A Rare Case of Thymic Carcinoma: Unusual Presentation of Multiple Lymph Node Metastases Masquerading as Lymphoproliferative Disorder

Abstract

Thymic carcinoma is known for its aggressive nature and low survival rates. Due to the rarity of its presentation, particularly with multiple lymph node metastasis resembling lymphoproliferative disorders, emphasizes the need to share our case in the literature. We aimed to raise awareness among surgeons regarding this atypical presentation. Our findings indicate that, in cases of higher stage thymic carcinoma, lymph node dissection should be considered in addition to thymectomy. This recommendation is based on our research and can help guide treatment decisions for similar cases in the future.

INTRODUCTION

Thymic tumors comprising thymoma, thymic carcinoma, and neuroendocrine carcinoma are rare malignancies that usually occur in the anterior mediastinum.[1] They are aggressive tumors, prone to their tendency to locally invade surrounding tissues and adjacent organs. Most often they are diagnosed at advanced stages. In view of rare occurrences, there is a limited amount of clinical research available, with most studies being comprised of case reports and small series.[2] Thymic tumors can metastasize and present with varying presentations. Due to the rarity, we are presenting here an unusual presentation of multiple lymph node metastases from thymic carcinoma mimicking lymphoproliferative disorder.

CASE REPORT

A 57-year-old male presented with a 1-month history of swelling in the right side of his neck. Within the past 10 days, the swelling rapidly increased in size. The patient also reported weight loss, loss of appetite, cough, and breathlessness. On examination, a firm, mobile swelling measuring 4 cm × 3 cm was palpable in the right side of the neck below the angle of the mandible. No warmth or tenderness was noted. Axillary lymph nodes were palpable <1 cm.

A contrast-enhanced computed tomography (CECT) scan of the neck revealed multiple enlarged lymph nodes at right level II and V, with the largest measuring 4 cm × 4 cm. Fine-needle aspiration cytology showed atypical cells in clusters, displaying increased nuclear-cytoplasmic ratio, and some cells with nucleoli. Focal areas of necrosis were observed, and no granulomas were seen. Excision biopsy was recommended to rule out the possibility of a metastatic deposit in the lymph node.

The cervical lymph node biopsy revealed partial effacement of architecture, with a monomorphous population of cells arranged in vague lobules and perivascular rosettes. Focal areas of necrosis and a sprinkling of lymphocytes were also observed. In addition, numerous mitotic figures high power field (69/10 HPF) were seen [Figure 1].

Figure 1.

(a) Lymph node with partial effacement of architecture by monomorphous population of cell (×10). (b) Monomorphic population of epithelial cells arranged in perivascular rosettes (×20). (c) High power view of atypical cells with numerous mitotic figures (×40). (d) Pan CK-membranous positivity in more than 60% tumor cells (×40). (e) CD117-diffuse (more than 80%) membranous positivity in tumor cells. (f) CD20-negative in tumor cells. Positive in stromal lymphocytes (×40). (g) CD3-negative in tumor cells. Positive in stromal lymphocytes (×40). (h) CD30-negative in tumor cells and stromal cells. (i) Ki67 shows proliferation rate of 60% (×40)

Based on these findings, it is crucial to consider the possibility of metastatic cancer. Further evaluation, including CECT chest and positron emission tomography scan, was suggested for a more accurate diagnosis and to determine the primary source of the metastasis. This will help to guide appropriate management and treatment options.

CECT chest showed heterogeneous enhancing lobulated soft-tissue density lesion involving anterior and middle mediastinum with superior vena cava obstruction [Figure 2]. Following this patient underwent mediastinal mass resection.

Figure 2.

Contrast-enhanced computed tomography chest revealed a heterogenous lesion involving anterior and superior mediastinum causing superior vena cava obstruction

Immunohistochemistry (lymph node): Ki67-60%, Pan CK (CLONE-AE1/AE2)-membranous positivity in more than 60% of tumor cells. CD45-negative in the tumor cells. CD20 (CLONE-Ks20.8)-negative in tumor cells, positive in stromal lymphocytes. CD3 (CLONE-PS1)-negative in tumor cells, positive in stromal lymphocytes. CD30 (CLONE-1G12)-negative in tumor cells and stromal cells. CD117-diffuse (more than 80%) membranous positivity in tumor cells.

The patient underwent radical thymectomy. Intraoperatively mass seemed to be attached to superior vena cava and lungs. Hence, incomplete resection was done and sent for histopathological examination.

A biopsy is done from the mediastinal mass which showed atypical epithelial cells arranged in vague lobules, sheets, and perivascular rosettes with interspersed lymphocytes, areas of necrosis, and numerous mitotic figures (40/10 HPF) similar to lymph node biopsy [Figure 3]. Four lymph nodes show tumor deposit.

Figure 3.

(a) Gross images of thymic carcinoma-tan white vaguely lobulated with areas of necrosis and cystic degeneration. (b) H and E image-atypical epithelial cells with areas of necrosis (×20). (c) Atypical epithelial cells arranged in sheets which are large having moderate cytoplasm with vesicular nuclei, inconspicuous nucleoli, and numerous mitotic figures (×40). (d) Tumors cells arranged in nest having clear cytoplasm separated by hyalinised area (×40). (e) Ki-67 shows proliferation rate of 65% (×40). (f) CD117-Diffuse and Intense staining in tumor cell (×40). (g) Pan-CK-Diffuse and intense staining in tumor cells (×40)

Immunohistochemistry (thymic resection mass): Ki67 65%, Pan CK (CLONE AE1/AE2) Membranous positivity in more than 60% of tumor cells. CD45 negative in the tumor cells. CD117 diffuse (more than 80%) membranous positivity in tumor cells. Synaptophysin showed focal positivity [Figure 4].

Figure 4.

Tumor cells showing synaptophysin positivity (×40)

With the above-mentioned histopathological and immunohistochemical findings, we gave a diagnosis of thymic carcinoma with neuroendocrine differentiation with lymph node metastasis.

DISCUSSION

The thymus is a small gland situated in the upper chest, behind the sternum. It plays a vital role in the immune system, specifically in the development and maturation of T-cells. T-cells are a type of white blood cell that is responsible for immune defense. The thymus is most active during childhood and adolescence, gradually decreasing in size, activity and involutes as a person ages. It is essential for the proper functioning of the immune system and aids in protecting the body against infections and diseases. According to the 2021 WHO classification, thymic epithelial tumors are categorized as thymoma (type A, AB, B1, B2, and B3), thymic carcinoma, and thymic neuroendocrine tumors.[3] Among thymic epithelial tumors thymic carcinoma accounts <1%–4%.[4] According to the previous available data prevalence of nodal metastasis in thymic carcinoma was reported to be 26.8%.[5] Thymic carcinoma is a rare and aggressive type of cancer that differs from thymoma in terms of its clinical behavior. Unlike thymoma, which tends to have a more indolent course, thymic carcinoma is associated with a more aggressive progression. Most patients with thymic carcinoma are diagnosed at an advanced stage, which contributes to a poor prognosis. Due to its rarity and aggressive nature, thymic carcinoma poses significant challenges in terms of treatment and management.[5,6] Thymic carcinomas typically occur in patients with a median age of 54–65.5-years-old, although cases have been reported in a wide age range from 12 to 96 years old. It is more common in males than females.[7] Thymic carcinoma is the fourth most common tumor presenting as a solitary lesion in the thymus followed by thymoma, benign cyst, and lymphoma.[8] Thymic epithelial tumors comprising thymoma, thymic carcinoma, and thymic neuroendocrine carcinoma can metastasize to different sites. Among that thymic carcinoma is more aggressive and can spread to various sites such as lymph nodes,[2] lungs, liver, pleura, spine, and breast.[9] Based on histological and immunohistochemical features, thymic carcinoma can be differentiated from thymic neuroendocrine carcinoma. Both have aggressive behavior and are prone to distant metastasis. Before diagnosing it as thymic primary, tumor metastasis from other sites should be ruled out. CD 117 and CD 5 positivity are suggestive of a thymic primary tumor. Thymic neuroendocrine markers will show diffuse and intense staining of neuroendocrine markers (synaptophysin and chromogranin).[10] The differentials considered in this case were lymphoma, thymoma, thymic carcinoma, and metastatic tumors. The lymphoproliferative disorder was ruled out due to the absence of CD3, CD20, CD30, and CD45 and the presence of Cytokeratin. Thymoma was ruled out due to the presence of CD 117. Metastatic tumors were ruled out based on CT findings. Based on immunohistochemical and clinicoradiological features, a diagnosis of thymic carcinoma with neuroendocrine differentiation was made. Thymic carcinoma can show focal neuroendocrine differentiation, whereas in thymic neuroendocrine carcinoma, neuroendocrine markers show diffuse and strong expression.[11] Primary thymic carcinoma and primary neuroendocrine carcinoma of the thymus should be diagnosed properly due to the variation in treatment modalities. Surgery plays an important role in the management of thymic carcinoma. Based on the resection method survival rate varies, complete resection of thymic carcinoma with 5-year survival rate ranges from 55% to 78%.[12] The recommended treatment for early-stage thymic malignancies is a radical thymectomy, which involves the removal of the thymus gland along with the surrounding tissue. This approach aims to completely remove the tumor and any potential areas of spread. On the other hand, for advanced stages of thymic malignancies, a multimodality therapy approach is typically employed. This means that a combination of different treatment modalities, such as surgery, radiation therapy, and chemotherapy, may be used to effectively manage the disease. The specific treatment plan will depend on the individual patient’s condition and the extent of the cancer.[13,14] Previous literature says that lymph node involvement is more common in thymic carcinoma and neuroendocrine carcinoma. Therefore, lymph node dissection is suggested for tumors with higher staging, thymic carcinoma, neuroendocrine carcinoma, and tumors with sizes more than 6 cm.[15]

CONCLUSION

Thymic carcinoma is an aggressive tumor with a poor survival rate. Due to the rare presentation of thymic carcinoma with multiple lymph node metastases mimicking lymphoproliferative disorder, we are adding our case to the literature to make aware of the surgeons about this unusual presentation. Our results suggest that lymph node dissection is recommended for higher-stage thymic carcinoma in addition to thymectomy.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.