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Postcricoid Area, Malignant Tumors
Updated: Jun 28, 2006
Introduction
The postcricoid region, pyriform sinus, and posterior hypopharyngeal wall comprise the hypopharynx. Tumors rarely appear in the posterior pharyngeal wall or postcricoid region without also involving the pyriform sinus. The lack of anatomic barriers between these sites and a propensity for these tumors to develop in the pyriform sinus and spread outward account for this phenomenon.
Overall prognosis for these tumors is poor. Because of the rich organic lymphatic and vascular networks, aggressive growth and early cervical metastases (compared with cancers at other head and neck sites) characterize these cancers.
Additionally, the nerve supply is relatively nonlocalizing (similar to that in the abdomen), which most often yields vague symptoms of discomfort as the initial presenting signs until the tumor has grown to an impressive size. Because of these factors, hypopharyngeal cancers are discovered at a later stage than other head and neck cancers. The delay in diagnosis from symptom onset averages 10 months. This fact requires that health care professionals investigate vague symptoms of a "lump in the throat" and swallowing difficulty more carefully if symptoms do not respond quickly to conservative intervention.
For excellent patient education resources, visit eMedicine's Cancer and Tumors Center. Also, see eMedicine's patient education article Cancer of the Mouth and Throat.
History of the Procedure
In the early part of the 20th century, x-ray technology was insufficiently advanced for applications in cancer treatment; thus, surgery was the only option. Coutard applied the maturing field of radiobiology to the hypopharynx in the 1920s, and his methods were improved into the 1950s. The development of megavoltage radiation enhanced cure rates to a significant degree, but surgery remained the mainstay of all major protocols. The issue of preoperative versus postoperative radiation delivery was addressed in the early 1970s, with strong evidence favoring the better survival and lower complication rates associated with postoperative radiation. In current practice, the postoperative radiation dose is usually 66-72 Gy. Delivery schedules have been the subject of much discussion, with many studies showing an advantage for hyperfractionated therapy (120 Gy/dose, twice/d) and other studies showing no difference for once-daily treatments at 180-200 Gy/dose.
Problem
Postcricoid cancer is an insidious disease that usually manifests late in its course, making treatment difficult and good cure rates hard to achieve. At present, surgery and radiation are needed to attain the highest cure rates, although improvements are being made with conservative therapy of radiation and concomitant chemotherapy.
Frequency
In the United States, the postcricoid cancer frequency rate is 2.4-3.1% of all hypopharyngeal cancers, which places its overall prevalence at approximately 0.01 cases per 100,000 persons. The rate is higher in the United Kingdom and India, with figures quoted from 3.5-40% of all hypopharyngeal tumors.
Etiology
Many factors influence the eventual progression to cancer in the postcricoid region. The most obvious of these is the well-known synergistic influence of tobacco and alcohol, whose combined carcinogenic effect promotes cancer in this region. More than 90% of patients with hypopharyngeal cancers smoke tobacco, and figures indicate 60-70% abuse alcohol. These data are extrapolated from hypopharyngeal studies because well-constructed inquiries addressing tobacco and alcohol involvement specifically with postcricoid carcinomas have not emerged.
Radiation therapy has also been implicated in hypopharyngeal tumor growth (after a 10- to 20-y delay). Moreover, a geographical component for this disease seems apparent, with such tumors most common in Anglo-Saxon countries and India but rare in Mediterranean countries and the United States.
The more-celebrated etiological association is with a condition called Plummer-Vinson syndrome (alternately termed Paterson-Brown-Kelly syndrome). This syndrome is associated with hypochromic (iron-deficient) anemia, usually below 12 g/dL. The syndrome includes a history of dysphagia elicited by hypopharyngeal webs, usually centered in the postcricoid area. Other aspects include glossitis, angular stomatitis, koilonychia, and microglossia. The latter abnormalities are encountered with much less frequency than dysphagia brought about by the webs and hypochromic anemia.
Various studies place the rate of Plummer-Vinson syndrome and postcricoid cancer coincidence at 4-16%. This number ranges quite widely, even within studies from the same country. Coincidence seems highest in the United Kingdom and areas with populations of Scandinavian descent and lowest in the United States and Asia. However, reports from India indicate increased coincidence of postcricoid carcinoma and variable Plummer-Vinson syndrome.
The sex of the patient sex also may increase the risk for postcricoid cancer. This is most notable in areas with relatively high rates of Plummer-Vinson syndrome. In these countries, women develop the disease more often than men by a female-to-male ratio of approximately 3:1. However, other countries demonstrate a slight male predominance.
Pathophysiology
The genesis of postcricoid carcinoma mirrors that of other head and neck cancers. Initial insults with carcinogens, generally from the synergistic effects of tobacco and alcohol, result in genetic alterations. Most commonly, TP53 obtains a mutation that makes it ineffective in controlling the cell growth rate. After this early event, a promoting event is thought to occur before these cells truly become cancerous. Much work has been accomplished to study the course of genetic events leading to carcinogenesis in the head and neck. Many studies focus on alterations on chromosomes 9 and 11. Ultimately, cancer cells form that escape host immunological surveillance and begin to grow as a tumor.
Presentation
Most patients report a globus or foreign-body sensation in the throat for months to years before diagnosis. This is the single common finding in all cases of postcricoid carcinoma. Generally, this dysphagia progresses to limit intake of solids and, eventually, liquids. As the tumor becomes more pronounced, generalized dysphagia turns into odynophagia, and a focal area of pain can often be elicited. An ominous sign at this point is referred otalgia; the stimulus initiates from the tumor and courses along the sensory distribution of the vagus nerve, where it meets with the Arnold nerve in the middle ear.
Extrapolating from hypopharyngeal data, up to 25% of these tumors are diagnosed initially based on the presence of an asymptomatic mass in the neck that proves to be metastatic disease to the cervical lymph nodes. Up to 75% of patients have cervical lymph node metastases at the time of presentation, with 10% having bilateral disease. The postcricoid area tends to spread into the paratracheal area and into the inferior jugular nodes. Occult metastases may occur in up to 80% of patients without clinically obvious nodes.
A less frequent presentation is hoarseness, which stems from growth of the tumor anteriorly into the posterior cricoarytenoid muscles or directly into the recurrent laryngeal nerve, thus interfering with vocal cord motion.
Indications
Once the tumor has been verified as a cancer, usually squamous cell carcinoma, it is assessed for conservative management. Many centers use neoadjuvant chemotherapy to determine whether laryngeal and hypopharyngeal tumors will respond to radiotherapy. Tumor volume can also be used; tumors of less than 6 cm3 often respond to radiation alone, provided cartilage destruction is insignificant. Therefore, any cancerous tumor unresponsive to chemotherapy or greater than 6 cm3 should undergo appropriate resection as the initial treatment.
Radiation treatment can be used alone in patients with low-volume T1 and T2 cancers and is added to surgery if the tumor is evaluated as stage III or IV. Additionally, perineural, perivascular, or soft tissue invasion (noted on final pathology results) or multiple positive nodes and/or extracapsular extension all indicate radiation treatment. Patients who are not surgical candidates but who have advanced disease that is potentially curable are best treated with concomitant chemotherapy and irradiation.
Relevant Anatomy
The postcricoid region of the hypopharynx includes the mucosa and submucosa extending from the inferior aspect of the arytenoids to the bottom of the cricoid cartilage. The lateral margins merge with the medial wall of each pyriform sinus at approximately that level where the cricoid cartilage makes an anterior bend. The nerve supply is from the pharyngeal plexus, which derives from the vagus and glossopharyngeal nerves (cranial nerves X and IX). The blood supply comes from both the external carotid system (ie, superior thyroid artery to superior laryngeal artery, ascending pharyngeal artery) and the thyrocervical trunk (ie, ascending cervical artery, inferior thyroid artery to inferior laryngeal artery).
The hypopharynx is shaped like a funnel with its most anterior segment missing. This corresponds to the introitus to the larynx. The hypopharynx is covered by mucosa of stratified squamous epithelium intermixed with goblet cells. It begins at the level of the hyoid bone and extends laterally along the pharyngoepiglottic fold. The posterior hypopharynx is divided from the oropharynx superiorly by a line drawn horizontally from the hyoid bone and is divided from the cervical esophagus inferiorly by a line drawn horizontally from the bottom of the cricoid cartilage. The pyriform sinuses are folds of the hypopharynx that encompass the larynx on its lateral edges. This sinus is tucked into a small area between the aryepiglottic folds of the larynx and the thyroid ala. The postcricoid region fills out the hypopharynx.
Contraindications
Several factors can make a postcricoid cancer unresectable. For tumors extending into the soft tissues of the neck, most surgeons use carotid encasement as an indicator of unresectability. While the technical aspects are not daunting, the overall survival rate after carotid resection is so poor that potential sequelae (eg, stroke, mental status changes, death) do not justify the small percentage of salvage cases. Extension into the prevertebral musculature, while rare, is also a contraindication for surgery. Finally, distant metastases preclude the possibility of surgical cure.
Relative contraindications include a patient with the inability to withstand lengthy anesthesia, whether due to cardiac (eg, poor ejection fraction, severe cardiomyopathy), pulmonary (eg, severe chronic obstructive pulmonary disease), renal, or a host of other causes. Reports from the 1970s also mention a size limit of 5 cm (vertical length) as the largest tumor amenable to cure, with a patient survival rate of 0% at 18 months for tumors exceeding this size. These reports ignore different radiotherapy delivery methods and/or the addition of chemotherapy. Advanced age no longer contraindicates treatment because successful operations (including repair with free flaps) on patients in their 90s have been performed.
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Further Reading
Keywords
malignant tumors of the postcricoid area, hypopharyngeal carcinoma, hypopharynx cancer, hypopharyngeal cancer, hypopharynx cancer, head and neck cancer, head and neck carcinoma, postcricoid cancer, post-cricoid cancer, postcricoid carcinoma, post-cricoid carcinoma, hypopharyngeal tumor, hypopharynx tumor, hypopharyngeal malignancy, postcricoid malignancy, Plummer-Vinson syndrome, Paterson-Brown-Kelly syndrome, squamous cell carcinoma, SCC, head and neck squamous cell carcinoma, head and neck SCC
