Evolution of superficial spreading melanoma to resemble desmoplastic melanoma: case report.

Desmoplastic melanoma commonly occurs on the head and neck in a pure form, but occasionally, it occurs in a mixed tumor with another type, usually superficial spreading melanoma (SSM), and rarely as a metastasis from a primary SSM. We report here a primary SSM on the leg of a 32-year-old male which metastasised to lymph nodes, and 10 years later recurred at the primary site initially with mixed features but evolving to resemble a uniformly desmoplastic, deeply invasive melanoma. This unusual case has implications for clinical management and is additionally notable for its reversal in behavior, from metastatic to local infiltrative type, correlating with the change in morphology.

The EORTC-DeCOG nomogram adequately predicts outcomes of patients with sentinel node-positive melanoma without the need for completion lymph node dissection.

PURPOSE: Based on recent advances in the management of patients with sentinel node (SN)-positive melanoma, we aimed to develop prediction models for recurrence, distant metastasis (DM) and overall mortality (OM). METHODS: The derivation cohort consisted of 1080 patients with SN-positive melanoma from nine European Organization for Research and Treatment of Cancer (EORTC) centres. Prognostic factors for recurrence, DM and OM were studied with Cox regression analysis. Significant factors were incorporated in the models. Performance was assessed by discrimination (c-index) and calibration in cross-validation across centres. The models were externally validated using a prospective cohort consisting of 705 German patients with SN-positive: 473 trial participants of the German Dermatologic Cooperative Oncology Group study (DeCOG-SLT) and 232 screened patients. A nomogram was developed for graphical presentation. RESULTS: The final model for recurrence and the calibrated models for DM and OM included ulceration, age, SN tumour burden and Breslow thickness. The models showed reasonable calibration. The c-index for the recurrence, DM and OM model was 0.68, 0.70 and 0.70, respectively, and 0.70, 0.72 and 0.74, respectively, in external validation. The EORTC-DeCOG model identified a robust low-risk group, with all identified low-risk patients (approximately 4% of the entire population) having a 5-year recurrence probability of <25% and an overall 5-year recurrence rate of 13%. A model including information on completion lymph node dissection (CLND) showed only marginal improvement in model performance. CONCLUSIONS: The EORTC-DeCOG nomogram provides an adequate prognostic tool for patients with SN-positive melanoma, without the need for CLND. It showed consistent results across validation. The nomogram could be used for patient counselling and might aid in adjuvant therapy decision-making.

Risk stratification of sentinel node-positive melanoma patients defines surgical management and adjuvant therapy treatment considerations.

BACKGROUND: In light of the evolving landscape of adjuvant therapy in melanoma and the recently confirmed absent survival benefit of completion lymph node dissection (CLND), it becomes important to explore possible consequences of omitting CLND, and whether it is possible to adequately stratify positive sentinel node (SN) patients solely based on information retrieved from the melanoma up to the sentinel lymph node biopsy (SLNB). METHODS: A retrospective cohort from nine European Organization for Research and Treatment of Cancer Melanoma Group centres was used. Patients were staged based on SLNB and CLND result according to the American Joint Committee on Cancer (AJCC) criteria and stratified by ulceration and SN tumour burden. These were incorporated in Cox regression models. Predictive ability was assessed using Harrell's concordance index (c-index) and the Akaike information criterion (AIC). RESULTS: In total, 1015 patients were eligible. CLND led to upstaging in N-category in 19% and in AJCC stage in 5-6%. The model incorporating only ulceration and SN tumour burden performed equally well as the model incorporating substages after CLND. The model incorporating substages based on SLNB had the lowest predictive ability. Stratifying by ulceration and SN tumour burden resulted in four positive SN groups from which low-, intermediate- and high-risk prognostic classes could be derived. CONCLUSIONS: Adequate stratification of positive SN patients was possible based on ulceration and SN tumour burden category. The identification of low-, intermediate- and high-risk patients could guide adjuvant therapy in clinical practice. Omitting CLND seems to have little consequences.

Is sentinel lymph node biopsy warranted for desmoplastic melanoma? A systematic review.

BACKGROUND: Desmoplastic melanoma (DM) is an uncommon malignancy associated with a high local recurrence rate. The aim of this systematic review was to determine the positivity rate of sentinel lymph node biopsy (SLNB) in patients with DM. The secondary outcome was to establish if SLNB is warranted for both pure DM (PDM) and mixed DM (MDM). METHODS: A full systematic literature review of SLNB in DM was performed by two authors in January 2016. Ovid MEDLINE, Ovid EMBASE and the Cochrane Central Register of Controlled Trials were searched. RESULTS: Sixteen studies involving 1519 patients having SLNB in DM were included, of which 99 patients had positive SLNB (6.5%). Two articles reported a significantly reduced disease-free survival (DFS) with positive SLNB and three published a reduced melanoma-specific survival (MSS). Six studies compared SLNB in MDM and PDM. Of the 275 patients, 38 (13.8%) had a positive SLNB in MDM compared to 17 of 313 patients (5.4%) with positive SLNB in PDM. CONCLUSIONS: Rates of positive SLNB in DM are reduced compared to other variants of melanoma; however, nodal status may still predict DFS and MSS. MDM is associated with a higher rate of micro-metastases to regional lymph nodes than PDM, and DFS and MSS may be lesser in MDM than in PDM. We would recommend the consideration of SLNB in MDM. However, with such low rates of positive SLNB in PDM, and in the absence of high-risk features to stratify patients, we would not recommend SLNB in PDM.

Assessment of proliferation markers in metastatic melanoma in sentinel lymph nodes.

AIM: Some views on sentinel nodes for melanoma seem to cast doubt on the relevance of micrometastases in the sentinel nodes of patients with melanoma, suggesting that small metastases or isolated tumour cells can be ignored. Tumour dormancy has been proposed for their postulated lack of progression. The implication of the argument seems to be that minute metastases are inactive and therefore non-threatening, whereas larger ones are proliferative and therefore have aggressive potential. METHODS: 54 sentinel lymph nodes were studied with histologically identified micrometastatic melanoma using the protocol accepted by the European Organisation for Research and Treatment of Cancer melanoma group. These were studied with respect to metastasis size and by use of immunohistochemical markers of proliferation (MIB-1) and dormancy (p16). RESULTS: The authors have demonstrated no correlation between the size of metastases and their proliferative activity. Very small metastases may not show proliferative activity, but this may be a reflection of the small number of assessable cells rather than a genuine reflection of the tumoural characteristics. Furthermore, the minute size of some of these metastases resulted in no residual tumour being present in adjacent sections. Where further sections did show more tumour, these small metastases were invariably p16 negative, suggesting dormancy was not the explanation for the lack of measurable proliferation. Occasionally, larger metastases, clearly not clinically insignificant, showed no proliferative activity presumably, considering their size, a transient phenomenon. CONCLUSION: These findings suggest that variable phases in proliferation occur in metastases, and no conclusion of clinical insignificance can be made on the basis of small size.

Is there increased risk of local and in-transit recurrence following sentinel lymph node biopsy?

Recent publications have suggested that sentinel lymph node biopsy (SLNB) and completion lymphadenectomy (CLND) increase the rate of local and in-transit disease up to 23% in sentinel node positive group of patients with cutaneous melanoma. This retrospective study combined the data from two national centres on local and in-transit disease in 972 melanoma patients who underwent SLNB procedure over 6.5 years period. In total, 77 patients (7.9%) developed loco-regional recurrence: 41 (4.2%) local recurrence only and 36 patients (3.7%) in-transit metastases during a mean follow-up of 42 months. Patients with positive sentinel lymph node were three times more likely to develop loco-regional metastases than those with no nodal disease (17 vs. 5.6%). Over one third of all recurrences developed following excision of thick (Breslow thickness over 4mm) primary tumours. In both centres age and Breslow thickness were found to be significantly higher in the recurrence group (p<0.001 for both). This study revealed a strong association between increased risk of loco-regional metastases and aggressive tumour biology and adverse patients factors. No conclusive evidence was found to support an increased incidence in patients undergoing SLNB and CLND compared to that published for patients undergoing wide local excision alone.

Successful live cell harvest from bisected sentinel lymph nodes research report.

Sentinel lymph nodes provide an excellent opportunity to study early immune responses to cancer. However, harvesting live cells has not previously been possible, because it conflicts with the need to preserve tissue for histological interpretation. This study used scrape cytology on 26 sentinel and 8 non-sentinel nodes, harvested from 17 stage I/II melanoma patients undergoing sentinel node biopsy. Numbers of viable cells harvested before and after cryopreservation were measured and the effect on subsequent histology assessed. The mean number of cells harvested from 26 sentinel nodes was 7.06 x 10(6) (range 0.1-32.2), with a mean viability of 99.5% (range 87-100, lower 95% CI 98.5%). Furthermore, counts and viabilities were well maintained after cryopreservation. Flow cytometry confirmed CD3+, CD20+ and lineage-1-/HLA-DR+ subpopulations, consistent with T-lymphocytes, B-lymphocytes and dendritic cells, respectively. Importantly, there was no discernible change in histological detail and the proportion of positive sentinel nodes remained unchanged. This technique will allow more functional and quantitative approaches to sentinel lymph node research.

The development of optimal pathological assessment of sentinel lymph nodes for melanoma.

1158 sentinel lymph nodes (SLNs), excised from patients with primary cutaneous melanoma, were assessed pathologically using histology with immunohistochemistry (IHC) on all nodes, and RT-PCR for Mart-1 and tyrosinase on 55 nodes. RT-PCR was compared with the histology and IHC assessed on the same nodes. The evaluation of progressively more detailed protocols for histology and IHC modulated by the RT-PCR results led to a procedure that consistently detects metastases in 34% of patients submitted to SLN biopsy for cutaneous melanomas with a vertical growth phase and a mean thickness of 2.02 mm (range 0.25, with regression, to 19 mm). As this technique is virtually free of false positives and produces only a marginally lower detection rate than RT-PCR, which was subject to false positives of 7% in our study, it is suggested that this extended protocol should be the basis on which further evaluation of the place of RT-PCR in SLN assessment takes place. The evolved protocol described here has been adopted by the EORTC as the standard procedure for pathological handling of sentinel lymph nodes for melanoma when SLN status is a criterion in their clinical trials or studies.