parakeratosis and accompanied by a sparse band-like upper dermal infiltrate composed of small lymphocytes, with some cells infiltrating the epidermis [Figure 1(A)]. CD30þ cells were almost absent [Figure 1(B)]. In synopsis with the clinical findings, the diagnosis of a large-plaque parapsoriasis was made, and the patient was treated successfully with ultraviolet (UV)-A1 phototherapy. Three months later, the same patient revealed an indolent, rapidly growing circumscribed subcutaneous tumor on his right forearm. Palpation and ultrasonography of regional lymph nodes were unsuspicious. Highresolution ultrasound (HRUS) with a 13 MHz probe (HI Vision Preirus; Hitachi Medical Systems GmbH, Wiesbaden, Germany) revealed an inhomogeneous echo-poor roundish structure mixed with echo-rich areas beneath an intact epidermis [Figure 1(C), right]. Because of the inhomogeneous B-mode pattern, which does not definitively discriminate between a benign and a malignant lesion [3,4], we decided to additionally use real time tissue elastography as a new ultrasound tool. After applying soft pressure with the transducer, the corresponding elastogram showed a predominance of dark blue areas within the lesion, representing tissue with a higher stiffness compared to the surrounding tissue [Figure 1(C), left]. In accordance with reports applying real time elastography for diagnosis of non-cutaneous malignancies such as breast and prostate cancer, we classified the subcutaneous lesion as being suspicious for a malignant tumor based on the elastogram color distribution [1,2]. A skin biopsy of the tumor was performed, and here, similar epidermal changes (acanthosis, parakeratosis) were seen as in the earlier biopsy, but the dermis was dominated by a dense lymphocytic infiltrate with large CD30þT cells, consistent with a CD30þ anaplastic large T-cell lymphoma [Figures 1(E) and 1(F)]. These findings were further supported by a biclonal rearrangement of the g-chain of the T-cell receptor [5]. The subcutaneous lesion was excised

Influence of sporting activity and smoking on peripheral lymph nodes in patients with melanoma analyzed by high-resolution ultrasound

BACKGROUND The sonographic examination of peripheral lymph nodes (LNs) plays an important role in the preoperative treatment and in the follow-up of patients with melanoma. OBJECTIVE A prospective study including 200 consecutive patients with a history of invasive cutaneous melanoma was performed at the Department of Dermatology and Allergy, University of Bonn, Germany, to examine the influence of sporting activity, physical workload, interferon alfa therapy, smoking habits, and infections of the upper respiratory tract on morphology and number of LNs analyzed by high-resolution ultrasound. METHODS Between May 2010 and June 2011, 106 men and 94 women (mean age 51.1 ± 12.8 years) were included in this study. During their follow-up visits for cutaneous melanoma, high-resolution ultrasound examination of cervical, axillary, and inguinal LN regions were performed. LN diameters and volumes were measured and correlated with the above given factors. RESULTS Sports-active patients had more LNs in inguinal regions, a higher volume and a larger LN diameter, and a higher maximum width of the hypoechoic LN margin in comparison with the nonactive patients. Patients with a hard physical workload in their occupations had a significantly higher volume of the biggest LN. Compared with nonsmoking patients smokers presented higher values in the total quantity of the LNs, in the greatest volume of LN, and in the greatest diameter of LN in the cervical regions. The other factors had no significant influence on the LN parameters. LIMITATIONS Our study population was too small to comment on influencing factors in more detail especially the influences of different sporting activities or smoking habits. CONCLUSION Sporting activity, physical workload, and smoking habits as associated cofactors influencing sonomorphologic aspects in patients with cutaneous melanoma should always be considered.