Isolated splenic metastasis from a thymic carcinoma: A case report

ABSTRACT

Thymic carcinomas are rare tumors that arise in the anterior mediastinum. Most of these malignancies develop local metastases limited in the thorax. Splenic metastases from thymic carcinomas are extremely rare. Here we report a case of isolated splenic metastasis from a 38-year-old female patient with Stage IV thymic carcinoma, who was treated with chemoradiotherapy. At twenty-2 months follow-up, the patient was found to have an isolated spleen metastasis, which was treated by Cyberknife with a reduced size of the metastasis, representing a partial response. Although splenic metastasis is a rare phenomenon, physicians need to be aware of the possibility of such metastases.

KEYWORDS:

• Chemotherapy
• oligometastasis
• PET/CT
• radiation
• SBRT
• spleen metastasis
• thymic carcinoma

Abbreviations

CT	=	computed tomography
FDG-PET	=	fluorodeoxyglucose positron emission tomography
SUVmax	=	maximum standardized uptake value
SBRT	=	stereotactic body radiation therapy
OS	=	overall survival

Introduction

Thymic carcinomas originate from thymic epithelial cells, which are significantly different from thymoma in biological characteristics and prognosis. It is mainly metastasized by regional intrusion and hematogenous spread. Extrathoracic metastases are seen in less than 7 percent of patients at presentation, most commonly to the kidney, extrathoracic lymph nodes, liver, brain, adrenals, thyroid, and bone.¹ Rare but not exceptional is metastasis occurring on spleen.

Case presentation

A 38-year-old female patient presented with the symptoms of chest tightness and dyspnea. The chest CT (CT) scan revealed a voluminous mass in the left anterior mediastinum that measured 8.9 cm × 8.0 cm, with pericardial and pleural effusion. The fluorodeoxyglucose positron emission tomography (FDG-PET)/CT confirmed involvement in left anterior mediastinum, hilar lymph nodes, pericardium, pulmonary artery and aorta. Distant metastasis was not detected at that time. Pericardiocentesis and drainage cytology analysis showed a small amount of atypical cells. The biopsy of thymic mass revealed a poorly differentiated squamous carcinoma with expression of cytokeratins 5/6, P63 and absence of neuroendocrine and adrenal markers such as CD56, synaptophysin and NapsinA (Fig. 1). The patient was diagnosed as thymic squamous carcinoma in Stage IVb according to Masaoka staging system and received 7 cycles of chemotherapy with gemcitabine, cisplatin and angiogenesis inhibitor endostar. Follow-up imaging showed that the size of primary thymic carcinoma was reduced by 26% after 6 cycles of treatment. The patients received concurrent chemoradiotherapy with taxane following the completion of the chemotherapy. The radiation therapy was delivered by 6 MV external beams with a dose of 66 Gy in 33 fractions for the primary tumor. She achieved complete response after radiotherapy and was followed with routine physical exam, abdominal ultrasound and chest CT scan every 3 months afterwards.

Figure 1. (A) Hematoxylin-Eosin staining of the thymic mass showed tumor cells grew diffusely. Immunohistochemical analysis demonstrated the tumor cells were strongly positive for (B) P63, (C) cytokeratins 5/6, immunostaining revealed negative for (D) CD56, (E) synaptophysin and (F) NapsinA respectively.

Abdominal CT scan revealed a moderate contrast enhanced lesion that measured 4.5 cm × 3.5 cm in her spleen at 22-month follow up visit. This finding was confirmed by PET/CT, with the maximum standardized uptake value (SUVmax) of 30.67 (Fig. 2). Whereas the thymic mass was stable with an SUVmax of 1.8 (Fig. 3). No metastatic lesions were detected in the liver, adrenal gland and abdominal lymph nodes. Biopsy of spleen metastasis was not performed due to patient's refusal. Patient also refused surgery resection for this splenic mass. She was then treated with stereotactic body radiation therapy (SBRT) on Cyberknife (30Gy in 5 fractions) as alternative treatment. Abdominal CT (Fig. 4) showed that the volume of spleen metastasis reduced to 2.6 cm × 3.5 cm at one month follow up, which indicates a partial response.

Figure 2. Abdominal computed tomography (CT) scan revealed a moderate contrast enhanced lesion that measured 4.5 cm × 3.5 cm in the spleen (A), which was confirmed by fluorodeoxyglucose positron emission tomography (PET/CT), with the SUVmax of 30.67 (B).

Figure 3. Chest CT and PET/CT showed the thymic mass was stable, which was not enhanced in chest contrast enhanced CT (A) and seen in PET/CT with a SUVmax of 1.8 (B).

Figure 4. Abdominal CT after radiotherapy: The patient was treated with Cyberknife for her spleen lesion. Abdominal CT showed that the spleen metastasis reduced to 2.6 cm × 3.5 cm at one month follow up.

Discussion

Thymic carcinomas are rare and aggressive thymic epithelial tumors, accounting for only 0.06% of all thymic neoplasms.² Thymic carcinomas are usually moderately differentiated squamous carcinomas, which account for 40.0%–77.5%.^3-5 Some authors agreed that squamous carcinomas have more favorable prognosis than other histologic subtypes, such as lymphoepithelioma, sarcomatoid carcinoma and undifferentiated carcinoma.⁶ There are several systems to stage thymic carcinomas. Currently the WHO system is widely used and well correlates with Masaoka staging. About 65% thymic carcinomas, in WHO type C, had stage III or IV diseases with Masaoka staging.⁷ The early stage thymic carcinomas occur locally and may require surgical resection with favorable prognosis. By contrast, stage III and IV thymic carcinomas appear to be more aggressive with distant metastases. The recommended therapy for invasive thymoma has been radical surgical resection. For the patients with inoperable or recurrent diseases, chemotherapy is the alternative treatment.⁸ If the tumor is not resectable after neoadjuvant chemotherapy, additional chemotherapy and/or radiotherapy can be used. Standard chemotherapy for thymic carcinomas remains undefined. Yusuke Okumaf and his colleagues believed that cisplatin-based chemotherapy might be superior to carboplatin-based chemotherapy for advanced thymic carcinomas, with the response rates of 53.6% and 32.8% respectively.⁹ Radiotherapy is necessary and important for this type of patients despite resection is complete or incomplete.¹⁰ The median survival time is 48 months in patients with thymic carcinomas¹¹ and 5-year survival rates ranges from 28% to 60%.^12,13

Splenic metastases present with an incidence of only 0.3%–7.3% in autopsy reports.¹⁴ The most common primary sites of splenic metastases originate from lung, breast, ovary, and colon. Rare metastatic sites reported are kidney, prostate, skin, endometrium.¹⁵ Most patients with splenic involvement usually present with multi-visceral disseminated diseases. Isolated splenic metastasis is exceedingly rare. There are some hypotheses that might explain this phenomenon. Anatomically, it is lack of afferent lymphatics and the acute angle of the splenic artery from the celiac artery, which may prevent large clumps of tumor cells from getting access to the spleen. Rhythmic contractions of the spleen force the blood flow from the sinusoids to the splenic veins, which, in case of constant blood flow, could prevent tumor fixation.¹⁶ In addition, the spleen, which includes amount of lymphocytes and macrophagocytes, serves the immune function to inhibit the induction and growth of tumor cells.¹⁷

Splenic metastasis primary from thymic carcinoma is quite uncommon. According to literature, only 2 cases have been reported so far.^18,19 The patient discussed in the paper revealed a limited disease in advanced carcinoma. As the patient refused to perform surgical resection for this mass, we performed localized therapy with Cyberknife instead of chemotherapy for this isolated metastasis. Hellmanand and Weichselbaum²⁰ proposed a theory that oligometastatic state was that for many cancers, a few metastases exist at first, before the malignant cells acquire widespread metastatic potential. Localized therapies including surgery and SBRT are radical treatment options to achieve control of metastatic sites. One recent study²¹ of SBRT for oligometastases reported that local control rates was 84.4%, the overall survival (OS) was 84.4% at 1 y and 63.2% at 2 y. A partial response was observed in our case with local Cyberknife therapy and patient is still followed by our group closely.

In summary, although it is extremely rare, splenic metastasis should be taken into consideration in patients with thymic carcinomas. Radiotherapy is radical treatment option for isolated metastasis. Long-term follow-up is crucial to detect disease progression since recurrences are frequent.

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.