Pathology Lab-Endocrine Flashcards
A 50-year-old male with an incidental neck mass found on routine physical examination. Thymic irradiation as an infant. No family history of thyroid or endocrine neoplasms. A 2cm diameter nodule is present in the right lobe of the thyroid gland. No adenopathy identified. All laboratory chemistries were WNL. Cold nodule on radioactive thyroid scan, fine needle aspiration performed and histology shown below. What is your diagnosis?
Papillary carcinoma. Note that you do not need to see papillae to make the diagnosis. You need to see optically clear nuclei (Orphan Annie nuclei), nuclear grooves
This 62-year-old woman complained of weight gain, cold intolerance, fatigue, and gradually enlarging firm painless neck mass for 4 years. Diffuse enlargement of thyroid without nodularity (goiter). TSH increased. Decreased T3/T4. Thyroid biopsy is shown below. What type of hypersensitivity is this condition?
Note the Hurthle cells, formation of germinal centers and inflammatory infiltrate typical of Hashimoto’s thyroiditis, a type IV hypersensitivity. CD8+ T-cells drive the majority of thyroid destruction. CD4+ T-cells drive macrophage destruction via IFN-gamma. B-cells form germinal centers ant anti-microsomal abs, anti-thyroid peroxidase abs and anti-thyroglobulin abs.
This 42-year-old patient presented for evaluation of persistent hypertension, obesity and easy bruising. Congenial middle age female in no acute distress with a round full face, prominent supraclavicular fat pads and numerous abdominal striae. BP was 196/96. 24 hr urine free cortisol 1000 mg (nl
Adrenal adenoma, adrenal carcinoma (more likely w/virilization) or ectopic ACTH production.
A 50-year-old woman presented with fatigue, bone pain and constipation. Hypercalcemia. Imaging studies disclose bilateral nephrolithiasis and abnormal foci of bone loss. What is the most common cause of symptomatic hypercalcemia? What about asymptomatic hypercalcemia?
Symptomatic = cancer. Asymptomatic = primary hyperparathyroidism.
A 50-year-old woman with chronic renal failure secondary to focal segmental glomerulosclerosis presents with a chief complain of “bone pain.” Serum calcium 7.8 mg/dL (8.5-10.5 mg/dL), phosphorus 6.6 mg/dL (3-4.5 mg/dL), PTH 75 pg/mL (10- 65 pg/mL). Imaging studies showed enlargement of all 4 parathyroid glands. Bone films show renal osteodystrophy. What is causing her condition?
Secondary hyperparathyroidism from increased PO4 retention due to renal failure.
Presentation of most thyroid tumors?
Most often presents as a solitary mass lesion, rarely presents as functional hyperthyroidism or hypothyroidism
What is the patient’s prognosis if you find a cold nodule on thyroid scan?
80% of these will be benign
Thyroid carcinoma related to ionizing radiation in the 1st decades of life
Papillary carcinoma
Thyroid carcinoma related to iodine deficiency
Follicular carcinoma. Iodine deficiency stimulates proliferation of the thyroid and makes fertile ground for cancer.
Most prevalent type of thyroid cancer
Papillary carcinoma (85%). These also tend to occur in young adults.
Which thyroid carcinoma is the only one that has equal prevalence in males and females?
Medullary carcinoma. Papillary, follicular and anaplastic carcinomas are all more common in women.
Most treatable type of thyroid cancer? Thyroid cancer with poorest prognosis?
Papillary carcinoma = good prognosis (90% 5-yr survival). Anaplastic carcinoma = poor prognosis (0% 5-yr survival).
What increases the probability of thyroid cancer being multifocal or bilateral?
Germline or familial mutations. This is why medullary carcinoma is more likely to be bilateral because it is associated with the familial mutation of RET1.
What would you expect FNA to look like in patient with papillary carcinoma?
Thick bubble gum colloid, a syncytium of malignant cells, nuclear grooves and ground glass appearance.
How would you tell that this is a follicular carcinoma vs. a follicular adenoma?
Note the thick irregular capsule. This is more likely to be a follicular carcinoma than a follicular adenoma. You would see closely packed neoplastic follicles w/colloid infiltrating through the fibrous capsule.
Why is pathological diagnosis of a metastatic endocrine tumor not the same as other types of tumors?
You must see some type of invasion or metastasis. You can’t make the diagnosis solely based on mitotic index, hyperchromasia etc.
What type of invasion do you see with follicular thyroid carcinoma?
Capsular and vascular invasion.
What would you expect to see on histological examination of the medullary carcinoma?
Lobular architecture, round tumor cells and pink amyloid deposition (from calcitonin over-production and deposition)
A patient presents with painful swelling of the thyroid shortly after a viral infection. What is your diagnosis?
deQuervain’s Granulomatous Thyroiditis
What underlies the clinical symptoms associated with hyperthyroidism?
Increased basal metabolic rate
How are glucocorticoids “immunosuppressants”?
It shifts the immune response from Th1 to Th2. This limits the injury that might occur to tissue during stressful insults.
This 42-year-old patient presented for evaluation of persistent hypertension, obesity and easy bruising. Congenial middle age female in no acute distress with a round full face, prominent supraclavicular fat pads and numerous abdominal striae. BP was 196/96. How are these symptoms caused by hypercortisolemia?
HTN = cortisol upregulates alpha-1 receptors on arterioles. Obesity = high glucose w/high insulin causes increased fat storage. Easy bruising = impaired collagen synthesis.
Most common reason for Cushing’s syndrome?
Exogenous administration
Most common endogenous cause of Cushing’s syndrome?
Pituitary ACTH-secreting adenoma.
What is causing Conn’s syndrome in this patient?
This is an adrenal adenoma secreting lots of aldosterone. Note the yellowish coloring of the adenoma from the high level of cholesterol needed to synthesize aldosterone.
What will the adrenal glands look like with a pituitary adenoma secreting ACTH?
Bilateral adrenal enlargement.
What will the adrenal glands look like in a patient on chronic prednisone use?
Bilateral adrenal atrophy.
What is the only condition shut off by the high dose dexamethasone suppression test?
Pituitary ACTH-secreting adenoma.
What would you expect histology of this adrenal tumor to look like?
Clear lipid-laden tumor cells in nests adjacent to a rim of non-tumorous adrenal tissue.
What is your diagnosis in this patient with hypercalcemia?
Parathyroid adenoma. Note the capsule surrounding the adenoma adjacent to normal adipose cells indicating normal thyroid tissue. If there are no adipose cells in multiple removed parathyroids you know there is parathyroid hyperplasia (shown below).
What happens to the surface of bone as a result of hyperparathyroidism?
Note the large activated osteoclasts that cause a “moth-eaten” tunneled appearance in the bone. You can also get “brown tumors of hyperparathyroidism” with osteolytic lesions filled by giant cells, macrophages, plump fibroblasts and hemorrhage (von Recklinghausen’s).
A 45-year-old man presented with a 2-year history of visual disturbances and occipital headaches. Imaging studies disclosed an enlarged sella turcica. What would you expect his MR to look like?
Many nonfunctional pituitary adenomas present with mass effect, that doesn’t manifest until it is rather large.
A newborn female infant (46 XX on prenatal amniocentesis) with ambiguous genitalia is delivered from a 28 year old G2 woman at 39 weeks gestation. The infant becomes hypotensive several hours after birth. TORCH titers negative. Clitoromegaly and partial fusion of labial folds. Low levels of sodium and increased levels of potassium. What is causing this child’s condition? What do you suspect the adrenal glands would look like?
21-hydroxylase deficiency. Ambiguous genitalia from excessive androgen production. Hypotension due to loss of production of aldosterone and cortisol. The adrenal cortex would be enlarged because of continuous pituitary release of ACTH.
A 45 year old man was found dead at home by his daughter. Two days earlier he had presented to his physician with chief complaint of fatigue. Vital signs at that time were BP 170/90 mmHg , BMI 35. UA dipstick was positive for glucose (4+). What is the likely cause of the patient’s hypertension prior to death?
Hyperglycemia glycation of proteins. Diabetes causes macroangiopathy (atherosclerosis) due to endothelial dysfunction and can result in MI and renal artery atherosclerosis. Microangiopathy (thickened basement membranes that are leaky and narrow the lumen) lies at the heart of retinopathy, nephropathy and neuropathies.
Three-month-old male with persistent watery diarrhea and left sided abdominal mass. Periorbital edema and hemorrhage, cutaneous purple lesions, large abdominal mass palpated. Elevated urine levels of vanillylmandelic and homovanillic acid were detected. A CT scan showed a large predominantly left sided mass with focal calcifications, in the region of the left kidney and extending across the midline. What is causing this child’s condition?
Wilms tumors and neuroblastomas (from adrenal medulla) can present as an abdominal mass. VIPomas and neuroblastomas (secretes catecholamines) can cause watery diarrhea. The lab values are indicative of something in the adrenal medulla and is likely a neuroblastoma.
What is your differential on this tumor?
You know that you are in the adrenal gland. The mass is hemorrhagic and brown, which means it is in the medulla (cortical tumors would be yellow). Medullary tumors include pheochromocytomas AND neuroblastomas.
What would this tumor look like histologically?
Note the nests of cells with a purple cytoplasm separated by thin fibrovascular septa (zellballen) and absence of glands. There is also separation by pink stroma. This is the classic presentation of a pheochromocytoma.
Which is the pituitary adenoma and what might it be secreting?
B is the adenoma because you only see acidophils and no basophils or chromophobes. Acidophils include somatotrophs that secrete GH and lactotrophs that secrete PRL. Basophils include Basophils include corticotrophs (ACTH = Cushing’s & Nelson’s), gonadotrophs (FSH, LH = hypogonadism & mass effect) and thyrotrophs (TSH = TSH adenoma + hyperthyroidism)
Histology of a patient with hyperplasia of the adrenal gland
Nodularity of the cortex
What are the physiologic contributors to diabetes in the setting of obesity?
High levels of adipocytes = lots of FFAs = activation of inflammosome = inflammatory mediators down regulate insulin receptors. Beta cells burn out producing loads of insulin to try to keep up with insulin resistance.
Type I diabetes is what type of hypersensitivity reaction?
Type IV (insulitis). Th1 cells make IF-gamma that injures the islets, CD8+ and NK cells also destroy the cells in the islets of Langerhans. Note that you have to knock out 90% of the islets to get hyperglycemia.
What histological features of a neuroblastoma help you to determine a patient’s prognosis?
Well-differentiated (into a ganglioneuroblastoma or a ganglioneuroma) and presence of Schwann cells. Neuroblastomas are poor because of poor differentiation.
