Causes
Circulatory disorders
Diabetic vasculopathy
Sepsis with peripheral necrosis
Peripheral artery disease which can lead to gangrene
A severe deep vein thrombosis (phlegmasia cerulea dolens) can cause compartment syndrome and gangrene

Neoplasm
Cancerous bone or soft tissue tumors (e.g. osteosarcoma, chondrosarcoma, fibrosarcoma, epithelioid sarcoma, Ewings sarcoma, synovial sarcoma, sacrococcygeal teratoma, liposarcoma), melanoma

Trauma
Severe limb injuries in which the limb cannot be saved or efforts to save the limb fail. Traumatic amputation (an unexpected amputation that occurs at the scene of an accident, where the limb is partially or entirely severed as a direct result of the accident, for example, a finger that is severed from the blade of a table saw)
Amputation in utero (Amniotic band)

Congenital anomalies
Deformities of digits and/or limbs (e.g., proximal femoral focal deficiency, Fibular hemimelia)
Extra digits and/or limbs (e.g., polydactyly)

Infection
Bone infection (osteomyelitis) and/or diabetic foot infections
Gangrene
Trench foot
Necrosis
Meningococcal meningitis
Streptococcus
Vibrio vulnificus
Necrotizing fasciitis
Gas gangrene
Legionella
Influenza A Virus
Animal bites
Sepsis
Bubonic plague

Frostbite
Frostbite is a cold-related injury occurring when an area (typically a limb or other extremity) is exposed to extreme low temperatures, causing the freezing of the skin or other tissues. Its pathophysiology involves the formation of ice crystals upon freezing and blood clots upon thawing, leading to cell damage and cell death. Treatment of severe frostbite may require surgical amputation of the affected tissue or limb; if there is deep injury autoamputation may occur. Athletic performance
Sometimes professional athletes may choose to have a non-essential digit amputated to relieve chronic pain and impaired performance. Australian Rules footballer Daniel Chick elected to have his left ring finger amputated as chronic pain and injury was limiting his performance.
A possible interplay between PTEN and SEC23B has recently been suggested, given emerging evidence of each having a role in ribosome biogenesis, but this has not been conclusively determined. Diagnosis
The revised clinical criteria for the diagnosis of Cowdens syndrome for an individual is dependent on either one of the following: 1) 3 major criteria are met or more that must include macrocephaly, Lhermitte-Duclos, or GI hamartomas 2) two major and three minor criteria. The major and minor criteria are listed below:

Screening
The management of Cowden syndrome centers on the early detection and prevention of cancer types that are known to occur as part of this syndrome. Specific screening guidelines for Cowden syndrome patients have been published by the National Comprehensive Cancer Network (NCCN). Surveillance focuses on the early detection of breast, endometrial, thyroid, colorectal, renal, and skin cancer. See below for a complete list of recommendations from the NCCN:

Treatment
Malignancies that occur in Cowden syndrome are usually treated in the same fashion as those that occur sporadically in patients without a hereditary cancer syndrome. Two notable exceptions are breast and thyroid cancer. In Cowden syndrome patients with a first-time diagnosis of breast cancer, treatment with mastectomy of the involved breast as well as prophylactic mastectomy of the uninvolved contralateral breast should be considered. In the setting of thyroid cancer or a follicular adenoma, a total thyroidectomy is recommended even in cases where it appears that only one lobe of the thyroid is affected.