MIB-1 immunohistometry of follicular adenoma and follicular carcinoma of the thyroid gland

OBJECTIVE: To analyze cellular proliferative activity, MIB-1 immunopositivity of normal tissue (n = 20), follicular adenoma (n = 30) and follicular carcinoma (n = 32) of the thyroid gland was analyzed by means of immunohistometry. STUDY DESIGN: Immunohistochemical reactions were performed on 3-micron sections from routinely formalin fixed and paraffin embedded surgical specimens using an indirect peroxidase method. The rate of immunostained cells was determined using the CM-2 TV image analysis system (Hund, Wetzlar, Federal Republic of Germany). Forty viewing fields (1.94 mm2) were measured with 20:1 objective magnification. An average of 5,965 cells were assessed in each case. RESULTS: Mean MIB-1 immunopositivity was higher in follicular carcinoma (average, 2.30%) and follicular adenoma (0.58%) than in normal thyroid tissue (0.14%). The distribution of single values differed significantly between groups (P < .001). To test the suitability of MIB-1 immunohistometry for the differential diagnosis of follicular adenoma and follicular carcinoma, different four-field tables with varying thresholds were calculated. Using a threshold of 0.9%, follicular carcinoma could be detected with a sensitivity of 75% (24/32) and a specificity of 83% (25/30). If a specificity of 90% is required (27/30), the sensitivity of the test decreases to 69% (22/32), based on a threshold of 1.1%. CONCLUSION: As some overlap of single values has to be considered, MIB-1 immunohistometry, although presenting new insights into the proliferative potential of thyroid lesions, is of only limited value for the differential diagnosis of follicular lesions in routine surgical pathology.     

Ultrastructural pathology of the thyroid folliculo-papillary and follicular carcinoma

Twenty cases of thyroid carcinoma (10 follicular and 10 folliculo-papillary) were ultrastructurally studied. In the follicular carcinoma the most striking features were: microfollicular cavities with microvilli from the apical surface of the tumorous cells, intracellular microlumens, swollen mitochondria sometimes containing electrondense bodies and tightly packed filaments. In the solid sheaths light and dark cells were present. Golgi complexes were disposed in small dense cristae. The nuclei were large, round, oval or with a folded appearance. In the folliculo-papillary carcinoma were found nuclei with an irregular shape containing stage I and stage II inclusions, dilated endoplasmic sacks, closely packed, sometimes dystrophic mitochondria, dense bodies or tightly packed parallel filaments and numerous phagolysosomes. The peroxidase activity wa present as black precipitates in the nuclear envelope or around colloid droplets. The acid phosphatase activity was found as unhomogeneous precipitates inside the lysosomes. From this study it could be concluded that the follicular and folliculo-papillary carcinomas have some common ultrastructural features; the ultrastructural and cytoenzymological patterns suggest marked alteration of the synthesis, storage and secretion of thyroid hormones.     

Planimetric studies on fine needle aspirates from follicular adenoma and follicular carcinoma of the thyroid

A planimetric study was performed on fine needle aspiration biopsy smears from 21 follicular thyroid adenomas, 13 follicular thyroid carcinomas and 7 nontoxic goiters. The nuclear and the cytoplasmic projected areas were measured in each smear on 50 cells with intact nuclei. The nuclear-cytoplasmic area was calculated. Significant differences in mean nuclear area were found between benign and malignant follicular neoplasms and between neoplastic cells and cells from nontoxic goiter. Planimetry of cells aspirated from follicular neoplasms permitted differentiation between carcinomas and adenomas with a high degree of statistical probability.     

Benign follicular thyroid lesions versus follicular variant of papillary carcinoma: differentiation by architectural pattern

Differentiation between benign and malignant follicular lesions is one of the difficult diagnostic areas in thyroid fine needle aspiration (FNA). Nuclear criteria are usually used to distinguish between them. In this study the microarchitectural pattern of common benign follicular lesions, namely nodular hyperplasia (NH) and follicular adenoma (FA) were analysed in comparison with those of follicular variant of papillary carcinoma (FVPC) in order to aid in their differentiation. The FNA smears of histologically proven cases of FVPC, NH and FA were reviewed and compared. The microarchitectural features of FVPC, NH and FA were described. Three cytological features--multi-layered rosettes, branching monolayered sheets and balls of thick pinkish colloid--were exclusively observed in FVPC. Hyperplastic papillae with intact follicles and colloid were frequently seen in NH, 83% and 100%, respectively. Albeit less frequently, they were also noted in FVPC, 25% and 75% of cases, respectively. These overlapping features make the distinction between FVPC and NH sometimes difficult; however, assessing the smears for the specific features of FVPC may help in their differentiation. None of the aforementioned microscopic findings with the exception of the seldom presence of colloid were documented in FA. The crowded clusters of follicular cells were seen both in FA and FVPC; however, they were complex and branching in the latter and round to oval in the former. Finally, smears with good recovery of material are indispensable for the identification of these helpful microarchitectural patterns.     

Fine needle aspiration cytology of follicular variant of papillary carcinoma of thyroid

In this retrospective study, we tried to ascertain the fine needle aspiration cytology (FNAC) features of six histopathologically proven cases of the follicular variant of papillary carcinoma of thyroid (FVPCT). These proven cases were diagnosed from 1998-2000. May-Grunwald-Giemsa and haematoxylin & eosin stained FNAC smears were studied independently by two observers (MP and PD) for detailed cytological features. A comparison of the cytological features was undertaken with those reported in the literature. There were six cases of which only one case was diagnosed as FVPCT while the other five cases were diagnosed as follicular neoplasm (four cases) and neoplasm unclassifiable (one case) on FNAC smears. All these cases showed abundant cellularity with a prominent follicular pattern. No papillae were identified in any of the cases. Syncytial clusters (five cases), nuclear grooves (six cases), nuclear inclusions (one case) and chewing gum colloid (three cases) were noted in variable proportions. We suggest that a differential diagnosis of FVPCT should be considered if the cytology smears show abundant cellularity, syncytial clusters and follicular arrangement along with thick colloid.     

Proliferative activity of papillary carcinoma and benign papillary hyperplasia of thyroid follicular cells

Papillary structures of follicular cells are observed in nodular goiter, cysts, hyperplastic areas of follicular tumors, Graves' disease, thyroiditis and carcinomas. The distinction of papillary carcinomas from benign lesions has important implication for clinical management. The aim of the study was to test a marker of proliferation activity (MIB-1) in the diagnosis of benign and malignant thyroid papillary proliferation. The study was carried out in 98 women with papillary carcinoma, nodular goiter. intracystic proliferation. Graves' disease and hyperplastic areas of follicular benign tumors. The formalin fixed, paraffin-embedded specimens were microscopically examined using HE staining and immunostaining with MIB-1 antibody (DAKO). The proliferative index (PI) was significantly higher in malignant than in benign papillary hyperplasia. Our results may provide additional information for differential papillary proliferation diagnosis by FNAB.     

Allelotyping of follicular thyroid tumors

To elucidate further the genetic mechanisms for follicular thyroid tumor development and progression, we allelotyped follicular thyroid tumors and other thyroid lesions from 92 patients. In general, a low frequency of loss of heterozygosity (LOH) was found, the highest being for chromosomes 3q, 10q, 11p, 11q, 13q, and 22q (10%–15%). However, detailed study of LOH of these chromosome arms with regard to the different histopathological diagnoses indicates that a locus on chromosome 10q may be involved in follicular thyroid tumor progression. In addition, the majority of Hürthle cell adenomas showed LOH on either chromosome 3q or 18q, in contrast to the other tumor types. This discrepancy in genetic alterations may contribute to the divergent clinical features occurring in these tumors.     

Cytologic findings in the follicular variant of papillary carcinoma of the thyroid.

Fine needle aspirates from 8 thyroid papillary carcinomas, follicular variant, were studied. Histologically the tumors were composed exclusively of follicles (four cases) or an admixture of follicular and trabecular structures (four cases). Follicles were identified in smears from seven cases (87.5%) and sheets reminiscent of a trabecular pattern in one (12.5%). Colloid material presented as intraluminal (one case) or extraluminal, dense, round masses (six cases). Nuclear cytoplasmic inclusions occurred in seven (87.5%) of the cases. All these features have been described for follicular lesions or neoplasia together with occasional nuclear grooves, as occurred in two (25%) of the studied cases. In the other six (75%) cases, a moderate to high proportion of neoplastic cells with nuclear grooves facilitated the diagnosis of papillary carcinoma. Our findings suggest that a careful microscopic search for nuclear grooves should be attempted in aspirates yielding a diagnosis of follicular neoplasia that could otherwise be indistinguishable from the follicular variant of papillary carcinoma of the thyroid.     

Osteolytic skull metastasis with dural involvement from a papillary thyroid carcinoma

Skull metastatic tumors are relatively rare medical entities and originate most often from the lungs, breast or prostate. We report a case of a 76-year-old woman who presented with a bulging, well-circumscribed mass on the right side of the forehead. Neuroimaging of the cranium detected an osteolytic lesion measuring 7 cm in the largest diameter while propagating outwards and intracranially. A thorough medical history revealed that patient had undergone surgery for invasive breast ductal carcinoma and also for a well-differentiated thyroid carcinoma 13 years ago. Considering patients medical history metastatic breast carcinoma was suspected. After a frontal craniotomy the tumour tissue was totally resected. Histological examination revealed metastatic papillary carcinoma characterized by ground-glass nuclei with intranuclear pseudo inclusion and nuclear grooves. We report clinical and neuroradiological features of this uncommon lesion and discussed the differential diagnosis of skull osteolytic lesion together with the treatment management.     

Pituitary resistance to thyroid hormones.

Pituitary thyroid hormone resistance (PRTH) refers to a particular form of thyroid hormone refractoriness that is accompanied by peripheral hyperthyroidism, as only the TSH-secreting pituitary cells appear to be resistant to the effects of thyroid hormones. The presence of PRTH is suspected and diagnosed on the basis of the finding of high free thyroid hormone levels along with unsuppressed TSH, clinical signs and symptoms of hyperthyroidism and values of at least one of the parameters evaluating peripheral thyroid hormone action in the hyperthyroid range. However, most patients with PRTH present with clinical signs and symptoms of thyroid dysfunction, particularly goiter and tachycardia, overlapping those recorded in patients with generalized thyroid hormone resistance (GRTH), i.e. refractoriness to thyroid hormones at both pituitary and peripheral tissue level. Moreover, most of them display normal values of other parameters evaluating the peripheral effects of thyroid hormones and bear mutations in the gene encoding for T3 nuclear receptors similar to those found in patients with GRTH. These findings are questioning the existence of PRTH as a separate clinical entity and support the view that the various forms of thyroid hormone resistance may be part of a spectrum of disease with variable expression in different issues.     

Chemotherapy with doxorubicin in progressive medullary and thyroid carcinoma of the follicular epithelium.

Twenty-two patients (mean age 61) with metastasizing, progressive, nonradioiodine-accumulating thyroid carcinoma of the follicular epithelium were treated with doxorubicin between 2000 and 2005. Tumors were histologically classified as follicular in 15 patients (68%) and papillary in 7 patients (32%). In addition, nine patients (mean age 51 years) with medullary thyroid carcinoma were treated with doxorubicin between 1997 and 2005. Treatment consisted of doxorubicin: either 8 cycles of 15 mg/m2 weekly or 3 cycles of 60 mg/m2 every 3 weeks, repeated once, depending on response and side effects. The effect of therapy was evaluated by radiographic imaging, [18F] FDG-PET, and bone scans. In patients with papillary or follicular thyroid carcinoma, 5% had a partial regression over 6 months, 42% had stable disease for a median of 7 months (range: 1-22), and 53% had continuous progression established over 5 months (range: 1-11). Three patients died before completing chemotherapy. In patients with medullary thyroid carcinoma, 11% had a partial regression over 6 months followed by stable disease for 3 months, 11% had stable disease over 7 months, and 79% demonstrated progressive disease established over 5 months (range: 2-12). Doxorubicin can be a valid chemotherapy option, especially for advanced or metastatic thyroid carcinoma of the follicular epithelium.     

Unusual metastasis of papillary thyroid carcinoma to larynx and hypopharynx a case report

Background  

Although direct infiltration of papillary carcinoma of thyroid to larynx, trachea and esophagus is well recognized, lymphatic and vascular metastases to larynx and hypopharynx have rarely been reported.     

Clinical predictors of right upper paraesophageal lymph node metastasis from papillary thyroid carcinoma

ABSTRACT: BACKGROUND: Central and lateral lymph node metastases are quite common in patients with papillary thyroid carcinoma, and the predictors for those metastases have been well studied. Right upper paraesophageal lymph node metastasis has rarely been studied. The aim of this study was to identify the clinicopathological characteristics that may be risk factors for right upper paraesophageal lymph node metastasis in patients with papillary thyroid carcinoma. METHODS: This was a prospective observational study of 243 patients with papillary thyroid carcinoma (PTC) who underwent total thyroidectomy and comprehensive central lymph node dissection with or without lateral lymph node dissection between April 2008 and January 2010. The clinicopathologic findings from these patients were investigated and the patterns of lymph node metastasis were analyzed in the patients who had right upper paraesophageal lymph node disease. RESULTS: Of the 243 patients undergoing lymph node dissection, 14 had right upper paraesophageal lymph node metastases. Two of these patients had right upper paraesophageal lymph node metastasis only, without central compartment metastasis. Univariate analysis of clinicopathologic findings showed that right upper paraesophageal lymph node metastasis had significant association with larger primary tumors, multifocal tumors, extrathyroid extension, and lymphatic invasion (p <0.05 for each factor). CONCLUSIONS: Although there were no independent predictors of right upper paraesophageal lymph node metastasis, it can be the only site of metastasis without other compartmental metastasis. Therefore, during surgery for patients with central or lateral lymph node metastases from PTC, it may be helpful to examine the right upper paraesophageal lymph nodes.