Chapter 24 - Neuroendocrine Neoplasms Flashcards
Why are neuroendocrine cells called “neuro”?
Their ultrastructural similarity to neurons (granules analogous to synaptic vesicles).
What are the neuroendocrine IHC markers? What else do they recognize?
Synaptophysin (SYN)
Chromogranin (CHR)
Neural-specific enolase (NSE)
CD56
(also recognizes primitive neuron/neuroblasts)
Describe the classic neuroendocrine cytologic and architectural features.
Cytology: Uniform & monotonous with smooth contours, “salt and pepper” chromatin, cytoplasmic granularity, and no nucleoli.
Architecture: Nests, rosettes, ribbons/trabeculae. Prominent vascularity.
What tissues qualify as neuroendocrine?
Which do not?
Adrenal medulla & paraganglia
Diffuse neuroendocrine system (C cells, langerhans islets, etc)
Parathyroid & anterior pituitary glands
Not: Thyroid, adrenal cortex, gonadal steroid cells.
What neuroendocrine cells can give rise to carcinoids in:
Intestine
Gastric fundus
Gastric antrum & duodenum
Lung
Intestine: ECL, D, L cells
Gastric fundus: ECL cell
Gastric antrum & duodenum: G cell (gastrin)
Lung: Kulchitsky (K) cell
What neuroendocrine cells exist, and what tumors can they form in:
Pancreas
Thyroid
Skin
Pancreas: A/B/D cells (pancreatic NETs)
Thyroid: C cells (medullary carcinoma)
Skin: Merkel cells (merkel cell carcinoma)
What neuroendocrine cells exist, and what tumors can they form in:
Anterior pituitary
Parathyroid
Anterior pituitary: Acidophils (PRL, GH), Basophils (ACTH, TSH, FSH/LH) - Various pituitary neoplasms
Parathyroid: Chief cells - Parathyroid neoplasms
What neuroendocrine tumors can arise from adrenal medulla?
Pheochromocytoma
Paraganglioma
Neuroblastoma
PNET?
What are primitive neuroectodermal neoplasms (PNETs?)
SYN/CHR-positive tumors with structural features of true primitive neurons.
Which neuroendocrine tumors are cytokeratin positive?
The “endoderm-derived / epithelial” tumors, like carcinoid, SCLC, pancreatic neuroendocrine tumor.
True “neural” neuroendocrine tumors like pheo/paraganglioma are cytokeratin negative.
What are APUD cells?
What is chromaffin? Enterochromaffin? Enterochromaffin-like cells?
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.
Name an argentaffin stain and an argyrophilic stain.
Argentaffin: Fontana-Masson (also stains melanin)
Argyrophil: Grimelius
*both are outdated*
What is neuroendocrine atypia?
Bizarre pleomorphism that actually represents degeneration, and has no correlation with malignant potential.
Describe the morphology of well-differentiated neuroendocrine tumor
(carcinoid)
Monotonous smooth nuclei with finely speckled chromatin and no nucleoli. Nested or trabecular with fibrovascular septae.
Describe the morphology of poorly differentiated neuroendocrine carcinoma
(small cell carcinoma)
Nuclear size is generally small. Chromatin is darker. Still no nucleoli. Nuclear molding, high N:C. Mitoses & apotoses. Crushing.
What is the Azzopardi phenomenon?
Crush artifact with DNA streaming around especially vessels. Seen in small cell carcinomas.
Describe the morphology of merkel cell carcinoma.
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.
Describe the morphology of medullary carcinoma of thyroid.
Plasmacytoid cytology. Usual features. Look for amyloid and large cellular islands.
Describe the morphology of large cell neuroendocrine carcinoma
Cytology is vesicular and can have prominent nucleoli. Look for architectural features like rosettes & nuclear palisading, as well as IHC.
Describe the morphology of pheochromocytoma.
Can be carcnoid-like, but more often bizarrre and large-celled. Amphophilic cytoplasm. Hyaline globules, sometimes nuclear pseudoinclusions.
Describe the morphology of paraganglioma.
More carcinoid-like than pheochromocytoma. Nested and occasionally trabecular Zellballen architecture with supporting sustentacular cells (S100+).
How can pheochromocytoma and paraganglioma be distinguished on IHC?
They cannot, they both stain neuroendocrine markers and S-100 but no keratins.
What happens if an unrelated tumor is incidentally found to express SYN/CHR?
What if a morphologically neuroendocrine tumor does not?
In either case, morphology triumphs. Append “with neuroendocrine differentiation” if needed.
How are lung neuroendocrine tumors graded?
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”.
How are primary GI neuroendocrine neoplasms graded?
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.
How are primary pancreatic neuroendocrine tumors graded?
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.
How are hepatic neuroendocrine metastases handled?
Usually signed out descriptively; cannot distinguish between pancreatic and GI origin without clinical correlation.
