Summary: Histopathologic Recognition

of Cutaneous Structures

¥The Mohs surgeon should be able to recognize different cutaneous structures and tumors with special reference to the histopathologic differential diagnosis.

¥Actinic keratosis should be differentiated from Bowenoid (full thickness) atypia and squameous cell carcinoma in situ.

¥Squamous eddies of irritated seborrheic keratosis or inverted follicular keratosis should be differentiated from the epithelial pearls of SCC. The former are numerous, small, monotonous rounded or oval collections of reactive keratinocytes, whereas the latter are less in number, variable in size, and larger with focal or diffuse keratinocytic atypia and mitoses.

¥Incidental acantholytic dyskeratosis or epidermolytic hyperkeratosis (granular degeneration) should be differentiated from acantholytic SCC.

¥Pseudoepitheliomatous hyperplasia should be differentiated from SCC by the lack of cytologic atypia and atypical mitoses.

¥The Mohs surgeon should be aware of the presence of large, atypical melanocytes in sun-damaged skin when interpreting Mohs slides for melanoma.

¥The Mohs surgeon should be able to recognize different cross-sections of hair follicles at different levels. The presence of perifollicular Þbrous tissue sheeth helps differentiate them from BCC tumor formations that are usually surrounded by immature mucinous stroma.

¥The bulge is the follicular protrusion at the site of attachment of the arrector pili muscle. Horizontal sections of the bulge may create a rounded or oval basaloid cell structure with a blend of suprabulbar and isthmic cellular features which should be differentiated from BCC tumor formations.

¥The mantle is a ribbon of basaloid cells extending from the upper portion of the hair follicles and they represent the origin of, or Òthe resting stage,Ó of mature sebaceous gland lobules. The mantle should be differentiated from BCC tumor formations.

¥Folliculocentric basaloid proliferations (funny looking follicles) are reactive irregular strands of basaloid cells emanating from the upper portion of some hair follicles and should be differentiated from BCC tumor formations. They are believed to be hyperplasia of the mantle epithelium.

¥Dense desmoplastic reaction can sometimes create a picture that mimics perineural invasion and is referred to as peritumoral Þbrosis.

¥Dense perineural inßammation has been associated with a higher incidence of perineural invasion. Examination of other tissue sections on the slide or deeper levels may be warranted to rule out perineural invasion.

¥Reactive endothelial cells may show prominent cytologic atypia and should be differentiated from different cutaneous neoplasms such as SCC.

13.3Histopathologic Recognition of Cutaneous Structures

13.3.1Recognition of Epidermal and Epithelial Components and Their Neoplasia

13.3.1.1 The Epidermis

The Mohs surgeon should be adept in understating the normal histology of the skin to recognize cutaneous pathology. The epidermal thickness varies depending on the site on the body, the age of the patient, and the degree of sun damage in sun-exposed areas. Mucosal epithelium is usually glycogenated and appears vacuolated, which could be interpreted as a freezing artifact by an inexperienced Mohs surgeon (Fig. 13.2). Tangential cutting of rete ridges and/or epidermis may sometimes resemble basal or squamous cell carcinoma tumor formations (Fig. 13.3).

A variable degree of keratinocytic atypia and rare normal mitotic Þgures at the basal cell layer can be seen in sun-damaged skin. The incidental presence of a common benign epidermal tumor should be evaluated cautiously with comparison to the original cancer. For instance, a focus of irritated seborrheic keratosis

with squamous eddies or clonal seborrheic keratosis poses a challenge in a case of SCC, but not BCC.

Furthermore, acantholysis (that could be mechanical due to a biopsy bandage) or the incidental focal acantholytic dyskeratosis or epidermolytic hyperkeratosis (granular degeneration) may mimic a focus of acantholytic SCC (Fig. 13.4). Inverted follicular keratosis and irritated seborrheic keratosis can mimic SCC. The former usually shows many small, uniform squamous eddies compared to the large, irregular squamous and keratin pearls seen in SCC (Fig. 13.5a, b). Adenoid and reticulated seborrheic keratosis (Fig. 13.6) show thin epithelial strands which interlace with each other, creating an adenoid feature that could be mistaken for adenoid BCC. The presence of horn cysts and the identiÞcation of keratinocytic desmosomes under high-power magniÞcation, together with the surrounding mature Þbrous stroma differentiate them from BCC (Fig. 13.7). The latter shows immature mucinous stroma around the basaloid tumor formations. Large cell acanthoma shows large keratinocytes with large nuclei and disordered arrangement, but without mitotic activity (Fig. 13.8) or overt dysplasia that differentiates it

from Bowen disease (Fig. 13.9). Actinic keratosis is usually easy to identify and differentiate from Bowen disease (Fig. 13.10). However, tangential cutting of the epidermis at the basal epidermal third may create a picture that mimics the full thickness atypia seen in Bowen disease. In this case, the differentiation can be tough, however, the oblique arrangement of cells and rete ridges, if present, would greatly help in such differentiation.

When interpreting Mohs slides for MMS of Paget disease, the Mohs surgeon should be careful in identifying freezing artifacts, and glycogenated clear mucosal cells that could mimic Paget cells or Pagetoid Bowen disease (Fig. 13.11). The latter are larger-showing paler vacuolated cytoplasm and lack intercellular bridges. When in doubt, and if immunohistochemistry laboratory is available, CEA immunostaining should decorate Paget cells, but not keratinocytes.

Finally, pseudoepitheliomatous (pseudocarcinomatous) hyperplasia [8] may create an indistinguishable picture from SCC for some Mohs surgeons. The most important and probably the only criteria for differentiation are the lack of cytologic atypia and lack of atypical/bizarre

Fig. 13.5 (a) High-power view of an irritated seborrheic keratosis showing multiple, monotonous small squamous eddies. Note there is no overt cytologic atypia or atypical mitoses.

(b) Intermediate-power view of a Mohs section showing prominent residual SCC with multiple, variably sized, larger epithelial pearls