Bilateral Reticulonodular Infiltrates Research Articles

P1122: EFFICACY OF ALPELISIB IN PI3K-DRIVEN LANGERHANS CELL HISTIOCYTOSIS

Background: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm characterized by the accumulation of clonal dendritic cells expressing CD1a and CD207 (Langerin). LCH affects both children and adults and typically ranges from an indolent unifocal form to a progressive multisystemic disease. In the past decade, in depth molecular profiling of LCH as well as other histiocytic neoplasms demonstrated that these diseases are fundamentally dependent on somatic MAPK activating mutations, with the canonical V600E BRAF mutation emerging in more than 50% of LCH patients. Nonetheless, MAPK independent driver mutations were previously reported and anecdotal evidence of successful targeted treatment of various histiocytoses harboring non-canonical drivers such as RET, ALK and CSF1R were previously described in the literature. Aims: To report a case of PI3K driven LCH treated with an isoform specific PIK3CA inhibitor. Methods: Case summary: a 46 year-old mother of 3 presented with complaints of progressive headaches, polydipsia and polyuria. Following a pathological water deprivation test and identification of pituitary stalk thickening on MRI, a diagnosis of central diabetes insipidus (CDI) was established and desmopressin treatment was initiated. However, 10 months following her CDI diagnosis, the patient began to complain of sub febrile episodes of fever and worsening dry cough. Imaging studies including PET/CT disclosed extensive bilateral reticulo-nodular infiltration, nodules with cystic transformation and ground glass opacity, suspicious of pulmonary LCH. Histological examination of a wedge biopsy specimen obtained from the lungs confirmed the diagnosis of LCH and consequent molecular studies identified the M1043V PIK3CA mutation. During her medical investigation, the patient’s conditioned worsened, with new disease foci emerging – including cervical lymphadenopathy and a lytic vertebral lesion involving D11. The patient then received palliative radiotherapy directed at the D11 lytic lesion followed by escalating systemic therapy with single agent Alpelisib, via the Managed Access Program at Novartis. Response to treatment was assessed clinically and using PET/CT. At the molecular level, the effect of Alpelisib was assessed by measuring PTEN expression levels and cell cycle regulating non-coding RNA molecules by using quantitative real-time polymerase chain reaction (qRT-PCR). Results: Treatment with Alpelisib resulted in rapid amelioration of night sweats within 6 days, decrease in back pain within 3 weeks and normalization of all abnormally FDG avid disease foci within 3 months of treatment. The complete metabolic response observed persists currently more than a year following treatment initiation. Treatment with Alpelisib is well tolerated except for a mild increase in HbA1C levels to 6.7%. Moreover, PTEN, the main regulator of the PI3K pathway was found to be upregulated following 3 and 9 months of treatment, in parallel to downregulation of small non-coding RNAs molecules that regulates its expression. Image:Summary/Conclusion: This is the first study demonstrating that the alpha catalytic subunit of PI3K is a targetable non-canonical driver of LCH.

Primary Pulmonary Plasmacytoma Presenting as Multiple Lung Nodules

Primary Pulmonary Plasmacytoma Presenting as Multiple Lung Nodules

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: 7-year follow-up of a rare clinicopathologic syndrome

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare clinical pathological syndrome. There have been only 49 cases of DIPNECH reported in the literature so far. We report a case of a 69-year-old nonsmoking man with a 7-year follow-up. The initial CT scan from December 2003 showed persistent nonspecific bilateral reticulonodular infiltrates. In January 2004, the patient underwent a video-assisted thoracoscopic wedge resection of his right lower lobe for further diagnostic workup. Pathology of the resected wedge of the right lower lobe revealed a diffuse idiopathic pulmonary cell hyperplasia (DIPNECH) highlighted by staining for the neuroendocrine typical carcinoid markers, such as marker CD 56. All the performed CT scans over a 7-year period showed no progression of the bilateral pulmonary lesion. The bilateral pulmonary nodules were stable in terms of size, number and form. The yearly control with chest CT scans will be continued. The neuroendocrine cell hyperplasia is confined to the airway mucosa without penetration through the basement membrane and appears in a diffuse pattern, generally in close association with obliterative bronchiolar fibrosis. DIPNECH is characterized by a mixed obstructive and/or restrictive ventilation pattern with bilateral reticulonodular infiltrates and a predilection for middle-aged women. Little is known about the clinical course and treatment for DIPNECH.

Pulmonary Lymphangitic Carcinomatosis from Rectal Cancer: Report of a Case

Pulmonary lymphangitic carcinomatosis (LC) is defined as the presence of tumor cells in the pulmonary lymphatic vessels and lung interstitium. Pulmonary LC is a rare form of lung metastasis from rectal cancer. Here, we report the case of a 57- year-old woman who developed dyspnea after neoadjuvant concurrent chemoradiation therapy (CCRT) for rectal cancer. Chest radiographs revealed bilateral reticulonodular infiltrates and pleural effusion but no obvious nodules. The patient was treated as a case of pneumonia initially but the dyspnea worsened rapidly. For lack of bacterial growth from sputum culture, and on account of the cytological examination of the pleural effusion which revealed malignant cells. pulmonary LC was suspected and systemic chemotherapy was prescribed; however, the treatment was ineffective and the patient died of acute progressive respiratory failure. We suggest if a patient having cancer presents with respiratory compromise and increased bilateral infiltration and/or reticulonodular changes on chest radiographs, the possibility of pulmonary LC should be considered. If the patient treated as a case of pneumonia or other benign diseases, has a rapidly worsening clinical course, early diagnosis and aggressive chemotherapy are essential for the proper management of pulmonary LC.

Biopsy Findings in Acute Pulmonary Histoplasmosis

Most examples of pulmonary histoplasmosis, including histoplasmoma and chronic histoplasmosis, are characterized by typical necrotizing granulomatous inflammation. Only disseminated histoplasmosis is recognized as causing a different reaction which consists of ingestion of organisms by macrophages without granuloma formation. The histologic features of acute pulmonary histoplasmosis are not well described as this form of the disease is rarely biopsied. We report the biopsy findings in 4 cases of acute pulmonary histoplasmosis, which seem to be unique to this form of Histoplasma infection. There were 3 men and 1 woman who ranged in age from 40 to 68 years. All presented acutely with fever and other flu-like symptoms. Radiographically, a solitary nodular infiltrate was present in 3 and bilateral reticulonodular infiltrates in one. Histologically, all 4 biopsies showed a nodular parenchymal inflammatory infiltrate composed of lymphocytes and histiocytes filling alveolar spaces and expanding the adjacent interstitium. Areas of parenchymal necrosis were additionally present in 3 cases. Vasculitis composed of lymphocytes and histiocytes was present in all, and was striking in 3, resulting in a resemblance to grade 1 lymphomatoid granulomatosis (LYG). Tip-offs to the correct diagnosis were small necrotizing granulomas scattered within the lymphohistiocytic infiltrate (3 cases), scattered histiocyte aggregates, and a few multinucleated giant cells. The diagnosis was confirmed in all by the presence of Histoplasma yeasts in Grocott methenamine silver-stained slides. Acute pulmonary histoplasmosis may cause a lymphohistiocytic infiltrate with necrosis and vasculitis that is suggestive of LYG. This observation emphasizes the importance of examining special stains for organisms before diagnosing grade 1 LYG.

Nonresolving pneumonia and rash in an adult: pulmonary involvements in Kawasaki's disease

To the Editors : Slowly resolving or nonresolving pneumonia is a challenge for physicians. The most common clinical error when approaching these patients is to subsequently treat the patient with different antibiotics over an extended period of time, without questioning the cause of treatment failure. Mostly, slowly resolving pneumonias are due to host defence or infectious causes. Nonresolving pneumonias are usually of noninfectious origin and, in the majority of cases, require invasive diagnostic techniques to be confirmed. Nonresolving or slowly resolving pneumonia should direct the clinician to a critical re-evaluation of the possible causes of the disease. A 19-yr-old male without known comorbidity reported to a general practitioner with fever, headache, sore throat and diarrhoea. A few days later, after being treated with amoxicillin/clavulanate, he developed a generalised erythema and rash, starting on the abdomen. Already severely impaired, he later went to a primary care centre. Based on his dermatological alterations, staphylococcal toxic shock syndrome was suspected and antibiotics where changed to penicillin and clindamycin. However, the condition worsened; the patient developed dyspnoea, dry cough and bilateral reticulo-nodular infiltrates on chest radiograph. He was transferred to our university hospital because of imminent respiratory failure. On admission he was still febrile (38.5°C), had generalised oedema and required 6 L·min−1 oxygen to achieve a saturation of 96% (arterial blood …

Fieber und Gewichtsverlust nach BCG-Instillation in die Harnblase bei Urothelkarzinom

We report the case of a patient, who suffered from an acute BCG-pneumonitis after the fourth treatment of his bladder cancer with intravesical instillation of BCG. The chest-x-ray presented a bilateral reticulonodular infiltration. Mycobacterium tuberculosis could not be detected by culture, biopsy or PCR assay. Under treatment with Rifampicine, Isoniazid and Ethambutol the patient recovered within a short time and the follow up chest-x-ray became normal. A supplementary steroid therapy was not needed.

Histiocytosis X in the lung

The histologic and clinical features of pulmonary histiocytosis X are discussed. The majority of patients are in the third and fourth decades of life. They present with nonspecific respiratory complaints and bilateral reticulonodular infiltrates that can be seen on chest radiographs. The histologic lesions of pulmonary histiocytosis X are scattered, discrete nodules that frequently center on small airways. The initially cellular nodules are replaced progressively by fibrous tissue. The cell infiltrates in active lesions contain variable numbers of eosinophils and histiocytes resembling Langerhans cells of the epidermis (Hx cells). In most patients the disease resolves or stabilizes, leaving few, if any, significant residues. A minority of patients develop progressive pulmonary disease that is ultimately fatal. The cause of pulmonary histiocytosis X is unknown, but two recent series suggest a relationship to cigarette smoking.

The Association of Progressive Multifocal Leukoencephalopathy and Sarcoidosis

A 59-year-old woman had a right homonymous hemianopsia, memory impairment for five months, a nonenhancing area in the left parieto-occipital region on CT scan, and bilateral reticulonodular infiltrates on chest x-ray film. Lung biopsy findings were consistent with sarcoidosis, a clinical diagnosis of CNS sarcoidosis made, and prednisone therapy begun. She deteriorated neurologically and died. At autopsy characteristic histologic and electron microscopic features of progressive multifocal leukoencephalopathy (PML) were found. We conclude that this and other cases demonstrate an association of PML and sarcoidosis and that steroid treatment is not a precondition. We also suggest an aggressive diagnostic approach in evaluating sarcoidosis with atypical neurologic deficits.