Mediastinum
Thymoma
Thymoma

Editor-in-Chief: Debra Zynger, M.D.
Anja C. Roden, M.D.

Topic Completed: 7 January 2020

Minor changes: 20 February 2020

Copyright: 2003-2020, PathologyOutlines.com, Inc.

PubMed Search: Thymoma mediastinum[TI] pathology

Anja C. Roden, M.D.
Page views in 2019: 17,618
Page views in 2020 to date: 19,670
Cite this page: Roden AC. Thymoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/mediastinumthymoma.html. Accessed September 23rd, 2020.
Definition / general
  • Malignant epithelial tumor of the thymic gland
  • Lobulated architecture
Essential features
  • Malignant
  • Lobulated architecture comprised of cellular lobules intersected by fibrous bands
  • Neoplastic cells: epithelial cells
  • Thymocytes are reactive
  • Prognostic parameters
    • Stage
    • Completeness of resection
    • Morphology (as defined by WHO)
Terminology
  • Spindle cell predominant or medullary (now WHO type A)
  • Lymphocytic, organoid, lymphocyte rich or predominantly cortical (now WHO type B1)
  • Mixed epithelial cell and lymphocyte or cortical (now WHO type B2)
  • Epithelial or atypical thymoma (WHO type B3)
ICD coding
  • ICD-11:
    • 2C27 - malignant neoplasm of thymus
    • XH3734 - Thymoma, NOS
    • XH6WN9 - WHO type A thymoma
    • XH0JH0 - WHO type AB thymoma
    • XH66U8 - WHO type B1 thymoma
    • XH2G89 - WHO type B2 thymoma
    • XH4EW9 - WHO type B3 thymoma
    • XH6QN6 - Sclerosing thymoma
    • XH1GA4 - Intrapulmonary thymoma
Epidemiology
  • Most common solitary lesion in mediastinum and anterior mediastinum in adults (J Thorac Oncol 2019 Dec 20 [Epub ahead of print])
  • 1 - 5 / million population / year
  • Any age, peak 40 - 60 years of age (Mayo Clin Proc 1993;68:1110, J Thorac Oncol 2015;10:691)
  • M = F
  • 34 - 40% associated with paraneoplastic / autoimmune syndromes
    • Myasthenia gravis
    • Other neuromuscular syndromes / diseases (Lambert-Eaton myasthenic syndrome, myotonic dystrophy)
    • Autoimmune diseases (systemic lupus erythematosus, polymyositis, myocarditis, Sjögren syndrome, ulcerative colitis)
    • Endocrine disorders (Addison disease, hyperthyroidism)
    • Hematologic diseases (hypogamaglobulinemia, red cell aplasia, pancytopenia)
    • Aplastic anemia
    • Others (hypertrophic pulmonary osteoarthropathy) (Mayo Clin Proc 1993;68:1110)
    • Patients with thymoma and paraneoplastic / autoimmune syndrome - more commonly younger, female, smaller tumors, B2 or B3 subtype, lower stage, R0 resection (J Thorac Oncol 2018;13:436)
Sites
Etiology
  • Tumor cells originate from thymic epithelial cells
Clinical features
  • Malignant; can invade, recur, metastasize and rarely lead to death (J Thorac Oncol 2015;10:691)
  • May be incidental and asymptomatic (Mayo Clin Proc 1993;68:1110)
  • Symptoms
    • Due to compression of adjacent structures: shortness of breath, cough, wheezing, superior vena cava syndrome
    • Systemic: fever, weight loss
    • Due to paraneoplastic syndrome
Diagnosis
  • Suggested on chest Xray, confirmed by CT; possibly MRI
  • Pre-resection biopsy usually not performed or necessary, only if strong clinical suspicion of a tumor other than thymoma
Laboratory
  • None for thymoma
  • Acetylcholine receptor binding antibodies if myasthenia gravis
  • Possibly workup for other paraneoplastic / autoimmune syndromes if clinically suspicious
Radiology description
  • Chest Xray: usually ovoid or lobulated, smooth, well marginated mass, projecting over the mediastinum, more commonly protruding unilaterally (J Thorac Oncol. 2010;5:S296)
  • Chest CT: typically well defined, round or lobulated, homogeneous lesion that enhances after contrast injection; can be heterogeneous or cystic; used to evaluate for invasion
  • MRI increasingly utilized, specifically in differentiating thymoma from thymic cyst or thymic hyperplasia, to identify phrenic nerve involvement or to evaluate for invasion in patients with contraindication to iodinated contrast (Magn Reson Imaging Clin N Am 2015;23:165)
Radiology images

Contributed by Anja C. Roden, M.D.

WHO type A thymoma

Prognostic factors
Case reports
Treatment
  • Thymectomy with or without resection of adjacent structures depending on extent of tumor, whenever possible
  • Possibly neoadjuvant chemotherapy or radiation or postoperative chemotherapy or radiation depending on stage and involvement of margins
  • Immune checkpoint inhibitors are controversial, possibly contraindicated; clinical trials with PD-1 / PD-L1 inhibitors showed response rates of approximately 30% but high incidence of immune related adverse events (15 - 62.5%), some of which were severe (Mediastinum 2019;3:35)
  • Target therapies are poorly active or ineffective (Lung Cancer 2018;126:25)
Gross description
  • Lobulated
  • Grey-tan
  • Often encapsulated
  • Possibly with cystic changes
  • Sampling of perithymic lymph nodes important for staging
Gross images

Contributed by Anja C. Roden, M.D.

Smooth outer surface

Lobulated cut surface

Frozen section description
  • Lobulated neoplasm with fibrous bands and cellular lobules
  • Sometimes only a few fibrous bands present
  • Cellular lobules comprised of (i) a mixture of lymphocytes and large polygonal (epithelial neoplastic) cells, (ii) polygonal cells only without or only with a few lymphocytes or (iii) bland short spindle cells
  • Associated cyst(s) possible
  • Evaluation of margins: discussion with surgeon important to identify surgical margin
  • Invasion into adjacent structures (mediastinal pleura, pericardium, phrenic nerve, lung, great vessels among others)
Frozen section images

Contributed by Anja C. Roden, M.D.

Lobulated architecture

Abundant lymphocytes

Hassall corpuscle like elements

Surgical margin negative

Microscopic (histologic) description
  • Low magnification: lobulated architecture with cellular lobules and intersecting fibrous bands; usually at least partially encapsulated
  • High magnification: neoplastic epithelial cells (polygonal or spindled), various numbers of lymphocytes (thymocytes)
  • Sometimes associated with cyst(s) or focal cystic changes
  • Might be almost entirely necrotic
  • Morphologic classification according to WHO
    • Letters based on shape of neoplastic cells (A = spindled, B = polygonal)
    • Numbers in type B thymoma (B1 - B3) based on
      • Increase in ratio of neoplastic cells to thymocytes
      • Increase in cytologic atypia of neoplastic cells
      • Medullary islands more common in B1 than B2; absent in B3
    • Type A
      • Bland oval / spindled cells
      • Rare or no thymocytes
      • Various patterns: hemangiopericytoma-like vascular pattern, rosettes / pseudorosettes, microcystic changes
    • Atypical A
      • Same as A and focal
      • ≥ 4 mitoses/10 high power fields or
      • Coagulative tumor necrosis or
      • Hypercellularity
    • Type AB
      • Morphology of A+B1 or A+B2, components can be intermingled or separated
    • Type B1
      • Medullary islands (Hassall corpuscle-like elements, paler areas), scattered neoplastic cells (< 3 contiguous epithelial cells)
    • Type B2
      • Mixed neoplastic cells and thymocytes, medullary islands occasionally present
    • Type B3
      • Neoplastic cells
      • Rare or no thymocytes
    • Subtyping not recommended on biopsies because of potential heterogeneity
  • Uncommon thymomas:
    • Micronodular thymoma with lymphoid stroma: nodular appearance due to demarcated nodules or interlacing strands of neoplastic cells that are reminiscent of those of type A thymoma; background predominantly B cells with scattered secondary follicles; only scattered thymocytes
    • Microscopic thymoma: incidental; < 1 mm in greatest dimension; morphology usually of type A thymoma; no distinct capsule
    • Metaplastic thymoma: biphasic; neoplastic cells reminiscent of type A thymoma; stromal spindled cells
    • Sclerosing thymoma: extensive sclerosis with only focal cellular component; keratin and TdT might help in the diagnosis
Microscopic (histologic) images

Contributed by Anja C. Roden, M.D.

WHO type A thymomas, various patterns and variant

WHO type B2 thymoma


WHO type B3 thymoma

WHO type AB thymoma


WHO type B1 thymoma

Sclerosing and ossifying thymoma


Thymoma - core needle biopsy


Micronodular thymoma with lymphoid stroma

Microscopic thymoma

Metaplastic thymoma

Cytology description
  • Dual cell population: small lymphocytes and polygonal epithelial cells (isolated or clustered); possibly sheets of bland, elongated or spindled cells or polygonal epithelial cells
  • Subtyping is not recommended
Cytology images

Contributed by Anja C. Roden, M.D.

Cytology with corresponding core biopsy

Positive stains
  • Neoplastic epithelial cells:
    • Keratins: AE1/AE3, CAM5.2, CK7 - diffuse meshwork of neoplastic epithelial cells
    • Markers of squamous differentiation: p40, p63, CK5/6
    • Polyclonal PAX8 (monoclonal PAX8 usually negative)
    • BCL2 variable
    • TTF1 rare in type A thymoma, clone SPT24 > 8G7G3/1
  • Thymocytes: TdT, CD1a, CD99 (might be absent in types A, B3)
Negative stains
  • CK20 (some type A and AB thymoma can express)
Molecular / cytogenetics description
Features to report
  • Report of resection specimen should include:
    • Procedure
    • Morphology (WHO classification); all components with percentages (in 10% increments)
    • Margin status
    • Extent of invasion
    • Treatment effect if applicable
    • Pleural or pericardial implants if applicable
    • Metastases if applicable
    • Lymph node status
    • Pathologic tumor stage (pTNM stage; modified Masaoka stage)
    • Background thymic gland if present
Sample pathology report
  • Thymus, thymectomy:
    • WHO type B1 invading into lung (see synoptic report)
    • Surgical margins are negative by < 0.1 cm
    • 6 regional lymph nodes are negative
Differential diagnosis
  • Lymphoma / leukemia (e.g. T-lymphoblastic lymphoma / leukemia, small B cell lymphomas, T cell lymphomas, classic Hodgkin lymphoma):
    • No diffuse meshwork of keratin positive neoplastic cells
    • Effaced architecture in lymphoma versus lobulated architecture in thymoma
    • LMO2 expressed in neoplastic lymphoblasts of T-acute lymphoblastic leukemia (T-ALL) and absent in thymoma (Am J Clin Pathol 2016;145:180)
    • CD20 positive B cells in small B cell lymphomas; classic Hodgkin lymphoma can show lobulated architecture but is comprised of mixed chronic inflammation often with eosinophils and scattered large Reed-Sternberg cells and Hodgkin cells
  • Thymic carcinoma:
    • Distorted architecture with desmoplasia and often increased cytologic atypia
    • Increased Ki67 labelling index (> 14% of tumor cell nuclei staining) in a subset of thymic carcinomas but not thymoma (Hum Pathol 2015;46:17)
  • Metastatic carcinoma:
    • Distorted architecture, increased cytologic atypia
  • Benign thymic gland (e.g. thymic follicular hyperplasia, true thymic hyperplasia, sampling bias):
    • Lacks lobulated architecture and lacks the diffuse meshwork of keratin positive neoplastic cells (although there are keratin positive epithelial cells scattered throughout the benign thymic gland)
    • Usually intimately associated with adipose tissue without capsule
    • Lymphoid follicles in thymic follicular hyperplasia (caveat: can also be seen in micronodular thymoma with lymphoid stroma or on rare occasions in thymoma)
  • Thymic cyst:
    • Cyst with adjacent benign thymic parenchyma with or without chronic inflammation
  • Germ cell tumor (e.g. seminoma):
    • Usually morphology different, however, seminoma can have lymphoid hyperplasia, fibrous bands and remnant thymic tissue; immunostains are important
  • Thymic carcinoid tumor:
    • Might have morphologic similarities with type A thymoma; expresses neuroendocrine markers
  • Solitary fibrous tumor:
    • Might have morphologic similarities with type A thymoma; expresses STAT6, CD34
Board review style question #1

    A thymic tumor is shown here. What is the neoplastic cell in this tumor?

  1. Epithelial cell
  2. Histiocyte
  3. Lymphocyte
  4. Reed-Sternberg cell
  5. Thymocyte
Board review answer #1
A. In thymomas, epithelial cells are the neoplastic cells

Explanation: A few scattered benign histiocytes might be present in these tumors (B). Lymphocytes, which are predominantly thymocytes, are considered reactive (C). Although classic Hodgkin lymphomas can exhibit a lobulated architecture, usually they do not have so sharply demarcated fibrous bands. Reed-Sternberg cells or Hodgkin cells are not identified (D). Thymocytes are considered reactive in these tumors (E).

Reference: Thymoma

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Board review style question #2
    What is an important prognostic parameter in thymomas?

  1. Association with a cyst
  2. Male sex
  3. Presence of fibrous bands
  4. Surgical resection margin
  5. Thymic follicular hyperplasia
Board review answer #2
D. Complete resection is an important prognostic parameter in thymomas

Explanation: Cystic changes have no impact on prognosis (A). Sex is not associated with prognosis (B). The presence of fibrous bands is not associated with prognosis. (C). Thymic follicular hyperplasia in the background thymic gland has no prognostic implication (E).

Reference: Thymoma

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