Computerized Cytological Features for Papillary Thyroid Cancer Diagnosis-Preliminary Report.

Fine needle aspiration cytology (FNAC) is the final diagnosis of thyroid nodules before surgery. It is important to further improve the indeterminate FNAC diagnosis results using computerized cytological features. This retrospective cross-sectional study included 240 cases, of whom 110 had histologic diagnosis of papillary thyroid cancers (PTC), 100 had nodular/adenomatous goiters/hyperplasia (benign goiters), 10 had follicular/Hurthle cell carcinomas, and 20 had follicular adenomas. Morphological and chromatic features of FNAC were quantified and analyzed. The result showed that six quantified cytological features were found significantly different between patients with a histologic diagnosis of PTC and patients with histologic diagnosis of benign goiters in multivariate analysis. These cytological features were used to estimate the malignancy risk in nodules with indeterminate FNAC results. The Area Under the Receiver Operating Characteristics (AUROC) of the diagnostic accuracy with a benign or malignant nature was 81.3% (p < 0.001), 78.7% (p = 0.014), and 56.8% (p = 0.52) for nodules with FNAC results of atypia, which is suspicious for malignancy and follicular neoplasm, respectively. In conclusion, quantification of cytological features could be used to develop a computer-aided tool for diagnosing PTC in thyroid nodules with indeterminate FNAC results.

Observing pretibial myxedema in patients with Graves' disease using digital infrared thermal imaging and high-resolution ultrasonography: for better records, early detection, and further investigation.

OBJECTIVE: Pretibial myxedema (PM) is a manifestation of Graves' disease (GD). Currently, its diagnosis depends on physicians' observation and biopsy. No satisfactory, objective, and non-invasive tool is available to record and investigate lesions. Digital infrared thermal imaging (DITI) detects surface temperature, and sonography reflects composition changes in soft tissue. This study was aimed to observe changes in DITI and sonography in PM, and to evaluate their clinical usefulness. METHODS: Nineteen GD patients with PM, 22 GD patients with mild diffuse non-pitting edema over lower legs, 46 GD patients with normal appearance of lower legs, and 14 normal volunteers were recruited for observation with DITI; 8, 21, 21, and 11 of them respectively also received soft tissue sonography for investigating the pathogenesis of DITI change. RESULTS: Lower leg temperatures of normal volunteers decreased gradually from proximal to distal parts. In all 19 patients with PM, DITI showed abnormally low focal temperatures over the lesions. In GD patients with mild diffuse non-pitting edema and GD patients with normal appearance of lower legs, DITI showed abnormally low focal temperature in 90.9 and 65.2% of the patients respectively. Areas of clinically visible PM and low focal temperature detected by DITI were sonographically characterized with increased skin thickness, hypoechoic substance deposition in the cutaneous tissue, and blurred boundary lines between dermis and subcutaneous tissue. TSH receptor antibody level correlated positively and significantly with skin thickness change and adjusted temperature difference between the center of temperature defect and the surrounding skin (P=0.046 and 0.033 respectively). CONCLUSIONS: By using DITI and sonography, we detected characteristic changes in PM. These techniques are helpful in recording and may be useful tools to detect early changes of PM.

The application of temperature measurement of the eyes by digital infrared thermal imaging as a prognostic factor of methylprednisolone pulse therapy for Graves' ophthalmopathy.

PURPOSE: Graves' ophthalmopathy (GO) involves autoimmune process resulting in proptosis, congestion, oedema and diplopia. Werner's NOSPECS classification and clinical activity score (CAS) of GO cannot objectively describe the inflammatory status. Digital infrared thermal imaging (DITI) detects local temperature and may reflect the degree of orbital inflammation. The aim of this study was to evaluate the clinical application of the eye temperature measured by DITI. METHODS: Forty-six patients with GO receiving intravenously methylprednisolone pulse therapy (MPT) were included in this study. Local temperatures of the lateral orbit, upper eyelid, inner caruncle, medial conjunctiva, lateral conjunctiva, lower eyelid and cornea were measured with DITI before and after MPT. CAS, proptosis, eye movement (EOM) and diplopia were also recorded. Improvement of CAS was defined as at least one point decrease at either side of the eye, which was 0.5 score decrease as to the average of bilateral CAS. RESULTS: Local temperatures of the eyes decreased after MPT. The mean value of temperature (MT) of 12 points including the lateral orbit, upper eyelid, inner caruncle, medial conjunctiva, lateral conjunctiva and lower eyelid of both eyes before MPT was 32.65 degrees . The mean change of MT after MPT (DeltaT) was -0.22 degrees. DeltaT significantly negative-correlated with basal MT (correlation coefficient=-0.54, p=0.004). Higher baseline MT and CAS before MPT correlated with higher possibility of improvement of CAS after MPT (p=0.013 and 0.012, respectively). Baseline MT and CAS together correlated with improvement of CAS after MPT better than baseline CAS alone could do (area under the receiver operating characteristic curve: 82.81% and 66.63%, respectively). CONCLUSIONS: Basal temperature of the eyes measured by DITI was an objective indicator of inflammation of GO. Combining CAS and MT could better predict the outcome of MPT than CAS alone.

Application of digital infrared thermal imaging in determining inflammatory state and follow-up effect of methylprednisolone pulse therapy in patients with Graves' ophthalmopathy.

BACKGROUND: Inflammation can cause a local increase in temperature. Digital infrared thermal imaging (DITI) has been used to monitor the temperature distribution of human skin. Graves' ophthalmopathy (GO) is an autoimmune disease, and patients are treated with immunosuppressive agents if the ophthalmopathy is at an inflammatory state. The aim of the present study was to elucidate the feasibility of DITI in determining inflammatory state and follow-up effect of methylprednisolone pulse therapy in patients with GO. METHODS: Digital infrared thermal imaging was used to measure local temperatures of lateral orbit (reference point), upper eyelid, caruncle, medial conjunctiva, lateral conjunctiva, lower eyelid, and cornea, and to make thermal density plots in 14 patients (28 eyes) with GO including inflammatory signs (mean clinical activity score 2.5), and 16 normal controls (32 eyes). We also performed methylprednisolone pulse therapy in 11 patients (22 eyes) with active GO, and measured clinical activity score and local temperatures before and after treatment. The focal change in temperature after treatment and the correlation between temperature variation and change in clinical activity score were then analyzed. Thermal density plots were also compared. RESULTS: Local temperatures of the caruncle, medial conjunctiva, lateral conjunctiva, and lower eyelid of the patients were significantly higher than those of normal controls. In the 11 GO patients treated with methylprednisolone pulse therapy, the temperatures of the caruncle, medial conjunctiva, and lower eyelid were significantly decreased after treatment. Temperature variation significantly and positively correlated with a change in clinical activity score (correlation coefficient = 0.8, n = 22, p = 0.000). The temperature decreased after treatment in patients who were responsive to methylprednisolone pulse therapy, and the thermal density plot was close to that of normal controls. CONCLUSIONS: Digital infrared thermal imaging might be helpful in evaluating the inflammatory state of GO and the follow-up effect of methylprednisolone pulse therapy.

Fine needle aspiration cytology stained with Rius method in quicker diagnosis of medullary thyroid carcinoma.

BACKGROUND/PURPOSE: The cytologic features of medullary thyroid carcinoma (MTC) have been described and documented in the literature. Most of the studies were related to the Papanicolaou stain or the May-Grnwald-Giemsa stain. The aim of the present study was to analyze detailed cytologic characteristics of MTC diagnosed by fine-needle aspiration cytology (FNAC) stained with a quick method, Rius stain. METHODS: We collected the FNAC slides of 38 cases with MTC that were proven by surgical pathology. The cytologic findings were reviewed under a light microscope. The median age at diagnosis was 46.5 years, ranging from 13 to 83 years; 20 were women and 18 were men. Among them, seven cases were familial forms and the others were sporadic. RESULTS: The majority of these cases showed moderate to abundant cellularity. Small round cells, spindle-shaped cells and large oval to polygonal cells formed the usual components. Twenty-seven cases were categorized as pleomorphic cell type and 11 cases as monomorphic type. Except in one case, cohesive and clustered small round cells predominated in all cases, alone or coupled with cohesive spindle cells and/or scattered large oval to polygonal cells. The diagnosis of mixed medullary-follicular thyroid carcinoma was made in the case composed solely of grouped polygonal cells. Cytoplasmic granularities were noted in 14 cases and vacuolations were seen in eight. Binucleated and multinucleated cells were not uncommon, while intranuclear cytoplasmic inclusions were less frequent. The diagnostic sensitivity for MTC by FNAC was 89%. CONCLUSION: The distinctive cytopathologic characteristics of MTC by Rius stain allowed us to make the diagnosis in aspiration biopsies accurately and quickly.

Prognostic significance of cytologic features in fine-needle aspiration cytology samples of papillary thyroid carcinoma: preliminary report.

BACKGROUND: The influence of clinicopathologic features on prognosis of papillary thyroid cancer has been examined. However, the relationship between cytologic features obtained by fine-needle aspiration (FNA) and prognosis has been minimally studied. METHODS: We retrospectively studied 85 patients with usual-type papillary thyroid cancer diagnosed by FNA who underwent total or near-total thyroidectomy, had disease confirmed by pathological study, and were followed for more than 10 years except for one patient with metastasis at diagnosis. Cytologic features of FNA and recurrence of cancer were examined statistically. RESULTS: Four cytologic features were significantly related to recurrence: bigger nuclei, more irregularly shaped nuclei, nuclear atypia, and simultaneous presence of lighter staining nuclei and apparent nucleoli. A prognostic score of 1 (light nuclei and apparent nucleoli) plus 1.5 (irregularly shaped nuclei away from fibrous cord) plus 1 (high nucleus-to-cytoplasm ratio) plus 1 (nuclear atypia) was generated statistically. Sensitivity and specificity using a cut point of 2.5 in predicting outcome were 83.33% and 77.55%, respectively. CONCLUSIONS: Cytologic features of FNA samples have prognostic significance. If the prognostic score of cytologic features is high, a more radical surgical procedure and aggressive treatment plan should be considered.

Medullary thyroid carcinoma: pitfalls in diagnosis by fine needle aspiration cytology and relationship of cytomorphology to RET proto-oncogene mutations.

OBJECTIVE: To elucidate the pitfalls in the diagnosis of medullary thyroid carcinoma (MTC) by fine needle aspiration cytology (FNAC) and the relationship of cytomorphology to RET proto-oncogene mutations. STUDY DESIGN: Cytomorphology was reviewed in the fine needle aspiration slides of 34 patients with MTC proven by surgery and pathology. Germline or somatic RET proto-oncogene mutations were determined using polymerase chain reaction-based sequencing in 15 of 34 patients, and the relationship to cytomorphology was evaluated. RESULTS: Twenty-eight (82.4%) of 34 cases were diagnosed correctly as MTC by FNAC, 3 cases were misdiagnosed as follicular neoplasm and 1 as desmoid, and 2 cases were suspicious for MTC. The main reason for misdiagnosis was overlooking the slight angular shape of the nuclei or atypical changes. In 15 of 34 cases with germline or somatic RET proto-oncogene mutations determined, 10 cases had a germline mutation, and 1 had only a somatic mutation. There were 4 cases that had neither germline nor somatic RET proto-oncogene mutations. Cells with small/round and spindled forms were the predominant findings of codon 918 ATG-->ACG mutation, and cells with small/round and large oval to polygonal forms were the main findings of codon 634 mutations. There were no misdiagnoses in patients with RET proto-oncogene mutations. CONCLUSION: FNAC is a good diagnostic method for MTC. Codon 918 mutation correlates mainly with small/round and spindled cells and codon 634 with small/round, large oval to polygonal forms.

Follicular variant of papillary thyroid carcinoma: diagnostic limitations of fine needle aspiration cytology.

OBJECTIVE: To study the diagnostic sensitivity and specificity of fine needle aspiration cytology (FNAC) offollicular variant of papillary thyroid carcinoma (FVPTC). STUDY DESIGN: The study group consisted of 390 papillary thyroid carcinoma (PTC) cases diagnosed histologically with thyroidectomy specimens. The FNAC and histopathologic classification were compared in terms of the appearance of FVPTC and non-FVPTC statistically with the chi squared test. Also, several features of the cytologic smears of FVPTC were reviewed. RESULTS: Twelve of the 390 PTC cases were classified as FVPTC histologically. Five of the 12 cases were also reported as FVPTC in the diagnosis by FNAC and the other 7 as the usual type of PTC (UTPTC). There was 1 case classified as UVPTC histologically but FVPTC cytologically. If we use histologic diagnosis as the gold standard, the sensitivity and specificity of FNAC diagnosis of FVPTC were 42% and 83%, respectively. CONCLUSION: FNAC may be a good tool for diagnosing PTC, but it is unreliable to differentiate between FVPTC and UTPTC.

Determining when to operate on patients with Hashimoto's thyroiditis with nodular lesions: the role of ultrasound-guided fine needle aspiration cytology.

OBJECTIVE: To elucidate the role of ultrasound-guided fine needle aspiration cytology (FNAC) in determining whether to request an operation. STUDY DESIGN: Twenty-four consecutive patients (23 women and 1 man) with Hashimoto's thyroiditis combined with nodular lesions revealed by ultrasonography were included in the study. Ultrasound-guided FNAC was performed on their thyroid tissue compatible with Hashimoto's thyroiditis and nodular lesions. RESULTS: Two of 24 patients (8.3%) had papillary thyroid cancer, which was diagnosed from aspirates of 31 nodular lesions and confirmed by operative pathologic findings. CONCLUSION: If a patient with Hashimoto's thyroiditis has nodular lesions shown by ultrasonography, ultrasound-guided FNAC is helpful in elucidating the nature of the lesion and determining whether to request an operation.

Three-dimensional cytomorphology in fine needle aspiration biopsy of subacute thyroiditis.

OBJECTIVE: To elucidate 3-dimensional (3-D) cytomorphology in fine needle aspiration biopsy (FNAB) of subacute thyroiditis. STUDY DESIGN: Ultrasound-guided FNAB was performed on the inflamed area of the thyroid from 4 patients with subacute thyroiditis. The aspirates were stained and observed under a light microscope (LM). The aspirates were also fixed, dehydrated, critical point dried, spattered with gold ions and observed with a scanning electron microscope (SEM). For transmission electron microscopy (TEM), the specimen was fixed, dehydrated, embedded in an Epon mixture, cut with an ultramicrotome, mounted on copper grids, electron doubly stained with uranium acetate and lead citrate, and observed with TEM. Findings with SEM were correlated with those with LM and TEM. RESULTS: Under SEM, 3-D cytomorphology of subacute thyroiditis displayed loss of a uniform, honeycomb cellular arrangement; variation in size; and decrease or shortening of microvilli in follicular cells, which corresponded to varying degrees of cellular degeneration under TEM. Giant cells that were round or ovoid were also noted with SEM. CONCLUSION: Loss of a uniform, honeycomb cellular arrangement; variation in size and decrease or shortening of microvilli in follicular cells; and appearance of round or ovoid giant cells were characteristic 3-D cytomorphology findings in FNAB of subacute thyroiditis.

Ultrasound-guided fine needle aspiration cytology of parathyroid lesions. A review of 72 cases.

OBJECTIVE: To elucidate the specific cytomorphologic patterns and diagnostic pitfalls in fine needle aspiration cytology (FNAC) of parathyroid lesions. STUDY DESIGN: Seventy-two cases of surgically excised and pathologically verified hyperparathyroidism (20 cases of parathyroid hyperplasia, 51 of parathyroid adenoma and one of parathyroid carcinoma) received preoperative, ultrasound-guided FNAC examination for enlarged parathyroid glands. The smears were reviewed and analyzed. RESULTS: Parathyroid lesions were diagnosed cytologically in 60 cases (83.3%). The presence of colloidlike substance, macrophages or follicular structures in smears led to six cases (8.3%) being misinterpreted as thyroid lesions. The cellularity of the smears was insufficient for interpretation in six cases (8.3%); however, two of these cases were diagnosed by determination of parathyroid hormone (PTH) levels in the fluid. Parathyroid hyperplasia had more tightly cohesive cell clusters with monomorphism, while parathyroid adenoma had more dispersed or loosely cohesive cells with pleomorphism and anisokaryosis. High PTH concentration in an aspirate was noted in all four cases of cystic lesions.

Cytologic features of metastatic papillary thyroid carcinoma in cervical lymph nodes.

OBJECTIVE: To elucidate the cytologic characteristics of metastatic papillary thyroid carcinoma (PTC) in cervical lymph nodes and the differences in cervical lymph nodes from those of stage I (intrathyroidal) PTC. STUDY DESIGN: Forty-seven cases of papillary thyroid carcinoma with cervical lymph node metastasis (group A) and 38 cases of intrathyroidal papillary carcinoma (group B) were included in this study. Preoperative fine needle aspiration cytology (FNAC) examination was performed on enlarged cervical lymph nodes (47 cases, group A) and enlarged thyroid nodules (13 cases, group A, and 38 cases, group B). All the cases were surgically excised and pathologically verified. The cytologic smears were reviewed and analyzed. RESULTS: The cytologic characteristics of metastatic PTC in cervical lymph nodes displayed a higher frequency of foamy macrophages (51.1% vs. 26.3%) and a lower frequency of distinct cell borders (38.3% vs. 71.1%) than those of stage I PTC. Metastatic PTC in cervical lymph nodes also had a higher frequency of cystic degeneration (44.7% vs. 5.3%) than intrathyroidal lesions. In 1 of the 47 cases with lymph node metastasis, the aspirate contained macrophages but no tumor cells. CONCLUSION: FNAC was useful in the diagnosis of metastatic PTC in cervical lymph nodes. However, because cystic degeneration appeared frequently, FNAC combined with thyroid ultrasonography to find the primary lesion is necessary in this situation.

Three-dimensional cytomorphology in fine needle aspiration biopsy of parathyroid lesions.

OBJECTIVE: To elucidate three-dimensional (3-D) cytomorphology in fine needle aspiration biopsy (FNAB) of parathyroid lesions. STUDY DESIGN: Ultrasound-guided FNAB was performed on parathyroid lesions from 10 patients with hyperparathyroidism. The aspirates were stained and observed under a light microscope (LM). The aspirates were also fixed, dehydrated, critical point dried, spattered with gold ions and observed with a scanning electron microscope (SEM). Findings under SEM were correlated with the appearances under LM as well as with serum parathyroid hormone (PTH) concentrations. RESULTS: Under LM, nine cases displayed isokaryosis and one case, anisokaryosis. These appearances corresponded to isocytosis or anisocytosis under SEM. Under SEM, 3-D cytomorphology of parathyroid lesions displayed isocytotic, scattered cells in five cases, uniform cellular arrangements in four cases and anisocytotic, scattered cells in one case. The cell surface was rather smooth in five cases. The other five cases had significant granules on the cell surfaces; these all had serum PTH concentrations > or = 268 pg/mL. CONCLUSION: 3-D cytomorphology in FNAB of parathyroid lesions was a rather smooth cell surface in cases with low serum PTH and a granular cell surface in cases with significantly increased serum PTH. These characteristics and the absence of microvilli might be helpful in the differential diagnosis between parathyroid and follicular thyroid lesions.