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
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
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.
