Title: Latent Primary Papillary micro tumor in Thyroglossal duct cyst wall - A rare case report with review of literature.

Abstract

Thyroglossal duct cyst (TDC) is a common congenital midline neck mass. Generally TDCs are

benign and incidence of malignancy in TDC is less than 1%. Majority of this tumors arise from

thyroid remnants in the wall of the cyst and the common histologic type is papillary

carcinoma.We here report a 25 year old man with a diagnosis of TDC based on clinical and

radiological findings. Histopathological examination confirmed TDC with an incidental

intracystic Latent papillary micro tumor. The papillary microtumor was confirmed with Immuno

histochemical study using cytokeratin 19 (CK 19) marker. The present case report emphasizes

the histopathological features and prognostic significance of papillary microtumor in TDC with

review of literature.

Keywords --- Thyroglossal duct cyst, papillary microtumor, cytokeratin.

Introduction

Thyroglossal duct cyst (TDC) is a common developmental cyst in the midline of neck. It results

from incomplete atrophy of thyroglossal tract and focal cystic dilatation by accumulation of

secretions from lining epithelial cells. It often manifests during childhood before 20 years of age

but may also be seen in adult population with an estimated prevalence rate of 7 % 1. Clinically all

TDCs are benign. Malignancy might have arisen from the thyroid remnants in the cyst wall or

from the lining epithelium 2. The percentage of different types of neoplasia in reported cases of

TDCs are Classical Papillary carcinoma - 81.7% , Mixed papillary & follicular carcinoma -

6.9%, Squamous cell carcinoma-5.2% , Follicular and Adenocarcinoma - 1.7% each , and

Anaplastic carcinoma - 0.9% 3. There are no previous documented reports of latent papillary

microtumor in TDC. Hence, this could be probably the first case report of this rare entity. Also,

the histopathological characteristics with prognostic significance of the microtumor is discussed.

Case Details

25 year old man presented with a swelling in the midline of neck for three months duration.

There was no other symptoms like pain, tenderness, difficulty in swallowing, voice change or

respiratory difficulty. There was no history of irradiation. Examination revealed a 5x4 cm cystic

swelling in front of the neck extending below hyoid bone. The swelling moved with deglutition

and also with protrusion of tongue. There was no visible thyroid swelling clinically nor

lymphadenopathy. Routine hematological and biochemical investigations were in the normal

reference range. Clinical findings and radiological diagnosis suggested Thyroglossal Duct cyst

and hence, Sistrunks procedure was performed. During the surgical exploration, cyst containing

yellowish hemorrhagic fluid was accidentally punctured. The TDC of size 8x1x0.5cm was sent

for histopathological examination. Macroscopy revealed a tract with cyst wall having smooth

inner wall. There was no significant solid tumor area. Multiple tissue bits from the entire TDC

were processed for microscopy. Microscopic examination showed features of thyroglossal duct

cyst. Focal areas within the cyst wall showed follicular cells arranged in microfollicles [Fig.1,

Arrow], solid pattern and tiny nests with nuclear clearing [Fig.2, Arrow head], grooving [Fig.2,

Short Arrow]and pseudoinclusions [Fig.2, Long Arrow]. Histopathological diagnosis of latent

papillary microtumor of TDC was made and confirmed with cytoplasmic positive cytokeratin-19

marker [Fig.3, Inset-Arrow].

Discussion

TDC carcinoma is rare and is seen in less than 1% of cases 4. Less than 250 cases have been

reported from different centers since 1911 5,6. Carcinoma arising from TDC has two origins.

Thyrogenic carcinoma from thyro embryonic remnants in the duct or cyst and squamous cell

carcinoma arising from metaplastic columnar cells that line the duct 7. Most of the TDC

malignancy are arising from thyroid remnants and common histologic type is papillary

carcinoma. However twin malignancies of papillary carcinoma and squamous cell carcinoma in

TDC have been reported 8. Classical papillary carcinoma usually presents in the third to fifth

decades with a female preponderance, while latent papillary micro tumor lacks the female

predominance 9. The risk factors for thyroid papillary carcinoma are irradiation and pre existing

thyroid diseases, but papillary microtumor in TDC arises denova 1. Gross morphology of typical

papillary carcinoma is whitish firm granular lesion with ill defined margins. So far reported

papillary carcinoma in TDC shows classical microscopic morphology of branching papillae with

fibro vascular core and nuclear features of papillary malignancy in the form of nuclear clearing,

grooving, crowding and pseudo inclusions. In our case, gross morphology revealed cyst wall

with inner smooth surface. There was no obvious thickening of the cyst wall and no solid mass

lesion. Microscopy showed cyst wall lined by various cells comprising of pseudo stratified

columnar, cuboidal and squamous epithelial cells at places with underlying inflamed stroma

[Fig.1, Inset-Arrow]. Focal areas identified solid, microfollicular and tiny nests of follicular

epithelial cells with nuclear crowding, clearing, grooves and nuclear pseudo inclusions. The

above classical morphology favors the histopathological diagnosis of incidental latent papillary

micro tumor of TDC. The gold standard for the diagnosis of follicular thyroid lesions particularly

papillary carcinoma is histology 10. However in order to prevent overdiagnosis,

immunohistochemistry was done. Various immunohistochemical markers are used to confirm

thyroid neoplasm like CD 56, P 63 , CK 19, Galectin-3, HBME-1,COX-2,TTF-1 and

Thyroglobulin(10,11).The sensitivity and specificity using cytokeratin-19 as a single marker is

reported as high as 92%, & 97% respectively 11 and hence, CK-19 marker was done. Normal

follicles, benign papillae of graves’ disease and nodular hyperplasia are negative for CK-19 12.

Though benign follicular lesions like follicular adenoma & carcinoma , reactive follicular cells in

thyroiditis show positive expression of CK-19 the distribution is focal and less intense(11). In

our case all neoplastic follicular cells showed strong & diffuse immuno reactivity for CK-19 and

confirms the histopathological diagnosis. Prognosis of papillary carcinoma arising in the TDC is

good and is similar to that of thyroid papillary carcinoma having cure rates in excess of 95 % 8.

But cases of invasive papillary carcinoma of TDC and with nodal metastasis have been reported

3,7. In Latent papillary micro tumor most of the cases remain dormant and do not grow to

clinically apparent disease 9. Thus, the prognosis is excellent. Treatment of papillary carcinoma

in TDC depends upon tumor size, local invasion to adjacent structures, thyroid and nodal

metastasis. Sistrunks operation followed by suppressive dose of thyroxin and regular follow up is

recommended for incidental papillary carcinoma in TDC without invasion 6. In Latent papillary

micro tumor regular follow up is sufficient if it is incidentally diagnosed after sistrunks

procedure and avoid over treatment 9.

This case is reported in view of its rarity, non aggressive behavior and to highlight the distinct

morphological features. Malignancy should be suspected and expected in all clinically benign

TDCs and whole tissues should be processed to avoid missing this rare entity. Regular follow up

alone is sufficient for this asymptomatic incidental tumor type.

Acknowledgements

The authors are grateful to the E.N.T department of MAPIMS, Melmaruvathur, Tamilnadu for

providing clinical details.

References

1. Chen-Shun Chao ,Shih-Yi Lin , Wayne Huey-Herng Sheu, William-Ho . Thyroglossal

duct cyst with papillary carcinoma. Chinese medical journal(Taiper)2002: 65:183-186.

2. A.Nadimi-Tehrani,A.R.Karimi-Yazdi and M.Kazemi. Primary papillary carcinoma in

thyroglosal duct cyst. Acta medica Iranica 2007:45(3):236-238.

3. Leila Aghaghazvini,Habib Mazaher,Hashem Sharifian, Shirin Aghaghavini and Majid

Assadi. Invasive Thyroglossal duct cyst papillary carcinoma:a case report. Journal of

medical case reports 2009,3:9308.

4. S.Smiti and Nabil Sherif Mahmood.Papillary carcinoma arising from a thyroglossal duct

cyst. Indian journal of Radiology and Imaging:2009 May;19(2):120-122.

5. S. Sinan KURKCUOGLU, Selahattin GENC, Umit TUNCEL, Funda DEMIRAG.

Papillary carcinoma on the thyroglossal cyst wall.Turk J.Med.Sci.2009;39(1)151-153.

6. Kanu Lal Saha, Pran Gopal Datta ,Utpal Kumar Datta, Ashim Kumar Biswas, Ferdousy

Begum.Primary papillary carcinomain thyroglossal cyst.Bangladesh Journal of

Otorhinolaryngology 2011;17(2):135-138.

7. Tolga Kandogan , Nazif Erkan and Enver Vardar. Papillary carcinoma arising in a

thyroglossal duct cyst with associated microcarcinoma of the thyroid and without

cervical lymphnode metastasis:a case report.Journal of Medical case reports.2008;2:42.

8. Ramachandran Vijay ,Karattuthazhath Karimbayil Rajan and Moosa Feroze. Inapparent

twin malignancy in thyroglossal cyst:Case Report. World Journal of Surgical Oncology

2003,1:15.

9. Fletcher. Diagnostic histopathology of Tumors. Third edition,Churchill livingstone

Elsvier publications 2007. Vol.2 (

10. Dina EI Demellawy ,Ahmed Nasr, and Salem Alowami. Application of CD56,P63,and

CK19 immunohistochemistry in the diagnosis of papillary carcinoma of the thyroid.

Diagn. Pathol.2008:3:5.

11. Sandra Fischer, Sylvia L. Asa. Application of immunohistochemistry to Thyroid

neoplasms.Arch Pathol Lab Med—Vol .132,March 2008.

12. Juan Rosai. Rosai and Ackermans Surgical pathology. Ninth edition ,Elsevier

publications 2004.. Vol.1 (8 ----535)

FIGURES

Fig – 1 Fig – 2

Fig – 3

Figure Legends

Figure -1

Photomicrograph showing Thyroglossal cyst wall with underlying focus of neoplastic follicles in cluster [Arrow]. (H&E x 50). Inset shows cyst wall lined by cuboidal cells [Arrow, Inset]. (H&E, x 400)

Figure-2

Photomicrograph showing follicular tumor cells with characteristic oval optically clear nucleus [Arrow-Head]. There are nuclear crowding, grooves [Short-Arrow] and occasional Pseudo inclusion [Long-Arrow]. . (H&E x 400)

Figure --3

Immunostaining for cytokeratin 19 in a follicular lesion of Thyroglossal cyst wall shows diffuse cytoplasmic reaction in tumor cells. (Cytokeratin x 100). Inset [Arrow] shows diffuse intense cytoplasmic reaction around optically clear nucleus. (Cytokeratin x 400)