Focal Lymphocytic Thyroiditis Research Articles

Lymphocytic Thyroiditis Transcriptomic Profiles Support the Role of Checkpoint Pathways and B Cells in Pathogenesis.

Background: Autoimmune thyroid diseases are the most common types of autoimmune diseases, but their physiopathology is still relatively unexplored. Genotype-tissue expression (GTEx) is a publicly available repository containing RNAseq data, including profiles from thyroid. Approximately 14.8% of these glands were affected by focal lymphocytic thyroiditis and 6.3% were annotated as Hashimoto. We interrogated these data to improve the characterization of infiltrating cells and to identify new molecular pathways active in autoimmune thyroiditis. Materials and Methods: Histological GTEx images of 336 thyroid samples were classified into three categories, that is, non-infiltrated thyroid, small focal infiltrated thyroid, and extensive lymphoid infiltrated thyroid. Differentially expressed genes among these categories were identified and subjected to in silico pathway enrichment analysis accordingly. CIBERSORTx deconvolution was used to characterize infiltrating cells. Results: As expected, most of the transcriptional changes were dependent on tissue infiltration. Upregulated genes in tissues include-in addition to lineage-specific B and T cell genes-a broad representation of inhibitory immune checkpoint receptors expressed by B and T lymphocytes. CIBERSORTx analysis identified 22 types of infiltrating cells showed that T cells predominate 3:1 over B cells in glands with small infiltrates, only by 1.7:1 in those with large infiltrates. Follicular helper and memory CD4 T cells were significantly more abundant in glands with large infiltrates (p < 0.0001), but the most prominent finding in these glands was an almost sixfold increase in the number of naive B cells (p < 0.0001). A predominance of M2 macrophages over M1 and M0 macrophages was observed in the three gland categories (p < 0.001). Conclusions: Analysis of transcriptomic RNA-seq profiles constitutes a rich source of information for the analysis of autoimmune tissues. High-resolution transcriptomic data analysis of thyroid glands indicates the following: (a) in all infiltrated glands, active autoimmune response coexists with suppressor counteracting mechanisms involving several inhibitory checkpoint receptor pairs, (b) glands with small infiltrates contain an unexpected relatively high proportion of B lymphocytes, and (c) in highly infiltrated glands, there is a distinct transcriptomic signature of active tertiary lymphoid organs. These results support the concept that the autoimmune response is amplified in the thyroid tissue.

Cytokeratin 5/6 and P63 immunophenotype of thyroid lymphoepithelial complexes.

Thyroid lymphoepithelial complexes (LECos) are rare, being reported in lymphoma, Graves-Basedow disease, Hashimoto thyroiditis, pericarcinomatous thyroid or in the context of branchial cleft-like cysts. Here we report immunohistochemical expression of cytokeratin 5/6, P63 and TTF1 in 6 cases of thyroid LECos. Two cases had carbimazole treatment for hyperthyroidia and Graves disease. Anti-thyroglobulin, -thyroperoxidase or -TSH antibodies were detected in 4 cases. NSAID or poviodone iodine allergy were present in 2 cases. The treatment consisted in total thyroidectomy or lobectomy. Microscopy showed nodular goiter and focal lymphocytic thyroiditis. Basaloid LECos were seen in all thyroids while squamoid LECos in 2. Associated lesions were papillary thyroid microcarcinoma (2 cases), solid cell nest, thyroglosal duct remnant, lymphoepithelial cyst and thymus-parathyroid unit (one case each). Cytokeratin 5/6 was expressed in both squamoid and basaloid LECos along with P63. TTF1 expression was faint or absent. In conclusion LECos may occur in the context of autoimmune thyroiditis or of a specific immune susceptibility background. The expression of CK5/6 and of P63 suggests a squamous differentiation including in the basaloid LECos. The etiologic relevance of these immunostainings remains limited although rather suggestive of a metaplastic process than of migration-abnormalities.

Focal Lymphocytic Thyroiditis Nodules Share the Features of Papillary Thyroid Cancer on Ultrasound.

PurposeIt is often difficult to discriminate focal lymphocytic thyroiditis (FLT) or adenomatous hyperplasia (AH) from thyroid cancer if they both have suspicious ultrasound (US) findings. We aimed to make a predictive model of FLT from papillary thyroid cancer (PTC) in suspicious nodules with benign cytologic results.Materials and MethodsWe evaluated 214 patients who had undergone fine-needle aspiration biopsy (FNAB) and had shown thyroid nodules with suspicious US features. PTC was confirmed by surgical pathology. FLT and AH were confirmed through more than two separate FNABs. Clinical and biochemical findings, as well as US features, were evaluated.ResultsOf 214 patients, 100 patients were diagnosed with PTC, 55 patients with FLT, and 59 patients with AH. The proportion of elevated thyrotropin (TSH) levels (p=0.014) and thyroglobulin antibody (Tg-Ab) or thyroid peroxidase antibody (TPO-Ab) positivity (p<0.001) in the FLT group was significantly higher than that in the PTC group. Regarding US features, absence of calcification (p=0.006) and "diffuse thyroid disease" (DTD) pattern on US (p<0.001) were frequently seen in the FLT group. On multivariate analysis, Tg-Ab positivity, presence of a DTD pattern on US, and absence of calcification in nodules were associated with FLT with the best specificity of 99% and positive predictive value of 96%. In contrast, a taller than wide shape of nodules was the only variable significant for differentiating AH from PTC.ConclusionSuspicious thyroid nodules with cytologic benign results could be followed up with US rather than repeat FNAB, if patients exhibit Tg-Ab positivity, no calcifications in nodules, and a DTD pattern on US.

Sonographically Suspicious Thyroid Nodules with Initially Benign Cytologic Results: The Role of a Core Needle Biopsy

To evaluate the diagnostic role of core needle biopsy (CNB) in sonographically suspicious thyroid nodules with initially benign cytologic results through a histologic analysis of CNB specimens. Between October 2008 and July 2011, 88 patients underwent ultrasound (US)-guided CNB for initially benign cytologic results with suspicious US features at our institution. In all, 85 patients with 85 focal thyroid nodules were included in the study after surgery or concordant benign readings following fine-needle aspiration biopsy (FNAB) and CNB. We evaluated the risk of malignancy, diagnostic performance of CNB, and histologic findings for these nodules. Of the 85 nodules, 28 (32.9%) were histologically upgraded on CNB specimens including one case of atypia of undetermined significance (AUS), seven cases of follicular neoplasm, one case of suspicious for malignancy, and 19 cases of malignancy. Of these, 27 (31.8%) were finally confirmed as malignant, and one as follicular adenoma at surgery. The 27 malignant nodules included 21 papillary thyroid carcinomas (PTCs), five follicular thyroid carcinomas, and one Hürthle cell carcinoma. All PTCs were diagnosed from CNB readings of AUS suspicious for malignancy or malignancy. Follicular thyroid carcinomas and Hürthle cell carcinoma were diagnosed from CNB readings of follicular neoplasm. Histologic analysis of benign CNB specimens revealed severe fibrosis (96.4%), hemosiderin (21.4%), calcification (17.9%), granulation tissue (12.5%), and focal lymphocytic thyroiditis (12.5%). The histologic information obtained by analysis of CNB specimens may enable more confident diagnosis for benign nodules with suspicious US features and reduce the need for repetitive FNABs or diagnostic surgery.

Cell-Type-Specific Expression of STAT Transcription Factors in Tissue Samples from Patients with Lymphocytic Thyroiditis

Expression of cytokine-regulated signal transducer and activator of transcription (STAT) proteins was histochemically assessed in patients diagnosed as having Hashimoto's disease or focal lymphocytic thyroiditis (n = 10). All surgical specimens showed histological features of lymphocytic thyroiditis, including a diffuse infiltration with mononuclear cells and an incomplete loss of thyroid follicles, resulting in the destruction of glandular tissue architecture. Immunohistochemical analysis demonstrated differential expression patterns of the various members of the STAT transcription factors examined, indicating that each member of this conserved protein family has its distinct functions in the development of the disease. Using an antibody that specifically recognized the phosphorylated tyrosine residue in position 701, we detected activated STAT1 dimers in numerous germinal macrophages and infiltrating lymphocytes as well as in oncocytes. In contrast, STAT3 expression was restricted to epithelial cells and showed a clear colocalization with the antiapoptotic protein Bcl-2. Moreover, expression of phospho-STAT3 was associated with low levels of stromal fibrosis, suggesting that STAT3 serves as a protective factor in the remodeling of the inflamed thyroid gland. Phospho-STAT5 immunoreactivity was detected in numerous infiltrating cells of hematopoietic origin and, additionally, in hyperplastic follicular epithelia. This tissue distribution demonstrated that activated STAT5 molecules participate in both lymphocytopoiesis and possibly also in the buildup of regenerating thyroid follicles. Taken together, the cell-type-specific expression patterns of STAT proteins in human lymphocytic thyroiditis reflect their distinct and partially antagonistic roles in orchestrating the balance between degenerating and regenerating processes within a changing cytokine environment.

Thyroid papillary carcinoma with solid sclerosing change in IgG4‐related sclerosing disease

IgG4-related sclerosing disease (IgG4-RSD) is an inflammatory and fibrosing disorder characterized by lymphoplasmacytic inflammation with infiltration of various organs, including the pancreas, bile ducts, lung, kidney, and retroperitoneum. As for malignancy in IgG4-RSD, only limited literature is available. We report here a case of thyroid papillary carcinoma showing unique morphology in IgG4-RSD. Solid tumor nests were surrounded by dense IgG4-positive plasma cells and fibrosis at both the primary site and metastatic lymph nodes. In contrast the background thyroid showed focal lymphocytic thyroiditis. IgG4-related sclerosing sialadenitis and autoimmune pancreatitis were also diagnosed, and prednisolone treatment improved symptoms and serum IgG4 abnormality. To the best of our knowledge, this is the first documentation of a malignancy of the thyroid gland occurring in a background of IgG4-RSD. A brief review of the literature on the relationship between IgG4 and malignancy is included.

Toxic Multinodular Goiter with Low Radioactive Iodine Uptake

A 74-year-old woman was referred to our hospital for goiter and persistent thyrotoxicosis. She had no signs of ophthalmopathy. She was not taking thyroid hormone. Thyroid CT revealed multiple nodules. The thyroid gland was not detected on (99m)Tc scintigraphy, (123)I uptake rate was 4.5% at 24 hours without hot nodules, and aberrant goiter was negative. After partial thyroidectomy, she was treated with levothyroxine. TRAb was undetectable during the disease course, and focal destructive change or chronic lymphocytic thyroiditis on the pathological specimens was not evident. We report a rare case of toxic multinodular goiter with low radioactive iodine uptake.

Measuring thyroglobulin autoantibodies by sensitive assay is important for assessing the presence of thyroid autoimmunity in areas with high iodine intake

There is some debate over the clinical utility of measuring serum TgAb to assess the presence of thyroid autoimmunity. To clarify the relationship between TgAb levels and thyroid autoimmunity, a histological examination of thyroid tissue was carried out on unselected living individuals with detectable serum TgAb. 146 patients with a pathological diagnosis of follicular adenoma were selected as subjects. Focal lymphocytic infiltration (FLI) was defined as lymphocytic aggregates of more than 200 in number. A thyroid gland in which 0-1 FLI was observed in a few visual fields of low magnification (20 x 4) in thyroid tissue adjacent to a tumor was judged to be normal and a thyroid gland in which 2 or more FLI were observed was diagnosed as focal lymphocytic thyroiditis (FLT). Serum levels of TgAb and TPOAb were measured by radioimmunoassay. Out of the 146 patients, 18 had detectable serum TgAb and 16 had detectable serum TPOAb. All but one (i.e. 94%) of the 18 TgAb positive patients had FLT and 14 out of the 16 TPOAb positive patients had FLT. The sensitivity (17/32; 53.1%) and specificity (113/114; 99.1%) of TgAb for detecting FLT were higher than those (14/32; 43.7% and 112/114; 98.2%) of TPOAb, but the differences were not significant. In 9 patients who were TgAb positive (but TPOAb negative), 8 (88.9%) had FLT. These results throw doubt on the Laboratory medicine practice guidelines published in Thyroid 2003, in which measuring TgAb is not usually necessary for detecting autoimmune thyroid disease. At least measuring TgAb by sensitive assay is useful for assessing the presence of thyroid autoimmunity in Japan, an area with high iodine intakes.

Human galectin-3 immunoexpression in thyroid follicular adenomas with cell atypia

Human galectin-3 (hgal-3) is a beta-galactoside binding protein involved in a number of physiological and pathological processes. Increasing hgal-3 immunoexpression has been reported in several human tumors, including thyroid carcinomas, but not in benign thyroid lesions. We analyzed the immunolocalization of hgal-3 in cell compartments of benign and malignant thyroid lesions. Hgal-3 immunoperoxidase reaction was carried out on 133 thyroid tissue samples obtained from 113 patients; 20 of these were normal (NT), 85 were benign thyroid lesions [20 colloid nodules (CN), 21 nodular hyperplasias (NH), 7 focal lymphocytic thyroiditis (FLT), 15 Hashimoto's thyroiditis (HT), 22 follicular adenomas (FA)], 25 differentiated carcinomas [15 papillary carcinomas (PC), 6 follicular carcinomas (FC) and 4 Hürthle cell carcinomas (HC)] and 3 anaplastic carcinomas (AC). Among the malignant thyroid lesions, hgal-3 was detected in 12/15 (80%) PC, 3/4 (75%) HC and in 4/6 (66.6%) FC, but in none of the 3 AC. Conversely, hgal-3 immunoexpression was absent in NT and in all benign thyroid lesions, but 1/15 HT and 10/22 (45.4%) FA. In the latter, hgal-3 was mostly expressed in microfollicular areas and in five of the six atypical FA. Hgal-3 cytoplasmic-perinuclear immunolocalization was observed in the majority of thyroid carcinomas and in more than half of the FA, theoretically suggesting an involvement of this protein in thyroid tumorigenesis throughout an antiapoptotic activity. Moreover, hgal-3 expression in FA might anticipate the likelihood of evolution of these benign lesions towards malignancy.

Cytologic Characterization of Postiodization Residual Goiter in Schoolchildren by Fine Needle Biopsy

To determine the relevance and utility of fine needle biopsy (FNB) for providing a tissue-level diagnosis during a community-based survey of postiodization residual goiter in schoolchildren in India. A total of 14,762 schoolchildren (56.0% girls and 44.0% boys), aged 6-18 years, with a countrywide representation, were clinically screened for the presence of goiter. FNB was performed under field conditions by means of a nonaspiration technique from both lobes of goitrous glands. The cytologic diagnosis and findings were correlated with age, sex, goiter grade and biochemical parameters of serum T4, TSH, thyroid microsomal (TMA) and thyroglobulin (TGA) antibodies. The overall prevalence of goiter was 23.0%, with a greater frequency in girls (27.1%) than boys (17.8%). FNB was successful in 75.6% of subjects without any significant complications. The cytologic diagnoses in 1,312 successful cases were colloid goiter (92.8%), Hashimoto's thyroiditis (4.6%), focal lymphocytic thyroiditis (1.7%) and hyperplastic goiter (0.9%). Autoimmune thyroiditis (AIT), which accounted for only 6.3% cases, showed a strikingly different age-specific prevalence between girls and boys. Serologic markers of TMA and TGA at various titers were observed to lack requisite sensitivity and specificity for establishing an accurate diagnosis of AIT. The nonaspiration technique of FNB is capable of yielding valuable diagnostic information during an epidemiologic survey of goiter. The technique can be easily performed under field conditions on children without significant complications. FNB is preferable to serologic markers for accurate diagnosis of AIT. A relatively low frequency of AIT, as observed in the present study, raises the possibility of a significant role of environmental goitrogens as the underlying pathogenetic factor in postiodization residual goiter in Indian schoolchildren.

Latent carcinoma of the thyroid in Austria: a systematic autopsy study.

Data concerning the incidence of latent thyroid carcinoma (LTC) in populations with endemic goiter are scarce. Despite the introduction of iodine goiter prophylaxis in the early sixties, iodine supply is still insufficient in Austria and goiter remains endemic. This is the first detailed study dealing with epidemiological features of LTC at autopsy in Austria. A total of 118 thyroid glands were included in the study. The glands were serially sectioned at 2- to 3-mm intervals, embedded in paraffin and histologically examined for the presence of LTC. In addition, the incidence and severity of lymphocytic thyroiditis (LT) were evaluated. Ten thyroids were found to contain LTC (8.6%). All were of the papillary type. The mean tumor dimension was 4.9 mm +/- 3.2, the smallest lesion measuring 1 mm. Only the largest tumor slightly exceeded the extent of a microcarcinoma and measured 10.5 mm. Multifocal disease was present in three cases (30%). The prevalence of latent papillary thyroid carcinoma (LPTC) was 6.6% (n = 4) in females and 10.5% (n = 6) in males. The mean age of the subjects with LPTC was 67.7 +/- 14.4 yr, range 37 to 77 yr. Goitrous thyroids were seen in 33 cases (28%): One gland was diffusely enlarged and 32 (27.1%) enlarged glands were nodular goiters. The overall prevalence of LT was 30.5% (n = 36) and the only type of thyroiditis observed was focal lymphocytic thyroiditis (FLT). There was no correlation between the presence of LPTC and goiter, the presence of FLT and the subjects' age and sex. The incidence of LPTC in Austria is similar to that in nongoitrous regions. The adult population at large seems to be uniformly exposed to factors involved in the initiation and early growth of papillary thyroid carcinoma (PTC). This suggests that the levels of iodine intake only play a minor role in the early phase of the carcinogenesis of PTC, but may be of some importance in the progression of LPTC to clinically evident PTC.

Measurement of anti-thyroglobulin and anti-thyroid peroxidase antibodies using highly sensitive radioimmunoassay: an effective method for detecting asymptomatic focal lymphocytic thyroiditis in the elderly.

Subclinical thyroiditis or thyroid dysfunction is relatively common in the elderly. To estimate the effectiveness of measurement of serum levels of anti-thyroglobulin and anti-microsomal or thyroid peroxidase antibodies for detecting focal lymphocytic thyroiditis (FLT) in the elderly, we examined the relationships between antibody titer and postmortem histological finding of the thyroid gland in 180 consecutive autopsies (69 women and 111 men) over 60 years of age without any overt clinical thyroid or collagen diseases. FLT was found in 25 cases (13.9%) with female predominance (21.7% in female vs. 9.0% in male). Measurements of serum levels of anti-thyroglobulin and anti-thyroid peroxidase antibodies by radioimmunoassay (TgAb and TPOAb, respectively) were compared with the measurements of anti-thyroglobulin and anti-microsomal antibodies by a hemagglutination technique (TGHA and MCHA, respectively), using sera from 25 patients with FLT and age- and sex-matched 51 patients without FLT. Among 25 cases with FLT, TgAb and TPOAb were positive in 17 (68%) and 12 (48%), respectively. There was a close relationship between degree of FLT and serum level of TgAb or TPOAb (P<0.0001). On the other hand, TGHA and MCHA were positive only in 8 (32%) and 10 (40%), respectively. TgAb and TPOAb were more sensitive than TGHA (68% vs. 32%, P<0.05) and MCHA (48% vs. 40%) to detect FLT. Positive findings in either TgAb or TPOAb significantly improved sensitivity (76%) compared with that of TGHA or MCHA (44%) (P<0.05). Specificities of combined measurements of TgAb and TPOAb (90%) were not significantly different from those of TGHA and MCHA (100%). These findings indicate that TgAb is a more sensitive method for detecting FLT and that its diagnostic sensitivity for FLT increases by using it in combination with TPOAb. Therefore, in the elderly without clinically or biochemically overt thyroid dysfunction, positive TgAb and/or TPOAb could imply presence of FLT, and their titers might reflect degree of inflammation.

Intrathyroidal Lymphoepithelial Cyst. A Report of Two Cases Not Associated with Hashimoto's Thyroiditis

Two cases of intrathyroidal lymphoepithelial cyst are described. Both of them were solitary, one being found incidentally in a patient operated on for a multinodular goiter, the other being clinically obvious as a cold nodule. They exhibited features of cysts of branchial cleft origin, i.e. squamous cell lining epithelium and abundant lymphoid tissue with reactive germinal centers. The thyroid gland parenchyma showed a discrete lymphoid infiltration consistent with the diagnosis of focal lymphocytic thyroiditis. In the first case a single epidermoid solid cell nest was found. The histogenesis of intrathyroidal lymphoepithelial cysts remains unclear, but their origin from cystically degenerated ultimobranchial body remnants (solid cell nests) seems to be most probable. This assumption is supported by a similar immunohistochemical profile of solid cell nests and epithelial cells lining the cysts and also by the presence of one solid cell nest in the proximity to the cyst in one of our cases.

Enhanced cellular proliferative activity and cell death in chronic thyroiditis and thyroid papillary carcinoma.

For the analysis of cellular proliferative activity and cell death in thyroid diseases, the Ki-67 labeling index, bcl-2 protein expression and cell death of follicular epithelia by immunohistochemistry and in situ DNA nick-end labeling methods were evaluated in normal thyroid tissues as well as in surgical specimens from cases of Hashimoto's disease (16 cases), focal lymphocytic thyroiditis (13 cases), Graves' disease (15 cases), follicular adenoma (20 cases) and papillary carcinoma (43 cases). Cellular proliferative activity and cell death were both enhanced in cases of thyroiditis, including Hashimoto's disease and focal lymphocytic thyroiditis. Thyroids from patients with follicular adenoma and papillary carcinoma also showed increased cellular proliferative activity and cell death. In addition, predominant high cellularity and partial loss of bcl-2 protein expression in papillary carcinoma suggested that the overgrowth and dedifferentiation were associated with malignancy.

Amyloid Goiter:A Clinicopathologic Study of 14 Cases and Review of the Literature

The authors report the clinicopathologic features of 14 cases of amyloid goiter (AG). Eleven patients were males and three females with ages ranging from 23 to 75 years (median, 54 years). Eight patients had secondary amyloidosis and six had primary amyloidosis. Nine cases were identified at autopsy. In symptomatic patients (n = 5), the clinical presentation included a nontender, rapidly enlarging neck mass with associated dysphagia, dyspnea or hoarseness. Clinical or laboratory evaluation failed to detect evidence of thyroid dysfunction. The histologic appearance of the thyroid predominantly consisted of diffuse amyloid deposition surrounding thyroid follicles. In two cases, a nodular pattern of amyloid deposition was seen resulting in compression and distortion of the follicular architecture. Areas of mature adipose tissue and focal lymphocytic thyroiditis with or without foreign-body type-giant cells were seen in approximately one third of the cases. Confirmation of amyloid was made by the presence of congophilia and apple-green birefringence under polarized-light microscopy. Immunohistochemical evaluation demonstrated the presence of amyloid A immunoreactivity. No Immunoreactivity was seen with calcitonin or thyroglobulin. Fine-needle aspiration may facilitate the diagnosis, as occurred in one the patients. In symptomatic patients, thyroidectomy is warranted to alleviate pressure symptoms.

ThinPrep versus conventional smear cytologic preparations in the analysis of thyroid fine-needle aspiration specimens.

Paired fine-needle aspiration specimens were analyzed from 41 surgically resected thyroid nodules, to compare diagnostic accuracy, amount (absent, mild, moderate, or marked) and pattern (diffuse, droplets, or both) of colloid, nuclear detail (poor, satisfactory, or excellent) and cytoplasmic detail (intact or disrupted) in ThinPrep (TP) (Cytyc, Marlborough, MA) versus conventional smear (CS) cytologic preparations. The 41 surgical specimens included 25 colloid nodules, 6 papillary carcinomas, 4 follicular adenomas, 2 minimally invasive (encapsulated) follicular carcinomas, 3 Hashimoto's thyroiditis, and 1 Grave's disease. Both techniques identified seven of the eight carcinomas with the minimally invasive follicular carcinomas categorized as hypercellular follicular nodule, possibly malignant (HCFN). One papillary carcinoma was classified as a HCFN by both TP and CS techniques. The four follicular adenomas were classified as HCFN based on the TP slides. One oxyphilic follicular adenoma, associated with focal lymphocytic thyroiditis, was misinterpreted as Hashimoto's thyroiditis on a conventional smear. Three colloid nodules were interpreted as HCFN based on the TP slides. Two of these were similarly classified based on the conventional smear. ThinPrep slides contained less colloid and the colloid occurred as droplets rather than a diffuse pattern. TP slides had better nuclear detail but more often disrupted cytoplasm. In conclusion, the TP process does alter some cellular features; however, we experienced similar diagnostic accuracy with the TP and conventional smear preparations.

Lymphocytic infiltration in focal thyroiditis: An ultrastructural case study

In autoimmune thyroiditis, infiltrating lymphocytes play an important role in the disease process since they are known to release cytokines which can alter thyroid functions. The degree and site of lymphocytic infiltration in the thyroid gland have been used to differentiate between Hashimoto's disease and focal lymphocytic thyroiditis. Intraluminal lymphocytes have been reported to be absent in focal thyroiditis but present in Hashimoto's disease. However, we demonstrate here by transmission electron microscopy, that extrafollicular and intrafollicular lymphocytes could be present in focal lymphocytic thyroiditis. This seems to support the notion that focal lymphocytic thyroiditis could represent part of the spectrum of autoimmune thyroiditis and Hashimoto's thyroiditis.

ONCOCYTES OF THE THYROID: A NEUTRAL RED DYE UPTAKE STUDY

Oncocytosis and oncocytomas have attracted attention because on the one hand there have been reports of the favourable prognosis and generally benign nature of oncocytic tumours, while on the other hand, Hurthle cell change in thyroid neoplasms have been reported to be correlated with aggressive biological behaviour and a significantly worse clinical course. Presently, there appear to be two schools of thought on the significance of oncocytosis: (i) a process where there is redifferentiation of cells with involvement in the pathogenesis of cancer; and (ii) a compensatory process for 'functional exhaustion' of the cell. Many aspects of oncocytosis seem unclear. In this study, transmission electron microscopy is used to demonstrate the presence of thyroid oncocytes in the hemithyroidectomy specimen of a patient with focal lymphocytic thyroiditis. Tissue sections from this specimen did not display preferential uptake of neutral red dye, a distinctive characteristic of M-phase cancer cells which was previously reported. The findings seem to suggest that oncocytes are not cells with distinctive proliferative potentials. If that were the case, then oncogenesis or cancer cell progression and oncocytosis may not be convergent processes.

Chronic Thyroiditis with Painful Tender Thyroid Enlargement and Transient Thyrotoxicosis

Clinical and laboratory findings and long term outcome (1.5-9 yr) in 7 women and 1 man with chronic thyroiditis (CT) who had painful tender thyroid enlargement were evaluated and compared with those in 11 women with subacute thyroiditis (SAT). Histological features consistent with SAT were not demonstrable, and various forms of CT (fibrous variant, diffuse, or focal lymphocytic thyroiditis) were observed. There were no differences in mean age, duration of symptoms, erythrocyte sedimentation rate, and C-reactive protein values in the 2 diseases. Seven patients had a history of goiter, and none had a history of a preceding upper respiratory tract infection. The mean white blood cell count was significantly lower in CT than in SAT patients. Six CT patients had transient thyrotoxicosis with a marked depression of radioactive iodine uptake. Mean serum T4 and T3 levels and T3 to T4 ratio in these 6 patients did not differ from those in the SAT patients. Five (all with high antimicrosomal antibody titers) of 8 CT patients developed persistent hypothyroidism. In contrast, none of the SAT patients became permanently hypothyroid. TSH binding inhibitory immunoglobulins and thyroid stimulation-blocking antibody at recent examination were negative in these 5 patients. Patients with this disorder present with transient thyrotoxicosis, with a marked depression of the thyroid radioactive iodine uptake, and often develop goitrous or atropic persistent hypothyroidism. This disorder may represent acute exacerbation of an underlying immunological process during the course of CT. To differentiate this syndrome from SAT, thyroid biopsy is necessary.

Studies of hypothyroidism in patients with high iodine intake.

Twenty-two patients with spontaneously occurring primary hypothyroidism were studied to evaluate the spontaneous reversibility of the hypothyroid state. Twelve (54.5%) became euthyroid after restriction of iodine intake for 3 weeks (reversible type). In the remaining 10 patients, thyroid function did not improve with restriction of iodine alone, and thus, replacement therapy was required, (irreversible type). In the reversible type, 1) radioactive iodine uptake after 1 week of restricted iodine intake was higher than in the irreversible type [50.0 +/- 12.2% (+/- SD) vs. 4.3 +/- 3.2%; P less than 0.01], 2) the perchlorate discharge test was positive in 2 of 10 patients, and 3) the iodine-perchlorate discharge test, carried out in 7 of 8 patients with negative perchlorate discharge test, was positive in 6. Seven patients with the reversible type were given 25 mg iodine daily for 2-4 weeks; all became hypothyroid again. Two patients had a history of habitual ingestion of seaweed (25.4 and 43.1 mg iodine, respectively), but the remaining 10 patients ingested ordinary amounts of iodine (1-5 mg) daily. The patients with reversible hypothyroidism had focal lymphocytic thyroiditis changes in the thyroid biopsy specimen, whereas those with irreversible hypothyroidism had more severe destruction of the thyroid gland. These results indicate the existence of a reversible type of hypothyroidism sensitive to iodine restriction and characterized by relatively minor changes in lymphocytic thyroiditis histologically. Attention should be directed to this type of hypothyroidism, because thyroid function may revert to normal with iodine restriction alone.