Melanoma in situ: The power of one (centimeter)?
Sept. 10, 2016
I remember Marie. She was a delightful elderly woman whom I would see for routine follow-up following an excision of her melanoma in situ (MIS) from her right arm. I will never forget my astonishment upon feeling the large lymph node in her right axilla, the first metastasis of her ultimate demise. I will always appreciate her grace in how she handled her illness; she realized how devastated I was — during our visits, she was more comforting to me than I ever was to her.
According to the AAD guidelines for excising MIS, “Based on consensus opinion, wide excision with 0.5- to 1.0-cm margin has been recommended. However, because of the characteristic, potentially extensive, subclinical extension of melanoma in situ, lentigo maligna [LM] type, alternative surgical approaches may be considered. Particularly for larger lesions on the head and neck, greater than 0.5-cm margins may be necessary to achieve negative margins.” (1).
Unfortunately, according to the Cochrane Database, “there is a lack of high-quality evidence for the treatment of MIS and LM, with no randomized clinical trials of surgical interventions aiming to optimise margin control (square method, perimeter technique, ‘slow Mohs,’ staged radial sections, staged “mapped” excisions, or Mohs micrographic surgery), which are the most widely used interventions recommended as first-line therapy.” The use of non-surgical therapies such as imiquimod may be effective and considered when surgery is contraindicated (2).
There is a plethora of literature regarding the proper surgical margins for MIS and LM, with the understanding margins may be ill-defined in LM, leading to more difficulty, and necessitating wider margins. For example, Duffy et al state that LM and non-LM are distinct and in their study of 36 cases of confirmed non-LM MIS, there was no clinical recurrence in 34 of these patients who had follow-up, although the follow-up time was short for several patients. Their average margin of clearance was 4.38 mm (range 1.3 – 7.75 mm), and they suggest that 5 mm margins are adequate for non-LM MIS (I’m not sure why they would reach this conclusion given the range). (3) Stigall et al, used a nonrandomized, single-institution, retrospective design, studying long-term outcomes in 882 cases of MIS treated with Mohs micrographic surgery that were analyzed and compared with historical controls. Rates of complete excision were determined for increasing surgical margin intervals. One local recurrence occurred in their cohort (0.1%). Only 83% of MIS were excised with a 6-mm margin. Margins of 9 mm were needed to excise 97% of MIS, statistically equivalent to thin melanomas. They concluded that Mohs micrographic surgery may cure the 17% of MIS that exceed traditional excision margins of 5 mm and is a valuable option for these patients. Surgical margins of at least 0.9 cm should be considered for MIS of the trunk and extremities when total margin evaluation is not used (4). In a study of 345 cases of MIS on the head and neck treated by Mohs surgery, it was determined that 65% cleared with a 5 mm margin; for 97% clearance, 15 mm was necessary. The authors concluded that when Mohs surgery is not an option, they would advocate excision margins of at least 10 mm (5).
Theoretically, the risk of metastasis of MIS that has been excised should be zero. Therefore, by definition, if a patient like Marie dies, she did not have MIS, but rather melanoma. The diagnosis would be missed either because microinvasion is not detected or the tissue block is not completely examined. To address this issue, Bax et al examined 34 unequivocal MIS cases (an index case and 33 consecutive patients — 20 LM, 13 superficial spreading, 1 acral lentiginous) without associated nevi or regression, utilizing routine microscopy (H&E), and immunohistochemistry (melan-A, SOX10). Occult invasive melanoma was detected in 11 of 33 consecutive cases (33%) of previously diagnosed unequivocal in situ melanoma. Six of 11 melanomas (55%) were diagnosable only by immunohistochemistry. The remaining 5 tumors (45%) were diagnosable by both melan-A and H-E staining, likely as a result of simply cutting deeper into the tissue block (6).
I agree with the authors that their study should not be used to justify either exhausting the tissue block by extensive serial sectioning or using immunohistochemistry excessively on such cases. I also concur with informing patients that because pathology is not perfect, with a diagnosis of MIS, there is a small risk of metastasis, they should be monitored. Finally, the authors state that “The implications for modification of current surgical margin recommendations for in situ melanoma are uncertain but probably unwarranted.” I will defer to the dermato-oncologists to make the official recommendations, however, my prediction is that with further studies, advocates of the 1 cm margin will prevail.
1. Bichakjian CK, et al. Guidelines of care for the management of primary cutaneous melanoma. American Academy of Dermatology. J Am Acad Dermatol 2011; 65: 1032-47.
2. Tzellos T, et al. Interventions for melanoma in situ, including lentigo maligna. Cochrane Database Syst Rev 2014; Dec 19; (12): CD010308.
3. Duffy KL, et al. Adequacy of 5-mm surgical excision margins for non-lentiginous melanoma in situ. J Am Acad Dermatol 2014; 71: 835-8.
4. Stigall LE, et al. The use of Mohs micrographic surgery (MMS) for melanoma in situ (MIS) of the trunk and extremities. J Am Acad Dermatol Jul 26 [Epub ahead of print].
5. Felton S, et al. Excision margins for melanoma in situ on the head and neck. Dermatol Surg 2016; 42: 327-34.
6. Bax MJ, et al. Detection of occult invasion of melanoma in situ. JAMA Dermatology 2016; August 10 [Epub ahead of print]
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