Thread by @TristanRutland7

Ampulla tumour, adult

#GIpath #BSTpath #Pathtwitter #Pathresidents

Question:

Based on the initial images, which of the following do you favour?

* Gastrointestinal stromal tumour
**Gangliocytic Paraganglioma

⚕️Diagnosis:

🔬Gangliocytic Paraganglioma

(Colleagues case)

Question:

This tumour contains how many types of cells?

1/ This tumour is more common in mean, with a large age range (average age 50s).

2/ It is composed of three types of cells:

🥕〰️Spindle-shaped Schwann cells

🧂🌶️Epithelioid neuroendocrine cells

🔘🧠Ganglion cells

ncbi.nlm.nih.gov/pmc/articles/P…

Question:

Which of the following immunohistochemical stains is most likely to ✅POSITIVE✅ in the neuroendocrine cells of this tumour?

3/ IHC for each component:

Schwann cell: S100, BCL-2 (66.7%)

Neuroendocrine cell: synaptophysin, CD56

Ganglion cell: S100, synaptophysin, CD56

4/ Note: in the neuroendocrine cells, keratin expression is can weak (+ only 33.3% of cases in below study).
bmccancer.biomedcentral.com/articles/10.11…

Question:

Which of the following hormone stains are often POSITIVE in the neuroendocrine cell component of this tumour?

5/ Interesting, the following hormones are often positive:

Pancreatic polypeptide (PP), somatostatin & progesterone.

6/ Others hormone expression is rarer.

7/ The above positive stains can be useful in differentiating this tumour from a G1 NET.
meridian.allenpress.com/aplm/article/1…

8/ Interesting, PP expression has led some to hypothesize that they may arise from the islet cells that are embryonic remnants from the enteropancreatic endoderm (however, these tumours don’t occur in the normal pancreas...🤷‍♂️)

pubmed.ncbi.nlm.nih.gov/2578747/

Last question:

Which of following molecular abnormalities can occasionally be seen in these tumours?

9/ The below study looked at 10 cases, and 2 cases had gain of function hypoxia-inducible factor 2 alpha (HIF2α) mutations, which is encoded by EPAS1.

10/ This leads to HIF2α having a longer half-life.

11/ HIF2α upregulates a bunch of downstream genes.

ncbi.nlm.nih.gov/pmc/articles/P…

12/ HIF2α normally becomes active under hypoxic conditions.

13/ Lastly, for a deeper dive on HIF2α related disease, check out below link.

nature.com/articles/s4146…