Salivary+Gland



​ ​Epidemiology: || Tumors of the salivary gland are rare and make up only 4-7% of all cancers of the head and neck region. The parotid gland is the site with the highest incidence of salivary gland tumors (85%). Tumors of the minor salivary gland account for 2-3% of all head and neck cancers, about 75% are malignant. The submandibular gland is involved in about 10% of all instances. 9 || Although some have favored fine needle aspiration to diagnose masses in the head and neck region, the heterogeneity of malignant salivary glands has led to the preference of an open biopsy technique where definitive surgery is performed if the diagnosis is confirmed.
 * Etiology: || Most major and minor salivary cancers are of unknown origin and etiologic factors are poorly understood. Low-dose ionizing radiation in childhood may account for some cases of malignant salivary gland tumors. Risk factors such as dental radiographs have been implicated for both benign and malignant salivary gland tumors. Exposure to hardwood dust has been linked to the development of minor salivary gland adenocarcinomas. The incidence of salivary gland tumors occurs equally between both genders. 9 ||
 * Signs & Symptoms: || Patients most often present with a fast growing, painless mass which is often present for years but the rapid growth sparks the decision to seek medical attention. Only about 10% of patients complain of pain even though as many as one-third of parotid cancers involve the facial nerve. Pain may also be likely with tumors involving deeper structures. Symptoms suggestive of a malignant salivary gland tumor are fast growth rate, pain, facial nerve palsy, childhood occurence, skin involvement, and cervical adenopathy. 1 ||
 * Diagnostic Procedures: || The diagnostic workup of the salivary glands includes a history and physical that includes good attention to signs of local fixation or regional adenopathy. X-rays may be taken if bone erosion is suspected and if they are negative, a bone scan can be done. CT's are very helpful to figure out the extent of the tumor growth and invasion especially the deep lobe. MRI give great detail but are not as good for inflammatory processes or diffuse disease. When a malignancy is suspected, MRI is the best option because the "lesions are highlighted against the hyperintense (fatty) background of the gland."

__**Diagnostic work-up for tumors of the salivary glands**__ General Radiographic Studies --Standard --Specific Laboratory studies In someone with a squamous cell carcinoma of the parotid, one must make sure to rule out a periparotid metastasis from a squamous cell skin cancer of the head or face. Histology plays an important role in survival. 2 || Metastatic spread: || Submandibular gland malignancies commonly present with lymph nodal involvement (44%). Malignant parotid patients present with lymph node metastases as often as 25%. All high grade salivary gland tumors, have a high 49% risk for lymph node metastasis, compared with 7% for intermediate , or low grade tumors. 3  On the face, the lymphatics drain laterally and diagonally posteriorly toward the parotid gland. The frontal region of the scalp, including parts of the eyelids, follow this downward drainage path as well. Lymphatics of the sublingual gland drain to the submandibular nodes and internal jugular chain. 3 
 * <span style="color: #208000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">History
 * <span style="color: #208000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">Physical Examination
 * <span style="color: #208000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">Radiograph of chest
 * <span style="color: #208000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">Craniofacial computed tomography scan
 * <span style="color: #208000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">Bone scan
 * <span style="color: #208000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">Sialogram
 * <span style="color: #208000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">Sinus series (minor salivary glands)
 * <span style="color: #208000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">Panorex of mandible
 * <span style="color: #208000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">Complete blood count
 * <span style="color: #208000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">SMA 12/18 <span style="color: #208000; font-family: 'Times New Roman',Times,serif; font-size: 99%; vertical-align: super;">1 ||
 * Histology: || <span style="color: #008000; font-family: 'Times New Roman',Times,serif; font-size: 110%;">“The most detailed classification of salivary gland malignancies was performed by Batsakis and Regezi. As a working model, one can group these tumors into two major categories:”
 * <span style="color: #008000; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Low Grade which consists of low-grade mucoepidermoid tumors, acinic cell tumors, and low-grade adenocarcinoma
 * <span style="color: #208000; font-family: 'Times New Roman',Times,serif; font-size: 110%;">High Grade which consists of high-grade mucoepidermoid tumors, most adenocarcinomas, carcinomas, pleomorphic adenomas, adenoid cystic carcinomas, malignant mixed tumors, and squamous cell tumors <span style="color: #008000; font-family: 'Times New Roman',Times,serif;">.
 * Lymph Node Drainage and

Diagram below taken from Salivary Glands notes DOS 380.

||
 * Grading: || <span style="color: #0000ff; font-family: Georgia,serif;">The following table is the grading for salivary gland cancer. <span style="color: #0000ff; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">7 <span style="color: #0000ff; font-family: Georgia,serif;">


 * Data form for Cancer Classification - Salivary Glands**
 * Histopathologic Grade**

GX: Grade cannot be assessed G1: Well differentiated G2: Moderately differentiated G3: Poorly differentiated G4: Undifferentiated || TX: Primary tumor cannot be assessed T0: No evidence of primary tumor T1: Tumor less than or equal to 2 cm in the greatest dimension without extraparenchymal extension T2: Tumor more than 2 cm but not over 4 cm in the greatest dimension without extraparenchymal extension T3: Tumor having extraparenchymal exension without seventh nerve involvement and/or more than 4 cm but not greater than 6 cm in greatest dimension T4: Tumor invades base of skull, seventh nerve, and/or exceeds 6 cm in greatest dimension
 * Staging: || <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> Primary tumor (T)

<span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 143%;">Regional lymph nodes (N) <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> NX: Regional lymph nodes connot be assessed N0: No regional lymph node metastasis N1: Metastasis in a single ipsilateral lymph node, less than or equal to 3 cm in greatest dimension N2: Metastasis in a single ipsilateral lymph node, greater than 3 cm but not over 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none over 6 cm in greatest dimension, or in bilateral or contralateral nodes, none greater than 6 cm in greatest dimension N2a:Metastasis in a single ipsilateral lymph node greater than 3 cm but not over 6 cm in greatest dimension N2b:Metastasis in multiple ipsilateral lymph nodes, none over 6 cm in greatest dimension N2c:Metastasis in bilateral or contralateral nodes, none greater than 6 cm in greatest dimension N3: Metastasis in a lymph node, over 6 cm in greatest dimension

<span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 143%;">Distant metastses (M) <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">MX: Presence of distant metastasis cannot be assessed M0: No distant metastasis M1: Distant metastasis



<span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">There is no formal staging system for the minor salivary tumors as of now, but significant local extension or lymph node metastases result in a poor prognosis. <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%; vertical-align: super;">10 || The treatment of choice for parotid tumors is surgery. For parotid tumors, surgery at minimum consists of a gross tumor removal through superficial ot total paridectomy depending onthe tumor location and size. Surgery alone is sufficent for low grade malignacies. Higher- grade tumors necessitate removal of the lymph nodes in continuity with the gland. In the case of positive neck nodes, a more complete neck disection is required. Surgical managment of submandibular tumors consists of a regional disection of the submandibular triangle, including the gland and the adjacent submandibular, submental and facial lymph nodes. extensive disease may require removal of additional structures such as muscle, mandible, or a portion of the floor of mouth. In the case of clinically apparent adenopathy, more extensive lymph node dissection, the details of which are dictated by the extent of nodal disease, is necessary. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">5 For minor salivary glands tumors, the location of the primary tumor and the extent of tumor involvement determine the extent of resection. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">3
 * Radiation Side Effects: || <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">The most notable complication of treatment of parotid malignancies is facial nerve paralysis, which often is caused by the initial surgery. Other side effects sometimes seen may include salivary fistulas and neuromas of the greater auricular nerve. Partial xerostomia after radiation in frequently observed and may be permanent. <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%; vertical-align: super;">10 ||
 * Prognosis: || Local control with conventional fractionated radiation therapy is only about 25%. Survival is influenced most by tumor grade, postsurgical residual disease, tumor size, facial nerve invasion, and presence of positive cervical nodes. 9,3 ||
 * Treatments: || __**Surgery**__

The role of chemotherapy has not been defined in malignant major and minor salivary gland cancers. Single agents such as 5-fluorouracil, hydroxyurea, methotrexate, cisplatin, bleomycin, doxorubin and cyclophosphamide have shown limited response rates. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">5
 * __Chemotherapy__**

-Radiation therapy is indicated for 1) high grade tumors, 2) positive margins, 3) perineural involvement, 4) positive neck nodes, or 5) recurrent disease. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">4
 * __Radiation Therapy__**

-For parotid cancers that involving the superficial lobe or the deep lobe in thin patients whom the target volume is 5 cm or less deep, a **combination of photons and electrons** can be used. A intraaoral device is used to shield the oral tongue and the contralateral oral mucosa. The external auditory canal is filled with water or wet gauze before each treatment. A lateral neck field is used to cover the parotid bed and upper neck nodes. The field borders include the zygomatic arch or higher, as indicated by tumor extension or scars superiorly. Anteriorly, the anterior edge of the masseter muscle is identified. Inferiorly, the thyroid notch is used. The field extends posteriorly just behind the mastoid process. The dose is delivered with a combination of electrons and photons, energy and dose ratio determined by planning system. An off cord reduction is made to limit the spinal cord to 45 Gy, and the posterior portion of the neck is supplemented using lower energy electrons. Another field reductioin is made after 60 Gy in 30 fractions to deliver a boost dose when indicated. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">5
 * __Parotid Gland__**


 * -Oblique Wedge Pair Technique**- Anterolateral and posterolateral oblique photon fields are used for deep-seated tumors or when the facial canal is part of the target volume. The anterolateral oblique field is on the spinal cord but off the spinal cord and off the oral cavity and contralateral parotid gland, and the posterolateral oblique field is off the spinal cord and off the contralateral parotid gland but exits through the oral cavity. An appositional electron field or AP photon field is used to treat the middle and lower neck nodes when indicated. No off-cord reduction is required for the wedge pair techniquebecause the fields are off the spinal cord the entire time. A field reduction for a boost is made after 60 Gy when indicated. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">5

-Typical ipsilateral postoperative target volumes can tolerate 2.0 Gy fractions to 60 Gy. Areas at high risk because of incomplete resection recieve 66 to 70 Gy in 33 to 35 fractions. The dose for elective neck irradiation is 50 Gy in 25 fractions. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">5 Figure 1: Typical Parotid Tumor Borders. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 80%; vertical-align: super;">4

Figure 2: Parotid field. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 80%; vertical-align: super;">6

Figure 3: Parotid Field on Skin. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">8

-The intial target volume includes the surgical bed for low-grade cancers with indications for postoperative radiation therapy. The target volume includes the surgical bed, the entire ipsilateral neck for high-grade cancers and cancers with lymph node metastases. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">5
 * __Submandibular glands__**

-Ipsilateral irradiation is sufficent for most patients. This technique can be accomplished with either a mixture of electrons and photons or an oblique wedged pair similar to that used in parotid cancer. Opposed anteropoterior-posteroanterior or opposed tangentials fields can also be used, depending on optimal tumor coverage given the tumor extent and the desire to aviod irradiation of uninvolved normal structures. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">5

Figure 4: Submandibular Field with neck node irradiation. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">8 The intital target volue for minor salivary gland cancers includes the primary tumor or surgical bed for small or low-grade cancers with indications for radiation therapy. Primary tumor/ surgicall bed and lymph nodes are included in high-grade cancers and those with lymph node metastases. Elective neck treatment varies with histological features, grade, and anatomic site of the primary cancer. Dose guidelines are the same as for the parotid and submandibular gland cancers. Specialized boost techniques such as intraoral cone of interstital or intracavitary implant are site specific. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">4
 * __Minor Salivary Glands__**

11 <span style="color: #208000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">3 3 3 || Additional TD 5/5 include the TMJ/mandible and oral cavity at 60 Gy. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">4 || 2. Rubin P//.// Clinical Oncology: A Multidisciplinary Approach for Physicians and Students. 8th edition. Philadelphia, PA: W.B. Saunders Company. 2001: p. 451. <span style="color: #0000ff; font-family: Georgia,serif;">3. Chao C, <span style="color: #0000ff; font-family: Georgia,serif;">Perez CA, Brady LW. //Radiation Oncology Management decisions// //. <span style="color: #0000ff; font-family: Georgia,serif;">second edition. Philadelphia, PA: Lippincott Williams & Wilkins. 1999; 213-215. // 4. Dasher, BG & Vann, AM. //<span style="font-family: 'Calibri','sans-serif';">Portal Design in Radiation Therapy //. 2nd edition. Philadelphia, PA: DWV Enterprises. 2006: 53-55.. 5.  Gunderson, LL & Tepper, JE. (Eds.) //<span style="font-family: 'Calibri','sans-serif';">Clinical Radiation Oncology //. 2nd edition. Philadelphia, PA: Elsevier, Churchill & Livingstone. 2007: 786-794.  6. Bentel, GC. //Radiation Therapy Planning//. 2nd edition. New York, NY:McGraw-Hill companies. 1996: 313 <span style="color: #0000ff; font-family: Georgia,serif;">7. Frontiers in Bioscience. http://www.aciniccell.org/stage_grade_sub8.html. accessed Jan. 13, 2110. 8 . Cox, JD & Ang, KK. //Radiation Oncology Rationale, Technique, Results.// 8th edition. St. Louis, MS: Mosby, Inc. 2003:145-156. 9. Washington,C.M & Leaver, D.(Eds.).(2004). //Principles and Practice of Radiation Therapy// (Second ed). St. Louis, Missouri; Mosby Inc: pg. 712-713. <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 121%;">10. <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Chao C, Perez CA, Brady LW. Radiation Ocology Management Decisions <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 121%;">//.// <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 131.76%;">2nd ed. <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;"><span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 99%;">Philadelphia, PA: Lippincott Williams & Wilkins. 1999//;// 216, 219.   11. Parotid RT. Dwights Blog on Radiation Treatments for Recurrent Pleomorphic Adenoma. Available at: []. Accessed Januaryy 17, 2010. ||
 * TD5/5: || [[image:td55parotid.jpg width="364" height="230"]]
 * References: || <span style="color: #208000; font-family: 'Comic Sans MS',cursive; font-size: 110%;">1. Perez CA, Brady LW, Halperin EC, Schmidt-Ullrich RK. //Principles and Practice of Radiation Oncology.// 4th edition. Philadelphia, PA: Lippincott Williams & Wilkins. 2004: p. 978-979.