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Endocrine Pathology Lab


Endocrine Pathology Lab 2006 version with answers Case 1 Clinical History: This 23 year old female had a 2 year history of a slowly enlarging neck mass. – PowerPoint PPT presentation

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Title: Endocrine Pathology Lab

Endocrine Pathology Lab
  • 2006 version with answers

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

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).

(No Transcript)
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

Papillary tumor with psammoma body
Note the clear nuclei
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
  • 2. What is the diagnosis?
  • This is a papillary carcinoma. All papillary
    neoplasms of the thyroid are considered to be
  • 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.

Answers to questions case 1 cont.
  • 4. What are the four major types of thyroid
  • 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.

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

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.

Enlarged, hypercellular parathyroid.
There is less fat than normal (should be 1/3
Tumor cells are uniform, have scanty cytoplasm,
are more evenly spaced than lymphocytes.
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

A different case parathyroid hyperplasia (all 4
glands are gt6 mm long).
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!

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

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
  • Both parathyroid hyperplasia, or a second
    adenoma, must be excluded.

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.

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.

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

Thyroid in Graves - increased cellularity
(hyperplasia) reduced colloid.
Thyroid in Graves - Papillae extend into the
Thyroid in Graves columnar epithelial cells
scalloping into the colloid.
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
  • 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

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.

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).

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

This large red to yellow tumor has a central
scar. It was found where an adrenal should be.
At bottom, dichromate-fixed tissue turned dark
Adrenal at right, tumor at left.
Tumor at right. Note the small nests of tumor
Tumor cells have abundant cytoplasm many small
blood vessels.
The cytoplasm is finely granular.
The granularity corresponds to neurosecretory
granules, as seen in the EM photo.
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
  • The tumor cells contain chromaffin granules with
    catecholamines that are oxidized by a fixative
    containing potassium dichromate. This reaction
    gives the characteristic brown color.

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
  • The characteristic EM feature is presence of
    neurosecretory granules.
  • 5. Where else in the body might such tumors
  • About 10 of pheos arise in extraadrenal

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.

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
  • Her serum T4 was 6.0 micrograms/dl. Thyroid
    scintillation scan revealed normal uptake.
    Because of the apparent nodularity, surgery was

Inflamed thyroid with germinal centers.
Germinal centers and thyroid epithelium with
atrophy (lack of colloid).
The thyroid epithelium has abundant pink
cytoplasm (Hurthle cells).
See the Hurthle cells, with intermingled
lymphocytes and plasma cells.
  • Microscopic Pathology
  • What histologic features are present?
  • Is this neoplastic, hyperplastic, or
  • 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).

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).

Answers to questions case 5 cont.
  • 3. Is lymphoid population polyclonal or
  • It is polyclonal (reactive).
  • 4. What laboratory studies would have been useful
  • 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.

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
  • Early in the course, T4 is normal or increased,
    but as the disease progresses, hypothyroidism

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.


This is a very monotonous proliferation of
anterior pituitary cells.

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

Different case this is a microadenoma.
Answers to questions case 6
  • 1. What is the diagnosis?
  • This is a pituitary adenoma located in the sella
  • 2. Why did this lesion present such clinical
  • 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.

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.

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
  • 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.

Kidney and large tumor above it.
Note the large tumor cells with abundant
Adrenal Cortical Carcinoma
Note the area of hemorrhage in the center.
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.

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.

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
  • Regional lymph nodes, liver, and lung are the
    most common sites.

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

Much of the thyroid is destroyed by inflammation.
There are granulomas with giant cells.
In addition to giant cells, macrophages,
lymphocytes, other inflammatory cells are
Even areas with polys are sometimes seen.
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.

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.

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
  • 5. What is the typical clinical course for these
  • 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.
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