Pathology Notes

Practice question I Pathology of thyroid © Jun Wang, MD, PhD 1. Use this case for the next four questions . A 45-year-old woman presents with fatigue, lack of motivation and difficult in concentrating for a year. She has gained 10 pound recently. She stated she is quite stressful at work recently. Her past medical history is significant for type II diabetes. She does not smoke cigarette or drink alcohol, but is a heavy coffee drinker. Physical examination reveals a pulse rate at 98 bpm and blood pressure at 135/80 mmHg. Mild bilateral ankle non pitting edema is noted. No other abnormality is noted. Her CBC is normal. What is a proper next step to approach her diagnosis? A. Bone marrow aspiration B. Consulting a psychiatrist for major depression management C. Head CT D. Sonographic examination for bilateral deep vein thrombosis E. Serum thyroid function test 2. A 45-year-old woman presents with fatigue, lack of motivation and difficult in concentrating for a y

Practice question answers Pathology of thyroid I © Jun Wang, MD, PhD 1. E. This patient has features of hypothyroidism , and thyroid function test should be included. Bone marrow aspiration/biopsy may be indicated for anemia or other hematopoietic disorders. Head CT is for intracranial abnormalities that usually have more neurological abnormalities. Bilateral deep vein thrombosis may cause pedal edema, but usually not associated other systemic presentations. 2. D. Abnormal TSH levels are the most sensitive test for thyroid functions . A high level of TSH is seen in hypothyroidism , and suppressed TSH is seen in thyrotoxicosis . 3. D. Follicular destruction in a background of diffuse polyclonal lymphoid infiltrate, with or without lymphoid follicle formations, is consistent with Hashimoto thyroiditis . Diffuse large B cell lymphoma has diffuse lymphocytic infiltration with marked cytological atypia. Follicular lymphoma is a monoclonal lymphoid proliferation. Graves dis

Thyroid storm   Updated: 01/13/2021 © Jun Wang, MD, PhD General features Thyrotoxic crisis Acute, life-threatening, hypermetabolic state Severely exacerbated thyroid hormone effects Associated with infection, surgery, cessation of antithyroid medication, or any form of stress Clinical diagnosis Improve within 24 hours with proper thyroid-suppressive therapy and sympathetic blockade, the crisis resolve within a week Pathogenesis Dramatically increased thyroid hormone release in individuals with thyrotoxicosis , especially those with Graves disease Clinical presentations Fever, tachycardia, hypertension, neurological and GI abnormalities May result in congestive heart failure, associated with hypotension and shock Diagnosis From uptodate.com Treatment Supportive Anti adrenergic Back to thyroid pathology Back to pathology of endocrine system Back to contents

Thyroid adenoma   Updated: 01/13/2021 © Jun Wang, MD, PhD General features Benign tumor with follicular differentiation Usually 20-50 years, more common   in women May be functional: toxic adenomas, causing hyperthyroidism Resection to rule out malignancy Clinical features Neck mass Radiologic features Cold or warm nodules Pathological features Usually solitary nodule Well-circumscribed mass Fine capsule and a rim of slightly darker normal thyroid parenchyma Closely packed follicles, trabeculae or solid sheets Cuboidal to low columnar cells, pale staining with round small nuclei If more than 75% hurthle cell changes, called Hurthle cell adenoma NO evidence of capsular and vascular invasion NO nuclear features of papillary thyroid carcinoma Treatment Usually do not need treatment Beta block if thyrotoxicosis Back to thyroid pathology Back to pathology of endocrine system Back to contents

Subacute lymphocytic thyroiditis   Updated: 01/25/2023 © Jun Wang, MD, PhD General features Transient, painless hyperthyroidism Relatively uncommon, usually women Unknown etiology Spontaneously resolves Key laboratory findings Elevated T3 and T4, low radioactive iodine uptake Pathological features Diffuse goiter or slightly enlarged thyroid gland Preserved lobular pattern Follicular destruction Variable lymphocytic infiltrate Rare/no oncocytic change, rare/no focal fibrosis Treatment Usually do not need treatment Beta block if hyperthyroidism Back to thyroid pathology Back to pathology of endocrine system Back to contents

Papillary thyroid carcinoma   Updated: 01/26/2023 © Jun Wang, MD, PhD General features Most common thyroid carcinoma Usually young women Risk factors Ionizing radiation Radioactive material Hashimoto’s thyroiditis May be Familial Diagnosed cytologically (fine needle aspiration, FNA) or histologically Usually excellent prognosis Indicators for poor prognosis: tall cell, columnar or diffuse sclerosing variants; vascular invasion; poorly differentiated areas Clinical features Painless nodule or mass in neck or cervical node Radiologic features Usually cold on scan Pathological features Most important morphological clue: nuclear features including clear chromatin, inclusion, grooves, etc Solid, white, firm, often multifocal , encapsulated or infiltrative May have calcification Papillae or follicles lined by follicular cells with overlapping nuclei Finely dispersed optically clear chromatin (also called ground-glass, Orphan-Annie nuclei ) Eosino

Medullary carcinoma Updated:4/23/2019 © Jun Wang, MD, PhD General features Neuroendocrine tumor derived from C cells Express calcitonin Either sporadic (nonhereditary) or hereditary (familial) If familial, associated with MEN2A or 2B Clinical features Neck mass Presentations due to local advance: hoarseness, dysphagia, and respiratory difficulty Paraneoplastic syndromes, including Cushing or carcinoid syndrome Other presentations associated with metastases, including bone pain, neurological defects Key pathological features Usually nonencapsulated solid, gray-tan-yellow, firm nodule May be infiltrative Round, polygonal or spindle cells in nests, cords or follicles Granular cytoplasm and uniform round/oval nuclei with punctate chromatin Amyloid deposits from calcitonin, prominent vascularity with glomeruloid configuration or long cords of vessels, coarse calcifications Key laboratory finding Elevated serum calcitonin and chromogranin A Marker

Hypothyroidism   Updated: 10/12/2022 © Jun Wang, MD, PhD General features Deficiency of thyroid hormone function Structural or functional derangement that reduces thyroid hormone production Etiology Primary Iodine deficiency Medications: lithium, iodides, etc Destruction of thyroid parenchyma: Hashimoto thyroiditis , S/P thyroidectomy, radioiodine therapy, etc Congenital defects of thyroid development Thyroid hormone resistance Secondary, rare Pituitary failure Hypothalamic failure Clinical presentations Symptoms: Fatigue, loss of energy, weight gain, etc Signs: Slowed speech and movements, nonpitting edema (myxedema), goiter , etc Cretinism Hypothyroidism in infancy or early childhood Due to an anatomic defect in the gland, an inborn error of thyroid metabolism, or iodine deficiency Impaired development of the skeletal system and central nervous system Severe mental retardation, short stature, coarse facial features, a protruding tongue,

Thyrotoxicosis   Updated: 01/13/2021 © Jun Wang, MD, PhD General features Hypermetabolic state due to elevated circulating free T3 and T4 Associated with hyperactivity of thyroid gland, inappropriate release of thyroid hormones due to follicular damage, etc Three most common causes Diffuse hyperplasia associated with Graves disease Hyperfunctional multinodular goiter Hyperfunctional thyroid adenoma Terms Hyperthyroidism: Status of thyroid hormone overproduction, may be clinically subtle, such as apathetic hyperthyroidism Thyrotoxicosis: Clinical presentations caused by excess circulating thyroid hormone Thyroid storm : Acute life threatening exacerbation of thyrotoxicosis Etiology Primary hyperthyroidism Diffuse hyperplasia (such as Graves disease ) Hyperfunctional goiter Hyperfunctional adenoma Iodine-induced hyperthyroidism Neonatal hyperthyroidism associated with maternal Graves disease Secondary hyperthyroidism, rare TSH producing pituitary t

Hashimoto thyroiditis   Updated: 10/13/2022 © Jun Wang, MD, PhD General features Autoimmune disease Predominantly women, more common in mid age More common in white Most common cause of sporadic goiter in children with sufficient iodine supply Higher clustering of other autoimmunity diseases Higher risk for thyroid carcinoma and lymphoma Pathogenesis Complex genetic background: HLA-DR5, HLA-DR3, CTLA4, protein tyrosine phosphatase-22 (PTPN22) Autoantibody against multiple thyroid proteins, anti-thyroid peroxidase and anti-thyroglobulin antibodies Autoimmune destruction of follicular cells by activated CD8+ T cells, cytokine-mediated process or autoantibodies Clinical presentations Adults Painless, gradual thyroid failure due to autoimmune destruction May initially have transient hyperthyroidism Children Variable hypothyroidism and reversion to euthyroidism Must monitor thyroid function Key laboratory findings Levels of TSH, T3 and T4 assoc

Graves disease Updated: 12/13/2018 © Jun Wang, MD, PhD General features Autoimmune disorder Most common cause of hyperthyroidism Peak incidence between 20 and 40 More common in women Risk for life threatening thyrotoxicosis if untreated Pathogenesis Autoantibody against multiple thyroid proteins, most importantly the TSH receptor   Autoantibody activate TSH receptor to promote thyroid hyperplasia and hyperfunction Clinical presentations Hyperthyroidism associated with diffuse enlargement of the gland Infiltrative ophthalmopathy with resultant exophthalmos Localized, infiltrative dermopathy, sometimes called pretibial myxedema , which is present in a minority of patients Infiltrative ophthalmopathy Proptosis in addition to other ocular presentations of hyperthyroidism Activated T-cells cross react with TSH receptor expressed in fibroblasts, causing cytokine production and subsequent edema and fibrosis Increased volume of the extraocular muscles an

Granulomatous thyroiditis Updated: 12/13/2018 © Jun Wang, MD, PhD General features AKA de Quervain's thyroiditis, subacute granulomatous thyroiditis Most common cause of thyroid pain Painful swallowing (odynophagia), sore throat, thyroid region tenderness, fever, fatigue, malaise May be associated with systemic viral infection Usually self limited, resolves in 6-8 weeks with transient hypothyroidism Key laboratory findings Early: Elevated T3 and T4, low radioactive iodine uptake Late: Hypothyroidism and anti-thyroid antibodies Pathological features Focal to diffuse enlargement of thyroid gland Early: neutrophils and destruction of follicles with colloid depletion Later : noncaseating granulomas surround follicles and engulf colloid Late: fibrosis Treatment Pain management: NSAID or corticosteroid Hyperthyroidism management: Beta blockers, etc Hypothyroidism management: Hormone replacement, etc Back to thyroid pathology Back to pathology