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Sentinel lymph node biopsy (SLNB) is often omitted in selected patients with advanced primary melanoma, although the justification/criteria for omission have been debated. We sought to determine whether assessment of frailty could serve as an objective marker to guide selection for SLNB in patients with advanced primary melanoma. Patients presenting with clinical stage IIC (ulcerated, > 4 mm Breslow thickness) cutaneous melanoma from January 1999 through June 2019 were included. Frailty was assessed using the Memorial Sloan Kettering Frailty Index (MSK FI), a composite score of functional status and medical comorbidities. Five-year melanoma-specific survival (MSS) and overall survival (OS) were estimated using Cox regression, and predictors of OS were identified using competing risk models. MSS did not differ between patients who did (n = 451) or did not undergo SLNB (n = 179) [63.2% vs. 65.0%, p = 0.14]; however, omission of SLNB was associated with decreased 5-year OS (29% vs. 44%, p

INTRODUCTION: Checkpoint inhibitors have improved outcomes in metastatic melanoma, with 4-year overall survival (OS) of 46% for anti-PD-1 alone or 53% in combination with anti-CTLA-4. However, the median progression free survival is 6.9 and 11.5 months, respectively. Many who progress have gone on to alternative treatments, including surgery, yet the outcome of patients selected for surgery after checkpoint blockade remains unclear. METHODS: Patients who were treated with checkpoint blockade from 2003 to 2017, followed by metastasectomy, were identified from a prospectively maintained institutional melanoma database. Response to immunotherapy was assessed at the time of surgery. Patients were categorized as having responding, isolated progressing, or multiple progressing lesions. RESULTS: Of the 237 total patients identified, 208 (88%) had stage IV disease and 29 (12%) had unresectable stage III disease at the start of immunotherapy. Median OS following first resection was 21 months. Median follow-up among survivors was 23 months. Complete resection at the first operation (n=87, 37%), was associated with improved survival compared with patients with incomplete resection (n=150, 63%) (median OS not reached (NR) versus 10.8 months, respectively; 95% CI: 7.3,14.8; p

Elevated peripheral blood neutrophil-to-lymphocyte ratio (NLR) is associated with poor oncologic outcomes in patients with stage IV melanoma and other solid tumors, but its impact has not been characterized for patients with high-risk, nonmetastatic melanoma. Retrospective review of a melanoma database identified patients with high-risk melanoma who underwent operation with curative intent at a single institution. NLR was calculated from blood samples obtained within 2 weeks before operation. Multiple primary melanomas and concurrent hematologic or other metastatic malignancies were excluded. Cumulative incidence of death due to disease was estimated, and Gray’s test was used to examine the effect of NLR on melanoma disease-specific death (DOD). Multivariable competing risks regression models assessed associated factors. Data on 1431 patients with high-risk, nonmetastatic melanoma were analyzed. Median follow-up for survivors was 4 years. High NLR (≥3 or as continuous variable) was associated with older age, male sex, thicker primaries, higher mitotic index, and more advanced nodal status. On multivariate analysis, high NLR (≥3 or as a continuous variable), older age, male sex, ulcerated primary, lymphovascular invasion, and positive nodal status were all independently associated with worse DOD. NLR is a readily available blood test that was independently associated with DOD in patients with high-risk, nonmetastatic melanoma. It is unclear whether high NLR is a passive indicator of poor prognosis or a potential therapeutic target. Further studies to evaluate the prognostic role of NLR to potentially identify those more likely to benefit from adjuvant immunotherapy may prove informative.

Melanoma patients with palpable nodal disease in more than one basin have a worse prognosis than those with single-basin disease. Little is known about the outcome of patients with microscopically positive nodal disease in more than one basin, or how they are currently managed at tertiary referral centers. We identified 97 patients with positive sentinel lymph nodes (SLNs) in more than one lymph node basin from 1994 to 2010 from three tertiary care centers. Clinical and pathologic outcome variables were analyzed. Ninety-seven patients (72 men, 25 women) were identified with at least one positive SLN in at least two node basins. Most primary tumors were truncal (68, 70 %) followed by extremity (16, 17 %) and head/neck (13, 13 %). The median Breslow depth was 3.2 mm (range 0.8–12 mm), and 49 (51 %) were ulcerated. The most frequently involved nodal basins were the axilla (112, 57 %), neck (40, 20 %), and groin (24, 12 %). Seventy-seven percent (153 of 198) of all positive SLN basins underwent completion lymph node dissection (CLND). Most patients (54, 56 %) developed recurrent disease, with a median time to recurrence of 20 months. The majority of first recurrences were distant (42, 43 %), followed by regional nonnodal metastases (17, 18 %) and regional nodal metastases (16, 16 %). There was no significant difference in median overall survival between CLND versus no-CLND groups (45 vs. 30 months, respectively). Most melanoma patients with more than one SLN-positive basin are currently managed with CLND. Outcomes after CLND and no CLND are similarly poor; therefore, consideration of close nodal observation may be more appropriate.

Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine neoplasm with propensity for lymphatic spread. The rarity of MCC has limited analysis of factors associated with a positive sentinel lymph node biopsy (SLNB) and survival. Review of a prospective MCC database was performed. Factors associated with SLNB positivity were analyzed. Univariate and multivariate analyses of factors associated with recurrence and survival were performed using the cumulative incidence (CI) function, treating death from other causes as a competing risk. From 1996 to 2010, a total of 153 patients with localized MCC underwent SLNB, of whom 45 (29%) were positive. Factors associated with SLNB positivity were primary tumor size (25% ≤2 cm vs. 45% >2 cm; P = 0.02) and presence of lymphovascular invasion (LVI) (55% LVI positive vs. 4% LVI negative; P

The pathologic status of the sentinel lymph node (SLN) is a powerful prognostic factor for patients with intermediate thickness melanoma. We hypothesize that a high number of SLNs identified may be associated with poor outcome. We evaluated the impact of number of SLNs removed in patients undergoing SLN mapping for cutaneous melanoma at our institution between 1996 and 2006. We excluded patients with multiple primary or synchronous primary lesions (n = 144) to eliminate any chance of erroneous association between a SLN and the wrong primary melanoma. We also excluded patients with in-transit disease (n = 37) and one patient in whom no SLN was identified, leaving 970 patients. We evaluated factors associated with the number of SLNs removed by multivariate Poisson regression and determined whether an increased number of SLNs was associated with poorer overall (OS) or recurrence-free survival (RFS). Clinical factors independently associated with increased number of SLNs were younger age and head and neck primary site. Pathologic factors associated with an increased number of SLNs were lymphovascular invasion and increased Breslow thickness. There was no association between number of SLNs removed and OS or RFS in all patients or in patients with negative SLNs (n = 803). The number of SLNs identified during staging of the regional nodal basin for primary melanoma is not an independent prognostic factor. Drainage to multiple SLNs is more common in the setting of an increased Breslow depth and lymphovascular invasion suggesting that tumors with these adverse features may enhance peritumoral lymphangiogenesis.

Desmoplastic melanoma (DM) is a rare variant characterized by the presence of fusiform melanocytes in a sclerotic stroma. Pathologic heterogeneity within DM may account for the controversy regarding the clinical presentation and prognosis of DM compared with conventional melanoma (CM).We identified 131 patients with a diagnosis of DM seen between 1979 and 2002. Tumors were categorized as either pure DM (pDM; n = 92), if desmoplasia was prominent throughout the entire invasive tumor, or mixed DM (mDM; n = 39), if fibrosis was well developed in only parts of an otherwise non-DM. Differences in clinical behavior among pDM, mDM, and CM (n = 3976) were examined.Seventy-three percent of patients with DM had tumors2 mm in depth, compared with 31% of patients with CM (P.001). Regional nodal metastasis was uncommon in patients who presented with clinically localized pDM (1%) compared with those with mDM (10%) or CM (6%) (P.05, pDM vs. CM). Five-year melanoma-specific mortality was lower for patients who presented with pDM compared with mDM (11% vs. 31%; P.01). Patients with pDM and CM had a similar melanoma-specific mortality despite a 3-fold difference in median tumor depth (3.6 vs. 1.2 mm, respectively).DMs can be divided into two subtypes based on a histological quantification of desmoplasia. Tumors with prominent fibrosis (pure subtype) are unlikely to disseminate to regional lymph nodes and are associated with a favorable outcome when compared with those with mixed desmoplasia or CM.

Background The overall prognosis of patients with thick cutaneous melanoma (TCM) is generally thought to be poor. Surgically staging these patients with sentinel lymph node (SLN) biopsy remains controversial. This study was performed to determine whether SLN status improved our ability to predict outcome over other known prognostic factors and to develop a model incorporating independent prognostic factors to estimate the risk of recurrence for an individual patient.

Acral melanoma (AM) is an unusual malignancy with poor survival. This study defines a cohort of patients, treated at a single institution, and the factors associated with survival and comparison with nonacral cutaneous melanoma (NACM). All patients with AM presenting from 1995 to 2010 were identified from a prospectively maintained database. Analysis of clinicopathologic features of AM associated with disease-specific survival (DSS) was performed. A stratified, stage-matched survival analysis compared the outcome of 281 acral to 843 extremity NACM patients. A total of 281 AM patients (170 volar, 111 subungual) were identified. Pathologic stage (p

An understanding of the methods of detection of recurrent melanoma after sentinel lymph node biopsy (SLNB) is essential for the coordination of a rational plan of follow-up.Clinical stage I/II melanoma patients who underwent SLNB from 1991 to 2004 were identified from a prospectively maintained single-institution database. Detection of recurrence by self (awareness of symptoms or abnormal physical findings) or physician (discovered on routine physical or scheduled test) and timing of clinic visit were recorded. Postoperative follow-up included physical exam every 3-4 months for the first year, every 3-6 months for the second year, and every 6-12 months thereafter. Serum lactate dehydrogenase (LDH) and chest X-ray (CXR) were obtained annually. Computed tomography (CT) and positron emission tomography (PET) were performed selectively.Of 1062 patients who underwent SLNB, 203 (19%) experienced 230 initial sites of recurrence; 198 patients were evaluable for follow-up. Median follow-up after first recurrence was 17 months. Symptoms and self-detected physical findings were present in 109 patients (55%); 85 patients (78%) were seen earlier than their scheduled visit. Self-detected physical findings identified in-transit (n = 26; 24%) and nodal (n = 25; 23%) disease. Physician detection occurred in 89 patients (45%), nearly half by a scheduled radiographic test (CXR, 16%; CT, 29%; PET, 1%). The method of detection significantly predicted post-recurrence survival (p0.05).More than half of melanoma recurrences are self-detected; these patients have the most favorable post-recurrence survival rates because of the type of recurrence detected. The mode of detection is a significant predictor of post-recurrence survival. This supports an aggressive program of patient education in self-examination after SLNB for melanoma.

The overall prognosis of patients with thick cutaneous melanoma (TCM) is generally thought to be poor. Surgically staging these patients with sentinel lymph node (SLN) biopsy remains controversial. This study was performed to determine whether SLN status improved our ability to predict outcome over other known prognostic factors and to develop a model incorporating independent prognostic factors to estimate the risk of recurrence for an individual patient.A prospective database identified patients with TCM (4.0 mm or Clark level V) and clinically negative nodes who underwent SLN biopsy. Univariate and multivariate analyses were performed.From 1991 to 2001, 126 patients were identified; 75 (60%) were male. The median age was 60 years. The median tumor thickness was 5.5 mm, and 43% were ulcerated. Thirty percent of patients had a positive SLN. Recurrence was seen in 50 patients (40%). Median follow-up, relapse-free survival, and overall survival were 25, 50, and 68 months, respectively. Factors independently predictive of recurrence were age/=60 years, depth5.5 mm, ulceration, and SLN positivity. SLN status was the most significant prognostic factor (P.001). The relative risk of recurrence for an individual patient ranged from 1 in patients for whom no adverse factors were present to 29.4 when all factors were present.SLN status was the strongest independent predictor of outcome in patients with TCM. However, patients with TCM are prognostically heterogeneous, and all independently predictive factors should be considered when an individual patient's risk of recurrence is assessed.