Non-Melanoma Skin Cancer

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Non-Melanoma Skin Cancer

Head and Neck Surgery
Author Credentials 

Arnaud F. Bewley, MD
Assistant Professor
Department of Otolaryngology
University of California – Davis
2521 Stockton Blvd. Suite 7200
Sacramento, CA 95819
 

Module Summary

Nonmelanoma skin cancers (NMSC) are the most common types of malignancy in the world and the incidence of this disease in the US is increasing due to high rates of sun exposure, the aging of our population and a greater number of individuals immunosuppressed for organ transplantation. Basal cell carcinomas make up about 80% of NMSCs however results in the fewest number of cancer related deaths. These tumors can be locally invasive, however very rarely metastasize. They are primarily treated with resection to negative margins which can achieved with primary resection or Mohs micrographic surgery. Tumors with morpheaform features or perineural invasion have a greater propensity for recurrence. Squamous cell carcinoma makes up most of the remaining 20% of the NMSCs. Like basal cell carcinoma, squamous cell carcinoma can be locally aggressive and primary treatment is oriented toward clearance of the primary tumor with surgery. Squamous cell carcinomas can however also metastasize and assessment of the regional lymphatic basin should be considered in cases of aggressive or recurrent disease.

Module Learning Objectives 
  • Review epidemiology of non-melanoma skin cancer and understand why incidence is increasing.
  • Identify high-risk features of both basal cell carcinomas and cutaneous squamous cell carcinoma.
  • Describe margin goals for NMSC for wide local excision.
  • List risk factors for nodal spread in patients with cutaneous squamous cell carcinoma.
  • Explain indications for adjuvant therapy in both basal cell carcinoma and cutaneous squamous cell carcinoma.
  • Describe the role of chenotherapy therapy both in the adjuvant and palliative setting.

Embryology

Learning Objectives 
  1. Identify the progenitor cells of cutaneous basal cell carcinoma.
  2. Identify the progenitor cells of cutaneous squamous cell carcinoma.
References 
  1. Rubin AI, Chen EH, Ratner D. Basal Cell Carcinoma. N Engl J Med. 2005;353:2262-2269. 
  2. Alam M, Ratner D. Cutaneous squamous-cell carcinoma. N Engl J Med. 2001;344(13):975-83. 

Anatomy

Learning Objectives 
  1. Describe the function of the skin.
  2. Diagram the histologic anatomy of the skin.
    1. Outline the different histologic layers and their cellular make-up, especially as it pertains to the development of different types of cutaneous malignancies.
References 
  1. Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, Tibes R, Weiss GJ, Borad MJ, Hann CL, Brahmer JR, Mackey HM, Lum BL, Darbonne WC, Marsters JC Jr, de Sauvage FJ, Low JA. Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med. 2009 Sep 17;361(12):1164-72.

Pathogenesis

Learning Objectives 
  1. Identify risk factors for developing non-melanoma skin cancer.
  2. Understand how UV damage has been implicated in the development of all non-melanoma skin cancer.
    1. Describe the role of p53 in the pathogenesis of cutaneous squamous cell carcinoma.
    2. Describe the role of mutations in the Hedge Hog pathway the pathogenesis of cutaneous basal cell carcinoma.
References 
  1. Rubin AI, Chen EH, Ratner D. Basal Cell Carcinoma. N Engl J Med. 2005;353:2262-2269.
  2. Alam M, Ratner D. Cutaneous squamous-cell carcinoma. N Engl J Med. 2001;344(13):975-83.

Incidence

Learning Objectives 
  1. Describe incidence trends in non-melanoma skin cancer over the past several decades.
  2. Understand why incidence in these malignancies is changing.
  3. Extrapolate the implications of an aging US population on the anticipated incidence trends for this disease process.
References 
  1. Chistenson LK, Borrowman TA, Vachon CM, et al. Incidence of basal cell and squamous cell carcinomas in a population younger than 40 years. JAMA. 2005;294: 681-690.
  2. Rogers HW, Weinstock MA, Harris AR et al. Incidence estimate of nonmelanoma skin cancer in the United States, 2006. Arch Dermatol 2010; 146:283-287.
  3. Clayman GL, Lee J, Holsinger FC et al. Mortality risk from squamous cell skin cancer. J Clin Oncol. 2005;23(4):759-765.
  4. Jensen P, Hansen S, Moller B, et al. Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens. J Am Acad Dermatol. 1999;40:177-86.

Patient Evaluation

Learning Objectives 
  1. Perform a thorough oncologic examination of head and neck, with emphasis on the skin and scalp exam as well as the associated at-risk lymphatic basins based on the location of the primary tumor.
    1. Perform a relevant sensory and cranial nerve examination based on the location of the tumor.
  2. Develop a differential diagnosis for pigmented and non-pigmented skin lesions.
  3. Describe the typical presentation of different types of skin cancer and recognize certain signs and symptoms that might suggest a more aggressive behavior.
  4. Analyze clinical findings and radiologic studies appropriately to distinguish surgically resectable from unresectable cutaneous lesions.
References 
  1. Stratigos, A., et al. Diagnosis and treatment of invasive squamous cell carcinoma of the skin: European consensus-based interdisciplinary guideline. Eur J Cancer. 2015 Sep;51(14):1989-2007.

Imaging

Learning Objectives 
  1. Recommend appropriate imaging studies for patients with non-melanoma skin cancer.
    1. Recognize the utility of MRI versus CT scan for the evaluation of local disease.
      1. Identify MRI as a critical study in patients with symptoms concerning for perineural invasion.
      2. Identify CT as critical study in patients with tumors that abutting osseous structure.
    2. Recommend imaging to rule out distant disease in patients with regionally metastatic or high-risk disease.
      1. Describe modality options for evaluation of distant disease in these patients.
References 
  1. Rubin AI, Chen EH, Ratner D. Basal Cell Carcinoma. N Engl J Med. 2005;353:2262-2269.
  2. Alam M, Ratner D. Cutaneous squamous-cell carcinoma. N Engl J Med. 2001;344(13):975-83.

Pathology

Learning Objectives 
  1. Identify basic cutaneous histopathology:
    1. Recognize the spectrum between normal, dysplastic and invasive skin lesions based on histopathology.
    2. Determine what immune-histochemical stains differentiate various skin lesions.
  2. Recognize tumor characteristics that have been associated with a higher rate of local recurrence including the following:
    1. Perineural invasion
    2. Poor differentiation
    3. Depth of Invasion
  3. Recognize tumor characteristics that have been associated with a higher rate of regional spread.
References 
  1. Schmults CD, Karia PS, Carter JB, Han J, Quereshi AA. Factors predictive of recurrence and death from cutaneous squamous cell carcinoma: a 10-year, single-institution cohort study. JAMA Dermatol. 2013;149(5):541-547.
  2. Brantsch KD, et al. Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: A prospective study. Lancet Oncol. 2008;9:713-20.
  3. Rowe DE, Carroll RJ, Day CL. Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. J Am Acad Dermatol. 1992;26:976-990.
  4. Goepfert H, et al. Perineural invasion in squamous cell skin carcinoma of the head and neck. Am J Surg. 1984;148:542-7.
  5. Moore BA, Weber RS, Prieto V, et al. Lymph node metastases from cutaneous squamous cell carcinoma of the head and neck. The Laryngoscope. 2005;115:1561-1567.
  6. Ch'ng S, Maitra A, Allison RS, et al. Parotid and cervical nodal status predict prognosis for patients with head and neck metastatic cutaneous squamous cell carcinoma. J Surg Onc. 2008;98:101-105.
  7. O’Brien CJ, McNeil EB, McMahon JD, et al. Significance of clinical stage, extent of surgery, and pathologic findings in metastatic cutaneous squamous carcinoma of the parotid gland. Head Neck. 2002;24:417-22.

Treatment

Learning Objectives 
  1. Formulate a treatment plan based on the characteristics of the disease and specific needs of the patient.
    1. Outline the treatment options: surgical, nonsurgical, palliative.
    2. For surgical patients, determine when it is appropriate to consult additional services to assist with management.
      1. Neuro-otology for aggressive periauricular/auricular lesions and/or those with complete facial paralysis.
      2. Head and neck reconstructive surgeon.
      3. Neurosurgery if skull or skull base involvement is present.
  2. Determine the appropriate surgical margins for primary tumor resection, based on stage for basal cell carcinoma and cutaneous squamous cell carcinomas.
  3. Cite the principles of Mohs Micrographic surgery as well as its indications and contraindications.
  4. Describe the indications for sentinel lymph node biopsy and/or elective neck dissection in N0 cutaneous squamous cell carcinoma.
  5. Determine when sentinel lymph node biopsy is indicated for Merkel cell carcinoma of the head and neck.
  6. Cite indications for adjuvant therapy following surgery for non-melanoma cancer and malignant melanoma, based on staging, pathologic characteristics and operative findings.
  7. Formulate an evidence-based surveillance program for skin cancer and melanoma survivors based on established guidelines (such as NCCN)
  8. Recognize the common signs and symptoms of recurrent disease and plan an appropriate work up plan.
  9. Recognize incurable diseases and plan appropriate palliative care.
References 
  1. Sweeny L, Zimmerman T, Carroll WR, Schmalbach CE, Day KE, Rosenthal EL. Head and neck cutaneous squamous cell carcinoma requiring parotidectomy: prognostic indicators and treatment selection. Otolaryngol-Head Neck Surg. 2014;150(4):610-617.
  2. McDowell LJ, Tan T, Bressel M et al. Outcomes of cutaneous squamous cell carcinoma of the head and neck with parotid metastases. J Medical Imaging and Radiation Oncology. 2016:1-9.
  3. Veness MJ, Morgan GJ, Palme CE, Gebski V. Surgery and adjuvant radiotherapy in patients with cutaneous head and neck squamous cell carcinoma metastatic to lymph nodes: combined treatment should be considered best practice. Laryngoscope. 2005;115:870-875.
  4. D’Souza J, Clark J. Management of the neck in metastatic cutaneous squamous cell carcinoma of the head and neck. Curr Opin Otolaryngol Head Neck Surg. 2011;19:99-105.
  5. Durham AB, Lowe L, Malloy KM, McHugh JB, Bradford CR, Chubb H, Johnson TM, McLean SA. Sentinel lymph node biopsy for cutaneous squamous cell carcinoma on the head and neck. JAMA Otolaryngol Head Neck. 2016;142(12):1171-1176.
  6. Ahmed M, Moore BA, Schmalbach CE. Utility of sentinel node biopsy in head & neck cutaneous squamous cell carcinoma: a systematic review. Otolaryngol Head Neck Surg.  2014;150(2):180-7.

Medical Therapies

Learning Objectives 
  1. State what non-surgical options there are to treat aggressive cutaneous malignancies.
  2. Understand why Hedge-Hog inhibitors are effective in treating basal cell carcinoma.
  3. Describe the indications for the use of Hedge Hog inhibitors in cutaneous basal cell carcinoma.
  4. Understand the indications for definitive and adjuvant chemotherapy in basal cell carcinoma.
  5. List chemotherapeutic options that have been described for palliative treatment of cutaneous squamous cell carcinoma.
References 
  1. Sekulic A, Migden MR, Oro AE et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012;366(23):2171-9.
  2. Von Hoff DD, LoRusso PM, Rudin CM et al. Inhibition of the hedgebog pathway in advanced basal-cell carcinoma. N Engl J Med. 2009; 361(12):1164-72.
  3. Tanvetyanon T, Padhya T, McCaffrey J et al. Postoperative concurrent chemotherapy and radiotherapy for high-risk cutaneous squamous cell carcinoma of the head and neck. Head & Neck. 2015;37(6):840-845.

Surgical Therapies

Learning Objectives 
  1. Recognize when reconstruction is needed following resection of skin cancers.
    1. Determine the best option for closure of small defects based on location and relaxed skin tension lines.
    2. Outline the options for reconstruction: Allografts, skin grafts, local flaps, regional flaps (submental, supraclavicular, pectoralis, SCM, Occipital, lower island trapezius), and free flaps (ALT, forearm, rectus abdominus, latissimus).
    3. Recognize what defects and scenarios are appropriate for delayed reconstruction.
    4. Recognize scalp defects that will require tissue expanders for reconstruction and formulate a plan for utilization of tissue expanders.
  2. Determine indications for a facial nerve drill-out and/or a lateral temporal bone resection.
  3. Perform core procedures in surgery on the skin of the head and neck, including design of local flap closures and sentinel lymph node biopsy, as defined by the curriculum, based on the attestation of the program director.
  4. Recognize common complications of following parotid surgery, neck surgery, and wide skin undermining.
    1. Plan appropriate course of action for treating surgical complications of skin cancer surgery.
References 
  1. Sweeny L, Zimmerman T, Carroll WR, Schmalbach CE, Day KE, Rosenthal EL. Head and neck cutaneous squamous cell carcinoma requiring parotidectomy: prognostic indicators and treatment selection. Otolaryngol-Head Neck Surg. 2014;150(4):610-617.
  2. McDowell LJ, Tan T, Bressel M et al. Outcomes of cutaneous squamous cell carcinoma of the head and neck with parotid metastases. J Medical Imaging and Radiation Oncology. 2016:1-9.
  3. Veness MJ, Morgan GJ, Palme CE, Gebski V. Surgery and adjuvant radiotherapy in patients with cutaneous head and neck squamous cell carcinoma metastatic to lymph nodes: combined treatment should be considered best practice. Laryngoscope. 2005;115:870-875.
  4. D’Souza J, Clark J. Management of the neck in metastatic cutaneous squamous cell carcinoma of the head and neck. Curr Opin Otolaryngol Head Neck Surg. 2011;19:99-105.

Rehabilitation

Learning Objectives 
  1. Utilize ancillary services such as nutrition and physical therapy appropriately in treatment planning and long term care of skin cancer patients.

Staging

Learning Objectives 
  1. Stage different cutaneous malignancies accurately based on AJCC classification system.
  2. Plan a staging work up for malignant skin lesions based on NCCN guidelines.
    1. Determine when additional testing such as MRI, Temporal bone imaging, chest imaging is indicated.
    2. Determine when is appropriate to consider PET/CT imaging in cutaneous malignancies.
    3. Determine when is appropriate to perform sentinel node biopsy for regional staging of cutaneous malignancies.
References 
  1. Jambusaria-Pahlajani A, Kanetsky PA, Karia PS, et al. Evaluation of AJCC tumor staging for cutaneous squamous cell carcinoma and a proposed alternative tumor staging system. JAMA Dermatol. 2013;149(4):402-410.

Case Studies

  • A 72 year male who is immunosuppressed for a kidney transplant, presents with a right sided parotid mass. He has a history of multiple prior cutaneous squamous cell carcinoma of this face and recently had a tumor removed with a wedge resection for his right auricle. The parotid mass is firm and non-tender. The overlying skin is mobile and facial nerve function is intact. An FNA demonstrates a regionally metastatic squamous cell carcinoma. Parotidectomy and neck dissection are performed which demonstrate a poorly differentiated tumor with lymphovascular invasion and two additional lymph nodes positive in level II.
  • A 48 year-old female presents with a painful, multiply recurrent tumor of her forehead which has undergone prior resection with MOHS. The lesion is ulcerative and has rolled edges. Punch biopsy demonstrates a basal cell carcinoma. The tumor is fixed to the underlying periosteum but a CT of the head demonstrates that the outer cortex of the cranium immediately beneath the tumor is intact.

Review

Review Questions 
  1. What are risk factors for the development of NMSC?
  2. What are the margin goals when resecting a:
    1. high-risk basal cell carcinoma?
    2. high-risk squamous cell carcinoma?
  3. What tumor characteristics are associated with a higher rate of recurrence for:
    1. Basal cell carcinoma?
    2. Squamous cell carcinoma?
  4. When would you consider an elective neck dissection for a patient with a cutaneous squamous cell carcinoma?
  5. What are the indications for adjuvant radiation therapy following resection of a:
    1. Basal cell carcinoma?
    2. Squamous cell carcinoma?
  6. What are the clinical indications for the use of Vismodegib?
Resources 

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  1. Annual Meeting Webcast (AMW):