Papillary thyroid carcinomas in patients under 21 years of age: clinical and histologic characteristics of tumors ≤10 mm.

OBJECTIVE: To compare clinical and histologic characteristics of papillary thyroid carcinomas (PTCs) ≤10 mm in patients ≤21 years old with larger ones and with microcarcinomas in adults. STUDY DESIGN: Retrospective study of patients with PTC diagnosed between 1983 and 2012. Medical records were reviewed and information about age, sex, tumor size, intra/extrathyroid extension, lymph node, and distant metastases were collected. RESULTS: Patients ≤21 years old (n = 93) and adults (n = 1235) with PTC were identified. Among the former, 34 had PTC ≤10 mm (37.4%) and among the latter, 584 had papillary thyroid microcarcinoma (PTM) (47.3%), P = .082. Patients with tumors ≤10 mm less frequently had extrathyroidal extension and lymph node metastases compared with larger tumors (8.8% vs 33.3%, P = .017, and 60.0% vs 95.2%, P = .001, respectively). The percentage of PTC ≤10 mm increased with age (7.1%, 32.0%, and 48.1% in age groups ≤15, 15-18, and >18 to ≤21 years old, respectively; P = .016). Mean tumor size was larger (6.8 ± 2.7 vs 5.8 ± 2.8 mm, P = .030), and lymph nodes metastases were more frequent (41.2% vs 18.6%, P = .003) in patients ≤21 years of age compared with adults with PTM. The frequency of multifocal cancers decreased between 1983-1992, 1993-2002, and 2003-2012 (66.7%, 53.6%, and 27.1%, respectively, P = .019). CONCLUSIONS: The frequency of PTC ≤10 mm is low in children, increases in adolescents, and reaches that of adults at 18-21 years of age. Mean tumor size is larger and metastases to regional lymph nodes more frequent in comparison with PTM in adults. Whether their treatment and follow-up could be based on guidelines used for PTM in adults is questionable.

Predictive factors that influence the course of medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid cancer (MTC) is an infrequent form of thyroid cancer. We aimed to examine how gender and histological characteristics influence the rate of recurrence/persistent disease, distant metastases and survival and also to define specific characteristics of MTC microcarcinomas. METHODS: The medical records of 85 patients with MTC were reviewed. The following characteristics were recorded: year of diagnosis, age at diagnosis, sex, tumor size, number of tumor foci, lymph node metastases, thyroid capsule and vascular invasion, infiltration of thyroid parenchyma and extrathyroid extension, and distant metastases. RESULTS: During follow-up (mean 78.8 months), persistent disease occurred in 40 patients, local recurrences in 5 and distant metastases in 32 patients. Local and distant disease appeared more frequently in patients with larger tumors (p < 0.005) and lymph node metastases (p < 0.01). In addition, patients with invasive tumors had local and distant disease more frequently. The percentage of males who had persistent disease and/or local recurrence was significantly higher than the percentage of males who did not (p < 0.05). Similar results were observed for distant disease (p < 0.01). Independent predictors of recurrence and persistent disease was the presence of lymph node metastases at diagnosis (risk ratio 11.66) and of distant metastases were the presence of lymph node metastases at diagnosis (risk ratio 17.42) and the presence of vascular invasion (risk ratio 2.41). Fifteen patients died due to MTC during follow-up (17.6 %). Patients who died were more frequently males, and had thyroid capsule invasion, extrathyroidal extension, vascular invasion and metastatic disease. CONCLUSIONS: Male sex, tumor size and invasive characteristics of the tumor are negative predictive factors for evolution of MTC.

Ectopic Cushing's syndrome due to CRH secreting liver metastasis in a patient with medullary thyroid carcinoma.

Ectopic production of CRH by a medullary thyroid carcinoma or its metastases is a rare cause of ectopic Cushing's syndrome (ECS). We report a 45-year old male with medullary thyroid carcinoma (MTC), who, 24 years following the initial diagnosis, presented with clinical and biochemical evidence of an ACTH dependent Cushing's syndrome. Rapid deterioration of his clinical condition and elevated cortisol levels were observed. Computed tomographic imaging of the abdomen revealed extensive liver metastases. The patient underwent fine needle aspiration biopsy of a liver lesion and immunohistochemistry showed that the cells expressed calcitonin, carcino-embryonic antigen and synaptophysin. Further analysis revealed that the material also expressed CRH. This is an unusual case of a CRH-secreting liver metastasis from a medullary thyroid carcinoma 24 years after the initial diagnosis of MTC.

Gastric signet-ring adenocarcinoma presenting with breast metastasis.

Breast metastases from gastric cancer are extremely rare. A case report of a 37-year-old female with breast inflammatory invasion and ascites is described. Breast biopsy revealed carcinomatous invasion of the lymphatics from adenocarcinoma cells with signet-ring features. Estrogen (ER) and progesterone receptors (PR) and c-erb-B2 were negative. Upper gastrointestinal endoscopy revealed a prepyloric ulcerative mass. Histopathologic examination of the lesion showed infiltration from a high-grade adenocarcinoma, identical with that of the breast. Immunostaining was positive for cytokeratins CK-7 and CK-20 and CEA and negative for ER and PR. Ascitic fluid cytology was positive for adenocarcinoma cells. Mammography was not diagnostic. Abdominal CT scanning revealed large ovarian masses suggestive of metastases (Krukenberg's tumor). A cisplatin-based regimen was given but no objective response was observed. The patient died six months after initial diagnosis. A review of the literature is performed.

Chronic lymphocytic thyroiditis is associated with invasive characteristics of differentiated thyroid carcinoma in children and adolescents.

BACKGROUND: The association between chronic lymphocytic thyroiditis (CLT) and thyroid cancer is an interesting topic. The aim of the present study was to evaluate if demographic and histological characteristics as well as the long-term outcome of thyroid cancer was different in children and adolescents with and without CLT. METHODS: The medical records of children and adolescents (≤21 years old) were reviewed. The following data were recorded: gender, year and age at diagnosis, family history of thyroid cancer, history of external radiation therapy, histological type (papillary and variants, follicular and variants), tumour size, multifocality, infiltration of thyroid parenchyma or surrounding soft tissues, vascular invasion, presence of lymph node and distant metastases. Information about the presence of TgAb and TPOAb was also collected. RESULTS: One hundred eight children and adolescents (median age 19.0, interquartile range 4.0 years) were diagnosed with differentiated thyroid carcinoma (DTC); 31 patients (28.7%) presented histological characteristics compatible with CLT. Infiltration of thyroid parenchyma was more frequent in patients with CLT compared to patients without (74.2% vs 48.1% respectively, P=0.024). Familial papillary thyroid carcinoma (PTC) was more frequent in patients with CLT compared to those without CLT (20.7% vs 2.8% respectively, P=0.009). There was no better outcome with respect to the presence of CLT or not. CONCLUSIONS: Children and adolescents with CLT present more frequently familial PTC as well as thyroid cancer with invasive characteristics.

Intranuclear Helioid Inclusions in a Case of Breast Carcinoma.

Helioid inclusions are single membrane-bounded intranuclear bodies of unknown nature which have been described in a case of breast adenoma, in mammary hyperplasia, and in a case of acinic cell carcinoma of the parotid gland. We report the detection of helioid inclusions in a case of breast carcinoma, which involves a 60-year-old woman with infiltrating ductal breast carcinoma of apocrine type. On electron microscopic examination we observed characteristic intranuclear helioid inclusions in some carcinoma cells. Occasionally intranuclear profiles of dense granules were present, some of which showed a just discernible filamentous border. The significance of these rare ultrastructural inclusions remains to be elucidated.

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.

BACKGROUND: Papillary 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. METHODS: We 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. RESULTS: Histological 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. CONCLUSIONS: Patients 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.

Mortality from thyroid cancer in patients with hyperthyroidism: the Theagenion Cancer Hospital experience.

BACKGROUND: Thyroid carcinoma has been reported in patients operated for different types of hyperthyroidism and the probability of a hot nodule being malignant seems to be low. The aim of the present study was to explore the relationship between thyroid cancer, hyperthyroidism and outcome in a large cohort of patients who presented to a tertiary cancer centre in Northern Greece. PATIENTS: Among 720 patients treated for thyroid cancer, 60 had a concomitant diagnosis of hyperthyroidism due to Graves' disease (n=14), solitary autonomous adenoma (n=17), or multinodular goiter (n=29). Adverse prognostic factors were common in patients with a previous history of hyperthyroidism at the time of diagnosis of thyroid cancer, including cases where the cancer was discovered coincidentally after thyroid surgery for hyperthyroidism and cases where tumor size was more than 10 mm. RESULTS: In 10 out of 17 patients with hyperthyroidism due to solitary autonomous adenomas, the tumor was located within the hot nodule and two of these patients developed local and distant metastases and died from the disease 4 and 15 years after thyroidectomy. CONCLUSION: Clinicians managing patients with hyperthyroidism need to be aware of the possible increased risk of thyroid cancer in this patient group.

Cerebellar metastasis as first metastasis from papillary thyroid carcinoma.

Brain metastasis is an uncommon complication of differentiated thyroid carcinoma. Even more, cerebellar metastases from papillary thyroid carcinoma (PTC) are exceptional. We report a 69-year-old male patient with infiltrative PTC who developed high levels of thyroglobulin (Tg) and deteriorated neurological symptoms four years after the initial diagnosis. Computerized tomography (CT) of the brain demonstrated a cerebellar mass and the patient underwent surgery. Pathology revealed metastasis from PTC. Immunochemistry was positive for Tg. The patient had no other sites of distant metastases. Although PTC has generally a good prognosis, metastases to the cerebellum can occur, even as the first metastatic site, despite the fact that appropriate therapy (surgery, radioactive iodine therapy, TSH suppression therapy, chemotherapy and external radiotherapy) had been given for the primary tumour.