Thymoma



Thymoma











Schematic representation of the chest cavity shows a round to ovoid, well-circumscribed thymoma in the anterior mediastinal compartment on top of the pericardium and protruding onto the left hemithorax.






Gross appearance of bisected thymoma shows a well-circumscribed, fleshy, lobulated mass composed of tan-white, homogeneous rubbery tissue with focal areas of congestion and hemorrhage.


TERMINOLOGY


Synonyms



  • Primary thymic epithelial neoplasm


Definitions



  • Primary thymic epithelial neoplasm composed of thymic epithelial cells admixed in varying proportions with immature T-lymphocytes


ETIOLOGY/PATHOGENESIS


Pathogenesis



  • Unknown


  • Close association with myasthenia gravis and other autoimmune disorders


CLINICAL ISSUES


Presentation



  • Chest pain


  • Shortness of breath


  • Paraneoplastic syndrome (myasthenia gravis, hypogammaglobulinemia, pure red cell aplasia, etc.)


  • Superior vena cava syndrome


  • Asymptomatic in up to 30% of cases


  • Incidental finding on routine chest x-ray or during coronary artery bypass surgery


Natural History



  • Majority of thymomas are very low-grade malignant neoplasms with generally indolent behavior


  • Size and status of capsular integrity are 2 important determinant factors for prognosis


  • Invasive tumors are associated with more aggressive behavior


  • Incompletely excised tumors have tendency to recur locally and spread along chest cavity


  • Recurrences can take place many years after initial resection (i.e., > 10-15 years)


  • Most common sites for metastases are lung, pleura, and thoracic lymph nodes


  • Extrathoracic metastases are extremely rare (< 2% of cases)


Treatment



  • Complete surgical excision for noninvasive tumors


  • Radiation therapy for incompletely resected tumors


  • Surgical excision + postoperative radiation therapy for invasive tumors


  • Repeat surgical excision + radiation for recurrent tumors


  • Combination chemotherapy for advanced stage and metastatic tumors


  • Best chance for cure is complete surgical excision with negative margins


Prognosis



  • Most important prognostic factor is clinical staging (Koga modified Masaoka scheme)


  • 80-90% survival at 15 years with stages I and II


  • 70% survival at 15 years with stage III


  • 60% survival at 5 years with stage IV


  • Stages I and II include infiltration of capsule and minimal invasion of perithymic fat (collectively regarded as “noninvasive” tumors; confined to anterior mediastinum)


  • Stages III and IV include infiltration of adjacent or neighboring structures, implants, and distant metastases (collectively regarded as “invasive”)


IMAGE FINDINGS


General Features



  • Best diagnostic clue



    • Smooth or lobulated anterior mediastinal mass


  • Location



    • Generally anterior mediastinum



    • May also occur in posterior mediastinum


    • May arise ectopically in pulmonary hilum, pleura, or head and neck


  • Size



    • Usually between 4-15 cm


Radiographic Findings



  • Round or oval anterior mediastinal mass


  • Usually centered over heart; best seen on lateral view


  • Linear and peripheral calcifications in capsule (10% of patients)


MR Findings



  • T1WI: Isointense relative to muscle


  • T2WI: Hyperintense, approaching that of fat


CT Findings



  • CECT best imaging tool for thymoma


  • Oval or lobulated mass within anterior mediastinum


  • Homogeneous enhancement is common in small tumors


  • Heterogeneous enhancement more common in large tumors


  • Thin and linear calcifications seen within capsule in 1/3 of patients


  • Cystic changes and necrosis common in larger tumors


  • Obliteration of mediastinal fat planes or mediastinal structures seen in invasive tumors


MACROSCOPIC FEATURES


General Features



  • Generally well-circumscribed, encapsulated, solid tumor


  • Homogeneous tan-white, rubbery tissue on cut surface


  • Lobulated cut surface


  • May be cystic and multilocular


  • May contain calcifications in capsule or within tumor


  • Rarely can be multifocal


  • Can be ectopically located in posterior mediastinum, lung, neck, or pleura


  • Can show areas of necrosis and hemorrhage


  • Invasive tumors usually compromise adjacent structures, including large vessels, pericardium, pleura


  • Distant metastases are rare


Sections to Be Submitted



  • At least 1 section per cm of greatest tumor diameter


  • Take additional sections if tumor shows variegated appearance


  • Sample solid areas in cyst walls in multicystic tumors


  • Always include sections of inked outer surface of specimen


  • Coordination with surgeon should be sought to establish “true” margins to be sampled


  • Any structures attached to specimen (i.e., pleura, lung, large vessels) should be inked and sampled separately as they represent “true” margins


MICROSCOPIC PATHOLOGY


Histologic Features



  • Histologic classification is controversial


  • Currently 2 systems are in use: Suster & Moran classification and WHO classification


  • Suster & Moran classification: Based on degree of organotypical differentiation, divided into 3-tiered system



    • Well-differentiated (thymoma)


    • Moderately differentiated (atypical thymoma)


    • Poorly differentiated (thymic carcinoma)


  • WHO classification is based primarily on cell type, cytologic atypia, and proportion of lymphocytes to epithelial cells



    • WHO type A: Composed of spindle cells without cytologic atypia


    • WHO type AB: Composed of spindle cells admixed with abundant lymphocytes


    • WHO type B1: Composed of round, epithelioid cells admixed with abundant lymphocytes


    • WHO type B2: Composed of round, epithelioid cells admixed with equal amounts of lymphocytes


    • WHO type B3: Composed predominantly of epithelial cells with cytologic atypia



  • WHO classification has a series of other distinctive histologic types that do not fit into the standard categories



    • “Metaplastic” thymoma


    • Multifocal thymoma


    • Microscopic thymoma


    • Micronodular thymoma


    • Anaplastic thymoma


  • Older (“traditional”) classification by Bernatz et al from Mayo Clinic is still used today by many and divides these tumors based on their cell composition



    • Lymphocyte-rich thymoma


    • Mixed, lymphoepithelial thymoma


    • Epithelial-rich thymoma


    • Spindle cell thymoma


Cytologic Features



  • 2 basic cell types are recognized



    • Oval/spindle cells (types A, AB)


    • Round/epithelioid cells (types B1-3)


  • Type A thymoma is composed of oval or spindle cells with scattered nuclear chromatin and inconspicuous or absent nucleoli and no mitotic activity



    • Spindle cell thymoma usually contains few lymphocytes


    • Majority of spindle cell thymomas are low grade and encapsulated


    • Invasive or atypical spindle cell thymoma can follow aggressive behavior


    • Distant metastases and death can occur in some cases of spindle cell thymoma


  • Type AB thymoma is composed of oval or spindle cells identical to those in type “A” but admixed with abundant small lymphocytes.



    • Spindle cells do not display mitotic activity


    • Lymphocytes admixed with epithelial cells are of T-cell type


    • Tumors usually contain admixture of lymphocyte-rich and lymphocyte-poor areas


    • Tumors may be composed exclusively of lymphocyte-rich areas and be confused for B1 thymoma


  • Type B1 thymoma is composed of round/epithelioid cells with single small eosinophilic nucleoli and abundant cytoplasm, admixed with numerous small T-lymphocytes



    • Small lymphocytes predominate and overshadow epithelial cells


    • Contains frequent perivascular spaces and areas of “medullary” differentiation


    • Equivalent to “lymphocyte-rich” or “lymphocytepredominant” in traditional classification (Mayo Clinic)


  • Type B2 thymoma is composed of approximately equal admixture of round epithelial cells and small lymphocytes



    • Epithelial cells may show mild degree of atypia and enlargement of nuclei


    • Admixtures with B1 areas may be seen in about 30% of cases


    • Equivalent to “mixed lymphoepithelial” thymoma of traditional classification (Mayo Clinic)


  • Type B3 thymoma is composed of sheets of large epithelioid cells admixed with scant lymphocytes



    • Epithelial cells are characterized by nuclear enlargement with dense chromatin pattern and prominent nucleoli


    • Mitotic figures can be encountered in epithelial cells


    • Cell nuclei show tendency to adopt raisin-like configuration


    • Cytoplasm of tumor cells is usually abundant, eosinophilic, and with sharp cell borders


    • Tendency for epithelial cells to palisade around perivascular spaces


    • Tumor cells can also be oval or spindle with similar nuclear features


  • Type A thymomas may exhibit unusual growth patterns



    • Hemangiopericytic growth pattern


    • Micronodular growth pattern with lymphoid B-cell hyperplasia


    • Biphasic pattern with pseudosarcomatous stroma (“metaplastic” thymoma)


    • Skin adnexal-like (“adenoid”) growth pattern


    • Sclerosing growth pattern


    • Rosette-forming growth pattern


  • Type B thymomas may exhibit unusual features



    • Extensive multilocular thymic cyst-like changes


    • Areas of infarction, hemorrhage, and necrosis


    • Massive infiltration by plasma cells in stroma


    • Clear cell changes


    • “Starry sky” appearance simulating lymphoma


  • Type C thymoma (thymic carcinoma) is characterized by overt cytologic evidence of malignancy and absence of organotypical features of thymic differentiation



    • Diagnosis of exclusion


    • Requires demonstration of absence of tumor elsewhere clinically and radiographically


Lymphatic/Vascular Invasion



  • Very rare; unknown significance but generally associated with worse prognosis


Margins



  • Very difficult to determine without assistance of surgeon


  • True resection margins need to be inked or tagged by surgeon before submitting to pathology


  • Inked anterior surface does not represent “margin” unless it was invading at time of surgery


  • True margins need to be inked for proper assessment


Lymph Nodes



  • Thymoma rarely metastasizes to lymph nodes


  • Majority of lymph node metastases in thymoma are to mediastinal nodes


  • Other intrathoracic lymph nodes may also be involved more rarely by metastatic thymoma


DIFFERENTIAL DIAGNOSIS


Lymphoblastic Lymphoma



  • Does not show scattered keratin-positive cells admixed with the immature T-lymphocytes



  • Shows rapid growth with sudden onset of symptoms



    • Thymoma is slow-growing tumor with slowly progressive symptoms


  • Most common age for lymphoblastic lymphoma is childhood and adolescence



    • Most common age for thymoma is in middle-aged adults; rare in children and adolescents


Acquired Multilocular Thymic Cyst



  • Multilocular cysts do not contain discrete areas attached to walls of cysts showing typical type B thymoma



    • Type A thymoma can undergo massive cystic changes, but the cells lining the cysts are spindle cells


  • Shows small cuboidal or squamous epithelial cells lining the cysts in continuity with dilated Hassall corpuscles


  • Shows prominent lymphoid follicular hyperplasia and severe acute and chronic inflammation with cholesterol cleft granulomas


Hemangiopericytoma/Solitary Fibrous Tumor



  • Spindle cells in solitary fibrous tumors are not keratin-positive


  • Spindle cells in solitary fibrous tumor are CD34, Bcl-2, and CD99 positive


  • Shows characteristic linear pattern of stromal collagenization resulting in deposition of rope-like collagen separating spindle cells


  • Devoid of immature T cells



    • Spindle cell thymoma may contain variable number of immature T cells admixed with epithelial cells


Neuroendocrine Carcinomas



  • Positive for neuroendocrine markers



    • Rosette-like structures in thymoma are only positive for cytokeratin


  • Thymic carcinoids usually show increased mitotic activity and tumor cells necrosis


  • Tumor cells in carcinoids show characteristic stippled (“salt and pepper”) chromatin pattern


  • Other features of thymic carcinoids include a nested growth pattern (“zellballen”) and formation of trabeculae, ribbons, and festoons


DIAGNOSTIC CHECKLIST


Clinically Relevant Pathologic Features



  • Encapsulation/circumscription


  • Presence or absence of cytologic atypia in epithelial cells


  • Size of tumor


  • Clinical stage


  • Presence or absence of myasthenia gravis


Pathologic Interpretation Pearls

Jul 9, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Thymoma

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