22' Female Breast

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22. Female Breast
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The Breast
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• Breast Carcinoma
• Arise from epithelial cells,
• one in nine women develops breast cancer during
  her life-time (1/3 fatal)
• Risk Factors-
• strong family history first-degree relatives with
  cancer,
• Specific genes linked to genetic inheritance ,
  p53 -Li-Fraumeni syndrome, ATM -ataxia-telangiecta
  sia BRCA1 and 2 (Genetic inheritance is in lt 10
  of all breast cancer cases)
• ? age (rare lt25 except if familial, average
  diagnosis is at 64)
• preexisting proliferative breast disease
  (particularly atypical Hyperplasia)
• Ca. of the contra lateral breast and Ca.
  endometrium
• Radiation exposure at a young age
• Early menarche and late menarche
• Nulliparous women (unremitting exposure to the
  ovarian cycle)
• Women having their first child after 30
• Obese postmenopausal women (increased synthesis
  of estrogens in fat deposits)
• Cellular changes increased expression of
  oncogenes (ex. c-erb-B2, INT2, c-ras, c-myc),
  decreased expression or function of
  tumor-suppressor genes (ex. NM23, p53, RB),
  alterations in cell structure (ex. increased
  expression of vimentin, decreased expression of
  fodrin), loss of cell adhesion (ex. E-cadherin,
  integrins), increased expression of cell cycle
  proteins (ex. cyclins, Ki-67, proliferating cell
  nuclear antigen), increased expression of
  angiogenic factors (ex. VEGF, FGF) increased
  expression of proteases (ex. cathepsin D,
  stromelysins)
• Site- 50 - upper outer quadrant

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• Breast Carcinoma
• Classified as in situ (noninvasive) - 15 to
  30 of all cancers can be ( DCIS (intraductal
  carcinoma), LCIS (lobular carcinoma)
• invasive (invasive) MC is invasive ductal
  carcinoma (80)
• Ductal carcinoma in situ (DCIS) -
  proliferations of tumor cells within ducts and
  lobules confined by the basement membrane, spread
  from lactiferous ducts into the contiguous skin
  of the nipple - Paget disease of the nipple
  (nipple -eczematous or ulcerated, not detected on
  the mammogram 1/3 can develop carcinoma over
  time if untreated
• Lobular carcinoma in situ- proliferation of
  small, uniform cells within ducts and lobules
  that fill, distend or distort at least 50 of the
  acinar units of a single lobule always an
  incidental finding ,never forms a mass ,
  calcifications are rare, invasive carcinoma
  develops in 25 to 30 of women with LCIS in
  contrast to DCIS, both breasts are at equal risk,
  
• Invasive ductal carcinoma (IDC) MC type - or
  cannot be classified or no special type (NST)
  malignant cells with a dense stromal reaction
  ?hard consistency (scirrhous carcinoma)
• Invasive Lobular Ca.-5 to 10 of invasive
  carcinomas, multifocal and bilateral diffusely
  invasive - difficult to detect clinically and
  mammographically composed of small, uniform
  cells forming strands of infiltrating tumor
  cells, sometimes arranged concentrically about
  ducts (bull's eye lesions) Behavior- frequently
  metastasize to CSF (carcinomatous meningitis),
  serosal surfaces, ovary and uterus, bone marrow
• Medullary carcinoma - younger age with BRCA1
  mutations Grossly- large, soft, well
  circumscribed no desmoplasia, a moderately
  dense lymphoblastic infiltrate,
• Others- Colloid (mucinous) ca. Tubular
  (cribriform) ca. Papillary carcinoma - have good
  prognosis

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Paget disease
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Lobular carcinoma
Lobular carcinoma in situ
Invasive Lobular carcinoma
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Breast carcinoma
Excess stromal proliferation. Desmoplasia
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Medullary carcinoma
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Colloid (mucinous) carcinoma
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• Stromal Tumors
• Fibroadenoma (Br. Mouse) - MC benign tumor of the
  female breast, during the reproductive period
  cyclosporine A therapy Clinically- well
  circumscribed palpable masses or mammographic
  densities, (during pregnancy- grow in size and
  sometimes infarct), in older women- calcify,
  Benign associated with proliferative changes
  slightly increased risk of cancer
  Grossly-solitary white, rubbery nodules from 1 to
  10 cm in diameter Histologically -biphasic
  (stroma and epithelium lining cystic spaces)
• 2. Phyllodes tumors - similar to fibroadenomas
  but seen as palpable masses in women 50 70 yrs.
  (10 to 20 years older than fibroadenomas)
  ?cellularity, mitotic activity, stromal
  overgrowth and invasiveness Behavior-Most -
  benign cured by local excision, few recur few
  are highly malignant
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• 3. Sarcomas -rare, can leiomyo, chondros and
  osteosarcoma Sarcomatous differentiation in
  phyllodes tumors and carcinomas -metaplastic
  carcinomas Lymphangio-sarcomas if arise after
  radiation therapy for breast cancer or skin of a
  chronically edematous arm in a post- mastectomy
  patient- Stewart-Treves syndrome

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Fibroadenoma (Br. MOUSE)
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• Mammographic Changes
• Densities - most Neoplasms - radiologically
  denser than the intermingled connective and
  adipose tissue of the normal breast Invasive
  carcinomas- spiculated density with irregular
  borders Benign lesions - well-circumscribed
  densities with smooth borders
• Calcifications - DCIS is the MC malignancy
  associated with calcifications malignancy -
  small, irregular, numerous and clustered or
  linear and branching,
• Changes over time -Relentless growth of
  malignancies may be seen by comparison of
  sequential mammograms for developing densities,
  architectural distortion or increased in the
  number of calcifications
• Limitations of Mammography-some carcinomas (even
  if palpable) may not be detected by mammography
  due to surrounding dense stroma (esp. in younger
  women), absence of calcification, small size,
  close to the chest wall in the periphery of the
  breast

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Mammogram of Young Beast
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Mammogram of aged Beast
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Multiple small Irregular clusters
Cause?
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Large density With Irregular Border
Cause ?
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• Features common to all invasive carcinomas
• Local invasion into adjacent structures produces
  tissue fixation, retraction of the nipple and
  dimpling of the skin,
• Extensive lymphatic blockage by tumor can result
  in Lymphedema, causing the breast skin to
  resemble an orange peal (peau d'orange)
• Inflammatory carcinomas present as a markedly
  enlarged erythematous and swollen breast,
  inflammation is absent
• 1/3rd of breast carcinomas present with lymph
  node metastases, can metastasize to axillary,
  supraclavicular or internal mammary nodes (tumors
  of outer quadrant - metastasize to axillary
  nodes, of inner quadrants and center to internal
  mammary nodes)

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• Prognostic indicators in Breast carcinomas
• Tumor size larger the tumor the worse the
  prognosis
• Locally advanced disease locally advanced
  disease (invasion into skin or chest wall) - poor
  prognosis,
• lymph node metastases Lymph node metastases
  -most important prognostic factor, ( no
  involvement, 10 year survival - 70 to 80, if 10
  are involved it is 10 to 15)
• distant metastases
• all special subtypes have a better prognosis when
  compared to NST cancers, (tubular and colloid ca.
  - best prognosis),
• Poorly differentiated ca. - worse prognosis
• carcinomas with hormone receptors have a slightly
  better prognosis (Rx. with less toxic hormonal
  therapies)
• Lymphovascular invasion - poor prognostic
• involvement of dermal lymphatics (inflammatory
  carcinoma) poor prognosis

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• Prognostic indicators in Breast carcinomas
• Tumor size larger the tumor the worse the
  prognosis
• Locally advanced disease locally advanced
  disease (invasion into skin or chest wall) - poor
  prognosis,
• lymph node metastases Lymph node metastases
  -most important prognostic factor, ( no
  involvement, 10 year survival - 70 to 80, if 10
  are involved it is 10 to 15)
• distant metastases
• all special subtypes have a better prognosis when
  compared to NST cancers, (tubular and colloid ca.
  - best prognosis),
• Poorly differentiated ca. - worse prognosis
• carcinomas with hormone receptors have a slightly
  better prognosis (Rx. with less toxic hormonal
  therapies)
• Lymphovascular invasion - poor prognostic
• involvement of dermal lymphatics (inflammatory
  carcinoma) poor prognosis

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• Breast carcinomas contd.
• Poor prognostic indicators - Increased
  angiogenesis, DNA content if abnormal, increased
  levels of proliferation markers, expression of
  Oncogenes (ex. c-erb-B2) and loss of expression
  of tumor-suppressor genes, proteases
• Current therapy includes -local and regional
  control using combinations of surgery (mastectomy
  or breast conservation - lumpectomy) and
  postoperative radiation and systemic control
  using hormonal treatment, chemotherapy or both,
  newer strategies include inhibition (by
  pharmacologic agents or specific antibodies) of
  membrane-bound growth receptors (ex. c-erb-B2),
  stromal proteases, angiogenesis
• Cytological features of malignancy ?
  Hyperchromatic nuclei dark staining, ? in DNA
  content, ? N C ratios large nucleoli,
  Irregular nuclear membrane, Atypical mitosis,
  Pleomorphic large and small cells ? all mixed
  not producing any recognizable pattern

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• Male breast-
• Gynecomastia - enlargement of the male breast,
  key indicator - imbalance between estrogens and
  androgens, (during puberty, in Klinfelter's
  syndrome, manifestation of hormone-producing
  tumors -ex. Leydig cell or Sertoli cell tumors)
  Cirrhosis side effect of drugs (ex. marijuana,
  anabolic steroids, some psychoactive agents)
  Histologically - proliferation of both epithelial
  and stromal components,
• Carcinoma of the male breast -risk factors,
  prognostic factors are similar to those of women,
  male breast cancer is strongly associated with
  BRCA2 in some families the same histological
  types of breast cancer are found in men and
  women, because the scant amount of surrounding
  breast tissue in men, carcinomas tend to invade
  the skin and chest wall earlier and present at
  higher stages

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Carcinoma of Breast Cytological features of
malignancy

• Hyperchromatic nuclei dark staining
• ? in DNA content
• ? NC ratios large nucleoli
• Irregular nuclear membrane
• Atypical mitosis
• Pleomorphic large and small cells ? all mixed
  in
• Not producing any recognizable pattern

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The Breast PathologyCarcinoma of Breast
Lymphangiosarcoma ST syndrome
Breast cancer
Huge breast cancer Metastasis in her axilla is
almost as big as the breast cancer Died within a
few days of the picture
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• Gynecomastia