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Surgical Pathology Criteria
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Invasive Micropapillary Carcinoma of the Breast

Definition

  • Breast carcinoma with a prominent (pseudo) micropapillary pattern

Diagnostic Criteria

  • Numerous small pseudo-papillary clusters of cells
    • No fibrovascular cores
    • Frequent central lumen formation in clusters
    • Peripherally located nuclei frequently bulge out with knobby appearance, "the hedgehog" tumor
  • Clusters surrounded by clear spaces
    • One or only a few clusters per space
    • Scant mucin rarely detectable in spaces
  • Spaces surrounded by loose fibrocollagenous stroma
  • Frequent high nuclear grade reported in some series
  • Frequently has abundant eosinophilic cytoplasm
  • Frequent lymphatic involvement
  • Occasional psammoma bodies
  • Associated DCIS may be of various types
  • Pattern may be predominant or focal
    • No clinical difference between predominant and focal cases
    • No reported cutoff for minimal significant amount of pattern
    • Report such cases as mixed
  • Frequently mixed with infiltrating ductal carcinoma
    • Rarely mixed with other type

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

  • Reported phenotype of micropapillary carcinomas
    E-cadherin 100%
    GCDFP15 50%
    ER/PR 20-90%
    Her2neu 35-100%
    p53 40-70%
    CK7 83%
    CK20 0%

Immunohistochemistry of micropapillary carcinomas of various sites
  CK7 CK20 GCDFP15 ER PR TTF1
Bladder 100% 90% ND ND ND ND
Breast 83% 0% 50% 20-90% 20-90% ND
Large Intestine 0% 100% ND ND ND ND
Lung 93% 13% ND ND ND 80%
Salivary Gland 100% 0% 83% 8% 8% ND
Ovary 100% 15% <5% 100% 90% 1%
No data available on ampullary/pancreatic/biliary tumors

Prognostic/Therapeutic Markers

  • 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
  • Her2neu status can be determined by either immunohistology or by FISH
    • The other technique can be used for borderline case

Genetic analysis

  • Her2neu status can be determined by either immunohistology or by FISH
    • The other technique can be used for borderline cases

Differential Diagnosis

Usual infiltrating carcinoma with retraction artifact

  • Retraction artifact usually occurs with dense stroma
  • Micropapillary carcinoma is characterized by:
    • Fine fibrocollagenous stroma
    • Uniformity and density of pattern in involved areas

 

Usual infiltrating carcinoma with extensive lymphovascular invasion

  • Lymphovascular invasion is delimited by CD31 positive endothelial cells
  • Micropapillary carcinoma is characterized by:
    • Lack of surrounding endothelium
    • Uniformity and density of pattern in involved areas

 

Mucinous Carcinoma Micropapillary Carcinoma
Prominent mucin in spaces Spaces generally clear with infrequent, scant stainable mucin
Irregular epithelial clusters Numerous, relatively uniform clusters, one or a few per space
Usually low grade cytology Frequently high grade cytology

Immunohistochemistry of micropapillary carcinomas of various sites
  CK7 CK20 GCDFP15 ER PR TTF1
Bladder 100% 90% ND ND ND ND
Breast 83% 0% 50% 20-90% 20-90% ND
Large Intestine 0% 100% ND ND ND ND
Lung 93% 13% ND ND ND 80%
Salivary Gland 100% 0% 83% 8% 8% ND
Ovary 100% 15% <5% 100% 90% 1%
No data available on ampullary/pancreatic/biliary tumors

  • Identification of adjacent DCIS strongly supports a breast primary
  • Clinical information and imaging studies will frequently be necessary to rule out other primary sites.

Clinical

  • Incidence
    • Pure about 1%
    • Mixed about 4-7%
  • Frequent local recurrence (70-90%)
  • Poor prognosis
    • Approximate 40% dead of disease in three years
    • Not independent of stage
      • Linked to high incidence of nodal involvement
  • Rare cases reported in males

Grading / Staging / Report

Grading

  • 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

  • Micropapillary carcinoma is associated with frequent lymph node metastases
    • Seen even with primary tumors <1 cm
    • Seen even with mixed tumors with small micropapillary component
    • Nodal involvement is frequently by micrometastases

  • 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

Micropapillary Carcinomas

  • Ampullo-pancreatobiliary region
  • Bladder
  • Breast
  • Large intestine
  • Lung
  • Major salivary glands
  • Ovary (serous)

Bibliography

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  • Kim MJ, Gong G, Joo HJ, Ahn SH, Ro JY. Immunohistochemical and clinicopathologic characteristics of invasive ductal carcinoma of breast with micropapillary carcinoma component. Arch Pathol Lab Med. 2005 Oct;129(10):1277-82.
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