Next generation sequence-based targeted somatic mutation analysis in thyroid nodules with pathologically diagnosed as indeterminate cytology.

PURPOSE: The management of indeterminate thyroid nodules remains a topic of ongoing debate, particularly regarding the differentiation of malignancy. Somatic mutation analysis offers crucial insights into tumor characteristics. This study aimed to assist the clinical management of indeterminate nodules with somatic mutation analysis. METHODS: Aspiration samples from 20 indeterminate thyroid nodules were included in the study. A next-generation sequencing panel containing 67 genes was used for molecular profiling. The results were compared with pathology data from surgical material, which is considered the gold standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: Variants in six genes (NRAS, BRAF, TP53, TERT, PTEN, PIK3CA) were detected in 10 out of 20 samples. We identified nine Tier 1 or 2 variants in 10 (67 %) out of 15 malignant nodules (NRAS, BRAF, TP53, TERT, PTEN, PIK3CA) and one Tier 2 (PIK3CA) variant in one out of five benign nodules. The study demonstrated an NPV of 40 %, a PPV of 90 %, a specificity of 80 %, and a sensitivity of 60 %. CONCLUSION: Based on the detected molecular markers, at least nine patients (45 %) could be managed correctly without needing a repeat FNAB attempt. This study underscores the clinical practicality of molecular tests in managing nodules with indeterminate cytology. Additionally, this study emphasizes the importance of considering the patient's age when determining the DNA- or RNA-based genetic testing method. Finally, we discussed the significance of the somatic mutation profile and its impact on the current pathological classification.

Comparison of ultrasound findings of papillary thyroid carcinoma subtypes based on the 2022 WHO classification of thyroid neoplasms.

Purpose: The present study aimed to analyze and compare sonographic features of papillary thyroid carcinoma (PTC) subtypes to determine whether ultrasound (US) may aid in differentiating particular subtypes. Methods: This retrospective study enrolled 133 patients diagnosed with 142 histopathologically proven PTCs as per the fifth edition of the World Health Organization classification of thyroid neoplasms between January 2013 and May 2023. US features based on the American College of Radiology and European Thyroid Imaging and Reporting Data Systems (TIRADS), and histopathological characteristics of nodules were assessed and compared. Results: Histopathological analysis yielded 55 (38.7%) classic PTC, 32 (22.5%) invasive encapsulated follicular variant (IEFV) PTC, 20 (14.1%) oncocytic subtype, 14 (9.9%) non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), 11 (7.8%) infiltrative follicular subtype, 7 (4.9%) tall cell subtype, 2 (1.4%) solid subtype, and 1 (0.7%) diffuse sclerosing subtype. The US findings indicating malignancy, such as taller-than-wide shape, irregular margins, echogenic foci, and higher TIRADS categories, were more frequently demonstrated in nodules with classic PTC and the tall cell subtype, in line with their histopathological features. Conversely, IEFV-PTC and NIFTP rarely exhibited these high-risk sonographic features. US appearance of the oncocytic subtype more frequently overlapped with IEFV-PTC, yet hypo/very hypoechoic nodules with larger nodular diameters and higher TIRADS scores may favor the diagnosis of this subtype. Conclusion: US features of certain subtypes may guide the differential diagnosis regarding shape, margin, echogenic foci, and TIRADS category of nodules; however, definitive subtyping is not yet possible using US images alone.

Distinguishing Pituitary Metastasis and Pituitary Neuroendocrine Tumors through Conventional MR Imaging and Clinical Features.

BACKGROUND AND PURPOSE: Given their overlapping features, pituitary metastases frequently imitate pituitary neuroendocrine tumors in neuroimaging studies. This study aimed to distinguish pituitary metastases from pituitary neuroendocrine tumors on the basis of conventional MR imaging and clinical features as a practical approach. MATERIALS AND METHODS: In this 2-center retrospective study, backward from January 2024, preoperative pituitary MR imaging examinations of 22 pituitary metastases and 74 pituitary neuroendocrine tumors were analyzed. Exclusion criteria were as follows: absence of a definitive histopathologic diagnosis, history of pituitary surgery or radiation therapy before MR imaging, and pituitary neuroendocrine tumors treated with medical therapy. Two radiologists systematically evaluated 13 conventional MR imaging features that have been reported more commonly as indicative of pituitary metastases and pituitary neuroendocrine tumors in the literature. Age, sex, history of cancer, and maximum tumor size constituted the clinical/epidemiologic features. The primary cancer origin for this study was also noted. Univariable and multivariable logistic regression was used for the selection of variables, determining independent predictors, and modeling. Interobserver agreement was evaluated for all imaging parameters using the Cohen κ statistic or intraclass correlation coefficient. RESULTS: A total of 22 patients with pituitary metastases (8 women; mean age, 49.5 [SD, 13] years) and 74 patients with pituitary neuroendocrine tumors (36 women; mean age, 50.1 [SD, 11] years) were enrolled. There was no statistically significant distributional difference in age, sex, or maximum tumor size between the 2 groups. Lung cancer (9/22; 41%) was the most commonly reported primary tumor, followed by breast (3/22; 13.6%) and unknown cancer (3/22; 13.6%). Logistic regression revealed 3 independent predictors: rapid growth on control MR imaging, masslike or nodular expansion of the pituitary stalk, and a history of cancer. The model based on these 3 features achieved an area under the curve, accuracy, sensitivity, specificity, and Brier score of 0.987 (95% CI, 0.964-1), 97.9% (95% CI, 92.7%-99.8%), 95.5% (95% CI, 77.2%-99.9%), 98.6% (95% CI, 92.7%-100%), and 0.025, respectively. CONCLUSIONS: Two conventional features based on pituitary MR imaging with the clinical variable of history of cancer had satisfying predictive performance, making them potential discriminators between pituitary metastases and pituitary neuroendocrine tumors. In cases in which differentiation between pituitary metastases and pituitary neuroendocrine tumors poses a challenge, the results of this study may help with the diagnosis.

Investigating the effects of PTEN mutations on cGAS-STING pathway in glioblastoma tumours.

BACKGROUND: PTEN is a tumour suppressor gene and well-known for being frequently mutated in several cancer types. Loss of immunogenicity can also be attributed to PTEN loss, because of its role in establishing the tumour microenvironment. Therefore, this study aimed to represent the link between PTEN and cGAS-STING activity, a key mediator of inflammation, in tumour samples of glioblastoma patients. METHODS: Tumour samples of 36 glioblastoma patients were collected. After DNA isolation, all coding regions of PTEN were sequenced and analysed. PTEN expression status was also evaluated by qRT-PCR, western blot, and immunohistochemical methods. Interferon-stimulated gene expressions, cGAMP activity, CD8 infiltration, and Granzyme B expression levels were determined especially for the evaluation of cGAS-STING activity and immunogenicity. RESULTS: Mutant PTEN patients had significantly lower PTEN expression, both at mRNA and protein levels. Decreased STING, IRF3, NF-KB1, and RELA mRNA expressions were also found in patients with mutant PTEN. Immunohistochemistry staining of PTEN displayed expressional loss in 38.1% of the patients. Besides, patients with PTEN loss had considerably lower amounts of IFNB and IFIT2 mRNA expressions. Furthermore, CD8 infiltration, cGAMP, and Granzyme B levels were reduced in the PTEN loss group. CONCLUSION: This study reveals the immunosuppressive effects of PTEN loss in glioblastoma tumours via the cGAS-STING pathway. Therefore, determining the PTEN status in tumours is of great importance, like in situations when considering the treatment of glioblastoma patients with immunotherapeutic agents.

Molecular dynamic simulation and functional analysis of pathogenic PTEN mutations in glioblastoma.

PTEN, a dual-phosphatase and scaffold protein, is one of the most commonly mutated tumour suppressor gene across various cancer types in human. The aim of this study therefore was to investigate the stability, structural and functional effects, and pathogenicity of 12 missense PTEN mutations (R15S, E18G, G36R, N49I, Y68H, I101T, C105F, D109N, V133I, C136Y, R173C and N276S) found by next generation sequencing of the PTEN gene in tissue samples obtained from glioblastoma patients. Computational tools and molecular dynamic simulation programs were used to identify the deleterious effects of these mutations. Furthermore, PTEN mRNA and protein expression levels were evaluated by qRT-PCR, Western Blot, and immunohistochemistry staining methods. Various computational tools predicted strong deleterious effects for the G36R, C105F, C136Y and N276S mutations. Molecular dynamic simulation revealed a significant decrease in protein stability for the Y68H and N276S mutations when compared with the wild type protein; whereas, C105F, D109N, V133I and R173C showed partial stability reduction. Significant residual fluctuations were observed in the R15S, N49I and C136Y mutations and radius of gyration graphs revealed the most compact structure for D109N and least for C136Y. In summary, our study is the first one to show the presence of PTEN E18G, N49I, D109N and N276S mutations in glioblastoma patients; where, D109N is neutral and N276S is a damaging and disease-associated mutation.Communicated by Ramaswamy H. Sarma.

Dysembryoplastic neuroepithelial tumors of childhood: Ege University experience.

BACKGROUND: Dysembryoplastic neuroepithelial tumors (DNETs) are rare, low-grade tumors of the central nervous system (CNS) of childhood. It is an important cause of intractable epilepsy, and it is surgically curable. We aimed to review our institutional experience with DNET in children. METHODS: Medical records of children aged less than 18 years of age diagnosed with DNET between 2009 and 2020 at Ege University Hospital were reviewed. Clinical features of the patients including age, gender, initial symptoms, duration of symptoms, medical treatments, age at the time of surgery, tumor location, degree of surgical resection, and outcome of the patients were documented. RESULTS: We reviewed the records of 17 patients with DNETs. Twelve of them were male (70%), 5 of them female (30%). The median age was 11 years (19 months-17 years). The major symptom was a seizure in all of the patients. Thirteen patients presented with complex partial seizures, whereas 2 had a simple partial seizure, and 2 generalized tonic-clonic seizures. Seven patients had drug resistant epilepsy and had received at least two anti-epileptic drugs before surgery. The median duration of symptoms was 6.6 months (0-48 months). In surgery, total surgical resection was performed in 15 patients, and 2 patients underwent partial resection. From these 15 patients, seven patients underwent lesionectomy of the tumor while the other eight patients had extended lesionectomy. The mean follow-up time was 107 months (54-144 months), the seizure control was achieved in 14 patients (82.4%) after surgery, but 3 patients experienced tumor recurrence in the follow-up. CONCLUSION: In DNETs, the complete total resection of the lesion is generally associated with seizure-free outcomes. In the patients with partial resection and lesionectomy, MRI follow-up is recommended for recurrence.

Composite pheochromocytoma with spindle cell sarcoma - a rare tumor of the adrenal gland: case report.

Composite pheochromocytomas with a non-pheochromocytoma component stemming from an embryological origin other than the neural crest comprise a unique entity. We present a patient diagnosed with a composite pheochromocytoma with spindle cell sarcoma, which is, to our knowledge, the first case reported in the current literature. A 45-year-old female patient with elevated blood pressure had undergone adrenalectomy for clinically and radiologically diagnosed pheochromocytoma. Macroscopic examination of the specimen showed an encapsulated mass containing two nodules. One tumor was composed of large polygonal neoplastic cells with round vesicular nuclei and granular cytoplasm forming the characteristic Zellballen pattern consistent with pheochromocytoma, while the other was composed of spindle cells with hyperchromatic nuclei and prominent nucleoli, thus resembling a sarcoma. The patient was discharged on the fourth post-operative day without any complications. Even though for both tumors surgical resection is the main treatment modality, our case report aims to shed light on and discuss the etiology and management of a rarely presented composite pheochromocytoma and spindle cell sarcoma.

Two challenging cases of pituicytoma.

INTRODUCTION: Pituicytoma is a rare tumor of the pituitary gland derived from neurohypophyseal pituicytes. CASE 1: A 58-year-old female presented with decreased vision; she was admitted to the neurosurgery department of Ege University after the detection of a pituitary macroadenoma. Magnetic resonance imaging (MRI) showed a 28 * 18 * 17-mm suprasellar mass, and laboratory tests revealed hypopituitarism. Hydrocortisone and L-thyroxine treatment were initiated, and the patient underwent resection through the endoscopic endonasal approach (EEA). The histopathological examination revealed a pituicytoma. The recurrence of tumor was detected during the 1-year follow-up, and the patient is awaiting surgery. CASE 2: A 70-year-old woman presented with visual changes; she had a past medical history of hypophyseal macroadenoma and pituicytoma resected through an EEA in 2012 and 2017, respectively. During follow-up, 2 years after the second surgery, MRI showed progression of the pituicytoma then measuring 38 × 23 × 22 mm; it had invaded the cavernous sinus and was causing hydrocephaly and panhypopituitarism. The patient underwent the third resection through the transcranial approach in order to minimize bleeding. After this surgery, the patient developed diabetes insipidus and underwent treatment with desmopressin. Histopathological examination revealed a pituicytoma. At 6-month follow-up, imaging showed a sellar suprasellar mass 37 × 22 × 24 mm invading the cavernous sinus, indicative of recurrence. In the postoperative period, the patient applied to the department of radiation oncology to have fractionated radiotherapy. DISCUSSION: Pituicytomas are known to be low-grade tumors; because of their rarity, they are a real challenge. These patients should be followed up closely.

Diagnostic performance rates of the ACR-TIRADS and EU-TIRADS based on histopathological evidence.

PURPOSE: In this study, we aimed to assess the effectiveness of malignancy stratification algorithms of the American College of Radiology (ACR) and European Thyroid Association (ETA) in the delineation of thyroid nodules using a database of nodules that were unequivocally diagnosed by means of histopathological examination and meticulously matched with the imaged nodules. METHODS: A total of 165 patients having 251 thyroid nodules with histopathologically proven definitive diagnoses during a 5-year period were included in this study. All patients had preoperatively undergone ultrasonography (US) examination, and US characteristics of the thyroid nodules were retrospectively analyzed and assigned in compliance with the thyroid imaging reporting and data system categories recommended by the ACR (ACR-TIRADS) and ETA (EU-TIRADS). The diagnostic effectiveness in the delineation of thyroid nodules and unnecessary fine-needle aspiration (FNAB) rates were evaluated. RESULTS: Overall, 189 nodules (75.30%) were diagnosed as benign, while 62 nodules (24.70%) were reported to be malignant based on histopathological assessment. Sensitivity and specificity rates were 71% and 75% for ACR-TIRADS and 73% and 80% for EU-TIRADS. The area under the curve values were 0.78 and 0.80 for ACR-TIRADS and EU-TIRADS, respectively. The unnecessary FNAB rates were 61% for ACR-TIRADS and 64% for EU-TIRADS as per the recommended criteria of each algorithm. CONCLUSION: The diagnostic performance of both malignancy stratification systems was signified to be moderate and sufficient in a cohort of nodules with definite histopathological diagnosis. In light of our results, we demonstrated the strengths and weaknesses of the ACR- and EU-TIRADS for physicians who should be familiar with them for optimal management of thyroid nodules.

The Correlation of Clinicopathological Findings and Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Papillary Thyroid Carcinoma

Objectives: Inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been recently introduced as potential biomarkers for tumor pathogenesis, development and prognosis in solid tumors. Our aim was to assess the correlation of clinicopathological features and NLR and PLR in patients with papillary thyroid carcinoma (PTC). Methods: A total of 201 papillary thyroid carcinoma patients were divided into groups with a cut-off preoperative median NLR and PLR value of 1,92 and 123.9, respectively. The correlation of NLR and PLR and clinicopathological features including age, tumor size, extra-thyroidal extension, thyroid capsule invasion, surgical margin positivity, multifocality, bilaterality of the patients were analyzed. Results: The mean NLR and PLR were 2.11±0.94, 129.69±42.81, respectively. Larger tumor size and higher positivity of extra-thyroidal spread were correlated with higher NLR values. No significant relationship was found between NLR and age, presence of thyroid capsule invasion, surgical margin positivity, multifocality, bilaterality, and lymph node metastasis. Also no significant association was observed between the clinicopathological features and PLR. Conclusion: High NLR was found to correlate with tumor size and extra-thyroidal extension. NLR may be used as a marker to determine the clinical behavior of disease in patients with papillary thyroid carcinoma (PTC).

Radiological nodule behavior: A critical parameter in the surgical management of pediatric pulmonary metastases.

Divarci E, Arslan S, Dökümcü Z, Kantar M, Demirag B, Öniz H, Ertan Y, Alper H, Erdener A, Özcan C. Radiological nodule behavior: A critical parameter in the surgical management of pediatric pulmonary metastases. Turk J Pediatr 2018; 60: 372-379. Radiological nodule behavior (RNB) means the course of nodule appearance on consecutive CT scans. In this study, we aimed to discuss the effects of RNB on prognosis of patients with pulmonary metastasis. Retrospective analysis of patients who underwent pulmonary metastasectomy (PM) between 2005-2015 was performed. RNBs were grouped as stable, enlarging or new rising nodules. The effects of RNBs were analyzed on recurrence, 1- and 3-year event free survival (EFS) and mortality. Twenty-seven patients (18 male) underwent PM with a median age of 15 years (3-18 years). The diagnoses were listed as osteosarcoma (13), Wilms` tumor (7), Ewing`s sarcoma (3), synovial sarcoma (2), rabdomyosarcoma (1) and mixed germ cell tumor of testis (1). RNBs were new rising in 15 patients (55%), enlarging in seven patients (26%) and stable in five patients (19%). Vital tumor metastasis was detected in all of the patients with enlarging nodules (100%); in 10 of the 15 patients with new rising nodules (66%) and none of the patients with stable nodules. None of the patients with stable nodules developed recurrence or died after PM (p˂0.05). In patients with enlarging nodules, metastases recurred and they died in the postoperative period. These findings were similar in different types of tumors. RNB could be used as a critical parameter in deciding surgical management strategies of pulmonary metastases. Stabile nodules should be observed by close follow-up with serial CT scans without surgery. All of the suspected new rising nodules should undergo surgical sampling to avoid unnecessary chemotherapy. Nodule progression under chemotherapy is a poor prognostic criteria for overall survival.

Laparoscopic adrenalectomy in children: A 25-case series and review of the literature.

BACKGROUND: Laparoscopic adrenalectomy (LA) is the gold standard and is widely performed in adults, but its use in children is relatively new. We aim to present our experience in twenty-five children with diverse adrenal pathologies and to discuss an extensive review of pediatric LA in English literature. METHODS: Medical records of children with adrenal tumors admitted to a tertiary center and treated with LA were reviewed. Characteristics and outcome of patients were compared with results of a systematic Pubmed/Medline literature review. RESULTS: Transperitoneal LAs were performed for 12 malignant and 14 benign adrenal masses (size range: 2-8cm) in 25 children (median age:63months). Fourteen lesions were on the right side, and there was one bilateral case. There were no conversion and no complication within 36months of follow-up. A literature review revealed 437 pediatric LAs with left side predomination (51.4%). The indication was a malignant lesion in 60.2% of the cases (sizes range: 1-10cm). The transperitoneal route was preferred in 94.2% of the procedures. Conversion and complication rates were 7.5% and 3.1%, respectively. CONCLUSION: LA should be preferred in selected children with adrenal pathologies. The transperitoneal route seems to be the standard approach for pediatric surgeons. Preoperative planning and surgical expertise are the keys to success. TYPE OF THE STUDY: Case series with systematic literature review. LEVEL OF EVIDENCE: IV.

Oncocytic Adreno Cortical Tumors: Pathological Features of 16 Cases and Review of the Literature.

Oncocytic neoplasms of the adrenal gland are extremely rare tumors. These tumors differ from their nononcocytic counterparts in some respects. The aim of this study was to review and discuss the clinical, histological, and immunohistochemical features of as well as the prognosis for these rare tumors. In total, 16 cases diagnosed as adrenocortical oncocytic neoplasms between January 2011 and December 2016 were included in the study. The demographic data, gross characteristics, histological data, and immunohistochemical data (Chromogranin-A, Synaptophysin, α-Inhibin, Melan-A, Ki67, PHH3) were reevaluated. The follow-up data for these patients were added in January 2017. Of the 16 cases, 12 were adrenocortical adenoma, 1 was borderline adrenocortical tumor, and 3 were adrenocortical carcinoma. The tumors equally affected both genders. The tumors were not generally large. Tumor cells had pleomorphic nuclei in ten cases, but it was more obvious in one case. The mitotic figure count was low in most tumors. Atypical mitosis and necrosis were observed in three and four tumors, respectively. None of cases included sinusoidal invasion, vascular invasion, or capsular invasion. We detected the expression of at least one specific marker (e.g., Melan-A, Inhibin-α) of the adrenal cortex in all tumors. None of the tumors were immunoreactive for Chromogranin-A. Ki-67 proliferation index was lower than 5% in all cases except three oncocytic carcinomas. In two cases, PHH3 positivity was not seen, while it was lower than 3 of 10 high-powered fields in ten cases and higher in 4 cases. All patients were alive and disease free except for two patients with adrenocortical carcinoma. In conclusion, determining the clinical, histological, and immunohistochemical characteristics of these extremely rare tumors can provide important information for early diagnosis, treatment, and follow-up of these cases.

Management of Childhood Thyroid Nodules: Surgical and Endocrinological Findings in a Large Group of Cases.

OBJECTIVE: The management of childhood thyroid nodules is still a big challenge for clinicians. In this study, we aimed to present our surgical and endocrinological experience in more than one hundred pediatric cases. METHODS: A retrospective analysis of patients admitted with a thyroid nodule between 2006 and 2014 was performed. Detailed ultrasonography and fine-needle aspiration biopsy (FNAB) were the cornerstones of the diagnostic approach. RESULTS: One hundred-three children (72 female, 31 male) with a mean age of 13.1±3.6 years (3-18 years) were admitted to our center. Management strategy was surgery in 58 patients and follow-up in 45 patients. Mean nodule size was 17±12.7 mm (2-45 mm). The diagnoses were listed as benign solitary nodule (48 patients), thyroid carcinoma (26 patients), multinodular goiter (23 patients), Hashimoto thyroiditis (4 patients), and Graves' disease (2 patients). Surgical procedures were nodulectomy/lobectomy (32 patients), total thyroidectomy (TT) (13 patients), or TT+ neck dissection (13 patients). The rate of malignancy was 25% in the total group and 44% in the surgery group. The malignancy rate was higher in patients younger than 12 years compared to older children (41% vs. 17%, p=0.040). Metastasis was seen in 38% of the malignant nodules. Postoperative complications were transient hypocalcemia (8%), permanent hypocalcemia (1.7%), and unilateral vocal cord paralysis (1.7%). Recurrence or mortality was not encountered in the 5.4±1.2-year follow-up period. CONCLUSION: Thyroid nodule in a child requires an aggressive diagnostic approach due to increased risk of malignancy and metastasis. Intraoperative frozen section examination must be done as a useful adjunct to determine the surgical strategy. Incidence of complications is small in thyroid surgery when performed by experienced surgeons.

Efficacy of simvastatin in reducing postoperative adhesions after thyroidectomy: an experimental study.

BACKGROUND: We aimed to investigate whether simvastatin had any impact on the prevention of adhesion formation after thyroidectomy in a rat model. METHODS: This study was performed in 66 Wistar albino rats randomized into three experimental groups. A right hemithyroidectomy was carried out in all the rats. Simvastatin was administered locally at a dose of 0.5 mg/kg and 0.8 mg/kg. Control rats received a saline solution only. Changes during the 1st week, 1st month and 3rd month were evaluated. Efficacy of the treatment was assessed by using a scoring system. RESULTS: The severity of adhesions in low-dose simvastatin group was significantly less than the control and high-dose groups during the 1st and 3rd month (p < .05). In addition, adhesions were less in the high dose group during the 3rd month, when compared to the control group (p < .05). Moreover, fibrosis and fibroblast scores, which represent adhesions, were significantly lower in low-dose and high-dose groups at 3rd month, compared to controls (p < .05). CONCLUSIONS: We investigated the influence of simvastatin application on post-thyroidectomy adhesion formation in rats. Whether adhesions, causing technical difficulties during neck redo surgery, can be reduced by the use of simvastatin in human, needs to be studied.

Management of Calvarial Tumors: A Retrospective Analysis and Literature Review.

AIM: Tumors of various organs that metastasize to bone do not neglect calvarium as a target. The aim of this study was to characterize the calvarial tumors. MATERIAL AND METHODS: We retrospectively reviewed 45 consecutive patients operated for calvarial masses from January 2002 till May 2012 at our hospital. Skull base tumors and patients ≤18 years were excluded. RESULTS: Three groups of lesions were found - calvarial metastases (15/45), primary tumors (5/45) and tumor-like lesions (25/45). Malignant lesions were equitable by gender distribution, higher age of onset (median age of primary =55; secondary = 60 years) and benign lesions by younger age (median = 35) and female bias (18/25). Calvarial metastases mostly presented with local swelling (10/15), local pain (6/15) and rarely neurologic deficit. There was associated dural sinus thrombosis (4/20 of malignant; 1/25 of benign lesions) and osteolysis (3/5 primary malignant, 13/15 secondary and 18/25 of benign lesions). Complete surgical excision was possible with minimal morbidity in all except one patient and nil mortality. CONCLUSION: Nearly half (20/45) of the calvarial lesions tend to be malignant with most of them presenting as silent painless masses. Surgical excision should be considered only after suitable investigation and appropriate neurosurgical set-up.

An unusual manifestation: Papillary thyroid carcinoma in a patient with ataxia-telengiectasia.

Ataxia-telangiectasia (A-T) is a rare autosomal recessive, multisystem, neurodegenerative disorder, characterized by oculocutaneous telangiectasias, variable immunodeficiency and progressive neurological impairment. Definitive diagnosis is made by revealing a disease causing mutation on ATM gene. Missense mutations and polymorphisms of ATM gene can play a role in the development of thyroid papillary carcinoma. A 13-year-old Turkish girl was diagnosed with ataxia telengiectasia at the age of 8 years. When she was 12 years old, multi-nodular goiter was detected by physical examination and ultrasonography. She underwent thyroidectomy and histopathologic investigation revealed a papillary carcinoma with follicular variant. The patient received post-operative radioiodine therapy as well as L-thyroxine treatment because she had residual lesions. Up until now, she is the first Turkish child wit A-T and thyroid carcinoma described in the literature.

Evaluation of the role of Epstein-Barr virus in cases of nodal or extranodal T- and NK-cell lymphoma using eber in situ hybridization.

Various racial and geographic differences have been observed in studies questioning the role of Epstein-Barr virus (EBV) infection in the etiology of T- and NK-cell lymphomas. The aim of this study was to evaluate the relationship of EBV with nodal or extranodal (skin excluded) T- and NK-cell lymphoma subtypes encountered in our geographic area. Sixty-two cases of peripheral T-cell lymphoma were included in the study. EBV-encoded early RNA (EBER) was detected by in situ hybridization. The distributions of T- and NK-cell lymphoma subtypes were as follows: 32 peripheral T-cell lymphomas, unspecified (PTCL, NOS), 13 anaplastic large-cell lymphomas (ALCL), 8 angioimmunoblastic T-cell lymphomas (AITCL), 4 extranodal NK/T-cell lymphomas, nasal type (NKTCL), 3 enteropathy-type T-cell lymphomas (ETTCL), 1 hepatosplenic T-cell lymphoma (HSTCL), and 1 subcutaneous panniculitis-like T-cell lymphoma (SPTCL). Using a cut-off value of >25% of EBER-positive neoplastic lymphoid cells, EBV was positive in 22.6% of all cases. According to subtype, the neoplastic cells of 31.3% of PTCL, NOS and 100% of extranodal NKTCL, nasal type were EBER positive, whereas some cases of ALCL, AITCL, and ETTCL presented EBER-positive non­neoplastic cells, and all cells of HSTCL and SPTCL were EBV negative. Extranodal NKTCL, nasal type, presented the strongest association with EBV, followed by PTCL, NOS.