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.

Neoplasias oncocíticas renales. Revisión crítica de un problema diagnóstico no resuelto / Oncocytic renal neoplasm. A critical review of an unresolved diagnostic problem

El oncocitoma y el carcinoma de células cromófobas sondos entidades perfectamente reconocidas en la clasificaciónvigente de las neoplasias renales. Ambas neoplasias estánmuy interrelacionadas y parece que se originan en la zonadistal de la nefrona. A pesar de estar perfectamente definidasdesde el punto de vista histológico, en la práctica diaria loslímites entre ambas neoplasias siguen siendo confusos y,desafortunadamente, la llegada de las nuevas técnicas diagnósticasa nuestros laboratorios no ha resuelto el problema.La aproximación actual consiste en considerar al conjunto detumores oncocíticos renales como un espectro de lesiones enel cual el oncocitoma y el carcinoma de células cromófobasson los dos extremos. Sin embargo, la experiencia clínicademuestra que hay demasiados casos a medio camino, en tierrade nadie, en los cuales el patólogo se encuentra con grandesdificultades diagnósticas y con la imposibilidad de predecirsu comportamiento biológico. El panorama se complicaaún más si se tiene en cuenta que el carcinoma renal decélulas claras muestra con cierta frecuencia citoplasmaseosinófilos granulares, lo cual hace aún más problemático eldiagnóstico diferencial. En este trabajo se revisa de maneracrítica la literatura existente en este campo (AU)

Oncocytoma and chromophobe cell carcinoma are twowell recognised histological entities in the current classificationof renal tumours. Both entities are closely relatedand arise in the distal nephron. In spite of the fact that bothtumours are sharply defined from the pathological point ofview, the boundary between them still remains confusing indaily practice and the arrival of new diagnostic techniquesto our Labs has not resolved the problem. The currentapproach to the issue considers all renal oncocytic neoplasmswithin a spectrum of lesions in which oncocytomaand chromophobe renal cell carcinoma are the two extremepoints. However, the clinical experience shows that thereare too many cases «in between», in which the pathologisthas a lot of difficulties for making a reliable diagnosis andoften is unable to predict the clinical behaviour. The differentialdiagnosis may be even more complicated if the eosinophilicvariant of clear cell carcinoma is taken intoaccount. This study reviews the literature on this topic incritical way (AU)

Carcinomas renales con células claras / Renal cell carcinomas with clear cells

En este trabajo se revisa el concepto del carcinoma renalconstituido por células claras, un hecho muy frecuentementeencontrado en la práctica diaria en nuestro medio. Esteabordaje es pertinente debido a que no todos los carcinomasrenales con células claras al microscopio son auténticos carcinomasrenales de células claras, sino que pueden ser otrasentidades. Dicha aproximación puramente morfológica noreniega de la nueva clasificación de la OMS vigente, sinoque la complementa. El trabajo está dirigido más al patólogogeneral que se enfrenta a casos muy variados con alta presiónasistencial, que al subespecialista acostumbrado a profundizaren casos complejos y con grandes medios técnicosen el campo del cáncer renal. Se revisa en primer lugar elcarcinoma renal asociado a la enfermedad de von Hippel-Lindau porque muchas de las alteraciones genéticas que provocanesta enfermedad están presentes en el carcinoma renalde células claras esporádico y con posterioridad, se hace lomismo con los carcinomas renales de células claras esporádicosconvencionales, los carcinomas familiares no asociadosa la enfermedad de von Hippel-Lindau, los carcinomascon translocación, el carcinoma papilar renal hereditario,algunos carcinomas asociados a Esclerosis Tuberosa y al síndromede Birt-Hogg-Dubé, el carcinoma de células cromófobasy el carcinoma asociado a enfermedad renal quística (AU)

We review in this paper the concept of renal cell carcinomawith clear cells, a quite frequent histological findingin the pathologist’s daily work. This viewpoint is pertinentbecause not all the renal cell carcinomas with clear cells areconventional clear cell renal cell carcinomas. In fact, someof them are other entities on the light of the new WHO classification.This purely morphological approach does notdissent from this classification of renal tumours in adults.The revision is addressed more to the general pathologistwho usually faces a wide variety of cases often under clinicalpressure than to the subspecialist, who in general analyzesmany complex cases of renal cancer in depth usingsophisticated technical tools. Renal cell carcinoma relatedto von Hippel-Lindau disease is reviewed first becausemany of the genetic disorders underlying this disease arealso present in sporadic, conventional renal cell clear cellcarcinoma. Latter, conventional renal cell clear cell carcinomas,other familial, non von Hippel-Lindau associated renalcell carcinomas, translocation carcinomas, the hereditarypapillary renal cell carcinoma, some carcinomas associatedto Tuberous Sclerosis and to Birt-Hogg-Dubé syndrome,chromophobe renal cell carcinomas and carcinomas associatedto end-stage renal disease are reviewed (AU)

Parámetros histológicos predictivos de la invasiónde las vesículas seminales en el cáncer de próstata / Predictive histological parameters of seminal vesicle invasion in prostate cancer

Antecedentes: La invasión de las vesículas seminales esun dato histológico de mal pronóstico en el cáncer de próstata.En la mayor parte de los casos es un hallazgo accidentalya que los pacientes con signos clínicos o histológicos deenfermedad extraprostática no se tratan mediante cirugía enla mayor parte de protocolos al uso. Nuestra intención escuantificar este hallazgo histológico en una serie homogéneade prostatectomías radicales y correlacionarlo con los hallazgosen las biopsias previas. Métodos: Durante un periodo de8 años (1998-2005), 363 pacientes con cáncer de próstatafueron tratados mediante prostatectomía radical en el Hospitalde Basurto. Los pacientes fueron seleccionados para lacirugía en función de la combinación de la estadificación clínica,niveles de PSA sérico y datos obtenidos de la biopsiaprevia. Los datos obtenidos en las prostatectomías se correlacionaron(rho de Spearman) con varios hallazgos histológicosprocedentes de las biopsias. Resultados: Se detectóinvasión seminal en 37 pacientes (10,2%). La invasiónmicroscópica de las vesículas seminales se correlacionó conlos milímetros totales de cáncer (media 20 mm, r=0,397),con el número de focos de tumor (media 3,8, r=0,383), conla invasión de ambos lados prostáticos (r=0,256), con elíndice de Gleason >7 (r=0,306), con la invasión perineural(r=0,318), y con el PIN de alto grado (r=0,142) en las biopsias,y con el índice de Gleason >7 (r=0,357), con el PIN dealto grado (r=0,211), con la extensión extraprostática(r=0,480), y con la invasión de márgenes quirúrgicos(r=0,287), invasión perineural (r=0,847), y afectación delápex (r=0,307), en las prostatectomías. Conclusiones: Lainvasión de las vesículas seminales es un hallazgo frecuenteen las piezas de prostatectomía radical, incluso después deuna selección correcta de pacientes para cirugía (..) (AU)

Background: Seminal vesicle invasion is a finding ofbad prognosis in prostate cancer. Its discovery in radicalprostatectomies is accidental in most cases becausepatients with clinical or histological evidence of extraprostaticdisease are not surgically treated in most clinical protocols.Our aim is to quantify this finding in a homogeneousseries of radical prostatectomies and to correlate itwith core biopsy findings. Methods: Over an 8-year period(1998-2005), a total of 363 patients with prostate cancerunderwent radical prostatectomy at Basurto Hospital. Thecombination of clinical staging, PSA levels and core biopsydata indicated the candidates for surgery. Data obtainedin prostatectomies were correlated (Spearman’s rho) withseveral histological parameters in biopsies. Results: Radicalprostatectomies showed seminal vesicle invasion in 37cases (10.2%). Microscopic seminal vesicle invasion correlatedwith total millimetres of cancer (average 20 mm,r=0.397), number of tumour foci (average 3.8, r=0.383),bilateral invasion (r=0.256), Gleason Index (GI) >7(r=0.306), perineurial invasion (r=0.318), and high gradePIN (HGPIN) (r=0.142) in biopsies, and with GI >7(r=0.357), HGPIN (r=0.211), extraprostatic extension(r=0.480), and margin (r=0.287), perineurial (r=0.847),and apex (r=0.307) invasions, in prostatectomies. Conclusions:Seminal invasion is a frequent finding in prostatectomies,even after a correct selection of patients for surgery.This finding correlates to tumour volume parameters,bilateral invasion, and other morphologic parameters ofbad prognosis in prostate cancer (AU)

Queratodermia acuagénica inducida por celecoxib / Celecoxib-induced aquagenic keratoderma

La queratodermia acuagénica es un cuadro poco frecuente caracterizado por pápulas y placas translúcidas con una superficie lisa y ductos ecrinos prominentes, limitado a palmas, que aparece o se hace más pronunciado tras la exposición del agua. Histopatológicamente se aprecia hiperqueratosis y dilatación de los ductos ecrinos. Este cuadro se ha descrito en adolescentes y mujeres jóvenes. Presentamos el caso de una mujer de 31 años de edad con una artritis reumatoide que había comenzado tratamiento con celecoxib un mes antes del inicio de sus síntomas cutáneos. Cambios similares se han descrito en asociación con fribosis quística y está descrito un caso inducido por rofecoxib. El incremento de sodio en la piel asociado a la toma de celecoxib podría causar un incremento en la capacidad de captación de agua por la queratina y ser el causante del cuadro clínico

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

[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.