Melanocytic lesions, commonly found in 23 percent of skin biopsies, can sometimes be challenging to diagnose based on morphologic criteria alone. However, utilizing diagnostic markers can make a significant difference in the accuracy of a melanocytic lesion diagnosis. 

As a dermatologist, you rely on your partnering dermatopathology laboratory to demonstrate expertise when it comes to diagnosing your melanocytic lesion cases. By understanding why diagnostic markers are ordered and examining the more prevalent types of immunohistochemical stains, you can play a greater role in providing your patients with optimal care.

Why are diagnostic markers ordered?

In a survey of 160 dermatopathologists, 99 percent indicated they ordered additional immunohistochemistry (IHC) or molecular tests out of concern for patient safety. Because melanocytic lesions can produce harmful results if a melanoma diagnosis is missed, laboratories often order diagnostic markers to make sure the results are as definitive as possible, utilizing the most reliable tests.

Medicare has released guidelines to cut costs, reduce overutilization, and ensure that orders for diagnostic markers meet medically necessary criteria. These directives indicate that “a pathologist must first review the H&E [hematoxylin and eosin] stain prior to ordering special stains or IHC.” They add that “the medical necessity for the special stain . . . must be documented in the surgical pathology report.”

The most proficient and ethical dermatopathologists avoid overbilling by ordering additional stains only when they are truly necessary. 

What are the different types of markers?

Immunohistochemical stains are used to help pathologists arrive at an accurate diagnosis. As a dermatologist, it’s essential to be familiar with the stains as they will eventually end up in your report.

These antibodies are the most familiar diagnostic markers: 

  • S100 – The S100 protein is found in 95 percent of primary cutaneous melanomas, making it a popular stain. Diagnostic challenges can occur if the tissue was formerly frozen, had a low fixation time, or underwent enzymatic pretreatment with trypsin. S100 protein detects melanocytes, as well as neoplasms of the nerve sheath such as schwannomas.
  • HMB45 Human Melanoma Black-45 was derived from extracts of pigmented melanoma in lymph nodes. HMB-45 antibody is specific for melanocytes and exposes patterns of nevi maturation. It can also detect patchy gp100 patterns in primary cutaneous melanomas.
  • MART1Melanoma Antigen Recognized by T Cells 1 identifies most melanocytic lesions. It is a cytoplasmic stain and can highlight the dendritic cell processes of melanocytes. It is also known as Melan A.

These markers have been discovered recently:

  • MiTF – Microphthalmia Transcription Factor is a sensitive and specific marker for melanocytes. MiTF has superior sensitivity and specificity to S100 and HMB45. This is a nuclear stain and can be used to quantify pagetoid spread of melanocytes. However, other cells can express MiTF, such as macrophages, smooth muscle cells, and fibroblasts.
  • SOX10  SRY-Related HMG-Box Gene 10 is a nuclear transcription factor seen in melanocytes with a similar staining pattern as MiTF. SOX10 is also seen in nerve sheath tumors. 
  • PRAME – Preferentially Expressed Antigen in Melanoma is a tumor-associated antigen expressed in cutaneous melanoma, ocular melanoma, and other nonmelanocytic malignant neoplasms such as lung and breast carcinoma. The PRAME immunohistochemical stain has been shown to be diffusely positive in the nuclei of most melanoma cells and negative in most benign nevi. In addition, its specificity for malignant cells has made it a candidate for targeted immunotherapy.

Because the diagnosis of melanoma can sometimes be difficult, additional stains or second opinions are sometimes utilized. 

A 2019 pathology study indicates “second opinions rendered by dermatopathologists improve reliability of melanocytic lesion diagnosis.” Utilizing digital slides from full-service dermpath labs like PathologyWatch enables multiple experts to collaborate on difficult cases simultaneously. When a dermatopathology group includes expert dermatopathologists that are trained and accustomed to a standardized laboratory process, there is no need to duplicate any ancillary staining, thereby reducing costs. Furthermore, seeking second opinions earlier in the process can help limit the number of stains required for definitive diagnosis. 

Performing biopsies on melanocytic lesions will be a constant cause of concern for patients and their dermatologists. With the high stakes of melanoma and the possibilities of missed diagnoses, it is critical to know why diagnostic markers are ordered while becoming familiar with the most popular immunohistochemical stains to keep your patients safe.