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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
  • Not related to micropapillary DCIS
• 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
• 
  

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 span="" 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="" span="">
  • 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