Hypopharyngeal cancer is defined as cancer of the hypopharnyx region consisting of the pyriform sinuses, postcricoid and lower posterior pharyngeal walls. 1 This type of cancer is difficult to detect due the significant advancement of cancer cells before the first symptoms arise. In addition, these cancers have a poor prognosis due to local nodal and neighboring structure invasion as well as other metastases. 2 Hypopharyngeal cancer is considered a rare cancer with an incidence of approximately 1 per 100,000 in the US.2 In addition, this disease only accounts for 3-5% of all head and neck cancers diagnosed. 2 This cancer is twice as common in men than in women and is most often seen in men 50 years of age or older. 2
Etiology:
Ashley
While the exact causes of hypopharyngeal cancer are unknown, there are several risk factors that are linked to its growth. Firstly, tobacco use and alcohol consumption are among the most important influences in the development of this cancer. In fact, almost 90% of patients who present with this cancer have used tobacco regularly at some point in their life. 2 Genetic factors are also among the risk factors for this disease. Almost 70% of the patients who are diagnosed with hypopharyngeal cancer have a mutation in the tumor suppressor gene p53.2 In fact, research supports a link between the p53 gene mutations and smoking putting these people at higher risk for developing the cancer. 2 Overexpression of specific oncogenes and abnormalities in chromosome 11 are other contributing genetic factors as well. Lastly, the role of HPV in hypopharyngeal cancer has proven to be the latest risk factor under investigation. The role of HPV is less defined in this type of cancer compared to that of oropharyngeal cancer, however, 20%-25% of hypopharyngeal cancer patients tested positive for HPV. 2 While the etiology of hypopharyngeal cancer remains under investigation, the risk factors are important in preventing the development and spread of the disease.
Signs & Symptoms:
Amanuel
Patients with carcinoma of hypopharynx present:3
- Mild sore throat
- Dysphagia (difficulty swallowing)
- Otalgia (ear pain)
- Odynophagia (painful swallowing)
- Blood streaked saliva (due to necrosis or trauma to tumor bed)
- Saliva drooling
- Neck stiffness
- ‘Hot potato’ voice (due to laryngeal or base of tongue invasion)
- Hoarsness (due to tumor invasion of the larynx or cricoarytenoid joint)
- Weight loss – in advanced disease
- Tongue paralysis (rare) (due to hypoglossal nerve invasion – lymph node level II and III)
5-15% of patients with hypopharynx require emergency tracheotomy
Diagnostic Procedures:
Amanuel
Diagnostic work-up for hypopharyngeal cancer include:3
- Physical examination: indirect laryngoscopy and a flexible endoscopic
- Panendoscopy
- Fine needle aspiration
- Bronchoscopy (to determine the inferior tumor extension)
- Esophagoscopy (to determine the inferior tumor extension)
- Radiologic evaluation
Chest radiograph
Computed tomography (CT) scan with contrast of head and neck region
Magnetic resonance imaging (MRI)
Contrast laryngography
Positron emission tomography (PET)
Histology:
Lindsey
-Over 95% of hypopharynx tumors are squamous cell carcinomas.4
-Tumor margins infiltrating in 80% and pushing in 20% of specimens.
-Whole sections of the pyriform fossa have shown unsuspected submucosal tumor spread well beyond 1cm of visible tumor margins.
Figure 1. Reprinted from Radiation Oncology Management Decisions. 4
Lymph node drainage:
Lindsey
-The lymphatics of the hypopharynx enter the jugulodigastric nodes and upper and middle jugular chain.4
-The extensive lymphatics of the hypopharynx along with the extensive primary disease at presentation cause a high incidence of metastases to regional lymph nodes.
-Midcervical nodes are most commonly involved.
-Contralateral submaxillary nodes are the most common contralateral neck sites.
-Regional lymph node metastases are often found at presentation.
Figure 2. Reprinted from Radiation Oncology Management Decisions. 4
Metastatic spread:
Kevin
Metastasis is a complex series of steps in which cancer cells leave the original tumor site and migrate to other parts of the body via the bloodstream, the lymphatic system, or by direct extension. To do so, malignant cells break away from the primary tumor and attach to and degrade proteins that make up the surrounding extracellular matrix (ECM), which separates the tumor from adjoining tissues. By degrading these proteins, cancer cells are able to breach the ECM and escape. The location of the metastases isn’t always random, with different types of cancer tending to spread to particular organs and tissues at a rate that is higher than expected by statistical chance alone.5
Figure 3. Reprinted from Wikipedia: The Free Encyclopedia. 5
The abundant lymphatics of the hypopharynx, coupled with extensive primary disease at presentation, accounts for the high incidence of metastases to the regional lymph nodes. The midcervical lymph nodes are most commonly involved. The incidence of metastases varies according to the site and origin in the hypopharynx.6
Figure 4. Reprinted from Radiation Oncology Management Decisions. 6
Grading:
Kevin
The grade of a cancer tells you what the cells look like under a microscope. The cells are graded according to how normal or abnormal they appear. There are 4 grades of the hypopharyngeal cancer cells. 7
Grade 1 (low grade)-the cancer cells look very much like normal hypopharyngeal cells.
Grade 2 (intermediate grade)-the cancer cells look slightly different to normal hypopharyngeal cells.
Grade 3 (high grade)-the cancer cells look very abnormal and not much like normal hypopharyngeal cells.
Grade 4 (high grade)-the cancer cells look very different to normal hypopharyngeal cells.
A specialist examines the cancer cells to see how different they are from normal cells. Doctors call this differentiation or grade.
Well differentiated cells are low grade. Poorly differentiated cells are high grade.
Usually, a low grade cancer (made of well differentiated cells) is likely to grow more slowly and be less likely to spread, than a high grade cancer (with poorly differentiated cells).
Over 95% of tumors of the hypopharynx are squamous cell carcinoma.
Staging:
Jenn
TX: Primary tumor cannot be evaluated.
T0: No evidence of tumor is found.
Tis: In situ carcinoma, where the cancer cells are found only in one layer of tissue.
T1: Tumor is small, no larger than 2 centimeters, and is limited to a single site in the lower throat.
T2: Tumor involves more than one site in the lower throat, but does not touch the voice box, tumor measures between 2cm and 4 cm.
T3: Tumor is larger than 4 cm or has spread to the larynx.
T4a: Tumor has spread into nearby structures, such as thyroid, arteries that carry blood to brain, or the esophagus.
T4b: Tumor has spread to the prevertebral fascia (space in front of spinal cord), encases the arteries, or involves mediastinal structures.
NX: regional lymph nodes cannot be evaluated.
N0: No evidence of cancer in the regional nodes.
N1: Cancer has spread to a single node on the same side as the primary tumor, <3cm or smaller.
N2: describes the following conditions:
N2a: Cancer has spread to a single lymph node on the same side as the primary; tumor is larger than 3cm but not larger than 6cm.
N2b: Cancer has spread to more than one lymph node on the same side as the primary, none larger than 6 cm.
N2c: Cancer has spread to more than one lymph node on either side of the body, and none measure larger than 6 cm.
N3: Cancer found in lymph nodes larger than 6 cm.
MX: Distant metastasis cannot be evaluated.
M0: Cancer has not spread to any other parts of the body.
M1: Cancer has spread to other parts of the body.
Stage 0: Carcinoma in situ (Tis), no spread to lymph nodes (N0), or distant metastasis (M0).
Stage I: Small tumor (T1), no spread to lymph nodes (N0), no distant metastasis (M0).
Stage II: Tumor has spread to some nearby areas (T2), no spread to lymph nodes (N0), no distant metastasis (M0).
Stage III: Large tumor (T3), no spread to regional lymph nodes or metastasis (M0), or a smaller tumor (T1, T2) that has spread to regional lymph nodes (N1) but has no sign of distant metastasis (M0).
Stage IVA: Any invasive tumor (T4a) that either has no lymph node involvement (N0) or that has spread to a single same-sided lymph node (N1), but without distant metastasis (M0).
Stage IVB: Any cancer (T) with extensive spread to the lymph nodes (N3) but no distant metastasis (M0).
Stage IVC: Evidence of distant spread ( any T, N and M1). 8
Radiation side effects:
Jenn
Some side effects after radiation are: 8
Redness or skin irritation
Dry mouth
Thickened saliva from damage to salivary glands (can be temporary or permanent)
Bone pain
Fatigue
Weight loss
Mouth sores
Dental problems if not taken care of before radiation
Change in voice
Taste changes
Prognosis:
Rachel
As age increases, survival rates decrease.4
Women have a much higher survival rate 3 to 20 years post therapy.
Positive surgical margins or tumor persistence in the irradiation field after initial therapy in pyriform fossa tumors has a very adverse effect on survival for these patients.
Higher cure rates for aryepiglottic fold and medial wall pyriform fossa tumors, which are usually small and more localized, as compared to postcricoid and pharyngeal wall tumors.
The poorest prognosis is seen for pyriform apex, postcricoid, and two- or three-wall tumors.
Regional metastases in pyriform fossa and aryepiglottic fold tumors reduces the cure rate by 28% and 26%. The presence of extracapsular tumor spread in the cervical lymph nodes and in the soft tissues of the neck greatly affects survival rates.
The size or the number of regional metastases affects survival (higher for N1 than N2 and N3) by an additional 12% to 18%.
Cure rates also depend on tumor location. Pyriform fossa usually has a higher cure rate. Tumors located in the pharyngeal walls have less of a survival rate. Tumors located in the postcricoid region have the least survival rates.
T stage also influences survival as well. The larger the tumor the poorer the outcome.
Treatments:
Rachel
For most Hypopharyngeal tumors the goal is local control while preserving respiration, deglutition and voice.4
T1 and T2: Surgery or radiation
A combined modality treatment should be used for larger and more advanced tumors.
Pre-op Radiation: portal should include larynx, pharynx and neck. Supraclavicular, anterior and posterior lymph nodes. Retropharyngeal nodes included if it's a pyriform sinus cancer. Dose is usually around 45-50 Gy.
Post-op Radiation: Portal includes the primary tumor from the base of the skull, upper and lower cervical nodes, and the trachesostoma. A shield for the spinal canal should be used after 45 Gy. Dose is usually around 60-66 Gy.
Figure 5. Reprinted from Radiation Oncology Management Decisions. 4
- Field Borders: (Figure 5)
Superior: inferior border of mandible and mastoid process to the base of skull.
Anterior: In front of the thyroid cartilage
Posterior: behind the spinous processes
Inferior: below the cricoid cartilage
- Irradiation Alone
Portals should include nasopharynx, oropharynx, hypopharynx and upper esophagus
Field arrangements: opposed Lats and Anterior low neck
Dose 60 Gy
Boost portal should include: the gross tumor volume and grossly involved nodes
Boost dose: 10-15 Gy
Total doses from 70-75 Gy
TD 5/5:
Brandon
TD 5/5: Total dose delivered by a standard fractionation schedule that causes a minimal (5%) complication rate within 5 years. 9
Esophagus: 5500cGy - Stricture / Perforation
Spinal Cord: 4500 cGy - Necrosis / Myelitis
Larynx: 7000cGy - Necrosis
References:
Washington C, Leaver D. Principles and Practice of Radiation Oncology. 3rd ed. St. Louis, MO. Mosby Elsevier; 2010: 724.
Krstevaska, V. Hypopharyngeal Cancer. In: Agulnik, M, ed. Head and Neck Cancer. Republic of Macedonia: Intec; 2012: 14-16.
Perez CA, Halperin EC, Brady LW. Principles & Practice of Radiation Oncology. 4th ed.U.S.A. Lippincott Williams &Wilkins; 2004: 1189-1190.
Chao KS, Perez CA, Brady LW. Radiation Oncology Management Decisions. 3rd ed. Philadelphia, PA: Lippincott, Williams, and Wilkins; 2011: 275-280.
Epidemiolgy:
Ashley
Hypopharyngeal cancer is defined as cancer of the hypopharnyx region consisting of the pyriform sinuses, postcricoid and lower posterior pharyngeal walls. 1 This type of cancer is difficult to detect due the significant advancement of cancer cells before the first symptoms arise. In addition, these cancers have a poor prognosis due to local nodal and neighboring structure invasion as well as other metastases. 2 Hypopharyngeal cancer is considered a rare cancer with an incidence of approximately 1 per 100,000 in the US.2 In addition, this disease only accounts for 3-5% of all head and neck cancers diagnosed. 2 This cancer is twice as common in men than in women and is most often seen in men 50 years of age or older. 2
Etiology:
Ashley
While the exact causes of hypopharyngeal cancer are unknown, there are several risk factors that are linked to its growth. Firstly, tobacco use and alcohol consumption are among the most important influences in the development of this cancer. In fact, almost 90% of patients who present with this cancer have used tobacco regularly at some point in their life. 2 Genetic factors are also among the risk factors for this disease. Almost 70% of the patients who are diagnosed with hypopharyngeal cancer have a mutation in the tumor suppressor gene p53.2 In fact, research supports a link between the p53 gene mutations and smoking putting these people at higher risk for developing the cancer. 2 Overexpression of specific oncogenes and abnormalities in chromosome 11 are other contributing genetic factors as well. Lastly, the role of HPV in hypopharyngeal cancer has proven to be the latest risk factor under investigation. The role of HPV is less defined in this type of cancer compared to that of oropharyngeal cancer, however, 20%-25% of hypopharyngeal cancer patients tested positive for HPV. 2 While the etiology of hypopharyngeal cancer remains under investigation, the risk factors are important in preventing the development and spread of the disease.
Amanuel
Patients with carcinoma of hypopharynx present:3
- Mild sore throat
- Dysphagia (difficulty swallowing)
- Otalgia (ear pain)
- Odynophagia (painful swallowing)
- Blood streaked saliva (due to necrosis or trauma to tumor bed)
- Saliva drooling
- Neck stiffness
- ‘Hot potato’ voice (due to laryngeal or base of tongue invasion)
- Hoarsness (due to tumor invasion of the larynx or cricoarytenoid joint)
- Weight loss – in advanced disease
- Tongue paralysis (rare) (due to hypoglossal nerve invasion – lymph node level II and III)
5-15% of patients with hypopharynx require emergency tracheotomy
Amanuel
Diagnostic work-up for hypopharyngeal cancer include:3
- Physical examination: indirect laryngoscopy and a flexible endoscopic
- Panendoscopy
- Fine needle aspiration
- Bronchoscopy (to determine the inferior tumor extension)
- Esophagoscopy (to determine the inferior tumor extension)
- Radiologic evaluation
Chest radiograph
Computed tomography (CT) scan with contrast of head and neck region
Magnetic resonance imaging (MRI)
Contrast laryngography
Positron emission tomography (PET)
Lindsey
-Over 95% of hypopharynx tumors are squamous cell carcinomas.4
-Tumor margins infiltrating in 80% and pushing in 20% of specimens.
-Whole sections of the pyriform fossa have shown unsuspected submucosal tumor spread well beyond 1cm of visible tumor margins.
Lindsey
-The lymphatics of the hypopharynx enter the jugulodigastric nodes and upper and middle jugular chain.4
-The extensive lymphatics of the hypopharynx along with the extensive primary disease at presentation cause a high incidence of metastases to regional lymph nodes.
-Midcervical nodes are most commonly involved.
-Contralateral submaxillary nodes are the most common contralateral neck sites.
-Regional lymph node metastases are often found at presentation.
Kevin
Metastasis is a complex series of steps in which cancer cells leave the original tumor site and migrate to other parts of the body via the bloodstream, the lymphatic system, or by direct extension. To do so, malignant cells break away from the primary tumor and attach to and degrade proteins that make up the surrounding extracellular matrix (ECM), which separates the tumor from adjoining tissues. By degrading these proteins, cancer cells are able to breach the ECM and escape. The location of the metastases isn’t always random, with different types of cancer tending to spread to particular organs and tissues at a rate that is higher than expected by statistical chance alone.5
The abundant lymphatics of the hypopharynx, coupled with extensive primary disease at presentation, accounts for the high incidence of metastases to the regional lymph nodes. The midcervical lymph nodes are most commonly involved. The incidence of metastases varies according to the site and origin in the hypopharynx.6
Kevin
The grade of a cancer tells you what the cells look like under a microscope. The cells are graded according to how normal or abnormal they appear. There are 4 grades of the hypopharyngeal cancer cells. 7
Grade 1 (low grade)-the cancer cells look very much like normal hypopharyngeal cells.
Grade 2 (intermediate grade)-the cancer cells look slightly different to normal hypopharyngeal cells.
Grade 3 (high grade)-the cancer cells look very abnormal and not much like normal hypopharyngeal cells.
Grade 4 (high grade)-the cancer cells look very different to normal hypopharyngeal cells.
A specialist examines the cancer cells to see how different they are from normal cells. Doctors call this differentiation or grade.
Well differentiated cells are low grade. Poorly differentiated cells are high grade.
Usually, a low grade cancer (made of well differentiated cells) is likely to grow more slowly and be less likely to spread, than a high grade cancer (with poorly differentiated cells).
Over 95% of tumors of the hypopharynx are squamous cell carcinoma.
Jenn
T0: No evidence of tumor is found.
Tis: In situ carcinoma, where the cancer cells are found only in one layer of tissue.
T1: Tumor is small, no larger than 2 centimeters, and is limited to a single site in the lower throat.
T2: Tumor involves more than one site in the lower throat, but does not touch the voice box, tumor measures between 2cm and 4 cm.
T3: Tumor is larger than 4 cm or has spread to the larynx.
T4a: Tumor has spread into nearby structures, such as thyroid, arteries that carry blood to brain, or the esophagus.
T4b: Tumor has spread to the prevertebral fascia (space in front of spinal cord), encases the arteries, or involves mediastinal structures.
NX: regional lymph nodes cannot be evaluated.
N0: No evidence of cancer in the regional nodes.
N1: Cancer has spread to a single node on the same side as the primary tumor, <3cm or smaller.
N2: describes the following conditions:
N2a: Cancer has spread to a single lymph node on the same side as the primary; tumor is larger than 3cm but not larger than 6cm.
N2b: Cancer has spread to more than one lymph node on the same side as the primary, none larger than 6 cm.
N2c: Cancer has spread to more than one lymph node on either side of the body, and none measure larger than 6 cm.
N3: Cancer found in lymph nodes larger than 6 cm.
MX: Distant metastasis cannot be evaluated.
M0: Cancer has not spread to any other parts of the body.
M1: Cancer has spread to other parts of the body.
Stage 0: Carcinoma in situ (Tis), no spread to lymph nodes (N0), or distant metastasis (M0).
Stage I: Small tumor (T1), no spread to lymph nodes (N0), no distant metastasis (M0).
Stage II: Tumor has spread to some nearby areas (T2), no spread to lymph nodes (N0), no distant metastasis (M0).
Stage III: Large tumor (T3), no spread to regional lymph nodes or metastasis (M0), or a smaller tumor (T1, T2) that has spread to regional lymph nodes (N1) but has no sign of distant metastasis (M0).
Stage IVA: Any invasive tumor (T4a) that either has no lymph node involvement (N0) or that has spread to a single same-sided lymph node (N1), but without distant metastasis (M0).
Stage IVB: Any cancer (T) with extensive spread to the lymph nodes (N3) but no distant metastasis (M0).
Stage IVC: Evidence of distant spread ( any T, N and M1). 8
Jenn
Some side effects after radiation are: 8
Redness or skin irritation
Dry mouth
Thickened saliva from damage to salivary glands (can be temporary or permanent)
Bone pain
Fatigue
Weight loss
Mouth sores
Dental problems if not taken care of before radiation
Change in voice
Taste changes
Rachel
Women have a much higher survival rate 3 to 20 years post therapy.
Positive surgical margins or tumor persistence in the irradiation field after initial therapy in pyriform fossa tumors has a very adverse effect on survival for these patients.
Higher cure rates for aryepiglottic fold and medial wall pyriform fossa tumors, which are usually small and more localized, as compared to postcricoid and pharyngeal wall tumors.
The poorest prognosis is seen for pyriform apex, postcricoid, and two- or three-wall tumors.
Regional metastases in pyriform fossa and aryepiglottic fold tumors reduces the cure rate by 28% and 26%. The presence of extracapsular tumor spread in the cervical lymph nodes and in the soft tissues of the neck greatly affects survival rates.
The size or the number of regional metastases affects survival (higher for N1 than N2 and N3) by an additional 12% to 18%.
Cure rates also depend on tumor location. Pyriform fossa usually has a higher cure rate. Tumors located in the pharyngeal walls have less of a survival rate. Tumors located in the postcricoid region have the least survival rates.
T stage also influences survival as well. The larger the tumor the poorer the outcome.
Rachel
T1 and T2: Surgery or radiation
A combined modality treatment should be used for larger and more advanced tumors.
Pre-op Radiation: portal should include larynx, pharynx and neck. Supraclavicular, anterior and posterior lymph nodes. Retropharyngeal nodes included if it's a pyriform sinus cancer. Dose is usually around 45-50 Gy.
Post-op Radiation: Portal includes the primary tumor from the base of the skull, upper and lower cervical nodes, and the trachesostoma. A shield for the spinal canal should be used after 45 Gy. Dose is usually around 60-66 Gy.
- Field Borders: (Figure 5)
Superior: inferior border of mandible and mastoid process to the base of skull.
Anterior: In front of the thyroid cartilage
Posterior: behind the spinous processes
Inferior: below the cricoid cartilage
- Irradiation Alone
Portals should include nasopharynx, oropharynx, hypopharynx and upper esophagus
Field arrangements: opposed Lats and Anterior low neck
Dose 60 Gy
Boost portal should include: the gross tumor volume and grossly involved nodes
Boost dose: 10-15 Gy
Total doses from 70-75 Gy
Brandon
TD 5/5: Total dose delivered by a standard fractionation schedule that causes a minimal (5%) complication rate within 5 years. 9
Esophagus: 5500cGy - Stricture / Perforation
Spinal Cord: 4500 cGy - Necrosis / Myelitis
Larynx: 7000cGy - Necrosis
Washington C, Leaver D. Principles and Practice of Radiation Oncology. 3rd ed. St. Louis, MO. Mosby Elsevier; 2010: 724.
Krstevaska, V. Hypopharyngeal Cancer. In: Agulnik, M, ed. Head and Neck Cancer. Republic of Macedonia: Intec; 2012: 14-16.
Perez CA, Halperin EC, Brady LW. Principles & Practice of Radiation Oncology. 4th ed.U.S.A. Lippincott Williams &Wilkins; 2004: 1189-1190.
Chao KS, Perez CA, Brady LW. Radiation Oncology Management Decisions. 3rd ed. Philadelphia, PA: Lippincott, Williams, and Wilkins; 2011: 275-280.
Metastasis-Wikipedia, the free encyclopedia.Avalable at http://www.wikipedia.org/wiki/Metastasis. Accessed on May 28, 2013.
Chao, K, Perez, C, Brady, L. Radiation Oncology Management Decisions. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011. 275.
Cancer research UK. Grade and stage of hypopharyngeal cancer. Available at http://www.cancerresearchuk.org/cancer.../grade-and-stage-of-hypopharyngeal-cancers. Accessed May 28, 2013.
Laryngeal and Hypopharyngeal Cancer.Oncologist- approved cancer information from the American Cancer Society of Clinical Oncology. Available at http://www.cancer.net/cancer-types/laryngeal-and-hypopharyngeal-cancer/stages-and-grades. Accessed May 31, 2013.
Washington C, Leaver D. Principles and Practice of Radiation Oncology. 3rd ed. St. Louis, MO. Mosby Elsevier; 2010: 80-82.
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