Slide Description:

This is a gross specimen of the uterus, particularly focusing on the cervix, showing an invasive tumor: infiltrating carcinoma of the cervix (exophytic growth).

(Recall Module IV slide 20)

Normal cervix:

Lab Questions:

1. What is the usual cause of death in carcinoma cervix?

Carcinoma of the cervix usually is of squamous cell type, which involves precursor CIN (cervical intraepithelial neoplasia).

CIN then can progress to a higher level and eventually become an invasive cancer, metastasizing to distant areas, such as pelvic and para-aortic nodes as well as organ involvement, and adjacent structure invasion (rectum and bladder). Hence death from widespread metastasis occurs, such as consequences of renal failure.

2. What is micro invasive cancer of the cervix?

Micro invasive cancer is metastatic cancer that hasn't quite reached "its full potential". It has broken through the basement membrane but has invaded < 5mm of underlying tissue, hence is easily treatable with exision or biopsy.

3. Why do they perform a cone biopsy of the cervix?

Cone biopsy serves two purposes: provides a biopsy sample for analysis; and removes the precursor tumor cells; diagnostic & therapeutic.

Alphabet Soup:

Identify:

Cervix

Morphology:

Invasive carcinoma

Disease:

Cervical carcinoma

Etiology (main):

Mostly associated with HPV. Invasive carcinomas of the cervix develop in the region of the transformation zone and range from the microscopic foci of early stromal invasion to grossly conspicuous tumors encircling the os

Pathogenic mechanism:

90% is associated with HPV, especially types -16, -18.

Squamous cell carcinoma usually evolve from precursor CIN (cervical intraepithelial neoplasia), but are usually slow growing, thus take some 10-15 years to develop after initial presence of CIN. May be due to overexpression of EGF (epidermal growth factor) as is associated with 80% of squamous cell carcinomas of the lung. Also, RAS gene mutation in which no downregulation of cell proliferation. TP53 gene, the "guardian of the genome" is involved in about 70% of all cancers causes, and eventually, all cancers will have some form of TP53 malfunction/mutation.

Structural changes (specific, gross, and micro):

• 75-90% of cervical cancers are squamous cell carcinoma, generally evolving from precursor CIN

Gross: proliferation with monoclonal origin with invasion of surrounding tissue and eventually invasion of basement membrane. Sarcomas usually metastasizes via route of blood while carcinomas use the lymph (and occassionally the blood).

Microscopically:

Squamous carcinoma appears as sheets and cords of malignant squamous cells infiltrating through the basement membrane and into the underlying soft tissue. Cells have abundant pink cytoplasm, cellular bridges and often show keratinization.

Additionally, cell layering with mitotic activity disperesed throughout and even reaching the superficial layers as opposed to just staying around the basement membrane area (>10mitotic activity/10 hpf)

adenocarcinoma arise from the endocervical crypts and show infiltrating glands that are usually mucin producing.

Are there any other sites of involvement in the body?

With metastasis in late stages of the diesease, can travel via the lymph or via the blood and attach to other areas, which will eventually proliferate and cause growth followed by invasion of other tissues.

Are there any other diseases where similar changes can be seen?

Other cancerous growths in later stages may be hard to differentiate by visual inspection only, hence will need biopsy confirmation of cellular changes

Signs / Symptoms:

Very early cancers (micro-invasive carcinoma) are asymptomatic and the cervix appears normal on routine pelvic exam. They are usually diagnosed during investigation of abnormal Pap test.

May be associated with abnormal vaginal discharge, metrorrhegia, dyspurunia, and with severe obstruction of the internal or external os, can cause dysmenorrhia or amenorrhea.

Investigations (confirmation / gauge extent):

• pap smear
• biopsy, which may involve complete removal of lesion.
• direct palpation: "barrel cervix" is a common sign of tumors that encircle the cervis and penetrate into the underlying stroma

Are there any other diseases you have studied where such tests can be positive?

Pap smear abnormalities can be observed in some STDs where cytologic changes can occur (herpes, HPV, etc.)

Course of disease progress (complications, monitoring, outcome):

It is important to keep a close eye and evaluate frequently for suspected neoplastic changes. With early detection, can completely remove the neoplasm (i.e., with a cone biopsy, laser, cryo, etc). More difficult to catch at an early age for internally growing neoplasms, and is usually detected once other symptoms occur.

Highlight 3 important points:

1. 75-90% are squamous cell carcinoma, followed by ~20% adenocarcinoma, and <5% owing to neuroendocrine carcinomas.

2. Peak incidence occurs around 45 years of age

3. Carcinomas usually develop 10-15 years after detection of precursor CIN

Vignette

A 45-year old African-American female presents to you with pain in her lower abdomen. She states she has had some slight bleeding between her periods. She has not been to the gynie for over 20 years, since she last had a baby when she was 21 & 23, when she did have regular prenatal care. She states that 12 years ago, she remarried a widower whose wife died of cervical cancer. Upon examination, her cervix has a growth around the external os. You take a biopsy and send it for path analysis. What do you expect to find?

Additional Information

Relevant Robbins: pp 688-689

uterine cancer