|Year : 2022 | Volume
| Issue : 2 | Page : 52-55
Thymic carcinoid presenting as cushing's syndrome
Anand Deodhar1, Dinesh Kulkarni2, Kishor Kharche3, Thomas George4
1 Department of Cardiotheracic Vascular Surgery, United Ciigma Hospital, Auranganbad, Maharastra, India
2 Department of Histopathology, Saurabh Histopathology Centre, Auranganbad, Maharastra, India
3 Department of Endocrinology, United Ciigma Hospital, Auranganbad, Maharastra, India
4 Department of Radiology, Kamal Nayan Bajaj Hospital, Auranganbad, Maharastra, India
|Date of Submission||18-Sep-2021|
|Date of Decision||10-Jul-2022|
|Date of Acceptance||11-Jul-2022|
|Date of Web Publication||29-Aug-2022|
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Source of Support: None, Conflict of Interest: None
Primary neuroendocrine tumors of the thymus (NETTs) are rare neoplasms and are biologically aggressive. These are more frequently seen in the third to fifth decade of life. Endocrinopathies such as Cushing's syndrome, acromegaly, or multiple endocrine neoplasia-1 are associated in 50% of cases. These tumors usually present with the invasion of surrounding mediastinal structures. The long-term outcome of NETT is poor due to high risk of recurrence or metastasis. Prognosis depends on the stage, invasion, resection, and possible association of endocrinopathies. We present this case of a 17-year-old male clinically diagnosed as Cushing's syndrome with hypothyroidism, without adrenal mass but with anterior mediastinal mass, and it histologically turned out to be carcinoid of the thymus. Although thymic carcinoids are known to present with Cushing's syndrome, we have not come across with its association of hypothyroidism. Total thymectomy was performed for the case. The patient is on regular follow-up for the past 3 years, he is totally asymptomatic and not on any medication.
Keywords: Cushing's syndrome, hypothyroidism, neuroendocrine tumor, thymus
|How to cite this article:|
Deodhar A, Kulkarni D, Kharche K, George T. Thymic carcinoid presenting as cushing's syndrome. Oncol J India 2022;6:52-5
| Introduction|| |
Thymic neuroendocrine tumors (TNETs) were first described by Rosai and Higa in 1972 as a distinct entity from thymoma. These are a rare entity which accounts for approximately 0.4% of all carcinoid tumors and about 5% of all tumors in the thymus and mediastinum.,, According to the 2015 World Health Organization classification of tumors, TNETs are separated into four histological entities such as typical (low grade) and atypical (intermediate grade) carcinoid tumors, large-cell neuroendocrine carcinomas, and small cell carcinomas.
Ectopic adrenocorticotropic hormone (ACTH) secretion is uncommon and contributes 10% of cases of endogenous Cushing's syndrome. Ectopic ACTH secretion in thymic carcinoid may be the rare cause of Cushing's syndrome. Thymic carcinoids are rare and believed to arise from thymic cells of neural crest origin (Kulchitsky cells) and have aggressive behavior than their counterparts in other sites, and hence, associated with a poor prognosis. Despite of treatment, most patients with TNET develop local relapse or distant metastasis within 5 years of diagnosis.
Here, we describe a case of thymic carcinoid in a 17-year-old male associated with Cushing's syndrome and hypothyroidism.
| Case Report|| |
A 17-year-old male overweight presented with swollen body and face with progressive weakness in upper and lower limbs for 10 months. On examination, he was obese, had Cushingoid striae and neck hump. A probable diagnosis of Cushing's syndrome was thought, and he was investigated accordingly. Special laboratory investigations revealed hypothyroid status, serum cortisol levels raised (Early morning 47.01 μg/dL [Normal 5–23 μg/dL], Evening 18.06 μg/dL (Normal 138–635 μg/dL]), and ACTH level of 41.82 pg/dL. With the above clinical and laboratory investigation findings, a provisional diagnosis of Cushing's syndrome with hypothyroidism and diabetes mellitus was considered. The contrast-enhanced computerized tomography (CECT) scan of the abdomen and pelvis revealed normal morphology of the liver, spleen, kidneys, adrenals, and urinary bladder. X-ray chest showed a well-defined lobulated mediastinal mass silhouetting the right heart border [Figure 1]. CECT scan of the thorax shows homogeneously enhancing mass of size 8.2 cm × 5 cm × 6.3 cm in the right paramedian anterior mediastinum [Figure 2] abutting ascending aorta and superior vena cava without infiltration and the absence of any internal dominant calcification or fat. There was evidence of single 6 mm × 6 mm size prevascular node. The trachea, major bronchi, pulmonary hila, heart, lung parenchyma, and bony cage appear normal. Hence, the case was suspected to be a case of ectopic Cushing's syndrome. His magnetic resonance imaging brain showed normal morphology. His routine hematology and biochemical tests, electrocardiogram, and 2-dimensional echocardiography were within normal limits. Serum alpha-fetoprotein and beta-human chorionic gonadotropin levels were within normal limits. With preoperative fitness, under general anesthesia, midline sternotomy was performed. On intra-operative findings, the right lobe of the thymus was enlarged of size 4 cm × 4 cm × 5 cm and a single firm nodule of 1 cm in the left lobe of the thymus, not attached to pericardium or vascular structures. Total thymectomy was performed with excision of single prevascular mediastinal lymph node. Hemostasis was confirmed. Bilateral pleural drains were inserted. The sternum was closed with eight steel wires. Presternal tissue was closed with vicryl. The skin was closed with skin clips. The specimen was sent for histopathology examination.
|Figure 2: Contrast-enhanced computerized tomography scan of thorax on coronal (a) and axial (b) sections showing homogeneously enhancing mass (arrows) in the right paramedian anterior mediastinum abutting ascending aorta and superior vena cava without infiltration and absence of any internal dominant calcification or fat|
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Gross examination of the specimen revealed as right lobe thymus of size 8 cm × 6 cm × 3 cm oval in shape with surrounding fat and surface capsulated with fleshy cut surface [Figure 3]. The left lobe thymus was 3 cm × 2 cm × 1 cm in size, flat in shape, surface capsulated, and the cut surface was grayish with a small-rounded nodule. Moreover, we received a single mediastinal lymph node of size 1 cm × 1 cm, capsulated with grayish cut surface.
|Figure 3: Cut surface of thymic mass (Rt) lobe shows fibrous capsule with fat and fleshy cut surface|
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Serial sections from both lobes of the thymus revealed fibrous capsule and underneath Hassel's corpuscles, along with nests and lobules of atypical cells. These atypical cells displayed fairly monomorphic round nuclei, fine granular cytoplasm, and moderate amount of cytoplasm [Figure 4]. Cellular atypia, significant mitotic activity, or necrosis are not identified. No capsular invasion was seen. Surrounding fat has scattered lymphoid collection. The lymph node showed reactive hyperplasia. With the above histological features, a diagnosis of typical carcinoid (low grade) of the thymus was made involving both the lobes and the blocks were subjected for further studies. On immunohistochemical examination, the tumor cells expressed cytokeratin. Synaptophysin [Figure 5] and chromogranin were positive [Figure 5], and the Mib labeling index was <1% and thus confirmed our diagnosis of low-grade typical carcinoid.
|Figure 4: Shows tumor cells composed of lymphocytoid cells in groups and lobules with rounded nuclei with fibrous septae and minimum mitoses (H and E, ×400)|
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He tolerated the procedure well, and the postoperative stay was uneventful. He was discharged on 8 postoperative day. After 2 months of surgery, his Cushing's syndrome resolved, and at the same time, his thyroid function tests and blood sugar returned to normal levels. Since then, he is not on any medication. The patient is on regular follow-up for the past 3 years and is asymptomatic without any evidence of disease.
| Discussion|| |
Thymic carcinoid tumors are rare neoplasms and constitute around 2% of all carcinoid tumors. These tumors are rare during childhood and adolescence, but when present are often associated with overproduction of ACTH causing Cushing's syndrome. Relatively, few cases of thymic carcinoid tumors in children and adolescents have been reported in the literature. Our patient of thymic carcinoid also presented with Cushing's syndrome, and the case was detected at 17-year-old age.
Primary neuroendocrine tumors of the thymus (NETTs) are unusual tumors with aggressive behavior. These tumors manifest in four different ways such as may be asymptomatic, may produce symptoms of mediastinal compressions, may present with associated endocrinopathies, and may have signs and symptoms related to distant metastasis. It is estimated that about one-third of the patients are asymptomatic and are incidentally detected. Almost 50% of TNET are functionally active and are associated with endocrinopathies such as Cushing's syndrome being the most common as seen in up to 25% of cases, and multiple endocrine neoplasia-1 (MEN-1) in up to 25%, MEN-2, and others. These tumors manifest as large, lobulated mediastinal masses and are usually indistinguishable from thymomas. The possible differential diagnoses for thymic carcinoids are other primary mediastinal tumors such as thymoma, paraganglioma, lymphoma, parathyroid adenoma or carcinoma, and medullary carcinoma of the thyroid of mediastinal location.
It has also been observed that typical carcinoids are capable of regional lymph node metastasis as well as distant metastasis, so it is recommended that the term benign is not to be used in relation to it. Approximately 50% of patients develop regional lymph node involvement at the time of surgical resection. Distant metastasis may occur with bone, and lungs are frequently involved sites; other rare sites include the liver, pancreas, and adrenal glands., In our patient, there was no regional lymph node metastasis. These tumors respond very well to surgical excision. Radical surgical excision of the thymus is the treatment of choice in thymic carcinoids. Even debulking should be considered the best option in nonresectable tumors. Survival of NETT depends on the stage of presentation, histologic degree of differentiation, invasivity, associated endocrine features, and complete resectability of mass. The patients who undergo surgery had better survival than nonsurgical treatment. Filosso et al. in a large series on NETT reported that ability to undergo surgery and completeness of resection were the strongest prognostic factors. Study-based data revealed the 5-year survival rate ranges from 50% to 100% for typical carcinoids. The present case underwent complete surgical resection of the thymus and is doing well without any evidence of disease recurrence still his last follow-up at 3 years.
| Conclusion|| |
Patients clinically presenting with Cushing's syndrome should be properly evaluated. If their ultrasonography/CECT abdomen does not reveal a lesion in the adrenal region, they must be subjected for X-ray and CECT chest for evidence of thymic mass. If thymic mass is present, then a diagnosis of TNET should be considered, confirmed, and treated accordingly. Ectopic Cushing's syndrome is a rare disease with varied manifestations and presents with clinical features similar to classical Cushing's. Surgery with the removal of primary tumor is the treatment of choice.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Rosai J, Higa E. Mediastinal endocrine neoplasm, of probable thymic origin, related to carcinoid tumor. Clinicopathologic study of 8 cases. Cancer 1972;29:1061-74.
Bohnenberger H, Dinter H, König A, Ströbel P. Neuroendocrine tumors of the thymus and mediastinum. J Thorac Dis 2017;9 Suppl 15:S1448-57.
Wang HB, Yang Y, Fan XW, Xu Y, Long J, Wu KL. Thymic neuroendocrine tumors: An analysis of 18 cases and a literature review. Transl Cancer Res 2016;5:789-96.
Filosso PL, Ruffini E, Solidoro P, Roffinella M, Lausi PO, Lyberis P, et al.
Neuroendocrine tumors of the thymus. J Thorac Dis 2017;9:S1484-90.
Marx A, Chan JK, Coindre JM, Detterbeck F, Girard N, Harris NL, et al.
The 2015 World Health Organization classification of tumors of the thymus: Continuity and changes. J Thorac Oncol 2015;10:1383-95.
Bhansali A, Walia R, Rana SS, Dutta P, Radotra BD, Khandelwal N, et al.
Ectopic Cushing's syndrome: Experience from a tertiary care centre. Indian J Med Res 2009;129:33-41.
] [Full text]
Arora R, Gupta R, Sharma A, Dinda AK. Primary neuroendocrine carcinoma of thymus: A rare cause of Cushing's syndrome. Indian J Pathol Microbiol 2010;53:148-51.
] [Full text]
McEvoy MP, Rich BS, Tang LH, Quaglia MP. Thymic carcinoid presenting with Cushing's syndrome in a 17-year old boy: A case report and review of literature. J Clin Oncol 2011;29:716-8.
Gaude GS, Hattiholi V, Malur PR, Hattiholi J. Primary neuroendocrine carcinoma of the thymus. Niger Med J 2013;54:68-71.
] [Full text]
Chaer R, Massad R, Evans A, Snow NJ, Geha AS. Primary neuroendocrine tumor of thymus. Ann Thorac Surg 2002;74:1733-40.
Moran CA, Suster S. Neuroendocrine carcinomas (carcinoid tumor) of the thymus. A clinicopathologic analysis of 80 cases. Am J Clin Pathol 2000;114:100-10.
Filosso PL, Yao X, Ahmad U, Zhan Y, Huang J, Ruffini E, et al.
Outcome of primary neuroendocrine tumors of the thymus: A joint analysis of the International Thymic Malignancy Interest Group and the European Society of Thoracic Surgeons databases. J Thorac Cardiovasc Surg 2015;149:103-9.e2.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]