Oxyphilic Changes Research Articles

Cytomorphological features of papillary thyroid carcinomas with the development of radioiodine-resistance

Background. The problem of diagnosis and treatment of papillary thyroid cancer (PTC) are radioiodine resistant metastases (RIRM). An urgent issue is the possibility of their early prediction and diagnosis based on the detection of cytomorphological features of the PTC and its metastases, which correlate with the development of radioiodine (RI) resistance. Purpose – detection of cytomorphological features of primary PTC and its metastases in patients who subsequently showed resistance to 131I therapy, compared with the control group of patients who achieved a positive effect of 131I therapy. Materials and Methods. A comparative analysis of morphological features in histological conclusions and the study of cytological characteristics in the fine-needle aspiration (FNA) smears of primary PTC and their primary metastases, as well RIRM оf experimental and control groups of patients were conducted. The experimental group consisted of 152 patients who showed resistance to RI therapy, the control group – 161 patients who achieved a positive effect of RI therapy. Statistical processing was done in Statistica 12. Results and discussion. It is shown that the frequency of follicular structures in the material of primary PTC of patients with a positive effect of 131I therapy is significantly higher, and the frequency of necrotic changes is significantly lower than in patients with the development of RIRM (p <0.05 by criterion χ2). The frequency of follicular structures in the histological material and FNA smears of primary metastases of patients with a positive effect of 131I therapy is significantly higher, and oxyphilic changes are significantly lower than in patients with the development of RIRM (p <0.05 by criterion χ2). Oxyphilic changes were observed significantly more often in the RIRM compared with primary metastases of the control group (p = 0.03). It was proved that cystic changes are significantly more common in FNA smears and histological material of RIRM in comparison with primary metastases of experimental and control groups of patients (p <0.05). Conclusions. TThe use of the presence of oxyphilic and cystic changes in the FNA smears and histological material of metastases of the PTC as prognostic factors of RI resistance is proposed. The presence of follicular structures in the materials of primary PTC and metastases can be a prognostic factor of effective RI therapy.

Morphological features of radioiodine-resistance metastases of thyroid papillary carcinoma

An important problem in the diagnosis, treatment and prediction of papillary thyroid cancer is radioiodine-resistant metastases, early prediction of which is possible on the condition of determining their cytological and histological characteristics. The purpose of this work was to identify the histological and cytological characteristics of metastases of papillary thyroid carcinomas correlated with their iodine-accumulative capacity, on the basis of which it will be possible to predict the radio-resistance of papillary thyroid carcinomas. A cytological examination of punctates of 30 papillary carcinomas and 45 of their metastases identified in the postoperative period and analysis of the histological characteristics of 100 papillary carcinomas of the general population, 47 primary papillary carcinomas and their radio-resistant metastasis and 17 primary papillary carcinomas of patients with radioiodine-uptake metastases were conducted. Statistical analysis was performed via the non-parametric criterion χ2 in the package Statistica 11.0. It has been shown a statistically significant difference between presence of sign of follicular structures in the histological material of primary papillary canсer of patients with radioiodine-resistance metastases and between of primary papillary canсer of patients with radioiodine-uptake metastases and common population of papillary thyroid cancer. It has been shown a statistically significant difference between punctuates of radioiodine-resistance and radioiodine-uptake metastases in presence of such cytological characteristics as different subpopulations of thyrocytes. It has been shown that the cytological characteristics of radioiodine-resistant metastases differ from radioiodine-uptake metastases and primary papillary carcinomas by the presence of different subpopulations of thyrocytes, particular structures and oxyphilic changes. It is shown that such histological characteristics as lack of follicular structures in the material of primary papillary carcinomas correlate with radio-resistance and can be prognostic factors of its appearance.

Bile Duct Adenoma with Oncocytic Features

Bile duct adenomas are benign bile duct proliferations usually encountered as an incidental finding. Oncocytic bile duct neoplasms are rare and the majority are malignant. A 61-year-old male with a diagnosis of colorectal adenocarcinoma was undergoing surgery when a small white nodule was discovered on the surface of the right lobe of his liver. This lesion was composed of cytologically bland cells arranged in tightly packed glands. These cells were immunopositive for cytokeratin 7, negative for Hep Par 1, contained mucin, and had a Ki67 proliferation index of 8%. The morphology, immunophenotype, presence of mucin, and normal appearing bile ducts, as well as the increased Ki67 proliferation rate, were consistent with a bile duct adenoma with oxyphilic (oncocytic) change. Oncocytic tumors in the liver are rare; the first described in 1992. Only two bile duct adenomas with oncocytic change have been reported and neither of them had reported mucin production or the presence of normal appearing bile ducts within the lesion.

A case of polymyositis associated with Hashimoto's thyroiditis

A case of polymyositis associated with Hashimoto's thyroiditis

Possible association of CEA expression with oxyphilic change but not with C-cell hyperplasia in Hashimoto's thyroiditis

Reactive C-cell hyperplasia (CCH) has been observed in cases of autoimmune Hashimoto's thyroiditis; however, its occurrence in Graves' disease, the other major autoimmune disorder, has not yet been investigated. On the other hand, although Carcinoembryonic Antigen (CEA) serum levels have been reported elevated in patients with autoimmune thyroid disease (ATD), the source of CEA production at the cellular level is not elucidated. The aim of this study was to evaluate CCH and CEA immunohistochemical expression and comparatively analyze them in 136 ATD cases (107 Hashimoto's and 29 Graves' disease cases) and 20 cases of nodular hyperplasia (NH). Immunohistochemistry using monoclonal antibodies to chromogranin and CEA was performed. A scoring system for CCH and semiquantitative evaluation for CEA expression were applied. C-cell hyperplasia was absent in NH cases. In contrast, it was detected in 11% of ATD cases being more frequently observed in Hashimoto's (12.1%) than Graves' disease (6.8%) CCH associated to male sex and older age of Hashimoto's patients. CEA was detected only in ATD cases (33.8%), in C-cells and in follicular cells as well, being more frequently detected in Graves' (44.8%) than Hashimoto's (30.8%) disease. An interesting finding was an emerging possible association of CEA expression with oxyphilic change but not with C-cell hyperplasia in Hashimoto's thyroiditis. No significant correlation was established between CCH and CEA follicular cell expression in neither disease. In conclusion, C-cell hyperplasia and CEA expression may be encountered in the setting of Hashimoto's thyroiditis and Graves' disease.

Immunohistochemistry of IgG4 can help subclassify Hashimoto's autoimmune thyroiditis

IgG4-related sclerosing disease has been recently recognized as a systemic disease entity characterized by an elevated serum IgG4 level, sclerosing fibrosis and diffuse lymphoplasmacytic infiltration by many IgG4-positive plasma cells. Similar histopathological features have often been noted in the fibrous variant of Hashimoto's autoimmune thyroiditis, but thyroid gland involvement has been only briefly mentioned with regard to IgG4, and no immunohistochemistry for IgG4 has been reported in Hashimoto's autoimmune thyroiditis. Herein, the purpose of the present study was to investigate the infiltration of IgG- and IgG4-positive plasma cells on immunohistochemistry for a panel of thyroiditis samples (Hashimoto's autoimmune thyroiditis, n= 13; subacute thyroiditis, n= 2; lymphocytic thyroiditis, n= 2). Cases of Hashimoto's thyroiditis could be classified into two groups based on immunostaining of IgG4: IgG4 thyroiditis (IgG4-related, IgG4-positive plasma cell-rich thyroiditis) and non-IgG4 thyroiditis (non-IgG4-related, IgG4-positive plasma cell-poor thyroiditis). IgG4 thyroiditis presents with severe lymphoplasmacytic infiltration, dense fibrosis, marked follicular cell degeneration, oxyphilic change and lymphoid follicle formation, while non-IgG4 thyroiditis presents with relatively mild or absent histopathological characteristics. In conclusion, immunostaining of IgG4 can help subclassify Hashimoto's thyroiditis; and IgG4 thyroiditis may have a close relationship with IgG4-related sclerosing disease.

Sudden unexpected death associated with lymphocytic thyroiditis

A forensic autopsy study comprising 125 cases was carried out retrospectively in order to evaluate pathological changes in the thyroid gland in different groups of death. The five groups selected consecutively were: (i) opiate addicts who died from an overdose, (ii) alcoholics who died as a result of their alcohol abuse, (iii) cases of fatal poisoning other than opiate addicts, (iv) unknown cause of death and (v) controls without prior disease. Tissue samples from the thyroid gland were cut and stained with haematoxylin and eosin and van Gieson. Histology examinations were subsequently performed blind with semiquantitative assessment of the following six parameters: (a) height of the follicular epithelium, (b) the amount of lymphocytes, (c) the presence of plasma cells, (d) hyperplastic follicular changes, (e) oxyphilic changes, and (f) fibrosis. The most striking result was the finding of extensive lymphocytic infiltration of the thyroid parenchyma in five of the 124 cases, of which four belonged in the group of 'unknown cause of death'. This discovery leads to reflections regarding lymphocytic thyroiditis as a cause of death, either by itself or in combination with other disorders. Silent (painless) thyroiditis, especially, is easily overlooked at autopsy as there are no macroscopic changes and often no prior symptoms or history of thyroid disease pointing towards this condition. Analyses of thyroid hormones are unreliable in predicting endocrine status in life. Routine microscopy of the thyroid gland is therefore advocated in cases of sudden unexpected death in order to diagnose thyroid disease, in particular silent (painless) thyroiditis.

Low-grade metaplastic adenocarcinoma (carcinosarcoma) of the uterus: report of an unusual case

An unusual low-grade metaplastic carcinoma (müllerian carcinosarcoma) of the uterine corpus occurring in a 45-year-old woman is presented. The tumor was polypoid and showed an initial invasion into the myometrium. The epithelial component was composed of low-grade endometrioid glands that focally showed an unusual oxyphilic change of the cytoplasm. These cells contained only a small amount of mitochondria detected with antimitochondrial antibody. The stromal component contained small round cells of bland appearance and appeared to arise from epithelial cells through a metaplastic process, as a gradual transition between epithelial and stromal cells was often seen. An invasive marginal zone of the tumor showed endometrioid adenocarcinoma pattern without any stromal component. The proliferative activity generally was low. Interestingly, it was clearly accentuated in the epithelial component especially in the peripheral invasive areas, whereas it was very low in the stromal component. The course of disease was indolent. Low-grade müllerian carcinosarcoma is to be distinguished from other biphasic müllerian tumors.

The Phenotype of Hurthle and Warthin-like Papillary Thyroid Carcinomas Is Distinct From Classic Papillary Carcinoma as to the Expression of Retinoblastoma Protein and E2F-1 Transcription Factor

Retinoblastoma protein plays an important role in controlling cell cycle progression. The active form of retinoblastoma protein binds to E2F-1 and inhibits transcription of S phase genes. Overexpression of E2F-1 has been suggested as an important factor in carcinogenesis. The Hurthle cell (HPCA) and Warthin-like (WLPCA) variants of papillary carcinoma are two closely related entities that arise in association with Hashimoto's thyroiditis and share the presence of oxyphilic changes in the lining of epithelial cells and the presence of papillary nuclear features. The current study included formalin-fixed, paraffin-embedded tissues from 58 cases of thyroid papillary carcinoma: 20 HPCA, 6 WLPCA, 22 conventional papillary carcinomas (PCA), and 10 follicular variants of papillary carcinoma (FVPCA). The immunohistochemical studies were performed for retinoblastoma (Rb-1) and E2F-1, (KH95) after heat-induced epitope retrieval. None of the PCA or FVPCA cases were in the positive range for Rb-1. All cases of HPCA and WLPCA of the thyroid showed reactivity in 50% or more of the nuclei in the neoplastic cell population. As for E2F-1, all cases of HPCA and WLPCA showed positive reactivity, whereas none of the PCA or FVPCA cases were in the positive range. In conclusion, HPCA and WLPCA are Rb-positive and E2F-1-positive; PCA and FVPCA are Rb-negative and E2F1-negative. Hurthle metaplastic epithelium in Hashimoto's thyroiditis is Rb-positive and E2F-1-negative. This phenotypic difference is also helpful in distinguishing hyperplastic Hurthle cell proliferation in Hashimoto's thyroiditis from HPCA or WLPCA.

Low frequency of numerical chromosomal aberrations in follicular thyroid tumors detected by comparative genomic hybridization

Follicular thyroid tumors vary from adenomas to widely invasive carcinomas, and a stepwise progression from normal thyrocyte to malignant tumor has been suggested to be due to an accumulation of genetic alterations. We have used comparative genomic hybridization to screen 21 follicular thyroid tumors (8 adenomas and 13 carcinomas) for gains and losses of DNA sequence copy numbers. In general, the tumors showed few alterations involving several different chromosomal regions. The frequency of alterations was similar in the benign (mean, 1.9) and malignant (mean, 1.5) tumors, as well as in minimally (mean, 1.5) and widely invasive carcinomas (mean, 1.6). However, specific loss of 9q13–q21.3 was detected in three tumors, which were all carcinomas showing oxyphilic changes (Hürthle cell carcinomas; P = 0.003). The fact that DNA copy number alterations were found with a similarly low frequency in both benign and malignant follicular thyroid tumors does not support the hypothesis of a multistep tumor progression in these tumors. Genes Chromosomes Cancer 25:349–353, 1999. © 1999 Wiley-Liss, Inc.

Low frequency of numerical chromosomal aberrations in follicular thyroid tumors detected by comparative genomic hybridization

Follicular thyroid tumors vary from adenomas to widely invasive carcinomas, and a stepwise progression from normal thyrocyte to malignant tumor has been suggested to be due to an accumulation of genetic alterations. We have used comparative genomic hybridization to screen 21 follicular thyroid tumors (8 adenomas and 13 carcinomas) for gains and losses of DNA sequence copy numbers. In general, the tumors showed few alterations involving several different chromosomal regions. The frequency of alterations was similar in the benign (mean, 1.9) and malignant (mean, 1.5) tumors, as well as in minimally (mean, 1.5) and widely invasive carcinomas (mean, 1.6). However, specific loss of 9q13-q21.3 was detected in three tumors, which were all carcinomas showing oxyphilic changes (Hürthle cell carcinomas; P = 0.003). The fact that DNA copy number alterations were found with a similarly low frequency in both benign and malignant follicular thyroid tumors does not support the hypothesis of a multistep tumor progression in these tumors. Genes Chromosomes Cancer 25:349-353, 1999.

Presence of endothelin-1 in the normal and pathological human thyroid

An immunohistochemical study with two rabbit polyclonal antibodies I-AR76 and CA-08-351 against Endothelin-1 (ET-1) was performed in 133 human thyroid specimens: 5 normal thyroids, 30 multinodular goiters (15 toxic and 15 nontoxic), 20 Graves' diseases, 5 Hashimoto's thyroiditis, 26 adenomas (6 Hürthle cell, 16 toxic and 4 nontoxic), 30 classic papillary carcinomas, 3 minimally invasive follicular carcinomas, 1 widely invasive follicular carcinoma, 3 undifferentiated carcinomas and 10 medullary carcinoma. All normal thyroids, non toxic multinodular goiters and non toxic adenomas, 4 (66%) Hürthle cell adenomas, 3 (15%) Graves' diseases, 1 (33%) case of minimally invasive follicular carcinoma showed rare follicular cells with weak cytoplasmic immunoreactivity. Many immunoreactive follicular cells, with or without oxyphilic changes, were observed in all specimens of Hashimoto's disease, while the lymphocytic infiltrate was always negative. Twenty-seven (90%) classic papillary carcinomas were positive. Immunoreactivity was intracytoplasmic, weak in 14 cases and intense in 13. The cells of toxic adenoma and toxic multinodular goiter were negative, whereas the acellular stroma was intensely positive in both cases. Medullary and undifferentiated carcinomas were negative. These results show ET-1 immunoreactivity in normal and pathological human thyroids. In particular, the high content of this peptide in the thyroid papillary carcinoma suggests that ET-1, whose mitogenic role has recently been emphasized, could be involved in the growth of this tumor.

Histologic changes in Graves' thyroid gland after 131I therapy for hyperthyroidism.

The effect of 131I therapy was examined in 13 thyroid glands affected by Graves' disease 3 to 29 years after irradiation for hyperthyroidism. All of the patients had clinically palpable thyroid nodules. Two patients were in a latent hypothyroid, 6 in a euthyroid and 5 in a hyperthyroid state. The microscopic changes in the thyroids showed a pattern of multiple adenomatous nodules with cystic changes, marked oxyphilic cell changes with nuclear atypism and various degrees of chronic thyroiditis. Immunohistochemical staining for TG and T4 was negative to mildly positive in these oxyphilic cells and entirely negative for EGF and CEA. The DNA ploidy pattern was diploid pattern in 6 cases. One papillary-type microcarcinoma occurred, but there was no evidence of a relationship between the tumor and the irradiation. The pathologic findings in Graves' thyroid gland after 131I therapy are not specific, but pathologists should differentiate this lesion from adenomatous goiter, which occurs with no apparent cause, or from thyroid carcinoma because of the marked nuclear atypism of this lesion.

Hashimoto's Thyroiditis as a Risk Factor of Thyroid Lymphoma

Hashimoto's thyroiditis (struma lymphomatosa), first described by Hashimoto in 1912, is an autoimmune inflammation of the thyroid commonly affecting middle-aged women. Histologic features of Hashimoto's thyroiditis (HT) include diffuse infiltration of lymphoid cells usually with formation of lymphoid follicles, varying degrees of fibrosis, oxyphilic change or squamous metaplasia in the epithelial cells. When the presence of focal lymphocytic infiltration is assumed to be an adequate criterion for diagnosis of autoimmune thyroiditis, the incidence appears to be as high as 16-23% in elderly females. An etiologically important role of HT in the development of thyroid lymphoma had been postulated, and recently, this was confirmed by epidemiological studies. In this article, a brief review of HT is given, together with results of our studies on thyroid lymphoma, and a discussion in the light of the pertinent literature. Immunologic and immunohistologic studies revealed that all of the thyroid lymphomas were of the B-cell type. Malignant lymphomas developing in patients with other autoimmune diseases such as Sjögren syndrome and rheumatoid arthritis have also been reported to be B-cell derived. Therefore it is suggested that immune deficiency is a causal factor for B-cell lymphoma.

A correlation between the function and the aspiration cytology in chronic thyroiditis (author's transl)

The correlation between the function and the aspiration cytology in chronic thyroiditis was studied. In 184 cases of chronic thyroiditis (hyperthyroid state: 19 cases, euthyroid state: 113 cases, hypothyroid state: 52 cases) and 36 cases of hyperthyroidism, aspiration biopsy was performed by a fine needle of 22 gauge. The smears were stained with May-Grünwald-Giemsa and Papanicolaou's stain. In all specimens, the cytological investigations were done as for follicular epithelial cells, oxyphilic changes of follicular epithelial cells and non-epithelial cells, oxyphilic changes of follicular epithelial cells and non-epithelial cells per se. The relationships between the thyroid function and cytological pictures in chronic thyroiditis were studied. The following conclusions were obtained by this study: 1. Compared to hyperthyroidism, chronic thyroiditis has the following characteristic cytological picture: i) Hyperplasia of small follicular cells with many lymphoid cells ii) Oxyphilic changes in follicular cells, lymphoid cells, plasma cells and reticulum cells 2. As for the correlation between the cytological findings and the thyroid function or thyroid antibodies, the following conclusions were obtained: i) There is a negative correlation between the grade of the number of oxyphilic cells or lymphocytes and the titer of the microsome test (MCHA). (p less than 0.005)