What is the treatment of choice for papillary carcinoma thyroid discovered in a!
Question:
We operated on a patient whose FNAC was a colloid nodule.. She was a case of Solitary Thyroid nodule.. Hemithyroidectomy was the procedure done. The biopsy report came back as PAPILLARY CARCINOMA THYROID without extra thyroid spread.. What is the next step.To perform a completion Thyroidectomy or Radioablation?
Answers:
Small thyroid carcinomas (< or = 1.5 cm), including microcarcinomas (< or = 1.0 cm) (n = 39), were found in 53 patients (41%) with a papillary (n = 130) and in 4 cases (4%) with a follicular (n = 110) carcinoma. The tumour was clinically manifested by palpability or by the presence of nodal metastases in 1/3 of patients. Concomitant diagnoses were colloid goitre (n = 24), cellular adenoma (n = 11), Graves' disease (n = 6), and Hashimoto's thyroiditis (n = 4). Nodal involvement, multifocal tumour, and extrathyroidal extent (pT4) were present in 9%, 19%, and 8% of cases respectively. Small follicular carcinomas were minimally invasive in all instances. According to the age-related prognostic TNM-classification, 52 patients (91%) were in the low risk category. 18% of the patients underwent uni- or bilateral partial lobectomy, 35% hemithyroidectomy, and 47% total thyroidectomy, according to the extent and nature of the concomitant benign disease, whereas hemi- or total thyroidectomy was performed in the patients with known cancer. Four of 5 patients with stage pT4 cancer and all patients with nodal involvement underwent total thyroidectomy with radioiodine (n = 8 [14%]). Postoperative morbidity was 0%. During the follow-up period of 1-17 (x = 5.5) years no tumour-related death and no serious recurrence was noted. One node recurrence was removed 1 year following treatment of a stage III pT1aN1b papillary carcinoma; the patient died 4 years later accidentally without residual disease. These results confirm that cases with a potentially favourable course can be defined and treated selectively by less radical measures. Small carcinomas (< or = 1.5 cm) belong to these favourable tumours with a cancer mortality rate of virtually 0%, and the aim of treatment is to prevent curable recurrences: node positivity is an important risk factor, and therefore radioiodine is reserved for carcinomas with nodal involvement and also for the occasional small pT4-tumour.
Materials and Methods :-
Thyroid tumor tissue was obtained at surgery from patients undergoing thyroidectomy (including hemi, subtotal, and total thyroidectomy). A pathologist dissected the tissue, and a small tumor tissue block from the dominant or suspicious nodule was snap-frozen in liquid nitrogen and stored at –80 C. The size and location of tumor samples were recorded in detail. All tumor samples were obtained with permission of and in accordance with the guidelines of our institutional review board, and informed consent was obtained from all patients. Histological classification was confirmed, the diagnosis was obtained from the final pathology report, and this diagnosis was reviewed and confirmed by an endocrine pathologist.
RNA extraction, purification, labeling, and hybridization
The methods described by Barden et al. (20) were employed for RNA extraction, purification, labeling, and hybridization. In brief, frozen tumor tissue was homogenized by sonication in TRIzol reagent (Invitrogen, Carlsbad, CA), and total RNA was prepared according to the manufacturer’s specifications. A total of 42 samples were analyzed by gene chip array (GeneChip Hu95 array, Affymetrix, Inc., Santa Clara, CA). The carcinoma samples included seven PTC and seven FVPTC. The benign samples consisted of 14 FA and seven hyperplastic nodules. An additional seven unknown samples were processed (blinded to preparer). All samples were processed in the same manner following the Affymetrix protocol. cDNA was synthesized from 8 µg sample RNA using T7 (dT)24 primer (GENSET Corp., La Jolla, CA). Second strand cDNA was then produced and purified. Biotin-labeled cRNA was made and used for hybridization to the Affymetrix oligonucleotide arrays. A sample aliquot was first hybridized to an Affymetrix test chip to confirm that the cRNA quality was adequate. All samples were of good quality. After staining with streptavidin-phycoerythrin, the chips were scanned in an HP ChipScanner (Affymetrix, Inc.) to detect hybridization signals.
Data analysis
The data were analyzed using MicroArray Suite version 5.0 (Affymetrix, Inc.). The intensity of each probe set of the array was captured, and the average intensity was calculated. Quantitative expression levels were calculated using intrachip-positive controls. Normalization of data was performed to account for variability in hybridization among duplicate probe sets and other hybridization artifacts. Transcripts were designated reliably detected (present) or not detected (absent) using the above analysis.
Data analysis was performed to identify genes that were differentially expressed between the papillary carcinoma (PTC and FVPTC) and benign groups (FA and hyperplasia). Data from the 21 benign tumors and 14 carcinomas that comprised the training set were used. First, the data were screened to identify signals counted as present by the Affymetrix software. These results were exported to GeneSpring (Silicon Genetics, Redwood City, CA), then analyzed with a parametric t test and multiple testing correction (Benjamini and Hochberg False Discovery Rate, with the P value set at <0.05), producing a gene list of 1149 genes differentially expressed. This list of 1149 differentially expressed genes was then used for unsupervised hierarchical clustering and statistical analysis. Cluster analysis was used to group the tumors based upon their similarities measured across the expression of 1149 genes.
To determine whether FVPTC could be differentiated from benign thyroid nodules, a second analysis, comparing only FVPTC tumors to benign thyroid nodules, was performed to identify genes differentially expressed between these groups. The data were exported to GeneSpring (Silicon Genetics) and using a nonparametric t test with a P value set at less than 0.01, the data were screened to produce a gene list of 843 differentially expressed genes between FVPTC and benign lesions. Finally, a similar analysis was performed to compare PTC to benign lesions. A total of 483 genes were differentially expressed between PTC and benign lesions. As described above, these gene lists were used for unsupervised hierarchical clustering and statistical analysis.
Evaluation of unknown samples
Once the hierarchical cluster analysis was established using gene expression profiles of differentially expressed genes in 35 tumors, the same analysis was performed on seven thyroid tumors (one PTC, four FVPTC, and two hyperplastic nodules) with investigators blinded to the final diagnosis. Gene profiles of the seven unknown tumors were produced using the 1149 differentially expressed genes for comparison. The unknown sample profiles were then added to the original 35 samples to create a combined group of 42 samples, which then underwent an unsupervised hierarchical clustering analysis.
To confirm the validity of the subset analysis of FVPTC vs. benign tumors, the unknown samples’ individual gene profiles were analyzed (excluding the one classical PTC), using the 843 differentially expressed genes produced by the analysis of FVPTC vs. benign tumors. The gene profiles of unknown samples combined with the test set (FVPTC vs. benign) samples underwent an unsupervised hierarchical cluster analysis, producing a dendrogram for the 34 samples. This same technique was repeated to analyze the PTC vs. benign tumor gene list. Unknown samples’ gene expression profiles were analyzed (excluding the four FVPTC) using the gene profile for 438 genes differentially expressed in the PTC vs. benign analysis. Once again the unknown samples were combined with the PTC vs. benign samples, and an unsupervised hierarchical clustering was performed. A dendrogram of the 31 samples (PTC vs. benign plus unknowns) was produced.
Semiquantitative RT-PCR
To verify the results of the Affymetrix gene chip array, a total of five genes were chosen that had expression levels with more than 2-fold difference, were implicated in the molecular pathogenesis of cancer, and had readily available primers or were made from the known mRNA sequences using Primer3 (21). One microgram of sample RNA was reverse transcribed with oligo(dT) primer in a total volume of 50 µl. A 1-µl aliquot of cDNA was used for PCR, and the product was electrophoresed in a 2.0% agarose gel and visualized with ethidium bromide and UV light. The band intensity for each sample was calculated using EagleSight software (version 3.2, Stratagene, La Jolla, CA), and a ratio of the intensity of the gene of interest to that of the housekeeping gene was calculated for each sample. These normalized intensity levels were then analyzed using a t test. The genes and primers are listed in Table 1.
Other Answers:
Near Total thyroidectomy followed by radioablation. This should be followed by whole body thyroid scanning to find residual disease in 6 months time.
PTC tend to be multifocal and have lymphatic spread,so there are chances of leaving the cancer in the residual tissue. Hemithyroidectomy and near total thyroidectomy have similar rates of survival, but monitoring with thyroid scans is easier when most of thyroid tissue is taken out.
Source(s):
Harrisons Internal Medicine 15th Ed
Answers: