Diseases of the Salivary Glands

Diseases of the salivary glands include sialadenosis, sialadenitis, sialolithiasis, and neoplasms. Sialadenosis is a chronic, bilateral, noninflammatory hypertrophy of the salivary glands. Sialadenitis results from inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation or infection of the glands, and sialolithiasis is due to stone formation in the glands or ducts. Neoplasms of the salivary gland may be benign or malignant. All of these conditions manifest as salivary gland enlargement. Other clinical factors help differentiate these conditions, such as symmetry, the presence of pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, associated conditions and risk factors, and growth or stability. The diagnosis is often clinical, though imaging and biopsy may be needed. Management varies depending on the disease.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Table of Contents

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Overview

Major salivary glands

  • Parotid glands
  • Submandibular glands
  • Sublingual glands
Location of the major salivary glands and their ducts

Diagram depicting the location of the major salivary glands and their ducts

Image: “2408 Salivary Glands Salivary glands The salivary glands are exocrine glands positioned in and around the oral cavity. These glands are responsible for secreting saliva into the mouth, which aids in digestion. There are 3 major paired salivary glands: the sublingual, submandibular, and parotid glands. Salivary Glands” by OpenStax College. License: CC BY 3.0

Physiology

The major salivary glands produce > 95% of an individual’s saliva.

  • Secreted by acinar cells
  • Concentration of ions modified by ductal cells
  • Composition: 
    • 99.5% water 
    • Electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes
    • Mucus
    • Glycoproteins
    • Enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
    • Antibacterial compounds
  • Function:
    • Lubricates food to aid in the swallowing process
    • Starts digestion of carbohydrates Digestion of carbohydrates Carbohydrates store energy and are used as a source of nutrition. To be used as energy by humans, most carbohydrates must be metabolized. Carbohydrate metabolism involves transforming complex starches into glucose, a monosaccharide that can subsequently be absorbed by the body. Digestion and Absorption of Carbohydrates and lipids
    • Immunologic defense against microbes in the oral cavity
    • Protects the oral mucosa and teeth Teeth Normally, an adult has 32 teeth: 16 maxillary and 16 mandibular. These teeth are divided into 4 quadrants with 8 teeth each. Each quadrant consists of 2 incisors (dentes incisivi), 1 canine (dens caninus), 2 premolars (dentes premolares), and 3 molars (dentes molares). Teeth are composed of enamel, dentin, and dental cement. Teeth
    • Aids in the sense of taste
Ion movement between the acinar cells and the ductal cells

Diagram displaying the differences in ion movement between the acinar cells (in charge of secretion) and the ductal cells (in charge of reabsorption)

Image by Lecturio.

Terminology for pathologic conditions

Since sialadenosis, sialadenitis, and sialithiasis are similar-appearing names, understanding the suffix may aid in differentiating the underlying process.

  • “-osis”: increase or pathologic condition
  • “-itis”: inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation or infection
  • “-lithiasis”: stone formation

Related videos

Sialadenosis

Definition

Sialadenosis (sialosis) is a chronic, benign, noninflammatory hypertrophy of the salivary glands.

Epidemiology

  • Most common cause of salivary gland swelling
  • Incidence and prevalence are unknown
  • Men = women

Etiology

  • Drug-induced:
    • Valproic acid
    • Thiouracil
    • Antihypertensives
  • Nutritional:
    • Vitamin deficiencies and malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries
    • Bulimia
  • Endocrine/metabolic disorders:
    • Diabetes
    • Hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto's disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism
    • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
  • Other medical conditions:
    • Sjögren syndrome
    • Cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
    • Alcoholism

Pathophysiology

  • The cause of hypertrophy is unknown.
  • Potential process: accumulation of secretory granules in acinar cells → acinar enlargement → fatty infiltration of the salivary glands

Clinical presentation

Patients will present with enlarged salivary glands with the following characteristics:

  • Usually bilateral
  • Symmetrical 
  • No fluctuation in size or progressive enlargement
  • Soft
  • Nontender
Bilateral parotid gland swelling due to sialadenosis

Bilateral parotid gland swelling due to sialadenosis (sialosis)

Image: “Buccal alterations in diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus” by Negrato CA, Tarzia O. License: CC BY 2.0

Diagnosis

  • Suspected based on history and physical examination
  • Ultrasonography: 
    • Diffuse salivary gland enlargement
    • Other abnormalities should be ruled out

Management

No treatment is needed, other than addressing the underlying medical condition.

Sialadenitis

Definition

Sialadenitis is inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation or infection of the salivary glands.

Epidemiology

  • The exact incidence is unknown.
  • No predilection for race or sex
  • Tends to occur in older, chronically ill, and dehydrated patients

Etiology

  • Infectious causes (most common): 
    • Viral:
      • Mumps Mumps Mumps is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. Mumps is typically a disease of childhood, which manifests initially with fever, muscle pain, headache, poor appetite, and a general feeling of malaise, and is classically followed by parotitis. Mumps Virus/Mumps
      • EBV
      • Parainfluenza
      • Adenovirus Adenovirus Adenovirus (member of the family Adenoviridae) is a nonenveloped, double-stranded DNA virus. Adenovirus is transmitted in a variety of ways, and it can have various presentations based on the site of entry. Presentation can include febrile pharyngitis, conjunctivitis, acute respiratory disease, atypical pneumonia, and gastroenteritis. Adenovirus
      • Enterovirus
      • Parvovirus
      • HHV-6 HHV-6 Human herpesvirus (HHV)-6 and HHV-7 are similar double-stranded DNA viruses belonging to the Herpesviridae family. Human herpesviruses are ubiquitous and infections are commonly contracted during childhood. Human Herpesvirus 6 & 7
    • Bacterial:
      • Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus
      • Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus viridans
      • Haemophilus Haemophilus Haemophilus is a genus of Gram-negative coccobacilli, all of whose strains require at least 1 of 2 factors for growth (factor V [NAD] and factor X [heme]); therefore, it is most often isolated on chocolate agar, which can supply both factors. The pathogenic species are H. influenzae and H. ducreyi. Haemophilus influenzae
      • Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus pyogenes
      • Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli
  • Iatrogenic causes:
    • Radiation treatment
    • Radioiodine or contrast exposure
  • Drug-induced:
    • Clozapine
    • Phenylbutazone
  • Juvenile recurrent parotitis

Risk factors

  • Age > 50 years
  • HIV 
  • Xerostomia
  • Dehydration
  • Anorexia or bulimia 
  • Sjögren syndrome 
  • Sialolithiasis

Pathophysiology

  • Bacterial: ductal obstruction or salivary hyposecretion → ascending bacterial contamination → secondary infection
  • Radiation or iodine-induced: inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation or damage to gland parenchyma → acute swelling → may or may not be associated with ductal blockage

Clinical presentation

  • Acute salivary gland swelling:
    • Usually unilateral 
    • Parotid gland is most commonly involved (parotitis)
    • Pain and swelling with meals
    • Firm and diffusely tender
  • Overlying erythema and edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
  • Purulent exudate can sometimes be massaged from the duct opening.
  • Fever and chills

Diagnosis

The diagnosis is clinical. An evaluation can be done if the diagnosis is uncertain or to determine an etiology:

  • Gram stain and culture of purulent exudate from the gland (if possible)
  • PCR or serology for mumps virus Mumps virus Mumps is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae and the subfamily Rublavirinae. The mumps virus is contagious and spreads only among humans by respiratory droplets or direct contact transmission from an infected person or fomite. Mumps Virus/Mumps
  • Imaging with CT, ultrasonography, or MRI to identify:
    • Stones in the duct
    • Abscess
    • Inflammation of the gland

Management

General measures:

  • Hydration
  • Good oral hygiene
  • Warm compresses
  • Massage of the gland
  • Sialagogues (↑ salivary flow):
    • Chewing gum
    • Lemon drops

For bacterial infection:

  • Initial antibiotics:
    • Community-acquired:
      • Ampicillin–sulbactam
      • Cefuroxime plus metronidazole
      • Nafcillin plus ceftriaxone (or levofloxacin) plus metronidazole (or clindamycin)
    • Hospital-acquired or immunocompromised: vancomycin plus any of the following:
      • Cefepime plus metronidazole
      • Carbapenem Carbapenem The carbapenems and aztreonam are both members of the bactericidal beta-lactam family of antibiotics (similar to penicillins). They work by preventing bacteria from producing their cell wall, ultimately leading to bacterial cell death. Carbapenems and Aztreonam
      • Piperacillin–tazobactam
  • Abscess drainage

Sialolithiasis

Definition

Sialolithiasis is the formation of calculi within the salivary glands or ducts.

Epidemiology

  • Estimated incidence: 0.3–1 in 10,000 people
  • Men > women
  • Age range: 30–60 years
  • Approximately 80% of stones occur in submandibular glands.

Etiology

  • Stagnation of salivary flow:
    • Anatomical duct stenosis
    • Inflammation
    • Dehydration
    • Anorexia
    • Allergies
    • Medications (e.g., anticholinergics)
  • ↑ Salivary calcium

Pathophysiology

  • The pathogenesis of stone formation is not well understood.
  • Calculi can obstruct ducts → ↑ pressure within the gland → pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain and swelling

Clinical presentation

  • Glandular swelling
  • May or may not have associated pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain and tenderness
  • Pain is worse with eating.
  • Digital palpation may reveal the presence of calculus.
Salivary gland stone (sialolithiasis)

Salivary gland stone (sialolithiasis)

Image: “Salivary gland stone removed” by Peternickson. License: CC0 1.0

Diagnosis

  • Usually a clinical diagnosis
  • The presence of a stone may be confirmed with:
    • X-ray
    • Ultrasonography
    • CT
    • Sialography (radiopaque dye is injected into the duct for visualization on X-ray)
X-ray demonstrating a massive opacity consistent with sialolithiasis

X-ray demonstrating a massive opacity (arrow) consistent with sialolithiasis

Image: “Massive Submandibular Sialolith: Complete Radiographic Registration and Biochemical Analysis through X-Ray Diffraction” by Franco, A., et al. License: CC BY 3.0

Management

  • Conservative management:
    • Hydration
    • Hot compresses
    • Gland massage
    • Analgesia with NSAIDs
    • Sialagogues
  • Stones close to the orifice of the duct may be removed with manual expression.
  • Other methods:
    • Sialendoscopy
    • Extracorporeal shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock-wave lithotripsy
    • Laser lithotripsy 
    • Basket retrieval
  • If the obstruction cannot be removed, surgical excision may be necessary.

Salivary Gland Neoplasms

Epidemiology

  • Salivary gland tumors are rare.
  • Incidence: approximately 5.5 cases per 100,000 people per year in the United States
  • Represent 6%–8% of all head and neck tumors
  • Age: 
    • Benign: > 40 years of age
    • Malignant: > 60 years of age
  • Sex:
    • Benign: women > men
    • Malignant: men = women
  • The parotid gland is the most common site (80%–85% of cases).

Classification

  • Benign neoplasms (majority):
    • Pleomorphic adenoma (most common)
    • Warthin tumor (also known as papillary cystadenoma lymphomatosum)
    • Myoepithelioma
    • Lymphadenoma
    • Sebaceous adenoma
    • Basal cell adenoma
    • Canalicular adenoma
    • Oncocytoma
    • Cystadenoma
    • Sialadenoma papilliferum
    • Ductal papilloma
  • Malignant neoplasms:
    • Mucoepidermoid carcinoma (most common)
    • Adenoid cystic carcinoma
    • Acinic cell carcinoma
    • Carcinoma ex pleomorphic adenoma (malignant transformation of pleomorphic adenoma)
    • Polymorphous low-grade adenocarcinoma
    • Salivary duct carcinoma
    • Primary squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma

Risk factors

The following are risk factors for malignant salivary tumors:

  • Ionizing radiation exposure
  • Environmental exposures:
    • Rubber manufacturing
    • Nickel compounds
    • Hair salon/beauty shop personnel
  • Viral infections:
    • EBV
    • HIV

Clinical presentation

  • Presentation based on involved glands:
    • Major salivary glands: painless mass or swelling
    • Minor salivary glands:
      • Submucosal mass 
      • Mucosal ulceration
  • Malignant tumors are characterized by: 
    • Rapid growth
    • Firm
    • Nodular
    • Can be fixed to adjacent tissue
    • Facial nerve involvement: 
      • Persistent pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
      • Asymmetry of facial motion 
      • Total facial paralysis
    • Associated with cervical lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy
  • Depending on the location, neoplasms can lead to:
    • Dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming "stuck." Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia or odynophagia
    • Nasal or airway obstruction Airway obstruction Airway obstruction is a partial or complete blockage of the airways that impedes airflow. An airway obstruction can be classified as upper, central, or lower depending on location. Lower airway obstruction (LAO) is usually a manifestation of chronic disease, such as asthma or chronic obstructive pulmonary disease (COPD). Airway Obstruction
    • Vocal hoarseness

Diagnosis

  • Fine-needle aspiration biopsy establishes the diagnosis.
  • Ultrasonography:
    • Usually an initial test to distinguish characteristics of the mass
    • Useful in guiding biopsy
  • CT or MRI can be used to define the extent of the tumor:
    • Assess the location
    • Detect local invasion
    • Identify metastatic disease
Ct neck soft tissue demonstrating an enhancing mass

CT of neck soft tissue demonstrates an enhancing mass (white arrow) within the left parotid gland. No enlarged lymph nodes or abnormal fluid collections are seen.

Image: “An unusual initial presentation of mantle cell lymphoma arising from the lymphoid stroma of warthin tumor” by Arcega RS, Feinstein AJ, Bhuta S, Blackwell KE, Rao NP, Pullarkat ST. License: CC BY 4.0

Management

  • Complete surgical excision:
    • Treatment of choice for all salivary gland neoplasms
    • Complications:
      • Facial nerve injury (most common early complication)
      • Frey’s syndrome: gustatory sweating and flushing due to abnormal regeneration of parasympathetic nerve fibers
  • Adjuvant radiation therapy may be used for malignant neoplasms.

Differential Diagnosis

  • Branchial cleft cyst: congenital defect resulting from incomplete obliteration of the branchial clefts during embryonic development. Branchial cleft cyst can cause a small, painless neck mass that can become infected, resulting in the cyst becoming tender and inflamed. The diagnosis is typically clinical, and excision can be considered.
  • Lymphadenopathy: palpable enlargement of the lymph nodes, which can result from a number of etiologies, including infection and malignancy. If there is concern for malignancy or worrisome physical exam findings, laboratory evaluation, peripheral blood smear, biopsy, or infectious workup should be performed. Management is directed at the underlying etiology.
  • Dental abscess: odontogenic infection that often arises because of dental caries. Patients with dental abscess can have severe tooth pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, facial erythema, and fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever. The diagnosis is made with physical examination and imaging. Management includes drainage of the abscess, antibiotics, and removal of the infected tooth.
  • Cellulitis Cellulitis Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. Cellulitis: common infection caused by bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview that affects the dermis and subcutaneous tissue of the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin. Cellulitis Cellulitis Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. Cellulitis can occur anywhere, including the face or neck. The infection presents as an erythematous, edematous area with warmth and tenderness. Diagnosis is usually clinical, and management involves antibiotics.
  • Hodgkin lymphoma Hodgkin lymphoma Hodgkin lymphoma (HL) is a malignancy of B lymphocytes originating in the lymph nodes. The pathognomonic histologic finding of HL is a Hodgkin/Reed-Sternberg (HRS) cell (giant multinucleated B cells with eosinophilic inclusions). The disease presents most commonly with lymphadenopathy, night sweats, weight loss, fever, splenomegaly and hepatomegaly. Hodgkin Lymphoma: malignancy of B lymphocytes B lymphocytes B lymphocytes, also known as B cells, are important components of the adaptive immune system. In the bone marrow, the hematopoietic stem cells go through a series of steps to become mature naive B cells. The cells migrate to secondary lymphoid organs for activation and further maturation. B Cells originating in the lymph nodes. The disease presents with lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy (most commonly involving the neck), night sweats, weight loss, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, and potentially splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly and hepatomegaly. Diagnostic testing includes lymph node histologic analysis, blood tests, and imaging. Management includes chemotherapy and radiotherapy.

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