Endocrine Flashcards
NIFTP
What are its ddx and how do you distinguish them?
Differential Diagnosis: NIFTP is differentiated from invasive FVPTC by its lack of invasion, from classic follicular predominant PTC by its very scant papillary component (<1% papillae) and from other PTC by the absence of the cytoarchitectural features of these subtypes (e.g. tall cells). Those rare non-invasive follicular patterned tumours with PTC nuclei that are excluded from NIFTP because of a mitotic count >3/ 2 mm2 are best reported as mitotically active encapsulated PTC with a predominant follicular growth pattern, and if the mitotic count is > 5 / 2 mm2 or if there is tumour necrosis they should be reported as non-invasive high grade FVPTC. Follicular adenoma are separated from NIFTP by the lack of PTC nuclear alterations (PTC nuclear score 0-1).
NIFTP
Essential and desireable diagnostic criteria
Essential:
1.Encapsulation or clear demarcation.
2.Follicular growth pattern with all of the following: <1% true papillae; No psammoma bodies; <30% solid/trabecular/insular growth pattern.
3.Nuclear features of papillary carcinoma (nuclear score of 2-3)
4.No vascular or capsular invasion
5.No tumour necrosis
6.Low mitotic count (<3 mitosis / 2mm2)
7.Lack of cytoarchitectural features of papillary carcinoma variants other than follicular variant (tall cell features, cribriform-morular variant, solid variant, etc).
Desirable:
Immunohistochemistry or molecular testing for BRAF and NRAS mutation (to exclude diagnosis). Because BRAF p.V600E mutation is exceptionally rare in NIFTP, its detection by genotyping or immunostaining should lead to a thorough search for papillae, psammoma bodies or tall cells by complete histologic examination of the entire tumour
PTC
Subtypes
Classic PTC
Encapsulated classic PTC
Infiltrative follicular PTC
Diffuse sclerosing PTC
Solid/trabecular PTC
Warthin-like PTC
Oncocytic PTC
Clear cell PTC
Spindle cell PTC
PTC with fibromatosis/fasciitis-like/desmoid-type stroma
Tall cell PTC
Hobnail PTC
Columnar cell PTC
PTC
IHC (+) vs (-)
(+) TTF-1, PAX8, throglobulin, cytokeratins (pan-CK, AE1/AE3, CAM5.2, CK7)
(-) CK20, calcitonin, neuroendocrine markers
thyroid lesion
dx
Key histo features
features demonstrated by image
Hyalinizing and trabecular tumour
Essential: follicular cell differentiation; pure trabecular architecture with intra-trabecular hyalinization and nuclear features characterized by prominent grooves, vacuoles, and membrane irregularities
Desirable: membranous Ki-67 staining (MIB-1 clone); detection of GLIS rearrangements
Image: The tumour cell nuclei are convoluted with prominent membrane irregularities that form grooves and pseudoinclusions (arrow).
retroperitoneal mass
dx?
Key features:
Ddx:
IHC:
Phaochromocytoma
A “Zellballen” pattern is most common, consisting of nests of tumour cells separated by peripheral capillaries
Tumour cells resembling normal chromaffin cells that display basophilic to amphophilic cytoplasmic granularity. The cells here show mild nuclear pleomorphism and occasional nuclear pseudoinclusions, which can also be seen in adrenal cortical carcinomas. PAS(+) hyaline globules can be seen and nuclear pseudoinclusions. Can have pleomorphism but no mitoses
IHC: (+) tyrosine hydroxylase, GATA3, dopamine beta-hydroxylase, neuro markers chromo A, syn, INSM1. Need to do Ki67 which is usu less < 10%.
(-): CK negative
DDx: adrenal cortical carcinoma.
(+) melan-A, SF1 (-) chromo, gata3, tyrosine hydroxylase
Phaeochromocytoma vs paraganglioma
px
mutations
All paragangliomas care considered to have metastatic potential , approx 30% of abdominal paragangliomas may metastasise vs 8% of phaeochromocytomas.
(The risk of metastasis ranges from ~5 to 15%)
Extra-adrenal abdominal paragangliomas often have SDHB mutations
poorly differentiated thyroid carcinoma
dx criteria
Essential:
PDTC
(i) solid/trabecular/insular pattern of growth in a tumour diagnosed as malignant based on the presence of invasion;
(ii) absence of conventional papillary carcinoma nuclear alterations;
(iii) at least one of the following features: convoluted nuclei, mitotic count ≥ 3 per 2 mm2, tumour necrosis;
(iv) retention of some (but not all) morphologic and immunohistochemical biomarkers of thyroid follicular epithelial cells.
(v) poorly differentiated but lacking anaplastic cellular morphology
adrenal neoplasms
describe weiss scoring system
follicular carcinoma
Name the 3 subtypes?
(1) minimally invasive (capsular invasion only), (2) encapsulated angioinvasive (venous invasion present with or without capsular penetration), and (3) widely invasive.
follicular carcinoma
discuss reporting of venous invasion, mitoses, necrosis and nuclear features
Tumours with limited invasion of vessels (<4 foci) have a better prognosis than do those with extensive vascular invasion (4 or more foci of invasion). Thus, foci of vascular invasion should be counted (with foci in adjacent vessels counted separately).
The mitotic count should be <3 per 2mm2 in areas of solid or trabecular growth and <5 per 2mm2 if the tumour has an entirely follicular architecture (see section of FTC high-grade features). Tumour necrosis should not be seen in FTC. FTC also lacks nuclear features of PTC. Instead, the nuclei are round and have coarse chromatin. All potential FTC should be examined for nuclear features of PTC to exclude a diagnosis of encapsulated follicular variant of papillary thyroid carcinoma.
follicular carcinoma
IHC
FTC is positive for CAM5.2, EMA, and CK7 and negative for CK20 . These tumours also have strong nuclear staining for the transcription factors PAX8 and TTF-1. The cytoplasm and associated colloid of FTC is positive for thyroglobulin
PTC tall cell vs columnar cell variants
Difference
Tall cell:
3:1 height:width, prominent nuclear pseudoinclusions; tram-track appearance, >/= 30% of this morphology for this to be counted as a PTC subtype
Columnar cell:
prominent pseudostratification; subnucelar vacuoles (appearance similar to secretory endometrium); need to exclude mets from colorectal ca/endometrium. NB can occasionally stain (+) CDX2
parathyroid gland adenoma
significant (+) and (-) stains
Cell type composition
PTH/GATA3/chromogranin A/Synopathophysin (+)
Thyroglobulin/TTF1/PAX8 (-)
The vast majority of sporadic parathyroid adenomas show nuclear parafibromin expression
Parathyroid gland adenomas may be composed of oncocytic cells, chief cells, or clear cells.
PTC
IHC significant (+) and (-)
(+): Pax8, TTF1, thyroglobulin, cytokeratin (CK7, AE1/AE3, CAM5.2)
(-): CK20, calcitonin, neuroendocrine markers
Encapsulated PTC vs follicular adenoma with papillary architecture
Differences in morphology
E-PTC:
- classic PTC enveloped by a thick fibrous capsule, which maybe intact or infiltrated by tumour with or without extension into surrounding thyroid parenchyma
Follicular adenoma with papillary architecture:
- encapsulated
- usually cystic and show a mixture of follicular and papillary architecture; large follicles with complex papillary infoldings of the lining epithelium; broad papillae showing an organized centripedal orientation and edematous cores with embedded follicles; The formation of Sanderson’s pollsters (subfollicles within follicles) is common; peripheral scalloping consistent with the rapid resorption of colloid; lack nuclear features of PTC; psammomma bodies not seen;
First image: FA with pap architecture. On high power the cells are often columnar. The nuclei are basally located and are small, round, and dark. Nuclear features of papillary thyroid carcinoma are always absent. The edematous fibrovascular cores show embedded follicles.
Below image; Follicular adenoma with papillary architecture - Low power view showing large colloid-filled follicles and complex papillary infoldings of the lining epithelium.
