Definition
Breast carcinoma with small cell neuroendocrine pattern
Alternate / historical names
Oat cell carcinoma
Small cell neuroendocrine carcinoma
Small cell undfferentiated carcinoma
Diagnostic Criteria
Scant cytoplasm
Fine granular chromatin
High mitotic rate
Necrosis common
In situ small cell component may be present
May be associated with other conventional breast carcinoma patterns
Very rare large cell neuroendocrine carcinomas may occur in the breast
Low grade neuroendocrine carcinoma and neuroendocrine carcinoma NOS are considered separately
Richard L Kempson MD
Original posting: May 1, 2006
Supplemental studies
Immunohistology
Keratin reactivity is higher than reported for many other small cell neuroendocrine carcinomas
CK7/20 pattern is typical of usual breast carcinomas
Not all cases have detectable neuroendocrine markers
TTF1 has been reported in a subset of non-pulmonary small cell carcinomas of various sites
ER is not reported to be positive in small cell carcinomas of other sites (Bacchi 1997)
This may support a breast primary
PR is not specific in the context of neuroendocrine carcinomas
Keratin
10/10
CK7
8/10
CK20
0/10
Neuron specific enolase
17/19
Synaptophysin
8/15
Chromogranin A
6/16
Calcitonin
3/12
Gastrin releasing peptide
5/13
E-cadherin
11/11
TTF1
2/10
ER
6/12
PR
9/11
Her2neu
0/10
Modified from Shin 2000
CK7 and CK20 do not distinguish breast from lung adenocarcinomas but may help in the distinction from ovary, pancreas, bile duct and GI carcinomas.
CK7 and CK20 expression in carcinomas
CK7+20+ CK7-20+
Ovary mucinous 90%
Colorectal adeno 80%
Transitional cell 65%
Merkel cell 70%
Pancreas adeno 65%
Gastric adeno 35%
Cholangio 65%
Gastric adeno 40%
Excluded tumors 5% or less
Carcinoid; Germ cell; Esoph squam; Head/neck squam; Hepato-cellular; Lung small cell & squam; Ovary non-mucinous; Renal adeno Excluded tumors 5% or less
Breast; Carcinoid lung; Cholangio; Esoph squam; Germ cell; Lung all types; Hepato-cellular; Ovary; Pancreas adeno; Renal adeno; Transitional cell; Uterus endometrioid
CK7+20- CK7-20-
Ovary non-mucinous 100%
Adrenal 100%
Thyroid (all 3 types) 100%
Seminoma & Yolk Sac 95%
Breast 90%
Prostate 85%
Lung adeno 90%
Hepatocellular 80%
Uterus endometrioid 85%
Renal adeno 80%
Embryonal 80%
Carcinoid intestinal & lung 80%
Mesothelioma 65%
Lung small cell & squam 75%
Transitional cell 35%
Esoph squam 70%
Pancreas adeno 30%
Head/neck squam 70%
Cholangio 30%
Mesothelioma 35%
Excluded tumors 5% or less
Colorectal adeno; Ovary mucinous; Yolk Sac; Seminoma Excluded tumors 5% or less
Breast; Cholangio; Lung adeno; Ovary; Pancreas adeno
Derived from Chu PG, Weiss LM. Histopathology 2002, 40:403-439 and other sources
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
Differential Diagnosis
Metastasis must be excluded whenever small cell carcinoma is found in the breast
ER positive supports a primary carcinoma
Small cell carcinomas of other sites are reported as negative
Negative result is non-contributory
TTF1 negative supports a breast primary
90% of lung small cell carcinomas are positive
Positive result is non-contributory
Clinical and imaging search for another primary site may be useful
Merkel cell carcinoma is 90% positive for CK20
Small cell carcinoma is CK20 negative
Clinical
Prognosis may be stage related
Earlier reported cases did poorly
More recent report (Shin 2000) found 7/9 without disease
Grading / Staging / Report
Grading
Low grade neuroendocrine carcinoma by definition has low grade cytologic features
Round, regular to mildly irregular nuclei up to 2-3x the size of a RBC
No comedo necrosis
Neuroendocrine carcinoma NOS
Behavior appears to be related to conventional Bloom-Scarff-Richardson grading
High grade neuroendocrine carcinoma
Most demonstrate features of small cell carcinoma
Very rare carcinomas have been reported that demonstrate features similar to pulmonary large cell neuroendocrine carcinomas
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
Regional lymph nodes
Report findings as described above
Lists
Infiltrating Breast Carcinomas
Bibliography
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.
Chu PG, Weiss LM. Keratin expression in human tissues and neoplasms. Histopathology. 2002 May;40(5):403-39.
Wade PM Jr, Mills SE, Read M, Cloud W, Lambert MJ 3rd, Smith RE. Small cell neuroendocrine (oat cell) carcinoma of the breast. Cancer. 1983 Jul 1;52(1):121-5.
Shin SJ, DeLellis RA, Ying L, Rosen PP. Small cell carcinoma of the breast: a clinicopathologic and immunohistochemical study of nine patients. Am J Surg Pathol. 2000 Sep;24(9):1231-8.
Shin SJ, DeLellis RA, Rosen PP. Small cell carcinoma of the breast--additional immunohistochemical studies. Am J Surg Pathol. 2001 Jun;25(6):831-2.
Bacchi CE, Garcia RL, Gown AM. Immunolocalization of estrogen and progesterone receptors in neuroendocrine tumors of the lung, skin, gastrointestinal and female genital tracts. Appl Immunohistochem 1997;5:17–22.
