Pathology of the Breast: Malignant Flashcards
Carcinoma In Situ
Definition: Pre-malignant population of neoplastic cells limited to ducts and lobules by myoepithelial cell layer and basement membrane; Neoplastic cells have not gained the capacity to invade or spread outside the breast.
- non invasive
- Ductal Carcinoma In Situ
- Lobular Carcinoma In Situ
- Paget’s Disease of the Nipple
Carcinoma In Situ - DCIS
- Increased incidence since mammography, most frequently found due to intraductal calcifications - linear branching
- Can be low, intermediate or high grade depending on degree of nuclear pleomorphism
- Various growth patterns within ducts: cribriform, solid, papillary, micropapillary or comedo patterns
- DCIS is generally not multicentric •
- It is most often segmental, implying contiguous involvement of an area of the ductal system in a single lobe – this is why the disease is amenable to breast conserving surgery
- Clinical significance: 8 – 10 X increased risk of invasive carcinoma
DCIS Grading
Grade 1:
- Monotonous nuclei, 1.5 to 2.0 RBC diameters
- finely dispersed chromatin & only occasional nucleoli
Grade 2:
• Intermediate
Grade 3:
- Markedly pleomorphic nuclei, usually greater than 2.5 RBC diameters
- coarse chromatin & prominent or multiple nucleoli
- Mitoses common
- Comedonecrosis: Cheesy necrotic tissue inside ducts
- Typically seen in high grade DCIS where cells are very rapidly
•Low Grade DCIS
•High Grade DCIS with calcifications
Paget’s Disease
•DCIS spreading up major ducts and out onto skin surface
- Rare breast cancer manifestation (1-2%)
- Unilateral, erythematous oozing nipple with ulceration
- Caused by DCIS cells extending from duct system into nipple skin
- 50-60% have underlying palpable mass with invasive poorly differentiated cancer, overexpressing Her2/neu receptor
Clinical:
- Older women
- Skin of nipple and areola: hyperemia, edema, bloody discharge and ulceration
- DDX includes infection, eczema, intraductal papilloma, skin cancer
- Diagnosis by punch biopsy necessary
Significance:
• Underlying malignancy: in situ and/or invasive disease generally present in 99% of cases
• DCIS of high grade large malignant cells with clear cytoplasm (halo cells) extending from nipple ducts to involve skin of nipple and areola
DCIS Treatment and Prognosis
• Treatment, general
- Excision of affected area(lobe) with adequate margins (removal of all DCIS with a rim of normal tissue surrounding it)
- +/- Radiation
- +/- Anti-estrogen such as Tamoxifen if ER positive
• Prognosis
- The most important factor influencing the possibility of recurrence is persistence of neoplastic cells post-excision
- The significance of margin evaluation by the pathologist is to ascertain complete excision of all detectable disease
- General: 5% recurrence rate
Carcinoma In Situ - LCIS
- Almost always an incidental finding; no calcifications
- Multifocal, bilateral in 20-40%
- Neoplastic cells fill and distend lobules
- Same risk for invasive carcinoma as DCIS
1. LCIS is NOT a surgical disease
2. No mammographic abnormalities or grossly recognizable features
3. Wide age range of patients 15-90 yoa
4. Multicentric in approx 85%
5. Bilateral in 30-70%
6. Considered a general risk factor
7. 25-35% develop invasive carcinoma over a period 20 years (carcinoma can be either ductal or lobular)
- LCIS
- Proliferation of monomorphic loosely cohesive cells filling and expanding in lobules
LCIS Treatment
- LN is Estrogen Receptor + in up to 90% of cases
- Treatment recommendation: life long follow-up with or without anti-estrogen (ie.tamoxifen) treatment
Invasive Carcinoma
•Ductal
- NST
- Special Type
*Tubular
*Mucinous (cooloid)
*Medullary
•Lobular
Invasive Ductal Carcinoma NST
- 90% of total breast cancers, arises from ductal epithelium (ductal cells in the TDLU)
- Present as palpable mass or mammographic density
- +/- retraction of nipple and dimpling of skin
- Gross: firm, irregular borders, gritty, and fibrotic with retraction
- Morphology: malignant cells forming tubules, nests, cords and sheets in a fibrotic stroma; pattern and cellular pleomorphism determines grade
- Hormone receptor status and overexpression of Her2/neu varies
- Regional metastasis usually first to regional lymph nodes; distant metastases to lung, pleura & bone
- Invasive Ductal Carcinoma NST
- Cords, solid nests, tubules and anastomosing masses of malignant cells
- Infiltrating in fibrotic stroma
- Grade depends on mitotic rate, nuclear pleomorphism and degree of tubule formation
- Increasing grade correlates with absence of hormone receptors and aneuploidy
Invasive Ductal Carcinoma - Tubular
- Small slow growing, excellent prognosis, rare metastasis
- Morphology: Exclusively consists of well-formed tubules but without myoepithelial cell layer; LCIS frequently present
- Well-differentiated and >95% hormone receptor positive
- Prognosis is excellent with axillary metastases in <10%
Invasive Ductal Carcinoma - Mucinous
- Patients frequently older
- Presents as circumscribed, slowly growing, soft mass
- Gross: Very soft with blue-gray gelatin-like consistency
- Morphology: Clusters of cells floating within lakes of mucin
- Usually hormone receptor positive
- Slightly better prognosis than carcinoma, NST
- More common in BRCA1 mutations
- Lakes of pale staining extracellular mucin containing small islands and isolated tumor cells
Invasive Ductal Carcinoma - Medullary
- Presents as well-circumscribed more yielding mass, frequently with rapid growth
- Gross: Well-circumscribed and softer, fleshy consistency
- Morphology: Sheets of large pleomorphic cells with lymphocytic infiltrate within and surrounding tumor
- Is negative for ER/PR and Her2/neu (triple negative)
- Slightly better prognosis than carcinoma, NST, lymph nodes usually negative
- Common in BRCA1 gene mutations
Invasive Ductal Carcinoma - Inflammatory
- Specific clinical presentation of swollen, erythematous breast, Peau de l’orange skin thickening that may mimic infection
- Symptoms caused by tumor invasion of dermal lymphatics
- Presentation can delay diagnosis
- Clinical course is aggressive with usual axillary metastases at presentation
- 50% survival at 5 years
Invasive Lobular Carcinoma
a. 10% of all breast cancers, arises from lobular epithelium (lobular cells of TDLU)
b. Presents as mass/density or in 25% of cases as vague thickening
c. Gross: most hard with irregular margin but less tissue fibrosis
d. Morphology: Single file poorly cohesive (E-cadherin negative) tumor cells frequently infiltrating around ductal structures
e. Usually ER/PR positive and do not overexpress Her2/neu
f. Distant metastatic pattern different than ductal; goes to lymph nodes, but also to peritoneum, retroperitoneum, leptomeninges, GI tract, ovaries and uterus
- Invasive Lobular Carcinoma
- Single file infiltration by poorly cohesive uniform tumor cells with bland nuclei
- Signet ring cells common
- Frequently arranged in concentric rings around normal lobules
Metastatic Pattern ILC vs IDC
- Both IDC and ILC metastasize to axillary LN’s
- Distant metastatic pattern: ILC has a greater propensity for GI tract, uterus, ovary, serosa (lung is most common distant site for IDC)
Staging
- Includes T, N, M
- Tumor grade
- Her2, ER, PR status
- Molecular testing using multi-gene panels
Male Breast Cancer
- Genetic
- BRACA2
- Klinefelter syndrome
- History of chest irradiation
- Exogenous estrogen
- Obesity
- Ductal
- 81% are Estrogen Receptor positive
