Cutaneous Malignancies

You won’t want to miss our 19th episode - Cutaneous Malignancies. Cutaneous malignancies are common presentations to otolaryngology and require a diligent workup. Pack your sunscreen and join us for this exciting new episode!

Show Notes

Hey everyone and welcome to The Oto Approach, a podcast created by medical students for medical students, to teach you about all things otolaryngology. I'm your host Aileen, and today we're going to talk about cutaneous malignancies. Tag along for a discussion about this common presentation within otolaryngology and primary care settings.

INTRODUCTION 

Approximately one third of cancers worldwide are skin cancer, and there are over 80 000 cases of skin cancer diagnosed in Canada each year (1). According to the Canadian Skin Cancer Foundation (2022), over 5000 of these cases are melanoma- which is the skin cancer with the worst prognosis- but we’ll dive into the different types of skin cancer throughout this episode (1). 

Skin cancer is an important topic in otolaryngology- head and neck surgery, because otolaryngologists are often involved in the treatment of skin cancer residing on the head and neck (2). In fact, because skin cancer commonly develops in areas that receive high sun exposure, the scalp, face, lips, ears, and neck are commonly affected (3). 

As a quick overview, there are a few main types of cutaneous malignancies that are broadly categorized as melanoma and non-melanoma skin cancers, which includes squamous cell carcinomas, basal cell carcinomas, and some other rare things like merkel’s cell carcinoma, dermatofibrosarcoma protuberans, adnexal tumors, and cutaneous lymphoma (1). There are also precancerous lesions that deserve some attention, including actinic keratoses, keratoacanthoma and Bowen’s disease. We’ll break down the most common types of skin cancer, and go over the presentation, diagnosis, staging, management, and prognosis of each. 

ANATOMY

First, let’s discuss the anatomy of the skin. The skin is divided into three main layers, the epidermis (the outermost layer), dermis (the middle layer), and hypodermis (the deepest layer) (4). The epidermis, or the outermost layer has 5 components: the stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and the stratum basale, also known as the stratum germinativum. This can be remembered by the acronym, Come Let's Get Sun Block. There are four main cell types within the epidermis: the keratinocytes, melanocytes, langerhans cells, and merkel’s cells (4). Keratinocytes are the predominant cell type, and produce keratin, while melanocytes produce melanin, responsible for skin pigmentation (4). Langerhan cells are a type of immune cell, and merkel cells serve a sensory function (4). As mentioned, the dermis is the layer following the epidermis, and it too has its own sublayers- the papillary layer, and the reticular layer (4). Sweat glands, hair follicles, muscles, sensory neurons, and blood vessels are found in the dermis (4). Finally, the hypodermis is the deepest layer (4). 

ACTINIC KERATOSES 

Actinic keratoses, sometimes called AKs or solar keratoses, are premalignant lesions that involve the epidermis (aka the outermost layer of the skin) only (5). They are caused by years of sun exposure (1,5). They usually present as a rough/ dry scaly patch of skin that is either flat or slightly raised (1,5). The patches may be erythematous, whitish-yellow, or brown (5). The patient may complain of itching, burning, bleeding, or crusting (5). 

Diagnosis can usually be made based on clinical examination (5). However, if in doubt, a biopsy can always be taken for confirmation (5). 

Although actinic keratosis sometimes self resolve, these lesions can develop into cutaneous squamous cell carcinomas (5). Therefore, they are usually treated preventatively. There are a variety of appropriate treatments for AKs. Topical pharmacotherapy may involve fluorouracil, imiquimod, ingenol mebutate or diclofenac (5). In particular, 5% fluorouracil cream is usually considered the first line treatment for actinic keratosis as it is effective, inexpensive, and well tolerated (6). Alternatively, actinic keratosis can be managed procedurally. Cryotherapy with liquid nitrogen is a commonly used method in clinic, as well as electrodesiccation and curettage, which is when, under local anesthesia, the cells are scraped off and destroyed with an electric current (5). Laser therapy is another way to destroy these lesions, as is photodynamic therapy, which is when a photosensitive solution is applied to the lesion and the lesion is then exposed to red or blue light (5).  

SQUAMOUS CELL CARCINOMA

Now, as mentioned, actinic keratosis can develop into cutaneous squamous cell carcinoma, often abbreviated to SCC (5,7). In fact, up to 1/10 AKs will become SCC, and this can occur within just two years (7). Squamous cell carcinoma in situ is also a precursor to invasive cutaneous squamous cell carcinoma, which can also be referred to as Bowen’s disease. However, cutaneous squamous cell carcinoma can also develop de novo. 

Cutaneous squamous cell carcinoma is a  malignancy of the keratinocytes of  squamous epithelium, which can affect cutaneous or mucosal surfaces (8). Cutaneous squamous cell carcinomas are the second most common type of skin cancer (1,7). 

Cutaneous SCCs can present in many different ways, including with an appearance of a wart-like lesion, a firm red nodule, an open sore that persists for weeks, an elevated growth, or a growth that rapidly increases in size. If advanced, they can become fungating, necrotic, bleeding and infected. (1,8). Patients often complain of a sore or scab that doesn’t seem to heal, or of a lesion that crusts and bleeds (1,8). As expected, they usually occur in areas of high sun exposure (7). 

Common risk factors for SCCs include: ultraviolet exposure, age, immunosuppression, chronically inflamed skin or chronic wounds (Marjolin’s ulcer), and certain phenotypic traits, such as those with lighter skin tones, light hair and eye color, and poor tanning ability as these traits all indicate the person has less melanin and therefore less protection from UV radiation (8). This type of phenotype would be considered a low number on the Fitzpatrick Scale. This scale describes 6 different skin types in terms of color and reaction to skin exposure (9). The scale ranges from 1-6, which describes very fair skin to very dark skin respectively (9). 

The diagnosis of a cutaneous squamous cell carcinoma usually involves a thorough examination of the lesion and a biopsy (8).  The type of biopsy performed may vary from a shave biopsy, a punch biopsy, or an excisional biopsy (8). 

Staging of cutaneous squamous cell carcinomas should involve risk stratification to determine the likelihood of locoregional metastasis - to date, there is no general consensus regarding which “high risk” SCC features consistently inform prognosis but this is an area of active research. These cancers are staged according to the most recent AJCC (American Joint Cancer Committee) TNM Guidelines, which describes tumor size and depth of invasion, and whether the cancer has spread to the lymph nodes or distantly (10). Complete staging can be determined from the results of the biopsy or based on the final surgical specimen, and may require axial imaging such as a CT or PET-CT scan (10). 

The key to managing squamous cell carcinomas is to treat them early, because the longer they are left unchecked, the more difficult they will become to treat and the more likely they will spread to local nodes and metastasize (11). 

Similar to AKs, there are many treatment options for cutaneous SCCs. This may include some of the same treatment options as with AKs, including topical medications, cryotherapy, photodynamic therapy, laser surgery, and curettage and electrodesiccation (11). Generally, though, surgery is first line therapy for this condition (11). In cosmetically sensitive areas, Mohs microsurgery can be utilized. Mohs is usually performed by fellowship trained dermatologists, and it involves precise mapping of the entire surgical margin while preserving maximal amount of normal skin. The same operator performs resection and tissue pathologic examination to ensure all cancer cells are removed (12). When SCC lesions are located in the head and neck region, they will often be treated by an otolaryngologist, or a surgical oncology subspecialist, although this will differ depending on the site and the established referral patterns. 

 For a patient presenting with a SCC that has a low risk of recurrence, which is most commonly the case, the recommendation for excisional margins is 4-6mm, with post operative margin assessment (13). Ideally, tissue rearrangements, for example, a flap reconstruction performed by an otolaryngologist, should not be performed until clear margins are confirmed, although in practice this is not always possible (14). If margins are clear, the follow up schedule will depend on risk of recurrence, but at the very least will occur every 3-12 months for 2 years, then every 6-12 months for 3 years, and then annually for life (13). If the margins are not clear, re-excision may be performed, or they may receive radiotherapy (13). If the patient is not a surgical candidate, they may receive radiation with curative intent. The protocols differ slightly if the SCC is considered high risk or very high risk, and includes larger excisional margins (13). 

Sometimes cutaneous SCC may present with palpable regional lymph nodes, or abnormal lymph nodes on imaging (13). These should undergo an FNA or core biopsy, and if positive, further imaging should be done to determine the size, number and location of the lymph nodes (13). If deemed operable, there are further specific guidelines to follow for excision of lesions located on the head and/or neck (13). Solitary or multiple ipsilateral lymph nodes require excision of the primary tumor, and ipsilateral neck dissection (13). Bilateral lymph nodes require excision of the primary tumor and bilateral neck dissection (13). If parotid lymph nodes are involved, primary tumor excision along with a parotidectomy and ipsilateral neck dissection are required (13). The pathology of these lymph nodes will determine further treatment, which may include observation, radiotherapy, and/or systemic therapies like chemotherapy (13).

The prognosis of cutaneous SCC is typically very good, and when detected early has a 5 year survival of 99% (14). However, it is important to note that in the transplant population, cSCC of the head and neck is more common than BCC, which is the inverse of the general population (15). 

BASAL CELL CARCINOMA

Basal cell carcinomas, or BCCs, are the most common form of skin cancer, accounting for 90% of all cases (1). The appearance of basal cell carcinomas can vary quite a bit, but they often look like open, non-healing sores, a reddish patch, or scars-like lesions or growths with an elevated edge and/or central indentation (aka rodent ulcer) (1;16). BCCs are pigmented in approximately ½  patients who have darker skin tones (16). The patient may complain of crusting, itching or bleeding within the lesion (16). It is important to note that there are multiple subtypes of basal cell carcinomas, including but not limited to nodular, superficial, morpheaform, and pigmented (17). Basal cell carcinomas most commonly occur on the head and neck (17). 

BCCs share similar risk factors to SCCs, including UV exposure, age, immunosuppression, and the phenotypic traits previously discussed (16), but may also more likely occur in skin regions that have been exposed to ionizing radiation. There are also some genetic syndromes that predispose you to these cancers including xeroderma pigmentosum, Gorlin syndrome and albinism.

 Basal cell carcinomas are also diagnosed similarly to squamous cell carcinoma, usually with a skin examination and biopsy (18). 

The management for basal cell carcinoma is once again similar to the options listed for squamous cell carcinomas. Surgical excision with postoperative margin evaluation is usually the first line treatment for basal cell carcinomas with low risk of recurrence, which is the case for most BCCs (19). For a patient presenting with a BCC that is low risk of recurrence, both clinically and histologically, the recommendation for excision margins is 4-5mm (19). This is then confirmed by pathology. If the margins are indeed clear, clinical followup every 6-12 months is recommended (19). Once again, tissue rearrangements such as reconstructive flaps should not be performed until clear margins are confirmed (19). If the margins are not clear, the risks and benefits of re-excision/ further treatment need to be weighed (19). Further treatment options would include conventional surgical re-excision, Mohs or radiotherapy if the patient is unable to tolerate another surgery (19). Once again, follow up for local recurrence every 6-12 months (19). As with squamous cell carcinomas, high risk basal cell carcinomas will be managed slightly differently than low risk, which includes wider surgical margins (19). 

The prognosis of basal cell carcinomas is excellent, with a 5 year survival rate of 100%, meaning that those diagnosed with BCC are just as likely to live 5 years or greater after receiving this diagnosis as the general population (20). Luckily, the incidence rate of metastatic basal cell carcinoma is extremely low, at <0.6% (21). 

MELANOMA 

Melanoma is a malignancy of the melanocytes, the cells that produce melanin, and can have cutaneous or mucosal involvement (22). They commonly have a similar appearance to that of a mole, and in fact, approximately 20-30% of melanomas arise from previously existing nevi, or “moles”, while the rest occur de novo (23). Luckily, an isolated common mole with no melanoma features is very unlikely to progress to melanoma (22). Melanoma is the most dangerous type of skin cancer, as it is able to quickly metastasize (23). In fact, there is a 99% 5 year survival rate if melanoma is caught early, but this drops to 68% when the disease invades the lymph nodes, and 30% when the disease invades distant organs (23). Therefore, it is incredibly important to inform patients to check their skin at least once a month for the ABCDEs of melanoma, which means Asymmetry, irregular Borders, more than one Color within a singular mole, a Diameter greater than 6mm, and Evolution of the mole (meaning a change in its appearance) (1,24). Lesions which have a change in their color, size, or elevation should increase your suspicions. In practice you must beware of amelanotic/ hypomelanotic melanomas (25). These are so named because they do not have the dark pigment characteristic of most nevi and melanomas and therefore are commonly missed or misdiagnosed (25). It is good to be aware of the fact that there are other subtypes of melanoma as well. 

Risk factors for melanoma include UV exposure, the classic phenotypic traits previously discussed, greater than 50-100 nevi, any atypical nevi, immunosuppression, and genetics, so be sure to ask about any genetic syndromes or family members with melanoma (23). 

Similarly to SCC and BCC, diagnosis of melanoma relies on a skin examination and biopsy. Dermoscopy is a very helpful tool for the clinical exam.

If a diagnosis of melanoma is confirmed, and the Breslow depth, i.e. the depth of the melanoma, is >1mm, a sentinel lymph node biopsy can  be performed (26). Depth of invasion of melanoma into the dermis is a powerful determinant of patient outcomes. The sentinel lymph node is the first draining lymph node of the affected area. The lymph node is examined by the pathologist and if negative, no further treatment is needed, but if positive, then the patient will undergo a complete lymph-node dissection, although this is actually a practice that remains debated because of the lack of survival benefit (26). However, neck dissection is valuable for the staging of melanoma, as it is staged based on the TNM system, or tumor size, spread to lymph nodes, and metastases, and is graded from I-IV (26). 

As with SCC and BCC the excisional margins of melanoma depend on the size of the tumor. Melanoma in situ should be excised with margins of 0.5mm, while tumors of less than or equal to 1mm should be excised with a 1cm margin (27). Melanomas >1-2mm should have excisional margins of 1-2cm (28). Finally, melanomas greater than 2mm should have excisional margins of 2cm. The exact treatment and follow up of melanomas will vary greatly by stage and health status of the patient (28). However, it is important to note that the treatment of melanoma is improving, and there are even targeted therapies for melanoma. For example, approximately 50% of melanomas are positive for BRAF gene mutations, which can be specifically targeted by tyrosine kinase inhibitors (29). 

We mentioned earlier that tissue rearrangements may be performed to reconstruct the skin defects for patients who have had skin cancer resected. This is a very important aspect of otolaryngology to restore form, function, and cosmetics for patients. In surgery, we often refer to the reconstructive ladder which describes the spectrum of wound closure options (30). The ladder begins with healing by secondary intention, which is when the wound is left open and allowed to heal on its own without intervention (30). Next is primary closure, which is when the wound edges are approximated and sutured closed (30). The next rung of the ladder is skin grafting, which is used when primary closure is not possible so a skin graft is used to cover the open wound (30). Next is local skin flaps, which can have either a random or named blood supply and include advancement, rotational, interpolation and interposition types of tissue transfer from the surrounding skin  (31). Skin cancer reconstruction can occasionally take advantage of tissue expansion, wherein mechanical stress is applied to the skin to allow it to naturally stretch, providing more skin to accomplish primary wound closure (30). The last two rungs of the reconstructive ladder are regional pedicled flaps and free tissue transfer, otherwise known as free flaps (31). Both remove tissue from it’s base and transpose it to the donor site. The difference is that regional pedicled flaps remain attached to its vascular pedicle, keeping its blood flow intact throughout the procedure. Whereas, free tissue transfer detaches the tissue from its vascular pedicle and is microsurgically re-anastamosed it to a new blood source (31). Regional pedicled flaps provide better color and texture match, shorter operative times and do not require microsurgical training, a common example you may see is the cervicofacial advancement flap (31). However, free tissue transfer may be required for better coverage, a common example you may see being used for skin cancer reconstruction is the radial forearm free flap (31). It is important to note that the ladder is not necessarily followed in order, but rather the treatment option that is least invasive and provides the best results will be chosen. Furthermore, many reconstructive components can be used together to address the same defect.

CLINICAL PEARLS - Please feel free to add any fun facts or things clerks are often pimped on. 

1. A commonly asked question is which skin cancers are the most common? In descending order: basal cell carcinomas, squamous cell carcinoma, and melanoma (32). 

2. If left alone, only about 10% of AKs will become SCC, but since there is no way to tell which will progress, they are usually treated (33). 

3. Cutaneous squamous cell carcinomas arise in the stratum spinosum layer of epidermis, while basal cell carcinomas arise in the stratum basale layer of epidermis (34). Melanoma arises from the melanocytes which arise in the stratum basale as well (34).

4. Finally, as mentioned, there are some other rarer forms of skin cancer, like Merkel cell carcinoma. In fact, this is 40 times more rare than melanoma, affecting approximately 1/130 000 people (35) . They have a high risk of recurrence and metastasis, and are often noticed by physicians due to their rapid speed of growth (35).

This script was developed by Aileen Feschuk. It was reviewed by Kalpesh Hathi, Yousef Omar, Gizelle Francis, Dr. Katie Oxford, Dr. Emily Cheng, Dr. Emily Deane, and Dr. Christopher Chin .We would like to extend our sincerest thanks to the Saint John Regional Hospital Department of Surgery within the Horizon Health Network for their generous support.

Thank you so much for listening to our podcast! We hope you’ll tune in to our next episode! Please head to our website at www.theotoapproach.com for our show notes, and to sign up for our newsletter to stay up to date with our latest episodes.

References

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35. Merkel cell carcinoma. The Skin Cancer Foundation. (2022, August 4). Retrieved September 21, 2022, from https://www.skincancer.org/skin-cancer-information/merkel-cell-carcinoma/