Histologic Variants of Squamous Cell Carcinoma of the Skin

Margaret H. Rinker, MD; Neil A. Fenske, MD; Leigh Ann Scalf, MD, and L. Frank Glass, MD, Division of Dermatology and Cutaneous Surgery, Department of Internal Medicine at the University of South Florida, Tampa, Fla.

Cancer Control. 2001;8(4) 

In This Article

Acantholytic Squamous Cell Carcinoma

Acantholytic SCC (ASCC) may also be referred to as adenoid SCC,adenoacanthoma, or pseudoglandular SCC. This variant was initially described in 1947 as a tumor composed of both solid and gland-like epithelial proliferations extending into the dermis, which was labeled adenoacanthoma of sweat glands.Most authors now regard ASCC as a variant of SCC rather than a sweat gland tumor.[9] It usually has a typical SCC pattern in combination with glandular formations, dyskeratotic cells, and acantholysis.

Clinically, this tumor is most often seen in the sun-exposed areas of the head and neck of elderly patients, and it most likely arises from acantholytic actinic keratoses.There have been reports, however,of this tumor occurring in sun-protected areas such as the dorsum of the foot.[9] There is a striking male predominance, with only three women affected in a total of 155 patients in a review by Johnson and Helwig,[10] and three women out of 49 patients in a review by Nappi et al.[11] ASCC may appear as a flesh colored, pink, red, or brown nodule. Crusting, scaling, or ulceration may be present.

Histologically, the tumor is composed of strands and islands of atypical epithelial cells extending into the dermis. Connection to the overlying epidermis is seen in most cases, which may show hyperkeratosis and parakeratosis. However,this connection may be only focal or, in some cases, absent. Many of the tumor strands may show tubular and alveolar formations, which are referred to as pseudoglandular appendages. These spaces contain acantholytic cells that result from loss of cohesion of the tumor cells (Fig 4). These acantholytic cells may appear extremely bizarre,large, or multinucleated. Mitotic figures are variably present. Classic SCC may also show cleft formation with dyskeratosis and acantholysis,but it does not have a definite wall or cohesive layer of cells surrounding the acantholytic cells,as seen in ASCC.[10]

Acantholytic squamous cell carcinoma. Many of the tumor strands may show tubular and alveolar formations, which are referred to as pseudoglandular appendages. These spaces contain acantholytic cells that result from loss of cohesion of the tumor cells.

ASCC may be mistaken for eccrine adenocarcinomas, metastatic adenocarcinomas, or epithelioid angiosarcomas. In the eccrine adenocarcinoma, the glandular spaces are lined with periodic acid-Schiff (PAS)-positive cells,whereas in ASCC, the cells are PAS negative.Also,ASCC lacks the production of carcinoembryonic antigen,S100 protein, and amylase,which can be seen in glandular malignancies.[11] In epithelioid angiosarcoma, the vascular spaces contain red blood cells, as opposed to the atypical keratinocytes seen in acantholytic SCC. ASCC may also contain red blood cells within the pseudoglandular spaces. In these cases, immunohistochemical stains may be required. Angiosarcomas are typically positive for vimentin and CD-34, whereas ASCC is positive for cytokeratin (CK) and epithelial membrane antigen (EMA).

It was initially thought that ASCC had less potential to metastasize to lymph nodes than did de novo SCC. In a 1966 review of 155 patients with 213 lesions,[10] only three patients died of metastatic disease and two patients died of local invasion. One of the deaths due to local invasion involved a patient who refused treatment. In a review of 20 patients in 1972,[12] no patients were noted to have lymph node metastases, but three patients died of local intracranial extension of tumor. This low propensity to metastasize was disputed in 1989 by Nappi et al.[11] In their review of 36 patients,11 patients had local recurrence, five had visceral metastases, and two died of local intracranial extension of tumor. Another review by Nappi and colleagues[13] in 1992 noted that three out of six patients with ASCC died of lymph node metastasis. However, two of these were immunocompromised. In a review by Toyama et al[9] in 1995, one out of four patients died of lymph node metastases. The lack of data regarding lesion sizes and the circumstances of the patients in several of these reviews makes it difficult to adequately assess the metastatic potential of ASCC. In a more recent review of 18 patients by Petter and Haustein[14] in 1998, only one patient developed a local recurrence.Although the literature has been conflicting, we believe that the malignant potential of ASCC is no higher than that of a typical invasive SCC.


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