ORLANDO – Mohs surgery with cytokeratin-7 immunohistochemistry staining effected complete removal of extramammary Paget disease and resulted in a 5-year, 95% recurrence-free cure rate.
The results are significantly better than the often-cited 77% cure rate seen with Mohs surgery alone, Dr. Ali Alexander Damavandy said at the annual meeting of the American College of Mohs Surgery.
“These are statistically significant and clinically substantial results,” said Dr. Damavandy, a procedural dermatology fellow at the University of Pennsylvania, Philadelphia. “With this method you can tell a patient that in 5 years, he has a 95% chance of still not having the tumor. The high recurrence-free rate we have seen supports the view that Mohs surgery with cytokeratin-7 [CK-7] immunohistochemistry should be considered the curative treatment of choice for both primary and recurrent extramammary Paget disease of the skin.”
Dr. Damavandy’s retrospective review of 49 cases may seem small, he said, but it is “far and away the biggest cohort that exists, and the only substantial cohort with immunohistochemistry staining of CK-7.” The 5-year follow-up is also a strength of the study, he added.
Extramammary Paget disease (EMPD) remains an “extraordinarily hard tumor to treat. It typically presents with widespread intraepithelial islands of disease that are not clinically apparent. Local recurrence rates range from 33% to 60%, “leaving a lot of room for improvement,” Dr. Damavandy said.
“The explanations for recurrence are twofold,” he added. “First there is difficulty visualizing tumor cells in frozen sections. Second, it is a multifocal tumor that grows in a discontinuous fashion.”
Although one simply has to deal with the tumor spread, improvements can be made in reading the histopathology. Immunohistochemistry staining with CK-7 allows highly accurate visualization of individual Paget tumor cells, which express a very high level of the protein.
“Our hypothesis was that combining this improved tumor cell visualization with Mohs total excision would really make a dent in the recurrence rates of this disease,” Dr. Damavandy said.
He conducted a review of patients who were treated at four practices from 2004 to 2012. The cohort comprised 49 patients with 62 tumors; 43 were primary and the rest were recurrences. The majority (90%) occurred in the urogenital and anogenital region; the rest were axial or facial. All were treated with Mohs microsurgery enhanced by CK-7 staining of frozen sections. Recurrences were biopsy proven.
The typical Mohs technique for EMPD is to delineate a tumor-free area peripherally, and then excise the central tumor and tumor-bearing islands. The procedure can be long and arduous. Many cases are multiday efforts with large areas of excision.
“These can be very difficult wounds to manage even in a hospital. It’s resource-intense surgery,” Dr. Damavandy said.
The mean margin necessary to clear the lesions in this cohort was 2.6 cm. A 4-cm margin cleared almost 80%; 10% required a 7-cm margin.
“If we were going to make a recommendation to a nonMohs surgeon, it would be that 7 cm are needed to clear 98% of the tumors. That seems to me not reasonable for these anatomically complex and delicate regions. At the same time, the most commonly reported margin in the literature is 2 cm. In this cohort that would only have cleared 40% of the tumors.”
A mean of 3.4 Mohs stages were needed to obtain clear margins, although the range was wide (1-14 stages). Surgery took a mean of 1.5 days (range 1-5 days). Four patients could not be cleared and needed multidisciplinary care. These included two with vaginal invasion and two with invasion of the anal canal.
By 5 years, the overall tumor-free survival rate was 97%; the tumor-free survival rate was slightly better for primary than recurrent tumors (98% vs. 95%). When these rates were compared with Mohs without CK-7 staining, “primary Mohs doesn’t compare very well,” Dr. Damavandy said. At 5 years, the literature-reported recurrence rate for primary tumors treated with Mohs alone was 16% vs. Dr. Damavandy’s report of 2.3% for Mohs plus CK-7 staining. For recurrent tumors, the recurrence rates were 50% vs. 5.3%.
Two tumors recurred; the mean time to recurrence was 31 months. One recurrence was of a primary tumor treated by peripheral Mohs surgery, which was an uncommon approach in this cohort. This patient had a deep recurrence at 16 months.
The other case was a recurrence of a vulvar tumor that extended into the vaginal epithelium and across the cervix. Despite a vaginectomy and vaginal hysterectomy with clear margins, the patient had a recurrence at 46 months.
The patients were retreated and at last follow-up were free of disease.