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Endocrine > Cancer > Flashcards

Cancer Flashcards

1
Q
  1. Solitary or miltifocal
  2. Move freely during swallowing
  3. Typically presents asymptomatically
  4. cold masses on scintiscans
  5. isolated cervical nodal metz = no prognostic significance
  6. finely dispersed chromatin impart optically clear, empty appearance “orphan annie eye nuclei” and invaginations that give the appear of inclusions, called pseudo inclusions
  7. Fibrosis, calcification, cystic, psammoma bodies
A
  1. papillary carcinoma
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2
Q

variant of papillary carcinoma

  1. more aggressive
  2. high freq RAS mutations
  3. lower freq RET/PTC
  4. lower freq of BRAF mutations
A

Poorly Circumscribed-infiltrative-papillary follicular carcinoma

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3
Q

Papillary carcinoma variant

  1. Tend to occur in older folks
  2. all columnar cells
  3. Intensely eosinophilic cytoplasm lining papillary structure
A

Papillary carcinoma tall cell variant

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4
Q

Papillary carcinoma tall cell variant: characteristics

A
  1. Higher frequencies of vascular invasion
  2. Higher frequencies of extrathyroidal extension
  3. Higher frequencies of cervical and distant metz
  4. BRAF (bad) mutations 55%-100% of cases
  5. RET/PTC translon often as well
  6. BRAD and RET/PTC synergistic
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5
Q
  1. Younger children/individuals
  2. LN metz in almost all cases
  3. NO BRAF mutations, ~50% have RET/PTC translocations
  4. Papillary patter + solid areas of squamous metaplasia “nests”
  5. Extensive fibrosis through thyroid
A

Diffuse sclerosing-papillary variant

  1. Younger children/individuals
  2. LN metz in almost all cases
  3. NO BRAF mutations, ~50% have RET/PTC translocations
  4. Papillary patter + solid areas of squamous metaplasia “nests”
  5. Extensive fibrosis through thyroid
  6. Often associated with lymphocytic infiltrate that simulates Hoshimoto’s thyroidits
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6
Q
A
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7
Q

thyroid neoplasms:

gender, age, malig vs benign, progressive vs indolent,

A

Solitary palpable nodules US adults: incidence1‐ 10%

  1. Significantly higher in endemic goitrous regions
  2. W>M
  3. Incidence increases throughout life
  4. Overwhelming majority of solitary nodules are benign
  5. < 1% of solitary thyroid nodules are malignant
  6. ~ 15,000 new cases of thyroid carcinoma per year in the US
  7. Most of these cancers are indolent
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8
Q

features more likely to make a nodule neoplastic vs benign

A

More likely neoplastic:
– Solitary nodules
– Nodules in younger patients
– Nodules in males
– History of radiation to the head and neck

More likely benign:

– Multiple nodules

– Nodules in older patients

– Nodules in females

– Functional nodules that take up radioactive iodine (hot nodules)

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9
Q

present as discrete, solitary, unilateral and painless masses during routine physical examination

– Larger masses may produce symptoms (e.g difficulty swallowing)

A

folliciular adenoma

in general non-functional, small subset are hot

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10
Q

Solitary, spherical, encapsulated lesion that is well demarcated from the surrounding thyroid and made up of uniform‐appearing follicles which typically contain colloid

  1. growth pattern is usually quite distinct from the adjacent thyroid
  2. Cells are uniform and bland
  3. Look like surrounding follicular epithelial cells
  4. Occasionally the cells have eosinophilic, granular cytoplasm (oxyphil or Hürthle cell change)

How do we distinguish it from carcinoma?

A

The integrity of the capsule is key in distinguishing follicular adenomas from follicular carcinomas

Folliciular adenomas:

  1. Solitary, spherical, encapsulated lesion
  2. Well demarcated from the surrounding thyroid • Made up of uniform‐appearing follicles that
  3. typically contain colloid
  4. The follicular growth pattern is usually quite distinct from the adjacent thyroid
  5. Cells are uniform and bland
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11
Q
A

Fine Needle Aspiration

With or without ultrasound guidance

Very useful in evaluation of thyroid nodules

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12
Q

Diagnosis of Follicular Adenomas: Radionuclide, US, FNA, and surgical resection

A
  1. Radionuclide scan
    1. Cold Nodules: Nonfunctioning adenomas take up less radioactive iodine than the normal thyroid parenchyma
      1. Up to 10% of cold nodules are malignant
  2. Ultrasonography and fine‐needle aspiration
    1. “Follicular neoplasm” with ddx of follicular adenoma, follicular carcinoma, or follicular variant of papillary carcinoma
    2. Ultimately need to evaluate capsule for a definitive diagnosis
  3. Surgically resected:
    1. capsule is evaluated grossly and histologically to exclude carcinoma
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13
Q

thyroid cancer: gender, age, RFs, association with iodine, types

A

W>M early and middle adult years; W≈M in childhood and late adult life

Exposure to ionizing radiation early in life leads to increased risk of Papillary carcinoma

Dietary iodine deficiency is linked with a higher frequency of follicular carcinomas

Types:
– Papillary carcinoma (>85% of cases)
– Follicular carcinoma (5% to 15% of cases)
– Anaplastic (undifferentiated) carcinoma (<5% of cases)

– Medullary carcinoma (5% of cases)

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14
Q

RET/PTC translocation/inversion

A

papillary T carcinoma, Tall Cell variant PTC often has this mutation

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15
Q

RAS

A

Follicular carcinoma and anaplastic carcinoma

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16
Q

PAX8; PPARG

A

Follicular carcinoma

17
Q

PI3K

A

Follicular and anaplastic carcinoma, point mutations and amplifications

18
Q

PTEN

A

folliciular and anaplastic carcinomas

19
Q

most common form of thyroid carcinoma

A

papillary carcinoma (86%), can occur at any age, 25-50 is the peak period

20
Q

papillary carcinoma

A
  1. Can be solitary or multifocal
  2. Can be well circumscribed, encapsulated, or infiltrative
  3. Usually has areas of fibrosis and calcification
  4. Often cystic
  5. Nuclei are the key to diagnosis:
    1. Finely dispersed chromatin, giving them an optically clear or empty appearance
    2. Ground‐glass or Orphan Annie eye nuclei
    3. Nuclear groove
    4. Invaginations of the cytoplasm gives the appearance of intranuclear inclusions (“pseudo‐inclusions”)
21
Q

pic

A

orphan annie nuclei- papillary carcinoma

23
Q

BRAF

A

Papillary carcinoma, tall cell variant (55%-100%), poor prognosis

24
Q

diagnosis. cervical nodal metastasis and PTC. Most common metz, clinical survival rate

A
  1. Radionuclide: cold nodule
  2. FNA can be diagnostic if nuclear features present
  3. ISOLATED LN metz does not have a significant influence of prognosis
  4. If metz to other locations beyond LNs, lung is the most common
  5. 10 yr survival > 95%, less than 40 not as good
25
Q

poor prognostic factors for papillary carcinoma

A

age less than 40, extrathyrodial extension/distant metz

26
Q

folliciular thyroid carcinoma: % of TC, geographic incidence, gender, age

A
  1. 5‐15% of primary thyroid cancers
  2. More frequent in areas with dietary iodine deficiency
  3. W>M
  4. More often in older patients than papillary carcinoma: Peaks 40‐60 yrs
27
Q

follicular carcinoma: major distinctions, normal morphology

A
  1. Distinguished from adenomas by capsular and/or vascular invasion
  2. Distinguished from papillary carcinoma by absence of nuclear features

Other general Morph features

  1. Single nodules that may be well circumscribed or widely infiltrative
  2. Sharply demarcated lesions are very difficult to distinguish from follicular adenomas
  3. May require examining the entire capsule microscopically to find invasion
  4. Small follicles with colloid with uniform cells
    1. Hürthle cell (oncocytic) variant: cells with abundant granular, eosinophilic cytoplasm
    2. Nuclei lack the features typical of papillary carcinoma
28
Q

folliciular carconoma clinical presentation, scintigram, metz characteristic, where they metz, prognosis

A
  1. Present as slowly growing painless nodules
  2. Typically “cold” nodules on scintigrams
  3. Rarely hyperfunctional and appear “warm”
  4. Don’t typically invade lymphatics, so lymph nodes are only rarely involved
  5. Vascular (hematogenous) dissemination is common – Metastasizes to bone, lungs, liver, etc
  6. Prognosis depends on the extent of invasion and stage at presentation
29
Q

folliciular carcinoma tx

A
  1. Total thyroidectomy followed by the radioactive iodine
    1. Can be used to identify metastases and to ablate them
  2. Also treated with thyroid hormone to suppress endogenous TSH levels
    1. Residual follicular carcinoma may respond to TSH stimulation
  3. Serum thyroglobulin levels are used for monitoring tumor recurrence
30
Q

what this secretes, how that can be used, incidence of major manifestations, genetic associations

A

Medullary Thyroid Carcinoma: those are parafollicular cells

  1. Secrete calcitonin
    1. Help in the diagnosis
    2. Can also use to follow patients after surgery
  2. Tumors also sometimes secrete other hormones
    1. Serotonin, ACTH, vasoactive intestinal peptide (VIP)
  3. ~70% are sporadic
  4. ~30% are familial
    1. MEN syndrome 2A or 2B
    2. Familial medullary thyroid carcinoma
      1. Familial form associated with germline RET mutations
        1. Constitutive activation of the receptor
      2. RET mutations are also seen in ~1/2 sporadic
31
Q

differentiating sporadic to familial medullary thyroid carcinoma

A
  1. sporadic usually unilateral, familial usually bilateral
  2. Tumor cells are positive for calcitonin by immunohistochemistry
  3. Amyloid deposits are present in the stroma
  4. Familial medullary cancers: Multicentric C‐cell hyperplasia in the surrounding thyroid parenchyma
32
Q

Sporadic medullary thyroid carcinoma: what do they secrete and how do they appear

A
  1. Mass in the neck
    1. Sometimes with dysphagia or hoarseness
  2. Some cases initially present with paraneoplastic syndrome caused by secretion of a hormone – e.g., diarrhea due to the secretion of VIP
  3. Can secrete serotonin, VIP, ACTH (cushings), CEA
  4. Interestingly, hypocalcemia is not a prominent feature, even though calcitonin levels are elevated
  5. Carcinoembryonic antigen (CEA) also secreted by many tumors (useful tumor marker for disease burden and follow‐up)
33
Q
A

Thyroductal Cyst

  1. Vestige of the tubular thyroid leading to a persistent sinus tract
  2. Parts of the tube remain to form cysts
  3. May not become evident until adulthood
  4. Cysts can collect mucinous, clear secretions
  5. Midline of the neck (anterior to the trachea)
34
Q

Morphology of thyroductal cysts: epithelial changes high and low in the neck, relationship to cancer, others

A

Epithelium with an intense lymphocytic infiltrate:

  1. High in the neck: lined by stratified squamous epithelium
  2. Lower neck: lined by epithelium resembling the thyroidal acinar epithelium

Can become infected and form abscess cavities

Rarely give rise to cancers

Endocrine (20 decks)

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