Prognostic impact of tumor location and gene expression profile in sporadic desmoid tumor.

PURPOSE: Prognostic biomarkers remain necessary in sporadic desmoid tumor (DT) because the clinical course is unpredictable. DT location along with gene expression between thoracic and abdominal wall locations was analyzed. METHOD: Sporadic DT patients (GEIS Registry) diagnosed between 1982 and 2018 who underwent upfront surgery were enrolled retrospectively in this study. The primary endpoint was relapse-free survival (RFS). Additionally, the gene expression profile was analyzed in DT localized in the thoracic or abdominal wall, harboring the most frequent CTNNB1 T41A mutation. RESULTS: From a total of 454 DT patients, 197 patients with sporadic DT were selected. The median age was 38.2 years (1.8-89.1) with a male/female distribution of 33.5/66.5. Most of them harbored the CTNNB1 T41A mutation (71.6 %), followed by S45F (17.8 %) and S45P (4.1 %). A significant worse median RFS was associated with males (p = 0.019), tumor size ≥ 6 cm (p = 0.001), extra-abdominal DT location (p < 0.001) and the presence of CTNNB1 S45F mutation (p = 0.013). In the multivariate analysis, extra-abdominal DT location, CTNNB1 S45F mutation and tumor size were independent prognostic biomarkers for worse RFS. DTs harboring the CTNNB1 T41A mutation showed overexpression of DUSP1, SOCS1, EGR1, FOS, LIF, MYC, SGK1, SLC2A3, and IER3, and underexpression of BMP4, PMS2, HOXA9, and WISP1 in thoracic versus abdominal wall locations. CONCLUSION: Sporadic DT location exhibits a different prognosis in terms of RFS favoring the abdominal wall compared to extra-abdominal sites. A differential gene expression profile under the same CTNNB1 T41A mutation is observed in the abdominal wall versus the thoracic wall, mainly affecting the Wnt/ß-catenin, TGFß, IFN, and TNF pathways.

Rate of non-invasive follicular thyroid neoplasms with papillary-like nuclear features depends on pathologist's criteria: a multicentre retrospective Southern European study with prolonged follow-up.

PURPOSE: To determine the rate of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in a multi-institutional series from the Iberian Peninsula and describing this NIFTP cohort. METHODS: Retrospective study of papillary thyroid carcinoma (PTC) or well-differentiated tumours of uncertain malignant potential (WDT-UMP) diagnosed between 2005 and 2015 and measuring ≥5 mm in adult patients from 17 hospitals. Pathological reports were reviewed to determine the cases that fulfil the original criteria of NIFTP and histology was reassessed. Rates were correlated with the number of PTC and its follicular variant (FVPTC) of each institution. Demographic data, histology, management, and follow-up of the reclassified NIFTP cohort were recorded. RESULTS: A total of 182 cases with NIFTP criteria were identified: 174/3372 PTC (rate: 5.2%; range: 0-12.1%) and 8/19 WDT-UMP (42.1%). NIFTP rate showed linear correlation with total PTC (p: 0.03) and FVPTC (p: 0.007) identified at each centre. Ultrasound findings were non-suspicious in 60.1%. Fine-needle cytology or core biopsy diagnoses were undetermined in 49.7%. Most patients were treated with total thyroidectomy. No case had nodal disease. Among patients with total thyroidectomy, 89.7% had an excellent response evaluated 1 year after surgery. There were no structural persistence or relapses. Five patients showed residual thyroglobulin after 90 months of mean follow-up. CONCLUSIONS: NIFTP rate is low but highly variable in neighbouring institutions of the Iberian Peninsula. This study suggests pathologist's interpretation of nuclear alterations as the main cause of these differences. Patients disclosed an excellent outcome, even without using the strictest criteria.

Core-needle biopsy in thyroid nodules: performance, accuracy, and complications.

OBJECTIVE: To evaluate the performance of core-needle biopsy (CNB) in thyroid using a cohort of patients in which it was used as first choice. METHODS: Our institutional review board approved this retrospective study. We reviewed all CNB performed in our center over a period of 11 years. Ultrasound-guided CNBs were performed using a spring-loaded 18-gauge biopsy needle. We used a classification with four diagnostic categories for CNB results: insufficient, benign, follicular lesion (indeterminate), and malignant. Final diagnosis was based on surgical diagnosis or follow-up of at least 2 years in non-operated patients. RESULTS: The study included 4412 CNB in 4112 nodules of 3768 patients, 300 of them repeated biopsies. Results were 148 insufficient (3.4%), 3706 benign (84%), 278 follicular lesions (6.3%), and 280 malignant (6.3%). Considering follicular lesion and malignancy CNB results as positive (both lead to the recommendation of surgery) sensitivity was 96% (CI 93.2-97.8) and specificity 93.7% (CI 92.9-94.5). Predictive positive value for a follicular lesion diagnosis was 12.2% and for a malignancy diagnosis, 98.6%. CNB likelihood ratio for malignancy of a malignant diagnosis was 841.9 (CI 315.8-2313.3), of a malignant/follicular lesion diagnosis was 23.4 (CI 20.1-27.3), and of a benign diagnosis was 0.04 (CI 0.02-0.07). Repeated CNB in 53 insufficient biopsies obtained 50 diagnostic results. Minor complications occurred in 2.2% of CNB, and major in four procedures (0.09%). CONCLUSIONS: CNB in thyroid nodules is accurate and has few complications and a low rate of non-diagnostic and indeterminate diagnoses. It can be an alternative method when FNAC has poor performance. Repeating biopsy is useful after non-diagnostic biopsies. KEY POINTS: • Core-needle biopsy of thyroid has a low ratio non-diagnostic and indeterminate results. • Core-needle biopsy results are highly reliable, especially benign results. • Complication rate of core-needle biopsy of thyroid is low.

Ultrasound-guided core-needle biopsy in thyroid nodules. A study of 676 consecutive cases with surgical correlation.

OBJECTIVES: To analyze the diagnostic accuracy of ultrasound-guided core-needle biopsy (CNB) of thyroid nodules. METHODS: Of 3517 CNBs performed using an 18G spring-loaded device in one institution, we retrospectively reviewed 676 nodules in 629 consecutive patients who underwent surgery. CNB and pathological examination were compared. CNB diagnosis was standardized in four categories: insufficient (I), benign (B), follicular lesion (FOL), and malignant (M). Main outcome measures were predictive positive values (PPV), false positives (FP), and false negatives (FN). RESULTS: CNB showed a low rate of insufficient and FOL diagnoses (5.8 % and 4.5 %). On surgery, there were eight FNs in 374 benign CNBs and three FPs in 148 malignant CNBs. The 154 nodules classified as FOL in CNB included, at surgery, 122 neoplasms; 28 of them malignant. PPV for malignancy of a malignant CNB was 98 %, and for a CNB diagnosis of FOL 18.2 %. Sensitivity for malignancy if CNB of FOL and M are considered positive was 95.6. Only one major complication was observed. CONCLUSIONS: CNB is reliable, safe, and accurate to evaluate thyroid nodules and can be an alternative technique to FNA. It has low rate of non-diagnostic and undetermined cases, with high sensitivity and PPV. KEY POINTS: Thyroid core-needle biopsy (CNB) has high sensitivity and PPV. Pitfalls of CNB are rare. Pitfalls are due to cystic cancer, histological heterogeneity, and mistakes in analysis. CNB is a reliable, safe, and accurate method to approach thyroid nodules. CNB can be used primarily or after insufficient or indeterminate FNA.

Expression of cannabinoid receptors in human kidney.

The presence of CB1 and CB2 cannabinoid receptors and their physiological role in the kidney has been described in animal models but not in humans. Our aim in this study was to evaluate the presence of these receptors in human kidney, adult and fetal. For this purpose, RT-PCR, western-blot and immunohisto-chemical assays were performed. RT-PCR confirmed the presence of CB1 receptor mRNA receptor and the absence of the CB2 receptor mRNA in adult and fetal kidney. Western-blot and immunohistochemical assays revealed the presence of the CB1 cannabinoid receptor protein, which displayed a similar distribution in fetal and adult kidneys. Proximal and distal convoluted tubule cells and intercalated cells in the collecting ducts showed marked positivity. Conversely, the CB2 cannabinoid receptor protein was consistently negative in all cases. Our data suggest a possible implication of the endocannabinoid system in the physiology and development of the human kidney.

Changes in cell-surface peptidase activity in papillary renal cell carcinoma.

BACKGROUND: Renal cancer is one of the ten most common malignant tumours in humans and its histological classification, best clinical management and treatment strategies are continuously debated. Roughly 10% of renal carcinomas are papillary renal cell carcinomas (RCCs), a histologically well characterized tumour subtype that is linked to alterations on chromosomes 7 and 17. Peptidases are proteolytic enzymes known to be involved in oncological processes, although their precise role in renal cancer is poorly understood. MATERIALS AND METHODS: Eighteen papillary RCCs were selected for the study. Tumour and normal tissue samples were frozen for enzymatic analysis. The catalytic activity for a pool of peptidases (EC numbers: 3.4.11.14; 3.4.11.2; 3.4.11.6; 3.4.11.21; 3.4.11.7; 3.4.14.5; 3.4.24.11; 3.4.21.26; 3.4.19.3) was measured fluorometrically. RESULTS: Statistically significant decreases were observed in the following cell surface activities: EC.3.4.11.2 (six-fold decrease in tumour vs. non-tumour); 3.4.11.6 (five-fold decrease); 3.4.11.7 (eight-fold decrease); 3.4.24.11 (four-fold decrease). No significant alterations were observed in the soluble activities. CONCLUSION: These data confirm the involvement of cell-surface peptidases in the mechanisms underlying RCC aetiogenesis and suggest that the peptidase activity profile in the RCC may be a diagnostic/prognostic marker.

Renal cell carcinoma in young adults: a study of 130 cases and a review of previous series.

OBJECTIVE: To characterize a large series of renal cell carcinomas (RCCs) in young patients and to compare the data obtained to previously published data. PATIENTS AND METHODS: A total of 130 RCCs diagnosed in patients <40 years of age were collected from 9 different hospitals in Spain. Cases were re-evaluated following the diagnostic criteria of the 2004 WHO classification of renal tumors. RESULTS: Histologically, tumors were classified as clear cell (50.7%), papillary (8.5%), chromophobe (14.6%), unclassified (16.9%) and clear cell papillary (9.3%) RCCs. Organ-confined disease (OCD) was detected in 83.6% of the cases. Tumor size and Fuhrman's grade were statistically correlated (Spearman's rho = 0.391). CD10 (p = 0.000), CK7 (p = 0.000), CD15 (p = 0.016), CD117 (p = 0.000), 34betaE12 cytokeratin (p = 0.034) and e-cadherin (p = 0.000) immunostaining significantly differentiated the five histological categories. CONCLUSIONS: OCD was more common in young RCC patients. The clear cell phenotype accounted for only 50% of RCCs in this age group, with an increasing number of chromophobe and unclassified RCCs. Clear cell RCCs with a papillary growth pattern accounted for a significant proportion of the cases.

[Celecoxib-induced aquagenic keratoderma]. / Queratodermia acuagénica inducida por celecoxib.

Aquagenic keratoderma is an infrequent condition characterized by translucent, smooth-surfaced papules and plaques and prominent eccrine ducts. It is limited to the palms and appears or becomes more pronounced after exposure to water. Histopathologically, hyperkeratosis and dilation of the eccrine ducts are seen. This condition has been described in adolescents and young women. We present the case of a 31-year-old woman with rheumatoid arthritis who had begun treatment with celecoxib one month before the onset of her cutaneous symptoms. Similar changes have been described in association with cystic fibrosis, and a case induced by rofecoxib has also been reported. Higher levels of sodium in the skin associated with celecoxib could increase the keratin's ability to take in water, and this may cause the clinical symptoms.