In situ assessment of PI3K and PTEN alterations in mycosis fungoides: correlation with clinicopathological features

Deregulated signalling through phosphatidylinositol 3‐kinase (PI3K) pathway plays a critical role in tumour initiation and progression. We have already shown that AKT is activated in skin lesions in Mycosis Fungoides (MF) and we herein further investigate the frequency and clinical significance of PTEN and PI3K at the protein and at the DNA level as well as the presence of AKT1 mutations in skin lesions from 50 patients with MF clinical stages I‐IV in relation to clinicopathological features. Increased p‐AKT expression correlated with poor prognosis in plaques (P = 0.0198), whereas p‐AKT was an independent predictor of poor survival in the entire cohort (P = 0.017, HR = 1.012). PTEN cytoplasmic expression was found low or absent in all 77.3% of cases and inversely correlated with advanced clinical stages (P = 0.0744). Molecular analysis showed no AKT1 mutation, no PI3KCA copy number gain, only 1 case with PI3KCA mutation in exon 9 and 3 cases with PTEN mutations (7%) in exons 7, 8 and 5. The latter correlated with disease (P = 0.0253) and progression (P < 0.0001) free survival in tumour stage. Although activation of PI3K/AKT signalling pathway due to PTEN alterations is rarely attributed to abnormalities in PTEN, PI3K, and AKT1 genes, PTEN mutations exert a negative effect on patients’ prognosis with tumours.     

Cleft palate and ADULT phenotype in a patient with a novel TP63 mutation suggests lumping of EEC/LM/ADULT syndromes into a unique entity: ELA syndrome

Acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome is a rare condition belonging to the group of ectodermal dysplasias caused by TP63 mutations. Its clinical phenotype is similar to ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) and limb-mammary syndrome (LMS), and differs from these disorders mainly by the absence of cleft lip and/or palate. We report on a 39-year-old patient who was found to be heterozygous for a c.401G > T (p.Gly134Val) de novo mutation of TP63. This patient had the ADULT phenotype associated with cleft palate. Our findings, rather than extend the clinical spectrum of ADULT syndrome, suggest that cleft palate can no longer be considered an element for differential diagnosis for ADULT, EEC, and LMS. Our data, added to other reports on overlapping phenotypes, support the combining of these three phenotypes into a unique entity that we propose to call "ELA syndrome," which is an acronym of ectrodactyly-ectodermal dysplasia-cleft lip and palate, limb-mammary, and ADULT syndromes.     

Thyroid nodule shape suggests malignancy

OBJECTIVE: To evaluate if a nodule with shape taller than wide (anteroposterior/transverse diameter ratio, A/T > or = 1) is a good predictor of malignancy independent of the size. METHODS: We retrospectively examined the cytological and histological results of 7455 nodules (5198 patients) referred for ultrasound-guided-fine needle aspiration cytology (US-FNAC) in our hospital from January 1991 to September 2004. RESULTS: A suitable FNAC was obtained from 6135 nodules (4495 patients); 34.6% were less than 1 cm in diameter (small nodules, SN). A diagnosis of carcinoma was histologically confirmed in 284/349 suspicious lesions after FNAC. The size of carcinoma nodules was not significantly associated with the occurrence of extracapsular growth (large nodules (LN): 10.5%, SN: 4.9%, NS) and lymph node metastasis (LN: 23.6%, SN: 25.0%, NS). Malignant lesions showed microcalcifications more frequently than benign nodules (72.2 vs 28.7%; P < 0.001; (odds ratio, OR(confidence intervals, CI) = 9.9(7.2-13.4)). Similarly, A/T > or = 1 (76 vs 40%; P < 0.001; OR(CI) = 8.6(5.5-13.1)), blurred margins (52.8 vs 18.8%; P < 0.001; OR(CI) = 7.7(5.6-10.2)), solid hypo-echoic appearance (80.6 vs 52.4%; P < 0.001; OR(CI) = 3.2(2.2-4.3)) and intranodular vascular pattern (type 2) (61.6 vs 49.7%; P < 0.001; OR(CI) = 1.7(1.3-2.3)) were significantly more frequent in malignant than in benign nodules. CONCLUSIONS: Our data show that no single parameter, including nodule size, satisfactorily identifies a subset of patients to be electively investigated by FNAC. We concluded that A/T > or = 1 with at least two of US features (microcalcification, blurred margins, hypo-echoic pattern) is today the best compromise between missing cancers and cost-benefit.