Normal thyroid tissue

Transcription

1 Thyroid Pathology

2 Overview

3 Normal thyroid tissue Normal thyroid tissue with follicles filled with colloid. Thyroid cells form follicles, spheres of epithelial cells (always single layered in health, usually more or less cuboidal, variably tall or short). The C cells (parafollicular l cells) of the thyroid are visible between the follicles

4 Normal thyroid tissue

5 Hashimoto s s Thyroiditis an autoimmune disease in which the immune system reacts against a variety of thyroid antigens overriding feature of is progressive depletion of thyroid epithelial cells (thyrocytes), y which are gradually replaced by mononuclear cell infiltration and fibrosis

6 Hashimoto s Pathogenesis s Sensitization of autoreactive CD4+ T helper cells to thyroid antigens appears to be the initiating event. The effector mechanisms for thyrocyte death include the following: CD8+ cytotoxic T cell mediated cell death: CD8+ cytotoxic T cells may cause thyrocyte destruction by one of two pathways: exocytosis of perforin/granzyme granules or engagement of death receptors, specifically CD95 (also known as Fas) on the target cell Cytokine mediated cell death: CD4+ T cells produce inflammatory cytokines such as IFN γ in the immediate thyrocyte milieu, with resultant recruitment and activation of macrophages and damage to follicles. Binding of antithyroid antibodies (anti TSH receptor antibodies, antithyroglobulin, and antithyroid peroxidase antibodies) followed by antibody dependent cell mediated ctotoicit cytotoxicity (ADCC)

7 Hashimoto s Pathogenesis Reference: Kumar: Robbins and Cotran: Pathologic Basis of Disease, 7th ed., Copyright 2005 Saunders

8 Hashimoto s Thyroiditis Lymphocytic infiltrate in the thyroid, with lymphoid follicle formation and fibrosis. Presence of oncocytes always y has oncocytic metaplasia

9 Hashimoto s Thyroiditis Reference: Kumar: Robbins and Cotran: Pathologic Basis of Disease, 7th ed., Copyright 2005 Saunders

10 Grave s Disease

11 Multi nodular Goiter

12 Follicular adenoma adenomas are not forerunners of cancer except in rare instances small proportion produce thyroid hormones and cause clinically apparent thyrotoxicosis T i ll li h i l l d l i Typically a solitary, spherical, encapsulated lesion that is well demarcated from the surrounding thyroid parenchyma

13 Follicular adenoma

14 Follicular adenoma Microscopically, the constituent cells often form uniform appearing follicles that t contain ti colloid The follicular growth pattern within the adenoma is usually quite distinct from the adjacent non neoplastic thyroid distinguishing feature b/w adenomas and MNGnodular and uninvolved thyroid parenchyma may have similar growth patterns

15 Follicular adenoma Mitotic figures are rare papillary change is not a typical feature of adenomas and, if extensive, should raise the suspicion of an encapsulated papillary carcinoma O i ll h l i ll i b i hl Occasionally, the neoplasticcells acquire brightly eosinophilic granular cytoplasm (oxyphil or Hürthle cell change)

16 Follicular Adenoma Follicular adenoma H/E preparation x 100 Follicular carcinoma account for less than 10% Microscopic

17 Follicular adenoma

18 Follicular Adenoma with Oncocytic or HurthleCell ll Change Also known as: Hurthle Cell Adenoma Occasionally, the neoplastic cells acquire brightly eosinophilic granular cytoplasm (oxyphil or Hürthle cell change) Eosinophilic granules due to enlarged, bizarre mitochondria

19 Follicular Adenoma with Oncocytic or HurthleCell ll Change

20 Thyroid Neoplasms with Follicular Architecture Non Neoplastic: N Neoplastic: Hyperplastic nodule in Goiter Follicular adenoma Follicular carcinoma Follicular l variant Papillary carcinoma

21 Papillary Thyroid Carcinoma solitary or multifocal lesions Some tumors well circumscribed and encapsulated; others infiltrate the adjacent parenchyma with ill defined margins i f fib i d lifi i d may contain areas of fibrosis and calcification and are often cystic

22 Papillary Thyroid Carcinoma NUCLEI

23 Papillary Thyroid Carcinoma Concentrically calcified structures termed psammoma bodies are often present within the lesion, usually within the cores of papillae

24 Papillary Thyroid Carcinoma Foci of lymphatic invasion by tumor are often present, but involvement of blood vessels is relatively uncommon Metastases to adjacent cervical lymph nodes are estimated to occur in up to half the cases???

25 Papillary Thyroid Carcinoma

26 Papillary Papillary Thyroid Thyroid Carcinoma Cancer calcified sphere, or psammoma body Papillary thyroid carcinoma accounts for about 80% of all thyroid carcinomas

27 Psammoma body Little Orphan Annie

28

29 Papillary Thyroid Carcinoma

30 Papillary Thyroid Cancer Variants constitutes about 10% of all papillary neoplasms has an excellent prognosis has the characteristic nuclei of papillary carcinoma but has an almost totally follicular architecture tall columnar cells with ih intensely eosinophiliccytoplasm l lining i the papillary structures Occur in older individuals and are usually large with prominent vascular invasion, extrathyroidal extension, and cervical and distant metastases

31 Papillary Thyroid Cancer Variants occurs in younger individuals, including children. These tumors do not present with a mass, but rather with a bilateral goiter nodal metastases are present in almost all cases includes both adenomas and carcinomas, have includes both adenomas and carcinomas, have recently been reconsidered as a variant of papillary carcinomas, based on the presence of ret/ptc gene rearrangements in 30% to 60% of these tumors

32 Follicular Thyroid Carcinoma 2nd most common thyroid cancer 10% to 20% of all thyroid cancers tend to present in women, and at an older age than do papillary carcinomas peak incidence in the forties and fifties incidence increased in areas of dietary iodine deficiency, suggesting that in some cases, nodular goiter may predispose to the development of the neoplasm high frequency of RAS mutations in follicular adenomas and carcinomas suggests that the two may be related tumors

33 Follicular Thyroid Carcinoma Gross Specimen T h li ht t Tumor has light tan appearance Contains small foci of hemorrhage

34 Follicular Thyroid Carcinoma Gross Specimen Most composed of fairly uniform cells forming small follicles containing colloid appearance of normal thyroid In other cases, follicular differentiation may be less apparent may be nests or sheets of cells without colloid Occasional tumors are dominated by cells with abundant granular, eosinophilic cytoplasm (Hürthle cells). nuclei lack the features typical of papillary carcinoma psammoma bodies are NOT present

35 Follicular Thyroid Carcinoma Microscopic Features Follicular lesions with nuclear features typical of papillary carcinomas should be treated as papillary cancers Nuclear features NOT helpful in distinguishing follicular adenomas from minimally invasive follicular carcinomas Requires extensive sampling of the tumorthyroid capsule interface to exclude capsular or vascular invasion. the presence of tumor plugs within intratumoral blood vessels has little prognostic significance Unlike in papillary cancers, lymphatic spread is distinctly uncommon in follicular cancers

36 Follicular Thyroid Carcinoma Microscopic Features

37 Follicular Thyroid Thyroid Carcinoma Microscopic Features Follicular Adenoma No Capsular invasion Compressed normal thyroid usu. present external to capsule Follicular Carcinoma Capsular invasion present May have vascular invasion

38 Medullary Thyroid Cancer (MTC)

39 Medullary Thyroid Carcinoma Gross Specimen Solid pattern of growth Do not have connective tissue capsules

40 Medullary Thyroid Carcinoma Microscopic Features

41 Medullary Thyroid Carcinoma Microscopic Features composed of polygonal to spindle shaped cells may form nests, trabeculae, and even follicles Small, more anaplastic cells are present in some tumors and may be the predominant cell type Acellular amyloid deposits, derived from altered calcitonin molecules, are present in the adjacent stroma in many cases Electron microscopy reveals variable numbers of membrane bound electron dense granules within the cytoplasm of the neoplastic cells.

42 Medullary Thyroid Carcinoma Microscopic Features Familial medullary cancers presence of multicentric C cell hyperplasia in the surrounding parenchyma, a feature that is usually absent in sporadic lesions

43 Medullary Thyroid Carcinoma Microscopic Features

44 Medullary Thyroid Carcinoma Microscopic Features

45 Anaplastic Carcinoma

46 Anaplastic carcinoma histology H/E preparation x 200