Comparison of the GenCut Core Biopsy System to Transbronchial Biopsy Forceps for Flexible Bronchoscopic Lung Biopsy.

BACKGROUND: Pulmonary nodules are increasingly detected on screening and routine chest imaging, leading to an increase in diagnostic procedures. Bronchoscopy with transbronchial biopsy (TBBx) is the most common diagnostic modality, with diagnostic yield between 43% and 86%, largely dependent on the use of navigational modalities. In 2015 a new biopsy tool by Medtronic, the GenCut core biopsy system [GenCut transbronchial needle aspiration (TBNA)], was developed with the intention of improving yield in lung nodule biopsies. Our goal was to determine the efficacy of this new device when used in addition to TBBx. PATIENTS AND METHODS: This is a prospective observational study of 324 consecutive bronchoscopic lung biopsies in which both TBBx and GenCut TBNA were performed on the same lesion. We recorded patient and nodule characteristics, along with the bronchoscopic modalities used. The primary outcome was the diagnostic yield with the addition of the GenCut TBNA, and the key secondary outcome was the complication rate. RESULTS: Of the 324 nodule biopsies analyzed, 164 (50.6%) were diagnostic via TBBx or GenCut TBNA.In all, 97 (59%) were positive in both TBBx and GenCut TBNA, 43 (26.2%) were positive only in TBBx, and 24 (14.6%) were positive only in GenCut TBNA. Overall, the addition of the GenCut TBNA increased the diagnostic yield by 7.4% (P<0.01). There were 7 complications: 5 pneumothoraxes and 2 episodes of bleeding. CONCLUSION: The diagnostic yield is improved by using the GenCut core biopsy system in addition to traditional TBBx forceps when performing bronchoscopy for pulmonary nodules, without an increase in complications. These biopsy methods should be used in tandem for the greatest yield.

Spindle epithelial tumor with thymus-like differentiation in fine needle aspiration of thyroid gland: Report of two cases.

Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare, malignant tumor of the thyroid gland that typically affects young males and has a propensity for late metastasis. With fine needle aspiration (FNA) being a primary tool for diagnosis of thyroid lesions, there are rare reports of cytological features of SETTLE on FNA since its initial characterization 30 years ago . Here we report two cases of SETTLE, involving 9-year-old and 15-year-old male patients. Both patients underwent US-guided FNA with a subsequent resection confirming the diagnosis of SETTLE. In the first patient the thymic origin of the tumor was suspected on FNA, but the diagnosis of SETTLE was established only after resection. Five years later, this patient presented with an enlarged ipsilateral cervical lymph node. Needle biopsy confirmed it to be a metastatic tumor compatible with SETTLE. In the second patient the diagnosis of SETTLE was suggested on FNA. Cytology of the thyroid gland nodule on FNA from both patients showed loosely cohesive and single spindle-shaped epithelial cells associated with metachromatic stroma. The differential diagnosis of spindle cell lesions of the thyroid should include SETTLE based on characteristic morphological features, after more common entities of thyroid gland such as medullary carcinoma are excluded.

Spindle cell lesion on fine needle aspiration as an initial step for diagnosis of lymphangioleiomyomatosis: Report of a rare case.

Lymphangioleiomyomatosis (LAM) is a rare systemic disease of women of reproductive age characterized by proliferation of abnormal smooth muscle like cells (LAM cells). Patients with LAM characteristically present with chronic dyspnea and cough and less commonly with spontaneous pneumothorax. Manifestation of extrapulmonary LAM as an initial presenting symptom is rare with a renal angiomyolipoma and lymphangioleiomyoma being most common. Although histologic findings of LAM are well-described, the cytological features; however, have been described only in few case reports, which focus on pulmonary LAM. Here, we report a case where initial diagnosis of LAM was made on pelvic "lymph node" fine needle aspiration (FNA) and biopsy in otherwise asymptomatic 25-year-old female, leading to further investigation and detection of developing cystic lung lesions. FNA cytology from the pelvic "lymph node" yielded proliferation of spindle cells without cytologic atypia. This case presented both clinical and histopathologic challenge, requiring clinical correlation and immunohistochemical staining for diagnosis. While rare, it is important to consider LAM in the differential diagnosis of spindle cell lesions in aspirate from nodules around vascular bundles in women of reproductive age even without history of lung lesion.

IgG4-Related Appendiceal Disease: A First Case Report Fulfilling All Pathological Diagnostic Criteria and With Concomitant S100-Positive Dendritic/Schwann Cell Hyperplasia.

IgG4-related disease is a recent entity that has been described in a wide variety of organ systems. A 46-year-old female presented with acute appendicitis accompanied by a mass-forming lesion, raising a concern for neoplasm, and therefore, hemicolectomy was performed. The lesion revealed a dense lymphoplasmacytic infiltrate accompanied by storiform fibrosis and obliterative phlebitis. The IgG4/IgG plasma cell ratio was >50%, and the number of IgG4-positive plasma cells was >100/high-power field. In order to assess the IgG4/IgG plasma cell ratio, MUM1 was employed instead of IgG to successfully estimate the plasma cell concentration. There was also a concomitant hyperplasia of S100-positive cell, which could represent dendritic or Schwannian origin and possibly play a pathophysiologic role. The hyperplasia was significant by itself that it may mimic a mass-forming lesion. This newly described entity of the past decade deserves increased recognition due to clinical implication and surgical morbidity. This is the first case of IgG4-related disease in the appendix to our knowledge that fully satisfied all the pathological diagnostic criteria. We would like to also highlight our innovative approach of evaluating the IgG4/IgG plasma cell.

Metastatic lymphoepithelioma-like carcinoma of the lung treated with nivolumab: a case report and focused review of literature.

In recent years, significant advances have been made in cancer immunotherapy. Here, we present the first report of a patient with lymphoepithelioma-like carcinoma (LELC) of the lung, an Epstein-Barr virus (EBV)-associated lung cancer, who was treated with nivolumab, a fully human IgG4 anti-PD-1 monoclonal antibody. We also carry out a focused review to identify and examine studies of LELC of the lung in the literature. This case report highlights the need to further assess the role of immune checkpoint inhibitors in LELC of the lung.

Pathologic collision of inverted papilloma with esthesioneuroblastoma.

BACKGROUND: Inverted papilloma (IP) of the nasal cavity is a benign tumor that represents 0.5-4% of all nasal tumors and have been known to rarely undergo malignant transformation to squamous carcinoma and even more rarely adenocarcinoma. Synchronous association with low-grade esthesioneuroblastoma (ENB) has been reported in only one case report where a small-sized lesion was treated with surgery alone. Here we report the first case of invasion of IP by high-grade ENB with nodal metastasis that was treated with combined modality therapy. CASE PRESENTATION: A case of a 64-year-old African American gentleman presented to the otolaryngology with a 3-month history of recurrent epistaxis. Imaging revealed a large right nasal cavity mass extending into the right sphenoid sinus but without intracranial extension. Surgical pathology revealed high-grade ENB invading IP. An orbitofrontal craniotomy approach was used to achieve complete resection of the mass but with positive margins. Post-operative positron emission tomography/computed tomography showed nodal metastasis. The patient was then treated with adjuvant chemoradiation and remains without evidence of disease at 42 months post-treatment. We discuss the disease presentation, histopathologic features, and disease management with literature support. CONCLUSION: In this very rare disease presentation where two extremely rare malignancies collide, we show that aggressive management with trimodality therapy of surgery, adjuvant radiation with stereotactic radiosurgical boost, and adjuvant chemotherapy gives excellent results. Given the natural history of the disease, however, long follow-up is needed to declare complete freedom from the disease.

Solid-pseudopapillary neoplasm of the pancreas: awareness of unusual clinical presentations and morphology of the clear cell variant can prevent diagnostic errors.

Solid-pseudopapillary neoplasm (SPN) of the pancreas is a rare neoplasm predominantly reported in young women. It classically presents as a large tumor with cystic and solid components. The major differential diagnosis includes pancreatic neuroendocrine tumor (PanNET). This study presents our experience with this tumor with emphasis on the morphologic features of the clear cell variant of SPN. Fifteen histologically confirmed SPN were identified in our files. Endoscopic ultrasound-guided fine needle aspirations (EUS-guided FNA) were performed in 8/15 cases. Patients' demographics, cytohistologic correlation and tumor characteristics were evaluated. Eleven of the 15 subjects were female and four were male with an age range of 17-73 years. Twelve SPN were located in the pancreatic body/tail, and three in the head. Tumor size ranged from 1.5 to 8.5 cm and 11 were solid. Of the eight EUS-guided FNA, four were diagnosed as SPN, two as SPN vs. PanNET, one as malignant with signet ring features, and one was nondiagnostic. Immunohistochemistry was performed on six/eight FNA cell blocks and 13/15 surgical specimens. Two of the 15 cases were classified as clear cell variants of SPN. Our study shows that SPN may occur in males and older adults, and present as a small or solid tumor. The clear cell variant of SPN, characterized by vacuolated cytoplasm and signet cell morphology, may pose a diagnostic challenge on FNA. Awareness of the wide spectrum of SPN clinical presentations, the morphology of its clear cell variant and the appropriate use of ancillary immunohistochemistry can prevent diagnostic errors.

Does on-site adequacy evaluation reduce the nondiagnostic rate in endoscopic ultrasound-guided fine-needle aspiration of pancreatic lesions?

BACKGROUND: This retrospective study compared the nondiagnostic rate for endoscopic ultrasound-guided (EUS) fine-needle aspiration (FNA) of pancreatic lesions in 2 settings: 1 with and 1 without on-site evaluation. METHODS: The authors reviewed 381 consecutive cases and divided them into groups with and without on-site adequacy evaluation. For the group with on-site evaluation, cytopathology personnel prepared and evaluated Diff-Quik-stained direct smears and rinsed the remaining material in CytoLyt solution (Cytyc Corporation, Marlborough, Mass). The group without on-site evaluation was divided into 2 subgroups: the clinical team either prepared an air-dried smear for each FNA pass and then rinsed the remaining material in CytoLyt, or the entire sample was rinsed in CytoLyt. The cytologic diagnoses were reviewed and the nondiagnostic rates for each group were calculated. RESULTS: On-site evaluation was provided for 167 cases with a nondiagnostic rate of 25.8% (43 of 167 cases). On-site evaluation was not provided for 214 cases with a nondiagnostic rate of 24.3% (52 of 214 cases). The nondiagnostic rate for the subgroup with air-dried smears prepared by the clinical team was 25.6% (43 of 168 cases) and that for the subgroup with the entire sample rinsed in CytoLyt was 19.6% (9 of 46 cases). There were no significant statistical differences in nondiagnostic rates noted among the different groups or subgroups. CONCLUSIONS: The results of the current study indicate that when experienced operators perform EUS FNA of pancreatic lesions, on-site adequacy evaluation offers no benefit in reducing the nondiagnostic rate. Optimizing visualization of the sampled material by omitting the preparation of direct smears and rinsing the entire sample in liquid-based media demonstrated a trend toward improving the diagnostic rate.

CyberKnife radiosurgery for inoperable stage IA non-small cell lung cancer: 18F-fluorodeoxyglucose positron emission tomography/computed tomography serial tumor response assessment.

OBJECTIVE: To report serial 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) tumor response following CyberKnife radiosurgery for stage IA non-small cell lung cancer (NSCLC). METHODS: Patients with biopsy-proven inoperable stage IA NSCLC were enrolled into this IRB-approved study. Targeting was based on 3-5 gold fiducial markers implanted in or near tumors. Gross tumor volumes (GTVs) were contoured using lung windows; margins were expanded by 5 mm to establish the planning treatment volumes (PTVs). Doses ranged from 42-60 Gy in 3 equal fractions. 18F-FDG PET/CT was performed prior to and at 3-6-month, 9-15 months and 18-24 months following treatment. The tumor maximum standardized uptake value (SUV(max)) was recorded for each time point. RESULTS: Twenty patients with an average maximum tumor diameter of 2.2 cm were treated over a 3-year period. A mean dose of 51 Gy was delivered to the PTV in 3 to 11 days (mean, 7 days). The 30-Gy isodose contour extended an average of 2 cm from the GTV. At a median follow-up of 43 months, the 2-year Kaplan-Meier overall survival estimate was 90% and the local control estimate was 95%. Mean tumor SUV(max) before treatment was 6.2 (range, 2.0 to 10.7). During early follow-up the mean tumor SUV(max) remained at 2.3 (range, 1.0 to 5.7), despite transient elevations in individual tumor SUV(max) levels attributed to peritumoral radiation-induced pneumonitis visible on CT imaging. At 18-24 months the mean tumor SUV(max) for controlled tumors was 2.0, with a narrow range of values (range, 1.5 to 2.8). A single local failure was confirmed at 24 months in a patient with an elevated tumor SUV(max) of 8.4. CONCLUSION: Local control and survival following CyberKnife radiosurgery for stage IA NSCLC is exceptional. Early transient increases in tumor SUV(max) are likely related to radiation-induced pneumonitis. Tumor SUV(max) values return to background levels at 18-24 months, enhancing 18F-FDG PET/CT detection of local failure. The value of 18F-FDG PET/CT imaging for surveillance following lung SBRT deserves further study.