Faculty Bibliography

BACKGROUND: Identification of primary melanoma patients at the highest risk of recurrence remains a critical challenge, and monitoring for recurrent disease is limited to costly imaging studies. We recently reported our array-based discovery of prognostic serum miRNAs in melanoma. In the current study, we examined the clinical utility of these serum-based miRNAs for prognosis as well as detection of melanoma recurrence. METHODS: Serum levels of 12 miRNAs were tested using qRT-PCR at diagnosis in 283 melanoma patients (training cohort, n = 201; independent validation, n = 82; median follow-up, 68.8 months). A refined miRNA signature was chosen and evaluated. We also tested the potential clinical utility of the miRNAs in early detection and monitoring of recurrence using multiple longitudinal samples (pre- and postrecurrence) in a subset of 82 patients (n = 225). In addition, we integrated our miRNA signature with publicly available Cancer Genome Atlas data to examine the relevance of these miRNAs to melanoma biology. RESULTS: Four miRNAs (miR-150, miR-30d, miR-15b, and miR-425) in combination with stage separated patients by recurrence-free survival (RFS) and overall survival (OS) and improved prediction of recurrence over stage alone in both the training and validation cohorts (training RFS and OS, P < .001; validation RFS, P < .001; OS, P = .005). Serum miR-15b levels significantly increased over time in recurrent patients (P < .001), adjusting for endogenous controls as well as age, sex, and initial stage. In nonrecurrent patients, miR-15b levels were not significantly changed with time (P =.17). CONCLUSIONS: Data demonstrate that serum miRNAs can improve melanoma patient stratification over stage and support further testing of miR-15b to guide patient surveillance. Cancer 2015;121:51-59. (c) 2014 American Cancer Society.

PURPOSE: Melanoma, the skin cancer with the lowest incidence, causes the majority of all skin cancer-related deaths. Early detection has led to the discovery of melanoma at less advanced stages, thus shifting the reconstructive paradigm from sole survivorship to the improvement of function and cosmesis while still maintaining an overall adequate outcome. Reconstructive approaches rely on two main factors: location of the lesion and size of the lesion. Due to the complexity of the hand, reconstructive options are quite heterogeneous. The purpose of this study is to explore the clinical data and reconstructive strategies of hand and digital cutaneous melanoma and subungual melanoma, review the current reconstructive options presented in the medical literature, and offer a reconstructive algorithm to surgically approach primary melanoma of the hand. METHODS: A retrospective chart review was conducted for all patients undergoing oncologic resection of primary melanoma of the hand at New York University Langone Medical Center (NYULMC) between April 2003 and October 2011. Variables collected included age, race, gender, type of melanoma, Breslow depth, stage, oncologic resection, reconstructive surgery, and outcomes. RESULTS: A total of 35 patients with primary melanoma of the hand comprised the study cohort. The mean age of presentation was 56 years with a total of 24 women and 11 men. The average Breslow depth of the cohort was 1.58 mm. There were 13 cases of melanoma in situ (MIS). All MIS cases were treated with wide local excision, yet the subungual group needed more extensive reconstruction including paronychial advancement flaps and full-thickness skin grafts (FTSG). Twenty-two cases presented as malignant melanoma. The majority of the patients with cutaneous melanoma underwent wide local excision with primary closure or FTSG. In the subungual group, all patients underwent amputation at the most distal interphalangeal joint or wide local excision. The reconstruction consisted of local advancement flaps, FTSG, or primary closure. CONCLUSION: Reconstructive options for primary melanoma of the hand are quite varied without strong guidelines as to which technique is superior. Location, size, and type of lesion (cutaneous or subungual) help shape which reconstructive strategies are optimal. With more conservative oncologic approaches and advanced reconstructive techniques, patients are able to maintain function with a satisfactory degree of cosmesis.

Background: Invasive micropapillary carcinoma (IMPC) of the breast is a rare and aggressive variant of invasive ductal carcinoma. IMPC has been reported to account for 3-6% of all breast cancers, and these tumors have been associated with a strong tendency to invade lymphatics with early spread to regional lymph nodes. Patients and methods: We present a case of this rare type of breast cancer diagnosed in a male patient and summarize the current literature to date. Results: Review of the literature on invasive micropapillary breast carcinoma revealed 27 retrospective cohort studies and case series. Significant heterogeneity of inclusion criteria and follow up data prevented meta-analysis. Tumors with an IMPC component demonstrated an early and high rate of lymphatic metastasis compared to invasive ductal carcinoma, however, no significant association was found between IMPC and decreased overall survival. Conclusions: The IMPC data currently available indicates a strong trend towards a higher initial stage at diagnosis and possibly an increased risk of loco-regional recurrence, but remains underpowered to elucidate the prognostic effect of IMPC phenotype on survival. Further studies are warranted to establish the potential of this unique histologic phenotype to serve as a prognostic indicator and guide tumor-specific oncologic therapy

Subungual melanoma is a rare but lethal form of melanoma. Amputation at the level of the interphalangeal joint or proximal has been described as appropriate surgical management for all stages of subungal melanoma. In cases of subungual melanoma in situ (SMIS), wide local excision can improve functional and aesthetic outcomes. We reviewed our experience of wide local excision for the treatment of SMIS. Between 2003 and 2010, we treated 9 cases of SMIS. We performed a retrospective review of this series looking at the primary outcomes of recurrence or metastasis. Average age was 40 years (range, 5-65 years). Presenting lesions were on the thumb (5) and index finger (4). All patients underwent definitive reconstruction with a combination of full-thickness skin graft (8) and paronychial advancement flap (6). Reexcision was performed when disease-free margins could not be confirmed. To date, there have been no cases of metastasis or local recurrence in any of our 9 patients (mean follow-up time of more than 4 years). Wide local excision can improve functional and aesthetic outcomes with similar success in rates of local recurrence and metastasis when compared to treatment by amputation in SMIS.

Current surgical treatment of primary melanoma is uniform for all histosubtypes, although certain types of melanoma, such as acral lentiginous melanoma (ALM), have a worse prognosis. No study has explored the effectiveness of standard melanoma treatment guidelines for managing ALM compared with nonacral melanoma (NAM). Study subjects were identified from a prospectively enrolled database of patients with primary melanoma at New York University. Patients with ALM were matched to those with NAM (1:3) by gender and melanoma stage, including substage (ALM, 61; NAM, 183). All patients received standard-of-care treatment. Recurrence and survival outcomes in both cohorts were compared. ALM histologic subtype was an independent negative predictor of recurrence-free survival (hazard ratio [HR], 2.24; P=.001) and melanoma-specific survival (HR, 2.58; P=.001) compared with NAM. Recurrence was significantly more common in patients with ALM than in those with NAM (49% vs 30%; P=.007). For tumors less than 2 mm in thickness, a significantly higher recurrence rate was seen with ALM versus NAM (P=.048). No significant difference was seen in recurrence for tumors greater than 2 mm (P=.12). Notably, the rate of locoregional recurrence was nearly double for ALM compared with NAM (P=.001). The data presented herein reveal a high rate of locoregional failure in ALM compared with NAM when controlling for AJCC stage. These results raise the question of whether ALM may require more aggressive surgical treatment than nonacral cutaneous melanomas of equal thickness, particularly in tumors less than 2 mm thick. Larger multicenter trials are necessary for further conclusions.

BACKGROUND: Reconstruction in the setting of prior breast irradiation is conventionally considered a higher-risk procedure. Limited data exist regarding nipple-sparing mastectomy in irradiated breasts, a higher-risk procedure in higher-risk patients. METHODS: The authors identified and reviewed the records of 501 nipple-sparing mastectomy breasts at their institution from 2006 to 2013. RESULTS: Of 501 nipple-sparing mastectomy breasts, 26 were irradiated. The average time between radiation and mastectomy was 12 years. Reconstruction methods in the 26 breasts included tissue expander (n = 14), microvascular free flap (n = 8), direct implant (n = 2), latissimus dorsi flap with implant (n = 1), and rotational perforator flap (n = 1). Rate of return to the operating room for mastectomy flap necrosis was 11.5 percent (three of 26). Nipple-areola complex complications included one complete necrosis (3.8 percent) and one partial necrosis (3.8 percent). Complications were compared between this subset of previously irradiated patients and the larger nipple-sparing mastectomy cohort. There was no significant difference in body mass index, but the irradiated group was significantly older (51 years versus 47.2 years; p = 0.05). There was no statistically significant difference with regard to mastectomy flap necrosis (p = 0.46), partial nipple-areola complex necrosis (p = 1.00), complete nipple-areola complex necrosis (p = 0.47), implant explantation (p = 0.06), hematoma (p = 1.00), seroma (p = 1.00), or capsular contracture (p = 1.00). CONCLUSION: In the largest study to date of nipple-sparing mastectomy in irradiated breasts, the authors demonstrate that implant-based and autologous reconstruction can be performed with complications comparable to those of the rest of their nipple-sparing mastectomy patients.