Correlation of molecular data with histopathological and clinical features in a series of 66 patients with medullary thyroid carcinoma.

PURPOSE: Medullary thyroid carcinoma (MTC) displays a wide variety of histopathological features, and several histological variants have been described. In follicular cell-derived thyroid carcinomas, there is a good correlation between genotype and phenotype. In this study, we investigated whether such a correlation is also present in MTC. METHODS: The histopathological features were evaluated in a series of 66 molecularly characterised tumours and correlated with the clinical characteristics. RESULTS: Most MTC exhibited the classical variant (83.3%). Other variants included spindle cell (6.1%), pseudopapillary (4.5%), paraganglioma-like (3.0%), angiosarcoma-like (1.5%), and oncocytic follicular (1.5%). Tumours were classified into four groups: group 1, with somatic p.Met918Thr and p.Ala883Phe RET mutations; group 2, with other RET mutations; group 3, with RAS mutations; and group 4, without RET or RAS mutations. Tumours from groups 1 and 4 were typically associated with the classical variant, with abundant fibrosis, lymphovascular invasion, extrathyroidal extension, and more advanced stages of disease, whereas group 2 included histological variants other than the classical variant (namely, pseudopapillary and paraganglioma-like), with tumours that were highly cellular, less invasive, and with a better overall prognosis. In tumours from group 4, amyloid deposition was characteristically absent or low. The spindle cell variant appeared only in tumours from group 3, which had high cellularity and a degree of invasion and prognosis intermediate between groups 1 and 2, but better than group 4. The grade of fibrosis correlated directly with the clinical outcome. CONCLUSION: Our results support the idea that a genotype-phenotype correlation does, indeed, exist in MTC. However, further studies are warranted to confirm these findings in a larger sample size.

The role of EIF1AX in thyroid cancer tumourigenesis and progression.

PURPOSE: The EIF1AX gene was recently described as a new thyroid cancer-related gene. Its mutations were mainly reported in poorly differentiated (PDTC) and anaplastic thyroid cancers (ATC), but also in well-differentiated thyroid cancer (WDTC) and in benign thyroid lesions, although less frequently. Our aim was to address whether EIF1AX mutations are present in the different stages of thyroid tumourigenesis (from hyperplasia to well-differentiated and to poorly differentiated/undifferentiated lesions), and to clarify its role in this process. METHODS: We analysed the EIF1AX gene in a series of 16 PDTC and ATC cases with coexistent well-differentiated regions and/or benign lesions. In EIF1AX mutant cases we also assessed the presence of RAS genes mutations. RESULTS: We identified the mutation p.Ala113_splice in the EIF1AX gene in two PDTCs (neither present in the well-differentiated counterparts nor in the benign areas). One of these tumours also evidenced the mutation p.Glu61Arg in NRAS in both poorly and well-differentiated regions, further suggesting that the EIF1AX p.Ala113_splice mutation could be associated with tumoural progression. In another patient we did not find any EIF1AX alteration in the PDTC component, but we detected the EIF1AX p.Gly6_splice mutation in the PTC area (both regions were RAS wild-type). This mutation did not seem to be related with dedifferentiation. CONCLUSIONS: According to our results, distinct mutations on EIF1AX may be related to different phenotypes/behaviours. Despite being a small series, which reflects the difficulty in retrieving PDTC and ATC surgical samples with well-differentiated and/or benign areas, our study may provide new insights into thyroid cancer tumourigenesis and dedifferentiation.

Kidney Graft Leiomyosarcoma: A Case Report.

BACKGROUND: Kidney transplant (KT) recipients have a higher incidence of malignancy than the general population. Smooth muscle tumors (SMT), including leiomyosarcoma, are rare in kidney transplant recipients, and most cases are associated with Epstein-Barr virus (EBV) infection. CASE REPORT: A 57-year-old man received a deceased donor kidney transplant at the age of 53 years, with 5 human leukocyte antigen (HLA) mismatches. Before the transplantation, the patient was IgG positive for EBV viral capsid antigen (VCA), negative for IgM EBV VCA, and also negative for IgG EBV nuclear antigen (EBNA), suggesting a prior EBV infection. He received immunosuppressive induction with basiliximab, and maintenance with tacrolimus, mycophenolate mofetil, and prednisolone. Two years after transplantation, he had an acute cellular rejection episode treated with methylprednisolone. An increased graft size was found 4 years after transplantation. A computed tomographic scan showed 3 solid tumors involving the renal graft with extension to the perinephric fat; no secondary localizations were found. A nephrectomy of the graft was performed. The histologic diagnosis was a high-grade leiomyosarcoma. In situ hybridization for EBV was negative. Nine months after nephrectomy, local recurrence was diagnosed. The surgical approach was unsuccessful, and the patient died after a brief period. CONCLUSION: Kidney leiomyosarcoma is a very rare clinical condition. Most of these neoplasms that arise in transplanted recipients are associated with EBV in tumor tissue. Only one case of renal graft leiomyosarcoma without EBV RNA in the tumor has been previously reported.

Impact of lactation length and piglet weaning weight on long-term growth and viability of progeny.

A total of 1,034 pigs produced by breeding PIC sows to 2 different PIC terminal sires were used to create 3 distinct weaning weight populations so that postweaning growth to 125 kg could be studied. The rearing strategies resulted in BW that ranged from 4.1 to 11.5 kg by 20 d of age. Sows and corresponding litters were allocated to 3 treatments: sow reared (SR; n = 367) for 20 d, sow reared for 14 d (14W; n = 330), and sow reared for 2 d (2W; n = 337). Sows were removed from 2W and 14W groups, but progeny remained in the crates and received milk replacer ad libitum (for 18 and 6 d, respectively) until the contemporary SR pigs were weaned at 20 d of age. The SR pigs (6.49 +/- 0.15 kg) weighed 1.01 kg less than 14W pigs (7.5 +/- 0.14 kg) and 2.26 kg less than 2W pigs (8.75 +/- 0.14 kg; P < 0.05). The 14W pigs weighed 1.25 kg less than 2W pigs (P < 0.05). Nursery ADG for the 2W group (547 g/d) was 35 g/d less (P < 0.05) than 14W pigs. The 14W pigs (165 d) required 3 fewer (P < 0.05) days to reach 125 kg of BW compared with SR pigs. The SR and 14W pigs gained BW 24 and 20 g/d faster (P < 0.05) in the postnursery period when compared with 2W pigs. The SR and 2W pigs consumed 0.10 and 0.12 kg/d less (P < 0.05) during this period when compared with 14W pigs (2.32 kg/d). Gain:feed of SR was improved (P < 0.05) when compared with the 14W and 2W pigs over 167 d of age (0.44 vs. 0.42 and 0.42, respectively). Lean percentage was 0.7% greater (P < 0.05) in carcasses from SR pigs (55.0%) compared with carcasses from 2W pigs (54.3%) when adjusted to a constant HCW. A study of the effect of weaning weight on days to 125 kg was limited to SR and 14W groups because maternal deprivation compromised the 2W group postweaning growth. Six weaning-weight groups were defined using a normal distribution: 4.6, 5.5, 6.4, 7.3, 8.2, and 9.5 kg. Pigs weighing 5.5 kg at 20 d of age were able to reach 125 kg 8 d sooner (168.8 d) than those weighing 4.6 kg (176.8 d). There was a linear relationship (P < 0.05) between weaning weight and ADG in the postnursery phase of growth. We conclude that 1) a weaning weight of less than 5.0 kg imposes the greatest marginal loss in production output for a 20-d weaning and 2) lactation length influences long-term growth, composition of growth, and viability of progeny.

Schwannoma of the esophagus: computed tomography and endosonographic findings of a special type of schwannoma.

Schwannomas of the digestive tract are uncommon benign tumors seldom located in the esophagus. We present a case of intramural esophageal schwannoma with histopathological correlation evaluated by computed tomography and endoscopic ultrasonography. The imaging findings are described and other relevant features of schwannomas of the esophagus are discussed.