FEMALE & MALE REPRODUCTIVE SYSTEMS

FIBROCYSTIC DISEASE

1.    Describe the morphological features of this specimen.
 
The organ shown is the cut section of the breast. It shows the presence of numerous small cysts ranging from 0.5 - 2cm diameter diffusely scattered around the breast tissue. The affected areas with cysts appear as firm, rubbery replacement of breast tissue.

2.    What are the histological features?
 
It is characterized by hyperplasia of the epithelial and stromal elements of the breast with overgrowth of ducts and acini, cysts and fibrosis. Cysts are lined by flattened epithelium and are filled with watery fluid.
 
There are three variants:
 
a.    Apocrine metaplasia: epithelium lining the hyperplastic ducts undergo metaplasia to a form similar to that of normal apocrine glands.
b.    Sclerosing adenosis: marked proliferation of stromal tissue and myoepithelial cells, separating and compressing acini and ducts into narrow ribbons of cells.
c.    Epithelial hyperplasia forming papillary infoldings.

3.    What is the likely cause?
 
The cause of fibrocystic disease is uncertain. It is believe to be caused by disturbances of cyclical ovarian estrogen and progesterone levels, accompanied by altered responsiveness of breast tissue in women approaching the menopause.

4.    What are your differential diagnoses?
 
a.    Lipoma.
b.    Leiomyoma.
c.    Duct papillomas.
d.    Phyllodes tumors.

FIBROADENOMA

A 30-year-old lady presents with a firm mobile lump in the breast. Surgery was done to remove it.
 
 2.    What are the histological features?
 
There are two histological components:
 
a.    Epithelial: forms gland-like structures lined by duct-type epithelium.
b.    Stroma: a loose, cellular fibrous tissue around epithelial areas. 

3.    What age group does it usually affect?
 
Most frequently seen in women aged 25 - 35 years as solitary discrete lesions. 

 A 44-year-old lady presented with a painless lump in the breast. Surgery was performed.
 
1.    What is the diagnosis?
 
Carcinoma of the breast.

2.    List three histological features that will affect the prognosis of the patient.
 
a.    Histologic subtypes: the 30-year survival of women with special subtypes of invasive carcinoma (tubular, colloid, medullary, lobular) is more than 60%, compared with less than 20% for women with cancers of no special type.
b.    Tumor grade: combines nuclear grade, tubule formation and mitotic rate.
c.    Lymphovascular invasion: presence of tumor cells in vascular spaces surrounding tumors is associated with the presence of lymph node metastases and is a poor prognosis factor in women without lymph node metastases. 

3.    List three immunohistochemical stainings that will help to assess the prognosis.
 
Antibodies to:
 
a.    Estrogen / progresterone receptors.
b.    Ki-67.
c.    Her2/neu.

4.    What are the likely mammography findings of this lesion?
 
a.    Densities: a spiculated density with irregular infiltration of the surrounding tissue.
b.    Architectural distortion.
c.    Calcifications.

5.    Correlate the clinical features with the underlying pathology.
 
a.    Increase in dense, fibrous tissue stroma give the tumor a hard consistency which appears as stony-hard nodules.
b.    Extension to skin cause fixation, retraction and dimpling of the skin.
c.    Involvement of lymphatics block local area of skin drainage and cause lympedema and thickening of the skin. 

CERVICAL CANCER

1.    What is the gross morphology?
 
The organ shown is the cervix and the uterus. There is a fungating nodular mass at the cervix which has infiltrated into the underlying mucosa and encircling the external os. The mass is white, fleshy with dark patches of hemorrhage. These features are consistent with that of cervical cancer.

2.    What are the histological findings that will help to confirm the diagnosis?
 
a.    Epithelial dysplasia with extensive proliferation of abnormal epithelial cells with no maturation throughout the full thickness.
b.    Breach of basement membrane with sheets, nests of atypical cells invading into subepithelial stroma.
c.    Cytology: abnormal nucleus, increased nucleus diameter, increased nuclear:cytoplasm ratio, hyperchromasia.

3.    What is the clinical presentation?
 
a.    General: loss of weight, malaise, anorexia.
b.    Post-coital bleeding, post-menstrual bleeding, inter-menstrual bleeding.
c.    Menorrhagia.
d.    Foul-smelling discharge.
e.    Bladder: penumaturia, hematuria, urine PV.
f.    Colon: hematochezia, feces PV.
g.    Ureters: hydronephrosis - loin to groin pain, fever, chills and rigors.

4.    What is the usual cause of death in this condition?
 
Renal failure secondary to uremia due to compression and subsequent occlusion of the ureters by invading tumor.

5.    What non-invasive methods can be employed for diagnosis?
 
Pap smear:
 
a.    Use of cytobrush to scrap the cervix directly to collect the cells.
b.    The cells are spread on a glass slide and fix immediately with alcohol.
c.    They are then seen under a microscope for cytological abnormalities. 

ENDOMETRIAL CARCINOMA

1.    What are the gross morphological features?
 
The organ shown is the cut section of the uterus. There is an exophytic hemorrhagic mass invading the uterine wall beneath and filling the entire endometrial cavity. The uterine wall is diffusely thickened. These features are consistent with that of endometrial carcinoma. 

2.    What are the risk factors for this condition?
 
a.    Obesity. 
b.    Impaired carbohydrate tolerance.
c.    Nulliparity.
d.    Late menopause.
e.    Unopposed estrogen therapy.
f.    Functioning ovarian tumors.
g.    Family history of carcinoma of breast, ovary or colon.
h.    Previous pelvic irradiation.

3.    What are the clinical manifestations of this condition?
 
a.    Post- or perimenopausal bleeding, inter-menstrual bleeding
b.    Menorrhagia.
c.    Watery vaginal discharge. 
d.    Abdominal mass.
e.    Loss of appetite and weight. 

4.    What tools can be used for screening?
 
a.    Endometrial pipelle.
b.    Endometrial aspiration.
c.    Hysteroscopy.
d.    Hysterosalpingography.
e.    Ultrasound.
 
ENDOMETRIAL HYPERPLASIA

A 52-year-old lady, post-menopausal, presents with a 2-month history of prolonged irregular vaginal bleeding. A hysterectomy was done. 
 
1.    What are the gross morphological features?
 
The endometrium is red, boggy and appears to be thickened. 

2.    What are the associated histologic findings?
 
Characterized by marked hyperplasia of endometrium due to proliferation of glandular and stromal component:
 
a.    Simple hyperplasia: epithelial lying may be cuboidal, tall columnar or multi-layered.
b.    Complex hyperplasia: increase in the number and size of endometrial glands which vary in size and irregularity of shape.
c.    Atypical hyperplasia: cellular atypia of hyperplastic epithelium. 

3.    Why is a hysterectomy performed for her?
 
Endometrial hyperplasia can give rise to endometrial carcinoma. An endometrial pipelle would have been done beforehand for this patient and histology reveals cellular atypia. Since she has completed her family, a hysterectomy was performed.

ADENOMYOSIS

1.    Give three differential diagnoses (based on the specimen).
 
a.    Adenomyosis.
b.    Uterine fibroids.
c.    Endometrial hyperplasia / carcinoma.

2.    What are the two tests the gynaecologist can do before operating?
 
a.    HCG: to exclude possibility of pregnancy. 
b.    FBC: Hb level.

3.    What investigations can be be done before the operation?
 
a.    Ultrasound of pelvis.
b.    Endometrial biospy.

4.    A smear was taken. What are the likely histological features?
 
Nests of endometrial stroma and glands in the myometrium between the interlacing muscle bundles

5.    What are the complications of this operation?
 
a.    Hemorrhage.
b.    Infection within the incision leading to pelvic or intraabdominal sepsis / abscess formation.
c.    Venous thrombosis leading to pulmonary embolism.
d.    Incisional hernia, intestinal obstruction from adhesions.
e.    Adhesion formation leading to intestinal obstruction.

UTERUS: LEIOMYOMA

A 40-year-old lady presented with lower abdominal swelling.
 
1.    What are the differential swellings?
 
a.    Uterine fibroids.
b.    Endometrioma.
c.    Pregnancy.
d.    Ovarian cyst.
e.    Ovarian cancer.

2.    What are the gross morphological features?
 
This is the cut surface of a uterus showing multiple sharply circumscribed unencapsulated, firm gray-white masses.

3.    What are the predisposing factors to this condition?
 
a.    Estrogen.
b.    African race.
c.    Subfertility / infertility.
d.    Women of reproductive age.
e.    Nulliparity.
f.    Obesity.

4.    What complications can arise during pregnancy?
 
a.    Higher risk of spontaneous miscarriages.
b.    Red degeneration causes sudden onset of pain.
c.    Antepartum haemorrhage: placenta previa and abruptio due to displacement of placenta by fibroids. 

FALLOPIAN TUBE: TUBO-OVARIAN ABSCESS

A 32-year-old lady presents with foul-smelling vaginal discharge and severe lower abdominal pain. A total hysterectomy and bilateral oophorectomy was done. This specimen shows the cross section of her fallopian tube.
 
1.    What history will you take from the patient.
 
a.    Pain: site, duration, nature of pain, aggravating and relieving factors.
b.    Discharge: color, nature, bleeding or clots.
c.    Fever, chills or rigors.
d.    Sexual history: last sexual intercourse, number of partners, type of contraception used.
e.    Menstrual history: intermenstrual or post-coital bleeding, irregular bleeds, menorhagia, subfertility and ectopic pregnancies.
f.    Urinary symptoms: dysuria, frequency, nocturia. 
g.    Abdominal symptoms: nausea and vomiting, diarrhoea.

2.    What are your differential diagnoses?
 
a.    Pelvic inflammatory disease.
b.    Ectopic pregnancy.
c.    Ovarian cyst rupture / hemorrhage.

3.    What investigations would you do to confirm your diagnosis?
 
a.    Infertility.
b.    Bowel: cyclical rectal bleeding or stricture.
c.    Bladder: cyclical haematuria.
d.    Abdominal wall: deposits in the umbilicus or abdominal wounds cause cyclical swelling and pain at the affected site.

3.    What are the likely physical findings on examination?
 
a.    FBC: Hb level for anemia and WBC for leucocytosis.
b.    Urine pregnancy test: to exclude an ectopic pregnancy.
c.    High vaginal swab for bacterial vaginosis, candidiasis, Trichomonas vaginalis and Escherichia coli.
d.    Endocervical swab for Neisseria gonorrhoea and Chlamydia trachomatis.
e.    Rectal and urethral swab.
f.    Urine FEME and culture to exclude urinary tract infection.
g.    Blood cultures.
h.    ESR and CRP to monitor response to treatment.

4.    What is the pathogenesis of this condition?
 
a.    Main cause is an ascending genital infection up to the fallopian tubes causing salpingitis.
b.    First stage of salpingitis involves mucosal inflammation with swelling, redness and deciliation.
c.    Inflammatory exudate fills the lumen of the tube and adhesions develop between mucosal folds.
d.    Inflammation extends to the serosal surface and pus exudes from the fimbriae to the ovaries and adnexae leading to the formation of a tubo-ovarian abscess. 

5.    How would you manage this patient?
 
a.    Empirical antibiotic therapy consisting of doxycycline, ceftriazone and metronidazole before culture results return.
b.    If patient remains afebrile for 2 days, she can be given oral antibiotic therapy consisting of a quinolone and metronidazole and discharge.
c.    If the patient does not respond to antibiotic treatment within 48 hours, a laparoscopy should be done. 

6.    What are the complications?
 
a.    Chronic persistent pelvic infections.
b.    Subfertility.
c.    Ectopic pregnancy.

FALLOPIAN TUBE: ECTOPIC PREGNANCY

A 30-year-old lady presents with sudden acute abdomen pain and is pale looking.
 
2.    Give 3 clinical differential diagnoses.
 
a.    Pelvic inflammatory disease.
b.    Ectopic pregnancy.
c.    Ovarian cyst rupture / hemorrhage.

3.    Why was she pale?
 
Rupture of ectopic pregnancy into the pelvic peritoneum and bleeding into it to form a hemoperitoneum.

4.    What investigations would you do?
 
a.    Urine hCG.
b.    Ultrasound scan.
c.    Laparoscopy.
d.    Preparation for operation: FBC, GXM.

5.    What are the predisposing factors for this condition?
 
a.    Pelvic inflammatory disease.
b.    Tubal surgery.
c.    Previous tubal pregnancy.
d.    Infertility. 
e.    Intrauterine contraceptive devices.

OVARY: DERMOID CYST

1.    What is the diagnosis?
 
Mature benign teratoma of the ovary.

2.    What are the gross morphological features?
 
This shows the cut section of a ovary. The ovary is covered by a glistening serosa and is lined by skin with skin appendages such as hair inside. The cystic space is filled with a thick sebaceous material containing teeth, bone and cartilage.

3.    Give 2 diagnoses of a right pelvic mass.
 
a.    Estrogen.
b.    African race.
c.    Subfertility / infertility.
d.    Women of reproductive age.
e.    Nulliparity.
f.    Obesity.

4.    What is the pathogenesis of this condition?
 
It is a germ cell tumor arising from totipotential germ cells capable of differentiating into the three germ cell layers. 

5.    Give 2 reasons for its removal.
 
a.    They may undergo torsion.
b.    They may rupture spontaneously: either suddenly causing an acute abdomen and a chemical peritonitis or slowly causing chronic granulomatous peritonitis.
c.    About 1% undergo malignant transformation with poor prognosis.

TESTIS: SEMINOMA

1.    Describe the morphological features.
 
The normal, pale-brown testicular tissue is replaced by a homogenous creamy-white tumor mass. There is no evidence of cyst formation or hemorrhage. The lesion is likely to be a seminoma.

2.    What are the risk factors for this condition?
 
a.    Cryptorchidism: associated with 10% of testicular tumors.
b.    Genetics: cytogenetic abnormalities involving chromosome 12 are common.
c.    Testicular dysgenesis: includes testicular feminization and Klinefelter syndrome.

3.    What is the value of biochemical markers in the management?
 
Serum biochemical markers are of value to:
 
a.    Evaluate testicular masses.
b.    Stage germ cell tumors.
c.    Assess tumor burden.
d.    Monitor response of tumor to therapy.
 
The serum levels of AFP and HCG should be measured before and after removal of any suspected testicular tumor. If a tumor is confined to the testis, levels of marker will drop after orchidectomy. If levels do not fall, there is an indication of metastatic disease.
 
In follow-up after treatment, increasing levels of a marker protein are an indication of tumor recurrence.
 
Lactic dehydrogenase is a useful marker of tumor bulk. Serial LDH measurements allow the monitoring of the effects of therapy on tumor bulk. 

BENIGN PROSTATE HYPERPLASIA

A 70 year old man was admitted for acute retention of urine. The PSA was slightly raised. A biopsy was taken.
 
1.    Describe the morphological features.
 
The organ shown is the prostate and the bladder. The prostate is enlarged and compress the urethra lumen into a slitlike orifice. There is marked hypertrophy of the bladder wall, with trabeculation of bladder muscle in response to the outlet obstruction imposed on by the enlarged prostate.

2.    What are the histological features seen?
 
The hyperplastic component of the prostate shows a nodular pattern of hyperplastic glandular acini separated by fibrous stroma. The acini are tightly packed, lined by tall columnar epithelial cells with small basal nuclei, and the epithelium is thrown up into irregular papillary folds.

3.    What is the pathophysiology?
 
A metabolite of testosterone called dehydrotestosterone (DHT) is the main stimulator of growth of prostatic glands and stroma. It is produced in the prostate in the stroma cells by the action of an enzyme, 5a reductase, on circulating testosterone. DHT acts on both stromal and epithelial cells in the prostate to increase mitotic activity by binding to nuclear receptors and stimulating the transcription of growth factors. However, there are many other factors involved including the possible role of estrogen levels, which increase with age. Estrogen may sensitize the prostate to the effects of DHT.
 
Glandular and fibromuscular hyperplasia begins in the peri-urethral prostate tissue and result in nodules which enlarge and compress the peripheral parts of the prostate to form a false capsule.

4.    How does this condition affects the urinary system?
 
Prolonged prostatic obstruction is the most common cause of chronic obstructive uropathy. It leads to marked hypertrophy of the bladder wall, with trabeculation of bladder muscle (occasionally with diverticula formation), and acute or chronic retention of urine in the bladder. In such cases the failure to empty the bladder may lead to reflux of urine into the pelvi-calyceal system, producing mega-ureter and hydronephrosis and predisposition to infection. 

5.    What are the clinical manifestations?
 
a.    Urinary frequency, nocturia, and difficulty starting and stopping the stream of urine.
b.    Acute urinary retention.
c.    Chronic urinary stasis with resultant bacterial overgrowth and urinary tract infection. 

6.    What are the likely findings on rectal examination?
 
a.    The gland bulges into the rectum.
b.    Its surface is smooth but the enlargement is asymmetrical and surface is bosselated.
c.    Consistence of gland is firm, rubbery and homogenous.
d.    Median sulcus is palpable.
e.    Rectal mucosa moves freely over gland.

7.    What investigations would you do?
 
a.    Mid-stream specimen of urine to exclude infection.
b.    Serum creatinine to assess renal function.
c.    PSA levels to exclude prostate cancer.
d.    KUB to exclude bladder stone.
e.    Ultrasound of kidneys, bladders and prostate.
f.    Uroflow test to assess degree of obstruction to bladder.

8.    What are the treatment modalities available?
 
a.    Medical: a-blockers, e.g. prazosin, 5a reductase inhibitor, e.g. finasteride provides relief of symptoms of obstruction and prevention of progression of prostate enlargement.
b.    Surgery: transurethral resection of prostate (TURP).

PROSTATE CANCER

A 72 man presents with difficulty of micturition and intractable back pain for a month.
 
1.    Where is this lesion likely to arise and what is the clinical significance?
 
Most cases arise in the peripheral part of the prostate, particularly in the posterior region. 
 
This has two implications:
 
a.    Because of its peripheral origin, prostatic cancer is often well-established before the patient develops symptoms of difficulty with micturition due to urethral obstruction.
b.    Local spread is likely to occur through the prostatic capsule, before the tumor infiltrates medially towards the urethra. For this reason, attempts to obtain biopsy samples of prostate to establish a diagnosis of malignancy by using the transurethral route may give false negative results; a needle biopsy of the outer prostate using a transrectal approach is more likely to be successful.

2.    How does this lesion grow and spread?
 
Carcinoma of the prostate metastasizes to bone and nodes and invade the bladder base:
 
a.    Direct spread to base of bladder and adjacent tissues causing obstruction of the urethra and may block the ureters, causing hydronephrosis.
b.    Lymphatic spread to pelvic and para-aortic nodes.
c.    Vascular spread to bone gives sclerotic lesions. 

3.    What are the likely findings on rectal examination?
 
a.    Prostate is asymmetrically enlarged or distorted.
b.    It is irregular in contour.
c.    It ha a well-defined nodule.
d.    Median sulcus may be absent.
e.    Rectal mucosa may be tethered to the gland. 

4.    What is involved in staging the disease?
 
a.    Rectal examination with determination of tumor size and local spread.
b.    Prostatic ultrasound.
c.    Bone scan.
d.    PSA estimation.

5.    What is the usefulness of PSA in screening?
 
Not very useful and not recommended for routine screening:
 
a.    Test is not very accurate: false positives will lead to more tests and needless anxiety.
b.    Even if the test is positive, it does not tell the patient how it will impinge on his health as prostate cancer runs an indolent course and many patients die of unrelated causes.
c.    There is no ideal treatment for it with each having its own risks and complications. For asymptomatic cases, it may be better to adopt a 'wait and see' approach.