Checkpoint blockade and BRAF/MEK therapy in the therapeutic setting improved the overall survival after sentinel node biopsy: A retrospective study comparing patients with primary care between 1998-2009 and 2010-2017.

Immunotherapies using checkpoint blockade and BRAF/MEK therapies have improved overall survival (OS) in patients with unresectable melanoma metastases. In this retrospective study, we aimed to demonstrate the resulting increase in melanoma-specific survival (MSS) and OS after the excision of primary melanomas (≥1 mm thick) and sentinel lymph node (SN) biopsy (SNB). Using Kaplan-Meier estimates and Cox models, we compared two consecutive cohorts. Patients in cohort 1 (N = 518) underwent SNB between 1998 and 2009, and patients in cohort 2 (N = 460) between 2010 and 2017, when checkpoint blockade and BRAF/(MEK) inhibition became available for the treatment of unresectable relapses. The median follow-up times were 120 and 73 months, respectively. While recurrence-free and distant metastasis-free survival rates remained very similar, MSS and OS increased in favor of cohort 2. The estimated 5-year OS rate of SN-positive patients increased by 14.3% (78.5% vs 64.2%, logrank test: P = .005). The MSS benefit was significant even with low SN tumor burden (metastasis diameter < 1 mm). On multivariate analyses, the risk-reduction in favor of cohort 2 was significant in the total population and in the SN-negative and SN-positive subgroups. In SN-positive patients, besides the availability of modern therapies, SN metastasis diameter and ulceration were independent factors of MSS and OS. Treatment of unresectable melanoma recurrences with modern drug therapies results in significantly higher survival rates in a population with SNB. The survival benefit measured from primary melanoma affects both the SN-positive and SN-negative subpopulations.

Left-sided excess in the laterality of cutaneous melanocytic nevi and melanomas.

BACKGROUND AND OBJECTIVES: Asymmetrical distribution of melanomas in favor of the left body half has been repeatedly described. PATIENTS AND METHODS: In a prospective cross-sectional study, we investigated the distribution of melanocytic nevi between the left and right halves of the body in 702 patients. In 2,004 consecutive cases with melanomas, we retrospectively determined left to right (L/R) ratios of primary melanomas, lymph node metastases, and melanocytic nevi in sentinel lymph nodes (SN). RESULTS: The L/R ratios for cutaneous nevi and melanomas were 1.23 (95 % confidence interval [CI] 1.12-1.36) and 1.6 (95 % CI 1.37-1.88), respectively. In both cutaneous nevi and melanomas, the left-sided excess was mainly found in intermittently light-exposed skin. Of the nevus patients, 92.4 % were right-handed. Breslow thickness and rates of ulceration did not differ significantly between the two body halves. CONCLUSIONS: Melanocytic nevi and melanomas are more frequently found on the left body half. We assume asymmetric solar radiation as the causative factor. The vast majority of right-handed people might unconsciously align their posture during outdoor activities so that the light falls in from the left. This avoids shadow cast by the dominant arm, shoulder, or head.

Linksüberhang in der Verteilung von melanozytären Nävi und Melanomen.

HINTERGRUND UND ZIELE: Eine asymmetrische Verteilung von Melanomen zugunsten der linken Körperhälfte wurde wiederholt beschrieben. PATIENTEN UND METHODIK: In einer prospektiven Querschnittstudie untersuchten wir bei 702 Patienten einer dermatologischen Klinik die Verteilung melanozytärer Nävi zwischen der linken und der rechten Körperhälfte. Außerdem bestimmten wir retrospektiv das Verhältnis von links zu rechts (L/R) von primären Melanomen, Lymphknotenmetastasen und Nävi in Sentinel-Lymphknoten (SN) bei 2004 konsekutiven Melanomfällen. ERGEBNISSE: Die L/R-Ratios für kutane Nävi und Melanome betrugen 1,23 (95 %-Konfidenzintervall [KI] 1,12-1,36) sowie 1,6 (95 %-KI 1,37-1,88). Sowohl bei kutanen Nävi als auch bei Melanomen wurde der Linksüberschuss hauptsächlich in intermittierend lichtexponierter Haut gefunden. In der Nävuspopulation waren 92,4 % Rechtshänder. Die Tumordicke nach Breslow und die Ulzerationsrate waren bei linksseitigen oder rechtsseitigen primären Melanomen ähnlich. SCHLUSSFOLGERUNGEN: Melanozytäre Nävi und Melanome sind numerisch häufiger auf der linken Körperhälfte zu finden. Wir nehmen asymmetrische Sonneneinstrahlung als ursächlich an. Die große Mehrheit der Rechtshänder könnte ihre Körperhaltung bei Aktivitäten im Freien unbewusst so ausrichteten, dass das Licht von links einfällt. Dadurch wird der Schattenwurf durch den dominanten Arm, die Schulter oder den Kopf vermieden.

Melanocytic nevi in sentinel lymph nodes: association with cutaneous nevi and clinical relevance in patients with cutaneous melanomas.

PURPOSE: Melanocytic nevi in lymph nodes (NNs) are an important histological differential diagnosis of initial sentinel lymph node (SN) metastasis in melanoma. Our aim was to associate NN in SNs with clinicopathologic features and survival rates in 1, 250 patients with SN biopsy for melanoma. METHODS: To compare patients with present and absent NN, we used Fisher's exact test, Mann-Whitney U test, and multivariate logistic regression models in this retrospective observational study based on a prospectively maintained institutional database. RESULTS: NN prevalence in axillary, cervical, and groin SNs was 16.5%, 19.4%, and 9.8%, respectively. NN were observed in combination with all growth patterns of melanoma, but more frequently when the primary was histologically associated with a cutaneous nevus. We observed a decreasing NN prevalence with increasing SN metastasis diameter. Multiple logistic regression determined a significantly increased NN probability for SNs of the neck or axilla, for individuals with ≥ 50 cutaneous nevi, midline primary melanomas, and for individuals who reported non-cutaneous malignancies in their parents. Cancer in parents was also significantly more frequently reported by melanoma patients who had more than 50 cutaneous nevi. In SN-negative patients, NN indicated a tendency for slightly lower melanoma-specific survival. CONCLUSIONS: We found a highly significant association between NN diagnosis and multiple cutaneous nevi and provided circumstantial evidence that cutaneous nevi in the drainage area of lymph nodes are particularly important. The trend toward lower melanoma-specific survival in SN-negative patients with NN suggests that careful differentiation of SN metastases is important.

The sentinel node invasion level (SNIL) as a prognostic parameter in melanoma.

Sentinel lymph node (SN) tumor burden is becoming increasingly important and is likely to be included in future N classifications in melanoma. Our aim was to investigate the prognostic significance of melanoma infiltration of various anatomically defined lymph node substructures. This retrospective cohort study included 1250 consecutive patients with SN biopsy. The pathology protocol required description of metastatic infiltration of each of the following lymph node substructures: intracapsular lymph vessels, subcapsular and transverse sinuses, cortex, paracortex, medulla, and capsule. Within the SN with the highest tumor burden, the SN invasion level (SNIL) was defined as follows: SNIL 1 = melanoma cells confined to intracapsular lymph vessels, subcapsular or transverse sinuses; SNIL 2 = melanoma infiltrating the cortex or paracortex; SNIL 3 = melanoma infiltrating the medulla or capsule. We classified 338 SN-positive patients according to the non-metric SNIL. Using Kaplan-Meier estimates and Cox models, recurrence-free survival (RFS), melanoma-specific survival (MSS) and nodal basin recurrence rates were analyzed. The median follow-up time was 75 months. The SNIL divided the SN-positive population into three groups with significantly different RFS, MSS, and nodal basin recurrence probabilities. The MSS of patients with SNIL 1 was virtually identical to that of SN-negative patients, whereas outgrowth of the metastasis from the parenchyma into the fibrous capsule or the medulla of the lymph node indicated a very poor prognosis. Thus, the SNIL may help to better assess the benefit-risk ratio of adjuvant therapies in patients with different SN metastasis patterns.

Embolia Cutis Medicamentosa after Subcutaneous Injection with Glatiramer Acetate.

Embolia cutis medicamentosa (ECM) is a rare and unpredictable injection site reaction, occurring after intramuscular, subcutaneous, and even after intraarticular injection of various drugs. We report a very rare case of necrotizing ECM after injection of glatiramer acetate for multiple sclerosis, include a photo documentation over the entire disease course, and discuss hypotheses as to etiology and treatment.

Axillary sentinel node biopsy in prone position for melanomas on the upper back or nape.

In patients with melanomas on the upper back or nape, axillary sentinel lymph node (SLN) biopsy (SLNB), when performed in the traditional supine position, is often disturbed by scattered radiation emitted from the primary tumor site. The results from the present study suggestthat axillary SLNB performed in the prone position can solve this problem. We compared two consecutive groups of patients with melanomas of the dorsal trunk or nape who received axillary SLNB performed either in the supine (n = 119) or in the prone position (n = 130). The number of SLNs detected and excised was significantly higher in prone position group (2.4 ± 1.5 SLNs versus 1.9 ± 0.95 SLNs, p = 0.002). Using the prone position, intra-operative repositioning of the patient for excision of a primary site of the upper back or neck was not necessary. The SLN identification rates and the SLN-positivity rates did not differ significantly between the two types of intraoperative patient positioning. There were no significant differences in survival outcomes or false-negative rates. In conclusion, axillary SLNB in prone position yields a higher number of excised SLNs in patients with melanomas of the upper back or nape. Axillary SLNB in prone position is easy to perform and reliable. Intraoperative repositioning of the patient is not necessary, which saves time and resources.

AL-Amyloidoma of the Skin-A Rare Manifestation of Primary Cutaneous Marginal Zone Lymphoma.

AL-amyloidoma is considered to be a variant of primary cutaneous marginal zone lymphoma (pcMZL). A 51-year-old white man presented a 2 × 2-cm erythematous to brownish waxy plaque on the back of the scalp. The plaque was first noticed 16 years ago. It was asymptomatic, and the patient was otherwise healthy. The lesion was excised. Histological examination revealed dermal deposits of amyloid and a subtle perivascular infiltrate, predominately consisting of plasma cells. Infiltrating cells expressed CD79a, bcl2, and IgG and were negative for bcl6, CD56, and IgM. A monoclonal light-chain expression of lambda (lambda:kappa = 10:1) was demonstrated by in situ hybridization. The diagnosis of pcMZL, presenting as an AL-amyloidoma, was made because staging procedures excluded systemic manifestation of lymphoma, monoclonal gammopathy, and systemic amyloidosis. Cutaneous amyloid deposits with monoclonal plasma cell proliferation can occur as a result of monoclonal gammopathy/plasmocytoma or as a rare manifestation of pcMZL. Systemic B-cell lymphoma and systemic monoclonal plasma cell proliferations have to be excluded.

Nodal Basin Recurrence After Sentinel Lymph Node Biopsy for Melanoma: A Retrospective Multicenter Study in 2653 Patients.

UNLABELLED: The objective of this study was to analyze different types of nodal basin recurrence after sentinel lymph node biopsy (SLNB) for melanoma. PATIENTS AND METHODS: Kaplan-Meier estimates and the Cox proportional hazards model were used to study 2653 patients from 3 German melanoma centers retrospectively.The estimated 5-year negative predictive value of SLNB was 96.4%. The estimated false-negative (FN) rates after 1, 2, 3, 5, and 10 years were 2.5%, 4.6%, 6.4%, 8.7%, and 12.6%, respectively. Independent factors associated with false negativity were older age, fewer SLNs excised, and head or neck location of the primary tumor. Compared with SLN-positive patients, the FNs had a significantly lower survival. In SLN-positive patients undergoing completion lymphadenectomy (CLND), the 5-year nodal basin recurrence rate was 18.3%. The recurrence rates for axilla, groin, and neck were 17.2%, 15.5%, and 44.1%, respectively. Significant factors predicting local relapse after CLND were older age, head, or neck location of the primary tumor, ulceration, deeper penetration of the metastasis into the SLN, tumor-positive CLND, and >2 lymph node metastases. All kinds of nodal relapse were associated with a higher prevalence of in-transit metastases.The FN rate after SLNB steadily increases over the observation period and should, therefore, be estimated by the Kaplan-Meier method. False-negativity is associated with fewer SLNs excised. The beneficial effect of CLND on nodal basin disease control varies considerably across different risk groups. This should be kept in mind about SLN-positive patients when individual decisions on prophylactic CLND are taken.

Repetitive injections of botulinum toxin A continuously increase the duration of efficacy in primary axillary hyperhidrosis: a retrospective analysis in 101 patients.

BACKGROUND AND OBJECTIVES: Botulinum toxin type A is an effective, well-tolerated, albeit temporary treatment for primary axillary hyperhidrosis. However, little is known about the influence of repetitive injections on the duration of efficacy. PATIENTS AND METHODS: 139 patients with primary axillary hyperhidrosis were injected with 50 units of botulinum toxin per axilla. In 101 patients, who received at least three treatments, the duration of efficacy after the first, second, and last treatment was evaluated. RESULTS: The median duration of efficacy was 4.0 months, 4.5 months, and 5.0 months after the first, second, and last injection, respectively. Overall, the duration of efficacy was significantly longer after the last injection compared to the duration of efficacy after the first injection (p = 0.0055, Wilcoxon matched-pairs signed-rank test). Likewise, the difference between the first and second injection (p = 0.0302) as well as the difference between the second and the last injection (p = 0.0381) were significant. In 25.7 % of patients, the duration of efficacy remained unchanged over the entire treatment period. CONCLUSIONS: Repetitive botulinum toxin treatments led to a significantly increased duration of efficacy in axillary hyperhidrosis. While the average duration of efficacy continued to increase with each treatment, there were considerable interindividual differences.