The Breast

Reading: Large Robbins, breast diseases (chapter 23), Small Robbins, Chapter 18, pages 704 - 714Wheater, 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 previous2 years. She had experienced menarche at 10 years of age and her first pregnancy at 36 years of age. Her mother and one sister haddied 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 diameterwas 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 thepast 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. Theseperiods 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. Twoyears 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?