Invasive Ductal Carcinoma (Adenocarcinomas of No Special Type)

Invasive Ductal Carcinoma (Adenocarcinomas of No Special Type)
Key Facts
Terminology
  • Invasive ductal carcinoma includes carcinomas not classified as a special histologic type
  • Synonymous with “no special type” or “not otherwise specified” carcinoma
Etiology/Pathogenesis
  • Heterogeneous with regard to pathologic features, prognosis, and clinical outcome
  • ˜ 75% of invasive breast cancers
  • 4 types based on ER, PR, HER2, & proliferation
    • Luminal A, luminal B, HER2, and basal types
  • ˜ 1 in 8 women will develop breast cancer during her lifetime
  • Median age at diagnosis: 61 years
    • < 15% diagnosed before age 44
Clinical Issues
  • For women < 40, 85% detected as a palpable mass and 15% by screening
  • For women > 40, 60% detected by screening and 40% as a palpable mass
Image Findings
  • Masses, calcifications, and architectural distortion
Top Differential Diagnoses
  • Special histologic types
  • Ductal carcinoma in situ
  • Sclerosing lesions
  • Microglandular adenosis
  • Epithelial displacement
  • Other types of malignant tumors
  • Metastatic tumors to the breast
Invasive carcinomas image typically form firm to hard radiodense white masses that replace radiolucent yellow adipose tissue image and thus may be detected as palpable masses or mammographic densities.
The border of an invasive carcinoma is characteristically irregular due to tumor cells infiltrating into the surrounding stroma. Less common are carcinomas with circumscribed or lobulated borders.
TERMINOLOGY
Abbreviations
  • Invasive ductal carcinoma (IDC)
Synonyms
  • Infiltrating ductal carcinoma
  • Not otherwise specified (NOS) carcinoma
  • No special type (NST) carcinoma
Definitions
  • IDC includes all adenocarcinomas of the breast that are not classified as a special histologic type
ETIOLOGY/PATHOGENESIS
Classification
  • IDC is a heterogeneous group of adenocarcinomas with regard to pathologic features, prognosis, and clinical outcome
    • Termed “ductal” because associated ductal carcinoma in situ expands and unfolds lobular units; thus resembles ducts more than lobules
      • In contrast, lobular carcinoma in situ expands but usually does not distort lobules; the type of associated invasive carcinoma was termed “lobular” carcinoma
    • All carcinomas are thought to arise from terminal duct lobular unit
    • Terms “ductal” and “lobular” do not indicate cell or structure of origin
  • ˜ 75% of invasive breast cancers
    • Remaining (˜ 25%) are defined as special histologic types based on morphologic features
    • For small screen-detected cancers, ˜ 60% are of special histologic type
  • Therefore, most studies of “breast cancer” are primarily of IDC
  • IDC can be divided into 4 major types: Luminal A, luminal B, HER2, and basal-like
    • Gene expression profiling demonstrates that each type shares global expression patterns
    • Same cancer types can be defined based on expression of ER, PR, HER2, and proliferation
    • Subtypes defined by profiling and IHC overlap by 80-85%
      • Although groups originally defined by expression profiling, convenient to use the same names to describe the very similar groups of cancers as defined by IHC
      • Here, basal-like carcinoma and triple negative breast carcinoma are described as 1 group
    • Classification by IHC has the advantage of organizing cancers according to therapeutic targets and likely response to chemotherapy
      • Some HER2 carcinomas defined by expression profiling do not overexpress HER2
      • Not yet clear if expression profiling adds sufficient additional information to warrant its use for routine classification
CLINICAL ISSUES
Epidemiology
  • Incidence
    • In USA, 1 woman in 8 (˜ 12%) will develop breast cancer in her lifetime
      • Highest incidence is for white women, and lowest incidence is for Native-American women
      • African-American women have a lower incidence compared to white women but higher mortality rates
      • Hispanic women have both lower incidence and lower mortality rates
  • Age
    • Median at diagnosis: 61 years
      • < 15% of cases diagnosed before age 44
  • Gender
    • All females are at high risk for breast cancer
      • Only 1 of 100 breast cancer cases occur in men
Presentation
  • Patients most commonly present with a palpable mass or abnormality on screening
    • For women < 40, 85% of carcinomas are detected as a palpable mass and 15% on breast imaging
      • Imaging may occur in this age group due to family history or as part of a work-up for a clinical finding (e.g., nipple discharge, pain, or skin changes)
    • For women > 40, 60% of carcinomas are detected by screening and 40% as a palpable mass
  • Some cancers are not detected by mammography
    • Obscured by dense breast tissue
    • Present in unusual location and missed by routine views
    • Become apparent between screenings due to rapid growth (“interval” cancer)
  • > 85% of palpable cancers are detected by the patient, the remainder by physician examination
    • Self breast examination has not been shown to decrease death rate from breast cancer
      • Suggests that cancers that are capable of metastasizing will have done so by the time they become palpable
  • Palpable cancers are typically larger (2-3 cm) than screen-detected (1-2 cm) cancers
    • Palpable cancers have a less favorable prognosis compared to nonpalpable cancers of the same size
  • Uncommon presentations of breast cancer are nipple discharge, Paget disease, pain, or metastasis
Treatment
  • Most patients will be treated with multiple modalities
  • Surgery: Controls local disease and may be curative for localized cancers
  • Radiation therapy: Reduces local recurrences and has a small effect on survival
  • Endocrine therapy: Improves survival for patients with hormone-sensitive cancers
  • Chemotherapy: Improves survival in subsets of patients with sensitive cancers; general correlation with higher proliferative rates
    • HER2-targeted therapy improves survival for carcinomas with overexpression
Prognosis
  • Wide range of probable survival for IDC depending upon prognostic and predictive factors
    • Stage: Based on size, chest wall or skin involvement, and lymph node involvement
    • Grade: Modified Bloom-Richardson grade should be provided for all breast carcinomas
    • Subtype: Includes ER, PR, HER2, and proliferation
    • Lymph-vascular invasion
    • Response to therapy: May be evaluated if neoadjuvant therapy is used
  • Gene expression profiling can also be used to determine prognosis in ER-positive IDC
    • Several different profiles are commercially available
    • Profiles are largely driven by genes related to proliferation
  • Outcome is highly dependent on treatment
    • Reduction in the death rate from cancer is attributed to both improved detection of earlier cancers by screening and to systemic therapy
IMAGE FINDINGS
Mammographic Findings
  • Masses, calcifications, and architectural distortion correlated with IDC
    • Vast majority of IDCs form irregular masses due to infiltration into surrounding stroma
      • Only benign lesions that typically have this appearance are radial sclerosing lesions or inflammatory lesions (e.g., prior surgical sites or infections)
    • Less common for IDC to have circumscribed or lobulated borders
      • Basal-like/triple negative cancer most likely to have this appearance
      • Special histologic types of mucinous carcinoma and medullary carcinoma also have circumscribed borders
    • Calcifications are most commonly present in associated DCIS
      • IDCs detected as calcifications without a mass are typically very small (< 1 cm)
      • Calcifications are occasionally present in secretory material or necrosis in the IDC
    • Architectural distortion is uncommon finding
      • Carcinomas with this appearance are usually diffusely invasive with minimal stromal response
      • Invasive lobular carcinomas are most common carcinoma with this finding
Ultrasonographic Findings
  • Borders of invasive carcinomas by ultrasound usually correlate with the shape seen on mammography
  • Almost all carcinomas are hypoechoic as cancers consist of tumor cells and fibrous desmoplastic stroma
    • Very rarely, cancers can be hyperechoic due to infiltrative pattern into adipose tissue with minimal stromal response
  • Not very useful as a screening modality due to low specificity
    • Most helpful to further define lesions detected by mammography or MR
    • Size by ultrasound has best correlation with gross tumor size
MR Findings
  • Carcinomas are detected by MR due to quick uptake of contrast agents, resulting in rapid enhancement
  • Shape of masses on imaging does not correlate well with actual borders of lesion
    • MR overestimates size in a significant percentage of patients
  • MR is very sensitive (few cancers are occult by this modality) but not very specific
    • Not recommended for screening except for very high-risk populations
MACROSCOPIC FEATURES
General Features
  • Majority of IDCs are very hard by palpation
    • Often “gritty” when cut
    • Cut surface is typically gray-white
  • Carcinomas typically have irregular borders
    • Less common are carcinomas with circumscribed or lobulated borders
Size
  • Important prognostic factor and is used for AJCC T classification
  • Best determined by palpation rather than visual inspection
    • Cancers are often white (like adjacent fibrous breast stroma); can be difficult to see edges
    • Usually a palpable shelf between edge of tumor and normal breast tissue
      • Extent can be determined by pinching the mass between 2 fingers
MICROSCOPIC PATHOLOGY
Histologic Features
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Jul 6, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Invasive Ductal Carcinoma (Adenocarcinomas of No Special Type)

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