DICER1 Hotspot Mutations in Pleuropulmonary Blastoma: A Case Series From a Tertiary Center.

Pleuropulmonary blastoma (PPB) is a potentially aggressive, rare childhood neoplasia. We investigated histopathological features, survival, and DICER1 hotspot mutations among PPB patients. Archive records at our institution were reviewed, covering a 20-year period. Thirteen children (6 males and 7 females) with a mean age of 30.5 (range 6-83) months were included. The tumor subtypes were type I in 6 (46%), type II in 4 (31%), and type III in 3 (23%). Only tumors with type II and type III histology showed anaplasia (4/7, 57%). Median follow-up was 28 (range 9-216) months. Three-year overall survival rate was 83.3% and 3-year progression-free survival rate was 25%. Progression was seen in 60% (3/5) of type I and 66.7% (4/6) of type II and type III cases. Two patients died of disseminated disease at 9 and 44 months. Hotspot missense mutations on DICER1 gene were detected in all 11 patients with available tumor tissue. We found an additional novel germline loss-of-function mutation (c.5436dupT; p.E1813*) in 1 case. To the best of our knowledge, this is the first study to investigate hotspot missense mutations on DICER1 gene among the largest series of Turkish children with PPB.

Comparison of conventional cytology and SurePath in split thyroid fine needle aspiration materials.

OBJECTIVE: The aim of the present study was to compare the cytomorphological features and cytopathological diagnoses in thyroid aspiration materials prepared by SurePath® (SP) and conventional cytology (CC). MATERIALS AND METHODS: Fine needle aspiration (FNA) materials from 180 thyroid nodules were divided into two groups to prepare three conventional smears and one SP slide. Twenty-nine cytomorphological features of thyroid lesions were compared in the CC and SP slides. The Kappa coefficiency was determined for each. The cytopathological diagnosis of CC and SP were compared. RESULTS: The feature with the lowest Kappa coefficient was the haemorrhagic background, whereas nuclear molding had the highest Kappa coefficient. The rates of the atypical and suspicious cytopathological diagnostic categories were decreased, whereas the rates of benign and malignant categories were increased in SP. When the cytopathological diagnoses of CC and SP were compared with the histopathological diagnoses of the 31 thyroidectomy materials, the results were similar. CONCLUSION: The common problems seen in CC, such as an excessive number of slides, a haemorrhagic background and air drying artefact in the SP method were not encountered. Through these advantages, the rate of the indeterminate cytopathological diagnosis was low in SP. In addition to those advantages, the increased rates of non-diagnostic cases, the difficulty in evaluating the cytomorphologic features owing to tridimensional structures and the smaller size of the cells and the presence of tridimensional structures uninterpreted microscopically were the disadvantages of SP. The present results showed that SP could be used instead of CC in thyroid cytopathology.

EGFR mutation testing using archival-stained smears in non-small cell lung carcinoma.

OBJECTIVE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown benefits regarding progression-free and overall survival in patients whose tumours show EGFR mutations. Most patients' lung cancer is metastatic when detected. Small tissue samples and cytological materials are widely used in diagnosis. The aim of the present study was to compare the EGFR mutation analysis results between cytology, small biopsies and resections. METHODS: Archival material for EGFR testing was reviewed. Cell blocks and/or stained smears and tissue blocks were used where appropriate. The tumour cell count and percentage were recorded as well as the DNA content. The influence of TTF-1 immunoreactivity on EGFR testing was also investigated. RESULTS: The study cohort included 300 unpaired specimens of 84 resections, 83 small biopsies and 133 cytological materials. EGFR mutation rates did not differ significantly for cytology, small biopsy and resections (P > 0.05). The higher tumour cell percentage in FNAs than in exfoliative cytology did not affect the EGFR mutation status. EGFR mutation rates were similar when either slides or cell blocks were used. Cytology slides revealed a higher tumour cell content and DNA concentration than the cell blocks. May-Grünwald-Giemsa (MGG)-stained smears had higher rates of the EGFR mutation than the Papanicolaou (Pap)-stained slides (P < 0.05). Tumours with negative immunoreactivity for TTF-1 are less likely to have an EGFR mutation (P < 0.05). CONCLUSIONS: Cytological materials can be used successfully for mutation analysis in lung cancer.

The preoperative exclusion of thyroid carcinoma in multinodular goiter: Dynamic contrast-enhanced magnetic resonance imaging versus ultrasonography-guided fine-needle aspiration biopsy.

BACKGROUND: We compared the diagnostic values of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and ultrasonography (USG)-guided fine-needle aspiration biopsy (FNAB) in the detection of thyroid carcinoma associated with multinodular goiter. METHODS: USG-guided FNAB and DCE-MRI were performed consecutively on 26 patients who had multinodular goiter with dominant nodules and clinical suspicion of malignancy. DCE-MRI findings, cytodiagnosis, and final histopathologic results were correlated. We compared the sensitivity, specificity, diagnostic accuracy, and positive (PPV) and negative predictive values (NPV) of DCE-MRI and USG-guided FNAB. RESULTS: Of 57 nodules in 26 patients, 16, 37, and 4 nodules showed delayed, plateau, and rapid washout patterns, respectively. Thyroid carcinoma was found in 8 patients (31%). Delayed washout pattern in a nodule was correlated with the histologic diagnosis of thyroid carcinoma (P < .001). None of the nodules with thyroid carcinoma had a plateau or rapid washout pattern. The sensitivity and NPV of DCE-MRI to diagnose thyroid carcinoma were greater when compared with those in USG-guided FNAB (100 vs 71.4%, and 100 vs 91.7%, respectively; P < .001). CONCLUSION: When other diagnostic methods are inconclusive, DCE-MRI is superior to USG-guided FNAB to exclude thyroid carcinoma in patients with multinodular goiter.

Isolated lung perfusion with Paclitaxel and docetaxel: comparison of the early effects on pulmonary physiology.

BACKGROUND: This study was designed to compare the early effects of docetaxel and paclitaxel on pulmonary physiology after isolated lung perfusion. METHODS: Rats underwent isolated left lung perfusion with docetaxel in group 1 (n = 5), paclitaxel in group 2 (n = 5), and 0.9 %NaCl in the control group (n = 5). Ventilation pressures, compliance of the lungs, blood gas analysis and histopathological results were compared between the groups. RESULTS: In group 1 and group 2, the decrease in PaO (2) (p = 0.008) and increase in ventilation pressures were significantly higher than in the control group ( P = 0.016). In group 2, pCO (2) retention was higher compared to the docetaxel perfusion group ( P = 0.016). In the histochemical assessment, intra-alveolar hemorrhage and mononuclear cell infiltration were dense and perivascular edema was not present in group 1. In group 2, perivascular and intraalveolar edema were found to be dense. CONCLUSION: Perfusion by either of the chemotherapeutics resulted in an alteration of lung physiology in rat lungs. If isolated lung perfusion is administered using chemotherapeutics from the taxanes group, it is suggested that docetaxel could be the first choice for isolated lung perfusion.

The value of fine-needle aspiration cytology in salivary gland lesions, 1994-2004.

OBJECTIVE: Fine-needle aspiration cytology (FNAC) of the salivary gland is a commonly accepted, sensitive and specific technique in the diagnosis of both neoplastic and nonneoplastic lesions of the salivary gland. The aim of this study was to investigate the efficacy of FNAC of salivary gland lesions and to decide whether the radiologist could perform it or not. METHODS: We aspirated 162 salivary gland lesions of 56 patients undergoing biopsy and excision. A cytopathologist and a surgical pathologist made histopathological and cytological examinations in a blinded fashion. RESULTS: In the present study, among the FNAC performed in 162 patients with salivary gland masses, 15 (9%) were inadequate, and the remaining 147 were diagnostic. Of the 162 cases, 56 (35%) were also checked histologically. With FNAC there were 89 (55%) nonneoplastic and 58 (36%) neoplastic lesions. With FNAC 45 of the neoplastic lesions were benign and 13 malignant tumors. When cytohistopathological correlation was performed, the overall accuracy in diagnosing benign and malignant lesions was 91 and 78%, respectively, except for 2 malignant lymphoma cases. The sensitivity and specificity for benign and malignant lesions were 72 and 100%, respectively. The diagnostic sensitivity for all neoplastic and nonneoplastic lesions was 84% and the specificity 92%. There was 1 false-positive result, in which a nonneoplastic lesion was misdiagnosed as a Warthin's tumor. Fifteen (26%) cases were false-negative, 12 of which were undefined. CONCLUSION: FNAC is a useful and reliable tool in the diagnosis of salivary gland masses when performed by a radiologist or a clinician. There are no contraindications, and complications are minimal.

Sarcoidosis after use of interferon for chronic hepatitis C: report of a case and review of the literature.

Although interferon has not been classified in the pathogenesis of sarcoidosis, it may rarely lead to this disease during treatment of chronic hepatitis C. The case of a 36-year-old woman with chronic hepatitis C who developed sarcoidosis within 10 weeks of treatment with recombinant interferon-alpha2a and ribavirin is described and all seven similar cases published in English from 1989 to 2001 are discussed.

An unusual radiographic finding in pulmonary parenchymal endometriosis.

Thoracic endometriosis is an uncommon disorder. In most cases, the diagnosis is based on history alone and radiographic findings depend on the menstrual cycle. CT findings include ill-defined or well-defined opacities, nodular lesions, cavities, cystic changes and bullous formation. We report a case of pulmonary parenchymal endometriosis with an unusual radiographic finding.

The value of labial biopsy in the differentiation of sarcoidosis from tuberculosis.

BACKGROUND: Since the clinical features of sarcoidosis and tuberculosis may mimic each other, and that differentiation is not easy on clinical grounds, a histologic diagnosis may be mandatory in countries where the prevalence of tuberculosis is high or in populations with large numbers of immigrants from those countries. Previous studies have suggested the minor salivary gland biopsy as a useful method in the diagnosis of sarcoidosis. The present study was undertaken to evaluate the value of labial biopsy in the differentiation of sarcoidosis from tuberculosis in patients with enlarged hilar and paratracheal lymph nodes. METHODS: Labial biopsy was performed in 50 consecutive patients with sarcoidosis, and in 35 consecutive patients with tuberculosis who had intrathoracic lympadenopathy. The files of all patients were reviewed for the clinical presentation, radiographic features, SACE levels, tuberculin skin test anergy, and the frequency of positive labial biopsy in each disease. RESULTS: Noncaseating granulomas were present in labial biopsies obtained from 24 patients (48%) of 50 patients with sarcoidosis. Labial biopsies were positive in 4 of 6 patients who had an abnormality on eye examination and in 3 of 5 patients who had noncaseating granulomas on biopsy material from skin. In two of 4 patients who underwent mediastinoscopy, noncaseating granulomas were detected on labial biopsy. In contrast to the patients with sarcoidosis labial biopsies revealed normal minor salivary glands in all patients with tuberculosis. CONCLUSIONS: Labial biopsy has a high discriminatory value as a diagnostic tool in the differentiation of sarcoidosis from tuberculosis. Although it has a rather lower diagnostic yield than transbronchial lung biopsy, labial biopsy should be considered as a first line approach prior to performing other more invasive procedures for the tissue confirmation of sarcoidosis.

Pulmonary alveolar lithiasis in two siblings.

Pulmonary alveolar microlithiasis (PAM) is a rare disease of unknown etiology and is characterized by the deposition of calcium phosphate microliths within the alveolar airspaces. We report 2 asymptomatic siblings, a 7-year-old girl and her 13-year-old brother, with PAM. In the girl, chest X-ray and computed tomography revealed diffuse interstitial changes but no uptake of technetium 99m (99mTc) on bone scan was noted in the lung. Microliths stained pink with Papanicolaou dye in bronchoalveolar lavage fluid (BALF) but did not stain with von Kossa. In the brother, characteristic radiological findings and 99mTc uptake in the lung were detected. The microliths stained pink with Papanicolaou in BALF and black with von Kossa as well. We hypothesize that the first case is in the early phase of PAM because of lack of 99mTc uptake.

Cushing's syndrome caused by ectopic corticotropin secretion by multiple peripheral pulmonary carcinoids and tumorlets of carcinoid type.

Multiple peripheral pulmonary carcinoid tumors or their smaller counterparts (tumorlets of carcinoid type) are the most unusual form of carcinoids as a cause of ectopic corticotropin syndrome. Only three case reports were found in the literature. We describe a 35 year-old female patient with ectopic corticotropin secretion due to multiple peripheral pulmonary carcinoid tumors and tumorlets. A high-dose dexamethasone suppression test result led to the diagnosis of Cushing's disease in our case. But no tumor was identified on sella imaging and bilateral inferior petrosal sinus sampling was non-diagnostic. Computed tomography of the lungs revealed multiple acinar-nodular parenchymal infiltrations confined to the left lung. Corticotropin-dependent hypercortisolism persisted after bilateral adrenalectomy. A second operation was necessary to remove the hyperplastic adrenal remnants. Meanwhile, computed tomography findings of the thorax were unchanged. We decided to explore these nodules by open lung biopsy. During the procedure multiple nodules ranging 12 to 3 mm in diameter scattered throughout the left lung were observed and left pneumonectomy was performed. Histopathological diagnosis was multiple peripheral carcinoid tumors and tumorlets of carcinoid type showing positive immunostaining with corticotropin. This observation emphasizes a rare form of carcinoids as a cause of ectopic corticotropin secretion and its unusual response to high dose dexamethasone suppression test.

Phantom steatosis of the liver: report of a case.

A patient, referred under a diagnosis of metastatic liver tumors, was found to have multiple areas of focal fatty change (FFC) which, during follow-up, exhibited discordant evolutions. To our knowledge, this phenomenon-regression of a FFC lesion with concurrent appearance or progression of other similar lesions in the same patient, has been reported in only one previous case. FFC can be strongly suggested by clinical, biochemical and radiologic criteria. However, an exact diagnosis can only be made with biopsy. To avoid misdiagnosing a malignancy as FFC and vice versa, biopsy should be performed without hesitation in all patients in whom a change in approach is possible.

Value of bronchoalveolar lavage in lipidoses with pulmonary involvement.

Adult lipid storage disorders with pulmonary involvement are rare and usually diagnosed at autopsy. We report a patient with splenomegaly and reticulonodular pattern on lung computed tomography. Bronchoalveolar lavage was performed and revealed the presence of lipid-containing foamy cells, with the demonstration of both periodic acid-Schiff (PAS) and scharlach red stain positive vacuoles in the cytoplasm of alveolar macrophages. The same cells were found in bone marrow biopsy. As in other rare disorders, bronchoalveolar lavage may be of diagnostic value in lipid storage disorders with pulmonary involvement.

Case of spontaneous haemothorax associated with an endodermal sinus tumour.

Spontaneous haemothorax is rare in infants. A case is reported of a nine month old infant who was found to have an endodermal sinus tumour.

Intussusception due to ectopic pancreatic tissue in a nine-month-old child.

Ileo-colic intussusception was diagnosed in a nine-month-old male infant who presented with abdominal distention, irritability, and bilious vomiting. After reduction of the invaginated segment, a mass measuring one cm was palpated at the antimesenteric border of the terminal ileum. Pathological examination of the mass revealed ectopic pancreatic tissue, which most likely caused the intussusception.