Adenoid basal cell carcinoma and its mimics.

Basal cell carcinoma (BCC) is the most common malignant tumor of skin. The most common site (80%) is head and neck. BCC exhibits a varied morphology such as adenoid, keratotic, sebaceous, basosquamous, apocrine, eccrine or fibroepithelial. Tumors with a similar histopathological picture are cutaneous adenoid cystic carcinoma and primary cutaneous cribriform apocrine carcinoma. Immunohistochemistry, along with clinical findings, acts as an adjunct in reaching an accurate diagnosis. Here, we present an interesting case of adenoid BCC in a 55-year-old man.

What was known?

Basal cell carcinoma is a common malignant tumour of the skin. Numerous histological subtypes have been described, one of which is adenoid BCC.

Introduction

Basal cell carcinoma (BCC), first described by Jacob in 1827, is the most common cutaneous tumor, accounting for approximately 70% of all malignant diseases of the skin.[1] Up to 80% of all the lesions are found on the head and neck, with a variable clinical presentation ranging from a papulonodular lesion, erythematous plaque to an ulcerated destructive lesion (“rodent ulcer”). BCCs can exhibit both a variety of growth patterns (superficial, nodular, micronodular or infiltrating) and a variety of types of differentiation, such as adenoid, keratotic, sebaceous, basosquamous/metatypical, pilar, apocrine, eccrine or fibroepithelial. We report one such interesting rare case of adenoid BCC.

Case Report

A 55-year-old man reported a slow-growing nodule on the right side of the nose since 3 years. The lesion had gradually increased to a size of 3.5 cm diameter when he reported to the Surgical Outpatient Department with complaints of ulceration of the nodule and superficial bleeding since the last 10 days [Figure 1]. The patient was a casual laborer by profession, which involved long hours of sun exposure. On examination, the regional lymph nodes were not enlarged and his general physical condition was stable. The clinical impression was of an ulcerated BCC, and the patient was taken up for a wide local excision of the ulcerated nodular mass. Gross examination showed a raised nodule with a thin rim of skin at the periphery. It showed a central ulcer with crusting and irregular rolled borders. Histological picture showed a predominant adenoid pattern with thin strands of basaloid cells in a reticulate arrangement, with many tubules and few cystically dilated spaces containing mucin [Figure 2]. Peripheral palisading of the basaloid cells was seen in some of the islands along with retraction artefact of the surrounding stroma and connection to the overlying epidermis was evident. Immunohistochemical studies were carried out and staining with anti-bcl-2 monoclonal antibody showed homogenous cytoplasmic staining throughout the lesion [Figure 3]. Staining for S-100, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA) and cytokeratin (CK-7) were done, and were found to be negative.

Figure 1

Clinical picture of nodulo-ulcerative lesion on the right side of the nose

Figure 2

Microphotograph showing adenoid pattern with connection of the lesion to the overlying epidermis (inset) (hematoxylin and eosin, ×100)

Figure 3

Bcl-2 expression in the tumor cells (immunochemistry, ×400)

Discussion

BCC has been described as the most common malignant neoplasm of humans.[2] It is a common neoplasm of the skin with well-known variability in morphology. Rare morphological variants, such as cystic, adenoid, morphoeiform, infundibulocystic, pigmented and miscellaneous (clear-cell, signet ring cell, granular, giant cell, adamantanoid, schwannoid), together, account for less than 10% of all BCCs.[3] A recent study reported an incidence of only 6.67% of the adenoid BCC among all the histopathological types of BCC of the eyelids, and this variant in its pure form is less often seen.[4]

Histologic criteria applied to hematoxylin and eosin-stained sections remain the cornerstone of histologic diagnosis, although immunohistochemistry has always been a useful adjunct. Immunohistochemical studies were carried out and staining with anti-bcl-2 monoclonal antibody showed homogenous cytoplasmic staining throughout the lesion but more prominent at the periphery of the lesion, a feature that is useful in differentiating BCCs from trichoepitheliomas. Also, S-100, EMA, CEA and CK-7 were done and were found to be negative, thereby excluding an adenoid cystic carcinoma (ACC).

Another rare tumor with a similar histopathological picture is the cutaneous ACC, which often presents as a firm, slow growing, ill-defined nodule, the scalp being the most common site. ACCs originate most commonly in the major and minor salivary glands. Rare primary locations include the breast, the primary bronchi, the uterine cervix, the external auditory canal and the skin. Cutaneous ACC was first reported by Boggio in 1975.[5] To date, just over 50 cases have been published in the English language literature. Cutaneous localization of the ACC may also result from direct extension of ACC of minor salivary glands situated in the paranasal sinuses, and rarely a distant cutaneous metastasis of a primary salivary gland ACC. Therefore, cutaneous and extracutaneous ACC can only be distinguished on clinical grounds, and the diagnosis of cutaneous ACC is generally established after excluding all past history and current evidence of ACC from an extracutaneous source. This differentiation is of significance as the ACC of salivary gland origin is characterized by local recurrence and widespread metastases; whereas cutaneous ACC is associated with an indolent course and a propensity for local recurrence.[6]

Histological features of cutaneous ACC are characterized by basaloid cells in the mid- to deep dermis in cords and tubules with a cribriform pattern and few small cystic spaces containing mucinous material that stains positively for hyaluronic acid. Lack of connection to the overlying epidermis or adnexal structures and perineural invasion are important distinguishing features from adenoid BCC. Whether cutaneous ACC is a tumor of eccrine or apocrine origin has not been determined. Some observational evidence suggests that this tumor might be apocrine in origin, as ACC often arises from ceruminous glands of the external ear canal, which are modified apocrine glands.

Another close mimic of adenoid BCC is primary cutaneous cribriform apocrine carcinoma, which is a rare low-grade cutaneous apocrine carcinoma (CAC). The histological appearance is of a non-encapsulated dermal tumor with a cribriform pattern. The aggregations of neoplastic cells are pleomorphic as opposed to the monomorphous appearance of BCC, and arranged in solid nests and tubules. In the lumina of tubules, some papillary protrusions of basophilic cells are seen. Cuboidal or cylindric cells with images of decapitation secretion line the ductal elements. No perineural invasion, which is a common feature of cutaneous ACC, is seen. Also, no metastatic potential or post-exicision recurrence has been associated with this tumor, which sets it apart from more aggressive cutaneous ACC. Similarly, a lack of connection to the overlying epidermis, peripheral palisading of the basaloid islands of cells and retraction artefact of the surrounding fibrous stroma excludes an adenoid BCC. The differential diagnosis between CAC and cutaneous metastases from breast carcinoma is difficult. Immunohistochemistry has a limited role to offer in the differentiation between these two, and clinical information provides a critical input in the final diagnosis. Markers like CEA, p53, CK 7 and, more recently, podoplanin have been used by various workers with limited success.[7] In conclusion, adenoid variant of BCC, in its pure form, is relatively less frequent. An awareness of its histologic mimics like the cutaneous ACC, the primary CAC (which also are rare skin lesions) helps in an accurate diagnosis.

What is new?

Adenoid basal cell carcinoma in its pure form is a rare lesion and needs to be differentiated from cutaneous Adenoid cystic carcinoma and cutaneous apocrine carcinoma. Prognosis and outcomes greatly differ and a correct histological diagnosis is vital in the management of these cases.