Other carcinomas
Large cell neuroendocrine carcinoma

Authors: Ximing J. Yang, M.D. Ph.D. (see Authors page)

Revised: 14 July 2016, last major update July 2016

Copyright: (c) 2003-2016,, Inc.

PubMed search: Large cell neuroendocrine carcinoma prostatic
Cite this page: Large cell neuroendocrine carcinoma . website. Accessed March 29th, 2017.
Definition / General
  • High grade prostatic carcinoma composed of large cells with diffuse neuroendocrine features
  • Neuroendocrine differentiation of prostate carcinoma is classified as follows (Am J Surg Pathol 2014;38:756, Endocr Pathol 2016;27:123):
    • Usual prostatic adenocarcinoma with neuroendocrine differentiation
    • Prostatic adenocarcinoma with Paneth cell neuroendocrine differentiation
    • Carcinoid tumor
    • Small cell carcinoma
    • Large cell neuroendocrine carcinoma
    • Mixed (small or large cell) neuroendocrine carcinoma with usual prostatic adenocarcinoma
Essential Features
  • Composed of tumor cells larger than those in small cell (neuroendocrine) carcinoma, also with slightly more cytoplasm (Am J Clin Exp Urol 2014;2:273, Am J Clin Exp Urol 2014;2:337); however the size cut-off point is not well established
  • This tumor is similar to small cell carcinoma (Am J Surg Pathol 2008;32:65) in the following features:
    • high grade, with no prominent glandular differentiation
    • diffuse, not focal neuroendocrine features
    • high rates of mitosis and apoptosis
    • poor prognosis
  • Can be pure or mixed with conventional high grade prostatic adenocarcinoma, either acinar or ductal type
  • Paraneoplastic syndromes such as Cushing syndrome (ACTH producing tumor induced) may be present but are rare
  • Same as prostatic adenocarcinoma
Clinical Features
  • Similar to prostatic adenocarcinoma
  • Although the serum PSA may be elevated, many cases do not show significant elevations, particularly considering the high tumor volume
  • Other symptoms and signs of advanced prostate cancer may occur
  • Serum neuroendocrine markers such as chromogranin may be elevated
  • Tissue diagnosis with histology is essential, either from needle core biopsy, transurethral resection or prostatectomy
  • Cytology diagnosis of a primary tumor is not generally accepted as an initial diagnosis, but may be used for metastatic sites
Prognostic Factors
  • Often advanced disease at the time of diagnosis
  • High volume disease is associated with poorer prognosis
Case Reports
  • There is very limited treatment experience, because it is rare and probably underreported
  • Generally requires systemic therapy similar to small cell carcinoma, but may not respond well to this treatment or to that for conventional prostatic adenocarcinoma
Gross Description
  • Usually large tumor nodule(s) with a high volume of disease in the prostate
Micro Description
  • Large islands or sheets of tumor cells
  • Large tumor cells with prominent neuroendocrine features such as salt and pepper chromatin and small nucleoli (see fig 1A)
  • High grade features such as lack of glandular formation (see fig 2A), frequent mitoses and apoptotic bodies and tumor necrosis are frequent findings
Micro Images

Images hosted on PathOut server:

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Contributed by Dr. Ximing J. Yang, Northwestern University Feinberg School of Medicine, Illinois (USA):

Fig 1A: Large tumor cells have
slightly more cytoplasm and
fine "salt-pepper" chromatin

Fig 1B: Strong/diffuse
chromogranin staining

Fig 2A: Sheets of large tumor cells
with "salt and pepper" chromatin

Fig 2B: Minor component of
prostatic adenocarcinoma

Fig 2C: Diffuse chromogranin+

Fig 2D: AMACR (triple stain)

Fig 2E: Negative HMWCK,
p63, PSA

Fig 2F: Ki67 proliferative index up to 50%

Positive Stains
  • At least one of these neuroendocrine markers should be positive: chromogranin A, synaptophysin, neuron specific enolase, CD56
  • May be positive:
    • TTF1 positive in less than 50% cases
    • AMACR positive, but may be focal or weaker than prostatic adenocarcinoma
    • Prostate markers such as PSA, PSMA, NKX3.1 prostein (P501S) are negative in most cases, but they can be focally positive in a small subset of tumors
Negative Stains
  • Urothelial markers such as GATA3, p63 and high molecular weight cytokeratins such as CK5 / 6
  • CD99
Differential Diagnosis