Signs and symptoms

Cholecystitis usually presents as a pain

Pain

Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...

 in the right upper quadrant. This is known as biliary colic

Biliary colic

Biliary colic is pain associated with irritation of the viscera secondary to cholecystitis and gallstones. Unlike renal colic, the phrase 'biliary colic' refers to the actual cholelithiasis....

. This is initially intermittent, but later usually presents as a constant, severe pain. During the initial stages, the pain may be felt in an area totally separate from the site of pathology, known as referred pain

Referred pain

Referred pain is pain perceived at a location other than the site of the painful stimulus. An example is the case of ischemia brought on by a myocardial infarction , where pain is often felt in the neck, shoulders, and back rather than in the chest, the site of the injury...

. The pain is originally located in the right upper quadrant but the referred pain may occur in the right scapula region.

This may also present with the above mentioned pain after eating greasy or fatty foods such as
pastries, pies, and fried foods.

This is usually accompanied by a low-grade fever, diarrhea, vomiting, nausea and granulocytosis. The gallbladder may be tender and distended.

More severe symptoms such as high fever, shock and jaundice

Jaundice

Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...

 indicate the development of complications such as abscess formation, perforation or ascending cholangitis

Ascending cholangitis

Ascending cholangitis or acute cholangitis is an infection of the bile duct , usually caused by bacteria ascending from its junction with the duodenum...

. Another complication, gallstone ileus, occurs if the gallbladder perforates and forms a fistula

Fistula

In medicine, a fistula is an abnormal connection or passageway between two epithelium-lined organs or vessels that normally do not connect. It is generally a disease condition, but a fistula may be surgically created for therapeutic reasons.-Locations:Fistulas can develop in various parts of the...

 with the nearby small bowel, leading to symptoms of intestinal obstruction.

Chronic cholecystitis manifests with non-specific symptoms such as nausea, vague abdominal pain, belching, and diarrhea.

Causes

Cholecystitis is often caused by cholelithiasis (the presence of choleliths, or gallstones, in the gallbladder), with choleliths most commonly blocking the cystic duct

Cystic duct

The cystic duct is the short duct that joins the gall bladder to the common bile duct. It usually lies next to the cystic artery. It is of variable length...

 directly. This leads to inspissation

Inspissation

-Intentional use:Inspissation is the process used when heating high-protein containing media; for example to enable recovery of bacteria for testing. Once inspissation has occurred, any stained bacteria, such as Mycobacteria, can then be isolated....

 (thickening) of bile

Bile

Bile or gall is a bitter-tasting, dark green to yellowish brown fluid, produced by the liver of most vertebrates, that aids the process of digestion of lipids in the small intestine. In many species, bile is stored in the gallbladder and upon eating is discharged into the duodenum...

, bile stasis

Stasis (medicine)

In medicine, stasis is the state in which the normal flow of a body liquid stops, for example the flow of blood through vessels or of intestinal contents through the digestive tract....

, and secondary infection by gut organisms, predominantly E. coli and Bacteroides

Bacteroides

Bacteroides is a genus of Gram-negative, bacillus bacteria. Bacteroides species are non-endospore-forming, anaerobes, and may be either motile or non-motile, depending on the species. The DNA base composition is 40-48% GC. Unusual in bacterial organisms, Bacteroides membranes contain sphingolipids...

species.

The gallbladder's wall becomes inflamed. Extreme cases may result in necrosis and rupture. Inflammation often spreads to its outer covering, thus irritating surrounding structures such as the diaphragm and bowel.

Less commonly, in debilitated and trauma patients, the gallbladder may become inflamed and infected in the absence of cholelithiasis, and is known as acute acalculous cholecystitis. This can arise in patients with anorexia nervosa

Anorexia nervosa

Anorexia nervosa is an eating disorder characterized by refusal to maintain a healthy body weight and an obsessive fear of gaining weight. Although commonly called "anorexia", that term on its own denotes any symptomatic loss of appetite and is not strictly accurate...

, as the lack of stimulation of the gallbladder leads to an infectious process.

Stones in the gallbladder may cause obstruction and the accompanying acute attack. The patient might develop a chronic, low-level inflammation which leads to a chronic cholecystitis, where the gallbladder is fibrotic and calcified.

Diagnosis

Cholecystitis is usually diagnosed by a history of the above symptoms, as well examination findings:

• fever (usually low grade in uncomplicated cases)
• tender right upper quadrant +/- Murphy's sign
  Murphy's sign
  In medicine, Murphy's sign refers to a maneuver during a physical examination as part of the abdominal examination and a finding elicited in ultrasonography. It is useful for differentiating pain in the right upper quadrant...
  
  
• Ortner's sign - tenderness when hand taps the edge of right costal arch.
• Georgievskiy - Myussi's sign (phrenic nerve sign) - pain when press between edges of sternocleidomastoid
• Boas' sign - Increased sensitivity below the right scapula (also due to phrenic nerve irritation).

Subsequent laboratory and imaging tests are used to confirm the diagnosis and exclude other possible causes.

Ultrasound can assist in the differential.

Acute cholecystitis

This should be suspected whenever there is acute right upper quadrant or epigastric pain, other possible causes include:

• Perforated peptic ulcer
• Acute peptic ulcer exacerbation
• Amoebic liver abscess
• Acute amoebic liver colitis
• Acute pancreatitis
  Acute pancreatitis
  Acute pancreatitis or acute pancreatic necrosis is a sudden inflammation of the pancreas. It can have severe complications and high mortality despite treatment...
  
  
• Acute intestinal obstruction
• Renal colic
• Acute retro-colic appendicitis

Chronic cholecystitis

The symptoms of chronic cholecystitis are non-specific, thus chronic cholecystitis may be mistaken for other common disorders:

• Peptic ulcer
• Hiatus hernia
  Hiatus hernia
  A hiatus hernia or hiatal hernia is the protrusion of the upper part of the stomach into the thorax through a tear or weakness in the diaphragm.- Classification :There are two major kinds of hiatus hernia:...
  
  
• Colitis
  Colitis
  In medicine, colitis refers to an inflammation of the colon and is often used to describe an inflammation of the large intestine .Colitides may be acute and self-limited or chronic, i.e...
  
  
• Functional bowel syndrome, it is defined pathologically by the columnar epithelium has reached down the muscular layer.

Quick Differential

• Biliary colic - Caused by obstruction of the cystic duct
  Cystic duct
  The cystic duct is the short duct that joins the gall bladder to the common bile duct. It usually lies next to the cystic artery. It is of variable length...
  
  . It is associated with sharp and constant epigastric pain in the absence of fever
  Fever
  Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
  
   and usually there is a negative Murphy's sign
  Murphy's sign
  In medicine, Murphy's sign refers to a maneuver during a physical examination as part of the abdominal examination and a finding elicited in ultrasonography. It is useful for differentiating pain in the right upper quadrant...
  
  . Liver function tests are within normal limits since the obstruction does not necessarily cause blockage in the common hepatic duct, thereby allowing normal bile excretion from the liver. An ultrasound scan is used to visualise the gallbladder and associated ducts, and also to determine the size and precise position of the obstruction.
• Cholecystitis - Caused by blockage of the cystic duct with surrounding inflammation, usually due to infection. Typically, the pain is initially 'colicky' (intermittent), and becomes constant and severe, mostly in the right upper quadrant. Infectious agents that cause cholecystitis include E. coli, Klebsiella
  Klebsiella
  Klebsiella is a genus of non-motile, Gram-negative, oxidase-negative, rod-shaped bacteria with a prominent polysaccharide-based capsule. It is named after the German microbiologist Edwin Klebs...
  
  , Pseudomonas
  Pseudomonas
  Pseudomonas is a genus of gammaproteobacteria, belonging to the family Pseudomonadaceae containing 191 validly described species.Recently, 16S rRNA sequence analysis has redefined the taxonomy of many bacterial species. As a result, the genus Pseudomonas includes strains formerly classified in the...
  
  , B. fragilis
  Bacteroides fragilis
  Bacteroides fragilis is a Gram-negative bacillus bacterium species, and an obligate anaerobe of the gut.B. fragilis group is the most commonly isolated bacteriodaceae in anaerobic infections especially those that originate from the gastrointestinal flora. B. fragilis is the most prevalent organism...
  
  and Enterococcus
  Enterococcus
  Enterococcus is a genus of lactic acid bacteria of the phylum Firmicutes. Enterococci are Gram-positive cocci that often occur in pairs or short chains, and are difficult to distinguish from streptococci on physical characteristics alone. Two species are common commensal organisms in the...
  
  . Murphy's sign is positive, particularly because of increased irritation of the gallbladder lining, and similarly this pain radiates (spreads) to the shoulder, flank or in a band like pattern around the lower abdomen. Laboratory tests frequently show raised hepatocellular liver enzymes (AST, ALT) with a high white cell count (WBC). Ultrasound is used to visualise the gallbladder and ducts.
• Choledocholithiasis - This refers to blockage of the common bile duct
  Common bile duct
  The common bile duct is a tube-like anatomic structure in the human gastrointestinal tract. It is formed by the union of the common hepatic duct and the cystic duct . It is later joined by the pancreatic duct to form the ampulla of Vater...
  
   where a gallstone has left the gallbladder or has formed in the common bile duct (primary cholelithiasis). As with other biliary tree obstructions it is usually associated with 'colicky' pain, and because there is direct obstruction of biliary output, obstructive jaundice
  Jaundice
  Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
  
  . Liver function tests will therefore show increased serum bilirubin
  Bilirubin
  Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
  
  , with high conjugated bilirubin. Liver enzymes will also be raised, predominately GGT and ALP
  Alkaline phosphatase
  Alkaline phosphatase is a hydrolase enzyme responsible for removing phosphate groups from many types of molecules, including nucleotides, proteins, and alkaloids. The process of removing the phosphate group is called dephosphorylation...
  
  , which are associated with biliary epithelium. The diagnosis is made using endoscopic retrograde cholangiopancreatography (ERCP), or the nuclear alternative (MRCP
  Magnetic resonance cholangiopancreatography
  Magnetic resonance cholangiopancreatography is a medical imaging technique that uses magnetic resonance imaging to visualise the biliary and pancreatic ducts in a non-invasive manner...
  
  ). One of the more serious complications of choledocholithiasis is acute pancreatitis
  Acute pancreatitis
  Acute pancreatitis or acute pancreatic necrosis is a sudden inflammation of the pancreas. It can have severe complications and high mortality despite treatment...
  
  , which may result in significant permanent pancreatic damage and brittle diabetes.
• Cholangitis - An infection of entire biliary tract, and may also be known as 'ascending cholangitis', which refers to the presence of pathogens that typically inhabit more distal regions of the bowel

Cholangitis is a medical emergency as it may be life threatening and patients can rapidly succumb to acute liver failure or bacterial sepsis. The classical sign of cholangitis is Charcot's triad

Charcot's triad

Charcot's neurologic triad is the combination of nystagmus, intention tremor, and scanning or staccato speech. This triad is associated with multiple sclerosis, where it was first described; however, it is not considered pathognomonic for it. It is named for Jean-Martin Charcot.-See also:*Charcot's...

, which is right upper quadrant pain, fever and jaundice. Liver function tests will likely show increases across all enzymes (AST, ALT, ALP, GGT) with raised bilirubin. As with choledocholithiasis, diagnosis is confirmed using cholangiopancreatography.

It is worth noting that bile is an extremely favourable growth medium for bacteria, and infections in this space develop rapidly and may become quite severe.

Blood

Laboratory values may be notable for an elevated alkaline phosphatase

Alkaline phosphatase

Alkaline phosphatase is a hydrolase enzyme responsible for removing phosphate groups from many types of molecules, including nucleotides, proteins, and alkaloids. The process of removing the phosphate group is called dephosphorylation...

, possibly an elevated bilirubin

Bilirubin

Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...

 (although this may indicate choledocholithiasis), and possibly an elevation of the WBC

White blood cell

White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...

 count. CRP (C-reactive protein) is often elevated. The degree of elevation of these laboratory values may depend on the degree of inflammation of the gallbladder. Patients with acute cholecystitis are much more likely to manifest abnormal laboratory values, while in chronic cholecystitis the laboratory values are frequently normal.

Radiology

Sonography

Ultrasound

Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...

 is a sensitive and specific modality for diagnosis of acute cholecystitis; adjusted sensitivity and specificity for diagnosis of acute cholecystitis are 88% and 80%, respectively. The diagnostic criteria are gallbladder wall thickening greater than 3mm, pericholecystic fluid and sonographic Murphy's sign

Murphy's sign

In medicine, Murphy's sign refers to a maneuver during a physical examination as part of the abdominal examination and a finding elicited in ultrasonography. It is useful for differentiating pain in the right upper quadrant...

. Gallstones are not part of the diagnostic criteria as acute cholecystitis may occur with or without them.

The reported sensitivity and specificity of CT scan findings are in the range of 90-95%. CT is more sensitive than ultrasonography in the depiction of pericholecystic inflammatory response and in localizing pericholecystic abscesses, pericholecystic gas, and calculi

Calculus (medicine)

A calculus is a stone that forms in an organ or duct of the body. Formation of calculi is known as lithiasis...

 outside the lumen

Lumen (anatomy)

A lumen in biology is the inside space of a tubular structure, such as an artery or intestine...

 of the gallbladder. CT cannot see noncalcified gallbladder calculi, and cannot assess for a Murphy's sign.

Hepatobiliary scintigraphy

Nuclear medicine

In nuclear medicine procedures, elemental radionuclides are combined with other elements to form chemical compounds, or else combined with existing pharmaceutical compounds, to form radiopharmaceuticals. These radiopharmaceuticals, once administered to the patient, can localize to specific organs...

 with technetium

Technetium

Technetium is the chemical element with atomic number 43 and symbol Tc. It is the lowest atomic number element without any stable isotopes; every form of it is radioactive. Nearly all technetium is produced synthetically and only minute amounts are found in nature...

-99m DISIDA (bilirubin

Bilirubin

Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...

) analog is also sensitive and accurate for diagnosis of chronic and acute cholecystitis. It can also assess the ability of the gall bladder to expel bile (gall bladder ejection fraction), and low gall bladder ejection fraction has been linked to chronic cholecystitis. However, since most patients with right upper quadrant pain do not have cholecystitis, primary evaluation is usually accomplished with a modality that can diagnose other causes, as well.

Management

For most patients, in most centres, the definitive treatment is surgical removal of the gallbladder. Supportive measures are instituted in the meantime and to prepare the patient for surgery. These measures include fluid resuscitation and antibiotic

Antibiotic

An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...

s. Antibiotic regimens usually consist of a broad spectrum antibiotic such as piperacillin-tazobactam

Piperacillin/tazobactam

Piperacillin/tazobactam is a combination antibiotic containing the extended-spectrum penicillin antibiotic piperacillin and the β-lactamase inhibitor tazobactam. It is marketed as Kilbac by Morepen and Tazocin or, in the USA, as Zosyn by Wyeth Pharms Inc .-External links:*...

 (Zosyn), ampicillin-sulbactam

Ampicillin/sulbactam

Ampicillin/sulbactam is a combination of the common penicillin-derived antibiotic ampicillin and sulbactam, an inhibitor of bacterial beta-lactamase. Two different forms of the drug exist. The first, developed in 1987 and marketed in the United States under the tradename Unasyn, is an intravenous...

 (Unasyn), ticarcillin

Ticarcillin

Ticarcillin is a carboxypenicillin. It is almost invariably sold and used in combination with clavulanate as Timentin. Because it is a penicillin, it also falls within the larger class of beta-lactam antibiotics. Its main clinical use is as an injectable antibiotic for the treatment of...

-clavulanate (Timentin), or a cephalosporin (e.g.ceftriaxone

Ceftriaxone

Ceftriaxone is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, it has broad spectrum activity against Gram-positive and Gram-negative bacteria. In most cases, it is considered to be equivalent to cefotaxime in terms of safety and efficacy...

) and an antibacterial with good coverage (fluoroquinolone such as ciprofloxacin

Ciprofloxacin

Ciprofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class.It is a second-generation fluoroquinolone antibacterial. It kills bacteria by interfering with the enzymes that cause DNA to rewind after being copied, which stops synthesis of DNA and of...

) and anaerobic bacteria coverage, such as metronidazole

Metronidazole

Metronidazole is a nitroimidazole antibiotic medication used particularly for anaerobic bacteria and protozoa. Metronidazole is an antibiotic, amebicide, and antiprotozoal....

. For penicillin allergic patients, aztreonam

Aztreonam

Aztreonam is a synthetic monocyclic beta-lactam antibiotic , with the nucleus based on a simpler monobactam isolated from Chromobacterium violaceum. It was approved by the U.S. Food and Drug Administration in 1986...

 and clindamycin

Clindamycin

Clindamycin rINN is a lincosamide antibiotic. It is usually used to treat infections with anaerobic bacteria but can also be used to treat some protozoal diseases, such as malaria...

 may be used.

Gallbladder removal, cholecystectomy

Cholecystectomy

Cholecystectomy is the surgical removal of the gallbladder. It is the most common method for treating symptomatic gallstones. Surgical options include the standard procedure, called laparoscopic cholecystectomy, and an older more invasive procedure, called open cholecystectomy.-Open surgery:A...

, can be accomplished via open surgery or a laparoscopic procedure. Laparoscopic procedures can have less morbidity and a shorter recovery stay. Open procedures are usually done if complications have developed or the patient has had prior surgery to the area, making laparoscopic surgery technically difficult. A laparoscopic procedure may also be 'converted' to an open procedure during the operation if the surgeon feels that further attempts at laparoscopic removal might harm the patient. Open procedure may also be done if the surgeon does not know how to perform a laparoscopic cholecystectomy.

In cases of severe inflammation, shock, or if the patient has higher risk for general anesthesia (required for cholecystectomy

Cholecystectomy

Cholecystectomy is the surgical removal of the gallbladder. It is the most common method for treating symptomatic gallstones. Surgical options include the standard procedure, called laparoscopic cholecystectomy, and an older more invasive procedure, called open cholecystectomy.-Open surgery:A...

), the managing physician may elect to have an interventional radiologist

Interventional radiology

Interventional radiology is a specialty of radiology, in which image-guided procedures are used to diagnose and treat a multitude of diseases across all body systems...

 insert a percutaneous

Percutaneous

In surgery, percutaneous pertains to any medical procedure where access to inner organs or other tissue is done via needle-puncture of the skin, rather than by using an "open" approach where inner organs or tissue are exposed .The percutaneous approach is commonly used in vascular procedures...

 drainage catheter into the gallbladder ('percutaneous cholecystostomy

Cholecystostomy

A cholecystostomy is a procedure where a stoma is created in the gallbladder, which can facilitate placement of a tube for drainage....

 tube') and treat the patient with antibiotics until the acute inflammation resolves. A cholecystectomy

Cholecystectomy

Cholecystectomy is the surgical removal of the gallbladder. It is the most common method for treating symptomatic gallstones. Surgical options include the standard procedure, called laparoscopic cholecystectomy, and an older more invasive procedure, called open cholecystectomy.-Open surgery:A...

 may then be warranted if the patient's condition improves.

Cholecystectomy

• emphysematous cholecystitis
• bile leak ("biloma")
• bile duct injury (about 5-7 out of 1000 operations. Open and laparoscopic surgeries have essentially equal rate of injuries, but the recent trend is towards fewer injuries with laparoscopy. It may be that the open cases often result because the gallbladder is too difficult or risky to remove with laparoscopy)
• abscess
• wound infection
• bleeding (liver surface and cystic artery are most common sites)
• hernia
• organ injury (intestine and liver are at highest risk, especially if the gallbladder has become adherent/scarred to other organs due to inflammation (e.g. transverse colon
  Transverse colon
  The transverse colon, the longest and most movable part of the colon, passes with a downward convexity from the right hypochondrium region across the abdomen, opposite the confines of the epigastric and umbilical zones, into the left hypochondrium region, where it curves sharply on itself beneath...
  
  )
• deep vein thrombosis
  Deep vein thrombosis
  Deep vein thrombosis is the formation of a blood clot in a deep vein. Deep vein thrombosis commonly affects the leg veins or the deep veins of the pelvis. Occasionally the veins of the arm are affected...
  
  /pulmonary embolism
  Pulmonary embolism
  Pulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
  
   (unusual- risk can be decreased through use of sequential compression devices on legs during surgery)
• fatty acid and fat-soluble vitamin malabsorption

Gall bladder perforation

Gall bladder perforation (GBP) is a rare but life-threatening complication of acute cholecystitis. The early diagnosis and treatment of GBP are crucial to decrease patient morbidity and mortality.

Approaches to this complication will vary based on the condition of an individual patient, the evaluation of the treating surgeon or physician, and the facilities' capability. Perforation can happen at the neck from pressure necrosis due to the impacted calculus

Calculus

Calculus is a branch of mathematics focused on limits, functions, derivatives, integrals, and infinite series. This subject constitutes a major part of modern mathematics education. It has two major branches, differential calculus and integral calculus, which are related by the fundamental theorem...

, or at the fundus. It can result in a local abscess

Abscess

An abscess is a collection of pus that has accumulated in a cavity formed by the tissue in which the pus resides due to an infectious process or other foreign materials...

, or perforation into the general peritoneal cavity. If the bile is infected, diffuse peritonitis may occur readily and rapidly and may result in death
A retrospective study looked at 332 patients who received medical and/or surgical treatment with the diagnosis of acute cholecystitis. Patients were treated with analgesics and antibiotics within the first 36 hours after admission (with a mean of 9 hours), and proceeded to surgery for a cholecystectomy

Cholecystectomy

Cholecystectomy is the surgical removal of the gallbladder. It is the most common method for treating symptomatic gallstones. Surgical options include the standard procedure, called laparoscopic cholecystectomy, and an older more invasive procedure, called open cholecystectomy.-Open surgery:A...

. Two patients died and 6 patients had further complications. The morbidity and mortality rates were 37.5% and 12.5%, respectively in the present study. The authors of this study suggests that early diagnosis and emergency surgical treatment of gallbladder perforation are of crucial importance.

Xanthogranulomatous cholecystitis

Xanthogranulomatous cholecystitis (XGC) is a rare form of gallbladder disease

Gallbladder disease

Gallbladder diseases are diseases involving the gallbladder.Gallstones may develop in the gallbladder as well as elsewhere in the biliary tract...

 which mimics gallbladder cancer

Gallbladder cancer

Gallbladder cancer is a relatively uncommon cancer. It has peculiar geographical distribution being common in central and South America, central and eastern Europe, Japan and northern India; it is also common in certain ethnic groups e.g. Native American Indians and Hispanics. If it is diagnosed...

although it is not cancerous. It was first discovered and reported in the medical literature in 1976 by J.J. McCoy, Jr., and colleagues.