Benign acanthomas/keratoses

2026-08-06   Paola Dal Cin, PhD , Stefano Sioletic, MD 

1.Brigham and Women\'s Hospital , Harvard Medical School, Boston , MA (USA)
2.San Camillo-Forlanin Hospital Rome (Italy)

Keywords
seborrhoeic keratosis, solar lentigo, lichen planus-like keratosis, clear cell acanthoma, large cell acanthoma, awarty dyskeratoma

Classification

Definition

This subgroup comprises seborrhoeic keratosis, solar lentigo, lichen planus-like keratosis, clear cell acanthoma, large cell acanthoma, and warty dyskeratoma. These entities are benign proliferations without intrinsic malignant potential, included here because of their relevance to the differential diagnosis of keratinocytic neoplasia. 1


Benign acanthomas/keratosesGenetic events
Seborrhoeic keratosisSeborrhoeic keratosis (SK) is an extremely common benign epidermal proliferation characterized mainly by FGFR3 mutations , followed by and ,in a substantial mutually exclusive subset, by mutation of PIK3CA , HRAS, BRAF, CDKN2A and TERT and DPH3 promotor mutations . TERT promoter mutations were more were present mainly in the lesions excised from head and neck of elderly people. 2 Familial SK reveals the same mutational spectrum as sporadic SK, none of these muations were presnet in the germine . 3
Solar lentigoSolar lentigo is a benign UV-associated pigmented lesion appering on sun-exposed areas especially in elderly people, which a remarkably similar genetic profile with seborrhoeic keratosis, featuring recurrent FGFR3 and PIK3CA activating mutation ,suggesting a coomon genetic basis. No BRAF V600E mutation were detected.4
Lichen planus-like keratosis Lichen planus-like keratosis (LPLK) represents a lichenoid inflammatory regression reaction, most often arising within a pre-existing solar lentigo or seborrhoeic keratosis. Therefore, no surprise the preence of FGFR3, PIK3CA ,HRAS and KRAS mutation. 5
Clear cell acanthomaClear cell acanthoma is an uncommon type of solitary benign epithelial tumor, found on the lower limbs , with an ongoing debate as to its classification as cutaneous neoplasia or reactive inflammatory dermatosis.6 Neither human papilloma virus nor human herpes virus have been identified by immunohistochemical or molecular genetic methods. 7
Large cell acanthoma Large cell acanthoma is a benign keratinocytic proliferation of large cells with mild nuclear enlargement, arising on chronically sun-exposed skin. It is closely related to solar lentigo and seborrhoeic keratosis with no distinct molecular profile has been established.6
Warty dyskeratoma Warty dyskeratoma is a benign ,solitary, non-hereditary keratotic nodule, predominantly on the head and neck arises from somatic mutations in ATP2A2 (encoding SERCA2), or ATP2C1 (encoding SPCA1), genes responsible for calcium homeostasis in keratinocytes. 8 These mutations represent mosaic or focal manifestations of the same molecular defects seen in the ATP2A2 germline disorder Darier disease OMIM:124200. 9
Other benign keratoses Heterogeneous group of benign epidermal proliferations with distinctive morphological patterns that do not meet the criteria for any of the entities previously described above e.g., tucco keratosis, epidermolytic acanthoma, and acantholytic acanthoma. These entities carry no malignant potential and lack consistent recurrent molecular alterations. 10,11

Article Bibliography

Reference NumberPubmed IDLast YearTitleAuthors
1188450882008Are all seborrheic keratoses benign? Review of the typical lesion and its variants.Noiles K et al
2284102312017Genetic alterations in seborrheic keratoses.Heidenreich B et al
3185036012008Somatic FGFR3 and PIK3CA mutations are present in familial seborrhoeic keratoses.Hafner C et al
4190769772009FGFR3 and PIK3CA mutations are involved in the molecular pathogenesis of solar lentigo.Hafner C et al
5221885342012FGFR3, PIK3CA and RAS mutations in benign lichenoid keratosis.Groesser L et al
6328541842020Clear Cell Acanthoma: A Review of Clinical and Histologic Variants.Usmani A et al
7329898992021Clear cell acanthoma.Wagner G et al
8400013392025A case of multiple warty dyskeratomas overexpressing SERCA2 in acantholytic cells.Matsuo M et al
9291421872017An ATP2A2 Missense Mutation in a Japanese Family with Darier Disease: A Case Report and Review of the Japanese Darier Disease Patients with ATP2A2 Mutations.Li M et al
10198456642010FGFR3 and PIK3CA mutations in stucco keratosis and dermatosis papulosa nigra.Hafner C et al
11205533612011Solitary epidermolytic acanthoma: a clinical and histopathological study.Abbas O et al

Citation

Paola Dal Cin, PhD ; Stefano Sioletic, MD

Benign acanthomas/keratoses

Atlas Genet Cytogenet Oncol Haematol. 2026-08-06

Online version: http://atlasgeneticsoncology.org/solid-tumor/209381