Color Pencil Illustration by Suzanne L. Adams, CT (ASCP), copyright
*Normal cells of the cervix consist basically of squamous, glandular, and metaplastic epithelial cells. The squamous cells line the ectocervix (outer portion) as well as the vagina, and the glandular cells line the endocervix (the inner portion). Squamous metaplastic cells originate from the transformation zone of the cervix where the inner (endocervix) and outer (ectocervix) meet. In order for the cell sample to be satisfactory, endocervical or metaplastic cells must be present as most cervical cancers originate at this highly active transformation zone. Normal appearing endometrial cells may occasionally be seen in association with menses (between Day 1 and12 of the menstrual cycle).
*Squamous cells of the cervix are stratified (have distinct layers) into four cell layers--the top superficial layer, the intermediate layer just underneath this layer, the parabasal layer, and finally, the basal or reserve cell layer. Under the influence of estrogen and progesterone, the top layers are continuously being sloughed off and replaced by new cells that mature, starting from beneath at the basal layer. There are generally three types of squamous cells seen on Pap Tests (named after Dr. George Papanicolaou, inventor of the multicolor "Pap" stain and sampling technique) --the superficial, intermediate, and parabasal cell types. The superficial cells are the largest of the three and have small pyknotic (degenerative) nuclei and cytoplasm that generally stains eosinophilic. The intermediate squamous cells are similar in appearance but are slightly smaller in size and have larger, clearly structured, round nuclei with cytoplasm that usually stains basophilic. Both cell types are polygonal in shape. The intermediate cell type is the most common cell type seen. The parabasal cell type is a smaller, more rounded, immature cell type that is located below the intermediate cell layer.
*It is generally accepted that estrogen stimulates cell maturation at all levels of the squamous epithelium (from basal to superficial) while progesterone stimulates cell maturation only to the intermediate level (Naib ZM, 1976). Contraceptive hormones and hormone replacement therapy (estrogen or progesterone alone or in combination) can further increase cell division and maturation to various levels. Depo-Provera (a progestin-only contraceptive) may only increase proliferation of parabasal cells (see Hormone Effect Illustration). Long-term use of steroid sex hormones can shorten the resting period of cells where micronutrient reserves are replenished for proper DNA synthesis and cell division. Thus, overly stimulated cervical and vaginal cells by steroid hormones can exhaust key micronutrients, especially folic acid and the antioxidant vitamins, resulting in cervical "cell anemia" with characteristic changes in cell morphology of cytomegaly and early dysplastic change (see folic acid deficiency illustrations). Micronutrient deficient DNA within the nuclei of these anemic cells is made highly vulnerable to viral, carcinogen, and mutagen insertion (see HPV). Good nutrition is of paramount importance in keeping the cells of the cervix healthy and dividing and differentiating properly, especially when under the influence of powerful steroid sex hormones.
*The glandular cells of the endocervix, the endocervical cells, are occasionally seen throughout the Pap sample. They are simple columnar epithelial cells that appear singly, in small clusters, in tight honeycomb-like groups, or are dispersed in streaks of mucous with stripped nuclei. Normal appearing endometrial cells may also be seen just prior to or during menstruation. Both endocervical and endometrial glands cells are stimulated to differentiate and divide under the influence of estrogen and progesterone. Too much hormonal stimulation can produce abnormal cell morphology and may lead to precancerous or cancerous change similar to that of squamous cells (Ljusa D, 2000).
*In the background of the cell sample it is common to see white blood cells, particularly histiocytes and PMN's (polymorphonuclear leukocytes), as well as varying numbers of RBC's (red blood cells). The amount depends on the day of the woman's cycle, her age, and whether she is pregnant or lactating. PMN's normally increase in number during the "exodus" phase, just before and during early menses. They are a normal finding in small to moderate numbers. White blood cells increase in number as well as in type during a true inflammatory response to organisms and/or injury. Chronic inflammation produces lymphocytes whereas acute inflammation produces a preponderance of PMN's.
*A healthy flora of doderlein bacteria (lactobacillus acidophilus) is what cytologists like to see in the cervical sample background. This type of natural flora is indicative of a strong acidic defense against invaders such as candida, trich, and other opportunistic and sexually transmitted agents. Antibiotics often destroy doderlein bacilli. After or during treatment, the common fungi, candida, may manifest as a result. A good B-complex vitamin with plenty of folic acid helps protect and maintain the desired acidic pH and healthy doderlein bacterial flora. Streaks of normal occurring mucous may also be seen in the background of the cell specimen.