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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 carcinomaâ€. 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 carcinomaâ€.
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, acanthosisâ€. Ask for an image of the lesion, even if it is taken from smart phone.
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 carcinomaâ€. 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 carcinomaâ€.
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, acanthosisâ€. Ask for an image of the lesion, even if it is taken from smart phone.
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