The Breast
Reading: Large Robbins, breast diseases (chapter 23), Small Robbins, Chapter 18, pages 704 714
Wheater, breast chapter. Breast slides from our set: 31, 51, 73, 96, 111.
Online: Case 9, A young woman with a breast mass.
Anatomy
Normal breast anatomy
Modified skin appendage
Anatomic structure
Normal breast anatomy
Modified skin appendage
Anatomic structure:
Histology terminal duct lobular unit (TDLU)
Duct branch to the TDLU
Nipple: squamous epithelium
Ducts: columnar epithelium
Two cell types line the ducts and lobules.
1.
2.
Breast stroma - 2 cell types
1.
2.
Male breast (also see last page of handout)
Development of female breast:
Prepubertal
Menstrual cycle change
Pregnancy
After delivery (postpartum)
Senescence:
Development disorders
Milk Line Remnants
Accessory Axillary Breast Tissue
Congenital Nipple Inversion
Clinical Presentation of Breast Disease
Breast pain (mastodynia)
Palpable Mass
Nipple Discharge
Diagnostic modalities used to diagnose breast lesions
Radiologic Imaging
Mammographic Screening versus diagnostic
Ultrasound
MRI
Tissue diagnosis
Biopsy
Lumpectomy
Inflammatory disorders
Acute mastitis
Periductal mastitis
Mammary duct ectasia (plasma cell mastitis)
Fat necrosis
Benign Stromal Lesions
Intralobular
Fibroadenoma
Phylloides tumor
Interlobular
Benign: Pseudoangiomatous stromal hyperplasia (PASH)
Malignant: Angiosarcoma (See malignant section)
Benign Epithelial Lesions
Nonproliferative Breast changes (Fibrocystic changes)
Risk of breast cancer
Clinical
Radiology
Histology
Proliferative breast disease without Atypia
Risk of breast cancer
Clinical
Radiology
Histology
Components
Usual ductal hyperplasia
Sclerosing Adenosis
Papillomas
Proliferative breast disease with Atypia
Atypical ductal hyperplasia (ADH)
Atypical lobular hyperplasia
Carcinoma of the Breast
Diagnosis
Histologic
Prognostic
Genetic profiling
Risk factors
Sporadic carcinoma=hormonal
Estrogen drives cell proliferation increasing changes
of DNA damage
Hereditary carcinoma=genetic mutations
BRCA1: Chromosome 17q21
52% of single gene hereditary cancers.
Only 2% of all breast cancers
Breast carcinomas usually basal-like (triple negative -ER/-PR/Her2 unamp).
Greater incidence in medullary carcinoma and poorly differentiated carcinomas
81% have both breast and ovarian carcinoma (increased ovarian cancer risk)
BRCA2: Chromosome 13q12
32% of single gene hereditary breast cancers
Only 1% of all breast cancers
14% have both breast and ovarian carcinoma (increased ovarian cancer risk)
P53: Chromosome 17q13
Li-Fraumeni syndrome (sarcoma, leukemia, brain tumors, others)
Breast Carcinoma histologic types
Ductal carcinoma in-situ (DCIS)
Radiology
Histology
IHC (p63)
Treatment
Paget’s disease
Lobular carcinoma in-situ (LCIS)
Radiology
Histology
Therapy
Invasive carcinoma
Radiology
Histology
Therapy
Histologic subtypes (Table)
Invasive ductal = No special type NST
Grading
Prognostic markers
Her-2: info and assays
Prognostic factors
Gene expression profiling:
Luminal A
Luminal B
Normal breast-like
Basal-like
Invasive lobular carcinoma
Clinical
E-Cadherin
Metastasis pattern
Histology
Other histologic subtypes
Medullary, mucinous, metaplastic, tubular, papillary
Inflammatory carcinoma
Angisarcoma
Male breast
Gynecomastia
Carcinoma
Staging
Treatment
Sentinel node biopsy
Breast related TBLs
Case 1.
HISTORY: This 39-year-old woman noted multiple nodules in both
breasts that had increased in number and size during the previous
2 years. She had experienced menarche at 10 years of age and her
first pregnancy at 36 years of age. Her mother and one sister had
died of carcinoma of the breast.
PHYSICAL FINDINGS: Multiple small, rubbery, non-tender
masses in both breasts, ranging in size from 0.5 - 1 cm. in
diameter.
LABORATORY RESULTS:
mammography: multiple ill-defined densities bilaterally
CLINICAL COURSE: A breast biopsy was performed.
The history, physical and mammographic findings are most suggestive of what condition?
Which of the following features in the clinical history and
physical findings carried the greatest risk that this patient might have breast carcinoma?
If the breast biopsy had revealed fibrocystic change, what histological changes would have carried the
greatest risk for later development of breast carcinoma?
If the biopsy had revealed lobular carcinoma, what would be a major concern and how would you go
about confirming your suspicions?
Case 2.
This 31-yr-old schoolteacher noticed a solitary mass in the right breast
10 days before a biopsy was performed. She had been on oral contraceptive
medication since the birth of her only child two years ago. The
mass was asymptomatic, non-tender, not fixed to skin or
underlying muscle. There was no nipple discharge or retraction.
At operation a very firm, well defined tumor 2.5 cm in diameter
was disclosed in the upper outer quadrant of the breast.
The most likely diagnosis in this case is what?
What histological findings would you expect?
Is there anything unusual in the history or physical findings of this patient?
Case 3.
This 45-yr-old woman had noted crusting of the right nipple for
four months with induration beneath the areola. At operation a
firm, irregular shaped and poorly defined mass 6 cm in largest diameter was found with
fixation and retraction of the overlying nipple.
What is the most likely diagnosis in this case?
What you would you expect to be the histological appearance of the mass?
Female Reproductive Disease TBLs
Case 4.
HISTORY: This 22-year-old graduate student stated that during the
past 4 days she has had continual vaginal bleeding and abdominal
cramps. During the past 6 hours she has had chills and fever
(39.5 C). She has been amenorrheic during the past 3 months.
PHYSICAL FINDINGS: General exam was negative, pelvic exam
revealed blood and tissue in the dilated cervical os.
LABORATORY RESULTS:
hemoglobin: 13.6 g/dl
hematocrit: 42%
CLINICAL COURSE: A dilatation and curettage was performed.
During the next 2 days mild vaginal bleeding was noted. A repeat
hematocrit was 40%.
What additional history and laboratory findings would you like to know?
What do expect the most likely finding on microscopic examination of the
curettings would be?
The least likely finding on microscopic examination of the curettings would be?
Case 5.
HISTORY: This 65-year-old married woman was admitted for
evaluation of vaginal bleeding. Menses ceased 15 years prior to
admission. For the last 2 years, however, she had experienced occasional
spotting and irregular periods of heavier vaginal bleeding. These
periods of irregular bleeding had been more or less cyclic but
the intervals between them varied. Duration and severity of the
bleeding also varied. She remarked that her breasts had become
somewhat enlarged during the past 3-4 months.
PHYSICAL FINDINGS: An orange-sized mass in the right pelvic
adnexa, uterus normal size.
LABORATORY RESULTS:
hematocrit: 30%
hemoglobin: 10.0 g/dl
MCHC: 28 g/dl
MCV: 70 cu microns
CLINICAL COURSE: A diagnostic dilatation and curettage was
performed.
What would expect the histology of the curetted endometrial tissue to show?
What would suspect to be the nature of the “right adnexal mass” and what is its possible association with
the endometrial lesion?
List several contributing factors for this condition in “average” female population..
Case 6.
HISTORY: This 55-year-old woman was admitted for evaluation of
menorrhagia. She had noted increasing size of the lower abdomen
over the last 10 years.
PHYSICAL FINDINGS: Slightly obese woman, the uterus was 4 times
normal size and nodular.
LABORATORY RESULTS:
hematocrit: 34%
hemoglobin: 10.5 g/dl
CLINICAL COURSE: A hysterectomy was performed. The uterus
measured 22 cm in diameter. A 3.5 cm pedunculated nodule was
present on the surface and several smaller nodules within the
myometrium. A 7 cm nodule contained soft liquid areas in its
center. The endometrial cavity was irregular and distorted by
submucosal nodules.
What does the hematological evaluation and from what you know about anemia evaluations, what other
determinations would be helpful?
How does the size of the uterus in the case compare with the expected size for a woman of the patient’s
age?
What do suspect is the nature of the multiple nodules described in the myometrium and subendomtrium?
Are these likely to be malignant or benign and what histological features will help with the distinction?
Case 7.
HISTORY: This 29-year-old gravida 3 para 3 woman was seen in
gynecology clinic with complaints of fatigue and dyspareunia. Two
years ago, after birth of her second child, metaplastic squamous
cells were present in a cytologic smear of her uterine cervix.
Another smear one year later, after the birth of her third child,
revealed atypical cells.
PHYSICAL FINDINGS: General physical exam negative. Several
whitish lesions on the uterine cervix and the cervix appears fixed and immovable.
LABORATORY RESULTS:
cervical cytology: many atypical cells
CLINICAL COURSE: The cervical lesions were biopsied and a further procedure was recommended.
What diagnoses are possible in this case? Histological features of each possibility?
What feature of the history and/or physical exam most concerns you?
What do suspect was the additional diagnostic procedure recommended in this case?
Supposing the biopsy results revealed squamous carcinoma, what factors do you think might have
contributed to its development?