Thyroid Pathology (5/20) Flashcards
List non-neoplastic lesions of the thyroid
- Nodular goiter
- Diffuse toxic goiter (Graves’)
- Chronic lymphocytic thyroiditis
List tumors of the thyroid
- Adenoma
- Malignant (papillary, follicular, medullary, anaplastic carcinoma)
How many lobes does the thyroid have?
2
Describe the histology of the follicles
Follicles of varying sizes contain colloid and are lined by low-cuboidal to columnar epithelial cells (aka follicular cells)
What is an oncocytic cell?
- A metaplastic follicular cell
- Eosinophilic due to increased number of mitochondria
- Rounder nucleus than a follicular cells’
- Prominent nucleolus
- Seen in both benign and malignant lesions
- Also known as a Hurthle cell
What are C-Cells?
- Parafollicular cells
- Derived from neural crest
- Produce calcitonin
- Located at lateral aspect of thyroid gland
- Rarely seen in regular histology until hyperplastic (MEN2 syndromes)
- Best seen with immunostains for calcitonin
What are two types of enlargements of thyroid disease
Nodular and diffuse
What does nodular look like?
Encapsulated
- Capsule can have smooth borders (benign)
- Capsule can have irregular borders with invasion of tumor cells into surrounding thyroid or outside thyroid gland
What types of lesion architecture/growth patterns are there?
- Follicular
- Papillary
- Solid
- Trabecular
What other lesion features do we look at besides cellular ones?
- Fibrosis
- Calcification (dystrophic)
- Amyloid (distinct for medullary thyroid carcinoma)
What do we look at with tumor cell cytology?
- Cell size
- Cytoplasm (indistinct or oncocytic)
- Nuclear morphology (shape, intranuc folds (grooves), holes (inclusions))
- Nucleoli are prominent (oncocytic) or central vs eccentric
What is papillary formation?
Finger-like projections or fronds which consist of single or mult layers of hyperplastic/neoplastic epithelium centered around a core/stalk containing blood vessels and connective tissue
What kinds of nodular thyroid enlargement can there be?
- Solitary nodule which can be neoplastic/benign (more suspicious for being a neoplasm)
- Multiple nodules which are usually benign, though one may not be
Describe the two diseases in which we see diffuse thyroid enlargement
- Graves’ (diffuse toxic goiter)
2. Hashimoto’s thyroiditis (chronic lymphocytic thyroiditis)
Are diffuse thyroid enlargements usually malig or benign?
benign, rarely tumors
What is the gross pathology of Graves’?
- Symmetric and diffuse enlargement of thyroid
- Red brown cut surface
- Decreased colloid
- Increased vascularity
- Smooth capsule, no nodules
What does Graves’ look like histologically?
Hyperplasia of follicular cells (papillary hyperplasia)
Lymphocytic infiltration in stroma (autoimmunity)
–non-destructive autoimmunity–>immunoglobulins stimulate hyperplasia
Why do papillary infolds occur in graves;?
There are inc numbers of cells, usually of inc size that cannot be accommodated in the follicles in the usually way so infoldings must occur. Eventually, the hyperplastic epithelium piles up in the lumen of the follicle and develops its own fibro-vascular core (ie BVs and fibrous tissue forming center and cells attached at the periphery)
What do the follicular epithelial cells look like in graves’?
They are tall, columnar, inc in number with enlarged nuclei
What occurs in the stroma in graves’?
Inc vascularity and lymphocytic infiltration
What does Hashimotos look like grossly?
Diffusely enlarged gland (early)
Lobulated cut surface (later)
- Thyroid is symmetrically enlarged from 2-5x normal
- Thyroid capsule is smooth
- Gland is rubbery, firm and the cut surface has a lobular yellow appearance
What is Hashimotos?
Autoimmune disease in which the thyroid is destroyed by inflammatory cells
- commonly found in pts with spontaneous hypothyroidism
- also called chronic lymphocytic thyroiditis
- cells get into gland and cause enlargement
What does hashimotos look like histologically?
- Infiltration of thyroid gland by lymphocytes and plasma cells
- Follicular atrophy (not hyperplastic)
- Hurthle cell/oncocytic metaplasia (hashimoto thyroiditis leads to less colloid)
What does hashimotos look like microscopically?
- Diffuse infiltration of lymphocytes
- Formation of lymphoid germinal centers
- Follicular atrophy
- Follicular epithelium has oncocytic metaplasia
- Marked dec in colloid
What is the difference between graves and hashimotos with regards to follicular cells?
G: papillary hyperplasia
H: atrophy
What is the difference between graves and hashimotos with regards to infiltration?
G: lymphocytic infiltration in the stroma
H: infiltration by lymphocytes and plasma cells throughout the gland
What is the difference between graves and hashimotos with regards to onocyctic metaplasia
OCcurs in hashimoto, not really in graves’
How common are thyroid nodules in USA?
4-7% of general pop has them
inc in places with iodine deficiency
What causes non-toxic nodular goiter?
- Endemic goiter: iodine def
- Sporadic goiter: not in iodine def country
- Chemically induced goiter
- Dyshormonogenetic goiter
What are the 2 types of gross path of non-toxic nodular goiter?
1.
- Firm gland
- Diffusely enlarged
- Cut surface is shiny and amber colored due to inc colloid accumulation
2.
- Asymmetric enlargement
- Multinodular
- Hemorrhage
- Calcification
- Fibrosis
- Cystic degeneration
- ->outgrowing its blood supply
What is the histology of non-toxic nodular goiter?
- Heterogeneous even within the same thyroid gland
- Variable sized follicles surrounded by tall columnar and/or flattened low cuboidal epithelium
- Can have papillary hyperplasia in nodular goiter
What causes fibrosis in non-toxic nodular goiter?
Thyroid nodules outgrow their blood supply leading to
- degeneration then
- fibrosis as a fxn of repair
Both benign and malignant neoplasms form…
thyroid nodules
What is the most common form of malignant primary epithelial neoplasm
Well diffrentiated
What is a benign primary epithelial neoplasm of the follicular cell? What does it look like grossly?
Follicular adenoma
- Solitary
- Well circumscribed
- Encapsulated (smooth)
How common are malig tumors of thyroid? Name some features
Uncommon, 1-2% of all cancers. More common in females who get thyroid nodules more commonly. Usually well-differentiated. Behave in indolent fashion
What is etiologically implicated for thyroid carcinoma?
- Irradiation is the most well known factor for papillary carcinoma
- Esp during childhood
- Often have ret rearrangements in these tumors
Name an oncogene in follicular cell pathogenesis
RET: rearranged in endocrine tumors
- over-activation of tyrosine kinase domain of ret protoconcogene
- more common in 60-80% of papillary thyroid carcinoma occurring after irradiation
What is ret rearrangement specific to?
Papillary thyroid carcinoma (PTC), commonly seen in radiation induced pap carcinoma
What carcinomas produce thyroglobulin
- Papillary carcinoma
- Follicular carcinoma
What is the most common type of thyroid cancer?
Papillary thyroid carcinoma (80% in non-endemic goiter regions-iodine sufficient)
-More common in women
What size is PTC?
Can come in all sizes
What is microcarcinomas?
Tumors measuring 1cm or less that can be seen as incidental lesions (no symptoms)
How fast do PTCs grow
slowly
How do PTCs metastasize?
Via lymphatics (not bvs)
What is common in PTC (cyst or solid)?
Cyst formation, some are solid with fibrosis and calcificaiton
What are the nuclear features of PTC?
- Elongation
- Chromatin clearing/ground glass appearance (orphan annie nuclei)
- Membrane thickening
- Grooves
- Inclusions (holes)
- Small peripheral nucleoli
What is PTC diagnosis based on?
Nuclear features
What are the growth patterns possible for PTC?
Papillary (forms papillae)
Follicular (forms follicles with colloid)
Tall cells (elongated height)
What is similar and dif between papillary formation in graves’ and PTC?
They are the same structure, the cells are different. PTC are cancer cells
What is the clinical behavior of PTC?
- 10 year survival over 90%
- Aggressive behavior if older, male, large, tall cell, distant metastases, solitary
What two cancers are derived from follicular cells and are well differentiated?
Papillary and follicular carcinoma
–>medullary carcinoma is also a well-differentiated tumor, but is derived from C cells
How common is follicular carcinoma?
Rare, 5% of all thyroid carcinoma with inc incidence with age. More common in iodide def regions.
What is the path of follicular carcinoma?
- Encapsulated tumor with tumor cells invading capsule (not smooth) and/or capsular vessels
- Hematogeneous spread to brain lungs and bone
- Prognosis dep on extent of invasion
Whats the difference between PTC and follicular carcinoma with regards to prevalence?
P: most common thyroid cancer
F: 5% of all thyroid cancers
Whats the difference between PTC and follicular carcinoma with regards to diagnosis?
P: diagnosed by classic nuc features
F: diagnosed by invasion into capsule and/or capsular vessels
Whats the difference between PTC and follicular carcinoma with regards to growth pattern?
P: Can show papillary and/or follicular growth patterns
F: Most tumors show follicular and/or solid growth pattern
Whats the difference between PTC and follicular carcinoma with regards to focality?
P: Multi-focal (mult tumors in thyroid)
F: Uni-focal
Whats the difference between PTC and follicular carcinoma with regards to encapsulation?
P: can be encap or non-encap
F: encapsulated
Whats the difference between PTC and follicular carcinoma with regards to route of metastases?
P: lymphatics
F: blood vessels so it is more likely to go to distant organs
Whats the difference between PTC and follicular carcinoma with regards to genes?
P: Specific ret oncogene rearrangements
F: No specific re oncogene rearrangements, usually shows ras mutations
What well-differentiated tumor is derived from C cells?
Medullary carcinoma
What does medullary carcinoma produce?
Calcitonin (functioning tumor)
What familial syndrome is associated with medullary carcinoma?
MEN-2 syndromes
What is more common cause of medullary carcinoma than familial syndormes?
Sporadic
What is the pathogenesis of medullary carcinoma?
-Germ line mut of ret-oncogene (chromo 10)
What is the prognosis of medullary carcinoma?
50% at 5 years (not great)
What is the pathology of medullary carcinoma?
- Tumor nest
- Amyloid deposition
- Calcitonin secretion
What is anaplastic carcinoma?
A malignant primary epithelial neoplasm of the thyroid . It is a fatal tumor and is only 5% of all thyroid malignancies.
Most common >60y.o
More common in women
Preceded often by hx of goiter (iodine insuff)
Usually invasive
Describe histology of anaplastic carcinoma
- Pleomorphic tumor cells can show spindle cells and multinuc giant cells
- Usually does not produce thyroglobulin as compared to well-differentiated malignant thyroid tumors
How fast does anaplastic carcinoma grow?
Very fast! Have necrosis and hemorrhage
