Ductal Carcinoma In Situ (DCIS) /Intraductal Carcinoma Pathology 1

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Significant increase in incidence after mammography screening:
    • 17-fold increase from 1970’s to 2004:
      • 1 in 1300 mammograms
    • Represents 20% of all screen-detected breast neoplasias diagnosed annually
  • DCIS by it self:
    • Is not a risk to life
  • DCIS may progress to invasion and compromise survival:
    • If left untreated:
      • 1 in 6 DCIS patients:
        • Progress to invasive breast cancer (IBC):
          • 70% estimated to remain indolent
  • At this time we do not have any robust biomarkers:
    • That can quantify the risk of progression to IBC or
    • Help us separate indolent disease:
      • From the potentially dangerous lesions
  • Risk of overtreament:
    • The increase incidence of DCIS in mammographically detected cases:
      • Has not lead to a decrease in the incidence of IBC or reduction of IBC morality
  • Risk factors for progression / recurrence of DCIS:
    • The risk factors for IBC recurrence may be different from the risks factors for DCIS recurrence?
      • Risk of IBC recurrence:
        • African American race
        • Premenopausal status
        • Detection by palpation
        • Involved margins
        • High histologic grade
        • High p16 expression
      • Risk of IBC or DCIS recurrence:
        • DCIS size
        • Histology type
        • Comedo necrosis
        • Grade
        • Young age
        • Close margins or positive margins
    • Patients with DICIS that recur with an IBC:
      • Some patients with DCIS may develop:
        • Progression of there disease
        • Some will have a de novo invasive breast cancer
        • Some might have a missed invasive cancer?
    • Patient that have a DCIS recurrence:
      • Might be a true in situ recurrence
      • De novo DCIS
      • Residual disease?
    • Studies are describing observations of events:
      • Synchronous IBC
      • Subsequent ipsilateral or contralateral DCIS or IBC (often a mixture)
      • We have limited data on DCIS progression with paired molecular profiles
  • The most consistent biological feature of DCIS:
    • Heterogeneity:
      • In clinical presentation
      • Morphology
      • Protein expression:
        • Including receptor status
      • Gene expression
      • Genetic alterations
      • Epigenetic alterations
    • The heterogeneity is:
      • Between patients – within the lesion – and within cells in a single duct
  • Morphological features that help us predict progression is:
    • Histologic grading:
      • Combing the nuclear grade 1 to 3 and necrosis into a three tier system (the good, the bad, and the ugly):
        • Low / intermediate / high grade
        • Grade 1 to 3
        • Van Nuys Group 1 to 3
        • DIN 1 to 3
      • We all know that there is regression towards the mean and substantial interobserver variation
Morphologic Features Suggestive of Progression
  • Unclear prognostic value of the 3-tier system:
    • We suspect that:
      • Low to intermediate grade = low risk of progression
      • High grade system = high risk of progression or shorter time to progression
    • Maxwell, A.J. Eur.J.Surg.Oncol.,2018, Ryser, MD. J.Natl Cancer Inst., 2019:
      • Risk of ipsilateral recurrence (DCIS / IBC) at 10 years:
        • High grade 17.6% (95% CI=12.1-25.2%)
        • Non high grade 12.2 (95% CI=8.6-17.1%):
          • Including grade 2
      • There is overlap in the confidence intervals
    • Low grade DCIS are the lesions that might have:
      • Discontinuous growth and skip lesions that might lead to a:
        • Greater likelihood of residual disease and recurrence?
    • Heterogeneity of grade within a lesion
  • Histology subtype as a prognostic factor:
    • Subtype:
      • Cribriform is more often a grade 1 lesion
      • Comedo type is more often a grade 3 lesion
    • Usually histology subtype correlates with grade but:
      • There is often a mixture of growth patterns:
        • Compromising the use for prognostication
Can we use histology as a prognostic feature?
  • Tumor micro environment:
    • Could potentially be the most important morphologic feature suggestive of progression especially:
      • Circumferential periductal fibrosis and associated tumor infiltrating lymphocytes (TIL):
        • Indicating host reaction to the tumor cells
    • Tumor micro environment includes:
      • Myoepithelial cell layer
      • Tumor infiltrating lymphocytes (TIL)
      • Adipocytes
      • Fibroblasts
      • Matrix
The border around the myoepithelial layer might have prognostic value.
  • The myoepithelial layer acts as a gatekeeper:
    • Has tumor suppressive functions
    • The largest gene expression change from normal tissue to DCIS:
      • Occurs in the myoepithelial layer
    • DCIS associated myoepithelial loss:
      • That leads the decrease tumor suppressor functions
    • The myoepithelial layer is lost in IBC
Myoepithelial layer acts as a GATEKEEPER
  • Disruption of the myoepithelial defense:
IBC with DCIS
Brown color – myoepithelium
Arrows point to the disrupted myoepithelial layer (micro-invasion)
  • Conflicting data on prognostic value of TIL:
    • Some studies have reported no prognostic value of stromal TIL for subsequent recurrences:
      • Does the spatial location of the immune cells matter?
        • The TIL in direct contact with the DCIS might be more important that the TIL that are further away
    • Other studies have shown a correlation between higher levels of TIL and increased risk of subsequent IBC and a shorter (ipsilateral) recurrence-free survival
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Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

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