Female genital tract - B/89

Question 1

Benign tumors of the breast

Answer 1

Fibroadenoma, Adenoma, Phyllodes tumor, intraductal papilloma

Question 2

Carcinomas of the breast

Answer 2

Non-invasive (in situ) carcinoma - Ductal carcinoma in situ, Lobular carcinoma in situ

Invasive carcinoma - Ductal carcinoma, invasive lobular carcinoma, medullary carcinoma, colloid (mucous) carcinoma, tubular carcinoma, inflammatory carcinoma

Question 3

Fibroadenoma

Answer 3

Due to increased amount of estrogen. Arises from CT and epithelium. Firm, usually solitary and well circumscribed.
Microscopy: Pericanalicular: ducts are open with regular structure, surrounded by fibroblastic stroma.
Intracanalicular: Duct are compressed by stromal proliferation. Star shaped ducts.

Question 4

Adenoma

Answer 4

Arise from epithelium only. Tubular and lactating adenoma may occur in young women. Nipple adenomas may appear in all ages - may ulcer the skin.

Question 5

Phylloides tumor

Answer 5

Arises from periductal stroma. May exhibit leaflike clefts and slits.
Increased stromal cellularity with anaplasia and high mitotic activity, accompanied by an increase in size.

Question 6

Intraductal papilloma

Answer 6

Solitary lesions within the large ducts. Appears as bloody or serous nipple discharge. Papilla has a CT core which is covered by benign, usually double layered epithelium. Multiple papillomas may become malignant.

Question 7

General information about carcinomas

Answer 7

Risk factors: geographic - higher incidence in North America and northern Europe, age - increased risk after age 30, genetic factors, menarche at a young age, obesity, benign breast disease, late age of first pregnancy

Question 8

Genetic factors involved with breast carcinoma

Answer 8

50% are associated with mutations in BRCA1, 1/3 with mutations in BRCA2. Both of them are tumor suppressor genes which act in DNA repair.

Less common hereditary mutations: Li Fraumeni syndrome (p53), mutations in ATM gene (ataxia telangiectasia), Cowden´s disease 10q mutation (multiple hamartoma).

Sporadic breast cancers: Over-expression of NEU/HER2, others are KRAS and MYC amplification.

Question 9

Pathology and morphology of breast carcinoma

Answer 9

Many of the risk factors are linked to increased expression of estrogen. Estrogen stimulates increased production of normal growth factors in the breast tissue and by cancer cells.

The left breast is slightly more affected than the right, and the upper right quadrant is usually the more favorable location of the tumor. Breast cancers are classified into two groups, non-invasive and invasive.

Question 10

Ductal carcinoma in situ (DCIS)

Answer 10

In this case the tumor is confined to the duct. Occurs unilaterally and has 6 histological subtypes.
Comedocarcinoma is the most characteristic with creamy necrotic material coming from the cut surface of the breast. The other histological types have less characteristic appearance. Frequently associated with calcification. If detection is delayed it is frequently detected as a palpable mass.
If the larger ducts are involved it can present with nipple discharge or Pagets disease of the nipple*. Treatment is surgical resection and tamoxifen.

Question 11

Pagets disease of the nipple

Answer 11

Erosion of the nipple which resembles eczema (roughening, reddening, slight ulceration). Associated with underlying DCIS or an invasive carcinoma

Question 12

Lobular carcinoma in situ (LCIS)

Answer 12

Tumor is confined to the acini. Occur in premenopausal women is often bilateral and multifocal. Cells are monomorphic. Approx. 1/3 of them will develop into an invasive carcinoma. Treatment can be clinical and radiological followup - prophylactic bilateral mastectomy.

Question 13

Invasive ductal carcinoma

Answer 13

A general classification to describe carcinomas which cannot be sub classified further. Usually associated with DCIS. Most produce a desmoplastic response and thus forms a hard palpable mass. 2/3 express estrogen and progesterone receptors, 1/3 overexposes HER2/NEU

Question 14

Invasive lobular carcinoma

Answer 14

2/3 of the cases are associated with adjacent LCIS, frequently they are multi centric and bilateral. Almost all of them express hormone receptors. The cells are uniform, usually arranged in stands or chains and invade the stroma. Occasionally they surround cancerous or normal cells, creating a Bulls-eye pattern.
Most of these cancers present as a palpable mass. Gives metastasis to the CSF, serosal surface, GI, ovary, uterus and bone marrow.

Question 15

Medullary carcinoma

Answer 15

Circumscribed and large. With areas of necrosis. Composed of large cells and little stroma. Cells show polymorphism and mitotic figures. No gland formation. and thus it is defined as a “poorly differentiated tumor”. Lymphoblastic infiltration around the tumor.

Question 16

Colloid (mucinous) carcinoma

Answer 16

Well circumscribed, soft or gelatinous. Form small nests and cords of tumors - little pleomorphism. Embedded in a large amount of mucin.

Question 17

Tubular carcinoma

Answer 17

Well differentiated carcinoma composed of cells arranged as tubules. Usually small and firm and has irregular outlines. Histo: well formed tubular structures, cells show little mitotic activity. Stroma is dense, often with elastosis. Express hormone receptors.

Question 18

Inflammatory carcinoma

Answer 18

Name refers mostly to the clinical presentation of a swollen and erythematous breast. Due to blockage of lymphatic vessels. Poorly differenciated and invades local parenchyma. Does not produce a palpable mass.

Question 19

Signs of invasive carcinoma

Answer 19

The lesion may adhere to the pectoral muscles or fascia - Fixation of the tumor.
The lesion may adhere to the overlying skin, leading to retraction of the nipple.
Involvement of the lymphatics - leads to lymphedema - skin becomes thickened around the hair follicles. The skin may appear as the skin of an orange.

Question 20

Spreading of breast carcinoma

Answer 20

Via lymphatics: outer and centeal quadrants typically spread to the axillary lymph nodes, inner quadrants often involve the lymph nodes along the internal maxillary arteries.
Supraclavicular lymph node “Virchow” node may also be involved.

Via the blood: distant metastasis. Practically every organ can be affected, but the most common sites are the lung, skeleton, liver, adrenals, brain.

Question 21

Prognostic factors of carcinoma

Answer 21

Size of primary carcinoma: under 1cm is good.
Lymph node involvement, number of involved lymph nodes
Distant metastasis
Grading: divides the carcinomas into 3 groups based on tubule formation, nuclear grade and mitotic rate (well, moderately or poorly differentiated)
Histologic type- carcinomas of no special type (such as ductal carcinomas) have worse prognosis
Presence of hormone receptors - if they are present it is better, as this means the patient can be susceptible to therapy
Aneuploidy (Abnormal DNA content) - worse
Overexpression of HER2/NEU - detected by immunohistochemistry or FISH

Question 22

TNM staging

Answer 22

Tx: tumor cannot be assessed
T1: tumor is 20 mm or less. No fixation or nipple retraction. Includes Paget disease.
T2: tumor is 20-50 mm or less than 20 mm, but wth tethering
T3: tumor is between 50-100mm or less than 50mm, but with infiltration, ulceration or fixation
T4: tumor is larger than 100mm or ulceration or infiltration is present or chest wall fixation.

N0: no lymph node involvement
N1: axillary lymph node mobile
N2:: axillary node is fixed
N3: Supraclavicular node or edema of the arm.

M0: no distant metastasis
M1: distant metastasis