Indocyanine green fluorescence-guided sentinel lymph node biopsy in dermato-oncology

Background: Sentinel lymph node biopsy (SLNB) for cutaneous malignancies usually carried out with radioactive nanocolloids (Tc‐99m). The SLNE is controversially discussed internationally. This is especially given to the high false‐negative rate up to 44 %. An alternative could be the fluorescent dye indocyanine green (ICG). Material and Methods: We investigated the advantage of intraoperative fluorescence detection of lymphatic vessels and SLN with a Near‐Infrared (NIR) camera in comparison to conventional methods using preoperative lymphoscintigraphy and SPECT/CT in 22 patients with malignant melanoma. Results: A total of 61 SLNs were removed in 22 operative procedures. In 7 SLN (10.3 %; 7/68) the histopathological assessment could demonstrate a metasta‐tic involvement. 11 additional SLN (19.1 %) in 8 patients were only identified using the fluorescent labeling. Two of these additional SLN (9.1 %; 2/22) showed metastatic involvement. Conclusion: The ICG fluorescence‐guided SLNB is an innovative imaging technique for dermato‐oncology, reliable and providing additional information in the detection of SLN. Therefore SLNB with fluorescence‐dye is an attractive option with intraoperative real‐time lymphoscintigraphy to improve the detection of SLN in cutaneous malignancies and potential reduction of the false negative rate in SLN.     

Advantages of preoperative hybrid SPECT/CT in detection of sentinel lymph nodes in cutaneous head and neck malignancies

Background There is some controversy around the value of sentinel lymph node excision (SLNE). Especially SLNE of cutaneous head and neck malignancies has been debated intensively, in part because of the complexity of the lymphatic drainage in this region associated with potential high morbidity. In order to improve preoperative three‐dimensional mapping of sentinel lymph nodes (SLN), in the head and neck region, by means of hybrid single photon emission computed tomography/computed tomography (SPECT/CT) is gaining significance. Our study seeks to identify the potential medical and economic advantages of preoperative SPECT/CT in direct comparison to standard SLNE without SPECT/CT in patients with cutaneous head and neck malignancies. Methods We retrospectively analysed the data of 48 clinically lymph node‐negative patients with early stage melanoma, high risk cutaneous squamous cell carcinoma and porocarcinoma, who underwent SLNE with or without preoperative SPECT/CT within 4 years. Results The SLNE in the head and neck region with SPECT/CT‐technique demonstrated better postoperative aesthetic results had lower morbidity and significantly reduced operating time. Moreover, SLNE with SPECT/CT‐technique in the head and neck region was feasible using local anaesthesia (LA) and significantly reduced resulting costs (€32.65/SLNE with LA vs. €334.57/SLNE with general anaesthesia, P < 0.0001). Conclusion SPECT/CT is an innovative imaging technique, reliably and readily providing additional anatomical/functional information to detect and to excise SLN in the head and neck region. Therefore, SLNE with SPECT/CT‐technique is an attractive option to improve the detection of SLN in cutaneous head and neck malignancies.     

Dose optimization for near‐infrared fluorescence sentinel lymph node mapping in patients with melanoma

Background Regional lymph node involvement is the most important prognostic factor in cutaneous melanoma. As only 20% of patients with melanoma have occult nodal disease and would benefit from a regional lymphadenectomy, the sentinel lymph node (SLN) biopsy was introduced. Near‐infrared (NIR) fluorescence has been hypothesized to improve SLN mapping. Objectives To assess the potential of intraoperative NIR fluorescence imaging to improve SLN mapping in patients with melanoma and to examine the optimal dose of indocyanine green adsorbed to human serum albumin (ICG:HSA). Methods Fifteen consecutive patients with cutaneous melanoma underwent the standard SLN procedure using ^99mtechnetium‐nancolloid and patent blue. In addition, intraoperative NIR fluorescence imaging was performed after injection of 1·6 mL of 600, 800, 1000 or 1200 μmol L^?1 of ICG:HSA in four quadrants around the primary excision scar. Results NIR fluorescence SLN mapping was successful in 93% of patients. In one patient, no SLN could be identified using either conventional methods or NIR fluorescence. A total of 30 SLNs (average 2·0, range 1–7) were detected, 30 radioactive (100%), 27 blue (73%) and 30 NIR fluorescent (100%). With regard to the effect of concentration on signal‐to‐background ratios a trend (P = 0·066) was found favouring the 600, 800 and 1000 μmol L^?1 groups over the 1200 μmol L^?1 group. Conclusion This study demonstrates feasibility and accuracy of SLN mapping using ICG:HSA. Considering safety, cost and pharmacological characteristics, an ICG:HSA concentration of 600 μmol L^?1 appears optimal for SLN mapping in cutaneous melanoma, although lower doses need to be assessed.     

Advantages of preoperative ultrasound in conjunction with lymphoscintigraphy in detecting malignant melanoma metastases in sentinel lymph nodes: a retrospective analysis in 221 patients with malignant melanoma AJCC Stages I and II

Background Sentinel lymph node excision (SLNE) for the detection of regional nodal metastases and staging of malignant melanoma has resulted in some controversies in international discussions as it is a surgical intervention with potential morbidity. Objective The present retrospective study seeks to clarify the reliability of preoperative ultrasonography (US) in direct comparison to the result of SLNE and seeks to identify potential advantages of preoperative ultrasound if performed in conjunction with lymphoscintigraphy in detecting malignant melanoma metastases in sentinel lymph node (SLN). Patients We retrospectively analysed data from 221 patients with primary malignant melanoma with a Breslow index of ≥1.0 mm. Results Of the 221 patients, 77.4% (n = 171) had a negative SLN. In 50 patients (22.6%), the histopathological investigation of 71 excised lymph nodes resulted in a positive SLN. The US examination demonstrated a sensitivity of 13.6%, a specificity of 96.9%, a positive predictive value of 97.2% and a negative predictive value of 12.6%. SLNE alone shows a sensitivity of 94%, a specificity of 98.6%, a positive predictive value of 100% and a negative predictive value of 98.3%. Preoperative US in conjunction with dynamic lymphoscintigraphy, followed by SLNE, demonstrated a detecting ratio of 100% (n = 28) for micrometastases and 98.6% (n = 42/43) for macrometastases. Conclusion In conclusion, this study confirms that preoperative US alone cannot replace the vital information obtained during dynamic lymphoscintigraphy. But preoperative US is an important component of the staging procedure in melanoma patients and has clear advantages when performed in conjunction with dynamic lymphoscintigraphy. Therefore, we recommend preoperative US before every SLNE.     

Sentinel lymph node status is the most important prognostic factor for thick (≥ 4 mm) melanomas

Background: The value of the status of the sentinel lymph node (SLN) in patients with thick melanomas (Breslow thickness ≥ 4 mm) is controversial. Patients and Methods: Using Kaplan‐Meier estimates and Cox regression models, we studied 152 patients with primary melanomas ≥ 4 mm thickness who underwent sentinel lymph node excision (SLNE) at the university hospitals of Hannover and Göttingen, Germany, between 1998 and 2006. Results: The median tumor thickness was 5.2 (4–18) mm; 58.5% of primary melanomas were ulcerated. Micrometastasis to a SLN was found in 48.7%. The patients with positive SLNs were significantly younger than those with negative SLN (p = 0.01). Of the complete lymph node dissections, 32% contained positive non‐SLN. The estimated 5 year recurrence‐free survival was 42.5 ± 5% (± standard error) (26.3 ± 6.6% after positive SLNE, 58.7 ± 7.1% after negative SLNE). The 5 year overall survival rate was 53.2 ± 5.4% (37.5 ± 8.1% after positive SLNE, 67.6 ± 6.7% after negative SLNE). By multivariate analysis, the SLN was a highly significant predictor for overall survival (p = 0.007, relative risk 2.3, 95%, confidence interval 1.2–4.2). The overall survival was significantly associated with penetration of nodal metastases into the SLN > 0.3 mm (p = 0.001). Other parameters such as tumor thickness, ulceration, age and sex were not significant. In the subgroup of patients with negative SLN, neither tumor thickness nor ulceration was significant. Conclusions: The status of the SLN represents the most important prognostic parameter in patients with thick melanomas, whereas other parameters such as tumor thickness and ulceration loose their prognostic value.     

Reliability and cost‐effectiveness of sentinel lymph node excision under local anaesthesia versus general anaesthesia for malignant melanoma: a retrospective analysis in 300 patients with malignant melanoma AJCC Stages I and II

Background Sentinel lymph node excision (SLNE) for the detection of regional nodal metastases and staging of malignant melanoma has resulted in some controversies in international discussions, as it is a cost‐intensive surgical intervention with potentially significant morbidity. Objective The present retrospective study seeks to clarify the effectiveness and reliability of SLNE performed under tumescent local anaesthesia (TLA) and whether SLNE performed under TLA can reduce costs and morbidity. Therefore, our study is a comparison of SLNE performed under TLA and general anaesthesia (GA). Patients We retrospectively analysed data from 300 patients with primary malignant melanoma with a Breslow index of ≥1.0 mm. Results Altogether, 211 (70.3%) patients underwent SLNE under TLA and 89 (29.7%) patients underwent SLNE under GA. A total of 637 sentinel lymph nodes (SLN) were removed. In the TLA group 1.98 SLN/patient and in the GA group 2.46 SLN/patient were removed (median value). Seventy patients (23.3%) had a positive SLN. No major complications occurred. The costs for SLNE were significantly less for the SLNE in a procedures room performed under TLA (mean € 30.64) compared with SLNE in an operating room under GA (mean € 326.14, P < 0.0001). Conclusion In conclusion, SLNE performed under TLA is safe, reliable, and cost‐efficient and could become the new gold standard in sentinel lymph node diagnostic procedures.     

Prognostic value of galectin‐3 in primary cutaneous melanoma

Background Galectin‐3, one of the β‐galactoside‐binding lectins, has been suggested as a marker of disease progression in melanoma patients because of its overexpression observed in recent studies. However, prognostic value of galectin‐3 in primary cutaneous melanoma (PCM) has not been clearly defined. Objectives The aim of the study was to analyse whether the intensity of galectin‐3 expression can predict survival in patients with PMC. Methods Galectin‐3 expression was evaluated using immunohistochemistry in 104 PCM samples, including 71 (68.2%) superficial spreading (SSM) and 33 (31.8%) nodular melanomas (NM). Results Significant difference of galectin‐3 expression between SSM and NM was determined (P < 0.001). Increased galectin‐3 expression was positively correlated with tumour thickness (P < 0.001), Clark (P < 0.001) and Breslow (P < 0.001) stage, mitotic rate (P < 0.001), presence of tumour ulceration (P < 0.001), lymphatic invasion (P = 0.018), positive sentinel lymph node (P < 0.022) and distant metastases (P < 0.001). Kaplan–Meier analysis showed an association between increased galectin‐3 expression and reduced recurrence‐free survival (RFS) (P = 0.001) and reduced disease‐specific survival (DSS) (P = 0.015). In Cox proportional hazards regression analysis, significant predictors of reduced RFS were positive sentinel lymph node (P = 0.025) and lymphovascular invasion (P = 0.021), whereas predictors of DSS were tumour thickness (P = 0.012), lymphovascular invasion (P = 0.047), Clark stage (P = 0.029) and location of tumour on upper extremities (P = 0.024). Conclusions Our results support the potential role of galectin‐3 in PCM development, progression and metastasis. Moreover, galectin‐3 could serve as an additional prognostic marker that might help in further stratifying the risk of disease progression and metastasis in patients with PMC.     

Aberrant hypermethylation in primary tumours and sentinel lymph node metastases in paediatric patients with cutaneous melanoma

Background Debate on how to manage paediatric patients with cutaneous melanoma continues, particularly in those with sentinel lymph node (SLN) metastases who are at higher risk of poor outcomes. Management is often based on adult algorithms, although differences in clinical outcomes between paediatric and adult patients suggest that melanoma in paediatric patients differs biologically. Yet, there are no molecular prognostic studies identifying these differences. Objectives We investigated the epigenetic (methylation) regulation of several tumour‐related genes (TRGs) known to be significant in adult melanoma progression in histopathology(+) SLN metastases (n = 17) and primary tumours (n = 20) of paediatric patients with melanoma to determine their clinical relevance. Methods Paediatric patients (n = 37; ≤ 21 years at diagnosis) with American Joint Committee on Cancer stage I–III cutaneous melanoma were analysed. Gene promoter methylation of the TRGs RASSF1A, RARβ2, WIF1 and APC was evaluated. Results Hypermethylation of RASSF1A, RARβ2, WIF1 and APC was found in 29% (5/17), 25% (4/16), 25% (4/16) and 19% (3/16) of histopathology(+) SLNs, respectively. When matched to adult cutaneous melanomas by Breslow thickness and ulceration, hypermethylation of all four TRGs in SLN(+) paediatric patients with melanoma was equivalent to or less than in adults. With a median follow‐up of 55 months, SLN(+) paediatric patients with melanoma with hypermethylation of > 1 TRG vs. ≤ 1 TRG had worse disease‐free (P = 0·02) and overall survival (P = 0·02). Conclusions Differences in the methylation status of these TRGs in SLN(+) paediatric and adult patients with melanoma may account for why SLN(+) paediatric patients have different clinical outcomes. SLN biopsy should continue to be performed; within SLN(+) paediatric patients with melanoma, hypermethylation of TRGs can be used to identify a subpopulation at highest risk for poor outcomes who warrant vigilant clinical follow‐up.     

Lymphatic mapping and sentinel lymphonodectomy in recurrent cutaneous squamous cell carcinomas

There are subsets of cutaneous squamous cell carcinoma (SCC), including recurrent tumours, that have a high-risk for both local recurrence and metastasis. Since the presence of regional lymph node metastases carries a poor prognosis, the early evaluation of the nodal status is crucial for staging and treatment planning. Recent trials have shown that the lymphatic mapping (LM) and sentinel lymphonodectomy (SLNE) may be successfully employed to screen nodal basins in patients with high-risk cutaneous SCCs at clinical stage N0. We report our experience with this procedure in five selected patients affected with recurrent cutaneous SCCs. A metastatic sentinel lymph node (SLN) was found in 1 of the 5 cases. No false negative result was observed. SLNE is a feasible and minimally invasive staging procedure in patients with high-risk cutaneous SCCs. It may select patients with clinically occult metastases in the regional nodal basins, who can be submitted to therapeutic lymph node dissection (LND), avoiding the morbidity of a prophylactic LND in patients without metastases in SLNs.     

Inverse correlation between microtubule‐associated protein 1A/1B‐light chain 3 and p62/sequestosome‐1 expression in the progression of cutaneous squamous cell carcinoma

The expression of autophagy‐related markers has occasionally been reported to correlate with the clinical stage of disease in patients with solid cancer, indicating autophagy activation. However, there have been no such reports for cutaneous squamous cell carcinoma. In this study, we investigated the expression levels of two autophagy‐related markers, microtubule‐associated protein IA/IB light chain 3 (LC3) and p62/sequestosome‐1 (p62), in cutaneous squamous cell carcinoma specimens and assessed their correlation to clinicopathological factors in patients with this type of cancer. As a marker of the autophagosome, LC3 expression increases with autophagosome formation/accumulation, whereas p62 expression decreases due to selective degradation via autophagy. We performed immunostaining for LC3 and p62 in 50 cutaneous squamous cell carcinoma specimens obtained from patients treated by surgical resection, counted the number of cells that showed positive staining, and calculated the percentage of positive cells per low‐power microscopic field. We next investigated the correlations between the expression levels of these markers and various clinicopathological factors. The results indicated that LC3 expression increased significantly with advanced clinical stage (P < 0.001) and increased tumor diameter (P = 0.046). By contrast, the expression of p62 decreased significantly with advanced clinical stage (P < 0.001) and increased tumor diameter (P = 0.001). These results suggest that autophagy becomes activated during disease progression in patients with cutaneous squamous cell carcinoma.     

Matrix metalloproteinase‐7 activates heparin‐binding epidermal growth factor‐like growth factor in cutaneous squamous cell carcinoma

Background Tumour‐specific expression of matrix metalloproteinase (MMP)‐7 has been noted in cutaneous squamous cell carcinomas (SCCs) in patients with recessive dystrophic epidermolysis bullosa (RDEB). Objectives To examine the potential role of MMP‐7 in shedding of heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF) in RDEB‐associated and sporadic SCCs. Methods Tissue microarrays of RDEB‐associated SCC (n = 20), non‐EB SCC (n = 60) and Bowen disease (n = 28) were immunostained for MMP‐7, CD44 variant 3 (CD44v3) and HB‐EGF. Shedding of HB‐EGF was studied in vitro using two cutaneous SCC cell lines. Results Immunohistochemical analysis showed that HB‐EGF was absent in tumour cells when MMP‐7 and CD44v3 colocalized, and that the absence of HB‐EGF was more pronounced in RDEB‐associated SCCs than in non‐EB SCCs. The loss of HB‐EGF in MMP‐7–CD44v3 double‐positive areas was interpreted to indicate shedding and activation of HB‐EGF; this was also detected in Bowen disease indicating its importance in the early phase of SCC development. Specific knockdown of MMP‐7 expression in human cutaneous SCC cells by small interfering RNA inhibited shedding of HB‐EGF and resulted in diminished activation of the EGF receptor (EGFR) and ERK1/2, and in reduced proliferation of SCC cells. Conclusions These findings provide evidence for the role of MMP‐7 in promoting the growth of cutaneous SCCs by shedding HB‐EGF, and identify EGFR signalling as a potential therapeutic target in RDEB‐associated SCC and unresectable sporadic cutaneous SCC.     

Multiple primary malignancies in patients with Merkel cell carcinoma1

Background Merkel cell carcinoma (MCC) is a rare malignant cutaneous tumour, the incidence of which is increasing. Second malignancies have been reported to occur with high incidence in these patients. Objectives We report the rate and nature of multiple malignancies in patients with MCC treated over a 10 year period in Addenbrooke’s Hospital in Cambridge, United Kingdom, as well as the temporal relationship of these additional malignancies to the diagnosis of MCC. Results The 27 patients had an approximately equal sex incidence with a median age at diagnosis of 79 years. Seventy percent (n=19) of patients had a second primary malignant tumour; and 7 of these patients had two or more tumours in addition to the MCC. Eighteen patients had additional cutaneous malignancies: melanoma, squamous cell carcinoma and basal cell carcinoma, and 8 patients presented non‐cutaneous malignancy including colorectal, haematological and breast tumours. Of the 28 additional tumours in our patients, half were diagnosed prior to presentation of MCC, 32% within 6 months of diagnosis, and 18% between 6 months and 3 years after diagnosis. Possible reasons for the high rate of additional tumours in this population are discussed. Conclusions Our figures reflect a higher incidence of multiple malignancies in those with Merkel cell tumour than has previously been reported. This has important implications for the care and surveillance of these patients.     

Risk of subsequent cutaneous malignancy in patients with prior melanoma: a systematic review and meta‐analysis

Melanoma patients are known to be at risk of developing multiple cutaneous (pre‐) malignancies, however, the exact dimensions of these risks are unknown. In this meta‐analysis, risks of developing a melanoma, basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) after a melanoma were investigated. An extensive systematic literature search was conducted (last performed on 18 January 2012). Studies reporting risks, i.e. proportions, standardized incidence ratios (SIR) and cumulative risks (CRs) were included. Fifty, of 233 fully read articles, met selection criteria. Two independent reviewers extracted data on study characteristics and risks measurements. Random‐effects meta‐analyses were used to pool the risk estimates for the three tumour combinations. In melanoma patients, pooled proportions for a subsequent melanoma, BCC or SCC were respectively 3.8% (n = 47), 2.8% (n = 5) and 1.0% (n = 6). The pooled SIRs for a subsequent melanoma, BCC or SCC in melanoma patients were respectively 10.4 (n = 12), 4.6 (n = 2) and 2.8 (n = 2). Mean 20‐year CRs of a subsequent melanoma, BCC or SCC in melanoma patients were respectively 5.4% (n = 3), 14.0% (n = 1) and 4.0% (n = 1). Subgroup analyses showed substantial differences in reported risks between continents and study design. In conclusion, a history of a prior melanoma is a strong predictor for development of a subsequent melanoma (approximately 10‐fold increased risk) and to a lesser extent BCC or SCC. This information could serve as information for health care systems. Further, secondary prevention seems pivotal in this patient group.     

Malignant T cells in cutaneous T‐cell lymphoma lesions contain decreased levels of the antiapoptotic protein Ku70

Background Malignant T cells in primary cutaneous T‐cell lymphoma (CTCL) are genetically unstable and exhibit prolonged lifespans potentially explained by dysregulation of apoptosis, yet are responsive to apoptosis‐inducing therapies. The heterodimeric protein Ku70/80 is known to play a role in DNA repair (Ku70 and Ku80) and inhibition of apoptosis (Ku70 only). Objectives To investigate the expression of Ku70/80 in CD3+ T cells derived from skin and blood in patients with CTCL and normal samples, as well as benign dermatoses. Methods Normal (n = 10), CTCL (n = 9) and benign dermatoses (n = 13) skin samples were stained for confocal imaging of Ku70/80 and CD3 and analysed using imaging software. Circulating CD4+ T cells in normal and CTCL peripheral blood were analysed by flow cytometry and Western blot for Ku70/80 expression (n = 6). Results Ku70 and Ku80 were significantly diminished in T cells of CTCL lesions relative to T cells of control skin. Decreased T‐cell Ku70 expression was not a feature of the benign dermatoses psoriasis and contact dermatitis, suggesting that loss of Ku70/80 in CTCL is not simply the result of cutaneous inflammation. Reduced Ku70 was also noted in circulating CD4+ T cells in patients with CTCL with peripheral blood involvement. Conclusions Deficient expression or lack of Ku70/80 may result in genomic instability and play a role in tumorigenesis, as well as account for the increased susceptibility of malignant T cells to apoptosis‐inducing treatment modalities in the setting of intrinsic resistance to apoptosis.     

Sentinel lymph node biopsy in patients with thick (= 4 mm) melanoma: a single-centre experience

Background and objective Lymphatic mapping/sentinel lymph node biopsy (LM/SLNB) have become routine techniques for staging the regional lymph nodes in early stage melanoma, yet their role in the management of thick (= 4 mm) melanoma is debated. The aim of the present study is to review our experience with LM/SLNB in a series of patients with thick primary melanoma, to evaluate its utility in this melanoma subset. Patients and methods Thirty patients (18 men and 12 women; mean age 70.6 years; median 75 years) with thick primary melanoma underwent LM/SLNB, using both radioisotope and blue dye. The statistical tests were performed by using SAS software for Windows, version 8.2. Results The primary tumour sites were head/neck (n = 5; 16.6%), trunk (n = 10; 33.3%), and extremities (n = 15; 50%). Tumour thickness ranged from 4 to 17 mm (mean 5.14 mm; median 4.5 mm). Ulceration was observed in 23 (76.6%) tumours. Eleven patients (36.6%) had at least a positive sentinel lymph node (SLN). The mean follow-up was 27.3 months (median 26 months; range 5–63 months). Patients without SLN metastases had a 5-year disease-free survival rate of 78.9%, vs. 18.2% for patients with SLN metastases (P = 0.0121 by log rank test). The 5-year overall survival rate for patients without SLN metastases was 89.5%, whereas patients with SLN metastases had a 5-year overall survival rate of 36.4% (P = 0.0272 by log rank test). Conclusion Our retrospective analysis indicates that the SLN status is predictive of recurrence and survival in patients with thick melanoma, and LM/SLNB should be routinely performed in this subset of melanoma patients.     

Sentinel lymph node excision (SLNE) and positron emission tomography in the staging of stage I-II melanoma patients

BACKGROUND AND OBJECTIVE: Sentinel lymph node excision (SLNE) and positron emission tomography (PET) were evaluated in the staging of 51 Stage I and II melanoma patients (staged according to the guidelines of the German Dermatological Society). PATIENTS/METHODS AND RESULTS: Tumor thickness ranged from 1.0 mm to 6.0 mm (median: 1.5 mm; mean: 2.07 mm). At least one sentinel lymph node (SLN) was excised in all patients; 80 SLN were excised from 69 lymphatic drainage areas. Positive SLN were detected in 6 patients (11.8%). Additional positive lymph nodes were not detected in any of these patients in the following complete lymph node dissection of the affected lymph node basin. Preoperative PET was performed in 40 patients and did not detect any of the micrometastases that were subsequently found by SLNE. During the follow up of 7-40 months (mean 21.9 months) 3 patients experienced tumor progression; 2 of 3 had a positive SLN. CONCLUSIONS: According to the current literature SLNE is recommended in primary tumors greater than 1 mm thickness. PET cannot be expected to give additional information in the staging of stage I-II patients.     

Sentinel lymph node biopsy in melanoma: Our 8-year clinical experience in a single French institute (2002–2009)

Since the introduction of sentinel lymph node biopsy (SLNB), its use as a standard of care for patients with clinically node-negative cutaneous melanoma remains controversial. We wished to evaluate our experience of SLNB for melanoma. A single center observational cohort of 203 melanoma patients with a primary cutaneous melanoma (tumour thickness > 1 mm) and without clinical evidence of metastasis was investigated from 2002 to 2009. Head and neck melanoma were excluded. SLN was identified following preoperative lymphoscintigraphy and intraoperative gamma probe interrogation. The SLN identification rate was 97%. The SLN was tumor positive in 44 patients (22%). Positive SLN was significantly associated with primary tumor thickness and microscopic ulceration. The median follow-up was 39.5 (5–97) months. Disease progression was significantly more frequent in SLN positive patients (32% vs 13%, p = 0.002). Five-year DFS and OS of the entire cohort were 79.6% and 84.6%, respectively, with a statistical significant difference between SLN positive (58.7% and 69.7%) and SLN negative (85% and 90.3%) patients (p = 0.0006 and p = 0.0096 respectively). Postoperative complications after SLNB were observed in 12% of patients. Our data confirm previous studies and support the clinical usefulness of SLNB as a reliable and accurate staging method in patients with cutaneous melanoma. However, the benefit of additional CLND in patients with positive SLN remains to be demonstrated.     

MUM1 expression in cutaneous CD30+ lymphoproliferative disorders: a valuable tool for the distinction between lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma

Background Primary cutaneous CD30+ lymphoproliferative disorders include lymphomatoid papulosis (LyP) and primary cutaneous CD30+ anaplastic large T‐cell lymphoma (ALCL). Because of overlapping histological features, it is impossible to distinguish ALCL from LyP on histological grounds. MUM1 (Multiple Myeloma oncogene 1) is expressed in systemic ALCL and classical Hodgkin lymphoma. MUM1 expression has not been studied in detail in CD30+ lymphoproliferative disorders. Objectives To examine the expression of MUM1 in CD30+ lymphoproliferative disorders and to assess its value as a diagnostic marker. Methods Thirty‐one formalin‐fixed paraffin‐embedded specimens of LyP (n = 15), primary cutaneous ALCL (n = 10), secondary cutaneous infiltrates of systemic ALCL (n = 4) and secondary cutaneous Hodgkin lymphoma (n = 2) were analysed by immunohistochemistry with a monoclonal antibody against MUM1. Results Positive staining for MUM1 was observed in 13 cases of LyP (87%), two cases of primary cutaneous ALCL (20%), four cases of secondary cutaneous ALCL (100%) and two cases of secondary cutaneous Hodgkin lymphoma (100%). In 11 of 13 LyP cases (85%), MUM1 was displayed by the majority, i.e. 50–90%, of the tumour cells. In contrast to LyP and secondary cutaneous ALCL, only two cases of primary cutaneous ALCL (20%) harboured MUM1‐positive tumour cells. There was a statistically significant difference in the expression of MUM1 between LyP and primary cutaneous ALCL (P = 0·002) and between primary cutaneous ALCL and secondary cutaneous ALCL (P = 0·015). Conclusions MUM1 expression is a valuable tool for the distinction of LyP and ALCL and thus represents a novel adjunctive diagnostic marker in CD30+ lymphoproliferative disorders.     

PHOTOGRAPHY WITHOUT FILM: LOW-COST DIGITAL CAMERAS COME OF AGE IN DERMATOLOGY

Background. Photography is integral to the practice of dermatology. Digital imaging techniques have only recently been used to assess cutaneous disorders. Previously reported imaging systems have been both expensive and cumbersome. Consequently, they have failed to gain widespread acceptance. Methods. We describe our experience using an inexpensive digital camera. Photographs taken with this portable digital camera (FotoMan) compare favorably to those obtained with conventional 35 mm cameras. Results. This inexpensive digital camera provides photographs of acceptable quality for a variety of dermatologic applications. Images created with this system are available within minutes and are less expensive than traditional photographs. Conclusions. Digital imaging is a new and exciting development. The digital camera described is simple to operate and provides a useful alternative or adjunct to conventional photography.