Margin-controlled surgery for squamous cell carcinoma (SCC) on the lower lip was first performed by Dr. Frederic Mohs on June 30, 1936. Since then, thousands of skin cancer surgeons have refined and adopted the technique. Due to the high cure rate and sparing of normal tissue, Mohs micrographic surgery (MMS) has become the gold standard treatment for facial and special-site nonmelanoma skin cancer worldwide. Mohs micrographic surgery is performed on more than 876,000 tumors annually in the United States.1 Among 3.5 million Americans diagnosed with nonmelanoma skin cancer in 2006, one-quarter were treated with MMS.2 In Japan, basal cell carcinoma (BCC) is the most common skin malignancy, with an incidence of 3.34 cases per 100,000 individuals; SCC is the second most common, with an incidence of 2.5 cases per 100,000 individuals.3
The essential element that makes MMS unique is the careful microscopic examination of the entire margin of the removed specimen. Tissue processing is done with careful en face orientation to ensure that circumferential and deep margins are entirely visible. The surgeon interprets the slides and proceeds to remove the additional tumor as necessary. Because the same physician performs both the surgery and the pathologic assessment throughout the procedure, a precise correlation between the microscopic and surgical findings can be made. The surgeon can begin with smaller margins, removing minimal healthy tissue while removing all the cancer cells, which results in the smallest-possible skin defect and the best prognosis for the malignancy (Figure 1).
At the only facility in Japan offering MMS, the lead author (S.S.) has treated 52 lesions with MMS in 46 patients (2020-2022). Of these patients, 40 were White, 5 were Japanese, and 1 was of African descent. In this case series, we present 5 Japanese patients who had BCC treated with MMS.
Case Series
Patient 1—A 50-year-old Japanese woman presented to dermatology with a brown papule on the nasal tip of 1.25 year’s duration (Figure 2). A biopsy revealed infiltrative BCC (Figure 3), and the patient was referred to the dermatology department at a nearby university hospital. Because the BCC was an aggressive variant, wide local excision (WLE) with subsequent flap reconstruction was recommended as well as radiation therapy. The patient learned about MMS through an internet search and refused both options, seeking MMS treatment at our clinic. Although Japanese health insurance does not cover MMS, the patient had supplemental private insurance that did cover the cost. She provided consent to undergo the procedure. Physical examination revealed a 7.5×6-mm, brown-red macule with ill-defined borders on the tip of the nose. We used a 1.5-mm margin for the first stage of MMS (Figure 4A). The frozen section revealed that the tumor had been entirely excised in the first stage, leaving only a 10.5×9-mm skin defect that was reconstructed with a Dufourmentel flap (Figure 4B). No signs of recurrence were noted at 3.5-year follow-up, and the cosmetic outcome was favorable (Figure 4C). National Comprehensive Cancer Network guidelines recommend a margin greater than 4 mm for infiltrative BCCs4; therefore, our technique reduced the total defect by at least 4 mm in a cosmetically sensitive area. The patient also did not need radiation therapy, which reduced morbidity. She continues to be recurrence free at 3.5-year follow-up.
FIGURE 1. Illustration of conventional wide local excision and Mohs micrographic surgery (MMS) specimens. In wide local excision, the tumor is removed with a 3- to 10-mm margin of normal skin. The specimen is fixed with formalin and then vertically sectioned every 2 to 3 mm (bread-loafed) to create a thin representative slice. Each representative slice appears to show clear margins. In reality, the tumor remains between the second and the third slices, which leads to a false-positive interpretation. Even when positive markings are identified on pathology, lacking precision on the exact location of the residual tumor will require the surgeon to excise the entire scar, resulting in an unnecessarily large surgical defect. With MMS, the tumor is excised with a 1- to 2-mm margin of normal skin. There are small incisions at the 12-, 3-, 6-, and 9-o’clock positions to provide orientation. The specimen’s entire cut surface is placed en face on a plane, frozen, cut, and mounted on a glass slide. It is stained with hematoxylin and eosin and evaluated by the Mohs surgeon, who examines the glass slide under a microscope to determine the presence of tumor cells and draws a map of any residual tumor location(s). In this example, tumor cells are seen as dark brown around the 4-o’clock position in the superficial to mid dermis. If any tumor cells remain at the margin, the process is repeated, with additional layers only taking residual tumor until the Mohs surgeon confirms that margins are clear. Once the tumor is excised entirely, the wound is repaired, usually by the same surgeon on the same day. Illustration courtesy of Moeno Watanabe.
FIGURE 2. A 50-year-old Japanese woman with a 7.5×6-mm brown papule with focally dense pigmentation on the tip of the nose that was confirmed via histopathology as an infiltrative basal cell carcinoma.
FIGURE 3. Histopathology of a lesion on the nose revealed infiltrative basal cell carcinoma (H&E, original magnification ×40). Reference bar indicates 100 μm.
FIGURE 4. An infiltrative basal cell carcinoma was treated with Mohs micrographic surgery. A, A 1.5-mm margin was taken for the initial stage. B, A 10.5×9-mm skin defect was reconstructed with a Dufourmentel flap. C, At 2.5-year follow-up, there were no signs of recurrence with a favorable outcome.
Patient 2—A 63-year-old Japanese man presented to dermatology with a brown macule on the right lower eyelid of 2 years’ duration. A biopsy of the lesion was positive for nodular BCC. After being advised to undergo WLE and extensive reconstruction with plastic surgery, the patient learned of MMS through an internet search and found our clinic. Physical examination revealed a 7×5-mm brown macule on the right lower eyelid. The patient had supplemental private insurance that covered the cost of MMS, and he provided consent for the procedure. A 1.5-mm margin was taken for the first stage, resulting in a 10×8-mm defect superficial to the orbicularis oculi muscle. The frozen section revealed residual tumor exposure in the dermis at the 9- to 10-o’clock position. A second-stage excision was performed to remove an additional 1.5 mm of skin at the 9- to 12-o’clock position with a thin layer of the orbicularis oculi muscle. The subsequent histologic examination revealed no residual BCC, and the final 13×9-mm skin defect was reconstructed with a rotation flap. There were no signs of recurrence at 2.5-year follow-up with an excellent cosmetic outcome.
Patient 3—A 73-year-old Japanese man presented to a local university dermatology clinic with a new papule on the nose. The dermatologist suggested WLE with 4-mm margins and reconstruction of the skin defect 2 weeks later by a plastic surgeon. The patient was not satisfied with the proposed surgical plan, which led him to learn about MMS on the internet; he subsequently found our clinic. Physical examination revealed a 4×3.5-mm brown papule on the tip of the nose. He understood the nature of MMS and chose to pay out-of-pocket because Japanese health insurance did not cover the procedure. We used a 2-mm margin for the first stage, which created a 7.5×7-mm skin defect. The frozen section pathology revealed no residual BCC at the cut surface. The skin defect was reconstructed with a Limberg rhombic flap. There were no signs of recurrence at 1.5-year follow-up with a favorable cosmetic outcome.
Patient 4—A 45-year-old man presented to a dermatology clinic with a papule on the right side of the nose of 1 year’s duration. A biopsy revealed the lesion was a nodular BCC. The dermatologist recommended WLE at a general hospital, but the patient refused after learning about MMS. He subsequently made an appointment with our clinic. Physical examination revealed a 7×4-mm white papule on the right side of the nose. The patient had private insurance that covered the cost of MMS. The first stage was performed with 1.5-mm margins and was clear of residual tumor. A Limberg rhombic flap from the adjacent cheek was used to repair the final 10×7-mm skin defect. There were no signs of recurrence at 1 year and 9 months’ follow-up with a favorable cosmetic outcome.
Patient 5—A 76-year-old Japanese woman presented to a university hospital near Tokyo with a black papule on the left cutaneous lip of 5 years’ duration. A biopsy revealed nodular BCC, and WLE with flap reconstruction was recommended. The patient’s son learned about MMS through internet research and referred her to our clinic. Physical examination revealed a 7×5-mm black papule on the left upper lip. The patient’s private insurance covered the cost of MMS, and she consented to the procedure. We used a 2-mm initial margin, and the immediate frozen section revealed no signs of BCC at the cut surface. The 11×9-mm skin defect was reconstructed with a Limberg rhombic flap. There were no signs of recurrence at 1.5-year follow-up with a favorable cosmetic outcome.