Small....but lethal

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

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)

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

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

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

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

Clinical core biopsy x 4 of the left breast lump

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

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)

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

Further investigations CT 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

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

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

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

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

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

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

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

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

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