Coexistence of Solid (Nodular) and Differentiated (Adenoid) Basal Cell Carcinoma at the Same Anatomical Site.

Coexistence of two different histopathological types of basal cell carcinomas (BCCs) in the same anatomical site is rare and interesting. Herein, we report a case of coexistence of nodular and adenoid BCC in a 78-year-old peasant who presented with a plaque and a globular swelling on left paranasal region of few years duration. Histopathology of skin biopsy with immunohistochemistry study using antibodies to S100, epithelial membrane antigen (EMA) and cytokeratin 7 (CK 7) from the margin of the ulcer and globular swelling confirmed the diagnosis that revealed features of nodular and adenoid basal cell carcinoma, respectively. Investigative work up did not reveal evidence of metastasis.

What was known?

Different types of BCC are known to occur at different anatomical sites.

Introduction

Basal cell carcinoma (BCC) was first described by Jacob in 1827,[1] and is the most common malignant neoplasm of skin.[23] Its annual incidence is estimated to be 2.75 million new cases worldwide. It usually occurs in fourth decade and above. Sun exposure plays an important role in the development and transformation of BCC. However, it is known to occur in both sun-exposed and sun-protected areas. Patients with light skin phenotype are predisposed. Furthermore, exposures to arsenic, coaltar and radiation are the additional risk factors.[4] It is known that impairment of the immune surveillance of oncogenic viruses leads to immune compromise which in turn leads to provocation of BCC.[5] BCC may also arise in scars, ulcers, draining sinuses, burn sites and foci of chronic inflammation.[6] Certain genodermatoses enhance the risk of BCC which include xeroderma pigmentosa, albinism, Darier's disease, Rasmussen syndrome, Rombo syndrome and Bazex–Christol–Dupre syndrome.[7]

Case Report

A 78-year-old man presented with a painless swelling and an ulcer on left side of the nose of few years duration. He gave history of development of a swelling initially which gradually increased to reach the present size. After a gap of 3-4 years, he developed a nodule on left side of the nose above the swelling which subsequently ulcerated. There was no history of injury. Cutaneous examination revealed a crusted plaque on left paranasal region of size 3 cm × 2.5 cm with a rolled border at the upper and lateral margins. The plaque was found to extend on to the infraorbital region superiorly, to the nose medially and to maxillary region laterally and filled with adherent dry dirty brownish black crusts. The lower border of the plaque was occupied by brownish black globular swelling of 3 × 3 cm in size, soft to firm in consistency, covered with crusts and it was non-tender [Figure 1]. Single submandibular lymph node on the left side was enlarged and non-tender. A clinical diagnosis of BCC was offered. However, squamous cell carcinoma, adenoid cystic carcinoma, scrofuloderma and deep mycosis were considered in the differential diagnosis. His routine blood investigations were unremarkable. Fine-needle aspiration cytology (FNAC) from left submandibular lymph node was negative for malignant cells and granuloma. Tissue culture for mycobacterium tuberculosis on Lowenstein–Jensen's medium and culture on Sabouraud's dextrose agar were negative. X-ray chest and ultrasonography of abdomen were unremarkable. Serology for human immunodeficiency virus (HIV) was non-reactive. As both the lesions were morphologically different, a punch biopsy was done from both the sites; one from the margin of the plaque (specimen1) and other from the globular swelling (specimen2). Specimen1 showed tumor nodules in the dermis consisting of basaloid cells with peripheral nuclear palisading. Around the tumor there was retractional artificial clefting and tumor cells showed coarse chromatin [Figure 2]. The features were consistent with nodular type of BCC. Specimen2 showed tumor formed by basaloid cells arranged in nests and trabeculae with peripheral nuclear palisading. The cells show moderate nuclear pleomorphism and coarse chromatin, consistent with adenoid BCC [Figure 3]. Immunohistochemistry study with antibodies to S100, epithelial membrane antigen (EMA) and cytokeratin 7 (CK 7) were negative, thus, confirming the diagnosis of adenoid BCC. Finally, he was diagnosed as nodular with adenoid BCC. As there was large area of involvement, the patient was referred to plastic surgeon for further management.

Figure 1

Ulcerated crusted plaque with globular swelling in the left paranasal region

Figure 2

(a) Specimen1: Histopathology H and E stain scanner view showing multiple tumor nodules in the dermis with surrounding retractional clefting. (b) Dermis showing basaloid cells forming nodules with peripheral nuclear palisading (×10) (c) Tumor nodules consisting of basaloid cells with peripheral nuclear palisading. Retractional clefting seen around tumor nodule. Melanin pigment is seen. (×40)

Figure 3

(a) Specimen2. Histopathology H and E stain. Scanner view. Tumor cells arranged in trabeculae and nests. (b) Tumor formed by basaloid cells arranged in trabeculae with peripheral palisading (×10). (c) Tumor cells arranged in trabeculae and nests with peripheral nuclear palisading. The cells show moderate nuclear pleomorphism and coarse chromatin (×40)

Discussion

BCCs have been broadly classified into two: undifferentiated (solid) and differentiated (toward eccrine, sebaceous or other cell lines). The undifferentiated BCC include superficial, nodular, micronodular, morpheaform and infiltrative growth BCC. Keratotic, infundibulocystic, follicular, pleomorphic, BCC with sweat duct differentiation, BCC with sebaceous differentiation, adenoid and fibroepithelioma of Pincus are included in differentiated BCCs. Nodular BCC is the most common type of BCC among the 66 variants of BCCs that have been described in the literature.[8] The adenoid type is one of the rare variants of BCCs and its exact incidence is not known.[9] However, reported incidence varies between 1.3% and 20.91% and has no site of predilection. However, Hussein et al. reported eyelids as preferential site for adenoid BCC.[10] BCCs are rarely known to metastasize.[11] There appears to be a correlation between the incidence of metastases and the size of the tumor. BCCs more than 5 cm in diameter have significant risk of morbidity and mortality. Furthermore, BCC arising in a young individual (less than 35 years of age) may have an aggressive clinical course.[12] The case under study presented with plaque with rolled margin, typical of nodular BCC, was confirmed by characteristic histopathology. However, the adenoid BCC presenting as globular swelling required to be differentiated from adenoid cystic carcinoma which presents with similar histopathological features. Immunohistochemistry with antibodies to S100, EMA and CK 7 was negative in the specimen2 of the index case which helped in confirming the diagnosis of adenoid BCC.

Coexistence of two different histopathological types of BCC in the same anatomical site as noted in the index case is rare and interesting. Of note is the development of adenoid BCC few years prior to the development of nodular BCC. In concert with this, Tas et al. have also reported similar coexistence of nodular and adenoid BCC involving right paranasal region in a 64-year-old peasant who developed both nodular and adenoid BCC in a gap of 2 months[13] [Table 1]. Additionally there have been few reports of association of BCC with other neoplasms in the same or nearby anatomical location. Crowson et al. have documented association of BCC with desmoplastic tricholemmoma in 19% of cases in their study.[14] Consideration of BCC with mixed histology (BCC-MH) is untenable in the index case as both the types of BCC (nodular and adenoid BCC) are not located in single sample. Pleomorphic BCC with ductal differentiation could not be entertained in the index case (specimen2) as there is the absence of large cells with convoluted nuclei, characteristic of pleomorphic BCC. Furthermore, the absence of irregular jagged tongues of tumor cells and the absence of cytoplasmic keratinization, typical of metatypical BCC (basosquamous carcinoma) ruled-out the possibility of metatypical BCC in the index case.

Table 1

Coexistence of nodular and adenoid BCC with time gap, skin type and occupation

Treatment modalities of BCC include curettage and electrodessication, photodynamic therapy, topical imiquimod, intralesional alpha interferon, topical 5-Flurouracil, cryotherapy, radiation therapy, standard surgical excision and Mohs micrographic surgical excision. Of all the treatment modalities, Mohs micrographic surgery has least recurrence rates (1-3.3%) followed by standard surgical excision (2-7%).[15] The recurrence of BCC depends on tumor treatment, biologic behavior of cancer and immune status of the patient. However, it is not known whether two different histopathological types of BCC have compounding effect on the occurrence of metastasis. Notably, hedgehog pathway inhibitors such as vismodegib offers new and promising therapy for metastatic or locally advanced BCC.[16]

In conclusion, coexistence of two different histopathological types of BCC in the same anatomical location is very rare. Nonetheless, one should suspect and investigate for such coexistence when confronted with BCC particularly, presenting with different morphology in the same anatomical location. Such coexistence may involve large area and necessitate extensive surgical excision and skin grafting. Moreover, these timely therapeutic procedures mitigate in averting recurrence and metastasis.

What is new?

Coexistence of two different histopathological types of BCC (nodular and adenoid) in the same anatomical location is unique and rare

Immunohistochemistry with S100, Epithelial membrane antigen (EMA) and cytokeratin 7 helps in differentiating adenoid BCC from adenoid cystic carcinoma

BCC more than 5 cm in diameter and occurring in younger individual of less than 35 years of age may have aggressive clinical course.