Breast carcinoma with abundant eosinophilic cytoplasm, large round nuclei and sharp cell borders
Alternate / Historical Names
Carcinoma with apocrine metaplasia
Sweat gland carcinoma of the breast
Diagnostic Criteria
Clinically significant criteria have not generally been agreed upon
Most describe some degree of abundant eosinophilic cytoplasm, sharp cell borders, round nuclei and prominent nucleoli
Some simply refer to GCDFP15 positive carcinomas as apocrine
Japaze 2005 has proposed the following criteria:
At least 75% of microscopic fields must demonstrate the following features:
Large cells with abundant eosinophilic cytoplasm
Usually granular
Nucleus to cytoplasm ratio of 1:2 or more
Nuclei round, large and vesicular
May be pleomorphic
Sharply defined cell borders
Minor (non-mandatory) criteria
Prominent nucleoli in >50% of fields
Apical cytoplasmic snouts into lumenal spaces
Japaze 2005 reported significantly improved survival when apocrine carcinomas were defined as above
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
Updates: February 9, 2009
Supplemental studies
Immunohistology and Histochemistry
GCDFP15 reactivity is generally considered to be strong and universal in apocrine lesions
Such reactivitiy is taken by some to define apocrine differentiation
Note that the criteria employed by Japaze et al. are not based on immunologic reactivity
PASd may show granular cytoplasmic positivity
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 have not been tested on a series of apocrine carcinomas, thus their utility is unknown
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
Indistinguishable on H&E stain; clinical significance of difference unknown
Clinical
Most studies have shown no clear difference in behavior from usual invasive breast carcinoma
One study, strictly applying the criteria outlined here, found a significantly better prognosis for apocrine carcinoma compared to infiltrating ductal carcinoma NOS (Japaze 2005)
Overall six year survival 72% vs. 52%
Grade 3 overall six year survival 83% vs. 51%
Another study, not using these criteria, found decreased lymph node metastases and decreased lymphatic invasion (Tanaka 2008)
Follow up was too short to evaluate survival
Grading / Staging / Report
Grading
The study of Japaze et al. found a better prognosis for apocrine carcinoma compared to grade matched infiltrating carcinoma NOS, raising the possibility that the grading scheme should be modified for apocrine lesions
Note that the grading scheme for DCIS is modified for apocrine DCIS
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
Japaze H, Emina J, Diaz C, Schwam RJ, Gercovich N, Demonty G, Morgenfeld E, Rivarola E, Gil Deza E, Gercovich FG. 'Pure' invasive apocrine carcinoma of the breast: a new clinicopathological entity? Breast. 2005 Feb;14(1):3-10.
Page DL. Apocrine carcinomas of the breast. Breast. 2005 Feb;14(1):1-2.
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.
Tanaka K, Imoto S, Wada N, Sakemura N, Hasebe K. Invasive apocrine carcinoma of the breast: clinicopathologic features of 57 patients. Breast J. 2008 Mar-Apr;14(2):164-8.
