papillary carcinoma

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PAPILLARY CARCINOMA THYROID PRESENTING AS LYMPH NODE SWELLINGS ALONE – A case report

Abdul Razik T

50TH Batch MBBS, Calicut medical college

Abstract

Papillary carcinoma is the most common malignancy of the thyroid gland.

This tumor characterized histologically by the typical nuclear features, is a fairly

indolent lesion. Though the common presentation is in the form of neck swellings;

either thyroid or lymph nodes or both, symptoms due to invasion to adjacent

structures or rarely due to blood borne metastases are also possible. However, this

tumour has a good prognosis. A large number of variants with histological, genetic,

molecular & clinical differences demand precise diagnosis & really pose a big

challenge before the pathologist & surgeon. Here is the report of a patient who

presented with multiple lymph node swellings alone

Keywords: Thyroid, Papillary, Orphan Annie, RET, BRAF

Introduction

Papillary carcinoma is the most common thyroid malignancy (75-80 % of

cases) 1 . Females are usually more affected. It can present at any age , but mostly in

the 3rd & 4th decade. 90% of thyroid malignancies in children are papillary

carcinomas. In 5-10 % of cases, there is history of radiation exposure to neck (82%

of all thyroid malignancies & 34% of all benign thyroid lesions post exposure)2 . A

thrice high incidence is noted with hashimoto’s thyroiditis3.

Almost all patients have clinically evident disease in the neck when first seen.

The disease is localized to the thyroid in 67 %, to both thyroid & lymph nodes in 13

% & lymph nodes alone in 20 %. The common sites for metastases are bone, brain,

lungs & soft tissue. Though local invasion to larynx, trachea, pharynx & oesophagus

are common, metastases to these sites are extremely rare4.

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Case report

A 38 year old male patient, smoker & alcoholic with no significant past or

family history, presented with history of severe loss of weigh, anorexia &

hoarseness of voice & progressively enlarging neck swellings for 6 months. There

was no history of dyspnoea, dysphagia or syncopial attacks. The patient had no

complaints of cold, facial edema, changing skin colour, chest pain, constipation.

Neither war there any complaints of heat intolerance, diarrhea, tremors, excessive

sweating, palpitations, anxiety or increased appetite.

On examination, multiple firm, spherical to oval masses of varying sizes were

present bilaterally, the largest being 4 by 3 centimeters in size, mobile & non tender.

No clubbing, pedal edema or pallor was noted.

Laboratory investigations revealed Hb 17.4 g/dl, total WBC count

17400/mm3, severe neutrophilia (96%), random blood sugar 106 mg/dl, ESR 35,

blood urea 39 mg/dl, s. creatinine 1.1 mg/dl, blood Na+ 125.6 meqt/l, K+ 4.68

meqt/l. X ray revealed hyperdense masses on either sides of trachea.

Two days later the patient had sudden onset of dyspnoea with low B.P and

tracheostomy had to be performed.

FNAC revealed moderately differentiated papillary carcinoma metastases. A

CT scan was advised, which revealed multiple lymph nodes bilaterally, that

compressed the trachea. Bronchoscopy revealed narrowed glottic space due to

compression by the tumour. The subglottic space & trachea were spared.

The patient underwent total thyroidectomy with lymph node dissection 2

weeks after the episode.

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Case Discussion

Grossly papillary carcinoma of thyroid can be microscopic to huge, solid,

white & firm. A few are encapsulated. Some show papillary formations, while some

show cystic changes.

Microscopically, numerous true but complex branching papillae are seen.

These contain a central fibro vascular core lined by a single or stratified cuboid cell

layer. The stroma is edematous or hyaline & contains scant lymphocytes, foamy

macrophages, hemosiderin, & adipose tissue. Follicular structures may also be

present, but even then they behave as papillary carcinoma.

But the characteristic pathognomic features of papillary carcinoma, even

when the papillae are absent are the nuclear features.

1. Ground glass (optically clear) or orphan Annie nucleus, which is large & of

overlapping quality. The nucleolus is inconspicuous & pushed against the

nuclear membrane, which appears thickened.

2. Nuclear pseudo inclusions, appearing as sharply outlined acidophilic

formations that represent invaginations of cytoplasm.

3. Nuclear grooves- they also are cytoplasmic infoldings and are arranged

along the longest axis of the oval/spindle nuclei.

4. Nuclear microfilaments.

Mitotic figures are very scant or absent. About half of cases show extensive

fibrosis ranging from sclerohyaline to highly cellular.

Another characteristic feature is psammoma body, seen in half of cases. They

may be located in the papillary stalk, in fibrous stroma or between tumor cells in

solid foci. They represent a very important clue to the diagnosis so much that, if they

are present in what is otherwise normal thyroid or lymph nodes in neck, a high

suspicion of papillary carcinoma must be kept. Psammoma bodies are concentric,

laminated basophilic structures that stain for calcium, mucin & iron. They arise from

necrosis of tumour cells. Osteopontin, produced by macrophages is responsible for

their development. When numerous, they can be detected even in X rays. They must

be differentiated from other calcification forms and from the inspissated secretions

in hurthle cell tumour.

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Other expected changes include solid/ trabecular pattern of growth (20%),

squamous metaplasia (20%), spindle cell component (metaplastic change), and

lymphocytic infiltration (25%).

Molecular genetic features involve molecular rearrangements of the tyrosine

kinase receptors RET or NTRK1 (neurotropic tyrosine kinase receptor) that are

normally not expressed in thyroid follicular cells. Para centric inversion or t(10; 17)

for RET (located on chromosome 10 q.11) and NTKRI (located on ch. 1q.21) ,

produce fusion products ret/PTC (ret/ papillary thyroid carcinoma)that result in

constitutive activation of tyrosine kinase of RET/NTRK1.The rare coincidence of

PTC with medullary carcinoma suggests that point mutations of RET could also

evoke PTC.5 About half of PTC harbors activated BRAF oncogene.

Several morphologic variants of PTC have been reported:

1. Papillary microcarcinoma – It includes all PTCs less than 1cm in diameter. This

variant, usually presenting with a stellate configuration, is a common incidental

finding in FNACs or thyroids removed for other studies especially in males.

Though cervical metastases do occur, distant mets are extremely rare & the

prognosis is generally excellent.

2. Encapsulated variant – This variant constituting 10% of PTCs is totally

surrounded by a capsule. It ha excellent prognosis. It should be diffentiated from

an adenoma or a hyperplastic nodule. In contrast to PTC, these are hot on thyroid

scan, microscopically contain pale, vacuolated colloid & papillary areas are

limited to the area facing the cystic cavity.

3. Follicular variant – It is composed of follicles that show nuclear features of PTC. It

has 2 further variants:

a. Solid variant - Proliferation predominates over secretion producing solid

sheets

b. Macrofollicular variant - Here secretion predominates resulting in large

dilated follicles. It should be differentiated from follicular carcinoma &

hyperplastic nodule.

Follicular variants behave biologically like PTCs & have a better prognosis.

4. Oncocytic (oxyphilic) variant – It has abundant cytoplasm of granular oxyphilic

quality, but nuclear features of PTC. It shows papillary/ follicular pattern & can

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be encapsulated/ invasive. It often has a large lymphocytic infiltrate & could be

confused for warthins tumour of salivary glands. The latter, which has an

excellent prognosis, differs in expression of Rb protein & E2F-1.

5. Diffuse sclerosing variant – It is characterized by diffuse involvement of one or

both lobes, dense sclerosis, abundant psammoma bodies, squamous metaplasia,

heavy lymphocytic infiltration & extensive lymph vessel permeation. It may be

misdiagnosed as hashimoto’s thyroiditis, but shows a higher incidence of distant

metastases.

6. Tall cell & columnar cell variant – The former shows papillae lined by a single

layer of tall cells (height twice width) having abundant acidophilic cytoplasm, in

atleast half of the tumor. It lacks the nuclear features of PTC & is more

aggressive. The latter shows prominent stratification & clear cytoplasm with sub

nuclear vacuolization. Both usually occur in the elderly.

7. Cribriform – morular variant

8. PTC with extensive nodular fasciitis like stroma – Here the extensive stromal

reaction obscures the neoplastic epithelial component. It can be misinterpreted

as nodular fasciitis, fibromatosis or fibradenoma.

9. Hyalinising trabecular tumors – It shows organoid growth pattern, with nests &

trabeculae of elongated tumor cells within a fibro vascular stroma6. Both intra &

extra cellular hyalinization are prominent & confer a pink hue to the tumor. The

nuclear features, psammoma bodies & RET/PTC translocation classifies it as a

variant of PTC. It shouldn’t be confused with an extradural paraganglioma.

DIAGNOSIS & TREATMENT

Most PTCs present as asymptomatic thyroid nodules, but the first

manifestations may be an enlarged cervical lymph node. But in many cases, they

could persist for long without producing any swelling. The importance is so much

that, by simple screening the risk groups a 37% rise7 in detection could be made.

The lesion moves freely during swallowing & is indistinguishable from a benign

nodule. Hoarseness, dysphasia, cough or dyspnoea suggest local invasion. Though

blood born mets are extremely uncommon, a few can be present at diagnosis,

most commonly in the lung.

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A variety of diagnostic tests differentiate PTC from benign nodules, including

radionuclide scanning & FNA. Most lesions are cold masses on scintiscans.

The mainstay of treatment is surgery. Lobectomy along with isthmectomy is

done in usual cases8. Total thyroidectomy is reserved for the high risk cases. If

nodal involvement is found, modified lymph node dissection is performed by

extension of the incision. Radical neck dissections have been considered

unnecessary. Suppression of thyroid function by exogenous administration of

thyroid hormone & post operative radioactive iodine are also sometimes used9.

External radiation is of limited use & limited for incompletely excised tumors.

PROGNOSIS

PTCs have excellent prognosis, with 10 year survival rates exceeding 95%. 5-

20% have local recurrences & 10-15% have distant metastases. The prognosis

depends on several factors including age (with excellent prognosis below 40

years), sex (females with better prognosis), extra thyroidal extension,

microscopic variants, tumor size, presence of capsule, multicentricity, distant

metastases, poorly differentiated squamous or anasplastic foci, BRAF mutation10,

EMA & Leu-M1 positivity, DNA ploidy (aneuploidy correlating with

aggressiveness), RB protein expression level & presence of circulating tumor

cells.

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