|Year : 2013 | Volume
| Issue : 2 | Page : 278-280
Primary neuroendocrine mediastinal tumor presenting with carcinoid syndrome and left supraclavicular lymphadenopathy: Clinico-radiological and pathological features
Amit Nandan D Dwivedi1, Kanika Goel1, Suchi Tripathi2, Sunny Garg2, Madhukar Rai2
1 Department of Radiodiagnosis and Imaging, Institute of Medical Sciences, Banaras Hindu University,Varanasi, Uttar Pradesh, India
2 Department of Internal Medicine, Institute of Medical Sciences, Banaras Hindu University,Varanasi, Uttar Pradesh, India
|Date of Web Publication||13-Jun-2013|
Amit Nandan D Dwivedi
Department of Radiodiagnosis and Imaging, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Primary mediastinal neuro-endocrine tumor is very rare. The primary modality to evaluate the lesion is computed tomography, to know disease extent, involvement of various structures, vascular invasion and metastasis. Histo-pathological and immuno-histochemical confirmation is mandatory. We report a rare case of primary neuroendocrine mediastinal tumor/atypical carcinoid in a young male who presented with carcinoid syndrome and left supraclavicular lymphadenopathy. Complete diagnostic work up was done followed by histo-pathological and immuno-histochemical confirmation. Later on patient underwent radical surgery followed by chemotherapy. The patient is currently on follow up.
Neuroendocrine carcinoma of the thymus generally follows an aggressive clinical course.The biologic behavior is directly related to grade and degree of differentiation. This case report of primary low grade neuroendocrine tumor/atypical carcinoid adds to the biological behavior of this tumor and sheds light on the radiological and pathological features of neuroendocrine carcinomas.
Keywords: Carcinoid, Contrast enhanced CT, Immunohistochemistry, Mediastinum, Neuro-endocrine tumor
|How to cite this article:|
Dwivedi AD, Goel K, Tripathi S, Garg S, Rai M. Primary neuroendocrine mediastinal tumor presenting with carcinoid syndrome and left supraclavicular lymphadenopathy: Clinico-radiological and pathological features. J Can Res Ther 2013;9:278-80
|How to cite this URL:|
Dwivedi AD, Goel K, Tripathi S, Garg S, Rai M. Primary neuroendocrine mediastinal tumor presenting with carcinoid syndrome and left supraclavicular lymphadenopathy: Clinico-radiological and pathological features. J Can Res Ther [serial online] 2013 [cited 2020 Feb 24];9:278-80. Available from: http://www.cancerjournal.net/text.asp?2013/9/2/278/113385
| > Introduction|| |
Carcinoid tumors are derived from primitive stem cells in the gut wall but can be seen in other organs. ,, In children, most tumors occur in the appendix and are indolent, benign and asymptomatic. However, aggressive, fast-growing forms of carcinoid cancer also exist. Carcinoid tumors can secrete a variety of functional hormones and chemicals e.g. serotonin, chromogranin A, histamine, pancreatic polypeptide and gastrin. Some carcinoid tumors are non functional. Carcinoid tumors are referred to as functioning if they secrete hormones that cause a clinical syndrome.  Primary mediastinalneuro-endocrine tumor is very rare. The primary modality to evaluate the lesion is computed tomography, to know disease extent, involvement of various structures, vascular invasion and metastasis. We report a rare case of neuroendocrine mediastinal tumor in a young male who presented with carcinoid syndrome and left supraclavicular lymphadenopathy. Complete diagnostic work up was done followed by histo-pathological confirmation. Later on patient underwent radical surgery followed by chemotherapy.
| > Case Report|| |
A twenty eight years old male presented with complaints of multiple episodes of heaviness in chest, anxiety, sweating, and palpitation for a year with increased frequency for last 2-3 months.There were episodes of dry cough and loose stools for last one month. There was history of acute onset swelling on left side of face, trunk and left arm which subsided after few days. There was no past history of tuberculosis, hypertension, COPD. Chest examination shows tracheal shift towards right with decreased breath sounds on left side. Abdominal examination revealed mild hepatomegaly. Multiple discrete enlarged left supraclavicular lymph nodes were seen. Blood examination and stool for occult blood was within normal limits. 24 hour urine HIAA was 8.5mg/24 hour.
Chest radiographs showed mediastinal widening with an ill-defined radio opacity filling the anterior mediastinum [Figure 1].
|Figure 1: Chest radiograph showing mediastinal expansion and tracheal shift|
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Contrast enhanced CT scan of thorax showed a large ill-defined lobulated moderately and hetrogenous enhancing mass lesion in anterior mediastinum with foci of punctate calcification and internal necrosis [Figure 2]. There was evidence of vascular encasement with hypodense thrombus in left brachiocephalic vein [Figure 3]. Left main bronchus was extrinsically compressed leading to sub segmental collapse of left lower lobe. Associated pericardial effusion and elevated left hemi diaphragm were noted. Multiple enlarged discrete hypo dense lymph nodes in pre tracheal, subcarinal, prevascular and left supraclavicular fossa were noted [Figure 4].
|Figure 2: Contrast enhanced ct showing moderately and hetrogenous enhancing mass lesion measuring 9.5×14×11 cm in anterior mediastinum with foci of punctate calcification and cystic changes/necrosis|
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|Figure 3: Contrast enhanced ct showing vascular encasement with hypodense thrombus in compressed left brachiocephalic vein|
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|Figure 4: Multiple enlarged discrete hypodense lymphnodes in pre tracheal, subcarinal, prevascular compartment|
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Bronchoscopy revealed right sided tracheal shift. Left main, segmental and subsegmental bronchi showed extrinsic partial occlusion. Bronchoalveolar lavage (BAL) was negative for Ziehl Neelsen (ZN) stain, Gram stain, KOH mount and any malignant cells.
Ultrasound and CECT abdomen and pelvis were within normal limits.
Biopsy from supra-clavicular nodes showed cells lying in sheets, clusters and ribbons in a vascular stroma. These cells had monomorphic nuclei with fine stippled chromatin; cytoplasm was scanty to moderate and finely vacuolated. Immunohistochemistry was found to be positive for creatinine kinase (CK) and synaptophysin suggestive of low grade neuroendocrine tumor. Ultrasound guided biopsy from the primary mediastinal mass lesion reported similar findings. The case was reported as primary low grade neuroendocrine tumor of mediastinum with carcinoid syndrome and left supraclavicular nodal metastasis. Later on patient underwent radical surgery followed by chemotherapy.
| > Discussion|| |
Neuroendocrine neoplasms are rare tumors of mediastinum that have been the source of much controversy in the literature. These may originate from the thymus proper or from paraganglionic structures within the mediastinum, or may be the result of neoplastic transformation in misplaced embryonal rests within the mediastinum. These tumors can often be the source of hormone secretion and thus come to the attention of the clinician owing to endocrinal abnormalities. The most common neuroendocrine neoplasms in the mediastinum are thymicneuro-endocrine carcinomas. Rarely, the mediastinum also can be the seat of tumors derived from aorticopulmonary or aortico-sympathetic paraganglia or from ectopic or supernumerary parathyroid glands.
Primary neuroendocrine tumors of the thymus are unusual tumors with less than 5% of all anterior mediastinal neoplasms. Klemm and Moran,  regard such tumors as part of a single spectrum of differentiation, ranging from well-differentiated to moderately differentiated to poorly-differentiated neuroendocrine neoplasms. Unlike carcinoids arising from the gastrointestinal tract or the lungs, these tumors are highly aggressive. It has been found that these tumors are malignant in approximately 82% of cases, as opposed to bronchial carcinoids, which are less aggressive and are malignant in approximately 26% of cases. 
Thymic neuroendocrine carcinomas generally manifest as anterosuperiormediastinal masses with a male predilection (male/female ratio, 3:1). The disease most often affects middle-aged adults between 40-50 years age group. , Clinically, these tumors manifest in one of four ways: (1) asymptomatic, found incidentally on routine chest radiography, (2) they may produce symptoms of thoracic structure displacement or compression, (3) they may present with symptoms related to an associated endocrinopathy, or (4) they may present with symptoms and signs relating to a distant metastasis, most commonly to the liver, lung, pancreas, pleura, and bone.  About a third of the patients may have endocrine symptoms. There is a strong clinical association with endocrine abnormalities, particularly the MEN-type 1 syndrome, and other conditions such as polyarthropathy, proximal myopathy, peripheral neuropathy, hyperparathyroidism,inappropriate antidiuretic hormone secretion, Eaton-Lambert syndrome, and hypertrophic osteoarthropathy. 
Chromogranin is the most reliable neuroendocrine marker for these tumors.  In a recent study on a large series of cases, positivity for chromogranin in 75% of cases and for synaptophysin in 72% was noted, with only 60% cases showed both chromogranin and synaptophysin positivity. Thus, both markers should be used in the panel of immunohistochemical stains when looking for the possibility of a neuroendocrine carcinoma.  Neuroendocrine carcinoma of the thymus generally follows an aggressive clinical course with a poor prognosis because of the high incidence of local recurrence and metastatic disease after surgical excision. The overall survival rate was 28% at 5 years and 10% at 10 years in one recent study. The biologic behavior was directly related to grade and degree of differentiation.  It also depends on the mitotic activity, associated endocrinopathy, capsular invasion, incomplete resection, lymph node status and presence of metastasis at the time of diagnosis. Follow-up of the patient includes clinical examination, chest radiographs, computed tomography, and metastatic workup every 6 to 12 months  and should be monitored closely for 10 years or less after primary diagnosis.
| > Conclusions|| |
This case report of primary low grade neuroendocrine tumor/atypical carcinoid of mediastinum in a young adult presenting with carcinoid syndrome and left supraclavicular nodal metastasis add to the biological behavior of this tumor and sheds light on the radiological and pathological features of neuroendocrine carcinomas.
| > References|| |
|1.||Broaddus RR, Herzog CE, Hicks MJ. Neuroendocrine tumors (carcinoid and neuroendocrine carcinoma) presenting at extra-appendiceal sites in childhood and adolescence. Arch Pathol Lab Med 2003;127:1200-3. |
|2.||Moraes TJ, Langer JC, Forte V, Shayan K, Sweezey N. Pediatric pulmonary carcinoid: A case report and review of the literature. Pediatr Pulmonol 2003;35:318-22. |
|3.||Soga J, Yakuwa Y, Osaka M. Evaluation of 342 cases of mediastinal/thymic carcinoids collected from literature: A comparative study between typical carcinoids and atypical varieties. Ann Thorac Cardiovasc Surg 1999;5:285-92. |
|4.||Reidy DL, Tang LH, Saltz LB. Treatment of advanced disease in patients with well-differentiated neuroendocrine tumors. Nat Clin Pract Oncol 2009;6:143-52. |
|5.||Klemm KM, Moran CA. Primary neuroendocrine carcinomas of the thymus. Semin Diagn Pathol 1999;16:32-41. |
|6.||Buck JL, Sobin LH. Carcinoids of the gastrointestinal tract. Radiographics 1990;10:1081-95. |
|7.||Dusmet ME, McKneally MF. Pulmonary and thymic carcinoid tumors. World J Surg 1996;20:189-95. |
|8.||Axelson J, Kobari M, Furukawa T, Matsuno S. Thymic carcinoid in the pancreas: Metastatic disease or new primary tumors. Eur J Surg 1999;165:270-3. |
|9.||Moran CA, Suster S. Neuroendocrine carcinoma (carcinoid tumor) of the thymus: Aclinicopathologic analysis of 80 cases. Am J Clin Pathol 2000;114:100-10. |
|10.||Fukai I, Masaoka A, Fujii Y, Yamakawa Y, Yokoyama T, Murase T, et al. Thymic neuroendocrine tumor (thymic carcinoid): Aclinicopathologic study in 15 patients. Ann Thorac Surg 1999;67:208-11. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4]