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38 Cards in this Set

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Lesion in women 30-70, symptoms: mass, nipple retraction and discharge (serous or creamy), and pain, although mostly are asymptomatic

Gross: dilated ducts with cheesy material

Micro:dilated ducts with amorphous material, periductal chronic inflammation, and fibrosis. Macrophages invade the epithelium.
U/S shows dilated ducts

May have inflammation
Duct ectasia
Young women, age 20-40,
h/o recent pregnancy, present with a palpable mass that is tender.
Often bilateral with axillary lymphadenopathy. Usually occurs at extra-areolar site

Gross: may be up to 8 cm
Micro: non-caseating granulomas on lobules, epithelioid macs and giant cells. Often, acute and chronic inflammation are present (microabscesses)
idiopathic granulomatous mastitis
patient with autoimmune disease (insulin-dep DM)presents with a breast mass causing pain, mass may be tender

autoimmune disease often seein with insulin-dependednt DM and hashimoto's thyroiditis.

Gross: rubbery/firm, grey mass
Micro:aggregates of lymphocytes around lobules and vessels. Fibrosis of the intralobular stroma. Mostly B cells.
Sclerotic lymphocytic lobulitis
woman with a history of trauma/surgery/radiation presents with a firm breast mass. May have skin retraction and thickening.

rads: hyerechogenicity
Gross: yello discoloration of the fat
Micro:foamy macs around adipose tissue. May have chronic inflammation, cholestrol clefts, hemosiderin-laden macs
R/O lobular breast CA
Fat necrosis
young woman with breast mass, skin retraction, nipple inversion. Mammogram: fibrous capsule
U/S: snowstorm

Gross: firm tissue, calcifications, liquid material
Micro: FBGCR
Tissue reaction to implant/rupture
commonly incidental breast lesion, although may rarely present as a solitary mass

Imaging: architectural distortion or mass with microcalcifications

Gross: imperceptible

Micro: "lobulocentric" pattern of elongated and distorted glands and tubules proliferating with a fibrotic stroma. Myoepithelial cells in fibrotic/sclerotic stroma

myoepithelial cells stain with P63, smooth muscle myosin, or Calponin
Sclerosing adenosis
Incidental breast lesion, is common (4-28%)

Imaging: rarely cause "spickled" appearance on mommography


Gross: rarely visible: may be seen as a stellate lesion

Micro: central zone of fibroelastosis from which ducts and tubules eminate. May contain apocrine metaplasia, microcysts, proliferative changes

2. If larger than 1 cm?
Radial scar

2. If larger than 1cm = complex sclerosing lesion

May increase risk of breast CA
Incidental breast lesion.

Imaging: may show increased density with irregular borders or microcalcifications

Gross: Ill-defined lesion of 3-4 cm

Micro: haphazarly arranged small, round tubules infiltrating the mammary stroma or fat. The glands are ligned by a single layer of cuboidal epithelium, without apical snouts. no cytologic atypia. No myoepithelial cells are seen, but the BM is intact. Glandular lumens show an eosinophilic material that is colloid-like and stains for PAS and mucicarmine

Epithelial cells are s100, CAM 5.2, CK, CK7, cathepsin D, and EGFR+; and ER/PR/HER2 -
Microglandular adenosis

associated with recurrence and carcinoma
Young woman with multiple peripheral occult lesions or older woman with single central mass; present with bloody or clear nipple discharge; lesions may be several cm

Imaging: smooth walled, well-defined mass with dilated adjecent ducts.

Gross: varibly-sized lesion within dilated ducts, may be soft to firm.

Micro: multiple branching papillaelined by two cell layers. Fibrovascular cores present. May have apocrine metaplasia. May show epithelial hyperplasia (stain with CK5), forming slit-like spaces
Intraductal Papilloma

If atypia is seen <3cm= ADH within a papilloma, if >3cm, DCIS
rare breast lesion in older women and men- palpable central mass, may have discharge

Imaging: round/lobular mass, may have papillary features and microcalcifications

Gross: 1-3 cm mass with fibrous capsule, cystic space common. Is firm/ hemorrhagic.

Micro: arborizing papillary network lined by 1 or more layers of epithelium, no myoepithelial layer in fibrovascular cores. May show cribiform or solid patterns.Nuclei show mild atypia. Fairly cellular, FNA mostly bloody.

Epithelial cells ER +, HER2-
Encapsulated Papillary Carcinoma

Good prognosis (95% OS)
AA young woman with a mobile, firm, painless breast mass.

Gross: round, rubbery, gray mass

Micro: fibroepithelial lesion in intracanalicular (1) and pericanalicular (2) variants. (1) compressed glandular structures in fibrous stroma that is whorled; (2) tubular ducts structures that are disorganized surrounded by fibrous stroma. No atypia, myoepithelial cells present.


IHC: not necessary
Fibroadenoma
Woman with rapidly growing well-defined breast mass.

Gross: Can be large, lobulated with bosselated borders

Micro: Fibroepithelial lesion with clefts lined by 2-layers of epithelium. Project into cystic spaces, forming leaf-like pattern. Atypia varies: borderline and malignant variants on degree of mitoses (<5->10) and spindle-cell atypia.

IHC: Ki-67 for proliferation
Phylloides tumor

True neoplasm
Incidental finding- typically adjancent to other lesions.

Gross: rubbery and smooth, up to 10cm

Micro: low power DX: intralobular stromal expansion with anasomizing angular slitlike spaces that look like vessels. Background of sclerotic collagen. No atypia.

IHC: CD34, vimentin, actin.
Psuedoangiomatous stromal hyperplasia (PASH)

Hormones may underlie pathogenesis

Prominent Golgi aparatus in spindle cells
woman with a painless hard breast mass

Gross: infitrative margins, hard to see lesion

Micro: broad sheets of interlacing fascicles of spindled cells forming herringbone or storiform pattern. Cells are bland with indistinct cell borders and myxoid background. Can have lymphocytes at the border

IHC: vimentin and SMA positive. CK panel (all, can be focal), S100, and P63 required to differentiate from malignant lesion.
Fibromatosis

Seen rarely, assc. with Gardner syn (APC)
rare breast lesion in men and women- slow painless mass

Gross: well-circumscribed rubbery mass, whorled surface.

Micro: unencapsulated well-circumscribed lesion, admixture of bland oval-to-spindled cells with thick eosinophilic collagen bands.

IHC: SMA, desmin, CD34, vimentin
Myofibroblastoma

Aunt Minne
young woman with a firm, painless breast mass

Gross: well-circumscribed, firm lesion with cystic/myxoid areas

Micro: partially-encapsulated, densley cellular lesion or spindle-cells with indistinct borders around thin-walled irregular vessels. May look "staghorn".

IHC: SMA, vimentin for spindle cells, endothelial cells are CD31,CD43, factor VIII
Hemangiopericytoma
Woman with a firm, painless mass in the breast (although can be anywhere)

Gross: yellow mass

Micro: sheets, nests, cords of oval/polygonal cells with abundant eosinophilic granular cytoplasm. Nuclei have inconspicuous nucleoli. cell aggregates separated by thin septa. No atypia.

IHC: NSE, S100
Granular cell tumor

Granules are lysozomes
Premenopausal woman with lumpy, painful breast mass (can be bilateral)

Gross: fibrosis and blue-domed or clear cysts up to 2 cm.

Micro: combination of B9 histologic changes that include stromal fibrosis, dilated ducts, cysts, apocrine metaplasia, and mild epthelial hyperplasia without atypia.
Fibrocystic change

in 60% of all normal breasts
No risk of CA
pre-perimenopasual woman with incidental breast lesion when biopsied for microcalcification (40%)

Gross: none

Micro: enlarged terminal duct units with dilated acini, epithelium with apical snouts present and a variety of histological subtypes:
(1)- epithelium replaced by 1-2 laters of columnar cells,
(2)- more than 2 layers and crowded nuclei
(3)- low-grade cytologic atypia without papillary tufts or bridges (small nucleoli, lack granularity, loss of polarity)

IHC: CK8/18, CK19, ER/PR. Negative for HMWCK
Columnar cell lesions
(1)columnar cell change
(2)columnar cell hyperplasia
(3)flat epithelial atypia

Often occurs with ADH, FEA with lobular neoplasm
premenopausal woman with incidental lesion on breast BX (20-30% of cases)

Gross: none

Micro: 3 or more cells in the ducts/lobular unit above the basal cell layer. Mild:3-4, moderate: >5, florid. Other features: mild variation in size, shape, and placement of cells. No significant atypia. Streaming pattern of growth. Secondary lumina and slit-like spaces form in florid cases.
Can be seen in gynecomastia with pyknotic nuclei
Usual Ductal Hyperplasia (UDH)

Mod/florid forms increase risk for CA 1.5-2x
40 YO woman with incidental breast lesion on BX (10%)

Gross: none

Micro: hyperplasia of the luminal cells of a duct or lubular unit that shows: A: at most focal areas of cellular uniformity, B: hyperchromatic nuclei, C:nuclei with fine chromatin D: rigid cellular bars and secondary spaces. Can invovle more than 1 duct, but total lesion <2mm
Atypical ductal hyperplasia (ADH)

4-5x risk of ipsilateral CA in 10-15 years
premenopausal women with microcalcifications on routine breast screening, may present with mass or Padget's

Gross: speckled, ill-defined

Micro: a uniform population of neoplastic cells lines the entire BM-bound space, creating uniform secondary spaces. Involves at least 2 such spaces, >2mm. Cells are small with nuclei 1.5-2x RBC, form micropapillae/cribiform pattern, and have well-defined borders. Mitoses are sparse

IHC: ER/PR +, HER2 -
Ductal carcinoma in-situ (DCIS), low-grade

Genetics: 16q del in 70%
premenopausal woman with a rare incidental multicentric (50%) or bilateral (2/3) breast lesion

Gross: none

Micro: distension of the lobules by uniform dyscohesive small cells with eccentric nuclei and inconspicuous nucleoli. Cells often have intracytoplasmic mucin vacuoles, may look "targetoid". These are contained to less than 50% of the lubules of a terminal ductal lobular unit

IHC: loss of E-cadherin
Atypical lobular hyperplasia (ALH)
4-5x risk of CA, ipsilateral 3x contralateral

Genetics: del 16 q E-cadherin/ gain 1q
premenopausal woman with a rare incidental multicentric (50%) or bilateral (2/3) breast lesion

Gross: none

Micro: distension of the lobules by uniform dyscohesive small cells with eccentric nuclei and inconspicuous nucleoli. Cells often have intracytoplasmic mucin vacuoles, may look "targetoid". These are in more than 50% of the lubules of a terminal ductal lobular unit, and fill up and distend the space. Cells can spread to nearby ducts/lobules in pagetoid fashion

IHC: loss of E-cadherin, ER/PR+, HEr2 -
Lobular carcinoma in-situ (LCIS)
8-10x risk of CA, ipsilateral 3x contralateral

Genetics: del 16 q E-cadherin/ gain 1q
Variant of LCIS with microcalcifications, large plump cells 3-4x lyphocyte, pleomorphism similar to DCIS grade 3

IHC: loss of E-cadherin, ER/PR/HER2 -, ki-67, p53+
pleomorphic LCIS (PLCIS)

Genetics: loss E-cadherin, ER/PR/ HER2
premenopausal women with microcalcifications on routine breast screening, may present with mass or Padget's

Gross: speckled, ill-defined

Micro: a uniform population of neoplastic cells lines the entire BM-bound space, creating uniform secondary spaces. Involves at least 2 such spaces, >2mm. Cells are large and pleomorphic with coarse chromatin and multiple nucleoli. 2.5x RBC, form cribiform/solid pattern, and have well-defined borders. Mitoses are frequent. Comedonecrosis with calcification present.

IHC: ER/PR +/-, HER2 +
DCIS, high-grade

Genetics: aneuploidy common.
Middle aged woman with a breast mass

Gross: well defined stellate mass

Micro: invasive breast cancer with 90% of the lesion forming angulated tubules with a single layer of epithelial cells. apical snouts present, desmoplasia.

IHC: ER/PR+, HER2 -
Tubular carcinoma

Genetics: 16q loss in ~80%, 1q gain in 50%
Middle aged woman with a breast mass

Gross: well defined stellate mass

Micro: infiltrating islands of tumor cells with 90% having cribiform architecture, amphophilic cytoplasm, and low-grade histology.

IHC: ER/PR+, HER2 -
Cribiform carcinoma
Middle aged woman with a breast mass

Gross: well defined stellate mass with gelatinous surface

Micro: nests of tumor cells floating in mucinous pools- must account for 90% of lesion.

IHC: ER/PER+, HER2
Mucinous Carcinoma

Confers a BETTER prognosis
Middle aged woman with a breast mass

Gross: well defined stellate mass

Micro: invasive breast CA with 5 distinctive criteria:
1. syncitial growth pattern
2. absence of glandular structures
3. diffuse mod/marked lymphocytic infitrate
4. grade 3 nuclear grade
5. histologic circumscription

IHC: ER-, PR+, HER2-, p53+,
Medullary carcinoma

Associated with BRCA1 mutations. Basal-like molecular phenotype
Elderly woman with palpable breast mass

Gross: large cystic mass
Breast lesion of invasive epithelial cells admixed with areas of spindle cells and areas of squamous differentiation.
variants:

(2) infitrating compressed glands with keratin inside surrounded by spindle cells
(3)- contain other malignant elements

IHC: triple neg, CK focally positive
Metaplastic CA

(2) adenosquamous CA

(3) metaplastic CA with heterologous mesenchymal elements
postmenopausal woman with a breast mass

Gross: well defined lesion

Micro: tubular/cribiform architecture with bi-phasic population of cells surrounding pseudocystic areas that contain amorphous esosinophilic material. true glands also seen

IHC: material stains with alcian blue, glands stain with PAS(lumen), CK7(cells).
Adenoid cystic CA
Breast CA Molecular subtypes/ histologic correlation:

1- Lumenal A:

2- Lumenal B:

3- Basal

4: HER2+
1- low grade and ER+, respond to estrogen therapy, indolent

2- ER+, but histologic grade 2/3, more aggressive

3- usually triple negative, still not classified

4- ER-, HER2 amplification. Grade 3, may have apocrine differentiation, lymphoid infiltrate. Agressive, may respond to trastuzumab
In order, critical prognostic factors in breast CA

1.
2.
3.
4.
1. LN status
2. tumor size
3. histologic grade
4. LVSI
Breast CA grading: 3 categories

1. (3 points)
2. (3 ponits)
3. (3 points)

Total grades:
1. Differentiation (1- >75%, 2-10-75%, 3- <10%
2. nuclear pleomorphism (1-small, uniform, 2- large with open chromatin, 3- pleomorphism
3. mitoses in 10 HPFs (1-3, varies on size of field)

Total:
grade 1: 3-5
grade 2: 6,7
grade 3: 8,9
Breast CA susceptibility genes, syndromes, locations, incidence, risk

1.
2.
3.
4.
5.
1. BRCA1- 17q, 0.1%, 37-80%R
2. BRCA2- 13q, 0.1%, 37-80% R
3. pTEN- COWDEN- 10q, 1:300K, 25-50%R
4.TP53- Li-Fraumeni- 17p, rare, 60%R
5. STK11/LKB1- Peutz-Jeghers, 19p, 7xR
What is Stewart-Treves sydrome?
angiosarcoma arising from chronic lymphedma 2/2 mestectomy
man or woman with breast mass

Micro: poorly circumscribed area of ductular hyperplasia (not lobular) with periductular fibrosis or edema.
gynecomastia