pattern is absent and there are many mitotic figures and pyknotic nuclei [4]. Special stains, such as Oil Red O, that stain lipid globules (Fig. 26.7), and immunochemistry (EMA, Cam 5.2) are usually helpful for identifying poorly differentiated SC [36, 37].

26.4.3 Mechanisms of Invasion

SC invades adjacent structures by three mechanisms:

(1) direct invasion, (2) pagetoid spread, and (3) multicentric discontinuous spread. The concept of “skip” areas is discussed. Additionally, the clinicopathologic parameters of poor prognosis are listed.

26.4.3.1 Direct Invasion

Direct invasion of local tissue by SC cells consists of lobules and cords of cells with sebaceous differentiation and is the most common mechanism of spread. Mohs surgeons are familiar with this infiltrative type of invasion as observed in nodular and infiltrative basal cell carcinoma, and infiltrative squamous cell carcinoma. Perineural invasion was observed in 7% [17, 34].

26.4.3.2 Pagetoid Spread

Pagetoid spread of atypical sebocytes within the epidermal or epithelial layers is present in about 50% of

the reported cases and 100% of advanced cases (Figs. 26.8, 26.9). The atypical sebocytes possess large nuclei with foamy cytoplasm and may be interspersed singly or in nests (pagetoid) or occupy the full thickness (bowenoid) of the epithelia [29]. For three decades, Mohs surgeons have been familiar with these clear cell characteristics as observed in cutaneous Bowen’s disease, squamous cell carcinoma in situ, melanoma, extramammary Paget’s disease [38], and other epidermotropic neoplasms. Multicentric pagetoid foci are considered unlikely because light and ultrastructural studies have revealed a lack of gradual transition of the overlying epithelia into pagetoid cells, indicating secondary spread (from below) rather than an in situ transformation [4].

26.4.3.3 Multicentric Origin

Historically, multicentric tumors have been observed in 19–36% of advanced cases and associated with the highest fatalities [4, 39, 40]. Multicentricity implies that there are different sebaceous gland cell types (e.g., meibomian, Zeis) [4] or different sites not previously involved with tumor. In a Zeis gland derived tumor, SC cells typically surround a hair shaft [4]. In this updated review, there were 57 cases of SC treated by Mohs surgery (see Table 26.1). There were seven local recurrent tumors. Multicentric SC was suspected in 5.3% (3 of 57).

By contrast, Shields et al. [45] reported that in their series of 60 cases, that 3 of 11 (27%) recurrences were multifocal because they recurred in new sites that were previously not involved with tumor. Pereira et al. [34] reviewed 44 cases of SC for degree of sebaceous differentiation, vacuoles, growth pattern, atypical mitoses, multicentricity, lymphatic, perineural invasion, and others. Of the 11 parameters evaluated, no cases were classifiedasmulticentric.FromtheMohssurgeryperspective,

isolated multicentric foci do not negate the validity of applying Mohs surgery to these cancers because each individual focus will be followed to its microscopic termination. Multicentric tumors, however, do confuse the surgeon into thinking that the tumor recurred after treatment rather than representing a separate new tumor. Mohs surgeons have an opportunity to assess this phenomenon through expert mapping of recurrent tumor and reexamination of recurrent SC and comparison of the

histopathology of the primary and recurrent SC tumors. Theoretically, different histopathology supports the thesis of multicentricity, while similar pathology to the original tumor suggests a local recurrence.

26.4.3.4 “Skip” Areas

The concept of a “skip” or “patchy” area of tumor is sometimes mentioned as a possible mechanism for

local persistence of pagetoid SC [14, 19]. An example would be the evaluation of the surgical margins on frozen sections that was read as negative and later found to have residual tumor on paraffin sections [15]. A discontinuous focus may occur in a recurrent tumor treated by curettage [14]. Every Mohs surgeon knows that deeper cuts are made into the tissue block when thawed frozen sections are submitted for paraffin