The Value of a Seven-Autoantibody Panel Combined with the Mayo Model in the Differential Diagnosis of Pulmonary Nodules.

BACKGROUND: Identifying malignant pulmonary nodules and detecting early-stage lung cancer (LC) could reduce mortality. This study investigated the clinical value of a seven-autoantibody (7-AAB) panel in combination with the Mayo model for the early detection of LC and distinguishing benign from malignant pulmonary nodules (MPNs). METHODS: The concentrations of the elements of a 7-AAB panel were quantitated by enzyme-linked immunosorbent assay (ELISA) in 806 participants. The probability of MPNs was calculated using the Mayo predictive model. The performances of the 7-AAB panel and the Mayo model were analyzed by receiver operating characteristic (ROC) analyses, and the difference between groups was evaluated by chi-square tests (χ 2). RESULTS: The combined area under the ROC curve (AUC) for all 7 AABs was higher than that of a single one. The sensitivities of the 7-AAB panel were 67.5% in the stage I-II LC patients and 60.3% in the stage III-IV patients, with a specificity of 89.6% for the healthy controls and 83.1% for benign lung disease patients. The detection rate of the 7-AAB panel in the early-stage LC patients was higher than that of traditional tumor markers. The AUC of the 7-AAB panel in combination with the Mayo model was higher than that of the 7-AAB panel alone or the Mayo model alone in distinguishing MPN from benign nodules. For early-stage MPN, the sensitivity and specificity of the combination were 93.5% and 58.0%, respectively. For advanced-stage MPN, the sensitivity and specificity of the combination were 91.4% and 72.8%, respectively. The combination of the 7-AAB panel with the Mayo model significantly improved the detection rate of MPN, but the positive predictive value (PPV) and the specificity were not improved when compared with either the 7-AAB panel alone or the Mayo model alone. CONCLUSION: Our study confirmed the clinical value of the 7-AAB panel for the early detection of lung cancer and in combination with the Mayo model could be used to distinguish benign from malignant pulmonary nodules.

Immune Response After Radiofrequency Ablation and Surgical Resection in Nonsmall Cell Lung Cancer.

The objective includes radiofrequency ablation (RFA) of a cancerous nodule results in immunogenic cell death. Tumor antigens are presented and the inflammatory environment may help stimulate adaptive and innate antitumor immunity. The objective of this study was to investigate the immune response following RFA and subsequent surgical resection in early stage non-small cell lung cancer (NSCLC). In methods, a single-session approach of computed tomography-guided tumor biopsy with immediate frozen section (and proof of NSCLC) was performed followed by RFA of the tumor in 4 patients with a solitary pulmonary nodule. Blood samples were collected before RFA and 3 days thereafter. All patients underwent radical surgical resection by video-assisted thoracoscopic lobectomy 8 days following RFA. In results, intense infiltrations of CD4+ and CD8+ lymphocytes were found along the perimeter of the RFA-treated tumor tissue, whereas the central tumor areas remained devoid of lymphocytes. In the peripheral blood, the frequency of proinflammatory, immunostimulatory IFNγ-secreting, and immunostimulatory BDCA-3+/B7-H3- dendritic cells increased after RFA. Furthermore, a significant increase in T-cell proliferation was detected in T-cell assays after RFA and tumor resection. In this article, a local and systemic immune response subsequent to RFA and complete surgical resection in patients with NSCLC was identified for the first time. Treatment of patients with NSCLC with RFA and surgery leads to an activated and highly T-cell-stimulatory phenotype of dendritic cells, which may promote long-term immunity against NSCLC. The data suggest that the RFA-induced necrotic tumor debris can serve as an in situ antigen source to induce an autologous antitumor immune response.

Antibody αPEP13h reacts with lymphangioleiomyomatosis cells in lung nodules.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is characterized by the proliferation in the lung, axial lymphatics (eg, lymphangioleiomyomas), and kidney (eg, angiomyolipomas) of abnormal smooth muscle-like LAM cells, which express melanoma antigens such as Pmel17/gp100 and have dysfunctional tumor suppressor tuberous sclerosis complex (TSC) genes TSC2 or TSC1. Histopathologic diagnosis of LAM in lung specimens is based on identification of the Pmel17 protein with the monoclonal antibody HMB-45. METHODS: We compared the sensitivity of HMB-45 to that of antipeptide antibody αPEP13h, which reacts with a C-terminal peptide of Pmel17. LAM lung nodules were laser-capture microdissected to identify proteins by Western blotting. RESULTS: HMB-45 recognized approximately 25% of LAM cells within the LAM lung nodules, whereas αPEP13h identified > 82% of LAM cells within these structures in approximately 90% of patients. Whereas HMB-45 reacted with epithelioid but not with spindle-shaped LAM cells, αPEP13h identified both spindle-shaped and epithelioid LAM cells, providing greater sensitivity for detection of all types of LAM cells. HMB-45 recognized Pmel17 in premelanosomal organelles; αPEP13h recognized proteins in the cytoplasm as well as in premelanosomal organelles. Both antibodies recognized a Pmel17 variant of approximately 50 kDa. CONCLUSIONS: Based on its sensitivity and specificity, αPEP13h may be useful in the diagnosis of LAM and more sensitive than HMB-45.

Pulmonary hyalinizing granuloma detected in a family member after confirmation of tuberculosis in his father.

Pulmonary hyalinizing granuloma (PHG) is an uncommon lung disease that usually presents as bilateral multiple nodules, and more rarely as a solitary nodule. An exaggerated immune response to antigenic stimuli resulting from infection or an autoimmune process has been suggested as the cause of PHG. Here, we describe a rare case of solitary PHG that was detected in a family member after tuberculosis had been confirmed in his father, without any background of infectious disease or autoimmune abnormality.

Post cardiac transplantation T-cell lymphoproliferative disorder presenting as a solitary lung nodule.

Post-transplantation lymphoproliferative disorder (PTLD) is an infrequent, but serious complication of solid organ and bone marrow transplantations. The vast majority of the cases are of B-cell origin and usually associated with Epstein-Barr virus (EBV) infection. The non-B (T and NK cell) PTLDs account for up to 14% of the PTLD cases in Western countries. We report a case of a 66-year-old man who received an orthotopic heart transplant for cardiomyopathy 7 years prior to presentation. He was referred to our institution with a hypermetabolic solitary right lower lobe lung nodule with an SUV of 9.2 on PET scan. The combined histomorphological and immunohistochemical pattern was most consistent with monomorphic PTLD, peripheral T-cell lymphoma with angioimmunoblastic features. Molecular studies showed clonal T-cell gamma receptor gene rearrangement. Primary pulmonary involvement of T-cell PTLD is extremely rare. This is the third reported case of T-cell PTLD after cardiac transplantation, primarily involving the lung. Further, studies will be required to determine the appropriate treatment and prognosis of this rare entity.

A case of primary solitary pulmonary plasmacytoma.

Most solitary extramedullary plasmacytomas are plasma cell tumors that tend to develop in mucosa-associated lymphoid tissues including the upper respiratory tract. We present a 43-year-old patient who was diagnosed with a solitary plasmacytoma in the lung. Primary plasmacytoma of the lung is exceedingly rare, and the treatment is surgical excision. This malignancy advances to multiple myeloma in a minority of patients. Multiple myeloma is a plasma cell malignancy that typically presents in the bone marrow.

[A case report of IgG4-related sclerosing disease with lung involvement].

IgG4-related sclerosing disease(IgG4-RSD) is a kind of lymphoplasmacytic disease with multi-organ involvement and is characterized by serum IgG4 elevation and tissue IgG4 positive plasma cell infiltration. Autoimmune pancreatitis, sclerosing cholangitis, sclerosing sialadenitis, retroperitoneal fibrosis and lymphadenopathy make up its main clinical manifestations. This difficult case was a middle-aged female with onset as muiltiple lymph nodes and glands enlargement, including lacrimal gland, salivary glands and pancreas. Meanwhile, repeated examinations of auto-antibodies and serum IgG4 were all negative. The patient didn't respond well to glucocorticoid therapy, and further progressed to rare lung involvement presenting as lung nodule. This complex entity was eventually diagnosed as IgG4-RSD by the support of histopathology evidence of IgG4 immunohistochemistry stain. Though IgG4-RSD has been known for years, it is still underappreciated in China and case reports are scarce. The case report here with literature review is just to enhance the recognition of this disease regarding its pathogenesis, various clinical manifestations, diagnosis and therapy.

Segmentectomy for giant pulmonary sclerosing haemangiomas with high serum KL-6 levels.

We describe a 61-year old female patient with a giant pulmonary sclerosing haemangioma (PSH) and an extremely high preoperative serum KL-6 level. During an annual health screening, the patient showed a posterior mediastinal mass on chest radiography. Chest computed tomography and magnetic resonance imaging revealed a well-circumscribed 60 mm diameter nodule with a marked contrast enhancement in the left lower lobe. The preoperative serum KL-6 level was elevated to 8204 U/ml. We performed a four-port thoracoscopic basal segmentectomy and lymph node sampling for diagnosis and therapy. The postoperative diagnosis showed PSH. The serum KL-6 level decreased dramatically with tumour resection. To the best of our knowledge, this is the first report of a patient with PSH showing a high serum KL-6 level.

Rhodococcus equi infection after lung transplantation.

Rhodococcus equi is an emerging opportunistic pathogen in immunocompromised patients. A lung-transplant recipient developed weight loss, nonproductive cough, dyspnea, and somnolence. Computed tomogram showed a pulmonary nodule and pleural changes in the right allograft that was due to R. equi infection. Alteration of cell-mediated immunity is a predisposing risk factor for R. equi infection in humans. Our patient developed R. equi infection soon after a course of high-dose corticosteroids for acute allograft infection and animal exposure. A course of intravenous vancomycin followed by single-agent long-term therapy with oral ciprofloxacin was successful.

Phenotypic characterization of chronic inflammation in a rare case of endobronchial carcinoma.

This report presents a phenotypical characterization of the immune cell infiltrate in a rare case of endobronchial carcinoma. A patient initially treated for an adenocarcinoma of the esophagus developed an endobronchial carcinoma surrounded by gastric metaplasia distal to a suspected gastrobronchial fistula, 11 years after esophagectomy. Our hypothesis is that the sustained exposure of the bronchial mucosa to a mixed acid and pancreatobiliary refluxate led to chronic inflammation and promoted malignant transformation. We performed an immunohistochemical study of the tumor microenvironment evaluating the density of CD3(+), CD8(+) T lymphocytes, CD20(+) B lymphocytes, CD68(+) macrophages and FoxP3(+) regulatory T cells. Quantification of immune cell density was completed using a novel software-based analysis method. Our results suggest that, within all the tissues analyzed, FoxP3(+) regulatory T cells were present at their highest density in the malignant and metaplastic tissues. The endobronchial metaplasia biopsied several years prior to the detection of the endobronchial adenocarcinoma was already densely infiltrated by B cells and macrophages, when compared to the immune cell infiltrate of the endobronchial carcinoma. Altogether, these observations support the current understanding of carcinogenesis promoted by chronic inflammation.

[Pulmonary nocardiosis with a large solitary cavitary nodule caused by Nocardia cyriacigeorgica in a patient receiving corticosteroid therapy]. / Kortikosteroid tedavisi alan hastada Nocardia cyriacigeorgica'nin neden oldugu soliter kaviter nodül yapan pulmoner nokardiyoz.

Nocardiosis is a rare disease generally caused by members of Nocardia asteroides complex, particularly in immunosupressed patients. Nocardia cyriacigeorgica is a newly described member of this complex. In this article, a case of pulmonary nocardiosis with a large solitary cavitary nodule caused by N. cyriacigeorgica, in a patient receiving corticosteroid therapy was presented. A 29 years old male patient receiving prednisolone for 5 months was admitted to our hospital with fever, cough, right thoracic pain and night sweats. Computed tomography scan of chest demonstrated a large solitary cavitary nodule in the right lower lobe. Gram stained smear of the sputum revealed gram-positive, beaded, branched filamentous bacilli. On the third day of his admission, a catalase positive, oxidase negative and immotile bacilli, compatible with Nocardia spp., were isolated from the sputum sample taken at the day of admission. The isolated bacterium was identified as N. cyriacigeorgica by reference laboratory (Lyon, France). Oral trimethoprim (320 mg/day) and sulfamethoxazole (1600 mg/day) therapy given for three months, resulted in complete cure of the lesion without any sequela. This was the fourth case of pulmonary nocardiosis caused by N. cyriacigeorgica reported from Turkey. Microbiological examination of sputum is the most important tool for the diagnosis. Treatment with appropriate antibiotics may achieve complete cure even in large cavitary lesions. In conclusion, pulmonary nocardiosis should be considered in differential diagnosis of solitary cavitary nodules, especially in immunocompromised patients.

Amyloid-like pulmonary nodules, including localized light-chain deposition: clinicopathologic analysis of three cases.

Amyloid-like pulmonary nodules have been described in patients with systemic light-chain deposition disease, but their significance in other clinical contexts is unknown. We examined biopsy specimens of amyloid-like pulmonary nodules from 3 women without systemic light-chain deposition disease. Patient 1 (aged 62 years) had multiple pulmonary nodules and underwent 2 separate lung biopsies, the first showing nodules composed of kappa light-chain deposits accompanied by low-grade lymphoplasmacytic lymphoma limited to the lung and the second, obtained after chemotherapy 9 months later, showing only residual nodules without persistent lymphoma. Patients 2 (aged 65 years) and 3 (aged 69 years) had asymptomatic solitary pulmonary nodules. In all cases, electron microscopic examination showed dense granular extracellular deposits without the fibrillary characteristics of amyloid. Amyloid-like nodules should be distinguished from nodular amyloidosis and, in some patients, might represent a localized form of light-chain deposition.

Pulmonary nodule due to Mycobacterium haemophilum in an immunocompetent host.

We present a case of a pulmonary nodular lesion in an immunocompetent patient documented at open lung biopsy to be due to Mycobacterium haemophilum. This organism has recently been recognized as a cause of disease in immunocompromised patients, presenting predominantly as skin lesions, arthritis, and rarely pneumonia. Because this mycobacterium is fastidious and difficult to grow without the use of special media and conditions, our case raises the possibility that M. haemophilum could be an underrecognized cause of granulomatous pulmonary lesions and should be considered particularly in cases where smears for acid-fast bacteria are positive but cultures are negative.

[Organ-specific nodular pulmonary amyloidosis of the A lambda type in Sjogren syndrome]. / Organ-limitierte noduläre pulmonale Amyloidose vom Typ A lambda bei Sjögren-Syndrom.

The exclusive involvement of the lungs with A lambda-type amyloidosis in nodular dispositions in a case of Sjögren's syndrome is very rare. An immunoglobulin lambda-type light chain, benign, monoclonal gammopathy has been verified as the ethological cause. The urine concentration of paraproteins was below the detection limit of the common examination methods and could only be found immunoelectrophoretically in urine concentrated 100-200 fold. The question of a possible relationship with Sjögren's syndrome is being discussed.

The pulmonary nodule after lung transplantation. Cause and outcome.

In the immunocompromised patient, the pulmonary nodule remains a diagnostic and therapeutic challenge. We studied the incidence, cause, diagnosis, and therapy of pulmonary nodules after lung transplantation (LTx). Eight out of 64 patients (12.5%) developed pulmonary nodules after a median follow-up of 5.8 months (range, 1 to 10 months). The median age was 30.5 years (range, 21 to 62 years). Solitary pulmonary nodules (n = 2) disappeared spontaneously within 3 weeks and were suspected to be of infectious origin. The cause of multiple nodules (n = 6) was posttransplant lymphoproliferative disorder (PTLD [n = 3]), aspergillosis (n = 2), and abscesses caused by Pseudomonas aeruginosa and Staphylococcus aureus (n = 1). After an initial chest radiograph, CT with fine-needle biopsy was the most valuable diagnostic tool. In six patients, nodules resolved within 10 weeks (median, 8 weeks). Two patients, however, died of sepsis (P aeruginosa and S aureus and Aspergillus, respectively). The differential diagnosis of pulmonary nodules after LTx primarily comprises PTLD and infection (bacterial or fungal). To improve the outcome, early, aggressive treatment is mandatory; therefore, serial CT scans are strongly recommended to be part of the diagnostic armamentarium in LTx recipients.

A prospective pilot study evaluating the effectiveness of secretory IgA measurements in bronchoalveolar lavage to detect non-small cell lung cancer.

Previous studies have described significant elevations in the concentrations of secretory immunoglobulin A (sIgA) in bronchial washings obtained from cancerous lungs. To date, there have been no prospective investigations examining the predictive value of sIgA measurements in clinically relevant settings. Our goal was to determine if measurement of sIgA in bronchoalveolar lavage (BAL) at the time of bronchoscopic evaluation of potentially malignant lung nodules might prospectively predict the presence of cancer. We observed no significant increase in the sIgA obtained from eight BALs obtained from cancerous lungs as compared with BALs taken from these same patients' contralateral cancer-free lungs. We also saw no significant difference in BAL (sIgA) obtained from patients eventually found to have cancer (N = 8) as compared with those found to have noncancer diagnoses (N = 6). In light of these findings, we think it unlikely that measurement of sIgA will be clinically useful in the diagnosis of pulmonary malignant neoplasms.