Hypopharyngeal Neoplasms

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Hypopharyngeal Neoplasms

Head and Neck Surgery
Author Credentials 

Bharat B. Yarlagadda, MD
Assistant Professor
Department of Otolaryngology – Head and Neck Surgery
Boston University School of Medicine, Boston, MA
Senior Surgeon
Division of Otolaryngology – Head and Neck Surgery
Lahey Hospital and Medical Center
Burlington, MA 01805

Module Summary

The most common neoplasm of the hypopharynx is squamous cell carcinoma. This is generally linked to traditional head and neck carcinogenic factors with an additional associated with conditions such as Plummer Vinson Syndrome. Patients present with dysphagia, throat pain, or nodal metastatic disease. Advanced presentation is common due to insidious nature of tumors in this subsite, and a rich lymphatic drainage leading to regional metastasis. Upfront treatment is generally non-surgical with single modality radiation for early stages, and chemoradiation for intermediate and advanced stages. Surgery is reserved for salvage cases, advanced tumors with laryngeal destruction or dysfunction at presentation, or in select early stage tumors. Despite advances in treatment, prognosis of this disease remains poor especially in the advanced stages.

Module Learning Objectives 
  1. Describe the embryogenesis and anatomy of the hypopharynx including the various subsites.
  2. Cite risk factors, epidemiology, and demographic descriptors for those who develop hypopharyngeal neoplasms.
  3. Demonstrate the ability to work-up and stage a patient with hypopharyngeal malignancy including clinical evaluation and imaging studies.
  4. Determine the treatment options, surgical and non-surgical, available to a patient with hypopharyngeal neoplasm.
  5. Be familiar with the various types of reconstructive techniques for the hypopharynx.
  6. Recognize and manage complications that can arise from treatment of hypopharyngeal malignancy.

Embryology

Learning Objectives 

Be familiar with the concept of the pharyngeal arch.

  1. 4th and 6th arches as the primary contributors.
  2. Presence of significant neural crest cell derivative structures.
References 
  1. Graham A. Development of the pharyngeal arches. Am J Med Genet A. 2003; 119A(3):251-6.

Anatomy

Learning Objectives 

Describe the subsites of the pharynx, muscular components and innervation, and relationship to contiguous structures.

  1. Anatomic subsites
    1. Pyriform sinuses
    2. Post cricoid mucosa
    3. Posterior pharyngeal wall
  2. Muscular components
    1. Outer circular layer – constrictor muscles
    2. Inner longitudinal layer
  3. Innervation
    1. Sensory from pharyngeal plexus with cranial nerve IX and X contributions
    2. Motor innervation from the pharyngeal plexus with cranial nerve IX and X contributions
  4. Relationship to other anatomy
    1. Transition to the esophagus and position of the cricopharyngeus
    2. Relationship to the laryngeal framework and position of the pyriform sinuses adjacent to the thyroid lamina
References 
  1. Frank H. Netter, MD. Atlas of Human Anatomy. 6th Edition. Elsevier. 2014.
  2. Jatin Shah’s Head and Surgery and Oncology. Chapter 9. Pharyngeal and Esophageal Carcinoma. Mosby Elsevier. 2012.

Pathogenesis

Learning Objectives 

Identify risk factors and the relevant patient populations for the development of hypopharyngeal neoplasm.

  1. Traditional carcinogenesis
    1. Alcohol and tobacco
    2. Males in the 6th and 7th decades of life
  2. Plummer Vinson Syndrome
    1. Females with iron deficiency anemia
    2. Post cricoid mucosal location of tumors
  3. Association with gastro-esophageal reflux disease
References 
  1. Bailey’s Head and Neck Surgery: Otolaryngology. Chapter 122. Hypopharyngeal and Cervical Esophageal Carcinoma. Lippincott Williams and Wilkins. 2014.
  2. Jatin Shah’s Head and Surgery and Oncology. Chapter 9. Pharyngeal and Esophageal Carcinoma. Mosby Elsevier. 2012.

Basic Science

Learning Objectives 

Associate specific genetic mutations and biomarkers with disease development, risk stratification, and likelihood to respond to therapy.

  1. The p53 tumor suppressor gene mutation as a pathogenetic mechanisms.
  2. PD-L1 expression as a biomarker for the success of immunotherapy for disease that progresses despite traditional treatment of surgery, radiation, and platinum-based chemotherapy.
References 
  1. Muller T, et al. PD-L1: a novel prognostic biomarker in head and neck squamous cell carcinoma. Oncotarget. 2017 Aug 8; 8(32): 52889–52900.
  2. Somers KD, Merrick MA, Lopez ME, et al. Frequent p53 mutations in head and neck cancer. Cancer Res. 1992;52:5997-6000.

Incidence

Learning Objectives 

Know the incidence of hypopharyngeal cancer.

  1. In the general population (approximately 0.7 per 100,000 person-years).
  2. Those at increased risk of development such as patient who use tobacco and alcohol, and those that have Plummer Vinson syndrome.
References 
  1. Kuo P, et al. Hypopharyngeal cancer incidence, treatment, and survival: temporal trends in the United States. Laryngoscope. 2014 Sep;124(9):2064-9.
  2. Jatin Shah’s Head and Surgery and Oncology. Chapter 9. Pharyngeal and Esophageal Carcinoma. Mosby Elsevier. 2012.

Genetics

Learning Objectives 

Know the genetic basis of carcinogenesis as it applies to hypopharyngeal cancer.

  1. Carcinogen exposure and p53 mutations
  2. Familial and hereditary implications such as with Plummer Vinson syndrome
References 

1.    Somers KD, Merrick MA, Lopez ME, et al. Frequent p53 mutations in head and neck cancer. Cancer Res. 1992;52:5997-6000.

Patient Evaluation

Learning Objectives 

Recognize the presenting symptoms of hypopharyngeal cancer and describe the steps needed to evaluate a patient with known or suspected hypopharyngeal malignancy.

  1. Presenting symptoms include dysphagia, odynophagia, referred otalgia, nodal metastases and can often present at advanced stages.
  2. Functional status, overall health, and frailty, see appropriate section elsewhere.
  3. Focused physical examination including laryngeal mobility, cervical nodal palpation, voice evaluation.
  4. Fiberoptic scope examination to identify and characterize the mucosal tumor and evaluate vocal fold function.
  5. Imaging studies, see appropriate section elsewhere.
References 

1.    Bailey’s Head and Neck Surgery: Otolaryngology. Chapter 122. Hypopharyngeal and Cervical Esophageal Carcinoma. Lippincott Williams and Wilkins. 2014.

Measurement of Functional Status

Learning Objectives 

Apply validated functional status parameters to patients undergoing evaluation for known or suspected hypopharyngeal cancer.

  1. Validated scales for oncology patients include ECOG-ACRIN performance status, Karnofsky scale, and the WHO/Zubrod score.
  2. Frailty indices especially for older patients.
  3. Laryngeal function
    1. Voice
    2. Breathing
    3. Swallowing evaluation with imaging studies such as modified barium swallow when appropriate.
References 

1.    NCCN Clinical Practice Guidelines in Oncology – Head and Neck Cancer. Version 2.2017. https://www.nccn.org/professionals/physician_gls/default.aspx

Imaging

Learning Objectives 

Determine the appropriateness of various imaging modalities in the evaluation of hypopharyngeal cancer.

  1. CT scan with contrast – evaluation of the primary tumor mass, nodal metastases.
  2. MRI with contrast – assessment of prevertebral space invasion, vascular invasion.
  3. PET scan imaging – regional and distant metastatic staging, restaging after treatment, assessment of potential recurrence.
  4. Barium swallow and/or modified barium – functional evaluation of tumor related obstruction or laryngeal dysfunction and aspiration.
References 
  1. Bailey’s Head and Neck Surgery: Otolaryngology. Chapter 122. Hypopharyngeal and Cervical Esophageal Carcinoma. Lippincott Williams and Wilkins. 2014.
  2. NCCN Clinical Practice Guidelines in Oncology – Head and Neck Cancer. Version 2.2017. https://www.nccn.org/professionals/physician_gls/default.aspx

Pathology

Learning Objectives 

Describe the common histopathologies of hypopharyngeal cancer and known patterns of spread.

  1. Histopathology
    1. Squamous cell carcinoma (primary pathology)
    2. Adenocarcinoma
    3. Minor salivary gland cancers
  2. Patterns of spread
    1. Submucosal spread
    2. Satellite lesions
    3. Involvement of proximal esophagus
    4. Involvement of adjacent structures including larynx, carotid artery, prevertebral fascia
    5. Retropharyngeal and jugular chain nodes
References 
  1. Bailey’s Head and Neck Surgery: Otolaryngology. Chapter 122. Hypopharyngeal and Cervical Esophageal Carcinoma. Lippincott Williams and Wilkins. 2014.
  2. Jatin Shah’s Head and Surgery and Oncology. Chapter 9. Pharyngeal and Esophageal Carcinoma. Mosby Elsevier. 2012.

Treatment

Learning Objectives 

Formulate a treatment plan with single or multiple modalities appropriate to the stage and functional status of a given patient.

  1. Early stage
    1. Single modality radiation, generally the preferred treatment
    2. Surgery
      1. Goal of tumor control and functional (laryngeal) preservation
      2. Adjuvant therapy as needed
  2. Intermediate stage
    1. Concurrent chemoradiation with surgery for salvage.
    2. Upfront surgery (laryngopharyngectomy and neck dissection) with adjuvant treatment as needed.
  3. Advanced stage, gross laryngeal dysfunction.
    1. Upfront surgery (laryngopharyngectomy and neck dissection) with adjuvant treatment as needed.
    2. Concurrent chemoradiation with surgery for salvage if there is intact laryngeal function or if patient not amenable to upfront surgery.
References 
  1. Lefevbre JL, et al. Laryngeal preservation with induction chemotherapy for hypopharyngeal squamous cell carcinoma: 10-year results of EORTC trial 24891. Ann Oncol. 2012 Oct;23(10):2708-14.
  2. NCCN Clinical Practice Guidelines in Oncology – Head and Neck Cancer. Version 2.2017. https://www.nccn.org/professionals/physician_gls/default.aspx
  3. Jatin Shah’s Head and Surgery and Oncology. Chapter 9. Pharyngeal and Esophageal Carcinoma. Mosby Elsevier. 2012.

Medical Therapies

Learning Objectives 

Know the role of radiation therapy for treatment and the roles platinum based chemotherapy and immunotherapy in treatment and palliation.

  1. Single modality radiation for early stage cancer
  2. Bimodality chemoradiation for advanced stages with “organ preservation” intention
  3. The role of radiation in the post operative adjuvant setting
  4. Platinum based chemotherapy.
    1. Radiation potentiation in concurrent regimens.
    2. Single agent for palliation of recurrent and untreatable disease, or with distant metastatic disease.
  5. Immunotherapy for palliation of recurrent and untreatable disease, or with distant metastatic disease.
References 
  1. Cooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004;350:1937-1944.
  2. Bernier J, Cooper JS, Pajak TF, et al. Defining risk levels in locally advanced head and neck cancers: A comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck 2005.
  3. Ling DC, Bakkenist CJ, Ferric RL, et al. Role of immunotherapy in head and neck cancer. Semin Radiat Oncol. 2018 Jan;28(1):12-16.
  4. Lefevbre JL, et al. Laryngeal preservation with induction chemotherapy for hypopharyngeal squamous cell carcinoma: 10-year results of EORTC trial 24891. Ann Oncol. 2012 Oct;23(10):2708-14.
  5. NCCN Clinical Practice Guidelines in Oncology – Head and Neck Cancer. Version 2.2017. https://www.nccn.org/professionals/physician_gls/default.aspx

Pharmacology

Learning Objectives 

Understand basic metabolic principles and limitations for the administration of platinum based agents and immunotherapy.

  1. Platinum based chemotherapy
    1. Dosed based on body surface area, requiring adequate renal function
    2. Weekly or Every-3-week dosing for radiation concurrent chemoradiation regimens
  2. Immunotherapy dosing
References 
  1. Cooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004;350:1937-1944.
  2. Bernier J, Cooper JS, Pajak TF, et al. Defining risk levels in locally advanced head and neck cancers: A comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck 2005.
  3. Ling DC, Bakkenist CJ, Ferric RL, et al. Role of immunotherapy in head and neck cancer. Semin Radiat Oncol. 2018 Jan;28(1):12-16.

Surgical Therapies

Learning Objectives 

Be familiar with the role of, and technical details pertaining to, surgery for removal and reconstruction of hypopharyngeal cancer. Know the role of nodal dissection for occult disease.

  1. Indications for surgery
    1. Early stage tumors when radiation is not preferable
    2. Advanced tumors with existing functional deficit (laryngeal dysfunction)
    3. Salvage surgery after initial non-surgical management
  2. Partial pharyngectomy
    1. Transoral approach with or without robotic equipment
    2. With or without partial laryngeal resection
  3. Total pharyngectomy with laryngectomy
    1. Performed in circumstance or existing or anticipated laryngeal dysfunction
    2. Extended laryngopharyngectomy to include esophageal resection
    3. Total laryngectomy with partial pharyngectomy if some mucosa can be spared
  4. Neck dissection—be familiar with the incidence of occult metastases with hypopharyngeal carcinoma and the treatment options for the nodal positive and negative neck.
  5. Be familiar with reconstructive options
    1. Partial pharyngeal defects
      1. Primary closure
      2. Regional flaps including pectoralis flap, supraclavicular island flap
      3. Free flaps including redial forearm or anterolateral thigh flap
    2. Total pharyngeal defect
      1. Tubed constructs such as a tubed radial forerm free flap or anterolateral thigh flap
      2. Gastric pullup
References 
  1. Disa JJ, et al. Microvascular reconstruction of the hypopharynx: defect classification, treatment, algorithm, and functional outcome based on 165 consecutive cases. Plast Reconstr Surg 2003;111(2):652-60.
  2. Fabian R. Reconstruction of the laryngopharynx and cervical esophagus. Laryngoscope 1984;94:1334-350.
  3. Ferlito A, et al. Selective neck dissection for hypopharyngeal cancer in the clinically negative neck: should it be bilateral? Acta Otolaryngol 2001;121(3):329-35.
  4. Martins A. Neck and mediastinal node dissection in pharyngolaryngoesophageal tumors. Head Neck 2001;23(9):772-79.
  5. Ujiki GT, et al. Mortality and morbidity of gastric ‘pull-up’ for replacement of the pharyngoesophagus. Arch Surg 1987;122(6):644-47.
  6. Jatin Shah’s Head and Surgery and Oncology. Chapter 9. Pharyngeal and Esophageal Carcinoma. Mosby Elsevier. 2012.
  7. NCCN Clinical Practice Guidelines in Oncology – Head and Neck Cancer. Version 2.2017. https://www.nccn.org/professionals/physician_gls/default.aspx

Rehabilitation

Learning Objectives 

Formulate a plan and recommendations for rehabilitation for patients who are undergoing or have completed therapy for hypopharyngeal cancer. This includes addressing speech rehabilitation, dysphagia management, and nutritional issues.

  1. Speech rehabilitation
    1. SLP referral
    2. TEP placement after laryngectomy
  2. Dysphagia management with SLP referral
  3. Nutritional counseling and feeding tube placement when appropriate
References 
  1. Rosenthal DI, et al. Prevention and treatment of dysphagia and aspiration after chemoradiation for head and neck cancer. J Clin Oncol. 2006;24(17):2636-43.

Staging

Learning Objectives 

Know the American Joint Committee on Cancer staging system for cancer of the hypopharynx.

References 
  1. Amin MB, Edge SB. AJCC cancer staging manual. Chicago: American Joint Committee on Cancer; 2017.
  2. NCCN Clinical Practice Guidelines in Oncology – Head and Neck Cancer. Version 2.2017. https://www.nccn.org/professionals/physician_gls/default.aspx

Case Studies

  1. A 64 year old male with history of alcohol and tobacco use presents with odynophagia and a right sided neck mass. He has not had any investigation or workup as of yet.
    1. Clinical examination and flexible fiberoptic examination indicate a tumor of the post cricoid region.
    2. Tissue diagnosis with either biopsy of the primary site or needle aspiration of the neck mass is indicated. Consider examination under anesthesia for tumor mapping and tissue diagnosis of the primary site
    3. Recommended imaging includes a CT scan of the neck and chest, or consider PET scan for staging. Modified barium swallow for functional evaluation.
    4. Treatment contingent on staging and would likely involve chemoradiation after multi-disciplinary evaluation
  2. A 55 year old male presents with throat pain, weight loss, difficulty breathing. He is noted to have a large tumor of the left pyriform sinus with laryngeal destruction. He has significant aspiration. His staging after workup is cT4aN2bM0.
    1. Given loss of laryngeal function and bulky disease on presentation, surgery is indicated including laryngopharyngectomy, bilateral neck dissection.
    2. Pharyngeal reconstruction may be needed. Appropriate options include pectoralis flap or radial forearm free flap.
    3. Adjuvant therapy with radiation or chemoradiation would be indicated pending final pathologic analysis.
  3. A 61 year old male has undergone chemoradiotherapy for an advanced hypopharyngeal cancer, completing treatment 6 months ago. He now has worsening throat pain, and is noted to have a recurrence in the pyriform sinus abutting the larynx.
    1. There is an indication for salvage surgery (laryngopharyngectomy) with reconstruction.
    2. Consider the role of palliative therapy if the patient cannot or will not undergo salvage surgery, or develops distant metastatic disease.

Complications

Learning Objectives 

Know and recognize the complications of treatment for hypopharyngeal cancer.

  1. Complications of surgical therapy
    1. Perioperative concerns – ex/ airway management, fistula, infection
    2. Post-operative concerns – ex/ dysphagia and aspiration, stricture formation
  2. Acute toxicities of non-surgical treatment
    1. Radiation related – ex/ dysphagia, mucositis
    2. Chemotherapy related – ex/ mucositis, myelosuppression, alopecia, renal failure
  3. Long term toxicities of non-surgical treatment – ex/ dysphagia, dysgeusia, strictures and stenoses, osteonecrosis and soft tissue necrosis
  4. Survivorship concerns
References 
  1. Jatin Shah’s Head and Surgery and Oncology. Chapter 9. Pharyngeal and Esophageal Carcinoma. Mosby Elsevier. 2012.
  2. Jatin Shah’s Head and Surgery and Oncology. Chapter 19. Radiation Therapy. Mosby Elsevier. 2012.
  3. Jatin Shah’s Head and Surgery and Oncology. Chapter 20. Chemotherapy. Mosby Elsevier. 2012.
Resources 

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