Chapter 24 - Neuroendocrine Neoplasms

Question 1

Why are neuroendocrine cells called “neuro”?

Answer 1

Their ultrastructural similarity to neurons (granules analogous to synaptic vesicles).

Question 2

What are the neuroendocrine IHC markers? What else do they recognize?

Answer 2

Synaptophysin (SYN)

Chromogranin (CHR)

Neural-specific enolase (NSE)

CD56

(also recognizes primitive neuron/neuroblasts)

Question 3

Describe the classic neuroendocrine cytologic and architectural features.

Answer 3

Cytology: Uniform & monotonous with smooth contours, “salt and pepper” chromatin, cytoplasmic granularity, and no nucleoli.

Architecture: Nests, rosettes, ribbons/trabeculae. Prominent vascularity.

Question 4

What tissues qualify as neuroendocrine?

Which do not?

Answer 4

Adrenal medulla & paraganglia

Diffuse neuroendocrine system (C cells, langerhans islets, etc)

Parathyroid & anterior pituitary glands

Not: Thyroid, adrenal cortex, gonadal steroid cells.

Question 5

What neuroendocrine cells can give rise to carcinoids in:

Intestine

Gastric fundus

Gastric antrum & duodenum

Lung

Answer 5

Intestine: ECL, D, L cells

Gastric fundus: ECL cell

Gastric antrum & duodenum: G cell (gastrin)

Lung: Kulchitsky (K) cell

Question 6

What neuroendocrine cells exist, and what tumors can they form in:

Pancreas

Thyroid

Skin

Answer 6

Pancreas: A/B/D cells (pancreatic NETs)

Thyroid: C cells (medullary carcinoma)

Skin: Merkel cells (merkel cell carcinoma)

Question 7

What neuroendocrine cells exist, and what tumors can they form in:

Anterior pituitary

Parathyroid

Answer 7

Anterior pituitary: Acidophils (PRL, GH), Basophils (ACTH, TSH, FSH/LH) - Various pituitary neoplasms

Parathyroid: Chief cells - Parathyroid neoplasms

Question 8

What neuroendocrine tumors can arise from adrenal medulla?

Answer 8

Pheochromocytoma

Paraganglioma

Neuroblastoma

PNET?

Question 9

What are primitive neuroectodermal neoplasms (PNETs?)

Answer 9

SYN/CHR-positive tumors with structural features of true primitive neurons.

Question 10

Which neuroendocrine tumors are cytokeratin positive?

Answer 10

The “endoderm-derived / epithelial” tumors, like carcinoid, SCLC, pancreatic neuroendocrine tumor.

True “neural” neuroendocrine tumors like pheo/paraganglioma are cytokeratin negative.

Question 11

What are APUD cells?

What is chromaffin? Enterochromaffin? Enterochromaffin-like cells?

Answer 11

Amine precursor uptake and decarboxylase, an old name for diffuse neuroendocrine cells.

Chromaffin is a tendency to stain with chromic salts. Enterochromaffin within the gut. ECL cells are histamine secreting cells in the gastric fundus.

Question 12

Name an argentaffin stain and an argyrophilic stain.

Answer 12

Argentaffin: Fontana-Masson (also stains melanin)

Argyrophil: Grimelius

*both are outdated*

Question 13

What is neuroendocrine atypia?

Answer 13

Bizarre pleomorphism that actually represents degeneration, and has no correlation with malignant potential.

Question 14

Describe the morphology of well-differentiated neuroendocrine tumor

Answer 14

(carcinoid)

Monotonous smooth nuclei with finely speckled chromatin and no nucleoli. Nested or trabecular with fibrovascular septae.

Question 15

Describe the morphology of poorly differentiated neuroendocrine carcinoma

Answer 15

(small cell carcinoma)

Nuclear size is generally small. Chromatin is darker. Still no nucleoli. Nuclear molding, high N:C. Mitoses & apotoses. Crushing.

Question 16

What is the Azzopardi phenomenon?

Answer 16

Crush artifact with DNA streaming around especially vessels. Seen in small cell carcinomas.

Question 17

Describe the morphology of merkel cell carcinoma.

Answer 17

Small round blue cell tumor resembling small cell carcinoma. Less molding. Sometimes trabecular architecture, but usually diffuse.

Stains for neurofilament, CK20.

TTF1 negative, unlike small cell carcinoma.

Question 18

Describe the morphology of medullary carcinoma of thyroid.

Answer 18

Plasmacytoid cytology. Usual features. Look for amyloid and large cellular islands.

Question 19

Describe the morphology of large cell neuroendocrine carcinoma

Answer 19

Cytology is vesicular and can have prominent nucleoli. Look for architectural features like rosettes & nuclear palisading, as well as IHC.

Question 20

Describe the morphology of pheochromocytoma.

Answer 20

Can be carcnoid-like, but more often bizarrre and large-celled. Amphophilic cytoplasm. Hyaline globules, sometimes nuclear pseudoinclusions.

Question 21

Describe the morphology of paraganglioma.

Answer 21

More carcinoid-like than pheochromocytoma. Nested and occasionally trabecular Zellballen architecture with supporting sustentacular cells (S100+).

Question 22

How can pheochromocytoma and paraganglioma be distinguished on IHC?

Answer 22

They cannot, they both stain neuroendocrine markers and S-100 but no keratins.

Question 23

What happens if an unrelated tumor is incidentally found to express SYN/CHR?

What if a morphologically neuroendocrine tumor does not?

Answer 23

In either case, morphology triumphs. Append “with neuroendocrine differentiation” if needed.

Question 24

How are lung neuroendocrine tumors graded?

Answer 24

Carcinoid: < 2 mitoses/10hpf.

Atypical carcinoid: 2 - 10 mitoses/10hpf.

Small cell carcinoma: > 10 mitoses/10hpf & small cell features.

Large cell carcinoma: > 10 mitoses/10hpf & “specific features”.

Question 25

How are primary GI neuroendocrine neoplasms graded?

Answer 25

Carcinoid tumor: No concerning features.

Malignant carcinoid tumor / well-diff neuroendocrine carcinoma: Concerning behavior such as metastasis.

Poor-diff neuroendocrine carcinoma: Frankly high-grade, both large and small cell.

Question 26

How are primary pancreatic neuroendocrine tumors graded?

Answer 26

Well-diff (islet cell tumor): Typical features, nothing concerning.

Well-diff malignant (malignant islet cell): Metastases, large vessel invasion, or invasion

Poor-diff malignant: Frankly high-grade.

Question 27

How are hepatic neuroendocrine metastases handled?

Answer 27

Usually signed out descriptively; cannot distinguish between pancreatic and GI origin without clinical correlation.