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Dr. Sook-Bin Woo's Blog

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Bluntly invasive squamous cell carcinoma



In 2002 or thereabouts, I saw a patient who fundamentally changed the way I think of, and diagnose dysplasias and invasive carcinomas. More about dysplasias later. Prior to me seeing her, I had received 2 biopsies from this middle aged woman for a lesion on the buccal mucosa within a short period of time, and each time, I had diagnosed it as “hyperkeratosis, acanthosis and chronic inflammation” without further comment. The oral surgeon sent the patient to me to be examined.

On examination, the patient had three separate areas of abnormality, the largest measuring 3 cm, the other two measuring 1 cm each, identical in appearance, but not obviously contiguous. The largest was an exophytic mass that clinically resembled a squamous cell carcinoma while the other two smaller lesions were consistent with leukoplakias that to me were all part of the same process, and were therefore likely to be dysplastic. I personally re-biopsied all three (from the center of the lesions), and to my utter amazement, none of them showed any evidence of cytologic dysplasia or atypia. The mass showed only hyperkeratosis and marked epithelial hyperplasia. I showed this to general and oral pathologists, and all agreed it looked benign until I showed them the photograph. Of course, there was no evidence of conventional squamous cell carcinoma either.

Since then, I have seen many more such lesions on biopsy correlated with clinical images and believe that there is a poorly-recognized form of squamous cell carcinoma that has an invasion pattern similar to that of verrucous carcinoma but yet is not a verrucous carcinoma. This is what I refer to as “bluntly invasive squamous cell carcinoma”. It is not a new concept and speaks to the importance of the pathologist and clinician working together to correlate histopathology with the clinical presentation.

Clinical and Histopathologic Findings

Lesions usually present as extremely thick, plaques – usually several mm thick, unlike leukoplakias which are usually raised 1-2 mm from the surface. The clinician may report that this has been biopsied in the past and the diagnosis was always “hyperkeratosis, acanthosis and chronic inflammation, with no evidence of dysplasia” but that the lesion has continued to slowly progress.

Histologic features include:

1. Variable parakeratosis or hyperkeratosis

2. Bulky epithelial proliferation that is exo- and/or endo-phytic in growth pattern and may also show a verrucous or papillary surface configuration. The epithelium may be 3-4 times the thickness normal for that site.

3. Rete ridges are usually very large, bulbous and thick; look for keratin pearls and intraepithelial microabscesses near the tips of the rete ridges. There is no single cell or small island infiltration of the stroma even in deep levels.

4. There is often a broad, pushing front.

4. Cytologic atypia is variable, and the most difficult cases are the ones that show minimal atypia. When atypia is present, many pathologists still find it difficult to diagnose these as squamous cell carcinomas because of reliance on single cell or small island invasion for the diagnosis.

5. Even if candidal infection is present, the degree of epithelial proliferation is beyond what one would expect for a reactive lesion.

The sign-out is “atypical endophytic (or exophytic or both) squamous proliferation consistent with bluntly invasive squamous cell carcinoma”.

The bulbous rete ridges bring to mind the frond-like rete ridges of verrucous carcinoma, a well-recognized form of bluntly invasive squamous carcinoma that also shows minimal cytologic atypia. Verrucous carcinomas show marked parakeratosis (not orthokeratosis by definition), verrucous and bulky exophytic and endophytic squamous proliferation and minimal cytologic atypia. As such, verrucous carcinoma should be considered a well-recognized form of this pathologic entity.

Clinical implications

Verrucous carcinomas rarely metastasize to the lymph nodes and the few studies that have examined the blunt pattern of invasion in oral squamous cell carcinoma have come to a similar conclusion. It would make sense that if the epithelial proliferation “holds together” and neoplastic cells do not break away from the surface epithelium, there would be little lympho-vascular or neural invasion. However, it is nevertheless a carcinoma and its relentlessly growth causes destruction of tissues and bone on a broad front.

As far as I know, there have been few studies that looked only at this pattern of invasion to correlate it with staging, prognosis and survival. It may be that such lesions do not need wide resection, or they may not require even a modified neck dissection. They may also not be radio-sensitive. These would have significant clinical implications if true.

It is so helpful if you have the clinical lesion to look at when you come across lesions with the characteristics described above. “Atypical endophytic squamous proliferation consistent with a bluntly invasive squamous cell carcinoma” looks very different from “hyperkeratosis, acanthosis”. Ask for an image of the lesion, even if it is taken from smart phone.


Recommended Comments

Dr. Phillip McKee


Great blog Sook. As someone who always passed on the oral biopsies to our oral pathologist, I have been spared this diagnostic dilema. Although the issue became a lot clearer when you sent me some examples to photograph. I think that the real take home message for me is the importance of clinicopathological correlation and the clinician photographing the lesion and sending the images to the pathologist is a fabulous idea. So many silly mistakes would be avoided if this became regular practice. It reminds me of an occasion when I received a 3mm punch biopsy of a lesion on the arm. It looked like an atypical DF but I added the comment that the deep margin could not be seen and therefore a sarcoma NOS could not be excluded. Chris Fletcher called me a week later and asked "did I know that the patient had an underlying soft tissue tumor measuring around 12 cm in diameter!
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Dr. Hafeez Diwan


I think you make an excellent point. I struggle quite often with the kinds of lesions you talk about. I have resorted to either calling them "Favor well-differentiated squamous cell carcinoma," or, if I am feeling exceptionally weak or unsure, "Well-differentiated squamous cell carcinoma cannot be ruled out."
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Dr. Mona Abdel-Halim


Great blog emphasizing the importance of clinicopathological correlation...but the problem is how to pick it when it is in an early stage clinically (before being exophytic masses) and not dismiss them as reactive pseudoepitheliomatous hyperplasia????? Any clues???
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Several important points here. One of the most important is you must know how thick the "normal" epithelium is for that site - for a more detailed description of this, I refer you to my atlas of Oral Pathology which explains this. But here is the short version. Eg. 25 cell-thickenss for the floor of mouth is abnormally thick while on the buccal mucosa, this would be fairly normal or slightly thickened only.

1. If you have a good biopsy that includes the adjacent more-or-less "normal" appearing mucosa (although generally, this will be hyperkeratotic), the endophytic extension of bulbous, elongated rete ridges beyond the level of the rete ridges on the adjacent "normal" is the most important clue.

2. Others include micro-abscesses at the tips of the rete ridges and of course, extension of the retes into the muscle (although still connected to the surface), or retes in contact with the periosteum for mucosa that directly abuts the epithelium such as hard palate and gingival mucosa.

3. If you do not have the adjacent "normal", that is the biopsy was taken from the center of the lesion, just the fact that the epithelial proliferation is bulky (>2x the thickness of the epithelium FOR THAT SITE), would make me very suspicious. Sometimes, I use the term atypical bulky endophytic squamous proliferation c/w bluntly invasive SCCA.
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Thank you Dr. Hurt. I completely agree with you that very well-differentiated squamous cell carcinomas do not have significant cytologic dysplasia and verrucous carcinoma is a prime example. But there are those that are not quite verrucous carcinoma which usually means, they are small lesions. But even a verrucous carcinoma has to start small and the very early lesions are usually what we call verrucous hyperplasia or better yet, atypical verrucous hyperplasia where the dysplasia if we want to call it that, is in the architecture and not the cells. Sometimes they have the "glassy" cytoplasm that we often see in squamous cell carcinomas with the keratoacanthomatous pattern of growth.

Unlike the cervix, where the term intra-epithelial neoplasia is used instead of dysplasia, among oral pathologists, the term dysplasia is still used to mean the same thing. We tend to use the term "atypia" if we see cytologic changes but are not sure if they represent truly neoplastically transformed albeit non-invasive and still within the confines of the epithelium vs. reactive atypia.

Thank you for your posting.
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