Tommaso Ricchetti

Circulating plasma DNA as diagnostic biomarker in non-small cell lung cancer

OBJECTIVES The presence of circulating DNA in plasma of patients with malignant neoplasm has been a known fact for over 30 years. Since then, the concentration of free circulating plasma DNA has been studied as well as the genetic alterations and epigenetic alterations of tumour DNA of patients that suffer from various types of tumours. The analysis of circulating plasma DNA may be a useful marker to get an early diagnosis on malignant neoplasms. This study has been specifically designed to validate the quantification of circulating DNA in order to design a test useful for the early identification of non-small cell lung cancer patients and the monitoring of lung cancer progression. A second aim of this work is the sensibility and specificity evaluation of such method for future applications. METHODS The quantity of plasma DNA was determined using quantitative Real-Time PCR with amplification of the human telomerase reverse transcriptase (hTERT) gene in 151 patients that suffer from lung cancer and 79 healthy controls. The performance of the test was evaluated with a ROC curve. The relationship between the DNA concentration and main demographic, clinical and pathological variables was examined with logistic regression models as well as multiple linear regression models. RESULTS The concentration of circulating plasma DNA was about four times higher in patients with lung cancer with respect to the controls (12.8 vs 2.9 ng/mL). The area under the ROC curve was 0.79 (95% CI, 0.710-0.83). The concentration of circulating DNA proved to be an important risk factor for the presence of the illness and a prognostic index in the follow-up. CONCLUSIONS The use of quantitative Real-Time PCR revealed that higher values of circulating DNA can be found in patients with lung neoplasm compared to the healthy controls. This could have practical implications such as the use in screening programs and a possible prognostic significance in the follow-up.

PET/CT assessment of neuroendocrine tumors of the lung with special emphasis on bronchial carcinoids

Pulmonary neuroendocrine tumors (pNETs) arise from bronchial mucosal cells known as enterochromaffin cells which are part of the diffuse neuroendocrine system. The pathological spectrum of pNETs ranges from low-/intermediate-grade neoplasms such as bronchial carcinoids (BCs), also known as typical or atypical carcinoids, to high-grade neoplasms as large-cell neuroendocrine carcinoma and small-cell lung cancer. The tumor biology of pNETs still represents a matter of open debate. The distinct features among the different pNETs include not only their pathologic characteristics but also their clinical behavior, epidemiology, treatment, and prognosis. In this sense, a correct pathological identification in the preoperative setting is a key element for planning the best strategy of care in pNETs and especially in BCs. Controversial results have been reported on the diagnostic accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography (F-18-FDG PET or PET/CT) in BCs. On the other hand, there is increasing evidence supporting the use of PET with somatostatin analogues (DOTA-TOC, DOTA-NOC, or DOTA-TATE) labeled with gallium-68 (Ga-68) in pNETs. Herein, we review the pertinent literature aiming to better define the current state of art of PET/CT in the detection and histological differentiation of pNETs with special emphasis on BCs.

Intra pulmonary migration of a Kirschner wire after glenohumeral fixation.

A 79-year-old asymptomatic woman underwent arthrodesiswith a double K-wire insertion for a posttraumatic invet-erate right glenohumeral dislocation. After removal of thefirst K-wire, chest X-ray showed intrathoracic migration ofthe foreign body, and the CT scan confirmed the pulmonarypenetration of the device within the right upper lobe withintraparenchymal surrounding hematoma (Fig. 1).Although the vital parameters were substantially within therange, the patient underwent urgent surgery. A combinedapproach was attempted: the K-wire was mobilized fromthe glenoid cavity to resect the distal hook and, at the sametime, a right lateral thoracotomy was performed to removesafely the device deeply slipped into the lung and suture theparenchyma (Fig. 2). The postoperative course wasuneventful, and the patient was discharged on the eighthpostoperative day.Improper uses or positioning of K-wires are widelydescribed in the literature and may expose patients toinsidious but potentially life-threatening complications [1];therefore, regular radiological follow-up may be advisablein patients with foreign body at risk of dislodgement intovital structures.

Cystic fibrohistiocytic tumor of the lung presenting as a solitary lesion

Cystic fibrohistiocytic tumor of the lung is a rare neoplasm. In many cases it represents a metastasis from a benign or low-grade fibrohistiocytic tumor of the skin, but occasionally it may be primary. Radiologically it usually occurs as a cystic change of multiple pulmonary nodules, and pneumothorax is the most frequent presenting symptom. We present here a 16-year-old man with recurrent right pneumothorax. The patient had no history of cutaneous fibrohistiocytic lesions. He underwent videothoracoscopic right apical segmentectomy, right lower lobe nodulectomy, and pleuroabrasion. Microscopy of the apical segmentectomy showed a cystic fibrohistiocytic tumor, whereas the nodule of the lower lobe was an intraparenchymal lymph node. The patient is alive with no tumor recurrence. The differential diagnosis includes Langerhans cell histiocytosis, lymphangioleiomyomatosis, pleuropulmonary blastoma, and metastatic endometrial stromal sarcoma. This disease usually occurs with multiple pulmonary cysts and cavitation. This case is the first reported presenting as a single lesion.

Extraskeletal Osteosarcoma Arising from the Pleura

A 75-year-old woman presented at Emergency Department with acute onset of right-sided chest pain and hemoptysis. Radiological examination revealed a large thoracic mass located in the right upper lung field. Chest CT scan showed a large round-shaped tumor (82 9 81 mm), heterogeneously enhanced after the injection of iodine contrast (Fig. 1a–c) with no clear signs of chest wall invasion. At 18-FDG PET/CT scan, the thoracic mass showed a moderate (SUVmax = 4.45), non-homogenous uptake of the tracer without further uptaking areas (Fig. 1d, e). Percutaneous needle biopsy showed malignant p63?, TTF1cells, raising the suspicion of squamous cell carcinoma of the lung. Accordingly, a surgical excision was planned for right lateral thoracotomy. At surgery, the tumor appeared as a well-encapsulated, cystic and huge mass arising from parietal pleura without involvement of chest wall but strictly adherent to the visceral pleura and pulmonary parenchyma. Radical resection was achieved with wedge resection of right upper lobe, while chest wall resection was not needed. En bloc resection of the tumor along with a peripheral portion of the right upper lobe was finally performed. Postoperative course was uneventful and the patient was discharged on the 5th post-op day. Final pathological examination revealed a grade 3 (FNCLCC) osteosarcoma (with telangiectasic features) with no involvement of the lung parenchyma. At immunohistochemistry, malignant cells were positive for SATB2; faint positive for MDM2, EMA, WT1, p63, and smooth muscle actin; and negative for S100 protein, CAM 5.2 keratin, desmin, caldesmon, calretinin, TTF1, CD31, achieving a final diagnosis of primary extraskeletal osteosarcoma (Fig. 2). Extraskeletal osteosarcomas (EO) are very rare neoplasms, accounting for only 1–2% of soft tissues sarcomas and for 4–5% of all osteosarcomas [1]. Computed and positron emission tomography findings usually show a large heterogeneous mass due to necrosis, spontaneous intra-lesional hemorrhage, and various grade of ossification; although all osteosarcomas contain an osteoid matrix at the time of histological analysis, mineralization may not be radiologically visible in up to 50% of cases [2]. The histological subtypes are the same as those of skeletal osteosarcomas, including osteoblastic, fibroblastic, and chondroblastic. Small cell, giant cell, and telangiectatic subtypes are less commonly diagnosed [3]. Only few cases of EO arising from parietal pleura have been reported in literature [4]; in the present case, the neoplasm was in continuum with the adipose tissue of the endothoracic fascia, the ‘‘outermost coat’’ of the thoracic cavity, firmly attached to the parietal pleura, so that, there is no surgical plane of cleavage between them. There are emerging evidences suggesting that the endothoracic fascia represents an anatomic site where different types of sarcomas, (i.e., liposarcoma, fibrosarcoma, and angiosarcoma) could occur [4]. Diagnosis requires exclusion of skeletal origin by radiographic or intraoperative findings and clinical correlation. Moreover, the differential diagnosis may be clinically with various benign diseases (hematoma, chronic pleural empyema, tuberculosis, calcifying fibrous pseudotumor) or with other malignant mesenchymal & Filippo Lococo filippo.lococo@asmn.re.it

Diagnostic pitfalls in the preoperative 18F-FDG PET/CT evaluation of a case of giant malignant solitary fibrous tumor of the pleura

Solitary fibrous tumor of the pleura (SFTP) is an uncommon entity, generally with an indolent behavior. Nevertheless, some malignant forms have been rarely reported. These, often have an aggressive biological behavior with pathological findings of invasiveness. The preoperative diagnosis and evaluation of the grade of malignancy are extremely challenging. Herein we report a case of a 64-year-old man who presented with a left giant intra-thoracic mass imaged with fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG/PET-CT) and sampled via fine-needle aspiration biopsy (FNAB). Imaging and FNAB findings showed suspicion of a benign form of SFTP. Surgical radical resection of the giant mass was performed. The definitive histological diagnosis showed a malignant SFTP. Based on this report, we take the opportunity to briefly discuss the insidious pitfalls concerning the radiological and (18)F-FDG/PET-CT features as well as cyto/histological findings in the pre-operative diagnostic work-up examination of this rare entity.

Is Age over 70 Years a Risk Factor for Pneumonectomy

The lengthening of life expectancy has led to more surgical procedures in elderly patients. The aim of this work was to determine whether age >70 years is a risk factor for pneumonectomy. All cases of pneumonectomy from January 1999 to December 2006 were retrospectively reviewed. The 40 patients aged > 70 years were compared with a group of 70 patients aged 40-68 years matched for sex, physical status, respiratory function, side of pneumonectomy, and pathologic stage. Postoperatively, significantly more older patients had atrial fibrillation (24% vs. 5.6%). There was a low incidence of respiratory complications in both groups, and reduced respiratory function did not increase respiratory morbidity. Thirty-day mortality was not significantly different (2.5% in older vs. 1.4% in younger patients), but long-term mortality rates evaluated at December 31, 2007 were 50% for those aged <70 years (35 patients) and 72.5% for the older group. Although age is a risk factor for morbidity and mortality in pneumonectomy, the risk is acceptable.

Cervical subcutaneous emphysema and pneumomediastinum as an unusual complication of idiopathic pulmonary fibrosis

A 52-year-old woman, an active heavy smoker, who was being followed for idiopathic pulmonary fibrosis (IPF), presented to our emergency department with acute-onset right-side chest pain, dysphagia and facial swelling. No fever or dyspnea was noted. Examination revealed palpable crepitus in the neck, particularly in the right supraclavicular region, but no fluid collection. There was no clinical or laboratory evidence of exacerbation of her interstitial lung disease at the time of admission. Chest X-rays and high-resolution computed tomography (CT) showed air in the mediastinum, ascending to the soft tissues of the neck (Figs 1,2, yellow arrows). No signs of pneumothorax or pleural effusion were found, while diffuse infiltrative fibrotic interstitial disease (Figs 1,2, red arrows) with a radiological ‘UIP pattern’ (according to the official 2011 ATS/ERS/JRS/ALAT guidelines) was observed. The patient was admitted for monitoring and treated with intravenous antibiotics and analgesics, while other causes of pneumomediastinum were excluded. Overall, the hospital course was unremarkable and the patient was discharged after her symptoms regressed and there was complete radiological resolution. Fig. 1. Chest X-ray revealed the presence of air in the mediastinum, ascending to the soft tissue of the neck (yellow arrows). No signs of pneumothorax or pleural effusions were found, while a diffuse infiltrative fibrotic interstitial disease (red arrows) with a radiological ‘UIP pattern’ was observed.

Occasional detection of thymic epithelial tumor 4 years after diagnosis of adult onset Still disease: A challenging case report and immuno-oncological considerations coming from pertinent literature review

Background:Thymoma is a T cell neoplasm arising from the thymic epithelium that due to its immunological role, frequently undercover derangements of immunity such a tumors and autoimmune diseases. Methods:Herein, we report, to the best of our knowledge, the first description of an association between thymoma and adult onset Still disease (AOSD) in a 47-year-old man. The first one was occasionally detected 4 years later the diagnosis of AOSD, and surgically removed via right lateral thoracotomy. Histology confirmed an encapsulated thymic tumor (type AB sec. WHO-classification). Results:The AOSD was particularly resistant to the therapy, requiring a combination of immunosuppressant followed by anti-IL1R, that was the only steroids-sparing treatment capable to induce and maintain the remission. The differential diagnosis was particularly challenging because of the severe myasthenic-like symptoms that, with normal laboratory tests, were initially misinterpreted as fibromyalgia. The pathogenic link of this association could be a thymus escape of autoreactive T lymphocytes causing autoimmunity. Conclusion:Clinicians should be always include the possibility of a thymoma in the differential diagnosis of an unusual new onset of weakness and normal laboratories data, in particular once autoimmune disease is present in the medical history.

Asymptomatic air-embolism following percutaneous radiofrequency ablation of lung tumor: Rare or underestimated complication?

Air embolism is an insidious but potentially life-threatening complication very rarely occurring after radio-frequency ablation (RFA). Its incidence has been reported to be 0.02% to 0.07% after trans-thoracic cutting needle biopsy (TTNB) of lung lesions. Clinical impact is devastating in most cases, with a high rate of death and catastrophic sequelae (myocardial infarction, stroke). Prompt recognition is crucial for a successful treatment.