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The thymoma is rare but is the most common malignancy in the anterior mediastinum. There is a frequent association with paraneoplastic syndrome and overall it has an indolent growth pattern. However, there are thymomas that have a more locally aggressive course and some tumors are frankly malignant. Approximately one half of the patients are asymptomatic, 25-30% of patients have symptoms related to compression of adjacent mediastinal structures including cough, chest pain, and shortness of breath.

Paraneoplastic syndromes associated with thymoma include myasthenia gravis (30-50%), pure red cell aplasia, hypogammoglobulinemia, endocrine disorders. About 15% of patients with myasthenia gravis have a thymoma.


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AGE RANGE-MEDIAN Middle aged adults



Thymoma Arising Within Cardiac Myxoma.

Miller DV, Tazelaar HD, Handy JR, Young DA, Hernandez JC.

From the *Division of Anatomic Pathology, Mayo Clinic, Rochester, MN; and the Departments of daggerUrology, double daggerCardiovascular Surgery, and section signPathology, Providence Portland Medical Center, Portland, OR.

Am J Surg Pathol. 2005 Sep;29(9):1208-1213. Abstract quote  

Hematopoietic, glandular, and mesenchymal elements can be found within cardiac myxomas; ectopic endocrine tissues and "thymic rests" have also rarely been described. Atrial tumors (one right and one left) from 2 patients (a 69-year-old man and a 77-year-old woman) were encountered among the atrial myxoma cases in one of the author's consultation files.

Both tumors were comprised of classic cardiac myxoma (with characteristic rings and syncytial chains of myxoma cells in a loose myxoid matrix) and cellular thymoma-like elements (characterized by a lobulated sheet-like growth of epithelioid spindle cells admixed with small lymphocytes punctuated by vessels with prominent perivascular spaces). Neither patient had evidence of thymoma elsewhere.

Immunophenotypically, the thymoma-like component reacted strongly with antibodies to keratins (AE1/AE3, Cam 5.2, wide spectrum, CK19, CK7) and CD57 and weakly with antibodies to CD31, CD34, and calretinin. This intermediate phenotypic expression of both epithelial and vascular antigens likely reflects the multipotential nature of the cells comprising this lesion.

The most likely explanation for this extremely unusual finding is neoplastic transformation of thymic rests within a myxoma.
Myasthenia gravis associated with different WHO histologic subtypes:
Am J Surg Pathol 2001;25:103-110




Proliferative Activity and Apoptosis in Thymic Epithelial Neoplasms
Kenzo Hiroshima, M.D., Akira Iyoda, M.D., Tetsuya Toyozaki, M.D., Yana Supriatna, M.D., Kiyoshi Shibuya, M.D., Fumihiko Shimamura, M.D., Yukiko Haga, M.D., Shigetoshi Yoshida, M.D., Takehiko Fujisawa, M.D. and Hidemi Ohwada, M.D.

Departments of Basic Pathology (KH, TT, KS, FS, YH, HO), Thoracic Surgery (AI, SY, TF), and Molecular Pathology (YS), Graduate School of Medicine, Chiba University, Chiba, Japan

Modern Pathology 2002;15:1326-1332 Abstract quote

The classification of thymic epithelial tumors is controversial because prediction of the biological behavior of these tumors from their morphologic appearance is difficult.

The aim of this study was to evaluate the proliferative activity and rate of apoptosis of thymic epithelial tumors classified according to World Health Organization histological classification. We also attempted to determine the importance of a number of proapoptotic factors in these processes.

We investigated 46 surgically resected thymic epithelial tumors (8 Type A, 8 Type AB, 7 Type B1, 7 Type B2, 6 Type B3, and 10 Type C). Immunohistochemical staining was performed to determine the tumor expression of p53 protein, Bax, Bcl-2, and survivin. In addition, the Ki-67 labeling index (LI) and apoptotic index (AI) of these tumors were evaluated. Type C thymoma had a higher LI (16.55 ± 12.12%) than did the other histological subtypes. Stage IV thymoma (12.36 ± 9.99%) had a higher LI than did Stage I tumor. The AI was significantly elevated in Type B1 thymoma (1.47 ± 0.55%). Overexpression of p53 protein was observed in Type B3 and C thymomas. p53 protein–positive tumors had a higher LI than did p53 protein–negative tumors (P < .0001). Bcl-2 expression was observed in Type A, AB, and C thymomas. Bcl-2–positive thymoma had a lower AI than did Bcl-2-negative thymoma (P = .0157).

These results suggest that overexpression of p53 protein is associated with a higher tumor proliferative activity and that Bcl-2 acts as an inhibitor of apoptosis in thymoma. Bcl-2 and p53 protein expression may be useful markers in differentiating thymoma subtypes.


Ectopic hamartomatous thymoma: a case report with immunohistochemical study and review of the literature.

Kushida Y, Haba R, Kobayashi S, Ishikawa M, Doi T, Kadota K.

Department of diagnostic pathology, Kagawa University, Kagawa, Japan.

J Cutan Pathol. 2006 May;33(5):369-72. Abstract quote  

Ectopic hamartomatous thymoma (EHT) is a rare benign tumor.

We present a case of EHT, which was seen as subcutaneous mass on the left supraclavicular area in a 19-year-old man. The tumor consisted of spindle cells, epithelial cells, adipose cells, and a small amount of lymphocytes, as described previously. Immunohistochemically, spindle cells were positive for keratin, a-smooth muscle actin, CD34 and vimentin, but negative for desmin and S-100 protein. Lymphocytes were positive for CD45RO but negative for CD20, CD1a, and CD99. Approximately, 5% of cells were positive for MIB-1 and no cells stained for p53 and bcl-2.

Recognition of EHT is important and needs to be differentiated from high-grade sarcomas such as synovial sarcoma or glandular malignant peripheral nerve sheath tumor.

WHO Classification of Thymic Epithelial Tumors (1999) This system is based upon the morphology of the epithelial cells as well as the lymphocyte to epithelial cell ratio
TYPE A Homogeneous population of neoplastic epithelial cells having spindle/oval shape, lacking nuclear atypia, and accompanied by few or no non-neoplastic lymphocytes
TYPE AB Foci having the features of type A admixed with foci rich in lymphocytes; the segregation of the two patterns can be sharp and distinct
TYPE B1 Resembles the normal functional thymus by combininglarge expanses with an appearance practically indistinguishable from normal thymic cortex with areas resembling thymic medulla
TYPE B2 Neoplastic epithelial component appears as scattered plump cells with vesicular nuclei and distinct nucleoli among a heavy population of lymphocytes; perivascular spaces are common
TYPE B3 Predominately composed of epithelial cells having round or polygonal shape and exhibiting mild atypia admixed with a minor component of lymphocytes, foci of squamous metaplasia and perivascular spaces are common
TYPE C Thymic carcinoma
Thymoma Classification
Current Status and Future Trends

Saul Suster, M and Cesar A. Moran, MD
Am J Clin Pathol 2006;125:542-554

Abstract quote

The classification of thymic epithelial neoplasms has been a controversial topic for many years. Recent advances in diagnostic methods and renewed interest in the biology of these tumors has led to efforts by investigators to shed new light on their biologic behavior and to offer novel perspectives on these unusual neoplasms.

Several new classification schemes have been proposed, including the new World Health Organization schema for the histologic typing of tumors of the thymus. We review the current status of thymoma classification and comment on problem areas and future trends that may offer a more pragmatic approach to these tumors.
"Ancient" (Sclerosing) Thymomas
A Clinicopathologic Study of 10 Cases

Cesar A. Moran, MD and Saul Suster, MD
Am J Clin Pathol 2004;121:867-871 Abstract quote

We present 10 cases of "ancient" (sclerosing) thymomas in 4 women and 6 men (age range, 34-73 years; mean, 53.5 years). Clinically, 4 patients had a history of shortness of breath and chest pain of several weeks' duration, 1 had a history of myasthenia gravis, and 5 were asymptomatic (anterior mediastinal masses discovered on routine chest radiographs).

All underwent complete surgical resection of the anterior mediastinal mass. The tumors were light tan and solid, without areas of hemorrhage or necrosis, and 5 to 10 cm in greatest diameter. Extensive areas of hyalinized fibroconnective tissue constituting about 85% to 90% of the tumor mass was the main tumor feature. Focal areas of conventional thymoma also were present in all tumors.

Follow-up information was obtained for 8 patients. Of these 8 patients, 6 died, all of unrelated causes (congestive heart failure, renal insufficiency, and pulmonary edema), and 2 were alive 1 and 6 years after surgical resection.

The present cases highlight an important histopathologic feature of thymomas, which can pose problems in diagnosis, namely when dealing with small mediastinoscopic biopsy specimens.

Adenocarcinoma of the thymus: report of two cases, including a previously undescribed mucinous subtype.

Choi WW, Lui YH, Lau WH, Crowley P, Khan A, Chan JK.


Am J Surg Pathol 2003 Jan;27(1):124-30 Abstract quote

We report two cases of primary thymic adenocarcinoma, a very uncommon neoplasm with limited information in the literature. Both patients were men (age 15 and 39 years).

The first case was a mucinous carcinoma, a subtype of adenocarcinoma not previously recognized in the thymus. It comprised islands and strips of mucin-rich tumor cells floating in large pools of extracellular mucin. There was transition of carcinomatous epithelium to the attenuated epithelium of a thymic cyst. Immunostaining for high molecular weight cytokeratin furthermore highlighted in one area negatively stained tumor islands wrapped by positively stained residual thymic medullary epithelium, suggesting in situ origin of the carcinoma from the thymic epithelium.

The second case was a papillary carcinoma with high nuclear grade and many psammoma bodies. It showed strong immunoreactivity for CD5 and did not stain for CA-125 as well as thyroid, pulmonary, and mesothelial markers. The findings in this study therefore broaden the morphologic spectrum of thymic adenocarcinomas to include a mucinous subtype.

Review of the literature indicates that thymic adenocarcinomas usually arise from thymic cyst or type A thymoma, and the clinical outcome is variable.

Thymic Tumor With Adenoid Cystic Carcinomalike Features: A Clinicopathologic Study of 4 Cases.

*Department of Pathology, IRCCS Istituto Clinico Humanitas of Rozzano, University of Milan School of Medicine †Centro Diagnostico Italiano, Milan, Italy ‡Department of Pathology, University Hospital, Zurich, Switzerland §Department of Pathology, University of Wurzburg, Wurzburg, Germany.


Am J Surg Pathol. 2007 Aug;31(8):1161-1167. Abstract quote

Thymic carcinomas are rare malignant neoplasms which comprise several histologic subtypes. Adenoid cystic carcinoma (ACC) is included among these subtypes even if it has never been formally reported.

We evaluated the clinical, radiologic, morphologic, immunohistochemical, and genetic features of 4 cases of thymic neoplasms with ACC-like features retrieved from the authors' consult files. Most cases affected adult/elderly males (mean 68.5 y; range: 63 to 77 y; M:F ratio=3:1), and were asymptomatic. The clinical history (no evidence of ACC in other sites), radiologic findings (a mass in the thymic region), and morphologic features (residual thymic tissue at the periphery of the neoplasm) strongly supported their primary thymic nature.

Grossly, most of the tumors presented as multicystic lesions. On microscopic examination there were true glandular spaces filled with periodic acid-Schiff+material, and pseudocysts containing stromal mucin, collagen IV, and laminin. Features favoring malignancy were overtly infiltrative margins (2/4), mitotic figures (2/4), cytologic atypia (1/4), vascular invasion (1/4), absence of organoid thymuslike pattern (4/4), and absence of immature (TdT+) T lymphocytes (3/3). Necrosis and nerve invasion were not observed. The tumor cells showed the following immunophenotype: p63+(3/3), CK34betaE12+(3/3), CD5+ in scattered cells (1/3), CD117- (3/3), chromogranin-(2/2), synaptophysin-(2/2), and CD56- (2/2). MIB-1 ranged from 1% to 10%. Comparative genomic hybridization revealed an isolated gain of chromosome 8 in 1/3 cases. One patient is alive and well after 20 months, 1 died of another cause 5 years later, and 2 were lost at follow-up. Exceptionally, primary thymic tumors may exhibit histologic features resembling those of ACC of salivary glands. They may be well circumscribed and cytologically bland or invasive and cytologically atypical. In either case they lack an organoid thymuslike pattern and immature T lymphocytes.

We have interpreted them as a microscopic subtype of well-differentiated thymic carcinoma of low-grade malignancy, an impression supported by the admittedly limited follow-up information.

Hepatoid Thymic Carcinoma: Report of a Case

Franke, A*; Ströbel, P†; Fackeldey, V*; Schäfer, R‡; Göller, T‡; Becker, H. P§; Schöneich, R‡; Müller-Hermelink, H. K†; Marx, A†

From the Departments of *Visceral and Thoracic Surgery, ‡Pathology, and §Radiology, Central Army Hospital, Koblenz, Germany, and †Institute of Pathology, University of Würzburg, Würzburg, Germany.

The American Journal of Surgical Pathology : Volume 28(2) February 2004 pp 250-256 Abstract quote

We describe the clinicopathologic findings in a so far unrecognized thymic tumor. The tumor occurred in a 70-year-old woman with respiratory distress but neither myasthenia gravis nor other symptoms. Metastases or another primary tumor were absent. The well-circumscribed neoplasm was located in the thymic region, measured 18 × 12 × 8 cm, and showed a homogeneous, tan-colored, soft cut surface. By histology, the tumor lacked a true capsule and a lobular growth pattern, was almost devoid of stroma, and infiltrated among remnant thymus lobules. The polygonal tumor cells formed solid sheets, trabeculae, or occurred as single cells that resembled hepatocytes. Proliferative activity was low. Portal structures, sinuses, and bile were absent as were areas of conventional thymoma, adenocarcinoma, or germ cell tumor.

The tumor expressed cytokeratins 7 and 19, a 1 -antitrypsin, a 1 -antichymotrypsin, and hep-Par-1. Alpha-fetoprotein (AFP), human ß-chorionic gonadotropin (ß-HCG), placental alkaline phosphatase, CD5, CD30, CD31, CD34, CD45, CD68, CD99, S-100, HMB45, desmin, actin, or neuroendocrine markers were not expressed, and intratumorous CD1a+ or TdT+ immature T cells were absent. AFP was repeatedly undetectable in the blood. Mediastinal tumor recurrence was detected 6 months after surgery. Following radiochemotherapy, the patient has remained free of disease for 26 months.

We conclude that this tumor is a thymic carcinoma (WHO type C thymoma). A diagnosis of hepatoid yolk sack tumor appears unlikely considering absence of a bona fide germ cell component, lack of AFP expression, and the patient's female gender. Because of its morphologic and immunohistochemical features, we propose the term hepatoid thymic carcinoma for this new type of thymic carcinoma.

Mucinous Adenocarcinomas of the Thymus: Report of 2 Cases and Review of the Literature.

Departments of *Pathology and Laboratory Medicine †Thoracic Surgery, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA.


Am J Surg Pathol. 2007 Sep;31(9):1330-1336. Abstract quote

BACKGROUND: Most adenocarcinomas of the mediastinum are metastatic lesions. Primary thymic adenocarcinomas are extremely rare neoplasms. We could find only 12 cases reported in the literature; of these 12, only 4 were of the mucinous subtype.

DESIGN: We report 2 additional cases of the mucinous subtype, including a previously unreported mucinous variant with numerous psammoma bodies.

RESULTS: The first case in a 61-year-old woman resembled a mucinous (colloid) carcinoma of other organs such as the breast and colon. It consisted of islands and strips of tumor cells floating in large pools of extracellular mucin. A unique feature of this tumor was the presence of numerous psammoma bodies. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) 7 and negative for CD5. The second case in an 82-year-old woman was a mucinous adenocarcinoma arising from a thymic cyst with areas of transition from benign to dysplastic epithelium. The tumor cells formed dilated glands, cords, and small nests that infiltrated the thymic cyst wall and exhibited evidence of mucin production. Immunohistochemically, the tumor cells were positive for CK 7 and focally positive for both CD5 and CK 5/6.

CONCLUSIONS: Mucinous adenocarcinoma, with or without, psammoma bodies, may be of primary thymic origin and should be considered in the differential diagnosis of malignant mediastinal tumors. These 2 cases provide further documentation of the rare occurrence of primary mucinous adenocarcinomas of the thymic gland.
Adenocarcinoma of the thymus: Mucinous subtype.

Takahashi F, Tsuta K, Matsuno Y, Takahashi K, Toba M, Sato K, Uekusa T, Izumi H, Nakamura K, Hirose S, Fukuchi Y.

Hum Pathol. 2005 Feb;36(2):219-23. Abstract quote  

Summary Primary thymic adenocarcinoma, mucinous subtype, is extremely rare with only one case reported to date.

We describe herein a case of thymic mucinous adenocarcinoma. A 59-year-old man was identified to have an anterior mediastinal tumor and was diagnosed as mucinous adenocarcinoma. Clinical and radiographic examinations disclosed no evidence of tumor elsewhere. The patient received radiotherapy, but the general condition deteriorated and died 11 months after tumor detection. Thoracic autopsy revealed an anterior mediastinal tumor measuring greater than 10 cm, uncapsulated, and white. The tumor had clear margins and was clearly isolated from the lung.

Histologically, the tumor demonstrated papillary, acinar, and cribriform structure and produced abundant extracellular mucin. Immunohistochemically, most tumor cells were positive for cytokeratin 7, were partially positive for CD5, and were negative for TTF-1, Sp-A, CDX-2, MUC2, napsin A, and cytokeratin 20. Collectively, the diagnosis of the tumor was primary mucinous adenocarcinoma of the thymus.

We propose that the mucinous subtype should be recognized as one of the histopathological entities of thymic adenocarcinoma.

Thymic carcinoma with rhabdoid features.

Toprani TH, Tamboli P, Amin MB, Ordonez NG, Ayala AG, Ro JY.

Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX.

Ann Diagn Pathol 2003 Apr;7(2):106-11 Abstract quote

A case of thymic carcinoma with rhabdoid differentiation is presented. A 67-year-old man who presented with chest pain and hemoptysis was referred to The University of Texas M. D. Anderson Cancer Center (Houston, TX). Radiologic studies revealed a large anterior mediastinal mass. After the initial biopsy and preoperative chemotherapy, a radical thymectomy revealed a stage III thymic carcinoma with a rhabdoid component.

The rhabdoid component was characterized by large cells with an eccentric nucleus, prominent nucleolus, and typical paranuclear cytoplasmic inclusions. Immunohistochemical and electron microscopic studies confirmed the presence of rhabdoid cells with the paranuclear cytoplasmic inclusions staining for both pancytokeratin and vimentin. The patient was given postoperative chemotherapy and radiation. He has since developed metastases to the pelvis and is alive with disease at 20 months of follow-up.

To our knowledge, this is the first reported case of thymic carcinoma with rhabdoid features.


Rhabdomyomatous Carcinoma of the Thymus.

Moreira De Queiroga E, Chikota H, Bacchi CE, Moran CA, Suster S.

*Department of Pathology, Ohio State University, Columbus, OH; daggerIMP Medical Laboratory, Florianopolis, Brazil; double daggerDepartment of Pathology, Sao Paulo State University, Botucatu, Brazil; and the section signDepartment of Pathology, M.D. Anderson Cancer Center, Houston, TX.
Am J Surg Pathol. 2004 Sep;28(9):1245-1250. Abstract quote  

Myoid cells have been described in the thymus in association with a variety of benign and malignant conditions. The presence of a benign rhabdomyomatous component in a malignant primary thymic epithelial neoplasm, however, is extremely rare.

A case of poorly differentiated carcinoma of the thymus arising in the posterior mediastinum containing a prominent rhabdomyomatous component is described. The patient, a 70-year-old woman, was seen for a large posterior mediastinal mass.

An open chest biopsy revealed an extensively necrotic tumor composed of islands of atypical cells with vesicular nuclei and prominent nucleoli with numerous mitotic figures admixed with abortive glandular structures. Interspersed with the malignant epithelial components were islands of large cells containing brightly eosinophilic cytoplasm and small, round, excentrically placed nuclei. Immunohistochemical studies showed strong positivity of the epithelial cells for cytokeratin and strong positivity of the myoid cells for pan-actin, desmin, and myogenin.

The possible relationship of the rhabdomyomatous component of this tumor with the myoid cells of the thymus is discussed.
Carcinoma Showing Thymus-like Differentiation of the Thyroid (CASTLE): A Comparative Study: Evidence of Thymic Differentiation and Solid Cell Nest Origin

Reimann JD, Dorfman DM, Nose V.

Brigham and Women's Hospital and Harvard Medical School, Boston, MA.


Am J Surg Pathol. 2006 Aug;30(8):994-1001 Abstract quote

Carcinoma showing thymus-like differentiation (CASTLE) is a rare intrathyroidal neoplasm, a member of a tumor family probably arising from ectopic thymus or branchial pouch remnants. Thyroid solid cell nests (SCNs) may also be derived from branchial pouch remnants. SCNs express p63, carcinoembryonic antigen (CEA), and high molecular weight keratin (HMWK).

To determine whether CASTLE and SCNs derive from similar embryologic origins/lines of differentiation, and to better differentiate CASTLE from other thyroid neoplasms, we compared p63, CD5, HMWK, and CEA staining of CASTLE and SCNs with other thyroid and thymic lesions. Seven CASTLE, 11 SCNs, 10 thymic carcinoma, 11 invasive thymoma, 12 thymoma, 28 papillary thyroid carcinoma, 4 thyroid squamous cell carcinoma, 2 childhood sclerosing carcinoma, 4 follicular adenoma, 6 follicular carcinoma, 4 poorly differentiated carcinoma, and 20 lymphocytic thyroiditis cases were analyzed. In normal thyroid, only SCNs stained for p63, HMWK, and CEA. The only CD5-positive cells in normal thyroid were T cells. Thymomas and normal thymus stained similarly to SCNs. All CASTLE and thymic carcinomas exhibited diffuse p63 and HMWK staining and all CASTLE cases and the majority of thymic carcinomas were positive for CEA and CD5. In contrast, none of the other thyroid neoplasms examined exhibited consistent staining for all 4 markers studied.

These findings provide further evidence that CASTLE is distinct from other thyroid neoplasms, is probably of thymic origin, and may arise from branchial pouch remnants, the thyroid SCNs. Moreover CD5, HMWK, CEA and p63 can be used to help distinguish CASTLE from other thyroid neoplasms.
Undifferentiated Large Cell Carcinoma of the Thymus Associated With Castleman Disease-Like Reaction: A Distinctive Type of Thymic Neoplasm Characterized by an Indolent Behavior.

Nonaka D, Rodriguez J, Rollo JL, Rosai J.

From the *Department of Pathology, National Cancer Institute, Milan, Italy; and daggerDepartment of Pathology, Jefferson Memorial Hospital, Crystal City, MO.
Am J Surg Pathol. 2005 Apr;29(4):490-495. Abstract quote  

Five cases of a distinctive type of undifferentiated large cell thymic carcinoma accompanied by an inflammatory reaction having morphologic features closely resembling those of Castleman disease (CD) of the hyaline vascular type (HVCD) are reported. The tumors occurred in 3 men and 2 women with a median age of 53 years.

Three patients were asymptomatic and the tumors were found incidentally; 1 patient presented with fatigue, weight loss, dyspnea, and chest pain, and another with acanthosis nigricans. The tumors were characterized by the admixture of two components: a neoplasm of cytokeratin (+)/CD5(-) undifferentiated large tumor cells and an inflammatory reaction resembling the late stage of HVCD. Some of the cases were associated with a remarkably indolent clinical course, especially when considering their high-grade morphology. Three patients were alive without disease at 1, 10, and 22 years. One patient was alive with persistent disease at 1 year. One patient's clinical course was unique in that the primary thymic tumor was found 16 years after a metastasis had been detected in two distant lymph nodes.

The two possible explanations for the coexistence here described are as follows: 1) a CD-like reaction to the tumor as the morphologic manifestation of a host immune response; and 2) a malignancy engrafted upon preexisting HVCD of the thymus, in a manner analogous to that operating in the reported cases of tumors of dendritic/reticulum cells complicating HVCD at other sites. The first hypothesis is favored, with the added suggestion that the CD-like reaction may bear a relationship to the peculiarly indolent behavior that these tumors exhibit.
Ectopic Hamartomatous Thymoma: A Clinicopathologic and Immunohistochemical Analysis of 21 Cases With Data Supporting Reclassification as a Branchial Anlage Mixed Tumor.

Fetsch JF, Laskin WB, Michal M, Remotti F, Heffner D, Ellis G, Furlong M, Miettinen M.

Departments of *Soft Tissue Pathology, daggerOtolaryngic Pathology, and double daggerOral Pathology, Armed Forces Institute of Pathology, Washington, DC; the section signDepartment of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL; the paragraph signDepartment of Pathology, Faculty Hospital, Pilsen, Czech Republic; the Department of Pathology, the College of Physicians and Surgeons of Columbia University, New York, NY; and the **Department of Pathology, Georgetown University School of Medicine, Washington, DC. Dr. Ellis is currently employed by ARUP Laboratories, Salt Lake City, UT.
Am J Surg Pathol. 2004 Oct;28(10):1360-1370. Abstract quote  

This report describes the clinicopathologic and immunohistochemical findings in 21 cases of a highly distinctive tumor with a strong predilection for the lower neck region of adult males.

Our study group consisted of 20 males and one female. The patients were 28 to 79 years old (mean age, 47 years; median age, 40 years), and they presented with solitary, lobular or multilobular masses ranging in size from 2.0 to 19.0 cm in greatest dimension (mean size, 5.1 cm; median, 4 cm). The tumors principally involved the lower neck region, usually in close proximity to the sternoclavicular joint. The preoperative duration of the lesions ranged from 2 months to 30 years.

Histologically, the tumors were typically well marginated and composed of plump spindled cells, delicate spindled cells, mature adipose tissue, and epithelial cells, including both squamous and glandular elements. Epithelial-lined cysts were a focal finding in most cases and measured up to 2 cm in greatest dimension. Mitotic counts for the tumors ranged from 0 to 7 mitotic figures per 50 high power fields (mean mitotic count, 1.1 mitotic figures per 50 HPFs). Our immunohistochemical analysis revealed a complex immunophenotype with a diverse keratin profile. The plump spindled cells had a myoepithelial phenotype, as evidenced by the coexpression of keratins (5, 5/6, and 14), α-smooth muscle actin, CD10, and to a lesser extent, calponin. No compelling evidence for thymic differentiation was observed. The patients were initially managed by biopsy or partial resection (n = 4), simple local excision (n = 16), or an unspecified procedure (n = 1). Clinical follow-up of ≥3 years was available for 10 patients (48%). Two patients had recurrent disease, but there were no metastases or tumor-related deaths. A derivation from sequestered branchial epithelium is likely, but evidence for a thymic component is tenuous, at best.

Our data support reclassification of this distinctive process as a branchial anlage mixed tumor. The differential diagnosis includes conventional mixed tumors of skin adnexal or salivary gland origin, synovial sarcoma, a peripheral nerve sheath tumor variant, and cystic teratoma.
Microthymoma: Definition of the Entity and Distinction From Nodular Hyperplasia of the Thymic Epithelium (So-called Microscopic Thymoma).

Cheuk W, Tsang WY, Chan JK.

From the Department of Pathology, Queen Elizabeth Hospital, Hong Kong.

Am J Surg Pathol. 2005 Mar;29(3):415-9. Abstract quote

We report 2 cases of microscopic-sized thymoma, which probably represents the earliest phase of thymoma development.

The 2 patients presented with pure red cell aplasia and myasthenia gravis, respectively. The thymectomy specimens did not reveal tumor on gross examination, but histologically each contained small thymomas measuring 5 mm and 7 mm in largest dimension, respectively. One of the tumors was unencapsulated and involved a single lobule only, and the other was encapsulated and comprised two lobules. The tumors consisted of ovoid epithelial cells with pale nuclei and distinct nucleoli, scattered in a background of small lymphocytes. Foci of medullary differentiation and perivascular space were identified in the 2 cases, respectively. The lymphocytes were confirmed to be immature T cells on immunohistochemical studies (CD3+, TdT+). Except for the microscopic size, the morphology of the two tumors conforms to conventional type B1/B2 and type B2 thymoma, respectively.

We propose calling such incidental small tumor "microthymoma" to distinguish it from the so-called microscopic thymoma, which is composed of small thymic epithelial nests and probably more appropriately termed "nodular hyperplasia" of the thymic epithelium.

Spindle Cell and Mixed Spindle/Lymphocytic Thymomas An Integrated Clinicopathologic and Immunohistochemical Study of 81 Cases

Chin-Chen Pan, M.D.; Winby York-Kwan Chen, M.D.; Hung Chiang, M.D.

From the Department of Pathology, National Yang-Ming University and Veterans General Hospital-Taipei, Taiwan.

Am J Surg Pathol 2001;25:111-120 Abstract quote

Forty-three cases of spindle cell thymoma (medullary, WHO type A) and 38 cases of mixed spindle/lymphocytic thymoma (WHO type AB) were studied for their clinicopathologic and immunohistochemical characteristics.

Three histologic patterns of spindle cell thymoma were observed: short-spindled (57%), long-spindled (31%), and micronodular (12%). The short-spindled variant was composed of oval to short spindle cells commonly arranged in a hemangiopericytic or microcystic pattern. The long-spindled variant chiefly consisted of fibroblast-like epithelial cells mimicking fibrohistiocytic neoplasms. The micronodular variant was characterized by small nests of short spindle cells dispersed among a lymphoid stroma with frequent germinal centers. All kinds of spindle cell could be admixed with lymphocyte-rich ``cortex''-like areas to constitute mixed spindle/lymphocytic thymomas. Immunohistochemically, the epithelial cells in up to 70% of the short-spindled and long-spindled variants of spindle cell thymoma and 90% of mixed spindle/lymphocytic thymomas were positive for CD20, whereas the epithelial cells in all micronodular spindle cell thymomas were negative. All of the spindle cell thymomas and most of the mixed spindle/lymphocytic thymomas in this study were found in stages I and II.

Follow up of the patients did not disclose relapse or mortality directly resulting from the tumors. However, the prognosis of stage I and II spindle cell and mixed spindle/lymphocytic thymomas did not significantly differ from those of stage I and II thymomas of other types by a stage-matched survival analysis.

Our data showed that spindle cell and mixed spindle/lymphocytic thymomas are distinctive in histologic pattern and immunohistochemical profile. When interpreted within the context of staging, spindle cell and mixed spindle/lymphocytic thymomas presenting in stages I and II most likely behave in an indolent fashion.

Thymic Mucoepidermoid Carcinomas: A Clinicopathologic Study of 10 Cases and Review of the Literature.

Nonaka D, Klimstra D, Rosai J.

From the *Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY; and the daggerDepartment of Pathology, National Cancer Institute, Milan, Italy.
Am J Surg Pathol. 2004 Nov;28(11):1526-1531. Abstract quote

BACKGROUND:: Primary thymic carcinomas are rare malignant neoplasms, of which at least 10 different histologic variants have been described. Among these variants, thymic mucoepidermoid carcinomas morphologically similar to the homonymous salivary gland counterparts are particularly unusual; only 9 cases for which clinicopathologic features were available have been reported.

OBJECTIVE:: To study the clinicopathologic features of primary thymic mucoepidermoid carcinoma in an effort to better define their histologic features and biologic behavior.

DESIGN:: The clinical and pathologic features of 10 cases of thymic mucoepidermoid carcinoma were reviewed and compared with those of previously reported cases.

RESULTS:: The patients ranged in age from 8 to 84 years (mean 49 years), with 6 men and 4 women. The initial manifestations included respiratory symptoms and weight loss. Some patients were asymptomatic. All tumors were located adjacent to residual benign thymic tissue, and 3 cases were associated with multilocular thymic cysts. Histologically, the tumors consisted of sheets, lobules and nests of squamous, mucinous and intermediate cells in densely fibrotic stroma. There were 8 low-grade cases and 2 high-grade cases. The 2 patients with high-grade tumors died 1 year after diagnosis, whereas all but 1 patient with low-grade tumors in which follow-up was available were found to be alive and well on follow-up examination. One patient with low-grade tumor but high-stage disease died after developing a local recurrence. Among the 9 cases reported in the literature, 4 cases resulted in fatal outcomes; 2 cases were high-stage disease and 2 were high-grade tumors.

CONCLUSIONS:: Thymic mucoepidermoid carcinomas are predominantly low-grade tumors, and may be associated with multilocular thymic cysts. Poor prognosis is related to high-grade histology and high-stage disease.



Expression of calretinin and other mesothelioma-related markers in thymic carcinoma and thymoma.

Pan CC, Chen PC, Chou TY, Chiang H.

Department of Pathology, National Yang-Ming University and Veterans General Hospital, Taipei, Taiwan.

Hum Pathol. 2003 Nov;34(11):1155-62. Abstract quote  

Thymic carcinoma and thymoma are primary neoplasms of the anterior mediastinum that can involve the lung and pleura in advanced stages or, in rare instances, occur as primary pleural tumors. Thus these tumors may be encountered in thoracic and pleural biopsy specimens. Recognizing the immunohistochemical patterns of calretinin and other mesothelioma-related markers in thymic carcinoma and thymoma may be helpful in avoiding confusion with malignant mesothelioma and pulmonary carcinoma, both of which are major differential diagnoses in this location. Accordingly, in the present study we examined the expression of calretinin, mesothelin, cytokeratin (CK) 5/6, thrombomodulin, HBME-1, Wilms' tumor-1 (WT-1), Ber-EP4, MOC-31, BG-8, B72.3, carcinoembryonic antigen (CEA), CD15, thyroid transcription factor-1 (TTF-1), p63, and CD5 in 22 thymic carcinomas and 35 thymomas, and compared the results with those of malignant mesothelioma and pulmonary adenocarcinoma.

Around 1/3 of thymic carcinomas were positive for calretinin and/or mesothelin. Both thymic carcinomas and thymomas were frequently positive for CK 5/6. Immunoreactivity for HBME-1 was seen in 4 thymic carcinomas and 10 thymomas. Except for 1 thymic carcinoma being positive for WT-1, all other thymic carcinomas and thymomas were negative for WT-1 and thrombomodulin. None of the thymic carcinomas and thymomas expressed TTF-1. More than 70% of the thymic carcinomas were positive for Ber-EP4, BG-8, and CD15. The positive rates of MOC-31, B72.3, and CEA in thymic carcinomas were in the middle between those in mesothelioma and pulmonary adenocarcinoma. All thymic epithelial tumors revealed nuclear immunoreactivity for p63. Nine thymic carcinomas (41%) expressed CD5.

We found that a panel of positive p63, negative thrombomodulin, WT-1, and TTF-1 is most discriminatory for thymic epithelial tumors. Other mesothelial (calretinin and mesothelin) and epithelial (Ber-EP4, BG-8, and CD15) markers are less contributory in discerning thymic epithelial tumors due to their overlapping expression with malignant mesothelioma and pulmonary adenocarcinoma.

Given the complexity of the staining patterns among the different entities, proper immunohistochemical stainings should be selected and interpreted with caution, and correlated with clinicopathologic findings in the differential diagnoses of thoracic biopsy specimens.
CD70 Expression in Thymic Carcinoma

Tsunekazu Hishima, M.D.; Masashi Fukayama, M.D.; Yukiko Hayashi, M.T.; Takeshi Fujii, M.D.; Takayo Ooba, M.T.; Nobuaki Funata, M.D.; Morio Koike, M.D.

From the Department of Pathology, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan (T.H., Y.H., T.O., N.F., M.K.); Department of Pathology, School of Medicine, The University of Tokyo, Tokyo, Japan (M.F.); and the Department of Pathology, Jichi Medical School, Tochigi, Japan (T.F.).

Am J Surg Pathol 2000;24:742-746 Abstract quote

CD70, a type II transmembrane glycoprotein, is a member of the tumor necrosis factor (TNF) family that mediates the interaction between B- and T-lymphocytes. CD70 has been shown to be expressed by malignant lymphoma, especially Hodgkin's disease, and by nasopharyngeal carcinoma, both of which are frequently associated with Epstein-Barr virus (EBV).

In this study, we investigated the expression of CD70 in epithelial cells of various types of thymic epithelial tumors and its association with EBV. Immunohistochemical expression of CD70 was studied on frozen tissue.

In a series of 27 thymic epithelial tumors, including thymic carcinomas (n = 8), atypical thymomas (n = 5), thymomas (n = 13), and thymic carcinoid (n = 1), 7 (88%) thymic carcinomas and 1 (20%) atypical thymoma showed positive immunoreactivity for CD70, whereas CD70 was not detected in other tumors. Twenty-four intrathoracic malignant epithelial tumors of nonthymic origin, including lung (n = 17), esophagus (n = 5), and mesothelium (n = 2), showed no immunoreactivity for CD70. Northern blot analysis also revealed that CD70 messenger RNA was expressed in 2 of 2 thymic carcinomas, 0 of 2 atypical thymomas, and 0 of 2 thymomas. All of the 27 thymic epithelial tumors were EBV-negative as assessed by EBV-encoded small RNA in situ hybridization.

The expression of CD70 is closely related to the pathogenesis of thymic carcinoma but unrelated to EBV infection in the thymus.

Clinicopathologic significance of intrathyroidal epithelial thymoma/carcinoma showing thymus-like differentiation: a collaborative study with Member Institutes of The Japanese Society of Thyroid Surgery.

Department of Surgery, Kuma Hospital, Kobe, Japan.


Am J Clin Pathol. 2007 Feb;127(2):230-6. Abstract quote

Intrathyroidal epithelial thymoma (ITET)/carcinoma showing thymus-like differentiation (CASTLE) is a rare malignant tumor having histopathologic features similar to those of squamous cell carcinoma of the thyroid and other organs and a more favorable prognosis. It is thought to originate from ectopic thymic tissue or embryonic thymic rest in or adjacent to the thyroid.

We investigated clinicopathologic features of 25 cases of ITET/CASTLE. The sensitivity and specificity of the pathologic diagnosis of ITET/CASTLE by immunohistochemical staining with CD5, a marker of carcinoma of thymic origin, were 82% and 100%, respectively. The 5- and 10-year cause-specific survival rates were 90% and 82%, respectively. Nodal metastasis and tumor extension predict a worse prognosis. Of 22 patients who had curative surgery, 10 (45%) underwent adjuvant radiation therapy, and no locoregional recurrence was seen in any of them. This is the first study demonstrating the survival curve for patients with ITET/CASTLE.

Our findings suggest that curative resection followed by radiation therapy may effectively prevent locoregional recurrence and CD5 immunostaining is useful for diagnosing ITET/CASTLE.

Giant cell tumor of rib masquerading as thymoma: a diagnostic pitfall in needle core biopsy of the mediastinum.

Volmar KE, Sporn TA, Toloza EM, Martinez S, Dodd LG, Xie HB.

Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Arch Pathol Lab Med. 2004 Apr;128(4):452-5. Abstract quote

Giant cell tumor of bone is rarely seen in the rib, where it may present as a mediastinal mass. The diagnosis of giant cell tumor of bone is generally straightforward by fine-needle aspiration or needle core biopsy, but sampling problems may lead to confusion with other neoplasms or inflammatory processes.

Here, we report a case of giant cell tumor of rib presenting as a mediastinal mass in a 36-year-old man. Because of inadequate sampling and inaccurate clinical information, the tumor was initially mistaken for thymoma. When the mass failed to respond to conventional chemotherapy, additional tissue was obtained and a giant cell tumor was diagnosed. Consequently, definitive therapy was delayed.

The case illustrates an important diagnostic pitfall in the biopsy of mediastinal masses.
Flow Cytometry in the Differential Diagnosis of Lymphocyte-Rich Thymoma From Precursor T-Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma

Shiyong Li, MD, PhD, Jonathan Juco, MD, Karen P. Mann, MD, PhD, and Jeannine T. Holden, MD
Am J Clin Pathol 2004;121:268-274 Abstract quote

We compared the antigen expression profile of thymocytes in lymphocyte-rich thymoma with that of precursor T-cell acute lymphoblastic leukemia/ lymphoblastic lymphoma (T-cell ALL/LBL) cells using 4-color flow cytometry. In all 15 thymoma cases, the thymocytes demonstrated 3 distinct subpopulations. The least mature cells (double-negative) expressed low-density CD2 and CD5, high-density CD7, CD10, CD34, and heterogeneous CD4 and CD8.

They had the lowest density CD45 expression and were surface CD3–. The immature cells (double-positive) expressed CD2, CD5, CD7, CD4, CD8, heterogeneous surface CD3, and intermediate-density CD45. They were CD10– and CD34–. The mature cells (single-positive) expressed CD2, surface CD3, CD5, CD7, and CD4 or CD8. The heterogeneous expression of surface CD3, CD4, and CD8 also created a characteristic smearing pattern for these antigens. In all 15 T-cell ALL/LBL cases, the lymphoblasts formed a tight cluster without discrete subpopulations or smearing pattern. Of 5 double-negative cases, 4 demonstrated loss of CD2, CD10, or CD34 expression. Of 7 double-positive cases, 5 showed complete loss of surface CD3, CD2, and/or CD5; 4 were CD10+; and 2 were CD34+. Of 3 single-positive cases, 2 showed loss of CD2 and/or aberrant expression of CD34.

Analysis of antigen expression pattern, the presence or absence of T cell–associated antigen deletion, and the expression of CD10 and CD34 by 4-color flow cytometry can help differentiate thymoma from T-cell ALL/LBL.
Low-Grade Serous Carcinoma of the Ovary Metastatic to the Anterior Mediastinum Simulating Multilocular Thymic Cysts: A Clinicopathologic and Immunohistochemical Study of 3 Cases.

Moran CA, Suster S, Silva EG.

From the *Department of Pathology, M. D. Anderson Cancer Center, Houston, TX; and daggerDepartment of Pathology, Ohio State University, Columbus, OH.
Am J Surg Pathol. 2005 Apr;29(4):496-499. Abstract quote  

Three cases of serous borderline tumors of the ovary with areas of serous low-grade carcinoma metastatic to the anterior mediastinum simulating multilocular thymic cysts are presented. The patients are women between the ages of 33 and 50 years. The 3 women had a prior history of primary ovarian neoplasms diagnosed over a period ranging from 3 to 20 years; the 3 patients were in stages IIIA, IIIB, and III. Follow-up radiologic examination revealed the presence of an anterior mediastinal tumor. The 3 patients underwent surgical resection of the mediastinal tumor. Grossly, the mediastinal tumors measured from 7 to 9 cm in greatest diameter and were described as cystic with solid areas. Focal areas of hemorrhage were present, but frank necrosis was not identified.

Histologically, all the tumors basically showed similar histopathologic features, namely, those described in multilocular thymic cysts, ie, cystic structures lined by either squamous or low cuboidal epithelium, lymphoid hyperplasia, cholesterol cleft granulomas, and remnants of thymic tissue. In addition, within the cystic structures, there was a neoplastic cellular proliferation with papillary architecture, nuclear atypia, and scattered mitotic figures. Immunohistochemical studies for keratin, MOC31, and CA-125 showed positive staining in tumor cells while placental-like alkaline phosphatase was negative.

Two patients remain alive and well after follow-up ranging from 6 to 18 months and 1 patient died of tumor 18 years after initial diagnosis.



Correlation of the WHO Schema for the Classification of Thymic Epithelial Neoplasms With Prognosis: A Retrospective Study of 90 Tumors.

Chalabreysse L, Roy P, Cordier JF, Loire R, Gamondes JP, Thivolet-Bejui F.


Am J Surg Pathol 2002 Dec;26(12):1605-11 Abstract quote

A series of 90 thymic epithelial tumors were reviewed and classified by histopathologic characteristics into the three major categories (A, B, and C) recognized by the WHO schema. Each tumor type was correlated with patient characteristics and clinical data (age, sex, presence of myasthenia gravis, tumor size and invasiveness, and completeness of resection), and with outcome (survival, recurrence, and metastasis).

All tumors were categorized by the WHO schema. Myasthenia gravis was present in 32 patients, mostly young and with type B thymic epithelial tumors. Tumors were invasive in 56% of cases, but resection was total in 67% of patients and only partial in the rest. Five factors were shown by univariate analysis to be associated with a favorable prognosis: presence of myasthenia gravis (p = 0.0389), younger age (p = 0.0022), completeness of resection (p = 0.0001), noninvasiveness (p = 0.0138), and tumor type A or B, as opposed to type C (p = 0.0001).

Prognosis for types A and B was not significantly different, suggesting that the subtypes of types A and B thymic epithelial tumors should be regarded as a morphologic continuum rather than as distinct histologic variants.

Invasive tumors associated with different WHO histologic subtypes:
Am J Surg Pathol 2001;25:103-110

Expression of matrix metalloproteinases 2 and 7 in tumor cells correlates with the World Health Organization classification subtype and clinical stage of thymic epithelial tumors.

Takahashi E, Tateyama H, Akatsu H, Fukai I, Yamakawa Y, Fujii Y, Eimoto T.

Department of Pathology, Nagoya City University Medical School, Aichi, Japan.

Hum Pathol. 2003 Dec;34(12):1253-8 Abstract quote.  

To investigate the roles of matrix metalloproteinases (MMPs) in thymic epithelial tumors, we examined the expression of MMP-2, -7, and -9; membrane-type 1 (MT1)-MMP; and tissue inhibitor of metalloproteinase-2 (TIMP-2) in 57 tumors by immunohistochemistry and in selected 15 cases by in situ hybridization.

The tumors consisted of 5 type A, 12 type AB, 11 type B1, 11 type B2, 9 type B3, and 9 type C thymomas according to the World Health Organization histologic classification system and of 22 stage I, 13 stage II, 8 stage III, and 14 stage IV thymomas according to the Masaoka staging system. In the positive cases, MMPs and TIMP-2 were expressed in both tumor cells and stromal cells. The cellular localization of MMPs detected by immunohistochemistry was almost identical with that of the mRNA signals detected by in situ hybridization. MMP-2 and MMP-7 were predominantly expressed in type B3 thymoma and type C thymoma, respectively. Expression of MT1-MMP and TIMP-2 correlated with that of MMP-2, indicating a proteolytic activation of the latter. MMP-9 was prominent in type B2 thymoma. Expression in tumor cells of MMP-2 or MMP-7 was also correlated with clinical stage.

The present study suggests that certain MMPs may play an important role in the tumor progression of different subtypes of thymic epithelial tumors and that MMP-2 and MMP-7 may contribute to the tumor aggressiveness and malignant potential.
RECURRENCE Local recurrence following surgery:
Less than 2% of patients who have surgery for encapsulated lesions
20% to 40% of those who had surgery for invasive disease

Am J Surg Pathol 2001;25:103-110

Study of 146 tumors
6 recurrent or metastatic tumors, all type B2 tumors

TREATMENT Surgical removal is adequate treatment for benign thymomas
Malignant thymomas (Thymic carcinomas)

Surgical removal with en bloc resection for invasive tumors

Preoperative radiation appears to offer no major survival advantage

Postoperative adjuvant radiation therapy is recommended for those patients with the invasive form of thymoma

Concomitant hypogammaglobulinemia or red cell aplasia occurs in a few patients and myasthenia gravis is also common

The multimodality treatment of thymic carcinoma.

Lucchi M, Mussi A, Basolo F, Ambrogi MC, Fontanini G, Angeletti CA.

Cardiac and Thoracic Department, Division of Thoracic Surgery, University of Pisa, Pisa, Italy.

Eur J Cardiothorac Surg 2001 May;19(5):566-9 Abstract quote

OBJECTIVES: Thymic carcinoma is a rare neoplasm more invasive and with a poorer prognosis than ordinary thymoma. Complete curative resection is sometimes not possible, but good response rates to chemotherapy are reported in literature. We report our experience with seven cases of thymic carcinoma, who took part to a multimodality treatment including neoadjuvant chemotherapy, surgery and post-operative radiotherapy in our center.

METHODS: Since June 1989, seven previously untreated patients were enrolled. The primary chemotherapy consisted of three courses of cisplatin (P; 75 mg/m(2) i.v., day 1), epidoxorubicin (E; 100 mg/m(2) i.v., day 1) and etoposide (VP16; 120 mg/m(2) i.v., days 1, 3 and 5), every 3 weeks. Surgery was performed following complete hematological recovery. After surgery, all patients underwent radiation therapy to the tumor areas, operatively marked with clips, at doses of 45 (complete resection) or 60 Gy (incomplete resection).

RESULTS: The pre-operative diagnosis of thymic carcinoma was performed in four cases by a mediastinotomy, and in the remaining cases, by an ultrasound-guided (n=2) or a computed tompography-guided (n=1) fine needle aspiration. All patients responded (one completely) to the chemotherapy regimen. Surgical resection was complete in four cases (histological examination negative in one case). Three patients are still alive and well (62-136 months from the diagnosis), two are alive with relapse at 16 and 85 months, one patient died at 86 months from another cause, and one patient died at 18 months from local relapse and lung metastases.

CONCLUSIONS: A pre-operative shrinkage of the thymic carcinoma by means of neoadjuvant multi-drug chemotherapy may improve the resectability, and therefore, the survival rate. Our experience, although preliminary, is encouraging and merits additional study in a multicenter trial with a sufficient number of patients to draw definitive conclusions.

RADIATION THERAPY Individual patients whose disease is considered unresectable can still achieve long-term survival with radiation therapy alone in some instances, but high doses of carefully planned radiation therapy are necessary

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