Martina Tavarelli

Descriptive Epidemiology of Human Thyroid Cancer: Experience From a Regional Registry and The “Volcanic Factor”

Thyroid cancer (TC), the most common endocrine tumor, has steadily increased worldwide due to the increase of the papillary histotype. The reasons for this spread have not been established. In addition to more sensitive thyroid nodule screening, the effect of environmental factors cannot be excluded. Because high incidences of TC were found in volcanic areas (Hawaii and Iceland), a volcanic environment may play a role in the pathogenesis of TC. In January 2002, the Regional Register for TC was instituted in Sicily. With a population of approximately five million inhabitants with similar genetic and lifestyle features, the coexistence in Sicily of rural, urban, industrial, moderate-to-low iodine intake, and volcanic areas provides a conducive setting for assessing the environmental influences on the etiology of TC. In Sicily, between 2002 and 2004, 1,950 new cases of TC were identified, with an age-standardized rate (world) ASR(w) = 17.8/105 in females and 3.7/105 in males and a high female/male ratio (4.3:1.0). The incidence of TC was heterogeneous within Sicily. There were 2.3 times more cases in the Catania province (where most of the inhabitants live in the volcanic area of Mt. Etna): ASR(w) = 31.7/105 in females and 6.4/105 in males vs. 14.1 in females and 3.0 in males in the rest of Sicily. Multivariate analysis documented that residents in the volcanic area of Mt. Etna had a higher risk of TC, compared to the residents in urban, industrial, and iodine deficient areas of Sicily. An abnormally high concentration of several chemicals was found in the drinking water of the Mt. Etna aquifer, which provides water to most of the residents in the Catania province. Our data suggest that environmental carcinogen(s) of volcanic origin may promote papillary TC. Additional analyses, including cancer biological and molecular features, will allow a better understanding of risk factors and etiopathogenetic mechanisms.

Familial Non-Medullary Thyroid Cancer Represents an Independent Risk Factor for Increased Cancer Aggressiveness: A Retrospective Analysis of 74 Families.

Objectives To assess whether familial non-medullary thyroid cancer (FNMTC) represents an independent risk factor for increased aggressiveness of the tumor, as concern as the clinical presentation and the long-term follow-up in respect of sporadic differentiated thyroid cancer (SDTC). Design Retrospective study; 1976–2014. Patients and Methods Seventy-four FNMTC families (151 affected individuals): family relationship and number of affected family members were evaluated. Clinical and histopathological features and outcome were compared to that of 643 SDTC patients followed in the same period according to the same institutional protocols. Median follow-up was 57.7 months (range 12–136) in FNMTC and 59.7 (range 15–94.6) in SDTC patients. Results Three cases occurred in 3 families and 2 cases in the other 71. F:M was 3.7:1 in FNMTC and 4.3:1 in SDTC (NS). The family relationship was siblings in 62.2%. Mean age at diagnosis was lower in FNMTC than in SDTC (p < 0.005). Papillary/follicular histotype distribution was similar (86%). Papillary tumors were more frequently multifocal in FNMTC (p = 0.004) and with lymph-node metastases (p = 0.016). Disease-free survival (DFS) was shorter in FNMTC vs. SDTC (p < 0.0001) with 74.8 vs. 90.8% patients free of disease at the last control (p < 0.005). Three patients died in FNMTC group vs. 1 in SDTC (p = 0.02). Conclusion Familial non-medullary thyroid cancer displays distinct characteristics as earlier age of onset and increased aggressiveness at diagnosis and a higher rate of persistent/recurrent disease and mortality with a shorter DFS in respect with SDTC. FNMTC patients, therefore, should be followed accurately. As the specific gene (or genes) responsible for susceptibility for FNMTC has not yet been identified, a low frequency periodic screening of relatives DTC patients may be useful to identify FNMTC patients at early stage of disease.

New Insights in Thyroid Cancer and p53 Family Proteins

Thyroid cancers are common endocrine malignancies that comprise tumors with different clinical and histological features. Indeed, papillary and follicular thyroid cancers are slow-growing, well-differentiated tumors, whereas anaplastic thyroid cancers are undifferentiated neoplasias that behave much more aggressively. Well-differentiated thyroid carcinomas are efficiently cured by surgery and radioiodine, unlike undifferentiated tumors that fail to uptake radioactive iodine and are usually resistant to chemotherapy. Therefore, novel and more effective therapies for these aggressive neoplasias are urgently needed. Whereas most genetic events underlying the pathogenesis of well-differentiated thyroid cancers have been identified, the molecular mechanisms that generate undifferentiated thyroid carcinomas are still unclear. To date, one of the best-characterized genetic alterations leading to the development of poorly differentiated thyroid tumors is the loss of the p53 tumor suppressor gene. In addition, the existence of a complex network among p53 family members (p63 and p73) and their interactions with other factors that promote thyroid cancer progression has been well documented. In this review, we provide an update on the current knowledge of the role of p53 family proteins in thyroid cancer and their possible use as a therapeutic target for the treatment of the most aggressive variants of this disease.

L’ipertiroidismo è un fattore di rischio di trombosi venosa e arteriosa: descrizione di un caso clinico

L’incidenza dell’associazione tra ipertiroidismo e trombosi non è nota. Le alterazioni coagulative che potrebbero essere coinvolte sono: l’aumentato turnover dei fattori della coagulazione con una loro aumentata sintesi endoteliale, emofilia A acquisita, sindrome da antifosfolipidi, ridotta attività fibrinolitica, un’eccessiva attività adrenergica. Il distretto più frequentemente interessato è quello cerebrale [1]. Il paziente, maschio di 57 anni con febbre, algie addominali, tachicardia e decremento ponderale, presentava TSH 0,0 microUI/ml (0,34–4,2), FT3 19,1 pmol/L (3,8–6), FT4 68,1 pmol/L (6,8–16), leucocitosi neutrofila (GB 14.600, Ne 80%), VES 99 mm (< 14), PCR 11,4 mg/dl (< 0,5), PT 65% (80–120), PTT 41 sec (23–35), fibrinogeno 668 mg/dl (1,5–4,5). L’esame obiettivo evidenziava una tiroide aumentata di volume, dolente alla deglutizione; l’ecografia tiroidea rilevava un volume aumentato (lobo destro 35 × 32 × 53 mm, lobo sinistro 32 × 34 × 49 mm); la scintigrafia tiroidea indicava scarsa fissazione del radioiodio. Veniva trattato con paracetamolo, corticosteroidi e beta bloccante con miglioramento clinico. Dopo circa 6 giorni il paziente lamentava dolore addominale a intensità crescente, con aumento degli indici di flogosi e D-Dimero. La TAC torace e addome evidenziava malattia trombo-embolica arteriosa e venosa (Fig. 1) e il paziente veniva sottoposto a terapia trombolitica e trasferito in UTIC.

Ruolo della 18FDG PET nel follow-up del carcinoma differenziato della tiroide (CDT) in presenza di valori di Tireoglobulina (Tg) indosabili, AAT elevati e TBS post-131-I negativo: esperienza clinica in una paziente

Circa il 20% dei pazienti tiroidectomizzati per carcinoma tiroideo differenziato (CDT) presentano alla diagnosi valori di anticorpi-anti-tireoglobulina (AAT) al di sopra del range di normalità che, nella maggior parte dei casi, si riducono progressivamente fino a negativizzarsi con una mediana di circa 3–5 anni [1]. Valori elevati di AAT possono interferire con il dosaggio della tireoglobulina (Tg) rendendola falsamente negativa pur in presenza di malattia residua. I pazienti in cui gli AAT non presentano alcun decremento temporale o si positivizzano durante il follow-up, o in cui si osserva un trend in ascesa richiedono un’attenta valutazione per escludere persistenza/recidiva di malattia.

Anaplastic Thyroid Cancer in Sicily: The Role of Environmental Characteristics

Background Anaplastic thyroid cancer (ATC) is a rare but extremely aggressive cancer of the thyroid, contributing up to 30–40% of thyroid cancer-specific mortality. We analyzed ATC characteristics and survival rates in Sicily to evaluate the possible influence of environmental factors. With this aim, data regarding ATC incidences in urban/rural and industrial, iodine-deficient, and volcanic vs control areas were compared in Sicily as well as ATC data from Sicily and USA. Methods Using the Sicilian Register of Thyroid Cancer (SRTC) database incidence, age, gender, tumor size and histotype, extrathyroidal extension, stage, and coexistence with pre-existing differentiated thyroid cancer (DTC) were evaluated in different areas of Sicily and also compared with Surveillance Epidemiology and End Results data in USA. Results Forty-three ATCs were identified in Sicily in the period 2002–2009. In our series only age <70 years at diagnosis (p = 0.01), coexistence with DTC (p = 0.027) and tumor size ≤6 cm (p = 0.012) were significant factors for increased survival at univariate analysis (only age at multivariate analysis). No difference in ATC incidence was found in urban vs rural areas and in iodine-deficient and industrial vs control areas. By contrast, in the volcanic area of Sicily, where DTC incidence is doubled relative to the rest of the island, also ATC incidence was increased. ATC data in Sicily were similar to those reported in the same period in the USA where overall survival rate at 6 and 12 months, however, was smaller. Conclusion The similar ATC data observed in Sicily and USA (having different genetic background and lifestyle) and the increased ATC incidence in the volcanic area of Sicily paralleling the increased incidence of papillary thyroid cancer are compatible with the possibility that casual additional mutations, more frequent in a background of increased cell replication like DCT, are the major causes of ATC rather than genetic background and/or direct environmental influences.

Metastatic malignant struma ovarii with coexistence of Hashimoto’s thyroiditis

Summary Struma ovarii is a rare ovarian teratoma characterized by the presence of thyroid tissue as the major component. Malignant transformation of the thyroidal component (malignant struma ovarii) has been reported in approximately 5% of struma ovarii. The management and follow-up of this unusual disease remain controversial. We report the case of a woman with a history of autoimmune thyroiditis and a previous resection of a benign struma ovarii that underwent hystero-annexiectomy for malignant struma ovarii with multiple papillary thyroid cancer foci and peritoneal involvement. Total thyroidectomy and subsequent radioiodine treatment lead to complete disease remission after 104 months of follow-up. The diagnosis and natural progression of malignant struma ovarii are difficult to discern, and relapses can occur several years after diagnosis. A multidisciplinary approach is mandatory; after surgical excision of malignant struma, thyroidectomy in combination with 131I therapy should be considered after risk stratification in accordance with a standard approach in differentiated thyroid cancer patients. Learning points Malignant struma ovarii is a rare disease; diagnosis is difficult and management is not well defined. Predominant sites of metastasis are adjacent pelvic structures. Thyroidectomy and 131I therapy should be considered after risk stratification in accordance with standard approaches in DTC patients.