Molavi Chapter 24 - Thyroid and Parathyroid Flashcards
Two basic cell types of the thyroid
Follicular epithelium (TTF-1, PAX8, thyroglobulin positive)
C cells (TTF-1, neuroendocrine marker, and calcitonin positive, thyroglobulin negative)
The only well to histologically differentiate a follicular adenoma from follicular carcinoma is. . .
. . . to examine the entire capsule margin
Follicular carcinomas can look just like adenomas
Hurthle cell adenoma
Adenoma of thyroid follicular cells displaying Hurthle cell change
Cells are large pink oncocytes with round nuclei which may be enlarged or slightly irregular. Nucleoli may be prominent.
Follicular thyroid carcinoma
- Since it can appear histologically identifical to adenomas, it is defined by the presence of EITHER: capsular OR vascular invasion (note that vascular invasion within the capsule does count).
- Dominated by a microfollicular pattern
- Said to be “poorly differentiated” if there is high mitotic rate and necrosis. Architecture may also be lost at this grade.
Poorly differentiated follicular thyroid carcinoma
Instead of follicles the tumor is more ribbon, cord, or slit-like. The grade is also higher.
Papillary thyroid cancer
- Classic Orphan Annie eye nuclei with peripheral chromatin – an articat produced by formalin fixation and not seen on frozen section or cytology. Stands out as glassy or pale on low-power
- Crowded, overlapping, pleomorphic nuclei, sometimes with coffee-bean grooves and pseudoinclusions (invaginations of cytoplasm)
- Overall papillary architecture
- Psamomma bodies may be present. Typically only seen when there is papillary arthitecture.
- Variants:
- Papillary microcarcinoma
- Follicular variant papillary thyroid carcinoma
- Noninvasive follicular neuplasm with papillary-like nuclear features (NIFTP)
- Diffuse sclerosing
- Tall cell
NIFTP algorithm
NIFTP vs FVPTC
NIFTP = Noninvasive follicular thyroid neoplasm with papillary-like nuclear features; benign
FVPTC = Follicular variant of papillary thyroid carcinoma; malignant
- The key to differentiating:
- If it is unencapsulated and infiltrative, it is FVPTC that behaves like papillary carcinoma and is signed out as such
- If it is encapsulated and invades the capsule or vasculature, it is FVPTC that behaves like follicular carcinoma and is signed out as such
- If it is surrounded by an intact capsule and behaves in a benign fashion, it is signed out as NIFTP
Thyroid papillary microcarcinoma
Papillary carcinoma variant
Histologically identical to papillary carcinoma, but by definition <1 cm and incidentally discovered.
If solitary, they are considered benign.
If they are clinically discovered, they fail to meet this definition and are considered papillary carcinoma, regardless of size.
Diffuse sclerosing papillary carcinoma
Rare, but important to recognize due to worse prognosis.
Widely infiltrative as opposed to discrete/mass forming.
Characteristics: desmoplastic or sclerotic stroma, squamous metaplasia, tons of psammoma bodies, dense lymphocytic infiltrate, extensive lymphovascular invasion
Anaplastic thyroid carcinoma
Aggressive tumor that arises from de-differentiation of papillary or follicular carcinoma.
Appear as “sheets” of pleomorphic cells. At this grade they have usually lost their TTF-1 and thyroglobulin expression. However, they retain PAX8 staining.
___ is a common mimicer of papillary carcinoma
Hashimoto’s thyroiditis is a common mimicer of papillary carcinoma
It an sometimes have Orphan Annie-like nuclei due to a fixation artifact. A carcinoma arising from Hashimoto’s should stand out sharply from its neighbors.
Hyalinizing trabecular tumor
Has textbook papillary nuclei, including the grooves and inclusions, but an architecture similar to medullary carcinoma: Well-circumscribed nodules of nests and cords (trabecular) set in a dense, pink, hyalinized stroma.
This is a benign lesion.
Differences in thyroid carcinoma spread
Follicular: Spreads locally.
Papillary: Spreads through lymph nodes.
Medullary thyroid carcinoma
Salt-and-pepper nucleated cells that grow in nests.
May look like anaplstic on low power, but nuclear features and IHC can differentiate it reliably.
Spindle Epithelial Tumor with Thymus-like Elements (SETTLE)
Thought to arise from entrapped ectopic thymus tissue within the thyroid, like CASTLE.
Has a biphasic pattern: spindle cells and epithelioid structures (cords, tubules, papillae, glandular formation). No or rare lymphocytes. Mitotic activity and focal necrosis are rare.
Carcinoma showing thymus-like elements
Thought to arise from entrapped ectopic thymus tissue within the thyroid, like SETTLE.
Fibrous bands separating islands/nests of cells. Variable lymphocytes and plasma cells.
Tumor cells have ill-defined borders, vesicular nuclei, prominent nucleoli, OR may show squamous differentiation with distinct cell borders and eosinophilic cytoplasm.
Oncocytic change is due to . . .
. . . accumulation of altered mitochondria in the cytoplasm.
Calcium oxalate and the thyroid
Calcium oxalate is present in normal thyroid tissue in the cholloid mixture
It can help differentiate thyroid from parathyroid in borderline cases.
Remember, calcium oxalate is best seen under the polarizer.
Classical triad of Hashiomoto’s thyroiditis
- Hurthle cell change
- Lymphocytes (often forming follicles/germinal centers)
- Plasma cells
Thyroglossal duct cyst
Anterior midline cyst
Lined by respiratory or squamous epithelium.
In many cases, there will be a small amount of thyroid tissue within the wall of the cyst.
Often resection and specimen will include the hyoid bone, because there may be thyroid tissue within the hyoid itself.
Ultimobranchial body cell nest / solid cell nest
Microscopic developmental remnant of the ultimobranchial body
The ultimobranchial stage of thyroid development includes both follicular and parafollicular cells.
Lining may be squamous, respiratory, or transitional.
Elongated, grooved nuclei with squamoid features. p40+ p63+. It is important to recognize these and not confuse them with microcarcinoma, and to know that C cells may be among them.
Lymphoepithelial cyst
Squamous epithelium with lymphoid stroma
May be a branchial cleft cyst within the thyroid
What’s this white stuff?
Calcium oxalate crystals
This is a sure way to identify thyroid tissue on frozen section.
Otherwise, parathyroid with pseudofollicles can be an incredibly convincing mimic on frozen.
The eponymous thyroididities
Hashimoto’s -> lymphocytic
de Quervain’s -> granulomatous
Reidel’s -> fibrosing (IgG4)
What’s goin’ on with this thyroid?
Treated Grave’s disease
The scalloping is gone, but macrofollicles and proliferations into the follicular lumen remain.
This is a good example of post-methimazole. Sometimes in post-radioactive iodine you will see diffuse scarring of the gland +/- oncocytic change.
Nonspecific thyroiditis
“Patchy lymphocytic thyroiditis”
Chronic inflammation without germinal centers, relatively normal follicles.
Multifactorial.
Palpation thyroiditis
Foamy macrophages and giant cells responding to a burst follicle
The best way to identify is to show that they are “intrafollicular”
Thought to be related to manual palpation or blunt trauma.
Granulomatous thyroiditis
Non-foamy granulomas
Could be due to recent infection, sarcoid, or could be a peri-tumorial response
Reidel’s thyroiditis
Diffusely effaced thyroid tissue replaced by storiform pattern fibrosis with clusters of lymphoplasmacytic infiltrate
“Woody” texture on clinical exam
For IgG4 Dz:
IgG4:IgG ratio >40%
IgG4+ plasma cells per hpf > 30
Dyshormonogenic Goiter
- Hypercellular nodules with solid/microfollicular architecture
- Minimal colloid
- Bizarre nuclear atypia with neuroendocrine-like features
- Diverse genetic anomalies resulting in defective thyroid hormone production/function
This is a major DDx for Grave’s, particularly in young / peripubertal individuals.
Bethesda criteria for thyroid FNA
If FNA yields an indeterminate category of Dx, we now proceed to. . .
Molecular testing
What thyroid cancers look like on FNA
Papillary: Densely clustered cells around vasculature, characteristic papillary nuclear features
Medullary: Plasmacytoid cellular features with eccentric nuclei, granular cytoplasm, sometimes cleared nuclei like papillary.
Follicular: Cellular with microfollicles, some of which still contain colloid. Round, bland nuclei.
Outcome for indeterminate-category FNA with negative molecular testing
Effective clinical rule-out of malignancy
No need for surgery!
Molecular for thyroid cancers
4 step approach to thyroid nodules
- Circumcision
- Capsule
- Follicles
- Nuclei
Water Clear Cell Adenoma of the Parathyroid
Functional parathyroid tumor composed of large clear cells separated by fine fibrovascular septa, with an abundant vacuolated cytoplasm, and a bland cytological appearance
The tumor does produce parathyroid hormone, but not at as rapid of a rate as more classical parathyroid adenomas.
Parathyroid carcinoma
90% of these are functional tumors.
Uniform cells resembling chief cells with mild to moderate atypia in a solid, nodular pattern with bands of fibrous tissue running throughout. Individual cells may be pinkish to relatively clear. Nuclear atypia with prominent nucleoli are common. Necrosis, increased mitotic activity, and atypical mitoses may be seen.
One of the following necessary to call malignancy:
Angioinvasion
Lymphoinvasion
Perineural invasion
Invasion of adjacent structures
Metastasis
Genetics: HRPT2 (CDC73, parafibromin) mutation is strongly associated with both sporadic and familial cases (>70%).
Papillary thyroid cancer, oncocytic type
NIFTP
Note the clear follicles with papillary-like nuclei
Water Clear Cell Adenoma of the Parathyroid or Water Clear Cell Hyperplasia (all 4 glands involved)
Very rare variant of parathyroid adenoma. PTH-secreting, but not at a very high level compared to conventional parathyroid adenomas.
Less likely to be malignant than other parathyroid neoplasms, however one case of malignant water clear cell carcinoma has been reported.
Histologically, cells arranged in cords or sheets exhibiting distinct
cell borders with a finely reticulated pattern on low power
magnification.
IHC: PTH+, GATA3+, GCM2+, CD10+, TTF1 neg
Parathyroid Lipoademona
Rare parathyroid functional tumor. Adenomatous parathyroid cells in abundant fatty stroma, which “resembles a lipoma more than an adenoma.”
The WHO describe it as “a hamartoma‑like benign neoplasm containing both chief cells and prominent stromal elements.”
Should be >50% fat , PTH+ , and there should be clinical response in the patient’s PTH following removal in order to make the diagnosis.
Oxyphil Parathyroid Adenoma
Relatively rare parathyroid adenoma, which does not often secrete PTH, but can.
May still be mixed, but should have >75% oxyphil cells to be called an oxyphil parathyroid adenoma.
This is an important Ddx for Hurthle cell thyroid adenoma, and vice/versa. Stains will clear this up no problem, but you have to be careful when there is no secreted hormone – you can’t rely on the clinical history!
In parathyroid tumors, what is the prevailing genetic phenotype?
MEN1 inactivation or loss (via loss of 11q13)
MEN type-1 syndrome is also due to an inactivating mutation in MEN1
Cyclin D1 mutations are the 2nd most common, and often accompany MEN1 anomalies.
Most parathyroid adenomas involve. . .
. . . one of the lower parathyroid glands (>75%)
Parathyroid adenoma
Classical-type. Often described as “cells with an intermediate appearance between chief cells and oxyphil cells.”
Example of the atypia which may be displayed in the oxyphil cells of a parathyroid adenoma. Giant cells may also be seen. This does not imply malignancy! Parathyroid carcinoma is still quite rare, and these features alone should not sway to into calling an adenoma a carcinoma. Even with these features though, you should NOT be seeing excess mitoses.
