Endocrine Pathology. Xu Enping Department of Pathology and Physiopathology School of Medicine, Zhejiang University.

Transcription

1 Endocrine Pathology Xu Enping Department of Pathology and Physiopathology School of Medicine, Zhejiang University

2 Thyroid

3 This is the normal appearance of the thyroid gland on the anterior trachea of the neck. The thyroid gland has a right lobe and a left lobe connected by a narrow isthmus. The normal weight of the thyroid is 25 to 30 grams. It cannot easily be palpated on physical examination.

4 Normal thyroid seen microscopically consists of follicles lined by a an epithelium and filled with colloid. The follicles vary somewhat in size.

5 Diffuse Nontoxic (Simple) Goiter diffusely involves the entire gland follicles are filled with colloid occurs in both an endemic and a sporadic distribution low levels of iodine a striking female preponderance and a peak incidence at puberty or in young adult life

6 Morphology Diffusely and symmetrically enlarged Enlarged, colloid-rich gland Follicular epithelium flattened and cuboidal

7 This thyroid gland is about normal in size, but there is a larger colloid cyst at the left lower pole and a smaller colloid cyst at the right lower pole.

8 This diffusely enlarged thyroid gland is somewhat nodular. This patient was euthyroid. This represents the most common cause for an enlarged thyroid gland and the most common disease of the thyroid--a nodular goiter.

9 Nodular goiter. The gland is coarsely nodular and contains areas of fibrosis and cystic change.

10 The follicles are irregularly enlarged, with flattened epithelium, consistent with inactivity, in this microscopic appearance at low power of a multinodular goiter.

11 Clinical Course Mass effects from the enlarged thyroid gland airway obstruction dysphagia, compression of large vessels in the neck and upper thorax

12 Diffuse Toxic Goiter Thyrotoxicosis, Grave s disease Hypermetabolic state caused by elevated circulating levels of free T3 and T4 an increase in the basal metabolic rate Sweating Arrhythmias, particularly atrial fibrillation tremor, hyperactivity, emotional lability, anxiety, inability to concentrate, and insomnia thyroid ophthalmopathy

13 A patient with hyperthyroidism. A wide-eyed, staring gaze, caused by overactivity of the sympathetic nervous system, is one of the features of this disorder. In Graves disease, one of the most important causes of hyperthyroidism, accumulation of loose connective tissue behind the eyeballs also adds to the protuberant appearance of the eyes.

14 Morphology symmetrically enlarged diffuse hypertrophy and hyperplasia of thyroid follicular epithelial cells the follicular epithelial cells are tall and more crowded than usual formation of small papillae the colloid within the follicular lumen is pale, with scalloped margins lymphoid infiltrates throughout the interstitium

15 A diffusely enlarged thyroid gland associated with hyperthyroidism is known as Grave's disease. At low power here, note the prominent infoldings of the hyperplastic epithelium.

16 At high power, the tall columnar thyroid epithelium with Grave's disease lines the hyperplastic infoldings into the colloid.

17 Diffusely hyperplastic thyroid in a case of Graves disease. The follicles are lined by tall, columnar epithelium. The crowded, enlarged epithelial cells project into the lumens of the follicles. These cells actively resorb the colloid in the centers of the follicles, resulting in the scalloped appearance of the edges of the colloid.

18 Thyroiditis Thyroiditis, or inflammation of the thyroid gland, encompasses a diverse group of disorders characterized by some form of thyroid inflammation. Hashimoto s thyroiditis (or chronic lymphocytic thyroiditis) Subacute thyroiditis Fibrous thyroiditis

19 Subacute thyroiditis granulomatous thyroiditis most common between the ages of 30 and 50 affects women considerably more often than men (3:1 to 5:1) occurs much less frequently than does Hashimoto disease.

20 Pathogenesis caused by a viral infection or a postviral inflammatory process association with coxsackievirus, mumps, measles, adenovirus, and other viral illnesses the immune response is virus-initiated and not self-perpetuating, so the process is limited.

21 Morphology unilaterally or bilaterally enlarged and firm, with an intact capsule scattered follicles may be entirely disrupted and replaced by neutrophils forming microabscesses aggregations of lymphocytes, histiocytes, and plasma cells about collapsed and damaged thyroid follicles Multinucleate giant cells

22 Subacute thyroiditis. The thyroid parenchyma contains a chronic inflammatory infiltrate with a multinucleate giant cell (above left) and a colloid follicle (bottom right).

23 Clinical Course characterized by pain in the neck variable enlargement of the thyroid asymptomatic hypothyroidism lasting from 2 to 8 weeks, recovery is virtually always complete. After recovery, generally in 6 to 8 weeks, normal thyroid function returns.

24 Hashimoto s thyroiditis The most common cause of hypothyroidism in areas of the world where iodine levels are sufficient. Most prevalent between 45 and 65 years of age and is more common in women than in men (10:1 to 20:1 ) Gradual thyroid failure because of autoimmune destruction of the thyroid gland

25 Pathogenesis an autoimmune disease, the immune system reacts against a variety of thyroid antigens progressive depletion of thyroid epithelial cells (thyrocytes) replaced by mononuclear cell infiltration and fibrosis

26 Pathogenesis of Hashimoto thyroiditis. Three proposed models for mechanism of thyrocyte destruction in Hashimoto disease. Sensitization of autoreactive CD4+ T cells to thyroid antigens appears to be the initiating event for all three mechanisms of thyroid cell death.

27 Morphology Diffusely enlarged thyroid Infiltration of the parenchyma by a mononuclear inflammatory infiltrate small lymphocytes, plasma cells, and welldeveloped germinal centers Thyroid follicles are atrophic Interstitial connective tissue is increased and may be abundant

28 This symmetrically small thyroid gland demonstrates atrophy. This patient was hypothyroid. This is the end result of Hashimoto's thyroiditis.

29 Here is a low power microscopic view of a thyroid with Hashimoto's thyroiditis.

30 Hashimoto thyroiditis. The thyroid parenchyma contains a dense lymphocytic infiltrate with germinal centers. Residual thyroid follicles lined by deeply eosinophilic Hürthle cells are also seen.

31 Clinical Course painless enlargement of the thyroid associated with hypothyroidism at increased risk for developing other concomitant autoimmune diseases, as type 1 diabetes, autoimmune adrenalitis and systemic lupus erythematosus

32 Fibrous thyroiditis Riedel thyroiditis a rare disorder of unknown etiology characterized by extensive fibrosis involving the thyroid and contiguous neck structures hard and fixed thyroid mass

33 Morphology multifocal follicular disruption inflammatory cells occasional giant cell formation abnormalities of thyroid function are not present

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35 Neoplasms of the Thyroid Solitary nodules, in general, are more likely to be neoplastic than are multiple nodules. Nodules in younger patients are more likely to be neoplastic than are those in older patients. Nodules in males are more likely to be neoplastic than are those in females. A history of radiation treatment to the head and neck region is associated with an increased incidence of thyroid malignancy. Nodules that take up radioactive iodine in imaging studies (hot nodules) are more likely to be benign than malignant.

36 Neoplasms of the Thyroid Adenomas Carcinomas Papillary carcinoma (75% to 85% of cases) Follicular carcinoma (10% to 20% of cases) Medullary carcinoma (5% of cases) Anaplastic carcinoma (<5% of cases)

37 Adenoma Follicular adenoma Colloid adenomas (macrofollicular adenomas) Fetal adenoma Embryonal adenoma Oxyphil cell adenoma Atypical adenoma Adenolipoma

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39 Here is a surgical excision of a small mass from the thyroid gland that has been cut in half. A rim of slightly darker thyroid parenchyma is seen at the left. The mass is well-circumscribed. This is a follicular adenoma.

40 Follicular adenoma of the thyroid. A solitary, wellcircumscribed nodule is seen.

41 Follicular adenoma. The photomicrograph shows welldifferentiated follicles resembling normal thyroid parenchyma.

42 Clinical Features A unilateral painless mass Difficulty in swallowing By radionuclide scanning, adenomas usually appear as cold nodules Some adenomas may progress to carcinomas

43 The difference between thyroid adenoma and nodular goiter Thyroid adenoma Nodular goiter number single multiple,often bilateral capsule complete incomplete follicle uniform inconsistent Adjacent tissue compressed no obvious compression distant tissue relatively normal abnormal

44 Carcinoma Papillary carcinoma (75% to 85% of cases) Follicular carcinoma (10% to 20% of cases) Medullary carcinoma (5% of cases) Anaplastic carcinoma (<5% of cases)

45 Papillary Thyroid Carcinomas the most common form of thyroid cancer most often in the twenties to forties ground glass or Orphan Annie eye nuclei psammoma bodies

46 Papillary carcinoma of the thyroid. A, The macroscopic appearance of a papillary carcinoma with grossly discernible papillary structures. This particular example contains well-formed papillae (B), lined by cells with characteristic empty-appearing nuclei, sometimes termed "Orphan Annie eye" nuclei.

47 (C). D, Cells obtained by fine-needle aspiration of a papillary carcinoma. Characteristic intranuclear inclusions are visible in some of the aspirated cells.

48 This is the microscopic appearance of a papillary carcinoma of the thyroid.

49 This is another papillary carcinoma of thyroid. Note the small psammoma body in the center.

50 Follicular Carcinoma the second most common form of thyroid cancer a peak incidence in the forties and fifties single nodules that may be well circumscribed or widely infiltrative composed of fairly uniform cells forming small follicles containing colloid

51 Follicular carcinoma. Cut surface of a follicular carcinoma with substantial replacement of the lobe of the thyroid. The tumor has a lighttan appearance and contains small foci of hemorrhage.

52 Follicular carcinoma of the thyroid. A few of the glandular lumens contain recognizable colloid.

53 Medullary Carcinoma Neuroendocrine neoplasms derived from the parafollicular cells, or C cells Secrete calcitonin Amyloid deposits

54 Medullary carcinoma of thyroid. These tumors typically show a solid pattern of growth and do not have connective tissue capsules.

55 Medullary carcinoma of the thyroid. These tumors typically contain amyloid, visible here as homogeneous extracellular material, derived from calcitonin molecules secreted by the neoplastic cells.

56 showing amyloid stroma and solid islands of monotonous tumor cells.

57 Anaplastic carcinoma undifferentiated tumors of the thyroid follicular epithelium aggressive tumors

58 shows solid nests and sheets of tumor cells with squamoid differentiation in the dense fibrous stroma.