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Magagnin et al., Porto
Alegre, RS, Brazil, reported on follicular cancer in patients
living in an area of iodine deficiency. It is well accepted that
differentiated thyroid carcinomas are among the cancers with the
highest ratio of cure. However, some patients may present
aggressive carcinoma, recurrence, or even death due to carcinoma.
Early identification of such patients is fundamental for its
management, and may favorably influence prognosis and costs.
Iodine deficiency has an influence not only on the incidence of
the different histologic types of thyroid carcinoma but also on
its biological behavior. In iodine-deficient areas, follicular
and anaplastic histologies have a relatively higher frequency
(Belfiore et al., Cancer 50:3096, 1987). The objective of the
study was to verify the prevalence and prognostic factors of
differentiated thyroid carcinoma in patients from an area
previously classified as mild to moderate deficient in iodine.
The authors have studied 260 medical records of patients
diagnosed with thyroid cancer attending at the Endocrinology
Service of Hospital de Clínicas de Porto Alegre, RS, Brazil,
from 1990 and 1998. Of these, 141 were selected because their
complete follow up data were available in the Hospital files. The
sample composed of 112 women; the most frequent histologic
subtype was the papillary (51.1%), followed by follicular
(41.1%), medullar (5%) and anaplastic (2.8%) carcinoma. The ratio
papillary/follicular cancer was 0.8, suggesting iodine
deficiency. For analysis of prognostic factors, patients were
divided in two groups based on remission (n=94) or non-remission
(n=47) of the disease within 5 years. Univariate analysis
indicated weight loss (p<0.0001), previous thyroid disease
(goiter and autoimmune thyroid disease) (p<0.0001), old age at
diagnosis (p=0.001), histologic subtype and tumor stage (p=0.01)
as factors statistically related to a worse prognosis of the
disease. When analyzing prognostic factors in relation to the
histologic subtypes, it was verified that dyspnoe (p=0.01), local
pain (p=0.03), weight loss (p=0.05), tumor stage and age at
diagnosis (p=0.01) were related to non-remission in papillary
carcinoma, while the stage of the tumor at diagnosis (p=0.005)
was the only independent variable to a worse prognosis in
logistic regression. When it comes to follicular carcinoma,
history of weight loss (p=0.04), tumor stage at diagnosis
(p=0.0001), old age at diagnosis (p=0.01), previous thyroid
disease (p=0.0003) and extent of treatment (p=0.008) were related
to prognosis. Nevertheless, in addition to the tumor stage
(p=0.02), previous goiter (p=0.03) was also an independent
variable associated to recurrent disease and death.
Similarly, Novelli et al. (Rosario, Argentina) evaluated 1,330 patients with a previous thyroid condition (mainly multinodular goiter and thyroid nodules). Surgery was performed in 660 patients (indication not mentioned) and thyroid cancer was found in 167 patients (25.2%). More than 90% were papillary and only 14 patients were diagnosed as having follicular cancer. They classified as low risk, patients younger than 40 years old, moderate risk over 40 years of age and high risk patients of any age with papillary cancer in stage III and IV and follicular cancer in stage II or higher. Seventeen patients were included in this high risk subgroup in which mortality rate was 41% after 60 months of surgery. They concluded that a minimum of 15 years follow up is necessary to detect the majority of possible recurrences and 25 years to detect all deaths due to thyroid cancer. Sansó et al., Mendoza, Argentina, reported on ret proto-oncogene mutations in Multiple Endocrine Neoplasia (MEN-2) patients. Different RET proto-oncogen mutations have been described associated to MEN-2 syndrome. The aim of the study was to characterize these mutations in an Argentinean population by studying patients with clinical signs of MEN-2 and their relatives in order to detect asymptomatic carriers. RET mutations were determined by PCR amplification of exons 10, 11 and 16 followed by direct sequencing and digestion with restriction enzymes. In 14 MEN-2A families (100 members, 15 index cases, aged 28–60 years) the following mutations were detected: TGC›CGC (Cys634Arg) in 8 families (25 cases), TGC›TAC (Cys634Tyr) in 3 families (14 cases), TGC›TTC (Cys634Phe) in 2 families (11 cases) and TGC›TGG (Cys634Trp) in 1 family (5 cases). In 13/15 index patients pheochromocytoma (Pheo) were detected. Pheo involvement was bilateral in 7 patients, unilateral in 4 and malignant in another 2. All 15 index patients underwent total thyroidectomy with complete central lymphnode resection. In all of them, Medullary Thyroid Cancer (MTC) with node metastases was histopathologically diagnosed. Five families with MEN-2B (18 members, 5 index cases 6–22 years) were studied. All 5 patients presented the ATG›ACG (Met9l8Thr) mutation. These patients showed characteristic phenotype and presented MTC with lymph node metastases but one patient who had also brain metastases. Bilateral Pheo was present in only one of these patients. Familial MTC (FMTC) was also studied (7 members, index case age 19) showing in 3 cases the mutation TGC›CGC (Cys634Arg), the most frequent mutation detected in MEN-2A. They concluded that the most frequent mutations in the Argentinean population of MEN-2A patients were (Cys634Arg 57%) and (Cys634Tyr: 21%). Also in concordance with other reports MEN-2B patients showed the typical 918 codon mutation. Since FMTC had the same mutation than the most frequent mutation found in MEN-2A, biochemical screening of Pheo is mandatory along the follow-up of FMTC. Iorcansky and co-authors, Buenos Aires, Argentina, reported on the identification of asymptomatic carriers for ret proto-oncogene mutations (Ret-mut) in multiple endocrine neoplasia type 2A families. As early diagnosis of MEN-2A syndrome is crucial since preventive early total thyroidectomy (PTT) is the only effective treatment for medullary thyroid carcinoma, the authors aimed to identify asymptomatic carriers of MEN-2A by molecular analysis. They have studied 86 relatives of 14 MEN-2A families. The relatives were very young (n=51, age 3–20y old) or adults (n=35, ages 21–80y old). In forty of the 86 relatives, different ret mutations in exon 11 were detected. Most of the young patients had no clinical or biochemical evidence of disease, whereas 87% of the adult relatives had previously undetected signs of medullary thyroid cancer. Fourteen of the 25 juvenile RET-positive relatives underwent total thyroidectomy with C-cell hyperplasia in all of them. All the adult patients who were thyroidectomized had spread MTC with lymph node metastases. The authors, as a conclusion, favor the early detection of RET-mutations in relatives of patients with MEN-2A followed by preventive total thyroidectomy. Biscolla et al., São Paulo, Brazil, reported on a new sensitive nested RT-PCR of Tg mRNA transcripts in peripheral blood for the diagnosis of residual and recurrent thyroid cancer. As serum Tg assays can be falsely influenced by the presence of anti-Tg antibodies (that may be present in 15% of thyroid cancer patients) the authors have compared the amplified serum Tg mRNA from peripheral blood with a serum Tg assay (Brahms RIA, sensitivity 1 mg/ml) in 35 patients with differentiated thyroid cancer (papillary 19, follicular 10 and 6 mixed). At the moment of study all patients were euthyroid and 28 had undetectable serum Tg levels (after thyroidectomy followed by RAI ablation). Blood Tg mRNA was detected in 14 of the 35 patients while serum Tg was undetectable in 8. The authors concluded that long term follow up will confirm if circulating Tg mRNA is a more sensitive marker of residual thyroid cancer than serum Tg. Thyroid follicular cancer was confirmed in a patient with congenital goiter and dyshormonogenesis by Figueiredo et al., Rio de Janeiro, Brazil. They reported a 26y-old male with a very large goiter and hypothyroidism since 4 months of life. A sibling also had congenital goiter but the parents are not consanguineous. Both siblings had a positive perchlorate discharge test with an elevated RAI uptake (35% at 24h). Serum Tg was 122 ng/ml. After thyroidectomy invasive follicular carcinoma was found in this patient. The authors comment on the rare association of congenital goiter and thyroid differentiated cancer. |
