Suroosh S. Marzban

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.

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.

Pathology Review of Thin Melanoma and Melanoma in Situ in a Multidisciplinary Melanoma Clinic: Impact on Treatment Decisions

PURPOSE Patients with thin melanoma (<or= 1.0 mm) and melanoma in situ (MIS) represent the majority of newly diagnosed melanoma. We estimated the impact of expert review of outside pathology material on the staging and thus treatment decisions affecting patients referred to a multidisciplinary clinic with early-stage melanoma. PATIENTS AND METHODS We studied patients with a diagnosis of thin melanoma or MIS referred to H. Lee Moffitt Cancer Center from 2006 to 2009. After comparing the referring laboratory and in-house dermatopathologic interpretations, we calculated any differences in diagnosis and tumor staging and the potential impact of differences in diagnosis and staging on prognosis and surgical treatment using the National Comprehensive Cancer Network clinical guidelines. RESULTS The overall pathologic discordance rate in diagnosis was 4% (15 of 420 patients; 95% CI, 2% to 6%). The overall change in tumor staging rate was 24% (97 of 405 patients; 95% CI, 20% to 28%). Pathology review led to changes in surgical excision margins in 12% of patients (52 of 420 patients; 95% CI, 9% to 16%) and in the decision about whether to perform a sentinel lymph node biopsy in 16% of patients (67 of 420 patients; 95% CI, 13% to 20%). Key pathologic factors, particularly mitotic rate, were frequently missing from outside pathology reports. CONCLUSION Our data suggest that review of thin melanoma or MIS by an expert dermatopathologist results in frequent, clinically meaningful alterations in diagnosis, staging, prognosis, and surgical treatment. Referral of these patients to a multidisciplinary melanoma clinic is appropriate, and management of such patients should include review of the biopsy whenever feasible.

Shave biopsy is a safe and accurate method for the initial evaluation of melanoma.

BACKGROUND Shave biopsy of cutaneous lesions is simple, efficient, and commonly used clinically. However, this technique has been criticized for its potential to hamper accurate diagnosis and microstaging of melanoma, thereby complicating treatment decision-making. STUDY DESIGN We retrospectively analyzed a consecutive series of patients referred to the University of Florida Shands Cancer Center or to the Moffitt Cancer Center for treatment of primary cutaneous melanoma, initially diagnosed on shave biopsy to have Breslow depth < 2 mm, to determine the accuracy of shave biopsy in T-staging and the potential impact on definitive surgical treatment and outcomes. RESULTS Six hundred patients undergoing shave biopsy were diagnosed with melanoma from extremity (42%), trunk (37%), and head or neck (21%). Mean (± SEM) Breslow thickness was 0.73 ± 0.02 mm; 6.2% of lesions were ulcerated. At the time of wide excision, residual melanoma was found in 133 (22%), resulting in T-stage upstaging for 18 patients (3%). Recommendations for additional wide excision or sentinel lymph node biopsy changed in 12 of 600 (2%) and 8 of 600 patients (1.3%), respectively. Locoregional recurrence occurred in 10 (1.7%) patients and distant recurrence in 4 (0.7%) patients. CONCLUSIONS These data challenge the surgical dogma that full-thickness excisional biopsy of suspicious cutaneous lesions is the only method that can lead to accurate diagnosis. Data obtained on shave biopsy of melanoma are reliable and accurate in the overwhelming majority of cases (97%). The use of shave biopsy does not complicate or compromise management of the overwhelming majority of patients with malignant melanoma.

Radiotherapy influences local control in patients with desmoplastic melanoma

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.

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.

Preoperative Ultrasound is Not Useful for Identifying Nodal Metastasis in Melanoma Patients Undergoing Sentinel Node Biopsy: Preoperative Ultrasound in Clinically Node-Negative Melanoma

BackgroundSentinel 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.MethodsFrom 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.ResultsA 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.ConclusionsRoutine 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.

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

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).

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.

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.

Abstract: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.