Small....but lethal

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

7. Mammogram

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

9. Histopathological diagnosis Core biopsy N T x20 x5

10. Immunohistochemistry Synaptophysin CLA

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

12. Further investigations • CT • Bronchoscopy

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

14. Incidence • Most cases are found in women • Age incidence 40-70 years

15. Diagnosis • Exclusion of an extra-mammary primary site • Demonstration of an in-situ component within the breast histopathologically

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