Thymic squamous cell carcinoma lurking in a growing large cyst : A case report

Abstract

An 81-year-old man was admitted for resection of an asymptomatic left anterior mediastinal tumor. Chest computed tomography showed that a small, homogeneous lesion had grown to a large, cystic lesion (80 mm) over a 5-year period. The cystic tumor was removed with adherent structures such as the left upper pulmonary parenchyma and lower part of the left innominate vein via median sternotomy with assistance from a left thoracoscopic procedure. Macroscopically, a solid tumor was located within the large multilocular cyst. The pathological diagnosis was cystic squamous cell carcinoma (12 mm), which had not infiltrated any surrounding organs. The patient has remained well without recurrence as of 4 years postoperatively.

Introduction

The majority of mediastinal tumors showing cystic findings are generally benign. In the clinical setting, radiological evaluations are crucial for cyst-like thymic neoplasms. Thymic carcinoma associated with multi-loculated thymic cyst has occasionally been reported. However, cystic transformation of thymic carcinoma is rare. We report a rare case of cystic thymic squamous cell carcinoma in the anterior mediastinum. The correct diagnosis was established postoperatively, highlighting the need for careful attention in surgical management.

Case report

An 81-year-old man was admitted for surgical treatment of an asymptomatic left anterior mediastinal tumor. He had a history of gastric cancer surgery in another hospital, and a large tumor was incidentally detected in the anterior mediastinum on follow-up CT of the gastric cancer. He was transferred to our hospital for further examinations. He was asymptomatic, and physical examinations and laboratory findings found no abnormalities. Examining findings from past CT, a small, heterogeneous lesion (1.5 cm) was found to be already present in the anterior mediastinum on CT from 5 years earlier (Figure 1(a)), growing to a cystic mass (diameter, 80 mm) that extended to the left innominate vein and left lung. The huge cystic lesion showed a thickened wall with the presence of intra-cystic separations (Figures 1(b)–(d)). No enlargement of mediastinal lymph nodes or other intra-thoracic lesions was seen. No obvious tumor lesion was found. Since the tumor had grown significantly and solid components within the cystic lesion were slightly suspected, a malignant thymic lesion such as cystic thymoma was suspected. Considering the possibility of tumor spreading due to incomplete tumor resection, complete resection was planned. To observe and remove the large lesion without injury to the left phrenic nerve, left-sided video-assisted thoracoscopic surgery and subsequent median sternotomy were performed with the patient in a left hemi-lateral supine position. Under video view, the intra-thoracic filed was assessed and mediastinal fat tissues were mobilized from the pericardium along the left phrenic nerve. The lung was divided, leaving adhesions to the lung on the resected side using an endo-stapler. The patient was moved to a supine position, and median sternotomy was performed. The remaining tumor with right thymic tissue was dissected from bottom to top, and the left innominate vein was exposed. Vascular control was applied to this vessel using vessel loops, and the tumor was removed with this involved vessel. The vessel wall underwent primary closure using prolene sutures. Negative surgical margins were confirmed by intra-operative pathological examination. The resected specimen showed a large multi-cystic tumor filled with gray to brown liquid, and containing only a limited white solid area (12 × 10 mm) (Figure 2(a)). The solid lesion represented poorly differentiated squamous cell carcinoma (Figures 2(b) and (c)). The cystic wall with some atypical cells lining were found. No infiltration of squamous carcinoma was seen beyond the cyst wall, and no lymph node metastasis was observed. Cytology of the brown liquid in the cyst was defined as class 2. In pathological T1N0M0 stage 1, the tumor was diagnosed as a cystic poorly differentiated squamous cell carcinoma. Complete surgical excision (R0) was performed without postoperative complications. No recurrence has been identified as of 4 years postoperatively without adjuvant treatment.

Figure 1.

(A) Initial CT 5 years before this presentation reveals a small, heterogeneous lesion (1.5 cm) at the anterior mediastinum. (B) CT reveals an enlarging cystic lesion (40 mm) (C) A cystic mass showing a thickened wall, intra-cystic septa. (D) A lesion extended to the left innominate vein.

Figure 2.

(A) Macroscopically, it was shown a thickened septum (arrow) is seen in the cyst. (B) Low magnification photomicrograph reveals a septum (arrow) lined with by squamous cell carcinoma. (C) High magnification photomicrograph reveals squamous cell carcinoma with poor tiny keratinization in the tissue.

Discussion

A thymic cyst is a benign congenital lesion, typically appearing as a small, oval, unilocular mass with well-defined but thin walls, and homogeneous attenuation, usually in the range of water attenuation (CT attenuation value: 0–20 Hounsfield units [HU]). In the clinical setting, radiological evaluations are crucial for cyst-like thymic lesions, due to the risk of thymic neoplasms. Large or increases in size, cystic wall thickness, intra-cystic separation and presence of a solid component resulting from malignant neoplasms must be kept in mind. However, unnecessary surgical resection should be avoided, especially for small lesions. There are no guidelines for management with incidental thymic lesions, but long-term repeated follow-up care is recommended to check tumor growth.^1,2 The present case involved a small, heterogeneous lesion (diameter, 10 mm) in the anterior mediastinum, and CT attenuation value of this lesion was between 25 and 98 in HU. Thymic cysts may show increased CT attenuation if hemorrhage or infection arises as a complication, ³ and the nature of the mass in the cystic lesion could not be determined at that point. Over the course of 5 years, the lesion developed into a large cyst with thickened walls, internal septa and internal debris. CT did not show any solid component within the cystic lesion, but malignant neoplasms such as cystic thymoma were suspected based on the characteristics of the cyst. In this case, the patient was asymptomatic, and the growing lesion was well circumscribed and clearly resectable. The treatment strategy for thymic epithelial tumors including thymima and thymic carcinoma is based on resectability of the tumor. ⁴ And then surgical resection was planned without preoperative biopsy. ⁵ The resected specimen showed a thymic epithelial tumor (diameter: 10 mm) in the wall of the multilocular cyst. Pathologically, localized thymic squamous cell carcinoma was confirmed in the cystic tumor. This cystic component was something like the multilocular thymic cysts (MTCs) reported by Suster and Rosai. ⁶ Those were acquired cysts that developed by various inflammatory processes arising within the thymic gland. MTC has sporadically been reported in association with thymic tumors, which include thymoma and thymic carcinoma. The present case was most likely to be an MTC-associated thymic cancer. The mechanism by which squamous cell carcinoma came to be contained within a large and growing cyst was considered to involve the following two possibilities. First, MTC might have developed in the thoracic tissue surrounding the squamous cell carcinoma, caused by inflammatory processes resulting from tumor growth, and then the tumor and cyst grew individually. ⁷ Second, MTC may have formed, then a thymic tumor may have developed from the cyst epithelium. ⁸ However, we could not conclude that the cystic component was MTC for the following reasons: 1) no continuity with thymic tissue was evident around the cyst, and 2) some atypical cells were found in the epithelium lining the cyst wall. Another possibility was that this tumor itself had undergone prominent cystic transformation, as reported by Weissferdt and Moran. ⁹ The diagnosis finally was cystic squamous cell carcinoma, based on the cyst-like development. Thymic carcinoma is believed to arise from epithelial cells or the thymus. Most thymic cancers be classified as squamous cell carcinomas. The well-differentiated type accounts for 74.3% of thymic squamous cell carcinomas. ¹⁰ Fluorodeoxyglucose-positron emission tomography (FDG-PET) is effective for distinguish thymic carcinoma from thymoma or other lesions, because a maximum standalized uptake values (SUV max) of the thymic carcinoma (>6.0) is very high. ¹¹ In most cases, thymic cancer has already invaded surrounding organs at the initial diagnosis. ¹⁰ This modality is used for patients with advance stage to select a proper biopsy site. ⁴ However, as shown in this case, for cystic squamous cell carcinoma or cyst-associated squamous cell carcinoma, tumor cells might be relatively retained within the cyst wall, despite the large cystic lesions.^9,12 FDG accumulation is diminished, and histological diagnosis requires samples containing tumor cells from within the cystic component. A false-negative result obtained by PET and CT glides percutaneous biopsy.^11,13 The true pathological condition can only be grasped after surgery. The prognosis of these tumors seems better than that of conventional thymic carcinoma.^9,12 Fortunately, in this case, tumor cells were confirmed to be confined to the cyst wall, regardless of the poorly differentiated nature of the tumor, and complete resection (R0) could be performed. After complete resection (R0) of thymic carcinoma, postoperative radiotherapy is effective for reducing local recurrence.^14,15 However, therapeutic effect for Stage 1 tumors is controversial. ¹⁵ And then radiotherapy was not given to this case, considering the patient’s age. This patient has remained well without recurrence for 4 years after surgery without adjuvant therapy.

In conclusion, clinical and radiological evaluations for cystic lesion that differ from congenital cysts are crucial. PET and preoperative biopsy have no diagnostic value in this case. Incomplete resections of a cystic lesion carry a surgical risk of disseminating or leaving tumor cells. ² Complete resection is required for diagnostic and therapeutic purposes.