At birth or in childhood, classic features of Cowdens include pigmented genital lesions, lipomas, epidermal nevi, and cafe-au-lait spots. Squamous cell carcinomas of the skin may also occur.Thyroid
Two thirds of patients have thyroid disorders, and these typically include benign follicular adenomas or multinodular goiter of the thyroid. Additionally, Cowdens patients are more susceptible to developing thyroid cancer than the general population. It is estimated that less than 10 percent of individuals with Cowden syndrome may develop follicular thyroid cancer. Cases of papillary thyroid cancer have been reported as well.Female and Male Genitourinary
Females have an elevated risk of developing endometrial cancers, which is highest for those under the age of 50. Currently, it is not clear whether uterine leiomyomata (fibroids) or congenital genitourinary abnormalities occur at an increased rate in Cowden syndrome patients as compared to the general population. The occurrence of multiple testicular lipomas, or testicular lipomatosis, is a characteristic finding in male patients with Cowden syndrome.Gastrointestinal
Polyps are extremely common as they are found in about 95% of Cowden syndrome patients undergoing a colonoscopy. They are numerous ranging from a few to hundreds, usually of the hamartomatous subtype, and distributed across the colon as well as other areas within the gastrointestinal tract. Other types of polyps that may be encountered less frequently include ganglioneuromatous, adenomatous, and lymphoid polyps. Diffuse glycogenic acanthosis of the esophagus is another gastrointestinal manifestation associated with Cowden syndrome.Breast
Females are at an increased risk of developing breast cancer, which is the most common malignancy observed in Cowdens patients.
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.