Introduction
Large cell acanthoma is a rare, benign neoplasm developing on the skin exposed to solar radiation, most commonly on the face, upper extremities, or back. Large cell acanthoma usually presents as a solitary lesion, up to 1 cm in diameter, rarely larger [1−3]. The aetiopathogenesis of the condition is not clearly understood. Because of the ongoing nosological debate, some authors regard large cell acanthoma as an independent disease entity, while others classify it as a subtype of lentigo, seborrhoeic keratosis, actinic keratosis, or even Bowen’s disease [4, 5]. Typical clinical features include hyperpigmentation and hyperkeratosis of a well-demarcated lesion, with diagnosis based on the distinctive histopathological picture.
Objective
Presentation of the characteristic clinical, videodermatoscopic, and histopathological features of this rare type of epidermal lesion.
Case report
A 76-year-old man presented to the outpatient clinic at the Department of Dermatology and Venereology because of an elevated flat-topped skin lesion, gradually spreading peripherally, well-demarcated from the surrounding skin, measuring about 1.5 cm in diameter, located over the left shoulder blade (fig. 1). The lesion was not preceded by any injury and caused no subjective complaints. The patient was unable to specify how long it had been present. He stated that he had often been exposed to solar radiation in the past.
During history-taking, the patient reported a past diagnosis of actinic keratosis lesions on the right auricle and in the right temporal region, which resolved after treatment. He is currently undergoing hypertensive therapy. The patient had no personal or family history of cancer.
Videodermatoscopic examination revealed a well-demarcated skin lesion with a tendency towards hyperpigmentation, covered with fine yellow-brown scale. Additionally, a network of blood vessels arranged in a linear and radial pattern was clearly visible (fig. 2). No blood vessel branches with a tree-like distribution, which are typical of basal cell carcinoma, or erosions were noted.
Histopathological examination of a specimen obtained using 4 mm punch biopsy showed a fragment of acanthotic hyperplasia of normotypic epidermis, formed by large keratinocytes compared to the cells in the surrounding epidermis (fig. 3). In addition, the nuclei in these keratinocytes were significantly larger than those in the unaffected epidermis.
Discussion
Large-cell acanthoma is an uncommon, benign neoplasm characterised by slow, peripheral growth occurring over many years, without any subjective complaints. The lesion often causes concern for patients and requires differentiation from other conditions, especially skin cancer. Most typically, large cell acanthoma appears in areas exposed to solar radiation, typically on the face, upper trunk, and upper extremities. Similar to the patient in the case report, large cell acanthoma usually presents as a solitary, elevated flat-topped lesion with a diameter of approximately 1 cm. Less commonly, the diameter is larger, up to 2 cm, or the lesion manifests as a domed nodule. The colour of the lesion can vary, ranging from light pink to light brown or brown-red, with a slightly shiny surface. Increased keratinisation and skin exfoliation are often visible on the surface, particularly around the edges [1−3].
Case reports of large cell acanthoma localised to the conjunctiva have also been reported in the literature [6].
Over time, perspectives on the aetiopathogenesis of the condition have sparked numerous debates and undergone multiple revisions. The disorder was first described by Pinkus in 1970 as a lesion sharply demarcated from the surrounding skin, with a tendency towards keratinisation. The author also highlighted keratinocyte enlargement seen on histopathology. He postulated that the lesion might represent a subtype of solar lentigo [7]. Subsequent scientific reports classified large cell acanthoma as either seborrhoeic keratosis or actinic keratosis. Due to excessive pleomorphism of cell nuclei and dyskeratosis, it was also regarded as a variant of Bowen’s disease [4, 5]. As a result, some researchers raised doubts about the need to categorise the condition as a distinct nosological entity.
In 2003, Mehregan et al. published a paper reporting the results of a comparative study of skin lesions with similar clinical characteristics. The authors reviewed the clinical and histological features of 19 patients diagnosed with large cell acanthoma, nine with actinic keratosis, and 10 with solar lentigo (lentigo solaris) [1].
Jung et al. conducted a study of 33 lesions to identify distinct dermatoscopic features of large cell acanthoma. The most commonly found characteristics included yellow scale against a homogeneous background, brown dots, radially arranged white streaks, avascularity or, less commonly, a linearly arranged irregular network of blood vessels, and moth-eaten borders [8]. Similar features were observed in the videodermatoscopic examination of the presented patient. The observed prominent network of blood vessels could be due to biopsy-associated injury.
The authors detailed the histopathological characteristics of the three aforementioned epidermal lesions – large cell acanthoma, solar lentigo, and actinic keratosis – as follows. Large cell acanthoma was characterised by the presence of large cell nuclei and abundant cytoplasm in the affected keratinocytes, with mild nuclear pleomorphism (variation in size and shape of cell nuclei). Figures of cell division were infrequently observed, especially above the basal layer, which showed intense pigmentation. The stratum corneum was compact or orthokeratotic [1].
Solar lentigo was characterised by elongation of the rete ridges and hyperpigmentation of the basal layer. However, there was no enlargement of nuclear structures, pleomorphism, or an increased number of mitoses. All cases of actinic keratosis revealed epidermal eosinophilia with a degree of disorganisation and nuclear pleomorphism. Additionally, an increased number of dividing cells and parakeratotic stratum corneum were observed [1].
The authors highlight that the defining clinical feature of these disorders is a discoloured patch within which histopathological evaluation reveals a higher number of melanocytes compared to the surrounding skin. This phenomenon is attributed to chronic sun-induced damage to the skin, which plays a major role in the formation of lesions. While increased epidermal cell proliferation was noted in all three disease entities, a statistically significant increase in the number of mitoses was observed only in actinic keratosis lesions [1].
Even though the study suggests that there are certain similarities between the disorders mentioned, researchers generally seem to conclude that large cell acanthoma either shares characteristics with or may even arise from lentigo.
Conclusions
Because large cell acanthoma is extremely rare and clinically resembles other types of epidermal proliferation, it is infrequently diagnosed. While dermatoscopic examination can be helpful in the diagnostic process, histological evaluation remains the cornerstone of accurate diagnosis [9].
In the presented case report, the distinctive clinical, dermatoscopic, and histopathological features of large cell acanthoma were highlighted. The lesion requires no treatment. In some cases, surgical removal of the lesion is advised due to cosmetic concerns.
Funding
The manuscript was supported by Medical University of Lodz.
Ethical approval
Not applicable.
Conflict of interest
The authors declare no conflict of interest.
References
1. Mehregan D.R., Hamzavi F., Brown K.: Large cell acanthoma. Int J Dermatol 2003, 42, 36-39.
2.
Sánchez Yus E., de Diego V., Urrutia S.: Large cell acanthoma. A cytologic variant of Bowen’s disease? Am J Dermatopathol 1988, 10, 197-208.
3.
Shahriari N., Grant-Kels J.M., Rabinovitz H.S., Oliviero M., Scope A:. In vivo reflectance confocal microscopy features of a large cell acanthoma: report of a case. Dermatol Pract Concept 2016, 6, 67-70.
4.
Sánchez Yus E., de Diego V., Urrutia S.: Large cell acanthoma. A cytologic variant of Bowen’s disease? Am J Dermatopathol 1988, 10, 197-208.
5.
Rahbari H., Pinkus H.: Large cell acanthoma. One of the actinic keratoses. Arch Dermatol 1978, 114, 49-52.
6.
Jakobiec F.A., Cortes Barrantes P., Ma L., Mandeville J.: Large cell acanthoma of the conjunctiva: clinicopathologic and immunohistochemical features. Ocul Oncol Pathol 2019, 5, 312-318.
7.
Pinkus H.: Epidermal mosaic in benign and precancerous neoplasia (with special reference to large-cell acanthomas). Hifuka Kiyo 1970, 65, 75-81.
8.
Jung J.H., Jeong S.M., Kwon D.I., Seong S.H., Jang J.Y., Kim J.H., et al.: Dermoscopic findings and histopathological correlation in large cell acanthoma. Australas J Dermatol 2022, 63, e340-e344.
9.
Patsatsi A., Lazaridou E., Fotiadou C., Kyriakou A., Sotiriadis D.: Large cell acanthoma: a debate throughout the decades. Dermatol Pract Concept 2014, 4, 43-45.
