Prognostic role of the histological subtype of melanoma on the hands and feet in Caucasians.

Acral melanoma (AM) is associated with a poor prognosis in part because of delayed diagnosis, but probably also because of other intrinsic characteristics of location. The aim of this study was to review the specific characteristics and outcome of AM in Caucasians. This was a cross-sectional retrospective clinical-pathological study of 274 patients identified with AM in the database of a referral unit in Europe from 1986 to 2010. The mean age of the patients was 56.6 (SD 17.7) years. 269 cases could be histologically classified and included in the study. In all, 222 (82.5%) were located on feet. According to melanoma subtype, 165 (61.3%) were acral lentiginous melanoma (ALM), 84 (31.2%) were superficial spreading melanoma (SSM), and 20 (7.5%) were nodular melanoma (NM). SSM patients were characterized by female predominance (77.4%), younger age, and classic melanoma-risk phenotype (fair skin and multiple nevi). Among the 198 invasive cases with a mean follow-up of 56.2 months, the mean (SD) Breslow's thickness was 3.1 (3.6) mm, being 1.4 (1.4) mm in SSM, 3.5 (4.1) mm in ALM and 4.9 (2.9) mm in NM (P<0.001). Ulceration was present in 33.3%, 2.9% in SSM, 38.6% in ALM, and 76.9% in NM (P<0.001). A total of 29.3% relapsed (7.3% of SSM, 35% of ALM and 55% of NM) and 24.2% died because of AM. In multivariate analysis, age at diagnosis, Breslow, and histopathological subtype were independent prognostic factors for both disease-free and AM-specific survival. The ALM and NM subtypes presented poorer outcome after weighting Breslow and age (P=0.02). Histological subtype of AM could have an impact on biological behavior, ALM and NM subtypes presenting a poorer prognosis after adjusting for age and Breslow's thickness.

Performance of diagnostic tests in an intensive follow-up protocol for patients with American Joint Committee on Cancer (AJCC) stage IIB, IIC, and III localized primary melanoma: A prospective cohort study.

BACKGROUND: There is no international consensus on optimal follow-up schedules and which supplementary tests should be used after resection of a primary melanoma. OBJECTIVE: We sought to analyze the performance of the follow-up components and identify procedures that detect melanoma metastasis earlier. METHODS: This was a prospective cohort from 290 consecutive patients given a diagnosis of stage IIB, IIC, and III melanoma. Patients were followed up with an intensive protocol based on imaging studies (computed tomography of the chest, abdomen, and pelvis, and brain magnetic resonance imaging), periodic laboratory tests, regular physical examinations, and patient self-examinations. RESULTS: A total of 2382 clinical examinations and 3069 imaging tests were performed. The patients completed 899.8 person-years of follow-up, with a median of 2.5 years. In all, 115 recurrences in 290 patients were recorded, of which computed tomography detected 48.3%; brain magnetic resonance imaging, 7.6%; laboratory test, 2.5%; physician, 23.7%; and patient, 17.8%. LIMITATIONS: Patients with stage III melanoma were not systematically classified into subgroups and overall survival was not evaluated. CONCLUSION: We observed that this intensive monitoring is appropriate for early detection of recurrence in stage IIB, IIC, and III melanoma. Prompt diagnosis of metastasis and the recent development of new therapeutic targets may improve overall survival.

High nevus counts confer a favorable prognosis in melanoma patients.

A high number of nevi is the most significant phenotypic risk factor for melanoma and is in part genetically determined. The number of nevi decreases from middle age onward but this senescence can be delayed in patients with melanoma. We investigated the effects of nevus number count on sentinel node status and melanoma survival in a large cohort of melanoma cases. Out of 2,184 melanoma cases, 684 (31.3%) had a high nevus count (>50). High nevus counts were associated with favorable prognostic factors such as lower Breslow thickness, less ulceration and lower mitotic rate, despite adjustment for age. Nevus count was not predictive of sentinel node status. The crude 5- and 10-year melanoma-specific survival rate was higher in melanomas cases with a high nevus count compared to those with a low nevus count (91.2 vs. 86.4% and 87.2 vs. 79%, respectively). The difference in survival remained significant after adjusting for all known melanoma prognostic factors (hazard ratio [HR] = 0.43, confidence interval [CI] = 0.21-0.89). The favorable prognostic value of a high nevus count was also seen within the positive sentinel node subgroup of patients (HR = 0.22, CI = 0.08-0.60). High nevus count is associated with a better melanoma survival, even in the subgroup of patients with positive sentinel lymph node. This suggests a different biological behavior of melanoma tumors in patients with an excess of nevi.

Loco-regional control after postoperative radiotherapy for patients with regional nodal metastases from melanoma.

INTRODUCTION: The role of adjuvant radiation therapy (RT) following nodal surgery in malignant melanoma remains controversial. There are no published randomised trials comparing surgery alone to surgery with postoperative RT. AIM AND METHODS: The purpose of the present retrospective study was to review the results of loco-regional control after postoperative RT in patients with nodal metastases of melanoma. Seventy-seven patients with high-risk disease (lymph nodes > or =3 cm, more than three lymph nodes involved, extracapsular extension and recurrent disease) were treated with adjuvant RT. Hypofractionation was used in 65 patients and conventional fractionation in 12 patients. RESULTS: Seventy-seven patients with nodal metastases from melanoma were managed with lymphadenectomy and radiation, with or without systemic therapy. The median age was 56 years old (range: 21-83). There were 47 males (61%) and 30 females (39%). Loco-regional control was observed in 95% of patients (73/77). The actuarial 5-year in-field loco-regional control rate was 90% (mean: 105 months; CI95%: 96-115 months). Median metastasis disease- free survival (MDFS) was 16 months (CI95%: 13-18 months). Median survival time (MST) for the entire group was 26 months (CI95%: 18-34 months). MST according to the localisation of node metastases (groin, axilla and cervical) was also analysed, without statistically significant differences (p=0.08). Concerning the number of risk factors score, analysis of survival did not show statistically significant differences (p=0.055). CONCLUSIONS: Despite the high incidence of distant metastases, loco-regional control remains an important goal in the management of melanoma. Surgery and adjuvant RT provides excellent loco-regional control, although distant metastases remain the major cause of mortality.

Small cell melanoma and ulceration as predictors of positive sentinel lymph node in malignant melanoma patients.

Malignant melanoma (MM) early lymph node (LN) metastasis usually appears first in the sentinel LN (SLN). Breslow thickness is the main factor considered in the selection of patients to be submitted to SLN biopsy. The present study aimed to describe other independent prognostic factors useful in SLN candidate selection. During one year, 94 MM patients (90 primary cutaneous MM with Breslow thickness > or = 0.76 mm, and four cutaneous relapses), were submitted to SLN biopsy in the Melanoma Unit at the Hospital Clinic, Barcelona, Spain. The prognostic factors studied were: Breslow thickness, Clark's level of invasion, mitotic rate, cellular type (small, epithelioid, fusocellular, sarcomatoid), vertical growth phase, regression > 50%, severe vascularization, infiltrate (lymphocytic, plasmocytic), ulceration, neurotropism, intravascular/intraneural invasion, protein p16 expression and recurrence. Nineteen SLN (20.2%) were positive and 75 (79.8%) negative. No positive SLN occurred in MM with Breslow thickness < or = 1.0 mm. Breslow thickness > or = 2 mm (P = 0.005), severe vascularization (P = 0.005), small cell (P = 0.000) and ulceration (P = 0.005) were significant prognostic factors by univariate analysis. Small cell (P = 0.008) and ulceration (P = 0.05) were also significant prognostic factors in a multivariate analysis. The probability of finding a positive SLN for small cell was 56.9% [95% confidence interval (CI), 26.8-82.6%]. The probability of positive SLN for ulceration was 35.5% (95% CI, 14.2-64.7%). For small cell and ulceration together the probability increased to 86.3% (95% CI, 54.3-97.1%). The results of this study corroborated ulceration as a prognostic factor for SLN candidate selection and for the first time we have described small cell melanoma morphology as a significant factor associated with positive SLN.

Brachytherapy with 192Ir as treatment of carcinoma of the tarsal structure of the eyelid.

PURPOSE: Some eyelid tumors present a great challenge for surgical therapy because of the cosmetic and functional impairment. Interstitial radiation with (192)Ir is an optimal alternative treatment modality. The aim of this study was to evaluate the local tumor control and cosmetic results in patients with eyelid tumors treated by interstitial (192)Ir wires. METHODS AND MATERIALS: Twenty-four previously untreated carcinomas involving the eyelid tarsal structure in 23 patients were treated with (192)Ir wire implantation. The tumor location was in the lower eyelid in 22 cases and in the upper eyelid in 2. The mean tumor size was 1.33 cm. Of the 24 tumors, 79.2% were basal cell carcinoma, 16.7% were squamous cell carcinoma, and 4.2% were adenocarcinoma. The total radiation dose was 4000 cGy, delivered to 2-mm depth (mean dose rate, 73 cGy/h). RESULTS: The mean follow-up was 43 months. Local control was obtained in 22 (91.6%) of 24 tumors. Good functional results were achieved in all patients. CONCLUSION: (192)Ir interstitial brachytherapy in a braided silk filament appears to be an excellent method to treat carcinomas involving the eyelid tarsal structure for tumor control and functional and cosmetic results.

Is the identification of in-transit sentinel lymph nodes in malignant melanoma patients really necessary?

The sentinel lymph node (SLN) is the first node in a nodal basin to receive the direct lymphatic flow from a malignant melanoma. However, in some patients, lymphoscintigraphic study reveals the presence of lymphatic nodes in the area between the primary melanoma and the regional basin. These nodes are called "in-transit nodes" or "interval nodes" and, by definition, are also SLNs. The purpose of this study was to determine the incidence and location of in-transit SLNs in patients with malignant melanoma and to assess whether it is really necessary to harvest them. The evaluation involved 600 consecutive malignant melanoma patients. Lymphoscintigraphy was performed on the day before surgery following intradermal injection of 74-111 MBq of (99m)Tc-nanocolloid in four doses around the primary melanoma or the biopsy scar. Dynamic and static images were obtained and revealed SLNs in 599 out of 600 patients. The SLN was intraoperatively identified with the aid of patent blue dye and a hand-held gamma probe. Lymphoscintigraphy showed in-transit SLNs in 59/599 patients (9.8%). During surgery, all these in-transit SLNs were harvested, with those in the popliteal and epitrochlear regions being the most difficult to identify and excise. Metastatic cell deposits were subsequently identified in ten (16.9%) of these in-transit SLNs. In conclusion, lymphoscintigraphy has a key role in the identification of in-transit SLNs. Although the incidence of these nodes is relatively low in malignant melanoma patients, such SLNs present metastatic deposits in a significant percentage of cases and therefore the identification of in-transit SLNs in these patients is really necessary.

Identification of the sentinel lymph node in patients with malignant melanoma: what are the reasons for mistakes?

Scintigraphic identification of the sentinel lymph node is achievable in nearly all patients with malignant melanoma. However, in a very small number of cases the sentinel node fails to be detected, and sometimes recurrence appears during follow-up in patients who had previously tested negative for metastatic disease. The purpose of this study was to review our experience in order to isolate the reasons for erroneous sentinel lymph node identification. The evaluation involved 435 consecutive malignant melanoma patients with AJCC stages I and II (clinically negative nodes) and Breslow thickness >0.76 mm. Lymphoscintigraphy was performed the day before surgery by intradermal administration of technetium-99m labelled nanocolloid. Dynamic and static images were obtained. The sentinel node was intraoperatively identified with the aid of patent blue dye and a hand-held gamma probe. After removal, routine histopathological examination with haematoxylin-eosin (H-E) and immunohistochemistry with S 100 and HMB45 (IHC) were performed. In those patients who developed regional recurrences during follow-up, sentinel nodes were further evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). Lymphoscintigraphy visualised at least one sentinel node in 434 out of 435 patients (99.8%). Uptake in in-transit sentinel lymph nodes was observed in 32 patients (7.4%). During surgery, localisation and removal of sentinel nodes was successful in 430/435 patients (98.8%). A total of 790 sentinel lymph nodes were harvested, with a mean of 1.8 per patient. Routine histopathological examination with H-E or IHC revealed metastatic disease in 72 patients (16.8%). During a mean follow-up of 26 months, seven of those patients with a negative sentinel node developed regional lymph node metastases. In five of them RT-PCR was positive for micrometastases within the sentinel node. In conclusion, erroneous sentinel lymph node identification can be due to changes in the surgical team, difficult lymph node location or absence of a thorough histological study. Nevertheless, it is not possible to explain completely why, in a very small percentage of cases, the sentinel node is erroneously identified.