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A. D’Amuri, F. Floccari, L. Aiello, A. T. Pede, S. A. Senatore

7 – 9 Settembre. 2009. Congresso. Nazionale. Firenze. SIAPEC. Pure type mucinous carcinoma of the breast with neuroendocrine differentiation: a case report and short review of literature. A. D’Amuri, F. Floccari, L. Aiello, A. T. Pede, S. A. Senatore .

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A. D’Amuri, F. Floccari, L. Aiello, A. T. Pede, S. A. Senatore

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  1. 7 – 9 Settembre 2009 Congresso Nazionale Firenze SIAPEC Pure type mucinous carcinoma of the breast with neuroendocrine differentiation: a case report and short review of literature A. D’Amuri, F. Floccari, L. Aiello, A. T. Pede, S. A. Senatore U.O.C. Anatomia Patologica Ospedale “S. Cuore di Gesù” P.O. Gallipoli ASL/LECCE

  2. INTRODUCTION • Mucinous carcinoma (MC) is a special type of invasive breast neoplasm grouped into pure and mixed types: the former contains only tumour with the typical mucinous carcinoma morphology; the latter is mixed with conventional infiltrating ductal carcinoma. • Some authors subdivided MC components on the basis of mucin content, epithelial growth pattern and associated figures in type A (tumors containing 60-90% of mucin) and type B (tumors containing 33-75% of mucin). • A large proportion of MC show a neuroendocrine differentiation and its significance is still unclear.

  3. INTRODUCTION • MC with or without neuroendocrine differentiation occurs in the elderly and the proportion of postmenopausal patients is high. • The symptom and sign is palpable mass and bloody nipple discharge. • The evaluation of MC outcome is difficult because of the short follow-up period due to the old age of the patients who may die of other unrelated causes. • The majority of patients do not show local recurrences or distant metastasis. Lymph nodes metastasis are rare.

  4. CASE REPORT • An 82 year old woman with no significant medical history showed a palpable mass in her retro-areolar right breast. • The patient underwent radical mastectomy and right axillary lymph nodes dissection.

  5. SURGICAL FEATURES • Grossly the right breast showed nipple retraction, discromic skin with a normal areolar gland. The remaining breast parenchima had a lipomatous aspect. • In the retro-areolar region a 4x4x2cm nodular lesion was observed. • The nodule had a hard-elastic consistency, a yellowish white appearance with interspersed brownish and gelatinous areas.

  6. MATERIALS & METHODS • Once removed specimens were fixed in 10% buffered formalin and paraffin embedded. 5mm serial sections were obtained and routinely stained with haematoxylin-eosin (H/E) and histochemically evaluated with Grimelius. • Immunohistochemical studies were performed for Neuron Specific Enolase (NSE), Chromogranin (CGA), Synaptophysin (SYN), Neurofilament (NF), estrogen (ER) and progesteron (PgR) receptors, c-erbB-2 and Ki-67 (MIB-1).

  7. MICROSCOPICAL FINDINGS • Microscopically we observed small clusters of tumor cells with abundant extracellular mucin accumulation (65%). • The cells were small to medium sized with a spindle shape. The nuclei appeared uniform and the cytoplasm eosinophilic and finely granular. • The 19 axillary lymph nodes were found all negative for metastasis.

  8. MICROSCOPICAL FINDINGS • Immunohistochemical stains for NSE, CGA, SYN and NF were positive with a marked histochemical expression of Grimelius (argyrophilic cells). The tumor was positive for estrogen (90%) and progesteron (80%) receptors, incompletely positive for c-erbB-2 (15%) with a low Ki-67 proliferative index (10%). • A diagnosis of pure type mucinous carcinoma (hypercellular variant) of the breast with neuroendocrine differentiation was performed.

  9. H & E H & E Grimelius

  10. NSE SYN CGA

  11. Estrogen receptors Progesteron receptors

  12. DISCUSSION • MC of the breast is a good prognostic type malignancy which may occur in elderly patients. • MC is most commonly associated with neuroendocrine differentiation. • Neuroendocrine differentiation has long been described but its significance is still unknown. • The criteria for diagnosing neuroendocrine differentiation is based on immunohistochemistry, histochemistry with Grimelius for argyrophil reaction and electron microscopy evaluation.

  13. DISCUSSION • As reported in literature some authors consider the expression of the neuroendocrine markers namely CGA, SYN and NSE definitive. • Other authors used two out of three positivity as diagnostic criteria. • It is also associated with higher expression of estrogen and progesteron receptors and lower c-erbB-2 oncoprotein expression and with a low Ki-67 proliferative index. • Lymph nodes metastasis are uncommon.

  14. DISCUSSION • In our case report the clinicopathological features were similar to those reported in literature and included the presence of clusters of tumor cells of moderate-grade with abundant extracellular mucin accumulation. • Our histochemical study (positive for Grimelius) and immunohistochemical findings (positive for CGA, SYN, NSE, NF; higher expression of ER and PgR receptors and lower expression of Ki-67 and c-erbB-2) strongly support the diagnosis. • This type of tumour occurred in an old patient and the axillary lymph nodes were found all negative for metastasis as reported in previous studies.

  15. REFERENCES • Kato N. et al. Mucinous carcinoma of the breast: A multifaceted study with special reference to histogenesis and neuroendocrine differentiation.Pathol Int 1999; 49: 947-955 • Nakagawa H. et al. Mucinous carcinoma of the breast with neuroendocrine differentiation. Pathol Int 2000; 50: 644-648 • David O. et al. Diffuse neuroendocrine differentiation in a morphologically composite mammary infiltrating ductal carcinoma. A case report and review of the literature. Arch Pathol Lab Med 2003; 127: e131-e134 • Tse GMK. et al. Neuroendocrine differentiation in pure type mammary mucinous carcinoma is associated with favorable histologic and immunohistochemical parameters. Mod Pathol 2004; 17: 568-572

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