Indian Journal of Pathology and Microbiology

: 2008  |  Volume : 51  |  Issue : 4  |  Page : 507--508

Mucin-producing signet ring cell adenoma of the thyroid

Hanni Gulwani, P Chopra 
 Department of Histopathology, Sir Ganga Ram Hospital, New Delhi 110 060, India

Correspondence Address:
Hanni Gulwani
Shri V.T.Gulwani, 553/151/5, Adarsh Nagar, Alambagh, Lucknow 226 005


Signet ring cell adenoma of the thyroid, though rare, is well documented. This change is chiefly due to intracellular accumulation of thyroglobulin that appears mucinous. Awareness of this entity is important as it may closely simulate a metastatic mucin-secreting signet ring cell carcinoma. Although the mucinous material in signet ring cells has been reported to stain positive with thyroglobulin, in some cases it may not be so. We herein describe a rare case of a 46-year-old man who was hypothyroid and the mass removed from the thyroid showed a mucin-producing signet ring cell adenoma of the thyroid.

How to cite this article:
Gulwani H, Chopra P. Mucin-producing signet ring cell adenoma of the thyroid.Indian J Pathol Microbiol 2008;51:507-508

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Gulwani H, Chopra P. Mucin-producing signet ring cell adenoma of the thyroid. Indian J Pathol Microbiol [serial online] 2008 [cited 2021 Dec 2 ];51:507-508
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Full Text


Follicular adenoma of the thyroid is a common benign tumor of the thyroid gland. Several variants of follicular adenoma have been described in medical literature. Rare variants include adenomas with clear cell change, adipose, and cartilaginous metaplasia [1],[2] of the stroma. Clear cell change in thyroid adenomas can be observed due to various reasons that include cytoplasmic vesicles (of mitochondrial, endoplasmic reticulum, or golgi origin), accumulation of glycogen (with or without the presence of fat), and deposition of intracellular thyroglobulin. [3] Of these, vesicle formation is the most common cause of clear cell change in Hurthle cell and follicular neoplasms of the thyroid. Glycogen accumulation is not uncommon in papillary, undifferentiated, and metastatic tumors in the thyroid. [3] Thyroglobulin deposition in a subgroup of follicular tumors can give rise to signet ring cell appearance of the tumor cells. We hereby describe a case of mucin-producing signet ring cell adenoma of thyroid gland.

 Case Report

A 46-year-old man presented with a gradually increasing swelling in the neck for the past 5 months. There was no history of pain, tenderness, dyspnea, or dysphagia. A physical examination revealed a solitary palpable swelling in the left side of the neck. There was no history of neoplastic disease in the thyroid or elsewhere in the body. The patient had been diagnosed with hypothyroidism for which he had been taking thyroid hormone supplementations for the last 4 months. Clinical and laboratory investigations were otherwise unremarkable. A fine needle aspiration performed at another hospital was reported as a follicular lesion in the thyroid.

A left hemithyroidectomy was performed. A gross examination showed a brown, well-circumscribed nodule measuring 4 cms in diameter. The nodule was smooth with focal areas of hemorrhage. A microscopic examination revealed a well-encapsulated nodular lesion. A fibrous capsule separates the lesion from the adjacent compressed thyroid tissue [Figure 1A]. Extracellular pools of mucin were also identified [Figure 1B]. The lesion is composed of variable sized follicles that were arranged compactly. Microacini were also observed. Nuclei were round to ovoid and vesicular with mild to moderate pleomorphism. A few large hyperchromatic nuclei were also seen. Thin colloid was recognized within some acini. A prominent feature was the signet ring cell appearance of the cells [Figure 2], which was seen in several foci. The nucleus was pushed eccentricallydue to a bluish myxoid to mucinous intracytoplasmic material. On careful examination, no capsular or vascular invasion was recognized in multiple sections. The surrounding thyroid tissue showed mild lymphocytic thyroiditis.

The vacuoles and the mucinous material within the signet ring cells appeared blue with an Alcian Blue Periodic Acid Schiff (ABPAS; pH 2.5) stain. A mucicarmine stain showed positive staining both within the microfollicles and the signet ring cells. Using immunohistochemistry, the mucinous material in the signet ring cells did not react with the thyroglobulin, whereas the epithelial lining of follicles showed strong positivity.


Clear cell change is rarely observed in follicular adenomas and can be due to glycogen, lipid, thyroglobulin, or mucin accumulation within the tumor cells. Signet ring cell follicular adenoma is a rare documented entity with only a few cases reported in literature. The signet ring cells in follicular adenoma are characterized by the presence of a large cytoplasmic vacuole that leads to the lateral displacement of the nucleus thus giving rise to a signet ring cell configuration. The intracellular accumulation of thyroglobulin results from the inability of the tumor cell to excrete it. It might result from the deletion of one or many proteins that are needed to perform the task.[4] Many of the published case reports have shown a positive immunohistochemical staining reaction with a thyroglobulin marker in the signet ring cells. In addition, these signet ring cells have been observed to be in close association with colloid filled thyroid follicular acini in the lesion suggesting that these signet ring cells are a result of thyroglobulin degeneration within the thyroid follicular cells. These secretions are also positive for mucin stains and thus have been alternatively termed as mucin-producing microfollicular adenoma. [5] It has been suggested that the mucin reactivity in these signet ring cells could be due to the presence of protein polysaccharide complexes derived from the partial degradation of thyroglobulin. Most of the signet ring cell neoplasms are adenomas, however, carcinomas with this appearance have also been described.

We searched the literature available and found 20 such cases of signet ring cell adenoma of the thyroid, the present case being the first one in Indian literature. Thyroglobulin staining was done in the majority of these cases and was found to be positive except in one case reported by Yoshida, et al. , [6] which had findings similar to our case that showed the predominance of mucin and poor staining for thyroglobulin. The negative staining for thyroglobulin can be due to the marked degradative changes in the secretions leading to a loss of the staining pattern. It can thus be stated that it is not necessary for all the cases of signet ring cell follicular adenoma of the thyroid to show positive staining for thyroglobulin in the secretions within the signet ring cells.

However, when signet ring cells are encountered in adenoma of the thyroid, the pathologist needs to be aware of this finding and be cautious in excluding a primary signet ring cell carcinoma elsewhere in the body before labeling it as a signet ring cell change within an adenoma of the thyroid. Immunohistochemical staining for thyroglobulin is an important useful marker in discriminating primary signet ring cell adenoma of the thyroid from the metastatic signet ring cell carcinoma in the thyroid. Metastases from an extrathyroidal site, although uncommon has been well documented in disseminated malignancies from bronchial, mammary, or renal carcinomas. [7] Also, one has to consider the possibility that the mucin-producing neoplasm has not arisen from some intrathyroid embryonic remnants such as the thyroglossal duct or the ultimobranchial derivatives.


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