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Flashcards in Pathology - Zafar Deck (57):
1

Breast Embryology

-largest skin gland: modified sweat gland
-at the end of first month, a solid bud develops and invaginates into underlying mesenchyme
-primary bud gives off several secondary buds that develop into lactiferous ducts which branch off further to form mammary gland
-during pregnancy the breast assumes it's complete morphologic and functional maturity

2

Breast Anatomy

-symmetric double organ
-reaches normal size b/w 16-19 yrs
-b/w 2nd & 6th ribs and sternum and axilla
-nipple & areola, superficial skin
-breast is divided into 10-20 lobes, each lobe (lobules: ducts+acini=TDLU)
-embedded in stroma

3

Breast Pathology: Classification

congenital or acquired

4

Accessory Breast Tissue

-in axillary fossa
-tumors here may be confused with ax. LN or mets

5

Ectopic Breast Tissue

-may develop along mammary line
-failure of any portion of mammary ridge to involute

6

Macromastia

-excessive breast tissue

7

Nipple Inversion

-associated with large pendulous breasts
-may be confused with CA

8

Supernumerary Breast/Nipples

-persistent epidermal thickenings along milk line from axilla to perineum

9

Acute Mastitis/Abscess

non-neoplastic-acquired
-tender, associated with lactation
-cracks in nipple
-staph and strep (pyogenic bacteria)

10

Silicone Implants

non-neoplastic-acquired
-for a fibrous capsule (synovial metaplasia)
-gel may seep through intact implant shells

11

Fibrocystic Changes/Disease of Breast

non-neoplastic-acquired
-considered a hyperplastic disorder
-proliferative vs. nonproliferative (cystic)
-women 25-45 (hormonal imbalance?)
-decreased risk with OTC
-increased mitotic and apoptotic rate
-may hamper adequate/optimal mammography

12

Sclerosing Adenosis

~30 y/o
-risk of CA 1.5-2x normal
-associated with clustered microcal
-low power diagnosis
-rarely involved by LCIS
--if palpable called adenosis tumor
-retains lobular architecture
-2 cell-layered
-actin immunohistochemistry + (myoepithelial cells)
-related lesion-Radial Scar

13

Atypical Ductal Hyperplasia

-features suggestive but not diagnostic of DCIS
-increased risk of carcinoma 2-4x5 times
-rick equal in both breast-maybe multicentric
-multilayering of cells with progressive loss of nuclear polarity, enlarged nuclei, and nucleoli
-most authors require 2+ involved ducts to call DCIS
-loss of heterozygosity to 16q (40% clonal)

14

Atypical Lobular Hyperplasia (ALH)

-resembles LCIS but does not fill or distend 50% or more acini within a lobule
-has focal preservation of luminal spaces
-4x5 usual risk of CA in either breast (greater in pre-menopausal)

15

Fibroadenoma

-most common benign tumor (breast mouse)
~20-35 age women (younger)
-Fibradenomatosis
-may have a neoplastic stromal component with polyclonal epithelial component
-hormonally responsive: may grow in pregnancy
-malignant transformation <0.1%

16

Fibroadenomatosis

-multifocal disease in post renal transplant and with EBV in immunosuppressed

17

Fibroadenoma: Gross Appearance

-sharply circumscribed
-freely mobile

18

Fibroadenoma: Microscopic

-stromal & epithelial component
-glandular epithelium without atypia
-myoepithelial cells are present
-stroma generally not very cellular (dd Phyllodes) but may have other stromal elements like cartilage, muscle
-coexisting features: fibrocysitc change, sclerosing adenosis
-FNAC very helpful in regular variant

19

Large Duct Papilloma

-48y/o, solitary, close to nipple-lactiferous ducts & sinuses
-1.5-2x risk of cancer, colonal
-serous/bloody nipple dischargee (80%), nipple retraction may be present

20

Large Duct Papilloma: Gross

-<3cm
-soft
-hemorrhagic

21

Fibroadenoma: Juvenile/Giant cell variant

-adolescent, often bilateral, often very large and may have very cellular stroma and glands (dd phyllodes tumor)

22

Large Duct Papilloma: Microscopic

-multiple papillae in complex arborizing pattern
-calcification possible
-myoepithelium present (S1000+)
-malignant if severe atypia, abnormal mitosis, single cell layered, pseudostradification no vascular core or cribriform morphology

23

Large Duct Papilloma: Treatment

-surgical excision

24

Fat Necrosis

-trauma: patient may not give history
-Generally related to lactation, pregnancy, or sports activity
-may present as ill-defined mass
-may show calcification
-may cause puckering of skin
-DD-carcinoma

25

Gynecomastia

-enlargement of male breast: hypertrophy & hyperplasia
-increased estrogen to androgen ratio
-puberty: alcohol, cirrhosis, drugs
-button or disc-like stromal enlargement
-periductal stromal edema or fibrosis "Halo" effect

26

Genetics of Breast Cancer?

-first degree relatives at increased risk
-higher if relative has bilateral disease, early incidence in relative or >1 relative affected
-heterogenous carriers for ataxia-telangiectasia

27

Li-Fraumeni syndrome

germline p53 mutations
-25% patients effected

28

BCRA 1 & 2

1 (17q21)
2 (13q12)
-tumor supressor genes involved in familial cancer
-5-10% of breast cancer cases
-1% of general population

29

Cowden Disease

-multiple hemartoma syndrome
-10q mutation
-much increased risk

30

Breast Cancer: Hormonal

increased risk:
-early menarche
-late menopause
-nulliparity
-having first child after 30
-recent use of oral contraceptives
-HRT (estrogen + progesterone) in postmenopausal women
-physical inactivity
-consumption of 1 or more alcoholic/day
-postmeno. w/obesity or estrogen producing ovarian tumor

31

Breast Cancer: Environmental

-US > Japan/Taiwan (5:1), also N. Europe, fatty diet & heavy alcohol use
-not associated with smoking
-in blacks: higher stage, high nuclear grade, higher mortality rate, more frequent in women <40, more likely ER/PR negative

32

Breast Cancer: Hormonal Receptors

-ER/PR - response to anti-estrogen therapy (Tamoxifen) and prognosis

33

Breast Cancer: Local Spread

-skin
-nipple
-chest wall

34

Breast Cancer: Nodal Mets

-axilla
-supraclavicular
-internal mammary

35

Breast Cancer: Distant Mets

-skeletal system
-liver
-lung/pleura
-ovary
-adrenal
-CNS
***lobular CA favors abdominal cavity/viscera***

36

Breast Cancer: Treatment

-surgery (lumpectomy/mastectomy)
-radiation
-chemotheraphy
-anti-estrogen
-Herceptin

37

Breast Cancer: Histological Grading

-score of 3-9 Modified Bloom and Richardson System

38

Breast Cancer: Her2 (c-erbB2)

-overexpression with gene amplification
-aggressive tumor behavior
-IHC and FISH 0-3+
-membranous staining

39

Breast Cancer: Prognostic Factors

-stage
-tumor size
-histologic grade
-ax LN status
-age <50 better
-histologic type (tubular, cribriform, medullary (better), signet ring, inflammatory (worse))
-skin invasion
-nipple inversion
-angiolymphatic invasion
-fibrotic focus

40

Breast Cancer: Predictive Variables

-ER/PR & Her2 Status
-ploidy & S-phase fraction have no predictive value

41

Breast Cancer: Axillary Lymph Node

-involvement most improtant prognostic factor for disease (free & overall survival & Rx regimen)

42

Breast Cancer: Sentinel Lymph Nodes

-first lymph node that receives breast drainage/mets
-usually ventral group (level 1)
-replacement for axillary dissection in T1 & T2 tumors
-cluster size of 0.2-2mm may indicate significant axillary dz.

43

Breast Cancer: Core Biopsy

-alternative to open biopsy
-large (14 gage 1st gen or 11g 2nd gen)
-computer (stereostactic) or US guided

44

Breast Cancer: FNAC

90% sensitive, 95% specific
-fibrotic areas difficult to aspirate
-false neg small tumors, tubular CA, cribriform CA
-false + w/florid ductal hyperplasia
-neg FNA with lingering suspicion - BX

45

Breast Cancer: Frozen Section

-real time evaluation in surgery

46

In-Situ

-stromal invasion is not seen

47

Ductal Carcinoma in situ

-tumor confined to glandular component - no stromal invasion, BM intact
-tumor can spread along ducts
-4x more common than LCIS
-15-30% of all cancer - mammography
-assoc. with development of invasive cancer at or near the site
-Rx: surgery + radiation
-cytologic features for grading: low vs. high grade
low (0-10%) high (40%) progress

48

Lobular Carcinoma in situ

-generally incidental: no distinguishing features at gross exam and no microcal
-50-70% bilateral (vs. 10% for DCIS)
-75% multicentric
-30% risk of invasive disease in either breast (relative risk 9x normal) Invasive dz may be of ductal or lobular type
-5% have coexisten invasive cancer
-lobular cancerization of ducts
-minimal risk of dying from cancer if periodically examined
-rx: watchful waiting vs. ip/bil mastectomy

49

Comedo Carcinoma (DCIS Variant)

-1/3 multicentric, 10% bilateral
-40% progressive (invasive)
-some patient have axillary mets
-high grade cells with central necrosis
-Her2 amplification, p53 mutation positive
-ER/PR negative, aneuploid

50

Paget's Disease of Breast

-from excretory ducts and extends into skin of nipple/areola
-assoc DCIS/Invasive
-50% underlying lump/mass
-Sir James Paget 1874
-Large cells with clear cytoplasm, nucleoli and abundant mucin (PAS Strain)

51

Ductal Carcinoma NOS

-most common type (80%) scirrhous
-penetrative (crab-like-cancer)
-calcification
-tumor may be fixed to the chest wall
-tubule formation, Nuclear pleomorphism and number of mitoses: MBR grading

52

Lobular Carcinoma

-10% of all breast cancers
-20% bilateral, often multicentric
-mets to CSF, BM, GIT, Serosal surfaces, ovary, uterus
-mass lesion may not be present
-single (Indian) file/targetoid, usually low grade appearance, signet ring cells
-morphologic variant forms

53

Inflammatory Carcinoma

-clinical diagnosis
-enlarged edematous breasts
-aggressive - need aggressive Rx
-Peau d'orange-lymphatic occlusion-thickened skin

54

Colloid Carcinoma

-"mucinous cancer"
-older women-slow growth
-better survival than ductal (12+ years after therapy)
-large lakes of mucin

55

Tubular Carcinoma

-2-6% of all malignant tumors
-well differentiated-very favorable prognosis
-avg age 50 yrs(younger than ductal)
-good prognosis even with lymph node +
-75% tubules (angulated)

56

Angiosarcoma

-usually younger women or older women (sp radiation)
-poor prognosis
-anastomosing vascular channels lined by atypical cells
-low and high grade

57

Carcinoma in Males (breast)

-1% the rate of women (10% in Egypt)
-similar risk factors as women
-usually painless subareolar mass
-advanced stage presentation
-prognosis same as women when stage-matched