Cytohistologic Characterization of Papillary Carcinoma of Thyroid a Prospective Study

8/3/2019 Cytohistologic Characterization of Papillary Carcinoma of Thyroid a Prospective Study

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Shashi A et al., IJSID 2011, 1 (3), 344-352

International Journal of Science Innovations and Discoveries, Volume 1, Issue 3, November-December 2011

344

CYTOHISTOLOGIC CHARACTERIZATION OF PAPILLARY CARCINOMA OF THYROID: A PROSPECTIVE STUDY

Shashi A*, Sharma N

*Department of Zoology, Punjabi University, Patiala- 147 002, India

INTRODUCTION

INTRODUCTION

ISSN:2249-5347IJSID

International Journal of Science Innovations and Discoveries An International peerReview Journal for Science

Research Article Available online through www.ijsidonline.info

Received: 13.09.2011

Modified: 16.10.2011

Published: 29.12.2011

Keywords:

Cytopathology;

FNAC;

Papillary carcinoma;

Thyroid

*Corresponding Author

Name:

Dr. Shashi AgarwalPlace:

Patiala, India

E-mail:

shashiuniindia@

yahoo.com

ABSTRACT

The aim of the study was to delineate the incidence of papillary thyroid

carcinoma in Himachal Pradesh, India and to put a cytohistological correlation inidentifying features of this carcinoma. Twenty three patients (17 females, 6 males)

suffering from papillary thyroid carcinoma in the age group of 40-60 years with

average age of 51.2 9.5 years were the subjects of present study . Thyroid stimulating

hormone (TSH), triiodothyronin (T3), and thyroxine (T4) of the patients were analyzed

by enzyme immunoassay methods. The fine needle aspiration cytology (FNAC) slides

were stained with May-Grunwald Giemsa and Papanicolau. The histological sections

were stained with hematoxylin and eosin. The cytopathological results were correlated

with clinical features, thyroid function and histopathological examination. The thyroid

hormonal status of papillary thyroid carcinoma patients revealed that 8 patients(34.7%) were hyperthyroid and 15 (65.3%) euthyroid. The hormonal profile of

hyperthyroid patients showed declined level of thyrotropin (2.10 ng/ml ) and thyroxine (T4>12 g/dl) levels. The

papillary carcinoma was characterized by presence of long and slender papillae having a

thin fibrovascular core, which was surrounded by monolayer of tumor cells. The large

tumour cells were cuboidal to columner in contour, have basophilic cytoplasm, and pale

nuclei with irregular nuclear outline. A monolayer sheet of pleomorphic hypertrophied

and atrophied tumour cells was observed in a fine needle aspiration cytology smear of

female patient aged fifty two years. Few cells exhibited elongated configuration withcytoplasmic tails. Some isolated neoplastic follicular cells showed longitudinal nuclear

grooves and folds, which appeared as a superficial notch, giving the nucleus a lobed

appearance, however these cells were not visible with in papillary structures. Some

follicular cells revealed presence of intranuclear inclusions. Psammoma bodies, the

small concentric calcified spherules, located within the papillary formation of follicles,

were visible. The nuclear features of pleomorphism, nuclear atypia, longitudinal

grooves, intranuclear inclusions and optically clear nucleus are reminiscent of papillary

carcinoma and are seen in both cytological as well as histological preparations.


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INTRODUCTION

The incidence of thyroid cancer has increased markedly over the past few decades in several countries,

reaching up to 3% in newly diagnosed malignancy [1]. Thyroid enlargement is a common occurrence in most

regions of the world. India has the worlds biggest goiter belt in the sub-himalayan region [2]. Thyroid nodules are

common, malignant lesions derived from thyroid epithelial cells are relatively rare. Papillary thyroid carcinoma is a

disease with good prognosis and few patients at the risk of death. It is a tumor with characteristic cytologic

features, shows a predominance of papillary structure but the papillae are usually admixed with neoplastic follicles

having similar nuclear features.[3] It consist primarily of enlarged, often overlapping nuclei with fine, dusty or

powdery chromatin; intranuclear cytoplasmic inclusions, and linear chromatin ridges with irregular nuclear

outlines.[4] Factors controlling the prognosis of this tumor are age, sex, extrathyroidal invasions, distant

metastasis, and size of primary tumor.[5] Thyroid carcinoma presenting with hyperthyroidism is rare.[6] The

present study was designed to study the incidence of papillary thyroid carcinoma in Himachal Pradesh, India and

to put a cytohistological correlation in identifying features of this carcinoma.

MATERIALS AND METHODS

Twenty three patients (17 females, 6 males) with papillary thyroid carcinoma (PTC) in the age group of 40-

60 years with average age of 51.2 9.5 years were included in the study. A physical examination was carried out

to note the mobility of the thyroid during swallowing, prior to aspiration. The patients were underwent complete

history taking, physical examination and hormonal assay (TSH, T3, T4). The thyropropin, triiodothyronine and

thyroxine levels of the patients were assayed by enzyme immunoassay method on ELISA Reader.

FNAC smears were air dried, fixed in methanol and stained with May- Grunwald Giemsa and Papanicolau

stains. Paraffin- embedded tissues of surgically-resected specimens were stained with hematoxylin and eosin. The

slides were examined under microscope and subsequently microphotographed. The cytopathological results were

correlated with clinical features, thyroid function and histopathological examination.

Permission to conduct the study was obtained from the Institutional Human Ethics Committee of the

Punjabi University, Patiala and Govt. Rajindra Prasad Medical College and hospital, Kangra.

RESULTS

The age of the patients ranged from 40 to 60 years with a mean age of 51.39.5 years and the female maleratio was 3.6:1. The major presenting symptom in all the patients was nodular swelling in the thyroid. Patients

gave a history of swelling being present for more than one year in 12 (52.18%) cases, between three months and

one year in 6 (26.09) cases and less than three months in 5 (21.73%) cases. Family history of thyroid disease was

negative in all the cases. Thyroid functional status of these patients revealed that 8 (34.7%) patients were

hyperthyroid, whereas 15 (65.3%) were euthyroid. The hyperthyroidism occurred in 8 patients with solitary

nodules of papillary thyroid carcinoma. The hormonal profile of hyperthyroid patients showed declined level of

thyrotropin (2.10 ng/ml ) and thyroxine (T4>12 g/dl) levels


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The FNAC smear of all the patients showed papillery arrangement of follicles with abundant cells and

almost no colloid present (Fig. 1). Histological examination revealed that papillae were long and slender with thin

fibrovascular cores, which were covered by monolayer of tumor cells. The cells were cuboidal to columner in

contour, charecterized by basophilic cytoplasm, and pale nuclei with irregular nuclear outline. Infiltration of

thyroid follicular cells by lymphocytes was prominent. The papillary structures have different morphologies and

dimensions (Fig. 2).


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A case of tall cell variant was observed in 23 cases of papillary thyroid carcinoma. The patient was female

of 52 years. A monolayered. Sheet of pleomorphic hypertrophied and atrophied tumour cells was observed. Few

cells exhibit elongated tadpole like configuration with cytoplasmic tails. A neoplastic cytoplasmic vacuole

formation was also noticed (Fig.3).


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Grooved nuclei were identified in papanicolaou- stained cytologic material from 17 cases of papillary

thyroid carcinoma. The groove consisted of a linear infolding of the nuclear envelope along the longitudinal axis of

the usually oval nucleus. Occesionally, there were multiple deep grooves or superficial notches resulting in a

lobulated appearance (Fig. 4). Nuclear grooves were also easily identified in hematoxylin-eosin stained histologic

sections. These cells were not visible in papillary structures (Fig. 5).


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The microscopic examination fine needle aspiration smear of papillary thyroid carcinoma of a male patient

aged 49 years revealed presence of microfollicular cells arranged in aciner pattern . Few follicular cells exhibited

intranuclear inclusions, the aggregates of stainable substances. (Fig. 6).

Psammoma bodies, large hyaline globules with concentric laminations, surrounded by tumor cells were present in

histologic sections of five papillary thyroid carcinoma patients. Psammoma bodies originate from thrombosis of

the fibrovascular core and subsequent infarction of the papillae in a tumor or from necrosis of metastatic tumor

cell nest in lymphatics. (Fig. 7).


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The histological sections of a male papillary thyroid carcinoma patient aged 56 years showed cluster of

cells with vacuolated cytoplasm and eccentrically placed nuclei exhibiting nuclear atypia and pleomorphism. Some

cells have optically clear orphan eye nuclei (Fig. 8).

DISCUSSION

The present study was conducted on 146 patients with thyroid swelling and papillary thyroid carcinoma

was seen in 23 (15.75%) cases in our study. Tsegaye and Ergate[7] reported 6.2% prevalence of thyroid carcinoma.

Our results showed female propandrance (73.95%) over males in papillary carcinoma, with mostly in the age

group of 40-60 years (mean age 51.39.5). Our results are in accordance with the findings of Handa et al[8] which

reported elderly female preponderance in thyroid carcinoma cases.

The risk of thyroid malignancy in a clinically hyperthyroid patient was considered quite low. But this

interesting coexistence hyperthyroidism and thyroid malignancy is being increasingly recognized. During present

investigation, 34.7% of papillary thyroid carcinoma patients were found to be hyperthyroid. Gulceliket al[9] found

12 cases of hyperthyroidism among 422 patients of thyroid carcinoma. Nine patients with papillary carcinoma, 1

patient with follicular carcinoma and 2 patients with follicular variant of papillary carcinoma presented with

hyperthyroidism.

In present study, the smears of papillary carcinoma were characterized by good cellularity. The cytological

study revealed presence of papillary clusters of cells with pale nuclei, intranuclear cytoplasmic invaginations,

irregular nuclear outlines with almost no colloid present. Papillary clusters were seen in all cases. The

cytopathology of papillary carcinoma has been reported by many workers[10] and the important cytomorphologic

fatures have been papillary clusters, monolayers, multilayered fragments and dense cytoplasm. Nguyen[11]

confirmed that papillary oncocytic carcinoma of the thyroid revealed presence of large and small papillary tumor

tissue fragments consisting of fibrovascular cores covered with polygonal cells showing abundant and granular

cytoplasm and small oval nuclei.

A set of distinctive nuclear features were observed during present investigation. The large tumor cells

having polygonal contour with irregular and enlarged nuclei were visible. Cluster of cells exhibiting nuclear atypia

and pleomorphism was visible in histologic view. Some neoplastic follicular cells showed longitudinal nuclear

grooves and folds with irregular nuclear outline. The classic cytologic criteria for papillary carcinoma of thyroidhave been studied and delineated by numerous authors. [12-14] Nuclear atypia is an important diagnostic feature of

papillary carcinoma. The nuclei are moderately large and vary in size and shape, with irregular thickened

membranes. [15] They often exhibit a very specific feature, a nuclear crease, which appear in light microscopy as a

vertical linear thickening of the chromatin and stained deeply with hematoxylin and eosin. [16] Khurana et al [17]

reported a spectrum of cytologic findings that include papillary clusters, nuclear atypia and pleomorphism,

presence of nuclear grooves, multinucleated giant cells and cells with vacuolated cytoplasm. Although the nuclear

feature are important for diagnosis of papillary carcinoma when seen, but previously they were also cited in other


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thyroid disorders. [18] Few follicular cells revealed presence of intranuclear inclusions in our study. These

intranuclear vacuoles were first noted by Soderstrome[19] to be an important criterion of malignancy in FNAC

smears of thyroid nodules. Subsequently it has been confirmed that these pseudonuclear inclusions are frequently

found in papillary and mixed papillary- follicular carcinoma. [20]

Psammoma bodies, which are concentrically laminated bodies formed of calcium apatite, were found in

histologic sections of 21.73% cases during present investigation. Psammoma bodies have been considered to be a

hallmark of papillary carcinoma by many pathologists. [21] Compared with histology, Psammoma bodies are much

less frequently found in FNA smears. Psammoma bodies observed in FNA smears of 11.1 % of papillary thyroid

carcinoma. [22] In the present study the frequency was almost nil. They occur predominantly in the classic form of

papillary carcinoma but also have been reported in other types of thyroid carcinoma. [23]

CONCLUSION

The nuclear features of pleomorphism, nuclear atypia, longitudinal grooves, intranuclear inclusions and

optically clear nucleus are reminiscent of papillary carcinoma and are seen in both cytological as well as

histological preparations.

ACKNOWLEDGEMENT

We thank the Pathology Department of Rajendra Prasad Medical College, Kangra, H.P., India for providing

cytologic and histologic follow up and University Grant Commission, Govt. of India for providing financial

assistance.

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Cytohistologic Characterization of Papillary Carcinoma of Thyroid a Prospective Study