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Utility of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) for the Diagnosis of Mediastinal Lymphoma
Abstracts malignant cases with cell blocks. Out of the 66 NSCLC, 57 (86.3) had adequate cell blocks and 100% of these had immunohistochemistry. Out of the 9 with inadequate cell blocks, 7 were finally given a diagnosis of NSCLC (10.6%). Conclusions: Cell blocks have become an essential part of the armamentarium of the cytopathologist in both benign and malignant cases. Immunohistochemistry has also become an essential ancillary tool and is being used not only to get to a definitive diagnosis but also to confirm the morphological diagnosis. Without IHC support, the rate of NSCLC was 58% and with IHC the rate of NSCLC decreased to 6%. Hence, effective communication with the clinician regarding getting adequate material, adequacy assessment and purpose is the cornerstone of the role of the cytopathologist and ancillary staff as effective members of the clinical team. 133 The Correlation of Concomitant Fungal Culture and GMS Staining of Bronchoalveolar Lavage Specimens: A 100 Case Institutional Review Ariana Beck, MD, Frances Cate, MD, Alice Coogan, MD. Vanderbilt University Medical Center, Nashville, Tennessee Introduction: Bronchoalveolar lavage (BAL) is a common procedure used for the diagnosis of fungal respiratory tract infections. Although microbiologic culture is the gold standard in the diagnosis and characterization of fungal species, the time frame is not ideal clinically. Therefore, Grocott’s methenamine silver (GMS) staining of concomitant cytologic specimens is used to screen for the presence of fungal elements. Our study aims to look at the correlation between GMS staining and culture results at our institution. Materials and Methods: Our database was queried for cytologic cases procured during BAL procedures with fungal elements seen on GMS staining from 2009 to 2013. 100 unique cases were retrieved. Culture results were ascertained from the medical record. Cases were considered consistent when the organism cultured matched the organism identified by cytology and inconsistent when the culture was negative or a different organism was identified. Results: Of 100 cases, 93 had concomitant fungal culture results. Of those cases, 68% had consistent cytology and microbiology and 32% of cases were inconsistent. 73% of inconsistent cases were due to negative microbiology (22 cases). This is attributed to sampling error or decreased viability secondary to treatment. In the remaining 8 inconsistent cases, the organism identified was different than that cultured. In 5 of these cases, the less commonly seen organisms Chrysosporium sp, Saccharomyces cerevisiae, Scopulariopsis brumptii, Scedosporium prolificans, and Penicillium sp were identified as Candida sp or Aspergillus sp by cytology. In 3 cases, commonly seen organisms were discrepant. In 2 of these cases, Aspergillus sp was incorrectly identified as Candida sp which is a common diagnostic pitfall. Conclusions: GMS staining of cytologic preparations collected during BAL is a pragmatic diagnostic test for the presence of fungal pathogens and correlates well with cultures. Inconsistencies in which incorrect organisms were identified were primarily seen with uncommon organisms. 134 Correlation of p16 Expression with p53, Cyclin D1 as Well as Clinical Outcomes in Non-small Cell Lung Carcinoma (NSCLC) Jamal Carter, MD, Susan Geddes, CT(ASCP), Zhen Zhang, PhD, Hui Zhang, PhD, Frederic Askin, MD, Edward Gabrielson, MD, Qing Kay Li, MD, PhD. The Johns Hopkins Medical Institutes, Baltimore, Maryland Introduction: Recent studies have identified a multitude of genetic and epigenetic changes affecting CDKN2A signaling in lung cancers, including mutations of CDKN2A, deletions or inactivating of p16INK4, mutations of RB1, and mutations affecting CDKN2A and RB1. These genetic alterations
S65 can result in an elevated p16 protein. The clinical significance of elevated p16 in lung cancer is not well understood. In this study, we correlated expressions of p16 with levels of p53 and cyclinD1 as well as clinical outcomes in NSCLC patients. Materials and Methods: Primary lung cancer TMAs (0.6 mm in diameter, 3-4 cores per cases) were constructed using surgically resected specimens retrieved from department archives, including 75 cases of pulmonary adenocarcinoma (ADC), 88 cases of pulmonary squamous cell carcinoma (SQCC), and 60 tumor-matched normal lung tissues. Immunohistochemistry (IHC) of p16 (clone INK4a/E6H4), p53 and cyclinD1 were performed. Nuclear staining patterns were scored semi-quantitatively as 0-3+ (from negative to strong positive staining). Clinical information was correlated. Results: The overall frequency of expression of p16 in ADCs and SQCCs was 50.7% and 35.2%, respectively. In ADCs, patients with p16 positive tumors had smaller tumor size, earlier tumor stage and longer survival compared to patients with p16 negative tumors, with mean survival of 41.1 vs. 28.9 month (PZ0.047). In SQCCs, a slightly worse survival for patients with p16 positive tumors (30.1 vs. 37.3 months) did not reach statistical significance (PZ0.382). In both SQCCs and ADCs, p16 expression was not significantly correlated with expressions of p53 and cyclinD1. Conclusions: p16 is aberrantly expressed in a large subset of ADC and SQCC. Elevated p16 levels appear to be correlated with better prognosis in patients with ADCs, suggesting that p16 expression might play different roles in different subtypes of NSCLC. Further studies are necessary to characterize the molecular role of p16 in lung cancers. 135 Utility of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) for the Diagnosis of Mediastinal Lymphoma Arivarasan Karunamurthy, MD1, Walid Khalbuss, MD, PhD, FIAC2, Liron Pantanowitz, MD1, Sara Monaco, MD1. 1University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; 2GE Clarient Diagnostic Services, Aliso Viejo, California Introduction: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive modality to evaluate thoracic malignancies and mediastinal lymph nodes. The utility of EBUSTBNA in the diagnosis and subtyping lymphomas is not as well defined. Our aim was to study the utility of EBUS-TBNA in the diagnosis and management of lymphoproliferative disorders. Materials and Methods: A retrospective review of all EBUS-TBNAs procured at our institution over a six-year period (2007 to 2013) was performed to find cases with a lymphoproliferative disorder. The adequacy, cytological diagnosis, histological follow-up and available ancillary studies were reviewed. Results: A total of 766 EBUS FNA specimens were obtained from 462 patients with a mean age of 53 years (range 23-90 years). There were 17 (4%) patients with a final diagnosis of lymphoma confirmed by histology and/or ancillary studies. Non-Hodgkin lymphomas (NHL; 11 cases) were more frequent than Hodgkin lymphoma (HL; 5 cases) and post-transplant lymphoproliferative disorder (PTLD; 1 case). [Table 1] A prior history of lymphoma was available in 11 cases (65%). EBUS-TBNA was diagnostic for lymphoma in 10 (58%) of these cases, indeterminate in 3 (18%), unsatisfactory in 3 (18%), and negative in one (6%). Histological follow-up was available in 8 (47%) cases. Confirmatory ancillary study results (immunostains, flow cytometry or FISH) were available in 6 (35%) cases. The sensitivity was 91% in adequate specimens. Conclusions: Lymphoproliferative disorders at our institution are uncommonly encountered in EBUS-TBNA, but pose a diagnostic challenge due to the high incidence of suboptimal or unsatisfactory specimens, particularly in large cell lymphomas. However, adequate specimens have a high sensitivity and low false negative rate for lymphoproliferative disorders in the setting of on-site evaluation and use of ancillary studies.
S66 Table 1
Abstracts EBUS Lymphoma Correlation
136 Evaluation of Bronchoalveolar Lavage Cytology (B.A.L) in the Diagnosis of Lung Cancer among Sudanese Patients in Khartoum State Hospitals Hassan Ebrahim, MSc. University of Khartoum, Khartoum, Sudan Introduction: Lung cancer is the most common cause of cancer mortality worldwide, causing approximately 1.2 million deaths per year. Bronchoalveolar Lavage (BAL) is a minimally invasive procedure that has gained acceptance and steady popularity as a tool for diagnosing lung cancer. The aim of this study was to compare the diagnostic efficacy of BAL in diagnosing lung cancer, taking bronchial biopsy as the ‘Gold Standard’ diagnostic test. Material and Methods: During the period from 2010 to 2012, 179 BAL cytology samples were prepared for cytology examination and smears were stained with Diff Quick stain. Bronchial biopsy histological sections were stained with H&E stain. Histo/Cytology correlation was performed in 83 cases to determine the sensitivity and specificity of BAL in diagnosis of lung carcinoma. Results: Out of the 179 cases, 118 (65.9%) were males and 61 (34.1%) were females. The ages ranged from 18 to 86 years old. BAL cytology cases reported with diagnoses of negative for malignant cells (nZ152, 84.9%), suspicious (nZ12, 6.7%), and carcinoma (nZ15, 8.4%). Bronchial biopsy specimens showed benign and malignant conditions in 69 (76.6%), and 21 (23.4%) respectively. Of the 21 malignant conditions, 11 were squamous cell carcinoma, 9 were adenocarcinoma, and one case was small cell carcinoma. The correlation between BAL cytology and histology results were performed in 83 cases. BAL sensitivity and specificity was 55%, and 95% respectively. Conclusion: Bronchoalveolar Lavage (BAL) is an easily performed, noninvasive, and well tolerated procedure that is useful in routine assessment of patients for lung carcinoma. The low sensitivity of BAL in our study stresses the importance of optimum sampling as well as cytopreperatory techniques using cyto-centrifugation. BAL combined to bronchial biopsy increases the accuracy of lung carcinoma diagnosis. 137 Cytologic Findings of Hematologic Malignancies in Bronchoalveolar Lavage Fluid Diana Murro, MD, Jamie Macagba Slade, MD, Paolo Gattuso, MD. Rush University Medical Center, Chicago, Illinois Introduction: Bronchoalveolar lavage (BAL) is often performed in leukemia and lymphoma patients who develop pulmonary infiltrates,
mainly to rule out infection. However, malignant hematopoietic infiltrates are an uncommon finding in BAL specimens. We present the clinical and cytologic features of 30 cases of hematologic malignancies diagnosed by bronchoalveolar lavage. Materials and Methods: We performed a retrospective review of all BAL samples performed at our institution, a large tertiary care medical center, for the past 22 years (January 1992-March 2014). A total of 30 cases of hematologic malignancies were identified on BAL specimens during this time period. Results: We identified 15 male and 15 female cases with age range of 22 to 77 years. Sixteen patients (53%) had symptoms at the time of initial diagnosis of their hematologic malignancy, including fever, dyspnea/ hypoxia and cough. The biopsy-proven cases were 20 acute leukemia (12 acute myeloid leukemia, 3 acute promyelocytic leukemia, 3 acute monocytic leukemia, and 2 acute myelomonocytic leukemia), 8 lymphoma (5 diffuse large B-cell lymphoma, 1 mantle cell lymphoma, 1 NK/T-cell lymphoma, and 1 cutaneous T-cell lymphoma), 1 large granular leukemia and 1 plasma cell myeloma. The time from diagnosis of hematologic malignancy to BAL ranged from 1 to 233 days. Chest X-ray findings included opacities, consolidation, and interstitial edema. Three patients (10%) had BAL specimens with concomitant microorganisms. Twelve patients (40%) subsequently died (2 days-4 years), 12 (40%) were alive (5 months-7 years follow-up), and 6 were lost to follow-up. Conclusions: BAL is especially important in distinguishing inflammatory/ infectious processes from neoplastic disorders since many patients with hematologic malignancies can have pneumonia-like symptoms as part of their initial disease presentation. Causative pathogens are identified in only a minority of malignant BAL specimens from these patients. Lung involvement in patients with hematologic malignancies carries a poor prognosis. 138 Untangling the Significance of Granulomas Diagnosed on Fine Needle Aspirations of Intrathoracic and Intraabdominal Sites Lisa Smith, DO, Swati Mehrotra, MD, Eva Wojcik, MD, MIAC, Razan Massarani-Wafai, MD, Guliz Barkan, MD, Mohammed Atieh, DO, Stefan Pambuccian, MD. Loyola University Medical Center, Maywood, llinois Introduction: Although granulomas (GR) are relatively rarely encountered in FNAs, it is important to recognize them during rapid on-site evaluation to triage them for ancillary studies and assign them a precise etiology. The aim of this study was to determine the etiology of GR encountered in intrathoracic and intraabdominal FNAs and describe specific cytomorphologic characteristics that can be utilized to triage cases with GR. Materials and Methods: We identified all patients diagnosed as GR on FNA during a 10 year period (2004-2013) and reviewed their clinical, imaging findings, microbiology and serological findings, and follow-up pathology results. An etiology was assigned to GR based on history, clinical and imaging findings and the results of special stains and cultures. Results: Of the 15,953 FNAs accessioned during the study period, 140 specimens (0.9%) from 110 patients were diagnosed as having GR. 75 patients had GR diagnosed in CT, ultrasound, EUS or EBUS- guided FNAs from deep sites [hilar or mediastinal lymph nodes (37), lung (24), esophagus (1), anterior mediastinum (1), intraabdominal lymph nodes (4), liver (2), pancreas (1), kidney (1), spleen (1), gastric wall (1), omentum (1), and peritoneum (1)]. The etiology was sarcoidosis (32), regional or distant malignancy-associated sarcoid reaction (SR, 20), infection (16), foreign body (1), Wegener granulomatosis (1) and unknown (6). GR were nonnecrotizing in all but 16 samples. One patient who had posttransplant lymphoma diagnosed in the same sample as GR. None of the patients with GR had malignancies diagnosed at the FNA site during the 6 months to 10 year follow-up time. Conclusions: 1) Most granulomas diagnosed on deep FNAs are nonnecrotizing and are caused by sarcoidosis and SRs, which are cytologically indistinguishable. 2) Although malignant cells are only rarely found in samples with GR, careful scrutiny of the background lymphocytes is recommended to avoid missing lymphomas.
S65 can result in an elevated p16 protein. The clinical significance of elevated p16 in lung cancer is not well understood. In this study, we correlated expressions of p16 with levels of p53 and cyclinD1 as well as clinical outcomes in NSCLC patients. Materials and Methods: Primary lung cancer TMAs (0.6 mm in diameter, 3-4 cores per cases) were constructed using surgically resected specimens retrieved from department archives, including 75 cases of pulmonary adenocarcinoma (ADC), 88 cases of pulmonary squamous cell carcinoma (SQCC), and 60 tumor-matched normal lung tissues. Immunohistochemistry (IHC) of p16 (clone INK4a/E6H4), p53 and cyclinD1 were performed. Nuclear staining patterns were scored semi-quantitatively as 0-3+ (from negative to strong positive staining). Clinical information was correlated. Results: The overall frequency of expression of p16 in ADCs and SQCCs was 50.7% and 35.2%, respectively. In ADCs, patients with p16 positive tumors had smaller tumor size, earlier tumor stage and longer survival compared to patients with p16 negative tumors, with mean survival of 41.1 vs. 28.9 month (PZ0.047). In SQCCs, a slightly worse survival for patients with p16 positive tumors (30.1 vs. 37.3 months) did not reach statistical significance (PZ0.382). In both SQCCs and ADCs, p16 expression was not significantly correlated with expressions of p53 and cyclinD1. Conclusions: p16 is aberrantly expressed in a large subset of ADC and SQCC. Elevated p16 levels appear to be correlated with better prognosis in patients with ADCs, suggesting that p16 expression might play different roles in different subtypes of NSCLC. Further studies are necessary to characterize the molecular role of p16 in lung cancers. 135 Utility of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) for the Diagnosis of Mediastinal Lymphoma Arivarasan Karunamurthy, MD1, Walid Khalbuss, MD, PhD, FIAC2, Liron Pantanowitz, MD1, Sara Monaco, MD1. 1University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; 2GE Clarient Diagnostic Services, Aliso Viejo, California Introduction: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive modality to evaluate thoracic malignancies and mediastinal lymph nodes. The utility of EBUSTBNA in the diagnosis and subtyping lymphomas is not as well defined. Our aim was to study the utility of EBUS-TBNA in the diagnosis and management of lymphoproliferative disorders. Materials and Methods: A retrospective review of all EBUS-TBNAs procured at our institution over a six-year period (2007 to 2013) was performed to find cases with a lymphoproliferative disorder. The adequacy, cytological diagnosis, histological follow-up and available ancillary studies were reviewed. Results: A total of 766 EBUS FNA specimens were obtained from 462 patients with a mean age of 53 years (range 23-90 years). There were 17 (4%) patients with a final diagnosis of lymphoma confirmed by histology and/or ancillary studies. Non-Hodgkin lymphomas (NHL; 11 cases) were more frequent than Hodgkin lymphoma (HL; 5 cases) and post-transplant lymphoproliferative disorder (PTLD; 1 case). [Table 1] A prior history of lymphoma was available in 11 cases (65%). EBUS-TBNA was diagnostic for lymphoma in 10 (58%) of these cases, indeterminate in 3 (18%), unsatisfactory in 3 (18%), and negative in one (6%). Histological follow-up was available in 8 (47%) cases. Confirmatory ancillary study results (immunostains, flow cytometry or FISH) were available in 6 (35%) cases. The sensitivity was 91% in adequate specimens. Conclusions: Lymphoproliferative disorders at our institution are uncommonly encountered in EBUS-TBNA, but pose a diagnostic challenge due to the high incidence of suboptimal or unsatisfactory specimens, particularly in large cell lymphomas. However, adequate specimens have a high sensitivity and low false negative rate for lymphoproliferative disorders in the setting of on-site evaluation and use of ancillary studies.
S66 Table 1
Abstracts EBUS Lymphoma Correlation
136 Evaluation of Bronchoalveolar Lavage Cytology (B.A.L) in the Diagnosis of Lung Cancer among Sudanese Patients in Khartoum State Hospitals Hassan Ebrahim, MSc. University of Khartoum, Khartoum, Sudan Introduction: Lung cancer is the most common cause of cancer mortality worldwide, causing approximately 1.2 million deaths per year. Bronchoalveolar Lavage (BAL) is a minimally invasive procedure that has gained acceptance and steady popularity as a tool for diagnosing lung cancer. The aim of this study was to compare the diagnostic efficacy of BAL in diagnosing lung cancer, taking bronchial biopsy as the ‘Gold Standard’ diagnostic test. Material and Methods: During the period from 2010 to 2012, 179 BAL cytology samples were prepared for cytology examination and smears were stained with Diff Quick stain. Bronchial biopsy histological sections were stained with H&E stain. Histo/Cytology correlation was performed in 83 cases to determine the sensitivity and specificity of BAL in diagnosis of lung carcinoma. Results: Out of the 179 cases, 118 (65.9%) were males and 61 (34.1%) were females. The ages ranged from 18 to 86 years old. BAL cytology cases reported with diagnoses of negative for malignant cells (nZ152, 84.9%), suspicious (nZ12, 6.7%), and carcinoma (nZ15, 8.4%). Bronchial biopsy specimens showed benign and malignant conditions in 69 (76.6%), and 21 (23.4%) respectively. Of the 21 malignant conditions, 11 were squamous cell carcinoma, 9 were adenocarcinoma, and one case was small cell carcinoma. The correlation between BAL cytology and histology results were performed in 83 cases. BAL sensitivity and specificity was 55%, and 95% respectively. Conclusion: Bronchoalveolar Lavage (BAL) is an easily performed, noninvasive, and well tolerated procedure that is useful in routine assessment of patients for lung carcinoma. The low sensitivity of BAL in our study stresses the importance of optimum sampling as well as cytopreperatory techniques using cyto-centrifugation. BAL combined to bronchial biopsy increases the accuracy of lung carcinoma diagnosis. 137 Cytologic Findings of Hematologic Malignancies in Bronchoalveolar Lavage Fluid Diana Murro, MD, Jamie Macagba Slade, MD, Paolo Gattuso, MD. Rush University Medical Center, Chicago, Illinois Introduction: Bronchoalveolar lavage (BAL) is often performed in leukemia and lymphoma patients who develop pulmonary infiltrates,
mainly to rule out infection. However, malignant hematopoietic infiltrates are an uncommon finding in BAL specimens. We present the clinical and cytologic features of 30 cases of hematologic malignancies diagnosed by bronchoalveolar lavage. Materials and Methods: We performed a retrospective review of all BAL samples performed at our institution, a large tertiary care medical center, for the past 22 years (January 1992-March 2014). A total of 30 cases of hematologic malignancies were identified on BAL specimens during this time period. Results: We identified 15 male and 15 female cases with age range of 22 to 77 years. Sixteen patients (53%) had symptoms at the time of initial diagnosis of their hematologic malignancy, including fever, dyspnea/ hypoxia and cough. The biopsy-proven cases were 20 acute leukemia (12 acute myeloid leukemia, 3 acute promyelocytic leukemia, 3 acute monocytic leukemia, and 2 acute myelomonocytic leukemia), 8 lymphoma (5 diffuse large B-cell lymphoma, 1 mantle cell lymphoma, 1 NK/T-cell lymphoma, and 1 cutaneous T-cell lymphoma), 1 large granular leukemia and 1 plasma cell myeloma. The time from diagnosis of hematologic malignancy to BAL ranged from 1 to 233 days. Chest X-ray findings included opacities, consolidation, and interstitial edema. Three patients (10%) had BAL specimens with concomitant microorganisms. Twelve patients (40%) subsequently died (2 days-4 years), 12 (40%) were alive (5 months-7 years follow-up), and 6 were lost to follow-up. Conclusions: BAL is especially important in distinguishing inflammatory/ infectious processes from neoplastic disorders since many patients with hematologic malignancies can have pneumonia-like symptoms as part of their initial disease presentation. Causative pathogens are identified in only a minority of malignant BAL specimens from these patients. Lung involvement in patients with hematologic malignancies carries a poor prognosis. 138 Untangling the Significance of Granulomas Diagnosed on Fine Needle Aspirations of Intrathoracic and Intraabdominal Sites Lisa Smith, DO, Swati Mehrotra, MD, Eva Wojcik, MD, MIAC, Razan Massarani-Wafai, MD, Guliz Barkan, MD, Mohammed Atieh, DO, Stefan Pambuccian, MD. Loyola University Medical Center, Maywood, llinois Introduction: Although granulomas (GR) are relatively rarely encountered in FNAs, it is important to recognize them during rapid on-site evaluation to triage them for ancillary studies and assign them a precise etiology. The aim of this study was to determine the etiology of GR encountered in intrathoracic and intraabdominal FNAs and describe specific cytomorphologic characteristics that can be utilized to triage cases with GR. Materials and Methods: We identified all patients diagnosed as GR on FNA during a 10 year period (2004-2013) and reviewed their clinical, imaging findings, microbiology and serological findings, and follow-up pathology results. An etiology was assigned to GR based on history, clinical and imaging findings and the results of special stains and cultures. Results: Of the 15,953 FNAs accessioned during the study period, 140 specimens (0.9%) from 110 patients were diagnosed as having GR. 75 patients had GR diagnosed in CT, ultrasound, EUS or EBUS- guided FNAs from deep sites [hilar or mediastinal lymph nodes (37), lung (24), esophagus (1), anterior mediastinum (1), intraabdominal lymph nodes (4), liver (2), pancreas (1), kidney (1), spleen (1), gastric wall (1), omentum (1), and peritoneum (1)]. The etiology was sarcoidosis (32), regional or distant malignancy-associated sarcoid reaction (SR, 20), infection (16), foreign body (1), Wegener granulomatosis (1) and unknown (6). GR were nonnecrotizing in all but 16 samples. One patient who had posttransplant lymphoma diagnosed in the same sample as GR. None of the patients with GR had malignancies diagnosed at the FNA site during the 6 months to 10 year follow-up time. Conclusions: 1) Most granulomas diagnosed on deep FNAs are nonnecrotizing and are caused by sarcoidosis and SRs, which are cytologically indistinguishable. 2) Although malignant cells are only rarely found in samples with GR, careful scrutiny of the background lymphocytes is recommended to avoid missing lymphomas.