NUT (Nuclear Protein in Testis) Carcinoma: A Report of Two Cases With Different Histopathologic Features.

NUT (nuclear protein in testis) carcinoma (NC) is an aggressive carcinoma characterized by rearrangements of the NUT gene on chromosome 15q14. Histologically, it is a poorly differentiated carcinoma composed of monotonous, medium-sized, round cells with scant amphophilic or eosinophilic cytoplasm. Foci of abrupt keratinization are often seen. In this report, we compare the morphology of 2 cases of NC. The first case shows characteristic features of uniform, round epithelioid cells admixed with foci of abrupt keratinization. The second case demonstrates nests of epithelioid-polygonal cells that appear to be loosely cribriform within a mucoid stroma. Although considered rare, the actual incidence of NC may be underestimated, as it is likely that many go undiagnosed because the morphology deviates from what is typical. Our report demonstrates that NC should always be considered in any case of an undifferentiated carcinoma and should not be excluded if typical histologic and immunohistochemical features of squamous differentiation are lacking.

Hot Tub Lung: A Diagnostic Challenge.

Hot tub lung (HTL) is a granulomatous lung disease thought to occur as a result of a hypersensitivity response to non-tuberculous mycobacteria (NTM). Typical radiographic findings are diffuse micronodular and/or ground glass opacities. We report an interesting case of HTL that presented with unique radiographic features, making its diagnosis a predicament. A 56-year-old immunocompetent female with chronic dyspnea and dry cough was found to have subcentimeter cavitary nodules, predominantly in the upper lung zones. Tissue culture obtained via bronchoscopy was positive for Mycobacterium avium complex (MAC). The patient's clinical and radiographic status, however, deteriorated on antimycobacterial therapy. Complete clinical and radiographic resolution was achieved only after avoidance of hot tub use and treatment with steroids. We believe this is the first reported case of HTL manifesting as cavitary lung nodules with mediastinal lymphadenopathy, and we recommend physicians keep HTL in consideration when encountering patients with these radiographic findings.

Patient With Slow-Growing Mediastinal Mass Presents With Chest Pain and Dyspnea.

A 52-year-old white woman presented with severe pain over the right upper abdomen and nonpleuritic, right-sided, lower chest-wall pain. Her pain had progressively gotten more frequent and severe over the last 5 months. It was also associated with a nonexertional, pressure-like sensation in the central chest. The patient denied any shortness of breath, fevers, cough, or any sputum production. She was taking levothyroxine for hypothyroidism and was a 30-pack-year current smoker; there was no history of drug abuse or occupational exposure. Previous chest radiographs dating back to 5 years consistently showed an elevated right-sided hemidiaphragm without any infiltrates or effusions; cardiomediastinal structures were unremarkable. She had not had a previous workup for these abnormal findings.

Treatment of isolated mediastinal and hilar recurrence of lung cancer with bronchoscopic endobronchial ultrasound guided intratumoral injection of chemotherapy with cisplatin.

PURPOSE: A common pattern of recurrence in lung cancer after receiving full dose external beam radiation therapy (EBRT) to targeted sites is isolated mediastinal and hilar recurrence (IMHR). Treatment options for these patients are limited to palliative radiation, chemotherapy, and/or best supportive care. We describe our experience with treating IMHR with bronchoscopic endobronchial ultrasound (EBUS) guided intratumoral injection of cisplatin (ITC). METHODS: Patients treated between Jan 2009-September 2014 with ITC for IMHR were included. Patient demographics, tumor histology, size, concurrent therapy, location, number of sites treated, treatment sessions, and encounters were abstracted. Responses were analyzed on follow-up scans 8-12 weeks after the last treatment session using RECIST 1.1 criteria. Locoregional recurrence, progression-free survival (PFS), and overall survival were measured. RESULTS: 50 sites were treated in 36 patients (19 males, 17 females) with mean age 61.9±8.5 years. Eight sites treated on subsequent encounters were excluded and one patient had an unevaluable response, leaving 35 patients and 41 sites for final analysis. 24/35 (69%) had complete or partial response (responders), whereas 11/35 (31%) had stable or progressive disease (non-responders). There were no significant differences in response based on histology, size, and concurrent therapy. Median survival for the group was 8 months (95% CI of 6-11 mo). Responders had significantly higher survival and PFS than non-responders. Two patients treated with concurrent EBRT, developed broncho-mediastinal fistula. CONCLUSION: EBUS guided intratumoral cisplatin for IMHR appears to be safe and effective, and may represent a new treatment paradigm for this patient population.

Restoration of Patency to Central Airways Occluded by Malignant Endobronchial Tumors Using Intratumoral Injection of Cisplatin.

RATIONALE: Malignant airway obstruction is commonly found in patients with lung cancer and is associated with significant morbidity and mortality. Relieving malignant obstruction may improve symptoms, quality of life, and life expectancy. OBJECTIVES: The objective of this study was to analyze our experience with bronchoscopic endobronchial intratumoral injection of cisplatin for malignant airway obstruction. METHODS: We conducted a retrospective analysis of patients with malignant airway obstruction treated with bronchoscopic intratumoral injection of cisplatin. Patient characteristics, histology, degree of airway obstruction, procedural methods, treatment cycles, performance status, and therapeutic outcomes were evaluated. Tumor response was analyzed based on bronchoscopic measurements performed on completion the of final treatment session. Adverse events and overall survival were abstracted. MEASUREMENTS AND MAIN RESULTS: Between January 2009 and September 2014, 22 patients (10 men, 12 women; mean age ± SD, 64.4 ± 9.5 yr) were treated with one to four injections of 40 mg of cisplatin mixed in 40 ml of 0.9% NaCl. Treatments were completed 1 week apart. The primary etiologies of airway obstruction included squamous cell carcinoma (n = 11), adenocarcinoma (n = 6), small cell carcinoma (n = 2), large cell undifferentiated carcinoma (n = 1), and metastatic endobronchial cancer (n = 2). Twenty-one of 22 patients were evaluable for response. The majority of patients (15/21, 71.4%) responded to therapy, defined as greater than 50% relative reduction in obstruction from baseline. Treatment response was obtained regardless of tumor histology, concurrent systemic therapy, number of treatment cycles administered, performance status, or use of additional ablative interventions. Responders had significantly improved overall survival as compared with nonresponders, although the difference was small. Severe treatment-related side effects or complications were not observed. CONCLUSIONS: Subject to the limitations of a single-center retrospective study and a subjective primary outcome measure, we have demonstrated the feasibility of improving the patency of central airways that are largely or completely occluded by endobronchial malignant tumor using intraluminal injection of cisplatin. Additional longer-term, larger-scale safety and comparative effectiveness studies of this palliative treatment modality are warranted.

Treatment of alveolar-pleural fistula with endobronchial application of synthetic hydrogel.

BACKGROUND: Alveolar-pleural fistula with persistent air leak is a common problem causing significant morbidity, prolonged hospital stay, and increased health-care costs. When conventional therapy fails, an alternative to prolonged chest-tube drainage or surgery is needed. New bronchoscopic techniques have been developed to close the air leak by reducing the flow of air through the leak. The objective of this study was to analyze our experience with bronchoscopic application of a synthetic hydrogel for the treatment of such fistulas. METHODS: We conducted a retrospective study of patients with alveolar-pleural fistula with persistent air leaks treated with synthetic hydrogel application via flexible bronchoscopy. Patient characteristics, underlying disease, and outcome of endoscopic treatment were analyzed. RESULTS: Between January 2009 and December 2013, 22 patients (14 men, eight women; mean age ± SD, 62 ± 10 years) were treated with one to three applications of a synthetic hydrogel per patient. The primary etiology of persistent air leak was necrotizing pneumonia (n = 8), post-thoracic surgery (n = 6), bullous emphysema (n = 5), idiopathic interstitial pneumonia (n = 2), and sarcoidosis (n = 1). Nineteen patients (86%) had complete resolution of the air leak, leading to successful removal of chest tube a mean ( ± SD) of 4.3 ± 0.9 days after last bronchoscopic application. The procedure was very well tolerated, with two patients coughing up the hydrogel and one having hypoxemia requiring bronchoscopic suctioning. CONCLUSIONS: Bronchoscopic administration of a synthetic hydrogel is an effective, nonsurgical, minimally invasive intervention for patients with persistent pulmonary air leaks secondary to alveolar-pleural fistula.

Rapid progression of pulmonary blastomycosis in an untreated patient of chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is associated with a state of immunosuppression characterized by hypogammaglobulinemia as well as B and T lymphocyte dysfunction. Though opportunistic infections are common in CLL patients, particularly after treatment, reports of infections by endemic dimorphic fungi are very few. Here we report a case of pulmonary blastomycosis in a CLL patient who initially presented with an indolent pulmonary mass lesion. The pulmonary lesions progressed rapidly over a two-week period. The diagnosis was established by transbronchial lung biopsy. He was treated with Amphotericin B lipid complex followed by oral itraconazole and recovered uneventfully. This case illustrates the importance of a timely diagnosis and treatment. The presentation of blastomycosis in immunocompromised patients, diagnosis, and treatment are discussed.