Thyroid Stroma Research Articles

Amyloid goiter with diffuse thyrolipomatosis: a rare entity

Diffuse thyroid lipomatosis with amyloid deposition is a rare entity. We report a case of a 42-year-old lady who presented with progressive enlargement of the thyroid gland with compressive symptoms. Her thyroid hormone levels were within normal limits. Imaging revealed enlarged thyroid gland with multiple fat density lesions. She underwent total thyroidectomy, and histopathology revealed diffuse infiltration of thyroid stroma by mature adipose tissue and an associated amyloid deposition. A diagnosis of amyloid goiter with diffuse lipomatosis of the thyroid gland was rendered. Only a few cases of diffuse lipomatosis with concurrent deposition of amyloid protein have been reported in the literature.

Histological Alterations in Hashimoto's Disease: A Case-Series Ultrastructural Study.

Hashimoto's thyroiditis (HT) is an autoimmune disease exhibiting stromal fibrosis and follicular cell destruction due to lymphoplasmacytic infiltration. Besides deprecated analyses, histopathological approaches have not employed the use of electron microscopy adequately toward delineating subcellular-level interactions. Biopsies for ultrastructural investigations were obtained from the thyroids of five patients with HT after a thyroidectomy. Transmission electron microscopy (TEM) was utilized to study representative tissue specimens. Examination indicated interstitial extravasated blood cells and a plethora of plasma cells, based on their subcellular identity landmarks. These antibody-secreting cells were profoundly spotted near follicular cells, fibroblasts, and cell debris entrenched in collagenous areas. Pathological changes persistently affected subcellular components of the thyrocytes, including the nucleus, endoplasmic reticulum (ER), Golgi apparatus, mitochondria, lysosomes, and other intracellular vesicles. Interestingly, significant endothelial destruction was observed, specifically in the larger blood vessels, while the smaller vessels appeared comparatively unaffected. Our TEM findings highlight the immune-related alterations occurring within the thyroid stroma. The impaired vasculature component and remodeling have not been described ultrastructurally before; thus, further exploration is needed with regards to angiogenesis in HT in order to achieve successful prognostic, diagnostic, and treatment-monitoring strategies.

Morphologic evidence of telocytes in human thyroid stromal tissue.

Despite the evidence accumulated over the past decade that telocytes (TCs) are a distinctive, though long neglected, cell entity of the stromal microenvironment of several organs of the human body, to date their localization in the endocrine glands remains almost unexplored. This study was therefore undertaken to examine the presence and characteristics of TCs in normal human thyroid stromal tissue through an integrated morphologic approach featuring light microscopy and ultrastructural analysis. TCs were first identified by immunohistochemistry that revealed the existence of an intricate network of CD34+ stromal cells spread throughout the thyroid interfollicular connective tissue. Double immunofluorescence allowed to clearly differentiate CD34+ stromal cells lacking CD31 immunoreactivity from neighbour CD31+ microvascular structures, and the evidence that these stromal cells coexpressed CD34 and platelet‐derived growth factor receptor α further strengthened their identification as TCs. Transmission electron microscopy confirmed the presence of stromal cells ultrastructurally identifiable as TCs projecting their characteristic cytoplasmic processes (i.e., telopodes) into the narrow interstitium between thyroid follicles and blood microvessels, where telopodes intimately surrounded the basement membrane of thyrocytes. Collectively, these morphologic findings provide the first comprehensive demonstration that TCs are main constituents of the human thyroid stroma and lay the necessary groundwork for further in‐depth studies aimed at clarifying their putative implications in glandular homeostasis and pathophysiology.

A targeted mass spectrometry method to screen collagen types I-V in the decellularized 3D extracellular matrix of the adult male rat thyroid

Here we have developed and validated an original LC-MS/MS SRM procedure flexible enough to quantitatively screen collagen types I-V in copies of the same type of stromal matrix prepared with different protocols of cell removal to retain the native 3D architecture of the ECM. In a first step, identification of tryptic sequences exclusive to specific chains (either α1 or α2) of mammalian collagen standards types I-V was pursued using a combination of LC-LIT-Orbitrap XL and LC-MS/MS SRM analyses. In a second step, the adult male rat thyroid was decellularized using three different protocols specifically set for engineering of bioartificial 3D thyroid organoids. In a third step, DNA analysis of the decellularized 3D thyroid stroma was pursued to exclude contamination by cell nuclear debris. In a final step, collagen standards and 3D thyroid matrices were digested using the same mechanical / enzymatic protocol, and quantitative profiles of collagen types I-V ensued using comparisons of ionic intensities between tryptic peptides of collagen standards and matrices, as derived from targeted LC-MS/MS SRM analysis. Collectively, the procedure allowed for detection and quantitation of collagen types I-V at a femtomolar level in thyroid gland stromal matrices initially maintaining their original 3D architecture, tryptically digested through a method common to collagen standards and thyroid ECM, with satisfactory reproducibility of results, moderate procedural cost, and limited analytical time.

Papillary thyroid carcinoma with nodular fasciitis-like stroma and β-catenin mutations should be renamed papillary thyroid carcinoma with desmoid-type fibromatosis

Various histological variants of papillary thyroid carcinoma have been reported, some with clinical implications, some with peculiar, sometimes misleading morphologies. One of these rare and poorly characterized variants is papillary thyroid carcinoma with nodular fasciitis-like stroma, of which fewer than 30 cases have been documented, mostly as isolated reports. It is a dual tumor comprising a malignant epithelial proliferation that harbors typical features of conventional papillary thyroid carcinoma, admixed with a prominent mesenchymal proliferation resembling nodular fasciitis or fibromatosis. Thus, the terms papillary thyroid carcinoma with nodular fasciitis-like stroma and papillary thyroid carcinoma with fibromatosis-like stroma are used interchangeably; however, the former term suggests a self-limited and regressing disease, whereas the latter one suggests a recurrent and potentially aggressive one. Better genetic and ultrastructural characterization could lead to more appropriate terminology and management. We performed detailed clinicopathological and molecular analyses of two cases of PTC with prominent mesenchymal proliferation that developed in the thyroid gland of two male patients aged 34 and 48. In both cases, the epithelial component harbored a heterozygous somatic activating BRAF mutation (p.V600E). Also, in both cases, the mesenchymal component showed typical aberrant nuclear and cytoplasmic immunoreactivity for β-catenin and harbored a heterozygous somatic activating mutation in the corresponding CTNNB1 gene (p.S45P). This mutation has never been reported in thyroid stroma; in other tissues, it is typical of desmoid-type fibromatosis rather than nodular fasciitis-like stroma. We therefore propose that in cases of papillary thyroid carcinoma with a prominent mesenchymal component, mutations in CTNNB1 should be sought; when they are present, the term ‘papillary thyroid carcinoma with desmoid-type fibromatosis’ should be used. As the mesenchymal component of these tumors is not expected to concentrate radioactive iodine, special considerations apply to clinical evaluation and follow-up, which should be brought to the attention of the treating specialist.

Isolated Aspergillus thyroiditis in an immunocompromised patient.

Sir, We describe a 30-year-old woman who presented with a progressively enlarging anterior neck mass with pain, local warmth and skin erythema. The patient had been on haemodialysis because of a 3-month history of renal failure due to lupus nephritis. She was also on monthly cyclophosphamide pulse therapy and daily prednisolone (30 mg daily). Her vital signs were as follows: temperature, 37.6°C; blood pressure, 130/80 mmHg; pulse rate, 95–105/min; and respiratory rate, 20/min. Her laboratory results, including thyroid studies, are shown in Table 1. A thyroid scan revealed large defects bilaterally. Initially, subacute thyroiditis was considered the most probable diagnosis, and the daily dose of oral prednisolone was increased to 60 mg. The patient complained of nervousness, irritability, hyperactivity and palpitation, and a β-adrenergic blocker and propylthiouracil were prescribed. When the patient revisited our clinic 3 weeks later, she complained of a progressively enlarging thyroid and respiratory distress. Her chest X-ray revealed tracheal compression and deviation. Because of respiratory failure, she required endotracheal intubation and mechanical ventilation followed by emergency total thyroidectomy. Table 1 Results of the patient’s laboratory tests Microscopy of the thyroid revealed infectious thyroiditis with suppurative inflammation, abscess formation, and considerable tissue destruction throughout the gland. Septate hyphae, < 5 μm in thickness, with branching at acute angles were identified. These findings were consistent with a fungal thyroiditis caused by Aspergillus. Blood vessels were invaded by the hyphae of the fungus (Figure 1). A culture of the aspirated fluid showed no growth. The results of repeated tests with an Aspergillus antigen (galactomannan) enzyme-linked immunosorbent assay (ELISA) were negative. There was no evidence of aspergillosis in the other organs. Blood and sputum cultures were negative. Intravenous liposomal amphotericin B (5 mg/kg daily) was initiated, and later switched to oral voriconazole (200 mg twice a day for 2 days, and then 100 mg twice a day) on the day of discharge, 2 weeks after the initiation of amphotericin B, and was continued for the following 12 weeks. Because tests showed a decreasing thyroid function, hormone replacement was begun 10 days after surgery. Fig. 1 Periodic acid–Schiff stain demonstrates numerous fungal profiles (arrows) in the thyroid stroma with angio-invasion (original magnification, × 200).

Expression of CD56 (NKH-1) differentiation antigen in human thyroid epithelium.

Leu-19 (CD56) MoAb is well known to recognize gp220 expressed on natural killer (NK) cells and is widely used as a NK cell marker. The expression of CD56 antigen was tested by means of sensitive alkaline phosphatase-anti-alkaline phosphatase (APAAP) immunohistochemical technique and the above mentioned MoAb as a primary antibody, on frozen sections of various fresh human tissues. Out of 11 organs examined only thyroid gland provided a distinct reaction confined to cell membranes of epithelial follicular cells. The reaction had a diffuse pattern in cases of Graves' disease and colloidal goitre while in Hashimoto's thyroiditis presented as a focal pattern. Other anti-NK cell MoAbs such as VD4 (CD16) and Leu-7 (CD57) reacted only with single cells of thyroid stroma. The results of APAAP staining were confirmed by the cytofluorimetric assessment of isolated thyroid cells. It is speculated that CD56 expression on thyroid cells may have a functional significance, perhaps related to neural-endocrine interactions.

Transthyretin Amyloid Goiter in a Renal Allograft Recipient

Amyloid deposition in the follicular, perifollicular blood vessels, and thyroid stroma can occur in systemic forms of amyloidosis, although diffuse enlargement of the thyroid is generally not present. Marked, widespread enlargement of the thyroid gland with amyloid deposits or amyloid goiter is a rare condition reported in association with primary and secondary amyloidosis but has not been described in association with transthyretin amyloid deposition. Senile transthyretin amyloidosis is primarily associated with amyloid deposits in the heart, while the familial forms of amyloidosis due to transthyretin gene mutations are associated with deposits of amyloid in multiple tissues, classically giving rise to polyneuropathy. In this report, we describe the findings of parathyroid and lymph node amyloid deposits and amyloid goiter with transthyretin reactivity in a recipient of a kidney allograft, reportedly for renal amyloidosis, initially assumed clinically to be due to inflammatory bowel disease-related secondary amyloid deposition. This case underscores the importance of routine immunohistochemical classification of amyloid deposits for accurate diagnosis and to guide clinical management decisions.

Early chemokine expression induced by interferon-gamma in a murine model of Hashimoto's thyroiditis

Chemokines represent a group of small, secreted proteins mainly involved in navigating leukocytes towards site of inflammation. Some chemokines have been implicated in the pathogenesis of autoimmune diseases, which are characterized by an ectopic retention of leukocytes within the target organ, ultimately leading to loss of function. To determine the chemokines profile expressed in the thyroid gland upon chronic exposure to interferon-gamma (IFNγ), we analyzed C57BL6 transgenic mice that aberrantly express IFNγ under control of the thyroglobulin promoter. We compared by reverse transcriptase PCR the thyroidal expression of 10 chemokines (CCL1 through 5 and CXCL9 through 13) in thyr-IFNγ transgenics and wild-type littermates. We found that transgenics exclusively expressed CCL4, CXCL9, and CXCL11, and showed increased expression of CCL5 and CXCL10. This chemokine profile was associated with moderate mononuclear cell infiltration of the thyroid stroma that, however, decreased significantly after 2 months of age and did not organize into lymphoid structures. Our findings indicate that the isolated expression of IFNγ is capable of recruiting mononuclear cells but they do not progress to full lymphoid transformation of the thyroid.

Морфофункциональные изменения щитовидной железы у лабораторных животных при действии холода

The functional activity of the thyroid in laboratory animals exposed to extreme cooling is studied. Male Wistar rats were used. Control animals were kept at 20-22° C, experimental at —10°C for 7 days. Thyroxin and triiodothyronine concentrations in the serum and thyroid hormones and thyroglobulin in the thyroid were measured. Morphometry of the thyroid was carried out. Thyroxin level decreased and the T3/T4 ratio increased in the serum of rats exposed to extreme cooling; the content of thyroid hormones in the gland, mainly triiodothyronine and thyroglobulin, increased under the effect of cold. The thyroid enlarged under the effect of cold. The bulk of follicular epithelium in thyroid tissue increased and colloid volume decreased. Structural transformations of follicles were paralleled by increase of the vascular network and number of degranulated mast cells in the connective tissue thyroid stroma. Therefore, exposure to low temperature results in increase of the thyroid functional activity in rats, despite the exhaustion of the adaptive reactions of the organism.

Evidence of iodine storage within thyroid stroma after iodine treatment: imaging by secondary ion mass spectometry (SIMS) microscopy in goitrous tissue.

We measured the 127I distribution within tyroid tissue to find out where intrathyroid iodine was deposited during iodine treatment in eight Tunisian female patients (aged 33-58 yr) with endemic euthyroid goiter. Before surgery, five patients were treated during 6 months either by Lugol's solution (group 1: three patients) or by Lugol's and L-thyroxine (group 2: two patients). All patients remained euthyroid during the course of the treatment, which supplied 3.8 mg/day iodine. Three other patients did not receive Lugol's solution (control group). Secondary ion mass spectrometry microscopy was used to map 127-I quantitatively on thyroid sections. Specimens obtained at thyroid surgery were divided macroscopically into nodular and extranodular tissue and chemically fixed to preserve organified iodine. The iodine profile of patients in group 1 did not differ from that in group 2: large amounts of iodine were localized in thyroid follicles and stroma of both nodular and extranodular tissues. In the control group, iodine within stroma was found only in the extranodular tissue. Despite the limited number of patients studied, these data suggest that stromal iodine might represent a storage compartment in times of large iodine supply.

Evidence of iodine storage within thyroid stroma after iodine treatment: imaging by secondary ion mass spectometry (SIMS) microscopy in goitrous tissue

Evidence of iodine storage within thyroid stroma after iodine treatment: imaging by secondary ion mass spectometry (SIMS) microscopy in goitrous tissue