A Collision Intrathyroidal Tumor Causing Primary Hyperparathyroidism: Evidence From an 18F-Choline PET/CT Study.

ABSTRACT: A 67-year-old man was diagnosed with primary hyperparathyroidism and normofunctioning left nodular goiter. Fine-needle aspiration cytology showed thyroid (Thy) 4 (suspicious of malignancy). After first-line imaging proved negative, integrated 18F-choline PET/4D contrast-enhanced CT revealed uptake by the thyroid nodule and by 3 nodules of the left central compartment. Thyroidectomy and lymphadenectomy were performed. Histopathology revealed a collision tumor (ie, 2 histologically distinct tumors occurring at the same anatomic site) composed of both PTC (papillary thyroid carcinoma) and parathyroid carcinoma within the left thyroid nodule. Lymph nodes showed PTC metastases. Primary hyperparathyroidism and calcium levels normalized, and the patient underwent radioiodine therapy.

Case report: lenvatinib in neoadjuvant setting in a patient affected by invasive poorly differentiated thyroid carcinoma.

We report a case of an elderly woman presenting with a huge cervical mass invading the tracheal lumen. Diagnosed as invasive poorly differentiated thyroid cancer, after an endotracheal biopsy, stenting and radiotherapy, it was judged eligible for total thyroidectomy, but surgery was delayed due to pulmonary thromboembolism. The patient was therefore treated with lenvatinib with a neoadjuvant intent until hemodynamic stability was obtained. Thyroidectomy and radioiodine therapy were then performed and the postdose scan revealed an area of modest uptake in the anterior part of the neck. The patient is now in a good clinical status and she continues her follow-up program without any adjuvant therapy.

Role of Strain Elastography and Shear-Wave Elastography in a Multiparametric Clinical Approach to Indeterminate Cytology Thyroid Nodules.

BACKGROUND In thyroid nodules with indeterminate cytology, further clinical assessment aimed at ruling out malignancy is often mandatory. Ancillary imaging techniques and genetic mutation analysis can improve the risk stratification of such lesions, thereby facilitating the clinician's decision to undertaken surgery or simple follow-up. The aim of this study was to evaluate the diagnostic performance of shear-wave elastography (SW), strain elastography (ELX 2/1), conventional ultrasound (US), contrast-enhanced ultrasound (CEUS), and BRAF V600E mutation analysis in the aforementioned lesions. MATERIAL AND METHODS We enrolled 81 patients, each with 1 indeterminate-cytology thyroid nodule. Thyroid function, thyroperoxidase antibodies and calcitonin were known in each case. SW, ELX 2/1, US, CEUS, and BRAF mutation analysis were subsequently performed, followed by a second FNAB. If the lesion was not downgraded to benign, surgery was recommended and histological reports collected. RESULTS There were 28 nodules (34%) that proved benign on the second FNAB; 38 nodules (47%) underwent surgery (17 benign, 21 malignant), and 15 nodules (19%) refused surgery. The only techniques related to histological outcome were US (AUC=0,766), ELX 2/1 (AUC=0.701), and BRAF analysis (AUC=0.762). ELX 2/1 and SW reports were not correlated with each other (P=0.45). A scoring system taking into account all the variables considered performed better than the single variables alone (AUC=0.831). CONCLUSIONS In indeterminate-cytology thyroid lesions, repeating FNAB can avoid unnecessary surgery. ELX 2/1 seems to perform better than SW in distinguishing malignancy; these techniques could, however, be complementary in describing such lesions. A multiparametric approach appears the most accurate in predicting nodule histology.

Retrospective cytological evaluation of indeterminate thyroid nodules according to the British Thyroid Association 2014 classification and comparison of clinical evaluation and outcomes.

The cytology of 130 indeterminate nodules (Thy 3) was retrospectively reviewed according to the British Thyroid Association 2014 classification. Nodules were divided into Thy 3a (atypical features) and Thy 3f (follicular lesion) categories. Histology was available as a reference for 97 nodules. Pre-surgical evaluations comprised biochemical tests, color-Doppler ultrasonography (US), semi-quantitative elastography-US (USE), contrast-enhanced US (CEUS), and mutation analysis from cytological slides. Thyroid malignancy was the final diagnosis for 19% of surgically-treated nodules. No statistically significant difference in the risk of malignancy was found between Thy 3a (26%) and Thy 3f (14%) nodules. Histology of the Thy 3a and Thy 3f nodules showed a higher incidence of Hurtle cell adenomas in Thy 3f (29%) than in Thy 3a (3%) nodules (P=0.01). The only pre-surgical difference concerned the BRAF V600E mutation, which was positive in some Thy 3a but not in any Thy 3f nodules (P=0.04). Receiver-operating characteristic (ROC) analysis was used to obtain cut-off values from US (score), USE (ELX 2/1 strain index), and CEUS (time-to-peak index and peak index) data. The cut-off values were similar for Thy 3a and Thy 3f nodules. Data showed that malignancy can be suspected if the US score is >2, ELX 1/2 strain index >1, time-to-peak index >1, and peak index <1. In a sub-group of 24 revised nodules (12 Thy 3a and 12 Thy 3f) with histology as a reference, the diagnostic power of cumulative pre-surgical analysis by means of US, USE, and CEUS showed high positive and negative predictive values (83% and 100%, respectively) for the presence of malignancy in Thy 3a and Thy 3f nodules. In conclusion, in our series of revised Thy 3 nodules, malignancy was low and displayed no significant differences between Thy 3a and Thy 3f categories. The use of cut-offs based on histology as a reference could reduce surgery. Our data support the conviction that, in mutation-negative Thy 3a and Thy 3f nodules, observation should be the first choice when not all instrumental results are suspect.

Metastases to the thyroid gland from renal cancer.

AIMS AND BACKGROUND: Metastases to the thyroid gland from renal cancer pose a challenge to physicians, due in part to the rarity of the phenomenon, the prolonged time interval between removal of the primary renal cancer and the appearance of metastases, the difficulty in diagnosis, and the uncertainty regarding long-term prognosis. We report our experience with diagnosis and management of patients affected by thyroid metastases from renal clear cell carcinoma. STUDY DESIGN: We report herein three clinical cases of thyroid metastases from renal clear cell carcinoma. We also present a review of the literature and examine common features of clinical presentation and management recommendations. RESULTS: Over the past 17 years, 918 patients underewent surgery for thyroid cancer in our institution. Histological examination demonstrated a thyroid secondary malignancy from kidney cancer in 3 cases. Two patients underwent total thyroidectomy, whereas in the third patient a palliative right lobectomy with homolateral latero-cervical lymphoadenectomy was performed. At a 5-year follow-up, only one patient survived and was disease-free. CONCLUSIONS: Thyroid metastases from renal clear cell carcinoma are a rare occurrence but should be taken into consideration in the differential diagnosis of a thyroid nodule. Preoperative diagnosis is often difficult. Nevertheless, an extensive diagnostic workup is recommended because the subsequent therapy must be tailored on the basis of the local extension of metastases. Surgical treatment of solitary thyroid metastases is recommended. However, patients with disseminated disease have a poor prognosis, and palliative care is the indicated recommendation. In these patients and in surgically untreatable patients, prolonged survival may be achieved by adjuvant medical therapy.

Pheochromocytoma during pregnancy treated by surgery. A case report and the review of the literature.

INTRODUCTION: Prenatal diagnosis of pheocromocytoma, although rare, is important as it allows a reduction in both maternal mortality and foetal loss. Pheocromocytoma operated on in the first trimester of pregnancy with survival of both patient and foetus is rare in literature. Our case was operated on with success after a correct and early diagnosis was obtained despite a chronic hypertension which existed long before pregnancy. Our case study well illustrates that a correct multidisciplinary approach involving endocrinologists, anesthesiologists, surgeons and gynecologists is fundamental for a positive outcome. CASE REPORT: The case of a white caucasian pregnant woman at 13th weeks of gestation with pheocromocytoma and severe and unstable hypertension that could not be pharmacologically controlled is described. Morphological diagnosis was safely obtained by Magnetic Resonance Imaging (MRI) without intravenous medium contrast agent. Pre-operative treatment consisted of therapy with alpha-blockers and rehydration. Adrenalectomy was performed through a laparotomy. Postoperative treatment consisted of rehydration and ephedrine continued until the fourth post-operative day. The post-operative period was uneventful and a new ultrasound (US) scan confirmed foetal vitality. The patient was discharged seven days after surgery. A live newborn was physiologically delivered after a nine-month pregnancy. CONCLUSION: A correct diagnosis in all pregnant women with severe hypertension particularly those not screened for secondary hypertension and a multidisciplinary management are mandatory to obtain optimal results and avoid deleterious effects at delivery.

Tako-tsubo cardiomyopathy as initial presentation of pheocromocytoma. A clinical case.

INTRODUCTION: Tako-tsubo cardiomyopathy is a rapidly reversible form of acute heart failure triggered by stressful events that occur more frequently in postmenopausal women. A central role is supposed to be played by catecholamines and the association with pheocromocytoma is rare. CASE PRESENTATION: We describe a patient admitted for abdominal pain and suffering of hypertension pharmacologically treated. During hospitalization the patient presented cephalea and precordial pain with nausea and profuse sweating. ECG showed ST elevation and deep negative T wave. Blood tests were moderately elevated. Echo-cardiography reported a left ventricular apex akynesia and hyperkynesia of the base while coronarography was negative. As hypertension persisted the suspicion of pheocromocytoma arose. Urinary and blood catecholamines were mildly elevated and echography and Magnetic Resonance revealed a left adrenal gland mass. The diagnosis of pheocromocytoma was thus confirmed Left laparoscopic adrenalectomy was performed after adequate stabilization and preoperative pharmacological preparation by hydration, a-and f-blockers. Intraoperatively blood pressure was controlled by nitroprussiate, rapid half life beta-blockers (esmolol cloridrate). Post-operative course was uneventful and arterial pressure returned to normal as well as catecholamines values. Patient was discharged on the 5th post-operative day Five months afterwards the patient had normal arterial pressure without anti-hypertensive therapy and symptom free. CONCLUSION: The case confirmed that tako-tsubo cardiomyopathy could be the first manifestation of tumors secreting catecholamines and that pheocromocytoma should be considered in patients with hypertension and acute stress-induced cardiomiopathy without evidence of acute coronary disease and with negative coronarography.

Anal metastasis from recurrent breast lobular carcinoma: a case report.

We report a case of isolated gastrointestinal metastasis from breast lobular carcinoma, which mimicked primary anal cancer. In July 2000, an 88-year-old woman presented with infiltrating lobular cancer (pT1/G2/N2). The patient received postoperative radiotherapy and hormonal therapy. Four years later, she presented with an anal polypoid lesion. The mass was removed for biopsy. Immunohistochemical staining suggested a breast origin. Radiotherapy was chosen for this patient, which resulted in complete regression of the lesion. The patient died 3 years after the first manifestation of gastrointestinal metastasis. According to the current literature, we consider the immunohistochemistry features that are essential to support the suspicion of gastrointestinal breast metastasis, and since we consider the gastrointestinal involvement as a sign of systemic disease, the therapy should be less aggressive and systemic.

A model to prioritize access to elective surgery on the basis of clinical urgency and waiting time.

BACKGROUND: Prioritization of waiting lists for elective surgery represents a major issue in public systems in view of the fact that patients often suffer from consequences of long waiting times. In addition, administrative and standardized data on waiting lists are generally lacking in Italy, where no detailed national reports are available. This is true although since 2002 the National Government has defined implicit Urgency-Related Groups (URGs) associated with Maximum Time Before Treatment (MTBT), similar to the Australian classification. The aim of this paper is to propose a model to manage waiting lists and prioritize admissions to elective surgery. METHODS: In 2001, the Italian Ministry of Health funded the Surgical Waiting List Info System (SWALIS) project, with the aim of experimenting solutions for managing elective surgery waiting lists. The project was split into two phases. In the first project phase, ten surgical units in the largest hospital of the Liguria Region were involved in the design of a pre-admission process model. The model was embedded in a Web based software, adopting Italian URGs with minor modifications. The SWALIS pre-admission process was based on the following steps: 1) urgency assessment into URGs; 2) correspondent assignment of a pre-set MTBT; 3) real time prioritization of every referral on the list, according to urgency and waiting time. In the second project phase a prospective descriptive study was performed, when a single general surgery unit was selected as the deployment and test bed, managing all registrations from March 2004 to March 2007 (1809 ordinary and 597 day cases). From August 2005, once the SWALIS model had been modified, waiting lists were monitored and analyzed, measuring the impact of the model by a set of performance indexes (average waiting time, length of the waiting list) and Appropriate Performance Index (API). RESULTS: The SWALIS pre-admission model was used for all registrations in the test period, fully covering the case mix of the patients referred to surgery. The software produced real time data and advanced parameters, providing patients and users useful tools to manage waiting lists and to schedule hospital admissions with ease and efficiency. The model protected patients from horizontal and vertical inequities, while positive changes in API were observed in the latest period, meaning that more patients were treated within their MTBT. CONCLUSION: The SWALIS model achieves the purpose of providing useful data to monitor waiting lists appropriately. It allows homogeneous and standardized prioritization, enhancing transparency, efficiency and equity. Due to its applicability, it might represent a pragmatic approach towards surgical waiting lists, useful in both clinical practice and strategic resource management.

CD8+ CD28- T regulatory lymphocytes inhibiting T cell proliferative and cytotoxic functions infiltrate human cancers.

Tumor growth is allowed by its ability to escape immune system surveillance. An important role in determining tumor evasion from immune control might be played by tumor-infiltrating regulatory lymphocytes. This study was aimed at characterizing phenotype and function of CD8+ CD28- T regulatory cells infiltrating human cancer. Lymphocytes infiltrating primitive tumor lesion and/or satellite lymph node from a series of 42 human cancers were phenotypically studied and functionally analyzed by suppressor assays. The unprecedented observation was made that CD8+ CD28- T regulatory lymphocytes are almost constantly present and functional in human tumors, being able to inhibit both T cell proliferation and cytotoxicity. CD4+ CD25+ T regulatory lymphocytes associate with CD8+ CD28- T regulatory cells so that the immunosuppressive activity of tumor-infiltrating regulatory T cell subsets, altogether considered, may become predominant. The infiltration of regulatory T cells seems tumor related, being present in metastatic but not in metastasis-free satellite lymph nodes; it likely depends on both in situ generation (via cytokine production) and recruitment from the periphery (via chemokine secretion). Collectively, these results have pathogenic relevance and implication for immunotherapy of cancer.

Gastrointestinal stromal tumors: clinical pathological review of a personal series.

The Authors report their experience on the management of gastrointestinal stromal tumors (GISTs). In addition to recent cases immediately diagnosed as GISTs, a pathological review of stored material from non-epithelial tumors of the gastrointestinal tract operated on over the past 20 years was performed. Twenty-three out of a total of 31 cases were shown to be positive for the immunophenotypic characteristics (CD117/CD34) of GISTs. Most cases (approximately 60%) were symptomatic, with hemorrhage being the most common presenting sign, followed by occlusion, pain and perforation. Asymptomatic cases were detected incidentally during procedures for other conditions. Diagnostic techniques (ultrasound, endoscopy, endoscopic ultrasound, X-ray, CT, MRI) allowed only the detection of wall (extraluminal) involvement. Apart from differentiating between benign and malignant, preoperative biopsy was seldom valuable. All cases were treated surgically, with intervention tailored to location and anatomical/surgical and anatomical/pathological features. Long-term follow-up was conducted in all patients and for most is still ongoing: five patients died from recurrent disease at varying intervals after surgery (from 17 to 102 months). Relationships between observed aggressiveness and risk were studied. Parameters that may prove useful for the early detection and appropriate management of these lesions are discussed.