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Debunking the myth of the aggressive nature of acantholytic squamous cell carcinomas

DII small banner By Warren R. Heymann, MD
Feb. 6, 2017
acantholytic squamous cell carcinomas
Acantholytic squamous cell carcinoma (aSCC), follicular pattern. The tumor is centered upon follicular epithelium but also involves epidermis. Some features of actinic keratosis (parakeratosis, basilar epidermal atypia) are present; by our definition, this example did not qualify for aSCC arising in association with actinic keratosis because there is invasive carcinoma in the directly underlying dermis. (Hematoxylin-eosin stain; original magnification: ×20; inset, ×100.)
Credit: JAAD

Although the term “debunked” had unparalleled use during the election last year, Oxford Dictionaries has declared “post-truth” as its 2016 international word of the year. It is defined as an adjective relating to circumstances in which objective facts are less influential in shaping public opinion than emotional appeals (1). For years, I have taught my residents that acantholytic squamous cell carcinomas (aSCCs, aka “pseudoglandular” SCCs) were more aggressive than typical SCCs. Two recent studies suggest otherwise. In medicine (and life) there should be no room for “post-truths” — we need facts to confirm or refute long-standing assumptions.

“High risk” cutaneous SCCs commonly occur on the head and neck and have an increased tendency toward recurrence, local invasion, and distant metastasis. Factors for high-risk cutaneous SCCs include a large size (>2 cm), a deeply invasive lesion (>2 mm), incomplete excision, perineural invasion (PNI), lymphovascular invasion, immunosuppression, and high-risk anatomic locations. Poorly differentiated lesions and certain histologic subtypes (acantholytic, adenosquamous [mucin producing], desmoplastic, and metaplastic) are also considered high risk.  Currently, the NCCN includes these histologic subtypes as high-risk factors in cutaneous SCC, whereas the AJCC does not (2).
How did aSCCs get their unsavory reputation? Perhaps it was Nappi’s study of 49 patients with aSCCs; although lesions generally behaved in an indolent manner, 19% of cases succumbed to widespread metastatic disease (3).

Pyne et al studied a total of 1658 consecutive invasive SCC cases, of which 4.9% were acantholytic SCC. Median tumor microscopic maximum diameter was 8 mm for acantholytic SCC and 7.3 mm for non-acantholytic SCC. Median tumor invasion depth was 1.0 mm for acantholytic SCC and 1.5 mm for non-acantholytic SCC. Well, moderate and poor differentiation were not significantly different between acantholytic SCC and non-acantholytic SCC. One case demonstrating perineural invasion (PNI) was found in 82 acantholytic SCC cases. A total of 77 acantholytic SCC cases were followed up over a median 25 months finding histologic proven recurrence at 3 acantholytic SCC excision sites. The authors suggested that with no fatalities, low PNI, and low recurrence rates,  acantholytic SCCs are low-risk (4).

Ogawa et al, in a study of 115 aSCCs (103 patients, mean age 71.8 years), actinic keratosis was present in 23% (27/115) but only 7.8% (9/115) exhibited associated an acantholytic actinic keratosis (aAK). Fifty of 115 (43%) of their aSCC cases exhibited predominant involvement of follicular epithelium rather than the epidermis. Clinical outcome (median follow-up, 36 months) was available in 106 of 115 (92%). One patient experienced regional extension (parotid), and 1 patient experienced a local recurrence (nose). No disease-related metastases or deaths were documented. The authors concluded that the presence of acantholysis in cutaneous SCC does not specifically confer aggressive behavior, a finding that may influence clinical practice guidelines.
While the aggressive reputation of aSCCs may now be debunked, these lesions, as do all SCCs, require respect; the other well-defined high risk attributes may be present in an individual patient. That’s the whole truth, not the “post-truth.”

1. “Post-truth” declared word of the year by Oxford Dictionaries. BBC News. Published 16 November 2016.
2. Skulsky SL, et al. Review of high-risk features of cutaneous squamous cell carcinoma and discrepancies between the American Joint Committed on Cancer and NCCN Clinical practice guidelines in Oncology. Head Neck 2016; Nov 24 [Epub ahead of print].
3. Nappi O, et al. Adenoid (acantholytic) squamous cell carcinoma of the skin. J Cutan Pathol 1989; 16: 114-21.
4. Pyne JH, et al. Acantholytic invasive squamous cell carcinoma: tumor differentiation, invasion, depth, grade of differentiation, surgical margins, perineural invasion, recurrence and death rate. J Cutan Pathol 2016; Dec 19 [Epub ahead of print]
5. Ogawa T, et al. Acantholytic squamous cell carcinoma is usually associated with hair follicles, not acantholytic keratosis, and is not “high risk”: Diagnosis, management, and clinical outcomes in a series of 115 cases. J Am Acad Dermatol 2017; 76: 327-33.

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