: 1 : 361 : 1 : 102 Diffuse TGCT occurs less frequently and is locally aggressive (in some cases, tumors may infiltrate surrounding soft tissue). : 245 : 1 : 102 : 1  It most commonly affects people under 40 years old, though the age of occurrence varies. : 102  Diffuse TGCT may occur inside a joint (intra-articular) or outside of a joint (extra-articular). Intra-articular tumors typically occur in the knee (approximately 75% of cases) and hip (approximately 15% of cases). : 102  Extra-articular tumors are usually found in the knee, thigh, and foot. : 101  Symptoms include swelling, pain, sensitivity, and/or limited range of motion. : 102  The rate of reoccurrence is estimated to be 18-46% for intra-articular tumors and 33-50% for extra-articular tumors. : 103 : 1

Complications
Diffuse TGCT is locally aggressive and can spread to surrounding tissues, causing bone erosion and tissue damage. If not treated early, it can spread to areas outside the joint, extra-articular, and potentially cause permanent loss of range as well as intense pain. Mechanism
TGCT tumors grow due to genetic overexpression of colony stimulating factor 1. This causes colony-stimulating factor-1 receptor (CSF1R) cells to accumulate in the joint tissue. Diagnosis
TGCT can be diagnosed by magnetic resonance imaging (MRI), by biopsy, or during surgery. The disorder is difficult to identify and is often not diagnosed for years due to nonspecific symptoms or a general paucity of symptoms. TGCT cases are often misdiagnosed as osteoarthritis, localized trauma, sports injuries, xanthomas, or other conditions. One study of 122 diffuse TGCT patients found that the average delay in diagnosis was 2.9 years.
Hereditary pancreatitis (HP) is an inflammation of the pancreas due to genetic causes. It was first described in 1952 by Comfort and Steinberg but it was not until 1996 that Whitcomb et al isolated the first responsible mutation in the trypsinogen gene (PRSS1) on the long arm of chromosome seven (7q35). The term "hereditary pancreatitis" is used when a genetic biomarker is identified, and "familial pancreatitis" otherwise. Presentation
HP is characterised by attacks of epigastric pain, which are often associated with nausea and vomiting. Symptoms may start shortly after birth but onset varies periodically, with some patients not exhibiting symptoms until adulthood. There is usually progression to chronic pancreatitis with endocrine and exocrine failure and a mortally increased risk of pancreatic cancer. Lifetime risk of cancer has been variously calculated as 35–54% to the age of 75 years and screening for early pancreatic cancer is being offered to HP sufferers on a scientific basis. Some patients may choose to have their pancreas surgically removed to prevent pancreatic cancer from developing in the future.The epidemiology of HP follows a similar pattern to alcohol-associated chronic pancreatitis, but there are important differences. For example, HP typically has an earlier age of pancreatitis onset; although malabsorption and diabetes mellitus occur at a later stage in the disease progression. Genetics
The vast majority of the cases of HP are caused by substitutions, at base 365 (c.365G>A) and base 86 of the cDNA (c.86A>T) on the PRSS1 gene.