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Mediastinum

Thymoma and related entities

Thymoma classification


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 24 March 2013, last major update December 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See also these types below: A, AB, B1, B2, B3, microthymoma, nodular hyperplasia

WHO Classification
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A: also called epithelial, spindle cell, medullary; atrophic, mimics adult thymus; homogenous population of neoplastic epithelial cells with spindle/oval shape, no nuclear atypia, and accompanied by few or no non-neoplastic lymphocytes
AB: mixed thymoma; tumor in which foci having the features of type A thymoma are mixed with foci rich in lymphocytes; the segregation of the two patterns can be sharp or indistinct (Am J Surg Pathol 1999;23:955)
B: bioreactive, resembles thymus in fetus and infant
B1: lymphocyte rich; resembles normal functional thymus by combining large expanses having normal thymic cortical areas with those resembling thymic medulla
B2: cortical; neoplastic epithelial component appears as scattered plump cells with vesicular nuclei, distinct nucleoli; heavy population of lymphocytes, perivascular spaces are common
B3: epithelial cells with round/polygonal shape and mild atypia, mixed with minor component of lymphocytes; foci of squamous metaplasia and perivascular spaces common
C: thymic carcinoma


Table

● World Health Organization histologic classification has some prognostic value (Int J Surg Pathol 2009;17:255, Hematol Oncol Clin North Am 2008;22:543, J Cardiovasc Surg (Torino) 2006;47:89), although interobserver variation is common (Histopathology 2008;53:483) and other problems exist ((Semin Diagn Pathol 2005;22:188)

Suster and Moran classification
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● References: Am J Clin Pathol 2006;125:542

Favorable prognostic categories: Groups I-III
Group I
  Encapsulated or minimally invasive thymoma
  Completely excised
  Equivalent to WHO histologic types A, AB, B1, B2

Group II
  Encapsulated or minimally invasive thymoma
  Completely excised
  Equivalent to WHO histologic type B3

Group III
  Widely invasive thymoma or thymoma with implants
  Completely excised
  All histologic types

Unfavorable prognostic categories: Groups IV-VI
Group IV
  Widely invasive thymoma or thymoma with implants
  Incompletely excised
  All histologic types

Group V
  Widely invasive thymoma with or without intrathoracic metastases
  Unresectable/biopsy only
  All histologic types

Group VI
  Widely invasive thymoma with distant metastases
  Unresectable/biopsy only
  All histologic types

Clinical features
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● All thymomas have the potential to become invasive tumors (Am J Clin Pathol 2012;137:444)
● The histopathological spectrum and clinical profile of thymic neoplasms (Indian J Pathol Microbiol 2006;49:1)
● Although much emphasis in recent years has been placed on the histological classification of thymoma, the bulk of the evidence continues to point to clinical staging as the most important parameter for prognostication (J Clin Pathol 2006;59:1238)
● Thymus cancer symptoms, diagnoses, and clinical staging (Biol 345 - Immunology)

Prognostic factors
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● Must distinguish types with benign behavior (A, AB, B, B1, B2) from those with atypical behavior (B3, Ann Thorac Cardiovasc Surg 2005;11:367) and those that are cytologically malignant (type C, also called thymic carcinoma Am J Surg Pathol 2002;26:1605)

Positive stains
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● p63 (also normal thymus, Am J Clin Pathol 2007;127:415)


WHO type A

General
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● Also called spindle cell thymoma
● Rosai believes composed of nonfunctional, postmature thymic epithelial cells that match epithelial cells of involuted thymus in adult life, not cortical or medullary cells

Clinical features
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● May have papillary and pseudopapillary features (Am J Surg Pathol 2011;35:372), adenomatoid like appearance with signet ring cell morphology (Am J Surg Pathol 2010;34:1544)
● May be associated with hematologic malignancies

Prognostic factors
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● Excellent prognosis

Gross description
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● Usually encapsulated or minimal capsular invasion

Gross images
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Well circumscribed with lobulated cut surface

Micro description
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● Epithelial predominant with fusiform epithelial tumor cells
● Gland like spaces, storiform patterns are common
● No / rare lymphocytes
● May have atypical features (Am J Surg Pathol 2012;36:889)
● Either short-spindled (57%), long-spindled (31%) or micronodular (12%) (Am J Surg Pathol 2001;25:111)
Desmoplastic spindle cell thymoma: extensive areas of young fibrocollagen and prominent fibroblastic proliferation with scattered areas of more conventional spindle cell thymoma (Hum Pathol 2013;44:623)
● Histologic features may not correlate with invasion or encapsulation because all thymomas may be capable of invasion (Am J Clin Pathol 2010;134:793)

Short-spindled:
● 57%, often in hemangiopericytic or microcystic pattern
● Epithelial cells often CD20+

Long-spindled:
● 31%, fibroblast-like epithelial cells resembling fibrohistiocytic neoplasms
● Epithelial cells often CD20+

Micronodular:
● 12%, small nests of short spindle cells without atypia in lymphoid stroma with frequent germinal centers
● No mitotic activity; epithelial cells are CAM5.2+, keratin+, CD20-
● Often incidental findings on chest Xray or at coronary artery bypass surgery
● Not associated with autoimmune disorders

Micro images
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Various images

Thymic epithelial cells without atypia

A: bland spindled epithelial cells with occasional small T cells

A: spindle epithelial cells (arrows) with lymphocytes (arrowheads)

Rosette-like structures mimicking a neuroendocrine neoplasm
Invasive spindle cell thymoma

Negative stains
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● CD5 (in epithelial cells)


WHO type AB

Micro images
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Various images

AB: immature T cells and scattered large, round thymic epithelial cells

AB: A (asterisk) and B (star) type lobules


WHO type B1

General
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● Also called lymphocyte predominant

Micro description
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● 2/3 or more small lymphocytes
● Lymphocytes efface thymic architecture
● Thick fibrous capsule present, also fibrous septae that intersect at acute angles
● Lymphocytes have folded nuclei (T cells) and mitotic figures
● Lymphocytes mixed with bland thymic epithelial cells, may have perivascular serum “lakes”, mast cells and focal medullary differentiation with loose aggregates of lymphocytes resembling thymic medulla

Micro images
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Case of Week #99


CD3

CD20

Keratin

CD68

Various images

B1: immature T cells (arrows), epithelial tumor cells with large nuclei (arrowheads)

Positive stains
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● Keratin demonstrates finely arborizing network of interconnecting epithelial cell processes
● T cells: CD1, CD2, CD3, CD99, BCL2, TdT

Electron microscopy description
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● Well-formed intercellular junctions between epithelial cell processes, numerous tonofilaments

Differential diagnosis
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Burkitt lymphoma: HIV+, different nuclear histology
Castleman disease: not centered in thymus, “onion-skinning” by lymphocytes, either fibrohyaline or plasma cell subtypes
Lymphoblastic lymphoma: usually teens/young adults, similar staining except negative for keratin, but beware of positive staining of trapped epithelial cells
● Thymic lymphoid hyperplasia: normal cortical and medullary glandular distinction is maintained, well-formed germinal centers present, does not produce a mass


WHO type B2

Micro images
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Various images

B2: abundant epithelial cells with irregular nuclei (arrowheads) and fewer lymphocytes (arrows) than B1


WHO type B3

Micro images
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Various images

B3: perivascular spaces, sheets of large polygonal epithelial cells with nuclear atypia, few lymphocytes

B3: polygonal epithelial cells (arrows) with irregular nuclei

Microthymoma

General
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● Incidental small thymomas, not grossly evident, morphologically identical to conventional B1/B2 thymoma (Am J Surg Pathol 2005;29:415)
● May represent early phase of thymoma development

Micro description
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● Ovoid epithelial cells with pale nuclei and distinct nucleoli, in background of small lymphocytes
● Foci of medullary differentiation and perivascular spaces present


Nodular hyperplasia of thymic epithelium

General
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● Nodular epithelial proliferations in normal sized or enlarged glands removed from adults for myasthenia gravis or as incidental findings during coronary bypass surgery (Indian J Pathol Microbiol 2011;54:539)
● Also called microthymoma, but epithelium have reactive, not thymoma-like appearance

Case reports
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● Two cases (Pathology 2006;38:586)

Micro description
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● Nodular aggregates of bland cells subdivided by fibrous bands

End of Mediastinum > Thymoma and related entities > Thymoma classification


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