Thyroid Adenoma of Probable Ultimobranchial Body Origin: A Case Report.

Solid cell nests are generally believed to represent remnants of the ultimobranchial body, which can be found in the normal thyroid gland, occasionally associated with other branchial pouch remnants such as salivary gland, cartilage, and adipose tissue. We describe the case of a 44-year-old man incidentally found to have a large tumor in the left lobe of the thyroid. The tumor was a circumscribed growth consisting of distinctly lobulated proliferation of solid to cystic epidermoid cell nests and thyroid follicles in a fibromatous stroma, which merged into abundant adipose tissue and focally myxoid matrix. The solid epidermoid cell nests resembled solid cell nests and exhibited a p63+, GATA3+, galectin-3+, TTF1-, PAX8-, thyroglobulin- phenotypes, while the follicles were p63-, GATA3-, galectin-3-, TTF1+, PAX8+, and thyroglobulin+. RAS mutations were not found. This thyroid tumor may represent a hitherto undescribed "ultimobranchial body adenoma" in human.

GATA3 expression in the solid cell nest of thyroid.

Solid cell nest (SCN) of thyroid is a benign histomorphological mimicker of papillary microcarcinoma. Previous studies have elucidated a few immunohistochemical markers of SCN that aid in its distinction from papillary microcarcinoma. The positivity of GATA3 in SCN has been demonstrated only recently. We also document GATA3 positivity in three cases of SCN.

Heterogeneity of Stem Cells in the Thyroid.

Identification of thyroid stem cells in the past few years has made important contributions to our understanding of the cellular and molecular mechanisms that induce tissue regeneration and repair. Embryonic stem (ES) cells and induced-pluripotent stem cells have been used to establish reliable protocols to obtain mature thyrocytes and functional follicles for the treatment of thyroid diseases in mice. In addition, the discovery of resident thyroid progenitor cells, along with other sources of stem cells, has defined in detail the mechanisms responsible for tissue repair upon moderate or severe organ injury.In this chapter, we highlight in detail the current state of research on thyroid stem cells by focusing on (1) the description of the first experiments performed to obtain thyroid follicles from embryonic stem cells, (2) the identification of resident stem cells in the thyroid gland, and (3) the definition of the current translational in vivo and in vitro models used for thyroid tissue repair and regeneration.

Solid Cell Nests Within a Parathyroid Gland-Report of an Exceptional Case.

The ultimobranchial body (UBB) denotes the cellular mass originating from the fourth branchial pouch, which migrates from the neural crest and infolds within the middle and upper poles of the thyroid lobes, thereby establishing the presence of calcitonin-secreting parafollicular C cells. In various numbers, UBB remnants (entitled "solid cell nests", or SCNs) are found in thyroid glands examined histologically. However, despite the close embryological relation between the UBB and the superior parathyroid glands, intraparathyroidal SCNs have to our knowledge not been previously reported. Here, we describe a patient presenting with a papillary thyroid carcinoma with central and lateral lymph node metastases. Upon postoperative analysis, an unintentionally removed parathyroid gland was observed adjacent to the superior aspect of the right thyroid lobe. Within a 0.6 × 0.5-mm area of the parathyroid gland, solid nests composed of epithelial cells with oval and slightly elongated nuclei were seen. The cells were positive for p40, p63, and GATA3, but negative for PTH. The final diagnosis was a SCN entrapped within the parathyroid gland. Empirically, we have not previously observed SCNs within the parathyroid glands. To our knowledge, our finding thus constitutes a very unusual histological manifestation, and could indicate an underlying aberrancy during embryogenesis given the close anatomical relationship between the UBB and the superior parathyroid glands.

Derivation of thyroid lymphoepithelial cysts from follicular cells.

The pathogenesis of thyroid lymphoepithelial cysts is controversial, and two hypotheses have been proposed, namely derivation from branchial-derived remnants or from squamous metaplasia of the follicular cells. The aim of this study was to clarify the pathogenesis of thyroid lymphoepithelial cysts. We performed pathological and immunohistochemical examination of 21 thyroid lymphoepithelial cysts, 13 non-neoplastic squamous metaplasia samples without thyroid carcinoma, 13 solid cell nests, and 14 lateral cervical cysts. On ultrasound, half of thyroid lymphoepithelial cysts were interpreted as calcified nodules regardless of no calcification. Thyroid lymphoepithelial cysts and squamous metaplasia tended to be located in the central and lower portions of the thyroid, while solid cell nests were located in the upper and central portions (p < 0.05). In 95.2% of patients with thyroid lymphoepithelial cysts and all patients with squamous metaplasia, lesions were histologically associated with chronic thyroiditis forming lymph follicles. Hashimoto's disease was serologically confirmed in 18 patients with lymphoepithelial cysts (85.7%) and 10 patients with squamous metaplasia (76.9%). Immunohistochemically, lymphoepithelial cysts showed nuclear positivity for PAX8, thyroid transcription factor 1, and p63. One lateral cervical cyst (7.1%) showed positive staining for PAX8, while solid cell nests were PAX8-negative. In three (14.3%) cases of thyroid lymphoepithelial cysts, squamous cells located on the superficial layer were focally and weakly positive for CEA. We concluded that thyroid lymphoepithelial cysts originate from follicular cells and are unrelated to solid cell nests and lateral cervical cysts arising from branchial-derived remnants.

Positivity for GATA3 and TTF-1 (SPT24), and Negativity for Monoclonal PAX8 Expand the Biomarker Profile of the Solid Cell Nests of the Thyroid Gland.

Solid cell nests (SCNs) are usually distinguished on conventional H&E-stained sections; however, the morphological heterogeneity in SCNs and hyperplasia of these ultimobranchial body remnants can mimic other diagnostic entities including but not limited to papillary microcarcinoma. In order to confirm the thyroid follicular epithelial origin and exclude the possibility of SCNs, most diagnosticians use immunohistochemical biomarkers of thyroid follicular epithelial cells and/or those of SCNs. While the expression profile of monoclonal PAX8 has not been reported previously in SCNs, the status of TTF-1 expression using the 8G7G3/1 clone has been inconsistent among several studies. Given the potential diagnostic pitfalls, this series investigated the expression profile of GATA3, monoclonal PAX8, and TTF-1 (SPT24), along with p63, p40, monoclonal calcitonin, monoclonal CEA, and HBME-1 in a tissue microarray (TMA) of 56 SCNs. SCNs were all diffusely and strongly positive for TTF-1 (SPT24), p63, and p40, and were negative for monoclonal PAX8 and calcitonin. Positivity for GATA3 and monoclonal CEA was identified in 41 (73.2%) and 36 (64.3%) of SCNs. In addition, 18 (32.1%) SCNs displayed HBME-1 reactivity. These findings expand the immunohistochemical correlates of SCNs by demonstrating positivity for GATA3 and TTF-1 (SPT24), and negativity for monoclonal PAX8. The identification of monoclonal CEA expression and HBME-1 in SCNs also underscores the limitations of these select biomarkers in the distinction of C cell proliferations and papillary microcarcinoma, respectively. The findings of this series also suggest that positivity for TTF-1 (SPT24) alone should not be used to confirm the thyroid follicular epithelial origin. Therefore, the combined use of TTF-1 (SPT24) and monoclonal PAX8 in association with p63 or p40 provides an accurate distinction of SCNs.

Spectrum of lesions derived from branchial arches occurring in the thyroid: from solid cell nests to tumors.

There is a group of lesions in the head and neck region derived from branchial arches and related structures which, when inflamed, are characterized by the formation of cysts lined by squamous or glandular epithelium and surrounded by a heavy inflammatory infiltrate rich in germinal centers. In the thyroid, the main source of various structures which may cause diagnostic dilemma is the ultimobranchial body. To investigate the spectrum of such thyroid lesions, the consultation files were reviewed for thyroid samples containing pathological structures regarded to arise from the ultimobranchial body. Positive reaction with antibodies against CK5/6, p63, galectin 3, and CEA, and negative reaction with antibodies against thyroglobulin, TTF-1, and calcitonin were used to confirm the diagnosis. The specific subtype of the ultimobranchial body-derived lesion was then determined based on histological examination of H&E-stained slides. Twenty-one cases of ultimobranchial body-derived lesions were retrieved from the consultation files, 20 of them along with clinical information (M/F = 6/14, mean age 55 years, range 36-68 years). Lesions derived from the ultimobranchial body were classified as follows: (hyperplastic) solid cell nests (nine cases), solid cell nests with focal cystic change (five cases), cystic solid cell nests (two cases), branchial cleft-like cyst (four cases), and finally a peculiar Warthin tumor-like lesion (one case). We suggest that the common denominator of these structures is that they all arise due to activation of inflammatory cells around the vestigial structures, which leads to cystic dilatation and proliferation of the epithelial component.

Solid cell nests of the thyroid gland: morphological, immunohistochemical and genetic features.

AIMS: The correct identification of solid cell nests (SCNs) is an important issue in thyroid pathology because of the spectrum of differential diagnoses of this type of lesion. METHODS AND RESULTS: Ten cases of 295 consecutive thyroidectomies showed the presence of SCNs at histological examination. The identification of the exact SCN type required the distinction of the cystic and solid pattern; SCNs were usually composed of a mixture of main cells (MCs) and C-cells (CCs). The immunohistochemical calcitonin stain identified CCs easily, both inside SCNs and dispersed in islets at the periphery. For the characterization of MCs, we added the utility of p40 to p63. The use of thyroid transcription factor-1 (TTF-1) helped in their identification, as MCs did not react with this marker; the combination of TTF-1 and p40 or p63 IHC stains was useful for the characterization of cystic SCNs of both types 3 and 4. The negativity of mouse monoclonal mesothelioma antibody (HMBE-1) and a very low proliferative index (MIB-1) supported the diagnosis. [Correction added on 23 November 2015, after online publication: MIB-1 was incorrectly defined, the expanded form was deleted.] We discourage the use of galectin-3 (Gal-3) and cytokeratin-19 (CK-19), as they have an important overlap with papillary thyroid carcinoma. The complete absence of any B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations is an additional fundamental finding. CONCLUSIONS: We reviewed the most relevant morphological and immunohistochemical features of SCNs and have provided a genetic analysis of the BRAF gene because of its expanding use in thyroid pathology.

Thyroid regeneration: how stem cells play a role?

Many tissues if not all are thought to contain stem cells that are responsible for regeneration and repair of the tissue after injury. Dysregulation of tissue regeneration may result in various pathological conditions, among which cancer is the most extensively studied. Notably, the so-called cancer stem cells or tumor-initiating cells, have been studied in order to understand the mechanisms of carcinogenesis and/or metastasis. However, the nature of cancer stem cells, let alone normal stem/progenitor cells, particularly those of the thyroid remains elusive. There remains a gap in knowledge between adult thyroid stem/progenitor cells and cancer stem cells of the thyroid, and if and/or how they are related to each other. Understanding of the mechanism for thyroid regeneration and mode of participation of normal adult thyroid stem/progenitor cells in this process will hopefully yield a more complete understanding of the nature of thyroid cancer stem cells, and/or help understand the pathogenesis of other thyroid diseases. This review summarizes the current understanding of adult thyroid stem/progenitor cells, with particular emphasis on how they contribute to thyroid regeneration.