Stains & CD markers
Synaptophysin


Last author update: 6 January 2022
Last staff update: 13 June 2022

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PubMed Search: Synaptophysin

Y. Albert Yeh, M.D., Ph.D.
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Cite this page: Yeh YA. Synaptophysin. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainssynaptophysin.html. Accessed August 11th, 2022.
Definition / general
  • A protein (38 kD), encoded by the SYP gene; is an integral membrane glycoprotein localized to presynaptic neurosecretory vesicles (Am J Hum Genet 1990;47:551)
Essential features
  • An integral membrane protein of small synaptic vesicles in brain and endocrine cells (Am J Hum Genet 1990;47:551)
  • Positive in well differentiated neuroendocrine tumor (carcinoid tumor), neuroendocrine carcinoma, neuroblastoma, adrenal cortical tumors, paraganglioma, pheochromocytoma, Merkel cell carcinoma, parathyroid tumors and medullary thyroid carcinoma
  • Used in conjunction with chromogranin A, INSM1 and CD56 for diagnosing neuroendocrine tumors (Am J Surg Pathol 2020;44:757)
Terminology
  • Major synaptic vesicle protein p38
  • MRX96
  • MRXSYP
  • XLID96
Pathophysiology
  • SYP gene is at Xp11.23 (Am J Hum Genet 1990;47:551)
  • Subcellular locations:
    • Synaptic vesicle membrane, cytoplasmic vesicles, secretory vesicles, synaptosome
  • SYP gene encodes an integral membrane protein of small synaptic vesicles in brain and endocrine cells (Am J Hum Genet 1990;47:551)
  • Involved in cholesterol binding and biogenesis and maturation of synaptic vesicles (Nat Cell Biol 2000;2:42)
  • Regulates endocytosis of synaptic vesicles
  • SYP mutations are associated with X linked intellectual developmental disorder (Nat Genet 2009;41:535)
Diagrams / tables

Images hosted on other servers:

Synaptophysin in synaptic vesicle endocytosis

Clinical features
Interpretation
  • Cytoplasmic staining
Uses by pathologists
Prognostic factors
  • Expression correlates with resistance to abiraterone and enzalutamide treatment in patients with castration resistance prostate cancer (Urol Oncol 2018;36:162.e1)
  • Synaptophysin positive, BRAF mutated colorectal cancers characterized by worse progression free survival and overall survival (Eur J Cancer 2021;146:145)
  • Expression associated with a longer median overall survival in patients with advanced nonsmall cell lung cancer (Respiration 2013;85:289)
  • Synaptophysin positive stage I squamous cell carcinoma and adenocarcinoma of the lung associated with worse prognosis (Cancer 2007;110:1776)
  • Aberrant expression in a small subset of epithelioid hemangioendothelioma associated with aggressive clinical course (Am J Surg Pathol 2021;45:616)
  • Associated with worse prognosis in extrahepatic cholangiocarcinoma (Hum Pathol 2005;36:732)
Microscopic (histologic) description
  • Diffuse cytoplasmic staining is regarded as positive
Microscopic (histologic) images

Contributed by Y. Albert Yeh, M.D., Ph.D.
Prostatic paraganglioma Prostatic paraganglioma

Prostatic paraganglioma

Merkel cell carcinoma Merkel cell carcinoma

Merkel cell carcinoma

Metastatic Merkel cell carcinoma Metastatic Merkel cell carcinoma

Metastatic Merkel cell carcinoma


Lung Lung small cell carcinoma

Lung small cell carcinoma

Bladder small cell neuroendocrine carcinoma Bladder small cell neuroendocrine carcinoma

Bladder small cell neuroendocrine carcinoma

Liver small cell neuroendocrine carcinoma Liver small cell neuroendocrine carcinoma

Liver small cell neuroendocrine carcinoma


Duodenal well differentiated neuroendocrine tumor Duodenal well differentiated neuroendocrine tumor

Duodenal well differentiated neuroendocrine tumor

Duodenal neuroendocrine dysplastic nodule Duodenal neuroendocrine nodule synaptophysin

Duodenal neuroendocrine dysplastic nodule




Cases #195, #110, #189, #185 and #17
Bladder paraganglioma Bladder paraganglioma

Bladder paraganglioma

Sacrococcygeal chordoma Sacrococcygeal chordoma

Sacrococcygeal chordoma

Colonic tubulovillous adenoma with microcarcinoids Colonic tubulovillous adenoma with microcarcinoids

Colonic tubulovillous adenoma with microcarcinoids


Retropharyngeal neuroblastoma Retropharyngeal neuroblastoma

Retropharyngeal neuroblastoma

Thymic carcinoma (type C thymoma), nonkeratinizing squamous cell carcinoma type Thymic carcinoma (type C thymoma), nonkeratinizing squamous cell carcinoma type

Thymic carcinoma (type C thymoma), nonkeratinizing squamous cell carcinoma type



Contributed by Jijgee Munkhdelger, M.D., Ph.D. and Andrey Bychkov, M.D., Ph.D.
Lung typical carcinoid immunoprofile

Lung typical carcinoid immunoprofile

Cytology images

Contributed by Y. Albert Yeh, M.D., Ph.D. and Ashley Moreland, B.S., C.T. (ASCP)
Medullary thyroid carcinoma Medullary thyroid carcinoma

Medullary thyroid carcinoma

Positive staining - normal
Positive staining - disease
Negative staining
  • Tumor with nonneuroendocrine cell origin
  • Squamous cell carcinoma
  • Adenocarcinoma
  • Renal cell carcinoma
  • Urothelial carcinoma
  • Endometrial carcinoma
  • Melanoma
  • Lymphoma
  • Reference: J Thorac Oncol 2017;12:334
Sample pathology report
  • Lung, right upper lobe, endobronchial biopsy:
    • Poorly differentiated carcinoma consistent with small cell neuroendocrine carcinoma (see comment)
    • Comment: The lung biopsy shows bronchial mucosa with infiltrating tumor cell with nuclei characterized by coarse and fine chromatin and arranged in nuclear molding pattern. Immunohistochemical stains synaptophysin, chromogranin and TTF1 are positive in the tumor cells. These findings support the diagnosis of small cell neuroendocrine carcinoma of the lung.
Board review style question #1

A 60 year old man presented to the urology clinic with obstructive urinary tract symptoms. Cystoscopy showed a tumor in the bladder neck. Transurethral urethral bladder tumor resection was performed. Microscopic examination of the sample is shown in the above photomicrograph. What are the best immunohistochemical stains to diagnose this tumor?

  1. Desmin, SMA, myoD
  2. CD45, CD3, CD20
  3. S100, melan A, SOX10
  4. Synaptophysin, chromogranin A, INSM1
Board review style answer #1
D. Synaptophysin, chromogranin A, INSM1. This is a small cell neuroendocrine carcinoma of the bladder.

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