917 Metaplastic Thymic Sarcoma of The Thyroid: A Case Report and A Review of The Literature

In this paper, the authors present a case diagnosed as ‘metaplastic thymic sarcoma’. Tumours of the thymus are extremely rare: there is a disparity in terminology and histology observed, although there have been efforts to make classification clearer. The reported case concerns a seventy-eight-year-old woman, who presented with a rapidly enlarging neck mass. Histological diagnosis was made challenging by the unusual characteristics of the tumour; the diagnosis of ‘metaplastic thymic sarcoma’ was eventually established, following consultation with an internationally renowned soft tissue pathologist. Review of the relevant literature demonstrated no comparable cases; the presentation of a thymic tumour within the thyroid is also considered unusual. The tumour observed did not conform to any previously sub type of thymic tumour and is therefore believed to be a distinct entity. The patient suffered aggressive recurrence of the disease shortly after her surgery. Genetic testing indicated the tumour was BRAF positive, and there was a dramatic clinical response to Dabrafenib/ Trametinib treatment. The successful use of immunotherapy is encouraging finding, however the diagnosis of another distinct sub type of thymic tumour, further demonstrates the diagnostic and therapeutic challenges presented by this rare and heterogenous group.

Mortality from extrathymic malignancy after thymic tumour resections: incidences and risk factors

OBJECTIVES To identify risk factors associated with extrathymic malignancy-related mortality after thymic epithelial tumour resection. METHODS The Japanese Association for Research on the Thymus database registered the records of 2835 patients collected from 32 Japanese institutions from 1991 to 2010. The cumulative incidence function of death due to extrathymic malignancies or recurrence was calculated, with other causes of death as competing risks. Relevant risk factors associated with extrathymic malignancy-related deaths in patients with thymoma were evaluated using the Fine and Gray model. RESULTS In total, 2701 patients were eligible for the analysis (thymoma, 2374; thymic carcinoma, 273; thymic neuroendocrine tumour, 54). The median follow-up period was 4.6 years. The cumulative incidence function of death due to extrathymic malignancies at 10 years was 2.2% (3.2% due to recurrence) in patients with thymoma, 1.6% (38.6% due to recurrence) in patients with thymic carcinoma and 0% (36.6% due to recurrence) in patients with thymic neuroendocrine tumour. In the multivariable analysis, age (every 10 years) at thymectomy [hazard ratio (HR) 2.19, 95% confidence interval (CI) 1.53–3.14; P < 0.001], male gender (HR 2.62, 95% CI 1.19–5.77; P = 0.017) and previous malignancies (HR 3.09, 95% CI 1.18–8.11; P = 0.022) were significant factors for death due to extrathymic malignancies after thymectomy. CONCLUSIONS Continued management and early detection of extrathymic malignancies may improve survival of patients with thymoma who are male, of advanced age, or have previous malignancies. Prospective studies are required to further investigate the management of extrathymic malignancies.

Primary pleural thymoma: A mimic in thoracic pathology

<p>We report a case of ectopic thymoma of the pleura with a growth pattern mimicking diffuse pleural mesothelioma. Diagnostic imaging showed that the pleural tumour encased the entire left lung. The specimen biopsied from the tumour was composed of lymphocytes and epithelial cells, consistent with the B1 type of thymoma. The surgical exploration of the anterosuperior mediastinum found no evidence of a thymic tumour. The thymoma was thought to originate from an ectopic thymic tissue in the pleura, as a lesion independent from the primary mediastinal thymoma, and it spreads along the pleura like a diffuse mesothelioma. Owing to their peculiar location and a variety of manifested histologic patterns, pleural thymomas may be confused with other neoplasms and may cause diagnostic problems clinically, radiologically, and morphologically. A combination of clinical information, histopathological appearance of the tumour, and immunohistochemical studies will often help to distinguish a primary pleural thymoma from other neoplasms. </p>

APPLICATION OF PHARMACEUTICAL KNOWLEDGE TO THE UNCONVENTIONAL USE OF A RARELY USED ANAESTHETIC AGENT

Case summaryA 6 yr old 45 kg child with severe Cushinoid features was admitted to PICU with probable hypertensive encephalopathy. She presented with increasing headaches, vomiting and seizures becoming unresponsive with a GCS of 3. She was profoundly hypertensive and her cortisol levels were significantly elevated (>2000 nmol/L). Rapid reduction in cortisol levels was required to stabilise her condition prior to surgery. Etomidate is the only readily available intravenous preparation which reliably suppresses adrenocortical function. A continuous infusion was started at 2.5 mg/hr and escalated to 3.5 mg/hr to reduce cortisol levels to 200 nmol/L. Cortisol levels were monitored after 1, 2, 4, 8, 12 and 24 hr on starting and at regular intervals subsequently. Hydrocortisone 20 mg/m2/24 hr was introduced to balance the adrenal suppression and optimise cortisol levels to 200–800 nmol/L. Mineralocorticoid replacement with fludrocortisone became necessary, together with significant electrolyte replacement therapy. Surgery was delayed due to sepsis, and block and replace therapy was continued for a period of 3 weeks. During this time she experienced minimal sedative effects from the etomidate.Pharmacy contributionAdvice was given on the potential toxicity of pharmaceutical excipients. The aqueous formulation of etomidate contains propylene glycol and prolonged infusion can result in significant intake. Calculations revealed an intake of 350 mg/kg/day for this child with an infusion of 2.5 mg/hr etomidate. The WHO limit is 25 mg/kg/day when propylene glycol is used as a food additive.1 An acceptable limit for intravenous exposure has not been established. Children under 4 years have limited ability to metabolise propylene glycol and accumulation can occur. Potential toxicity includes hyperosmolality, metabolic acidosis, nephrotoxicity, arrhythmias and CNS toxicity. To obviate these risks, the alternative lipid formulation of etomidate was obtained. Blood samples were subsequently reported to be lipaemic and concerns were raised about the lipid load of this formulation. Calculations revealed that 0.3–0.5 g/kg/day lipid was being infused, which is significantly less than parenteral nutrition would provide. It is possible that blood samples were withdrawn from the line infusing etomidate resulting in lipaemia, but it is also likely that hypertriglyceridaemia was a result of her underlying condition.The pharmacist was involved in many other aspects of this child's care including advice on intravenous access, infusion preparation, drug compatibility and stability issues, electrolyte management and dosing of various drugs in obesity.OutcomeAn ACTH secreting thymic tumour was resected. Hydrocortisone doses were adjusted perioperatively to cover the stress of surgery, and subsequently weaned post-operatively. Complete resection was not achieved and further block and replace therapy was used prior to bilateral adrenalectomy, followed by chemotherapy and radiotherapy.Lessons to be learntPharmacists should evaluate the potential toxicity of excipients in medication, particularly when formulations are given by an unlicensed method of administration in children. Other parenteral products with a significant propylene glycol load include lorazepam, phenobarbital, phenytoin and co-trimoxazole.