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.

Analysis of tumor mitotic rate in thin metastatic melanomas compared with thin melanomas without metastasis using both the hematoxylin and eosin and anti-phosphohistone 3 IHC stain.

Studies have suggested that elevated tumor mitotic rate (MR) is linked to overall survival in thin melanoma. Recently, promising data regarding anti-phosphohistone 3 (pHH3) immunohistochemistry and its ability to aid in calculation of MR have emerged. The authors retrospectively analyzed original biopsies from 13 thin melanomas with positive sentinel node (SN) status and 16 thin melanomas with negative SN status. Both anti-pHH3 immunohistochemistry and the hematoxylin and eosin (H&E) stain were used to evaluate MR by 2 dermatopathologists blinded to SN status using the "hot spot" method. Intraclass coefficient values were attained to measure interobserver concordance and reliability of the pHH3 stain. By generating a receiver operating characteristic curve and analyzing the overall area under the curve, pHH3 was found to have good interobserver reliability. The relationship between MR and SN involvement was also evaluated, but this correlation was not statistically significant.

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.

Clinicopathologic predictors of sentinel lymph node metastasis in thin melanoma.

PURPOSE: Indications for sentinel lymph node biopsy (SLNB) for thin melanoma are continually evolving. We present a large multi-institutional study to determine factors predictive of sentinel lymph node (SLN) metastasis in thin melanoma. PATIENTS AND METHODS: Retrospective review of the Sentinel Lymph Node Working Group database from 1994 to 2012 identified 1,250 patients who had an SLNB and thin melanomas (≤ 1 mm). Clinicopathologic characteristics were correlated with SLN status and outcome. RESULTS: SLN metastases were detected in 65 (5.2%) of 1,250 patients. On univariable analysis, rates of Breslow thickness ≥ 0.75 mm, Clark level ≥ IV, ulceration, and absence of regression differed significantly between positive and negative SLN groups (all P < .05). These four variables and mitotic rate were used in multivariable analysis, which demonstrated that Breslow thickness ≥ 0.75 mm (P = .03), Clark level ≥ IV (P = .05), and ulceration (P = .01) significantly predicted SLN metastasis with 6.3%, 7.0%, and 11.6% of the patients with these respective characteristics having SLN disease. Melanomas < 0.75 mm had positive SLN rates of < 5% regardless of Clark level and ulceration status. Median follow-up was 2.6 years. Melanoma-specific survival was significantly worse for patients with positive versus negative SLNs (P = .001). CONCLUSION: Breslow thickness ≥ 0.75 mm, Clark level ≥ IV, and ulceration significantly predict SLN disease in thin melanoma. Most SLN metastases (86.2%) occur in melanomas ≥ 0.75 mm, with 6.3% of these patients having SLN disease, whereas in melanomas < 0.75 mm, SLN metastasis rates are < 5%. By using a 5% metastasis risk threshold, SLNB is indicated for melanomas ≥ 0.75 mm, but further study is needed to define indications for SLNB in melanomas < 0.75 mm.

Identifying risk factors using a skin cancer screening program.

BACKGROUND: The incidence of melanoma and nonmelanoma skin cancer continues to increase. To detect lesions at an earlier phase in their progression, skin cancer screening programs have been advocated by some. However, the effectiveness of skin cancer screening and the ideal population that these screenings should target have yet to be firmly established. This study details the relationship of a group of well-known risk factors with presumptive diagnoses in a large series of individuals self-referred for free skin cancer screening. METHODS: Data obtained during 2007 to 2010 from a descriptive cross-sectional study skin cancer screening program are presented. Participant history was recorded using standardized medical history forms prior to skin examination. Screeners conducted a skin examination varying from whole-body to limited areas (per participant preference) and recorded diagnoses. Diagnoses were assigned to the nonmelanoma cancer (NMC) or suspicious pigmented lesion group for analysis. RESULTS: A presumptive diagnosis of NMC was associated with male sex, age ≥ 50 years, personal history of skin cancer, lower skin phototype, increased sunscreen use, and increased chronic sun exposure (all P values ≤ .0001). After controlling for skin phototype, increased sunscreen use was not associated with a presumptive diagnosis of NMC (P = .96). Presumptive diagnosis of a suspicious pigmented lesion was associated with a reported history of "changing mole" (P < .0001) and negatively associated with age ≥ 50 years (P < .0001) and a personal history of skin cancer (P = .0119). CONCLUSIONS: Several known risk factors for nonmelanoma skin cancer correlated with a presumptive diagnosis of NMC. The yield of presumptive atypical pigmented lesions was increased in participants aged < 50 years, supporting the notion that this population may benefit from screening.

Cutaneous leiomyosarcoma: treatment and outcomes with a standardized margin of resection.

BACKGROUND: Cutaneous leiomyosarcoma is primarily a low-grade malignancy that affects elderly male Caucasians. It is a rare dermal-based tumor for which treatment algorithms have been poorly defined. METHODS: We retrospectively reviewed the use of a median 1-cm margin for resection to treat patients with cutaneous leiomyosarcoma referred for treatment between 2005 and 2010. RESULTS: Thirty-three patients with cutaneous leiomyosarcoma were treated. Of these, 76% were male, 97% were Caucasian (median age: 63.5 years), and 67% of tumors were located on the extremities. Preoperative staging was negative for distant metastasis in all patients. A majority of the tumors (88%) were low grade (median size: 1.3 cm). All of the tumors were positive for smooth-muscle actin. A total of 94% of patients underwent primary surgical resection with a median margin of 1 cm. Final resection margin was negative in 97% of patients. Adjuvant radiotherapy was used in 15%. No metastatic spread or recurrences were present, and 100% of patients were alive at last follow-up (median: 15.5 months). CONCLUSIONS: Good oncological control and excellent outcomes are possible with a 1-cm resection margin in most cases of cutaneous leiomyosarcoma.

Single-institution outcome experience using AlloDerm® as temporary coverage or definitive reconstruction for cutaneous and soft tissue malignancy defects.

Definitive reconstruction after excision of cutaneous and soft tissue malignancies is sometimes limited as a result of lack of native tissue coverage options, patient comorbidities, or pending permanent margin analysis. Acellular dermis (AlloDerm®) reconstruction offers an excellent coverage alternative in these situations. We describe our experience using AlloDerm for coverage of skin and soft tissue defects. An Institutional Review Board approved review of patients undergoing skin/soft tissue coverage with AlloDerm from 2006 to 2012 was performed. Clinicopathologic variables, early postoperative findings, and subjective final cosmetic outcome were analyzed. Sixty-seven patients underwent AlloDerm reconstruction. Melanoma (67%) was the most frequent diagnosis. The median defect size was 42 cm(2) (range, 2 to 340 cm(2)), involving predominantly the lower extremity (45%) or head and neck (32%). AlloDerm was intended for use as a temporary dressing in 64 per cent (43 of 67) and permanent coverage in 24 (36%). Ten patients required reexcision for positive margins. Twenty-five (37%) underwent split-thickness skin graft or flap coverage after AlloDerm placement. Radiation was administered to 16 patients (24%) after AlloDerm reconstruction within a median of 53 days after surgery (range, 18 to 118 days). At first postoperative examination (median, 11 days after surgery), 85 per cent had evidence of healthy AlloDerm incorporation. Cellulitis was the most frequent complication (13%), all resolving with oral antibiotics. AlloDerm reconstruction after skin and soft tissue resection offers a suitable coverage alternative and may serve as a bridge to permanent reconstruction or as a permanent biologic dressing of complex surgical defects. In situations in which adjuvant radiation is needed, AlloDerm can be used without major complications.

Gene variants in angiogenesis and lymphangiogenesis and cutaneous melanoma progression.

BACKGROUND: Angiogenesis and lymphangiogenesis are important in the progression of melanoma. We investigated associations between genetic variants in these pathways with sentinel lymph node (SLN) metastasis and mortality in 2 independent series of patients with melanoma. METHODS: Participants at Moffitt Cancer Center were 552 patients, all Caucasian, with primary cutaneous melanoma referred for SLN biopsy. A total of 177 patients had SLN metastasis, among whom 60 died from melanoma. Associations between 238 single-nucleotide polymorphisms (SNP) in 26 genes and SLN metastasis were estimated as ORs and 95% confidence intervals (CI) using logistic regression. Competing risk regression was used to estimate HRs and 95% CI for each SNP and melanoma-specific mortality. We attempted to replicate significant findings using data from a genome-wide association study comprising 1,115 patients with melanoma who were referred for SLN biopsy from MD Anderson Cancer Center (MDACC), among whom 189 patients had SLN metastasis and 92 patients died from melanoma. RESULTS: In the Moffitt dataset, we observed significant associations in 18 SNPs with SLN metastasis and 17 SNPs with mortality. Multiple SNPs in COL18A1, EGF receptor (EGFR), FLT1, interleukin (IL)-10, platelet-derived growth factor D (PDGFD), PIK3CA, and toll-like receptor (TLR)-3 were associated with the risk of SLN metastasis and/or patient mortality. The MDACC data set replicated an association between mortality and rs2220377 in PDGFD. Furthermore, in a meta-analysis, 3 additional SNPs were significantly associated with SLN metastasis (EGFR rs723526 and TLR3 rs3775292) and melanoma-specific death (TLR3 rs7668666). CONCLUSIONS: These findings suggest that genetic variation in angiogenesis and lymphangiogenesis contributes to regional nodal metastasis and progression of melanoma. IMPACT: Additional research attempting to replicate these results is warranted.

Desmoplastic melanoma: is there a role for sentinel lymph node biopsy?

BACKGROUND: The utility of sentinel lymph node biopsy (SLNB) for desmoplastic melanoma (DM) is debated. We describe a large single-institution experience with SLNB for DM to determine clinicopathologic factors predictive of SLN metastasis. METHODS: Retrospective review identified 205 patients with DM who underwent SLNB from 1992 to 2010. Clinicopathologic characteristics were correlated with SLN status and outcome. RESULTS: Median age was 66 years, and 69 % of patients were male. Median Breslow thickness was 3.7 mm. In 128 cases (62 %), histologic subtype data was available; 61 cases (47.7 %) were mixed and 67 cases (52.3 %) were pure DM. A positive SLN was found in 28 cases (13.7 %); 24.6 % of mixed and 9 % of pure DM had SLN metastases. Multivariable analysis demonstrated that after controlling for age, histologic subtype correlated with SLN status [odds ratio: 3.0 for mixed vs pure, 95 % confidence interval: 1.1-8.7; p < .05]. Completion lymph node dissection was performed in 24 of 28 positive SLN patients with 16.7 % of cases having additional nodal disease. After a median follow-up of 6.3 years, 38 patients developed recurrence and 61 patients died. Positive SLN patients had a significantly higher risk of melanoma-related death compared with negative SLN patients (p = .01). CONCLUSIONS: The overall risk for SLN metastasis for DM is 13.7 % and is significantly higher for mixed (24.6 %) compared with pure (9.0 %) DM. We believe that these rates are sufficient to justify consideration of SLNB for both histologic variants, especially since detection of SLN disease appears to predict a higher risk for melanoma-related death.

A collision of diseases: chronic lymphocytic leukemia discovered during lymph node biopsy for melanoma.

BACKGROUND: In the United States in 2012, there were 16,060 new cases of chronic lymphocytic leukemia (CLL). Often CLL is clinically occult and first detected during pathologic evaluation of the sentinel lymph node biopsy (SLNB). We reviewed our experience of patients with the coexisting diagnosis of melanoma and CLL. METHODS: An institutional review board-approved review was performed on patients with CLL and melanoma treated from 1995 to 2009 at Moffitt Cancer Center and compared with the incidence of melanoma and CLL in our tumor registry patients with breast, prostate, lung, and colon cancer. RESULTS: Fifty-two patients (44 males; median age, 71 years [range, 46-88]) were identified with concurrent diagnoses of melanoma and CLL. Twenty-two patients (42 %) had CLL on SLNB for their melanoma. Thirty-two patients (62 %) were diagnosed with melanoma before CLL. Concomitant or prior cancer diagnoses included nonmelanoma skin cancers (N = 29), prostate (N = 6), colorectal (N = 2), and Merkel cell carcinoma (N = 2). Five of 20 patients (25 %) had metastatic melanoma found at the time of SLNB. Patients with melanoma had a tenfold increase of CLL diagnosis compared with colorectal cancer patients, an eightfold increase compared to prostate cancer patients, and a fourfold increase compared with breast cancer patients. CONCLUSIONS: We have confirmed an increased association of CLL and melanoma. This may be related to an underlying immunologic defect; however, there has been scant investigation into this phenomenon. Surgeons and pathologists should understand this occurrence and recognize that not all grossly enlarged or abnormal sentinel lymph nodes in melanoma patients represent melanoma.

Efficacy of adoptive cell transfer of tumor-infiltrating lymphocytes after lymphopenia induction for metastatic melanoma.

A single-institution pilot clinical trial was performed combining nonmyeloablative chemotherapy and the adoptive transfer of tumor-infiltrating lymphocytes with interleukin-2 in patients with metastatic melanoma. Nineteen patients were enrolled with 13 patients (68%) successfully completing treatment. An overall response rate (partial and complete responses) of 26% by intention to treat was achieved with a median follow-up time of 10 months. Of the 13 treated patients, there were 2 complete responses and 3 partial responses (38% response rate among treated patients), along with 4 patients with stable disease ranging from 2+ to 24+months. Three of the 4 patients with stable disease have had disease control without additional therapy, including one at 24+ months. Adoptive therapy with infiltrating lymphocytes is labor intensive but feasible and has a high response rate in treated patients.

The unique clinical characteristics of melanoma diagnosed in children.

BACKGROUND: Studies have demonstrated a higher rate of nodal metastases in melanoma of childhood, but there is controversy about the overall prognosis relative to adults. We describe a large single-institution experience with pediatric melanoma and assess prognostic characteristics. METHODS: Retrospective review identified 126 patients diagnosed with melanoma at <21 years of age and referred for treatment from 1986 to 2011. Atypical lesions were excluded. Clinicopathologic characteristics were correlated with sentinel lymph node (SLN) status and outcomes. RESULTS: SLN biopsy was positive in 18 of 62 cases (29 %). Increasing Breslow thickness correlated with a positive SLN (p < 0.05). After a median follow-up of 5 years, there were 27 recurrences and 20 deaths. Positive SLN patients had significantly worse recurrence-free survival (RFS, p < 0.05) and significantly worse melanoma-specific survival (MSS, p = 0.05) compared with negative SLN patients. The 5-year RFS and MSS for positive SLN patients were 59.5 and 77.8 %, compared with 93.7 and 96.8 % for negative SLN patients. Recurrences and melanoma-related deaths were often seen beyond 5 years. No deaths have occurred in patients <12 years, but 9.1 % of patients 12-17 years and 17.2 % of patients 18-20 years died from melanoma (p = 0.291). CONCLUSIONS: Children with melanoma have higher rates of SLN metastases (29 %) than adults with comparable melanomas. Despite the higher incidence of nodal metastases, survival is equal to or better than what is reported for adults. However, long-term follow-up is necessary in this population since recurrences and deaths are often seen beyond 5 years.

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.

A multicenter prospective evaluation of the clinical utility of F-18 FDG-PET/CT in patients with AJCC stage IIIB or IIIC extremity melanoma.

OBJECTIVE/BACKGROUND: There is a high risk of relapse in stage IIIB/IIIC melanoma. The utility of 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography integrated with computed tomography (FDG-PET/CT) in these patients to evaluate response to treatment or for surveillance after treatment is currently not well defined. METHODS: Prospective data from 2 centers identified 97 patients with stage IIIB/IIIC extremity melanoma undergoing isolated limb infusion (ILI) who had whole body FDG-PET/CT scans before and every 3 months after treatment. Clinical response was determined at 3 months by Response Evaluation Criteria In Solid Tumors. RESULTS: Complete response (CR) after ILI occurred in 33% (32/97) of patients. FDG-PET/CT accurately identified 59% of patients who were CRs (19/32), whereas 41% (13/32) had residual metabolic activity in the extremity that was histologically negative for melanoma. The 3-year disease-free rate was 62.2% (95% CI: 40.1%-96.4%) for those patients who were CRs by both clinical/pathologic examination and FDG-PET/CT (n = 19) compared to only 29.4% (95% CI: 9.9%-87.2%) of those CRs who still had residual FDG-PET/CT activity (n = 13). FDG-PET/CT was utilized for surveillance of disease recurrence outside the regional field of treatment. Fifty-two percent (51/97) of patients developed disease outside the extremity at a median time of 212 days from pre-ILI FDG-PET/CT. In 47% (29/62) of these cases, the recurrence was resected. CONCLUSIONS: Although FDG-PET/CT does not appear to accurately identify patients who appear to be CRs to ILI, it does appear to identify a subgroup of patients whose regional progression-free survival is markedly worse. However, FDG-PET/CT appears to be an excellent method for surveillance in stage IIIB/IIIC patients after ILI with ability to identify surgically resectable recurrent disease in these high-risk patients.

Sentinel node biopsy in atypical melanocytic neoplasms in childhood: a single institution experience in 24 patients.

INTRODUCTION: Sentinel lymph node biopsy (SLNB) is a controversial but frequently used adjunct to wide excision of difficult-to-diagnose melanocytic proliferations of childhood. We herein report our institutional experience with SLNB in pediatric patients with these lesions, hereafter referred to as 'atypical melanocytic proliferations'. METHODS: Our prospectively collected melanoma database was queried for patients ≤21 years of age status post-SLNB for a diagnosis of atypical melanocytic proliferation in which the diagnosis of melanoma ≥1 mm in depth was considered in the differential diagnosis by one or more expert dermatopathologists and for which no diagnostic consensus could be reached. RESULTS: Of 24 patients identified over 17 years, 7 patients (29%) had a positive sentinel lymph node (SLN). Six SLN-positive patients underwent complete lymph node dissection, with one (14%) having additional nodal involvement identified. With a median follow-up of 4.1 years (range < 0.1 to 14.8 years), all patients showed no evidence of disease. CONCLUSIONS: Despite a significant rate of identification of melanocytes in SLNs of children with atypical melanocytic proliferations, survival appears favorable and controversy surrounding the significance of nodal involvement remains. Further studies with larger numbers of patients and long-term follow-up are needed before the true prognostic value of SLNB in this setting can be determined.

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.

The role of radical amputations for extremity tumors: a single institution experience and review of the literature.

BACKGROUND: Major amputations are indicated for advanced tumors when limb-preservation techniques have been exhausted. Radical surgery can result in significant palliation and possible cure. METHODS: We identified 40 patients who underwent forequarter (FQ) or hindquarter (HQ) amputations between May 2000 and January 2011. Patient demographics, tumor-related factors, and outcomes were reviewed. RESULTS: There were 30 FQ and 10 HQ amputations. The most common diagnoses were sarcoma (55%) and squamous cell carcinoma (25%). Patients presented with primary tumors (35%), regional recurrence (57.5%), or unresectable limb metastatic disease (7.5%). Presenting symptoms included fungating wounds (35%), intractable pain (78%), and limb dysfunction (65%). Operations were performed with curative intent (10%), curative/palliative intent (70%), or palliation alone (20%). Wound complications occurred in 35%. Pain was improved in 78% of patients following surgery. Despite a 91% negative margin rate, 79% of patients recurred either locally or distantly. Median overall survival was 10.9, 13.2, and 3.4 months in the curative, curative/palliative, and palliative groups, respectively. CONCLUSIONS: In the absence of conservative options, major amputations are indicated for the management of advanced tumors. These operations can be performed safely, resulting in effective palliation of debilitating symptoms. While recurrence rates remain high, some patients can achieve prolonged survival.

Preoperative ultrasound is not useful for identifying nodal metastasis in melanoma patients undergoing sentinel node biopsy: preoperative ultrasound in clinically node-negative melanoma.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is widely used in melanoma. Identifying nodal involvement preoperatively by high-resolution ultrasound may offer less invasive staging. This study assessed feasibility and staging results of clinically targeted ultrasound (before lymphoscintigraphy) compared to SLNB. METHODS: From 2005 to 2009, a total of 325 patients with melanoma underwent ultrasound before SLNB. We reviewed demographics and histopathologic characteristics, then compared ultrasound and SLNB results. Sensitivity, specificity, and positive and negative predictive value were determined. RESULTS: A total of 325 patients were included, 58% men and 42% women with a median age of 58 (range 18-86) years. A total of 471 basins were examined with ultrasound. Only six patients (1.8%) avoided SLNB by undergoing ultrasound-guided fine-needle aspiration of involved nodes, then therapeutic lymphadenectomy. Sixty-five patients (20.4%) had 69 SLNB positive nodal basins; 17 nodal basins from 15 patients with positive ultrasounds were considered truly positive. Forty-five SLNB positive basins had negative ultrasounds (falsely negative). Seven node-positive basins did not undergo ultrasound because of unpredicted drainage. A total of 253 patients with negative SLNBs had negative ultrasounds in 240 nodal basins (truly negative) but falsely positive ultrasounds occurred in 40 basins. Overall, sensitivity of ultrasound was 33.8%, specificity 85.7%, positive predictive value 36.5%, and negative predictive value 84.2%. Sensitivity and specificity improved somewhat with increasing Breslow depth. Sensitivity was highest for the neck, but specificity was highest for the groin. CONCLUSIONS: Routine preoperative ultrasound in clinically node-negative melanoma is impractical because of its low sensitivity. Selected patients with thick or ulcerated lesions may benefit. Because of variable lymphatic drainage patterns, preoperative ultrasound without lymphoscintigraphic localization will provide incomplete evaluation in many cases.

A multi-institutional experience of repeat regional chemotherapy for recurrent melanoma of extremities.

BACKGROUND: Hyperthermic isolated limb perfusion (HILP) or isolated limb infusion (ILI) are well-accepted regional chemotherapy techniques for in-transit melanoma of extremity. The role and efficacy of repeat regional chemotherapy for recurrence and which salvage procedure is better remains debatable. We aimed to compare toxicities and clinical outcomes by procedure types and the sequence. METHODS: Data from 44 patients, who underwent repeat HILPs or ILIs from 3 institutions beginning 1997 to 2010, were retrospectively reviewed. Regional toxicity assessed by Wieberdink grade, systemic toxicity assessed by serum creatine phosphokinase level, length of hospital stay (LOS), response rates at 3 months after the procedure, and time to in-field progression (TTP) were analyzed. RESULTS: Of 44 patients, 46% were men and 54% women with a median age of 66 (range 29-85) years at diagnosis. The median follow-up was 21.4 (range 4-153) months. Of 70 ILIs and 28 HILPs, the following groups were identified: group A, ILI → ILI (n = 25); group B, ILI → HILP (n = 10); group C, HILP → ILI (n = 12); and group D, HILP → HILP (n = 3). The comparison of Wieberdink grade, serum creatine phosphokinase level, LOS, and response rate between procedures (HILP vs. ILI), between sequence (initial vs. repeat), and among their interactions showed no statistically significant differences. TTP after initial procedure did not differ between HILP and ILI (P = 0.08), and no survival difference was seen (P = 0.65) when TTP after repeat procedure was compared. CONCLUSIONS: Most patients tolerated repeat regional chemotherapy without increased toxicity or LOS. No statistical difference in clinical outcomes was noted when comparing repeat procedures, even though repeat HILPs showed higher complete response compared to repeat ILIs.