Nonmelanoma Skin Cancer: Introduction

Nonmelanoma Skin Cancer: Introduction

Nonmelanoma Skin Cancer: Introduction | Johns Hopkins Medicine

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Cancer is when cells in the body change and grow control. To help you understand what happens when you have cancer, let’s look at how your body works normally. Your body is made up of tiny building blocks called cells. Normal cells grow when your body needs them, and die when your body does not need them any longer.

Cancer is made up of abnormal cells that grow even though your body doesn’t need them. In most cancers, the abnormal cells grow to form a lump or mass called a tumor. If cancer cells are in the body long enough, they can grow into (invade) nearby areas. They can even spread to other parts of the body (metastasis).

What is nonmelanoma skin cancer?

Skin cancer is a disease that begins in the cells of the skin. The area of skin with the cancer is often called a lesion. There are several types of skin cancer (carcinoma). Melanoma is the most serious. But there are others that are known as nonmelanoma skin cancer. These include:

  • Basal cell carcinoma
  • Squamous cell carcinoma
  • Merkel cell carcinoma
  • Cutaneous T-cell lymphoma
  • Kaposi sarcoma

Basal cell carcinoma and squamous cell carcinoma are by far the most common.

Understanding the skin

Click image to enlarge.

The skin is the largest organ of the body. Skin protects us from heat, sunlight, injury, and infection. It also stores water and fat, and makes vitamin D. The skin has 3 layers:

  • The outer layer called the epidermis
  • The middle layer called the dermis
  • The inner layer called the subcutis (subcutaneous)

The epidermis is made of flat cells called squamous cells. Round basal cells are under the squamous cells. The lower part of the epidermis has pigment-producing cells called melanocytes. These cells darken the skin when exposed to the sun.

The dermis has blood vessels, lymphatic vessels, hair follicles, and glands. Some of these glands make sweat, which helps keep the body cool. Other glands make an oily substance called sebum. Sebum helps keep the skin from getting dry. Sweat and sebum reach the skin's surface through tiny openings called pores.

The subcutis and the lowest part of the dermis form a network of collagen and fat cells. This layer conserves heat and helps protect the body's organs from injury.

What are the different types of nonmelanoma skin cancer?

Basal cell carcinomas form in places exposed to the sun and look raised and pearly.

Basal cell carcinoma, also known as basal cell cancer, is the most common type of skin cancer. It begins in basal cells in the deepest part of the epidermis.

It often starts in areas of skin exposed to the sun, such as the face, head, neck, arms, and hands. The cancer lesion often appears as small, raised, shiny, or pearly bumps, but it can have various kinds of appearance.

They tend to grow slowly and rarely spread to other parts of the body.

Nearly all basal cell cancers can be treated and cured. In some cases they may come back after treatment. Although this type of cancer rarely spreads to other parts of the body, if not treated it can extend below the skin to the bone. This can cause serious damage to the bone. Having a basal cell carcinoma also puts you at higher risk for other types of skin cancer.

Squamous cell carcinomas may form in places exposed to the sun, or on other places.

Squamous cell carcinoma, also known as squamous cell cancer, is the second most common type of skin cancer. It begins in flat cells called squamous cells in the upper part of the epidermis.

basal cell cancer, it often starts in areas of skin exposed to the sun, such as the face, head, neck, arms, and hands. But it can also start in other parts of the body, such as skin in the genital area.

Squamous cell carcinoma lesions often appear as a rough or scaly reddish patch on the skin that tends to grow quickly. But it can also have various kinds of appearance.

Squamous cell carcinoma is more ly to grow and spread to other parts of the body than basal cell carcinoma, although this is still uncommon. Most squamous cell carcinoma is found early enough to be treated and cured.

Merkel cell carcinoma

Merkel cell cancer is a rare type of skin cancer. Merkel cells are types of cells in the upper layer of the skin. The cells are very close to nerve endings, and help the skin sense light touch. Merkel cell cancer occurs when these cells grow control. Merkel cell cancer can be dangerous because it tends to grow quickly. It can be hard to treat if it spreads beyond the skin.

Merkel cell cancer tumors are most often found on sun-exposed areas of skin, such as the face, neck, and arms. But they can start anywhere on the body. They usually appear as firm, shiny skin lumps that do not hurt. The lumps may be red, pink, or blue. They tend to grow very quickly.

Cutaneous T-cell lymphoma

Cutaneous T-cell lymphoma is a type of cancer that starts in blood cells called T-lymphocytes. These are white blood cells that are part of your immune system. They normally fight infection in the body. The cancer then affects the skin (cutaneous). It causes scaly patches or bumps. The cancer is also known as lymphoma of the skin. It is a type of non-Hodgkin lymphoma.

It is usually a slow-growing cancer. It develops over many years. The two most common types of this cancer are mycosis fungoides and the Sezary syndrome.

Talk with your healthcare provider

If you have questions about nonmelanoma skin cancer, talk with your healthcare provider. Your healthcare provider can help you understand more about this cancer.


Many skin cancer patients still too ly to sunburn

Nonmelanoma Skin Cancer: Introduction | Johns Hopkins Medicine

A recent study by researchers at Johns Hopkins concludes that a substantial number of people with a history of the most frequent kind of nonmelanoma skin cancers still get sunburned at the same rate as those without previous history, probably because they are not using sun-protective methods the right way or in the right amounts.

The findings, which were self-reporting of sunburn and sun protection practices gathered from the National Health Interview Survey, urge skin doctors and other health care providers to better educate their patients about protective skin care practices, especially for those with history of nonmelanoma skin cancer.

The findings were published in May ahead of print in the Journal of the American Academy of Dermatology.

“It is important to look at how patients are currently practicing sun protection and what they are doing that is not very effective,” says Anna Chien, M.D.

, co-director of the Cutaneous Translational Research Program in the Department of Dermatology at the Johns Hopkins University School of Medicine. “Only then can we make strides in helping patients improve their sun protective practices by ensuring they do them the correct way.

” Sun exposure is the leading cause of nonmelanoma skin cancers, and treatment is estimated to cost $4.8 billion in the U.S. annually.

In the United States, Chien says, approximately 13 million white non-Hispanic individuals have a history of at least one type of nonmelanoma skin cancer, including basal cell and squamous cell cancers, putting them at a well-documented higher risk for subsequent nonmelanoma skin cancer. For example, studies show that 40 percent of those with a history of basal cell carcinoma are diagnosed with another lesion within five years.

For the new study, investigators analyzed self-reported survey results about sun protective practices from 758 people with previous nonmelanoma skin cancer and from 34,161 people without a history of skin cancer.

The study focused on non-Hispanic whites, the population most affected by nonmelanoma skin cancer.

Of the people without history, 18,933 were female and 15,228 were male, and of those with history, 390 were female and 368 were male.

The researchers defined protective practices as using sunscreen when going outside on a sunny day for more than an hour, wearing long sleeves or a wide-brimmed hat, and staying in the shade when outside on a sunny day for more than one hour. They defined sun avoidance as not going out into the sun.

Overall, they concluded that 44.3 percent of people with nonmelanoma skin cancer history reported frequent use of shade, compared to 27 percent of people without a history of skin cancer, and 20.5 percent of those with a history of nonmelanoma skin cancer wore long sleeves, compared to 7.7 percent of those with no history.

Additionally, 26.1 percent of those with a history of nonmelanoma skin cancer said they wore a wide-brimmed hat when outside in the sun, compared to 10.5 percent of people without a history, and 53.7 percent of those with a history of nonmelanoma skin cancer said they wore sunscreen, compared to 33.1 percent of those without a history.

Moreover, 44.7 percent of those with a history of nonmelanoma skin cancer reported using more than one form of sun protection, while only 19.

4 percent of those without a history of nonmelanoma skin cancer said they did so. Multimodality, the use of multiple skin-protective practices at a time, was associated with lower odds of sunburn.

It also offers a highly beneficial approach to those with previous nonmelanoma skin cancer, says Chien.

Most importantly, the researchers say, was the finding that although people with previous nonmelanoma skin cancer tend to use one or all of the protective practices, there was not a significant difference in reporting of sunburn compared to those without a history — 29.

7 percent versus 40.7 percent. This means, Chien says, that although those with a history of skin cancer are proactively using protective methods, they may not be doing so effectively, especially among younger patients. Approximately two-thirds (66.

9 percent) of individuals ages 18 to 39 reported sunburn.

Chien says that while sunscreen was the most common use of sun protection reported by participants, it was not associated with lower rates of sunburn in those with previous nonmelanoma skin cancer.

While noting that self-reports, such as those on which the study is based, are not entirely reliable, the disconnect among those who use sunscreen and still get burned may occur because individuals are not applying sunscreen effectively.

Explaining the correct ways — such as how much and how often — to apply sunscreen to patients is key, says Chien.

“These results suggest that physicians need to go the extra step in educating patients on the most optimal way of utilizing sun protection methods. Public health messages should also emphasize not only sun protection but how to do it correctly,” Chien says.

The researchers caution that although the data were pulled from a national survey, the results are self-reported and therefore may have some bias. In addition, Chien says, nonmelanoma skin cancer tends to be considered less important than melanoma and is thus underreported.

“The bottom line is that people should be using multiple forms of skin protective practices,” says Chien. “That means incorporating shade or sun avoidance into a daily routine, or wearing a wide-brimmed hat while also applying sunscreen correctly.”

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About Melanoma & Other Serious Skin Cancers: The Johns Hopkins Melanoma Program

Nonmelanoma Skin Cancer: Introduction | Johns Hopkins Medicine

Melanoma is a cancer of the pigment-producing cells of the skin called “melanocytes.” These are the cells that make dark skin dark, and allow fair skin to tan. Melanoma is an important cancer to know about, because if it is diagnosed and removed at an early stage, the cure rate is high. However, if it is diagnosed late, spread of disease is ly to occur.


Melanoma is not as common as other “nonmelanoma” skin cancers. It strikes more than 70,000 people in the United States annually as compared to more than one million cases of nonmelanoma skin cancer.

Nonmelanoma skin cancers rarely spread to other parts of the body, but melanomas are far more prone to spread.  Melanomas account for less than 5 percent of all skin cancers, but result in approximately 75 percent of all skin cancer-related deaths.

Each year, over 9,000 people with melanoma will die of the disease.

Over the years the incidence and mortality rates of melanoma have increased. Melanoma most often affects those with lighter skin; however, some areas Japan and Puerto Rico have recently seen a rise in melanoma cases.

A study comparing Hispanics, Asians, and African-Americans suggested that racial differences may contribute to the risk of developing this disease.

In this investigation, more than half of Hispanics studied developed melanoma in the head and neck as well as extremities; Asians have the lowest incidence of melanoma, although studies have not yet discovered why; and African-Americans, more often in males, were diagnosed with melanoma mostly on the foot.

Be Aware

Trends suggest that an increase in awareness and surveillance has influenced the number of melanoma cases diagnosed each year, although there is no solid evidence to support this.

Increasing the use of sunscreens and limiting sun exposure may be having an impact as well.

Early detection and diagnosis through consistent skin surveillance programs are proactive approaches to building awareness of the disease.

Melanoma can appear anywhere on the skin surface. In men, it is most common on the back or the head and neck, and in women, on the back or the back of the legs.

Melanoma can develop in a pre-existing mole, or arise on normal-appearing skin. It is suspected when a “mole” looks uneven in terms of its border, shape, or color.

The American Academy of Dermatology has more information on the clinical appearance of melanoma. Diagnosis is confirmed with a simple skin biopsy.

Types of Skin Cancer and Johns Hopkins Expertise

Three types of skin cancer account for about 95% of all the skin cancers that occur: melanoma, squamous cell carcinoma and basal cell carcinoma. Basal cell and squamous cell carcinomas are sometimes called “nonmelanoma skin cancers.”

However, there are a number of uncommon and even rare types of skin cancer that benefit from a multidisciplinary approach to diagnosis and treatment. A partial list is presented below. The Johns Hopkins Melanoma Program provide multidisciplinary care to a wide range of serious skin cancers, in addition to melanoma.

  • Melanoma
  • Merkel cell carcinoma
  • Microcystic adnexal carcinoma
  • Apocrine carcinoma
  • Paget’s and extramammary Paget’s disease
  • Dermatofibrosarcoma protuberans
  • Sebaceous carcinoma
  • Angiosarcoma
  • Cutaneous leiomyosarcoma
  • Advanced or metastatic squamous cell or basal cell carcinoma


Actively Recruiting Clinical Trials Focused on Nonmelanoma Skin Cancers

Nonmelanoma Skin Cancer: Introduction | Johns Hopkins Medicine

By Liz Janetschek
May 10, 2018

THE INFORMATION contained in this Clinical Trials Resource Guide includes actively recruiting clinical studies focused on nonmelanoma skin cancers—basal cell carcinoma; merkel cell carcinoma; cutaneous lymphoma; and squamous cell carcinoma. These studies are investigating brachytherapy; topical treatments; novel chemotherapeutic agents; antibiotics; immunotherapy; and more. All of the studies are listed on the National Institutes of Health website at 


Study Title: A Pilot Study Investigating Antitumorigenic Potential of Topical Itraconazole in the Treatment of Basal Cell Carcinoma 

Study Type: Interventional/single-group assignment 

Study Sponsor and Collaborators: Johns Hopkins University 

Purpose: To determine if topically applied itraconazole, an antifungal medication which may affect the hedgehog signaling pathway, affects the growth of basal cell carcinomas 

Primary Outcome Measures: Downregulation in glucagon- immunoreactivity expression [time frame: day 8] 

Principal Investigator: Nikki Tang, MD, Johns Hopkins University; (410) 502-7546, Identifier: NCT02120677 


Study Title: Phase I, Single-Arm, Open-Label, Dose Escalation Trial of MNA-Doxorubicin in Patients-Subjects With Cutaneous T-Cell Lymphoma 

Study Type: Interventional/single-group assignment 

Study Sponsor and Collaborators: University of Pittsburgh 

Purpose: To test a new method of experimental treatment for CTCL using small adhesive- patches (a micro-needle applicator), which have dozens of microneedles loaded with extremely low doses of doxorubicin 

Primary Outcome Measures: Evaluate the safety of the micro array needle doxorubicin system confirmed by vital signs, hematology, comprehensive metabolic panel, assessment for skin toxicity, and adverse event evaluation [time frame: 9 weeks] 

Principal Investigator: Oleg E. Akilov, MD, PhD, University of Pittsburgh; (412) 864-3681, Identifier: NCT02192021 


Study Title: Clinical and Biological Evaluation of the Novel CD30/CD16A Tetravalent Bispecific Antibody (AFM13) in Relapsed or Refractory CD30-Positive Lymphoma With Cutaneous Presentation: A Biomarker Phase Ib/IIa Study 

Study Type: Interventional/nonrandomized/sequential assignment 

Study Sponsor and Collaborators: Columbia University 

Purpose: To investigate AFM13 and evaluate its ability to facilitate and redirect natural killer (NK) cells in eliminating CD30-positive lymphoma targets in the skin and, by inference, other organs involved by lymphoma 

Primary Outcome Measures: Percentage of intratumoral NK-cells and T-cells infiltration into tumors; number of immune cells in tumor and peripheral blood; level of plasma cytokine production plus release in tumor and peripheral blood as a function of treatment [time frame: up to 2 years] 

Principal Investigator: Ahmed Sawas, MD, Columbia University Medical Center; contact Celeste Rojas, (212) 326-5720, Identifier: NCT03192202 


Study Title: A Phase II Study of Talimogene Laherparepvec Followed by Talimogene Laherparepvec + Nivolumab in Refractory T Cell and NK Cell Lymphomas, Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma, and Other Rare Skin Tumors 

Study Type: Interventional/single-group assignment 

Study Sponsor and Collaborators: National Cancer Institute 

Purpose: To study the effectiveness of talimogene laherparepvec and nivolumab in treating patients with lymphomas or nonmelanoma skin cancers 

Primary Outcome Measures: Best overall response rate to talimogene laherparepvec alone as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [time frame: up to 1 year] 

Principal Investigator: Ann Silk, MD, Rutgers University Cancer Institute of New Jersey; visit for various location contacts Identifier: NCT02978625 


Study Title: Doxycycline in Patients With Relapsed Cutaneous T-Cell Lymphoma 

Study Type: Interventional/single-group assignment 

Study Sponsor and Collaborators: Rochester General Hospital 

Purpose: To study the efficacy of doxycycline, an antibiotic, for the treatment of cutaneous T-cell lymphomas 

Primary Outcome Measures: Efficacy of doxycycline in relapsed cutaneous T-cell lymphoma [time frame: from baseline to 5 months or 1 year, depending on response] 

Principal Investigator: Brian Poligone, MD, PhD, Rochester General Hospital; (585) 364-1188 Identifier: NCT02341209 


Study Title: A Multicenter, Randomized, Double-Blinded, Placebo-Controlled, Phase III Trial of Adjuvant Avelumab in Merkel Cell Carcinoma Patients With Clinically Detected Lymph Node Metastases 

Study Type: Interventional/randomized/parallel assignment 

Study Sponsor and Collaborators: University of Washington, National Cancer Institute 

Purpose: To study how well avelumab works in treating patients with Merkel cell cancer that has spread to the lymph nodes and have undergone surgery with or without radiation therapy 

Primary Outcome Measures: Relapse-free survival [time frame: from date of randomization and the date of first recurrence or death (whatever the cause), whichever occurs first, assessed for up to 5 years] 

Principal Investigator: Shailender Bhatia, MD, Fred Hutch/ University of Washington Cancer Consortium; contact Nichole Pelz, (206) 606-7476, Identifier: NCT03271372 

Editor’s Note: The clinical trials presented here do not represent all the trials listed on For the complete list, go to ■