Reproductive Pathology Case Studies 1

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Reproductive Pathology Case Studies 1

• Web Path
• http//bb.westernu.edu/web/Pathology/webpath60/web
  path/webpath.htm

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CASE 1

• History
• While showering, a 24 year-old woman noted a
  somewhat firm mass in the upper-outer quadrant of
  her left breast. She went to see her family
  physician who also felt the mass, and he
  determined that it was firm with a rubbery
  consistency and appeared to be movable.

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Slide 1.1The biopsy reveals a small mass lesion
marked with blue dye. The excised breast mass was
found to be light tan in color, rubbery in
consistency, and well demarcated from the
surrounding normal breast tissue. The mass was
located radiographically prior to surgery and
marked with blue dye to facilitate finding it for
removal.
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Slide 1.2The mass lesion from the breast is seen
microscopically at low power.
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Slide 1.3The microscopic appearance of the mass
is shown at low and high power. Note the presence
of both a stromal and epithelial proliferation in
large rounded and demarcated nodules. Describe
the appearance.
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Case 1 Question

1. What is the diagnosis and the prognosis?

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CASE 1 Fibroadenoma

• Answers
• What is the diagnosis and the prognosis? This is
  a fibroadenoma of the breast. This is not
  considered to be a premalignant lesion.

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CASE 2

• History
• The patient in case 1 visited her 49 year old
  mother and told her about the biopsy and the
  results. Her mother remarked, "You know, maybe I
  should go and see my doctor, because my aunt died
  of breast cancer." She sees her doctor, who
  palpates a large irregular firm fixed mass in the
  right breast as well as overlying skin with a
  rough, reddened appearance. Mammographically, the
  mass has irregular borders. A fine needle
  aspirate is performed of the mass and then a
  mastectomy is done.

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Slide 2.1Note the irregular borders of the mass
in the photograph. The mass has a central
irregular whitish scar. There are scattered foci
of yellow to white necrosis and calcification.
Axillary lymph nodes were also found to be
enlarged and firm. A frozen section confirmed the
diagnosis of malignancy, specimens were sent for
estrogen-progesterone receptors.
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Slide 2.2Dermal lymphatics are dilated and
contain small clusters of malignant cells.
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Slide 2.3Histologically at medium power, the
breast lesion is shown here.
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Slide 2.4An axillary lymph node is shown here at
medium power magnification.
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Slide 2.5For comparison, normal breast tissue is
seen here histologically.
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Case 2 Questions

1. What is the diagnosis?
2. Why did the skin appear to be inflamed?
3. What is the significance of the family history?

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CASE 2 Infiltrating ductal carcinoma

• Answers
• What is the diagnosis? This is an infiltrating
  ductal carcinoma of breast with an inflammatory
  (dermal lymphatic) component and metastases to
  hilar lymph nodes.
• Why did the skin appear to be inflamed? This is
  caused by invasion of the carcinoma into the
  dermal lymphatics. "Inflammatory carcinoma" does
  not refer to a specific type or histological
  subset of breast cancer, only to dermal lymphatic
  involvement.
• What is the significance of the family history?
  The risk of breast cancer is increased if a first
  degree relative, such as a mother, or aunt, has a
  history of breast cancer. The lifetime risk for
  breast cancer with affected first degree
  relatives is as follows
• Number Age Risk One relative less than 50 years
  13 - 21 One relative greater than 50 years 9 -
  11 Two relatives less than 50 years 35 - 48 Two
  relatives greater than 50 years 11 - 24 Of
  course, BRCA-1 and BRCA-2 genes are the best
  known mechanisms for the appearance of early
  breast carcinoma that is familial. However, most
  of the important susceptibility genes have yet to
  be identified!

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CASE 3

• History
• A 39 year-old woman complained of a sensation of
  pelvic heaviness and a mucinous vaginal
  discharge. Pelvic examination revealed the uterus
  to be enlarged and a thick, creamy- yellow
  discharge to be exuding from the external
  cervical os. In addition there was a 5 mm
  diameter translucent mucosal nodule adjacent to
  the external os. At hysterectomy the uterine
  enlargement was found to be secondary to an
  intramural, fundic leiomyoma (benign smooth
  muscle tumor). Your section is taken from the
  cervix.
• There are multiple, discreet tumor masses arising
  in the myometrium but impinging upon both
  endometrial and serosal surfaces. These masses
  are firm and white to tan on sectioning.

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Slide 3.1The uterus has been opened and reveals
multiple subserosal, intramural, and submucosal
mass lesions. The cervix is shown here. Describe
the changes present. Remember, the endocervical
glands are not true glands, but only
invaginations of the surface endocervical
mucinous epithelium into the fibromuscular
stroma.
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Slide 3.2Grossly, the cervix is erythematous,
and the reason is apparent here.
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Slide 3.3Histologically, the cervix is seen here
at medium power.
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Slide 3.4Histologically, the cervix is seen here
at high magnification.
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Case 3 Questions

1. What cell types compose the inflammatory
   infiltrate?
2. What is the diagnosis for the (a) uterine masses
   and (b) cervix?
3. Is further workup indicated?

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CASE 3 Chronic cervicitis

• Answers
• What cell types compose the inflammatory
  infiltrate? There is an intense chronic
  inflammatory cell infiltrate, composed of
  lymphocytes, plasma cells, and histiocytes, in
  the stroma adjacent to the endocervical
  epithelium. There is also hemorrhage. The
  gland-neck narrowing may result from stromal
  chronic inflammation. Some degree of nonspecific,
  chronic cervicitis is present in most women but
  in this case, the degree of inflammation is
  greater than what is usually observed.
• What is the diagnosis for the (a) uterine masses
  and (b) cervix? The uterine masses are benign
  leiomyomata. The cervix demonstrates severe
  chronic cervicitis.
• Is further workup indicated? One might suspect
  Chlamydia cervicitis on the basis of the vaginal
  discharge, but culture or immunohistologic
  studies would be needed to confirm this diagnosis.

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CASE 4

• History
• A 38 year-old woman was found to have highly
  atypical cells on a Pap smear. A colposcopically
  directed biopsy of the cervix was read as severe
  dysplasia. Because the dysplastic-appearing
  epithelium involved the endocervical canal and
  its deep border within the canal could not be
  visualized, a cone biopsy was proposed. However,
  after further discussion with her physician, the
  patient decided to have a vaginal hysterectomy.

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Slide 4.1A Pap smear shown here demonstrates
abnormal cells present (compare with the normal
squamous epithelial cells that have a large
amount of cytoplasm and a small pyknotic
nucleus).
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Slide 4.2A biopsy of the lesion demonstrates the
histologic pattern seen here.
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Slide 4.3An adjacent area of squamous metaplasia
is shown here.
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Slide 4.4Dysplasia involving the full thickness
of the cervical epithelium is seen here.
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Case 4 Questions

1. Has the patient been having yearly Pap smears?
2. Is there stromal invasion?
3. What is the diagnosis?
4. What is the natural history of this process?

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CASE 4 CIN III

• Answers
• Has the patient been having yearly Pap smears?
  The development of dysplasia to this degree would
  take several years. It is obvious that the
  patient has not been having yearly Pap smears.
  There is up to a 4 false negative rate for each
  Pap smear, but with yearly Pap smears, the chance
  of missing a significant lesion is low.
• Is there stromal invasion? Endocervical glands
  are involved by the CIN process, but there is no
  evidence of stromal invasion.
• What is the diagnosis? Much of the histology
  shows severe dysplasia however, there are a few
  areas that could be called carcinoma in situ.
  This distinction is somewhat subjective, and
  different pathologists may have slightly varying
  criteria for making this division. The concept of
  cervical intraepithelial neoplasia, Grade III
  (CIN III) is useful because severe dysplasia and
  carcinoma in situ, which are treated in the same
  manner, are included in the same category. The
  patient is cured.
• What is the natural history of this process? The
  process often starts with human papillomavirus
  (HPV) infection. There is a natural history
  starting with squamous metaplasia with
  progression to dysplasia of worsening degree,
  then carcinoma in situ, then invasive carcinoma.
  This takes more than a decade.

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CASE 5

• History
• A 42 year-old woman, who had not had a medical
  pelvic examination for many years, noted the
  onset of postcoital bleeding. When she did seek
  medical attention, she was noted to have a red,
  roughened, friable area on the anterior lip of
  the cervix near the external os. A biopsy was
  followed by a radical hysterectomy. One pelvic
  lymph node contained a small focus of metastatic
  squamous cell carcinoma.

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Slide 5.1A fungating mass lesion of the cervix
is seen here grossly.
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Slide 5.2Normal cervical epithelium is seen here
histologically.
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Slide 5.3At low magnification, the microscopic
appearance of the lesion is seen here.
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Slide 5.4At higher magnification, the
microscopic appearance of the lesion is seen
here.
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Questions

1. Grade the degree of differentiation of this
   lesion.
2. Is this a microinvasive carcinoma?

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CASE 5 Squamous cell carcinoma of cervix

• Answers
• Grade the degree of differentiation of this
  lesion. The slide shows a well-differentiated
  squamous cell carcinoma. Occasional keratin
  pearls are present.
• Is this a microinvasive carcinoma? Multiple
  sections of the original tumor demonstrated
  invasion into the stroma greater than 3mm below
  the surface epithelial basement membrane thus,
  this is not a microinvasive carcinoma.

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CASE 6

• History
• A 30 year-old woman noted a white plaque on the
  vulva. Following a punch biopsy, an excisional
  biopsy was performed. Sections of the lesion are
  shown here.

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Slide 6.1The vulvar lesion is seen here at the
left at low power microscopically.
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Slide 6.2The vulvar lesion is seen here at high
power microscopically.
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Case 6 Questions

1. Does the tissue represent labia minora or labia
   majora?
2. Why did the lesion appear white?
3. Is there stromal invasion?
4. Should any additional examinations be performed?

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CASE 6 Squamous cell carcinoma in situ of vulva

• Answers
• Does the tissue represent labia minora or labia
  majora? Most of the tissue is from the labia
  minora in that sebaceous glands are present, but
  few if any hair follicles are noted.
• Why did the lesion appear white? Vulvar carcinoma
  in situ with associated areas of dysplasia is
  present. Note the areas of hyperkeratosis with an
  underlying granular cell layer. The thickened
  stratum corneum appears white when moist. The
  areas of rapid cell turnover, characterized by
  parakeratosis (persistence of nucleated cells in
  the stratum corneum), are not associated with a
  granular cell layer.
• Is there stromal invasion? Dermal (stromal)
  invasion is not seen.
• Should any additional examinations be performed?
  Vulva CIS may be associated with vaginal or
  cervical squamous cell carcinoma (lower genital
  tract neoplastic syndrome). The patient should be
  followed carefully.

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CASE 7

• History
• A 23 year-old woman, who had not had a menstrual
  period for seven weeks, began to experience
  vaginal bleeding and right lower quadrant pain.
  The urine HCG level was elevated. A small amount
  of tan tissue was passed per vagina. An
  incomplete abortion was suspected clinically.

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Slide 7.1At laparotomy the right fallopian tube
was dilated and ruptured with surrounding
hemorrhage. A right salpingectomy was performed
and the specimen is shown here.
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Slide 7.2Histologic sections of tissue removed
at DC from the uterus showed only decidua and
gestational endomentrium. This is a histologic
section of the lesion in the fallopian tube, with
tubal epithelium at the upper left. What is at
the lower right?
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Slide 7.3Histologic sections of blood clot
outside of the tube reveal the appearance seen
here. What are these structures?
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Case 7 Questions

1. What is the diagnosis?
2. What is a risk factor for this condition?

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CASE 7 Tubal ectopic pregnancy

1. Answers
2. What is the diagnosis? Tubal ectopic pregnancy.
   The fallopian tube is the most common site of an
   ectopic pregnancy. Less common sites include
   ovary, abdominal peritoneum, and the intramural
   (uterine cornual) portion of the tube. Rupture of
   the tube may cause extensive life-threatening,
   intraabdominal hemorrhage.
3. What is a risk factor for this condition?
   Gonorrheal infection with tubal inflammation and
   scarring can increase the risk for ectopic
   pregnancy. Previous surgery, or other causes for
   chronic salpingitis, can also increase the risk.
   However, half the time, no risk factor is
   identified.