Policies and Reporting Guidelines for Small Biopsy Specimens of Mediastinal Masses

Abstract

Mediastinal tumors, cysts, and other lesions can be diagnosed using fluoroscopy, transthoracic ultrasound (US), or computed tomography (CT)-guided biopsies, right, left, and bilateral video-assisted thoracoscopic surgery (VATS), anterior mediastinotomy, and minithoracotomy/Chamberlain procedure.1Shimosato Y Mukai K Matsuno Y Tumor of the Mediastinum. AR Press, Washington, DC2010Google Scholar Biopsy specimens include fine-needle aspiration (FNA) biopsies, needle core biopsies, and incisional biopsies.2Cameron SE Andrade RS Pambuccian SE Endobronchial ultrasound-guided transbronchial needle aspiration cytology: a state of the art review.Cytopathology. 2010; 21: 6-26Crossref PubMed Scopus (94) Google Scholar, 3Storch I Shah M Thurer R et al.Endoscopic ultrasound-guided fine-needle aspiration and Trucut biopsy in thoracic lesions: when tissue is the issue.Surg Endosc. 2008; 22: 86-90Crossref PubMed Scopus (49) Google Scholar, 4Wakely Jr, PE Fine needle aspiration in the diagnosis of thymic epithelial neoplasms.Hematol Oncol Clin North Am. 2008; 22: 433-442Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 5Wakely Jr, PE Cytopathology of thymic epithelial neoplasms.Semin Diagn Pathol. 2005; 22: 213-222Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar, 6Wildi SM Hoda RS Fickling W et al.Diagnosis of benign cysts of the mediastinum: the role and risks of EUS and FNA.Gastrointest Endosc. 2003; 58: 362-368Abstract Full Text Full Text PDF PubMed Google Scholar, 7Zakowski MF Huang J Bramlage MP The role of fine needle aspiration cytology in the diagnosis and management of thymic neoplasia.J Thorac Oncol. 2010; 5: S281-S285Crossref PubMed Scopus (17) Google Scholar A detailed discussion of the technical advantages and disadvantages of each diagnostic procedure is beyond the scope of this document. In general, these procedures are safe with complications such as pneumothorax, bleeding, and others in less than 5% of patients. Nevertheless, incidences of pneumothorax of up to 34% have been described in patient undergoing transthoracic needle biopsies of hilar lesions. Biopsies of mediastinal cystic lesions are generally approached with particular caution because of occasional reports of infection after the procedure.6Wildi SM Hoda RS Fickling W et al.Diagnosis of benign cysts of the mediastinum: the role and risks of EUS and FNA.Gastrointest Endosc. 2003; 58: 362-368Abstract Full Text Full Text PDF PubMed Google Scholar Seeding of the site after biopsies of thymomas has been limited to a few rare cases.8Kattach H Hasan S Clelland C et al.Seeding of stage I thymoma into the chest wall 12 years after needle biopsy.Ann Thorac Surg. 2005; 79: 323-324Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar, 9Detterbeck FC Does an anecdote substantiate dogma?.Ann Thorac Surg. 2006; 81 (author reply: 1182–1183.): 1182Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar In general, mediastinal tumors located in the anterior mediastinum are approached using transthoracic US or CT-guided FNA and core needle biopsies or minithoracotomy.2Cameron SE Andrade RS Pambuccian SE Endobronchial ultrasound-guided transbronchial needle aspiration cytology: a state of the art review.Cytopathology. 2010; 21: 6-26Crossref PubMed Scopus (94) Google Scholar, 3Storch I Shah M Thurer R et al.Endoscopic ultrasound-guided fine-needle aspiration and Trucut biopsy in thoracic lesions: when tissue is the issue.Surg Endosc. 2008; 22: 86-90Crossref PubMed Scopus (49) Google Scholar, 6Wildi SM Hoda RS Fickling W et al.Diagnosis of benign cysts of the mediastinum: the role and risks of EUS and FNA.Gastrointest Endosc. 2003; 58: 362-368Abstract Full Text Full Text PDF PubMed Google Scholar, 8Kattach H Hasan S Clelland C et al.Seeding of stage I thymoma into the chest wall 12 years after needle biopsy.Ann Thorac Surg. 2005; 79: 323-324Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar, 9Detterbeck FC Does an anecdote substantiate dogma?.Ann Thorac Surg. 2006; 81 (author reply: 1182–1183.): 1182Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar, 10Bhatia V Endoscopic ultrasound: imaging techniques and applications in the mediastinum.Trop Gastroenterol. 2010; 30: S4-S19PubMed Google Scholar, 11Cerfolio RJ Bryant AS Eloubeidi MA et al.The true false negative rates of esophageal and endobronchial ultrasound in the staging of mediastinal lymph nodes in patients with non-small cell lung cancer.Ann Thorac Surg. 2010; 90: 427-434Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar, 12Diederich S Padge B Vossas U et al.Application of a single needle type for all image-guided biopsies: results of 100 consecutive core biopsies in various organs using a novel tri-axial, end-cut needle.Cancer Imaging. 2006; 6: 43-50Crossref PubMed Scopus (24) Google Scholar, 13Fang WT Xu MY Chen G et al.Minimally invasive approaches for histological diagnosis of anterior mediastinal masses.Chin Med J (Engl). 2007; 120: 675-679PubMed Google Scholar, 14Gupta S Wallace MJ Morello Jr, FA et al.CT-guided percutaneous needle biopsy of intrathoracic lesions by using the transsternal approach: experience in 37 patients.Radiology. 2002; 222: 57-62Crossref PubMed Scopus (41) Google Scholar, 15Protopapas Z Westcott JL Transthoracic hilar and mediastinal biopsy.Radiol Clin North Am. 2000; 38: 281-291Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, 16Venuta F Rendina EA Pescarmona EO et al.Ambulatory mediastinal biopsy for hematologic malignancies.Eur J Cardiothorac Surg. 1997; 11: 218-221Crossref PubMed Scopus (28) Google Scholar, 17Zinzani PL Corneli G Cancellieri A et al.Core needle biopsy is effective in the initial diagnosis of mediastinal lymphoma.Haematologica. 1999; 84: 600-603PubMed Google Scholar Middle mediastinal lesions can be diagnosed using mediastinoscopy, endobronchial US-guided biopsy, and transesophageal US-guided biopsy.17Zinzani PL Corneli G Cancellieri A et al.Core needle biopsy is effective in the initial diagnosis of mediastinal lymphoma.Haematologica. 1999; 84: 600-603PubMed Google Scholar Posterior mediastinal lesions can be diagnosed using US- or CT-guided transthoracic biopsies but often require VATS.18Rendina EA Venuta F De Giacomo T et al.Comparative merits of thoracoscopy, mediastinoscopy, and mediastinotomy for mediastinal biopsy.Ann Thorac Surg. 1994; 57: 992-995Abstract Full Text PDF PubMed Scopus (78) Google Scholar Table 1 shows the sensitivity and specificity of these various diagnostic procedures.1Shimosato Y Mukai K Matsuno Y Tumor of the Mediastinum. AR Press, Washington, DC2010Google Scholar, 2Cameron SE Andrade RS Pambuccian SE Endobronchial ultrasound-guided transbronchial needle aspiration cytology: a state of the art review.Cytopathology. 2010; 21: 6-26Crossref PubMed Scopus (94) Google Scholar, 3Storch I Shah M Thurer R et al.Endoscopic ultrasound-guided fine-needle aspiration and Trucut biopsy in thoracic lesions: when tissue is the issue.Surg Endosc. 2008; 22: 86-90Crossref PubMed Scopus (49) Google Scholar, 6Wildi SM Hoda RS Fickling W et al.Diagnosis of benign cysts of the mediastinum: the role and risks of EUS and FNA.Gastrointest Endosc. 2003; 58: 362-368Abstract Full Text Full Text PDF PubMed Google Scholar, 7Zakowski MF Huang J Bramlage MP The role of fine needle aspiration cytology in the diagnosis and management of thymic neoplasia.J Thorac Oncol. 2010; 5: S281-S285Crossref PubMed Scopus (17) Google Scholar, 10Bhatia V Endoscopic ultrasound: imaging techniques and applications in the mediastinum.Trop Gastroenterol. 2010; 30: S4-S19PubMed Google Scholar, 11Cerfolio RJ Bryant AS Eloubeidi MA et al.The true false negative rates of esophageal and endobronchial ultrasound in the staging of mediastinal lymph nodes in patients with non-small cell lung cancer.Ann Thorac Surg. 2010; 90: 427-434Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar, 12Diederich S Padge B Vossas U et al.Application of a single needle type for all image-guided biopsies: results of 100 consecutive core biopsies in various organs using a novel tri-axial, end-cut needle.Cancer Imaging. 2006; 6: 43-50Crossref PubMed Scopus (24) Google Scholar, 13Fang WT Xu MY Chen G et al.Minimally invasive approaches for histological diagnosis of anterior mediastinal masses.Chin Med J (Engl). 2007; 120: 675-679PubMed Google Scholar, 14Gupta S Wallace MJ Morello Jr, FA et al.CT-guided percutaneous needle biopsy of intrathoracic lesions by using the transsternal approach: experience in 37 patients.Radiology. 2002; 222: 57-62Crossref PubMed Scopus (41) Google Scholar, 15Protopapas Z Westcott JL Transthoracic hilar and mediastinal biopsy.Radiol Clin North Am. 2000; 38: 281-291Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, 17Zinzani PL Corneli G Cancellieri A et al.Core needle biopsy is effective in the initial diagnosis of mediastinal lymphoma.Haematologica. 1999; 84: 600-603PubMed Google Scholar, 19Morikawa T Ohtake S Kaji M et al.An extrapleural approach to the anterior mediastinum using video-assisted thoracic surgery (VATS).Surg Endosc. 2003; 17: 1851Crossref PubMed Scopus (2) Google Scholar, 20Hagberg H Ahlström HK Magnusson A et al.Value of transsternal core biopsy in patients with a newly diagnosed mediastinal mass.Acta Oncol. 2000; 39: 195-198Crossref PubMed Scopus (17) Google Scholar, 21Rendina EA Venuta F De Giacomo T et al.Biopsy of anterior mediastinal masses under local anesthesia.Ann Thorac Surg. 2002; 74: 1720-1722Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar, 22Siebert JD Weeks LM List LW et al.Utility of flow cytometry immunophenotyping for the diagnosis and classification of lymphoma in community hospital clinical needle aspiration/biopsies.Arch Pathol Lab Med. 2000; 124: 1792-1799PubMed Google ScholarTABLE 1Sensitivity and Specificity of Mediastinal Biopsies for the Diagnosis of Mediastinal LesionsaMost studies report sensitivity and specificity values for various mediastinal lesions and recognize that the diagnosis of thymoma can be difficult on FNA and needle biopsies.1–3'6'7'10–15'17'19–22 Zakowski et al.7 have reported 100% accuracy for the diagnosis of thymoma and thymic carcinomas using FNA.Biopsy ProcedureSensitivity (%)Specificity (%)PPV (%)Transthoracic FNA71–10077–10069–100EBUS or EUS FNA38–8865–10090–100Percutaneous core biopsy40–9376–9083–91EBUS, endobronchial ultrasound; EUS, esophageal ultrasound; FNA, fine-needle aspiration; PPV, positive predictive value.a Most studies report sensitivity and specificity values for various mediastinal lesions and recognize that the diagnosis of thymoma can be difficult on FNA and needle biopsies.1–3'6'7'10–15'17'19–22 Zakowski et al.7 have reported 100% accuracy for the diagnosis of thymoma and thymic carcinomas using FNA. Open table in a new tab EBUS, endobronchial ultrasound; EUS, esophageal ultrasound; FNA, fine-needle aspiration; PPV, positive predictive value. Progress in the field of mediastinal malignancies requires widespread collaboration, which necessitate some consistency in how specimens are handled, interpreted, and reported. This article provides recommendations that should serve as a framework for such consistency. This article refers only to biopsy specimens obtained for diagnosis; specimens obtained during a potentially curative resection are addressed elsewhere.23Detterbeck FC Moran C Huang J et al.Which way is up? Policies and procedures for surgeons and pathologists regarding resection specimens of thymic malignancy.J Thorac Oncol. 2011; 6: S1730-S1738Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar These standard policies are not meant to stifle research or exploration of new methods; on the contrary, the proposed recommendations are designed to facilitate this. The standard operating procedures and policies outlined in this study merely provide a baseline framework and should be viewed as a minimal consistent standard that permits comparison of results from multiple institutions. These standards have been adopted by members of the International Thymic Malignancy Interest Group (ITMIG) for use in collective initiatives. It is hoped that it will be used by others as well, both in routine practice and in reporting in the literature. An initial workgroup consisting of pathologists and surgeons (Alberto Marchevsky, Alexander Marx, Saul Suster, Maureen Zakowski, Federico Venuta, Sam Youssem, and Philipp Ströbel) was assembled to review literature relevant to the issues and formulate preliminary recommendations. These were refined after discussion in an ITMIG broad multidisciplinary workshop meeting, which was supported by the International Association for the Study of Lung Cancer. A draft of this article, containing the proposed policies and standard operating procedures, was then disseminated to all ITMIG members for further discussion. With this input, this article with the final recommendations was written and ultimately approved for adoption by the ITMIG members for use in ITMIG collaborative initiatives. A detailed discussion of the differential diagnosis of various mediastinal lesions is beyond the scope of this document. It is often very helpful for pathologists to gather information regarding the age and gender of the patients and the location and radiological appearance of lesions before examination of biopsy materials. For example, if a child or young adult in his or her second to third decade of life presents with an anterior mediastinal mass, the differential diagnosis would include germ cell tumors, cystic hygroma, Hodgkin lymphoma, and lymphoblastic lymphoma, whereas if the patient is older, the differential diagnosis would include thymoma and other thymic epithelial lesions, mediastinal B-cell lymphoma, and other malignancies.1Shimosato Y Mukai K Matsuno Y Tumor of the Mediastinum. AR Press, Washington, DC2010Google Scholar Lesions in the upper anterior mediastinum are often of thyroid origin, whereas tumors of the anterior mediastinum in adults with myasthenia gravis are usually thymoma. Tumors and cysts in the middle mediastinum often occur in adults and are Hodgkin or non-Hodgkin lymphomas and other lymphoid lesions, mediastinal cysts, metastasis from lung or other cancers, sclerosing mediastinitis, and other conditions.1Shimosato Y Mukai K Matsuno Y Tumor of the Mediastinum. AR Press, Washington, DC2010Google Scholar The differential diagnosis of posterior mediastinal lesions includes neurogenic tumors, gastroenteric cysts, and other lesions.1Shimosato Y Mukai K Matsuno Y Tumor of the Mediastinum. AR Press, Washington, DC2010Google Scholar Table 2 provides a summary of primary mediastinal lesions by location and age. Nevertheless, it is important for pathologists to remember that the most common mediastinal lesions remain metastases, often from lung primaries.TABLE 2Common Mediastinal Lesions by Location and AgeConditionMediastinal LocationAgeThymomaAnteriorAdultsThymic carcinomaAnteriorAdultsThymic hyperplasiaAnteriorAdults' childrenNeuroendocrine neoplasmsAnteriorAdultsGerm cell tumorsAnteriorChildren' young adultsLymphoblastic lymphomaAnteriorChildren' adultsHodgkin lymphomaAnterior' middleChildren' adultsDiffuse large cell lymphomaAnteriorYoung adultsThymolipomaAnteriorAdultsSclerosing mediastinitisAnterior' middleAdultsCastleman's diseaseAnterior' middleAdultsMultilocular thymic cystsAnteriorAdultsCongenital thymic cystsAnteriorChildren' young adultsEctopic thyroid tumorsAnteriorAdultsEctopic parathyroid tumorsAnteriorAdultsParagangliomaAnteriorAdultsBronchogenic cystsMiddleAdultsMesothelial/pericardial cystsMiddleAdultsMetastatic tumorsMiddle' anteriorAdultsNeurogenic tumorsPosteriorChildren' adultsEnteric cystsPosteriorAdults Open table in a new tab There are no expert-consensus or evidence-based guidelines or standards for the performance of mediastinal biopsies. Most of the studies have reported good results for transthoracic and other FNA procedures using 22-gauge needles.2Cameron SE Andrade RS Pambuccian SE Endobronchial ultrasound-guided transbronchial needle aspiration cytology: a state of the art review.Cytopathology. 2010; 21: 6-26Crossref PubMed Scopus (94) Google Scholar, 3Storch I Shah M Thurer R et al.Endoscopic ultrasound-guided fine-needle aspiration and Trucut biopsy in thoracic lesions: when tissue is the issue.Surg Endosc. 2008; 22: 86-90Crossref PubMed Scopus (49) Google Scholar, 4Wakely Jr, PE Fine needle aspiration in the diagnosis of thymic epithelial neoplasms.Hematol Oncol Clin North Am. 2008; 22: 433-442Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 5Wakely Jr, PE Cytopathology of thymic epithelial neoplasms.Semin Diagn Pathol. 2005; 22: 213-222Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar, 6Wildi SM Hoda RS Fickling W et al.Diagnosis of benign cysts of the mediastinum: the role and risks of EUS and FNA.Gastrointest Endosc. 2003; 58: 362-368Abstract Full Text Full Text PDF PubMed Google Scholar, 7Zakowski MF Huang J Bramlage MP The role of fine needle aspiration cytology in the diagnosis and management of thymic neoplasia.J Thorac Oncol. 2010; 5: S281-S285Crossref PubMed Scopus (17) Google Scholar Therefore, we suggest that a reasonable minimal baseline is the use of 22-gauge needles to obtain transthoracic FNA biopsies (Table 3).TABLE 3Policies Regarding FNA Biopsies of Mediastinal LesionsTechnical aspects when obtaining FNA biopsies 22-guage needle (or larger) Either ROSE or at least three passes Either ROSE or at least six smears (two smears per pass) and collection of materials in CYTORICH Red collection fluid or similar solution Preparation of a cell block is suggested A sample for flow cytometry is recommended if lymphoma is suspectedInterpretation and reporting of FNA biopsies Interpretation should be correlated with clinical and radiologic findings Specimen adequacy should be reportedaNo general criteria are possible but should be assessed relative to the clinically applicable differential diagnosis. Immunostains should be used as suggested by the differential diagnosis Consultation with an experienced second pathologist is recommended whenever there is any diagnostic difficultyFNA, fine-needle aspiration; ROSE, real-time on-site examination.a No general criteria are possible but should be assessed relative to the clinically applicable differential diagnosis. Open table in a new tab FNA, fine-needle aspiration; ROSE, real-time on-site examination. There are no expert-consensus or evidence-based guidelines regarding the minimum number of passes required to obtain adequate FNA samples, the number of smears, and other slides that should be prepared and other technical standards. It is important that smears stained with Diff-Quick or other rapid staining procedure be evaluated by a cytopathologist or cytotechnologist for adequacy at the time of FNA procedures to ensure that the samples are sufficient for diagnosis and additional studies.4Wakely Jr, PE Fine needle aspiration in the diagnosis of thymic epithelial neoplasms.Hematol Oncol Clin North Am. 2008; 22: 433-442Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 5Wakely Jr, PE Cytopathology of thymic epithelial neoplasms.Semin Diagn Pathol. 2005; 22: 213-222Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar This is not possible in some practice situations because of staff shortages or other logistical considerations. In most patients, a minimum of three biopsy passes is sufficient to prepare multiple smears that can be stained with Diff-Quick, Papanicolau stain, and various immunostains. In general, two or more smears should be prepared per biopsy pass with the remainder of the material placed in a collection fluid such as CYTORICH Red (Thermo Fisher Scientific, Pittsburgh, PA) or others for cell block preparation. We propose that these practices be adopted as the standard policy for FNA biopsies. FNA cytological samples are generally fixed in 95% alcohol.4Wakely Jr, PE Fine needle aspiration in the diagnosis of thymic epithelial neoplasms.Hematol Oncol Clin North Am. 2008; 22: 433-442Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 5Wakely Jr, PE Cytopathology of thymic epithelial neoplasms.Semin Diagn Pathol. 2005; 22: 213-222Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar, 7Zakowski MF Huang J Bramlage MP The role of fine needle aspiration cytology in the diagnosis and management of thymic neoplasia.J Thorac Oncol. 2010; 5: S281-S285Crossref PubMed Scopus (17) Google Scholar There are no criteria for adequacy or of the minimum number of slides needed. Generally, on-site evaluation assures that enough material is obtained in most cases. If this is not available, we suggest that a minimum number of six smears (two per biopsy pass) should be prepared with additional materials placed in appropriate collection fluids for cell block preparation as explained earlier in the text. The slides are usually stained with Diff-Quick, Papanicolau, and hematoxylin and eosin (HE) stains. Whenever possible, materials should also be collected for the preparation of cell blocks that can be used to cut multiple sections stained with HE, various histochemical stains, and immunostains. In cases where a diagnosis of malignant lymphoma is being considered, materials should be collected in media appropriate for flow cytometry (such as Roswell Park Memorial Institute media fluid). There are no available evidence-based or expert-consensus guidelines for the interpretation of mediastinal FNA biopsies.4Wakely Jr, PE Fine needle aspiration in the diagnosis of thymic epithelial neoplasms.Hematol Oncol Clin North Am. 2008; 22: 433-442Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 5Wakely Jr, PE Cytopathology of thymic epithelial neoplasms.Semin Diagn Pathol. 2005; 22: 213-222Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar, 7Zakowski MF Huang J Bramlage MP The role of fine needle aspiration cytology in the diagnosis and management of thymic neoplasia.J Thorac Oncol. 2010; 5: S281-S285Crossref PubMed Scopus (17) Google Scholar The diagnosis can be rendered using synoptic reports or narrative reports, depending on the preferences of each pathologist, but should include a statement regarding specimen adequacy (Table 3). In contrast to other biopsy sites (e.g., thyroid), it is not possible to recommend quantitative criteria, such as a minimum number of cells or cell clusters, to assess the adequacy of a needle biopsy of a mediastinal lesion. It is recommended that the cytological findings be correlated with the clinical and imaging findings to establish whether the available cytological materials are sufficient to render a specific diagnosis or a clinically applicable differential diagnosis. It is important that FNA biopsies of mediastinal lesions be closely correlated with imaging findings and the clinical differential diagnosis, so that the report provides clinically relevant information.4Wakely Jr, PE Fine needle aspiration in the diagnosis of thymic epithelial neoplasms.Hematol Oncol Clin North Am. 2008; 22: 433-442Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 7Zakowski MF Huang J Bramlage MP The role of fine needle aspiration cytology in the diagnosis and management of thymic neoplasia.J Thorac Oncol. 2010; 5: S281-S285Crossref PubMed Scopus (17) Google Scholar In patients where malignant lymphoma is being considered in the differential diagnosis, information regarding immunostains and flow cytometry information should be incorporated in the cytological report.22Siebert JD Weeks LM List LW et al.Utility of flow cytometry immunophenotyping for the diagnosis and classification of lymphoma in community hospital clinical needle aspiration/biopsies.Arch Pathol Lab Med. 2000; 124: 1792-1799PubMed Google Scholar Immunostains are particularly helpful for the diagnosis of mediastinal tumors using FNA biopsies.1Shimosato Y Mukai K Matsuno Y Tumor of the Mediastinum. AR Press, Washington, DC2010Google Scholar Immunostains for keratin AE1/AE3 are helpful to confirm the presence of epithelial cells that may be present in lesions located near the thymus but are not diagnostic of thymic tumors. Immunostains for α-fetoprotein, human chorionic gonadotropin, placental alkaline acid phosphatase, and OCT 3/4 are helpful for differentiating germ cell tumors from thymic tumors. Table 4 lists various immunostains that can be helpful for the diagnosis of selected mediastinal lesions.TABLE 4Selected Immunohistochemical Markers Used in the Differential Diagnosis of Selected Mediastinal LesionsEpithelial MarkersMiscellaneous Markers of Thymic CarcinomaNeuroendocrine MarkersGerm Cell Tumor MarkersMarkers of Pulmonary OriginLymphoid Markers of Mature T PhenotypeLymphoid Markers of Immaturet PhenotypeLymphoid Markers:CytokeratinCD117, CD5aAdenocarcinomas of extrathymic origin frequently express CD5 and EMA immunoreactivity., CD70, and EMAaAdenocarcinomas of extrathymic origin frequently express CD5 and EMA immunoreactivity.Synaptophysin, Chromogranin, and CD56OCT ¾, α Fetoprotein, CD30, and PLAPTTF-1, Napsin, and Surfactant ApoproteinCD3 and CD45CD99, Tdt, and CD laCD20LYECThymoma+−−−−++−− / +Thymic hyperplasia+−−−−+++−Thymic carcinoma+++/–−−+−−−Thymic neuroendocrine tumors+−+−−−−−−Lymphoma−−−+ (CD30bCD30 is expressed in mediastinal lymphomas, CD30 is expressed (in different settings) in Hodgkin lymphoma and sometimes in primary mediastinal B-cell lymphoma.)−+++−Germ cell tumors+/–−−+−−−−−Metastases+/–−aAdenocarcinomas of extrathymic origin frequently express CD5 and EMA immunoreactivity.+/–−+−−−−Among several antibodies useful in the evaluation of anterior mediastinal masses, it should be remembered that some markers have to be evaluated for the epithelial cell (EC) component or for putative germ cells, whereas other are useful in the evaluation of the lymphoid cell (LY) component. Moreover, some few ntibodies originally established to characterize hematolymphoid cells (CD5, CD20, and CD117) proved to be of value in the diagnosis of thymic epithelial tumors, because aberrantly expressed in selected thymoma subtypes or in thymic carcinomas. Morphological criteria and antibody panels should be applied in selected cases in order to establish the diagnosis.26Chilosi M Castelli P Martignoni G et al.Neoplastic epithelial cells in a subset of human thymomas express the B cell-associated CD20 antigen.Am J Surg Pathol. 1992; 16: 988-997Crossref PubMed Scopus (35) Google Scholar, 27Hishima T Fukayama M Fujisawa M et al.CD5 expression in thymic carcinoma.Am J Pathol. 1994; 145: 268-275PubMed Google Scholar, 28Dorfman DM Shahsafaei A Chan JK Thymic carcinomas, but not thymomas and carcinomas of other sites, show CD5 immunoreactivity.Am J Surg Pathol. 1997; 21: 936-940Crossref PubMed Scopus (119) Google Scholar, 29Kornstein MJ Rosai J CD5 labeling of thymic carcinomas and other nonlymphoid neoplasms.Am J Clin Pathol. 1998; 109: 722-726Crossref PubMed Scopus (66) Google Scholar, 30Tateyama H Eimoto T Tada T et al.Immunoreactivity of a new CD5 antibody with normal epithelium and malignant tumors including thymic carcinoma.Am J Clin Pathol. 1999; 111: 235-240PubMed Google Scholar, 31Pan CC Chen PC Chiang H KIT (CD117) is frequently overexpressed in thymic carcinomas but is absent in thymomas.J Pathol. 2004; 202: 375-381Crossref PubMed Scopus (146) Google Scholar, 32Henley JD Cummings OW Loehrer Sr, PJ Tyrosine kinase receptor expression in thymomas.J Cancer Res Clin Oncol. 2004; 130: 222-224Crossref PubMed Scopus (77) Google Scholara Adenocarcinomas of extrathymic origin frequently express CD5 and EMA immunoreactivity.b CD30 is expressed in mediastinal lymphomas, CD30 is expressed (in different settings) in Hodgkin lymphoma and sometimes in primary mediastinal B-cell lymphoma. Open table in a new tab Among several antibodies useful in the evaluation of anterior mediastinal masses, it should be remembered that some markers have to be evaluated for the epithelial cell (EC) component or for putative germ cells, whereas other are useful in the evaluation of the lymphoid cell (LY) component. Moreover, some few ntibodies originally established to characterize hematolymphoid cells (CD5, CD20, and CD117) proved to be of value in the diagnosis of thymic epithelial tumors, because aberrantly expressed in selected thymoma subtypes or in thymic carcinomas. Morphological criteria and antibody panels should be applied in selected cases in order to establish the diagnosis.26Chilosi M Castelli P Martignoni G et al.Neoplastic epithelial cells in a subset of human thymomas express the B cell-associated CD20 antigen.Am J Surg Pathol. 1992; 16: 988-997Crossref PubMed Scopus (35) Google Scholar, 27Hishima T Fukayama M Fujisawa M et al.CD5 expression in thymic carcinoma.Am J Pathol. 1994; 145: 268-275PubMed Google Scholar, 28Dorfman DM Shahsafaei A Chan JK Thymic carcinomas, but not thymomas and carcinomas of other sites, show CD5 immunoreactivity.Am J Surg Pathol. 1997; 21: 936-940Crossref PubMed Scopus (119) Google Scholar, 29Kornstein MJ Rosai J CD5 labeling of thymic carcinomas and other nonlymphoid neoplasms.Am J Clin Pathol. 1998; 109: 722-726Crossref PubMed Scopus (66) Google Scholar, 30Tateyama H Eimoto T Tada T et al.Immunoreactivity of a new CD5 antibody with normal epithelium and malignant tumors including thymic carcinoma.Am J Clin Pathol. 1999; 111: 235-240PubMed Google Scholar, 31Pan CC Chen PC Chiang H KIT (CD117) is freque