Are You Confident of the Diagnosis?

What you should be alert for in the history

Lesions of large-cell acanthoma (LCA) are generally asymptomatic.

Characteristic findings on physical examination

Well-demarcated, pink to slightly hyperpigmented macule with superficial scale, usually less than 1cm, on sun-damaged skin, most common on the head and extremities. Solitary lesions are more common but cases of multiple lesions have been reported.

Expected results of diagnostic studies

Uniformly large keratinocytes (both nuclei and cytoplasm), roughly twice the size of cells of normal neighboring uninvolved epidermis, hypergranulosis, and hyperorthokeratosis. There is hyperpigmentation of the basal layer with slight increased number of melanocytes. No cellular atypia or dyskeratotic cells are seen. Mitoses, if present, are restricted to the basal layer. A mild inflammatory infiltrate may be seen in the dermis (Figure 2, Figure 3). DNA analysis shows that the nuclei of the enlarged keratinocytes are hyperploid.

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Figure 1.

LCA clinical photo

Figure 2.

Large-cell acanthoma pathology, low power

Figure 3.

Large-cell acanthoma pathology, medium power

Diagnosis confirmation

The clinical differential diagnosis includes solar lentigo, pigmented actinic keratosis, flat pigmented seborrheic keratosis, stucco keratosis, and Bowen’s disease. Clinically these can be hard to distinguish. Biopsy may be required for a definitive diagnosis. The pathologic features are thought to be pathognomonic. Three pathologic types of LCA have been described: classic, verrucous hyperkeratotic, and flat hyperkeratotic. The histologic differential includes lentigo senilis, flat seborrheic keratosis, and early actinic keratosis.

Who is at Risk for Developing this Disease?

More common in women and the elderly. Lesions are likely to develop in photodamaged skin.

What is the Cause of the Disease?

LCA is an epidermal neoplasm, which may possibly be related to lentigo senilis.


Unknown. Multiple strains of human papillomavirus (HPV) have been identified as a cofactor in the pathogenesis. There is a definite epidemiologic association with chronic photodamage.

Systemic Implications and Complications

There are no systemic disorders associated with LCA. Further workup is not required.

Treatment Options

LCA is considered a benign lesion. Treatment of the remaining lesion after biopsy consists of cryotherapy with liquid nitrogen and may be initiated for cosmetic purposes. No therapy is another option.

Optimal Therapeutic Approach for this Disease

A definitive diagnosis of LCA will likely require pathologic evaluation. Therefore, if the entire lesion is biopsied, further treatment will not be required.

Should portions of the lesion remain, cryotherapy is a non-invasive treatment modality that is easily employed. Lesions treated with cryotherapy usually resolve within a week. Side effects of cryotherapy may include a scar, hypo- or hyperpigmentation.

Alternative treatment includes a shave excision. Pathologic evaluation of the excised lesion can determine whether the lesion has been completely removed. Excision will result in a scar.

Observation without treatment is also an option, as LCAs are not premalignant or malignant lesions.

Patient Management

LCA tends to develop in actinic damaged skin. Therefore, a patient who has an LCA is likely to be at risk for other conditions known to develop in areas of actinic damage including actinic keratoses and skin cancer. Patients should have regular full body skin examinations by a dermatologist and should be counseled on photoprotection and the use of sunscreen.

Unusual Clinical Scenarios to Consider in Patient Management

Although LCA is considered to be a lesion of benign biologic behavior, a case of LCA of the conjunctiva that recurred twice following surgical excision has been reported. The second recurrence was found to be a carcinoma in situ.

What is the Evidence?

Argenyi, ZB, Hutson, BM, Argenyi, EE, Maillet, MW, Hurt, MA. “Large-cell acanthoma of the skin: A study by image analysis cytometry and immunohistochemistry”. Am J Dermatopathol. vol. 16. 1994. pp. 140-4. (Seven cases of LCA were studied using image analysis cytometry for DNA content and by immunohistochemistry, using antibodies to proliferating cell nuclear antigen [PCNA]/cyclin. Data were compared with individual cases of seborrheic keratosis, actinic keratosis, and Bowen's disease. The DNA distribution of LCA was abnormal in all cases. Low-grade aneuploidy was detected by DNA analysis in LCA, however, the lesion carries a benign or indolent biologic behavior. No full-thickness cytologic atypia or significant numbers of mitotic figures were found.)

Berger, T, Stockfleth, E, Meyer, T, Kiesewetter, F, Funk, JO. “Multiple disseminated large-cell acanthomas of the skin associated with human papillomavirus type 6”. J Am Acad Dermatol. vol. 53. 2005. pp. 335-7. (This article describes a patient with multiple nodules on the skin of the upper limbs histologically diagnosed as LCAs. HPV-6 was present in these lesions and should be considered a cofactor in LCA pathogenesis.)

Ghazi, NG, Patel, BS, Olsakovsky, LA, White, K, Patterson, JW, Carter, B. “A conjunctival lesion with histological features similar to large-cell acanthoma of the skin”. J Cut Pathol. vol. 37. 2010. pp. 1103-6. (This article describes the first occurrence of LCA in the conjunctiva. This lesion recurred following initial excision and later recurred as a carcinoma in situ upon second excision, suggesting LCA may have the potential for malignant transformation.)

Mehregan, DR, Hamzavi, F, Brown, K. “Large cell acanthoma”. Int J Dermatol. vol. 42. 2008. pp. 36-9. (Nineteen cases of LCA were studied and found to have epidermal keratinocytes with nuclei roughly twice the size of adjacent epidermal or adnexal keratinocytes, and as having minimal nuclear pleomorphism. Melanocyte density and cellular proliferation of LCA, actinic keratosis and lentigo senilis were compared using HMB-45 staining of melanocytes and PCNA staining of epidermal keratinocytes. Lentigo senilis and LCA showed increased numbers of melanocytes. Based on clinical, histologic and immunohistochemical staining similarities, LCA should be considered as a reaction pattern, possibly related to lentigo senilis.)

Pinkus, H. “Epidermal mosaic in benign and precancerous neoplasia (with special reference to large-cell acanthomas)”. Hifuko Kiyo. vol. 65. 1970. pp. 75-81. (Pinkus discusses the possibility that the epidermis is a mosaic, that is, that adjacent keratinocytes could have different biologic behavior. He cites actinic keratosis as a malignant example of epidermal mosaicism and LCA as a benign example. He gives the first description of the LCA as having keratinocytes roughly twice the size of neighboring epidermal cells.)

Roewert, HJ, Ackerman, AB. “Large-cell acanthoma is a solar lentigo”. Am J Dermatopathol. vol. 14. 1992. pp. 122-32. (On the basis of a study of 54 specimens each of LCA, solar lentigo, reticulated seborrheic keratosis, and lichen planus-like keratosis, it is concluded that clinically, histopathologically, and biologically, LCA is a variant of solar lentigo, and solar lentigo (including the large-cell variant) is a stage in the evolution of reticulated seborrheic keratosis and of lichen planus-like keratosis.)

Sanchez Yus, E, del Rio, E, Requena, L. “Large-cell acanthoma is a distinctive condition”. Am J Dermatopathol. vol. 14. 1992. pp. 140-7. (Forty-four biopsy specimens of LCA from 35 patients were studied. Histologically, 41 of the specimens could be classified into three patterns: basic, verrucous, and flat-hyperkeratotic. It was concluded that LCA is a distinctive condition with various stages of development and is probably related to stucco keratosis. It can clearly be separated histologically from solar lentigo and from solar keratosis. As other epidermal tumors, LCA can sometimes exhibit features of Bowen's disease.)

Weinstock, MA. “Large-cell acanthoma”. Am J Dermatopathol. vol. 14. 1992. pp. 133-4. (This article states that LCA is histologically distinguishable from a solar lentigo and that the biologically distinctive characteristic of LCA may be that it is a benign proliferation of a clone of tetraploid keratinocytes. Maintaining it as a separate diagnostic entity is justified.)