Cancer rates and characteristics of thyroid nodules with macrocalcification.

AIMS: The aim of this study was to determine the malignant potential of thyroid nodules with macrocalcifications and to evaluate the role of other sonographic findings in the diagnosis of malignancy in thyroid nodules besides macrocalcifications. METHODS: The findings of 8250 patients who applied to our outpatient clinic and underwent thyroid ultrasonography(US) between 2008 and 2021 were retrospectively reviewed. We included a total of 296 patients with 296 macrocalcified nodules (macrocalcification group) and an age- and sex matched group of 300 patients (control group) with the cytopathologic and/or histopathologic data of fine-needle aspiration biopsy (FNAB) of thyroid nodules without calcification. Demographic characteristics of these patients, US characteristics of the nodules, and thyroid function tests were recorded. Cytopathological data of FNAB were classified according to BETHESDA. RESULTS: The malignancy rate was 14.2% (42/296) in the macrocalcification group and 5.3% (16/300) in the control group (p < 0.001). There was no significant relationship between interrupted peripheral calcification and malignancy. Hypoechoic or markedly hypoechoic appearance, irregular border, solid structure, presence of accompanying pathological lymphadenopathy on sonographic examination and upper and middle zone localization were other sonographic features that increased the risk of malignancy of a nodule. The presence of autoimmunity was not found to be associated with the risk of malignancy. TSH and calcitonin levels of malignant nodules were higher than benign nodules. There was no significant difference between gender and malignancy. In the univariate analysis, it was found that the presence of macrocalcification increased the risk of malignancy 2.935 times. (OR:2.935, p < 0.001.95% CI for OR 1.611-5.349) In addition, being younger, being in the high TIRADS category, and being in the upper and middle zones were factors that increased the risk of malignancy. Gender, TSH level, nodule volume and structure were not associated with malignancy. However, after multivariate analysis, factors that significantly increased the risk of malignancy were younger age, higher TIRADS category, and nodule localization. CONCLUSION: In our study, the malignancy rate was higher in the macrocalcification group than in the control group. However, no correlation was found after multivariate analysis. In the multivariate analysis, younger age, higher TIRADS category, and nodules located in the upper and middle zone were other factors associated with malignancy. There was no association between peripheral interrupted calcification and malignancy risk.

The relationship between 18F-FCH uptake intensity and cell content in parathyroid lesions.

PURPOSE: To investigate the relationship between cell content and histopathological features of parathyroid lesions and 18F-FCH uptake intensity on PET/CT images. METHODS: Patients with primary hyperparathyroidism (age > 18) who were referred to 18F-FCH PET/CT were involved. All patients underwent parathyroidectomy. Correlation of SUVmax with following factors were statistically analysed: serum PTH, Ca, P levels and histopathological parameters, total absolute amounts of chief cell, oxyphyllic cell and clear cell components calculated by the multiplication of the volume of the parathyroid lesion and the percentage of each type of cell content (called as Absolutechief, Absoluteoxyphyllic and Absoluteclear reflecting the total amount of each cell group). RESULTS: A total of 34 samples from 34 patients (6M, 28F, mean age: 53.32 ± 15.15, min: 14, max: 84) who had a positive 18F-FCH PET/CT localizing at least one parathyroid lesion were involved. In the whole study group, SUVmax was found to be correlated with the greatest diameter and volume of the lesion and Absolutechief (p = 0.004, p = 0.002 and p = 0.035, respectively). In the subgroup analysis of 28 samples with longest diameter > 1 cm, the correlation between SUVmax and Absolutechief remained significant (p = 0.036) and correlation between SUVmax and volume and longest diameter became stronger (p = 0.011 and p > 0.001, respectively). No correlation was found between SUVmax and Absoluteoxyphyllic or Absoluteclear. CONCLUSIONS: There might be a relationship between 18F-FCH uptake intensity and chief cell content in patients with parathyroid adenoma. Further studies with larger patient groups would be beneficial to support the data.

Contribution of small tissue biopsy and flow cytometry to preoperative cytological categorization of salivary gland fine needle aspirates according to the Milan System: Single center experience on 287 cases.

BACKGROUND: Milan system for reporting salivary gland cytopathology (MSRSGC) was proposed to provide a standardized reporting system for salivary gland fine needle aspiration biopsies. Modified Menghini type semi-automatic aspiration biopsy needles provide small tissue fragments (STFs), as well as cellular smears, and immunohistochemical and molecular studies can be performed using the STFs. AIMS: We aimed to evaluate the contribution of STFs and ancillary techniques to pre-operative diagnosis of salivary gland lesions. MATERIALS AND METHODS: In this study, smears of 287 cases with histopathological correlation were re-reviewed and assigned to one of the MSRSGC categories. In the second step, histopathological and immunohistochemical findings in STFs were evaluated together with cytological findings. Final diagnoses were obtained with the inclusion of flow cytometry (FC) results when available. Risk of malignancy (ROM) was calculated for each diagnostic category. RESULTS: In the evaluation based on smears, a specific diagnosis could be obtained in 64.8% of the cases. ROMs were 0% for nondiagnostic (ND), 5.6% for non-neoplastic (NN), 55% for atypia of undetermined significance (AUS), 0.6% for benign neoplasm (BN), 27.8% for salivary gland neoplasm of uncertain malignant potential (SUMP), and 100% for suspicious for malignancy (SFM) and malignant (M) categories. With the addition of histopathological and immunohistochemical findings and FC results, a specific diagnosis could be obtained in 75.2% of the cases. ROMs were 0% for ND, 4.5% for NN, 53.8% for AUS, 0.6% for BN, 0% for SUMP, and 100% for SFM/M categories. CONCLUSIONS: STFs contribute correct categorization of salivary gland lesions. The major contribution of ancillary methods is in the SUMP category.

Pulmonary sclerosing pneumocytoma with mediastinal lymph node metastasis: a case report.

Pulmonary sclerosing pneumocytoma (PSP) is a rare tumor and the imaging appearance is usually a well-circumscribed nodule. Herein we present the clinicopathological features of a 25-year-old female patient with a 4 cm mass in the left upper lobe. She had undergone lobectomy with lymph node dissection with an incorrect intraoperative frozen section diagnosis of adenocarcinoma and diagnosed as a PSP with lymph node metastasis on permanent sections. The 3-year follow-up of the patient is uneventful.

Different View on Tumor Size Dilemma in Tumor-Node-Metastasis Staging System for Thymoma.

BACKGROUND: Although tumor size is included in the definition of T descriptor in the tumor-node-metastasis (TNM) classification of many solid tumors, it is not considered for thymomas. This study aimed to assess the relationship of tumor diameters (the largest tumor diameter [LTD] and the mean tumor diameter [MTD]) with survival in thymoma patients undergoing surgical resection in a single center. METHODS: The study included 127 thymoma patients (age, 49.2 ± 15.2 years; 65 males), who were evaluated based on pathological tumor sizes according to the LTD and MTD ([largest diameter + shortest diameter] / 2) and divided into three subgroups for each parameter as: patients with an LTD of ≤5 cm, 5.1 to 10 cm, and >10 cm and patients with an MTD of ≤5, 5.1 to 10, and >10 cm. RESULTS: In thymoma patients, survival significantly differed according to the presence of myasthenia gravis (p = 0.018), resection status (R0 or R1; p = 0.001), T status (p = 0.015), and the Masaoka-Koga stage (p = 0.003). In the LTD subgroups, the overall survival of those with R0 resection was lower in those with an LTD of 5.1 to 10 cm than in those with an LTD of ≤5 cm (p = 0.051) and significantly lower in those with an MTD of 5.1 to 10 cm than in those with an MTD of ≤5 cm (p = 0.027). In the MTD subgroups, survival decreased as the tumor size increased. CONCLUSION: Both smaller tumor size and complete resection are associated with better survival in thymoma patients. Therefore, the largest or the mean tumor size might be considered as a criterion in the TNM staging for thymoma.

The Association of Histologically Proven Chronic Lymphocytic Thyroiditis with Clinicopathological Features, Lymph Node Metastasis, and Recurrence Rates of Differentiated Thyroid Cancer.

The influence of chronic lymphocytic thyroiditis (CLT) on clinicopathological features and behavior of differentiated thyroid carcinoma (DTC) is still debated. In the present study, we aimed to evaluate the prognosis of DTC on the presence of CLT. A total of 649 total thyroidectomized patients (379 female, 270 male) with DTC, who had follow-up data for at least 36 months were included. Clinical, histopathological data, preoperative thyroid peroxidase antibody (TPO-ab), thyroglobulin antibody (Tg-ab), thyroid-stimulating hormone (TSH) levels, and presence of recurrent/persistent disease (R/PD) were evaluated retrospectively. Presence of CLT was defined by histopathology. Frequency of CLT was 32% (n = 208) among DTC patients. Mean tumor size (maximal diameter) was smaller in CLT group when compared to non-CLTs (p = 0.006). Capsular invasion, vascular invasion, tumor stage, risk groups, and R/PD were negatively associated with CLT (p < 0.01, p = 0.04, p = 0.03, p = 0.02, p < 0.01, respectively). Extrathyroidal extension was more frequent in non-CLT group when compared CLT (p = 0.052). Preoperative TSH level was positively associated with lymph node metastasis (LNM) and higher in patients with lateral LNM when compared to central LNM (p < 0.01). Central LNM, lateral LNM, stage 4 tumor, and intermediate- and high-risk tumor groups increased the risk of R/PH, 2.5-, 2.9-, 12.7-, 2.3-, and 4.2-fold, respectively. Presence of CLT was independently related with favorable outcomes, as the risk of R/PD was decreased by 0.49-fold. In conclusion, coexistence of CLT was negatively associated with tumor size, capsular invasion, vascular invasion, and tumor stage in DTC. Risk of R/PD was decreased by approximately half in patients with CLT.

Evaluation of epidermal growth factor receptor mutations and thyroid transcription factor-1 status in Turkish non-small cell lung carcinoma patients: A study of 600 cases from a single center.

BACKGROUND: This study aims to investigate the frequency, distribution, and morphological/immunohistochemical features of epidermal growth factor receptor mutations and to examine the possible relationship between the material type and technical success of mutation analysis in Turkish population with non-small cell lung cancer. METHODS: Between September 2012 and December 2015, a total of 499 consecutive, treatment-naïve patients (437 males, 163 females; mean age 61 years; range, 30 to 84 years) with primary or metastatic non-small cell lung cancer who underwent epidermal growth factor receptor mutation testing using Sanger sequencing method were retrospectively analyzed. Archival records and hematoxylin-eosine and immunohistochemically stained sections were re-examined. The thyroid transcription factor-1 and napsin A immunohistochemical stains were performed on tissue array blocks. RESULTS: Seventy-five mutations were detected in 70 patients (14%). The success rate of testing and intact deoxyribonucleic acid fragment length were significantly higher in the cytological material, compared to tissue specimens (p<0.001). The mutation rate in adenocarcinomas was 33.9% for women and 9.4% for men. The most common mutation was L746-E750del in exon 19 (29.3%), followed by the L858R mutation in exon 21 (28%). The mutation rate was the highest in micropapillary (40%) and lowest in solid (5.4%) adenocarcinomas. All epidermal growth factor receptor mutations, except for one, were positive for the thyroid transcription factor-1. The single nucleotide polymorphism Q787Q in exon 20 was observed in 79.6% of patients. CONCLUSION: The frequency and distribution of epidermal growth factor receptor mutations in the Turkish patients with non-small cell lung cancer are similar to the European populations. These results also demonstrate that cytological materials are highly reliable for epidermal growth factor receptor mutation testing, and the probability of detection of wild-type epidermal growth factor receptor is low in cases of thyroid transcription factor-1 negativity.

Intrapericardial goiter.

Intrapericardial goiter cases are only a few in the literature. We present a 53-year-old woman who was operated for 8-cm anterior mediastinal mass located completely intrapericardial and histopathological examination revealed an ectopic goiter. It may be difficult to distinguish between mediastinal masses within or outside the pericardium. Thoracoscopy may be needed in such cases.

Clinical Impact of p27Kip1 and CaSR Expression on Primary Hyperparathyroidism.

We aimed to investigate the expressions of p27 kinase inhibitory protein 1 (p27Kip1) and calcium sensing receptor (CaSR) in adenomas and normal parathyroid tissue and to evaluate the relationship of these molecules with clinical and biochemical parameters in primary hyperparathyroidism (PHPT). Fifty-one patients with histopathologically confirmed parathyroid adenomas and 20 patients with normal parathyroid glands (which were removed incidentally during thyroid resection) were included. Immunohistochemical stainings of CaSR and p27Kip1 were performed in surgical specimens. Clinical features, biochemical parameters, and BMD measurements of patients with PHPT were evaluated retrospectively. Expressions of p27Kip1 and CaSR were decreased in parathyroid adenomas, compared to normal glands (p < 0.05). High intensity of CaSR staining (3+) was more frequent in normal parathyroid tissue (75%) than adenomas (12%) (p < 0.01). Hypertension was not observed in patients with high staining intensity of CaSR (p = 0.032). There was a negative association between CaSR expression and body mass index (BMI) (p = 0.027, r = - 0.313). There was no significant relationship between p27Kip1 and CaSR expressions, serum calcium, plasma parathormone, 25-hydroxy vitamin D levels, and bone density (p > 0.05). The expressions of p27Kip1 and CaSR were decreased in PHPT patients. This reduction may play an important role in the pathogenesis of PHPT. However, neither p27Kip1 nor CaSR expression was found to be useful in predicting prognosis or severity of disease.

Prognostic factors for stage I lung adenocarcinoma and surgical management of subsolid nodules.

BACKGROUND: This study aims to identify the prognostic factors for stage I lung adenocarcinoma and to evaluate the surgical management of subsolid nodules. METHODS: The study included 133 patients (90 males, 43 females; mean age 64.9 years; range, 29 to 82 years) who had undergone operation in our clinic for stage I lung adenocarcinoma between January 2007 and December 2015. Clinical, radiological and pathological data were retrospectively evaluated and their effects on recurrence and survival were examined by Kaplan-Meier and Cox regression analyses. RESULTS: Comparing the histopathological tumor types according to the pathological tumors size, we determined that the prevalence of invasive adenocarcinoma significantly increased with increasing tumor size (p<0.001). For all nodules, a tumor disappearance rate lower than 25% negatively influenced disease-free survival and a maximum standardized uptake value higher than 5.6 negatively influenced overall survival (p=0.027 for both). The grouping, which was performed considering the maximum standardized uptake value 5.6 as the cut-off value, was an independent prognostic factor for overall survival (hazard ratio: 5.973, 95% confidence interval: 1.186-30.073, p=0.03). Five-year overall survival rate was statistically significantly higher in patients who underwent wedge resection or segmentectomy for subsolid nodules compared to those who underwent lobectomy (100% vs. 79.3%, p=0.044). CONCLUSION: Sublobar resections can be safely performed in subsolid nodules smaller than 2 cm in diameter with tumor disappearance rate ≥25% and maximum standardized uptake value ≤5.6.

Thyroid Gland Metastasis from Cancer of the Uterine Cervix: An Extremely Rare Case Report.

The thyroid gland is a relatively uncommon site for a metastatic disease, although it is richly supplied with blood. The metastases may originate from various primary sites, mainly kidney, lung, head and neck, and breast. Thyroid metastasis from cervical carcinomas is extremely rare; and only a few cases have been previously reported in the literature. In patient with thyroid nodules and an oncological history, the possibility of thyroid metastasis should be seriously considered. Despite the rarity of the metastasis of cervical carcinoma to the thyroid, it is difficult to say appropriate treatment approach for these lesions. When managing such patients, decision-making should balance the possibility of gaining long-term survival against estimation of the aggressiveness of the disease and its possible complications. Here, a case of thyroid metastasis from a squamous cell carcinoma of the uterine cervix presenting with cervical mass and difficulty in swallowing and its treatment is reported.

Variants of Papillary Thyroid Carcinoma: Multiple Faces of a Familiar Tumor.

Classically characterized by its papillary appearance, papillary thyroid carcinoma is the most common malignant neoplasm of the thyroid. Several variants of papillary carcinoma have been described considering size (microcarcinoma); nature of the tumor boundaries (encapsulated); architecture (follicular, macrofollicular, cribriform-morular, solid, micropapillary); cellular characteristics (tall cell, columnar, oncocytic, clear cell, hobnail); additional tumor components (papillary carcinoma with focal insular component, papillary carcinoma with spindle and giant cell carcinoma, papillary carcinoma with squamous cell carcinoma, papillary carcinoma with mucoepidermoid carcinoma); stromal features (papillary carcinoma with fasciitis like stroma); or a combination of the abovementioned characteristics (diffuse sclerosing, Warthin-like). Although most variants do not pose any diagnostic problems; some histological variants can be challenging to the pathologist and some are of clinical significance, because of prognostic implications or accompanying clinical conditions. It is not rare to find a papillary carcinoma showing characteristics of more than one variant. For example: an individual tumor can show hobnail features and present as a microcarcinoma; another case can show solid architecture and clear cytoplasm. In such cases, it is more important to comment on clinically relevant morphological characteristics of the tumor, rather than religiously trying to classify an individual tumor into a particular variant. In this review, pathologic and clinical features of papillary carcinoma variants are summarized.

In situ hybridization analysis of invasive breast carcinomas with immunohistochemically negative Her-2 status (a national multicenter study).

OBJECTIVE: The aim of this study was to determine the rate of Her-2 gene amplification in breast cancer cases with a previous negative Her-2 result as determined by immunohistochemistry (score 0 or 1). MATERIAL AND METHOD: 552 cases of invasive breast carcinoma were assessed with the contribution of 9 centers. Previous immunohistochemistry score was either 0 or 1+ in all cases. These cases were re-tested by Her-2 silver in situ hybridization in the central laboratory. Her-2 gene amplification was defined as Her-2/CEP 17 ratio of more than 2.2. Cases with a ratio between 1.8 and 2.0 were defined as equivocal and cases with a ratio of less than 1.8 were defined as negative. RESULTS: Re-testing of the 552 cases with silver in situ hybridization showed a total of 22 cases with Her-2 gene amplification, of which 11 (3.2%) were found to be score 0, and 11 were found to be score 1+ (5.3%) by immunohistochemistry previously. Her-2 gene amplification rate of cases (score 0 and 1+) ranged from 0% to 10.48% among the centers. Polysomy was found in 28 (8.1%) of the score 0 cases and 25 (12.1%) among the score 1+ cases. Five (9.4%) of the cases with polysomy were found to be amplified, and 48 (90.6%) were not. CONCLUSION: The results of the study show that a group of cases (3.98%) with a potential to benefit from anti-Her-2 therapy may be missed with the immunohistochemical method. This indicates the importance of quality assurance, especially in central laboratories with many breast cancer cases in daily practice.

Benign localized fibrous tumor of the pleura: report of 25 new cases.

OBJECTIVE: Benign localized fibrous tumors (BLFT) of the pleura are very rare slow-growing neoplasms that generally have a favorable prognosis. The aim of this manuscript is to evaluate the predictors of outcome with the review of the literature in a series of 25 patients with BLFT. METHODS: Between January 1985 and November 2009, 25 patients underwent an operation due to BLFT. Of these patients, 14 (56%) were male; mean age was 41.1 (25 to 64) years. All patients underwent thoracotomy. Left thoracotomy approach was used in 16 patients. The mass lesions were totally excised. The histopathological examinations were performed with hematoxylin-eosin and immunohistochemical staining methods. RESULTS: Of the patients, 18 (72%) were symptomatic. Symptoms were cough in 36%, shortness of breath in 32%, and chest pain in 20% of the patients. One patient (4%) appeared to have some symptoms (pain and swelling of the joints) associated with pulmonary osteoarthropathy. Seven patients (28%) underwent an operation due to mass lesion detected at routine control visits. None of the patients had a history of exposure to asbestos. Radiological investigations revealed 16 (64%) mass lesions in the left. Of the lesions found on exploration, 5 (20%) were intrapulmonary localized lesion without pedicle and 20 were pedicled. Of the pedicled masses, 5 were connected to parietal pleura and 15 to visceral pleura and all were intrathoracic extrapulmonary localized lesions. Eight (32%) lesions connected to left lower lobe. Additionally, three pedicled lesions were located in the lung fissure. Pedicled lesions were totally excised together with their pedicles. Intraparenchymal mass lesions were resected using wedge resection. The diameter of the resected masses was ranging between 3 and 22 cm (mean: 8.7). Macroscopically, all were encapsulated with a homogeneous cut surface. Intraoperative mortality and morbidity was not observed. The average hospitalization duration for all patients was 8.6 days (5 to 12). The mean follow-up was 33.6 (9 to 142) months with no recurrence. CONCLUSIONS: Benign localized fibrous tumors are uncommon and treated by surgical means. According to our data obtained from literature review, clinicians should be aware of recurrence possibility even after complete resection of benign localized fibrous tumor and the risk of malign transformation.

Hazards of the 'hard cash': hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) is a nonimmunoglobulin E-related immune-mediated parenchymal lung disease. A 45-year-old woman who was a lifelong nonsmoker with a six-month history of frequent episodes of cough and dyspnea was admitted to hospital. She had been working as a money counter for 20 years at a central bank. Bibasilar crackles on lung auscultation, ground-glass opacities and a mosaic pattern on high-resolution computed tomography, restrictive abnormality on pulmonary function tests and mild hypoxemia were the prominent findings. Bronchoalveolar lavage fluid analysis revealed a predominance of CD4-positive T cells, and she tested positive on her natural challenge test. She was diagnosed with subacute HP based on established criteria. She was advised to discontinue counting fresh banknotes. Prednisolone was commenced, then tapered to discontinue in the ensuing six months. Clinical and radiological improvement was achieved within two months. To the authors' knowledge, the present report is the first to describe 'hard cash HP', possibly caused by chipping dust or printing dye.

A case of Riedel's thyroiditis with pleural and pericardial effusions.

Riedel's thyroiditis (RT) is a rare type of chronic thyroiditis of unproven etiology and definite treatment. It can be associated with retroperitoneal, mediastinal, orbital, and hepatic fibrosis. Symptoms arise mainly due to compression of neighboring structures. Surgery is usually required for a definite diagnosis and decompression to relieve the symptoms. Glucocorticoids and tamoxifen are commonly used agents for the pharmacotherapy. We hereby describe the development of pleural and pericardial effusions during the clinical course of an RT case. A 39-year-old woman suffering from neck compression symptoms was admitted to the hospital. After a decompression isthmectomy, RT was diagnosed. She responded well to glucocorticoid therapy after surgery. However, symptoms reoccurred shortly after glucocorticoid withdrawal and the disease process extended to the mediastinum. Tamoxifen was started and the neck and mediastinal mass regressed and her symptoms disappeared considerably for more than 6 months. However, she was readmitted with severe dyspnea and chest pain. Further investigation revealed an exudative pleural and pericardial effusion and mediastinal enlargement. A thorough evaluation of the patient's effusions did not disclose any specific etiological insult. The patient was symptom-free with a considerable reduction of the soft tissue mass and no effusions, and treated successfully with colchicine, azathioprine, and glucocorticoids. To the best of our knowledge, this is the first case reported in the literature as an RT presenting with pleuropericardial effusions.

The coexistence of thymic carcinoma and multiple granulomas in a Turkish child.

Thymic carcinoma, which is a thymic epithelial neoplasm with obvious cytologic atypia, is a rare neoplasm. The authors report on a 10-year-old boy who presented with respiratory distress due to bulky anterior mediastinal mass. Histological and immunohistochemical studies confirmed a lymphoepithelioma-like pattern thymic carcinoma. In addition, evaluation of the specimen showed foci of caseation and multiple granulomas with extensive central necrosis within the thymic tissue. The child received chemotherapy, followed by surgery and radiotherapy. To rule out difficulties of tuberculosis he also received antituberculosis therapy. Two years after cessation of treatment, he is still in remission for thymic carcinoma.