Meeting News CoveragePerspective

SLNB in pure desmoplastic melanoma remains controversial

NEW YORK — Medically fit patients with mixed desmoplastic melanoma should be offered sentinel lymph node biopsy, according to a presenter at the HemOnc Today Melanoma and Cutaneous Malignancies meeting.

However, use of the procedure in pure desmoplastic cases remains controversial and requires additional investigation, Dale Han, MD, professor of surgery at Yale School of Medicine and Smilow Cancer Hospital at Yale-New Haven, said during a presentation.

‘Unique biology’

Desmoplastic melanoma (DM) — a rare spindle cell variant of melanoma that demonstrates aggressive clinical behavior — accounts for less than 4% of all melanomas.

Median thickness of DM tumors is 2.5 mm to 3.7 mm, compared with approximately 1 mm for all newly diagnosed melanomas.

DM tumors are more common in men and often present in older patients, with a median age of diagnosis between 60 and 65 years.

DM tumors are divided histologically into two types. Pure DM is defined as spindle cell melanoma with 90% or greater desmoplasia, and mixed DM is defined as more than 10% but less than 90% desmoplasia.

Histologic subtype correlates with outcome.

A study by Busam and colleagues showed patients with mixed DM demonstrated a threefold increased risk for death or metastases compared with patients with pure DM (HR = 3.5; 95% CI, 1.3-9.5). Hawkins and colleagues determined patients with mixed DM were at three times greater risk for 5-year melanoma-specific morality than those with pure DM (31% vs. 11%; P < .01).

“These results suggest DM is a melanoma variant with unique biology,” Han said.

Nodal status

Many studies of DM have not been able to accurately assess the prognostic significance of nodal status due to small sample sizes. However, a retrospective study by Han and colleagues showed nodal status predicted melanoma-specific survival in patients with DM.

The researchers identified 316 patients with primary DM treated between 1993 and 2011. Fifty-five (17.4%) had nodal disease.

Multivariable analysis showed nodal status significantly predicted melanoma-specific survival (P < .05).

Early reports suggested the rate of nodal metastases in DM was high, ranging from 30.8% to 42.9%. Larger, more recent studies conducted since 2001 show considerably lower overall nodal metastases rates, ranging from 2.8% to 4.3% in SEER-based studies and from 9% to 18% in single-institution studies.

A case–control comparison by Livestro and colleagues — which included 267 patients treated at a single institution — showed rates of sentinel lymph node metastasis were lower for DM than non-DM (8% vs. 33.8%; P = .13). However, survival rates were similar.

“Given the lower nodal metastasis rate for DM, use of sentinel lymph node biopsy in these cases is debated,” Han said.

Prognostic significance

The majority of studies in DM have been unable to evaluate prognostic significance of sentinel lymph node disease because of small sample sizes. However, in a single-institution retrospective review published in 2013 in Annals of Surgical Oncology, Han and colleagues concluded positive sentinel lymph node status significantly correlated with a higher rate of melanoma-specific survival.

The review included 205 patients (median age, 66 years; 69% men) with DM who underwent sentinel lymph node biopsy between 1992 and 2010. Median Breslow thickness was 3.7 mm. Of the 128 cases with available histologic subtype data, 61 (47.7%) were mixed DM and 67 (52.3%) were pure DM.

Researchers identified sentinel lymph node metastases in 24.6% of mixed DM cases and 9% of pure DM cases.

Median follow-up was 6.3 years, during which 38 patients developed recurrence and 61 patients died. Han and colleagues determined patients with positive sentinel lymph nodes were at significantly greater risk for melanoma-related death than those with negative sentinel lymph nodes (P = .01).

Studies also suggest the false-negative rate for sentinel lymph node biopsy in DM is consistent with that reported in literature for melanoma overall, Han said.

Patient selection

The rate of sentinel lymph node positivity varies considerably by DM subtype. Pawlik and colleagues determined the positive sentinel lymph node rate for mixed DM was 15.8%, comparable to the 17.5% rate for non-DM cases. However, the sentinel lymph node disease rate for pure DM ranges from 2.2% to 9%.

When considering which patients with DM should be offered sentinel lymph node biopsy, age and comorbidities must be considered, Han said.

“Based on the 5% risk threshold for nodal disease, sentinel lymph node biopsy should be offered for mixed DM,” he said. “However, there is controversy over the use of sentinel lymph node biopsy for pure DM. Although they are often thicker, they have a lower positive sentinel lymph node rate.” – by Mark Leiser

References:

Han D. Unanswered questions: What is the role of sentinel node biopsy in desmoplastic melanoma? Presented at: HemOnc Today Melanoma and Cutaneous Malignancies; April 10-11, 2015; New York.

Busam KJ, et al. Am J Surg Pathol. 2004;28:1518-1525.

Han D, et al. PLoS One. 2015;doi:10.1371/journal.pone.0119716.

Han D, et al. Ann Surg Oncol. 2013;doi:10.1245/s10434-013-2883-z.

Hawkins WG, et al. Ann Surg Oncol. 2005;12:207-213.

Livestro DP, et al. J Clin Oncol. 2005;23:6739-6746.

Disclosure: Han reports no relevant financial disclosures.

NEW YORK — Medically fit patients with mixed desmoplastic melanoma should be offered sentinel lymph node biopsy, according to a presenter at the HemOnc Today Melanoma and Cutaneous Malignancies meeting.

However, use of the procedure in pure desmoplastic cases remains controversial and requires additional investigation, Dale Han, MD, professor of surgery at Yale School of Medicine and Smilow Cancer Hospital at Yale-New Haven, said during a presentation.

‘Unique biology’

Desmoplastic melanoma (DM) — a rare spindle cell variant of melanoma that demonstrates aggressive clinical behavior — accounts for less than 4% of all melanomas.

Median thickness of DM tumors is 2.5 mm to 3.7 mm, compared with approximately 1 mm for all newly diagnosed melanomas.

DM tumors are more common in men and often present in older patients, with a median age of diagnosis between 60 and 65 years.

DM tumors are divided histologically into two types. Pure DM is defined as spindle cell melanoma with 90% or greater desmoplasia, and mixed DM is defined as more than 10% but less than 90% desmoplasia.

Histologic subtype correlates with outcome.

A study by Busam and colleagues showed patients with mixed DM demonstrated a threefold increased risk for death or metastases compared with patients with pure DM (HR = 3.5; 95% CI, 1.3-9.5). Hawkins and colleagues determined patients with mixed DM were at three times greater risk for 5-year melanoma-specific morality than those with pure DM (31% vs. 11%; P < .01).

“These results suggest DM is a melanoma variant with unique biology,” Han said.

Nodal status

Many studies of DM have not been able to accurately assess the prognostic significance of nodal status due to small sample sizes. However, a retrospective study by Han and colleagues showed nodal status predicted melanoma-specific survival in patients with DM.

The researchers identified 316 patients with primary DM treated between 1993 and 2011. Fifty-five (17.4%) had nodal disease.

Multivariable analysis showed nodal status significantly predicted melanoma-specific survival (P < .05).

Early reports suggested the rate of nodal metastases in DM was high, ranging from 30.8% to 42.9%. Larger, more recent studies conducted since 2001 show considerably lower overall nodal metastases rates, ranging from 2.8% to 4.3% in SEER-based studies and from 9% to 18% in single-institution studies.

A case–control comparison by Livestro and colleagues — which included 267 patients treated at a single institution — showed rates of sentinel lymph node metastasis were lower for DM than non-DM (8% vs. 33.8%; P = .13). However, survival rates were similar.

“Given the lower nodal metastasis rate for DM, use of sentinel lymph node biopsy in these cases is debated,” Han said.

Prognostic significance

The majority of studies in DM have been unable to evaluate prognostic significance of sentinel lymph node disease because of small sample sizes. However, in a single-institution retrospective review published in 2013 in Annals of Surgical Oncology, Han and colleagues concluded positive sentinel lymph node status significantly correlated with a higher rate of melanoma-specific survival.

The review included 205 patients (median age, 66 years; 69% men) with DM who underwent sentinel lymph node biopsy between 1992 and 2010. Median Breslow thickness was 3.7 mm. Of the 128 cases with available histologic subtype data, 61 (47.7%) were mixed DM and 67 (52.3%) were pure DM.

Researchers identified sentinel lymph node metastases in 24.6% of mixed DM cases and 9% of pure DM cases.

Median follow-up was 6.3 years, during which 38 patients developed recurrence and 61 patients died. Han and colleagues determined patients with positive sentinel lymph nodes were at significantly greater risk for melanoma-related death than those with negative sentinel lymph nodes (P = .01).

Studies also suggest the false-negative rate for sentinel lymph node biopsy in DM is consistent with that reported in literature for melanoma overall, Han said.

Patient selection

The rate of sentinel lymph node positivity varies considerably by DM subtype. Pawlik and colleagues determined the positive sentinel lymph node rate for mixed DM was 15.8%, comparable to the 17.5% rate for non-DM cases. However, the sentinel lymph node disease rate for pure DM ranges from 2.2% to 9%.

When considering which patients with DM should be offered sentinel lymph node biopsy, age and comorbidities must be considered, Han said.

“Based on the 5% risk threshold for nodal disease, sentinel lymph node biopsy should be offered for mixed DM,” he said. “However, there is controversy over the use of sentinel lymph node biopsy for pure DM. Although they are often thicker, they have a lower positive sentinel lymph node rate.” – by Mark Leiser

References:

Han D. Unanswered questions: What is the role of sentinel node biopsy in desmoplastic melanoma? Presented at: HemOnc Today Melanoma and Cutaneous Malignancies; April 10-11, 2015; New York.

Busam KJ, et al. Am J Surg Pathol. 2004;28:1518-1525.

Han D, et al. PLoS One. 2015;doi:10.1371/journal.pone.0119716.

Han D, et al. Ann Surg Oncol. 2013;doi:10.1245/s10434-013-2883-z.

Hawkins WG, et al. Ann Surg Oncol. 2005;12:207-213.

Livestro DP, et al. J Clin Oncol. 2005;23:6739-6746.

Disclosure: Han reports no relevant financial disclosures.

    Perspective

    There is a significantly higher rate of sentinel lymph node positivity with mixed DM compared with pure DM, so differentiating the two is very important. That’s something we should make sure our pathologists tell us. At my institution, we are treating these — until further notice — like melanomas. The idea we have always had is, ‘Treat it like it is the worst thing it can potentially be and you won’t have regrets later on.’ Doing more is probably better than doing less, but perhaps with pure DM, you don’t have to. I think that’s the best way to interpret this.

    • Sanjiv S. Agarwala, MD
    • Program director, HemOnc Today Melanoma and Cutaneous Malignancies HemOnc Today Editorial Board member St. Luke’s Cancer Center Temple University School of Medicine

    Disclosures: Agarwala reports no relevant financial disclosures.

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