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Thyroid Tumors


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Thyroid Tumors

  3. 3. THYROID CARCINOMASPapillary carcinomaFollicular carcinomaPoorly differentiated carcinomaUndifferentiated (anaplastic) carcinomaSquamous cell carcinomaMucoepidermoid carcinomaSclerosing mucoepidermoid carcinoma with eosinophiliaMedullary carcinomaMixed medullary and follicular carcinomaSpindle cell tumor with thymus-like differentiationCarcinoma showing thymus-like differentiation
  4. 4. THYROID ADENOMA AND RELATEDTUMORS Follicular adenoma Hyalinizing trabecular tumor
  5. 5. OTHER THYROID TUMORS Teratoma  Peripheral nerve sheath Primary lymphoma and tumors plasmacytoma  Paraganglioma Ectopic thymoma  Solitary fibrous tumor Angiosarcoma  Follicular dendritic cell tumor Smooth muscle tumors  Langerhans cell histiocytosis  Secondary tumors
  6. 6. Papillary carcinoma “A malignant epithelial tumor showing evidence of follicular cell differentiation and characterized by distinctive nuclear features” -W.H.O.
  7. 7.  Most common thyroid malignancy Palpable nodule Nodule in multinodular goitre (in iodine insufficient areas) More common in females, rare before 15 years Mean age at diagnosis approximately 40 years Accounts for >90% of thyroid malignancies in children. In 5–10% , history of neck irradiation Increased incidence in Hashimotos thyroiditis Disease localized to: thyroid gland in 67% thyroid and lymph nodes in 13% lymph nodes alone in 20% Overall survival excellent
  8. 8. GROSS pathology Size of the primary ranges from microscopic to huge Many thyroid cancers measuring <1 cm in diameter are papillary Most:  solid  whitish  firm  clearly invasive <10% are surrounded by a complete capsule
  9. 9. Histopathology(PTC)  Numerous true papillae  Papillae are usually: complex, branching, and randomly oriented, with a central fibrovascular core and a single or stratified lining of cuboidal cells  Stroma of the papillae:  edematous or hyaline  may contain lymphocytes, foamy macrophages, hemosiderin, or - exceptionally - adipose tissue  Follicles tend to be irregularly shaped, tubular, and branching  Cells have characteristic nuclear features
  10. 10. NUCLEAR FEATURES (optically clear) nuclei:  often large with an overlapping quality  nucleolus usually inconspicuous and pushed against the nuclear membrane, which appears thickened  particularly prominent in tissue fixed in high concentrations of formalin
  11. 11.  Nuclear pseudoinclusions: represent invaginations of the cytoplasm appear as sharply outlined acidophilic formation readily apparent in frozen section specimens and aspirations immunoreactivity for β-catenin and sometimes type IV collagen
  12. 12. Nuclear grooves  Occur in oval or spindle nuclei  Arranged along the longest nuclear axis  Represent infoldings of a redundant nuclear membraneMitoses are scanty orabsent  intranuclear grooves (400×).
  13. 13. Psammoma bodies  Laminatedated basophilic structures that:  stain for mucin, calcium, and iron  appear to arise from necrosis of individual tumor cells, which occasionally may be seen at their center  in approximately 50% of cases may be located in:  the papillary stalk  fibrous stroma  between tumor cells in solid foci
  14. 14. Psammoma body formation in papillary carcinoma beneath the capsule of a if found in normal cervical lymph node, without identifiable thyroid tissue or lymph nodes from the neck, a papillary carcinoma is likely in the immediate vicinity
  15. 15. OTHER CHANGES LYMPHOCYTIC SCATTERED MULTINUCLEATED INFILTRATION OF THE GIANT CELLS: STROMA: -may be present -25% of cases -probably a response to MANY TUMORS ALSO leakage of colloid.  BLOOD VESSEL INVASION: EXHIBIT: -5% of cases -a heavy infiltrate S-100 protein-positive dendritic/Langerhans cells
  16. 16. Metastasis Papillary carcinoma invades the glandular lymphatics Cervical lymph nodes metastases:  common (particularly in young patients)  may be the first manifestation Blood-borne metastases:  less frequent than with other thyroid carcinomas  most common site is lung  also in bones, central nervous system, other organs
  17. 17. MetastasisRegional lymph node metastasesare extremely common (≥50%)This feature does not adverselyaffect long-term prognosis.Frequently the nodal metastasiswill involve onenode that may be cystic
  18. 18. Special Stains andImmunohistochemistry (PTC)
  19. 19.  Tumors with papillary and follicular structures should be classified as papillary carcinoma Thyroglobulin and TTF-1:  crucial markers when a papillary neoplasm is in a lymph node or other extrathyroidal site to establish whether the tumor is of thyroid nature or not  most specific marker in existence (shared with the pulmonary epithelium)
  20. 20. Morphological variants of PTC Papillary microcarcinoma Encapsulated variant Follicular variant Diffuse sclerosing variant Oncocytic (oxyphilic) variant Tall cell and columnar cell carcinoma Cribriform-morular variant Papillary carcinoma with exuberant nodular fasciitis-like stroma
  21. 21.  Found incidentally 1 cm or less Papillary microcarcinoma Common incidental finding (≥25%) in thyroids removed for other reasons More common in males Most common form of papillary carcinoma Stellate appearance Nonencapsulated, white to tan nodule often located subcapsularly. Histologically, the tumors may be totally follicular or show papillary areas as well the lesions can infiltrate the surrounding thyroid
  22. 22. Papillary microcarcinoma.
  23. 23. Microscopic features mutational profilesame as their larger counterpart
  24. 24. Incidentally found microcarcinoma confined within the thyroid is probably of no clinical importance and should not be overtreated
  25. 25. Encapsulated variant of PTC presents grossly as an adenoma comprises from 8% to 13% of papillary cancers Microscopically, such lesions usually show total encapsulation; however, there are cytologic features of papillary cancer, including nuclear changes and psammoma bodies. The prognosis is excellent.
  26. 26. Follicular variant of PTC PTC composed of entirely or almost entirely of follicles. Diagnosis is largely based on the nuclear features Supportive features for the diagnosis are:  invasive growth pattern  psammoma bodies  strongly eosinophilic colloid with scalloped edges  abortive papillae
  27. 27. Follicular variant of papillary carcinoma.Note the clear overlapping nuclei. PIPELLE,
  28. 28. FVPTC Solid Variant Particularly common in children Proliferation predominates over secretion Characterized by solid nests of generally round shape that can be viewed as filled-up follicles Distinguish from poorly differentiated carcinoma:  the nuclear features are those of papillary carcinoma  behavior is that of papillary carcinoma (or a little worse), but notably different from that of poorly differentiated neoplasms Solid variant of papillary carcinoma. The nests are separated by fibrohyaline strands
  29. 29. Macrofollicular Variant  Rarest form of PTC  Opposite of the solid variant in that secretory activity results in large dilated follicles so it resembles a hyperplastic nodule  Some follicles are lined by cells with large clear nuclei with grooves and pseudoinclusions  Low incidence of metastasis Macrofollicular variant’ of papillary carcinoma. This lesion simulates nodular hyperplasia. The nuclear features that allow the diagnosis cannot be seen at this magnification.
  30. 30. Diffuse Sclerosis Variant 3% of all papillary carcinomas affects children and young adults, may present as bilateral goiter. permeates the gland outlining the intraglandular lymphatics. Characterized by:  diffuse involvement of one or both thyroid lobes without formation of dominant mass  dense sclerosis  abundant psammoma bodies  extensive solid foci  squamous metaplasia  heavy lymphocytic infiltration  extensive lymph vessel permeation  Numerous psammoma bodies are found
  31. 31. Oncocytic variant Nuclear features are those of papillary carcinoma Cytoplasm is abundant and has a granular oxyphilic quality Pattern of growth may be papillary or follicular May be encapsulated or invasive, resulting in a number of possible combinations:  oncocytic  encapsulated oncocytic  oncocytic follicular  encapsulated oncocytic follicular variants important to recognize this variant because it may be confusedwith a Hurthle cell neoplasm
  32. 32. Tall cell variant important subtype because of its potentially aggressive clinical course. elderly patients, and often presents as a large tumor with extrathyroidal extension and metastases.
  33. 33.  composed predominantly of cells whose heights are at least twice times their widths. characterized by:  papillae lined by a single layer of ‘tall’ cells (the height being at least twice the width)  an abundant acidophilic, quasi-oncocytic cytoplasm These features should be present in at least 50% of the tumor Growth pattern is usually highly papillary Nuclei usually lack the optically clear appearance, grooves, and pseudoinclusions of papillary carcinoma and its other variants More aggressive behaviour
  34. 34. PTC, tall cell variant.The cells contain abundant cytoplasmand are about three times as tall as they are wide.H&E.)
  35. 35. Tall cell variant of papillary carcinoma. Notethe abundant granular acidophilic cytoplasmwith oncocyte-like features.
  36. 36. Columnar cell variant In the columnar cell carcinoma: there is prominent stratification The cytoplasm is clear (sometimes with subnuclear vacuolization) Outcome is largely predicated by tumor stage Encapsulated columnar cell carcinomas have a favorable course Occasionally tall and columnar cells coexist in papillary carcinoma These tumors have advanced local growth and extrathyroidal extension and show aggressive clinical behaviour
  37. 37. Columnar cell variant of papillary carcinoma. Thepapillae are lined by a pseudostratified layer of spindletumor cells.
  38. 38.  Cardinal molecular alteration is an alteration of RET,which:  is a proto-oncogene on chromosome 10q11.2  encodes a transmembrane receptor with tyrosine kinase activity Alteration of RET  not a germline point mutation (as in familial medullary carcinoma)
  39. 39. PROGNOSIS Age  Nearly all the deaths occur when the tumor manifests after the age of 40 years Gender, Females usually have a better prognosis Extrathyroidal extension ,Adversely affects prognosis Microscopic variant History of previous irradiation, Does not affect prognosis Tumor size  Roughly an inverse correlation between tumor size and prognosis Capsule and margins  Tumors that are encapsulated or have pushing margins have a better outcome Multicentricity  If this is prominent there is a greater incidence of metastasis and a lower chance of disease-free survival Distant metastases  Lung metastases have an adverse influence on prognosis  This influence is even greater for distant metastases in other sites, such as the skeletal system
  40. 40.  Poorly differentiated, squamous, or anaplastic foci  These features have a markedly detrimental effect on prognosis  Present in <5% of cases EMA and Leu-M1 positivity  Immunoreactivity for EMA and Leu-M1 may be associated with a more aggressive clinical course DNA ploidy  A good correlation has sometimes been shown between aneuploidy and aggressive behavior, Rb protein  pRB expression level is a reliable predictor of recurrence Circulating tumor cells  Presence of circulating tumor cells (as determined with an RT- PCR assay for thyroglobulin mRNA) seems to be associated with a higher likelihood of metastatic disease
  41. 41. Follicular carcinoma  “A malignant epithelial tumor showing evidence of follicular cell differentiation and lacking the diagnostic nuclear features of papillary carcinoma” - W.H.O
  42. 42. Follicular carcinoma Relatively rare (10 to 15% of thyroid malignancies ) Predilection for females Incidence higher in iodine deficient areas Mean age at diagnosis approximately 50 years Almost always:  solitary  not occult Two types minimally invasive and widely invasive
  43. 43.  Asymptomatic intrathyroidal mass lesion Hoarsness dysphasia rare Peak incidence between 40 and 60 years
  44. 44. TYPES OF FOLLICULAR CA.Minimally invasive typeWidely invasive type
  45. 45.  Grossly encapsulated tumor Often:  solid and fleshy cut surface.  Most of the tumor is bound by a capsule (irregular whitish band around the lighter central nodule).  the capsule is breached
  46. 46. Capsular invasion in minimallyinvasive follicular carcinoma.
  47. 47. Vascular invasion in minimallyinvasive follicular carcinoma.
  48. 48. Widely invasive follicularcarcinoma High-risk counterpart of the minimally invasive subtype Widespread infiltration of blood vessels and/or adjacent thyroid tissue Often lacks encapsulation Many are poorly differentiated carcinomas at the cytoarchitectural level
  49. 49.  Diagnosis of malignancy:  depends entirely on blood vessel or capsular invasion  blood vessel invasion is almost never evident grossly. The vessels should:  be venous caliber  be in or immediately outside the capsule (rather than within the tumor)  contain one or more clusters of tumor cells attached to the wall and protruding into the lumen  interruption of the capsule must be full thickness to qualify as capsular invasion  distinguish foci of capsular invasion:  from capsular rupture from fine needle aspiration, which results in a fissure-like quality with foci of recent or old hemorrhage and florid stromal reparative changes
  50. 50. Metastases  common with the widely invasive type <5% of minimally invasive tumors with blood vessel invasion  <1% of tumors diagnosed as carcinoma only on the basis of minimal capsular invasion Usually blood-borne (particularly to lung and bones) rather than regional nodes Skeletal metastases:  usually multicentric  have a predilection for the shoulder girdle, sternum, skull, and iliac bone6  sometimes pulsate because of their vascularity (a feature shared with metastatic renal cell carcinoma)
  51. 51. TERMINOLOGY Capsular invasion: tumor penetration through the tumour capsule unassosiated with the site of previous FNAC Vascular Invasion: presence of intravascular tumour cells either covered by endothelium or associated with thrombus INVOLVED VESSELS MUST BE WITHIN OR BEYOND CAPSULE FOCI OF VASCULAR INVASION SHOULD BE DISTINGUISHED FROM SUBENDOTHELIAL COLLECTION Of tumor cells
  52. 52. Special Stains andImmunohistochemistry Thyroglobulin Ttf-1 LMW-keratin
  53. 53. Poorly differentiated carcinoma Thyroid tumor that is, in differentiation and behavior, intermediate between well- differentiated (papillary and follicular carcinoma) and anaplastic thyroid carcinomas.
  54. 54.  Occurs in an older group than well- differentiated tumors Can occur in adolescents. More common in some parts of Europe and South America than in the United States Behavior is generally aggressive High incidence of nodal and blood-borne metastases
  55. 55.  Usually grossly invasive Can be encapsulated
  56. 56. Histopathology Distinguishing features:  nesting (‘insular’) pattern of growth  solid-to-microfollicular arrangement  small uniform tumor cells  variable mitotic activity  fresh tumor necrosis resulting in a peritheliomatous pattern
  57. 57. On high power, the cells show round, medium-sizednuclei with a smooth contour and hyperchromasia
  58. 58. Poorly differentiated carcinoma showingtrabecular growth pattern rather than insularformations
  59. 59. Special Stains andImmunohistochemistry Thyroglobulin 60% TTF-1: 40% Not reactive for:  calcitonin Usually:  focal reactivity for neuroendocrine markers  concentrate radioiodine (unlike undifferentiated carcinoma) bcl-2  in over 80% of cases (rare in undifferentiated carcinoma) p53  may be expressed  restricted to foci of infiltrative growth
  60. 60. Undifferentiated(anaplastic) thyroidcarcinoma UTC are malignant tumours that histologically appear wholely or partially composed of undifferentiated cells that exhibit immunohistochemical or ultrastructural features indicative of epithelial differentiation
  61. 61.  Usually elderly 5% of thyroid malignancies Presentation:  rapidly growing mass  hoarseness  dysphagia  dyspnea  usually extrathyroidal extension Rapid evolution:  massive growth in neck  infiltration of ribbon muscles, esophagus, trachea, skin, and contiguous bones  commonly nodal and distant metastases  cause of death usually involvement of vital structures in the neck  extremely poor prognosis, with many patients surviving less than 6 months following diagnosis
  62. 62.  Pathogenesis Usually a result of anaplastic transformation of a pre-existing well- differentiated tumor (or a metastatic focus):  commonly papillary carcinoma Anaplastic thyroid carcinoma showing residual papillary carcinoma.
  63. 63. Gross anaplastic thyroid carcinoma showing alarge yellow, tan, white mass with areas ofhemorrhage.
  64. 64. HISTOPATHOLOGY Squamoid Sarcomatoid: spindle cell and giant cell
  65. 65.  Sarcomatoid: spindle cell and giant cell: Composed of two patterns, often seen together may exhibit:  a fascicular or storiform growth pattern  heavy neutrophilic infiltration  prominent vascularization  cartilaginous/osseous metaplasia May be osteoclast-like multinucleated giant cells:  giving an appearance reminiscent of giant cell tumor of bone or soft tissues
  66. 66. Anaplastic carcinoma of thespindle cell type.
  67. 67. Anaplastic carcinoma of giantcell type
  68. 68. Special Stains andImmunohistochemistry Keratin 50-100% CEA 50% Throglobulin 5% Vimentin: (consistently present in the spindle cell component) TTF-1 (generally negative)
  69. 69. Medullary carcinoma Thyroid malignancy with C (parafollicular) cell differentiation. 5% of thyroid neoplasms secrete calcitonin, elaborate other polypeptide hormones, such as serotonin, ACTH, and vasoactive intestinal peptide (VIP). Two forms:  sporadic (approximately 80% of cases)  familial The remainder 20% occurs in the setting of MEN syndrome 2A or 2B Cases associated with MEN types 2A or 2B occur in younger patients, and may even arise during the first decade of life. sporadic as well as familial medullary carcinomas are lesions of adulthood, with a peak incidence in the 40s and 50s.
  70. 70. Sporadic medullary carcinoma Occurs in adults (mean age 45 years) Almost always solitary Presents as a thyroid mass that is cold on thyroid scan Sometimes accompanied by intractable diarrhea or Cushings syndrome
  71. 71. Familial medullary carcinoma Autosomal dominant inheritance with virtually complete penetrance. Becomes clinically apparent at mean age 35 years Most cases in children are familial medullary carcinoma Often multiple and bilateral
  72. 72.  Typically:  solid  firm  nonencapsulated  relatively well circumscribed  in the midportion or upper half of the gland, corresponding to a greater Unencapsulated quality, solid concentration of C cells in appearance, and yellowish tan this region color
  73. 73.  Histopathology Classically:  solid proliferation of round to polygonal cells with:  granular amphophilic cytoplasm  medium-sized nuclei  highly vascular stroma  hyalinized collagen  amyloid Low-power microscopic view  coarse calcification showing solid pattern of growth and deposition of amyloid.
  74. 74.  Pattern of growth can be:carcinoid-like,paraganglioma- liketrabecularglandular (tubular and follicular)pseudopapillary pseudopapillary pattern of growth resulting from lack of cohesiveness of tumor cells.
  75. 75. Special Stains and Immunohistochemistry Calcitonin+ 95 % CEA++100% Chromogranin+1 00 Keratin AE 1/3+100 TTF-1+90 Thyroglobulin NSE Synaptophysin  Medullary carcinoma showing immunocytochemical positivity for calcitonin and congo red
  76. 76. Metastases Cervical and mediastinal lymph nodes Distant organs, particularly lung, liver, and skeletal system More common with sporadic and multiple endocrine neoplasia (MEN)-IIB than MEN-IIA May be the first manifestation and a source of confusion
  77. 77. Follicular adenoma Benign encapsulated thyroid tumor that shows evidence of follicular cell differentiation. Most common thyroid neoplasm Usually occurs in euthyroid adult Thyroid lump Elevated thyroglobulin levels common but clinical hyperthyroidism (toxic adenomas) uncommon Autonomously functioning tumors may be more common in regions with iodine deficiency
  78. 78. Gross Pathology Characteristically:  solitary  secondary degenerative changes, especially for larger tumors such as  hemorrhage  edema  fibrosis  calcification  bone formation  cystic degeneration  surrounded by a generally thin capsule that is grossly and microscopically complete Architectural and cytologic features differ from those of surrounding gland, which usually shows signs of compression
  79. 79. Gross appearance of follicular adenoma showing focal hemorrhagic areas 
  80. 80. Histopathology A variety of patterns, singly or in combination:  normofollicular (simple)  macrofollicular (colloid)  microfollicular (fetal;)  trabecular/solid (embryonal) Mitoses:  rare or absent  not necessarily indicators of malignancy  Microfollicular pattern of growth in a follicular adenoma
  81. 81. Intact fibrous capsule around afollicular adenoma.
  82. 82. Special Stains and Immunohistochemistry Thyroglobulin+100 % TTF+100 % Reactivity for:  low-molecular-weight keratin and thyroglobulin in the cytoplasm  laminin and other basement membrane components around the follicles DNA aneuploidy:  found in about one-quarter of follicular adenomas  slightly more common in cellular types  not an indicator of clinical malignancy or increased risk of tumor recurrence
  83. 83. Several variants  Hürthle cell adenoma  hyalinizing trabecular adenoma Atypical adenoma:  pronounced cellular proliferation  less regular cytoarchitectural patterns  no capsular or blood vessel invasion Adenoma with bizarre nuclei:  huge hyperchromatic nuclei, usually in clusters  no features of malignancy Rare types of follicular adenoma:  clear cell changes (including signet ring, mucin-producing, and lipid-rich types)  adipose metaplasia of the stroma (adenolipoma)  cartilaginous metaplasia (adenochondroma)  massive deposition of cytoplasmic black pigment following minocycline therapy (black adenoma)
  84. 84. Adenoma with bizarre nuclei
  85. 85. Hürthle Cell Tumors Follicular neoplasms composed of oncocytes which are characterized by deeply eosinophilic cytoplasm.
  86. 86.  Usually adult Predominance of females Decrease or loss of bcl-2 expression suggests that this is an early event
  87. 87. Histopathology Cytoplasmic granularity:  due to accumulation of mitochondria  ultrastructurally many mitochondria show morphologic abnormalities  deeply eosinophilic quality in H&E-stained sections  follicular (most common)  trabecular/solid  papillary May be:  large follicles separated by long and thin fibrovascular septa inspissated intraluminal colloid with concentric laminations (an appearance similar to psammoma bodies associated with papillary carcinoma, from which they are distinguished by location) Nuclei may show:  pleomorphism  prominent nucleoli  isolated bizarre forms
  88. 88. Hurthle Cell Carcinomas Hürthle Cell CarcinomasPredominantly or exclusively solid/trabecular growth patternHighly invasive Metastases:  mainly to lungs and bone  less commonly cervical nodes
  89. 89. Gross Pathology Characteristically:  solid  tan  well vascularized Usually well encapsulated throughout Invasive tumors tend to grow into the parenchyma in a multinodular fashion  Gross appearance of Hürthle (can be underinterpreted cell carcinoma. The cut as nodular hyperplasia) surface shows a tan color and a necrotic hemorrhagic center
  90. 90. Hurthle cell carcinoma  Older age group  Less female predominance  Larger  Tends to have a solid/trabecular rather than a follicular growth pattern Cells:  often smaller  higher nucleocytoplasmic ratio  Proliferative activity is higher, but the difference is not sufficient for diagnostic or prognostic purposes/  Hürthle cell carcinoma with a predominantly solid pattern of growth
  91. 91. Marked blood vessel invasion(hurthle cell carcinoma)
  92. 92. Special Stains andImmunohistochemistry CK 7+ 66% TTF+ 33% Thyroglobulin: 100%( Establishes thyroid origin) Reactivity for:  thyroglobulin (less reactive than nononcocytic follicular cells)  keratin (CK14 is emerging as a selective marker for oncocytes)  CEA  S-100 protein  surprisingly, HMB-45
  93. 93. Prognosis  Hürthle Cell Carcinomas Hürthle Cell Adenomas 5-year mortality rateAlmost always cured by 20–40% excision Unfavorable prognostic factors: older patient age large tumor size extrathyroidal extension distant metastases regional lymph node involvement possibly aneuploidy
  94. 94. Hyalinizing trabecular tumour HTT is a rare tumour of follicular cell origin with a trabecular pattern of growth and marked intra- trabecular hyalinization Female predilection Mean age 47 years Solitary nodule
  95. 95.  Suggestion that it may be a morphologic variant of papillary carcinoma  features traditionally associated with papillary carcinoma, such as nuclear grooves and pseudoinclusions and psammoma bodies  expression of similar types of stratified epithelial-type keratins  occasional cases contain foci of typical papillary carcinoma  occasional cervical lymph node metastases of papillary carcinoma have an HTA-like pattern  detection of RET/PTC mutations with a frequency similar to or higher than that in papillary carcinoma
  96. 96. Histopathology A peculiar adenoma exhibiting:  prominent trabecular arrangement:  trabeculae may be straight or curved, resulting in in the cytoplasm of tumor cells due to accumulation of intermediate filaments Growth pattern may simulate that of paraganglioma and medullary carcinoma Distinct features:  nuclear grooves and psammoma bodies:  may suggest papillary carcinoma, particularly fine  Hyalinizing trabecular adenoma. A wide trabecula is seen in the center of the picture, with the tumor cells arranged perpendicularly to the longest axis.
  97. 97. Psammoma body formation inhyalinizing trabecular adenoma.
  98. 98. Special stains and immunohistochemistry Consistent positivity for thyroglobulin Distinctive cell membrane staining with MIB-1 Focal and inconstant reactivity for neuroendocrine markers such as:  neuron-specific enolase (NSE)  neurotensin Heavy deposition of type IV collagen:  around tumor cells (partially explaining ‘hyaline’ appearance)
  99. 99. OTHER THYROID TUMORS Teratoma  Peripheral nerve sheath Primary lymphoma and tumors plasmacytoma  Paraganglioma Ectopic thymoma  Solitary fibrous tumor Angiosarcoma  Follicular dendritic cell Smooth muscle tumors tumor  Langerhans cell histiocytosis  Secondary tumors
  100. 100. TERATOMA. neonates or infants under the age of 1 year as huge midline neck masses. Approximately 35% of women who deliver babies with teratomas experience polyhydramnios in pregnancy. predominantly or partially cystic. contained elements of all three germ layers and have been benign. Teratomas of the thyroid in adults differ from those in newborns because they are more frequently malignant
  101. 101. Thyroid gland almost replaced by manyprimitive neuroepithelial rossettes
  102. 102. Malignant Lymphoma involve the thyroid as part of systemic lymphoma (secondary lymphoma) or may arise primarily in the thyroid Approximately 20% of patients dying of generalized malignant lymphoma will show thyroid involvement Thyroid replacement is rarely extensive enough to produce clinical hypothyroidism
  103. 103.  1% to 3.5% thyroid cancers are malignant lymphomas. Primary malignant lymphoma of the thyroid usually arises in an immunologically abnormal gland, usually one affected by chronic lymphocytic thyroiditis Clinically, thyroid lymphoma affects women more frequently than men (ratio of 2.5 to 8.4:1). Most patients are older (age 50 to 80 years). Grossly, appear as large fleshy tan or gray masses often extending outside the thyroid capsule. The most common histologic subtype is large-cell diffuse lymphoma Most thyroid lymphomas are of B-cell lineage
  104. 104. Diffuse large-cell lymphoma arising in thyroid
  105. 105. METASTATIC TUMORS TO THETHYROID. Metastases may reach the thyroid by direct extension retrograde lymphatic spread, or hematogenously. Carcinomas of the larynx, pharynx, trachea, and esophagus may invade the thyroid directly.. Hematogenous metastases to the thyroid vary according to tumor type A metastasis should always be considered when the histology is unusual for a thyroid primary. In surgical series, carcinomas of the kidney and colon and melanoma are most commonly found to metastasize to thyroid Grossly, such lesions are often solitary, circumscribed masses;.