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CASE REPORT |
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| Ahead of print
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| A case of thymoma presenting as pyrexia of unknown origin |
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Vikas Marwah1, Robin Choudhary1, V Shrinath1, Gourang Paliwal2
1 Department of Pulmonary, Critical Care and Sleep Medicine, AICTS, Pune, Maharashtra, India
2 Department of Pathology, AFMC, Pune, Maharashtra, India
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| Date of Submission | 03-Jul-2021 |
| Date of Decision | 25-Nov-2021 |
| Date of Acceptance | 30-Dec-2021 |
| Date of Web Publication | 11-May-2023 |
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 Abstract | | |
Pyrexia of unknown origin can be caused due to numerous infective and noninfective causes. It poses a diagnostic dilemma to the clinicians and requires a myriad of investigations for the confirmation of diagnosis. Thymomas are rare mediastinal tumors that present as anterior mediastinal mass; however, thymomas presenting as pyrexia of unknown origin has rarely been reported in the literature. We report an interesting case of a middle-aged male who presented as pyrexia of unknown origin due to thymoma.
Keywords: Hyperthyroidism, pyrexia of unknown origin, thymoma
| Introduction | |  |
Pyrexia of unknown origin can be caused due to numerous infective and noninfective causes. It requires an extensive clinical, radiological, and laboratory investigations to confirm the diagnosis. Thymomas are rare mediastinal tumors that usually present as anterior mediastinal mass. However, thymomas presenting as PUO has rarely been reported in literature. We present a case of middle-aged male who presented with PUO due thymoma and was managed conservatively at a tertiary care hospital.
| Case Presentation | | |
A 50-year-old male, nonsmoker, initially presented with complaints of fever of 3 weeks duration. The fever (maximum temperature 100° F) and was associated with chills, generalized malaise, loss of appetite and with history of evening rise of temperature. He also gave a history of loss of appetite and unintentional loss of weight of four kilograms of same duration. There was no history of joint pains, rash or muscle weakness. He did not give any history of traveling to endemic areas. He gave history of increased sweating and heat intolerance but there was no history of neck swelling, diarrhea, loss of hairs or burning micturition. There was no history of any major medical or surgical illness in past. General physical findings revealed normal pulse (70/minute), blood pressure (138/80 mmHg), respiratory rate (18 breaths/min), and saturation at room air was 98%. He had a palpable soft swelling of lower pole of thyroid in neck (grade-II). There was no neck rigidity, digital tremors or focal neurological deficits. The breath and heart sounds were normal on auscultation.
On evaluation, he had normal blood counts, liver and renal function tests and his tropical disease panel of malaria and dengue was normal. His peripheral blood smear showed normocytic normochromic anemia with activated lymphocytes and no evidence of malignancy. He had a normal Erythrocyte sedimentation rate (ESR) and lactate dehydrogenase levels while his C-reactive protein (CRP) was elevated. His Mantoux test showed no induration after 72 hours. He had normal widal titers and his viral panel of Hepatitis B, C, and HIV were negative. His routine blood, urine, and sputum culture showed no growth. His antinuclear antibodies (ANA), rheumatoid factor, and anti-cyclic citrullinated peptide (anti-CCP) levels were negative. He had deranged thyroid profile in form of raised T3 (17.32 ng/dl), T4 (1.83 ng/ml) levels and decreased thyroid-stimulating hormone (TSH) levels (0.0002 mIU/L); however, the TSH receptors antibodies level was normal [Table 1] The ECG showed normal sinus rhythm. He underwent a high-resolution computed tomography (HRCT) of chest which revealed small (2.4 cm × 2 cm) mildly enhancing soft tissue density lesion in anterior mediastinum with few subcentimetric paratracheal and para-aortic lymph nodes however there was no consolidation or mass lesions in both the lungs [Figure 1]a. | Figure 1: (a): Computed tomography of chest showing small mild enhancing soft tissue density lesion in anterior mediastinum with few sub centimetric paratracheal and para-aortic lymph nodes. (b): Positron emission tomography images showing FDG avid large anterior mediastinal mass with FDG avid unilateral enlarged thyroid gland with intense uptake
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He was further subjected to Positron emission tomography-computed tomography which showed fluorodeoxyglucose (FDG) avid unilateral enlarged thyroid gland with intense uptake and mild FDG avid cervical lymph nodes. It also showed FDG avid large anterior mediastinal mass [Figure 1]b. We did a trucut biopsy of the anterior mediastinal mass which showed thick fibrous bands with sheet of lymphoid cells with admixed round to polygonal epithelial cells. The lymphocytes were small and mature. On immunohistochemical studies, it showed Pan CK positivity in epithelial cells and showed basket weave appearance. The lymphoid cells showed positivity of CD3 and Tdt and were negative for CD20 and Ki67 [Figure 2]. He was diagnosed as a case of thymoma presenting as Pyrexia of unknown origin. He was started on oral propranolol and prednisolone to which he responded with abatement of his symptoms. We discussed his case with the cardiothoracic surgeons and he was offered surgery however the patient was unwilling for the same. He was discharged on tapering doses of steroids and oral propranolol and has been on follow-up. | Figure 2: Histopathology of mediastinal biopsy reported as Thymoma (a) biopsy tissue consists of thick fibrous bands with sheets of lymphoid cells and polygonal to spindled epithelial cells (H & E, ×40). (b) & (c). The polygonal and spindle epithelial cells admixed with lymphoid cells (H & E, ×200 & ×400). Immunohistochemistry showed (d) Epithelial cells positive for Cytokeratins (×400), (e) & (f) Lymphoid cells positive for CD3 & TdT (×400)
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| Discussion | | |
Fever of unknown origin has been originally described by Petersdorf and Beeson as fever which is higher than 38.3° Celsius on several occasions and the duration should be more than 3 weeks with uncertain diagnosis even after one week of study in the hospital. This definition has undergone numerous changes and presently can be classified into Classical, Nosocomial, Neutropenic and HIV-associated pyrexia of unknown origin (PUO). There can be numerous causes of PUO including infectious diseases like mycobacterium tuberculosis, viral infections (HIV, Epstein-Barr virus, cytomegalovirus, Hepatitis A, B, and E), urinary tract infections and occult abscesses, neoplastic diseases like lymphoma, leukemia and solid organ tumors, inflammatory diseases like adult-onset still's disease, systemic lupus erythematosus, polymyalgia rheumatica, temporal arteritis, rheumatoid arthritis, sarcoidosis, Kawasaki's disease and inflammatory bowel diseases, tropical diseases including malaria, dengue fever, rickettsial diseases, leptospirosis and schistosomiasis and there can be miscellaneous diseases like drug fever, chronic pulmonary embolism, hyperthyroidism, necrotizing lymphadenitis, hematoma and rarely Hemophagocytic lymphohistiocytosis.[1],[2] The diagnostic algorithm for diagnosing cause of PUO includes pertinent history, clinical findings and relevant laboratory investigations. Infectious causes like tuberculosis, urinary tract infections and atypical infections constitutes a significant percentage of PUO in developing countries and usually presents as fever with chills while inflammatory conditions which are more common in developed countries, can have additional findings like oral ulcers, skin rash, joint pains and generalized lymphadenopathy. Malignancies like leukemia, lymphoma, multiple myeloma and gastrointestinal cancers cause PUO due to production of pyrogenic cytokines or by predisposing to secondary infections and can present as PUO with anorexia and significant weight loss. Tropical diseases generally have a history of travel to endemic areas.[1],[2]
Thymomas are rare neoplasms that arise in the anterior mediastinum and account for about 20 percent of mediastinal tumors with equal predilection for male and females. It is generally diagnosed incidentally or due to local pressure symptoms or paraneoplastic syndromes. The thoracic symptoms include chest pain, breathlessness, phrenic nerve palsy of superior vena cava syndromes while the paraneoplastic syndrome associated with thymomas include myasthenia gravis, red cell aplasia, hypo-gammaglobulinemia and other associated multiorgan autoimmunity. However, thymomas can rarely present with PUO as in our patient. Thymomas have been generally associated with thyrotoxicosis and Grave's disease and is most likely due to the thyrotropin receptor which may act as autoantigen leading to development of Grave's disease however there is minimal enlargement of thymus gland in these cases. Our patient had raised T3 and T4 levels however the TSH antibodies level were not raised. The diagnosis requires thoracic imaging with computed and Positron emission tomography while tissue diagnosis is required for confirmation. They are usually well circumscribed and but can show infiltration in nearby structures. On histopathology thymoma tissue consists of thick fibrous bands with sheets of lymphoid cells and polygonal to spindled epithelial cells admixed with lymphoid cells which on Immunohistochemistry show epithelial cells positive for Cytokeratin and lymphoid cells positive for CD3 & TdT (×100). The staging of thymomas is based on their extent and presence on invasion into nearby structures.[3],[4],[5],[6],[7]
The management of thymomas includes surgical resection of the thymic tissue with lymph nodes but it requires a prerequisite of well-defined tumor but patients with tumor invasion into innominate vein, phrenic nerve or heart or great vessels require multimodality intervention including preoperative chemotherapy and postoperative radiotherapy. The thymic hyperplasia due to Grave's disease also show decrease in size with antithyroid medications.[4],[8]
Our patient was evaluated extensively and no evidence of any other infection or connective diseases was found. He was started on oral propranolol and prednisolone to which he responded with abatement of his symptoms. We discussed his case with the cardiothoracic surgeons and he was offered surgery however the patient was unwilling for the same. He was discharged on tapering doses of steroids and oral propranolol and has been on follow-up.
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.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Cunha BA, Lortholary O, Cunha CB. Fever of unknown origin: A clinical approach. Am J Med 2015;128:1138.e1-15.  |
| 2. | Wright WF, Auwaerter PG. Fever and fever of unknown origin: Review, recent advances, and lingering dogma. Open Forum Infect Dis 2020;7:1-12. |
| 3. | Chung SM, Kim K-J, Moon JS, Hong YH, Kang SH. Fever of unknown origin caused by intrathyroidal thymic carcinoma. Korean J Intern Med 2019;34:683-4. |
| 4. | Sperling B, Marschall J, Kennedy R, Pahwa P, Chibbar R. Thymoma: A review of the clinical and pathological findings in 65 cases. Can J Surg 2003;46:37-42. |
| 5. | Katragadda R, Fribourg D. Anterior mediastinal mass-thyroid-induced pseudo-thymoma: A pure thymic hyperplasia. Chest 2020;158:a1204. |
| 6. | Boyd JD, Juskevicius R. Mediastinal neoplasms in patients with Graves disease: A possible link between sustained hyperthyroidism and thymic neoplasia? Thyroid Res 2012;5:5. doi: 10.1186/1756-6614-5-5. |
| 7. | Yamanaka K, Nakayama H, Watanabe K, Kameda Y. Anterior mediastinal mass in a patient with Graves' disease. Ann Thorac Surg 2006;81:1904-6. |
| 8. | Falkson CB, Bezjak A, Darling G, Gregg R, Malthaner R, Maziak DE, et al. The management of thymoma: A systematic review and practice guideline. J Thorac Oncol 2009;4:911-9. |
Correspondence Address:
Robin Choudhary,
Senior Resident, Department of Pulmonary, Critical Care and Sleep Medicine, AICTS, Pune - 411 040, Maharashtra
India
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/ijpm.ijpm_681_21
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