Path Lab with Answers (PPT)

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 surgery.

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).

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).

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 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.

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.

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.

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 fat).

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 hyperplasia.

A different case: parathyroid hyperplasia (all 4 glands are >6 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!


• 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).

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.


• 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 (>15) 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 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.

Thyroid in Graves - increased cellularity (hyperplasia) & reduced colloid.

Thyroid in Graves - Papillae extend into the colloid.

Thyroid in Graves – columnar epithelial cells & scalloping into the colloid.

Answers to questions Case 3• 1. What is the diagnosis?

– This is Grave’s disease. The main differential diagnosis is Plummer’s 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).

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 brown.

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 brown.

Adrenal at right, tumor at left.

Tumor at right. Note the small nests of tumor cells.

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 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.


• 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.


• 6. What other tumors could be associated with this lesion when inherited as an autosomal dominant syndrome?– Multiple endocrine neoplasia type IIa (Sipple’s

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 thyroid.

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

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 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).


• 1. What is the diagnosis?– This is Hashimoto’s 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).


• 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.


• 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.

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 cytoplasm.

Different case: this is a microadenoma.


• 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.


• 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. Cushing’s 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 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.

Kidney and large tumor above it.

Note the large tumor cells with abundant cytoplasm.

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.


• 1. What is the diagnosis?– This is an adrenal cortical carcinoma with Cushing’s

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.


• 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 >5 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.

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.

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 present.

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 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.

Path Lab with Answers (PPT)

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