Groups or trabeculae >2 cells thick infiltrate between collagen bundles
Signet ring variant
Architectural and cytologic features of lobular carcinoma
>20% signet ring differentiation
Mucin positive vacuoles
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
Last update: December 30, 2008
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
E-cadherin is reported to be negative in the pleomorphic variant and positive in the tubulo-lobular variant
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.
The most important prognostic indicators are nodal status, grade and size
See Grading/Staging/Report link at left for guidelines on reporting prognostic factors
Classic lobular carcinoma is reported to have better prognosis than infiltrating ductal carcinoma
May reflect higher grade of many ductal carcinomas
Classic lobular carcinoma is nearly always grade I
In most, but not all studies, infiltrating lobular carcinoma implies a significantly increased risk of developing carcinoma in the contralateral breast
The clinical differences between infiltrating lobular and ductal carcinomas do not translate into any therapeutic importance
Behavior of pleomorphic lobular is roughly that of grade II infiltrating ductal carcinoma
Behavior of tubulo-lobular is roughly that of grade I infiltrating ductal carcinoma
Grading / Staging / Report
Grading
Although classic lobular carcinoma by definition is scored as 3 for lack of tubule formation, cases will receive scores of 1 for nuclear pleomorphism and mitotic count will usually be low, resulting in an overall score of 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
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.
Wick MR, Lillemoe TJ, Copland GT, Swanson PE, Manivel JC, Kiang DT. Gross cystic disease fluid protein-15 as a marker for breast cancer: immunohistochemical analysis of 690 human neoplasms and comparison with alpha-lactalbumin. Hum Pathol. 1989 Mar;20(3):281-7.
Chu PG, Weiss LM. Keratin expression in human tissues and neoplasms. Histopathology. 2002 May;40(5):403-39.
Wheeler DT, Tai LH, Bratthauer GL, Waldner DL, Tavassoli FA. Tubulolobular carcinoma of the breast: an analysis of 27 cases of a tumor with a hybrid morphology and immunoprofile. Am J Surg Pathol. 2004 Dec;28(12):1587-93.
Green I, McCormick B, Cranor M, Rosen PP. A comparative study of pure tubular and tubulolobular carcinoma of the breast. Am J Surg Pathol. 1997 Jun;21(6):653-7.
Fisher ER, Gregorio RM, Redmond C, Fisher B. Tubulolobular invasive breast cancer: a variant of lobular invasive cancer. Hum Pathol. 1977 Nov;8(6):679-83.
Middleton LP, Palacios DM, Bryant BR, Krebs P, Otis CN, Merino MJ. Pleomorphic lobular carcinoma: morphology, immunohistochemistry, and molecular analysis. Am J Surg Pathol. 2000 Dec;24(12):1650-6.
Bentz JS, Yassa N, Clayton F. Pleomorphic lobular carcinoma of the breast: clinicopathologic features of 12 cases. Mod Pathol. 1998 Sep;11(9):814-22.
Weidner N, Semple JP. Pleomorphic variant of invasive lobular carcinoma of the breast. Hum Pathol. 1992 Oct;23(10):1167-71.
Eusebi V, Magalhaes F, Azzopardi JG. Pleomorphic lobular carcinoma of the breast: an aggressive tumor showing apocrine differentiation. Hum Pathol. 1992 Jun;23(6):655-62.
DiCostanzo D, Rosen PP, Gareen I, Franklin S, Lesser M. Prognosis in infiltrating lobular carcinoma. An analysis of "classical" and variant tumors. Am J Surg Pathol. 1990 Jan;14(1):12-23.
Sneige N, Wang J, Baker BA, Krishnamurthy S, Middleton LP. Clinical, histopathologic, and biologic features of pleomorphic lobular (ductal-lobular) carcinoma in situ of the breast: a report of 24 cases. Mod Pathol. 2002 Oct;15(10):1044-50.
Dixon JM, Anderson TJ, Page DL, Lee D, Duffy SW. Infiltrating lobular carcinoma of the breast. Histopathology. 1982 Mar;6(2):149-61.
Fechner RE. Histologic variants of infiltrating lobular carcinoma of the breast. Hum Pathol. 1975 May;6(3):373-8.
Martinez V, Azzopardi JG. Invasive lobular carcinoma of the breast: incidence and variants. Histopathology. 1979 Nov;3(6):467-88.
Shousha S, Backhous CM, Alaghband-Zadeh J, Burn I. Alveolar variant of invasive lobular carcinoma of the breast. A tumor rich in estrogen receptors. Am J Clin Pathol. 1986 Jan;85(1):1-5.
DiCostanzo D, Rosen PP, Gareen I, Franklin S, Lesser M. Prognosis in infiltrating lobular carcinoma. An analysis of "classical" and variant tumors. Am J Surg Pathol. 1990 Jan;14(1):12-23.
Gupta D, Croitoru CM, Ayala AG, Sahin AA, Middleton LP. E-cadherin immunohistochemical analysis of histiocytoid carcinoma of the breast. Ann Diagn Pathol. 2002 Jun;6(3):141-7.
Shimizu S, Kitamura H, Ito T, Nakamura T, Fujisawa J, Matsukawa H. Histiocytoid breast carcinoma: histological, immunohistochemical, ultrastructural, cytological and clinicopathological studies. Pathol Int. 1998 Jul;48(7):549-56.
Eusebi V, Foschini MP, Bussolati G, Rosen PP. Myoblastomatoid (histiocytoid) carcinoma of the breast. A type of apocrine carcinoma. Am J Surg Pathol. 1995 May;19(5):553-62.
Walford N, ten Velden J. Histiocytoid breast carcinoma: an apocrine variant of lobular carcinoma. Histopathology. 1989 May;14(5):515-22.
Nonaka D, Chiriboga L, Soslow RA. Expression of pax8 as a useful marker in distinguishing ovarian carcinomas from mammary carcinomas. Am J Surg Pathol. 2008 Oct;32(10):1566-71.
