Diagnostic Markers for Melanocytic Lesions

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. 

Better Communication with Your Dermatopathology Laboratory Equals Better Results

As a dermatologist, you rely on your lab partner to provide correct diagnoses to ensure your patients receive the highest level of care. However, since communication errors are a major factor in up to 70 percent of adverse events, it’s easy to see how better communication with your dermatopathology laboratory can lead to better results.

Producing accurate results is a team effort. By identifying the information required for a definitive diagnosis, developing a communicative relationship, and enhancing communication through technology, you can help your dermatopathology lab consistently produce more valuable reports. 

Facilitating Definitive Diagnoses

When it comes to complicated diagnoses (such as rashes/eruptions), it’s safe to say dermatologists get out of it as much as they put into it. In cases like these, the value of the report you receive from the lab sometimes reflects the amount and quality of clinical information you share with the dermatopathologist.

For instance, including your differential diagnosis in the requisition form can help steer the dermatopathologist in the right direction. This is particularly helpful when it comes to the diagnosis of inflammatory skin diseases. The histological findings may be subtle, and comprehensive clinical information, including photos, may be needed to arrive at the most accurate diagnosis.  

By providing your dermatopathologist with clinical features, you can help ensure they have the required data to make a definitive diagnosis.

Relationships of Communication

When a dermatologist receives a report that is not definitive, it could be the result of the dermatopathologist not fully understanding the clinical scenario. In these cases, the dermatologist should be proactive and communicate with the dermatopathologist, providing any additional details for a more definitive diagnosis. For example, relevant information for an eruption may include the distribution, duration, symptoms, extent, and color. The dermatopathologist should also reach out to the dermatologist for more information when needed.

Meanwhile, dermatologists who value turnaround time and accurate results should make improving the relationship with the lab a priority. A survey of dermatopathologists showed that diagnoses were delayed due to lack of clinical information, as 45 percent of respondents spend more than 30 minutes a day tracking down clinical information that was not present on the order form. By voluntarily providing information upfront, following up as needed, and building relationships based on communication, you can help your dermatopathologist improve the quality of the lab results. 

Technology-Enhanced Information 

Digital tools can enhance laboratory reporting and enable clinicians to better correlate findings. For example, an EMR interface can simplify the transfer of data between your clinic and the lab. This can reduce the chances of errors by replacing handwriting and carbon copies. In clinics where handwritten requisition forms are used, digital tools provided by PathologyWatch enhance clinic flexibility by providing various reporting options. 

PathologyWatch also supports clients interested in enhanced EMR reporting options. Where available, these EMR interfaces can provide the dermatopathologist with valuable clinical information, including clinical photos, visit notes, and the history of present illness to the laboratory. In addition, PathologyWatch is able to deliver results that speed up dermatologist report review and sign-off within their clinic. 

By providing clinical features, taking a proactive role in communicating, and considering technology options to support your communication, you can experience better communication with your dermatopathology laboratory to produce better results.

Critical Value in Dermatopathology—Where Time and Communication Are Essential

Critical values are defined as “laboratory results that indicate a life-threatening situation for the patient.” Because of their demanding nature, the appropriate healthcare professional must be notified urgently of a critical value. 

In the field of dermatopathology, the College of American Pathologists defines a critical value as a critical diagnosis such as “a medical condition that is clinically unusual or unforeseen and should be addressed at some point in the patient’s course.”

All laboratories, including dermatopathology labs, are required to exercise effective communication when it comes to reporting critical diagnoses and must have a written protocol in place. This is in accordance with laboratory regulations outlined by CLIA (Clinical Laboratory Improvement Amendments; CLIA ’88) and the Joint Commission (TJC) National Safety Goals.

Dermatology clinics should understand what qualifies as a critical or a significant unexpected diagnosis. By examining how labs identify and manage critical diagnoses, defining the referring provider/lab partnership, and understanding how results are shared, we can expedite treatment and improve patient care.

Management of Critical Diagnosis in the Lab

Immediate and decisive action is required in the dermatopathology lab to identify and report critical diagnoses to the dermatologist as soon as possible. Every dermatopathology laboratory should have a written protocol outlining the diagnoses that are considered critical. In most instances, a new diagnosis of invasive melanoma is considered a critical diagnosis, as well as a life-threatening diagnosis such as staphylococcal scalded skin syndrome, graft versus host disease, or toxic epidermal necrolysis. Unalarming in appearance, each of these skin disorders could lead to serious health complications if not treated quickly. 

Once identified as critical or significant, the laboratory is responsible for documenting how and when the results are communicated with the dermatology clinic. If the diagnosis is shared over the phone, there should be a record of who made and received the call. In addition to ensuring the clinic accepts and understands the results, the lab keeps a record to comply with existing laboratory regulations.

The Referring Provider/Lab Partnership

When a clinic and laboratory form a new partnership, the dermatologist and lab open communication lines to clarify the types of results they define as urgent or critical.

Though 75 percent of laboratories have a written policy for handling critical and significant unexpected diagnoses, clinics need to ensure their lab’s processes meet the needs of patients and practices (for instance, if a dermatologist establishes that he or she wants a notification for melanoma in-situ as well as invasive melanoma, or for unexpected cases of Tinea spp). By communicating regularly regarding cases, mutual trust will develop over time between the lab and the clinic.

Sharing Urgent Results

The most crucial step in the critical diagnosis process comes when the dermatologist shares the results with patients and points them towards treatment. The urgency is real, as the rate of survival decreases 5 percent for patients with stage I melanoma treated between 30 and 59 days compared with those treated in the first 30 days after diagnosis. 

To ensure fast and precise action, it is helpful when labs share critical values directly to the EMR in addition to a phone call. Full-service dermpath labs like PathologyWatch transfer results and digital images electronically, enabling clinics to correlate with dermatopathologists instantly. At the same time, accessing the diagnosis in the EMR makes it easy for dermatologists to quickly share the results with patients on a tablet or laptop, reducing worrisome waiting periods.

Whenever a dermatology clinic sends a batch of request sheets to the lab, there are chances for revealing critical diagnoses. By clarifying what constitutes a critical value, defining the referring physician/lab partnership, and examining the best way to share results, you can increase optimal treatment and recovery for patients.

Dollars and Cents: How to Ensure Your Dermatopathology Lab Is Billing Appropriately 

Dermatology clinics who send out to labs rely on accurate pathologic diagnoses to provide optimal patient care. With 44 percent of patient specimens being billed out of network in the United States, it’s also essential to ensure your dermatopathology lab is billing appropriately and in-network.

Your patients trust you to deliver a precise diagnosis and to ward off any surprise billing. By evaluating insurance coverage, looking at common overbilling issues, and defining necessary tests, you can be sure your lab is practicing proper and ethical billing.

Insurance Coverage

Aligning your dermatology practice with a lab contracted with a wide variety of insurance providers is paramount to serving your patients. With more than 900 health insurance companies offering coverage in the United States, it’s crucial to affiliate with a lab that meets the most common demands of the population in your area. 

While clinics can access diverse insurance relationships by working with multiple labs, breaking up samples can be inefficient and lead to confusion. Labs will accept all incoming samples regardless of whether their insurance network covers them. This results in some patients receiving surprise bills from out-of-network labs that could use up their entire deductible. Even though patients can contact their insurance companies or the laboratories directly to negotiate lower invoices, these frustrations impact patient satisfaction and reflect poorly on your clinic.


Safeguard your reputation by partnering with a dermatopathology lab that avoids overbilling or performing unnecessary tests. The costs of excessive medical testing and treatment in the United States is estimated to reach $200 billion annually. Different dermatopathologists and dermatopathology laboratories have different policies on ordering special stains and immunostains. Sometimes increased staining is unnecessary and results in increased bills to your patients. Laboratories that focus exclusively on dermatopathology typically optimize H&E staining for skin diseases, which decrease the utilization and need for immunostains and special stains. Hospital-based dermatopathology or laboratories that do not focus exclusively on dermatopathology sometimes do not optimize for this use case, which can result in increased staining and higher bills to your patients. 

Testing Criteria

In 2014, many Medicare providers responded to growing overbilling concerns by issuing the local coverage determinations (LCD). The rule was designed to boost transparency and raise accountability, indicating that providers can no longer order reflex testing. Labs that violate these standards can be subject to Medicare audits and expensive fines. 

It is up to the laboratory to determine which tests qualify as LCD-approved medical necessities. Dermatopathologists are expected to hold off on billing for costly stains unless documented and necessary. Because most diagnoses can be rendered without a special/immunostain, labs should no longer automatically order stains on cases, also known as reflex testing. 

“Most skin lesions are diagnosed with routine H&E slides,” Medicare reports. “That is the case for most melanomas and other pigmented lesions as well. A minority of skin lesions require immunostains (e.g., atypical fibroxanthomas, Merkel cell lesions, lymphomas). Most common skin lesions (e.g., seborrheic keratosis) do not require IHC stains.”

The LCD provides clear guidelines when it comes to pathologists ordering additional tests: 

  • Tests must be medically necessary to reach a complete and accurate diagnosis. 
  • Results must be shared with—and used by—the treating physician/practitioner.
  • Justification for tests must be documented in the pathologist’s report.

Partnering with a full-service dermpath lab like PathologyWatch that has a broad network of insurance coverage and doesn’t send surprise bills is a smart way to maintain your patients’ confidence and loyalty. Knowing what to look for when it comes to insurance coverage, understanding overbilling practices, and being aware of the LCD testing criteria can help you ensure your dermatopathology lab is billing appropriately.

Identifying Delays in Dermatopathology Lab Turnaround Time

When patients bring their business to your dermatology clinic, they trust you will provide optimal diagnoses and treatment decisions promptly. You share the same expectations regarding dermatopathology lab turnaround time, which the College of American Pathologists (CAP) suggests should require no more than 48 hours in standard cases.

Several factors can increase or cut down the time between receipt in the lab to a verified report. By carefully considering transportation, laboratory workflow, diagnostic hurdles, report delivery, clinical findings, slide requests, and processes in your dermatology clinic, you can improve turnaround time and your patients’ satisfaction and care.


While The College of American Pathologists in the above-mentioned recommendation measures turnaround time from the moment a specimen reaches the lab until the result is signed out to the ordering dermatology provider, we at PathologyWatch measure turnaround time from the moment a specimen is picked up until the result is signed out. Regardless, reliable transportation is required to ensure tissue samples are delivered safely and on time. 

Delays in transportation are not uncommon, as couriers may have to battle traffic or mechanical issues as they carry specimens from the dermatology clinic to a local lab. Meanwhile, overnight providers such as FedEx and UPS may face weather challenges as they move samples greater distances to labs in other parts of the country. Dermatology clinics should expect their partnering labs to provide a reliable and secure system to transport specimens on time in a consistent fashion.

Laboratory Workflow

Running a productive dermatopathology lab requires cooperation from many vital team members. While dermatopathologists read their slides, lab technicians maintain the equipment, and office managers oversee incoming and outgoing reports, they all share in the responsibility of providing acceptable turnaround times.

National holidays, vacation days, and the 2.5 sick days American professionals take every year add up to many missing hours for smaller labs to work around. However, locum tenens provide a reliable source of dermatopathology talent to keep labs working at capacity. While some labs are open 24 hours a day, seven days a week, it’s important to note the majority hold traditional weekday hours when calculating turnaround time.

Diagnostic Dilemmas

After a dermatology clinic sends out a batch of specimens, they can reasonably expect to receive results from the lab within a few days. However, since complex cases can increase turnaround time by 40 percent, it’s essential to be aware of the tissue samples that could require possible delays.

For instance, a dermatopathologist may order additional studies, like special stains, to determine if a specimen contains an infection. And if an immunohistochemical stain is needed, it can require up to two additional days, depending on the availability of the particular stain.

Intradepartmental consultations cause delays in obtaining a second colleague’s opinion on complicated specimens. However, labs using digital slides can collaborate with experts around the world in real time and avoid longer turnaround times. 


After the lab completes a diagnostic report, the priority shifts to returning the report to the dermatology clinic as efficiently as possible. Delays can occur for providers working with paper, as this requires fax, mail, or overnight couriers. Once the paper reports are received, they need to be collated in the patient files.

The majority of providers utilize electronic medical/health (EMR/EHR) systems to enhance patient care. This makes integration with digital pathology reporting the next step and a dependable time-saver offered by full-service dermpath labs like PathologyWatch. Instead of waiting for deliveries, diagnostic results and digital pathology images are transferred instantaneously from the lab to each patient’s EMR. The digital results are easy to search and convenient to share with patients on tablets and laptops. 

Clinical Findings

Experienced dermatologists can quicken the turnaround time by providing detailed clinical information, impressions, and differential diagnoses on their pathology request forms before they are sent to the lab. 

Because labs don’t always have access to the patient’s clinical history, providing a clinical impression on the request form is always helpful. This is particularly true for inflammatory lesions, which can be subtle and nonspecific under a microscope. Without a clinical impression, the dermatopathologist can struggle to diagnose the findings with confidence, sometimes leading to a descriptive diagnosis, which should include differential considerations, as well. 

One factor that can impede clinical interpretation is the lack of access to the interpreting dermatopathologist for any questions about the interpretation. You should be able to contact your dermatopathologist directly. At PathologyWatch, for example, our dermatopathologists are directly available by cell phone or text message for consultations, which significantly speeds up the turnaround time.

Slide Requests

Many dermatologists feel that reviewing their own biopsy slides improves the quality of care they can render to their patients. Requesting traditional glass slides to be mailed can sometimes take up to two weeks for clinics to receive. Digital pathology providers such as PathologyWatch provide 24/7 access to digital slides from anywhere globally, which dramatically improves turnaround time on slide requests.

Take PathologyWatch’s partnership with Allen-Taintor Dermatology. Before collaborating with PathologyWatch, the Utah dermatology clinic waited up to two weeks for slides to return from the lab. PathologyWatch was able to deliver faster results by interfacing directly with the EMR, providing academic-level reads, and providing direct digital access to each patient’s pathology slides. The result was a 75 percent turnaround time improvement in most cases.

Improving Turnaround Time

Dermatology clinics can make an impact on dermatopathology lab turnaround time. Begin by opening the lines of communication with the lab and staying in contact about the status of your cases. Being proactive will allow the lab to identify issues with transportation or particular specimens that require additional information from the clinic to help expedite the diagnosis.

Securing accurate and timely results from the lab is better for your dermatology clinic and your patients. Identifying the cause of delays in transportation, staffing workflow, reports, slide requests, and clinical findings, while being proactive in your dermatology practice, can help you speed up dermatopathology lab turnaround time. 

Meet Maren Chan, MD, MS, Director of Laboratory Operations and Dermatopathologist at PathologyWatch

Maren Chan, MD, MS, is a board-certified dermatopathologist. She completed her residency and dermatopathology fellowship at Beth Israel Deaconess Medical Center/Harvard Medical School. Her early career was spent as an active-duty Army dermatopathologist at San Antonio Military Medical Center.

Thereafter, Maren was the medical director of Aurora Diagnostics, an established, primarily dermatology-trained dermatopathology laboratory in South Texas. She received her BS in chemical engineering from Montana State University and MS in chemical engineering from the University of Washington, with an interest in mathematical modeling of airway gas exchange.

Combining her experiences in laboratory operations, engineering, medical research, and high-volume dermatopathology interpretation, she is focused on large-scale implementation of digital pathology and other technological advances in medicine.

We sat down with Maren to talk about her experiences at Harvard Medical School, her work with PathologyWatch, and her choice of the pathology field.

At what point did you decide to go into pathology?

I was doing a research fellowship in general surgery at the Dana Farber Cancer Institute in Boston. While studying mammary tumors in mice, I became interested in histology and pathology.

What is it about PathologyWatch that appeals to you?

My life has typically been a search for opportunities, not necessarily a preplanned path. Even as a young teenager, I was always in pursuit of something that I felt passionate about. Since then, when an opportunity has presented itself, I’ve taken it. Pathology was like that, and I feel so fortunate to be a part of it. I felt an instant connection with dermatopathology, and once I made that decision, I ran into people by chance who helped me move forward in that field. That is how I met Greg Osmond and April Larson at PathologyWatch. These connections just fell into place at the ideal time. 

I truly believe the future of pathology is digital pathology. As this technology expands, I plan to devote the rest of my career to this field. I am a visual person, and it’s extremely satisfying to have a job where I can make diagnoses entirely by what I see.

What do you bring to PathologyWatch?

I really thrive on process management, quality control, and unifying all aspects of this business. I enjoy making sure we have a great product at all levels. At this moment, we have a product that is truly fabulous, but I always like to ask myself, “How can we make it better?” That’s what I find exciting. I like to focus on the physical operational functionality of our company to ensure it is both compliant and efficient and that we give the clinician and patient the best that healthcare can provide.

When it comes to serving dermatologists, what matters most to you?

I’m an efficient person. I have a propensity for that, but I also had to learn to manage my time better and work quickly because I was raising a family while going to school and having a busy career. I recognize the need for efficiency in the dermatology clinic where dermatologists expect a careful, well-thought-out, rapid diagnosis with clear communication. I think it’s important to provide that combination of diagnostic expertise, efficiency, and safe operational quality control. It’s essential in dermatology—more so than any other field—and I know digital technology will be instrumental in supporting that.

How is PathologyWatch impacting patient care?

Digital pathology tremendously improves the accuracy of pathologic diagnoses. A key to a good pathologic diagnosis is clinical correlation and histologic expertise. This technology makes it easier for pathologists to collaborate between themselves and clinicians, which provides better patient care. It’s accessible at home or in the clinic—anywhere and anytime. I believe digital technology is going to change the entire field of pathology.

What do you do in your free time? 

I don’t have a lot of free time. My focus is on PathologyWatch—I spend a lot of time doing that and enjoy it. But I also enjoy spending time with my boys. My kids partake in various sports, and watching them grow and become their own unique human beings is something I cherish. We split our time between Utah and San Antonio, TX—two very different and wonderful places to live.