Thymoma is a rare mediastinal tumour that can be accompanied by different paraneoplastic syndromes. Here we report a case of Type A thymoma associated with relapsing minimal change disease (MCD). This case highlights: (1) The need to balance rapid prednisolone weaning against risk for relapse in an elderly patient at risk for steroid-induced complications. (2) The addition of calcineurin inhibitor in relapsed thymoma-related MCD, to achieve steroid sparing effects. Resection of the offending tumour and prompt immunosuppressive therapy are critical in getting best renal and overall outcomes in this rare entity.
Thymic carcinoma is a rare thymic epithelial cancer which is not only locally invasive but also highly aggressive disease. The prognosis for this cancer is poor and the surgery remains the mainstay of treatment. Thymic carcinomas have been shown to metastasize to the lymph nodes, lung, and liver. A 63-year old male who was successfully treated for thymic cancer in 2015, presented with metastatic disease recurrence to the spinal cord. We share interesting images of the spinal cord lesions as well as pituitary metastases that were incidentally detected on restaging 18F-fluorodeoxyglucose positron emission tomography-computed tomography.
Thymomas comprise about 1% of all mediastinal tumours and are rare in children. Typically, these tumours are aggressive, with a poor outcome. The current treatment of invasive thymoma is often multidisciplinary. We report a 16-year-old boy with invasive thymoma who was successfully treated with systemic chemotherapy, surgical resection and irradiation. The patient has been in continuous remission for 6 years without radiographic evidence of tumour recurrence.
Primary mediastinal large B-cell lymphoma (PMLBL) is an uncommon non-Hodgkin lymphoma with a distinct clinicopathological entity in the WHO classification of lymphoid malignancies. It is known to originate from B-cells of the thymus. It mimics thymic neoplasms and other lymphomas clinically and histopathologically. We reported a 33-year-old obese man who presented with shortness of breath off and on for 4 years. Radiologically, there was a huge anterior mediastinal mass. Tru-cut biopsy was initially diagnosed as type-A thymoma. Histopathological examination of the excised specimen revealed PMLBL with stromal fibrosis and sclerosis which created a diagnostic difficulty. The neoplastic cells varied from medium-sized to large pleomorphic cells, including mononuclear cells with centroblastic and immunoblastic features as well as bi-lobed Reed Sternberg (RS)-like cells and horse-shoe like hallmark cells. Some interlacing spindle cells and epithelioid cells were also present. Immunohistochemically, tumour cells expressed diffuse positivity for LCA, CD20, CD79a, CD23, Bcl2, MUM-1 and heterogenous positivity for CD30 and EMA, and were negative for CD10, CD15 and ALK. Ki67 scoring was very high. Tumour cells infiltrated into peri-thymic fat and pericardium. No malignant cells were detected in the pleural fluid and there was no bone marrow infiltration. The patient showed partial response to 6 cycles of RICE chemotherapy, and was planned for second line chemotherapy using hyper-CVAD regimen followed by autologous stem cell transplantation. This case illustrates the importance of thorough sampling and immunohistochemistry in differentiating PMLBL from its differential diagnoses.
We describe a patient with myasthenia gravis and thymoma who developed recurrent severe myasthenic crises associated with the use of combination chemotherapy.
Thyroid carcinoma showing thymic-like differentiation (CASTLE) is a rare malignancy of the thyroid gland, and it accounts for 0.1-0.15% of all thyroid cancers. As the name suggests, it has a histological and immunophenotypic resemblance to thymic carcinoma. Preoperative diagnosis of CASTLE can be difficult as its clinical manifestations, and histological characteristic resembles other aggressive and advanced thyroid carcinomas. It is essential to distinguish CASTLE from other aggressive neoplasms as the former has a more favourable prognosis. Immunohistochemical staining with CD5 can help to differentiate thyroid CASTLE from other aggressive thyroid neoplasms. Due to the rarity of this disease, there is no clear definitive treatment strategy. Surgical resection of CASTLE is usually attempted initially. Nodal involvement and extrathyroidal extension are shown to be the main prognostic factors that influenced the survival of patients. Therefore, complete resection of the tumour is vital to reduce local recurrence rates and to improve the chance of long-term survival. Radiotherapy (RT) for CASTLE is an effective treatment. Curative surgery followed by adjuvant RT should be considered in cases with extrathyroidal extension and nodal metastases. With RT, shrinkage of the tumour and reduction of local recurrence rate is possible. With that in mind, we present a case of CASTLE who presented with airway compression symptoms three years after thyroid surgery. He subsequently underwent tumour debulking surgery and a tracheostomy. The patient refused adjuvant chemoradiotherapy, and during our serial follow-up, he is well and symptom-free.
Thymoma is associated with a wide spectrum of autoimmune paraneoplastic syndromes, though it is uncommon for multiple paraneoplastic syndromes to be present in a single individual. We report a rare case of an elderly gentleman who was found to have thymoma-associated myasthenia gravis and LGI1-encephalitis with myokymia, who presented with nephrotic syndrome (minimal change glomerulopathy) after thymectomy. The latter two paraneoplastic syndromes had manifested when prednisolone was tapered down to low dose. This case serves to remind neurologists that apart from paraneoplastic neurological manifestations, thymoma may also be associated with renal disease. Nephropathy in myasthenia patients with thymoma should be properly evaluated, as it is treatable with immunotherapy, and it may even occur post-thymectomy.
Respiratory distress after thyroidectomy and thymectomy can be challenging. We encountered a 70-year-old lady with a long-standing goiter with concomitant thymoma. She underwent the surgery and developed respiratory distress upon extubation with loss of laryngeal sensation causing severe aspiration. She was diagnosed myasthenia gravis and symptoms resolved with MG treatments.
The Fau gene (Finkel-Biskis-Reilly murine sarcoma virus (FBR-MuSV)-associated ubiquitously expressed gene) was identified as a potential tumor suppressor gene using a forward genetics approach. Downregulation of Fau by overexpression of its reverse sequence has been shown to inhibit apoptosis induced by DNA-damaging agents. To address a potential role of Fau in benzene toxicity, we investigated the apoptotic effects of hydroquinone (HQ), a major benzene metabolite, in W7.2 mouse thymoma cells transfected with either a plasmid construct expressing the antisense sequence of Fau (rfau) or the empty vector (pcDNA3.1) as a control. HQ induced apoptosis via increased production of reactive oxygen species and DNA damage, measured using dihydroethidine (HE) staining and alkaline Comet assay, respectively, in W7.2 pcDNA3.1 cells. In contrast, when Fau was downregulated by the antisense sequence in W7.2 rfau cells, HQ treatment did not cause DNA damage and oxidative stress and these cells were markedly more resistant to HQ-induced apoptosis. Further investigation revealed that there was an upregulation of NAD(P)H: quinone oxidoreductase 1 (NQO1), a detoxification enzyme for benzene-derived quinones, in W7.2 rfau cells. Compromising cellular NQO1 by use of a specific mechanism-based inhibitor (MAC 220) and NQO1 siRNA resensitized W7.2 rfau cells to HQ-induced apoptosis. Silencing of Fau in W7.2 wild-type cells resulted in increased levels of NQO1, confirming that downregulation of Fau results in NQO1 upregulation which protects against HQ-induced apoptosis.
Myasthenia gravis (MG) is an autoantibody-mediated disorder affecting the neuromuscular junction causing characteristic fatigable muscle weakness. Though it can be associated with tumours of the thymus as well as thyroid disorders, it is rare for both to coexist. The exact prevalence of thyroid carcinoma in MG with thymoma is not known but only about a dozen cases have been reported in the literature. We report a case of a 38-year-old Myanmar lady who presented with weakness and breathlessness due to MG with neck swelling. On examination, she had fatigable proximal muscle weakness and thyroid enlargement with no obvious features of hyperthyroidism. Mediastinal widening and an enlarged thyroid gland were noted on her chest X-ray and chest CT. A subtotal thyroidectomy and thymectomy were done. The histology showed follicular carcinoma of the thyroid and benign thymoma. The majority of the reported cases of thyroid carcinoma in association with MG were papillary carcinoma. Follicular carcinoma thyroid associated with MG has not yet been reported in the literature.
We report a patient who presented with severe cold-induced allodynia and hyperhidrosis, and found to have acquired neuromyotonia (Isaacs syndrome) with high voltage-gated potassium channel (VGKC) antibody titre,positive contactin-associated protein 2 (CASPR2) and leucine-rich glioma-inactivated 1 (LGI1) antibodies. The patient also had positive anti-dsDNA and acetylcholine receptor (AChR) antibodies without clinical features of SLE or myasthenia gravis, suggesting a strong underlying autoimmune tendency. CT thorax showed no thymoma. Her symptoms improved with intravenous immunoglobulin infusion but recurred despite maintenance oral corticosteroids and carbamazepine. She has since been on regular IVIG infusions. Cold allodynia is an unusual presentation in acquired neuromyotonia.