Pathology | Comments | Reference |
---|---|---|
Cancers | Several cancers are known to be associated with PIK3CA somatic mutations such as cancer of the breast, colon, stomach, liver, lung and ovaries | [13] |
Benign skin lesions/ Tumors | Seborrheic keratosis, epidermal nevi, Lichenoid keratosis, hydradenomapapilliferum are associated with PIK3CAsomaticmutations | |
Cowden syndrome type5 | Cowden syndrome (multiple hamartomas of the mucous membrane and skin lesions) is put in a separate group because it is associated with PIK3CA germline and not somatic mutations | [16] |
Isolated vascular malformations | Isolated lymphatic, venous and lymphatico-venous malformation are associated with PIK3CA somatic mutations. | |
PROS (PIK3CA – Related overgrowth spectrum) with brain involvement | MCAP (Megalencephaly, capillarymalformation, polymicrogyria, syndactyly, polydactyly), MPPH (Megalencephaly polymicrogyria, polydactyly, hydrocephalus), DMEG (Dysplastic megalencephaly), Hemi-megalencephaly, and Focal cortical dysplasiaare associated with PIK3CA somatic mutations | |
PROS with multiple lipomatosis as the main presenting feature | HHML (Hemihyperplasia-multiple lipomatosis), facial infiltrating lipomatosis (facial lipomatosis, skeletal overgrowth, macrodontia, hemi-macroglossia, oral mucosal neuromas), mesenteric lipomatosis (Mesenteric lipomatosis, and insulin hypersensitivity are the main presenting features. Although the skin may have subcutaneous lipomas, there is relative lack of subcutaneous adipose tissue), multiple subcutaneous lipomatosis-scoliosis-multiple internal organ lymphatic malformations described by Yeung et al. [12]. All of these disorders are associated with PIK3CA somatic mutations | |
Other PROS disorders | CLOVES syndrome (Congenital, lipomatous overgrowth, vascular malformations, epidermal nevi and skeletal/spinal anomalies.Splayed feet with macrodactyly and wide sandal gap are characteristic), fibro-adipose overgrowth (FAO, progressive segmental overgrowth of subcutaneous, muscular and visceral fibro-adipose tissue. Skeletal overgrowth of the lower limb with macrodactyly of the feet are characteristic), isolated macrodactyly of the hands/feet, nerve-oriented macrodactyly (known in the hand surgery literature as lipo-fibromatous hamartoma of nerve with macrodactyly because the macrodactyly is seen in the digital rays supplied by the affected nerve). Rios et al. [24] reported on a case with nerve -oriented-macrodactyly and concurrent muscle hypertrophy. Klippel-Trenaunay syndrome (progressive growth of the lower limb with cutaneous capillary malformations and deep vascular malformations), and upper limb MO - hypoplasia IF are also included in this group. All of these disorders are associated with PIK3CA somatic mutations |