Mohs Micrographic Surgery

Number: 0383

Policy

1. Aetna considers surgery with the Mohs technique medically necessary for any of the following skin conditions:

   1. Areas of important tissue preservation (ears, face, feet, hands, genitalia, and perianal); or
   2. Dermatofibrosarcoma protuberans; or
   3. For exceptionally large (2 cm or larger in diameter) or rapidly growing lesions in any anatomic region; or
   4. Lesions located in anatomic areas with high-risk of recurrence of tumor.  These areas would include involvement of the face (especially around eyes, mouth, nose, and central third of face), external ear and tragus, mucosal lesions, nail bed, periungual areas, scalp, and temple; or
   5. Previously irradiated skin areas in any anatomic region; or
   6. Recurrent or incompletely excised malignant lesions, regardless of anatomic region; or
   7. Squamous cell carcinomas associated with high-risk of metastasis, including those arising in the following: adenoid type lesions, Bowen's disease (squamous cell carcinoma in situ), chronic osteomyelitis, chronic sinuses and ulcers, discoid lupus erythematosus, lichen sclerosis et atrophicus, and thermal or radiation injury; or
   8. Superficial malignant melanoma (in situ melanoma and lentigo maligna) in areas of important tissue preservation (i.e., ears, face, feet, hands, genitalia, and perianal); or
   9. Tumors with aggressive histologic patterns: basal cell carcinoma (BCC) morpheaform [sclerosing], basosquamous [metatypical or keratinizing], perineural or perivascular involvement, infiltrating tumors, multi-centric tumors, contiguous tumors (i.e., BCC and squamous cell carcinomas [SCCs]), SCCs ranging from undifferentiated to poorly differentiated and SCCs that are adenoid (acantholytic), adenosquamous, desmoplastic, infiltrative, perineural, periadnexal, or perivascular; or
   10. Tumors with ill-defined borders.

2. Aetna considers Mohs micrographic surgery experimental and investigational for all other indications because its effectiveness for indications other than the ones listed above has not been established.

3. Aetna considers the use of optical coherence tomography for margin definition of basal cell carcinoma before Mohs micrographic surgery experimental and investigational because the effectiveness of this approach has not been established.

Note: Mohs micrographic surgery requires a single physician to act in 2 integrated, but separate and distinct capacities: surgeon and pathologist.  If either of these responsibilities is delegated to another physician who reports his/her services separately, the use of the Mohs micrographic surgery CPT codes is inappropriate.

Background

Mohs micrographic surgery (MMS) is a method of excising complex or ill-defined skin cancers in such a way as to conserve maximal amounts of normal tissue while allowing for histological examination of the entire surgical margin to ensure complete removal of the skin cancer.  The tumor tissue is fixed in place and then removed layer by layer.  Each layer is microscopically reviewed by the Mohs surgeon to ensure that the entire tumor is removed.  The procedure is generally performed on an outpatient basis under local anesthesia.

Mosterd et al (2008) stated that basal cell carcinoma (BCC) is the most common form of skin cancer and its incidence is still rising worldwide.  Surgery is the most frequently used treatment for BCC, but large randomized controlled trials with 5-year follow-up to compare treatment modalities are rare.  These researchers performed a prospective randomized controlled trial (RCT) to compare the effectiveness of surgical excision with MMS for the treatment of primary and recurrent facial BCC.  A total of 408 primary BCCs (pBCCs) and 204 recurrent BCCs (rBCCs) in patients from 7 hospitals in the Netherlands were randomly assigned to surgical excision or MMS.  Randomization and allocation were carried out separately for both groups by a computer-generated allocation scheme.  Tumors had a follow-up of 5 years.  Analyses were done on an intention-to-treat basis.  The primary outcome was recurrence of carcinoma, diagnosed clinically by visual inspection with histological confirmation.  Secondary outcomes were determinants of failure and cost-effectiveness.  Of the 397 pBCCs that were treated, 127 pBCCs in 113 patients were lost to follow-up.  Of the 11 recurrences that occurred in patients with pBCC, 7 (4.1 %) occurred in patients treated with surgical excision and 4 (2.5 %) occurred in patients treated with MMS (log-rank test chi(2) 0.718, p = 0.397).  Of the 202 rBCCs that were treated, 56 BCCs in 52 patients were lost to follow-up.  Two BCCs (2.4 %) in 2 patients treated with MMS recurred, versus 10 BCCs (12.1 %) in 10 patients treated with surgical excision (log-rank test chi(2) 5.958, p = 0.015).  The difference in the number of recurrences between treatments was not significant for pBCC, but significantly favored MMS in rBCC.  In pBCC, Cox-regression analysis showed no significant effects from risk factors measured in the study.  In rBCC, aggressive histological subtype was a significant risk factor for recurrence in the Cox-regression analysis.  For pBCC, total treatment costs were Euro1248 for MMS and Euro990 for surgical excision, whereas for rBCC, treatment costs were Euro1284 and Euro1043, respectively.  Dividing the difference in costs between MMS and surgical excision by their difference in effectiveness leads to an incremental cost-effectiveness ratio of Euro23,454 for pBCC and Euro3171 for rBCC.  The authors concluded that Mohs' micrographic surgery is preferred over surgical excision for the treatment of facial rBCC, on the basis of significantly fewer recurrences after MMS than after surgical excision.  However, because there was no significant difference in recurrence of pBCC between treatment groups, treatment with surgical excision is probably sufficient in most cases of pBCC.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon tumor of the skin with high rates of local recurrence.  Clinically, it often masquerades as a benign, indolent tumor on the trunk and extremities.  Microscopically, it extends far beyond assessed clinical margins, spreading locally in the dermis, subcutaneous tissue, and muscle.  The local recurrence rate in patients with DFSP who undergo wide local excision (WLE) ranges from 0 % to 21 %.  Recent preliminary reports indicated more consistently favorable cure rates with MMS.  However, to date only a few scattered reports have documented long-term (5-year) follow-up.

Snow et al (2004) conducted a retrospective review of a series of 40 consecutive patients with DFSP who underwent MMS over the last 20 years.  Of these, there were 29 patients with greater than 5 years of follow-up who formed the basis of the this review.  There were 16 women and 13 men; 8 patients developed recurrent disease after previous non-Mohs treatment.  Site distribution was 45 % head and neck and 55 % trunk and extremities.  In the current series, there were no local recurrences, with a local 5-year cure rate of 100 %.  In the literature review, which included the current series, there were 136 patients with DFSP who underwent Mohs surgery with greater than 5 years of follow-up.  Nine patients in the current series developed local recurrences, including 5 patients who underwent a second Mohs procedure.  The local cure rates after the 1st and 2nd Mohs surgeries were 93.4 % and 98.5 %, respectively.  The rate (%) and time to local recurrence was 50 % at 3 years and 75 % at 5 years.  However, 25 % of local recurrences appeared late, after the usual 5-year recommendation.  The authors found that in a series of 29 patients with of DFSP and in an accompanying update of the medical literature, 136 patients with DFSP underwent MMS with greater than 5 years of follow-up.  There were no regional and/or distant metastases.  However, late recurrences beyond the usual recommended 5-year follow-up may occur.  Therefore, all patients with DFSP, especially those with recurrent tumors, should be followed for an extended period.  The accumulated data continue to confirm that, when DFSP is discovered early and is accessible readily to excision by MMS, a favorable outcome can be expected with minimal trauma or sacrifice of adjacent normal structures and with a low recurrence rate.

DuBay and associates (2004) reviewed the experience with a multi-disciplinary approach employing WLE and MMS selectively in the treatment of patients (n = 62) with DFSP at a single academic institution over the past 10 years.  Primary endpoints included the ability to extirpate the DFSP lesion completely, the tumor recurrence rate, and the need for skin grafts or local tissue flaps.  A total of 63 DFSP lesions were removed from 62 patients.  At a median follow-up of 4.4 years, no local or distant recurrences were detected in any patient.  Forty-three lesions were treated with WLE, 11 lesions were treated with MMS, and 9 lesions were treated with a combination approach.  Ninety-five percent of lesions that were approached initially with WLE were cleared histologically.  Two patients (5 %) received post-operative radiation for positive margins after undergoing maximal excision.  Eighty-five percent of lesions that were approached initially with MMS were cleared histologically.  The remaining 15 % of lesions subsequently were cleared surgically with a WLE.  Dermatofibrosarcoma protuberans lesions that were approached initially with MMS tended to be smaller.  Patients with head and neck lesions most often underwent MMS or were treated with a multi-disciplinary combination approach (87 %).  The authors concluded that WLE, MMS, and a multi-disciplinary combination approach, selected based on both tumor and patient factors, were capable of achieving very high local control rates in the treatment of DFSP.

It has been debated if MMS involves lower recurrence rates than WLE.  Recent preliminary reports indicated more consistently favorable cure rates with MMS.  Paradisi et al (2008) reported comparative observational data on 41 patients who underwent MMS and 38 who underwent WLE.  Their data were then pooled with those available in the medical literature to obtain more precise estimates of recurrence rates with MMS and WLE.  The primary endpoint was tumor recurrence rate.  The PubMed database was searched for DFSP case series treated with WLE or MMS, and the recurrence proportions reported for the two separate procedures were pooled.  Five of the 38 WLE patients (follow-up = 4.8 years) had recurrences (13.2 %, 95 % confidence interval [CI]: 4.4 % to 28.1 %) as opposed to none (95 % CI: 0 % to 8.6%) of the 41 MMS patients (follow-up = 5.4 years).  Pooling of these data with those from the literature yielded 6/463 recurrences for MMS (1.3 %, 95 % CI: 0.5 % to 2.8%) and 288/1,394 recurrences for WLE (20.7 %, 95 % CI: 18.6 % to 22.9 %).  The relative risk of recurrence for WLE versus MMS patients was 15.9 (95 % CI: 7.2 to 35.5).  The authors concluded that significantly lower recurrence rates were recorded in patients subjected to MMS compared with those treated with WLE.  The pooled data also indicated a clear advantage of MMS.  There is inconclusive evidence for any advantage of MMS in non-primary cases, while MMS was most effective in treating head and neck tumors.

Yu and colleagues (2008) conducted a retrospective analysis of 25 patients with DFSP who received either WLE, modified wide excision (with horizontal processing), Mohs micrographic surgery, or combination surgery.  Follow-up ranged from 15 to 133 months, with a median of 68 months.  Fourteen patients were treated with WLE, 4 with modified wide excision, 6 with MMS followed by modified wide excision, and 1 with MMS.  No recurrences were reported.  Patients with lesions arising from "cosmetically sensitive" areas (head and neck) most often underwent MMS or modified wide excision.  These findings supported that all 4 surgical treatment methods were successful in achieving recurrence-free survival, but emphasis on pre-surgical planning and patient selection for each surgical approach is key to allow for the least complicated repair while maximizing tissue preservation.

Although ultrasound imaging is employed ubiquitously today, its use to examine and assess the skin is a relatively new technology.  High-resolution ultrasound has shown promise in evaluating the extent of no-nmelanoma skin cancer (NMSC).  Jambusaria-Pahlajani et al (2009) determined the accuracy of high-resolution ultrasound to assess the margins of basal cell (BCC) and squamous cell carcinomas (SCC) before MMS.  A total of 100 patients with invasive SCC or BCC were enrolled in this study.  Before the 1st stage of MMS, a Mohs surgeon delineated the intended surgical margin.  Subsequently, a trained ultrasound technologist independently evaluated disease extent using the EPISCAN I-200 to evaluate tumor extent beyond this margin.  The accuracy of high-resolution ultrasound was subsequently tested by comparison with pathology from frozen sections.  The test characteristics of the high-resolution ultrasound were sensitivity = 32 %, specificity = 88 %, positive predictive value = 47 %, and negative predictive value = 79 %.  Subgroup analyses demonstrated better test characteristics for tumors larger than the median (area greater than 1.74 cm(2)).  Qualitative analyses showed that high-resolution ultrasound was less likely to identify extension from tumors with subtle areas of extension, such as small foci of dermal invasion from infiltrative SCC and micro-nodular BCC.  The authors concluded that high-resolution ultrasound requires additional refinements to improve the pre-operative determination of tumor extent before surgical treatment of NMSC.

Marmur and colleagues (2010) explored the clinical application and use of high-frequency, high-resolution ultrasound in MMS.  In a single-center study, these researchers evaluated the ability of ultrasound to accurately determine lesion length and width of tumor borders in order to reduce the number of surgical stages (n = 26 MMS patients).  Ultrasound images were taken to record lesion dimensions, and then the investigator documented clinical estimation of the first stage.  Extirpation of the tumor and histological analysis were performed thereafter.  The results of 20 patients were included in the analysis.  A paired-samples t-test revealed no significant difference between clinical and ultrasound widths (t = -1.324, p = 0.20).  Similarly, there was no significant difference between the lengths found from clinical assessment and ultrasound (t = -1.093, p = 0.29).  For different tumor types, there was no significant difference between clinical and ultrasound widths or lengths for basal cell carcinoma (t = -1.307, p = 0.23; t = -1.389, p = 0.20) or squamous cell cancer (t = -0.342, p = 0.73; t = 0.427, p = 0.68).  The authors concluded that there is a diagnostic role for high-resolution ultrasound in MMS regarding the delineation of surgical margins, but its limitations preclude its practical adoption at this time.

In a Cochrane review, Narayanan et al (2012) compared the effectiveness, cost, complications and acceptability of periocular BCCs when operated by MMS or surgical excision (SE).  These investigators searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 11), MEDLINE (January 1950 to November 2011), EMBASE (January 1980 to November 2011), the metaRegister of Controlled Trials (mRCT), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP). There were no date or language restrictions in the electronic searches for trials.  The electronic databases were last searched on November 23, 2011.  These researchers planned to include only RCTs comparing SE with MMS for treatment of peri-ocular BCC.  They did not find any studies that met the inclusion criteria for this review and hence none was included for analysis.  Results of non-RCTs describing the individual techniques were reported.  The authors concluded that no reliable conclusions could be reached regarding which method of treatment (SE or MMS) resulted in a lower recurrence or complication rate for peri-ocular BCC.  No studies were found comparing the cost of either method directly.  They stated that high quality RCTs are therefore needed to improve the evidence base for the management of this condition.

Bae and colleagues (2013) stated that extra-mammary Paget disease (EMPD) is a rare intraepithelial neoplasm of the skin characterized by ill-defined margins and high recurrence rates after wide local excision.  Although MMS has been proposed to decrease the rate of local recurrence, the efficacy of MMS for this condition has not yet been established.  These investigators evaluated the effectiveness of MMS for the treatment of EMPD.  A comprehensive systematic review and individual patient data meta-analysis was performed including all available clinical studies and case reports with 5 or more subjects describing the use of MMS for EMPD.  A total of 8 studies were identified and included in the current review: 3 retrospective studies and 5 case series.  In all, 81 patients with 90 cases of MMS were included from these 8 studies.  The overall recurrence rate for EMPD after MMS was 12.2 % correlating with an estimated 5-year tumor-free rate of 83.6 % by using Kaplan-Meier curve analysis.  The treatment of EMPD with MMS resulted in significantly lower recurrence rates than wide local excision in this meta-analysis of 3 observational studies with comparators (odds ratio 0.20; 95 % CI: 0.05 to 0.81).  The authors concluded that the current evidence supports the effectiveness of MMS in the treatment of EMPD.  Moreover, they stated that further controlled clinical trials are needed.  The main drawbacks of this analysis included a lack of controlled trials, small sample sizes in the included studies, as well as publication bias.

Alam et al (2013) stated that floaters are dislodged pieces of tumor tissue than can obscure MMS frozen sections and confound their interpretation.  These researchers described the common causes of floaters and identified management strategies.  An initial virtual consensus of Mohs surgeons based on a 60-item questionnaire was performed.  Data were validated in interviews with randomly selected Mohs surgeons.  Based on retrospective reporting of 230 surgeon-years and 170,404 cases of MMS by 26 surgeons, the mean rate of floaters per tumor treated was 1.8 %, and the rate of floaters per tissue block was 0.70 %.  Not wiping blades between cuts when a stage is separated into subunits can predispose to floaters.  There was also strong consensus that BCCs, ulcerated tumors, and tissue from the 1st stage were more likely to yield floaters.  There was little consensus on how to manage floaters, with possibilities including taking additional sections, taking an additional stage, or simply noting the floater.  The authors concluded that floaters are not rare and can complicate MMS margin assessment.  They stated that there is significant expert consensus regarding the causes of floaters and the tissue features that may predispose to them.  Moreover, they noted that floaters may be prevented by minimizing their likely cause; but there is less consensus on what to do with a floater.

Hou et al (2015) stated that WLE with 5-mm margins is the standard of care for the treatment of lentigo maligna (LM).  Mohs micrographic surgery is used increasingly to treat this tumor.  The authors reported their experience with these 2 approaches.  Primary LM cases treated at the authors' institution from January 1, 1995, through December 31, 2005, were studied retrospectively.  Main outcome measures were recurrence and outcomes after treatment for recurrence.  In total, 423 LM lesions were treated in 407 patients: 269 (64 %) with WLE and 154 (36 %) with MMS.  In the MMS group (primarily larger head and neck lesions with indistinct clinical margins), recurrence rates were 3 of 154 (1.9 %).  In the WLE group (primarily smaller, non-head and neck, or more distinct lesions), recurrence rates were 16 of 269 (5.9 %).  Each of the 16 recurrences was biopsy proven and treated surgically: 6 by SE and 10 by MMS.  The authors concluded that this follow-up study of LM surgical treatments showed excellent outcomes for WLE and MMS.  They stated that because this was a non-randomized retrospective study, no direct comparisons between the 2 treatments can be made.  When recurrences occurred, repeat surgery, either SE or MMS, was usually sufficient to provide definitive cure.

Alcalay et al (2015) noted that vismodegib, a hedgehog pathway inhibitor has been recently introduced as an oral therapy for locally advanced and metastatic BCC.  Although treatment of patients with BCC with vismodegib has been associated with partial or complete clinical response, it is still unclear if it is also associated with histological cure.  Two patients with 3 large and aggressive BCC were treated with vismodegib for 6 months.  The treatment was followed by MMS.  Two tumors disappeared clinically and 1 was reduced dramatically in its size following treatment with vismodegib.  Mohs surgery in all 3 tumors revealed residual islands of BCC although margins were cleared at the end of surgery.  The authors concluded that neoadjuvant therapy with vismodegib for 6 months prior to Mohs surgery was effective in reducing the size of primary and recurrent aggressive BCC.  However, residual tumor nests were found during surgery.  They stated that further larger studies are needed to evaluate the effectiveness of vismodegib as a neoadjuvant treatment prior to Mohs surgery.

National Comprehensive Cancer Network’s clinical practice guideline on “Penile cancer” (Version 1.2017) states that “Tis, Ta, and T1 penile cancer lesions may be amenable to conservative penile organ-sparing approaches, including topical therapy, wide local excision, laser therapy, glansectomy, and Mohs surgery …. Mohs surgery is an alternative to wide local excision  in select cases, it may be preferable for a small superficial lesion on the proximal shaft to avoid total penectomy for an otherwise fairly low-risk lesion (category 2 B recommendation)”.

National Comprehensive Cancer Network’s clinical practice guideline on “Merkel cell carcinoma” (Version 1.2017) states that “Techniques for more exhaustive histologic margin assessment may be considered (Mohs micrographic surgery, modified Mohs micrographic surgery, complete circumferential peripheral and deep-margin assessment [CCPDMA]), provided they do not interfere with sentinel lymph node biopsy [SLNB] when indicated …. Mohs micrographic surgery is superior to conventional surgical excision in high-risk basal cell carcinoma and squamous cell carcinoma.  In Merkel cell carcinoma, it may be used to ensure complete tumor removal and clear margins, while secondarily sparing surrounding healthy tissue”.

Merkel Cell Carcinoma:

Singh and colleagues (2018) noted that the optimal surgical approach (WLE versus MMS) for treating Merkel cell carcinoma (MCC) is yet to be determined.  These researchers compared survival outcomes in patients with early stage MCC treated with Mohs versus WLE.  A retrospective review of all cases in the National Cancer Data Base (NCDB) of MCC of clinical Stage I to II MCC treated with WLE or MMS was performed.  A total of 1,795 cases of Stage I to II MCC were identified who underwent WLE (n = 1,685) or MMS (n = 110).  There was no difference in residual tumor on surgical margins between the 2 treatment groups (p = 0.588).  On multi-variate analysis, there was no difference in overall survival (OS) between the treatment modalities (adjusted hazard ratio [HR] 1.02; 95 % CI: 0.72 to 1.45, p = 0.897).  There was no difference in OS between the 2 groups on propensity score matched analysis.  The authors concluded that MMS appeared to be as effective as WLE in treating early stage MCC.

Aggressive Digital Papillary Adenocarcinoma:

Haynes and colleagues (2017) stated that aggressive digital papillary adenocarcinoma (ADPA) is a rare and histologically challenging malignant eccrine neoplasm with a high propensity for local recurrence and metastasis.  Classically, the lesion presents as a non-painful, firm, tan-gray to white-pink, rubbery nodule on the volar surface of the upper digits.  Treatment of ADPA has thus far been primarily limited to wide excision with or without digital amputation and subsequent close, long-term follow-up for recurrence and metastatic disease.  While effective in providing local control, amputation may leave the patient with disfigurement and disability.  The authors presented a case of ADPA treated with MMS as a digit-sparing alternative to amputation with no evidence of recurrence or metastasis 2 years post-operatively.

Knackstedt and associates (2017) reported the treatment of 2 cases of ADPA with MMS and reviewed the presentation, management, and prognosis of this rare malignancy.  Cases of ADPA were identified from recent surgery logs.  Demographic, tumor, and treatment characteristics were extracted.  A PubMed database search for English language full-text articles of ADPA was performed, and relevant articles were summarized.  Two cases of ADPA were identified.  A 53-year old man presented with ADPA on his right 3rd fingernail, and a 65-year old man presented with ADPA on his right thumb.  Both patients underwent MMS and negative sentinel lymph node biopsy, remaining recurrence free at 34 and 9 months, respectively.  These researchers noted that ADPA frequently presents as a solitary mass on the digit.  Treatment of ADPA with local excision or amputation has historically been fraught with high recurrence rates.  Regional lymph node spread and distant metastasis have been reported; MMS may be an alternative treatment for ADPA.  The authors concluded that MMS is a viable option for ADPA and warrants further exploration; long-term follow-up is important, and additional studies are needed to identify the role of sentinel lymph node biopsy.

Optical Coherence Tomography for Margin Definition of Basal Cell Carcinoma Before Mohs:

De Carvalho and colleagues (2018) stated that MMS is the preferred therapeutic treatment for high-risk BCC.  Optical Coherence Tomography (OCT) is a non-invasive imaging technique that enables the diagnosis of BCC.  In a pilot study, these researchers determined the margins of BCCs with OCT, prior to MMS, to reduce the number of surgical steps.  Different permanent markers were tested on the skin regarding line width, resistance against disinfection and brightness in the OCT image.  The visible tumor margins of BCCs were defined by dermoscopy, adding a safety margin of 2 mm and labeled using the selected pen, causing a signal shadow in OCT.  Scans of the center and of entire margin were performed.  If parts of the BCC were visible outside the margin, another 2 mm were added and the scan was repeated until the tissue outside the labeling looked tumor free; 8 out of 10 BCCs were totally excised in a single stage when margin delineation was done by OCT.  Macroscopic margins were enlarged after OCT scanning in 4 patients, saving further stages of MMS.  The authors concluded that OCT may help to better define the microscopic dimensions of BCCs and therefore reduce the number of stages of MMS.

The authors stated that this pilot study was limited by the small number of tumors (n = 10), which underwent this procedure of pre-surgical margin mapping.  The intention of this work was to develop, evaluate and describe a simple, fast and reliable method for margin definition of BCC relying on microscopic analysis of the tumor by means of OCT.  These investigators stated that further work with a larger number of cases is needed, in order to  quantitatively evaluate whether and how OCT reduces the excision of large safe margins and the number of stages of MMS, which are needed for reaching complete excision.  If this new method proves to statistically reduce the number  of surgical stages and also reduce the average size of surgical defect, the pre-surgical margin definition of BCCs may enable an improvement of the MMS technique, which the authors may term “OCT- assisted MMS”, which is more time-  and resource-efficient and may enable extension of the benefits of MMS to more patients.

The above policy is based on the following references: