Richard L Kempson MD
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342
Original posting: August 4, 2007
Updates: February 13, 2009
Tubulolobular Carcinoma Is Not Really Tubular
Serial sections with 3-D reconstruction shows the actual structure is not tubular
No continuous and/or branching tubules
Pattern is better described as a necklace formed by a string of beads
Oval to spherical cavitated blebs with tapering ends
Connected by moderately long strands of cells
Tubular carcinoma has a similar pattern but with short connecting strands of cells
These findings explain the observed pattern that always appears to be cross-sections or oblique sections of tubules, but never longitudinal sections
See Marchio et al. 2006 for the full story
Supplemental studies
Immunohistology
E-cadherin is consistently (and definitionally) positive in tubulolobular carcinoma
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
Immunologic markers useful for identification of breast carcinoma
GCDFP15 (BRST2)
Estrogen Receptor
Progesterone Receptor
PAX8
Infiltrating ductal carcinoma
60-70%
75%
50-60%
0%
Infiltrating lobular carcinoma
60-70%
>95%
80%
0%
Lung adenocarcinoma
0-1%
<5%
<5%
0%
Ovarian adenocarcinoma
1-5%
50-100%
40-90%
90-100%
Endometrioid adenocarcinoma
negative
70%
70%
GI adenocarcinoma
negative
<5%
1-10%
0%
Pancreatic adenocarcinoma
negative
negative
0-5%
0%
Cholangiocarcinoma
negative
negative
30%
Thyroid carcinoma
negative
20%
30%
100%
Sweat gland and salivary gland neoplasms may also be positive for GCDFP15, ER and PR
Prostatic adenocarcinoma may be positive for GCDFP15
CK7 and CK20 do not distinguish breast from lung adenocarcinomas but may help in the distinction from ovary, pancreas, bile duct and GI carcinomas.
Behavior of tubulolobular is roughly that of grade I infiltrating ductal carcinoma
Rare, constitutes approximately 1% of breast carcinomas
Grading / Staging / Report
Grading
Tubulolobular carcinoma is by definition nuclear grade I
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
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