David R. Crowe

Endoscopic ultrasound‐guided FNA biopsy of bile duct and gallbladder: analysis of 53 cases

Objective:  Endoscopic retrograde cholangiopancreaticography (ERCP)‐guided brushing has been the standard of practice for surveillance and detection of carcinoma in the biliary tree. Few studies have evaluated the role of endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) in diagnosing clinically suspected cholangiocarcinoma. The role of this method in diagnosing clinically suspected gallbladder malignancies has not been extensively evaluated in the USA. This study investigates the role of EUS‐FNA in the diagnosis of clinically suspected biliary tree and gallbladder malignancies in a large patient series.

Cumulative sum procedure in evaluation of EUS‐guided FNA cytology: the learning curve and diagnostic performance beyond sensitivity and specificity

Background:  Using cumulative sum (CUSUM) chart, we address two questions: (i) Over time, how will an EUS‐FNA (endoscopic ultrasound guided fine needle aspiration) service maintain an acceptable non‐diagnostic rate defined as technical failures, unsatisfactory specimens and atypical and suspicious diagnoses? (ii) Over time, how will EUS‐FNA maintain acceptable diagnostic errors (false‐positives plus false‐negative diagnosis)?

Dynamic telecytopathology of on site rapid cytology diagnoses for pancreatic carcinoma

Background Diagnosis of pancreatic lesions can be accurately performed by endoscopic ultrasound guided fine needle aspiration (EUS-FNA) with onsite cytopathologists to assess specimen adequacy and to determine a preliminary diagnosis. Considerable time is needed to perform on-site assessments. This takes away work time of cytopathologists and prohibits them from serving remote locations. It is therefore logical to ask if real-time telecytopathology could be used to assess specimen adequacy and if telecytopathology diagnosis has the same level of agreement to the final diagnosis as that of onsite evaluation. In this study, we compare agreement between cytodiagnoses rendered using telecytopathology with onsite and final interpretations. Method 40 Diff-Quik-stained EUS-FNA were re-evaluated retrospectively (patient ages 31–62, 19:21 male:female, 15 non-malignant lesions, 25 malignant lesions as classified by final diagnosis). Each previously assessed by a cytopathologist and finally reviewed by the same or different cytopathologist. Blinded to the final diagnosis, a resident pathologist re-screened all slides for each case, selected a slide and marked the diagnostic cells most representative of the lesion. Blinded to the diagnosis, one cytopathologist assessed the marked cells through a real time remotely operated telecytopathology system (MedMicroscopy). Diagnosis and time spent were recorded. Kappa statistic was used to compare agreements between telecytopathology vs. original onsite vs. final diagnoses. Results Time spent for prescreening ranged from 1 to 5 minutes (mean 2.6 +/- 1.3 minutes) and time spent for telecytopathology diagnosis ranged from 2–20 minutes (mean 7.5 +/- 4.5 minutes). Kappa statistics, K, was as follows: telecytopathology versus onsite diagnosis K, 95% CI = 0.65, 0.41–0.88, for telecytopathology versus final K, 95% CI = 0.61, 0.37–0.85 and for onsite diagnosis versus final K, 95% CI = 0.79, 0.61–0.98. There is no significant difference in agreement between onsite and telecytopathology diagnoses. Kappa values for telecytopathology were less than onsite evaluation when compared to the final diagnosis; however, the difference was not statistically significant. Conclusion This retrospective study demonstrates the potential use of telecytopathology as a valid substitute for onsite evaluation of pancreatic carcinoma by EUS-FNA.

Mitochondrial-nuclear genome interactions in non-alcoholic fatty liver disease in mice.

NAFLD (non-alcoholic fatty liver disease) involves significant changes in liver metabolism characterized by oxidative stress, lipid accumulation and fibrogenesis. Mitochondrial dysfunction and bioenergetic defects also contribute to NAFLD. In the present study, we examined whether differences in mtDNA influence NAFLD. To determine the role of mitochondrial and nuclear genomes in NAFLD, MNX (mitochondrial-nuclear exchange) mice were fed an atherogenic diet. MNX mice have mtDNA from C57BL/6J mice on a C3H/HeN nuclear background and vice versa. Results from MNX mice were compared with wild-type C57BL/6J and C3H/HeN mice fed a control or atherogenic diet. Mice with the C57BL/6J nuclear genome developed more macrosteatosis, inflammation and fibrosis compared with mice containing the C3H/HeN nuclear genome when fed the atherogenic diet. These changes were associated with parallel alterations in inflammation and fibrosis gene expression in wild-type mice, with intermediate responses in MNX mice. Mice with the C57BL/6J nuclear genome had increased State 4 respiration, whereas MNX mice had decreased State 3 respiration and RCR (respiratory control ratio) when fed the atherogenic diet. Complex IV activity and most mitochondrial biogenesis genes were increased in mice with the C57BL/6J nuclear or mitochondrial genome, or both fed the atherogenic diet. These results reveal new interactions between mitochondrial and nuclear genomes and support the concept that mtDNA influences mitochondrial function and metabolic pathways implicated in NAFLD.

Involvement of the mitochondrial permeability transition pore in chronic ethanol-mediated liver injury in mice

Chronic ethanol consumption increases sensitivity of the mitochondrial permeability transition (MPT) pore induction in liver. Ca(2+) promotes MPT pore opening, and genetic ablation of cyclophilin D (CypD) increases the Ca(2+) threshold for the MPT. We used wild-type (WT) and CypD-null (CypD(-/-)) mice fed a control or an ethanol-containing diet to investigate the role of the MPT in ethanol-mediated liver injury. Ca(2+)-mediated induction of the MPT and mitochondrial respiration were measured in isolated liver mitochondria. Steatosis was present in WT and CypD(-/-) mice fed ethanol and accompanied by increased terminal deoxynucleotidyl transferase dUTP-mediated nick-end label-positive nuclei. Autophagy was increased in ethanol-fed WT mice compared with ethanol-fed CypD(-/-) mice, as reflected by an increase in the ratio of microtubule protein 1 light chain 3B II to microtubule protein 1 light chain 3B I. Higher levels of p62 were measured in CypD(-/-) than WT mice. Ethanol decreased mitochondrial respiratory control ratios and select complex activities in WT and CypD(-/-) mice. Ethanol also increased CypD protein in liver of WT mice. Mitochondria from control- and ethanol-fed WT mice were more sensitive to Ca(2+)-mediated MPT pore induction than mitochondria from their CypD(-/-) counterparts. Mitochondria from ethanol-fed CypD(-/-) mice were also more sensitive to Ca(2+)-induced swelling than mitochondria from control-fed CypD(-/-) mice but were less sensitive than mitochondria from ethanol-fed WT mice. In summary, CypD deficiency was associated with impaired autophagy and did not prevent ethanol-mediated steatosis. Furthermore, increased MPT sensitivity was observed in mitochondria from ethanol-fed WT and CypD(-/-) mice. We conclude that chronic ethanol consumption likely lowers the threshold for CypD-regulated and -independent characteristics of the ethanol-mediated MPT pore in liver mitochondria.

Bilateral adrenal gland enlargement secondary to histoplasmosis mimicking adrenal metastases: diagnosis with EUS-guided FNA.

While adrenal gland histoplasmosis has been previously diagnosed by fine needle aspiration utilizing the percutaneous approach, EUS‐FNA has not been employed in the diagnosis of this infection affecting both adrenal glands. We report a patient with massive bilateral adrenal enlargement due to histoplasmosis that was diagnosed by EUS‐FNA. Trans‐duodenal and trans‐gastric fine needle aspiration biopsy of both adrenal glands was performed. Rapid onsite cytopathologic evaluation (ROSE) revealed epithelioid histiocytes, singly and in clusters consistent with granulomas. Apparent intracytoplasmic inclusions suggestive of organisms were visible. A Gomori Methenamine Silver stain (GMS) revealed abundant small intracellular budding yeasts, morphologically consistent with Histoplasma; the patient was admitted for amphotericin B intravenous infusion. His fever abated on the second day after amphotericin B was started. His urine Histoplasma antigen was positive. Fungal cultures from both adrenal EUS‐FNA samples grew Histoplasma capsulatum. After a one week hospital stay, he was discharged home on itraconazole 200 mg po bid for one year. Four months after initiation of treatment, his urine Histoplasma antigen was undetectable. Nine months after initial diagnosis, the patient regained his energy level, and returned to work with complete resolution of his initial symptoms. This case highlights that EUS‐FNA with ROSE can be a highly effective tool in the diagnosis of uncommon infections of the adrenal glands. Diagn. Cytopathol. 2010.

Combined use of EUS-guided FNA and immunocytochemical stains discloses metastatic and unusual diseases in the evaluation of mediastinal lymphadenopathy of unknown etiology

PURPOSE: Mediastinal lymphadenopathy (ML) is a cause for concern, especially in patients with previous malignancy. We report our experience with the use of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with immunocytochemical stains in patients being evaluated for ML. METHODS: Retrospective analysis of patients with ML of unknown origin who underwent EUS-FNA. On-site evaluation was performed by experienced cytologist, and special immunocytochemical stains were requested as indicated. RESULTS: A total of 116 patients were included, and a total of 136 mediastinal LN were sampled. Prior malignancy was present in 45%. The most common site of examined lymph node (LN) were subcarinal (76%, 103 LN). The median long and short axis diameters were 28 mm and 13 mm, respectively. FNA was read on-site as malignant, 21 (16%); benign, 100 (76.9%); suspicious, six (4%); atypical, 3 (2%); and inadequate sample, six (4%). Sixty-four LN were deferred for additional studies; 22 for immunocytochemical and 26 for Gimesa (GMS) stain and 21 for flow cytometry. Final FNA read was malignant in 28 (21%), benign in 103 (76%), suspicious in three (2%), and atypical in two (1%). Metastatic malignancies disclosed included Hodgkins and Non-Hodgkins lymphoma, melanoma, hepatoma, breast, lung, colon, renal, endometrial, Fallopian tube, and unknown carcinoma. The sensitivity, specificity, and accuracy of the final FNA read to predict malignancy were 100%. CONCLUSION: EUS-guided FNA with additional ancillary studies is useful in disclosing metastatic ML from a variety of neoplasms. Due to its safety and accuracy profile, it should be considered the test of choice in evaluating abnormal ML in appropriately selected patients.

Multiple metastases to the pancreas from primary maxillary osteosarcoma: diagnosis with EUS-guided FNA

Primary pancreatic cancer is the fourth leading cause of cancer-related death in the United States among both genders. 1 Metastases to the pancreas are less common. Osteosarcoma is a relatively uncommon malignancy, and metastases to the pancreas are even more rare. 2 To our knowledge, there are no cases that were diagnosed by EUS-guided FNA (EUS-FNA). We report a case of osteosarcoma metastatic to the pancreas diagnosed with EUS-FNA with positive on-site pathology evaluation.

Incidentally detected ectopic thyroid in juxta cardiac location—Imaging and pathology

Ectopic thyroid gland is a developmental anomaly that results from the arrest of thyroid tissue along its path of descent from the floor of mouth to the pre tracheal position in the lower neck. It is typically found along the thyroglossal duct with the base of the tongue being the most common site. Apart from mediastinal extension of goiter, the incidence of true intrathoracic ectopic thyroid tissue is rare. Presence of ectopic thyroid has been reported not only in the chest but also in the abdomen and pelvis. Pericardial and intracardiac locations are extremely uncommon and right ventricle location is predominant among the described cases. We describe a case of incidentally detected ectopic thyroid tissue in a rarer location—adjacent to the left atrium. The patient, who had undergone a nephrectomy for renal oncocytoma 5 years ago, presented with unintentional weight loss and left sided flank pain, prompting a workup to rule out abdominal malignancy. Findings on the computed tomography (CT) scan of the abdomen and pelvis prompted further investigation including a chest CT which showed a heterogeneously enhancing mass near the left atrium. Given its location, further radiological investigations played an important role in eliminating the differential diagnosis of paraganglioma. The mass was surgically resected and discovered to be a hyperplastic thyroid nodule on histologic examination.

Progressive lung calcification after orthotopic heart transplant

Focal, asymmetrical pulmonary airspace opacities in post-transplant setting are commonly from infection, hemorrhage, edema or infarction. Rarely, stable or mildly progressive dense pulmonary opacities are due to pulmonary calcifications. In the majority of cases, these are asymptomatic and warrant no further intervention.