1. Small....but lethal

2. History P/C: 44 yr female, presented with symptoms left breast
Painless lump
Not sure of the duration
No skin changes
HOPC & Past history
No nipple discharge, no previous h/o similar complaint
Smoker 20 cig/day, non-diabetic
3 children
No previous h/o benign breast disease

3. History Family History
Mother had breast cancer at the age of 76 (now well)
Paternal aunt had breast cancer at the age of 52 (now well)

4. Clinical Examination Examination finding
Lump on the left upper quadrant
Size 10 cms
Mobile
Non-tender
No skin changes, no nipple discharge
no lymphadenopathy

5. TBC Referral to triple assessment clinic Clinical score: 4 Mammogram
Ultrasound
Core biopsy

6. Ultrasound
10cm x 9.8 cm lobulated homogenous solid lesion with smooth margins at 11 o'clock of left breast

7. Mammogram
large very well defined lesion on the upper central left breast , no microcalcification , right breast is normal. Radiological score of 4

8. Clinical core biopsy x 4 of the left breast lump

9. Histopathological diagnosis
Core biopsy
Presence of partially necrotic infiltrating anaplastic cells suggestive of small cell carcinoma (oat cell carcinoma). On a higher power, the tumour is composed of small cells with hyperchromatic nuclei and minimal cytoplasm. The low power view shows diffuse sheets of tumour cells (T) and extensive necrosis (N) N T x5
x20

10. Immunohistochemistry
Synaptophysin
CLA
Synaptophysin is a neuroendocrine marker and is positive in tumour cells (i.e. brown staining)
CLA, a lymphoid marker, is negative in tumour cells (i.e. no staining)

11. Immunohistochemistry
Positive for CD56 and synaptophysin
Negative for CK7 and CK20
ER,PR and HER-2 negative

12. Further investigationsCT
Bronchoscopy
The lady lost hearing. Due to cisplatin. Fumatidine can reverse the effect of cisplatin. MRI after breast neoadjuvant therapy.
The tumour was growingly rapidly
The patient responded very well after the first cycle of chemotherapy clinically

13. Oat cell carcinoma in breast
Extrapulmonary small-cell neuroendocrine carcinomas account for 2.5% - 5% of all small-cell neuroendocrine tumours
Primary neuroendocrine carcinoma of the breast are a group of neoplasms with morphological features similar to those of neuroendocrine tumours of the gastrointestinal tract and lung.
Primary small cell neuroendocrine carcinoma of the breast (SCNC) is one of the most uncommon variants
Small cell neuroendocrine carcinoma (SCNC) has been described in many extrapulmonary sites including breast, larynx, gastrointestinal tract, prostate, bladder, ovary, and cervix.
WHO classification describe
Although extrapulmonary small-cell neuroendocrine carcinoma has been described in nearly every organ system

14. Most cases are found in women
Incidence
Most cases are found in women
Age incidence years

15. Exclusion of an extra-mammary primary site
Diagnosis
Exclusion of an extra-mammary primary site
Demonstration of an in-situ component within the breast histopathologically
Primary small-cell neuroendocrine carcinoma of the breast can be diagnosed with confidence

16. Histopathology
The morphological and immunohistochemical patterns of this tumour are very similar to its pulmonary counterpart
Some believe that SCNC is a distinct type of breast carcinoma different from the usual types of carcinoma
It is important that the in situ ductal component is truly a precursor lesion of small-cell neuroendocrine carcinoma and supports a primary breast origin

17. Immunohistochemical pattern
Expression of neuroendocrine markers (CAM 5.2, CK7, neuron specific enolase NSE, PGP9.5, chromogranin and synaptophysin) strongly supports the diagnosis
However this expression is inconsistent

18. Hormone receptor expression
Positive expression of ER and PR has been reported in lungs and other sites
Their expression in SCNC is not proof of mammary origin
Varied expression in literature of primary breast SCNC

19. Treatment No standard treatment due to its rarity
Surgery and adjuvant chemoradiotherapy is the mainstay

20. Clinical outcome
Controversial due to the lack of differentiation between primary neuroendocrine tumours and usual carcinoma with foci of neuroendocrine cells
Most SCNC show poor prognosis
Size is an important prognostic factor
Prognosis may not be as poor as originally thought

21. Summary
Primary small cell neuroendocrine carcinoma of the breast (SCNC) is one of the most uncommon variants
The morphological and immunohistochemical patterns of this tumour are similar to its pulmonary counterpart
Size is a very important prognostic factor in this tumour
The prognosis may not be as poor as previously thought, particularly for early stage disease
Early detection and multimodality approach like surgery, chemotherapy and radiotherapy should be used