黑色素瘤薄的患者不要急于行淋巴结活检

旧金山——斯坦福大学皮肤病学教授Susan Swetter医生在太平洋皮肤病学会(PDA)年会上指出，对于黑色素瘤厚度≤0.75 mm的患者，不建议进行前哨淋巴结活检，除非存在真正的高危特征。


Susan Swetter医生

由于基于有丝分裂率上调T1a和T1b黑色素瘤分期，越来越多的黑色素瘤薄的患者被推荐到学术中心进行前哨淋巴结活检，这促使2013年美国国立综合癌症网络(NCCN)黑色素瘤指南对临床分期、患者检查和治疗方面进行了一些修改。

2012年美国国立综合癌症网络(NCCN)召集修订指南的专家审查证据发现，对于≤1 mm的薄黑色素瘤而言，厚度是前哨淋巴结阳性的唯一一致的预测因素。专家组根据前哨淋巴结转移风险（而不根据美国癌症联合委员会分期）来修订ⅠA期和ⅠB期黑色素瘤的分层。

基本上，厚度为0.75 mm的肿瘤的转移风险低(2%~2.5%)，不管有丝分裂率如何。厚度0.76~1 mm的肿瘤，特别是有丝分裂率高的肿瘤，转移风险较高(约5%)，并且“非常适合”进行前哨淋巴结活检。0.75 mm临界值并不改变患者的分期，但可作为对阳性前哨淋巴结活检风险进行分层的方法(J. Natl. Compr. Canc. Netw. 2013;11:395-407)。

2011年美国皮肤病学会(AAD)指南不建议对1 mm的任何T1a肿瘤进行前哨淋巴结活检，因为AAD委员会认为阳性活检结果风险应至少为10%才有必要进行活检。

NCCN 2013年指南的一个关键脚注是：不建议对厚度为0.75 mm的原发性黑色素瘤进行前哨淋巴结活检，除非对微分期的适当性存在明显不确定，“意味着其为切除的肿瘤或非代表性活检。”在适当临床情况下，可考虑对厚度为0.76~1 mm的黑色素瘤进行前哨淋巴结活检。

除了原发性肿瘤厚度之外，究竟还有什么因素导致薄(1 mm)黑色素瘤具有高转移风险，这方面尚未形成共识。危险因素包括高有丝分裂率(但NCCN指南未给出具体数字)。溃疡和淋巴血管浸润可导致风险增加，但较为罕见。

Swetter医生表示，应基于个体情况考虑对薄黑色素瘤患者进行前哨淋巴结活检。一般而言，不建议对厚度为0.75 mm的原发性黑色素瘤进行前哨淋巴结活检，除非存在非常高的有丝分裂率、淋巴血管浸润、溃疡、非代表性活检(涉及大的临床残余病灶)、或部分活检(特别是涉及深部切除肿瘤和微分期不适当)。Clark等级为Ⅳ或Ⅴ也可能是对薄黑色素瘤进行前哨淋巴结活检的原因，但仅在无法评估有丝分裂率时才使用Clark等级。

另一个前哨淋巴结活检的“危险因素”是患者对该活检的强烈偏好，甚至在黑色素瘤厚度非常薄且有丝分裂率低的患者中也是如此。皮肤科医生应试图教育患者，并解释阳性结果风险简直可忽略不计，但如果患者仍决定进行前哨淋巴结活检，则应遵循患者意愿。

Swetter医生声明无相关经济利益冲突。

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By: SHERRY BOSCHERT, Internal Medicine News Digital Network

SAN FRANCISCO – Don’t recommend sentinel lymph node biopsy in patients with a melanoma depth of 0.75 mm or thinner unless there are true high-risk features, Dr. Susan Swetter advised at the annual meeting of the Pacific Dermatologic Association.

Increasing numbers of patients with thin melanomas being referred for consideration of sentinel lymph node biopsy inspired some revisions in the 2013 National Comprehensive Cancer Network melanoma guidelines regarding clinical stage, patient work-up, and treatment, said Dr. Swetter, professor of dermatology at Stanford (Calif.) University.

"Because of the issue of upstaging T1a and T1b melanomas based on the mitotic rate, we have seen a dramatic rise in cases referred to the academic centers for sentinel lymph node biopsy consideration," Dr. Swetter said.

The experts convened by the National Comprehensive Cancer Network (NCCN) in 2012 to revise the guidelines reviewed the evidence and found that thickness is the only consistent predictor of sentinel lymph node positivity for thin melanomas 1 mm or less in depth. They revised the stratification of stage IA and IB melanomas according to their risk for sentinel node metastasis rather than on the basis of the American Joint Committee on Cancer stage.

Essentially, tumors up to 0.75 mm in thickness have a low risk of metastasis (2%-2.5%) regardless of the mitotic rate. Tumors with a thickness of 0.76-1mm, particularly those with a high mitotic rate, have a higher risk of metastasis (approximately 5%), and are "very eligible" for sentinel lymph node biopsy, said Dr. Swetter, who was a member of the guidelines committee. "The 0.75-mm cutoff does not change the stage of the patient" but is a way of stratifying the risk for a positive sentinel node biopsy (J. Natl. Compr. Canc. Netw. 2013;11:395-407).

Guidelines from the American Academy of Dermatology in 2011 did not recommend sentinel lymph node biopsy for any T1a tumor up to 1 mm in depth because the AAD committee felt that the risk of a positive biopsy result should be at least 10% to justify the procedure, said Dr. Swetter, who also was on the committee that drafted those guidelines.

A key footnote in the NCCN 2013 recommendations: Sentinel node biopsy is not recommended for primary melanomas up to 0.75 mm unless there is significant uncertainty about the adequacy of microstaging, "meaning it’s a transected tumor or a nonrepresentative biopsy," Dr. Swetter explained. Sentinel node biopsy may be considered for melanomas 0.76-1 mm thick in the appropriate clinical context.

There is little consensus on what puts a thin melanoma (up to 1 mm) at high risk for metastasis, other than primary tumor thickness. Risk factors include a high mitotic rate (though the NCCN guidelines don’t specify a number), Dr. Swetter noted. Ulceration and lymphovascular invasion increase the risk but are rare.

"Consider sentinel lymph node biopsy in thin melanomas on an individual basis," Dr. Swetter said.

In general, don’t recommend sentinel lymph node biopsy for primary melanomas up to 0.75 mm thick unless there is a very high mitotic rate, lymphovascular invasion, ulceration, a nonrepresentative biopsy (with a large clinical residual lesion), or a partial biopsy (particularly one with deep transection of the tumor and inadequate microstaging), she said. A Clark level IV or V also might be cause for a sentinel node biopsy for a thin tumor, but "we only use Clark level when the mitotic rate can’t be assessed," she noted. "I can’t think of a case in the last 4 years where I’ve paid attention to the Clark level as a reason to pursue treatment in a patient."

One other "risk factor" for sentinel lymph node biopsy, even in a patient with a very thin melanoma and low mitotic rate, is a strong patient preference for the procedure, Dr. Swetter added. Dermatologists should try to educate patients and explain that their chances of a positive result may be fairly negligible, but if "they are determined to have sentinel lymph node biopsy, they will have it done," she said.

Dr. Swetter reported having no relevant financial disclosures.