Mohs Micrographic Surgery

Number: 0383

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses Mohs micrographic surgery.

1. Medical Necessity

   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. Atypical fibroxanthoma; or
   3. Dermatofibrosarcoma protuberans; or
   4. For exceptionally large (2 cm or larger in diameter) or rapidly growing lesions in any anatomic region; or
   5. 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
   6. Previously irradiated skin areas in any anatomic region; or
   7. Recurrent or incompletely excised malignant lesions, regardless of anatomic region; or
   8. Sebaceous carcinoma of highly sensitive areas (e.g., head and neck including eyelids); or
   9. 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
   10. 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
   11. 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
   12. Tumors with ill-defined borders.

2. Experimental and Investigational

   The following procedures are considered experimental and investigational because the effectiveness of these approaches has not been established:

   1. Mohs micrographic surgery for all other indications not listed in Section I (e.g., deep cutaneous fungal infections);
   2. Use of optical coherence tomography for margin definition of basal cell carcinoma before Mohs micrographic surgery;
   3. Skin substitutes for the management of Mohs micrographic surgery wounds. See CPB 0244 - Skin and Soft Tissue Substitutes;
   4. Mohs micrographic surgery for the treatment of vulvar malignancies.

3. 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.

4. Related Policies

   1. CPB 0244 - Skin and Soft Tissue Substitutes

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
CPT codes covered if selection criteria are met:
17311	Mohs micrographic technique, including removal of all gross tumor, surgical excision of tissue specimens, mapping, color coding of specimens, microscopic examination of specimens by the surgeon, and histopathologic preparation including routine stain(s) (eg, hematoxylin and eosin, toluidine blue), head, neck, hands, feet, genitalia, or any location with surgery directly involving muscle, cartilage, bone, tendon, major nerves, or vessels; first stage, up to 5 tissue blocks
+ 17312	each additional stage after the first stage, up to 5 tissue blocks (List separately in addition to code for primary procedure)
17313	Mohs micrographic technique, including removal of all gross tumor, surgical excision of tissue specimens, mapping, color coding of specimens, microscopic examination of specimens by the surgeon, and histopathologic preparation including routine stain(s) (eg, hematoxylin and eosin, toluidine blue), of the trunk, arms, or legs; first stage, up to 5 tissue blocks
+ 17314	each additional stage after the first stage, up to 5 tissue blocks (List separately in addition to code for primary procedure)
+ 17315	Mohs micrographic technique, including removal of all gross tumor, surgical excision of tissue specimens, mapping, color coding of specimens, microscopic examination of specimens by the surgeon, and histopathologic preparation including routine stain(s) (eg, hematoxylin and eosin, toluidine blue) each additional block after the first 5 tissue blocks, any stage (List separately in addition to code for primary procedure)
88331	Pathology consultation during surgery; first tissue block, with frozen section(s), single specimen
88332	each additional tissue block with frozen section(s) (list separatley in addition to code for primary procedure)
Other CPT codes related to the CPB:
15271 – 15278	Application of skin substitute graft
Other HCPCS codes related to the CPB:
A4100	Skin substitute, fda cleared as a device, not otherwise specified
C1849	Skin substitute, synthetic, resorbable, per square centimeter
C5271 – C5278	Application of low-cost skin substitute graft
C9363	Skin substitute, integra meshed bilayer wound matrix, per square centimeter
Q4100 – Q4255	Skin substitutes
ICD-10 codes covered if selection criteria are met:
C00.0 - C00.9	Malignant neoplasm of lip
C01 - C02.9	Malignant neoplasm of tongue
C03.0 - C03.9	Malignant neoplasm of gum
C04.0 - C04.9	Malignant neoplasm of floor of mouth
C05.0 - C06.9	Malignant neoplasm of other and unspecified parts of mouth
C30.0	Malignant neoplasm of nasal cavity
C43.0 - C43.9	Malignant melanoma of skin
C44.09	Other specified malignant neoplasm of skin of lip [sebaceous carcinoma]
C44.131 - C44.1392	Sebaceous cell carcinoma of skin of eyelid, including canthus [sebaceous carcinoma]
C44.291 - C44.299	Other specified malignant neoplasm of skin of ear and external auricular canal [sebaceous carcinoma]
C44.390 - C44.399	Other specified malignant neoplasm of skin of other and unspecified parts of face [sebaceous carcinoma]
C44.49	Other specified malignant neoplasm of skin of scalp and neck [sebaceous carcinoma]
C44.590 - C44.599	Other specified malignant neoplasm of skin of trunk [sebaceous carcinoma]
C44.691 - C44.699	Other specified malignant neoplasm of skin of upper limb, including shoulder [sebaceous carcinoma]
C44.791 - C44.799	Other specified malignant neoplasm of skin of lower limb, including hip [sebaceous carcinoma]
C44.89	Other specified malignant neoplasm of overlapping sites of skin [sebaceous carcinoma]
C44.90	Unspecified malignant neoplasm of skin, unspecified [atypical fibroxanthoma]
C44.02, C44.121 - C44.129 C44.221 - C44.229, C44.320 - C44.329 C44.42, C44.520 - C44.529 C44.621 - C44.629, C44.721 - C44.729 C44.82, C44.92	Squamous cell carcinoma
C44.01, C44.111 - C44.119, C44.211 - C44.219, C44.310 - C44.319, C44.41, C44.510 - C44.519, C44.611 - C44.619, C44.711 - C44.719, C44.81, C44.91	Basal cell carcinoma
C44.99	Other specified malignant neoplasm of skin, unspecified [sebaceous carcinoma]
C60.0 - C60.9, C63.00 - C63.9	Malignant neoplasm of penis and other and unspecified male genital organs
D04.0 - D04.9	Carcinoma in situ of skin [Bowen's disease]
D07.60 - D07.69	Carcinoma in situ of other and unspecified male genital organs
D48.5	Neoplasm of uncertain behavior of skin [dermatofibrosarcoma protuberans] [atypical fibroxanthoma]
ICD-10 codes not covered for indications listed in the CPB:
B35.0 – B35.9	Dermatophytosis
B36.0 – B36.9	Other superficial mycoses
B37.2	Candidiasis of skin and nail
B37.31 - B37.32	Candidiasis of vulva and vagina
B37.84	Candidal otitis externa
B40.3	Cutaneous blastomycosis
B43.0	Cutaneous chromomycosis
B43.2	Subcutaneous pheomycotic abscess and cyst
B45.2	Cutaneous cryptococcosis
B46.3	Cutaneous mucormycosis
B47.0 – B47.9	Mycetoma
B48.0	Lobomycosis
B48.8	Other specified mycoses
C51.0 - C51.9, C57.7 - C57.9	Malignant neoplasm of vulva and other and unspecified female genital organs
D07.1 - D07.39	Carcinoma in situ of vulva and other and unspecified female genital organs
Optical coherence tomography:
CPT codes not covered for indications listed in the CPB:
0470T	Optical coherence tomography (OCT) for microstructural and morphological imaging of skin, image acquisition, interpretation, and report; first lesion
0471T	Optical coherence tomography (OCT) for microstructural and morphological imaging of skin, image acquisition, interpretation, and report; each additional lesion (List separately in addition to code for primary procedure)
ICD-10 codes not covered for indications listed in the CPB:
C44.01, C44.111 - C44.119, C44.211 - C44.219, C44.310 - C44.319, C44.41, C44.510 - C44.519, C44.611 - C44.619, C44.711 - C44.719, C44.81, C44.91	Basal cell carcinoma

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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 first and second 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 first 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 first 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.

Carrasquillo et al (2022) stated that MCC is an aggressive neoplasm with high rates of recurrences.  Current guidelines recommend WLE with 1 to 2 cm margins; however, MMS offers a potential advantage over WLE because of its ability of sparing healthy tissue and assessing 100 % of margins.  In a systematic review, these investigators examined the surgical modalities for the treatment of MCC.  Eligible studies were identified using Medline, Scopus, Embase, and Cochrane Library.  All available studies examining surgical treatment of MCC with WLE, or MMS were considered.  A total of 40 studies met the inclusion criteria; 31 studies described patients treated with WLE, 3 with MMS, and 6 with either WLE or MMS.  Subgroup analysis of stage I MCC showed recurrence rates similar in both surgical modalities with local recurrence rate of 6.8 % for WLE versus 8.5 % for MMS (p = 0.64) and a regional recurrence rate of 15.2 % for WLE versus 15.3 % for MMS (p = 0.99).  The authors concluded that overall WLE cases were at a higher stage at presentation.  Subgroup analysis showed that MMS was not inferior to WLE excision for the treatment of stage I MCC and was a reasonable therapeutic option for anatomic locations where tissue sparing was important.

Uitentuis et al (2022) noted that when treating MCC, the relation between WLE margin and recurrence or survival is unclear; and MMS is an alternative surgical option for MCC.  However, it is unknown whether the local recurrence rate differs between MMS and WLE.  In a systematic review, these investigators examined the available evidence on the recurrence and survival rates when treating MCC with MMS and different clinical excision margins.  The Medline, Embase, and CENTRAL databases were searched; 2 independent reviewers selected studies that defined clear excision margins and either recurrence or survival.  When possible, individual cases were extracted from case series and included in the analyses.  Other studies were reviewed narratively.  A total of 1,108 studies were identified; of which, 19 case series (168 cases) and 12 cohort studies were eligible.  None of the cohort studies showed significant differences in recurrence or survival for either excision margins or MMS.  Equally, logistic and Cox regression analyses of the case series revealed no significant differences in recurrence or survival between different excision margins and MMS.  The authors concluded that synthesis of the available data did not indicate differences in recurrence and/or survival rates for MCC between different clinical excision margins and MMS.

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 third 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.

Mohs for Atypical Fibroxanthoma

Koch and co-workers (2015) noted that atypical fibroxanthoma (AFX) is an uncommon, rapidly growing cutaneous neoplasm of uncertain histogenesis.  Thus far, there are no guidelines for diagnosis and therapy of this tumor.  These researchers included 18 patients with 21 AFX, and 2,912 patients with a total of 2,939 AFX cited in the literature between 1962 and 2014.  In this cohort, excision with safety margin was performed in 100 % of primary tumors.  Local recurrences were observed in 25 % of primary tumors and parotid metastases in 5 %; 10-year disease-specific survival (DSS) was 100 %.  The literature research yielded 280 relevant publications.  Over 90 % of the reported cases were negative for cytokeratins, S100, desmin and human melanoma black 45 (HMB-45).  Recurrent AFX was reported in 7.6 % and metastasizing AFX in 2.75 % cases.  No significant differences in the recurrence and survival rates following WLE versus MMS were observed; 20-year DSS rate was 97.8 %.  The authors concluded that a well-selected panel of immuno-histochemical markers is necessary to establish AFX diagnosis with sufficient certainty.  These investigators stated that adequately treated, AFX has an excellent prognosis, but long-term follow-up is recommended due to the potential for aggressive behavior.

Polcz and  associates (2018) stated that AFX is a rare spindle cell neoplasm predominantly found on the head and neck of elderly individuals with sun-damaged skin, with no evidence-based guidelines for their management.  A systematic retrospective review of the literature focusing on treatments found a recurrence and metastasis rate of 8.0 % (5.6 % when adjusted for incomplete excisions) and 0.5 % for local excision and 4.6 % and 3.2 % for MMS, respectively.  The authors concluded that these findings suggested that with clear surgical margins, AFX is unlikely to recur and metastases are rare, with significantly higher rates in the immunosuppressed population.

Tolkachjov and colleagues (2018) noted that AFX is a fibro-histiocytic tumor with relatively high local recurrence rates but low metastatic potential; WLE and MMS are common therapeutic modalities, although no consensus exists regarding optimal therapy.  In a systematic review and meta-analysis, these investigators evaluated evidence of AFX recurrence and metastatic rates after different surgical modalities.  They carried out a comprehensive search for articles published from 1946 or database inception to March 20, 2017.  Studies selected included those that had 5 or more patients with AFX treated surgically.  Two reviewers independently abstracted the data.  Risk of bias was assessed with the Newcastle-Ottawa scale.  Main outcome measures included recurrence and metastasis.  A total of 23 studies were selected (907 patients and 914 tumors); 175 patients were treated with MMS (recurrence rate 2.0 %, 95 % CI: 0 % to 4.1 %; metastatic rate 1.9 %, 95 % CI: 0.1 % to 3.8 %), and 732 were treated with WLE (recurrence rate 8.7 %, 95 % CI: 5 % to 12.3 %; metastasis rate 1 %, 95 % CI: 0.2 % to 1.9 %).  Among immunocompromised patients, no recurrence or metastases developed in the MMS subgroup, although 4 of 10 recurred and 1 of 10 metastasized in the WLE subgroup.  The authors concluded that MMS for AFX was associated with a lower recurrence rate than WLE. 

Mohs for Sebaceous Carcinoma

Su and colleagues (2019) compared Mohs surgery and surgical excision for treating patients with localized sebaceous carcinoma (SC).  The US National Cancer Database was used to identify patients with histologically confirmed Stage 0 to 2 SC from 2004 to 2014.  Clinicopathologic and socio-economic factors were compared between treatment groups using the Chi-square test; OS was evaluated by log-rank test, multi-variable Cox proportional hazard regression, and propensity score-matched analysis.  Relative survival analyses compared with age- and sex-matched US population were performed.  Of 1,265 patients, 234 received Mohs surgery and 1,031 received surgical excision.  Mohs surgery had a higher rate of negative margin (p = 0.004).  On multi-variate Cox regression analysis, Mohs surgery was associated with longer OS than surgical excision (HR: 0.703, 95 % CI: 0.496 to 0.995, p = 0.047).  The survival benefit of Mohs surgery persisted on relative survival analysis and propensity score-matched analysis (p = 0.0385), after matching the 2 groups on patient and disease characteristics.  The authors concluded that patients who received Mohs surgery had significantly longer OS when compared with those who received surgical excision.

In a multi-center, cohort study, Zhou and associates (2019) compared local recurrence, metastasis, and tumor-related mortality of patients with eyelid SC who were initially treated with MMS versus WLE.  Medical records were reviewed for factors associated with recurrence, metastasis and tumor-related mortality.  All eligible patients were followed-up.  The impact of initial surgical modality on the prognoses were determined by Cox analyses after controlling all confounders.  Among 360 patients included in this cohort, 115 (31.9 %) of them underwent MMS as primary resection, whereas 245 (68.1 %) cases underwent WLE.  After a median follow-up period of 60.0 months, local recurrence was observed in 18 (15.7 %) patients of the MMS group and 97 (39.6 %) patients of the WLE group.  Metastasis occurred in 9 (7.8 %) patients who underwent MMS and 38 (15.5 %) who underwent WLE; 6 (5.2 %) patients in the MMS group and 21 (8.6 %) in the WLE group died of metastatic SC.  Multi-variable Cox regression indicated that, compared with the WLE group, the MMS group exhibited more favorable local recurrence control (HR = 0.42; 95 % CI: 0.24 to 0.73; p = 0.002), but a comparable metastasis rate (HR = 1.38; 95 % CI: 0.60 to 3.18; p = 0.453) and tumor-related mortality (HR = 1.70; 95 % CI: 0.59 to 4.93; p = 0.329).  However, this beneficial effect became non-remarkable for patients with pagetoid intra-epithelial neoplasia (HR = 1.73; 95 % CI: 0.37 to 8.21; p = 0.488).  The authors concluded that MMS should be proposed for eyelid SC without orbital involvement to achieve recurrence control, however, this surgery did not change the long-term outcomes in terms of metastasis and tumor-related mortality.  Patients with pagetoid intraepithelial neoplasia may require adjuvant measures.

Furthermore, an UpToDate review on "Sebaceous carcinoma" (Tai, 2019) states that "Wide local excision with frozen section margin control or, if available, Mohs micrographic surgery is the first-line treatment for sebaceous carcinoma of the head and neck region, including eyelid tumors".

Mohs in Children and Adolescents

Wang and colleagues (2020) stated that although there is a large body of evidence demonstrating the safety and efficacy of MMS in adults, little is known regarding the safety and efficacy of MMS in children and adolescents.  These investigators searched all publications from 1993 to 2018 reporting on the use of MMS for the treatment of cutaneous neoplasms in patients aged 0 to 18 years.  Patient demographics, surgical characteristics, outcomes, and complications were extracted from each report.  A total of 49 publications describing 58 patients were included in the final analysis.  The mean age was 8.3 years, and the most commonly treated tumor was dermato-fibrosarcoma protuberans.  There were no recurrences noted at a mean follow-up of 2 years; 2 (3.4 %) patients experienced complications after MMS.  The authors presented aggregate data demonstrating high safety and efficacy of MMS in children and adolescents.  Moreover, these researchers stated that further research is needed to develop guidelines for the use of MMS in children and adolescents.

Zargham and Khachemoune (2021) noted that few data exist to guide the application of MMS in the pediatric population.  In a systematic review, these investigators examined the clinical characteristics of children undergoing MMS, identified challenges that limit the use of MMS in this population, and determined how these challenges could be overcome.  They searched PubMed and Embase from inception of databases to November 2, 2019 to identify cases of pediatric skin lesions treated with MMS.  A total of 111 patients were included.  The median patient age was 11 years (range of 6 weeks to 17 years).  The most commonly treated tumor was dermatofibrosarcoma protuberans (DFSP; n = 62), followed by basal cell carcinoma (BCC; n = 30).  The most common location was the head and neck (n = 34), followed by trunk (n = 28) and extremities (n = 23).  The most commonly cited challenges in the application of MMS in children included: patient cooperation, concerns for safety of prolonged general anesthesia, availability of a Mohs surgery service in the pediatric setting, and access to a histopathology laboratory experienced in MMS sectioning.  The authors concluded that multiple obstacles limited the application of MMS in pediatrics.  This review described practical methods to circumvent these obstacles in order to facilitate the appropriate use of MMS in children.  These researchers stated that the main drawback of this systematic review was that many articles did not report specific patient characteristics.

Mohs for Superficial Leiomyosarcoma

Murphy-Chutorian and colleagues (2019) noted that wide local excision (WLE) with 2 to 5 cm margins has been conventionally used for the treatment of superficial leiomyosarcoma (LMS).  Because margin control is the strongest predictor of clinical recurrence, many dermatologic surgeons have recently recommended MMS over WLE as the primary treatment modality.  These researchers determined the aggregate rate of local recurrence following treatment of superficial LMS with MMS among the few reports in the literature.  They carried out a systematic literature search using the PubMed/Medline database and the Cochrane Library from inception to June 2017; 1 case report from the authors’ institution was included.  A meta-analysis of 14 reports of 48 cases of superficial LMS treated with MMS showed a mean recurrence rate of 2.08 % to 6.25 % with a mean follow-up period of 1,570.9 days, compared to reported recurrence rates of 30 % to 50 % for WLE.  Among these cases there were no reports of distant metastases.  The authors concluded that treatment of superficial LMS with MMS showed markedly lower rates of recurrence compared to reported rates of recurrence after WLE.  Moreover, these researchers stated that further prospective trials with larger sample sizes are needed to compare both modalities.

Mohs for Deep Cutaneous Fungal Infections

Zargham and colleagues (2021) noted that deep cutaneous fungal infections (DCFIs) can cause significant morbidity in immunocompromised patients and often fail medical and standard surgical treatments because of significant sub-clinical extension.  Although rarely considered in this setting, MMS offers the advantages of comprehensive margin control and tissue conservation, which may be beneficial in the treatment of DCFIs that have failed standard therapeutic options.  In a systematic review, these investigators examined the benefits, limitations, and practicality of MMS in patients with DCFIs.  They searches PubMed and Embase to identify all cases of fungal skin lesions treated with MMS.  A total of 8 case reports were identified consisting of a total of 8 patients.  A majority of patients had a predisposing co-morbidity (75 %), with the most common being a solid organ transplant (n = 3, 37.5 %).  The most commonly diagnosed fungal infection was phaeohyphomycosis (n = 5, 62.5 %), followed by mucormycosis (n = 2, 25 %).  No recurrence or complication post-MMS was noted at a mean follow-up of 11.66 months.  The authors concluded that although not a 1st-line treatment, MMS could be considered as an effective treatment alternative for DCFIs in cases of treatment failure and could be especially helpful in areas where tissue conservation was imperative.  These preliminary findings need to be validated by well-designed studies.

Skin Substitutes for the Management of Mohs Micrographic Surgery Wounds

Lu and Khachemoune (2023) stated that the data on skin substitute usage for managing Mohs micrographic surgery (MMS) wounds remain limited.  In a systematic review, these investigators provided an overview of skin substitutes employed for MMS reconstruction, summarized clinical characteristics of patients undergoing skin substitute-based repair following MMS, and identified advantages and limitations of skin substitute implementation.  A systematic review of Ovid Medline, Embase, Cochrane Library, and Web of Science databases, from inception to April 7, 2021, identified all cases of MMS defects repaired using skin substitutes.  A total of 687 patients were included.  The mean patient age was 70 years (range of 6 to 98 years).  Commonly used skin substitutes were porcine collagen (n = 397), bovine collagen (n = 78), Integra (n = 53), Hyalofill (n = 43), amnion/chorion-derived grafts (n = 40), and allogeneic epidermal-dermal composite grafts (n = 35).  Common factors influencing skin substitute selection were cost, healing efficacy, cosmetic outcome, patient comfort, and ease of use.  Some articles did not specify patient and wound characteristics.  The authors concluded that skin substitute usage in MMS reconstruction is not well-guided.  These researchers stated that blinded randomized control trials (RCTs) comparing the effectiveness of skin substitutes and traditional repair methods are imperative for establishing evidence-based guidelines on skin substitute usage following MMS.

Vulvar Malignancies

Shwe et al (2022) stated that MMS is a promising treatment for vulvar cutaneous malignancies, allowing tumor-free margins while preserving structural and functional integrity.  In a recent study evaluating MMS for male genital tumors, low local recurrence rates and high patient-reported satisfaction were observed, and other reviews have shown favorable outcomes of MMS for genital malignancies.  However, a systematic review of vulvar MMS is lacking.  In a systematic review, these researchers included 29 studies representing 107 cases.  MMS was indicated for the following vulvar malignancies: SCC not involving lymph nodes (n = 38), BCC (n = 25), EMPD (n = 31), DFSP (n = 9), verrucous carcinoma (n = 2), basosquamous carcinoma (n = 1), and nodular infiltrating adenocarcinoma of mammary-like glands (n = 1).  These investigators stated that the conventional treatment of vulvar cutaneous malignancy is WLE/partial vulvectomy or total vulvectomy, procedures that have been known to be associated with disfigurement and functional deficits, with psychologic, social, and sexual ramifications.  The current National Comprehensive Cancer Network (NCCN) guidelines recommend MMS for BCC and DFSP.  While the NCCCN guidelines recommend MMS for certain cases of penile SCC, they do not recommend MMS for vulvar SCC.  The findings of this systematic review suggested that MMS is useful for certain cases of vulvar SCC (early stage) and EMPD.  In prior studies of genital EMPD, higher rates of positive margins and recurrence have been found after WLE than after MMS.  However, in a recent study, it was found that women are more frequently offered total skinning procedures for genital EMPD, whereas men are more frequently offered MMS.  The authors concluded that the findings of this review suggested that MMS is an effective modality for primary and recurrent vulvar cutaneous malignancies.  These investigators highlighted the existing deficit in the surgical treatment of women with vulvar malignancies, most notably SCC.  Furthermore, these researchers stated that more robust studies of MMS for cutaneous vulvar malignancies are needed to establish guidelines for optimal patient care.

In addition, National Comprehensive Cancer Network’s clinical practice guideline on “vulvar Cancer” (Version 1.2023) does not mention Mohs micrographic surgery as a management option.

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References