The path to a better biomarker: application of a risk management framework for the implementation of PD-L1 and TILs as immuno-oncology biomarkers in breast cancer clinical trials and daily practice.

Immune checkpoint inhibitor therapies targeting PD-1/PD-L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD-L1 expression on immune cells occupying ≥1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab-paclitaxel. However, concerns regarding variability between immunohistochemical PD-L1 assay performance and inter-reader reproducibility have been raised. High tumor-infiltrating lymphocytes (TILs) have also been associated with response to PD-1/PD-L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin-stained slides and have shown reliable inter-reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD-L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD-L1 and TIL analyses as a more comprehensive immuno-oncological biomarker for patient selection for PD-1/PD-L1 inhibition-based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk-management framework that may help mitigate the risks of suboptimal patient selection for immuno-therapeutic approaches in clinical trials and daily practice based on combined TILs/PD-L1 assessment in BC. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Endobronchial ultrasound-guided Transbronchial needle aspiration (EBUS-TBNA) in simulator lesions of pulmonary pathology: a case report of pulmonary Myospherulosis.

BACKGROUND: Myospherulosis develops as the result of a reaction between exogenous lipids and red blood cells (RBC) of the patient, being the latter injured when perceived as a foreign body by the immune system, triggering an intense inflammatory response. CASE PRESENTATION: A 63-year-old man with a history of dyslipidemia, Barret's esophagus, and coronary disease, who was taken to thoracoscopy and left inferior lobectomy due to the presence of a pulmonary mass. A primary pulmonary adenocarcinoma was diagnosed. On follow up a PET-CT was performed, in which a metabolically active lesion was described adjacent to the prior lobectomy, suggesting a local relapse. EBUS-TBNA was then performed, obtaining a sample from which histopathological pattern compatible with myospherulosis was obtained. CONCLUSIONS: Although it is a rare entity, myospherulosis has a well-defined morphological pattern. By not recognizing myospherulosis as a benign lesion, a patient's risk of invasive cancer can be overestimated. It is a phenomenon found with increasing frequency and has been reported in different tissues, however, this is the first report in the literature of myospherulosis of the lung. Greater awareness is required regarding the existence of this phenomenon.

Sternal cavernous hemangioma and reconstruction of the anterior chest wall: a case report.

BACKGROUND: The sternum is considered an unusual tumor site, corresponding to 15% of all thoracic wall tumors. Primary sternal tumors are even rarer and most commonly malignant. We present the case of a young man who consulted with a painful sternal mass, which after its resection is confirmed to be a cavernous hemangioma. CASE PRESENTATION: A 39-year-old man, with unremarkable medical history besides a 2-year-long sternal pain, non-irradiated, which worsens over the last few months and is accompanied by the appearance of a sternal palpable mass. On physical exam, there was a bulging of the sternal manubrium, with no inflammatory changes. Thoracic CT scan shows an expansive and lytic lesion of the sternum, compromising the manubrium and extending to the third sternocostal joint, without intrathoracic compromise nor cleavage plane with mediastinal vascular structures. The patient is taken to resection of the mass and sternal reconstruction using prosthetic material and pectoral and fasciocutaneous muscular flaps. Histopathological findings: cavernous hemangioma with negative borders and no other malignant findings. CONCLUSIONS: Sternal hemangiomas can cause defects in the bone structure and show an expansive growth, challenging the differentiation between a benign or malignant lesion. Therefore, they should be considered malignant until shown otherwise. Management involves radical surgery with curative purposes and posterior reconstruction to improve quality of life, as shown with our patient.

Chronic disease prevalence in a population with structural hemoglobin disorders undergoing diabetes diagnosis: A bayesian approach.

Background: Structural disorders of hemoglobin are a group of rare and fatal genetic diseases that disrupt the transport and exchange of oxygen in the blood, causing tissue damage and ultimately leading to chronic conditions. The hemoglobin (Hb) S variant predominantly impacts individuals of Afro-descendant heritage. A significant concentration of the Afro-descendant population in Colombia, notably 12.5 %, is found in the city of Cali. Previous research has identified this city's structural hemoglobin disorders prevalence rate of 3.78 %. The aim of this study was to determine the prevalence of HbC, HbS, HbF, and HbA2 variants within a population who underwent HbA1c testing, as well as the prevalence of chronic diseases among patients with these hemoglobin alterations, at a high-complexity hospital in the city of Cali from 2015 to 2019. Methods: A descriptive observational study was conducted, involving a study population that comprised patients with both suspected and monitored diagnoses of diabetes. The cohort was selected from a high-complexity hospital in Cali. A total of 15,608 patients were included in the analysis, all of whom underwent HbA1C measurement through capillary electrophoresis, which also offers an indirect diagnosis of certain structural disorders of hemoglobin. Bayesian methods were employed for frequency analysis. Results: Among the 15,608 patients assessed, 63.6 % (n = 9920) were women. The overall prevalence of structural hemoglobin disorders was 1.98 % (n = 287, 95 % CI = 1.77 %-2.21 %). The co-occurrence of diabetes and kidney disease emerged as the most prevalent combination of pathologies observed in individuals with HbC, for both men and women across various age groups: 18-42 (58.3 % and 50.0 % respectively), 43-55 (50.0 % for both), 56-65 (50.0 % and 37.5 % respectively), and >65 years (66.7 % and 57.1 % respectively). Conclusions: The observed prevalence of the studied variants exceeded 1 %, a threshold underscored by the World Health Organization (WHO) as epidemiologically significant. Among HbC and HbS-positive patients, the elevated prevalence of diabetes and kidney disease is a guiding factor in developing proactive prevention strategies.

Pulmonary Alveolar Microlithiasis in a Young Man Undergoing Lung Transplantation: A Case Report.

Pulmonary alveolar microlithiasis is a rare disease characterized by the deposition of microliths in the alveoli, attributed to mutations in the solute carrier family 34 member 2 (SLC34A2) gene. Diagnosis is often incidental to chest imaging, most frequently occurring between the second and fourth decades of life. The disease follows a progressive course and manifests with a clinical-radiological dissociation. No effective treatment is known except for lung transplantation.We report on a 28-year-old Hispanic male patient with no relevant personal or family history, presenting with progressive exertional dyspnea and intermittent dry cough. He was referred for evaluation by pulmonology due to abnormal findings on chest x-ray. High-resolution computed tomography revealed diffuse lung opacities caused by multiple microcalcifications, suggesting pulmonary alveolar microlithiasis with additional signs of pulmonary hypertension. Throughout his clinical course, he experienced a decline in functional class with severe impairment in pulmonary function tests. He underwent transplant evaluation, and the procedure was performed, with reported complications including airway stenosis, which were managed. Despite these challenges, the patient eventually showed positive progress and maintained an adequate functional class.Pulmonary alveolar microlithiasis is a rare disease with a chronic clinical course and variable manifestations. Its progressive deterioration leads to chronic respiratory failure. A high index of suspicion is required when evaluating characteristic radiological findings and conducting relevant differential diagnoses. No specific treatment guidelines are available, and lung transplantation emerges as the only effective therapy, as illustrated in the described patient.

Importance of Testing for ROS1 Rearrangements in Non-Small Cell Lung Cancer in the Era of Targeted Therapy in a Latin American Country.

Purpose: Lung cancer is the leading cause of cancer-related deaths worldwide. However, with the optimization of screening strategies and advances in treatment, mortality has been decreasing in recent years. In this study, we describe non-small cell lung cancer patients diagnosed between 2021 and 2022 at a high-complexity hospital in Latin America, as well as the immunohistochemistry techniques used to screen for ROS1 rearrangements, in the context of the recent approval of crizotinib for the treatment of ROS1 rearrangements in non-small cell lung cancer in Colombia. Methods: A descriptive cross-sectional study was conducted. Sociodemographic, clinical, and molecular pathology information from non-small cell lung cancer individuals who underwent immunohistochemistry to detect ROS1 rearrangements between 2021 and 2022 at Fundación Valle del Lili (Cali, Colombia) was recorded. The clinical outcomes of confirmed ROS1 rearrangements in non-small cell lung cancer patients were reported. Results: One hundred and thirty-six patients with non-small cell lung cancer were included. The median age at diagnosis was 69.8 years (interquartile range 61.9-77.7). At diagnosis, 69.8% (n = 95) were at stage IV. ROS1 immunohistochemistry was performed using the monoclonal D4D6 antibody clone in 54.4% (n = 74) of the cases, while 45.6% (n = 62) were done with the monoclonal SP384 antibody clone. Two patients were confirmed to have ROS1 rearrangements in non-small cell lung cancer using next-generation sequencing and received crizotinib. On follow-up at months 5.3 and 7.0, one patient had a partial response, and the other had oligo-progression, respectively. Conclusion: Screening for ROS1 rearrangements in non-small cell lung cancer is imperative, as multiple prospective studies have shown improved clinical outcomes with tyrosine kinase inhibitors. Given the recent approval of crizotinib in Colombia, public health policies must be oriented toward early detection of driver mutations and prompt treatment. Additionally, future approvals of newly tested tyrosine kinase inhibitors should be anticipated.

Invasive Aspergillosis in a Patient With Diabetes Mellitus as the Only Risk Factor: Case Report and Literature Review.

Infection by Aspergillus covers a broad clinical spectrum, including invasive pulmonary aspergillosis (IPA) and its disseminated extrapulmonary form, invasive aspergillosis (IA). It typically occurs in severely immunocompromised hosts, but it sometimes affects the immunocompetent population, especially patients with acute diseases being treated at the intensive care unit (ICU) and less often those with chronic conditions. In this article, we report the case of a 50-year-old male, with diabetes mellitus (DM) as the only risk factor, treated for IPA and IA with cardiac and central nervous system (CNS) involvement at a high complexity institution in Cali-Colombia. Clinical presentation and radiological findings are unspecific and require a high level of suspicion. To confirm the case, histological or cytological of the fungus is required; histopathological examination of lung tissue is the gold standard, but it is difficult to perform due to respiratory compromise and high risk of bleeding, so bronchoscopy and bronchoalveolar lavage (BAL) plays an essential role in the diagnostic process. A diagnostic algorithm that includes risk assessment, symptoms, imaging findings, and isolation in cultures is essential to allow the diagnosis and initiation of treatment promptly, which includes a combination of surgery and antifungal medications for long periods, even life-long treatment.

Organizing pneumonia as presenting feature of primary Sjögren's syndrome: A case report.

Sjögren's Syndrome (SS) is an autoimmune inflammatory disease, characterized by lymphocytic infiltration of exocrine glands. Approximately 10% of patients with SS have pulmonary involvement as the first manifestation of their disease, the most common being non-specific interstitial pneumonia. We present the case of a 51-year-old man with organizing pneumonia as the presenting feature of primary SS. Pulmonary involvement as the presenting feature of SS is uncommon, especially when the pattern on CT-scan is that of organized pneumonia. Initial management includes steroids and other immunosuppressants agents, with a better response in organized pneumonia secondary SS cases.

Severe Central Airway Obstruction Secondary to a Giant Endobronchial Hamartoma: A Case Report.

Central airway obstruction refers to the occlusion of more than 50% of the trachea, main stem bronchi, or lobar bronchus. It can potentially become a life-threatening condition. Pulmonary hamartomas (PH) are rare tumors with an incidence of 0.25%, constituting about 8% of all benign lung neoplasms. Only 10% of PH occur endobronchially, while the remaining appear peripherally. We present the case of a women with an endobronchial hamartoma that required emergent resection by bronchoscopy. This is 44-year-old woman, with a history of an endobronchial mass on the right main stem bronchus (RMSB) without histopathological diagnosis or surgical management. She presented with a history of chronic cough and expectoration. Upon admission, a chest X-ray was performed, showing opacities of the right lung and amputations of the RMSB. Bronchoscopy was performed and a tumor-like mass that occludes the RMSB was found, with valve effect causing intermittent occlusion. In anesthetic induction, she presents severe airway obstruction and cardiorespiratory arrest. During resuscitation maneuvers, the lesion that was obstructing the light is seen and resection was performed with electrocautery and cryotherapy probes. Histopathological report described an endobronchial chondromesenchymal hamartoma, with no signs of malignancy. The control X-ray showed adequate re-expansion of the right lung. In conclusion, although endobronchial hamartoma has a low incidence and has a slow growth rate, it can manifest as severe airway obstruction. To achieve a complete resection of an endobronchial lesion, both rigid and/or flexible bronchoscopy plus multimodal interventions are recommended.

In situ mantle cell lymphoma: clinical implications of an incidental finding with indolent clinical behavior.

BACKGROUND: Cyclin D1-positive B cells are occasionally found in the mantle zones of reactive lymphoid follicles, a condition that has been called "in situ mantle cell lymphoma". The clinical significance of this lesion remains uncertain. DESIGN AND METHODS: The clinical and pathological characteristics, including SOX11 expression, of 23 cases initially diagnosed as in situ mantle cell lymphoma were studied. RESULTS: Seventeen of the 23 cases fulfilled the criteria for in situ mantle cell lymphoma. In most cases, the lesions were incidental findings in reactive lymph nodes. The t(11;14) was detected in all eight cases examined. SOX11 was positive in seven of 16 cases (44%). Five cases were associated with other small B-cell lymphomas. In two cases, both SOX11-positive, the in situ mantle cell lymphoma lesions were discovered after the diagnosis of overt lymphoma; one 4 years earlier, and one 3 years later. Twelve of the remaining 15 patients had a follow-up of at least 1 year (median 2 years; range, 1-19.5), of whom 11 showed no evidence of progression, including seven who were not treated. Only one of 12 patients with an in situ mantle cell lymphoma lesion and no diagnosis of mantle cell lymphoma at the time developed an overt lymphoma, 4 years later; this case was also SOX11-positive. The six remaining cases were diagnosed as mantle cell lymphoma with a mantle zone pattern. Five were SOX11-positive and four of them were associated with lymphoma without a mantle zone pattern. CONCLUSIONS: In situ mantle cell lymphoma lesions are usually an incidental finding with a very indolent behavior. These cases must be distinguished from mantle cell lymphoma with a mantle zone pattern and overt mantle cell lymphoma because they may not require therapeutic intervention.

Association of genetic ancestry with HER2, GRB7 AND estrogen receptor expression among Colombian women with breast cancer.

Background: Our previous study reported higher mRNA levels of the human epidermal growth factor receptor 2 (HER2)-amplicon genes ERBB2 and GRB7 in estrogen receptor (ER)-positive breast cancer patients with relatively high Indigenous American (IA) ancestry from Colombia. Even though the protein expression of HER2 and GRB7 is highly correlated, they may also express independently, an event that could change the patients' prognosis. In this study, we aimed to explore the differences in ER, HER2 and GRB7 protein expression according to genetic ancestry, to further assess the clinical implications of this association. Methods: We estimated genetic ancestry from non-tumoral breast tissue DNA and assessed tumoral protein expression of ER, HER2, and GRB7 by immunohistochemistry in a cohort of Colombian patients from different health institutions. We used binomial and multinomial logistic regression models to test the association between genetic ancestry and protein expression. Kaplan-Meier and log-rank tests were used to evaluate the effect of HER2/GRB7 co-expression on patients' survival. Results: Our results show that patients with higher IA ancestry have higher odds of having HER2+/GRB7- breast tumors, compared to the HER2-/GRB7- subtype, and this association seems to be stronger among ER-positive tumors (ER+/HER2+/GRB7-: OR=3.04, 95% CI, 1.47-6.37, p<0.05). However, in the multivariate model this association was attenuated (OR=1.80, 95% CI, 0.72-4.44, p=0.19). On the other hand, it was observed that having a higher European ancestry patients presented lower odds of ER+/HER2+/GRB7- breast tumors, this association remained significant in the multivariate model (OR=0.36, 95% CI, 0.13 - 0.93, p= 0.0395). The survival analysis according to HER2/GRB7 co-expression did not show statistically significant differences in the overall survival and recurrence-free survival. Conclusions: Our results suggest that Colombian patients with higher IA ancestry and a lower European fraction have higher odds of ER+/HER2+/GRB7- tumors compared to ER+/HER2-/GRB7- disease. However, this association does not seem to be associated with patients' overall or recurrence-free survival.

NGS in Lung, Breast, and Unknown Primary Cancer in Colombia: A Multidisciplinary Consensus on Challenges and Opportunities.

Given the benefits and likely future applications, there is an urgent need to expand the use of next-generation sequencing (NGS) in breast, lung, and unknown primary cancers in Colombia. The objective of this review is to address the barriers limiting access to the use of NGS in Colombia, specifically for patients with breast, lung, and unknown primary cancers in the public health care system. A selected Panel of Colombian experts in NGS were provided with a series of relevant questions to address in a multiday conference. Each narrative was discussed and edited by the Panel through numerous drafts and rounds of discussion until consensus was achieved. There are limitations to the widespread adoption of innovative technology inherent to the Colombian health care system. Barriers identified to implementing NGS in Colombia include availability, accessibility, and affordability; limited infrastructure; training and awareness of health personnel; quality-control procedures; and collection of local data. Stakeholders must align to adapt the implementation of NGS to the constraints of resource-limited environments. Diagnostic algorithms were developed to guide molecular testing for lung, breast, and unknown primary cancers. Recommendations on overcoming the barriers to the widespread adoption of NGS include country-specific molecular testing guidelines, creating a national genetic registry, improving infrastructure, and creating health policy that favors the adoption of innovative technology.

Detection of mycobacteria in paraffin-embedded Ziehl-Neelsen-Stained tissues using digital pathology.

INTRODUCTION: Early diagnosis of paucibacillary tuberculosis represents a challenge, even with direct tissue examination. Digital pathology allows the digital analysis of tissues to identify microorganisms. We aim to develop a program to detect and quantify typical and atypical mycobacteria in paraffin-embedded Ziehl-Neelsen-stained tissues. MATERIAL AND METHODS: Program development: The building of the program, named Pat-Scan, included pathology, systems engineering, and scientific applications. The iScan Coreo Au scanner® was used, and 9 variables were adjusted. Ten Ziehl-Neelsen-stained samples were fragmented into 2000 images and analyzed to validate the reproducibility of the bacilli images in the tissue, as detected by the software. RESULTS: Pat-Scan included software and a scanner that were used to detect and quantify bacilli in paraffin-embedded Ziehl-Neelsen-stained tissues. All samples containing mycobacteria were successfully analyzed by the scanner, and the bacilli could be detected; these results were validated by expert pathologists by microscopy examination, and the presence of bacilli was confirmed in all cases. CONCLUSIONS: Pat-Scan allowed the identification and quantification of mycobacteria in paraffin-embedded Ziehl-Neelsen-stained tissues, offering a reproducible diagnostic method that reduces the time for diagnosis and does not affect precision. Further validation is needed for application in the clinical setting.

The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group.

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.

Intimal angiosarcoma of the thoracic aorta diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration: a case report.

BACKGROUND: Primary malignant tumors of the aorta are extremely rare. They are frequently located in the abdominal aorta, followed by the thoracic aorta. Sarcomas are the most common histological type. These tumors originate from the middle or intimal layer, the latter being the most common. Symptoms and radiological findings are generally nonspecific. Since their growth is endovascular, embolic phenomena can occur leading to occlusive signs and symptoms. CASE PRESENTATION: We describe the case of a 75-year-old Hispanic man, a former tobacco smoker, with a history of pain and epigastric tenderness, dysphagia, and weight loss of approximately 6 kg. A thorax computed tomography scan showed a mass within the posterior mediastinum with poorly defined borders and heterogeneous density, located between thoracic vertebra 5-8, with a size of 78 × 53 × 76 mm, with left main bronchus compression. Endobronchial ultrasound-guided transbronchial needle aspiration was performed; it found an extrinsic posterior compression of the left main bronchus with no endobronchial injury. An intimal angiosarcoma of the thoracic aorta was diagnosed. CONCLUSION: Tumors of the aorta are rare and difficult to diagnose; they are a challenge during the diagnosis, since they usually require open surgical procedures. Endobronchial ultrasound-guided transbronchial needle aspiration associated with rapid on-site examination offered, in this case, the possibility of a successful diagnosis, avoiding major procedures. This is the first case reported in the literature of an intimal angiosarcoma of the thoracic aorta diagnosed using endobronchial ultrasound-guided transbronchial needle aspiration.

Clinical characteristics and PD-L1 expression in primary lung squamous cell carcinoma: A case series.

BACKGROUND: Squamous cell lung carcinoma(SCLC), accounts for 20% of lung cancer(LC). The binding of programmed cell death 1(PD-1) to its ligand PD-L1 is a key checkpoint regulator of immune response, and overexpression of the latter leads to immune surveillance escape. This might represent an important oncogenic mechanism, as well as a predictor for immunotherapy treatment success in SCLC. METHODS: A retrospective series of 24 patients with SCLC was included(2009-2013). These patients presented with a single pulmonary lesion and no history of previous cancer. Expression of PD-L1 was evaluated on tumoral biopsies with immunohistochemistry. PD-L1 tumor proportion score(TPS) was considered high when ≥50%. Clinical characteristics regarding diagnosis were reviewed and recorded. Data were analysed in STATA v.14®. RESULTS: Twenty four patients were included in this series. Mean age was 67 + 14 years, and 62.5% were men. Smoking status was positive in 54%. Cancer stage IV was present in 54%. PD-L1 was positive in 13(54%). (+)PD-L1 was more frequent in smokers than in non-smokers(11 vs 2)(p = 0.001), as well as in COPD patients(p = 0.006). General overall survival was 21.8% at 5 years. Overall survival at one year in PD-L1(+) was 30.7% and 72.7% for PD-L1(-) patients. Survival median for PD-L1(+) patients was 10.5mo, as well as for the whole series. CONCLUSION: Patients with primary SCLC who have a high PD-L1 TPS, had a worse overall survival than their counterparts. PD-L1 expression in SCLC in a Colombian sample lies between the one found in the literature.

Immune Thrombocytopenic Purpura, a rare manifestation of active tuberculosis: Case report.

Tuberculosis is currently considered a public health issue worldwide. Although a large number of hematological disorders related to tuberculosis have been described, immune thrombocytopenic purpura in patients with active tuberculosis is very rare but must be considered in a patient with no other evident cause.

Pathologic features and clinical course of a non-functioning primary pulmonary paraganglioma: A case report.

INTRODUCTION: Paragangliomas (PGGL) are rare neuroendocrine tumors arising from non-epithelial extra-adrenal chromaffin cells. They have been described in different sites: abdomen, pelvis, head, neck and thorax. Incidence is very low, occurring in less than 2-8/million per year. PGGL's of the lung are extremely rare, they have a slow growth and present as painless lesions. Biopsy is the method of choice for diagnosis and prognosis. PRESENTATION OF CASE: This is a 70-year-old woman with chronic cough, with a CT-scan showing a 3.3-cm mass in the left lower lobe. After video-assisted thoracic surgery, histologic findings confirmed a non-functioning pulmonary paraganglioma. We present the clinical, radiological, pathological findings and clinical course. DISCUSSION: Primary pulmonary PGGL's are extremely rare neuroendocrine tumors with low-grade malignancy, difficult to distinguish from other pulmonary tumors relying only on imaging techniques. In this case, PGGL presented as an incidentaloma during the evaluation of chronic cough. After histological diagnosis, genetic testing are ideally performed to identify somatic or germline mutations that may condition a higher risk of malignancy and metastasis. CONCLUSION: PGGL's must be considered when other diagnoses are unlikely due to immunohistochemistry findings. Larger studies in this field are needed to determine the risk factors for its development and to determine which populations have the greatest potential for malignant transformation.

Giant Intrathoracic Goiter of Atypical Presentation: A Case Report.

BACKGROUND: The term goiter is used to describe any abnormal growth of the thyroid gland, which can be diffuse or nodular, and can be associated with normal, diminished, or increased thyroid function. Multinodular goiter is a common disease whose prevalence increases at age 50. Clinical manifestations can be due to thyroid function impairment or related to size and location of the gland with compressive symptoms. Intrathoracic location is less frequent, can be mistaken with pulmonary lesions and usually implies a difficult surgical approach. CASE PRESENTATION: A 66-year-old woman with a history of subtotal thyroidectomy presented with 7-month dyspnea, dry cough. There was no evidence of neck masses, or jugular engorgement. Physical examination was normal. Chest x-ray showed an 11 cm mass in the upper right hemithorax. Computed tomography (CT)-scan, showed calcifications, and compression of the superior vena cava without infiltration, the right subclavian vein and left displacement of the trachea. Distinction between intrapulmonary or mediastinal location was not clear. Biopsy showed thyroid origin, and bilateral thoracotomy was performed with confirmation of a giant multinodular goiter. CONCLUSIONS: Intrathoracic goiter should undergo surgical or ablative management if compressive symptoms of the airway and cervical or thoracic vessels are present. The large size of the tumor along with the presentation after thyroidectomy and the seeming location in the right upper lobe made this particular case striking. Specially in the elderly, multidisciplinary perioperative management is key for a successful recovery.

Acute respiratory failure as initial manifestation of conventional osteosarcoma rich in giant cells: a case report.

BACKGROUND: Osteosarcoma is a malignant tumor of the bone. The giant cell-rich osteosarcoma (GCRO) is a rare histological variant of the conventional osteosarcoma, accounting for 3% of all osteosarcomas. It has a variable clinical presentation, ranging from asymptomatic to multiple pathological fractures, mainly involving long bones, and less frequently the axial skeleton and soft tissues. CASE PRESENTATION: We present the case of a 25-year-old Hispanic woman, previously healthy, with a 1-month history of dyspnea on exertion, intermittent dry cough, hyporexia, and intermittent unquantified fever. She presented to the emergency department with a sudden increase in dyspnea during which she quickly entered ventilatory failure and cardiorespiratory arrest with pulseless electrical activity. Resuscitation maneuvers and orotracheal intubation were initiated, but effective ventilation was not achieved despite intubation and she was transferred to the intensive care unit of our institution. The chest radiograph showed a mediastinal mass that occluded and displaced the airway. The chest tomography showed a large mediastinal mass that involved the pleura and vertebral bodies. A thoracoscopic biopsy was performed that documented a conventional giant cell-rich osteosarcoma. The patient was considered to be inoperable due to the size and extent of the tumor and subsequently died. CONCLUSIONS: The giant cell-rich osteosarcoma is a very rare histological variant of conventional osteosarcoma. Few cases of this type of osteosarcoma originating from the spine have been reported in the literature, and to our knowledge none of the reported cases included invasion to the chest cavity with airway compression and fatal acute respiratory failure that was present our case. Radiological and histological features of the GCRO must be taken into account to make a prompt diagnosis.