92.

Gusa nodulara

Definitie:

Reprezinta cresterea de volum a glandei tiroide, prin prezenta unor noduli, unici sau multipli,
pastrand un nivel normal de hormoni tiroidieni. Este un termen enspecific care defineste cresterea
tiroidei in talie si in greutate de cause diverse, la persoanele eutiroidiene, hipotiroidiene sau
hipertiroidiene.

Se intalneste mai frecvent la femei (raport F/M, 8:1).

Etiopatogenie:

1. Cauza cea mai frecventa este carenta de iod creste reflex TSH stimuleaza hiperplazia si
hipertrofia glandei tiroide; insa deoarece majoritatea pacientilor are nivel de TSH normal, se
presupune ca tesutul tiroidian raspunde anomral la prezenta TSH.
2. Defectul genetic de sinteza de hormone tiroidieni, apare in gusa congenitala- hormonii
tiroidieni fiind insuficienti, hipofiza stimuleaza sinteza de hormone tropi, cee ace implica
proliferarea epiteliului follicular tiroidian cu hiperplazia secundara a acestuia.
3. Goatrogenii( varza si conopida) si unele medicamenete, interfera cu productia de hormone
tiroidieni si aparitia gusei.
4. Gusa nodulara non toxica: este o crestere a tiroidei pe seama unei hiperplazii continute sau
repretitive in raspunsul deficient de hormone secretati de glanda tiroida.

Clinic:

Se observa masa cervicala ce comprima structurile din jur si determina simptome ca dispnee si
disfagie; uneori poate fi prezent un nodul tiroidian hiperfunctional (toxic), si se numeste sd. Plummer,
iar clinic pacientul prezinta hipertiroidism. Tiroida poate fi crescuta in talie, sa ajunga pana la 250 de
grame. Se poate extinde substernal sis a determine detresa respiratorie.

Macroscopic:

- gusa difuza: glanda marita uniform de volum ( mai mult de 40g), simetric, cu aspect cenusiu,
translucid, sticlos din cauza prezentei coloidului;

- gusa nodulara – marire de volum asimetrica, cu aspect multinodular pe sectiune; nodulii au

aspect brun-galbui sau brun-roscat, gelatinos, in functie de cantitatea de coloid; nodulii sunt incapsulati;
frecvent se observa zone hemoragice, chistice de scleroza si de calcificare.

Microscopic:

Gusa difuza prezinta hiperplazie si hipertrofie difuza a epiteliului folicular, ocazional formand
structuri papilare; pe masura ce afectiunea se cronicizeaza, cu episoade de stimulare si involutie
(administrare de iod), aspectul coloid si nodular devind evident, cu foliculi dilatati chistic si epiteliu
aplatizat sau cuboidal, nodulii au dimensiuni variabile si sunt separati prin septuri fibroase; frecvent se
identifica zone de calcificare, scleroza, hemoragie si depozite de hemosiderina.
 Hiperplazie adenomatoasa= cand focarele de hiperplazie sunt mari si circumscrise
GOITRE

The term goitre is defined as thyroid enlargement caused by compensatory hyperplasia and hypertrophy of the
follicular epithelium in response to thyroid hormone deficiency. The end-result of this hyperplasia is generally a euthyroid state
(in contrast to thyrotoxicosis occurring in diffuse toxic goitre or Graves’ disease) though at some stages there may be hypoor
hyperthyroidism. Two morphologic forms of goitre are distinguished: A. Diffuse goitre (simple nontoxic goitre or colloid goitre).
B. Nodular goitre (multinodular goitre or adenomatous goitre).

Pathogenesis of Goitre

The pathogenetic mechanisms of both forms of goitre can be considered together since nodular goitre is generally
regarded as the end-stage of long-standing simple goitre (Fig. 27.9). The fundamental defect is deficient production of thyroid
hormones due to various etiologic factors described below, but most common is dietary lack of iodine. Deficient thyroid
hormone production causes excessive TSH stimulation which leads to hyperplasia of follicular epithelium as well as formation of
new thyroid follicles. Cyclical hyperplastic stage followed by involution stage completes the picture of simple goitre. Repeated
and prolonged changes of hyperplasia result in continued growth of thyroid tissue while involuted areas undergo fibrosis, thus
completing the picture of nodular goitre.

Diffuse Goitre (Simple Non-toxic Goitre, Colloid Goitre)

Diffuse, nontoxic simple or colloid goitre is the name given to diffuse enlargement of the thyroid gland,
unaccompanied by hyperthyroidism. Most cases are in a state of euthyroid though they may have passed through preceding
stage of hypothyroidism due to inadequate supply of iodine. TSH levels are invariably elevated. In general, goitre is more
common in females. Simple goitre often appears at puberty or in adolescence, following which it may either regress or may
progress to nodular goitre.

ETIOLOGY. Epidemiologically, goitre occurs in 2 forms: endemic, and non-endemic or sporadic. Endemic goitre.
Prevalence of goitre in a geographic area in more than 10% of the population is termed endemic goitre. Such endemic areas are
several high mountainous regions far from the sea where iodine content of drinking water and food is low such as in the regions
of the Himalayas, the Alps and the Ande. Of late, however, the prevalence in these areas has declined due to prophylactic use of
iodised salt. Though most endemic goitres are caused by dietary lack of iodine, some cases occur due to goitrogens and genetic
factors. Goitrogens are substances which interfere with the synthesis of thyroid hormones. These substances are drugs used in
the treatment of hyperthyroidism and certain items of food such as
cabbage, cauliflower, turnips and cassava roots. Sporadic (non-
endemic) goitre. Non-endemic or sporadic simple goitre is less
common than the endemic variety. In most cases, the etiology of
sporadic goitre is unknown. A number of causal influences have
been attributed. These include the following: Suboptimal iodine
intake in conditions of increased demand as in puberty and
pregnancy.Genetic factors. Dietary goitrogenes. Hereditary defect
in thyroid hormone synthesis and transport (dyshormonogenesis).
Inborn errors of iodine metabolism.

MORPHOLOGIC FEATURES.

Grossly, the enlargement of the thyroid gland in simple goitre is

moderate (weighing up to 100-150 gm), symmetric and diffuse. Cut
surface is gelatinous and translucent brown (Fig. 27.10).

Histologically, two stages are distinguished: 1. Hyperplastic stage

is the early stage and is characterised by tall columnar follicular
epithelium showing papillary infoldings and formation of small new
follicles. 2. Involution stage generally follows hyperplastic stage
after variable period of time. This stage is characterised by large
follicles distended by colloid and lined by flattened follicular epithelium (Fig. 27.11).

Nodular Goitre (Multinodular Goitre, Adenomatous Goitre)

As already stated, nodular goitre is regarded as the

end-stage of long-standing simple goitre. It is characterised by
most extreme degree of tumour-like enlargement of the thyroid
gland and characteristic nodularity. The enlargement of the gland
may be sufficient to not only cause cosmetic disfigurement, but in
many cases may cause dsyphagia and choking due to
compression of oesophagus and trachea. Most cases are in a
euthyroid state but about 10% cases may develop thyrotoxicosis
resulting in toxic nodular goitre or Plummer’s disease. However,
thyrotoxicosis of Plummer’s disease (toxic nodular goitre) differs
from that of Graves’ disease (diffuse toxic goitre) in lacking
features of ophthalmopathy and dermatopathy. Such ‘hot
nodules’ may be picked up by CT scan or by RAIU studies. Since
nodular goitre is derived from simple goitre, it has the same
female preponderance but affects older individuals because it is a
late complication of simple goitre. ETIOLOGY. Etiologic factors
implicated in endemic and nonendemic or sporadic variety of
simple goitre are involved in the etiology of nodular goitre too.
However, how nodular pattern is produced is not clearly
understood. Possibly, epithelial hyperplasia, generation of new
follicles, and irregular accumulation of colloid in the follicles—all
contribute to produce increased tension and stress in the thyroid gland causing rupture of follicles and vessels. This is followed
by haemorrhages, scarring and sometimes calcification, resulting in development of nodular pattern.

MORPHOLOGIC FEATURES.

Grossly, the thyroid in nodular goitre shows asymmetric and extreme enlargement, weighing 100-500 gm or even
more. The five cardinal macroscopic features are as under (Fig. 27.12):

1. Nodularity with poor encapsulation

2. Fibrous scarring

3. Haemorrhages

4. Focal calcification

5. Cystic degeneration.

Cut surface generally shows multinodularity but occasionally there may be only one or two nodules which are poorly-
circumscribed (unlike complete encapsulation of thyroid adenoma, described below).

Histologically, the same heterogenicity as seen on gross appearance is seen. Corresponding microscopic features are
as follows (Fig. 27.13): 1. Partial or incomplete encapsulation of nodules. 2. The follicles varying from small to large and lined by
flat to high epithelium. A few may show macropapillary formation. 3. Areas of haemorrhages, haemosiderin-laden macrophages
and cholesterol crystals. 4. Fibrous scarring with foci of calcification. 5. Micro-macrocystic change.
 93. Boala Basedow-Graves

Definitie:

Boala inflamatorie autoimuna a tiroidei caracterizata prin gusa difuza, hipertiroidism endogen
(100%), exoftalmie (40%), si ocazional dermopatie (edem pretibial).( din cauza de adenoma functional
tiroidian sau cancer).

Este cea mai frecventa cauza de hipertiroidism la persoanele sub 40 de ani, are incidenta
maxima intre 20-40 ani si un raport de 7:1 in favoarea femeilor.

Etiologie: factori genetici, mecanisme imune. Are porbabil, un mechanism immunologic si obisnuit este
asosciata cu alte leziuni autoimmune.

Patogenie: anticorpi anti-receptor TSH cu actiune bio-moleculara similara TSH-ului.

Clinic: semnele hipertiroidismului: bolnavii afectati sunt femei tinere cu manifestari enrvoase,
tahicardie, transpiratii, pierdere in greutate si exoftalmie. Nivelul tireotropinei este scazut sau
nesesizabil.

Paraclinic: nivele crescute de T3 si T4 si TSH scazut.

Macroscopic:

Tiroida este marita difuz de 2-4 ori, bilateral; gusa are o consistenta ferma, aspect neted si o
culoare rosu-brun pe suprafata de sectiune.

Microscopic:

Foliculii tiroidieni sunt hiperplazici, cu epiteliu cubic-cilindric si proeminente papilare fara ax

conjunctiv in lumen; la polul apical al celulelor exista vacuole de resorbtie, sugestive pentru hiperfunctie
metabolica a celulelor foliculare; Coloidul este redus, cu aspect crestat (festonat) marginal; interstitial se
gaseste infiltrat inflamator si chiar agregate limfocitare nodulare fomate din limfocite T; administrarea
preoperatorie de iod determina involutia si dilatarea foliculilor, cu aplatizarea epiteliului si fibroza
interstiala; - tesutul periorbital prezinta initial edem apoi fibroza in infiltrare limfocitara. Celulele
foliculare sunt inalte, columnare, cu nuclei amrita. Stroma este intens vascularizata si infiltrate cu limfo
monocyte.

GRAVES’ DISEASE (DIFFUSE TOXIC GOITRE)

Graves’ disease, also known as Basedow’s disease, primary hyperplasia, exophthalmic goitre, and diffuse toxic goitre,
is characterised by a triad of features: Hyperthyroidism (thyrotoxicosis) Diffuse thyroid enlargement Ophthalmopathy. The
disease is more frequent between the age of 30 and 40 years and has five-fold increased prevalence among females.
ETIOPATHOGENESIS. Graves’ disease is an autoimmune disease and, as already stated, there are many immunologic similarities
between this condition and Hashimoto’s thyroiditis. These are as follows:

1. Genetic factor association. Like in Hashimoto’s thyroiditis. Graves’disease too has genetic predisposition. A familial
occurrence has been observed. Susceptibility to develop Graves’ disease has been found associated with HLA-DR3 (Hashimoto’s
thyroiditis has both HLA-DR3 and HLA-DR5 association, page 804), CTLA-4 and PTPN22 (a T-cell regulatory gene).
 2. Autoimmune disease association. Graves’ disease may be found in association with other organ-specific
autoimmune diseases. Hashimoto’s thyroiditis and Graves’ disease are frequently present in the same families and the two
diseases may coexist in the same patient.

3. Other factors. Besides these two factors, Graves’ disease has higher prevalence in women (7 to 10 times), and
association with emotional stress and smoking.

4. Autoantibodies. Autoantibodies against thyroid antigens are detectable in the serum of these patients too but their
sites of action are different from that of Hashimoto’s thyroiditis. In Graves’ disease, TSH-receptor autoantigen is the main
antigen against which autoantibodies are directed. These are as under:

i) Thyroid-stimulating immunoglobulin (TSI): It binds to TSH receptor and stimulates increased release of thyroid
hormone.
ii) Thyroid growth-stimulating immunoglobulins (TGI): It stimulates proliferation of follicular epithelium.
iii) TSH-binding inhibitor immunoglobulins (TBII): It is inhibitory to binding of TSH to its own receptor. Depending
upon its action as inhibitory or stimulatory to follicular epithelium, it may result in alternate episodes of hypo-
and hyperthyroidism. However, it is not quite clear what stimulates B cells to form these autoantibodies in
Graves’ disease. Possibly, intrathyroidal CD4+ helper T cells are responsible for stimulating B cells to secrete
autoantibodies. The pathogenesis of Graves’ infiltrative ophthalmopathy is also of autoimmune origin. The
evidence in support is the intense lymphocytic infiltrate around the ocular muscles and detection of circulating
autoantibodies against muscle antigen that cross-react with thyroid microsomes.

MORPHOLOGIC FEATURES.

Grossly, the thyroid is moderately, diffusely and

symmetrically enlarged and may weigh up to 70-90 gm. On cut
section, the thyroid parenchyma is typically homogeneous, red-
brown and meaty and lacks the normal translucency.

Histologically, the following features are found (Fig. 27.8):

1. There is considerable epithelial hyperplasia and

hypertrophy as seen by increased height of the follicular lining
cells and formation of papillary infoldings of piled up epithelium
into the lumina of follicles which are small.

2. The colloid is markedly diminished and is lightly staining,

watery and finely vacuolated.

3. The stroma shows increased vascularity and

accumulation of lymphoid cells. However, the pathologic changes
in gross specimen as well as on histologic examination are
considerably altered if preoperative medication has been
administered. Iodine administration results in accumulation of
colloid in the follicles and decrease in vascularity and height of
follicular cells, while antithyroid drugs such as thiouracil cause
marked hyperplasia.

CLINICAL FEATURES. Graves’ disease generally develops slowly and insidiously. Patients are usually young women who
present with symmetric, moderate enlargement of the thyroid gland with features of thyrotoxicosis (page 802),
ophthalmopathy and dermatopathy. Ocular abnormalities are lid lag, upper lid retraction, stare, weakness of eye muscles
and proptosis. In extreme cases, the lids can no longer close and may produce corneal injuries and ulcerations.
Dermatopathy in Graves’ disease most often consists of pretibial (localised) myxoedema in the form of firm plaques. Like in
Hashimoto’s thyroiditis, there is no increased risk of development of thyroid cancer in Graves’ disease.
 94. Troidita Hashimoto

Definitie:

Boala inflamatorie autoimuna a tiroidei caracterizata prin prezenta de anticorpi ce distrug

treptat foliculii tiroidieni.

Etiopatogenie:

- frecvent la femei in decada 4-6 de viata

- se asociaza cu alte boli autoimune: LES, artita reumatoida, hepatita autoimuna, vitiligo, DZ,
anemie pernicioasa, etc

- e implicata imunitate celulara dar si cea umorala (anticorpi anti-TSH, anti-tireoglobulina, anti-
tireoperoxidaza[ATPO],

- determinism genetic: asociat frecvent cu HLA DR3 si DR5, incidenta familiala

- Gusa evolueaza lent, cu hipotiroidie progresiva, ce poate intercala episoade de tireotoxicoza

(foliculii distrusi elibereaza cantitati crescute de hormoni tiroidieni)

- Diagnosticul se face pe baza autoanticorpilor circulanti

- tratament medicamentos de substitutie si chirurgical cand gusa determina compresie pe

structurile invecinate;

- Pacientii asociaza risc crescut de dezvoltare a unui limfom tiroidian non-Hodgkin cu celule B

Clinic:

Bolavele sunt letargice, intolerante la frig, greoaie, cu piele groasa si bradicardie. Frecvent se
asociaza si alte leziuni de natura autoimuna, inclusive leziuni endocrine.

Macroscopic:

Glanda tiroida marita de volum de 2-4 ori, difuz, simetric, bilateral; are o consistenta ferma
greutate intre 60-300 g, capsula intacta; pe suprafata de sectiune are aspect carnos, de culoare galben-
cenusiu, palid, lobulatia este accentuate si lobii individuali proemina.

Microscopic:

Interstitul tiroidian (intre foliculi) prezinta un bogat infiltrat inflamator limfo-mononuclear (limfocite
si plasmocite), cu formare de foliculi limfoizi cu centru germinativ;

- Foliculii tiroidieni sunt atrofici si redusi numeric si mici.

- Celulele epiteliului folicular pot fi metaplaziate cu numeroase celule Hurthle (celule oxifile) cu
citoplasma abundenta, eozinofila, datorita continutului crescut de mitocondrii; celulele oxifile
prezinte frecvent atipii; cronic, interstitiul asociaza fibroza. Infiltratul de limfoplasmocite cu
formarea de centri clari asemeni unui limfom nodular este proeminent iar fibroza are grade
variate de extindere.
HASHIMOTO’S (AUTOIMMUNE, CHRONIC LYMPHOCYTIC) THYROIDITIS

Hashimoto’s thyroiditis, also called diffuse lymphocytic thyroiditis, struma lymphomatosa or goitrous autoimmune
thyroiditis, is characterised by 3 principal features:

1. Diffuse goitrous enlargement of the thyroid.

2. Lymphocytic infiltration of the thyroid gland.

3. Occurrence of thyroid autoantibodies.

Hashimoto’s thyroiditis occurs more frequently between the age of 30 and 50 years and shows an approximately
tenfold preponderance among females. Though rare in children, about half the cases of adolescent goitre are owing to
autoimmune thyroiditis. Hashimoto’s thyroiditis is the most common cause of goitrous hypothyroidism in regions where
iodine supplies are adequate. Regions where iodine intake is highest have higher incidence of Hashimoto’s thyroiditis e.g. in
Japan and the United States.

ETIOPATHOGENESIS. Hashimoto’s thyroiditis is an autoimmune disease is well established. Hashimoto, a Japanese

surgeon, described it in 1912 as the first auto immune disease of any organ. Autoimmune pathogenesis of Hashimoto’s
thyroiditis is explained by the following observations:

1. Other autoimmune disease association: Like in other autoimmune diseases, Hashimoto’s disease has been found in
association with other autoimmune diseases such as Graves’ disease, SLE, Sjögren’s syndrome, rheumatoid arthritis,
pernicious anaemia and Type 1 diabetes mellitus.

2. Immune destruction of thyroid cells: The sequence of immune phenomena is initial activation of CD4+ T helper cells.
These cells then induce infiltration of CD8+ T cytotoxic cells in the thyroid parenchyma as well as activate B cells to form
autoantibodies, which bring about immune destruction of thyroid parenchyma.

3. Detection of autoantibodies: The following autoantibodies against different thyroid cell antigens are detectable in the
sera of most patients with Hashimoto’s thyroiditis

i) Thyroid microsomal autoantibodies (against the microsomes of the follicular cells).

ii) Thyroglobulin autoantibodies.

iv) TSH receptor autoantibodies

v) Less constantly found are thyroid autoantibodies against follicular cell membranes, thyroid hormones
themselves, and colloid component other than thyroglobulin.

4. Inhibitory TSH-receptor antibodies: TSH-receptor antibody seen on the surface of thyroid cells in Hashimoto’s thyroiditis
is inhibitory to TSH, producing hypothyroidism. Similar antibody is observed in Graves’ disease where it causes
hyperthyroidism. It appears that TSH-receptor antibody may act both to depress or stimulate the thyroid cells to produce
hypo- or hyperthyroidism respectively. Thus, these patients may have alternate episodes of hypo- or hyperthyroidism. 5.
Genetic basis: The disease has higher incidence in firstdegree relatives of affected patients. Hashimoto’s thyroiditis is seen
more often with HLA-DR3 and HLA-DR5 subtypes.

MORPHOLOGIC FEATURES.

Pathologically, two varieties of Hashimoto’s thyroiditis are seen: classic form, the usual and more common, and
fibrosing variant found in only 10% cases of Hashimoto’s thyroiditis.

Grossly, the classic form is characterised by diffuse, symmetric, firm and rubbery enlargement of the thyroid which
may weigh 100-300 gm. Sectioned surface of the thyroid is fleshly with accentuation of normal lobulations but with
retained normal shape of the gland. The fibrosing variant has a firm, enlarged thyroid with compression of the surrounding
tissues.
 Histologically, the classic form shows the following features (Fig. 27.7):

1. There is extensive infiltration of the gland by

lymphocytes, plasma cells, immunoblasts and
macrophages, with formation of lymphoid follicles having
germinal centres.

2. There is decreased number of thyroid follicles which are

generally atrophic and are often devoid of colloid.

3. The follicular epithelial cells are transformed into their

degenerated state termed Hurthle cells (also called
Askanazy cells, or oxyphil cells, or oncocytes). These cells
have abundant oxyphilic or eosinophilic and granular
cytoplasm due to large number of mitochondria and
contain large bizarre nuclei.

4. There is slight fibrous thickening of the septa separating

the thyroid lobules. The less common fibrosing variant of
Hashimoto’s thyroiditis shows considerable fibrous
replacement of thyroid parenchyma and a less prominent
lymphoid infiltrate.

CLINICAL FEATURES. The presenting feature of Hashimoto’s thyroiditis is a painless, firm and moderate goitrous
enlargement of the thyroid gland, usually associated with hypothyroidism, in an elderly woman. At this stage, serum T3
and T4 levels are decreased and RAIU is also reduced. A few cases, however, develop hyperthyroidism, termed
hashitoxicosis, further substantiating the similarities in the autoimmune phenomena between Hashimoto’s thyroiditis and
Graves’ thyrotoxicosis. There is no increased risk of developing thyroid carcinoma in Hashimoto’s thyroiditis but there is
increased frequency of malignant lymphoma in these cases.

95. Carcinoamele tiroidiene

Pentru lb romana vezi carte poagina 444-445

Papillary Thyroid Carcinoma

Papillary carcinoma is the most common type of thyroid carcinoma, comprising 75-85% of cases. It can occur at all
ages including children and young adults but the incidence is higher with advancing age. The tumour is found about three times
more frequently in females than in males. Papillary carcinoma is typically a slow-growing malignant tumour, most often
presenting as an asymptomatic solitary nodule. Involvement of the regional lymph nodes is common but distant metastases to
organs are rare. Some cases first come to attention by spread to regional lymph nodes and cause cervical lymphadenopathy.
‘Lateral aberrant thyroid’ is the term used for occurrence of thyroid tissue in the lateral cervical lymph node, which in most
patients represents a well-differentiated metastasis of an occult papillary carcinoma of the thyroid.

MORPHOLOGIC FEATURES.

Grossly, papillary carcinoma may range from microscopic foci to nodules upto 10 cm in diameter and is generally
poorly delineated. Cut surface of the tumour is greyish-white, hard and scar-like (Fig. 27.16). Sometimes the tumour is
transformed into a cyst, into which numerous papillae project and is termed papillary cystadenocarcinoma.
 Histologically, the following features are present (Fig. 27.17):

1. Papillary pattern. Papillae composed

of fibrovascular stalk and covered by single layer
of tumour cells is the predominant feature.
Papillae are often accompanied by follicles.

2. Tumour cells. The tumour cells have

characteristic nuclear features due to dispersed
nuclear chromatin imparting it ground glass or
optically clear appearance and clear or oxyphilic
cytoplasm. These tumour cells, besides covering
the papillae, may form follicles and solid sheets.

3. Invasion. The tumour cells invade the

capsule and intrathyroid lymphatics but invasion
of blood vessels is rare.

4. Psammoma bodies. Half of papillary

carcinomas show typical small, concentric,
calcified spherules called psammoma bodies in
the stroma.

The prognosis of papillary carcinoma is

good: 10-year survival rate is 80-95%,
irrespective of whether the tumour is pure
papillary or mixed papillary-follicular carcinoma.

Follicular Thyroid

Carcinoma Follicular carcinoma is the other common type of thyroid cancer, next only to papillary carcinoma and
comprises about 10-20% of all thyroid carcinomas. It is more common in middle and old age and has preponderance in females
(female-male ratio 2.5:1). In contrast to papillary carcinoma, follicular carcinoma has a positive correlation with endemic goitre
but the role of external radiation in its etiology is unclear. Follicular carcinoma presents clinically either as a solitary nodule or as
an irregular, firm and nodular thyroid enlargement. The tumour is slow-growing but more rapid than the papillary carcinoma. In
contrast to papillary carcinoma, regional lymph node metastases are rare but distant metastases by haematogenous route are
common, especially to the lungs and bones.

MORPHOLOGIC FEATURES.

Grossly, follicular carcinoma may be either in the form of a solitary adenomalike circumscribed nodule or as an
obvious cancerous irregular thyroid enlargement. The cut surface of the tumour is grey-white with areas of haemorrhages,
necrosis and cyst formation and may extend to involve adjacent structures.
 Microscopically, the features are as under (Fig. 27.18):

1. Follicular pattern: Follicular carcinoma,

like follicular adenoma, is composed of follicles of
various sizes and may show trabecular or solid
pattern. The tumour cells have hyperchromatic
nuclei and the cytoplasm resembles that of normal
follicular cells. However, variants like clear cell type
and Hurthle cell (oxyphilic) type of follicular
carcinoma may occur. The tumour differs from
papillary carcinoma in lacking: papillae, ground-
glass nuclei of tumour cells and psammoma bodies.

2. Vascular invasion and direct extension:

Vascular invasion and direct extension to involve
the adjacent structures (e.g. into the capsule) are
significant features but lymphatic invasion is rare.

The prognosis of follicular carcinoma is

between that of papillary and undifferentiated
carcinoma: 10-year survival rate is 50-70%.

Medullary Thyroid Carcinoma

Medullary carcinoma is a less frequent type derived from parafollicular or C-cells present in the thyroid and comprises
about 5% of thyroid carcinomas. It is equally common in men and women. There are 3 distinctive features which distinguish
medullary carcinoma from the other thyroid carcinomas. These are: its familial occurrence, secretion of calcitonin and other
peptides, and amyloid stroma.

1. Familial occurrence. Most cases of medullary carcinoma occur sporadically, but about 10% have a genetic
background with point mutation in RET-protooncogene located on chromosome 10q. The familial form of medullary carcinoma
has association with pheochromocytoma and parathyroid adenoma (multiple endocrine neoplasia, MEN II A), or with
pheochromocytoma and multiple mucosal neuromas (MEN II B). The sporadic cases occur in the middle and old age (5th-6th
decades) and are generally unilateral, while the familial cases are found at younger age (2nd-3rd decades) and are usually
bilateral and multicentric.

2. Secretion of calcitonin and other peptides. Like normal C-cells, tumour cells of medullary carcinoma secrete
calcitonin, the hypocalcaemic hormone. In addition, the tumour may also elaborate prostaglandins, histaminase, somatostatin,
vasoactive intestinal peptide (VIP) and ACTH. These hormone elaborations are responsible for a number of clinical syndromes
such as carcinoid syndrome, Cushing’s syndrome and diarrhoea.

3. Amyloid stroma. Most medullary carcinomas have amyloid deposits in the stroma which stains positively with usual
amyloid stains such as Congo red. The amyloid deposits are believed to represent stored calcitonin derived from neoplastic C-
cells in the form of prohormone. Most cases of medullary carcinoma present as solitary thyroid nodule but sometimes an
enlarged cervical lymph node may be the first manifestation.

MORPHOLOGIC FEATURES
 . Grossly, the tumour may either appear as a unilateral solitary nodule (sporadic form), or have bilateral and
multicentric involvement (familial form). However, sporadic neoplasms also eventually spread to the contralateral lobe. Cut
surface of tumour in both forms shows well-defined tumour areas which are firm to hard, grey-white to yellow-brown with areas
of haemorrhages and necrosis.

Histologically, the features are as

under (Fig. 27.19):

1. Tumour cells: Like other

neuroendocrine tumours (e.g. carcinoid, islet
cell tumour, paraganglioma etc), medullary
carcinoma of the thyroid too has a well-defined
organoid pattern, forming nests of tumour cells
separated by fibrovascular septa. Sometimes,
the tumour cells may be arranged in sheets,
ribbons pseudopapillae or small follicles. The
tumour cells are uniform and have the
structural and functional characteristics of C-
cells. Less often, the neoplastic cells are spindle-
shaped.

2. Amyloid stroma: The tumour cells

are separated by amyloid stroma derived from
altered calcitonin which can be demonstrated
by immunostain for calcitonin. The staining
properties of amyloid are similar to that seen in
systemic amyloidosis and may have areas of
irregular calcification but without regular
laminations seen in psammoma bodies.

3. C-cell hyperplasia: Familial cases generally have C-cell hyperplasia as a precursor lesion but not in sporadic cases.

Most medullary carcinomas are slow-growing. Regional lymph node metastases may occur but distant organ
metastases are infrequent. The prognosis is better in familial form than in the sporadic form: overall 10-year survival rate is 60-
70%.

Anaplastic Carcinoma Undifferentiated or anaplastic carcinoma of the thyroid comprises less than 5% of all thyroid
cancers and is one of the most malignant tumour in humans. The tumour is predominantly found in old age (7th-8th decades)
and is slightly more common in females than in males (female-male ratio 1.5:1). The tumour is widely aggressive and rapidly
growing. The features at presentation are usually those of extensive invasion of adjacent soft tissue, trachea and oesophagus.
These features include: dyspnoea, dysphagia and hoarseness, in association with rapidly-growing tumour in the neck. The
tumour metastasises both to regional lymph nodes and to distant organs such as the lungs.

MORPHOLOGIC FEATURES.

Grossly, the tumour is generally large and irregular, often invading the adjacent strap muscles of the neck and other
structures in the vicinity of the thyroid. Cut surface of the tumour is white and firm with areas of necrosis and haemorrhages.

Histologically, the tumour is too poorly-differentiated to be placed in any other histologic type of thyroid cancer, but
usually shows a component of either papillary or follicular carcinoma in better differentiated areas. The tumour is generally
composed of 3 types of cells occurring in varying proportions: small cells, spindle cells and giant cells. When one of these cell
types is predominant, the histologic variant of undifferentiated carcinoma is named accordingly. Thus, there are 3 histologic
variants:

1. Small cell carcinoma: This type of tumour is composed of closely packed small cells having hyperchromatic nuclei
and numerous mitoses. This variant closely resembles malignant lymphoma.
 2. Spindle cell carcinoma: These tumours are composed of spindle cells resembling sarcoma. Some tumours may
contain obvious sarcomatous component such as areas of osteosarcoma, chondrosarcoma or rhabdomyosarcoma.

3. Giant cell carcinoma: This type is composed of highly anaplastic giant cells showing numerous atypical mitoses,
bizarre and lobed nuclei and some assuming spindle shapes.

The prognosis is poor: 5-year survival rate is less than 10% and median survival after the diagnosis is about 2 months.

96. Adenoamele hipofizare

Vezi care pagina 441

Pituitary Adenomas

Adenomas are the most common pituitary tumours. They are conventionally classified according to their H & E
staining characteristics of granules into acidophil, basophil and chromophobe adenomas. However, this morphologic
classification is considered quite inadequate because of the significant functional characteristics of each type of adenoma
including the chromophobe adenoma, which on H & E staining does not show visible granules. As a result of advances in the
ultrastructural and immunocytochemical studies, a functional classification of pituitary adenoma has emerged. Table 27.1
presents a classification of pituitary adenomas based on functional features as correlated with morphologic features of older
classification. The syndromes produced by the tumours have been described already.

MORPHOLOGIC FEATURES.

Grossly, pituitary adenomas range in size from small foci of less than 10 mm in size (termed microadenoma) to large
adenomas several centimeters in diameter. They are spherical, soft and encapsulated.

Histologically, by light microscopy of H & E stained sections, an adenoma is composed predominantly of one of the
normal cell types of the anterior pituitary i.e. acidophil, basophil or chromophobe cells. These cells may have following 3 types of
patterns:

1. Diffuse pattern is composed of polygonal cells arranged in sheets with scanty stroma.

2. Sinusoidal pattern consists of columnar or fusiform cells with fibrovascular stroma around which the tumour cells
are arranged (Fig. 27.2).

3. Papillary pattern is composed of columnar or fusiform cells arranged about fibrovascular papillae.

Functionally, most common pituitary adenomas, in decreasing order of frequency, are: lactotroph (PRL-secreting)
adenoma, somatotroph (GH-secreting) adenoma and corticotroph (ACTH-secreting) adenoma. Infrequently, mixed
somatotroph-lactotroph (GH-PRL-secreting) adenoma, gonadotroph (FSH-LH-secreting) adenomas and null-cell
(endocrinologically inactive) adenomas or oncocytoma are found. Pleurihormonal-pituitary adenoma, on the other hand, may
have multiple hormone elaborations. Functional classification of pituitary adenoma can be done by carrying out specific
immunostains against the hormone products. Pituitary adenoma may also occur as a part of multiple endocrine neoplasia type I
(MEN-I) in which adenomas of pancreatic islets, parathyroids and the pituitary are found (page 829). Clinically, the patients are
characterised by combination of features of Zollinger-Ellison’s syndrome, hyperparathyroidism and hyperpituitarism.