Thyroid malignancy

1. THYROID NEOPLASMS

2. 15-25
grams

4. “NODULES”
• Solitary vs. Multiple
• Younger vs. Older
• Male vs. Female
• Hx. neck radiation vs. NO Rx.
• “Cold” vs. HOT (really NOT-cold)

5. • SOLITARY NODULES
• YOUNGER AGE
• MALES
• RADIATION
• HOT NODULES

6. ADENOMA THYROID
• Discrete,solitary,from thyroid epithelial cells
• DD:1. dominant nodule
• 2.follicular carcinoma
nonfunctional.

7. pathogenesis
• Mutations of TSH receptor signelling pathway.
• Gain of function in TSHR or GNAS-
Independent secretion of TSH-THYROID
AUTONOMY-HOT NODULE
• RAS OR PIK3 CA

8. MORPHOLOGY
• solitary spherical encapsulated
• Compressing the adjacent thyroid
• Hge,necrosis,fibrosis and cystic changes

9. • Well formed capsule
• Uniform follicles
• Uniform cell size
• Compression of adjacent thyroid

11. Clinical features
• Painless
• Difficulty in swalowing
• Non functioning-cold nodules
• USG ,FNAC

13. HÜRTHLE CELL ADENOMA, note “atypia”

14. CARCINOMAS
• 4 MAJOR TYPES
• 1.PAPILLARY CA
• 2.FOLLICULAR CA
• 3.ANAPLASTIC CA
• 4.MEDULLARY CA

16. Papillary carcinoma
• 1.RET gene in chr 10-TK receptor expression-
RET PTC fusion gene-transcriptional activation
• 2.BRAF MUTATION-Prognostic significance

20. ORPHAN ANNIE CELLS in PAPILLARY CARCINOMA

21. Follicular carcinoma
• Mutations that activates RAS OR PI3K AKT of
TK receptor pathway
• Translocation of (2;3)(q13;p25)producing PAX8
PPARG FUSION GENE-thyroid development
and terminal differentiation of cells

23. Anaplastic or undifferentiated
carcinoma
• RAS ,PIK3CA MUTATION
• INACTIVATION OF TP53 or activation of beta
catenin

24. Medullary carcinoma
• MEN 2
• RET mutation

25. MEDULLARY CARCINOMA of the thyroid with “HYALINIZATION”, i.e.,
AMYLOID!!!

26. HYALINIZATION showing APPLE GREEN birefringence in
CONGO RED stain, i.e., AMYLOID

27. Papillary Carcinoma
• Most common
• Morphology
– Branching papillae with central fibro vascular core
– Uniform cuboidal cells
– Nuclear Feature
• Dispersed Chromatin
• Clear or empty nucleus – Ground glass / Orphan annie eye
nucleus
• Pseudoinclusion , intranuclear grooves
– psammoma bodies – concentric calcified structure

28. Variants
• Tall cell variant
• Diffuse sclerosing variant
• Papillary microcarcinoma
• Follicular variant
• Columnar cell variant
• Solid variant
• Cribriform morular variant
• Hobnail variant

33. Clinical Course
• Hoarseness
• Dysphagia
• Cough
• Dyspnea

34. Follicular Carcinoma
• 5 – 15 %
• Associated with Dietary iodine deficiency

35. Morphology
• Gross
– Similar to Follicular adenoma
• Microscopy
– Uniform follicles with colloid , capsular and
vascular invasion present
Benign Malignant
Complete capsule Circumferential fibrosis
Compression of adjacent thyroid No compression
No Capsular or Vascular invasion Capsular or Vascular invasion seen

36. Clinical Features
• Cold Nodules
• Hematogenous Spread
• Total Thyroidectomy
• Serum thyroglobulin – To monitor tumor
recurrence

37. Anaplastic (Undifferentiated )
Carcinoma
• < 5 %
• Aggressive
• Arising from well differentiated thyroid
carcinoma

38. Morphology
• Highly anaplastic cells including
– 1)Large pleomorphic giant cells
– 2) Sarcomatpus spindle cells
– 3) Mixed spindle and giant cells
• Positive for cytokeratin

39. Clinical Features
• Rapidly enlarging neck mass
• No surgical treatement

40. Medullary Carcinoma
• Neuroendocrine neoplasm dervied from
parafollicular cells or ‘C’ cells
• Secrete Calcitonin
• Sporadic or Associated with MEN 2A or MEN
2B
• Familial Medullary thyroid carcinoma

41. • Gross –
– Solitary nodule
– Infiltrative
– Necrosis
– Hemorrhage
– Polygonal to spindle shaped cells forming nests,
trabeculae and follicles
– Amyloid deposits
– C Cell hyperplasia

42. Clinical course
• Mass in neck
• Dysphagia
• Hoarseness
• Cushing syndrome
• Diarrhea
• Serum Calcitonin Elevated
• CEA - Biomarker