Neck neoplasms include not only metastatic squamous cell carcinoma but also a number of other primary neck tumors. Metastatic squamous cell carcinoma arises from the upper aerodigestive tract and is present in the lymph nodes and in the neck; other primary tumors arise from the soft tissue in the neck, such as fat, fibrous tissue, muscle, blood vessels, lymphatic vessels, nerves, and paraganglia (Table 28–1). These primary tumors are fairly uncommon, often making a pathologic diagnosis difficult. The evaluation of all neck masses consists of obtaining a complete history and conducting a physical exam.
Table 28–1. Differential Diagnosis of Benign and Malignant Neck Neoplasms. |Favorite Table|Download (.pdf)
Table 28–1. Differential Diagnosis of Benign and Malignant Neck Neoplasms.
|Paraganglioma—glomus vagale, carotid body tumor||Synovial sarcomas|
|Neural—Schwannoma, neurofibroma||Malignant peripheral nerve sheath tumor|
The presenting symptom of a neck neoplasm is a painless enlarging neck mass that may grow extremely slowly or very rapidly. On physical examination, there is often a well-circumscribed mass in the neck. The location of the mass sometimes suggests its cause.
Imaging with computed tomography (CT) or magnetic resonance imaging (MRI) is critical for these lesions, especially if these studies are performed before a biopsy is obtained. A preoperative study can better assess both the size and the extent of the lesion without confounding factors such as bleeding and edema. An MRI is often the study of choice because it allows a greater differentiation of soft tissue. A positron emission tomography (PET) scan in evaluating patients with metastatic disease can identify additional tumor masses. Additional studies such as angiography and, recently, magnetic resonance angiography (MRA) add valuable information to the diagnosis of vascular lesions (eg, carotid body tumors and vascular malformations).
Fine-Needle Aspiration (FNA) Biopsy
A tissue specimen is vital for the diagnosis of neck neoplasms and can be obtained via a fine-needle aspiration biopsy (FNAB). Metastatic squamous cell carcinoma has an excellent specificity and sensitivity for FNAB. Additional studies such as flow studies, immunohistochemistry techniques, or electron microscopy may be required for an accurate diagnosis of these specimens.
Open biopsies consist of incisional and excisional biopsies. A small superficial lesion or any lesion smaller than 3 cm should undergo an excisional biopsy with sufficient normal surrounding tissue for adequate, clear margins. An incisional biopsy should only be entertained if the mass is larger than 3 cm. If metastatic squamous cell carcinoma is suspected, an open biopsy should not be considered unless all other avenues have been exhausted and at least two inconclusive FNAB.
After either an FNAB or open biopsy is performed, the specimen then undergoes evaluation with light microscopy. Immunohistochemistry techniques can stain for cytokeratin, leukocyte common antigen, S-100, and myoglobin to differentiate sarcomas, melanomas, and epithelial carcinomas. Electron microscopy is used to aid in the diagnosis in patients where light microscopy and immunohistochemistry techniques prove ineffective.
The most common benign masses in the neck are inflammatory lymph nodes and masses of salivary and thyroid gland origins. True soft-tissue benign tumors in the neck are relatively uncommon.
Paragangliomas arise from paraganglia, islands of cells derived from neural crest cells, associated with arteries and cranial nerves located at the carotid body, vagal body, along laryngeal nerves, and in the jugulotympanic region. The tumors derived from these regions are carotid body tumors, intravagal paragangliomas, and glomus tympanicum and glomus jugulare. While paraganglia cells are capable of producing catecholamines, the incidence of catecholamine-producing head and neck paragangliomas is exceedingly rare.
Carotid body tumors are the most common head and neck paragangliomas. The carotid body is found at the bifurcation of the common carotid artery and responds to changes in arterial pH, oxygen, and carbon dioxide.
Symptoms are present only with large tumors and include pressure, dysphagia, cough, and hoarseness. On examination, the mass is palpated at the anterior border of the sternocleidomastoid muscle. It is typically mobile laterally but not vertically.
The diagnosis requires a high index of suspicion as the location is similar to that of many other masses (eg, branchial cleft cysts and enlarged lymph nodes). Fine-needle aspiration of these lesions often yields only blood; however, if cells are obtained, FNA can offer a definitive diagnosis.
The angiogram in Figure 28–1 shows the typical findings of a splayed bifurcation of the carotid artery with a vascular blush. An MRI often proves useful in identifying other paragangliomas as synchronous and metachronous lesions occur in 25–48% of cases. Familial paragangliomas occur in 7–9% of cases.
Angiogram of a patient with a carotid body tumor showing the classic splaying of the carotid bifurcation.
The treatment of these lesions is predominantly surgical. Preoperative embolization is useful to minimize blood loss in order to allow for a cleaner dissection. Surgical excision requires the following measures: (1) identification of the proximal and distal carotid artery and (2) identification and preservation of the vagus, hypoglossal, and spinal accessory nerves. Patients with large or recurrent tumors often require vascular reconstruction, which should be planned preoperatively.
Radiation therapy is not the primary mode of therapy but has been used as the sole method of treatment in some cases such as elderly patients who are poor surgical candidates. In patients with carotid body and vagale tumors, radiation therapy alone has been shown to provide a local control rate of as much as 96%. Control rates with surgery alone range from 88% to 100%. Treatment decisions are based on surgical risks and complications; therefore, small tumors should usually be treated surgically, with radiation therapy reserved for large tumors.
Intravagal paragangliomas typically occur in association with one of the vagal ganglia, most commonly the ganglion nodosum. Intravagal paragangliomas account for approximately 3% of all head and neck paragangliomas. Symptoms can include hoarseness, dysphagia, aspiration, tongue weakness, and Horner syndrome. Angiographic imaging shows a mass located above the carotid bifurcation, with lateral and medial displacement of the external and internal carotid arteries. FNA has been useful in the diagnosis of these tumors.
The treatment involves surgical resection, with radiation therapy reserved for patients with high surgical risk, incomplete resection, recurrent disease, and bilateral tumors. Most intravagal paragangliomas can be resected via a cervical approach. If there is intracranial extension, a middle or posterior fossa approach may be needed.
Karaman E. Isildak H, Yilmaz M et al. Management of paragangliomas in otolaryngology practice: review of a 7-year experience. J Craniofac Surg
. (The primary treatment remains surgical excision with preoperative embolization in selective cases.)
Peripheral Nerve Cell Tumors
Tumors arising from peripheral nerves typically arise from the Schwann cells in the nerve sheath. Of the many names used to describe these tumors, two in particular—schwannomas and neurofibromas—have significant clinical differences that warrant discussion. As a group, neurogenous tumors occur most commonly in the head and neck regions. They are often asymptomatic and present as lateral neck masses.
Peripheral nerve schwannomas, more appropriately termed neurilemomas, are solitary, well-encapsulated tumors. Histologically, these tumors have characteristic Antoni A and Antoni B tissues. Antoni A tissue consists of palisading nuclei around central cytoplasm and Antoni B tissue is comprised of a loose edematous matrix. These tumors can arise from cranial nerves, peripheral motor and sensory nerves, and the sympathetic chain. They can sometimes present with a displaced tonsil or a lateral pharyngeal wall when the mass is located in the parapharyngeal space.
Neurofibromas differ from neurilemomas in that they are not encapsulated. The nerves in neurofibromas tend to traverse the tumors and are integral to them. While solitary neurofibromas are very rare, multiple neurofibromas are common especially in patients with von Recklinghausen disease. von Recklinghausen disease is an autosomal dominant disease with clinical findings of cafè-au-lait spots and neurofibromas.
The treatment of both neurilemomas and neurofibromas consists of simple surgical resection. The function of the affected nerve can typically be preserved with neurilemomas unless the neoplasms are intimately involved with some cranial nerves. These tumors rarely recur and malignant transformation is exceedingly rare.
Lipomas are the most common benign soft-tissue neoplasms. They arise from the subcutaneous tissue and present as painless, smooth, encapsulated, and round masses. Fifteen to twenty percent of all lipomas occur in the head and neck. Most of these neoplasms are solitary lesions and are easily treated with excision. Recurrences are very rare.
The most common malignant neoplasm in the neck is a cervical metastasis from a primary tumor in the upper aerodigestive tract. In most cases, when a lymph node metastasis in the neck is identified, the primary tumor also can be identified and the treatment proceeds according to the principles dictated by the stage of the primary disease. In less than 10% of cases, the primary site is not located and further evaluation is required. Malignant neoplasms of the salivary, thyroid, and parathyroid glands also can present as malignant cervical masses or with metastases to cervical lymph nodes. (See the following chapters for information on these neoplasms: Chapter 17, Malignant Diseases of the Salivary Glands; Chapter 41, Malignant Thyroid Disorders; and Chapter 42, Parathyroid Disorders.) Other common primary malignant neoplasms of the head and neck are lymphomas. Rarely are sarcomas seen in the head and neck.
Unknown Primary Squamous Cell Carcinoma
A common problem with an unknown primary squamous cell carcinoma is determining the site of the primary tumor when a known metastatic node has been identified. The incidence of an unknown primary tumor is between 2% and 8% of all patients with head and neck squamous cell carcinoma. The patient examination shows a mass in the neck with no masses or abnormalities in the upper aerodigestive tract. It is often on an FNAB that the diagnosis of squamous cell carcinoma is made.
Positron Emission Tomography (PET)
The PET scan with a combination of CT scan is now preferred over an MRI as an initial imaging modality. It shows increased glycolytic activity of tumor cells identifying a potential tumor site. PET scans can identify small tumors, typically in the base of the tongue and in the tonsil, which would have otherwise escaped detection. PET/CT combination scans have been used to follow patients after treatment to evaluate for recurrence.
If better imaging is required for a therapeutic intervention, such as surgical planning, an MRI can be advantageous as it allows for better soft-tissue distinction (Figure 28–2).
Coronal T1-weighted MRI showing a cervical metastasis from an unknown primary site.
All patients with unknown primary tumors should undergo an exhaustive search for the primary site so that (1) site-specific treatment can be employed; (2) the area can be closely monitored for recurrence; and (3) treatment morbidity, especially with radiotherapy, is markedly reduced.
The next step in the site search is a direct laryngoscopy with biopsy, esophagoscopy, bronchoscopy, and tonsillectomy. If studies suggest a primary site that can be confirmed on direct laryngoscopy, a directed biopsy is often sufficient for the diagnosis. It is more likely that no abnormalities are noted and blind biopsies are obtained. The typical sites harboring a primary cancer are in the nasopharynx, the palatine tonsil, the base of tongue, and the pyriform sinus. The mucosa can be easily biopsied from the nasopharynx, the base of tongue, and the pyriform sinus. A tonsillectomy should be performed rather than just a biopsy as 18–26% of patients can harbor a primary tumor in the tonsil.
The staging of neck tumors is based upon the system created by the American Joint Committee on Cancer. This system takes into account the number and size of lymph nodes in the neck; a portion of this staging system is shown in Table 28–2.
Table 28–2. Staging of Regional Lymph Node Metastasis. |Favorite Table|Download (.pdf)
Table 28–2. Staging of Regional Lymph Node Metastasis.
|Nx||Regional lymph nodes cannot be assessed|
|N0||No regional lymph nodes|
|N1||Single ipsilateral lymph node, <3 cm|
|N2a||Single ipsilateral lymph node, 3–6 cm|
|N2b||Multiple ipsilateral lymph nodes, none >6 cm|
|N2c||Multiple bilateral or contralateral lymph nodes, none >6 cm|
|N3||Lymph node >6 cm|
The treatment of patients with an unknown primary tumor has been controversial. While the necessity of treating the neck is undisputed, the order of surgery and radiation therapy is debated, as is the extent of the surgery needed. Some clinicians advocate primary radiotherapy with surgery to follow, while others promote primary neck dissection with postoperative radiation therapy. The advantage of primary radiotherapy is that all potential tumor sites can be treated and the neck mass may decrease in size to facilitate or in some cases avoid the neck dissection. The advantage of primary surgery is that a lower total dose of radiation may be given to the neck to prevent some complications of radiation therapy.
The need to treat all potential primary sites also is debated. Wide-field radiation therapy to encompass all potential mucosal sites carries significant morbidity, though intensity-modulated radiotherapy (IMRT) does reduce the toxicity to vital structures such as the parotid glands, optic nerve, and spinal column. Proponents of this treatment maintain that wide-field radiation therapy decreases the risk of future tumor emergence. The emergence rates of primary tumors are estimated to be 3–8% a year in patients with primary sites treated with radiation, compared to a 32–44% in patients who do not undergo this treatment modality.
The complications of radiation treatment can be severe and include xerostomia, mucositis, and persistent dysphagia. For large, unresectable tumors, palliation is an option.
Cianchetti M, Mancuso AA, Amdur RJ et al. Diagnostic evaluation of squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site. Laryngoscope
. (Diagnosis should still continue to include a complete examination, imaging with PET/CT and panendoscopy with biopsy.)
Waltonen JD, Ozer E, Hall NC, Schuller DE, Agrawal A. Metastatic carcinoma of the neck of unknown primary origin: evolution and efficacy of the modern workup. Arch Otolaryngol Head Neck Surg
. (A complete examination, imaging with PET/CT and biopsies with tonsillectomy is best for identifying an occult primary.)
Miller FR, Karnad AB, Eng T et al. Management of the unknown primary carcinoma: long-term follow-up on a negative PET scan and negative panendoscopy. Head Neck
. (The risk of identifying a primary tumor after treatment in a patient with a negative PET and negative panendoscopy is less than 6%.)
Frank SJ, Rosenthal DI, Petsuksiri J et al. Intensity-modulated radiotherapy for cervical node squamous cell carcinoma metastases from unknown head-and-neck primary site: M.D. Anderson Cancer Center outcomes and patterns of failure. Int J Radiat Oncol Biol Phys
. (IMRT delivers excellent outcomes in treating the tumor with few severe late complications.)
Chen AM, Li BQ, Farwell DG et al. Improved dosimetric and clinical outcomes with intensity-modulated radiotherapy for head-and-neck cancer of unknown primary origin. Int J Radiat Oncol Biol Phys
. (IMRT is better at reducing treatment related late complications such as xerostomia.)