PathWiki: ModuleFour: Slides 20 & 21

 

 

 

Slide Description:

Gross macroscopic cervix with ulcerated carcinoma. Note the external os. Lumenal irregularity may indicate this sample came from a postpartum female.

 

Compare this to a slide showing a normal cervix:

 

 

IMDEPSAASIAC:

Identify:

Cervix with exophytic carcinaomic growth

 

Morphology:

Presence of ulcerated carcinoma on ventromedial surface of uterine cervix.

 

Disease:

Cervical squamous cell carcinoma.

 

NOTE: Squamous cell carcinoma indicates a cancer in which the tumor cells resemble stratified squamous epithelium.

 

Etiology (main):

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:

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. AND, cannot forget about the TP53 gene "guardian of the genome" since is involved in about 70% of all cancers causes, and eventually, all cancers will have some form of TP53 malfuntion/mutation.

 

Structural changes (specific, gross, and micro):

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, will see changes of cell layering with mitotic activity disperesed throughout and even reaching the superficial layers as opposed to just staying around the basement membrane area.

 

Are there any other sites of involvement in the body?

Initially: anywhere squamous epithelium is present: skin, GI, urinary tract.

With metastasis: 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:

may be associated with abnormal vaginal discharge, metrorrhegia, pain with coitus.

 

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?

Not without metastais since we are looking at the uterine cervix.

 

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

Important to keep a close eye and evaluate frequently for suspected neoplastic changes. With early detection, can completely remove the neoplasm. More difficult to catch at an early age for internally growing neoplasms, and is usually detected once other symptoms occur.

 

 

 

Highlight 3 important points:

i) early detection is key (pap smear)

ii) most common (75%) of cervical carcinomas

iii) distant metastases occurs late in the course of carcinoma proliferation

 

Lab Questions:

NONE

 

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 "female doctor" for over 20 years, since she last had a baby when she was 21 & 23, when she did have regular prenatal care. 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?

 

 

 

 

Slide Description:

Presence of "pearls" (keratinized epithelium) in a uterine cervical biopsy stained with H&E, indicative of a well differentiated squamous carcinoma. Normally, keratinized epithelium is shed from the surface, however, the pattern of growth in which the cells are growing down and away from the surface prevents their shedding, hence forming "pearls". This is an example of endophytic growth as in contrast to the previous slide,exhibiting endophytic growth.

 

 

 

IMDEPSAASIAC:

Identify:

Microscopic slide preparation of invasive squamous cell carcinoma.

 

Morphology:

This is normal cervical non-keratinizing squamous epithelium. The squamous cells show maturation from basal layer to surface:

 

At high magnification, nests of neoplastic squamous cells are invaded through a chronically inflamed stroma. This cancer is well- differentiated, as evidenced by keratin pearls. However, most cervical squamous carcinomas are non-keratinizing.

 

Disease:

Squamous cell carcinoma.

 

Etiology (main):

see previous slide

 

Pathogenic mechanism:

see previous slide

Additionally, incorporation of keratin into the endophytic growth.

 

Structural changes (specific, gross, and micro):

Gross: may appear as raised areas with respect to the skin, will be more noticeable. For internally growing "pearls", may just be palpable bumps.

 

Are there any other sites of involvement in the body?

anywhere squamous epithelium is present: skin, GI, urinary tract.

 

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

Yes: GI tract, especially stomach and colon; skin (see Robbins, pg 169)-giving rise to the second most common form of skin cancer, after basal cell carcinoma; lung (?)

 

Signs / Symptoms:

Invasive squamous cell carcinomas of the skin are usually discovered while small and resectable, less than 5% have metastases to regional lymph nodes at diagnosis.

 

However, s/s depends on location:

*Skin: usually asymptomatic, but physical appearance including rapid proliferation may cause itchiness, pain, discomfort.

*GI: depending on stage of proliferation, may cause obstruction leading to dysphagia, upper or lower GI-bleed.

*Urinary: depending on stage of proliferation, may cause obstruction leading to dysuria and hematuria.

 

Investigations (confirmation / gauge extent):

biopsy.

 

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

Other benign neoplasias (?).

 

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

Highlight 3 important points:

i) most common cause due to UV light with inability for repair (TP53 damage)

ii) immunosuppressed individuals (from chemotherapy) are most at risk for developing these tumors

iii)usually slow growing

 

 

Lab Questions:

 

1) What is the transition zone in the cervix? What is its relation to dysplasia and neoplasia?

The transitional zone in the cervix is the squamo-columnar junction, and is a common site where irritation/trauma can causes dysplasia and neoplasia (columnar being replaced by uncontrolled squamous epithelial growth).

 

2) What is the histologic type of cervical cancer?

Squamous cell carcinoma.

 

3) What do the terms exophytic and endophytic mean?

Exophytic means growing outwards like a plant; denoting a neoplasm or lesion that grows outward from an epithelial surface.

 

Endophytic means growing inwards, denoting a neoplasm or lesion that grows inward from an epithelial surface, perhaps into a lumen or into the tissue (?)

 

 

Vignette

A 73 year old caucasian male presents with a lesion on his right forehead. He states that it has been there for many years but is concerned that it has gotten a lot bigger over the past 6 months. He thought it was just because he wears a hat and always irritated that area. You take a biopsy and sent it for analysis. The lab results confirm a squamous cell carcinoma. What other tests can you do to rule out a metastatic origin?

 

 

(also see previous slide...dealing along the same lines

 

Additional info: Renal carcinoma with bone metastasis