1. THYROID TUMOURS

2.  THYROID CARCINOMAS
 THYROID ADENOMA AND RELATED TUMORS
 OTHER THYROID TUMORS

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. THYROID ADENOMA AND RELATED
TUMORS
 Follicular adenoma
 Hyalinizing trabecular tumor

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. Papillary carcinoma
 “A malignant epithelial tumor showing evidence of follicular cell
differentiation and characterized by distinctive nuclear features”
-W.H.O.

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 Hashimoto's thyroiditis
Disease localized to:
 thyroid gland in 67%
 thyroid and lymph nodes in 13%
 lymph nodes alone in 20%
 Overall survival excellent

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. 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. 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.  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. Nuclear grooves
 Occur in oval or
spindle nuclei
 Arranged along the
longest nuclear
axis
 Represent
infoldings of a
redundant nuclear
membrane
Mitoses are scanty or
absent
 intranuclear grooves (400×).

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. 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. 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. 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. Metastasis
Regional lymph node metastases
are extremely common (≥50%)
This feature does not adversely
affect long-term prognosis.
Frequently the nodal metastasis
will involve one
node that may be cystic

18. Special Stains and
Immunohistochemistry (PTC)

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. 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.  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. Papillary microcarcinoma.

23. Microscopic features mutational profile
same as their larger counterpart

24. Incidentally found microcarcinoma
confined within the thyroid is probably
of no clinical importance and should not
be overtreated

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. 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. Follicular variant of papillary carcinoma.
Note the clear overlapping nuclei.
PIPELLE,

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. 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. 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. 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. 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.  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. PTC, tall cell variant.The cells contain abundant cytoplasm
and are about three times as tall as they are wide.
H&E.)

35. Tall cell variant of papillary carcinoma. Note
the abundant granular acidophilic cytoplasm
with oncocyte-like features.

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. Columnar cell variant of papillary carcinoma. The
papillae are lined by a pseudostratified layer of spindle
tumor cells.

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. 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.  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. 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. 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.  Asymptomatic intrathyroidal mass lesion
 Hoarsness dysphasia rare
 Peak incidence between 40 and 60 years

44. TYPES OF FOLLICULAR CA.
Minimally invasive type
Widely invasive type

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. Capsular invasion in minimally
invasive follicular carcinoma.

47. Vascular invasion in minimally
invasive follicular carcinoma.

48. Widely invasive follicular
carcinoma
 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.  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. 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. 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. Special Stains and
Immunohistochemistry
 Thyroglobulin
 Ttf-1
 LMW-keratin

54. Poorly differentiated carcinoma
 Thyroid tumor that is, in differentiation and
behavior, intermediate between well-
differentiated (papillary and follicular
carcinoma) and anaplastic thyroid carcinomas.

55.  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

56.  Usually grossly invasive
 Can be encapsulated

57. 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

58. On high power, the cells show round, medium-sized
nuclei with a smooth contour and hyperchromasia

59. Poorly differentiated carcinoma showing
trabecular growth pattern rather than insular
formations

60. Special Stains and
Immunohistochemistry
 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

61. Undifferentiated(anaplastic) thyroid
carcinoma
 UTC are malignant tumours that histologically
appear wholely or partially composed of
undifferentiated cells that exhibit
immunohistochemical or ultrastructural
features indicative of epithelial differentiation

62.  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

63.  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.

64. Gross anaplastic thyroid carcinoma showing a
large yellow, tan, white mass with areas of
hemorrhage.

65. HISTOPATHOLOGY
 Squamoid
 Sarcomatoid: spindle cell and giant cell

66.  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

67. Anaplastic carcinoma of the
spindle cell type.

68. Anaplastic carcinoma of giant
cell type

69. Special Stains and
Immunohistochemistry
 Keratin 50-100%
 CEA 50%
 Throglobulin 5%
 Vimentin: (consistently present in the spindle
cell component)
 TTF-1 (generally negative)

70. 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.

71. 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 Cushing's syndrome

72. 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

73.  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

74.  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.

75.  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.

76. 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

77. 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

78. 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

79. 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

80. Gross appearance of follicular adenoma
showing focal hemorrhagic areas


81. 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

82. Intact fibrous capsule around a
follicular adenoma.

83. 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

84. 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)

85. Adenoma with bizarre nuclei

86. Hürthle Cell Tumors
 Follicular neoplasms composed of oncocytes
which are characterized by deeply eosinophilic
cytoplasm.

87.  Usually adult
 Predominance of females
 Decrease or loss of bcl-2 expression suggests
that this is an early event

88. 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

89. 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

90. 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

91. 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

92. Marked blood vessel invasion
(hurthle cell carcinoma)

93. Special Stains and
Immunohistochemistry
 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

94. 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

95. 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

96.  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

97. 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.

98. Psammoma body formation in
hyalinizing trabecular adenoma.

99. 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)

100. 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

101. 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

102. Thyroid gland almost replaced by many
primitive neuroepithelial rossettes

103. 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

104.  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

105. Diffuse large-cell lymphoma arising in thyroid

106. METASTATIC TUMORS TO THE
THYROID.
 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;.