Term
| what role does estrogen play in cervicitis? |
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Definition
| estrogen stimulates the maturation of cervical/vaginal squamous mucosa and the formation of *intracellular glycogen vacuoles in the squamous cells. as these cells are shed, the glycogen provides a substrate for endogenous vaginal aerobes/anaerobes - however lactobacilli produce lactic acid, which produces bacteriotoxic hydrogen peroxide. however, if pH increases, the lactobacilli will decrease hydrogen peroxide production - causing an overgrowth of bacteria, leading to cervicitis. |
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Term
| can cervical inflammation alter the findings of a PAP smear? |
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Definition
| yes. a hx for each individual pt will help the pathologist suss out the dx. |
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Term
| what is characteristic of HSV on a pap smear? |
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Definition
| *multinucleated cells*, *viral intranuclear inclusions*, and fragmentation of the epithelial cells. |
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Term
| what are the non-neoplastic glandular lesions of the cervix? |
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Definition
| endocervical polyps, nabothian cysts, tunnel clusters, microglandular hyperplasia, diffuse laminar endocervical glandular hyperplasia, and mesonephric duct rests |
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Term
| what are endocervical polyps? how do they appear? |
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Definition
| endocervical polyps result from chronic inflammatory changes (reactive, not true neoplasms), and consist of *dilated glands w/an *edematous, inflamed *fibrotic/dense stroma. their surface endothelium (endocervical columnar epithelium) often shows *squamous metaplasia, there may be a *branching papillary structures and they range in size from relatively small to several cm in diameter. these benign growths found in adult women *may cause bleeding and most are found in the endocervical canal (and may protrude from the cervical os). |
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Term
| what are nabothian cysts? how do they appear microscopically? what can they mimic? |
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Definition
| these are common cystic spaces (filled w/mucoid material) that occur due to *blockage of endocervical glands by inflammation. microscopically: cystically dilated glands lined by *flattened epithelium. they may extend into the cervical wall and mimic malignancy. |
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Term
| what are tunnel clusters? |
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Definition
| localized proliferation of endocervical glands w/side channels growing out. there may be secretions dilating the lumens and some have florid glandular proliferation and a *certain degree of atypia (increased N/C ratios). |
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Term
| what is microglandular hyperplasia? |
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Definition
| complex proliferation of glands lined by flat epithelial cells *w/little or no atypia which involves the endocervical epithelium. *chronic inflammation is usually present in the stroma and *squamous metaplasia may also be present. |
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Term
| what is diffuse laminar endocervical glandular hyperplasia? |
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Definition
| proliferation of medium sized, evenly spaced, well differentiated glands in the inner third of the cervical wall which are *separated from the stroma*. there is often *chronic inflammation. |
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Term
| what are mesonephric duct rests? |
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Definition
| structures which undergo cystic dilatation or have *atypical hyperplastic changes. mesonephric duct rests may have lobular, diffuse, or ductal patterns and they *may be involved by CIN - but rarely give rise to malignant tumors. |
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Term
| what has dramatically decreased the incidence of deaths due to cervical CA? |
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Definition
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Term
| what risks are associated with cervical CA? |
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Definition
| multiple sexual partners (higher HPV exposure), male partner with multiple sexual partners, young age at first intercourse, high parity, persistent HPV infection w/16 or 18, immunosuppression, certain HLA subtypes, use of OCP, and use of nicotine |
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Term
| what characterizes most HPV infections? |
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Definition
| HPV infections are fairly common - most are transient and are eliminated by the immune response over several months. however, persistent infections increase the risk of precancerous and cancerous lesions. |
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Term
| how does HPV infect the tissue of the cervix? |
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Definition
| HPV infects the *immature basal cells of the *squamous epithelium in areas of epithelial *breaks or *immature metaplastic squamous cells at the squamocolumnar junction. typically, HPV does not infect the mature squamous cells covering the ectocervix, vagina, or vulva (infection at these sites requires damage to the surface epithelium) - but the cervix is susceptible due to a large number of immature squamous metaplastic epithelium. |
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Term
| where does HPV replication occur? |
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Definition
| in the maturing squamous cells - resulting in cytopathic change: *koilocytotic atypia (shrunken, “raisin-oid” with peri-nuclear halo)* |
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Term
| what does HPV replication require? |
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Definition
| DNA synthesis in the host cells. |
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Term
| how does HPV replication occur? |
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Definition
| HPV replicates by activating mitotic activity in the maturing cells. *viral E6 and E7 proteins bind to Rb and up regulate cyclin E - interfering w/p53 (both are tumor suppressors). this induces *centrosome duplication and *genomic instability (gives rise to shrunken, abnormal nucleus). HPV also prevents replicative senescence by upregulating telomerase. ultimately, the result is cellular life span extension - which can lead to tumor development. |
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Term
| can HPV infect other cells beyond squamous cells? |
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Definition
| yes, HPV can infect glandular cells or neuroendocrine cells - which can lead to adenocarcinoma, adenosquamous and neuroendocrine CA (these infections are less common since these cell types do not support effective HPV replication). |
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Term
| what was the older (possibly better) method of classifying cervical intraepithelial neoplasia? |
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Definition
| CIN I: mild dysplasia, CIN II: moderate dysplasia, CIN III: severe dysplasia/CA in situ (CIS). |
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Term
| what is the newer method of classifying CIN? |
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Definition
| LSIL: low grade intraepithelial lesion and HSIL: high grade intraepithelial lesion |
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Term
| what characterizes the LSIL? |
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Definition
| LSIL encompasses both the older classifications of CIN I & II and shows *no significant disruption of the host cell cycle. most regress spontaneously, while a *small percentage progress to HSIL. LSIL *does not progress to invasive CA and is *not considered premalignant. |
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Term
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Definition
| HSIL is associated with a *progressive deregulation of the cell cycle by HPV - causing *increased cell proliferation and/or *decreased cell maturation and a lower rate of viral replications (over time). HSILs are 1/10 as common as LSILs. |
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Term
| what is the morphology of CINs? |
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Definition
| high N/C ratio, hyperchromatic nuclei, coarse chromatin granules, nuclear pleomorphism, and possible association w/perinuclear halos caused by disruption of the cytoskeleton (if HPV infection is involved). however, there can be koilocytosis without atypia and vice versa. |
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Term
| what is the CIN grade based on? |
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Definition
| normally as cells become more superficial, they mature - but in CIN, surface cells may be very immature. therefore CIN grading is based on the expansion of the immature cell layer from the basal location to more superficial locations. in *LSIL, atypical immature squamous cells are limited to the lower 1/3 of the epithelium and if atypical immature squamous cells expand to the *upper 2/3 of the epithelial thickness, it is classified as HSIL. |
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Term
| what are markers for CIN? |
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Definition
| staining for *Ki-67 and *p16 can aid in identifying HPV infections and make SIL dx |
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Term
| where do most HSILs develop from? how long does it take to become invasive CA? |
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Definition
| *most HSILs develop from LSILs, however some cases of HSIL can develop de novo. progression from SIL to invasive CA may take place in a few months or more than a decade. |
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Term
| what is the most common kind of cervical CA? |
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Definition
| *squamous cell, followed by adenocarcinoma (then there may be adenosquamous and neuroendocrine tumors - which are *less detectable by PAP smear). regardless, all are associated w/oncogenic risk HPVs. |
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Term
| what is the peak incidence of invasive cervical CA? |
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Definition
| 45 yrs (need encourage patients to start getting PAP smears in early 20’s are earlier) |
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Term
| what characterizes microinvasive squamous cell CA in the cervix? |
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Definition
| the depth of invasion is *5 mm or less. the area of microinvasion *almost always originates from a CIN focus*. the natural hx is different than ordinary invasive CA and *tx is more conservative. these will breach the basement membrane and often have a *desmoplastic stroma. LN met risk is ~ 1%. |
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Term
| what is the most common malignant tumor in the cervix? |
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Definition
| invasive squamous cell CA, which incidence of has dropped in the US over the last several decades (due to better screening protocols). in terms of etiology, high risk types of HPV are implicated as well as other cofactors (HIV, immune status, other types of immunosuppression, etc.). |
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Term
| what characterizes invasive squamous cell CA morphologically? |
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Definition
| polyploid growth outward (can lead to bleeding, hemorrhage and fragmentation of malignant cells) and/or infiltrative growth downward (easier access to lymphatics and blood vessels). |
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Term
| what are the three categories of invasive squamous cell CA of the cervix? |
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Definition
| large cell non-keratinizing, keratinizing (*better differentiated, better prognosis, less association w/HPV+CIN), and small cell |
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Term
| how does invasive squamous cell CA of the cervix spread? |
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Definition
| via *lymphatics or *localized direct spread to the vagina, corpus of the uterus, urinary tract, uterosacral ligaments, and if really severe: bladder/ureters |
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Term
| how does invasive squamous cell CA of the cervix present initially? as it progresses? |
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Definition
| early on, invasive squamous cell CA of the cervix will be *asymptomatic - as it progresses, bleeding, discharge, dysuria, and dyspareunia. |
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Term
| how would a cervical SCC present if it invaded the rectum? |
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Definition
| similar to a primary adenocarcinoma in the same area - constipation, crampy feeling etc |
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Term
| what % of cervical CA is adenocarcinoma? |
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Definition
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Term
| what characterizes incidence of adenocarcinoma of the cervix? |
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Definition
| there are *no distinguishing gross features, but histologically, there is a *well differentiated glandular pattern w/mucin secretion. *HPV 16+18 is found in most endocervical adenocarcinomas and overall prognosis is *less favorable than for SCC (may spread faster due to mucin production or less sensitive on PAP smear). |
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Term
| how does a conventional adenocarcinoma of the cervix appear histologically? |
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Definition
| well differentiated glands, many of which will have papillary structure, *lined by dysplastic cells (columnar cells w/high N:C ratio). many times there will be stratification of the nuclei (another indication of atypia). these glands may be back-back or coalescing. |
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Term
| what characterizes a mucinous adenocarcinoma? |
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Definition
| histologically, there is lots of gelatinous, mucoid material - which may lend itself to localized extension of the tumor. often mucinous adenocarcinoma is aggressive and associated with a poorer prognosis. |
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Term
| what is adenoma malignum? histologic presentation? |
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Definition
| adenoma malignum (minimal deviation adenocarcinoma) is very *well differentiated, but the *glands tend to be distorted w/irregular outlines. adenoma malignum tends to be positioned *deep in the cervix and *is not associated with HPV. adenoma malignum *may be seen with peutz-jeghers syndrome. histologically: the cells lining the glands tend to be more benign and bland-looking. there may be a prominent stromal response lining the glands. |
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Term
| what is adenosquamous CA of the cervix? |
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Definition
| adenosquamous CA combines the patterns of adenocarcinoma w/a well defined squamous component. these are common during *pregnancy and are poorly differentiated. adenosquamous CA of the cervix therefore does have a *worse overall prognosis than either pure squamous or adenocarcinoma. |
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Term
| how does adenosquamous CA of the cervix appear histologically? |
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Definition
| there are some glands being formed, but there is also a squamous component w/in the glands which may be accompanied by necrosis. |
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Term
| what characterizes neuroendocrine CA of the cervix? |
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Definition
| neuroendocrine CA of the cervix is similar to small cell CA of the lung and its age distribution is similar to SCC of the cervix (~45). most are pure tumors, but some are combined w/adenocarcinoma or SCC. |
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Term
| how do neuroendocrine CA of the cervix appear histologically? |
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Definition
| there may be trabecular, glandular, and spindle cells growth patterns. neuroendocrine CA of the cervix may stain for *chromogranin (like most neuroendocrine tumors). the nuclei are smaller (but not much cytoplasm either), cells are monomorphic (but can still be aggressive). mitoses and necrosis is common, and these are histologically and clinically aggressive. |
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