Jamie Poust, PharmD, BCOP

  • Oncology Pharmacy Specialist, University of Colorado Hospital, Aurora, Colorado

Enlargement of the submandibular nodes can be difficult to distinguish from a primary tumor of the submandibular gland allergy treatment medications safe seroflo 250 mcg, and a metastatic process within these nodes may also invade the adjacent gland by direct extension allergy shots vancouver quality seroflo 250 mcg. Similar to the parotid allergy medicine zantrex order discount seroflo online, the submandibular gland lies in anatomical proximity to the facial nerve allergy symptoms night sweats buy seroflo with mastercard. The marginal mandibular branch runs along the inferior border of the mandible allergy notes cheap generic seroflo canada, just deep to the platysma muscle and lateral to the fascia of the gland allergy treatment honey buy seroflo 250mcg line. They are located deep to the mucosa of the floor of the mouth and drain directly into the oral cavity through numerous small ducts. Tumors of the sublingual glands can be difficult to distinguish from those arising within the submucosal minor salivary glands of the floor of the mouth. Minor Salivary Glands There are over 600 minor salivary glands distributed throughout the length of the upper aerodigestive tract, and approximately half of them are located on the hard palate. Tumors can arise in these glands in such diverse sites as the oral cavity, oropharynx, larynx, pharynx, nose, nasopharynx, and paranasal sinuses. Additionally, small rests of heterotopic salivary tissue can be located within the cervical lymph nodes, mandible, thyroid gland, and the middle ear. The likelihood of a submandibular gland lesion being benign is much less, around 43%. Relative ratio of benign versus malignant salivary neoplasms at various anatomic sites. The basic functional unit of a salivary gland is an acinus, made up of serous and mucinous cells. The acini release their secretions into an intercalated duct, which later becomes a larger striated duct, which eventually empties into an excretory duct. The submandibular and sublingual glands are both mixed, but the serous component predominates in submandibular glands, whereas the mucinous element is dominant in sublingual glands. According to the multicellular theory, each cancer arises from a particular cell type within the secretory unit. According to this model, pleuripotent intercalated duct basal cells give rise to salivary neoplasms of adenomatoid origin (pleomorphic adenoma, oncocytic tumors, acinic cell and adenoid cystic carcinomas). The epidermoid tumors (squamous cell and mucoepidermoid carcinomas) are then thought to be derived from the excretory duct reserve cells. Cutaneous carcinomas and melanomas of the scalp and face often drain into intraparotid lymph nodes and comprise 70% to 80% of metastases to intraparotid lymph nodes. The frequency of encountering a certain neoplasm depends on the specific anatomic subsite of interest. Mucoepidermoid carcinoma is the most commonly encountered cancer in the parotid gland, whereas the submandibular gland is more likely to give rise to adenoid cystic carcinoma. Both entities occur at approximately the same rate within the minor salivary glands, followed by adenocarcinoma. The significance of both hereditary and environmental influences has been proposed. For example, a higher incidence of salivary gland tumors has been shown in some ethnic groups, such as Eskimos. Despite these reports, a clear understanding of the etiology of salivary tumors remains elusive. The symptoms that arise from minor salivary gland tumors depend upon the anatomic regions involved. Thus, cancers of the paranasal sinuses can cause facial pain and/or swelling, whereas cancers of the nasal cavity can lead to obstruction of the nasal passages and/or epistaxis. Cancers of minor salivary glands of the oral cavity can lead to a mass effect, which can result in ill-fitting dentures. Cancers arising in the larynx commonly present with hoarseness and/or sore throat. Sun exposure and the presence of current or previously excised skin lesions should be ascertained when squamous cancer or melanoma is found in parotid lymph nodes. Pain is more common in patients with malignant compared to benign salivary gland neoplasms. Salivary lesions of the parapharyngeal space, however, may not be palpable; hence, the lateral pharyngeal walls should be examined transorally for asymmetry. Although facial nerve paresis or paralysis is present in fewer than a quarter of cases, it is generally associated with a poor prognosis. Cervical lymph nodes are found to be positive at presentation in ~13% to 25% of patients with cancers of the parotid,28,39,43,48 14% to 33% of patients with cancer of the submandibular gland,41,49,50 and 14% in patients with cancers of the minor salivary glands. Most minor salivary gland tumors require radiographic evaluation to better delineate the extent of disease, including the involvement of adjacent structures. A thorough history and physical examination are generally sufficient to establish the diagnosis and extent of a tumor in the major salivary glands. Imaging is usually warranted to define the extent of the primary cancer as well as the presence of any regional metastases. This is particularly true of deep lobe parotid tumors extending into the parapharyngeal space. Several imaging modalities are available as adjuncts in evaluating a tumor of the salivary glands. In expert hands, ultrasonography is an appropriate initial step in evaluation of the major salivary gland tumors and the status of the neck. Ultrasonography also allows for precise localization of the tumor within the gland and readily differentiates between cystic and solid components, thereby enabling accurate fine needle aspiration or core biopsy. Heterogeneous echogenicity, ill-defined margins, and extension beyond the borders of the gland with involvement of adjacent structures are ultrasonographic signs of a malignant process. Irregular borders, extraglandular extension, and hypointensity on T2-weighed images are suggestive of malignancy. This is due to the fact that some benign salivary gland lesions, such as pleomorphic adenomas and Warthin tumors, are capable of high glucose uptake. Up to one-third of patients can be spared an unnecessary operation and risk to the facial nerve. For differentiation between a benign and malignant salivary lesion, the positive and negative predictive values were 90% and 94%, respectively. The concordance rates are lower for particular histologic types of salivary tumors: 63% for mucoepidermoid carcinomas and 70% for adenoid cystic carcinomas. Small-volume care center providers should maintain a low threshold for pathology consultation within large academic institutions. Histologic architecture is preserved within the sample provided by the larger needle used (14 to 21 gauge). Also, larger tissue sample size eliminates the need for a cytopathologist to assess the specimen adequacy. Staging Oncologic staging is critically important in the assessment of disease extent, prediction of prognosis, formulation of a treatment plan, and follow-up evaluations. It is an integral tool in communication between the treating surgeon and the patient and within the clinical and research medical communities. A study from Memorial Hospital demonstrated that the staging system used for squamous carcinoma of the upper aerodigestive tract can be used in evaluation of the minor salivary gland malignancies arising in the same anatomic regions and has a similar prognostic value. Pathology Mucoepidermoid Carcinoma Mucoepidermoid carcinoma is the most common cancer of salivary gland origin. The key morphologic feature is multicystic arrangement of mucous and epidermoid cells. Based on the proportion of cystic component, neural invasion, degree of anaplasia, mitoses, and presence of necrosis, mucoepidermoid carcinomas are classified into lowgrade, intermediate-grade, or high-grade categories. In high-grade mucoepidermoid carcinomas, the glandular structure is less defined or may be absent altogether. These tumors have a propensity for early and aggressive spread, with a rate of regional metastasis up to 70%. Adenoid Cystic Carcinoma Adenoid cystic carcinoma is the most common cancer of the submandibular gland, and it is as common as mucoepidermoid carcinoma in the minor salivary glands. It most commonly presents as a slow-growing mass and can be associated with pain, due to its propensity for neural invasion and lack of a capsule barrier. The lung is the primary site for distant metastases; however, patients can often live for many years with asymptomatic pulmonary metastases that remain stable or progress slowly. Predominantly, tubular and cribriform lesions tend to be less aggressive than tumors with >30% solid component. Also, the survival decreases significantly from 5 to 10 years after treatment, which warrants a long-term surveillance in these patients. These cancers manifest as a rapidly growing mass and occur in patients over 50 years of age, with a male to female ratio of 4:1. Most patients present with advanced stage disease: one-third of them suffer recurrence, 46% develop distant metastases, and 65% die of the disease, usually within 4 years of diagnosis. The malignant component usually features a poorly differentiated adenocarcinoma or an undifferentiated carcinoma. Despite its overall good prognosis, the potential of local recurrence or distant metastases exists, especially in advanced stage or improperly treated tumors. Lymphomas of the salivary glands arise either from intraglandular lymph nodes (nodal) or from the nondiscrete lymphoid tissue within the gland parenchyma (extranodal). Although extranodal lymphomas affect salivary glands in only ~5% of cases, the overwhelming majority of these occur in the parotid gland. Lymphoma of the salivary glands either can be the only manifestation of the disease in primary cases or can also be a part of a disseminated lymphomatous process. Therefore, every patient with a parotid mass with cutaneous histology should undergo careful examination of the skin of the head and neck. Involvement of the salivary glands by the distant infraclavicular metastatic cancers is extremely rare. When it does occur, the parotid gland is most commonly affected, and the most common sites giving rise to these metastases are the lung, kidney, and breast. In order to guide the prognostic and management decision making, it was proposed to grade salivary tumors based on their clinical behavior. The association between tumor histology and local, regional, and distal control and overall outcomes has been demonstrated. For instance, grading is the most important consideration in prognosis and management of mucoepidermoid carcinoma. Surgical excision is sufficient for low-grade cancers, rendering an overall 5-year survival of over 90%. However, for high-grade cancers, overall survival drops below 50% and adjuvant radiation and neck dissections are required. Based on the constructed Cox models, this intermediated group has an individual prognostic value: One step elevation from low- to intermediateto high-risk level resulted in 2. Molecular Alterations Malignancy in Salivary the goal of analysis of molecular oncologic details is to identify diagnostic biomarkers and markers prognostic of clinical behavior and to broaden the spectrum of potential therapeutic targets and therapies. For example, mutations in genes responsible for chromatin-state regulators were identified, which may suggest chromatin deregulation as the inciting event for carcinoma development. The next few paragraphs will review the details of surgical management for both major and minor salivary glands, indications for neck dissection, and usefulness of intraoperative frozen section analysis. Parotid Gland A general thought process when considering treatment options for patients with cancer of the salivary glands is summarized in Table 21. Surgery remains the primary treatment modality for primary and/or regionally metastatic cancer of the parotid gland. The minimum operation appropriate for early-stage cancers is lateral or superficial parotidectomy with dissection and preservation of the facial nerve. More extensive cancers may require more extensive operations with resection of adjacent structures, such as portions of the mandible, zygoma, temporal bone, overlying skin, and facial nerve. Unless there is gross infiltration of the nerve by the tumor, every attempt at preservation should be made. When planning the management of the facial nerve, histologic characteristics of the cancer must be taken into consideration. Submandibular and Sublingual Glands En bloc resection of the entire submandibular triangle for cancer of the submandibular gland has been popularized in the earlier literature. For small early-stage cancers confined to the submandibular gland, a simple excision of the gland may be adequate. For a more extensive cancer, a more anatomically aggressive operation may be needed with resection of the adjacent lymph nodes, overlying skin, nearby muscles, lingual and/or hypoglossal nerve(s), bone, and the floor of the mouth. The extent of such resection is a balance between optimal oncologic result and optimal functional outcome. Minor Salivary Glands the surgical approach to the management of cancer of minor salivary origin is location specific. An individualized and tailored to the patient and tumor characteristics surgical approach and operation are chosen. Neck Dissection Metastases of cancer of the salivary glands to the regional lymph nodes have an adverse impact on prognosis. For cancers of the major salivary glands, the reported rates of cervical lymphatic involvement are between 14% and 25%. Although cervical metastases are present in 10% of cancers arising within minor salivary glands of the oral cavity, this number rises to 33% for pharyngeal and laryngeal sites of origin. The histology of the cancer and its anatomic dimensions determine the rate of occult metastases. Intraoperative Frozen Section Analysis Advocates of the intraoperative use of frozen section pathologic analysis in surgery for cancer of the salivary glands find it useful in planning of the extent of local resection and the need for elective neck dissection. The accuracy of the analysis was found to be consistent across a number of study centers.

Sabin allergy medicine gsk discount seroflo online visa, Sandeep Samant Introduction Epidemiology It is estimated that 15 allergy forecast worcester ma buy generic seroflo 250 mcg,780 new cases of cancer and 1 kaiser oakland allergy shots cheap seroflo 250 mcg visa,960 cancer-related deaths occurred among children and adolescents below age 20 in the United States in 2014 allergy relief radiance remedies cheap seroflo express. Dominant histologic categorizations included lymphoma (27%) allergy forecast jacksonville nc buy discount seroflo 250mcg line, neural tumors (including neuroblastoma and retinoblastoma allergy symptoms cigarette smoke buy seroflo 250 mcg cheap, 23%), thyroid cancers (21%), and soft tissue sarcomas (12%). Unlike cancers of the head and neck among adults, squamous cell carcinomas in pediatric patients are rare, accounting for fewer than 2% of cases. Among children and adolescents above age 10 years, dominant malignancies of the head and neck include thyroid cancer, Hodgkin and non-Hodgkin lymphoma, and melanoma. Of note, clinical reviews of malignancies of the head and neck do not consistently include important differential diagnoses such as retinoblastoma in the pediatric age group, and leukemia presenting with chloromas. In addition to primary cancers arising in the head and neck, conditions such as malignant germ cell tumor, lymphoma, and neuroblastoma may also metastasize to the nodes, soft tissue, or bones of the head and neck. Secondary malignant tumors of the head and neck, that is, those resulting from prior therapy including radiation therapy and alkylating chemotherapy agents, account for about 0. Conditions to be considered include lesions primarily arising in the head and neck, those that are metastatic to the head and neck, and secondary malignancies. Primary head and neck lesions can include congenital or developmental lesions, inflammatory or infectious masses, benign tumors, or malignant tumors (Table 24. Assessment of a child with a mass in the head and neck should start with a detailed clinical, past medical, and family history, immunization history, and recent and current medications. History should detail the onset, nature, and timing of any changes associated with the mass, along with potential exposures and risk factors for infection. Congenital or developmental lesions may first be evident in the early postnatal period, but in some cases they can manifest later in life, with gradual growth over time or with concomitant secondary infection. Benign tumors can similarly sometimes be brought to medical attention in the setting of concurrent infection. Whereas inflammatory/infectious etiologies are typically first considered for masses that acutely enlarge and are associated with acute fever, tenderness, or skin changes such as erythema or warmth, red flags should prompt consideration of an underlying malignancy. Relevant clinical and functional impairments to assess on history and to observe on examination may include abnormal eye movements; distorted vision; proptosis; Horner syndrome; cranial nerve palsies; paresthesias; recurrent epistaxis; increasing nasal congestion; evidence of recent suspected/confirmed infections; loss of smell; stridor; dysphagia and odynophagia; impaired gag; trismus; deviated tongue; dental health; change in tooth position; change in voice or hoarseness; otorrhea; progressive tinnitus or hearing loss; otalgia; vertigo; neck tilt or torticollis; facial and/or neck swelling; deviated trachea; increased vascular markings, pulsatility, or overlying skin changes; or features of hypothyroidism or hyperthyroidism. Physical examination should also include evaluation for movement of the mass with tongue protrusion. Any concern for potential airway compromise must be immediately evaluated and managed as an oncologic emergency. As tumors in the head and neck may expand into cavities such as the maxillary sinus with relatively limited innervation, pain is not necessarily a dominant symptom and more likely becomes prominent with nerve compression or periosteal impingement. Once oncologic emergencies have been ruled out or definitively managed, a broad differential diagnosis should be considered. Targeted laboratory studies should be considered to further evaluate suspected conditions based on initial history and physical examination. Targeted imaging should also be considered to help with diagnosis and further management planning, with sample modalities outlined in Table 24. These can include situations when one suspects a mediastinal mass, an oncologic emergency that requires care in patient positioning during the evaluation, as well as for suspected lesions extending into the chest or for gross metastatic disease. Key considerations for imaging in children with head and neck malignancies are outlined in Table 24. Primary presentations of the same diagnosis outside of the head and neck may also preferentially warrant other modalities. Early consultation with a multidisciplinary specialist team, including providers in pediatric surgery and pediatric hematology/oncology, is warranted for any concerns of potential malignancy. Functional sequelae to be considered and optimally prevented may include more immediate concerns involving compromised swallowing and the risk of aspiration or ophthalmologic complications,21 as well as longer-term implications of the cancer or therapy on orofacial development and dentition,22,23 jaw function,24 cosmesis, and cognitive function. For instance, patients with a history of dysphagia would benefit from clinical bedside swallowing evaluation by speech language pathologist, as well as barium swallow examination if clinically indicated. Vigilant supportive care is also required to evaluate and address the known toxicities of cancer therapy that may be exacerbated by the location of the tumor of the head and neck, including oral mucositis. Young patients require nutritional and growth monitoring and may benefit from feeding tubes for enteral nutrition as well as for selected administration of medication. As many effects of the cancer therapy may initially become manifest or progress months or years beyond the treatment period, long-term follow-up for potential late effects is warranted. Updated general guidance for the core personnel and resources essential to provide care for children and adolescents with cancer has been recently articulated by the American Academy of Pediatrics. Outcomes for children with malignancy have been demonstrated to be better when core management is at least initiated by specialist pediatric cancer centers. Typical specialist multidisciplinary team members engaged closely with families of children with malignant masses in the head and neck should include pediatric physicians, nurses, pharmacists, social workers, and other allied health team members working in hematology/oncology; surgery, otolaryngology, and neurosurgery; ophthalmology; dental oncology and orthodontics; radiation oncology; plastic and reconstructive surgery; radiology and diagnostic imaging; pathology; nutrition; speech/language pathology; and child life. In many cases, the expert consultative input of other pediatric team members in anesthesiology, critical care, endocrinology, genetics, infectious diseases, neurology, ocular prosthesis, palliative care, psychology, rehabilitation specialists including occupational and physical therapy, and team members experienced in late effects of therapy is also invaluable. In all cases, the pediatric patient, the family, and the community-based or primary care team members engaged by the family remain central partners with the multidisciplinary specialist team in decision-making and family-centered care delivery. Surgical Considerations: An Overview Surgical management of pediatric age group cancer of the head and neck has undergone many significant changes during the past two decades. Most of these changes have occurred as a result of technologic advances, including better imaging, more precise delivery of radiation, advances in surgical technique, and a better understanding of anatomy. The improved understanding of anatomy has had its greatest impact on the development of better and more reliable reconstructive techniques that allow us to perform surgery that, in the past, would have been impossible. We can now be more certain that the defects that we create surgically can, for the most part, be reliably reconstructed. However, in the pediatric age group, cancer of the head and neck is uniquely affected by the need to account for the growing and developing facial skeleton and associated structures. Evaluation for surgery is first dependent on accurate tissue diagnosis, requiring incisional or excisional biopsies for the vast majority of solid tumors. Exceptions include salivary or thyroid masses, for which fine needle aspiration is an option. Unlike in cancer in adults, pediatric resections must balance the extent of surgical resection with functional and aesthetic concerns, and thus, radical resection with negative margins (R0) resections is not always possible. Some pediatric tumors, in fact, are so responsive to nonsurgical therapies or are so indolent in nature. As with adult malignancies, patients are frequently candidates for either chemotherapy and/or radiation therapy in either a neoadjuvant or an adjuvant setting. Finally, reconstructive concerns share many similarities with cancers in adults, but have specific differences with regard to the developing pediatric facial skeleton and associated structures. Role of Radiation Therapy: An Overview Radiotherapy is a critical component of the multimodality management in the pediatric age group of cancer of the head and neck. Although some tumors involving the head and neck are surgically accessible, complete extirpation of lesions occupying anterior craniofacial spaces or the base of the skull is often impossible without significant morbidity necessitating a management plan that relies on nonsurgical modalities either as surgical adjuncts or for definitive tumor control. Microscopic residual disease is a source of local failure that can be addressed via the use of adjuvant radiotherapy or chemoradiotherapy. Clinical studies of pediatric head and neck cancer seek optimal combinations of multimodality therapy in order to reduce late effects while simultaneously increasing rates of long-term disease control. Conformal radiotherapy with or without intensity-modulated radiation therapy has been the primary mechanism of radiation dose delivery during the past two decades. Although some advances, like respiratory gating and breathing management (deep inspiration breath hold), have been developed to address organ and target volume motion, most treatment of the head and neck in the pediatric age group can be accomplished without resorting to these specialized measures. Frequently, these tumors afflict young children and infants requiring sedation to achieve adequate immobilization suitable for treatment. Most institutions choose to sedate with propofol and avoid airway management when possible, although occasional management of the airway is required to ensure patient safety through a full course of radiation, as determined by the anesthesiologist. Although a major objective of proton therapy is reduction of toxicity, protons do not inherently promise a more efficacious means of disease control (unless normal tissue sparing through improved tumor targeting is enhanced such that dose escalation of residual tumor can result in improved disease control). Proton therapy requires prospective study design to provide evidence for the appropriate indications and degree of benefit that may be obtainable. The mainstay of therapy is multimodal, including multiagent systemic chemotherapy for all patients and either radiation therapy, surgery, or both, as local control for most patients. Across the pediatric age spectrum, outcomes for patients who have rhabdomyosarcoma have improved since 1975, with 5-year survival rates increasing by more than 10% to ~65% or higher for patients younger than 15 years old and to ~50% for patients 15 to 19 years old. The embryonal subtype is the most common among children, noted in approximately two-thirds of the patients, with common locations including the head and neck and the genitourinary tract. Botryoid and spindle cell variants of embryonal rhabdomyosarcoma have a particularly favorable prognosis. Within the head and neck, rhabdomyosarcomas are further classified as originating from the orbit (including eyelid), parameningeal (including middle ear/mastoid, nasopharyngeal/nasal cavity, paranasal sinus, parapharyngeal region, and pterygopalatine/infratemporal fossa), or nonparameningeal sites (including the scalp, ear lobe, parotid, oropharynx, and hypopharyngeal region). Standard prognostic factors include age (best age 1 to 9 years), primary site (favorable sites including orbit, nonparameningeal head and neck, genitourinary sites excluding bladder and prostate, and biliary tract), tumor size (smaller, 5 cm better), tumor resectability, disease spread (better prognosis with localized disease without regional lymph node involvement or distant metastases), and tumor histopathology (embryonal more favorable than alveolar subtype). Rhabdomyosarcomas of the head and neck have a variable imaging appearance but are often heterogeneous and may contain areas of necrosis and/or hemorrhage. A recent review of more than 1,600 children with rhabdomyosarcoma from 1991 to 2004 on intergroup studies suggested that staging procedures can be adapted in an algorithmic fashion based on presenting clinical factors, such that patients at low risk of distant metastatic disease-approximately one-third of patients-may be spared bone marrow studies and bone scans. Comprehensive staging of rhabdomyosarcoma in children typically involves designating a stage (Table 24. The nature and intensity of treatment, and subsequent outcomes, depend on appropriate staging and pathologic delineation of rhabdomyosarcomas, including tumor biology. In comparison with children and adolescents with rhabdomyosarcoma, adult patients are more likely to present with disease in unfavorable primary sites, and exhibit pleomorphic histology, which is rarely seen in the pediatric population. For patients who initially present with localized rhabdomyosarcoma, preventing local recurrence with surgery and/or radiotherapy remains vital. Local therapy for rhabdomyosarcoma follows an approach of risk-adapted therapy with selection of modality (surgery vs. Maximal safe resection is performed at diagnosis when possible, followed by systemic therapy and additional local control measures including radiation therapy and additional surgery as determined by tumor histology, resectability, and the status of the surgical margins. Second-look surgery is an acceptable approach in order to balance outcome with toxicity. Defining appropriate patients for postoperative adjuvant radiotherapy remains somewhat controversial. Historically, patients have been selected for adjuvant radiotherapy based on histology (alveolar vs. Aggressive primary surgical approaches are not recommended, as attempts to debulk the tumor (with gross residual tumor) are not associated with improved outcomes compared to biopsy alone. For nonparameningeal and nonorbital rhabdomyosarcomas of the head and neck, such as those with superficial facial tumors, primary tumor excision (accepting narrow margins due to anatomy) and ipsilateral neck sampling of clinically concerning nodes can be considered. The detection of viable tumor at the time of second-look surgery has not been found to impact overall survival. Patients with parameningeal rhabdomyosarcoma are typically associated with poorer prognosis. Urgent management typically includes earlier initiation of radiation therapy, with incomplete or longer-term clinical neurologic recovery from cranial nerve palsies possible. Wide local excision was favorably associated with event-free survival for localized tumors. Axial (A) and coronal (B) T2-weighted images through the neck of a 7year-old child show a heterogeneous, fairly well-marginated mass (arrows) involving the retrostyloid parapharyngeal space. Axial fat-saturated T2-weighted (A) and coronal postgadolinium fatsaturated T1-weighted (B) images of the neck of a 27-year-old survivor of childhood neuroblastoma demonstrate a mildly heterogeneous well-defined mass in the left parapharyngeal space. Rates for event-free and overall survival at 10 years were 53% and 63% respectively. High grade, large size (>5 cm), invasiveness, and gross residual disease after surgery were associated with worse prognosis. Bone Sarcomas and Related Tumors Pediatric bone sarcomas of the head and neck are generally rare and typically are localized at diagnosis. Complete surgical resection remains the foundation for improved failure-free and survival outcomes. The presentation of Ewing sarcoma in the head and neck is heterogeneous and can involve varied parts of the skull. Ewing sarcoma may also present in the soft tissues, cutaneously and subcutaneously, as extraosseous lesions constituting the established Ewing sarcoma family of tumors, with reported pediatric cases in the head and neck. Systemic chemotherapy, coupled with surgery and/or radiation therapy, is typically a mainstay in management, with a less clearly defined role for aggressive surgery as compared to the use of surgery in the management of osteosarcoma or other bone sarcomas of the head and neck in children. Sagittal (C) and axial (D) postgadolinium T1-weighted images reveal diffuse mildly heterogeneous enhancement within the mass. Chondrosarcoma can also occur in children and adolescents and is usually low grade, but can also include higher-grade and aggressive subtypes. The mainstay of therapy is typically surgical resection, with exploration of radiation therapy and chemotherapy in selected cases. The lesion extends into the left nasal cavity and left orbit and through the left side of the hard palate. C: A fat-saturated T2-weighted image demonstrates hyper- and hypointense areas within the mass (arrows) that correspond to noncalcified and calcified tumor components respectively. D: A postgadolinium fat-saturated coronal T1-weighted image shows heterogeneous enhancement of the tumor (arrows) which, after resection, was determined to be a mesenchymal chondrosarcoma. Concurrent research has focused on the search for prognostic indicators for the purpose of patient risk stratification. Surgery has been considered the mainstay of treatment, with studies indicating that local recurrence rates after surgical resection range from 10% to 80%, when margins are negative or positive, respectively. Chemotherapy may be used for tumors that are unresectable, recurrent, or whose surgical removal would result in significant morbidity. Although most defects could be closed primarily, head and neck defects, in particular, more frequently required flap closure. Similarly, long-term issues with appearance, facial nerve function, and functional outcomes including dental rehabilitation were more common in lesions in the head and neck. The trend of delivering low-dose irradiation to sites with gross disease remained standard for many years, until the advent of effective systemic chemotherapy. In the interim, Henry Kaplan and Saul Rosenberg helped to optimize survival outcomes with radiotherapy.

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Tracheal resection and reconstruction have limited application for tumors that involve the trachea secondarily allergy relief for dogs best seroflo 250mcg. The detailed management of thyroid cancer is discussed separately in this textbook; however allergy itchy skin buy seroflo online now, a recent publication suggests that with a variety of resection techniques and adjuvant radiotherapy new allergy treatment 2012 purchase seroflo with amex, overall survival in this population of patients is 79% and 71% at 3 and 5 years allergy treatment systems inc buy generic seroflo 250mcg online, respectively allergy treatment breastfeeding purchase 250 mcg seroflo. Generally dog allergy symptoms uk generic 250 mcg seroflo free shipping, resectability includes patients with tumor involving <50% of the length of the trachea without significant involvement of extratracheal structures including the esophagus and mediastinal structures. In the setting of a resectable lesion, the primary treatment options include primary surgery alone, surgery and postoperative radiotherapy or chemoradiation, and primary chemoradiation without surgery. Neoadjuvant or preoperative radiotherapy is usually not indicated as it may compromise wound healing, a particularly important issue in the setting of trachea resection. In patients with adenoid cystic carcinoma, the degree of radicality needs to be evaluated carefully. This group of patients will have a long survival and a high rate of distant metastases regardless of margin status. Inflicting significant surgical morbidity or risk of perioperative mortality needs to be considered in the context of probability of long-term survival. In the patients who have unresectable cancer, most advocate primary radiotherapy or concomitant chemoradiation usually with cisplatinum-based chemotherapy protocols. A few series have reported complete responses in advanced cancers; however, the numbers of patients treated is extremely small. Controversy exists over the importance of clear margins in adenoid cystic carcinoma with some authors showing significant impact on locoregional control and survival and others suggesting a less dramatic effect. The surgeon must know the blood supply of the trachea, the course of the recurrent laryngeal nerves, and the options for reconstruction. Each case must be carefully studied and each operation carefully planned before such a procedure is undertaken. Positioning and Incision the patient should be positioned to allow full access to the operative field. This usually means neck extension using an inflatable placed as a shoulder bolster. This incision may be extended through the upper portion of the sternum if access to the mediastinal trachea as required. Exposure of the larynx is obtained by carrying the flap elevation to the level of the hyoid. If the tumor appears to be extensive, as is sometimes the case with adenoid cystic carcinoma, the patient should be positioned in a manner that allows extension of the incision into the right fourth interspace to the posterior axillary line. Some thoracic surgeons will free drape the right arm so that it can be moved back and forth as necessary. Resection the surgical approach for benign tumors of the trachea varies somewhat more than that for malignant tumors. For benign tumors, dissection is maintained adjacent to the trachea; in this approach, which is similar to tracheal or cricotracheal resection, the recurrent nerves are not visualized. This approach is safe as long as the plane of dissection is maintained directly on the surface of the trachea. When malignant tumors are resected, the recurrent laryngeal nerves are identified at a distance from the cancer and are followed toward the area of the cancer. It may be necessary to sacrifice a recurrent laryngeal nerve on the side of the tumor due to its involvement with the tumor. However, such a dissection should be limited because it may endanger the blood supply of the trachea. A compromise must be made between the potential of leaving behind paratracheal tissue that may contain positive lymph nodes and avoiding devascularization of the trachea. Circumferential dissection of the trachea over a great distance should be avoided because this may endanger the blood supply and can lead to problems with healing and/or stenosis. It is best not to circumferentially free more than 1 to 2 cm of trachea from the point at which the trachea is to be transected. Once the trachea has been identified, the entire pretracheal plane is freed bluntly to the carina and often down the proximal anterior surfaces of the mainstem bronchi. Care is taken to spare the lateral pedicles because these contain the blood supply to the trachea. Isolation of the portion of the trachea containing the cancer is begun on the side of the trachea away from the cancer, and an effort is made to include appropriate lymph nodes. Once the inferior-most extent of the cancer is identified, preparations are then made for transection of the trachea. A sterile anesthetic circuit is passed to the anesthesiologist, and a sterile cuffed endotracheal tube is brought into the operative field. The trachea is then opened in a transverse manner immediately distal to the inferior aspect of the cancer, and the lumen is carefully inspected. If it seems that the division will occur at an appropriate level, the transection is completed; if the level is inappropriate, a more distal level is chosen under direct vision. After transection of the distal trachea, the airway is intubated across the field with the flexible endotracheal tube. At this point, the orotracheal tube may be withdrawn to a level proximal to the anticipated proximal extent of tumor; it is wise to place a suture to the tip of the tube so that if it is withdrawn above the vocal cords, it may be reintroduced with ease at the end of the case. A small portion of tracheal tissue distal to the line of transection is removed and sent for frozen section analysis so that the adequacy of the distal margin can be determined. The transected end of the trachea is now grasped with forceps and is placed on gentle traction to facilitate proximal dissection. However, it may be necessary to include a full-thickness segment of the anterolateral wall of the esophagus; at other times, only the muscularis may be excised. Any defect in the esophagus is repaired primarily in two layers with fine interrupted sutures and is reinforced with autologous tissue such as a strap muscle. With the dissection carried proximally, the proximal extent of the cancer is identified from within the tracheal lumen, and a point of transection is chosen. At times, it may be necessary to bevel obliquely a portion of the inferior aspect of the larynx, such as half or more of the cricoid cartilage, to obtain an adequate proximal margin. Once the proximal point of transection is determined, traction sutures are placed in the proximal trachea in a manner similar to those placed distally, if the transection point is relatively high, the sutures may be placed in the larynx. The trachea is then transected, and a specimen is submitted for frozen section analysis of the proximal margin. Reconstruction After removal of the specimen and after establishment of clear margins of resection both proximally and distally, reconstruction can begin. The anesthesiologist is asked to temporarily flex the neck as the surgeon and assistant simultaneously draw together the traction sutures on each side of the trachea. Excessive tension on the anastomosis markedly increases the likelihood of separation or stenosis, both potentially disastrous complications. If further relaxation is deemed necessary to avoid excessive tension, a variety of release maneuvers may be used. The suprahyoid laryngeal release is particularly effective, especially after resection of the proximal trachea. Other maneuvers may be performed, but they require entry into the thoracic cavity. These include mobilization of the inferior pulmonary ligament, intrapericardial release of the right hilum, and, rarely, bronchial transplantation. Once it has been demonstrated that tracheal approximation can be obtained without excessive tension, the neck is again extended and the anastomosis completed. The use of absorbable suture material has dramatically reduced the incidence of suture line granulomas, a problem that was encountered with the use of nonabsorbable suture. Our approach is to place two stay sutures at the posterior edge of the cartilaginous trachea and then close the back wall with a running 4-0 suture. The endotracheal tube is removed from across the operative field, and the orotracheal tube is once again advanced and placed into the distal airway under direct vision. If the thyroid isthmus is intact, the isthmus may be sutured over the anastomosis. Although it is not necessary to interpose a pedicled strap muscle between the innominate artery and the anastomosis, some surgeons may wish to do so to add a measure of security. Suction drains are placed in the substernal and/or paratracheal areas, and the incision is closed in layers. A heavy suture (Grillo stitch) is placed from the crease below the chin to the presternal skin. This serves as a guardian suture in the postoperative phase, reminding the patient not to suddenly hyperextend the neck. Except in rare circumstances, every effort is made to extubate the patient at the conclusion of the operation. In patients with high tracheal or cricoid cancers where a cricotracheal resection has been performed, some authors advocate the use of silastic T-tubes. These tubes are usually positioned with the proximal limb just above the vocal cords with the external limb exiting the trachea one to two rings below the repair through a small tracheotomy. T-tubes have a role in patients at risk of supraglottic edema and potential airway obstruction and where the quality of the proximal or distal trachea is in question. Postoperative Care Throughout the performance of tracheal resection and reconstruction, care is taken to avoid the entry of blood and secretions into the tracheobronchial tree. This helps to prevent postoperative pneumonitis and shunting, the end result of which may be a requirement for mechanical ventilation, which is an extremely hazardous procedure for a patient with a recently completed tracheal reconstruction. During the operation, the assistant must be vigilant in the clearance of blood and secretions by careful suctioning and must not allow them entry into the airway (even in the presence of an inflated cuff). Postoperatively, the patient is instructed to maintain airway clearance with gentle coughing and other chest physical therapy maneuvers. If all of these maneuvers prove unsuccessful, then the flexible bronchoscope is used to clear secretions. Palliation and the Use of Airway Stents Patients presenting with advanced unresectable cancers or with locoregional recurrence and airway compromise represent a unique challenge both clinically and ethically. Expandable airway stents can relieve airway obstruction, providing an opportunity for patients to recover from interventions and be actively involved in treatment or palliative decision making. Expandable stents can however be problematic with issues including migration, perforation, and retained secretions in up to 15% of patients. Outcomes Treatment-related outcomes for cervical tracheal cancers are dependent on histology, stage of presentation, and resectability. In this series, nodal involvement regardless of histology was associated with a 10. Patients with a diagnosis of adenoid cystic carcinoma had a 5-year survival of 74. The largest single institution series has been reported from the Massachusetts General Hospital with 191 patients treated for primary tracheal tumors between 1962 and 2002. In the same publication, they report a series of 101 adenoid cystic carcinomas with 5- and 10-year survivals of 52% and 29%. A number of centers have attempted tracheal reconstruction using nontraditional techniques particularly where primary repair is not feasible. The majority of these patients have been previously treated with radiotherapy or have low-grade tumors with a good prognosis such as papillary carcinoma of the thyroid or chondrosarcoma of the trachea or cricoid. A number of centers have reported the use of cutaneous free flaps with either intraluminal or extraluminal stenting. Long segments of skin lead to airway crusting and an inability to clear secretions from the lower airway as a result of the absence of a ciliated lubricated mucosal surface. A and B: Vascularized composite allograft concept, concept for cricoid and upper tracheal reconstruction of partial cricoid or tracheal defects. Delaere and his group have used decellularized allografts vascularized by placing them in the forearm site. Once vascularized, they introduce recipient mucosal grafts from the nasal mucosa to recreate the luminal epithelium and then transfer the construct as a partial tracheal transplant vascularized through the radial artery and its venae commitantes. This technique clearly has no application in high-grade cancer of the trachea but has been used in low-grade tumors with success. Macchiarini and colleagues29 have attempted a number of allograft tracheal transplants. In this approach restricted to patients with stenosis and congenital deformities, a decellularized allograft is recellularized in a bioreactor with autologous stem cells to recreate the supported structure and epithelial components. This technique is interesting but currently has no role in the management of malignant tracheal tumors. Early reports have demonstrated the need for continuous stenting putting in question the success and probability of long-term success with this technique of airway reconstruction. Airway management at presentation can be extremely challenging even to the most experienced airway surgeon and require an experienced team including anesthesia. Primary treatment for malignant tumors is multimodal with surgery and adjuvant radiotherapy or chemoradiation advocated for the majority of resectable patients. Surgical resection is best performed by teams with significant volume expertise in airway surgery. Extensive resection and reconstruction of mediastinal trachea without prosthesis or graft: an anatomical study in man. The effect of extension of the head and neck upon the infrahyoid respiratory passage and the supraclavicular portion of the human trachea. The contribution of the inferior thyroid artery to the blood supply of the human trachea. Long-term survival after resection of primary adenoid cystic and squamous cell carcinoma of the trachea and carina. Results and prognostic factors in resections of primary tracheal tumors: a multicenter retrospective study. Well-differentiated thyroid cancer with aerodigestive tract invasion: long-term control and functional outcomes. Treatment of locally advanced adenoid cystic carcinoma of the trachea with neutron radiotherapy.

Robotic system-based fractionated stereotactic radiotherapy in locally recurrent nasopharyngeal carcinoma allergy forecast stamford ct buy seroflo overnight delivery. A retrospective comparison of robotic stereotactic body radiotherapy and three-dimensional conformal radiotherapy for the reirradiation of locally recurrent nasopharyngeal carcinoma gluten allergy symptoms yahoo discount seroflo 250 mcg with amex. Reirradiation of locally recurrent nasopharynx cancer with external beam radiotherapy with or without brachytherapy allergy medicine with adderall trusted 250mcg seroflo. Initial experience using intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma allergy drops for eyes order seroflo without prescription. Long-term outcomes and prognostic factors of re-irradiation for locally recurrent nasopharyngeal carcinoma using intensity-modulated radiotherapy allergy medicine you rub on your nose 250 mcg seroflo otc. Effectiveness and toxicities of intensity-modulated radiotherapy for patients with locally recurrent nasopharyngeal carcinoma allergy testing scottsdale buy discount seroflo. Intensity-modulated radiation therapy in the salvage of locally recurrent nasopharyngeal carcinoma. Linear accelerator-based stereotactic radiosurgery for limited, locally persistent, and recurrent nasopharyngeal carcinoma: efficacy and complications. Comparison of single versus fractionated dose of stereotactic radiotherapy for salvaging local failures of nasopharyngeal carcinoma: a matched-cohort analysis. Linear accelerator based radiosurgery as a salvage treatment for skull base and intracranial invasion of recurrent nasopharyngeal carcinomas. Prognostic model for survival of local recurrent nasopharyngeal carcinoma with intensity-modulated radiotherapy. Endoscopic nasopharyngectomy for salvage in nasopharyngeal carcinoma: a novel anatomic orientation. Endoscopic microwave coagulation therapy for early recurrent T1 nasopharyngeal carcinoma. Transcervico-mandibulo-palatal approach for surgical salvage of recurrent nasopharyngeal cancer. Surgical management of recurrent nasopharyngeal carcinoma after radiation failure at the primary site. Nasopharyngectomy for locally advanced recurrent nasopharyngeal carcinoma: exploring the limits. Prognosticators determining survival subsequent to distant metastasis from nasopharyngeal carcinoma. Lung metastasis alone in nasopharyngeal carcinoma: a relatively favorable prognostic group. Comparative survival analysis in patients with pulmonary metastases from nasopharyngeal carcinoma treated with radiofrequency ablation. Risk subset of the survival for nasopharyngeal carcinoma patients with bone metastases: who will benefit from combined treatment Long-term disease-free survivors in metastatic undifferentiated carcinoma of nasopharyngeal type. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. Nasopharyngeal cancers: which method should be used to measure these irregularly shaped tumors on cross-sectional imaging Controlled trials of chemotherapy as an adjuvant or palliative treatment of nasopharyngeal carcinoma. Excellent response to cis-platinum-based chemotherapy in patients with recurrent or previously untreated advanced nasopharyngeal carcinoma. Chemotherapy of metastatic and/or recurrent undifferentiated nasopharyngeal carcinoma with cisplatin, bleomycin, and fluorouracil. Cisplatin and 5-fluorouracil continuous infusion for metastatic nasopharyngeal carcinoma. Carboplatin plus taxol is an effective third-line regimen in recurrent undifferentiated nasopharyngeal carcinoma. Docetaxel is effective in heavily pretreated patients with disseminated nasopharyngeal carcinoma. Consensus recommendations for management of head and neck cancer in Asian countries: a review of international guidelines. Genome wide detection of oncogene amplifications in nasopharyngeal carcinoma by array based comparative genomic hybridization. Frequency of Epstein-Barr virus-specific cytotoxic T lymphocytes in the blood of Southern Chinese blood donors and nasopharyngeal carcinoma patients. Effective treatment of metastatic forms of Epstein-Barr virus-associated nasopharyngeal carcinoma with a novel adenovirus-based adoptive immunotherapy. Adoptive T-cell transfer and chemotherapy in the first-line treatment of metastatic and/or locally recurrent nasopharyngeal carcinoma. Wax Approximately 25% of all carcinomas of the oral cavity involve the lips, making the lips the most commonly affected subsite in the oral cavity. The prominent location of cancers of the lip allows for early detection of pathology. The lips play such a prominent role in how we present ourselves to the outside world that any abnormality is immediately noticed and reacted to . The fact that lesions of the lips are detected so early makes treatment relatively easy and successful, making cancer of the lip one of the most curable cancers of the head and neck. Unfortunately, even with the prominent location and ease of detection, as many as 15% of the cases, the disease will demonstrate aggressive behavior manifested by recurrence, metastasis, and death from disease. Late presentation due to neglect or poor access to health care accounts for a portion of these cases. The vast majority of cancers of the lip are treated with local resection followed by repair through local tissue rearrangement. Reconstruction of larger defects after resection of larger tumors may require complex composite flaps to optimize both function and cosmesis. The area of the lips extends vertically from the subnasale to the mental crease and horizontally to each oral commissure. The upper lip is formed from the two lateral maxillary processes that fuse centrally with the frontomedian process, whereas two mandibular processes meet in the midline to form the lower lip. The lip is a complex anatomical structure, which includes a muscular layer that is a part of the oral sphincter, lying between a mucosal layer and the overlying skin. This muscular layer is composed of the orbicularis oris muscle, which is derived from the second branchial arch. The muscle fills most of the body of the lip and completely encircles the mouth creating the oral sphincter. This skeletal muscle helps in the regulation of food entrance and maintenance within the oral cavity. The orbicularis muscle of the lip is not a simple sphincter because, in its periphery, it receives fibers from the many different surrounding facial muscles. These act together with the orbicularis to produce the various shapes and functions that are possible with the lips, such as smiling, frowning, kissing, blowing, whistling, articulating speech, and closing the lips. The most characteristic feature of the lip is the vermilion-a transitional mucosal surface that covers the free margin of the lip and bridges the external skin with the internal mucosa. The mucocutaneous junction forms the anterior vermilion border, whereas the posterior point of contact of the lips, when they are held closed, marks the posterior vermilion border. Sensory innervation of the lip is supplied by the second and third division of the trigeminal nerve. The upper lip is supplied by the infraorbital branch of the maxillary nerve (V2), exiting from the infraorbital foramen. The oral commissure is supplied by the buccal branch of the mandibular nerve (V3). Lower lip sensation is supplied by the mental branch of the mandibular nerve, which enters the mandible as the inferior alveolar nerve at the inferior alveolar foramen. The nerve traverses the mandible and exits through the mental foramen as the mental nerve. The nerve transitions from posterior to the mandible to anterior as it passes through the mandible. As the nerve of the second branchial arch, the facial nerve provides lip motor innervation via the buccal and marginal mandibular branches. The buccal branch of the facial nerve supplies the upper lip, whereas the lower lip motor functions are supplied through the marginal mandibular branch. The arterial supply to the lips is provided principally by the left and right facial arteries, from which arise first the inferior and then the superior labial arteries. These vessels encircle the left and right side of the mouth passing between the respective orbicularis and submucosa. Interconnections are abundant, and the total lip complex can survive on the contralateral supply. Lymphatic drainage of the upper lip and oral commissure is accomplished by an interconnecting network of delicate vascular structures found in both the submucosal and subcutaneous tissue planes. This network goes on to drain into five collecting trunks on either side, which in turn drain laterally to the preauricular, infraparotid, submandibular, and submental lymph nodes. Embryonically, the central frontonasal process separates the lateral maxillary processes. By contrast, the mandibular processes of the lower lip fuse at midline, allowing numerous crossing anastomoses to occur. Lymphatic drainage to the lower lip therefore occurs to the submental and submandibular nodes bilaterally. It is presumed that the variations are due to such factors as race, environment, and personal habits. Overall, cancer of the lip is most commonly observed in the white, male, smoker, over the age of 50, with fair complexion and blue eyes. Thus, it should not be surprising that the highest incidence of lip cancer is reported among the white populations of Canada and Australia. Lip cancer is rare in the nonwhite populations, as darkly pigmented populations have greater amounts of protective pigment within their vermilion. Because the lips are located on the face, they are subjected to greater exposure to ultraviolet light than most of the other areas of the body. Eighty-eight percent to ninety-eight percent of cancers of the lip are found in the vermillion of the lower lip. On the lower lip, cancer is most frequently found on the exposed vermilion border, arising at the point midway between the oral commissure and midline. Although the upper lip is also outwardly projected, its vermilion surface faces downward, away from direct sunlight. Malignancy arising in the upper lip vermilion constitutes only 2% to 7% of reported cases. Much of the evidence that has implicated ultraviolet light exposure as etiologic in cancer of the lip is derived from associations that have been made in case series studies and epidemiologic surveys. These studies and surveys show that at least one-third of patients who develop cancer of the lip have outdoor occupations, presumably subjecting them to substantial ultraviolet light exposure. Typical findings include generalized atrophy of the vermilion, loss of elastic fibers, atrophy of adipose tissue, and glandular elements, as well as cellular changes such as hyperkeratosis and atypia. Advanced chronic solar injury to the lip often produces fading of the sharp color contrast normally seen at the mucocutaneous line. Areas of the vermilion that have sustained particularly severe solar injury may display areas of chronic scaling or crusting (actinic cheilitis) that are analogous to actinic keratoses found in sun-damaged skin. In general, patients with cancer of the lip will often be found to have other sun- induced malignancies or premalignant changes in the surrounding vermilion and facial skin. Exposure to tobacco products has clearly been shown to increase the risk for malignancy particularly within the oral cavity. The relationship between tobacco use and the development of cancer of the lip is less clear. The data so far have been based primarily on information obtained from various case series that have identified a large proportion of patients with cancer of the lip that has regularly used tobacco products. Some case controlled studies, however, have failed to support a distinct relationship of tobacco use with cancer of the vermilion of the lip. The increased risk of lip cancer among renal allograft patients on immunosuppressive therapies may be as great as 30-fold. These patients are also at an increased risk for development of second primary cancers of the lip. A variety of other factors have been reported to have some association with the development of cancer of the lip. These include thermal injury, mechanical irritants, trauma, use of alcohol, poor oral hygiene, chemical exposure, influence of various infectious diseases, and prolonged exposure to harsh weather conditions. Currently, most of these can be considered only associations, because well-designed and controlled studies to establish a firm causative relationship are lacking. The external skin is keratinizing stratified squamous epithelium with a rich complex of hair follicles, sweat, and sebaceous glands located in the dermis, whereas the lip vermilion is composed of nonkeratinizing stratified squamous epithelium, adapted for external exposure. It remains smooth and dry, due to the paucity of glandular structures in the submucosal layer. Finally, the labial mucosa contains many serous, mucous, and mixed salivary glands in its submucosal layer, keeping the epithelial surface moist. Both the vermilion and labial layers are pink due to the presence of many elongated, vascular connective tissue papillae that project into the epithelial layer. This cancer first appears as a nonhealing blister, recurrent crusting, lip induration, or an exophytic growth. Clinically, it may be impossible to distinguish between actinic cheilitis and early squamous cancer, creating a low index of suspicion for biopsy. The exophytic form develops as an area of thickened epithelium that rises up from the surrounding tissue as it develops. This base extends only a few millimeters under the epithelium, but externally, the lesion becomes heaped up upon itself extending outwardly a centimeter or more. Laterally, lesions may extend several centimeters with relative little invasion or metastasis.

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