Postmenopausal onset of androgen excess: a diagnostic and therapeutic algorithm based on extensive clinical experience.

PURPOSE: Postmenopausal hyperandrogenism is a rare condition that requires identifying those women bearing a life-threatening tumor. We aimed to study diagnostic work-up and management of postmenopausal androgen excess, proposing an algorithm for clinical decision supporting. METHODS: We conducted an observational cross-sectional study and longitudinal follow-up including 51 consecutive menopausal patients reported for hyperandrogenism between 2003 and 2023 to our clinics. We assessed diagnostic testing accuracy and performance by receiver operating characteristic curves, their respective areas under the curve (AUCROC), and 95% confidence intervals (95%CI), for distinguishing between benign and malignant conditions, and androgen excess source. RESULTS: Most commonly, postmenopausal hyperandrogenism derived from benign conditions such as ovarian hyperthecosis (n = 9). However, four (8%) patients had borderline/malignant tumors arising at the ovaries (n = 3) or adrenals (n = 1). These latter were more likely to develop virilization than those with benign disorders [specificity(95%CI)]: 0.87 (0.69; 0.92)]. Circulating total testosterone [AUCROC(95%CI): 0.899 (0.795; 1.000)] and estradiol [AUCROC(95%CI): 0.912 (0.812; 1.000)] concentrations showed good performances for discriminating between both conditions. Transvaginal-ultrasonography found two out of three potentially malignant ovarian neoplasms, and another was apparent on a pelvic computed tomography scan. An adrenal computed tomography scan also located an androgen-secreting carcinoma. CONCLUSIONS: Clinical or biochemical features of an aggressive androgen-secreting tumor should lead to urgently obtaining a targeted imaging. At first, an abdominal-pelvic CT scan represents the best choice to perceive adrenal malignancy, and may identify aggressive ovarian tumors. When warning signs are lacking, a calm and orderly work-up allows properly addressing the diagnostic challenge of postmenopausal hyperandrogenism.

The ever-evolving role of pathologists in the management of breast cancer with neoadjuvant treatment: recommendations based on the Spanish clinical experience

Purpose. To compare the current international standards for neoadjuvant systemic therapy (NAST) protocols, and establish consensus recommendations by Spanish breast pathologists; and to look into the Spanish reality of defining pathological complete response in daily practice. Materials and methods. A modified Delphi technique was used to gain consensus among a panel of 46 experts with regard to important issues about NAST specimens, with the objective of standardize handling and analysis of these breast cancer specimens. In addition, a survey was conducted among 174 pathologists to explore the Spanish reality of post-NAST breast cancer specimens handling. Results. Our survey shows that pathologists in Spain follow the same guidelines as their international colleagues and face the same problems and controversies. Among the experts, 94.1% agreed on the recommendation for a pre-treatment evaluation with a core needle biopsy, and 100% of experts agreed on the need of having properly indicated information for the post-NAST surgical specimens. However, only 82.7% of them receive properly labelled specimens and even less receive specimens where markers are identified and the degree of clinical/radiological response is mentioned. Among participants 59.9% were familiar with the residual cancer burden system for post-NAST response quantification, but only 16.1% used it regularly. Conclusions. Active participation on breast cancer multidisciplinary teams, optimal usage of core needle biopsy for timely and standardized procedures for the diagnostic analysis, and accurate diagnosis of pathological complete response and complete evaluation of the response to NAST need to become the standard practice when handling breast cancer specimens in Spain (AU)

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The ever-evolving role of pathologists in the management of breast cancer with neoadjuvant treatment: recommendations based on the Spanish clinical experience.

PURPOSE: To compare the current international standards for neoadjuvant systemic therapy (NAST) protocols, and establish consensus recommendations by Spanish breast pathologists; and to look into the Spanish reality of defining pathological complete response in daily practice. MATERIALS AND METHODS: A modified Delphi technique was used to gain consensus among a panel of 46 experts with regard to important issues about NAST specimens, with the objective of standardize handling and analysis of these breast cancer specimens. In addition, a survey was conducted among 174 pathologists to explore the Spanish reality of post-NAST breast cancer specimens handling. RESULTS: Our survey shows that pathologists in Spain follow the same guidelines as their international colleagues and face the same problems and controversies. Among the experts, 94.1% agreed on the recommendation for a pre-treatment evaluation with a core needle biopsy, and 100% of experts agreed on the need of having properly indicated information for the post-NAST surgical specimens. However, only 82.7% of them receive properly labelled specimens and even less receive specimens where markers are identified and the degree of clinical/radiological response is mentioned. Among participants 59.9% were familiar with the residual cancer burden system for post-NAST response quantification, but only 16.1% used it regularly. CONCLUSIONS: Active participation on breast cancer multidisciplinary teams, optimal usage of core needle biopsy for timely and standardized procedures for the diagnostic analysis, and accurate diagnosis of pathological complete response and complete evaluation of the response to NAST need to become the standard practice when handling breast cancer specimens in Spain.

Hiperandrogenismo por tumor ovárico de células de Leydig / Hyperandrogenism secondary to Leydig ovarian tumor

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Metastatic meningioma to the eleventh dorsal vertebral body: total en bloc spondylectomy. Case report and review of the literature.

INTRODUCTION: One in every thousand intracranial meningiomas metastatize extracranially. Lung and intraabdominal organs are most frequently affected. Only 7% involve vertebrae and just a dozen cases have been reported in the literature. To our knowledge, this is the first description of a total en bloc spondylectomy through a posterior approach for the treatment of an intraosseous metastatic meningioma to the eleventh dorsal vertebra. CASE REPORT: In March 1996, a 37 year-old male underwent surgical resection for a left occipital intraventricular benign meningioma (WHO I). He was reoperated in February 2002 due to local recurrence. By the end on 2003 he developed progressively invalidating dorsolumbar pain. MRI studies revealed a T11 intraosseous mass. In March 2004, a percutaneous biopsy and vertebroplasty were performed. The pathological specimen was identified as adenocarcinoma and he initiated chemotherapy. Advice from a second pathologist was seeked, who suggested the diagnosis of intraosseous meningioma. Workup studies failed to reveal any primary tumor. In May 2004 the patient was admitted to our department and a new transpedicular biopsy confirmed the diagnosis. In June 2004 he underwent T11 total en bloc spondylectomy (Tomita's procedure), fusion with bone and calcium substitute-filled stackable carbon-fiber cages, and T9 to L1 transpedicular screw fixation. No postoperative complications ocurred and he is, so far, free from primary and secondary disease. Definite pathology: benign meningioma (WHO I). DISCUSSION: Distant metastases from intracranial meningiomas are rare entities, arising from benign lesions in, at least, 60% of cases. Enam et al proposed a specific pathological score to differentiate benign, atypic and malignant meningiomas. Such score correlates with the chance of metastatizing: more than 40% in malignant meningiomas compared to 3.8% of brain tumors overall. The ability to metastatize seems to be linked to vascular or lifatic invasiveness. Metastases ocurr more frequently in angioblastic, papillary and meningothelial variants. Hematogenous (especially venous; Batson's perivertebral plexus), linfatic and cerebrospinal fluid are the main routes involved in the spreading of the tumor. Craniotomy itself may also play a role, for the majority of patients have been previously operated on repeatedly. The interval between the onset of the intracranial disease and the appearance of the metastasis varies from months to many years. The value of transpedicular biopsy is widely recognized (efficacy over 80%) and the suitability of the specimen for pathological examination improves when wide inner caliber trephines are used. In the case presented we applied the oncologic concept of vertebral en bloc resection. We believe this case represents a paradigmatic indication of this technique because it respects the concepts of radical resection and spinal stability, and offers an opportunity for the curation of the disease.

Metastatic meningioma to the eleventh dorsal vertebral body: total en bloc spondylectomy. Case report and review of the literature

Introducción. Las metástasis distantes de meningioma intracraneal ocurren en uno de cada milmeningiomas. La mayor parte afectan a pulmón u órganos intraabdominales. Sólo un 7% aparecen en vértebras. Se han publicado en torno a una docena de casos. Presentamos la primera descripción hasta la fecha de una vertebrectomía completa por vía posterior para tratar una metástasis intraósea de meningioma benigno en el cuerpo de T11.Caso clínico. Varón de 37 años de edad, intervenido en otro centro en Marzo de 1996 de meningioma benigno intraventricular occipital izquierdo de tipo transicional(OMS tipo I). Precisó reintervención por recidiva local en Febrero de 2002. A finales de 2003 comenzó con dolor dorso lumbar intenso y el estudio de RM espinal evidenció una masa intrósea en T11. En Marzo de 2004se realizó biopsia transpedicular y vertebroplastia acrílica. El resultado histológico fue de adenocarcinoma y el paciente comenzó a recibir quimioterapia. Una segunda opinión sobre las muestras histológicas sugirió el diagnóstico de meningioma. El estudio de extensión tumoral no evidenció otra neoplasia primaria. En Mayo de 2004 ingresó en nuestro servicio donde se repite la biopsia transpedicular que confirma el diagnóstico de meningioma. En Junio de 2004 se realizó vertebrectomíaT11 completa por vía posterior, según técnica de Tomita, artrodesis intersomática con cajas apilables de fibra de carbono rellenas de injerto óseo y sustituto cálcico, y fijación transpedicular T9 a L1. La evolución postoperatoria fue satisfactoria y, actualmente, se encuentra libre de enfermedad primaria y secundaria. Anatomía patológica definitiva: meningioma benigno(OMS I).Discusión. Las metástasis distantes de meningiomas intracraneales son entidades raras que en más del 60%de los casos provienen de meningiomas benignos. Enamy cols diseñaron una gradación según parámetros histológicos para diferenciar los meningiomas benignos e los atípicos y malignos. Dicha gradación correlaciona con la probabilidad de producir metástasis distantes: más del 40% en los meningiomas malignos frente a una media del 3.8% de todos los tumores cerebrales. La posibilidad de metastatizar parece relacionarse con la capacidad de invasividad vascular o linfática. Las metástasis son más frecuentes en las variantes angioblástica, papilar y meningotelial. Se describen tres vías de diseminación: hematógena (sobre todo venosa; plexo perivertebral de Batson) linfática y por LCR. La craneotomía podría ser otra vía de diseminación pues la mayoría de los pacientes han sido previamente multioperados del tumor craneal. El tiempo transcurrido entre el diagnóstico del meningioma intracraneal y la aparición de la metástasis vertebral puede variar entremeses y años. La rentabilidad diagnóstica de la biopsia transpedicular es mayor del 80% y mejora cuanto mayor es el diámetro interno de la trefina utilizada. En el caso descrito, aplicamos el concepto oncológico de resección en bloque de la vértebra afectada. Creemos que se trata de una indicación paradigmática de esta técnica pues respeta los conceptos de resección radical y estabilidad de la columna, y otorga una oportunidad de curación de la enfermedad

Introduction. One in every thousand intracranial meningiomas metastatize extracranially. Lung andintra abdominal organs are most frequently affected. Only 7% involve vertebrae and just a dozen cases have been reported in the literature. To our knowledge, this is the first description of a total en bloc spondylectomy through a posterior approach for the treatment of an intraosseous metastatic meningioma to the eleventh dorsal vertebra. Case report. In March 1996, a 37 year-old male underwent surgical resection for a left occipital intraventricular benign meningioma (WHO I). He wasreoperated in February 2002 due to local recurrence. By the end on 2003 he developed progressively invalidating dorso lumbar pain. MRI studies revealed a T11 intraosseous mass. In March 2004, a percutaneous biopsy and vertebroplasty were performed. The pathological specimen was identified as adenocarcinoma and he initiated chemotherapy. Advice from a second pathologist was seeked, who suggested the diagnosis of intraosseous meningioma. Workup studies failed to reveal any primary tumor. In May 2004 the patient was admitted to our department and a new transpedicular biopsy confirmed the diagnosis. In June 2004 he underwentT11 total en bloc spondylectomy (Tomita's procedure),fusion with bone and calcium substitute-filled stackable carbon-fiber cages, and T9 to L1 transpedicular screw fixation. No postoperative complications ocurred and he is, so far, free from primary and secondary disease. Definite pathology: benign meningioma (WHO I).Discussion. Distant metastases from intracranial meningioma’s are rare entities, arising from benign lesions in, at least, 60% of cases. En am et al proposed a specific pathological score to differentiate benign, atypic and malignant meningiomas. Such score correlates with the chance of metastatizing: more than 40%in malignant meningiomas compared to 3.8% of brain tumors overall. The ability to metastatize seems to be linked to vascular or lifatic invasiveness. Metastases ocurr more frequently in angioblastic, papillary and meningothelial variants. Hematogenous (especially venous; Batson's perivertebral plexus), linfatic and cerebrospinal fluid are the main routes involved in the spreading of the tumor. Craniotomy itself may also play a role, for the majority of patients have been previously operated on repeatedly. The interval between the onset of the intracranial disease and the appearance of the metastasis varies from months to many years. The value of transpedicular biopsy is widely recognized (efficacy over 80%) and the suitability of the specimen for pathological examination improves when wide inner caliber trephines are used. In the case presented we applied the oncologic concept of vertebral en bloc resection. We believe this case represents a paradigmatic indication of this technique because it respects the concepts of radical resection and spinal stability, and offers an opportunity for the curation of the disease

Linfoma no hodgkiniano T periférico diagnosticado en linfadenectomía axilar por carcinoma de mama / Peripheral T-cell non-Hodgkin’s lymphoma diagnosed during axillary lymphadenectomy for breast cancer

Presentamos un caso en el que coexisten un carcinoma de mama y un linfoma no hodgkiniano T diagnosticado fortuitamente en los ganglios axilares ipsilaterales, al practicar linfadenectomía por un carcinoma de mama diagnosticado en el programa de detección precoz del cáncer de mama. La coincidencia de un carcinoma de mama infiltrante y un linfoma no hodgkiniano T en los ganglios axilares ipsilaterales no ha sido publicada previamente en la bibliografía consultada

We report a case of breast carcinoma co-existing with T-cell non-Hodgkin’s lymphoma of the ipsilateral axillary lymph nodes detected fortuitously during lymphadenectomy for breast carcinoma diagnosed by population screening. No cases of breast cancer occurring simultaneously with ipsilateral axillary T-cell non-Hodgkin’s lymphoma have previously been reported

Nefropatía con trombos oclusivos intracapilares de IgA y vasculitis necrotizante, exteriorizada como insuficiencia renal rápidamente progresiva / Rapidly progressive nephropathy, with necrotizing vasculitis and IgA intracapilary occlusive thrombus

Varón de 57 años sin antecedentes destacables,salvo que refería haber sido rechazado como donantede sangre por «dudosa hepatitis». Doce díasantes del ingreso en nuestro Hospital fue diagnosticadoen otro Centro de fracaso renal agudo con unaCreatinina sérica (Crs) de 2,6 mg/dl, que fue atribuidoal tratamiento con AINEs indicado por una inflamaciónungueal. Tratado con fluidoterapia parenteraly Amoxicilina/Clavulánico, se observó undescenso de la Crs a 1,6 mg/dl. Cuatro días despuésacudió a Urgencias de otro Centro por cefalea,donde comprobaron HTA, hematuria, proteinuria,leucocituria y Crs de 1,7 mg/dl, recomendándole tratamientocon Amlodipino, Metamizol y Amoxicilina/Clavulánico.El 9/5/99 acudió a nuestro Hospital por persistenciade cefalea, astenia, y disminución de diuresis enlos últimos cinco días. No refería vómitos, diarrea,prurito, lesiones cutáneas, fiebre, tos, expectoración,hematuria macroscópica, disuria, edemas, polaquiuria,ortopnea ni disnea paroxística nocturna.Al comprobar la existencia de anemia (Hb: 9,2g/dl; Hto: 27,8%), leucocitosis con neutrofilia(14.300; 78%, respectivamente), insuficiencia renal(Urea 137 g/dl; Crs 5,0 mg/dl) con microhematuria(+++) y proteinuria (+++), es ingresado. En la exploración física, como datos más relevantes,se comprobó: presencia de un «rash» inguinal bilateral, crepitantes en base derecha, soplo sistólicoen focos mitral y pulmonar y TA de 200/90 mmHg. No se observó presencia de edemas, púrpura, signos de trombosis venosa profunda, adenopatías periféricas ni alteraciones abdominales

[Lafora disease. A new case of confirmation of diagnosis on molecular genetic studies]. / Enfermedad de Lafora. Confirmación diagnóstica por genética molecular de un nuevo caso.

INTRODUCTION: Lafora s disease is a type of progressive myoclonic epilepsy with bad prognosis. Until now diagnosis was based on finding characteristic intracytoplasmatic polyglucosan bodies in biopsies of sweat secreting cells in the skin. Recently the gene responsible has been discovered. This permits firm diagnosis and screening of carriers. We present the case of a child diagnosed on molecular genetic studies. CLINICAL CASE: A 12 year old boy with a clinical history of three febrile seizures at the age of one year but no other abnormalities, presented a seizure of visual disorder with secondary generalization. There was no family history of seizures. Following a period of normality he had further seizures (clonic, visual and generalized myoclonic). The EEG showed generalized spike and wave activity, which was more marked after stimulation by light and became progressively worse. Neuroimaging studies were normal. In spite of treatment there was a progressive increase in visual and generalized myoclonic seizures together with deterioration of cognitive function and ataxia. Histological studies of the sweat glands showed homogeneous nodular deposits of intracytoplasmatic PAS+. Molecular studies of the EPM2A gene linked to chromosome 6q24 showed the presence of two mutations on the 1 and 4 exons. CONCLUSIONS: We describe a 12 year old patient with all the clinical features of Lafora type progressive myoclonic epilepsy in whom characteristic cytoplasmic bodies were found in the sweat gland biopsy. Molecular genetic studies of the EPM2A gene confirmed diagnosis of the disorder.

Enfermedad de Lafora. Confirmación diagnóstica por genética molecular de un nuevo caso / Lafora disease. A new case of confirmation of diagnosis on molecular genetic studies

Introducción. La enfermedad de Lafora es un tipo de epilepsia mioclónica progresiva de evolución grave. Hasta la actualidad el diagnóstico se basaba en el hallazgo de los característicos cuerpos poliglucosanos intracitoplasmáticos en las células sudoríparas a través de la biopsia cutánea. El reciente descubrimiento del gen responsable nos permite un diagnóstico de certeza y el cribado de portadores. Presentamos un caso pediátrico diagnosticado por genética molecular. Caso clínico. Varón de 12 años de edad, con el único antecedente de tres crisis febriles al año de edad, que presenta una crisis de sintomatología visual con generalización secundaria. No existían antecedentes familiares de crisis convulsivas. Tras un período libre las crisis reaparecen, tanto clónicas, visuales como mioclónicas generalizadas. El EEG muestra una actividad generalizada de punta y polipunta-onda más evidente durante la estimulación luminosa, con empeoramiento progresivo. Los estudios de euroimagen fueron normales. A pesar del tratamiento se observa un progresivo aumento de las crisis visuales y mioclónicas generalizadas junto con deterioro de las funciones cognitivas y ataxia. El estudio histológico de glándulas sudoríparas muestra depósitos homogéneos nodulares intracitoplasmáticos PAS+. El estudio molecular del gen EPM2A ligado al cromosoma 6q24 muestra la presencia de dos mutaciones en los exones 1 y 4. Conclusiones. Describimos un paciente de 12 años que presenta todos los aspectos clínicos de la epilepsia mioclónica progresiva tipo Lafora con el hallazgo de los característicos de cuerpos citoplasmáticos en la biopsia de glándulas sudoríparas. El estudio por genética molecular del gen EPM2A confirma el diagnóstico de la enfermedad (AU)

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Architecture and function of the gastroesophageal barrier in the piglet.

We describe the anatomy and function of the gastroesophageal barrier in the piglet. Male piglets underwent dissection (N = 6) and gastroesophageal muscle layer histometry (N = 6). Sedated, nonintubated animals (N = 13) underwent four-probe perfusion esophageal manometry and the pressure profiles were related to the muscular thickness in the four quadrants. Hiatal and gastroesophageal anatomy are similar to our own. The muscle is thicker at the point where the clasp (on the right side) and sling fibers (on the left) concentrate. The pressure profiles were axially and radially asymmetric in coincidence with the thickness variations of the corresponding muscle layers. Sphincteric pressure was recorded as a plateau, whereas diaphragmatic crural pressure appeared as phasic oscillations in synchrony with respiration. The sphincter relaxed upon deglutition. In conclusion, the gastroesophageal structure and physiology are so similar in men and piglets that piglets are excellent models for research in this area.