Paget’s cell compared to more uniform cytoplasmic staining for the normal eccrine and apocrine glands established the diagnosis of Paget’s disease [53].

Summary: Other Rare Tumors

•Granular cell tumor (GCT) is a benign neural tumor that may rarely become malignant with the possibility of metastases.

•S100 is an immunostain useful during MMS for detecting granular cell tumor, especially through the proper identification of perineural extension.

•Primary mucinous carcinoma (PMC) is a sweat gland tumor that can be identified in FS with low molecular weight cytokeratin (LMW CK).

•Trichilemmal carcinoma (TC), an adnexal tumor that in rare cases can demonstrate local invasion, can be detected by Cytokeratin 17 (CK 17) staining in difficult cases.

15.7Other Rare Tumors

15.7.1 Granular Cell Tumor

Granular cell tumors (GCT) are rare soft tissue tumors of neural origin, likely derived from Schwann cells [54, 55]. The majority of these tumors are benign, while 1–3% can become malignant, with a possibility of metastases [54, 55]. Histologically, the cells have a granular cytoplasm with small, round, centrally located basophilic nuclei [56]. An aggressive tumor is identified by increased mitosis, necrosis, and spindling of the cells [56]. If excised with adequate margins, the recurrence rate ranges from 2% to 8% [54, 56].

MMS has been utilized for the treatment of GCT and is especially helpful in determining perineural involvement. In 2002, a group reported the use of the S-100 immunostain on FS material during MMS, as this antigen is expressed in the nucleus and cytoplasm of granular cells [57]. Later studies reported similar findings, where the use of S100 compared to H & E staining was particularly beneficial in preventing additional unnecessary layers due to the proper identification of perineural extension [56, 57].

15.7.2 Primary Mucinous Carcinoma

Primary Mucinous Carcinoma (PMC) is an extremely rare sweat gland tumor, possibly related to the eccrine secretory coils [58]. Cutaneous metastases from a visceral adenocarcinoma would have similar histology, and although it would be extremely uncommon, it would be imperative to exclude the possibility. Histologically, it is characterized by pools of pale-stain- ing mucin surrounding islands of basaloid nests which can have duct-like differentiation with dark and pale cells [58, 59]. PMC is a locally recurrent tumor (27%); however, it can rarely present with regional and distant metastases of 11% and 3%, respectively [59]. MMS was reported for the treatment of PMC in a few cases in the literature, and patients were found to have no recurrences in the 2–5 year follow-up period [59, 60].

PMC has stained positively on FFPES with LMW CK and epithelial membrane antigen (EMA), while CEA and S100 are variable [58, 61]. One study utilized the immunostains LMW CK, pan-keratin, EMA, CEA, and a vimentin-specific monoclonal antibody during MMS for the treatment of PMC. The authors found that the LMW CK immunostain stained strongly positive, while EMA was weakly positive. CEA and vimentin immunostains were negative. They concluded that LMW CK, which labels the nonsquamous epithelium, not the neural tissue or mesenchyme, is a useful stain when residual tumor is difficult to identify on H & E. The patient was reported to be tumor free for the 3-year follow-up period [58].

15.7.3 Trichilemmal Carcinoma

Trichilemmal carcinoma (TC) is a rare adnexal cutaneous malignancy that is not generally associated with perineural spread or vascular invasion. However, one study reported the utility of MMS with immunostaining for a rare case that recurred many times and demonstrated perineural extension. They employed CK 17, CK 15, and c-erb-B2 immunostains and found strong cytoplasmic staining on FS material with CK17 and c-erb-B2. CK17 is typically expressed in the outer root sheath (ORS) of hair follicles, while CK 15 is normally expressed in the bulge area of the ORS. The authors suggested that since TC can demonstrate follicular ORS differentiation, CK 17 is a helpful immunostain