Massive solitary fibrous intrathoracic tumor presented as primary lung cancer.

Solitary fibrous tumours (SFT) are rare soft tissue tumours with a primarily benign course. Complete surgical resection is the mainstay treatment. In this case report, a 75-year-old man had a massive intrathoracic SFT which was subsequently surgically resected without complications. Although the clinical presentation and CT features of these tumours can mimic lung cancer, the clinical course is significantly more favourable. Diagnostic examination and surgical treatment of intrathoracic SFT should be considered even in patients with increased post-operative risk.

Asymptomatic lung nodules in dental professionals: A diagnostic challenge.

Dental care workers are frequently exposed to various types of volatile organic and inorganic compounds. In addition to biological materials, these compounds include silica, heavy metals, and acrylic plastics. Such exposures may cause respiratory symptoms, but the nonspecific nature of these symptoms often means that the etiology is difficult to discern. The disease severity depends on the particle size and type of the inhaled compounds, as well as the duration and intensity of exposure, which varies markedly among dental workers. Here, we present two unique cases with the same occupational exposure. Both patients showed radiological changes in the lungs that were suspicious for lung cancer. The first patient did not undergo a biopsy due to cardiac comorbidities and risk of bleeding, and the diagnosis was based on thoracic computer tomography (CT) which confirmed multiple, bilateral, solid, smooth, partly calcified lung nodules, normal positron emission tomography (PET)-CT and the relevant occupational exposure. In the second case, a CT-guided biopsy and thoracoscopic resection was done with histopathological findings consistent with granuloma. The multi-disciplinary team decision of both cases was consistent with occupational exposure related lunge disease. This is the first case study report whereby same occupational exposure related health condition is compared with two different approaches. Respiratory clinicians should be aware of this potential diagnosis, especially for asymptomatic patients with relevant exposures. Careful attention to the occupational history may help to prevent unnecessary, invasive diagnostic procedures or surgeries.

Adult pulmonary blastoma in an adult with urothelial cancer: A case report.

Pulmonary blastoma is an aggressive lung cancer with incidence ranging from 0.25-0.5 of all the reported lung cancers. Although, pulmonary blastoma is seen commonly in childhood its very rare in adults. Surgical treatment is often the treatment of choice, but benefits of neoadjuvant chemotherapy are unclear. People with DICER1 syndrome commonly develop Pulmonary blastoma and do have concomitant or previous history of benign or malignant tumours in extra pulmonary site like kidney, thyroid, ovary cervix testicle and eye. As per our knowledge, this is the first case of adult pulmonary blastoma previously diagnosed with urothelial cancer and a strong familial predilection of malignancy, with negative genetic test for DICER1 mutations.

Forecasting lung cancer incidence, mortality, and prevalence to year 2030.

BACKGROUND: Lung cancer incidence and prevalence is increasing worldwide and there is a focus on prevention, early detection, and development of new treatments which will impact the epidemiological patterns of lung cancer. The clinical characteristics and the trends in incidence, mortality, and prevalence of lung cancer in Denmark from 2006 through 2015 are described and a model for predicting the future epidemiological profile of lung cancer through 2030 is introduced. METHODS: The study population comprised all cases of lung cancer, registered in the Danish Cancer Registry, who were alive on January 1, 2006 or had a first-time ever diagnosis of lung cancer during 2006 through 2015. Information on morphology, stage of the disease, comorbidity and survival was obtained from other Danish health registers. Based on NORDCAN data and estimated patient mortality rates as well as prevalence proportions for the period 2006 through 2015, future case numbers of annual incidence, deaths, and resulting prevalence were projected. RESULTS: A total of 44.291 patients were included in the study. A shift towards more patients diagnosed with lower stages and with adenocarcinoma was observed. The incidence increased and the patient mortality rate decreased significantly, with a doubling of the prevalence during the observation period. We project that the numbers of prevalent cases of lung cancer in Denmark most likely will increase from about 10,000 at the end of 2015 to about 23,000 at the end of 2030. CONCLUSIONS: Our findings support that lung cancer is being diagnosed at an earlier stage, that incidence will stop increasing, that mortality will decrease further, and that the prevalence will continue to increase substantially. Projections of cancer incidence, mortality, and prevalence are important for planning health services and should be updated at regular intervals.

Outcome of treatment in patients with small cell lung cancer in poor performance status.

Background: Patients with small cell lung cancer (SCLC) with poor performance status (PS) especially in the elderly may not benefit from chemotherapy. The aim of this study was to compare survival of treated patients with PS 3-4 with untreated patients.Material and methods: We reviewed the medical records and pathology data for 448 patients diagnosed with small cell carcinoma from 2010 to 2015 and selected all patients in PS 3-4 for review.Results: A total of 87 patients fulfilled the inclusion criteria. Of these, 53 (61%) received chemotherapy (CT), while 34 (39%) did not. The median overall survival (OS) was 5.1 months for the treated patients and 0.7 month for the untreated (p < .001). Multivariate analysis identified lack of treatment with chemotherapy, extensive disease, and PS 4 as independent factors associated with poor prognosis, while age and gender were not. Also, patients with aged ≥70 years who had extended disease had significant improved OS when treated with CT. However, the chance of being treated with CT was significantly influenced by age.Conclusion: CT was associated with improved survival in patients with SCLC with PS 3-4 independent of age and stage of disease. Neither ED, high age, nor poor PS should be used as criteria for omitting CT.

Dual time-point FDG PET/CT and FDG uptake and related enzymes in lymphadenopathies: preliminary results.

PURPOSE: The purpose of this study was to determine the ability of dual time-point (DTP) PET/CT with (18)F-FDG to discriminate between malignant and benign lymphadenopathies. The relationship between DTP FDG uptake and glucose metabolism/hypoxia markers in lymphadenopathies was also assessed. METHODS: Patients with suspected lymphoma or recently diagnosed treatment-naive lymphoma were prospectively enrolled for DTP FDG PET/CT (scans 60 min and 180 min after FDG administration). FDG-avid nodal lesions were segmented to yield volume and standardized uptake values (SUV), including SUVmax, SUVmean, cSUVmean (with partial volume correction), total lesion glycolysis (TLG) and cTLG (with partial volume correction). Expression of glucose transporter-1 (GLUT-1), hexokinase-II (HK-II), glucose-6-phosphatase (G6Pase) and hypoxia-inducible factor-1alpha (HIF-1alpha) were assessed with immunohistochemistry and enzyme activity was determined for HK and G6Pase. RESULTS: FDG uptake was assessed in 203 lesions (146 malignant and 57 benign). Besides volume, there were significant increases over time for all parameters, with generally higher levels in the malignant lesions. The retention index (RI) was not able to discriminate between malignant and benign lesions. Volume, SUVmax, TLG and cTLG for both scans were able to discriminate between the two groups statistically, but without complete separation. Glucose metabolism/hypoxia markers were assessed in 15 lesions. TLG and cTLG were correlated with GLUT-1 expression on the 60-min scan. RI-max and RI-mean and SUVmax, SUVmean and cSUVmean on the 60-min scan were significantly correlated with HK-II expression. CONCLUSION: RI was not able to discriminate between malignant and benign lesions, but some of the SUVs were able to discriminate on the 60-min and 180-min scans. Furthermore, FDG uptake was correlated with GLUT-1 and HK-II expression.

Keratin 34betaE12/keratin7 expression is a prognostic factor of cancer-specific and overall survival in patients with early stage non-small cell lung cancer.

BACKGROUND: Carcinomas and their metastases often retain the keratin patterns of their epithelial origin, and are therefore useful as lineage-specific markers in diagnostic pathology. Recently, it has become clear that intermediate filaments composed by keratins play a role in modulation of cell proliferation, migration, and possibly cancer invasion, factors impacting prognosis in early stage non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Tumor tissue from a retrospective Danish cohort of 177 patients with completely resected NSCLC, stage I-IIIA tumors, were analyzed for keratin 7 (K7) and keratin 34ßE12 expression by immunohistochemistry and validated in a comparable independent Norwegian cohort of 276 stage I-IIIA NSCLC patients. RESULTS: Based on keratin 34ßE12/K7 expression, three subgroups with significantly different median cancer-specific survival rates were identified (34ßE12+/K7+, 168 months vs. 34ßE12+/K7+, 73 months vs. 34ßE12-/K7+, 30 months; p = 0.0004). In multivariate analysis, stage II-IIIA (HR 2.9), 34ßE12+/K7+ (HR 1.90) and 34ßE12-/K7+ (HR 3.7), were prognostic factors of poor cancer-specific survival (CSS) (p < 0.001). Validation in the Norwegian cohort confirmed that stage II-IIIA (HR 2.3), 34ßE12+/K7+ (HR 1.6), and 34ßE12-/K7+ (HR 2.0) were prognostic factors of poor CSS (p < 0.05). Multivariate Cox proportional-hazard analysis demonstrated that 34ßE12+/K7 + and 34ßE12+/K7 + status was significantly associated with poor overall survival (p < 0.05). CONCLUSION: Keratin 34ßE12/K7 expression is a prognostic parameter in resected early stage NSCLC that allows identification of high-risk NSCLC patients with poor cancer-specific and overall survival.

Stromal CD8+ T-cell Density­A Promising Supplement to TNM Staging in Non-Small Cell Lung Cancer.

PURPOSE: Immunoscore is a prognostic tool defined to quantify in situ immune cell infiltrates, which appears to be superior to the tumor-node-metastasis (TNM) classification in colorectal cancer. In non-small cell lung cancer (NSCLC), no immunoscore has been established, but in situ tumor immunology is recognized as highly important. We have previously evaluated the prognostic impact of several immunological markers in NSCLC, yielding the density of stromal CD8(+) tumor-infiltrating lymphocytes (TIL) as the most promising candidate. Hence, we validate the impact of stromal CD8(+) TIL density as an immunoscore in NSCLC. EXPERIMENTAL DESIGN: The prognostic impact of stromal CD8(+) TILs was evaluated in four different cohorts from Norway and Denmark consisting of 797 stage I-IIIA NSCLC patients. The Tromso cohort (n = 155) was used as training set, and the results were further validated in the cohorts from Bodo (n = 169), Oslo (n = 295), and Denmark (n = 178). Tissue microarrays and clinical routine CD8 staining were used for all cohorts. RESULTS: Stromal CD8(+) TIL density was an independent prognostic factor in the total material (n = 797) regardless of the endpoint: disease-free survival (P < 0.001), disease-specific survival (P < 0.001), or overall survival (P < 0.001). Subgroup analyses revealed significant prognostic impact of stromal CD8(+) TIL density within each pathologic stage (pStage). In multivariate analysis, stromal CD8(+) TIL density and pStage were independent prognostic variables. CONCLUSIONS: Stromal CD8(+) TIL density has independent prognostic impact in resected NSCLC, adds prognostic impact within each pStage, and is a good candidate marker for establishing a TNM-Immunoscore.

Can EGFR mutation status be reliably determined in pre-operative needle biopsies from adenocarcinomas of the lung?

The identification of EGFR mutations in non-small-cell lung cancer is important for selecting patients, who may benefit from treatment with EGFR tyrosine kinase inhibitors. The analysis is usually performed on cytological aspirates and/or histological needle biopsies, representing a small fraction of the tumour volume. The aim of the present investigation was to evaluate the diagnostic performance of this molecular test. We retrospectively included 201 patients with primary adenocarcinoma of the lung. EGFR mutation status (exon 19 deletions and exon 21 L858R point mutation) was evaluated on both pre-operative biopsies (131 histological and 70 cytological) and on the surgical specimens, using PCR. Samples with low tumour cell fraction were assigned to laser micro-dissection (LMD). We found nine (4.5%) patients with EGFR mutation in the lung tumour resections, but failed to identify mutation in one of the corresponding pre-operative, cytological specimens. Several (18.4%) analyses of the pre-operative biopsies were inconclusive, especially in case of biopsies undergoing LMD and regarding exon 21 analysis. Discrepancy of mutation status in one patient may reflect intra-tumoural heterogeneity or technical issues. Moreover, several inconclusive results in the diagnostic biopsies reveal that attention must be paid on the suitability of pre-operative biopsies for EGFR mutation analysis.

Tissue microarrays in non-small-cell lung cancer: reliability of immunohistochemically-determined biomarkers.

BACKGROUND: The reliability of immunohistochemically-determined biomarkers using tissue microarrays (TMAs) of clinical specimens has long been open to question. Heterogeneity related to tumor biology might compromise determination of accurate biomarker expression in tumors, especially in small core biopsies. We evaluated the reliability of immunohistochemical staining scoring in small core biopsies using 11 biomarkers in non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Four 1-mm tumor cores from 178 NSCLCs, 2 representing peripheral areas close to the border of normal lung tissue and 2 representing central areas, were examined. The biomarkers analyzed included p63, p40, cytokeratin 1/5/10/14, cytokeratin 7, thyroid transcription factor-1, napsin A, cyclin-D1, p53, Ki-67, integrin beta-1, and thymidylate synthase. RESULTS: Using a random intercept logistic regression model, immunohistochemical marker expression of TMAs had a moderate to high reliability measured using the intraclass correlation coefficient (0.67-0.99) between cores within the same tumor. Reliability was dependent on the selected biomarker, with lineage-specific biomarkers being less heterogeneously expressed than functional biomarkers. Expressions of most biomarkers showed no significant difference between central versus peripheral tumor cores. CONCLUSION: Our results demonstrated that biomarkers involved in clinical tumor classification (cell lineage markers) of NSCLC can be adequately assessed using 1 or 2 biopsy samples. However, the optimal number of cores required for biomarkers with functional properties varied from 1 to > 4 cores. The results indicate that the optimal number of biopsies required to compensate for potential biomarker heterogeneity should be determined individually for each biomarker used in clinical settings.

Occupational asbestos exposure and lung cancer--a systematic review of the literature.

The objective of this study was to evaluate the scientific literature concerning asbestos and lung cancer, emphasizing low-level exposure. A literature search in PubMed and Embase resulted in 5,864 citations. Information from included studies was extracted using SIGN. Twenty-one statements were evidence graded. The results show that histology and location are not helpful in differentiating asbestos-related lung cancer. Pleural plaques, asbestos bodies, or asbestos fibers are useful as markers of asbestos exposure. The interaction between asbestos and smoking regarding lung cancer risk is between additive and multiplicative. The findings indicate that the association between asbestos exposure and lung cancer risk is basically linear, but may level off at very high exposures. The relative risk for lung cancer increases between 1% and 4% per fiber-year (f-y)/mL, corresponding to a doubling of risk at 25-100 f-y/mL. However, one high-quality case-control study showed a doubling at 4 f-y/mL.

Metastasis in the subcarinal lymph node with unknown primary tumor.

A 59-year-old man with previous anaplastic large cell T-cell lymphoma stage 3A was admitted with an isolated positron emission tomography(PET)-positive spot in a subcarinal lymph node. Diagnosis was achieved with endobronchial ultrasound-guided fine-needle aspiration demonstrating a well-differentiated squamous cell carcinoma but no primary tumor was visible on PET-computed tomography. Because of his previous lymphoma the patient was scheduled for mediastinoscopy where the diagnosis was confirmed. Subsequent gastroscopy was normal and a right-sided thoracotomy showed no evidence of cancer elsewhere, only an inoperable metastasis in a subcarinal lymph node which infiltrated the trachea, esophagus and aorta. Such isolated squamous cell carcinoma in a subcarinal lymph node without a primary tumor despite invasive work-up has not been reported before.

Handling of radical prostatectomy specimens: total or partial embedding?

AIMS: Proper examination and accurate reporting of radical prostatectomy specimens (RPS) is essential in determining post-surgical treatment and predicting patient outcome. Surveys have demonstrated the absence of consensus on handling of RPS. The aim of this study was to determine whether significant information is lost when only half the horizontal tissue sections are examined. METHODS AND RESULTS: During a 1-year period, 238 RPS were sectioned into horizontal slices. Apex and basis was cut sagittally, and remaining slices were embedded in quadrants. Glass slides from every second horizontal slice were withheld. The remaining slides were evaluated microscopically, and essential pathological parameters were recorded. Subsequently, a full report was compiled, including the withheld slides. A median of 12 slides (30%) were withheld during initial assessment. In eight RPS (3.2%) the pTNM stage had to be changed; in six cases (2.6%) from pT2b to pT2c and in two cases (0.8%) from pT2c to pT3a. In one RPS (0.4%) the surgical margin status was changed. CONCLUSIONS: Only little information is lost with systematic partial embedding, overlooking features significant for the postoperative treatment in only 1.2%. Partial embedding as suggested, decreasing the laboratory workload by 30%, is concluded to be acceptable for valid histopathological assessment.

Mediastinal staging for lung cancer: the influence of biopsy volume.

OBJECTIVE: Mediastinal staging is of paramount importance prior to surgery for non-small-cell lung cancer (NSCLC) to identify patients with N2-disease. Mediastinoscopy remains the gold standard, and sampling from at least three lymph node stations is generally recommended. It is unknown whether biopsy volume has any influence on the result of conventional cervical mediastinoscopy. In this study, we investigated the influence of biopsy volume and the number of lymph node stations biopsied during mediastinoscopy on the probability of demonstrating N2-disease in patients with NSCLC. METHODS: We identified 678 consecutive patients who underwent mediastinoscopy for staging of NSCLC during an 8-year period (1999-2007), but 111 patients were later excluded from analysis because of misclassification or of missing data. All patient charts and pathology reports of the remaining 567 patients were reviewed retrospectively. Demographics and the number of lymph node stations biopsied were recorded, and the volume of biopsies from each lymph node station was calculated. RESULTS: Multivariate logistic regression analysis demonstrated that larger biopsy volume was significantly associated with increased probability of demonstrating N2-disease (p<0.001). However, sampling from several lymph node stations was significantly associated with a decreased probability of demonstrating N2-disease (p=0.015) and volume was significantly larger per station when fewer stations were sampled (p<0.001). CONCLUSIONS: Biopsy volume from lymph nodes during mediastinoscopy was significantly associated with the probability of demonstrating N2-disease; however, contrary to common belief, sampling from several lymph node stations was not associated with an increased probability of detecting N2-disease. Although purely speculative, these findings may be explained by a perioperative clinical decision by the surgeon: large volumes are secured from macroscopically large and suspicious lymph nodes if detected. Consequently, further dissection and possible complications were avoided.

The value of mediastinal staging with endobronchial ultrasound-guided transbronchial needle aspiration in patients with lung cancer.

OBJECTIVE: To evaluate the diagnostic yield, the learning curve and the safety of endobronchial ultrasound-guided transbronchial needle biopsy (EBUS-TBNA) in mediastinal staging of patients with lung cancer. METHODS: Mediastinal staging was performed with EBUS-TBNA according to the Danish national guidelines in patients fulfilling one or more of the following criteria: (1) central tumour; (2) enlarged (>10 mm) mediastinal lymph nodes on computed tomography; or (3) positron emission tomography (PET)-positive mediastinal lymph nodes. The study period began in January 2006 when EBUS-TBNA was introduced in the department and ended in December 2007. All records were reviewed retrospectively. None of the four examiners had any previous experience with EBUS-TBNA or ultrasound when the study began. All examinations were performed under general anaesthesia. Patients without useful cytological material from the EBUS-TBNA were subjected to a supplementary standard cervical mediastinoscopy if the mediastinal lymph nodes were found to be enlarged (>10 mm), PET positive or if the examiner was insecure of the result of the EBUS-TBNA. Patients with mediastinal lymph node involvement, detected by EBUS-TBNA or standard cervical mediastinoscopy, were referred to oncological treatment, while those without mediastinal lymph node involvement underwent--if they were otherwise eligible for surgery--resection and systematic lymph node sampling either by thoracotomy or by video-assisted thoracoscopy. Final mediastinal staging was defined as positive if mediastinal lymph node involvement was detected by EBUS-TBNA, standard cervical mediastinoscopy or surgery, or defined as negative otherwise. RESULTS: A total of 157 patients were included in the study. N2/N3 disease was found in 67 patients (42.6%). EBUS-TBNA missed the mediastinal spread in 10 patients. Five of the ten patients had lymph node metastases in station 5, 6 or 8--out of reach of EBUS-TBNA or standard cervical mediastinoscopy. EBUS-TBNA had a sensitivity of 0.85 (0.74-0.93) and a negative predictive value of 0.90 (0.82-0.95). No complications occurred from EBUS-TBNA. The number of supplementary standard cervical mediastinoscopies decreased significantly in the study period. CONCLUSION: The results of this study suggest that staging of the mediastinum with EBUS-TBNA is safe and easy to learn--even without previous experience with ultrasound. The diagnostic yield of EBUS-TBNA is in accordance with the yield of standard cervical mediastinoscopy reported in the literature. We do not find any indications in the present study of the recommended necessity for mediastinoscopy in all EBUS-TBNA-negative patients.

Loss of heterozygosity at BRCA2 in a ductal carcinoma in situ and three invasive breast carcinomas in a family with a germline BRCA2 mutation.

We have examined a family with a germline BRCA2 mutation in three cases of invasive breast cancer and one case of ductal carcinoma in situ (DCIS). Loss of heterozygosity (LOH) has been demonstrated at the BRCA2 locus in all cases. This result may suggest that the germline mutation in BRCA2 is the initiating step of DCIS and support the theory that DCIS is a precursor of invasive breast carcinoma in hereditary breast cancer.