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CASE PRESENTATION: A 62-year-old woman came to our hospital with worsening cough and dyspnea over the preceding week, during which time she had been treated with azithromycin and prednisone for suspected pneumonia. She had no fever, chills, or sweats, but her cough had become productive of clear to blood-tinged phlegm during the interval. Medical history was significant for insulin-dependent diabetes mellitus and OSA. She had quit smoking 44 years earlier and had no history of lung disease. She was a bank teller residing in southeastern Minnesota and described no relevant inhalational or environmental exposures, drug use, aspiration, or travels preceding her illness.
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Tosse , Dispneia , Tomografia Computadorizada por Raios X , Humanos , Feminino , Pessoa de Meia-Idade , Tosse/etiologia , Tosse/diagnóstico , Dispneia/etiologia , Dispneia/diagnóstico , Diagnóstico Diferencial , Nódulos Pulmonares Múltiplos/diagnóstico , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/etiologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/complicaçõesAssuntos
Neoplasias do Sistema Nervoso , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Adolescente , Adulto Jovem , Neoplasias do Sistema Nervoso/terapia , Neoplasias do Sistema Nervoso/diagnóstico , Neoplasias do Sistema Nervoso/patologia , Criança , Idoso de 80 Anos ou mais , Resultado do Tratamento , Pré-EscolarRESUMO
Background: Lung involvement in the context of idiopathic inflammatory myopathies has significant impact on outcome; early and accurate diagnosis is important but can be difficult to achieve. In particular, patients without clinically evident muscle involvement pose a significant diagnostic challenge. Methods: A computer-assisted search was conducted to identify patients with amyopathic interstitial lung disease associated with the presence of myositis-specific autoantibodies. Medical records and chest imaging studies were reviewed to identify clinical and radiologic features at presentation. Results: Of the 35 patients with amyopathic interstitial lung disease associated with myositis-specific autoantibodies, the median age was 65 years (range 43-78) and 20 were women (57%). Of the patients, 34% had previously visited the rheumatology department. Presenting symptoms consisted of dyspnea (94%), cough (43%), and arthritis (23%). Raynaud phenomenon, "mechanic hands," Gottron papules, and inspiratory crackles were present in 23, 31, 9, and 74% of patients, respectively. After a detailed history, none of the patients reported muscle weakness, while four (11%) exhibited increased CK levels; of these four, two had a concomitant increase in aldolase levels. Median FVC was 79% predicted (range: 49-135) and median DLco was 50% predicted (range: 17-103). HRCT pattern was suggestive of an alternative to UIP pattern in 31/33 (94%) patients; the most common imaging patterns were NSIP (49%) and NSIP/OP (39%). Conclusion: In patients with NSIP and NSIP/OP pattern, the presence of amyopathic interstitial lung disease associated with myositis-specific autoantibodies should be considered even in the absence of clinical evident myositis.
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Histopathologic criteria of usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) were defined over the years and endorsed by leading organizations decades after Dr. Averill A. Liebow first coined the term UIP in the 1960s as a distinct pathologic pattern of fibrotic interstitial lung disease. Novel technology and recent research on interstitial lung diseases with genetic component shed light on molecular pathogenesis of UIP/IPF. Two antifibrotic agents introduced in the mid-2010s opened a new era of therapeutic approaches to UIP/IPF, albeit contentious issues regarding their efficacy, side effects, and costs. Recently, the concept of progressive pulmonary fibrosis was introduced to acknowledge additional types of progressive fibrosing interstitial lung diseases with the clinical and pathologic phenotypes comparable to those of UIP/IPF. Likewise, some authors have proposed a paradigm shift by considering UIP as a stand-alone diagnostic entity to encompass other fibrosing interstitial lung diseases that manifest a relentless progression as in IPF. These trends signal a pendulum moving toward the tendency of lumping diagnoses, which poses a risk of obscuring potentially important information crucial to both clinical and research purposes. Recent advances in whole slide imaging for digital pathology and artificial intelligence technology could offer an unprecedented opportunity to enhance histopathologic evaluation of interstitial lung diseases. However, current clinical practice trends of moving away from surgical lung biopsies in interstitial lung disease patients may become a limiting factor in this endeavor as it would be difficult to build a large histopathologic database with correlative clinical data required for artificial intelligence models.
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BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in Western countries. Although various patterns of lung involvement with CLL have been reported, data on clinicoradiologic presentation are sparse. METHODS: A computer-assisted search was conducted to identify patients encountered at Mayo Clinic from 1998 to 2022 and had leukemic pulmonary infiltrates (LPI) with CLL demonstrated on lung biopsy. Medical records and chest imaging studies were reviewed to identify clinical and radiologic features. RESULTS: Among 13 patients, median age was 77 years (range: 60-88) and included 10 men (77 %). All patients were known to have CLL with a median duration of 96 months (range: 50-408), and none were on treatment. Most common symptoms were dyspnea (62 %), cough (54 %), and fatigue (46 %); 2 patients (15 %) were asymptomatic. Dominant abnormality on CT consisted of single or multiple nodular/mass-like opacities in 10 patients (77 %), while diffuse centrilobular nodules, pleural mass, and diffuse bronchial wall thickening were each seen in one patient, respectively; intrathoracic lymphadenopathy was present in all. After diagnosis of LPI, treatment for CLL was administered to 7 patients (54 %); 6 patients (86 %) exhibited improvement. During follow-up (median 41 months), 8 (62 %) patients died. Causes of death included progressive CLL or treatment-related complications (2 patients), pneumonia (1 patient), unrelated causes (3 patients), and unknown in 2 patients. CONCLUSIONS: LPI in CLL is generally encountered in patients with known untreated CLL. The main imaging feature is single mass-like opacity or multiple nodular/mass-like opacities, associated with intrathoracic lymphadenopathy.
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Leucemia Linfocítica Crônica de Células B , Linfadenopatia , Pneumonia , Masculino , Humanos , Idoso , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/diagnóstico por imagem , Leucemia Linfocítica Crônica de Células B/patologia , Linfadenopatia/etiologia , Linfadenopatia/complicaçõesRESUMO
Combined pulmonary fibrosis and emphysema (CPFE) syndrome refers to co-occurrence of two disease processes in the lung that can be difficult to diagnose but is associated with high morbidity and mortality burden. Diagnosis of CPFE is challenging because the two diseases can counterbalance respective impairments resulting in deceivingly normal-appearing chest radiography and spirometry in a dyspneic patient. Although an international committee published the terminology and definitions of CPFE in 2022, consensus on exact diagnostic criteria and optimal management strategy is yet to be determined. Herein, we provide a narrative review summarizing the literature on CPFE from 1990 to 2022, including historical background, epidemiology, pathogenesis, clinical features, imaging and pulmonary function findings, diagnosis, prognosis, complications, and treatment. Although CPFE was initially conceived as a variant presentation of idiopathic pulmonary fibrosis, it has been recognized to occur in patients with a wide variety of interstitial lung diseases, including connective tissue disease-associated interstitial lung diseases, and hypersensitivity pneumonitis. The affected patients have a heightened risk for pulmonary hypertension and lung cancer. Clinicians need to recognize the characteristic presenting features of CPFE along with prognostic implications of this entity.
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Enfisema , Doenças Pulmonares Intersticiais , Enfisema Pulmonar , Fibrose Pulmonar , Humanos , Fibrose Pulmonar/complicações , Fibrose Pulmonar/diagnóstico , Enfisema Pulmonar/complicações , Enfisema Pulmonar/diagnóstico , Pulmão/patologia , Doenças Pulmonares Intersticiais/epidemiologia , Enfisema/patologia , Estudos RetrospectivosRESUMO
CASE PRESENTATION: A 68-year-old patient with obesity (BMI, 4 7 kg/m2) was transferred to the ED of our hospital because of dyspnea and pronounced hypoxemia. The patient underwent total right hip arthroplasty in an outside hospital because of osteoarthritis; there was no history of trauma. After 48 h, she experienced dyspnea with severe hypoxemia. The next day she was transferred to our hospital. Her history was notable for arterial hypertension and depression, but not heart failure. Her medications included candesartan (16 mg once daily) and sertraline (100 mg once daily). Perioperatively, she received enoxaparin 4.000 International Units subcutaneously once daily. There was no family history of respiratory diseases. The patient currently smokes (50 pack-years) with no recent increase in her habit and denied vaping, alcohol consumption, illicit drug use, and any home or occupational exposures. Prior to surgery, the family of the patient reported that she maintained modest mobility despite her osteoarthritis and was able to fulfill her daily activities. Interestingly, she reported a similar event of severe dyspnea and hypoxemia after total knee arthroplasty 3 years earlier; however, no further details were available.
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Artroplastia de Quadril , Dispneia , Hipóxia , Osteoartrite , Idoso , Feminino , Humanos , Artroplastia de Quadril/efeitos adversos , Dispneia/etiologia , Hipóxia/etiologia , Osteoartrite/complicações , Osteoartrite/cirurgia , Obesidade/complicações , Articulação do Quadril/cirurgiaRESUMO
Advances in the treatment of Langerhans cell histiocytosis (LCH) have resulted in a growing survivor population. There is a lack of data on long-term outcomes among adults with LCH. We conducted a retrospective record review of 219 adults (aged ≥18 years) with LCH. Most common presentation was multisystem (34.2%), followed by single-system pulmonary (32%), unifocal (28.3%), and single-system multifocal (5.5%) LCH. Risk organ involvement (the liver, spleen, or bone marrow) was seen in 8.7% of cases, and 40 of 88 (45.5%) tested cases were BRAFV600E. At a median follow-up of 74 months, 5-year progression-free survival (PFS) was 58.3% and estimated median PFS was 83 months. Median overall survival (OS) was not reached; 5- and 10-year OS rates were 88.7% and 74.5%, respectively. Risk organ involvement was associated with worse PFS (hazard ratio [HR], 4.5) and OS (HR, 10.8). BRAFV600E was not associated with risk organ involvement or survival. When compared with matched unaffected US population, individuals with LCH had a significantly higher risk of overall mortality (standardized mortality ratio [SMR], 2.66), specifically among those aged <55 years at diagnosis (SMR, 5.94) and those with multisystem disease (SMR, 4.12). Second cancers occurred in 16.4% cases, including diverse hematologic and solid organ malignancies. LCH-associated deaths constituted 36.1% of deaths and occurred within 5 years of diagnosis. After 5 years, non-LCH causes of death, including second cancers, chronic obstructive pulmonary disease, and cardiovascular diseases, predominated. Our study highlights, to our knowledge, for the first time, that adults with LCH experience early and late mortality from non-LCH causes and the need for development of targeted survivorship programs to improve outcomes.
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Histiocitose de Células de Langerhans , Segunda Neoplasia Primária , Neoplasias , Humanos , Adulto , Adolescente , Estudos Retrospectivos , Histiocitose de Células de Langerhans/epidemiologia , BaçoRESUMO
In this retrospective study, BRAF mutation status did not correlate with disease extent or (event-free) survival in 156 adults with Langerhans cell histiocytosis. BRAFV600E was associated with an increased incidence of second malignancies, often comprising hematological cancers, which may be clonally related.
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Histiocitose de Células de Langerhans , Segunda Neoplasia Primária , Humanos , Adulto , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/genética , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Incidência , Histiocitose de Células de Langerhans/epidemiologia , Histiocitose de Células de Langerhans/genética , Histiocitose de Células de Langerhans/patologia , MutaçãoRESUMO
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare, but increasingly recognized entity that primarily affects middle-aged and elderly women. It is characterized by abnormal proliferation of pulmonary neuroendocrine cells (PNECs) and is considered a preinvasive lesion for carcinoid tumorlets/tumors. Sometimes, DIPNECH is accompanied by constrictive bronchiolitis which usually manifests as chronic cough and/or dyspnea, along with airflow limitation on spirometry. The telltale imaging sign of DIPNECH is the presence of multiple noncalcified pulmonary nodules and mosaic attenuation on CT. However, these clinico-radiologic features of DIPNECH are characteristic but nonspecific; thus, histopathologic confirmation is usually necessary. DIPNECH has an indolent course and only rarely leads to respiratory failure or death; progression to overt neuroendocrine tumor (carcinoid) of the lung occurs in a minority of patients. Of available therapies, somatostatin analogs and mechanistic target of rapamycin inhibitors are the most promising. In this review, we provide an update regarding the diagnosis and management of DIPNECH and describe critical gaps in our understanding of this entity, including the central terms 'diffuse' and 'idiopathic.' We also summarize the inconsistencies in definitions employed by recent studies and discuss the pitfalls of the DIPNECH definitions proposed by the World Health Organization in 2021. In this context, we propose an objective and reproducible radio-pathologic case definition intended for implementation in the research realm and seeks to enhance homogeneity across cohorts. Furthermore, we discuss aspects of PNECs biology which suggest that PNEC hyperplasia may contribute to the pathogenesis of phenotypes of lung disease aside from constrictive bronchiolitis and carcinoid tumorlets/tumors. Finally, we steer attention to some of the most pressing and impactful research questions awaiting to be unraveled.
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Bronquiolite Obliterante , Tumor Carcinoide , Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Células Neuroendócrinas , Lesões Pré-Cancerosas , Feminino , Humanos , Hiperplasia/complicações , Hiperplasia/patologia , Células Neuroendócrinas/patologia , Pulmão , Nódulos Pulmonares Múltiplos/complicações , Nódulos Pulmonares Múltiplos/patologia , Tumor Carcinoide/complicações , Tumor Carcinoide/patologia , Bronquiolite Obliterante/complicações , Bronquiolite Obliterante/patologia , Neoplasias Pulmonares/patologiaRESUMO
Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized disease that often results in heart failure and death. Traditionally, biological staging systems are used to stratify disease severity. Reduced aerobic capacity has recently been described as useful in identifying higher risk of cardiovascular events and death. Assessment of lung volume via simple spirometry might also hold prognostic relevance. We aimed to assess the combined prognostic value of spirometry, cardiopulmonary exercise testing (CPET) and biomarker staging in ATTR-CA patients in a multi-parametric approach. We retrospectively reviewed patient records with pulmonary function and CPET testing. Patients were followed until study endpoint (MACE: composite of heart-failure-related hospitalization and all-cause death) or censure (1 April 2022). In total, 82 patients were enrolled. Median follow-up was 9 months with 31 (38%) MACE. Impaired peak VO2 and forced vital capacity (FVC) were independent predictors of MACE-free survival, with peak VO2 < 50% and FVC < 70% defining the highest risk group (HR 26, 95% CI: 5-142, mean survival: 15 months) compared to patients with the lowest risk (peak VO2 ≥ 50% and FVC ≥ 70%). Combined peak VO2, FVC and ATTR biomarker staging significantly improved MACE prediction by 35% compared to ATTR staging alone, with 67% patients reassigned a higher risk category (p < 0.01). In conclusion, combining functional and biological markers might synergistically improve risk stratification in ATTR-CA. Integrating simple, non-invasive and easily applicable CPET and spirometry in the routine management of ATTR-CA patients might prove useful for improved risk prediction, optimized monitoring and timely introduction of newer-generation therapies.
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CASE PRESENTATION: A 79-year-old man was examined because of recurrent dyspnea and constitutional symptoms that included malaise, fatigue, fevers, and arthralgias over the past 7 years. He was a nonsmoker who was a retired farmer. Elevated levels of acute phase reactants and C-reactive protein and a high erythrocyte sedimentation rate were noted often in his health records. However, an extensive rheumatologic evaluation, which included serologic studies (antinuclear antibodies, cyclic citrullinated peptide antibodies, antineutrophil cytoplasmic antibodies) and temporal artery biopsy, had not shown an identifiable autoimmune disease. The patient had been treated intermittently with prednisone, with partial symptomatic improvement. Various cytopenias had been present over the preceding years; however, three bone marrow biopsy specimens showed moderately hypercellular bone marrow with no diagnostic findings.
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Pancitopenia , Masculino , Humanos , Idoso , Pancitopenia/diagnóstico , Pancitopenia/etiologia , Proteínas de Fase Aguda , Febre , Anticorpos Anticitoplasma de Neutrófilos , PrednisonaRESUMO
BACKGROUND: The pathogenic variants responsible for Birt-Hogg-Dubé syndrome (BHDS) in folliculin (FLCN) gene mostly consist of point mutations. Although large intragenic deletions/duplications have been reported in several case reports, the relationship between large intragenic deletions/duplications and phenotype in BHDS remains unclear. METHODS: We retrospectively identified and reviewed patients with a large intragenic deletion spanning exons 1-3 and analyzed their phenotypic features to compare with those of point mutation carriers in our hospital from January 1, 2017 to August 31, 2022. RESULTS: Twenty unique point mutations (including 4 novel mutations) were detected in 62 patients from 45 families (90%). Exons 1-3 deletion were identified in 8 patients from 5 families (10%) that resided in the same region, Feidong County of Anhui Province, China. Breakpoint analysis indicated that all the deletion breakpoints were flanked by Alu repeats. The prevalence of exons 1-3 deletion carriers in Feidong County was 8.1-times higher than that for BHDS in Anhui Province, suggesting a clustered phenomenon of exons 1-3 deletion. Significantly increased risk of pneumothorax was observed in those with exons 1-3 deletion compared with point mutations (91% vs. 58%, p value 0.047). The risk of renal cancer may be higher in those with exons 1-3 deletion than for those with point mutations (18% vs. 4%, p > 0.05). CONCLUSIONS: Large intragenic deletion of exons 1-3 in FLCN was identified as a local aggregation phenomenon in Feidong County, China, and was associated with a significantly higher risk of pneumothorax compared to those with point mutations.
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Síndrome de Birt-Hogg-Dubé , Neoplasias Renais , Pneumotórax , Humanos , Pneumotórax/genética , Síndrome de Birt-Hogg-Dubé/genética , População do Leste Asiático , Estudos Retrospectivos , Éxons/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
PURPOSE OF REVIEW: Histiocytic disorders, including Erdheim-Chester disease (ECD), Langerhans cell histiocytosis (LCH), and Rosai-Dorfman disease (RDD), are rare neoplasms that may present with a spectrum of neurologic involvement. Diagnostic delay is common due to heterogeneity in presentation and challenging pathology. RECENT FINDINGS: Recent advances in the treatment of these diseases targeted towards mutations in the MAP kinase pathway have led to an improved prognosis in these patients with neurologic involvement. It is critical for clinicians to have a high index of suspicion to allow for early targeted treatment and optimize neurologic outcomes. A systematic approach to diagnosis is presented in this article to allow for accurate diagnosis of these rare diseases.
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Doença de Erdheim-Chester , Histiocitose de Células de Langerhans , Histiocitose Sinusal , Humanos , Diagnóstico Tardio , Histiocitose de Células de Langerhans/complicações , Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/genética , Doença de Erdheim-Chester/complicações , Doença de Erdheim-Chester/diagnóstico , Doença de Erdheim-Chester/genética , Histiocitose Sinusal/diagnóstico , Histiocitose Sinusal/patologia , Histiocitose Sinusal/terapia , PrognósticoRESUMO
BACKGROUND: Paragangliomas are rarely found in the mediastinum, where they account for a small proportion of mediastinal masses. This study aimed to better characterize the presenting features and relevant aspects in optimizing the diagnosis and treatment of mediastinal paragangliomas. METHODS: A computer-assisted search of electronic health records was performed to identify adult patients (≥18 years) who underwent evaluation for a primary mediastinal paraganglioma at Mayo Clinic between January 2000 and April 2022. Medical charts, laboratory tests and radiology images were reviewed to collect data. RESULTS: The study included 51 patients, each with a single mediastinal paraganglioma. The median age was 47 years (IQR: 39-67), 67% females. Symptoms of catecholamine excess were manifest in 39% of patients, and 14% presented with mass effect, while the remaining 47% had no paraganglioma-related symptoms. Genetic testing was performed in 35 patients; 66% harbored a pathogenic variant in the succinate dehydrogenase enzyme complex. Most paragangliomas (71%) were in the middle mediastinum and showed uptake of intravenous contrast on chest imaging. Biopsies were performed in 30 (59%) patients; 27% were inconclusive and 10% resulted in major complications. Surgical resection occurred in 75%, primarily for relief of symptoms (50%) followed by proximity to critical structures (45%). Perioperative complications were common (66%), but there were no cases of local tumor recurrence during the follow-up period (median 8 years; IQR: 4-13). CONCLUSION: Mediastinal paragangliomas are most located in the middle mediastinum and can often be diagnosed noninvasively using a combination of clinical, biochemical, and radiological features.
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Neoplasias do Mediastino , Paraganglioma Extrassuprarrenal , Paraganglioma , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Paraganglioma Extrassuprarrenal/diagnóstico por imagem , Paraganglioma Extrassuprarrenal/cirurgia , Paraganglioma/diagnóstico por imagem , Paraganglioma/cirurgia , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/cirurgia , Mediastino/diagnóstico por imagem , Mediastino/patologiaRESUMO
Smoking-related interstitial lung diseases (ILDs) are a group of heterogeneous, diffuse pulmonary parenchymal disease processes associated with tobacco exposure. These disorders include pulmonary Langerhans cell histiocytosis, respiratory bronchiolitis-associated ILD, desquamative interstitial pneumonia, acute eosinophilic pneumonia, and combined pulmonary fibrosis and emphysema. This review summarizes the current evidence of pathogenesis, clinical manifestations, diagnostic approach, prognosis, and treatment modalities for these diseases. We also discuss the interstitial lung abnormalities incidentally detected in radiologic studies and smoking-related fibrosis identified on lung biopsies.
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Bronquiolite , Doenças Pulmonares Intersticiais , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/terapia , Fumar/efeitos adversos , Bronquiolite/etiologia , Bronquiolite/patologia , Pulmão/patologiaRESUMO
BACKGROUND: Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a recently recognized multisystem disorder caused by somatic mutations in the UBA1 gene. METHODS: A retrospective cohort study was conducted on all patients with VEXAS syndrome evaluated at our institution from June 2020 through May 2022. Medical records and chest imaging studies were reviewed. RESULTS: We identified 45 subjects with median age of 68 years (range, 57-89), all men. Prior to VEXAS diagnosis, most patients had been diagnosed with various hematologic, rheumatologic, and dermatologic disorders. Most patients (84%) demonstrated canonical UBA1 methionine-41 (p.Met41) somatic mutations in hematopoietic cells. Fever (82%), skin lesions (91%), and respiratory symptoms (93%) were common presenting features. Chest CT manifested abnormalities in 91% of patients including parenchymal opacities in 25 (74%), most commonly ground-glass opacities (47%), along with mediastinal lymphadenopathy (29%), airway abnormalities (29%), and pleural effusion (24%). Pulmonary function test results available in 18 (40%) patients demonstrated mild restrictive impairment or normal results. Bronchoalveolar lavage and lung biopsy performed in a minority of patients demonstrated neutrophilic alveolitis and parenchymal inflammation, respectively. All patients received glucocorticoid therapy with at least partial response, but relapses were common and other immunosuppressive agents were employed in most patients. Pulmonary involvement appeared to improve in patients who received tocilizumab and JAK inhibitors. CONCLUSION: The pulmonary manifestations in VEXAS are relatively nonspecific and nonsevere, occur in the context of systemic inflammation and are responsive to escalation in glucocorticoid dosing.