Squamous metaplasia
Another lesion that can be mistaken for dysplasia is squamous metaplasia, which we often see in biopsy specimens. There is normal endocervical glandular epithelium. What happens with squamous metaplasia is that the normal endocervical glandular epithelium – mucin producing columnar epithelium – becomes replaced by squamous epithelium. One can on lower power see a bit of disorganization but it can be mistaken for dysplasia. However, on high power, one can see normal endocervical glandular epithelium and squamous epithelium. The cells are very organized, there is no cytologic atypia, there are no mitoses, they have abundant eosinophilic cytoplasm. All these features say that this is not dysplasia; this is squamous metaplasia. This is very common in biopsy specimens. Our case represents cervical adenocarcinoma in situ. There are no precursor lesions, no morphologic biologic precursor lesions identified. The mean age is around 39 to 46 years. Most of these are associated with the human papilloma virus, in particular human papilloma virus 18, similar to severe dysplasia. The prevalence is less than the SILs or the CINs. The natural history is not as well documented or known as the SILs.
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The next case is a 50-year-old female who presented with vaginal bleeding. The gynecologist noted on physical examination that the cervix appeared slightly thickened and a biopsy was performed. The biopsy revealed, in the underlying stroma, very irregular complex glandular structures infiltrating deeply into the cervical stroma; they were not superficial at all. The normal endocervical gland level or depth is usually about 5 to 7 mm below the base of the epithelium. In our case, they infiltrated deeply and were very complex. Some of them had out-pouchings. In other areas, they had what is known as a cribriform arrangement, where there are multiple glands within glands and multiple lumina. In addition, the stroma was quite reactive and there were numerous inflammatory cells, with a somewhat desmoplastic appearance. Cytologically, besides architecturally being very malignant, cytologically it was extremely malignant. Numerous mitoses were seen and one should not see normal endocervical glands; there were papillary enfoldings, which should not be seen, and the cells had prominent, angry-appearing nucleoli, vesicular-looking chromatin and large nuclei. This is an example of an invasive adenocarcinoma as opposed to adenocarcinoma in situ. It is invasive, it has malignant cytology, the stromal reaction shows that it is invasive and it is deeply infiltrative.
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There are seven histologic subtypes of invasive adenocarcinoma. The first is the mucinous adenocarcinoma, which the above case actually represents. There was very little mucin, but in some areas, one could appreciate mucin. Mucinous adenocarcinomas can be divided into three histologic subtypes – the endocervical subtype, which basically has cells similar to the normal endocervical glandular epithelium; the intestinal subtype, where you actually see goblet cells, similar to what is seen in the intestine; and the signet-ring subtype. These three types are similar in prognosis. The mucinous adenocarcinoma is the most common.