The most common cervical carcinomas are squamous cell carcinomas (75%), followed by adenocarcinomas and mixed adenosquamous carcinomas (20%) and small cell neuroendocrine carcinomas (<5%). All of these types of carcinomas are associated with HPV. Of interest, the relative proportion of adenocarcinomas has been increasing in recent decades owing to the decreasing incidence of invasive squamous carcinoma and suboptimal detection of glandular lesions by Pap smear.
Squamous cell carcinoma has a peak incidence at the age of about 45 years, some 10 to 15 years after detection of precursor SIL. As already discussed, progression of SIL to invasive carcinoma is variable and unpredictable and requires HPV infection as well as mutations in tumor suppressor genes and oncogenes. Risk factors for progression include cigarette smoking and human immunodeficiency virus (HIV) infection, the latter finding suggesting that immune surveillance plays a role in preventing progression. Although risk factors may help identify patients who are likely to progress from SIL to carcinoma, the only reliable way to monitor the disease course is with frequent physical examinations coupled with Pap smears and biopsy of suspicious lesions.
Fig.19.8 ).Microscopically,theinvasivetumorsoftenconsistoftonguesandnestsofsquamouscellsthatproduceadesmoplasticstromalresponse.Gradingisbasedonthedegreeofsquamousdifferentiation,whichrangesfromminimaltowell-differentiatedtumorsthatelaboratekeratinpearls.Raretumorswithneuroendocrinedifferentiationresemblesmallcellcarcinomasofthelungmorphologically.Tumorsencirclingthecervixandpenetratingintotheunderlyingstromaproduceabarrelcervix,whichcanbeidentifiedbydirectpalpation.Extensionintotheparametrialsofttissuescanaffixtheuterustothesurroundingpelvicstructures.Thelikelihoodofspreadtopelviclymphnodescorrelateswiththedepthoftumorinvasionandthepresenceoftumorcellsinvascularspaces.Theriskofmetastasisincreasesfromlessthan1%fortumorslessthan3mmindepthtomorethan10%afterinvasionexceeds3mm.
Fig.19.8Cervicaloswithsurrounding,invasive,exophyticcervicalcarcinoma.
Invasive cervical cancer most often is seen in women who have never had a Pap smear or who have not been screened for many years. In such cases, cervical cancer often is symptomatic, with patients coming to medical attention for unexpected vaginal bleeding, leukorrhea, painful coitus (dyspareunia), or dysuria. The primary treatment is hysterectomy and lymph node dissection; small microinvasive carcinomas may be treated with cone biopsy. Radiation and chemotherapy are also of benefit in instances where surgery alone is not curative. Mortality is most strongly predicted by tumor stage and, in the case of neuroendocrine carcinomas (which pursue an aggressive course) to cell type.
Endocervical polyps are benign polypoid masses seen protruding from the endocervical mucosa (sometimes through the exocervix). They can be as large as a few centimeters and have a smooth, glistening surface with underlying cystically dilated spaces filled with mucinous secretions. The surface epithelium and lining of the underlying cysts are composed of the same mucus-secreting columnar cells that line the endocervical canal. The stroma is edematous and may contain scattered mononuclear cells. Superimposed chronic inflammation may lead to squamous metaplasia of the overlying epithelium and ulcerations. These lesions may bleed, thereby arousing concern, but they have no malignant potential.