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On the Endless Dilemma of Neuroendocrine Neoplasms of the Breast: a Journey Through Concepts and Entities

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Abstract

Neuroendocrine differentiation in breast carcinomas has been a matter of discussion since it was first described almost 60 years ago. Indeed, so-called neuroendocrine neoplasms of the breast (Br-NENs) are a less well-defined group of neoplasms than analogous entities in other anatomic sites, such as the lung and the gastroenteropancreatic (GEP) tract. Pure neuroendocrine phenotype is extremely rare, whereas the expression of neuroendocrine markers in usual breast carcinomas, both of special and of non-special type, without evident neuroendocrine morphology, is more common. In this context, the diagnostic criteria and the classification scheme for Br-NENs have been continuously changing over time and real consensus on this topic is still lacking, despite the recent publication of the 5th edition of the WHO classification of breast tumors. In this review, we will recapitulate the evolution of the concept of Br-NEN; revise the available knowledge on their morphological, molecular, and clinical features; and critically discuss the current classification scheme.

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References

  1. Lloyd RV, Osamura RY, Klöppel G, Rosai J (eds) (2017) WHO classification of tumours of endocrine organs, 4th edition. IARC Press, Lyon

    Google Scholar 

  2. Klimstra DS, Klöppel G, La Rosa S, Rindi G (2019) Classification of neuroendocrine neoplasms of the digestives system. In: Carneiro F, Chan JKC, Cheung NYA, et al (eds) WHO classification of the digestive system tumours, 5th edition. IARC Press, Lyon, pp 16-19

    Google Scholar 

  3. Rindi G, Klimstra DS, Abedi-Ardekani B, et al (2018) A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal. Mod Pathol 31:1770-1786

    PubMed  PubMed Central  Google Scholar 

  4. Feyrter F, Hartmann G (1963) Uber die carcinoide Wuchsform der Carcinoma mammae, insbesondere das Carcinoma Solidum (gelatinosum) mammae. Frankf Z Pathol 73:24–39

    CAS  PubMed  Google Scholar 

  5. Cubilia AL, Woodruff JM (1977) Primary carcinoid tumors of the breast: a report of 8 cases. Am J Surg Pathol 1:283–292

    Google Scholar 

  6. Capella C, Eusebi V, Mann B, Azzopardi JG (1980) Endocrine differentiation in mucoid carcinoma of the breast. Histopathology 4:613-630

    CAS  PubMed  Google Scholar 

  7. Ferguson DJP, Anderson TJ (1985) Distribution of dense core granules in normal, benign and malignant breast tissue. J Pathol 147:59-65

    CAS  PubMed  Google Scholar 

  8. Nesland JM, Memoli VA, Holm R, Gould VE, Johannessen JV (1985) Breast carcinoma with neuroendocrine differentiation. Ultrastruct Pathol 8:225-240

    CAS  PubMed  Google Scholar 

  9. Capella C, Usellini L, Papotti M, Macri L, Finzi G, Eusebi V, Bussolati G (1990) Ultrastructural features of neuroendocrine differentiated carcinomas of the breast. Ultrastruct Pathol 14:321-334

    CAS  PubMed  Google Scholar 

  10. Bussolati G, Gugliotta P, Sapino A, Eusebi V, Lloyd RV (1985) Chromogranin reactive endocrine cells in argyrophilic carcinomas (“carcinoids”) and normal tissue of the breast. Am J Pathol 120:186–192

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Nesland JM, Holm R, Johannessen JV (1986) Breast carcinomas with neuroendocrine activity. In: Hollmann K.H., Verley J.M. (eds) New frontiers in mammary pathology 1986. Developments in Oncology, vol 49. Springer, Dordrecht, pp 187-196

    Google Scholar 

  12. La Rosa S, Usellini L, Riva C, Capella C (2007) Well-differentiated neurotensin-producing neuroendocrine carcinoma of the breast. Report of a case. Histopathology 51:846-847

    PubMed  Google Scholar 

  13. Papotti M, Macri L, Finzi G, Capella C, Eusebi V, Bussolati G (1989) Neuroendocrine differentiation in carcinomas of the breast: a study of 51 cases. Semin Diagn Pathol 61:174-188

    Google Scholar 

  14. Maluf HM, Koerner FC (1994) Carcinomas of the breast with endocrine differentiation: a review. Virchows Arch 425:449-457

    CAS  PubMed  Google Scholar 

  15. Ellis P, Schnitt SJ, Sastre-Garau X, et al (2003) Invasive breast carcinoma In: Tavassoli FA, Devilee P (eds) Tumours of the breast and female genital organs: pathology and genetics. IARC Press, Lyon, pp 13-59

    Google Scholar 

  16. Uccella S, Sessa F, La Rosa S (2015) Diagnostic approach to neuroendocrine neoplasms of the gastrointestinal tract and pancreas. Turk Patoloji Derg 31(Suppl 1):113-127

    PubMed  Google Scholar 

  17. Bussolati G, Badve S (2012) Carcinomas with neuroendocrine features. In: Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver MJ (eds) WHO classification of tumours of the breast. IARC Press, Lyon, pp 62-63

    Google Scholar 

  18. Rosen LE, Gattuso P. Neuroendocrine tumors of the breast (2017) Arch Pathol Lab Med 141:1577-1581.

    CAS  PubMed  Google Scholar 

  19. Rakha EA, Reis-Filho JS, Sasano H, Wu Y (2019) Neuroendocrine neoplasms: introduction. In: WHO classification of tumours editorial board. Breast tumours. WHO classification of tumours series, 5th ed. IARC, Lyon, pp 155

    Google Scholar 

  20. Rakha EA, Reis-Filho JS, Wu Y (2019) Neuroendocrine carcinoma. In: WHO classification of tumours editorial board. Breast tumours. WHO classification of tumours series, 5th ed. IARC, Lyon, pp 159-161

    Google Scholar 

  21. McCullar B, Pandey M, Yaghmour G, Hare F, Patel K, Stein K, Feldman R, Chandler JC, Martin MG (2016) Genomic landscape of small cell carcinoma of the breast contrasted to small cell carcinoma of the lung. Breast Cancer Res Treat 158:195-202

    CAS  PubMed  Google Scholar 

  22. Hare F, Giri S, Patel JK, Hahn A, Martin MG (2015) A population-based analysis of outcomes for small cell carcinoma of the breast by tumor stage and the use of radiation therapy. Springerplus 4:138

    PubMed  PubMed Central  Google Scholar 

  23. Shin SJ, DeLellis RA, Ying L, Rosen PP (2000) Small cell carcinoma of the breast: a clinicopathologic and immunohistochemical study of nine patients. Am J Surg Pathol 24:1231-1238

    CAS  PubMed  Google Scholar 

  24. Mirza IA, Shahab N (2007) Small cell carcinoma of the breast. Semin Oncol 34:64-66

    CAS  PubMed  Google Scholar 

  25. Uccella S, La Rosa S, Volante M, Papotti M (2018) Immunohistochemical biomarkers of gastrointestinal, pancreatic, pulmonary, and thymic neuroendocrine neoplasms. Endocr Pathol 29:150-168

    PubMed  Google Scholar 

  26. Wang J, Wei B, Albarracin CT, Hu J, Abraham SC, Wu Y (2014) Invasive neuroendocrine carcinoma of the breast: a population-based study from the surveillance, epidemiology, and end results (SEER) database. BMC Cancer 14:147

    PubMed  PubMed Central  Google Scholar 

  27. Abou Dalle I, Abbas J, Boulos F, Salem Z, Assi HI (2017) Primary small cell carcinoma of the breast: a case report. J Med Case Rep 11:290

    PubMed  PubMed Central  Google Scholar 

  28. Tremelling A, Samuel S, Murray M (2017) Primary small cell neuroendocrine carcinoma of the breast—a case report and review of the literature. Int J Surg Case Rep 38:29-31

    PubMed  PubMed Central  Google Scholar 

  29. Alkaied H, Harris K, Brenner A, Awasum M, Varma S (2012) Does hormonal therapy have a therapeutic role in metastatic primary small cell neuroendocrine breast carcinoma? Case report and literature review. Clin Breast Cancer 12:226-230

    PubMed  Google Scholar 

  30. Jesinghaus M, Konukiewitz B, Keller G, et al (2017) Colorectal mixed adenoneuroendocrine carcinomas and neuroendocrine carcinomas are genetically closely related to colorectal adenocarcinomas. Mod. Pathol 30:610-619

    CAS  PubMed  Google Scholar 

  31. Woischke C, Schaaf CW, Yang HM et al (2017) In-depth mutational analyses of colorectal neuroendocrine carcinomas with adenoma or adenocarcinoma components. Mod Pathol 30: 95-103

    CAS  PubMed  Google Scholar 

  32. Rakha EA, Reis-Filho JS, Sasano H, Wu Y (2019) Neuroendocrine tumor. In: WHO classification of tumours editorial board. Breast tumours. WHO classification of tumours series, 5th ed. IARC, Lyon, pp 156-158

    Google Scholar 

  33. Sapino A, Righi L, Cassoni P, Papotti M, Gugliotta P, Bussolati G (2001) Expression of apocrine differentiation markers in neuroendocrine breast carcinomas of aged women. Mod Pathol 14:768-776

    CAS  PubMed  Google Scholar 

  34. Marchiò C, Geyer FC, Ng CKY, et al (2017) The genetic landscape of breast carcinomas with neuroendocrine differentiation. J Pathol 241:405–419

    PubMed  Google Scholar 

  35. Terlević R, Perić Balja M, Tomas D, Skkenderi F, Kruslin B, Vranic S, Demirovic A (2019) Somatostatin receptor SSTR2A and SSTR5 expression in neuroendocrine breast cancer. Ann Diagn Pathol 38:62-66

    PubMed  Google Scholar 

  36. Kumar U, Grigorakis SI, Watt HL, Sasi R, Snell L, Watson P, Chaudhari S (2005) Somatostatin receptors in primary human breast cancer: quantitative analysis of mRNA for subtypes 1–5 and correlation with receptor protein expression and tumor pathology. Breast Cancer Res Treat 92:175–86

    CAS  PubMed  Google Scholar 

  37. Frati A, Rouzier R, Lesieur B, Werkoff G, Antoine M, Rodenas A, Darai E, Chereau E (2014) Expression of somatostatin type-2 and -4 receptor and correlation with histological type in breast cancer. Anticancer Re 34:3997–4003

    Google Scholar 

  38. Mohanty SK, Kim SA, DeLair DF, Bose S, Laury AR, Shefali C, Mertens RB, Dhall D (2016) Comparison of metastatic neuroendocrine neoplasms to the breast and primary invasive mammary carcinomas with neuroendocrine differentiation. Mod Pathol 29:788-798

    CAS  PubMed  Google Scholar 

  39. Papalampros A, Mpaili E, Moris D, Sarlanis H, Tsoli M, Felekouras E, Trafalis DT, Kontos M (2019) A case report on metastatic ileal neuroendocrine neoplasm to the breast masquerading as primary breast cancer: a diagnostic challenge and management dilemma. Medicine 98:e14989

    PubMed  PubMed Central  Google Scholar 

  40. La Rosa S, Casnedi S, Maragliano R, Goyault G, Weber JC, Louis B, Schlund E, Sessa F (2015) Breast metastasis as the first clinical manifestation of ileal neuroendocrine tumor. A challenging diagnosis with relevant clinical implications. Endocr Pathol 26:145–51

    PubMed  Google Scholar 

  41. Uccella S, Mathias-Guiu X, La Rosa S (2020) Genitourinary neuroendocrine neoplasms. In: Asa SL, La Rosa S, Mete O (eds) The spectrum of neuroendocrine neoplasia. Practical approach to diagnosis, classification and therapy. New York, Springer, in press

    Google Scholar 

  42. Uccella S, La Rosa S (2020) Neuroendocrine neoplasms of the upper aerodigestive tract, ear and salivary glands. In: Asa SL, La Rosa S, Mete O (eds) The spectrum of neuroendocrine neoplasia. Practical approach to diagnosis, classification and therapy. New York, Springer, in press

    Google Scholar 

  43. Uccella S, Ottini G, Facco C, Maragliano R, Asioli S, Sessa F, La Rosa S (2017) Neuroendocrine neoplasms of the head and neck and olfactory neuroblastoma. Diagnosis and classification. Pathologica 109:14-30

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Pathology Unit, Department of Medicine and Surgery, University of Insubria, Varese, Italy

    Silvia Uccella & Fausto Sessa

  2. Department of Pathology, ASST dei Sette Laghi, Varese, Italy

    Giovanna Finzi

  3. Institute of Pathology, University Hospital and University of Lausanne, Lausanne, Switzerland

    Stefano La Rosa

Authors
  1. Silvia Uccella
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  2. Giovanna Finzi
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  3. Fausto Sessa
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  4. Stefano La Rosa
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Correspondence to Silvia Uccella.

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Uccella, S., Finzi, G., Sessa, F. et al. On the Endless Dilemma of Neuroendocrine Neoplasms of the Breast: a Journey Through Concepts and Entities. Endocr Pathol 31, 321–329 (2020). https://doi.org/10.1007/s12022-020-09637-y

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