Management of Sentinel Lymph Node Metastasis in Merkel Cell Carcinoma: Completion Lymphadenectomy, Radiation, or Both?

BACKGROUND: Approximately 30% of patients with clinically localized Merkel cell carcinoma (MCC) show nodal involvement on sentinel lymph node biopsy (SLNB). Optimal management of SLNB-positive disease has not been defined. This study compared outcomes after completion lymphadenectomy (CLND), radiation, and combined CLND plus radiation after a positive SLNB. METHODS: All patients treated at a single institution for SLNB-positive MCC (1998-2015) were retrospectively evaluated, with examination of patient demographics, clinicopathologic characteristics, outcomes, and regional toxicity. RESULTS: The study identified 71 evaluable patients with SLNB-positive disease. The median age of these patients was 76 years, and 76.1% were men. Of the 71 patients, 11 (15.5%) underwent CLND, 40 (56.3%) received radiation, and 20 (28.2%) underwent CLND plus postoperative radiation. Lymphovascular invasion was significantly more common in the radiation-alone cohort (p = 0.04). For the three cohorts, the median percentages of nodal involvement were respectively 2, 10, and 30% (p = 0.06). After a median follow-up period of 22.3 months, four patients had recurrence in their regional nodal basin (3 radiation-alone patients and 1 CLND + radiation patient). The three cohorts did not differ significantly in the development of distant metastases (p = 0.68) or overall survival (p = 0.72). Six patients experienced surgical-site infections (2 CLND and 4 CLND + radiation patients), and three patients experienced symptomatic lymphedema (1 CLND patient and 2 CLND + radiation patients). CONCLUSIONS: Regional failure was infrequent (≤ 10%) regardless of treatment, and morbidity appeared to be low with all approaches. Given that multiple treatment approaches can be successful in treating micrometastatic MCC, future efforts should be directed at refining criteria for allocating patients to a specific method, or possibly no further nodal basin treatment, in an effort to maximize regional control at the lowest cost and morbidity.

Resection Margins in Merkel Cell Carcinoma: Is a 1-cm Margin Wide Enough?

BACKGROUND: Guidelines regarding specific resection margins for primary Merkel cell carcinoma (MCC) are not well established. The current National Comprehensive Cancer Network (NCCN) guidelines recommend 1- to 2-cm resection margins. This study aimed to determine the impact of margin width on local recurrence (LR), disease-specific survival (DSS), overall survival (OS), and type of wound closure. METHODS: All patients who underwent resection of primary MCC at a single institution from 2000 to 2015 were reviewed. Patient demographics, clinicopathologic characteristics, treatments, and outcomes were reviewed. RESULTS: A total of 240 patients underwent resection of primary MCC with resection margin width identified in the operative report. The median age was 76 years, and 65.8% of the patients were men. Of the 240 patients, 85 (35.4%) had head and neck primaries, 140 (58.3%) had extremity primaries, and 15 (6.3%) had trunk primaries. In terms of margins, 69 patients (28.8%) had a margin of 1 cm, 36 patients (15%) had a margin of 1.1-1.9 cm, and 135 patients (56.2%) had a margin of 2 cm or more. The median follow-up period was 21 months. The LR rate was 2.9% for a margin of 1 cm, 2.8% for a margin of 1.1-1.9 cm, and 5.2% for a margin of 2 cm or more (p = 0.80). The 5-year OS was 63.6% for a margin of 1 cm, 59.7% for a margin of 1.1-1.9, and 70.7% for a margin of 2 cm or more (p = 0.66). The 5-year DSS was 80.3% for a margin of 1 cm, 66.2% for a margin of 1.1-1.9 cm, and 91.8% for a margin of 2 cm or more (p = 0.28). For wound closure, 43.5, 50, and 65.9% of the patients respectively required a flap or graft with a margin of 1, 1.1-1.9, and 2 cm or more (p = 0.006). CONCLUSIONS: A 1-cm resection margins did not increase the risk of LR. Margin width did not make a significant difference in DSS or OS. Larger resection margins increase the need for a graft or flap closure.

A Comparative Study of the ReCell® Device and Autologous Spit-Thickness Meshed Skin Graft in the Treatment of Acute Burn Injuries.

Early excision and autografting are standard care for deeper burns. However, donor sites are a source of significant morbidity. To address this, the ReCell® Autologous Cell Harvesting Device (ReCell) was designed for use at the point-of-care to prepare a noncultured, autologous skin cell suspension (ASCS) capable of epidermal regeneration using minimal donor skin. A prospective study was conducted to evaluate the clinical performance of ReCell vs meshed split-thickness skin grafts (STSG, Control) for the treatment of deep partial-thickness burns. Effectiveness measures were assessed to 1 year for both ASCS and Control treatment sites and donor sites, including the incidence of healing, scarring, and pain. At 4 weeks, 98% of the ASCS-treated sites were healed compared with 100% of the Controls. Pain and assessments of scarring at the treatment sites were reported to be similar between groups. Significant differences were observed between ReCell and Control donor sites. The mean ReCell donor area was approximately 40 times smaller than that of the Control (P < .0001), and after 1 week, significantly more ReCell donor sites were healed than Controls (P = .04). Over the first 16 weeks, patients reported significantly less pain at the ReCell donor sites compared with Controls (P ≤ .05 at each time point). Long-term patients reported higher satisfaction with ReCell donor site outcomes compared with the Controls. This study provides evidence that the treatment of deep partial-thickness burns with ASCS results in comparable healing, with significantly reduced donor site size and pain and improved appearance relative to STSG.

Treatment of Head and Neck Melanoma In Situ With Staged Contoured Marginal Excisions.

Staged marginal evaluation of melanoma in situ (MIS) is performed to avoid reconstruction on positive margins. Contoured marginal excision (CME) is an excision of a 2-mm wide strip of normal-appearing skin taken approximately 5 mm from the visible tumor periphery. If positive, a new CME is excised; the tumor is resected once negative margins are confirmed. The purpose of this study is to report our experience using this technique for the treatment of head/neck MIS. Clinicopathological data were abstracted for all patients who underwent staged CME followed by central tumor resection for head/neck MIS; patients with invasive melanoma were excluded. Statistical analyses included χ test and t test. Overall, 127 patients with MIS were identified. Fifty-six percent were men; the average age was 68 years. The median number of CME procedures per patient was 1 (range, 1-4). Twenty-three percent of patients required more than 1 CME procedure to achieve negative margins. Local recurrence occurred in 3 of 127 patients after a median follow-up of 5 months. Patients requiring multiple CME procedures were more likely to experience local recurrence (P < 0.001). In conclusion, this technique is an effective method to avoid reconstruction on positive MIS margins with high local disease control rates.

Primary Gangrenous Cutaneous Mold Infections in a Patient With Cancer and Neutropenia.

BACKGROUND: Opportunistic fungal infections caused by Aspergillus and Candida followed by infections with Fusarium, Rhizopus, Mucor, and Alternaria species are an important cause of morbidity and mortality in patients with hematological malignancies. Cutaneous mucormycosis infections are rare, and the incidence, outcomes, and factors associated with survival in the setting of hematological malignancies are not clear. METHODS: A literature search was conducted for all cases of primary cutaneous mold infections in patients with hematological malignancy, of which 50 cases were found. Our case of a patient with a hematological malignancy who sustained a cat bite that in turn caused a primary cutaneous mold infection is also included. RESULTS: In the 51 cases identified, 66.7% were neutropenic upon presentation, and 54.9% were male with an average age of 32 years. Aspergillus species (33.3%) was the most cited followed by Rhizopus species (19.6%). Overall mortality rate was 29.4% and was observed more frequently in patients with neutropenia (60.0%) and without surgical intervention (73.3%). Survival rate was higher (35.3%) for cases utilizing both antifungal and surgical intervention. The antifungal agent with the highest survival rate was amphotericin B and its formulations (58.8%). CONCLUSIONS: Neutropenia within hematological malignancies demonstrate a risk for developing severe cutaneous fungal infections, of which primary cutaneous mucormycosis can carry significant mortality. Combination antifungal therapy and surgical debridement appears to be associated with higher survival outcomes and warrants further investigation.

Radiation Therapy is Associated with Improved Outcomes in Merkel Cell Carcinoma.

BACKGROUND: Following wide excision of Merkel cell carcinoma (MCC), postoperative radiation therapy (RT) is typically recommended. Controversy remains as to whether RT can be avoided in selected cases, such as those with negative margins. Additionally, there is evidence that RT can influence survival. METHODS: We included 171 patients treated for non-metastatic MCC from 1994 through 2012 at a single institution. Patients without pathologic nodal evaluation (clinical N0 disease) were excluded to reflect modern treatment practice. The endpoints included local control (LC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS). RESULTS: Median follow-up was 33 months. Treatment with RT was associated with improved 3-year LC (91.2 vs. 76.9 %, respectively; p = 0.01), LRC (79.5 vs. 59.1 %; p = 0.004), DFS (57.0 vs. 30.2 %; p < 0.001), and OS (73 vs. 66 %; p = 0.02), and was associated with improved 3-year DSS among node-positive patients (76.2 vs. 48.1 %; p = 0.035), but not node-negative patients (90.1 vs. 80.8 %; p = 0.79). On multivariate analysis, RT was associated with improved LC [hazard ratio (HR) 0.18, 95 % confidence interval (CI) 0.07-0.46; p < 0.001], LRC (HR 0.28, 95 % CI 0.14-0.56; p < 0.001), DFS (HR 0.42, 95 % CI 0.26-0.70; p = 0.001), OS (HR 0.53, 95 % CI 0.31-0.93; p = 0.03), and DSS (HR 0.42, 95 % CI 0.26-0.70; p = 0.001). Patients with negative margins had significant improvements in 3-year LC (90.1 vs. 75.4 %; p < 0.001) with RT. Deaths not attributable to MCC were relatively evenly distributed between the RT and no RT groups (28.5 and 29.3 % of patients, respectively). CONCLUSIONS: RT for MCC was associated with improved LRC and survival. RT appeared to be beneficial regardless of margin status.

Both tumor depth and diameter are predictive of sentinel lymph node status and survival in Merkel cell carcinoma.

BACKGROUND: The purposes of this study were 1) to determine the impact of primary tumor-related factors on the prediction of the sentinel lymph node (SLN) status and 2) to identify clinical and pathologic factors associated with survival in Merkel cell carcinoma (MCC). METHODS: An institutional review board-approved, retrospective review of patients with MCC treated between 1988 and 2011 at a single center was performed. Patients were categorized into 5 groups: 1) negative SLN, 2) positive SLN, 3) clinically node-negative but SLN biopsy not performed, 4) regional nodal disease without a known primary tumor, and 5) primary MCC with synchronous clinically evident regional nodal disease. Factors predictive of the SLN status were analyzed with logistic regressions, and overall survival (OS) and disease-specific survival (DSS) were analyzed with Cox models and competing risk models assuming proportional hazards, respectively. RESULTS: Three hundred seventy-five patients were analyzed, and 70% were male; the median age was 75 years. The median tumor diameter was 1.5 cm (range, 0.2-12.5 cm), and the median tumor depth was 4.8 mm (range, 0.3-45.0 mm). One hundred ninety-one patients underwent SLN biopsy, and 59 (31%) were SLN-positive. Increasing primary tumor diameter and increasing tumor depth were associated with SLN positivity (P = .007 and P = .017, respectively). Age and sex were not associated with the SLN status. Immunosuppression, increasing tumor diameter, and increasing tumor depth were associated with worse OS (P = .007, P = .003, and P = .025, respectively). DSS differed significantly by group and was best for patients with a negative SLN and worst for those with primary MCC and synchronous clinically evident nodal disease (P = .018). CONCLUSION: For patients with MCC, increasing primary tumor diameter and increasing tumor depth are independently predictive of a positive SLN, worse OS, and worse DSS. Tumor depth should be routinely reported when primary MCC specimens are being evaluated histopathologically.

Clinicopathologic predictors of survival in patients with desmoplastic melanoma.

BACKGROUND AND OBJECTIVES: Desmoplastic melanoma is a unique subtype of melanoma which typically affects older patients who often have comorbidities that can adversely affect survival. We sought to identify melanoma-specific factors influencing survival in patients with desmoplastic melanoma. METHODS: Retrospective review from 1993 to 2011 identified 316 patients with primary desmoplastic melanoma. Clinicopathologic characteristics were correlated with nodal status and outcome. RESULTS: Fifty-five patients (17.4%) had nodal disease: 33 had a positive sentinel lymph node biopsy and 22 developed nodal recurrences (no sentinel lymph node biopsy or false-negative sentinel lymph node biopsy). Nodal disease occurred more often in younger patients and in cases with mixed compared with pure histology (26.7% vs. 14.6%); both of these variables significantly predicted nodal status on multivariable analysis (p<0.05). After a median follow-up of 5.3 years, recurrence developed in 87 patients (27.5%), and 111 deaths occurred. The cause of death was known in 79 cases, with 47 deaths (59.5%) being melanoma-related. On multivariable analysis, Breslow thickness, mitotic rate ≥ 1/mm(2) and nodal status significantly predicted melanoma-specific survival (p<0.05). CONCLUSIONS: Nodal status predicts melanoma-specific survival in patients with desmoplastic melanoma. However, since patients with desmoplastic melanoma represent an older population, and a considerable proportion of deaths are not melanoma-related (40.5%), comorbidities should be carefully considered in making staging and treatment decisions in this population.

The impact of neoadjuvant hedgehog inhibitor therapy on the surgical treatment of extensive basal cell carcinoma.

BACKGROUND: Although hedgehog inhibitor therapy (HHIT) is offered as isolated medical treatment for extensive basal cell carcinoma (BCC), there is little evidence on the use of HHIT before definitive surgical intervention. In order to better define the utilization of HHIT for extensive BCC, we evaluated the impact of neoadjuvant HHIT on the subsequent surgical resection and reconstruction. METHODS: An IRB-approved, retrospective chart review was performed of patients who received HHIT as initial treatment for extensive BCC. Patients who discontinued HHIT and underwent surgical resection were included. Evaluation included BCC tumor response to HHIT, operative data, pathological data, radiation requirements, and evidence of tumor recurrence. RESULTS: Six patients were identified with tumors of the face/scalp (n = 4), trunk (n = 1) and upper extremity (n = 1). Hedgehog inhibitor therapy continued until tumors became unresponsive (n = 3, mean = 71 weeks) or side effects became intolerable (n = 3, mean = 31 weeks). In each case, a less extensive surgery was performed than estimated before HHIT. In 3 cases, significant bone resection was avoided. All resected specimens contained BCC. Four specimens exhibited clear margins. Postoperative radiation was performed in cases with positive margins (n = 2), and 1 patient experienced local recurrence. Length of follow-up was 5.7 to 11.8 months (mean = 8.23 months). CONCLUSIONS: Although HHIT was not curative for extensive BCC, HHIT can decrease the morbidity of surgical treatment and increase the likelihood of curative resection. For patients with extensive BCC, a combined neoadjuvant use of HHIT and surgical treatment should be considered.

Sentinel lymph node biopsy is indicated for patients with thick clinically lymph node-negative melanoma.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is indicated for the staging of clinically lymph node-negative melanoma of intermediate thickness, but its use is controversial in patients with thick melanoma. METHODS: From 2002 to 2012, patients with melanoma measuring ≥4 mm in thickness were evaluated at a single institution. Associations between survival and clinicopathologic characteristics were explored. RESULTS: Of 571 patients with melanomas measuring ≥4 mm in thickness and no distant metastases, the median age was 66 years and 401 patients (70.2%) were male. The median Breslow thickness was 6.2 mm; the predominant subtype was nodular (45.4%). SLNB was performed in 412 patients (72%) whereas 46 patients (8.1%) presented with clinically lymph node-positive disease and 113 patients (20%) did not undergo SLNB. A positive SLN was found in 161 of 412 patients (39.1%). For SLNB performed at the study institution, 14 patients with a negative SLNB developed disease recurrence in the mapped lymph node basin (false-negative rate, 12.3%). The median disease-specific survival (DSS), overall survival (OS), and recurrence-free survival (RFS) for the entire cohort were 62.1 months, 42.5 months, and 21.2 months, respectively. The DSS and OS for patients with a negative SLNB were 82.4 months and 53.4 months, respectively; 41.2 months and 34.7 months, respectively, for patients with positive SLNB; and 26.8 months and 22 months, respectively, for patients with clinically lymph node-positive disease (P<.0001). The median RFS was 32.4 months for patients who were SLNB negative, 14.3 months for patients who were SLNB positive, and 6.8 months for patients with clinically lymph node-positive disease (P<.0001). CONCLUSIONS: With an acceptably low false-negative rate, patients with thick melanoma and a negative SLNB appear to have significantly prolonged RFS, DSS, and OS compared with those with a positive SLNB. Therefore, SLNB should be considered as indicated for patients with thick, clinically lymph node-negative melanoma.

Radiotherapy influences local control in patients with desmoplastic melanoma.

BACKGROUND: Desmoplastic melanoma may have a high risk of local recurrence after wide excision. The authors hypothesized that adjuvant radiotherapy (RT) would improve local control in patients with desmoplastic melanoma, resulting in at least a 10% absolute decrease in local recurrence rate. METHODS: A total of 277 patients from 1989 through 2010 who were treated for nonmetastatic desmoplastic melanoma by surgery with or without adjuvant RT were reviewed. Clinicopathologic and treatment variables were assessed with regard to their role in local control. RESULTS: A total of 113 patients (40.8%) received adjuvant RT. After a median follow-up of 43.1 months, adjuvant RT was found to be independently associated with improved local control on multivariable analysis (hazards ratio, 0.15; 95% confidence interval, 0.06-0.39 [P<.001]). Among 35 patients with positive resection margins, 14% who received RT developed a local recurrence versus 54% who did not (P=.004). In patients with negative resection margins, there was a trend (P=.09) toward improved local control with RT. In patients with negative resection margins and traditionally high-risk features, including a head and neck tumor location, a Breslow depth >4 mm, or a Clark level V tumor, RT was found to significantly improve local control (P< .05). The data from the current study would suggest that patients who would be good candidates for omitting RT included those with negative resection margins, a Breslow depth ≤ 4 mm, and either no perineural invasion present or a non-head and neck tumor location. CONCLUSIONS: RT for desmoplastic melanoma was independently associated with improved local control. Patients with positive resection margins or deeper tumors appeared to benefit the most from RT, whereas selected low-risk patients can safely omit RT.

The Use of EZ Derm® in Partial-Thickness Burns: An Institutional Review of 157 Patients.

OBJECTIVES: To evaluate the use of EZ Derm® (Molnlycke Health Care, US, LLC, Norcross, GA) on partial-thickness burns. METHODS: A retrospective review of medical records from patients presenting to the Tampa General Regional Burn Center from January 1, 2008, through January 1, 2012, was conducted. A hospitalwide list of patients was generated on the basis of the presence of charge codes for EZ Derm®. All encounters that did not pass through the Burn Unit were excluded. Applicable charts were reviewed for basic patient characteristics, burn characteristics, outcomes, and complications. Complications were defined as premature separation of EZ Derm®, deviation from a flat fully epithelized wound at the time of final EZ Derm® separation and hypertrophic/keloid scaring. RESULTS: A total of 157 patients were identified and met the study criteria. Eighteen complications were reported from 16 of the 157 patients. Complications were attributed to positioning (2/133 = 1.5%), infection (4/133 = 3.0%), incomplete epithelialization at time of separation (3/133 = 2.2%), need for additional excision and grafting (6/133 = 4.5%), hypertrophic scaring (2/60 = 3.3), and cryptogenic (1/133 = 0.75). CONCLUSIONS: EZ Derm® has proven to be a robust wound dressing that provides cost-effective, consistent durable wound coverage with minimal complications that resolve without long-term sequela.

Sentinel node biopsy is indicated for thin melanomas ≥0.76 mm.

BACKGROUND: A consensus for which patients with thin melanomas (≤1 mm) should undergo sentinel lymph node biopsy (SLNB) is not established. We describe a large single institution experience with SLNB for thin melanomas to determine factors predictive of nodal metastases. METHODS: Retrospective review from 2005 to 2010 identified 271 patients with thin melanomas who underwent SLNB, along with 13 additional patients not treated with SLNB who developed a nodal recurrence as first site of recurrence. Clinicopathologic characteristics were correlated with nodal status and outcome. RESULTS: Median age was 55 years, and 53% of patients were male. Median Breslow thickness was 0.85 mm. Overall, a positive sentinel lymph node (SLN) was found in 22 (8.1%) of 271 cases; 8.4% of melanomas ≥0.76 mm were SLN positive with 5% of T1a melanomas ≥0.76 mm and 13% of T1b melanomas ≥0.76 mm having SLN metastases. Only two of 33 highly selected patients with melanomas <0.76 mm (both T1b) had a positive SLN. Logistic regression analysis demonstrated that mitotic rate ≥1/mm(2) significantly correlated with nodal disease (p < 0.05) and ulceration correlated with SLN metastases (p < 0.05). Median follow-up was 2.1 years. Overall survival did not differ between positive and negative SLN patients (p = 0.53) but was worse for patients presenting with a nodal recurrence (p < 0.01). CONCLUSIONS: SLN metastases were seen in 8.4% of thin melanomas ≥0.76 mm, including 5% of T1a melanomas ≥0.76 mm. We believe these rates are sufficient to justify consideration of SLNB in these patients, while the indications for SLNB in melanomas <0.76 mm remain to be defined.

Merkel cell carcinoma of unknown primary origin.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin. MCC from an unknown primary origin (MCCUP) can present a diagnostic and therapeutic challenge. We describe our single-institution experience with the diagnosis and management of MCCUP presenting as metastases to lymph nodes. METHODS: After institutional review board approval, our institutional database spanning the years 1998-2010 was queried for patients with MCCUP. Clinicopathologic variables and outcomes were assessed. RESULTS: From a database of 321 patients with MCC, 38 (12%) were identified as having nodal MCCUP. Median age was 67 years, and 79% were men. Nodal basins involved at presentation were cervical (58%), axillary/epitrochlear (21%), or inguinal/iliac (21%). CK20 staining was positive in 93% of tumors tested, and all were negative for thyroid transcription factor-1. Twenty-nine patients (76%) underwent complete regional lymph node dissection (LND): 3 had LND alone, ten had LND and adjuvant radiotherapy, and 16 underwent LND followed by chemoradiotherapy. Definitive chemoradiotherapy without surgery was provided to six patients (16%), while radiotherapy alone was provided to three (8%). Recurrence was observed in 34% of patients. Median recurrence-free survival was 35 months. Ten patients (26%) died, five of disease and five of other causes. The median overall survival was 104 months. CONCLUSIONS: Nodal MCCUP is a rare disease affecting primarily elderly white men. Recurrence is observed in approximately one-third of patients, with a 104 month median overall survival after a multimodal treatment approach consisting of surgery along with adjuvant chemotherapy and radiotherapy in the majority of patients.

Amnion-derived cellular cytokine solution (ACCS) promotes migration of keratinocytes and fibroblasts.

Amnion-derived Multipotent Progenitor cells appear to be useful as adjuvants in wound healing. Amnion-derived multipotent progenitor cells secrete a unique combination of cytokines and growth factors, known as amnion-derived cellular cytokine solution (ACCS). In the skin, a cytokine communication network between mesenchymal and epithelial cells tightly controls keratinocyte and fibroblast migration, proliferation and differentiation-key determinants of wound healing. To evaluate the influence of ACCS on the migratory behavior of keratinocytes and fibroblasts, cell migration was assayed quantitatively using a Boyden chamber. Chemotactic migration activity of fibroblasts or keratinocytes through the membrane determined the influence of ACCS. In the presence of ACCS, fibroblasts and keratinocytes demonstrated a statistically significant (P < 0.05) increase in migration when compared with controls. These cell types, critical to normal wound healing, may be influenced to accelerate migration in wounds, thus accelerating wound repair/healing.

Surgical management of melanoma-in-situ using a staged marginal and central excision technique.

Melanoma-in-situ (MIS) represents 45% of all melanomas. The margins of MIS are often poorly defined with extensive subclinical disease. Standard fusiform excision with 5-mm margins results in positive margins in up to a third of cases. To decrease the incidence of involved margins, we use a staged excision approach for MIS. First, patients undergo excision under local anesthesia of a 2- to 3-mm "contoured" rim of tissue optimally 5 mm beyond the visible extent of the lesion. Formalin-fixed paraffin-embedded en face sections from this excision are then evaluated, if necessary with the aid of immunohistochemical stains. Any positive margins are further excised. When all margins are negative, the central area is then excised and reconstructed. A total of 61 patients with MIS or lentigo maligna melanoma underwent staged contoured excisions from 2004 to 2007 at Moffitt Cancer Center. We analyzed data only from patients with MIS of the head and neck. Patients with known invasive melanoma or non-head and neck primary disease were excluded. Demographics, tumor characteristics, margin status, number of stages, and type of reconstruction and recurrences were evaluated. Forty-nine patients with MIS of the head and neck, 28 (57%) male and 21 (43%) female, 42 to 88-years-old (median 72; mean 70), underwent staged contoured margin excision before definitive central tumor excision and reconstruction. The final surgical defect size ranged from 2 to 130 cm(2) (median 16 cm(2)). Twelve patients (24%) required reexcision of at least one margin; the median number of reexcisions was 1 (range 1-2). There seemed to be a positive association between lesion size and margin status (as well as number of excisions needed to clear the margin). Unsuspected invasive melanoma was found in the central specimen in six patients (12%). Even small tumors could have unsuspected invasive melanoma: invasive cancer was seen in 4 (21%) of 19 tumors < or =2 cm in greatest dimension and 2 (7%) of 30 > 2 cm, respectively. Surgical defects were reconstructed with flaps in 18 (37%), full-thickness grafts in 20 (41%), and split-thickness grafts in 10 patients (20%). Median time from first margin excision to completion/final reconstruction was 7 days (range 7-63 days). No local recurrences have been reported at a median follow-up of 14 months (range 1-36 months). This technique allows for careful margin analysis and subsequent central tumor excision with simultaneous reconstruction. This approach minimizes the need for a second major operation, which would have been necessary in 24% of our patients if treated by a one-stage excisional approach. It is noteworthy that 12% of MIS patients had invasive melanoma in the final excision specimen. This reinforces the importance of adequate full-thickness biopsies of suspicious pigmented lesions before any type of surgical management. With short follow-up, local control has been achieved by this technique in 100% of cases.