Endocrine Pathology Lab

1
Endocrine Pathology Lab

• 2006 version with answers

2
Case 1

• Clinical History
• This 23 year old female had a 2 year history of a
  slowly enlarging neck mass.
• Examination showed a single firm, non-tender
  nodule with the right lobe of the thyroid.
  Laboratory data revealed a T4 of 7.2
  micrograms/dl (normal 4.8 to 11.2). Serum
  calcitonin was normal. Ultrasound examination
  suggested a solid mass, while a thyroid
  scintillation scan revealed decreased uptake in
  the nodule (a cold" nodule). She was taken to
  surgery.

3
Case 1 cont.

• Gross Pathology
• This thyroid nodule is similar to that found in
  the patient. It is difficult to tell a benign
  from a malignant endocrine neoplasm from gross
  appearance, though the cut surface has
  papillations, and there is another nodule (the
  lesion is multifocal).

4
(No Transcript)
5
Case 1 cont.

• Microscopic Pathology
• This tumor is composed of papillary fronds with
  fibrovascular cores. A psammoma body is seen, a
  feature highly suggestive of papillary carcinoma.
  At high power, the fronds are lined by cells
  with prominent clear nuclei which are
  occasionally indented or grooved (this is the
  main basis for classification as a papillary
  carcinoma).

6
Papillary tumor with psammoma body
7
Note the clear nuclei
8
Answers to questions case 1

• 1. How do you determine if the neoplasm is benign
  or malignant?
• Metastases and invasion are the best indicators.
  In endocrine tumors, cellular anaplasia is less
  reliable.
• 2. What is the diagnosis?
• This is a papillary carcinoma. All papillary
  neoplasms of the thyroid are considered to be
  malignant.
• 3. What is the behavior of this tumor?
• Most papillary carcinomas of thyroid are
  indolent, even when metastatic. They can be
  multifocal. They often metastasize to cervical
  lymph nodes.

9
Answers to questions case 1 cont.

• 4. What are the four major types of thyroid
  carcinoma?
• These are papillary, follicular, medullary, and
  anaplastic. How do they differ microscopically?
  Papillary carcinomas have a branching, tree-like
  pattern, prominent clear nuclei, and psammoma
  bodies. Follicular carcinomas have follicles and
  lack the distinctive nuclei of papillary
  carcinoma. Medullary carcinomas have polygonal
  cells in sheets and nests with a prominent
  amyloid stroma (and often make calcitonin).
  Anaplastic (undifferentiated) carcinomas are very
  pleomorphic (spindle cells, giant cells, small
  cells) and are very aggressive.

10
Case 2

• Clinical History
• A 30 year old healthy active male had a serum
  calcium of 11.5 mg/dl (normal 8.6 to 10.7) with a
  normal serum albumin and a serum phosphorus of
  2.0 mg/dl (normal 2.4 to 4.1) on a chemical
  survey obtained as part of an employment physical
  examination. His CBC, serum creatinine, and
  chest x-ray were normal. He took no medications
  or vitamins. He denied abdominal pain or bone
  pain.

11
Case 2 cont.

• Clinical History Cont.
• What additional laboratory test would you order
  to confirm the diagnosis?
• He was taken to surgery, and a single enlarged
  parathyroid gland was found and removed after
  frozen section consultation with the pathologist.
  The remaining parathyroid glands were identified
  and were not enlarged.

12
Enlarged, hypercellular parathyroid.
13
There is less fat than normal (should be 1/3
fat).
14
Tumor cells are uniform, have scanty cytoplasm,
are more evenly spaced than lymphocytes.
15
Case 2 cont.

• Microscopic Pathology
• The lesion is circumscribed. The cells are
  uniform, with small round nuclei and pink
  cytoplasm. Vascularity is prominent.
• Differential Diagnosis
• Seen grossly here is another condition that must
  be distinguished. This is parathyroid
  hyperplasia.

16
A different case parathyroid hyperplasia (all 4
glands are gt6 mm long).
17
Answers to questions case 2

• 1. What is the diagnosis?
• This is a parathyroid adenoma. What is the
  diagnosis in the last slide? It is parathyroid
  hyperplasia. Both cause hyperparathyroidism,
  i.e. both calcium parathormone are elevated.
  Lower parathyroids thymus have similar
  embryologic origin (third branchial pouch)
  parathyroids can be in the mediastinum!

18
Answers to questions case 2 cont.

• 2. How is it usually detected?
• Now, with routine biochemical screening tests,
  most are found because of a high calcium. Many
  patients, like this man, are asymptomatic.
  However, many cases of hypercalcemia are not due
  to hyperparathyroidism (1/3 of cases are due to
  hyperparathyroidism, 1/3 to malignancies, and 1/3
  to other causes like vitamin D changes renal
  failure).

19
Answers to questions case 2 cont

• 3. What happens if it is untreated?
• Clinical symptoms of hypercalcemia can include
  weakness and fatigue, depression, psychosis,
  coma, renal stones, osteitis fibrosa cystica,
  peptic ulcers, hypertension, cholelithiasis, and
  soft tissue calcification.
• 4. Why did the surgeon to have identify all four
  parathyroids?
• Both parathyroid hyperplasia, or a second
  adenoma, must be excluded.

20
Answers to questions case 2 cont.

• 5. What are the criteria for malignancy in
  parathyroid tumors?
• Parathyroid carcinomas are far less common than
  adenoma. They are diagnosed by metastases,
  invasion of contiguous structure (making the
  tumor adherent to surrounding tissues at
  surgery), tumor thrombi in veins, fibrous bands,
  mitotic figures, and a very high (gt15) calcium.

21
Case 3

• Clinical History
• This 30 year old female presented with weakness,
  weight loss, and nervousness. Further
  questioning revealed complaints of insomnia,
  excess perspiration, frequent bowel movements,
  infrequent menses, heat intolerance. Physical
  examination showed a restless woman with warm,
  moist skin, palmar erythema, fine hair, and a
  resting pulse rate of 110/minute. On neck exam,
  the thyroid was diffusely enlarged. A fine
  tremor was noted of her outstretched fingers.

22
Case 3 Cont.

• Clinical History Cont.
• Deep tendon reflexes were 3 bilaterally.
• Serum T4 was 14.0 micrograms/ml (normal 4.8 to
  11.2).
• Thyroid scan showed increased uptake in both
  lobes.
• A subtotal thyroidectomy was performed. The
  tissue removed weighed 60 grams (normal thyroid
  is up to 30 grams). It was symmetrical and soft.

23
Thyroid in Graves - increased cellularity
(hyperplasia) reduced colloid.
24
Thyroid in Graves - Papillae extend into the
colloid.
25
Thyroid in Graves columnar epithelial cells
scalloping into the colloid.
26
Answers to questions Case 3

• 1. What is the diagnosis?
• This is Graves disease. The main differential
  diagnosis is Plummers disease (toxic
  multinodular goiter).
• 2. What immunologic mechanism might be at work
  here?
• There might be anti-TSH receptor antibodies.
  These can be thyroid-stimulating
  immunoglobulins (TSI) that increase hormone
  production, thyroid-growth immunoglobulins (TGI)
  that cause the hyperplasia (or a mixture of both.
  Some patients also have inhibitory antibodies
  (TBII).

27
Answers to questions case 3 cont

• 3. What neoplasms could produce similar findings?
• A toxic thyroid adenoma could produce
  hyperthyroidism. Rarely, a thyroid carcinoma or
  a pituitary adenoma secreting TSH could be
  etiologies. Even more rarely, struma ovarii
  (thyroid tissue in an ovarian teratoma) or
  choriocarcinoma could do the same.

28
Case 4

• Clinical History
• A 30 year old female presented with periodic
  headaches, palpitations, nervousness, and
  perspiration. She also had lost 15 pounds
  without dieting or a change in appetite.
  Physical examination revealed a pulse of 100/min
  and a blood pressure of 160/110. Serum T4 was
  7.0 micrograms/dl with normal T3 uptake and
  normal T3 (94 ng/dl with normal range 74-166).

29
Case 4 Continued

• Clinical History Cont.
• What additional tests might prove helpful?
• Gross Pathology
• A large red to yellow mass with a central scar
  is seen above the kidney. A portion of the mass
  was fixed in a dichromate fixative and turned
  brown.

30
This large red to yellow tumor has a central
scar. It was found where an adrenal should be.
31
At bottom, dichromate-fixed tissue turned dark
brown.
32
Adrenal at right, tumor at left.
33
Tumor at right. Note the small nests of tumor
cells.
34
Tumor cells have abundant cytoplasm many small
blood vessels.
35
The cytoplasm is finely granular.
36
The granularity corresponds to neurosecretory
granules, as seen in the EM photo.
37
Answers to questions case 4

• 1. What is the diagnosis?
• This is a pheochromocytoma arising in the
  adrenal medulla.
• 2. Why did the tumor turn brown in dichromate
  fixative?
• The tumor cells contain chromaffin granules with
  catecholamines that are oxidized by a fixative
  containing potassium dichromate. This reaction
  gives the characteristic brown color.

38
Answers to questions case 4 cont.

• 3. How would you tell if this were malignant?
• The only reliable way is metastasis.
• 4. What would be seen in this tumor by electron
  microscopy?
• The characteristic EM feature is presence of
  neurosecretory granules.
• 5. Where else in the body might such tumors
  arise?
• About 10 of pheos arise in extraadrenal
  paraganglia.

39
Answers to questions case 4 cont.

• 6. What other tumors could be associated with
  this lesion when inherited as an autosomal
  dominant syndrome?
• Multiple endocrine neoplasia type IIa (Sipples
  syndrome) could have associated medullary
  carcinoma of thyroid and parathyroid hyperplasia
  or adenoma.

40
Case 5

• Clinical History
• A 50 year old female presented with a slowly
  enlarging, non-tender neck mass. Physical
  examination showed an enlarged, firm, nodular
  thyroid.
• Her serum T4 was 6.0 micrograms/dl. Thyroid
  scintillation scan revealed normal uptake.
  Because of the apparent nodularity, surgery was
  performed.

41
Inflamed thyroid with germinal centers.
42
Germinal centers and thyroid epithelium with
atrophy (lack of colloid).
43
The thyroid epithelium has abundant pink
cytoplasm (Hurthle cells).
44
See the Hurthle cells, with intermingled
lymphocytes and plasma cells.
45

• Microscopic Pathology
• What histologic features are present?
• Is this neoplastic, hyperplastic, or
  inflammatory?
• At low power, thyroid follicles can be seen, but
  much of the gland has collections of lymphocytes,
  and there are some germinal centers. At higher
  power, the lymphoid stroma has small and large
  lymphocytes with plasma cells. The remaining
  thyroid epithelial cells are large with abundant
  pink cytoplasm (Hurthle cell change).

46
Answers to questions case 5

• 1. What is the diagnosis?
• This is Hashimotos thyroiditis.
• 2. What is the etiology?
• This is an autoimmune disease. There are TSH
  receptor antibodies (predominantly of the TGI
  type). Serologic testing can also find
  anti-thyroglobulin antibodies and anti-thyroid
  peroxidase, or TPO, antibodies (formerly known as
  anti-microsomal antibodies).

47
Answers to questions case 5 cont.

• 3. Is lymphoid population polyclonal or
  monoclonal?
• It is polyclonal (reactive).
• 4. What laboratory studies would have been useful
  preoperatively?
• Anti-TSH receptor, anti-thyroglobulin and
  anti-microsomal (thyroid peroxidase) antibody
  tests would have been helpful. Aspiration
  cytology would have helped if a neoplasm were in
  the differential diagnosis.

48
Answers to questions case 5 cont.

• 5. What are the indications for surgery?
• Lymphadenopathy, rapid growth, or lack of
  response to thyroid suppressive therapy are
  indications for surgery.
• 6. What is the typical clinical course for these
  patients?
• Early in the course, T4 is normal or increased,
  but as the disease progresses, hypothyroidism
  occurs.

49
Case 6

• Clinical History
• A 40 year old male truck driver consulted his
  optometrist because he was having headaches and
  having trouble using rear view mirrors and
  thought he needed new glasses. The optometrist
  recognized that his patient had visual field
  deficits and referred him to a physician. A CT
  scan of the head showed a 2.5 cm mass in the
  sella turcica.

50

This is a very monotonous proliferation of
anterior pituitary cells.
51

At higher power, the cells are very monomorphic.
They have round nuclei and granular basophilic
cytoplasm.
52

Different case this is a microadenoma.
53
MRI
54
Answers to questions case 6

• 1. What is the diagnosis?
• This is a pituitary adenoma located in the sella
  turcica.
• 2. Why did this lesion present such clinical
  symptoms?
• Some symptoms such as headache and visual field
  disturbances are caused by pressure effects of
  this neoplasm growing in the sella turcica. Why
  did the lesion seen in the last slide cause no
  symptoms? That is a tiny microadenoma too
  small to produce pressure symptoms and probably
  secreting prolactin, which would not have
  noticeable effects in a male.

55
Answers to questions case 6 cont.

• 3. What are some other syndromes associated with
  lesions of this nature?
• Amenorrhea-galactorrhea and infertility can occur
  from prolactin secretion in a female, acromegaly
  can result from growth hormone secretion.
  Cushings syndrome from corticotropin secretion,
  and hyperthyroidism from TSH secretion.

56
Case 7

• Clinical History
• A 40 year old female presented with complaints of
  weight gain, acne, and increased facial hair.
  Physical examination revealed a blood pressure of
  154/98, truncal obesity, a round face, acne,
  ecchymoses of the arms and legs, purplish
  abdominal striae, and hirsutism.
  Hyperpigmentation of the skin and proximal
  muscular weakness were not apparent. She had not
  been seeing a physician and was taking no
  medications.
• Why is the medication history important?
• What laboratory tests should be ordered?
• A CT scan of the abdomen revealed a large
  retroperitoneal mass. Surgery was performed.

57
Kidney and large tumor above it.
58
Note the large tumor cells with abundant
cytoplasm.
59
Adrenal Cortical Carcinoma
60
Note the area of hemorrhage in the center.
61
Case 7 Cont.

• Gross Pathology
• A circumscribed tan-white mass with areas of
  hemorrhage and necrosis is seen above the kidney.
• Microscopic Pathology
• At low power, the tumor is adjacent to compressed
  normal adrenal gland. At high power, the
  neoplastic cells are in large nests. The cells
  have pale pink to clear cytoplasm nuclei show
  pleomorphism focal hemorrhage is present.

62
Answers to questions case 7

• 1. What is the diagnosis?
• This is an adrenal cortical carcinoma with
  Cushings syndrome. Where is the origin of this
  neoplasm, compared to case 4? It arises in the
  adrenal cortex, not the medulla, as
  pheochromocytomas do.
• 2. What do such lesions secrete?
• The majority of adrenal cortical carcinomas
  secrete hormones, often corticosteroids and their
  precursors. Some secrete androgenic or
  estrogenic hormones, leading to virilization or
  femininization. Adrenal carcinomas very rarely
  produce aldosterone.

63
Answers to questions case 7 cont.

• 3. What are the signs of malignancy?
• Reliable indications of malignancy include
  metastases, invasion of vasculature or adjacent
  tissue, spindle cells, and numerous mitotic
  figures. Tumor size gt5 cm is also an indicator.
• 4. What are the most common sites of metastatic
  disease?
• Regional lymph nodes, liver, and lung are the
  most common sites.

64
Case 8

• Clinical History
• An otherwise healthy 40 year old female presented
  with an enlarged, nodular, firm thyroid. The
  serum T4 was normal and a thyroid scan showed
  decreased 131I uptake. There was a clinical
  suspicion of carcinoma, so the thyroid was
  removed.

65
Much of the thyroid is destroyed by inflammation.
66
There are granulomas with giant cells.
67
In addition to giant cells, macrophages,
lymphocytes, other inflammatory cells are
present.
68
Even areas with polys are sometimes seen.
69
Case 8 Cont.

• Microscopic Pathology
• Describe the histologic features. Is this
  process neoplastic, hyperplastic, or
  inflammatory? At lower powers, much of the
  normal thyroid follicular structure is destroyed.
  At higher magnification, the thyroid parenchyma
  contains a prominent granulomatous inflammatory
  reaction with lymphocytes, neutrophils,
  macrophages, and large multinucleated giant cells
  seen around damaged thyroid follicles.

70
Answer to questions case 8

• 1. What is the diagnosis?
• This is subacute granulomatous thyroiditis (De
  Quervain's disease).
• 2. What is the etiology?
• It is thought to be caused by viral infection
  (more likely a post viral inflammatory process).
  It typically follows a respiratory infection.
• 3. How do these patients usually present?
• They usually have fever, neck pain, and an
  enlarged tender thyroid, but in some cases, as in
  this one, such a history may not be present and
  the enlarged, firm thyroid misinterpreted as
  possible carcinoma.

71
Answer to questions case 8 cont.

• 4. Who gets this disease?
• Middle aged women. In fact, all of the thyroid
  diseases we have discussed have a female
  predominance.
• 5. What is the typical clinical course for these
  patients?
• The natural history of this disease is that mild
  hyperthyroidism will progress to transient
  hypothyroidism and then eventually return to a
  euthyroid state. This occurs over a matter of
  months. The glacial nature of the appointment
  and referral process in some health care systems
  may mean that the patient is cured by the time he
  or she is seen by the endocrinologist.