Squamous Epithelium in the Human Thyroid Gland

J Clin Pathol: first published as 10.1136/jcp.19.4.384 on 1 July 1966. Downloaded from

J. clin. Path. (1966), 19, 384.

Squamous epithelium in the human thyroid gland

J. N. HARCOURT-WEBSTER1 From the Department ofPathology, University ofEdinburgh

SYNOPSIS Four cases are reported in each of which squamous epithelium was an incidental finding in surgically excised thyroid gland tissue. The occasional thyroid cyst lined throughout by squamous cells probably represents a persistent ultimo-branchial body, but the evidence indicates that the usual source of such cells in this gland is metaplasia of the follicular epithelium. An explanation is offered for the infrequency of this transformation in the thyroid, despite the frequent occurrence of the changes which predispose to epithelial metaplasia at other sites. There is no evidence to suggest that squamous cells arising in this gland by either of these means have any sinister significance.

Squamous epithelium was first described in a human iodine uptake studies were normal but serological anti- thyroid gland by Nicholson (1922); he attributed body tests were positive (ADT: +ve on second day; this finding to metaplasia of the follicular epithelium TCH: 1/250,000; CFT: 1/250). The provisional diagnosis was Hashimoto's disease; a biopsy was taken from the induced by severe chronic inflammatory and fibrotic right lobe with a wedge resection of the isthmus. changes in the gland. Epithelial metaplasia occurs in Histology Sections of the rock-hard, pale fawn tissue response to altered function or at least as the result show abundant, interwoven, thick bands of hyaline col- of altered environment (Boyd, 1961). Such condi- lagen. Within the meshwork so formed there are dense tions are a feature of many of the pathological states foci of plasma cell and lymphocyte infiltration. Small affecting the human thyroid; nevertheless, although numbers of tiny follicles in various stages of degeneration it has been reported in some of these, squamous and solid clusters of epithelial cells lie amidst this in- epithelium remains an unusual finding in this gland. filtrate; occasionally the cells are of Askanazy type. http://jcp.bmj.com/ Whilst metaplasia remains as a possible explanation Towards the periphery of some of these foci there are Klinck small groups of non-keratin-forming squamous cells for its presence (Wegelin, 1926; Jaffe, 1937; (Figs. 1 and 2); an occasional cluster of similar cells is and Menk, 1951), there is evidence that such epi- embedded in the collagen but there is no evidence of thelium may represent a persistent vestigeal remnant neoplasia. or congenital rest (Meeker, 1925; Goldberg and Harvey, 1956). CASE 2 A 43-year-old woman gave a history of one This paper records four cases in which clusters of month for a slowly enlarging, firm, slightly mobile, on September 28, 2021 by guest. Protected copyright. squamous cells were an incidental finding in surgi- solitary nodule at the lower pole of the left lobe of the cally excised thyroid tissue and discusses the factors thyroid. There were no other symptoms or signs and determining their presence and their significance. there was no family history of goitre. The nodule was excised for histological examination. CASE REPORTS Histology The nodule, 16 cm. in all external diameters, includes an irregularly shaped degeneration cyst CASE 1 A 56-year-old woman complained of a gradual filled with turbid, brown fluid and bounded by a wall of loss of weight for two years and a diffuse goitre enlarging varied thickness. It consists of occasional small foci of progressively for a year; the swelling first appeared on the atrophic follicles embedded in a collagenous tissue in- left side after a severe cold and then slowly spread to filtrated by moderate numbers of plasma cells, lympho- include the right side, always being temporarily exacer- cytes, and haemosiderin-laden macrophages. There are bated by menstruation. She found increasing difficulty in also larger groups of both small and moderate sized, keeping warm and had noticed slight exophthalmos, but colloid-filled, follicles, some of which are undergoing there was no dyspnoea, dysphagia, hoarseness, or other degeneration; in an occasional follicle a cluster of symptom. Her mother and sister both had a goitre. squamous cells interrupts the usual cuboidal or flat cell The two lobes, particularly the left, and the isthmus of lining with transition between the two types (Fig. 3). In the thyroid were enlarged, nodular and hard. Radio- addition a few similar clusters, some with keratin plugs, Received for publication 21 January 1966. are embedded in the collagen but with no continuity 'Present address: Department of Pathology, St. George's Hospital between them and the degenerate cells lining the cavity Medical School, Hyde Park Corner, London, S.W.1. of the cyst. 384 J Clin Pathol: first published as 10.1136/jcp.19.4.384 on 1 July 1966. Downloaded from

Squamous epithelium in the human thyroid gland 385

FIG. 1. FIG. 2. FIG. 1. Case 1. Small groups of squamous cells amidst plasma cells, lymphocytes, and proliferating fibrous tissue in sclerosing Hashimoto's disease. Haematoxylin and eosin x 220. http://jcp.bmj.com/ FIG. 2. Case 1. Higher-power view of a group ofsquamous cells showing inter-cellular bridges but no keratin. Haema- toxylin and eosin x 450. on September 28, 2021 by guest. Protected copyright.

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Wt_*i;-,J FIG. 3. Case 2. A cluster ofsquamous I X _ cellsa>s forms# so- parti* of the lining of a large, colloid-filledfollicle. ~~Haematoxylin~~~*~~~~~~~~~~~~~ and eosin x 325. J Clin Pathol: first published as 10.1136/jcp.19.4.384 on 1 July 1966. Downloaded from

386 J. N. Harcourt- Webster

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FIG. 4. FIG. 5. FIG. 4. Case 3. Flat, non-secretory epithelial cells line part of the cyst. Colloid-filled follicles and loose connective tissue form the wall. Haematoxylin and eosin x 225. http://jcp.bmj.com/ FIG. 5. Case 3. A short strip of squamous epithelium lines another part of the cyst. Atrophic follicles are embedded in the dense collagen ofthe wall. Haematoxylin and eosin x 325.

CASE 3 A 60-year-old woman gave a 20-year history of CASE 4 A 58-year-old man with a five-month history of a tense swelling in the left lobe of the thyroid; during the progressively increasing hoarseness culminating in a total last six months she had become increasingly agitated but loss of voice was found to have a paralysed left vocal cord the swelling had not changed its characteristics. There and a solitary, firm, almost immobile, nodule in the on September 28, 2021 by guest. Protected copyright. were no other symptoms or signs. The lesion was pro- left lobe of the thyroid. There was no abnormality visionally diagnosed as a cyst and a partial hemithyroid- in the other systems. The nodule was suspected ectomy performed. of being a carcinoma and a hemithyroidectomy was Histology A multilocular cyst, 3-0 x 3-0 x 2-5 cm., attempted. enclosed by a wall of irregular thickness, was embedded Histology A unilocular cyst, approximately 3-5 cm. in normal thyroid tissue. The cavity is incompletely lined in all diameters, containing turbid yellow-red fluid was by epithelium, usually flat and non-secretory but here and partially embedded in the posterior part of an otherwise there pseudostratified or squamous (Figs. 4 and 5.) normal left lobe of the thyroid. The cyst wall is composed Substantial areas of the supporting wall are formed of of two zones each of uniform width (Fig. 6). The inner dense collagen amidst which are atrophic follicles and one is lined by a thin layer of squamous epithelium and occasional cholesterol deposits; elsewhere there are zones includes numerous islets of squamous cells, some with a of loose connective tissue containing small and moderate central plug of keratin, enmeshed in fibrous tissue in- sized, colloid-filled follicles lined by a single layer of flat filtrated by small numbers of chronic inflammatory cells. cells (Fig. 4), and small numbers of chronic inflammatory There are no hair follicles or sweat glands nor is there any cells. continuity between the islets and the cyst lining. A few small follicles almost devoid of colloid and The outer zone of the wall consists of mature fibrous partially lined by pseudostratified, but not squamous, tissue containing clusters of atrophic follicles (Fig. 6); one epithelium are embedded in the collagen of the thinner area includes several moderate sized bundles of nerve parts of the cyst wall, but there is no continuity between fibres and a fragment of parathyroid tissue. There is no this epithelium and that lining the cyst. evidence of neoplasia. J Clin Pathol: first published as 10.1136/jcp.19.4.384 on 1 July 1966. Downloaded from

Squamous epithelium in the human thyroid gland 387 cells is not uncommon in disease of the thyroid, but the usually slow rate of cell turnover indicated by the rarity of mitoses, and the negligible uptake of tri- tiated thymidine in experimental animals, may make metaplasia of the follicular epithelium unlikely. It is of interest that in most of the reports of squamous change in this gland it is associated, as in case 1, with chronic thyroiditis, an abnormality in which foci of epithelial regeneration are occasionally found. The vast majority of cysts in the thyroid arise by degeneration of the parenchyma and show no evidence of epithelial regeneration, either in their lining or wall. Nevertheless, the finding of occasional small foci of squamous cells in continuity with those of follicular type, as in cases 2 and 3, leaves no doubt that metaplasia can occur; in both cases the squamous epithelium lies on chronically inflamed collagenous tissue, whilst the immediately adjacent epithelial cells are less degenerate than those usually found in such cysts. By contrast the features of case 4, in particular the almost complete lining of the cyst by squamous epithelium and the numerous islets of similar epithelium embedded in the inner zone of the wall, are similar to those seen in the thyroid cysts reported in a of animals Mason, FIG. 6. Case 4. The cyst wall clearly divided into an inner variety (Badertscher, 1918; and outer zone. A thin layer of squamous epithelium lines 1931; Van Dyke, 1943 and 1944) and in two human the cyst Rf<--wsrXwith islets A9L,of squamousvly,*b.cells*%S_*enmeshed2 ^;s¢ inA,fibrous e.. cases (Goldberg and Harvey, 1956). There is no tissue forming the inner zone. Haematoxylin and eosin indication of recognizable thyroid epithelium either x 70. in the lining or in the adjacent zone of the wall in this case; furthermore, the site of the cyst and the http://jcp.bmj.com/ presence of parathyroid tissue and bundles of the DISCUSSION recurrent laryngeal nerve in part of its wall support the suggestion that such a cyst originates in a rem- Squamous epithelium is undoubtedly an unusual nant of the ultimo-branchial body. This structure finding in the human thyroid gland; these four cases usually disappears at an early stage in the develop- are the only examples of this occurrence in over 1,200 ment of the human thyroid (Kingsbury, 1939) but is consecutive thyroid biopsies examined in this believed to persist occasionally at the exact location on September 28, 2021 by guest. Protected copyright. laboratory, an infrequency supported by the litera- where these cysts are found. ture. No other type of non-thyroid epithelium was Primary squamous cell carcinoma of the thyroid found in this series. is even more infrequent than the finding of squamous Alterations in the conditions of life of the cells epithelium (Harcourt-Webster, 1965); with both lining the thyroid follicles may result in metaplasia categories the total number of recorded cases is in- just as they do with epithelial cells at other sites, the sufficient to allow any definite conclusion on rela- transformation probably representing an adaptation tionship, and there is no published evidence to sup- to these changes. There is no evidence of disturbed port the opinion of Jaffd (1937) that epithelial function in any of the cases being reported, but the metaplasia is the source of squamous cell carcinomas chronic inflammation and fibrosis present in all four of the thyroid gland. Similarly, there is no justifica- would have produced an altered environment for tion for attaching any sinister significance to the small groups of follicular cells. Chronic inflamma- finding of squamous epithelium in either chronically tion and fibrosis are frequent findings in the ab- inflamed thyroid glands or their cysts. normal thyroid; however, in addition to such ante- I wish to thank Professor G. L. Montgomery for criticism cedent factors, for epithelial metaplasia to occur it is and advice and Mr. J. R. Cameron for permission to necessary that while old cells degenerate, young and publish these cases. Grateful thanks are also due to Mr. J. as yet not fully differentiated cells proliferate Paul for the illustrations and to the Lawson Tait (Lubarsch, 1930). Degeneration of the follicular Memorial Trust for defraying my expenses. J Clin Pathol: first published as 10.1136/jcp.19.4.384 on 1 July 1966. Downloaded from

388 J. N. Harcourt- Webster

REFERENCES Klinck, G. H., and Menk, K. F. (1951). Milit. Surg., 109, 406. Lubarsch, 0. (1930). Dtsch. Z. Chir., 227, 48. Mason, V. A. (1931). Amer. J. Anat., 49, 43. Badertscher, J. A. (1918). Amer. J. Anat., 23, 89. Meeker, L. H. (1925). Amer. J. Path., 1, 57. Boyd. W. A. (1961). Textbook ofPathology. 7th ed., p. 249. Kimpton, Nicholson, G. W. (1922). Guy's Hosp. Rep., 72,, 75. London. Van Dyke, J. H. (1943). Anat. Rec., 82, 451. Goldberg, H. M., and Harvey, P. (1956). Brit. J. Surg., 43, 565. - (1944). Ibid., 88, 369. Harcourt-Webster, J. N. (1965). J. clin. Path., 18, 282. Wegelin, C. (1926). In Handbuch der speziellin pathologischen Anatomie Jaff6, R. H. (1937). Arch. Path., 23, 821. und Histologie, edited by F. Henke and 0. Lubarsch, vol. 8, Kingsbury, B. F. (1939). Amer. J. Anat., 65, 333. p. 280. Springer, Berlin.

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