Michael Lee, MD

Introduction

As the most common human malignancy, skin cancers have an annual incidence in the United States exceeding five-hundred thousand.  Though common, the mortality is less that one percent.   Melanoma will be excluded from this presentation as it was discussed in a previous lecture.  Approximately two thirds of these tumors are basal cell carcinomas and one third squamous cell.  There are several other rare types of cutaneous malignancies that will be briefly discussed.  A majority of cutaneous malignancies occur in sun-exposed regions of the body; the head and neck is the most common.  Factors that predispose individuals to these tumors are fair complexion, sun exposure, altered immune status, chemical exposure, and genetic influence.   Ultraviolet light is responsible for the traumatic injury that leads to skin cancer.  UVB is the most carcinogenic with a wavelength between 280-320nm.  UVA has synergistic effect with a wavelength between 320-400nm. 

Basal Cell Carcinoma

There are multiple clinical subtypes of basal cell carcinoma.  Nodular type is the most common and typically what we think about when we discuss basal cell carcinoma.  Clinically the lesion exhibits a pearly raised lesion with visible capillaries.  The borders are rolled and the central aspect may be ulcerated.  Morpheaform type is the most aggressive and presents as a white-yellowish macule or papule with indistinct borders.  These indistinct borders make excision difficult and results in higher recurrence.  Superficial multicentric basal cell carcinoma usually occurs in a younger population and appears as a region of scaling and atrophy.  These lesions also have irregular borders and are less common on the head and neck.  The pigmented type of basal cell carcinoma behaves similar to the nodular form but simply displays pigmentation.  These tumors can be confused with other pigmented lesions such as melanoma.  Finally, the fibroepithelioma type usually presents as pedunculated mass and also is uncommon on the head and neck.

Histologically, basal cell carcinoma displays proliferation of connective tissue stroma in parallel orientation.  This leads to peripheral cellular palisading.  Keratotic basal cell carcinoma includes histologic features of squamous cell carcinoma and is more aggressive.  Basal cell carcinoma metastasizes less than one percent of the time.  However, when metastases are present the prognosis is poor; six month survival is fifty percent and at twelve months this falls to twenty percent.  These tumors demonstrate both hematologic and lymphatic routes of spread.  Metastatic disease presents on average seven to nine months after initial presentation.   This delay in presentation emphasizes the importance of close surveillance.  The most common sites of metastasis in descending order are lung, bone, cervical nodes, subcutaneous tissue, and liver. 

Nevoid basal cell carcinoma syndrome is the result of an autosomal dominant mutation.  Patients with this syndrome display hundreds of cutaneous nodules in childhood.  These lesions, though initially indolent, can develop into aggressive tumors later in life.  This syndrome is also associated with frontal bossing, bifid ribs, mental retardation, and odontogenic keratocyst.

Squamous Cell Carcinoma

The most common sites for cutaneous squamous cell carcinoma are the ear, forehead, temple, lips, and nose.  These tumors are often erythematous and friable with surrounding induration.  They may be ulcerative or exophytic.  Histologically they display a variety of differentiation.  The Broder classification provides grouping based on differentiation.  Keratin pearls are often seen in the more well-differentiated tumors. 

The most common premalignant lesion is actinic keratosis.   Twenty percent of actinic keratosis will progress to squamous cell carcinoma.  These lesions are scaly and erythematous with an appearance similar to squamous cell carcinoma.  Occasionally they develop a cutaneous horn.  Surgical resection or topical treatment is recommended.  Bowen disease is synonymous with carcinoma in situ.  These lesions are typically seen as a well-circumscribed erythematous patch with irregular borders; treatment is usually surgical excision.   Keratoacanthoma is a benign tumor that may mimic squamous cell carcinoma that presents as a smooth, round nodule with central keratinous material.  These lesions exhibit rapid growth and surgical treatment is recommended. 

Xeroderma pigmentosum is an autosomal recessive disease resulting from a defect in DNA repair.  Patients experience photosensitivity and pigmentary changes.  Epidermodysplasia verruciformis is an autosomal recessive disease associated with chronic HPV infection and an increased propensity to develop squamous cell carcinoma. 

Treatment of Cutaneous Malignancies

Curettage with electrodessication, also known as electrosurgery, is a process used primarily for select cases of basal cell carcinoma.  This process involves curetting all abnormal tissue followed by cauteriziation of the tumor bed to destroy remaining cells and achieve hemostasis.  This procedure is repeated several times and has cure rates above ninety percent.

Cryotherapy utilizes temperatures below freezing to destroy malignant cells and is also able to treat adjacent tissue.  With good cure rates this treatment may result in hypopigmentation and patients should be informed prior to treatment.   Liquid nitrogen is the most common cryogen used. 

Medical treatment is also a common treatment of pre-malignant and smaller malignant lesions.  Cure rates are comparable to other treatment methods.

Radiation therapy for cutaneous malignancies is less commonly used today than in past years due to the development of less morbid treatment options.  These other modalities are more expedient and offer fewer side effects.  Radiation is also ineffective for tumors involving bone and cartilage.  There is also the possibility of radiation carcinogenesis with this modality of treatment.   

 Photodynamic therapy is an investigational intervention in which a photosensitizing drug is administered to the patient which is localized in the tumor.  A laser, most commonly Argon, is then delivered to the tumor and necrosis is induced.  This method has cure rates above ninety percent.  Though painful, this procedure has good cosmetic results.

Interferon-alpha is being investigated as a primary treatment for cutaneous malignancies.  To date there appears to be good response with basal and squamous cell carcinomas.  Though the dose is low, patients may experience flu-like symptoms and hematologic side-effects. 

Wide local excision is the method preferred by most head and neck surgeons.  With cure rates that exceed ninety percent, lesions can be excised with a scalpel or carbon dioxide laser. 

Mohs surgery has the best cure rates of all methods concerning treatment of these lesions.  As a medical student Mohs developed this technique which would later be modified to the method used today.  Tumors are excised with margins actively being evaluated under the microscope.  This method typically provides entire tumor resection with minimal tissue defect.  With negative margins reconstruction can be immediate.  

Reconstruction after resection most commonly consists of primary repair.  However, in select cases healing by secondary intention may yield good results.  In high risk lesions delayed repair or prosthesis may be considered.  In all cases health and desire the patient must be considered.

Prognosis and Staging

Factors that influence tumor behavior are location, size, thickness, and histology.  Pertaining to location, tumors that involve the facial H zone have a more aggressive nature.  This zone consist of the ears, anterior scalp, nose, and periorbital regions.  Lesions two centimeters or greater in size have higher risk of recurrence and metastasis.  Tumors with invasion greater than four millimeters also have higher rates of metastasis.  Histologically, poorly differentiated tumors are more aggressive.  Finally, certain malignancies are historically known to behave more aggressively.  These include those tumors associated with scars, genetic syndromes, and those that develop in the immunosuppressed host.    

The AJCC Classification is used for staging purposes:

§          Tumor stage (T)

§          TX: Primary can not be assessed

§          T0: Unknown primary

§          Tis: Carcinoma in situ

§          T1: Tumor ≤ 2cm

§          T2: Tumor >2 and ≤ 5cm

§          T3: Tumor >5cm

§          T4: Tumor invades deep structures

§          Nodal staging (N)

§          N0: No regional lymph node metastasis

§          N1: Regional lymph node metastasis

§          Distant metastasis (M)

§          M0: No distant metastasis

§          M1: Distant metastasis

§          TMN stage

§          Stage 0: TisNOMO

§          Stage 1: T1NOMO

§          Stage 2: T2NOMO/ T3NOMO

§          Stage 3: T4NOMO/ TXN1MO

§          Stage 4: TXNXM1

 The use of the AJCC staging system for prognosis is controversial and thought to be incomplete.  Important factors that influence tumor behavior such as those previously mentioned are not taken into account.  Recent literature also supports a difference in prognosis as it pertains to parotid versus cervical lymphatic metastasis.  Regional nodal metastases are rare in both basal and squamous cell carcinoma with percentages of 0.5 and 3 respectively.  Imaging is recommended in high risk lesions or those patients with suspicious exams.   CT or MRI can be useful in these situations. 

Management of the N0 neck in patients with cutaneous malignancies is also divisive.  Most agree that the neck should be treated in patients with high risk lesions.  There is a paucity of literature comparing neck dissection to expectant management.  Lymphatic drainage of skin cancers is primarily based on studies of melanoma.  Most believe these drainage patterns hold true for other skin cancers.  Lesions anterior to a vertical line through the tragus are more likely to spread to the parotid gland.  Lesions posterior to this line may spread to the posterior triangle.  Nodes that follow the external jugular vein just beneath the platysma and lateral to the sternocleidomastoid muscle should also be removed with neck dissections for cutaneous malignancies.  These nodes are not part of the classic neck dissection. 

Less Common Cutaneous Malignancies

There are several other less common skin cancers worth mention.  Merkel cell carcinomas are mostly found in the head and neck.  These tumors are aggressive with high rates of recurrence and metastasis.   Dermatofibrosarcoma protuberans is a soft tissue sarcoma that occasionally occurs in the head and neck.  These tumors present as firm red plaques or nodules and are usually low-grade lesions.  Atypical fibroxanthoma is a spindle cell neoplasm that is often mistaken for squamous cell carcinoma.  Finally cutaneous carcinosarcoma is a mixed tumor with histologic findings of epithelial and mesenchymal tissue.  All of these lesions are treated with wide local excision.

LSU 38                        Ohio State 24