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Surgical Pathology Criteria
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Cribriform Carcinoma of the Breast

Definition

  • Low grade infiltrating carcinoma with a cribriform pattern

Diagnostic Criteria

  • Irregular cribriform growth pattern
    • Round and angular masses of cells embedded in desmoplastic stroma
    • Sharply punched out round spaces
    • Tubular carcinoma has same behavior so may constitute more than 10%
      • Report mixtures of these two simply as the predominant type
  • Nuclear grade I in at least 90% of cells
    • Slightly enlarged cells
    • Uniform nuclei, inconspicuous nucleoli, uniform chromatin
    • Pleomorphism minimal or absent
    • Mitotic figures unusual
    • Remaining 10% must not show nuclear grade III
      • Behavior may be that of the high grade component
      • Report such tumors as mixtures of two types
  • Myoepithelial cells absent on immunohistochemical stains

Richard L Kempson MD
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting:: May 1, 2006

Supplemental studies

Immunohistology

  • Demonstration of myoepithelial cells can confirm the in situ nature of a process while their absence supports invasion
    • We prefer to use both p63 and calponin on problematic cases
    • A variety of markers have been used for myoepithelial cells:
    Marker Sensitivity Specificity
    Calponin Excellent Very good
    p63 Excellent Excellent
    Smooth muscle myosin heavy chain Good Excellent
    CD10 (CALLA) Good Good
    High molecular weight cytokeratin Very good Poor
    Maspin Good Poor
    S100 Good Very poor
    Actin Good Very poor
  • E-cadherin appears to be a sensitive marker of ductal differentiation vs lobular differentiation; its utility in borderline lesions is currently uncertain
  • Estrogen receptor (ER) and progesterone receptor (PR) are important markers for directing therapy and determining prognosis
    • Current consensus is that any level of positivity should be reported as positive
    • Cribriform carcinoma is reported to be 100% ER positive
  • Her2neu status can be determined by either immunohistology or by FISH
    • The other technique can be used for borderline cases

Differential Diagnosis

Tubular Carcinoma vs Cribriform Carcinoma

  • Low grade cribriform carcinoma and tubular carcinoma both have nearly 100% survival
  • We report mixtures of these two types simply as the predominant type
    • 90% pure architectural pattern rule does not apply

Adenoid Cystic Carcinoma Cribriform Carcinoma
Cores of PASd positive basement membrane No basment membrane cores
Myoepithelial component present No myoepithelial component
ckit positive population No ckit positivity
Estrogen receptor generally negative Estrogen receptor uniformly positive
No DCIS DCIS may be present
Low grade cribriform carcinoma and adenoid cystic carcinoma both have nearly 100% survival

Cribriform Carcinoma Collagenous Spherulosis
Grossly visible or palpable lesion Nearly always an incidental microscopic finding
Invasive architecture Circumscribed, intraductal or intralobular
May have intralumenal mucin but lacks fibrillar or laminated appearance Frequently fibrillar or laminated spherules
Lacks myoepithelial component Myoepithelial cells surround spherules
Nuclei slightly enlarged compared to normal (2-3 times larger than RBC) Nuclei identical in size and appearance to normal

Clinical

  • Long term survival reported to be 100% if pure or mixed only with tubular
  • Incidence of axillary lymph node metastases unclear
    • Page 1983 reported 14%
      • Series included both low and moderate nuclear grade
    • Venable 1990 reported 40%
      • Of 8 cases with positive nodes, only one was pure with low grade nuclei
        • Others had grade II nuclei or were mixed
    • 100% survival reported even with axillary metastases in above two series
    • Incidence of axillary metastases in nuclear grade I cribriform carcinoma is unknown
  • Systemic metastases very rare
  • Low stage grade I infiltrating ductal carcinoma has nearly the same prognosis
    • Distinction in difficult cases may not be critical

Grading / Staging / Report

Grading

  • Cribriform carcinoma is by definition low grade

  • Bloom-Scarff-Richardson grading scheme is most widely used
  • Total score and each of the three components should be reported
  • Based on invasive area only
Tubule formation Score
>75% tubules 1
10-75% tubules 2
<10% tubules 3

 

Nuclear pleomorphism (most anaplastic area) Score
Small, regular, uniform nuclei, uniform chromatin 1
Moderate varibility in size and shape, vesicular, with visible nucleoli 2
Marked variation, vesicular, often with multiple nucleoli 3

 

Mitotic figure count per 10 40x fields (depends on area of field, see key below) Score
0.096 mm2 0.12 mm2 0.16 mm2 0.27 mm2 0.31 mm2
0-3 0-4 0-5 0-9 0-11 1
4-7 5-8 6-10 10-19 12-22 2
>7 >8 >10 >19 >22 3
  • Olympus BX50, BX40 or BH2 or AO or Nikon with 15x eyepiece: 0.096 mm2
  • AO with 10x eyepiece: 0.12 mm2
  • Nikon or Olympus with 10x eyepiece: 0.16 mm2
  • Leitz Ortholux: 0.27 mm2
  • Leitz Diaplan: 0.31 mm2
  • Mitotic count figures based on original data presented for Leitz Ortholux by Elston and Ellis 1991, with modifications based on pubished and measured areas of view
  • Evaluate regions of most active growth, usually in cellular areas at periphery
  • We employ strict criteria for identification of mitotic figures
Sum of above three components Overall grade
3-5 points Grade I (well differentiated)
6-7 points Grade II (moderately differentiated)
8-9 points Grade III (poorly differentiated)

Staging

  • TNM staging is the most widely used scheme for breast carcinomas but is not universally employed
  • Critical staging criteria for regional lymph nodes
    • Isolated tumor cell clusters
      • Usually identified by immunohistochemistry
        • Term also applies if cells identified by close examination of H&E stain
      • No cluster may be greater than 0.2 mm
      • Multiple such clusters may be present in the same or other nodes
    • Micrometastasis
        • Greater than 0.2 mm, none greater than 2.0 mm
    • Metastasis
      • At least one carcinoma focus over 2.0 mm
        • If one node qualifies as >2.0 mm, count all other nodes even with smaller foci as involved
      • Critical numbers of involved nodes: 1-3, 4-9 and 10 and over
    • Note extranodal extension

Report

  • Excisions: the following are important elements that must be addressed in the report for infiltrative breast carcinomas
    • Grade
      • Total score and individual components
    • Size of neoplasm
      • Give 3 dimensions or greatest dimension
      • Critical cutoffs occur at 0.5 cm and at 2 cm
    • Margins of resection
      • Measure and report the actual distance of both invasive and in situ carcinoma
    • Angiolymphatic invasion
      • Indicate if confined to tumor mass, outside tumor mass or in dermis
    • (Extensive DCIS is not currently felt to be a significant predictor of behavior)
    • Results of special studies performed for diagnosis
    • Results of prognostic special studies performed
      • ER, PR, Proliferation marker, Her2neu
      • If studies were performed on a prior specimen, refer to that report and give results
  • Needle or core biopsies
    • Provisional grade may be given but may defer to excision for definitive grade
    • Presence of absence of angiolymphatic invasion
    • Results of special studies performed for diagnosis
    • Results of prognostic special studies if performed
      • ER, PR, Proliferation marker, Her2neu
      • State if studies are deferred for a later excision specimen
  • Regional lymph nodes
    • Report findings as described above

Lists

Infiltrating Breast Carcinomas

Bibliography

  • Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991 Nov;19(5):403-10.
  • Page DL. Special types of invasive breast cancer, with clinical implications. Am J Surg Pathol. 2003 Jun;27(6):832-5.
  • Venable JG, Schwartz AM, Silverberg SG. Infiltrating cribriform carcinoma of the breast: a distinctive clinicopathologic entity. Hum Pathol. 1990 Mar;21(3):333-8.
  • Page DL, Dixon JM, Anderson TJ, et al. Invasive cribriform carcinoma of the breast. Histopathol. 1983;7:525-36.
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