Thymoma mimicking an aortic aneurysm: always expect the unexpected

Abstract

Thymic epithelial tumours (TETs) are rare lesions that represent less than 1% of all malignancies in adults. Presentation occurs in three ways: asymptomatic, with local thoracic symptoms or with paraneoplastic symptoms. Heterotopic ossifications are rare histological features in neoplasms and non-neoplastic lesions. Here, we present a 49-year-old male patient with a thymoma type B2 mimicking an aortic aneurysm. Alongside the thymoma, a cholesterol granuloma with unusual ossification features was found as well. This clinical presentation and pathological diagnosis are unusual findings.

Background

Thymic epithelial tumours (TETs) are rare lesions that represent less than 1% of all malignancies in adults. The two main types are thymoma and thymic carcinoma.¹ The incidence of thymoma is estimated at 1.5 cases per million and it is the most common primary neoplasm found in the prevascular mediastinum.² Thymomas typically present in one of three major ways: (1) in 30% as an incidental finding on thoracic imaging in an asymptomatic patient, (2) in 40% with local thoracic symptoms such as chest pain, cough, dyspnoea and phrenic nerve palsy or (3) in 30% during the evaluation of a paraneoplastic syndrome such as myasthenia gravis (MG) and pure red cell aplasia among others.³ In approximately 10%–15% of patients diagnosed with MG, a thymoma is found on imaging and up to 50% of all thymoma patients develop MG as a paraneoplastic syndrome.⁴ There are several histological subtypes of thymoma which are classified by the WHO. The subtypes are A, AB, B1, B2, B3 and C with type B2 being the most common histological subtype, accounting for 28% of all thymomas.^{5 6}

Cholesterol granulomas are considered to be an inflammatory response to the deposition of cholesterol crystals.⁷ Typical locations of cholesterol granulomas are the middle ear and mastoid process; however, there are reported cases of cholesterol granulomas in other locations such as the thymus, testis, kidney, parotid gland, thyroglossal duct, peritoneum and in lymph nodes.⁸ Osseous metaplasia is a very rare histological finding in cholesterol granulomas.⁹

We report an unusual case of a 49-year-old male patient who presented with acute retrosternal pain radiating to the interscapular area and the neck. CT-scan of the chest suggested an aortic aneurysm. However, during surgery a mass was found in the prevascular mediastinum, which consisted of a type B2 thymoma and a cholesterol granuloma with areas of ossification. This unusual presentation of thymoma and the simultaneous occurrence of an ossified cholesterol granuloma demonstrate that unexpected findings may be encountered in the evaluation of mediastinal lesions.

Case presentation

A 49-year-old male patient presented at our emergency department (ED) with retrosternal pain, describing it as a heavy pressure on the chest radiating to both shoulders and the neck. The pain lasted for more than 30 min and worsened in a supine position. Other complaints were diaphoresis and malaise. There was no dyspnoea, coughing, haemoptysis, fever or chills. The patient had experienced similar complaints 1 year earlier, but a transthoracic echocardiogram did not reveal any abnormalities at the time. Medical history revealed hypertension and dyslipidaemia for which the patient was treated with an ACE-inhibitor and a statin, respectively. The patient did not report any surgical interventions in the past or in a recent period of immobilisation.

On admission, the patient had a blood pressure of 145/88 mm Hg and tachycardia of 101 beats/minute. Temperature and saturation were normal and clinical examination of the heart and lungs did not reveal any abnormalities. Arterial blood gas, ECG and transthoracic echocardiogram were normal as well. Laboratory studies showed a minor leucocytosis. A chest X-ray was performed which revealed a ring-shaped calcified density adjacent to the right side of the heart. Subsequently, a contrast-enhanced chest CT scan was performed which showed an 8.5 cm wide multilocular structure with eggshell calcifications and hyperdense components in close contact with the ascending aorta. The image suggested a saccular aneurysm of the aorta or mediastinal mass and the patient was scheduled for an exploratory sternotomy to correct the potential aneurysm.

During surgery, no abnormalities of the heart or aorta could be found, thus excluding the diagnosis of a saccular aneurysm of the aorta. However, a cystic mass was present extruding into the pericardium on the right side of the heart. The mass was excised and sent for pathological investigation. Final histological diagnosis was a thymoma type B2 along with a cystic cholesterol granuloma with areas of calcification and ossification (figures 1–3). The tumour was staged as pT1aN0M0 according to the 8th tumour, node, metastasis (TNM) classification for TETs.¹⁰ The postoperative course was uneventful.

Figure 1.

Macroscopic image of the specimen after formaldehyde fixation, showing the central thymoma with an adjacent cyst-like component. The capsula is completely calcified.

Figure 2.

H&E-stained microscopic image of the thymoma (upper left) as confirmed by the terminal deoxynucleotidyl transferase (upper right) and pan-cytokeratin immunohistochemical (below) stains. A small cholesterol granuloma is present in the capsula.

Figure 3.

H&E-stained microscopic image showing extensive calcification of the large cholesterol granuloma.

Investigations

ECG at admission showed no signs of myocardial infarction such as ST segment changes and hyperacute or negative T waves. Furthermore, the ECG showed a normal sinus rhythm, no changes in the PR interval, no QRS complex abnormalities or prolonged QTc lengths. The normal ECG findings combined with the negative troponin I levels and a normal cardiac ultrasound investigation provided sufficient evidence to exclude myocardial infarction and cardiac arrhythmia as possible diagnoses.¹¹

The initial chest X-ray showed signs of cardiomegaly and a ring-shaped calcified density on the right side of the heart (figure 4). Abnormal densities on chest X-rays are often difficult to delineate due to similar densities of surrounding structures. Therefore, it is advised to perform cross-sectional imaging for characterising these types of lesions.¹² The aetiology of the calcified density could not be specified on the chest X-ray and had to be investigated by a chest CT scan for further workup.

Figure 4.

Anteroposterior chest X-ray showing cardiomegaly and a ring-shaped calcified density on the right side of the heart.

Contrast-enhanced chest CT scan suggested that the calcified structure was in close contact with the ascending aorta showing hyperdense components (figure 5). These findings could signify a recent bleeding, a saccular aneurysm or a mediastinal mass. To prevent rupture of a possible saccular aneurysm, an exploratory sternotomy was performed.

Figure 5.

Contrast-enhanced chest CT scan showing a non-circular calcified density with hyperdense components in the prevascular mediastinum extruding into the visceral compartment.

Differential diagnosis

Myocardial infarction

Laboratory values at admission in the ED revealed a normal troponin I level <0.015 µg/L (<ref 0.046 µg/L). Postoperative troponin I level reached a maximum of 0.063 µg/L approximately 12 hours postoperatively and normalised during following measurements. ECG did not show any ST segment or T wave changes. Due to normal troponin I level, a normal ECG and the normal cardiac findings on the contrast-enhanced chest CT scan, a myocardial infarction was excluded as diagnosis. A combination of troponin I level <0.05 µg/L and a normal ECG at admission rules out myocardial infarctions with a negative predictive value of 99.6%.¹³

Pulmonary embolism

A simplified Wells score was calculated and laboratory values for D-dimers were analysed. The simplified Wells score was 1.5 due to a heart rate of 101 beats/min. D-dimers were 0.2 µg/mL (ref <0.48 µg/mL). Furthermore, a chest CT scan did not show any signs of pulmonary embolism (PE). A simplified Wells score of <4 combined with a negative age-adjusted D-dimer test results and a negative chest CT scan provided enough evidence to rule out PE.¹⁴

Aortic dissection

Intravenous contrast-enhanced chest CT scan reliably confirms and excludes aortic dissection and may elucidate alternative diagnoses.¹⁵ The chest CT scan did not reveal any features of aortic dissection and the perioperative surgical findings showed no abnormalities of the heart or aorta.

Saccular thoracic aneurysm

An explorative sternotomy was performed and showed no abnormalities of the aorta. Furthermore, perioperative surgical findings did not show a saccular thoracic aneurysm.

Thymoma

During surgery, a cystic mass was present and postoperative pathological examination revealed a thymoma B2 together with an ossified cholesterol granuloma.

Treatment

Under general anaesthesia, a median sternotomy was performed to explore the prevascular mediastinum and the lesion found on the chest CT scan. The pericardium was opened and revealed no abnormalities of the aorta or other cardiac structures. On the right side of the heart, a cystic-like mass was visualised which was partially covered by pleura and pericardium and originated from the thymus. A complete resection was possible.

Outcome and follow-up

At follow-up 5 weeks postoperatively, the patient showed an excellent clinical recovery with no recurrence of restrosternal pain or pressure. A follow-up contrast-enhanced chest CT scan did not reveal any residual tumour or metastases. Final pathology of the resected mass showed a complete resection of the cholesterol granuloma and type B2 thymoma. The thymoma was staged as pT1aN0M0 according to the 8th TNM classification which corresponds to stage I of the Masaoka-Koga staging system.^16–18 After multidisciplinary consultation, it was decided that there was no need for adjuvant radiotherapy or chemotherapy due to the fact that the lesion was classified completely resected.^{19 20} Further follow-up will be according to the guidelines of the European Society for Medical Oncology and will consist of a chest CT scan every year for 5 years and then a chest CT scan every 2 years indefinitely.²¹

Discussion

Our patient was treated for a mediastinal calcified mass that was found on a chest CT scan after clinical complaints of retrosternal pain. Pathology showed that the mass consisted of a thymoma type B2 and a cholesterol granuloma with regions of ossification. The patient did not have a history of MG or other paraneoplastic syndromes. Cholesterol granulomas are generally caused by microscopic haemorrhages which lead to haemolysis and a release of cholesterol from cell membranes of degenerating erythrocytes. The cholesterol then forms crystals, which stimulate a foreign body type giant cell reaction, and results in inflammation and granuloma formation.²² Intratumoural calcification can occur in the presence of degenerative or necrotic tissues, in mucus-producing areas adjacent to tumour cells or in pre-existing calcified scar tissue or granulomatous tissue.²³ The pathogenesis of heterotopic ossification is complex and not fully understood.²⁴ However, it is known that the following conditions are required to induce heterotopic ossification: the presence of an osteoinductive factor, chondrocyte progenitor and osteoblast progenitor cells, and an environment allowing osteogenesis. When these conditions are met, the production of ectopic bone formation can be induced.²⁴ In our patient, regions of osseous metaplasia were present within the cholesterol granuloma, which is a very rare histological finding. A 10-year study on tissue distribution of heterotopic ossification in neoplastic and non-neoplastic lesions found only 0.067% of cases of neoplasm with heterotopic ossification.²⁵ Until now, only three cases of patients with histological confirmation of osseous metaplasia inside a cholesterol granuloma have been reported. The osseous cholesterol granulomas in these three patients were found in the prevascular mediastinum, breast and fallopian tube.^{9 26 27}

Although chronic chest pain is a symptom that can occur in patients with thymoma, acute retrosternal pain radiating to the interscapular area has not been reported yet.²⁸ In the last few decades, a number of classification systems for thymoma have been introduced.²⁹ The WHO classification system is a routinely used histopathological classification system.³ However, this classification system is limited due to histological heterogeneity of thymoma, as different thymoma subtypes may coexist within the same lesion.³⁰ The Masaoka-Kaga surgical pathology system is widely used and correlates well with overall survival.¹ The staging system is divided into four stages according to the degree of invasiveness (see table 1).³¹

Table 1.

Masaoka-Koga staging system

Stage	Description
I	Macroscopically encapsulated with no microscopic invasion of the capsule
II
A	Macroscopic invasion into mediastinal fat or pleura
B	Microscopic invasion of the capsule
III	Invasion into neighbouring organs
IV
A	Pleural or pericardial metastasis
B	Lymphatic or haematogenous metastasis

More recently, the International Association for the Study of Lung Cancer (IASLC) together with the International Thymic Malignancy Interest Group (ITMIG) proposed a TNM classification for all thymic malignancies. This staging system is based on a retrospective analysis of more than 10 000 cases and has the advantage of being relevant for both thymoma and thymic carcinoma (table 2).³² Hopefully, this staging system will provide clinicians a useful tool for prognostication for this rare and heterogeneous group of malignancies.

Table 2.

IASLC/ITMIG TNM staging system and corresponding Masaoka-Koga stage

Stage	Definition
T1
A	Encapsulated or unencapsulated, with or without extension into mediastinal fat
B	Direct invasion of mediastinal pleura
T2	Direct invasion of the pericardium
T3	Direct invasion into any of the following: lung, brachiocephalic vein, superior vena cava, phrenic nerve, chest wall or extrapericardial pulmonary artery or veins
T4	Direct invasion into any of the following: aorta, arch vessels, main pulmonary artery, myocardium, trachea or oesophagus
N0	No nodal involvement
N1	Involvement of anterior (perithymic) nodes
N2	Involvement of deep intrathoracic or cervical lymph nodes
M0	No pleural, pericardial or distant metastasis
M1
A	Separate pleural or pericardial nodule(s)
B	Pulmonary intraparenchymal nodule or distant organ metastasis

TNM Stage	Tumour	Node	Metastasis	Masaoka-Koga Stage
I	T1a	N0	M0	I and II
	T1b	N0	M0	III
II	T2	N0	M0	III
IIIa	T3	N0	M0	III
IIIb	T4	N0	M0	III
IVa	Any T	N1	M0	IVb
	Any T	N0	M1a	IVa
	Any T	N1	M1a	IVb
IVb	Any T	N2	M0	IVb
	Any T	N2	M1a	IVb
	Any T	Any N	M1b	IVb

IASLC, International Association for the Study of Lung Cancer; ITMIG, International Thymic Malignancy Interest Group; TNM, tumour, node, metastasis.

For thymoma, tumour stage and completeness of resection are the most important prognostic factors (table 3). Other prognostic factors are histological subtype, age and presence of MG.^{21 33 34} Five-year overall survival for thymoma and thymic carcinoma are 69% and 36%, respectively.³⁴ In most cases, patients younger than 30–40 years old tend to have a better prognosis.³⁵ Recurrent disease is possible for thymic malignancies, but is not always associated with higher mortality rates. Recurrence rates for Masaoka-Koga stages I, II and III are 3%, 16% and 26%, respectively. For patients with stage IV, variable results have been reported.³¹

Table 3.

Overall survival of TETs according to Masaoka-Koga stage and WHO classification

	5-year OS (%)	10-year OS (%)
Stage
I	89–100	81–86
II	70–100	79–87
III	50–87	64–75
IV	46–50	26–73
WHO classification
A	100	90–100
AB	100	90–100
B1	93	81–95
B2	75–83	70
B3	43–70	33
C	30	ND

ND, not determinable; OS, overall survival; TETs, thymic epithelial tumours.

Patient’s perspective.

I remember that I was asleep and suddenly I woke up in the middle of the night with pain on my chest which radiated to my back and throat. It felt like someone was standing on my chest. The pain did not stop after a couple of minutes and I started to get worried so I woke up my wife who was sleeping next to me. She said I looked very pale and I started to get more nauseous as well. My wife and I drove to the out-of-hours general practitioner’s service near us. After a short visit, the doctor sent us to the emergency department. My wife thought I had a bronchitis because I had had a cold a few days before. The doctors in the emergency department performed all sorts of tests and scans. They checked my heart, my lungs, my abdomen, my legs … After the CT scan they told me it looked like I had a large aneurysm of my aorta near my heart and that they had to operate urgently. It all went very fast in those few hours. After the operation, the doctors told me that I did not have an aneurysm but a tumour in my thymus which they were able to remove completely. This was quite the shock for me because suddenly I was a ‘cancer patient’. The doctors told me that they discussed my case and that I did not need any further treatments. After 5 days I left the hospital and went home. I expected to have more pain and I was surprised that the pain was minimal. However, as the days passed I noticed that I still had so many questions such as ‘Will my cancer come back in the future?’ ‘How often do I need to be checked?’ even though the doctors told me all the information. After 3 weeks at home, I had a new CT scan and appointment in the outpatient clinic. Luckily, the results of the new scan were OK and the doctors reassured me that no further treatment was necessary at the moment. That was a great weight off my shoulders.

Learning points.

• Thymomas can present with atypical clinical symptoms.

• Thymic malignancies may pose a diagnostic challenge on imaging.

• Multidisciplinary consultation are essential for delivering optimal care.