Basal Cell Carcinoma

M.P. McLeod • S. Choudhary

Department of Dermatology and Cutaneous Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA

Y.A. Alqubaisy

Department of Dermatology and Cutaneous Surgery,

University of Miami Hospital, Miami, FL, USA

K. Nouri (*)

Department of Dermatology and Cutaneous Surgery,

University of Miami Leonard M. Miller School of Medicine,

Miami, FL, USA

Sylvester Comprehensive Cancer Center, University of Miami Hospital and Clinics, Miami, FL, USA

e-mail: knouri@med.miami.edu

Summary: Introduction

•Basal cell carcinoma (BCC) is the most common malignant neoplasm found in humans.

•Approximately 800,000 new cases of BCC are diagnosed in the USA per annum.

•Mohs micrographic surgery (MMS) has a 99% 5-year cure rate for primary BCCs and a 96% 5-year cure rate for recurrent BCCs.

16.1Introduction

Basal cell carcinoma (BCC) is the most common malignant process encountered in humans as well as the most common indication for Mohs micrographic surgery (MMS) [1]. In fact, nearly 30% of all BCCs are treated with MMS in the USA [2]. Approximately 800,000 new BCC cases are diagnosed in the USA per year [3]. BCC accounts for approximately 90% of all known skin cancers [4]. Fair skin, sun exposure, immunosuppression, and a low Fitzpatrick skin type are known risk factors for BCC; additionally, the average Caucasian individual has a 30% chance of developing BCC [5]. Individuals with darker skin types are 19 times less likely to develop BCC [6]. As stated in Chap. 2 on General Indications, MMS has a 99% 5-year cure rate for primary tumors and a 96% cure rate with recurrent tumors [7–9].

Summary: Etiology

•The predominant cause of BCC is thought to be an interaction between UVB and DNA resulting in the formation of dipyrimidine dimers in the DNA.

•The dipyrimidine dimers are formed in three genes, PTCH1, SMO, and SHH, and cause the Sonic hedgehog pathway to become constitutively activated.

16.2Etiology

BCC is thought to occur largely as a result of interactions between UVB and DNA forming DNA pyrimidines [10, 11]. These mutations cause inappropriate activation of the hedgehog signaling pathway so that it becomes constitutively active [12]. Within the hedgehog pathway, these mutations occur in primarily three genes, PTCH1, SMO, and SHH. Mutations leading to PTCH1 inactivation or deletion are believed to occur in 30–60% of sporadic BCCs [13, 14], while mutations in SMO (Smoothened) are thought to account for 10–20% of sporadic BCC. If one combines the mutations in PTCH1 and SMO, they account for 90% of sporadic BCCs [15].

Summary: Histological Findings Using

Horizontal Frozen Sections

•BCC tumors are comprised of nests of small, uniform, round basaloid cells.

•BCC usually demonstrates cytologic atypia, mitotic activity, and peripheral palisading.

•Nodular BCC consists of dermal, nodular aggregates of tumor that commonly arises from the epidermis and extends into the epidermis.

•In superficial BCC, the basaloid cells usually only penetrate to the papillary dermis. The tumor tends to have buds which branch in different directions with palisading along the periphery of the tumor.

•In morpheaform BCC, a firm, dense stroma develops, and the basaloid cells are found in the “crevices” of the stroma.

•Infiltrative BCCs have elongated strands of cells only a few layers thick that can deeply invade the tissue.

•Micronodular BCC exhibits micronodules of basaloid tumor cells.

•Adenoid BCCs have tubular or gland-like structures.

•Granular BCCs contain basaloid cells with clear cytoplasm.

16.3Histological Findings Using Horizontal Frozen Sections

BCC tumors are comprised of nests of small, uniform, and round basaloid cells. In distinction to SCC, the BCC cells are considered more immature in their differentiation and are less eosinophilic in their cytoplasm. BCC usually demonstrates cytologic atypia, mitotic activity, and peripheral palisading. BCCs usually do not demonstrate abnormal mitoses even in rare cases where metastasis occurs. Cystic spaces due to cellular dyshesion as well as necrosis of the tumor may be observed [16]. Mucin has also been noted in the stroma around the nests of BCCs leading to the stromal retraction that is often observed on sectioning (Fig. 16.1). Another characteristic feature is calcification. In rare cases, basaloid cells can be multi-nucleated, exhibit large hyperchromatic nuclei, and demonstrate “starburst” mitoses. Despite these findings, the clinical outcome remains the same as BCCs that do not exhibit these findings [17, 18].

Fig. 16.1 Mucinous BCC (a) cystic to reticulated appearing basaloid neoplasm with large sometimes interconnecting spaces in which (b) large amounts of mucin can be observed. Courtesy of Dr. Evangelos Badiavas

There are several histologic subtypes that are often observed when using MMS. BCC is comprised of multiple subtypes, and a biopsy suggesting one subtype does not necessarily mean that a tumor will be entirely comprised of that one subtype.

Nodular BCC consists of nodular aggregates of tumor that commonly arises from the dermis and extends into the epidermis (Fig. 16.2). Clinically, nodular BCC resembles a pearly papule that can be ulcerated or even eroded, and often demonstrates telangiectasia.

In superficial BCC, the basaloid cells only penetrate to the papillary dermis. The tumor tends to have buds, which branch into different directions with palisading along the periphery of the tumor (Fig. 16.3). An inflammatory infiltrate is often observed in the papillary dermis. When viewed under the microscope, it may look as though the different buds are not connected, and the term multifocal

Fig. 16.3 Superficial BCC: Neoplasm extends into the superficial dermis and is multifocal. Larger surface areas can be involved with limited invasion into the mid or deep dermis. Courtesy of Dr. Evangelos Badiavas

has been used to describe the tumor. Indeed, the buds are actually connected and have been described as “net-like.” The “net-like” histological morphology can complicate the Mohs procedure, and one has to be careful not to leave a bud outside the margin of sectioning. Clinically, superficial BCC tends to be macular to slightly papular and has an eczematous or scaly appearance.

In morpheaform BCC, a firm, dense stroma develops, and the basaloid cells tend to be found within the “crevices” of the stroma (Fig. 16.4). Morpheaform is less well demarcated than nodular BCC and tends to resemble a flat, yellow plaque. It appears similar to morphea or scleroderma, hence its name. Morpheaform BCC can be associated with significant subclinical spread as the average tumor spread is 7.2 mm outside the clinically observed tumor [19].

Fig. 16.4 Morpheaform BCC: Strands of basaloid cells extending into a fibrotic dermis and between thickened eosinophilic collagen bundles. The central portion of the neoplasm can often appear more scar-like. Courtesy of Dr. Evangelos Badiavas

Infiltrative BCC typically has elongated strands of cells only a few layers thick that can deeply invade the tissue. There is usually little to no peripheral palisading. This BCC subtype is also known to frequently invade nerves and can also invade bone (Fig. 16.5).

Micronodular BCC usually exhibits micronodules of basaloid tumor cells just as the name implies. Adenoid BCCs have tubular or gland-like structures. The basaloid cells form nodular-appearing structures with a “lace” type of pattern within those structures. Granular BCCs are exemplified by basaloid cells with clear cytoplasm (Fig. 16.6). Pigmented BCCs are histologically very similar to nodular BCCs except that they contain brown pigment in areas of the tumor, and may require smaller surgical margins than nodular BCC [20] (Fig. 16.7). Their biological behavior is also similar to nodular BCCs.

In general, perineural invasion is known to occur in BCC approximately 1% of the time [21]. When it does