Microcystic Adnexal Carcinoma Treatment & Management

Updated: Feb 20, 2019
  • Author: Nektarios I Lountzis, MD; Chief Editor: Dirk M Elston, MD  more...
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Treatment

Medical Care

Surgery is the mainstay of treatment (see Surgical Care). However, in one report of metastatic microcystic adnexal carcinoma (MAC), a systemic antineoplastic chemotherapy regimen of carboplatin and paclitaxel revealed a therapeutic response supported by imaging studies. [6] Oral S1 therapy, a fluoropyrimidine-derived treatment regimen that consists of tegafur, 5-chloro-2, 4-dihydroxypyridine (CDHP), and potassium oxonate, also successfully treated MAC on the philtrum. [75] Chromosomal aberrations have also been noted in MAC (deletion on arm 6q (q23q25), mutations in TP53 (chromosome 17), and chromosomal losses in cyclin-dependent kinase inhibitor 2A (CDKN2A) (chromosome 9) and cyclin-dependent kinase inhibitor 2B (CDKN2B) (chromosome 9), [5, 6] and these genetic mutations could serve as potential targets for future inhibitor chemotherapy.

Radiation therapy has also been used with some success as either primary therapy [76] or as an adjuvant to surgery in approximately 30 cases to date. [37, 77, 78, 79, 80, 81, 82] However, radiation alone often results in recurrence. One case of a lesion of the upper lip received radiation monotherapy with recurrence in 48 months. Reirradiation revealed remission at 15-month follow-up. Only one case report of a sweat gland carcinoma of the lower lip, suspected of being a MAC, described success with radiation monotherapy but with only a 6-month follow-up period. [83]

Of note, some tumors also are radioresistant, [76] and, as a caveat, radiation therapy/exposure is also implicated as a cause of MAC. [27, 84, 85] In two studies, a prior history of radiation exposure was found in 19.5% (14 of 84) to 50% (5 of 10) of patients with MAC. [4, 10]

Overall, the use of radiation therapy, as either primary or adjuvant, is inconclusive but may have a role in complicated or nonoperable cases. If considered, doses of 66-70 Gy in standard fractionation is typically recommended, extrapolating from the squamous cell head and neck literature, with target volume of the clinically apparent lesion plus 3-cm margins where possible. [79]

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Surgical Care

Mohs micrographic surgery (MMS) is the current treatment of choice for microcystic adnexal carcinoma (MAC). Clinical margins are difficult to define, and MMS offers an excellent way of following the infiltrating nature of the tumor and tracing perineural involvement. The discrepancy between clinical and histologic extent can be marked, in that the size of the defect after complete tumor removal following MMS can be as much as four [13] to six [22] times that of the clinically apparent size. Therefore, standardized, predictable, predetermined surgical margins cannot be used in the treatment of MAC.

MMS versus simple excision

In the largest series to date (48 patients), Chiller et al [13] found little difference in the overall recurrence rate between tumors treated with MMS (2.4% per person-year) versus standard surgical excision (1.5% per person-year) at a mean follow-up of 3.2 years. However, MMS exhibited a clear benefit over simple excision in that 30% of tumors treated with simple excision required at least another office visit to clear the patient of histological tumor findings, with one patient still not tumor free after four simple excisions. This rate was compared with 0% if treated by MMS. A study by Abbate et al [4] reported similar findings (MMS with 0 recurrences out of 4 cases vs excision with 1 recurrence out of 6 cases).

In a large prospective study of patients with MAC, only one case of recurrence was reported out of 20 (5%) at a 5-year follow-up period after MMS. [56] A similar recurrence rate, 4.7%, was noted in a study by Tolkachjov. [86] A study by Friedman et al, [27] with a mean follow-up period of 5-years, had no noted recurrences in 11 patients treated with MMS (0%). Thomas et al [22] found a 12% recurrence rate with a mean follow-up of 3.3 years in their study. This was similar to the 10.3% recurrence rate noted in a 2-year follow up study by Snow et al. [87] In all, the overall recurrence rates for MMS appear to range from 0-12%.

Local recurrence rates of up to 30-47% have been reported with standard surgical excision. Recurrences have also been noted from 5 months to 30 years after excision; thus, longer follow-up is necessary to fully assess both treatment modalities.

Some have suggested the use of an additional layer after complete clearance of margins with MMS for further histologic control. [25, 88] No outcome data exist on this technique.

Staged excision or delayed-closure MMS (slow MMS)

Problems can also be encountered in interpreting frozen sections during MMS, when microscopic invasion can be elusive. Barlow et al [89] proposed that delayed-closure MMS using formalin-fixed, paraffin-embedded specimens improves the histologic assessment and decreases the risk of missing a strand of tumor. Some advocate the use of tangential frozen sections with MMS plus formalin-fixed paraffin sections for the final layer, and this is a workable compromise. Moreover, other reports advocate the use of toluidine-blue staining on frozen sections to highlight MAC extension. Tumor stroma has a pink halo, owing to the presence of mucopolysaccharide and hyaluronic acid, and perineural involvement has a magenta hue, thereby augmenting visualization and clearance with MMS. [63]

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Complications

Local recurrence is a complication if it is not properly excised. Additionally, because of the deep penetration of the tumor, destruction of underlying tissue (eg, bone, cartilage, muscle) can lead to structural changes and increased morbidity.

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Prevention

Sun avoidance minimizes UV exposure, which may be a predisposing factor.

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Long-Term Monitoring

The longest latent period for microcystic adnexal carcinoma (MAC) recurrence following simple excision is 30 years. This particular patient underwent a simple excision for adnexal adenoma in 1953. When he presented again 30 years later, the initial slides were reviewed, and a retrospective diagnosis of MAC was made. This case illustrates the indolent nature of MAC and supports the view that simple excision may not be adequate and long-term follow-up care is required.

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