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Breslow depth, ulceration, and mitotic rate

American Melanoma Institute · 4 min read

The 3 microscope measurements that matter most in early melanoma, the AJCC thickness cutoffs, and how each one affects staging.

For a melanoma that hasn't spread, 3 findings from the microscope carry most of the information about risk: how thick the tumor is, whether its surface is ulcerated, and how fast its cells are dividing. All 3 come from the same glass slides. None requires an extra procedure.

How the pathologist measures thickness

Breslow thickness is named for Alexander Breslow, the pathologist who showed in 1970 that depth predicts outcome. The pathologist uses a calibrated ruler built into the microscope eyepiece. The measurement runs straight down from the granular layer near the top of the epidermis to the deepest melanoma cell in the dermis.

The AJCC 8th edition staging system asks for thickness to the nearest 0.1 mm. Earlier reports often used 2 decimal places. The expert panel dropped the second decimal because thickness can vary by 0.1 mm or more between different slices cut from the same tumor.

Rounding follows the usual rules. A melanoma that measures 0.75 mm is recorded as 0.8 mm, and one that measures 1.04 mm is recorded as 1.0 mm.

The thickness cutoffs

  • T1: 1.0 mm or less. T1a is under 0.8 mm without ulceration. T1b is 0.8 to 1.0 mm with or without ulceration, or under 0.8 mm with ulceration.
  • T2: over 1.0 to 2.0 mm.
  • T3: over 2.0 to 4.0 mm.
  • T4: over 4.0 mm.

In T2 through T4, the letter a means no ulceration and b means ulceration. Melanoma in situ, which has no invasive part to measure, is written Tis.

What ulceration means under the microscope

Ulceration on a pathology report has a strict definition. The full thickness of the epidermis is missing over part of the tumor, and the tissue shows the body's reaction to that loss, such as a layer of fibrin and inflammatory cells. A scrape from the biopsy blade or a scratch from the day before doesn't produce that reaction, so pathologists can usually tell the difference.

Ulceration signals a more aggressive tumor. In the AJCC data, an ulcerated melanoma behaved much like a non-ulcerated melanoma in the next thicker category. For example, 5-year melanoma-specific survival was 93% for T2b tumors and 94% for T3a tumors.

Mitotic rate and why it left T1 staging

Mitotic rate is the number of cells caught in the act of dividing, counted per square millimeter. The pathologist starts in the most active area of the invasive tumor, called the hot spot, and counts across neighboring fields.

In the 7th edition, a thin melanoma with 1 or more mitoses per square millimeter was classified as T1b. For the 8th edition, the AJCC panel reanalyzed 7,568 patients with T1 melanoma and no lymph node spread (Gershenwald and colleagues, CA: A Cancer Journal for Clinicians, 2017). In that group, the 0.8 mm thickness threshold and ulceration predicted survival more strongly than mitotic rate did. Mitotic rate was not statistically significant in the combined model, so the panel removed it from the T1 definition.

That change applies to one narrow staging rule. Across melanomas of all thicknesses in the same database, 5-year melanoma-specific survival ranged from 99% for tumors with fewer than 1 mitosis per square millimeter down to 84% for tumors with 11 or more. The panel strongly recommends that pathologists keep recording mitotic rate for every invasive melanoma.

The count still has practical uses. Mitotic activity in a thin melanoma has been linked with a higher chance of finding melanoma in a sentinel lymph node, so some doctors weigh it when discussing that procedure. The panel also expects mitotic rate to be part of future tools that estimate risk for an individual patient.

How the 3 findings guide the next step

Thickness and ulceration together set the T category, and the T category shapes the conversation about a sentinel lymph node biopsy. The joint guideline from the American Society of Clinical Oncology and the Society of Surgical Oncology does not recommend the procedure routinely for T1a tumors. It says the procedure may be considered for T1b, recommends it for T2 and T3, and says it may be recommended for T4 after a discussion of benefits and risks.

Survival figures follow the same gradient. For melanomas with no lymph node spread in the AJCC database, 5-year melanoma-specific survival ran from 99% for T1a to 82% for T4b. These percentages describe large groups of patients diagnosed from 1998 onward, most of them before current drug treatments existed. They can't predict what will happen to one person.

When the number comes with a caveat

Sometimes a biopsy cuts through the bottom of a melanoma. The report then reads at least 0.6 mm, or uses similar wording, and notes that the tumor touches the deep margin. The final thickness is settled after the wide excision, when the pathologist examines any tumor left behind.

If the tissue was cut at a slant or came out in fragments, the pathologist may record the T category as TX, meaning thickness can't be assessed. Doctors then rely on the remaining findings and the wide excision specimen.

Small differences between readers are normal. Even 2 experienced pathologists measuring different slices of one tumor can differ by 0.1 mm. When a thickness sits on a boundary such as 0.8 mm or 1.0 mm, that tenth of a millimeter can change the T category, and asking for a second measurement is a reasonable request.

The information provided on this website is not intended to serve as a replacement for the advice, diagnosis, or treatment provided by a qualified medical professional. If you have any questions about a medical condition, you should never hesitate to consult with either your primary care physician or another qualified healthcare provider. You should never disregard the advice of a qualified medical professional or put off getting treatment because of something you have read on this website.
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