FOLLICULAR ADENOMA THYROID WITH CLEAR CELL CHANGES-A RARE CASE REPORT

Dr. Parul Gupta 1 , Dr. Pankhudi Gupta 2 , Dr. Nirupma Lal 3 and *Dr. A.N. Srivastava 4 . 1. Associate Professor, Department of Pathology, Era’s Lucknow Medical College & Hospital, Lucknow, U.P. India. 2. Junior Resident, Department of Pathology, Era’s Lucknow Medical College & Hospital, Lucknow, U.P. India. 3. Professor, Department of Pathology, Era’s Lucknow Medical College & Hospital, Lucknow, U.P. India. 4. Professor & Head, Department of Pathology, Era’s Lucknow Medical College & Hospital, Lucknow, U.P. India.

Follicular lesions in thyroid nodule are common findings while investigating them by fine-needle aspiration cytology (FNAC). Histologically, these lesions may represent a cellular nodule in a goiter, a follicular adenoma, or a carcinoma. Cellular changes that occur in clear cytoplasm in thyroid lesions are caused by glycogenation, intracellular accumulation of thyroglobulin, dialatation and hypertrophy of mitochondrial cells and golgi complex hypertrophy which is due to excessive secretion of Thyroid stimulating hormone(TSH). A 28 year female, housewife, presented with a gradually increasing swelling in midline of neck since 2 years. On examination, swelling was present on anterior border of sternocledomastoid, 3x2cm in size, oval and with diffuse margins. It was non-tender, moved on deglutition, non-reducible and transillumination negative. The patient had normal thyroid functions with free T4 and TSH within normal range. No capsular or vascular invasion was seen. A diagnosis of Clear cell Follicular adenoma thyroid was made. Pure Follicular adenomas are the common lesions of thyroid and arise from follicular epithelium. They are usually single and well-encapsulated lesions. These lesions are more common in females and are mostly benign. Any thyroid lesion with clear cell features warrants further histopathological assessment as clear cell changes are not appreciated in cytological smears. Our case presents the pathology of pure clear cell Follicular adenoma which is rarely seen.

Introduction:-
Follicular lesions in thyroid nodule are common findings while investigating them by fine-needle aspiration cytology (FNAC). Histologically, these lesions may represent a cellular nodule in a goiter, a follicular adenoma, or a carcinoma. According to growth pattern, several variants exist such as follicular, trabecular, solid and also according to cell types variants are common, oxyphilic, and clear cell type. Clear cell changes in thyroid lesions can be seen in wide variety of non-neoplastic and neoplastic thyroid lesions. These include Hashimoto thyroiditis, Dyshormogenetic goitre, variants of Follicular adenoma, Follicular carcinoma, Papillary carcinoma, Clear cell variant of medullary carcinoma, Signet ring lipoblast like tumors and undifferentiated tumors. However, non thyroid lesions can also mimic clear cell changes like Parathyroid neoplasm, metastatic Renal cell carcinoma and rarely artefact of formalin fixation or paraffin embedding procedure. Therefore, a clear cell change in a thyroid lesion should always be interpreted with caution and a thyroglobulin stain is essential for diagnosis. Cellular changes that occur in a clear cytoplasm in thyroid lesions are caused by glycogenation, intracellular accumulation of thyroglobulin, dialatation and hypertrophy of mitochondrial cells and golgi complex hypertrophy which is due to excessive secretion of Thyroid stimulating hormone(TSH) 1 . Clear cell changes have been described in many reported cases of thyroid lesion but clear cell adenoma are very rare.

Case history:-
A 28 year female, housewife, presented with a gradually increasing swelling in midline of neck since 2 yrs. There is history of increased sweating, decrease in weight and heat intolerance for the last 2 months. There is no history of tremors in hand, difficulty in breathing, restlessness, easy fatiguability or any addictions. There is also no history of similar complaints in any of the family members.
On examination, swelling was present on anterior border of sternocledomastoid, 3x2cm in size, oval and with diffuse margins. It was non-tender, moved on deglutition, non-reducible and transillumination negative. The patient had normal thyroid function with free T4 and TSH within normal range. On ultrasonography, findings were suggestive of Benign thyroid nodule in left thyroid lobe with left Thyromegaly. Cytological findings were consistent with a neoplasm and Left Hemithyroidectomy was performed. Grossly, hemithyroidectomy specimen measuring 6x3x1 was received. Cut surface showed a well circumscribed tumor with a smooth, thin capsule and a soft consistency. Rest of the areas were pale brown with foci of hemorrhage. Microscopically, sections showed encapsulated tumor composed of variable sized follicles. These follicles at places were lined by cuboidal cells with lumen showing eosinophilic homogenous colloid. Few areas of these follicles showed scalloping, whereas other predominant areas showed closely packed small follicles lined by cells having round to oval nucleus and clear cytoplasm. Areas of haemorrhage and fibrosis were seen. Pericapsular area showed compressed normal thyroid tissue. No capsular or vascular invasion was seen. A diagnosis of Clear cell Follicular adenoma thyroid was made.  5 show clear cell changes due to uncontrolled fatty chain synthesis, Papillary carcinoma 6 , Undifferentiated carcinoma and Medullary carcinoma 7 . Thyroglobulin stain is usually positive in all these neoplasms except Medullary carcinoma, although sometimes in a focal and faint fashion 8 . Although clear cell change in a follicular neoplasm is not an indication of malignancy but as it occurs more frequently in carcinomas than adenomas, it should be viewed with suspicion when present. In Papillary carcinoma and undifferentiated carcinoma the clear cell cell changes are due to cytoplasmic glycogen. CT scans and MRI scans are important in these lesions as they detect spread to local, mediastinal and regional lymph nodes.But it is still to be evaluated that follicular nodules have potential to develop carcinoma or not. Signet ring cell type is a peculiar variant of thyroid tumor with clear cell changes in which signet ring cells or lipoblasts are due to formation of variously sized cytoplasmic vacuoles. Most of these lesion are adenomas but rarely carcinomas may also occur 9 . Rarely, clear cell change is seen in lipid-rich cell adenoma, where accumulation of neutral fat results in cytoplasmic vacuolation 10 . Cytoplasmic clear cell changes are also seen in dyshormonogenetic goiter and hashimotos thyroiditis which are nonneoplastic thyroid disorders 11 . Main differential diagnosis of primary thyroid tumors with clear cells change is with Metastatic Renal cell carcinoma 12 and Parathyroid neoplasms. Both of these lesions can be intrathyroidal and also thyroid clear cell tumors can occur in ectopic locations 13 . Incidence of true intrathyroidal parathyroid tissue is estimated as 0.2% approximately and if these parathyroidal glands have hyperplasia or neoplasia it may result in hyperthyroidism. There is higher incidence of solitary renal cancer metastasis to thyroid and thyroid metastasis may be the initial manifestation of kidney neoplasm or it may only represent the spread of disease. Reason for the spread of renal tumors to thyroid is still not clear. Distinction between clear cell thyroid tumor thyroid and renal cancer metastasis is difficult on haematoxylin and eosin stained sections alone. Markers such as TTF-1 are specific for thyroid tumors and CD10 marker is of importance in renal neoplasms while PAX8 labels both of these tumors.

Conclusion:-
Any thyroid lesion with clear cell features warrants further histopathological assessment as clear cell changes are not appreciated in cytological smears. A morphological examination must be done first when patient presents with a thyroid lesion with clear cells. Next, other differential diagnosis including thyroid and parathyroid tissues with clear cytoplasmic changes and clear cell tumor metastasis such as Renal cell carcinoma must be carefully considered. Our present case is of intrest due to the pathology of pure clear cell Follicular adenoma which is rarely seen.

Conflict of interest:-
There are no conflict of interests to disclose.