Thymic carcinoma with pulmonary metastasis
The chest radiograph shows a large left mediastinal soft tissue mass
with smoothly marginated borders and no calciﬁcation (Figure 1A). A
rounded soft tissue opacity was seen in the retrosternal clear space on
the lateral projection (Figure 1B).
The CT scan showed a
lobulated left anterior mediastinal soft tissue mass with eccentrically
placed clumps of calciﬁcation (Figure 2B). The tumor shows moderate
heterogeneous enhancement following contrast administration with few
areas of decreased attenuation—likely corresponding to cystic changes or
foci of hemorrhage and necrosis. The mass shows obliteration of
mediastinal fat (Figure 2C), and the absence of fat planes between the
mass and mediastinal structures is also evident, suggesting invasion.
Postcontrast scans taken at the level of the arch of the aorta and main
pulmonary artery show focal loss of planes with the great vessels. There
are also enlarged lymph node(s) in the aorto-pulmonary window region
(Figure 3) and small metastatic lesions in the left lung (Figure 4). In
view of the clinico-radiological ﬁndings, a diagnosis of malignant
anterior mediastinal mass was suggested—likely invasive thymoma or
thymic carcinoma. Ultrasound-guided ﬁne-needle aspiration and core
biopsy conﬁrmed a diagnosis of thymic carcinoma.
The patient was
examined again to rule out possible associated immunological disorders,
such as myasthenia gravis, red cell aplasia, etc. There was no history
of muscle weakness, difﬁculty swallowing, or ptosis, and further
immunological investigations, electromyography, and nerve conduction
study results were within normal limits. The patient was treated with an
intravenous (IV) chemotherapeutic regimen consisting of cisplatin,
doxorubicin, and cyclophosphamide, with amifostine.
Thymoma is the most common tumor of the anterior mediastinum and the
most common primary tumor of the thymus. Since thymomas are rare in
children and young adults, 70% of them are found in adults in the ﬁfth
and sixth decades of life. There is an approximately equal
male-to-female ratio. The majority of thymomas are found in the anterior
mediastinum. Other locations may be the neck and posterior mediastinum.
Approximately 20% to 50% of thymomas are asymptomatic, and the
frequency of thoracic symptoms is related to compression or invasion of
adjacent mediastinal structures. Compression of the trachea, recurrent
laryngeal nerve, or esophagus may produce cough, dyspnea, chest pain,
respiratory infection, hoarseness, or dysphagia. Invasion of the
adjacent cardiovascular structures may produce superior vena caval
syndrome. Thymomas can also be associated with autoimmune and
paraneoplastic syndromes, such as pure red cell aplasia (50% of patients
with red cell aplasia will have thymoma, and 5% of patients with
thymoma will have red cell aplasia), hypogammaglobulinemia (10% of
patients with thymoma will have hypogammaglobulinemia, and 5% of
patients with hypogammaglobulinemia will have thymoma), endocrine
disorders, cutaneous disorders, and connective tissue disorders.1 Evidence
linking thymoma with other second malignancies (of the rectum, thyroid,
breast, and lung) has been suggested by clinical studies. Distant
metastases are uncommon at initial presentation. However, when present,
the most common metastatic site at presentation is the pleura.
is the modality of choice because it is more sensitive than chest
radiography for the detection of small thymomas and in revealing tumor
inﬁltration of the surrounding mediastinal structures and adjacent lung.
Furthermore, CT is an excellent modality for the evaluation of pleural
and extrapleural seeding by the tumor. Calciﬁcation, even if subtle, can
be easily detected with CT. Magnetic resonance imaging is an excellent
noninvasive method of evaluating possible vascular involvement by
thymoma without the need for IV contrast medium. Thymomas are isointense
relative to skeletal muscle on T1-weighted images and have increased
signal intensity (approaching that of fat) on T2-weighted images. Cystic
areas are seen as low signal intensity on T1-weighted images and high
signal intensity on T2-weighted images.
diagnosis of solid invasive anterior mediastinal masses includes
lymphoma (ill-deﬁned mass with associated regional lymphadenopathy),
bronchogenic carcinoma, neuroendocrine tumors, benign germ cell tumors
(sharply deﬁned masses with cystic areas and mixed areas of calciﬁcation
and fat), and nonseminomatous germ cell tumors (large, poorly deﬁned
masses with zones of hemorrhage and necrosis).
classiﬁcation of thymic epithelial tumors and its relationship with
prognosis still remains controversial. Several classiﬁcations, based on
different pathologic criteria, have been proposed in the past. Bernatz
et al2 classiﬁed thymomas on the basis of the ratio of
lymphocytes to epithelial cells and the shape of epithelial cells into 4
subtypes: predominantly spindle cell; predominantly lymphocytic;
predominantly mixed; and predominantly epithelial.2 Müller-Hermelink et al3 classiﬁed
thymomas into 6 categories based on resemblance of tumor to cortex or
medulla of normal thymus (from well-differentiated to poorly
differentiated tumors): medullary thymomas; mixed thymomas;
predominantly cortical (organoid) thymomas; cortical thymomas;
well-differentiated thymic carcinomas; and high-grade thymic carcinomas.3 This
system has prognostic signiﬁcance, independent of tumor stage. The
World Health Organization (WHO) established a new system based on the
morphology of the epithelial cells as well as the
lymphocyte-to-epithelial cell ratio. Six categories of thymomas divided
into 2 subtypes were deﬁned: unique thymic tumors (types A, AB, B1, B2,
and B3); and malignant thymomas (type C). The relationship of the WHO
classiﬁcation and previous histologic classiﬁcations is as follows: type
A corresponds to spindle cell type or medullary type thymoma; AB
corresponds to mixed type; B1 corresponds to lymphocyte-rich type,
lymphocytic type, predominantly cortical type, or organoid type; B2
corresponds to cortical type; B3 corresponds to epithelial type,
squamoid type, or atypical thymoma, or well-differentiated thymic
carcinoma; and type C corresponds to thymic carcinoma. This
classiﬁcation tries to reﬂect both the clinical and the functional
features of thymic epithelial tumors.4 Although CT is of
limited value in differentiating histologic subtypes according to the
WHO classiﬁcation, CT ﬁndings may serve as predictors of postoperative
recurrence or metastasis for thymic epithelial tumors.5 Low-risk
thymomas include subtypes A, AB, B1; high-risk thymomas consist of
types B2 and B3. The presence of smooth contours and a round shape are
most suggestive of a type A tumor, while a lobulated, irregular contour
is more often seen in high-risk thymomas. The combination of homogeneous
enhancement and a high degree of enhancement is suggestive of type A
and AB tumors. CT is of limited value, however, in differentiating type
AB, B1, B2, and B3 tumors. Mediastinal lymphadenopathy, great vessel
invasion, and mediastinal fat inﬁltration are most suggestive of type C
tumor or thymic carcinomas. Tumors with a lobulated or irregular
contour, an oval shape, mediastinal fat, or great vessel invasion, and
pleural seeding show signiﬁcantly more frequent recurrence and
metastasis. Type A, AB, or B1 thymomas have a less aggressive nature
than type B2 or B3 thymomas and, therefore, have more chances of
Recently, it has been suggested that it may
be possible to differentiate between atypical thymoma and thymic
carcinoma based on CT ﬁndings. Thymic carcinomas are larger tumors, and
the ﬁndings of invasion of the great vessels, lymphadenopathy, phrenic
nerve palsy, and lung or distant metastases are seen only in patients
with thymic carcinoma. The tumors occur in a broad age range of patients
(average age 46 years), have a low incidence of paraneoplastic
syndromes, and have a poor prognosis.6
histology may inﬂuence overall prognosis, tumor stage is a more
important overall survival indicator, as conﬁrmed by a number of
published studies. Staging of thymoma is based on the presence or
absence of an intact tumor capsule. The staging system proposed by
Masaoka et al7 is postsurgical and has been widely adopted.
Stage I thymomas do not show capsular invasion. Stage II lesions show
microscopic invasion of the capsule, mediastinal fat, or surrounding
pleura. Stage III tumors invade surrounding organs and structures such
as the lung, pericardium, superior vena cava, and aorta. Stage IVa
involves pleural or pericardial dissemination. Stage IVb involves
lymphogenous or hematogenous metastases. For the majority of patients
who present with a localized tumor, surgical extirpation by median
sternotomy remains the standard of choice. However, since thymomas may
have either pleural or pericardial implants, both pleural cavities
should be widely opened and explored at surgery. Adjuvant radiotherapy
seems to improve local control and survival. In more advanced disease,
systemic therapy has been shown to produce a 50% to 80% objective
response rate. These observations have led to the development of
multimodality therapy for the treatment of patients with advanced
We have discussed the various histological classiﬁcations for thymomas
as well as the widely accepted postsurgical Masaoka staging, which is an
independent predictor of outcome and survival. Though CT cannot be used
to distinguish between various histological subtypes, it can be used to
identify thymomas as low risk or high risk. Also, when a large thymic
tumor is associated with the invasion of great vessels, lymph node
enlargement, phrenic nerve palsy, or extrathymic metastases on CT,
thymic carcinoma rather than atypical thymoma should be considered, as
in our case.
- Souadjian JV, Enriquez P, Silverstein MN, Pépin JM. The
spectrum of diseases associated with thymoma. Coincidence or syndrome?
Arch Intern Med. 1974;134:374-379.
- Bernatz PE, Harrison EG, Clagett OT. Thymoma: A clinicopathologic study. J Thorac Cardiovasc Surg. 1961;42:424-444.
- Müller-Hermelink HK, Marx A. Thymoma.Curr Opin Oncol.2000;12:426-433.
- Okumura M, Ohta M, Tateyama H, et al. The World Health Organization
histologic classiﬁcation system reﬂects the oncological behavior of
thymoma: A clinical study of 273 patients. Cancer. 2002; 94:624 -632.
- Jeong YJ, Lee KS, Kim J, et al. Does CT of thymic epithelial tumors
enable us to differentiate histologic subtypes and predict prognosis?
AJR Am J Roentgenol. 2004;183:283-289.
- Jung KJ, Lee KS, Han J, et al. Malignant thymic epithelial tumors:
CT-pathologic correlation. AJR Am J Roentgenol. 2001;176:433-439.
- Masaoka A, Monden Y, Nakahara K, Tanioka T. Follow-up study of
thymomas with special reference to their clinical stages. Cancer.