To The Editor:
Follicular squamous cell carcinoma (SCC) is a rare variant. It is briefly mentioned in some textbooks of dermatopathology,1 and Diaz-Cascajo et al2 published a series of 16 cases in 2004. In the 31st symposium of the International Society of Dermatopathology in Barcelona, Carter et al3 presented a series of 56 cases emphasizing some of the morphologic features of this variant. Follicular SCC shows the following features as most remarkable2:
- It arises from the pre-existing hair follicles.
- The interfollicular epidermis is not involved and there is a minimal spread of the tumor beyond the follicular ostium.
- The tumor totally or partially involves the infundibullum or the sebaceous glands.
- In some tumors, palisade of the tumoral cells is seen.
Follicular SCC “apparently exhibits low-grade behavior”.4 Such good behavior could be related, at least partly, with tumoral thickness. It is well recognized that thickness is one of the most important prognostic factors of SCC.5,6 Increasing tumor thickness has been related with an increased risk of metastases.7–9 Tumoral thickness has also been related to tumoral recurrence.10 Common SCC with a tumoral thickness ≤2 mm do not metastisize at all, whereas the metastasis rate of common SCC is 2.9% for a thickness of 2–5 mm and 17.5% for a thickness >5 mm.11 Similar rates and conclusions on the influence of the tumoral thickness on the metastatic potentiality of the tumor have been obtained in different decades by other groups.7,8,12 As a consequence, measuring correctly the tumoral thickness of any variant of SCC is not a trivial matter because the prognosis of metastatic SCC is poor, with 5-year survival rates of less than 35%.10
In the “cancer protocols and checklists” of the College of American Pathologists (CAP) (updated, February 2010), it is recommended to measure the maximum tumor thickness with Breslow procedures, that is, to measure “with a calibrated ocular micrometer at right angle to the adjacent normal skin…” from “the granular layer of the epidermis of the overlying skin or, if the lesion is ulcerated, the base of the ulcer.”13 Some other publications also use these same measuring parameters.5
Khanna et al5 considered their SCCs with a tumoral thickness under 2 mm as “very low-risk tumors” because studies from literature did not demonstrate any metastatic potential in them. SCCs with a thickness between 2 and 5 mm were considered as “intermediate risk” and the ones over 5 mm were considered as “high-risk SCCs”.5 Similar considerations are also mentioned in the protocols of the CAP, where a tumoral thickness over 2 mm is defined as a high-risk feature. In these, it is also emphasized how the evidence of 2 or more high-risk features determines if the tumor is categorized as pT2 instead of pT1 and therefore, the stage would be II instead of I.13 From this, it is easy to understand that a mistake in measurement, even of 0.1 mm, can cause an error with prognostic and therapeutic connotations.
Follicular SCC, by definition, originates “in the upper parts of the follicle” and invades in a lobular way. Therefore, the point is that measurement of the invasion of follicular SCC could be wrong if calculated from the granular layer of the epidermis because this tumoral variant is not related to the epidermis but to the follicle. Alternatively, tumoral thickness could be measured from the lumen of the follicle (Fig. 1). However, the complete length of the follicles is rarely seen in skin biopsies, whereas an oblique section of them is more commonly observed (Fig. 2). It is therefore highly probable that a section from a follicular SCC originated from a follicle shows several spaces correspondent to the distorted follicular lumen (Fig. 3). The most appropriate would be to measure the tumoral invasion from the deepest luminal space. It is logical to think that this would provide more realistic information on the invasion of this tumoral variant.
When measuring tumoral thickness this way, the figures obtained are, obviously, much more inferior than the ones measured by standard procedure.
Figure 4 shows the lesion already drawn in Figure 3. Tumoral thickness measured by the conventional procedure (from the granular layer of the epidermis) would probably be superior to 2 mm (Fig. 4A). Such a lesion would therefore accomplish one of the high-risk criteria given by the CAP (thickness over 2 mm). Because the tumor invades the reticular dermis, it shows a Clark level IV, which is another high-risk criterion. With 2 high-risk criteria, the tumor would be assigned as pT2 and it would be, at least, staged as II. If, on the contrary, the lesion is measured from the deepest section of the lumen (Fig. 4B), the thickness would be more inferior, probably not even reaching 1 mm, and the lesion would be staged as pT1, stage I.
The over-measurement of the follicular SCC could perhaps be responsible for its paradoxical good behavior, despite its anatomic location. Follicular SCC mainly appears on exposed areas such as the face, cheek, nose, nasolabial fold, or front.2 However, many of these locations have been categorized as “the areas most prone to metastases”.6,10,14–17 In this context, it is interesting to remember that none of the patients from the series of Diaz-Cascajo et al2 developed a metastasis after follow-up periods of up to 144 months.
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