Alexandra Chrisoulidou

The diagnosis and management of malignant phaeochromocytoma and paraganglioma

Malignant phaeochromocytomas are rare tumours accounting for ~10% of all phaeochromocytomas; the prevalence of malignancy among paragangliomas is higher, especially those associated with succinate dehydrogenase subunit B gene mutations. Although a subset of these tumours has metastatic disease at initial presentation, a significant number develops metastases during follow-up after excision of an apparently benign tumour. Clinical, biochemical and histological features cannot reliably distinguish malignant from benign tumours. Although a number of recently introduced molecular markers have been explored, their clinical significance remains to be elucidated from further studies. Several imaging modalities have been utilised for the diagnosis and staging of these tumours. Functional imaging using radiolabelled metaiodobenzylguanidine (MIBG) and more recently, (18)F-fluorodopamine and (18)F-fluorodopa positron emission tomography offer substantial sensitivity and specificity to correctly detect metastatic phaeochromocytoma and paraganglioma and helps identify patients suitable for treatment with radiopharmaceuticals. The 5-year mortality rate of patients with malignant phaeochromocytomas and paragangliomas greater than 50% indicates that there is considerable room for the improvement of currently available therapies. The main therapeutic target is tumour reduction and control of symptoms of excessive catecholamine secretion. Currently, the best adjunctive therapy to surgery is treatment with radiopharmaceuticals using (131)I-MIBG; however, this is very rarely curative. Chemotherapy has been used for metastatic disease with only a partial and mainly palliative effect. The role of other forms of radionuclide treatment either alone or in combination with chemotherapy is currently evolving. Ongoing microarray studies may provide novel intracellular pathways of importance for proliferation/cell cycle control, and lead to the development of novel pharmacological agents.

The diagnosis and management of parasellar tumours of the pituitary

The sellar and parasellar region is an anatomically complex area where a number of neoplastic, inflammatory, infectious, developmental and vascular diseases can develop. Although most sellar lesions are due to pituitary adenomas, a number of other pathologies involving the parasellar region can present in a similar manner. The diagnosis of such lesions involves a multidisciplinary approach, and detailed endocrinological, ophthalmological, neuroimaging, neurological and finally histological studies are required. Correct diagnosis prior to any intervention is essential as the treatment of choice will be different for each disorder, particularly in the case of primary malignant parasellar tumours. The complexity of structures that define the parasellar region can produce a variety of neoplastic processes, the malignant potential of which relies on histological grading. In the majority of parasellar tumours, a multimodal therapeutic approach is frequently necessary including surgery, radiotherapy, primary or adjuvant medical treatment and replacement of apparent endocrine deficits. Disease-specific medical therapies are mandatory in order to prevent recurrence or further tumour growth. This is particularly important as neoplastic lesions of the parasellar region tend to recur after prolonged follow-up, even when optimally treated. Apart from the type of treatment, identification of clinical and radiological features that could predict patients with different prognosis seems necessary in order to identify high-risk patients. Due to their rarity, central registration of parasellar tumours is required in order to be able to provide evidence-based diagnostic and mainly therapeutic approaches.

Current status and controversies in adrenal incidentalomas

Adrenal incidentalomas (AI) are serendipitously discovered lesions during abdominal imaging studies that need to be investigated for evidence of hormonal hypersecretion and/or malignancy. Because imaging modalities can reliably identify lesions that carry a high risk of malignancy, we focus on the identification of hypersecretory lesions and those with subclinical activity, particularly Cushing syndrome. Because diverse diagnostic tests and cut-offs are employed, the prevalence of hypersecretory AI varies widely, and there is controversy regarding their long-term sequelae. In this article we provide information regarding current radiological means to define the nature of AI, and the most appropriate biochemical tests for delineating hypersecretory states. We also discuss the duration and intensity of AI follow-up as well as the identification of AI that require specific therapeutic intervention.

Thyroglossal duct cyst carcinomas: is there a need for thyroidectomy?

OBJECTIVE: Thyroglossal duct cyst (TGDC) carcinoma is a rare entity and its management is controversial. The aim of this retrospective study was to: (a) identify patients with TGDC carcinoma followed up in our clinic and (b) study specific characteristics of the disease and their association with thyroid carcinoma. DESIGN: Medical files of patients with TGDC carcinoma were reviewed and tumour characteristics, lymph node metastases, treatment and follow-up were evaluated. RESULTS: A total of 6 patients, 4 females and 2 males, mean age 39.3 years (median 33.5), were treated for papillary thyroid carcinoma arising in a TGDC carcinoma of the thyroid gland was found simultaneously in 4 of these patients, while in one patient thyroid carcinoma developed 10 years after the diagnosis of TGDC carcinoma. A variable clinical picture and presentation was recorded. The most aggressive manifestation of the disease in terms of local infiltration, local recurrence and lymph node metastases was observed in our youngest patients. CONCLUSIONS: Long-term follow-up is necessary for patients with thyroid carcinoma arising in a TGDC. In view of the frequent co-existence of thyroid cancer in these patients, we would recommend detailed thyroid evaluation and, eventually, total thyroidectomy at initial diagnosis of TGDC carcinoma.

Histological subtype is the most important determinant of survival in metastatic papillary thyroid cancer.

BackgroundPapillary thyroid cancer (PTC) comprises the commonest type of thyroid cancer and carries the highest rate of survival. However, when metastatic disease occurs, survival is significantly affected.MethodsWe aimed to identify prognostic histopathological and clinical factors that modify survival in metastatic PTC. All cases of metastatic PTC treated at our department in the last 20 years were reviewed and analyzed.ResultsHistological subtype was the most important determinant of survival, as classic PTC demonstrated clearly improved survival compared to follicular subtype of PTC and other less frequently seen histological subtypes. The instant risk of death for the other histological subtypes was 4.56 times higher than the risk for the classic papillary type. Overall, a 10-year survival of 76.6% in our patients was seen.ConclusionsPatients with aggressive variants of PTC are more at risk for the development of metastatic disease. In these patients, established treatment modalities (surgery, radioiodine therapy) should be offered promptly, as well as close follow-up.

Parathyroid involvement in thyroid cancer: an unforeseen event

BackgroundParathyroid metastatic disease from thyroid cancer has not been studied extensively, mainly due to the need for parathyroid preservation during thyroid surgery.MethodsWe reviewed files from 1,770 patients with thyroid cancer followed up in our department and 10 patients with parathyroid metastases (0.5%) were identified. Patient and tumor characteristics were recorded.ResultsSix out of ten patients had metastases from papillary thyroid cancer, three from follicular thyroid cancer and one from anaplastic thyroid cancer. In nine patients parathyroid infiltration from thyroid cancer was found in direct contact with the thyroid cancer, and in one patient metastatic foci were observed not in continuity with the thyroid cancer.ConclusionsParathyroid involvement, although infrequent, may occur in thyroid cancer independently of patient age and tumor size. The clinical significance of such event is not clear. The influence on disease outcome remains to be elucidated.

Treatment compliance and severe adverse events limit the use of tyrosine kinase inhibitors in refractory thyroid cancer.

Objective The aim of the present study was to assess patient compliance with tyrosine kinase inhibitor (TKI) treatment used for refractory and progressive thyroid cancer, in addition to the efficacy and serious adverse events associated with these agents. Methods We retrospectively analyzed data from adult patients with metastatic differentiated or medullary thyroid cancer unresponsive to conventional treatment and treated with TKIs. Patients received treatment until disease progression or onset of serious adverse events, or until they expressed an intention to stop treatment. Results Twenty-four patients received TKIs. The median duration of treatment was four (range: 1–19) cycles. The most frequent adverse events were fatigue, nausea, diarrhea, hypertension, and stomatitis, and the most severe were nasal bleeding, diarrhea, heart failure, rhabdomyolysis, renal failure, QT prolongation, neutropenia, and severe fatigue. Dose reduction was required in eight patients, while five decided to terminate TKI therapy because adverse events impaired their everyday activities. During therapy, two patients showed a partial response and three showed stable disease. The lungs were the metastatic sites favoring a response to treatment. Conclusion Patient selection and meticulous pretreatment education are necessary in order to ensure adherence with TKI therapy. If adverse events appear, dose reduction or temporary treatment interruption may be offered because some adverse events resolve with continuation of treatment. In the event of serious adverse events, treatment discontinuation is necessary.

Breast metastasis from medullary thyroid carcinoma in a male patient: case report and review of the literature

Medullary thyroid carcinoma (MTC) is a rare malignancy that may metastasize to liver, lungs and bones. Breast is an unusual metastatic site for MTC and only 20 female cases have been reported in the literature. We present a male patient in whom histological examination and immunohistochemistry of a breast mass were indicative of breast metastasis from MTC. A 67-year-old man with recent diagnosis of MTC and metastases to cervical and upper mediastinum lymph nodes was referred to our department for further treatment. At first evaluation, diagnostic imaging techniques showed lung and bone metastases and three months later the presence of liver metastases. Due to the extension of the disease, treatment with vandetanib was decided, but serious adverse events led to its interruption after two weeks. During follow-up, patient developed a painful swelling in the right breast. Ultrasound and mammography showed the presence of multiple masses to the right breast suspicious for malignancy. Core needle biopsy and histological examination of the specimen confirmed the presence of metastatic MTC. Palliative external beam irradiation was used to relieve local pain and, after one month, the patient died. Consequently, breast masses should be cautiously evaluated, mainly in the presence of a known primary malignancy. Histological and/or cytopathological examination are requisite diagnostic tools, while external beam irradiation and tyrosine kinase inhibitors may be used as palliative therapies in the concurrent presence of breast metastases from MTC.

99mTc pertechnetate thyroid scan leads to serendipitous detection of metastatic thyroid cancer.

99mTc pertechnetate is considered insensitive in detecting thyroid carcinoma metastases. We report the case of a 71-year-old male patient, in whom metastasis of an unknown thyroid cancer was diagnosed incidentally on a routine 99mTc pertechnetate scan, performed for the assessment of nodular thyroid disease. Marked tracer accumulation was unexpectedly noted on the left frontal region, where a palpable, painless, soft tissue mass was present. Surgical excision of the mass revealed metastatic poorly differentiated thyroid carcinoma synchronous to soft tissue and adjacent bone.

Loss of Efficacy of Pasireotide after its Re-Administration: is There a Reason Why?

Pasireotide is a recently approved medical treatment for persistent or recurrent Cushing’s disease (CD). However, an escape from the initial successful response has not yet been described. A 42-year-old female presented with several symptoms indicative of hypercortisolism. Biochemical evaluation and imaging were consistent with CD due to a pituitary adenoma. Surgical excision of the adenoma was unsuccessful and gamma-knife radiosurgery was followed. Our patient remained hypercortisolemic thus treatment with pasireotide (900 mg subcutaneously twice daily) was decided. Biochemical and clinical remission was noted shortly thereafter. Moderate adverse events led to dose reduction to 600 mg subcutaneously twice daily. The patient remained in remission for 6 months, when treatment was discontinued due to cholecystitis. One month after cholecystectomy, pasireotide was restarted with no clinical or biochemical benefit that time. Pasireotide is an effective medical treatment for CD. Nevertheless, a loss of its initial efficacy may rarely be described.