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Follicular thyroid differential diagnosis

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Follicular thyroid differential diagnosis

  1. 1. THYROID TUMOR WITH FOLLICULAR GROWTH PATTERN, PROBLEM IN DIFFERNTIAL DIAGNOSIS Dr. Vikram Prabhakar (DCP,DNB Pathology)
  2. 2. Anatomy • 2 lateral lobes; • 1 isthmus • 15 to 25 grams • Blood supply
  3. 3. Normal Histology
  4. 4. Major patterns of thyroid carcinoma • Follicular - Well formed colloid containing follicles - Solid - Trabecular - Cribriform( poorly formed) • Papillary • Medullary • Undifferentiated ( Anaplastic )
  5. 5. D/D in Follicular growth pattern 1) Adenomatous (Hyperplastic , adenomatoid) nodules 2) Follicular adenoma 3) Follicular carcinoma 4) Follicular variant of Papillary carcinoma 5) Follicular variant of Medullary carcinoma 6) Poorly differentiated carcinoma 7) Undifferentialed ( Anaplastic) carcinoma
  6. 6. Hyperplasia – Neoplasia sequence Follicular cell Hyperplasia Adenoma Carcinoma
  7. 7. Adenomatous nodules • Also called hyperplastic or adenomatoid • Unilateral painless mass • Arises in a background of nodular goiter • Can show complete or partial encapsulation
  8. 8. • Usually contain a mixture of macrofollicules and microfollicules or indl single pattern. • Asymptomatic & accidentally discovered. • Pressure symptoms • Toxic adenomas • Investigations : USG, FNAC, excision biopsy Adenomatous nodules
  9. 9. • Nodules are not showing any specific growth pattern even if they are solitary. • It occurs in a normal thyroid showing only microscopic evidence of nodular goiter( so called dominant hyperplastic nodule) • Some nodules may be hyperfunctional and morphologically represent hyperplastic nodule or adenoma • If multiple nodules are hyperfunctioning than it called Toxic nodular goiter. Adenomatous nodules
  10. 10. Points to remember • Solitary nodules • Nodules in younger pts • Nodules in males • H/O radiation therapy to head & neck region • Hot nodules are more likely to be benign More likely to be neoplastic
  11. 11. FOLLICULAR Adenomas • Discrete solitary masses (follicular adenomas) Simple colloid adenomas [macrofollicular] Fetal/microfollicular, embryonal, trabecular Mixed patterns • Nonfunctional, most of the times • Hormone production in functional adenomas is independent of TSH stimulation( Toxic Adenomas)
  12. 12. CYTOLOGY • Cellular smear with numerous follicular cells and little or no colloid. • Most of the follicular cells arranged in syncytial fragments and exhibit a microfollicular pattern. • Microfollicules consists of 6-12 nuclei in a small ring with central dot of colloid •In macrofollicular adenoma cells are arranged in monolayer sheets with abundant colloid.
  13. 13. Follicular adenoma showing microfollicular pattern
  14. 14. Gross • Solitary, spherical, encapsulated • Average 3cm, upto 10cm • C/S gray-white to red-brown, bulges • Hemorrhage, calcification, fibrosis, cystic change
  15. 15. Microscopy • Uniform follicles containing scant colloid • Follicles distinct from surrounding thyroid • Hurthle cell adenoma, clear cell, signet ring cell • Endocrine atypia : focal nuclear pleomorphism, atypia, prominent nucleoli • Atypical adenoma : ↑↑ anisonucleosis, mitotic activity
  16. 16. TRABECULAR PATTERN TUMOR CELLS HAVE DEEPLY EOSINOPHILIC WITH GRANULAR CYTOPLASM
  17. 17. IHC • FA are immunoreactive for Cytokeratins, Thyroglobuline and TTF-1. • But non reactive for CK-19, Calcitonin or pan- neuroendocrine markers
  18. 18. Variants of FA - Oncocytic Adenoma - FA with papillary hyperplasia - Fetal Adenoma - Singnet ring cell FA - Mucinous FA - Lipoadenoma - Clear cell FA - Toxic Adenoma - Atypical Adenoma - FA with bizarre nuclei
  19. 19. FOLLICULAR CARCINOMA • Malignant epithelial tumor showing evidence of follicular cell differentiation and lacking of diagnostic nuclear features of papillary carcinoma. • 10-15% of thyroid malignancy. • More common in female and peak age 50 yrs. • Rarely occur in children
  20. 20. • Incidence is dramatically decreased due to adequate dietary supplementation of iodine and exclusion of FVPTC from this category. • Iodine deficiency and irradiation is the most common etiological factor. • Most common site is normally situated thyroid and ectopic thyroid tissue( struma ovarii)
  21. 21. Clinical features • Most common presentation asymptomatic intrathyroidal mass lesions. • Ipsilateral lymphadenopathy is less common than PC ( less than 5%) • Cold on scintigraphic scan. • Hoarseness, dysphegia and dyspnea rare but may occur in widely invasive FC.
  22. 22. • No definit precursor lesions but may arise from FA • Multifocality is uncommon. • Recurrence rate is high in residual tumor after partial thyoidectomy. • Lymph node metastases uncommon. • Most common site for distant metastases are lung and bone.
  23. 23. Cytology: Follicular carcinoma • Hypercellular with a dispersed microfollicular arrangement of tumor cells and scant colloid. • Microfollicules consists of 6-12 nuclei forming a small ring like structure. • Presence of nuclear atypia does not correlate with malignancy since FC may shows bland cytological characteristic and FA may shows considerable nuclear atypia.
  24. 24. Cellular smear single cell & microfollicles pattern, diagnosed by histopath as follicular carcinoma with vascular invasion.
  25. 25. Microfollicular cell cluster/rosette with nuclear hyperchromesia and coarseness
  26. 26. Histopathology • Depending on degree of invasiveness FC has two major category - minimally invasive - widely invasive
  27. 27. • FC shows variable morphological pattern ranging from well formed colloid containing follicles, solid, trabecular to poorly form follicles to atypical pattern ( cribriform). • Neither architectural pattern nor cytological features are reliable for its diagnosis
  28. 28. • FC diagnosed on the basis of invasiveness. • Minimally invasive FC have limited capsular and vascular invasion. • Widely invasive FC have widespread infiltration of adjacent thyroid tissue or blood vessels.
  29. 29. • Capsular invasion- Defined by tumor penetrating through the tumor capsule unassociated with the site of previous FNAC. • Vascular invasion- Defined by presence of intravascular tumor cells either covered by endothelium or associated with thrombus. Criteria - Involved vessels must be within or beyond the tumor capsule. - Foci of vascular invasion should be distinguish from sub endothelial collection of tumor cells and retraction artifacts.
  30. 30. FOLLICULAR CARCINOMA MINIMALLY INVASIVE TYPE: (A) TUMOR DEMONESTRATE COMPLETE PENETRATION OF THE CAPSULE AND HAS MUSHROOM LIKE CONFIGURATION. (B) MINIMAL CAPSULAR AND VASCULAR INVASION. (C) FOCAL INVASION OF A CAPSULAR VESSELS.
  31. 31. FOLLICULAR CARCINOMA WIDELY INVASIVE TYPE (A) MULTIFOCAL AREAS OF INVASION OF CAPSULAR VESSELS. (B) TUMOR HAS EXTENDED BEYOUND THE CAPSULE AND IS PRESENTS WITHIN VASCULAR SPACE. (C) MULTIPLE FOCI OF VASCULAR INVASION ARE SEEN.
  32. 32. Variants of FC • Oncocytic variant - 3-4% thyroid malignancy. - other name oxyphil and hurthle cell carcinoma. - Median age 61yrs - 30% cases associated with nodal metastases. Distant metastases is rare
  33. 33. • Clear cell variant - Composed predominantly of clear cells. - Contain glycogen, mucin, lipid or dilated mitochondria. - Signet ring follicular cell may sometime major component of this variant.
  34. 34. IHC-FC • Immunoreactive to Thyroglobulin, TTF-1 and LMW CK • CK-19 and lewis blood antigen are focally positive but rare in FA and NG. But strong positivity in PC • Galectin-3, HBME-1, CD-15 & CD44v6 positive.
  35. 35. • E-cdherin and beta catenin shows membranous positivity but also positive in case of normal thyroid, benign follicular lesions and FVPTC. • Bcl-2 positive, TP53 negative, display low level of cyclin D1 and high levels of P27 with low proliferation rate. • Telomerase expression is higher than FA and PC IHC-FC
  36. 36. Follicular variant of PC • Tumors resemble encapsulated follicular neoplasm composed of small to medium sized irregularly shaped follicles with virtually no papillary structures. • Variable amount of colloid may appear hypereosinophilic and scalloped. • Majority of the cells lining in the follicles contain large clear nuclei with grooves and nuclear pseudoinclusion.
  37. 37. • Intrafollicular multinucleated giant cells are frequent but stromal sclerosis and psammoma bodies are occasional. • Despite complete encapsulation, lymph node and rarely distant metastases can occur.
  38. 38. Cytology -FVPTC • Cytology smear shows non-cohesive cells arranged in follicles found in a background of little colloid. Nuclear crowding with powdery chromatin and grooves are seen. Intranuclear inclusions are less as compared to conventional PTC.
  39. 39. FVPTC, tumor is encapsulated and grossly resemble a follicular adenoma FNAC shows nuclear crowding with powdery chromatin and grooves.
  40. 40. Follicular variant of medullary carcinoma • Extremely rare and also called mixed medullary-follicular carcinoma. • Presence of follicular or glandular structures in a medullary carcinoma can result true follicular pattern growth or entrapment of neighboring follicles by invasive tumor. • Immunoreactivity to calcitonin and thyroglobulin
  41. 41. Poorly differentiated carcinoma • Morphologically and behaviorally an intermediate position between differentiated ( FC, PC) and undifferentiated carcinoma (anaplastic). • Etiology is unknown but most likely arise de novo or preexisting Papillary and follicular carcinoma. • Large solitary thyroid masses, cold by scintigraphy and with or without concurrent enlargement of regional lymph node.
  42. 42. Cytology -Highly cellular with numerous dyscohesive small to medium sized cells, microfollicules and scant colloid. - Nuclei are bland with fine chromatin and small nucleoli. - Necrosis and mitosis are common. - Definitive diagnosis is made out in histopathology.
  43. 43. Syncytial clusters of crowded small cells with hyperchromatic nuclei and high NC ratio
  44. 44. Gross -More than 3 cm in diameter at the time of diagnosis - Solid gray white with frequent foci of necrosis. - Most tumor have pushing borders and rarely thick capsule. -Invasive peritumoral growth leads to satellite nodules within the thyroid parenchyma
  45. 45. Histopathology • Three different growth pattern Insular, trabecular and solid. • Diagnosis relies on the identification of these pattern. • Infiltrative growth pattern, necrosis and vascular invasion. • Well defined nest surrounded by fibrovascular septae. Tumor cells are small, uniform, round hyperchromatic to vesicular nuclei with indistinct nucleoli. Mitotic figures are common.
  46. 46. IHC • Immunoreactive for thyroglobuline and TTF-1. • Focal TP53 nuclear positivity. • Increased Ki-67 (MIB-1) index. • Absence of E-cadherin membranous expresion
  47. 47. Undifferentiated (anaplstic) carcinoma • Highly malignant tumors that histologically appear wholly or partially composed of undifferentiated cells. • Occurs mainly in the elderly, only 25% patients are younger than 60yrs. • Female are affected more M:F = 1: 1.5
  48. 48. • Presented as rapidly expanded neck mass. • Most important sign and symptoms are - Hoarseness (80%) - dysphagia (60%) - Vocal cord paralysis (50%) -Cervical pain (30%) - Dyspnea (20%)
  49. 49. • Tumor may fixed and hard(75%), single(60%), multiple nodules(40%) and B/L (25%) cases • Surrounding structures are frequently involved, muscles(65%), trachea(50%), esophagus(45%), laryngeal nerve(30%) and larynx(15%) cases. • 40% patients have cervical lymphadenopathy and distant metastases. • 50% involved lungs, 15% bone and 10% brain.
  50. 50. Cytology • Highly cellular, cells are singly or clusters and marked nuclear pleomorphism. • The cells types are squamoid, giant and spindle with bizarre single and multiple nuclei. • Coarsely clumped chromatin, single and multiple prominent nucleoli. • Mitotic figures are numerous. • Background shows necrotic debris, inflammatory cells and occasional osteoclast like giant cells.
  51. 51. Gross -Tumors are large, fleshy and white-tan in color. - Infiltrative, areas, hemorrhage and necrosis are common.
  52. 52. Histopathology • Majority of UTC are widely invasive tumor composed of an admixture of spindle cell, pleomorphic giant cells and epithelioid cells. • Percentage of cells component varies. • Extensive coagulative necrosis with irregular borders and palisading is often seen. • Infiltration of vascular walls accompanied by obliteration of the vascular lamina is common.
  53. 53. (A) Anaplastic carcinoma undermining laryngeal mucosa. Note the large atypical cells. (B) High-power view of anaplastic carcinoma showing large atypical cells with mitoses. (C) Anaplastic carcinoma with sheets of intermediate cells associated with focal osteoclast-like giant cells and extensive hemorrhage. (D) A focus of well-differentiated thyroid carcinoma identified adjacent to an anaplastic carcinoma A B C D
  54. 54. IHC • Cytokeratin - most frequently expressed about 40-100% of cases. • EMA (30-50%) and CEA(< 10%) less commonly expressed. • TTF-1 rarely expressed and thyroglobulin is invariably negative. • TP-53 strongly positive.
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