Thymoma

IEditor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amr Marawan, M.D. [2] Ahmad Al Maradni, M.D. [3]

• Thymoma is a benign thymic neoplasm located in the anterior mediastinum, behind the sternum and in front of the great vessels that involutes during puberty, it takes part in lymphocytes maturation throughout adulthood.
• The incidence of thymoma is approximately 0.13 per 100,000 individuals.
• Thymic neoplasm can be divided into two major groups: thymoma and thymic carcinomathymoma
• Thymoma is the most common tumor of the anterior mediastinum, consisting of any type of thymic epithelial cell as well as lymphocytes that are usually abundant and probably not neoplastic.
• Thymoma usually is benign, and frequently encapsulated uncommon tumor, best known for its association with the autoimmune disorder such as myasthenia gravis. Thymoma is found in 15% of patients with myasthenia gravis.
• Once diagnosed, thymomas may be removed surgically. If left untreated thymoma may progress to invade the mediastinum and the surrounding structure.
• Depending on the stage of the tumor at the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as good.
• Common complications of the thymoma include the pressure effect of the mass itself, autoimmune diseases, and rarely, malignancy. Metastasis is extremely rare. In the rare case of a malignant tumor, chemotherapy may be used.
• Malignant lymphomas that involve the thymus, e.g., lymphosarcoma, Hodgkin’s disease (termed “granulomatous thymoma” in the past), should not be regarded as thymoma.
• Thymomas associated with autoimmune disorders usually are benign. Malignant thymomas can metastasize, generally to pleura, kidney, bone, liver, or brain.

• The thymic epithelial tumors staging was initially proposed by Bergh and his colleagues in 1978, modified by Wilkins and Castleman in 1979, and advanced by Masaoka et al. in 1981.

• In 1999, a World Health Organization (WHO) Working group suggested a non-committal terminology (Masaoka classification), preserving the distinct categories of the histogenetic classification, but using letters and numbers to designate tumour entities.
• Recently, it has been very well accepted as it provides an easy comparison of clinical, pathological and immunological studies.

• On gross pathology, well circumscribed mass, that is locally invasive is a characteristic finding of thymoma.
• On microscopic histopathological analysis, round cells, with ample vacuolated cytoplasms, and fat droplets are characteristic findings of thymoma.

• There are no established causes for thymoma.

Thymoma must be differentiated from other thymic diseases such as

• thymic carcinoma
• Thymic cyst
• Thymic hyperplasia
• germ cell tumors.

• The incidence of thymoma is approximately 0.13 per 100,000 individuals.
• Thymic neoplasms are the most common tumors located in the anterior mediastinum (20%).
• Incidence increases in middle age, and peaks in the seventh decade of life.
• Men and women are equally affected.

• There are no established risk factors for thymoma.

• If left untreated thymoma may progress to invade the mediastinum and the surrounding structure. Depending on the stage of the tumor at the time of diagnosis, the prognosis may vary.
• The prognosis is generally regarded as good.
• Common complications of the thymoma include the pressure effect of the mass itself, autoimmune diseases, and rarely, malignancy.

Symptoms of thymoma include

• muscle weakness
• cough
• wheezing
• dysphagia.

In addition to the symptoms of associated immune syndromes such as,

• anemia
• arthralgia
• skin rash.

Patients with thymoma usually appear asymptomatic. Physical examination of patients with thymoma is may be remarkable for,

• Neck lump,
• Facial swelling
• wheezing.

• Staging of thymic epithelial tumors was initially proposed by Bergh and his colleagues in 1978, modified by Wilkins and Castleman in 1979, and advanced by Masaoka et al. in 1981.
• Modified Masaoka staging grouped with TNM classification is the most widely adopted system for thymic epithelial tumors currently in use.

Laboratory findings associated with thymoma may include,

• Antibodies to the acetylcholine receptor,
• Abnormal electrolytes, renal, and liver function tests.

• On chest x-ray, thymoma is characterized by oval to rounded, well demarcated, asymmetric, homogeneous mass of soft tissue density on one side of the midline.

• Computed Tomography scan may be diagnostic of thymoma. The tumor is generally located inside the thymus, and can be calcified.
• Increased vascular enhancement can be indicative of malignancy, as can be pleural deposits.

• On thoracic MRI, thymoma is characterized by increased heterogenous signal on T2WI.

• Ultrasound is used to guide fine needle aspiration or core needle biopsy in patients with thymoma.

• PET scan may be used in the diagnosis of thymoma.

Other diagnostic studies for Thymoma include

• CT scan guided core needle biopsy
• CT scan guided fine needle aspiration
• mediastinoscopy
• Videothoracoscopy.

• Chemotherapy and radiotherapy are used as adjuvant or neoadjuvant therapies.
• Neoadjuvant therpy may be administered prior to surgery to make the tumor resectable.

• Surgery is the mainstay of treatment of thymoma.

• There are no primary preventive measures available for thymoma.

• Complete surgical resection may help to prevent the recurrence of thymoma.

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmad Al Maradni, M.D. [2]

The thymic epithelial tumor staging system was initially proposed by Bergh and his colleagues in 1978, modified by Wilkins and Castleman in 1979, and further developed by Masaoka et al. in 1981.

• Staging of thymic epithelial tumors was initially proposed by Bergh and his colleagues in 1978.^[1]
• Staging of thymic epithelial tumors was modified by Wilkins and Castleman in 1979.^[2]
• It went through further development by Masaoka et al. in 1981.^[3][4]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amr Marawan, M.D. [2] Ahmad Al Maradni, M.D. [3]Sabawoon Mirwais, M.B.B.S, M.D.[4]

On gross pathology, a well-circumscribed mass, that is locally invasive, is a characteristic finding of thymoma. On microscopic histopathological analysis, round cells with ample vacuolated cytoplasms and fat droplets are characteristic findings of thymoma.

• Thymus is the site of maturation of T cells.
• This makes thymus the primary center responsible for adaptive immunity.

• The exact pathogenesis of the primary tumor development is not completely understood.

• Primary tumors of thymus are relatively rare.
• Thymoma is the most common type of primary tumor of thymus.
• Thymoma is histologically comprised of abnormally conditioned T cells.
• The mingling of these abnormal T cells into the circulation is believed to be involved in the causality of the associated autoimmune disorders.^[1][2]

Genetic Alterations Reported for the Different WHO Histological Thymoma sub-types^[3]

WHO Type	Chromosomal Gains	Chromosomal Losses
Type A	None	-6p
Type AB	None	-5q21 – 22 -6q -12p -16q
Type B3	+1q	-6 -13q

Approximately 30% of the patients have their thymomas discovered because of a symptomatic associated autoimmune disorder. These disorders include:^[4]

Type	Diseases
Neuromuscular diseases	Myasthenia gravis Neuromyotonia Rippling muscle disease Polymyositis/dermatomyositis Encephalitis (limbic, cortical and brain stem) Intestinal pseudoobstruction
Hematologic autoimmune diseases	Anemia: Pure red cell aplasia, pernicious anemia, hemolytic anemia, aplastic anemia. Other isolated cytopenia: Eosinophils, basophils, neutrophils Immunodeficiencies: Hypogammaglobulinaemia, Good syndrome
Dermatologic disorders	Pemphigus (foliaceus or paraneoplastic) Lichen planus Alopecia areata
Endocrine disorders	Addison disease Graves disease Cushing’s disease
Renal and hepatic diseases	Glomerulonephritis Autoimmune hepatitis
Systemic autoimmune diseases	SLE Sjögren’s syndrome Systemic sclerosis Graft-versus-host disease

On gross pathology, a well circumscribed mass, that is locally invasive, is a characteristic finding of thymoma.

On microscopic histopathological analysis, round cells, with ample vacuolated cytoplasms, and fat droplets are characteristic findings of thymoma.

{{#ev:youtube|wfyixp6JxQM}}

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmad Al Maradni, M.D. [2]

There are no established causes of thymoma.

There are no established causes of thymoma.

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Amr Marawan, M.D. [2] Ahmad Al Maradni, M.D. [3] Khuram Nouman, M.D. [4]

Thymoma must be differentiated from thymic carcinoma, mediastinal germ cell tumor, thymic masses, lymphoma, and sub-sternal thyroid.

Diseases	Site	Clinical Features			Pathology			Labs
	Mediastinal Part	Systemic Symptoms	Obstructive Symptoms	Additional Features	Cell Organization	Tumor Cells	Lymphoid Cells	Additional Tests
Mediastinal Germ Cell Tumor	Anterior	Chest pain, Cough Difficulty breathing Weight loss	Superior vena cava syndrome	Post-obstructive pneumonia	Non-adhesive	Cells with large nuclei and prominent nucleoli	Mature looking Small	PLAP+ Serum AFP
Thymic masses Thymoma Cyst Thymic carcinoma Thymolipoma Parathyroid hyperplasia)	Anterior	Fever Night sweats Weight loss (depending on the type of mass)	Stridor Superior vena cava syndrome Facial swelling Painful swallowing	Horner syndrome due to mass effect	Varies	Varies with type	Varies with type	Varies with type Serum PTH CBC TSH, T3, T4 beta-HCG Serum AFP Gamma Globulins
Lymphoma Non-Hodgkin lymphoma Hodgkin’s lymphoma	Anterior Middle	Fever Weight loss Night sweats Shortness of breath	Phrenic nerve palsy Hoarseness Superior vena cava syndrome	Pleural effusion Pericardial effusion	Non-adhesive	Immature lymphoid cells (Non-Hodgkin lymphoma) Reed-Sternberg cells and variants (Hodgkin’s lymphoma)	Immature(Non-Hodgkin lymphoma) Mature, small (Hodgkin’s lymphoma)	LCA+ Light chain restriction in B-NHL CD15+, CD30+ in Hodgkin’s lymphoma
Sub-sternal goiter & thyroid lymphoma	Anterior	Symptoms of hypothyroidism(cold intolerance, weight gain, andconstipation) Hyperthyroidism (heat intolerance, weight loss, and diarrhea)	Positional dyspnea Choking sensation Wheezing Superior vena cava syndrome	Vocal cord palsy Horner’s syndrome	Varies	Hurthle cells Prominent nucleoli Abundant cytoplasm	Non-Hodgkin type is more common in thyroid lymphoma	Antibodies against thyroid peroxidase Antibodies against thyroglobulin

• The following table highlights the difference between thymoma and thymic carcinoma:

Thymoma must be differentiated from other similar conditions which lead to multiple endocrine disorders, such as autoimmune polyendocrine syndrome, POEMS syndrome, Hirata’s syndrome, Kearns–Sayre syndrome, and Wolfram syndromes.

Disease	Addison’s Disease	Type 1 Diabetes Mellitus	Hypothyroidism	Other Disorders Present
APS type 1	+	Less common	Less common	Hypoparathyroidism Candidiasis Hypogonadism
APS type 2	+	+	+	Hypogonadism Malabsorption
APS type 3	–	+	+	Malabsorption
Thymoma	+	–	+	Myasthenia gravis Cushing syndrome
Chromosomal abnormalities (Turner syndrome, Down’s syndrome)	–	+	+	Cardiac dysfunction
Kearns–Sayre syndrome	–	+	–	Myopathy Hypoparathyroidism Hypogonadism
Wolfram syndrome	–	+	–	Diabetes insipidus Optic atrophy Deafness
POEMS syndrome	–	+	–	Polyneuropathy Hypogonadism Plasma cell dyscrasias

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amr Marawan, M.D. [2] Ahmad Al Maradni, M.D. [3]

The incidence of thymoma is approximately 0.13 per 100,000 individuals. Thymic neoplasms are the most common tumors located in the anterior mediastinum (20%). Incidence increases in the fourth and fifth decade of life, and peaks in the seventh decade. Men and women are equally affected. The disease predominantly affects Asians and Pacific Islanders in the U.S.

• The incidence of thymoma is 0.13 per 100,000 individuals.^[1][2]

• Thymoma is very uncommon in children and young adults.
• Incidence rises in the fourth and fifth decade of life and peaks in the seventh decade.

• For unknown reasons, it predominates among Asians and Pacific Islanders in the U.S.^[3]

• Men and women are equally affected.^[4]

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amr Marawan, M.D. [2] Ahmad Al Maradni, M.D. [3]

There are no established risk factors for thymoma.

• There are no environmental risk factors for thymoma; however, several case reports have described an association with:^[1]
  • Human foamy virus
  • Epstein-Barr virus
  • Human T-cell lymphotropic virus
  • Infections
• Thymoma may be observed in patients with MEN 1 syndrome

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sabawoon Mirwais, M.B.B.S, M.D.[2]

There is insufficient evidence to recommend routine screening for thymoma.

There is insufficient evidence to recommend routine screening for thymoma.

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Amr Marawan, M.D. [2] Ahmad Al Maradni, M.D. [3]

If left untreated, thymoma may progress to invade the mediastinum and the surrounding structures. Depending on the stage of the tumor at the time of diagnosis, the prognosis may vary. The prognosis is generally regarded as good. Common complications of thymoma include the pressure effect of the mass itself, autoimmune diseases, and rarely, progression to malignancy.

• One-third of the tumors are discovered because of an associated autoimmune disorder.
• The most common of these autoimmune disorders is myasthenia gravis: 10 – 15% of patients with myasthenia gravis have thymoma. And 30 – 45% of patients with thymoma have myasthenia gravis.
• Patients with thymoma demonstrate a tendency for local mediastinal recurrence and pleural ‘‘droplet’’ recurrence presumably caused by mediastinal pleural invasion after resection.^[1]

Complications associated with thymoma include:

• Pressure effect associated with thymoma (sometimes presenting as superior vena cava syndrome)
• Autoimmune diseases associated with thymoma (myasthenia gravis and pure red cell aplasia)
• Thymic malignancy of unknown etiology
• Rarely (approximately 7% of cases), metastasis to pleura, bones, liver, or brain^[2]

The most common complications of radiotherapy are:^[1]

• Pulmonary fibrosis
• Pericarditis
• Myelitis

The most common complications of thymectomy are:

• Complications of the procedure, such as:
  • Bleeding
  • Infection
  • Damage to other organs
  • Nerve injuries (bilateral phrenic nerve injury)
  • Respiratory failure
• Recurrence has been described 10 to 20 years after removal of the primary lesion, necessitating long-term follow up.
• Live attenuated vaccines, such as yellow fever vaccine, may have adverse effects after thymectomy due to an inadequate T-cell response.

The complications of taking thymic biopsy include:

• Pneumothorax
• Mediastinitis

The prognosis of thymoma depends on the following:

• Location of the tumor
• Stage of the tumor

• The prognosis is much worse for stage III or IV thymoma as compared to stage I and II tumors
• Patients with stage III and IV tumors may nonetheless survive for several years with appropriate oncological management

• Resectability of the tumor
• Patient’s general health
• Primary diagnosis vs. recurrence
• Histologic type (mixed histologic type is associated with the worst prognosis)^[1]

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amr Marawan, M.D. [2]

Pathology Evaluation

R0 Resection

R1 Resection

R2 Resection

Thymoma, no capsular invasion or thymic carcinoma, stage I

Thymoma or thymic carcinoma, capsular invasion present, stages II-IV

Thymoma

Thymic carcinoma

Thymoma

Thymic carcinoma

Postoperative RT

Postoperative RT

Postoperative RT + Chemotherapy

RT ± Chemotherapy

RT + Chemotherapy

Surveillance for recurrence with CT every 6 month for 2 y, then annually every 5 y for thymic carcinoma and 10 y for thymoma

Thymoma or Thymic Carcinoma

Locally Advanced

Solitary Metastasis

Distant metastasis

Chemotherapy

Chemotherapy

Surgery

Chemotherapy

Re-evaluate for surgery

Chemotherapy or RT

Resectable

Unresectable

Surgery ± Postoperative RT

RT ± Chemotherapy

Return to top

FIRST-LINE COMBINATION CHEMOTHERAPY REGIMENS		SECOND-LINE CHEMOTHERAPY
CAP (preferred for thymoma) * Cisplatin 50 mg/m² IV day 1 * Doxorubicin 50 mg/m² IV day 1 * Cyclophosphamide 500 mg/m² IV day 1 Administered every 3 weeks	PE * Cisplatin 60 mg/m² IV day 1 * Etoposide 120 mg/m²/d IV days 1 -3 Administered every 3 weeks	Etoposide Ifosfamide Pemetrexed Octreotide (including LAR) + prednisone 5-FU and leucovirin Gemcitabine Paclitaxel
CAP with Prednisone * Cisplatin 30 mg/m² IV days 1-3 * Doxorubicin 20 mg/m²/d IV continuous infusion on days 1 to 3 * Cyclophosphamide 500 mg/m² IV on day 1 * Prednisone 100 mg/day on days 1-5 Administered every 3 weeks	VIP * Etoposide 75 mg/m² on days 1-4 * Ifosfamide 1.2 g/m² on days 1-4 * Cisplatin 20 mg/m² on days 1-4 Administered every 3 weeks
ADOC * Cisplatin 50 mg/m² IV day 1 * Doxorubicin 40 mg/m² IV day 1 * Vincristine 0.6 mg/m² IV day 3 * Cyclophosphamide 700 mg/m² IV day 4 Administered every 3 weeks	Carboplatin/Paclitaxel (preferred for Thymic Carcinoma) * Carboplatin AUC 6 * Paclitaxel 225 mg/m² Administered every 3 weeks

Return to top

• A dose of 60-70 Gy should be given to patients with unresectable disease.

• For adjuvant treatment, the radiation dose consists of 45-50 Gy for clear/close margins and 54 Gy for microscopically positive resection margins. A total dose of 60 Gy and above should be given to patients with gross residual disease (similar to patients with unresectable disease), when conventional fractionation (1.8 to 2.0 Gy per daily fraction) is applied.

Template:WikiDoc Sources