Reproductive Tract Pathology

Question 1

What is cervical cancer and how is HPV implicated?

Answer 1

• Affects ~450,000 women worldwide each year

• Most tumors of the cervix of epithelial origin

• Cervical cancer - Cervical intraepithelial neoplasia (CIN)
• Most common between 30 and 50 years



Risk factors: Frequent cervical inflammation, sexual transmitted infections (STIs) in particular oncogenic strains of Human Papilloma Virus (HPV)

- If detected early, cells often only pre-cancerous 
(Regular Pap (Papanicolaou) smears for early detection
)

Endometrium of the Cervix

- Cervix = neck of the uterus to the vagina

- Mucus secreting simple columnar epithelium on luminal surface

- Continues with the moist non-keratinized stratified squamous epithelium covering the external (vaginal) surface of the cervix

- Transformation (transitional) zone - area between columnar and squamous cells -> most common place on thecervixfor abnormal cells to develop



• HPV has tropism for immature squamous cells of the transformation zone

• If HPV infection persist sometimes progression to cervical intraepithelial neoplasia (CIN)

Question 2

What is breast cancer?

Answer 2

• Invasive breast cancer most common cancer of women
- Usually arises from epithelial cells of ducts
  
- Detected by breast self-examination and mammography

• Also very common in men

• If metastatic, often spread to liver, lung, brain, adrenal glands and ovaries

• Treatment: 

  
  • Radiation and chemotherapy

  • Surgery (radical mastectomy or lumpectomy)



Risk factors:

- 75% older than 50 years

- Geography – environment -> US 5x higher than Japan

- Ethnicity: social factors and lifestyle choice, genetic differences



Genetic risk:

- Hereditary forms (~ 10% of all cases) 

- Mutations in cancer susceptibility genes BRCA1 and BRCA2

- BRACA is classical tumor suppressor gene -> both alleles have to be affected

- Mutations in tumor suppressors RB and TP53

- Overexpression of proto-oncogene HER2/NEU in 30%
 - Amplification of proto-oncogenes Ras and Myc



Question 3

What are non-invasive and invasive breast cancers?

Answer 3

Non-invasive breast cancers:

- Nearly all women with this early stage of breast cancer can be cured

- Adenocarcinomas of breast start in glands (ducts or lobules) 

- Ductal carcinoma in situ (DCIS): 

- grows in ducts

- Lobular carcinoma in situ (LCIS): 

- grows in the lobules (milk-producing glands)


Invasive breast cancers:

- Have spread outside the ducts or lobules

- Invasive ductal carcinoma (IDC): 80%

- Invasive lobular carcinoma (ILC)


Question 4

What is prostate cancer?

Answer 4


- Most common form of cancer in men

- Adenocarcinoma of the prostate occurs mainly in men > 50 years

- Most carcinomas detected clinically not visible grossly

- Androgens are central in the pathogenesis

- Decreased prostate cancer mortality over last decades due to effective screening programs

- Symptoms: frequent urination, pain urinating, blood in the urine or semen, a weak stream, pain the back or pelvis


















- Prostate specific antigen (PSA) blood test, biopsy, MRI, CT



Risk factors:

- Androgens promote growth and survival of prostate cells

- Heredity: mutations near Myc oncogene

- Acquired somatic mutations (Fusion gene of androgen regulated promoter and ETC transcription factor, Mutations of tumor suppressor PTEN)
- Environment, diet etc.

Question 5

What is the histology of prostate cancer?

Answer 5

Proste Cancers
- Prostatic Intraepithelial Neoplasia (PIN)

Question 6

What is testicular cancer and its histology?

Answer 6

• ~6:100.000 males

• Most common tumor in 15-34 old men

• Cause of most testicular neoplasms is unknown
  
- Heterogenous group of tumors but often germ cell tumors
  
- 3-5x greater risk if undescended testicle
  
- Genes: Brothers of males with germ cell tumors have 8-10 x increased risk