INTRODUCTION — The differential diagnosis of a mass in the neck is broad, extensive, and includes both serious and benign etiologies. Accurate diagnosis of a neck mass is critical.
It is helpful to consider the differential diagnosis in three broad categories:
The patient's history and physical examination will often allow designation of the neck mass into one of these three categories. However, particularly in adult patients, the potential for malignancy in any neck mass should be adequately excluded before a benign diagnosis is established.
This topic aims to present a framework for the differential diagnosis of a mass in the neck. The evaluation of a patient with a neck mass is discussed elsewhere. (See "Evaluation of a neck mass in adults".)
ANATOMY OF THE NECK AND LYMPH NODE DRAINAGE — The location of the mass can focus the differential [1,2]. Familiarity with neck anatomy is critical for diagnosis and management of disease processes affecting this region. The neck is traditionally divided into the central and the lateral necks, with the lateral neck further subdivided into anterior and posterior triangles (figure 1).
Additionally, patterns of lymph node drainage can identify areas of concern when metastatic disease is suspected or correlating with potential sources of infection. The localization of lymph nodes in the neck is shown in a figure (figure 2), and patterns of lymphatic drainage are shown in a table (table 1).
CONGENITAL NECK MASS — Congenital neck masses are usually present at birth but may present at any age. They are the most common noninflammatory neck mass in children. (See "Congenital anomalies of the jaw, mouth, oral cavity, and pharynx".)
For masses presenting in adulthood, the patient should be approached with a presumption of malignancy until proven otherwise. Although cystic lesions such as branchial cleft cysts can present in adulthood, these lesions should be approached with a keen diagnostic eye to ensure malignancy is not present. Carcinomas of the tonsil, tongue base, and thyroid may all present as cystic neck masses.
Branchial cleft cyst — Branchial cleft cysts account for almost 20 percent of pediatric neck masses . They usually present in late childhood or early adulthood when a previously unrecognized cyst becomes infected. Only a very small percentage first present in adulthood. The cysts are relatively consistent in their location in the neck, anterior to the sternocleidomastoid muscle. Branchial cleft cysts are further subdivided based on the developmental origin (figure 3).
First branchial cleft cysts account for less than 1 percent of branchial cleft anomalies. They typically appear on the face near the auricle. First branchial cleft cysts are further divided into types I and II . Type I first branchial cleft cysts are duplication anomalies of the external auditory canal and are of ectodermal origin. They pass through the parotid gland often in close proximity to the facial nerve. Type II branchial cleft cysts are more common and typically present below the angle of the mandible. They contain both ectoderm and mesoderm and pass through the parotid gland medial or lateral to the facial nerve and end either inferior to the external auditory canal or at the bony cartilaginous junction of the external auditory canal.
Second branchial cleft cysts are the most common type of branchial cleft anomaly. They are usually located just inferior to the angle of the mandible and anterior to the sternocleidomastoid muscle in the corresponding level II region of lymph nodes. The sinus tract of a second branchial cleft cyst will travel through the deep structures of the neck and open into the tonsillar fossa. The location and cystic nature of second branchial cleft cysts may lead to difficulty in distinguishing these from cystic lymph node metastasis of human papilloma virus (HPV)-related oropharynx squamous cell carcinoma. (See "Epidemiology, staging, and clinical presentation of human papillomavirus associated head and neck cancer".)
Third branchial cleft cysts also are located anterior to the sternocleidomastoid muscle but are typically lower in the neck than a second branchial cleft cyst. These anomalies end in the pharynx at the thyrohyoid membrane or pyriform sinus.
Recurrent infections of branchial cysts can occur, and a fistula tract to the skin may develop. Recurrent infections may complicate surgical removal, increasing the risk of injury to important structures such as the facial nerve when the parotid is involved. Acute severe infections of third or fourth branchial cleft cysts can cause pharyngeal edema and airway and swallowing problems. Management of branchial cleft cysts begins with controlling infection, if present. Once the infection has resolved, the mass is usually excised to prevent future problems .
Thyroglossal duct cyst — In contrast to branchial cleft cysts, thyroglossal duct cysts present as a midline mass in the anterior neck. They are often asymptomatic until they become infected in the setting of an upper respiratory tract infection. Thyroglossal duct cysts are usually diagnosed in childhood, but up to 40 percent may present after age 20 . (See "Thyroglossal duct cyst, thyroglossal duct cyst cancer, and ectopic thyroid".)
Surgical treatment is the standard in the management of thyroglossal duct cysts. Since thyroid carcinoma can be present in a small percentage (1 to 2 percent) of thyroglossal duct cysts, all thyroglossal duct cysts and tracts should undergo a careful histologic examination . Management is discussed in detail elsewhere. (See "Thyroglossal duct cyst, thyroglossal duct cyst cancer, and ectopic thyroid".)
Vascular anomalies — Vascular anomalies can be considered as two groups: vascular tumors and vascular malformations. Both types of anomalies can present as a neck mass . (See "Vascular lesions in the newborn".)
●Vascular tumors – Vascular tumors are endothelial neoplasms characterized by increased cellular proliferation. The most common type is a hemangioma, although rare tumors (eg, hemangiopericytoma, hemangioendothelioma, and angiosarcoma) may also occur.
Hemangiomas occur almost exclusively in infants and have a characteristic rapid growth phase followed by a slow regression. Typically, overlying skin changes will suggest this diagnosis. Hemangiomas often appear as a compressible red or bluish soft mass. An associated bruit may be present on auscultation. A full physical examination should be performed since a second hemangioma may be present in the subglottis, gastrointestinal tract, or spine. (See "Infantile hemangiomas: Evaluation and diagnosis".)
Management of hemangiomas consists initially of watchful waiting, since the majority will resolve spontaneously and the benign tumor will not recur. Intervention is necessary when the lesion is symptomatic (eg, airway compromise or bleeding). Systemic glucocorticoids, surgical laser excision, and occasionally beta blockers are the treatment options in this setting; management in reviewed in detail elsewhere. (See "Infantile hemangiomas: Management".)
●Vascular malformations – Vascular malformations describe a group of anomalies arising from errors of embryonic and fetal development. The classification is based on the clinical, radiographic, and histologic appearance of abnormal channels. These channels can be arterial, venous, lymphatic, or a combination. Lymphatic malformations are the most likely to present as a neck mass. (See "Vascular lesions in the newborn".)
On physical examination, these masses are typically soft, nontender, and compressible. The overlying skin is usually normal and the mass can be transilluminated.
Treatment is directed at preventing recurrent bleeding or infection, correcting contour deformity, and improving function. Surgery has historically been the main treatment modality for masses causing distortion or aerodigestive tract obstruction. However, complete excision can be very difficult and may require staged procedures. Interventional radiology procedures have become an alternative to surgical procedures; management is reviewed in detail elsewhere. (See "Infantile hemangiomas: Management".)
Laryngocele — A laryngocele is a herniation of the saccule of the larynx. The herniation can be limited to the anatomic boundaries of the larynx (internal laryngocele), or extend through the thyrohyoid membrane (external or mixed laryngocele). When it extends beyond the larynx, it often presents as an air-filled cyst in the anterior neck. (See "Congenital anomalies of the larynx".)
Patients most often present with hoarseness, cough, and a foreign body sensation. Laryngoscopy often will demonstrate a smooth dilation at the level of the false cord, involving both the false cord and aryepiglottic fold.
Management of a laryngocele is primarily surgical. Laryngoscopic decompression may be performed for small lesions, whereas external approaches are necessary for larger lesions .
Ranula — A ranula is a mucocele or retention cyst arising from an obstruction in the sublingual glands in the floor of mouth. The obstructed sublingual gland leads to pseudocyst formation due to mucous extravasation. (See "Congenital anomalies of the jaw, mouth, oral cavity, and pharynx".)
Ranulas are often painless and slow growing. They are most often located in the submentum. When they extend through the mylohyoid muscle into the neck, they are referred to as "plunging ranula" (image 1). Ranulas are managed by transoral surgical resection of the mucocele with the sublingual gland .
Teratoma — Teratomas arise from pluripotential cells and contain all three germ layers. They are classically large, encapsulated, and contain a cystic component. (See "Congenital anomalies of the jaw, mouth, oral cavity, and pharynx".)
Teratomas typically arise in the first year of life and can cause significant aerodigestive obstruction. Surgical excision is recommended . (See "Extragonadal germ cell tumors involving the mediastinum and retroperitoneum".)
Dermoid cyst — Dermoid cysts are due to entrapment of epithelium in deeper tissue, occurring either developmentally or post-trauma. Congenital lesions are usually midline, nontender, mobile, submental neck masses. They are treated by surgical excision.
Thymic cyst — Thymic cysts result from implantation of thymic tissue during its embryologic descent. As a result, they often present in a midline position. However, they can present anywhere between the angle of the mandible and the midline of the neck. Thymic cysts are managed with surgical excision. (See "Approach to the adult patient with a mediastinal mass", section on 'Other thymic masses'.)
INFLAMMATORY NECK MASS — Inflammatory masses are typically related to enlarged lymph nodes. Lymph node enlargement can result from infectious processes as well as inflammatory, noninfectious illnesses. An overview of causes of peripheral lymphadenopathy is shown in a table (table 2). (See "Evaluation of peripheral lymphadenopathy in adults" and "Cervical lymphadenitis in children: Etiology and clinical manifestations".)
Infectious inflammatory disorders
Reactive viral lymphadenopathy — Reactive viral lymphadenopathy is the most common cause of cervical lymphadenopathy, especially in children. Typically, viral lymphadenopathy arises in the setting of routine upper respiratory infections caused by adenovirus, rhinovirus, or enterovirus. Epstein-Barr virus causes infectious mononucleosis and has a unique course.
Typical viral infections cause symptoms for one to two weeks; lymphadenopathy generally resolves within one to two weeks of symptom resolution. The lymphadenopathy is typically tender and located in the submandibular region or jugular chain. Computed tomography (CT) findings of lymph nodes less than 1 cm (or 1.5 cm in the upper jugulodigastric chain), oblong in shape, with no evidence of central hypodensity, and a preserved vascular hilum are reassuring features. Lymphadenopathy that appears benign should be closely followed; failure to improve in the following weeks requires additional workup including possible biopsy and/or serologic testing for chronic infectious or inflammatory disorders.
Lymphadenopathy attributable to mononucleosis is often associated with neck nodes that are quite large (>2 cm) and may also occur in the posterior triangle. Typically there is accompanying axillary and inguinal lymphadenopathy as well as tonsillar hypertrophy. Mononucleosis has a characteristic prodrome of fatigue, malaise, fever, and severe pharyngitis. This lymphadenopathy may routinely take four to six weeks to resolve. (See "Infectious mononucleosis".)
Bacterial lymphadenopathy — Suppurative lymphadenopathy results from a bacterial infection, typically in the pharynx or skin, which causes suppuration within the enlarged lymph nodes. The most common organisms are Staphylococcus aureus and group A beta-Streptococcus. Patients should be treated initially with antibiotic therapy directed at these organisms. MRSA is an increasing problem, but is still low in incidence as a cause of suppurative lymphadenopathy. Methicillin-resistant S. aureus (MRSA) should be considered in patients who have been recently hospitalized, have an occupational exposure, or have other risk factors (table 3). Patients with a poor response to initial antibiotic therapy may require needle aspiration or incision and drainage of the abscess, with subsequent culture for bacterial diagnosis.
A few specific bacteria merit individual mention.
●Tularemia is caused by Francisella tularensis. Transmission via rabbits is best known, but it can also be passed by ticks or contaminated water. Patients commonly present with tonsillitis/pharyngitis as well as painful lymphadenopathy. Systemic symptoms of fever, chills, fatigue, and headache are common. Throat culture and serologic testing confirm the diagnosis. (See "Tularemia: Clinical manifestations, diagnosis, treatment, and prevention".)
●Brucellosis (also called undulant, Mediterranean, or Malta fever) is caused by one of four species of Brucella, a gram-negative organism, and can be acquired from one of several farm animals by direct contact or by eating the butter or milk from one of these animals. (See "Brucellosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)
Cows, pigs, goats, elk and bison are all known to be potential carriers. A constellation of symptoms including generalized weakness, sweating, chills, malaise, headache, backache, and arthralgia typically occur. Afternoon fever peaks are part of the classic presentation.
●Cat-scratch disease usually presents with submandibular and/or preauricular lymphadenopathy. Cat-scratch disease is caused by Rochalimaea henselae, which is carried by felines. An exposure to cats can nearly always be elicited to aid in the diagnosis. Lymphadenopathy is often quite painful and accompanied by fevers and generalized malaise. Despite the discomfort the disease is usually self-limiting and requires only supportive treatment. (See "Microbiology, epidemiology, clinical manifestations, and diagnosis of cat scratch disease" and "Treatment of cat scratch disease".)
●Actinomycosis commonly presents in the submandibular region and can be associated with dental procedures. Often the mass is painless and fluctuant. Confirmation of the diagnosis requires biopsy, which demonstrates granulomas with sulfur granules. Penicillin is the first line treatment. (See "Cervicofacial actinomycosis".)
●Mycobacterial infections present in a variety of forms. Tuberculosis is caused by Mycobacterium tuberculosis. The lymphadenopathy is typically unilateral, although multiple nodes may be involved at the location. (See "Tuberculous lymphadenitis".)
Unlike tuberculosis, atypical mycobacteria are more common among the pediatric population and usually presents as a unilateral mass in the parotid or anterior neck. The overlying skin commonly becomes brawny and can appear as a hue of purple, which is almost pathognomonic. Skin testing is usually only weakly positive, so often core needle or excision is needed to obtain tissue for culture in order to confirm the diagnosis. If a focal node is the limit of the disease, surgical excision can be considered as definitive treatment. More extensive disease may be better treated with incision and curettage and antibiotics. (See "Cervical lymphadenitis in children: Diagnostic approach and initial management" and "Nontuberculous mycobacterial lymphadenitis in children".)
●HIV-associated lymphadenopathy is very common, present in up to 45 percent of patients with HIV infection . Adenopathy is typically caused by idiopathic hyperplasia. However, it is important to consider possible other infectious or malignant etiologies such as M. tuberculosis, Pneumocystis carinii, lymphoma, and Kaposi sarcoma. (See "The natural history and clinical features of HIV infection in adults and adolescents".)
Parasitic lymphadenopathy — Toxoplasma gondii, a protozoan parasite, is typically acquired through ingestion of inadequately cooked meat or the ingestion of cat feces. These patients often have a prolonged course of fever, malaise, myalgias, sore throat, and cervical lymphadenopathy that can be present for weeks. Other complications such as intracranial abscesses may be present. (See "Toxoplasmosis: Acute systemic disease".)
Noninfectious inflammatory disorders — Noninfectious inflammatory conditions are less common than the other etiologies of lymphadenopathy. However, it is important to consider these disorders, which are often difficult to diagnose and require a thorough workup. Conditions to be considered, especially when symptoms and signs involve areas other than head and neck, include sarcoidosis, Castleman disease, Rosai-Dorfman disease, and Kawasaki disease. (See "Evaluation of peripheral lymphadenopathy in adults" and "HHV-8/KSHV-associated multicentric Castleman disease" and "Kawasaki disease: Clinical features and diagnosis" and "Peripheral lymphadenopathy in children: Etiology", section on 'Uncommon but important causes'.)
NEOPLASTIC DISORDERS — Both benign and malignant neoplasm can present in the neck, as noted above. The adult patient should be approached with a presumption of malignancy until proven otherwise. Carcinomas of the tonsil, tongue base, and thyroid may all present as cystic neck masses and may be initially misdiagnosed as benign disease.
Metastatic head and neck carcinoma — Neck masses that result from metastatic disease are predominantly related to metastatic squamous cell carcinoma arising from the aerodigestive tract . This diagnosis should be at the forefront of the differential diagnosis for an adult with a new-onset neck mass.
Despite malignancy, these masses are usually asymptomatic. Symptoms related to the primary site of the tumor, however, can often be elicited. Diagnosis is confirmed with fine-needle aspiration.
Once the diagnosis of metastatic squamous cell carcinoma is made, a search for the primary tumor must be performed. The probable primary site can often be identified by history and physical examination; panendoscopy and directed imaging may be required.
There is a consistent lymphatic drainage pattern for the mucosa of the aerodigestive tract (figure 2 and table 1). Therefore, the location of the mass may provide some guidance as to the location of the primary tumor. Metastatic nodes in the posterior triangle are often related to nasopharyngeal carcinoma, whereas nodes along the upper jugular chain drain from the oral cavity, oropharynx, and larynx. Isolated supraclavicular nodes should raise concern or a tracheobronchial, distal esophageal, or stomach carcinoma .
While the overwhelming majority of metastatic carcinomas are squamous cell arising from the aerodigestive tract, other primary cancers should be kept in the differential. Cutaneous malignancies of the face and scalp are becoming more common. This should be considered especially for a neck mass in an older patient or in a solid organ transplant recipient with a history of skin cancer and no history of tobacco use. Melanoma and aggressive squamous cell carcinomas, as well as rarer cutaneous malignancies such as Merkel cell, can metastasize to the parotid gland and neck lymph nodes.
Thyroid masses — A primary thyroid tumor will usually present as a mass in the anterior neck. While the majority of these masses represent benign thyroid nodules and cysts, malignancy must be considered. (See "Diagnostic approach to and treatment of thyroid nodules" and "Cystic thyroid nodules".)
Symptoms of hoarseness or a history of radiation exposure in the setting of a new thyroid mass should increase the suspicion for malignancy .
Salivary gland neoplasm — Approximately 80 percent of salivary neoplasms arise in the parotid gland. Eighty percent of parotid tumors are benign, most commonly pleomorphic adenoma . The incidence of malignancy in tumors of the submandibular gland is much higher, approaching 50 percent. (See "Salivary gland tumors: Epidemiology, diagnosis, evaluation, and staging".)
There are several subtypes of benign salivary neoplasm, including pleomorphic adenoma, Warthin's tumor, lymphoepithelioma, oncocytoma, and monomorphic adenoma. Pleomorphic adenomas comprise approximately 80 to 85 percent of these benign tumors.
There is a large spectrum of malignant histologies as well, including mucoepidermoid carcinoma, adenoid cystic carcinoma, varieties of adenocarcinomas, salivary duct carcinoma, squamous cell carcinoma, and carcinoma ex pleomorphic adenoma.
Benign tumors classically present as asymptomatic enlarging masses. Signs or symptoms such as pain, cranial nerve deficits, or overlying skin changes usually herald the presence of malignancy. Computed tomography (CT), magnetic resonance imaging (MRI), and fine-needle biopsy (FNA) all have roles in the diagnosis and evaluation of these tumors.
Paragangliomas — Paragangliomas of the carotid body (previously called chemodectomas) and jugulotympanic paraganglia (previously called glomus jugulare and glomus tympanicum tumors) are highly vascular, typically benign tumors that can present as a neck mass. Paragangliomas are neoplasms that arise from extraadrenal chromaffin cells of the sympathetic and parasympathetic paraganglia; in the neck, paragangliomas arise almost exclusively from the parasympathetic paraganglia.
Within the head and neck, carotid body tumors are the most common followed by jugulotympanic glomus tumors. Carotid body tumors are often pulsatile and a bruit can be heard on auscultation. Classically, they are described as being mobile in a side to side direction but not in a vertical direction (the so-called positive Fontaine’s sign). Approximately one-third are inherited as part of a genetic syndrome, and genetic screening is advised for all patients because of the implications for malignant behavior and multifocality. (See "Paragangliomas: Epidemiology, clinical presentation, diagnosis, and histology", section on 'Definition and anatomic origin' and "Paragangliomas: Epidemiology, clinical presentation, diagnosis, and histology", section on 'Familial paraganglioma and SDH pathogenic variants' and "Paragangliomas: Epidemiology, clinical presentation, diagnosis, and histology", section on 'Head and neck paragangliomas'.)
Up to 10 percent of patients have a family history. Specific genes have been identified that help predict risk of malignancy or future development for family members . Ten to 20 percent of paragangliomas are multicentric. While generally considered benign histologically, up to 10 percent demonstrate malignant features and clinical course. Diagnosis is usually made based on characteristic features demonstrated on MRI/magnetic resonance angiography (MRA).
Schwannoma — Schwannomas result from neoplastic proliferation of Schwann cells and generally occur as growths that are closely associated with, but relatively circumscribed from, peripheral nerves. Schwannomas can arise from any peripheral nerve; in the neck, they most often arise from the vagus nerve or superior cervical sympathetic chain.
Schwannoma can have an insidious onset as a slow-growing mass but may also present with neurologic deficits. Vagal schwannomas may cause hoarseness or aspiration when they occur below the skull base. Sympathetic chain tumors often present with Horner syndrome.
The diagnosis of a Schwannoma is made with imaging. CT scanning may not reliably distinguish a carotid body tumor from a Schwannoma, although lack of flow voids with contrast enhancement suggests schwannoma. MRI/MRA or angiography is commonly indicated to establish the diagnosis.
Expectant management of Schwannomas is typically the best strategy in the absence of neural deficit, although intervention may be appropriate in other clinical scenarios. Management of schwannomas is reviewed in detail elsewhere. (See "Peripheral nerve tumors", section on 'Schwannoma'.)
Lymphoma — Lymphoma can present in the head and neck. Neck involvement is very common in children with Hodgkin lymphoma, found in up to 80 percent of patients. Hodgkin lymphoma should be suspected, especially in young patients with a history of fever, night sweats, chills, and diffuse lymphadenopathy. (See "Clinical presentation and initial evaluation of non-Hodgkin lymphoma" and "Clinical presentation and diagnosis of classic Hodgkin lymphoma in adults" and "Overview of Hodgkin lymphoma in children and adolescents".)
Lipoma and benign skin cysts — Lipomas are benign neoplasms comprised of fat and are typically asymptomatic. They are slowly enlarging masses that can occur in any location on the neck. Lipomas are soft and have ill-defined borders. These characteristics give lipomas a distinctive quality on physical examination.
Pain, rapid growth, or radiographic abnormality may suggest the presence of liposarcoma and should prompt excision to rule out this aggressive lesion.
Benign skin cysts such as epidermoid inclusion cysts, dermoids, or pilomatrixoma can also present as neck masses.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Neck mass".)
SUMMARY AND RECOMMENDATIONS
●The differential diagnosis of neck masses can be considered in three categories: congenital, inflammatory, and neoplastic. The adult patient should be approached with a presumption of malignancy until proven otherwise. (See 'Introduction' above.)
●Congenital neck masses are usually present at birth but may present at any age and are the most common noninflammatory neck mass in children. Branchial cleft cysts usually present in late childhood or early adulthood when a cyst becomes infected. Other benign lesions include thyroglossal duct cysts, vascular anomalies, laryngocele, ranula (mucocele), teratoma, dermoid cyst, and thymic cyst. (See 'Congenital neck mass' above.)
●Inflammatory neck masses are most commonly due to infection, typically reactive viral lymphadenopathy. Lymph node enlargement due to infectious mononucleosis may take up to six weeks to resolve; other viral adenopathy generally resolves in two weeks. Suppurative lymphadenopathy usually results from Staphylococcus aureus and group A beta streptococcal infections of the pharynx or skin. (See 'Infectious inflammatory disorders' above.)
●Neck masses that result from metastatic disease are predominantly related to metastatic squamous cell carcinoma arising from the aerodigestive tract but may be due to metastatic skin cancer (figure 2). Metastatic nodes in the posterior triangle are often related to nasopharyngeal carcinoma, whereas nodes along the upper jugular chain drain from the oral cavity, oropharynx, and larynx. Isolated supraclavicular nodes should raise concern for tracheobronchial, distal esophageal, or stomach carcinoma. (See 'Metastatic head and neck carcinoma' above.)
●While the majority of thyroid masses are benign nodules and cysts, malignancy must be considered. Symptoms of hoarseness or a history of radiation exposure in the setting of a new thyroid mass should increase the suspicion for malignancy. (See 'Thyroid masses' above.)
●Malignancy is more common in tumors of the submandibular gland than the parotid gland (50 versus 20 percent of tumors, respectively). Most benign salivary gland tumors are pleomorphic adenomas and present as asymptomatic enlarging masses. Pain, cranial nerve deficits, or overlying skin changes herald the presence of malignancy. (See 'Salivary gland neoplasm' above.)
●Other neoplastic disorders presenting as neck masses include paragangliomas, lymphoma, and lipomas. (See 'Neoplastic disorders' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Derrick Lin, MD, who contributed to an earlier version of this topic review.
12 : Long-standing lateral neck mass as the initial manifestation of well-differentiated thyroid carcinoma.
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