Thymic Carcinoids: A Case Study and Review of an Uncommon Association with AV Malformations

INTRODUCTION

Thymic carcinoids (TCs) are rare mediastinal tumors, representing 2–5% of thymic malignancies and 0.4% of neuroendocrine tumors.¹ Notably, 25% of thymic carcinoids are associated with MEN-1 syndrome. They are often detected incidentally, though some patients present with hormone-related symptoms namely carcinoid syndrome, Cushing’s syndrome and very rarely acromegaly.² Functional evaluation, syndromic evaluation, radiological evaluation to look for extent of the disease, functional scan to detect metastasis followed by surgery remains the ideal management of these patients.³ We hereby present our case of a male diagnosed with multiple AV-malformations had incidental detection of thymic carcinoid and management.

CASE DESCRIPTION

A 37-year-old male, who is a teacher by occupation, presented with recurrent swelling above the left ear, and was initially operated on for AV malformation at a peripheral center. After 4 months of initial surgery, he developed recurrent swelling at the operated site. The initial evaluation was done with an MRI of the head and neck, which detected multiple neck and scalp AV malformations and an anterior mediastinal mass. He was referred for further evaluation. He had no symptoms of cough, chest pain, hemoptysis, or Cushing’s syndrome. On clinical examination, there was a 5 × 4 cm soft compressible swelling above and in front of the left ear, with and an underlying scar healed by primary intention extending below and behind the left ear (Fig. 1). Further, contrast enhanced computed tomography (CT) of the neck and chest was done which showed large enhancing bulky lymph nodal masses in the anterior mediastinum, largest on the left side measuring about 9.8 × 9.6 cm, right side measuring about 6.2 × 5.7 cm with few calcifications on the right side lymph nodal mass, mild compression on the left brachiocephalic vein- SVC confluence (Fig. 2). Computed tomography guided biopsy was done in which morphology showed features of small round blue cell tumor. Immunohistochemistry was positive for synaptophysin and chromogranin A confirming as carcinoid tumor (Table 1). Endocrinology opinion was sought for syndromic and functional evaluation, which were all normal. Ga-68 DOTANOC scan showed uptake in the anterior mediastinal mass and also in AV- malformations (Fig. 3). The case was discussed in tumor board meeting and planned for surgical resection of the thymic mass. Sternotomy, excision of the tumor and lymph node dissection done in association with cardiothoracic surgeon (Fig. 4). Postoperatively, patient recovered well. The histopathology showed TC, with 7 out of 8 lymph nodes positive (Fig. 5). The case was re-discussed in tumor board meeting. As it was R0 resection decision was taken for follow-up, hence the patient remains under regular follow-up.

DISCUSSION

Thymic carcinoid is a rare neuroendocrine tumor, representing 2–5% of all foregut derived thymic tumors and 0.4% of neuroendocrine tumor Carcinoid “ term was coined by Oberndorfer in 1907 which is a misnomer.^1,4 Thymic carcinoid was first described in 1972 by Rosai and Higa in 1972 by describing eight primary mediastinal tumors.⁵ Thymic carcinoids have a gender predilection for adult males, with male-to-female ratio of 3:1 in their 30 and 40 seconds.⁶ They are sporadic tumors, 25% of which are associated with MEN1 syndrome.⁷ Lokich described two female patients with MEN -1 with carcinoid thymic tumor.⁸ They can be asymptomatic being, unrecognized until advanced stages, or present with ambiguous symptoms, compressive symptoms, but they are also known to be associated with paraneoplastic syndromes. Cushing’s syndrome is seen in 35% of cases due to ectopic ACTH production, humoral hypercalcemia of malignancy is seen in 30% of cases secondary to the secretion of parathyroid hormone related peptide(PTH-rP) but they rarely manifest with carcinoid syndrome, unlike other gastrointestinal carcinoids, acromegaly due to increased growth hormone.^9,10 The symptoms of mass effects due to compression on local structures depend on the organ involved, and extent of involvement, which includes cough, dyspnea, chest pain, hoarseness, and superior vena cava syndrome (20% of patients).⁶

Thymic carcinoids are a diagnostic challenge that require a high level of suspicion. The initial evaluation is to be done with contrast-enhanced computed tomography (CECT) of the chest to look for location, characterization, invasion of surrounding structures, and regional metastasis, like in our patient who had compression of the left brachiocephalic vein-SVC confluence. Based on the CT findings, character of mass, size, and extent of involvement, the treating team can plan for surgical excision or tissue biopsy. In patients with large lesions with suspected local invasion, a CT guided biopsy is recommended to identify the pathology and plan further management. These lesions need differentiation from other mediastinal lesions, namely germ cell tumors and lymphomas, in which the treatment modality is mainly medical, in contrast to carcinoids, where treatment is mainly surgical.¹¹ Biochemical evaluation is to be done to look for the functionality of the tumor as mentioned above and syndromic association with MEN-1. Thymic carcinoids, like other neuroendocrine tumors, over express somatostatin receptors which helps us in using Ga-68 DOTANOC scan to identify, locate, differentiate from other tumors. World Health Organization (WHO) in 2015 grouped lung and thymic neuroendocrine tumors in group and formed four categories namely, TC, atypical carcinoid (AC), small cell lung cancer (SCLC), large cell neuroendocrine carcinoma (LNEC). Patients with carcinoids have better prognosis compared to SCLC, LNEC.¹² Treatment of the thymic carcinoids depends on their functionality, size of the lesion and, resectability. Functional tumors need to be managed initially by medical treatment to antagonize the effects of the secretion of the hormones. A complete surgical resection, which includes resection of all the anterior mediastinal compartment, including the hilar and mediastinal lymph nodes, is the treatment of choice for a localized disease. In R0 resection, there is no role for adjuvant therapy like our patient, who is on follow-up. Whereas in patients with incomplete resection, radiotherapy preferably with chemotherapy, is recommended, but evidence is lacking. The prognosis is determined by tumor stage, resectability, histologic grade, and proliferation index. Thymic carcinoids have a poor prognosis compared to carcinoids in the gastrointestinal tract.¹³

CONCLUSION

Thymic carcinoids, though rare, require a high index of suspicion and comprehensive evaluation. This case underscores the need for thorough imaging and histopathological assessment in patients with mediastinal masses. Radiological, biochemical evaluation assisted by functional scans followed by surgical management remains the treatment of choice.

ORCID

Jnaneshwari Jayaram https://orcid.org/0000-0002-8241-4041

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