Thyroid Nodules: Clinical, Pathologic Flashcards
Thyroid Nodules
a. Thyroid nodules are lumps which commonly arise within an otherwise normal thyroid gland.
i. They indicate a thyroid neoplasm, but only a small percentage of these are thyroid cancers.
b. Often these abnormal growths of thyroid tissue are located at the edge of the thyroid gland and can be felt as a lump in the throat.
i. When they are large or when they occur in very thin individuals, they can sometimes be seen as a lump in the front of the neck.
c. Only a small percentage of lumps in the neck are malignant (around 4 – 6.5%[11]), and most thyroid nodules are benign colloid nodules.
Prevalence of Endocrine Disorders in U.S.
Metabolic syndrome 35% Obesity 20-30% Diabetes 6-22% Hypercholesterolemia 17% Osteoporosis 6-7%
Thyroid nodules—> 30-60%
25 year-old 10%
70 year-old 55%
How are Thyroid Nodules Discovered?
- Noted by pateient–> 40%
- Noted by third party—> 30%
- Detected by other test—> 30%
i. Ultrasound, CT scan, MRI
Retrospective cohort study
299 patients referred to surgical clinic
Thyroid Nodules- The problem
a. Thyroid nodules are common (nearly 60%)
b. The risk of cancer in a thyroid nodule is small
i. (10-15% malignant), BUT not insignificant
Normal Thyroid
a. See normal follicular cells surrounding the lumen space of the thyroid
i. should be orderly
C cells (calcitonin stain)
a. Hard to see
Thyroid Neoplasms
a. Benign
Adenoma
NIFTP (rare, non-invasive follicular thyroid neoplasm with papillary nuclear features)
b. Malignant
1. Papillary (85-90%) multifocal, LN
- Follicular/Hurthle (5%) vascular spread
- Anaplastic (<2%) very aggressive
- Medullary (5%) familial
Others malignant
Lymphoma (rare)
Sarcoma (rare)
Metastatic (rare)
Thyroid adenoma
a. Benign neoplasm
b. Solitary nodule
c. Follicular / Hurthle cell
d. DDx: hyperplastic nodule
i. follicular ca
- Critical–>Careful evaluation of the capsule
i. if there invasive lesion in capsule–> It is Thyroid Carcinoma
Follicular/Hurthle cell Carcinoma
Two types of Carcinoma:
- Minimally invasive:
i. Vascular or capsular invasion - Widely invasive:
More extensive invasion into the surrounding muscle, vessels, trachea ect.
Follicular Carcinoma, Minimally invasive
Minimally invasive carcinoma:
i. Vascular or capsular invasion
b. A bunch of micro follicules that are invading potentially into vessel
c. Abornmal lesion or growth
Follicular Carcinoma, Widely invasive
Widely invasive:
More extensive invasion into the surrounding muscle, vessels, trachea ect.
Papillary Carcinoma
a. Most common
i. papillary due to finger like
b. Well-differentiated
c. Multifocal
d. Lymphatic spread
e. Excellent prognosis
i. even if it invades lymph nodes
Papillary Carcinoma- Histology
- Papillae with vascular core
- Optically clear nuclei
i. Nucleus is pushed to edge of cell
ii. Clear center of cell *Critical to know - Nuclear pseudoinclusions
i. little round inclusions inside the nuclei - Nuclear grooves
- Rare or absent mitoses
- Psammoma Bodies
i. little areas of calcifications
Follicular Variant of Papillary Thyroid Cancer
a. Variant of the highly common papillary thyroid cancer
Papillary Carcinoma
Summary points
a. Most common
b. Well-differentiated
i. Multifocal
ii. Lymphatic spread
c. Excellent prognosis
d. Histology: Papillae with vascular core *Optically clear nuclei *Nuclear pseudoinclusions Nuclear grooves Rare or absent mitoses *Psammoma Bodies-->Ca2+ deposits
Thyroid Gland - Anaplastic Carcinoma
a. Older age group (poor survival)
b. Rapidly growing mass
c. Three patterns:
1) Spindle cell
2) Giant cells
3) Squamoid cells
d. Necrosis and hemorrhage
i. more common in anaplastic, not seen in thyroid carcinoma
Transition to Anaplastic
a. Will see transition from carcinoma to aplastic
i. see more ugly and undifferentiated cells
b. Will see Necrosis and hemorrhage
Anaplastic Thyroid Carcinoma
a. Metastasis can be anywhere (lungs, liver, ect)
Thyroid Gland - Medullary Carcinoma
a. Solid proliferation of cells with granular cytoplasm (C cells)
b. Highly vascular stroma
c. Hyalinized collagen and/or amyloid
i. will see these deposited*
d. May have Psammoma bodies (Ca2+ deposits)
Immunostains:
Thyroglobulin -, Calcitonin +, Chromogranin +
Thyroid Gland - Lymphomas
a. Often arise in long-standing autoimmune thyroiditis
b. Large fleshy masses
c. DDx : anaplastic carcinoma of thyroid
d. Positive LCA, usually B-cell Lymphoma
e. Gene rearrangement can prove clonality
f. Immunophenotyping can be performed on FNA
Thyroid Gland - Other Tumors
a. Sarcomas: (RARE)
b. Metastatic Tumors: (RARE)
Melanoma Renal
Lung Breast
Head & neck Colon
Clinical Evaluation
a. HistoryL
Growth
Pain
Cough, voice change
b. Irradiation
i. radiation will increase in risk, find out in history
c. Family history—> possible genetics
d. Physical examination: Size Consistency Fixation Lymphadenopathy
Clinical Evaluation
High clinical suspicion
a. High clinical suspicion:
- Rapid tumor growth
- Very firm nodule (rock hard)
- Fixation to adjacent structures
- Vocal cord paresis
- Enlarged regional lymph nodes
b. Genetic suspicion:
i. Family history of PTC or MEN 2
c. Distant metastases
d. Predictive value
i. Positive Predictive Value (PPV) – good (70-75%)
- these signs/symptoms are VERY predictive of possible neoplasm
ii. Negative Predictive Value (NPV) – unacceptable (85%)
Approach to the Patient with Thyroid Nodules
Things to Do:
- Measure Serum TSH
i. low TSH means there unlikely to be cancer - Diagnostic Ultrasound of neck
- Fine Needle Biposy
i. can help us determine if malignant, benign, non-diagnostic, intermediate
Thyroid Nodules- Streamlined work-up
TSH
Ultrasound
Fine-needle aspiration biopsy
Thyroid Nodule Biopsy
a. One approach used to determine whether the nodule is malignant is the fine needle biopsy (FNB), which some have described as the most cost-effective, sensitive and accurate test.
b. FNB or ultrasound-guided FNA usually yields sufficient thyroid cells to assess the risk of malignancy, although in some cases, the suspected nodule may need to be removed surgically for pathological examination.
c. The report may be done according to the Bethesda System for Reporting Thyroid Cytopathology.
Fine-Needle Aspiration Biopsy/Accuracy
a. Very accurate at finding malignant (98%)
i. good for finding malignant
b. Will find benign and suspicious DX at a lower rate
c. We have a scan for suspicious tumors that we cannot determine if malignant or benign
Papillary Carcinoma of Thyroid - Cytologic Features
- Highly cellular aspirate
- +/- colloid
- Nuclear enlargement, elongation
- Nuclear grooves, pseudoinclusions
- Multiple small to large nucleoli
- Psammoma bodies
- Papillary cellular aggregates
Bethesda System
a. The Bethesda system (TBS) is a system for reporting cervical or vaginal cytologic diagnoses, used for reporting Pap smear results
b. Can be used for thyroid pathology, will be able to use this report to share info with pathology
c. There are six categories: Non-Diagnostic, Benign, ACUS, suspicition for follow up neoplasm, Suspicious for Malignant, and Malignant
Genetics of cancer
a. Proto-oncogene—> Normal gene which codes for a protein that promotes normal cell division
b. Oncogene—> Mutated gene which codes for a protein that causes unregulated cell division
c. Tumor Suppressor Gene–> Normal gene which codes for a protein that restrains cell division or that promotes cell differentiation, DNA repair or apoptosis
Basic Concepts
a, Tumors result from oncogene activation or tumor suppressor gene loss
b. Cells transformed by genetic mutations are likely to develop more mutations
c. Cancers result from multiple sequential genetic mutations
Malignant thyroid neoplasms to know
- Papillary (85-90%) multifocal, LN
- Follicular/Hurthle (5%) vascular spread
- Anaplastic (<2%) very aggressive
- Medullary (5%) familial
Others malignant
Lymphoma (rare)
Sarcoma (rare)
Metastatic (rare)
Solid proliferation of cells with granular cytoplasm (C cells)
i. Highly vascular stroma
ii. Hyalinized collagen and/or amyloid
Thyroid Gland - Medullary Carcinoma
a. Solid proliferation of cells with granular cytoplasm (C cells)
b. Highly vascular stroma
c. Hyalinized collagen and/or amyloid
i. will see these deposited*
d. May have Psammoma bodies (Ca2+ deposits)
Immunostains:
Thyroglobulin -, Calcitonin +, Chromogranin +
Molecular Mechanisms (Papillary Ca)
RET/PTC
Rearrangement
20%
a. Mutations associated with papillary thyroid cancer are mainly two forms of chromosomal translocation and one form of point mutation.
i. These alterations lead to activation of a common carcinogenic pathway—the MAPK/ERK pathway.
b. Chromosomal translocations involving the RET proto-oncogene (encoding a tyrosine kinase receptor that plays essential roles in the development of neuroendocrine cells) occur in approximately a fifth of papillary thyroid cancers.
c. The fusion oncoproteins generated are termed RET/PTC proteins (ret/papillary thyroid carcinoma), and constitutively activate RET and the downstream MAPK/ERK pathway.
d. The frequency of ret/PTC translocations is significantly higher in papillary cancers arising in children and after radiation exposure.[1] The gene NTRK1 (encoding the TrkA receptor
e. Approximately a third to a half of papillary thyroid carcinomas harbor point mutations in the BRAF oncogene, also activating the MAPK/ERK pathway.
i. In those cases the BRAF mutations found were V600E mutation
p53 in thyroid cancer
a. Oncogene gain of function is the most frequent molecular alteration described in thyroid cancer.
i. It mainly includes the aberrant activation of the RAS/RAF/MEK/ERK pathway\
ii. These alterations regard the rearrangements of Ret/PTC and Trk tyrosine kinase receptors and point mutations of RAS or BRAF genes
b. Loss of function of tumor suppressor proteins may also occur in thyroid cancer and includes PAX-8/PPARγ rearrangement, PTEN down-regulation, β-catenin, and p53 mutations
c. While inactivating mutations of the p53 gene is very frequent in human cancers (50% of all human malignancies), they have been found in only 10% of thyroid carcinomasand mainly in poorly differentiated and aggressive histotypes.
d. These observations and the indolent progression of most thyroid carcinomas have brought to the paradigm that p53 role is minor in thyroid cancer initiation and early stages, while it is important only in the rare case of progression to aggressive phenotypes
i. However, the role of p53 functional inactivation in thyroid cancer has never been carefully studied and remains controversial.
Poorly differentiated thyroid cancers
- P53 mutation can lead to anaplastic carcinoma
i. know this
While inactivating mutations of the p53 gene is very frequent in human cancers (50% of all human malignancies), they have been found in only 10% of thyroid carcinomasand mainly in poorly differentiated and aggressive histotypes.
