Endocrine Pathology

                            Thyroid

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 10 to 30 grams. It cannot easily be palpated on physical examination.

Normal thyroid seen microscopically consists of follicles lined by a an epithelium and filled with colloid. The follicles vary somewhat in size. The interstitium, which may contain "C" cells, is not prominent.

This immunoperoxidase stain with antibody to calcitonin identifies the "C" cells (parafollicular cells) of the thyroid interstitium between the follicles or adjacent to the epithelium of follicles. These cells secrete calcitonin.

This symmetrically small thyroid gland demonstrates atrophy. This patient was hypothyroid. This is the end result of Hashimoto's thyroiditis. Initially, the thyroid is enlarged and there may be transient hyperthyroidism, followed by a euthyroid state and then hypothyroidism with eventual atrophy years later. Hashimoto's thyroiditis results from abnormal T cell activation and subsequent B cell stimulation to secrete a variety of autoantibodies.

This high power microscopic view of the thyroid with Hashimoto's thyroiditis demonstrates the pink Hürthle cells at the center and right. The lymphoid follicle is at the left. Hashimoto's thyroiditis initially leads to painless enlargement of the thyroid, followed by atrophy years later.

This is an example of an immunofluorescence test positive for anti-microsomal antibody, one of the autoantibodies that can be seen with autoimmune diseases of the thyroid. A major component of the antimicrosomal antigen is thyroid peroxidase (TPO) which is often measured serologically. Note the bright green fluorescence in the thyroid epithelial cells, whereas the colloid in the center of the follicles is dark.

This is subacute granulomatous thyroiditis (DeQuervain's disease), which probably follows a viral infection and leads to a painful enlarged thyroid. This disease is usually self-limited over weeks to months and the patients return to a euthyroid state. Note the foreign body giant cells with destruction of thyroid follicles.

This thyroid gland is about normal in size, but there is a larger colloid cyst at the left lower pole and a smaller colloid cystat the right lower pole. Such cysts could appear as "cold" nodules on a thyroid scan. They are incidental benign lesions but can appear as a mass to be distinguished from possible carcinoma.

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.

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. In this autoimmune disease the action of TSI's predominates over that of TGI's.

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. Grossly it felt firm. By scintigraphic scan it was "cold." This is a follicular adenoma.

Normal thyroid follicles appear at the lower right. The follicular adenoma is at the center to upper left. This adenoma is a well- differentiated neoplasm because it closely resemble normal tissue. The follicles of the adenoma contain colloid, but there is greater variability in size than normal.

Sectioning through a lobe of excised thyroid gland reveals papillary carcinoma. This neoplasm can be multifocal, as seen here, because of the propensity to invade lymphatics within thyroid, and lymph node metastases are common. The larger mass is cystic and contains papillary excresences. These tumors most often arise in middle-aged females.

This is another papillary carcinoma of thyroid. Note the small psammoma body in the center. The cells of the neoplasm have clear nuclei. Papillary carcinomas are indolent tumors that have a long survival, even with metastases. The most favorite site of metastasis is to local lymph nodes in the neck. In fact, some papillary carcinomas may first present as nodal metastases.

At the center and to the right is a medullary carcinoma of thyroid. At the far right is pink hyaline material with the appearance of amyloid. These neoplasms are derived from the thyroid "C" cells and, therefore, have neuroendocrine features such as secretion of calcitonin.

Here the amyloid stroma of the medullary thyroid carcinoma has been stained with Congo red. Medullary carcinomas can be sporadic or familial. The familial kind are associated with multiple endocrine neoplasia syndrome.

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                           Pituitary

The normal gross appearance of the pituitary gland removed from the sella turcica is shown here. The larger portion, the anterior pituitary (adenohypophysis), is toward the top. The image at the left shows the superior aspect of the pituitary with the stalk coming from the hypothalamus entering it. The inferior aspect of the pituitary is shown at the right. The posterior pituitary (neurohypophysis) is the smaller portion at the bottom.

The normal microscopic appearance of the pituitary gland is shown here. The adenohypophysis is at the right and the neurohypophysis is at the left. The normal microscopic appearance of the adenohypophysis is shown here. The adenohypophysis contains three major cell types: acidophils, basophils, and chromophobes. The staining is variable, and to properly identify specific hormone secretion, immunohistochemical staining is necessary. A simplistic classification is as follows: The pink acidophils secrete growth hormone (GH) and prolactin (PRL) The dark purple basophils secrete corticotrophin (ACTH), thyroid stimulating hormone (TSH), and gonadotrophins follicle stimulating hormone-luteinizing hormone (FSH and LH) The pale staining chromophobes have few cytoplasmic granules, but may have secretory activity.

Here is a high power microscopic view of an adenohypophyseal adenoma. Endocrine neoplasms are composed of small round cells with small round nuclei and pink to blue cytoplasm. The cells may be arranged in nests or cords and endocrine tumors also have prominent vascularity.

The circumscribed mass lesion present here in the sella turcica is a pituitary adenoma. Though pituitary adenomas are benign, they can produce problems either from a mass effect (usually visual problems from pressing on the optic chiasm and/or headaches) or from production of hormones such as prolactin or ACTH.

The microscopic appearance of the pituitary adenoma is shown here. Note the monotonous appearance of these small round cells. _________________________________________________________________             Parathyroid Parathyroid hyperplasia is shown here. Three and one-half glands have been removed (only half the gland at the lower left is present). Parathyroid hyperplasia is the second most common form of primary hyperparathyroidism, with parathyroid carcinoma the least common form. Here is a parathyroid adenoma, which is the most common cause for primary hyperparathyroidism. A rim of normal parathyroid tissue admixed with adipose tissue cells is seen compressed to the right and lower edge of the adenoma This is the gross appearance of a parathyroid carcinoma. The serum calcium can be quite high. Note the large size and irregular cut surface. These carcinomas have a tendency to invade surrounding tissues in the neck, complicating their removal. This is a parathyroid carcinoma seen at medium power on the left and higher power on the right. The nests of neoplastic cells that are not very pleomorphic. Note the bands of fibrous tissue between the nests. Parathyroid carcinomas infiltrate surrounding structures in the neck. ________________________________________________________  Adrenal   Here are normal adrenal glands. Each adult adrenal gland weighs from 4 to 6 grams.    Sectioning across the adrenals reveals a golden yellow outer cortex and an inner red to grey medulla. The pair of adrenals in the center are normal. Those at the top come from a patient with adrenal atrophy (with either Addison's disease or long-term corticosteroid therapy). The adrenals at the bottom represent bilateral cortical hyperplasia. This could be due to a pituitary adenoma secreting ACTH (Cushing's disease), or Cushing's syndrome from ectopic ACTH production, or idiopathic adrenal hyperplasia. These adrenals are black-red from extensive hemorrhage in a patient with meningococcemia. This produces the Waterhouse-Friderichsen syndrome. These sections through an enlarged adrenal gland demonstrate tan-white metastatic carcinoma infiltrating in and around the residual golden yellow cortex. The most common primary site for adrenal metastases is lung. This neonate had a congenital neuroblastoma of the right adrenal. This neoplasm (marked by the white arrow) is displacing the liver to the left of the body This adrenal gland removed surgically in a patient with Cushing's syndrome has been sectioned in half to reveal an adenoma. Some remaining atrophic adrenal is seen at the right. The adenoma is composed of yellow firm tissue just like adrenal cortex. This neoplasm is well-circumscribed. Histologically, it is composed of well-differentiated cells resembling cortical fasciculata zone. It is benign. This is a large adrenal cortical carcinoma which is displacing the left kidney downward. Such neoplasms are usually functional (secreting corticosteroids or sex steroids). They have a poor prognosis. This large adrenal neoplasm has been sectioned in half. Note the grey-tan color of the tumor compared to the yellow cortex stretched around it and a small remnant of remaining adrenal at the lower right. This patient had episodic hypertension. This is a tumor arising in the adrenal medulla--a pheochromocytoma. ____________________________________________________________ Islets of Langerhans This is an insulitis of an islet of Langerhans in a patient who will eventually develop type I diabetes mellitus. The presence of the lymphocytic infiltrates in this edematous islet suggests an autoimmune mechanism for this process. The destruction of the islets leads to an absolute lack of insulin that characterizes type I diabetes mellitus. This islet of Langerhans demonstrates pink hyalinization (with deposition of amyloid) in many of the islet cells. This change is common in the islets of patients with type II diabetes mellitus. An islet cell adenoma is seen here, separated from the pancreas by a thin collagenous capsule. A few normal islets are seen in the pancreas at the right for comparison. This is an immunohistochemical stain for insulin in the islet cell adenoma. Thus, it is an insulinoma.