Franco Rongioletti - Rare Malignant Skin Tumors

(1)

(2)

Cutaneous acantholytic squamous cell carcinoma (ASCC) was initially described in 1947 by Lever as a tumor composed of both solid and gland-like epithelial nests and was called adenoacanthoma of the sweat glands. He later revised his classification, and actually, ASCC is considered an uncommon, distinctive variant of squamous cell carcinoma, characterized by a typical SCC pattern in combination with acantholytic pseudoglandular space formation. Although ASCC is considered as a more aggressive variant of SCC, its prognosis seems mostly to be more related to the characteristics of the host and the grading of tumor rather than the histopathological features.

ASCC generally presents as a reddish, scaling, often cup-shaped, and ulcerated lesion on sun-exposed areas of elderly patients, predominantly on the head (Fig. ) and neck, although other sites such as the vulva, penis, breast, foot, leg, and arm can be involved. It is more common in males than females, with a mean age at diagnosis of 70 years.

Histologically, the tumor is composed of cords and nests of atypical keratinocytes with an infiltrative pattern of growth. Connection to the overlying epidermis, which may show hyperkeratosis and parakeratosis, is present in most cases, even if sometimes it may be only focal or absent (Fig. ). ASCC stains positively for immunohistochemical markers towards pankeratin and epithelial membrane antigen (EMA), but immunostains for carcinoembryonic antigen (CEA) give invariably negative results. In the literature, a decreased expression of intercellular adhesion proteins, such as of Dsg3, E-cadherin, and syndecan-1, has been described in ASCC compared to conventional SCC, and it has been suggested that this may contribute to the development of acantholysis and of the controversially more aggressive biological behavior.

Acantholytic cells may appear extremely bizarre, large, with glassy eosinophilic cytoplasm. Nuclei may vary from atypical to pleomorphic and may be single or multiple, and mitotic figures are variably present.

Differential diagnosis is only histological and is directed mainly towards gland-forming malignancies, as eccrine adenocarcinoma, adenosquamous carcinoma, and metastatic adenocarcinoma. Another important differential diagnosis concerns epithelioid angiosarcoma. In eccrine adenocarcinoma as in adenosquamous carcinoma, the glandular spaces are lined with periodic acidSchiff (PAS)-positive cells, whereas in ASCC, the cells are PAS negative. Moreover, ASCC shows no mucin secretion, and pseudoglandular spaces are due to acantholysis, not to real glandular differentiation, and tumor cells in ASCC lack the immunohistochemical positivity to CEA, S100 protein, and keratin 7 that can be seen in glandular malignancies. In epithelioid angiosarcoma, the vascular spaces contain red blood cells and not acantholytic keratinocytes, although cases of ASCC containing red blood cells within the pseudoglandular spaces have been notoriously described. In these cases, immunohistochemical stains are required. Angiosarcomas are typically positive for vimentin and CD-34, whereas ASCC shows positivity for cytokeratin and EMA.

It is difficult to assess the real biological behavior and metastatic potential of ASCC, because of the lack of adequate data regarding tumor size and site and circumstances of the patients in several of the largest published series. In the literature, the recurrence and metastasis rates reported are variable and range from 6 % to 10 % and from 2 % to 43 %, but, according to a recent analysis, the aggressive biological behavior of ASCC seems to correlate more with factors such as tumor size greater than 1,5 cm, recurrence, site of involvement, infiltration depth >3 mm, immunosuppression, and radiation therapy rather than with histopathological features. Moreover, recurrent tumors and metastases do not always reproduce the adenoid pattern of origin.

The treatment and follow-up of the patients should be similar to that for conventional SCC. Early wide surgical excision of the tumor has to be considered the treatment of choice.

Bibliography