Brown tumors of the jaw: an atypical manifestation of primary hyperparathyroidism.

Brown tumors represent the terminal stage of bone remodeling processes in primary hyperparathyroidism. Currently they are rare, and typically affect long bones, pelvis and ribs. Brown tumors may be not included in the initial differential diagnosis of bone disease, especially when they are present in atypical localizations. We reported two cases of oral brown tumors as the initial presentation of primary hyperparathyroidism. In the first case, a 44-year-old woman presented a painful and sessile lesion of 4 × 3 cm over the central body of the mandible which progressively increased in 4-month. The second case involved a 23-year-old woman who was referred with a 3-month history of a painful and ulcerated mass of 2 cm arising from left maxilla, episodes of gingival hemorrhage and difficulty of breathing. Both cases were solitary tumors with no evidence of palpable cervical lymphadenopathy. Incisional biopsy of oral tumors resulted in giant cell and primary hyperparathyroidism was confirmed by laboratory tests. After parathyroidectomy, histology confirmed adenoma in both cases. Although this type of clinical presentation has almost disappeared in the recent decades, brown tumors should be considered in the differential diagnosis of bone oral masses.

Los tumores pardos son raros y, por lo general, afectan huesos largos, pelvis y costillas. Pueden no estar incluidos en el diagnóstico diferencial inicial como manifestación de enfermedad esquelética, especialmente cuando se presentan en localizaciones atípicas. Comunicamos dos casos de tumores pardos orales como presentación inicial de hiperparatiroidismo primario. En el primer caso, una mujer de 44 años presentó una lesión dolorosa y sésil de 4 × 3 cm sobre el cuerpo central de la mandíbula que aumentó de tamaño progresivamente en 4 meses. El segundo caso corresponde a una mujer de 23 años que acudió por presentar una masa dolorosa y ulcerada de 2 cm en maxilar izquierdo de 3 meses de evolución, episodios de hemorragia gingival y dificultad para respirar. Todos fueron tumores solitarios sin evidencia de linfadenopatía cervical palpable. La biopsia incisional de los tumores orales resultó en células gigantes, y las pruebas de laboratorio confirmaron el hiperparatiroidismo primario. Tras la paratiroidectomía, la histología confirmó adenoma en ambos casos. Los tumores pardos representan la etapa terminal de los procesos de remodelación ósea en el hiperparatiroidismo primario. Aunque este tipo de presentación clínica casi ha desaparecido en las últimas décadas, los tumores pardos deben ser considerados en el diagnóstico diferencial de las masas óseas orales.

[Malignant psoas syndrome secondary to uterine cervical carcinoma]. / Síndrome del psoas maligno secundario a cáncer de cuello uterino.

A 40-year-old woman was scheduled to receive chemotherapy for a high-risk common B-cell acute lymphoblastic leukemia (ALL), diagnosed 10 months earlier in the wake of lower limb bruising and petechiae, and metrorrhagia. At that time, she had thrombocytopenia and a normal transvaginal gynecological ultrasound. Upon admission, she complained of a 3-month history of incapacitating left groin pain radiated to the thigh, and right lower quadrant abdominal pain associated with diarrhea. On physical examination, she had tenderness in the right iliac fossa and a positive psoas sign on the left. Computerized scan of the abdomen and pelvis reported an image compatible with a left psoas abscess and signs of typhlitis. The biopsy of the left psoas muscle demonstrated infiltration by nests and cords of moderately differentiated keratinizing squamous carcinoma. Gynecological examination revealed macroscopic abnormalities of the cervix correlated with the same histopathological diagnosis. The second primary cancers most frequently associated with ALL are Hodgkin lymphoma, squamous skin cancer, endocrine tumors, kidney cancer, non-Hodgkin lymphoma, and breast cancer. Muscle metastases from solid tumors are rare, and usually arise from the lung, kidney, thyroid, and melanoma. Malignant psoas syndrome is caused by neoplastic infiltration of the muscle. The differential diagnosis should be made with a psoas abscess, which may arise from typhlitis if secondary. We have not been able to find records of cervical cancer as second primary cancer after ALL.

Una mujer de 40 años se internó de forma programada para recibir quimioterapia por una leucemia linfoblástica aguda (LLA) B común de alto riesgo, diagnosticada 10 meses antes a raíz de hematomas y petequias en los miembros inferiores, y metrorragia. En ese momento, presentaba trombocitopenia y una ecografía ginecológica transvaginal normal. Al ingreso de la internación programada, se quejó de dolor inguinal izquierdo con irradiación al muslo e impotencia funcional de 3 meses de evolución, dolor en fosa ilíaca derecha y diarrea. En el examen físico tenía dolor a la palpación profunda en la fosa ilíaca derecha y signo del psoas positivo a la izquierda. La tomografía de abdomen y pelvis reveló una imagen compatible con un absceso del psoas izquierdo y signos de tiflitis. La biopsia del psoas izquierdo demostró infiltración por nidos y cordones de carcinoma escamoso queratinizante moderadamente diferenciado. El examen ginecológico dirigido evidenció anomalías macroscópicas del cuello uterino correlacionadas con el mismo diagnóstico histopatológico. Los segundos cánceres primarios más frecuentemente asociados a LLA son linfoma de Hodgkin, cáncer escamoso de piel, tumores endocrinos, cáncer renal, linfoma no-Hodgkin y cáncer de mama. Las metástasis musculares de tumores sólidos son infrecuentes, y habitualmente provienen del pulmón, riñón, tiroides y melanoma. El síndrome del psoas maligno es causado por infiltración neoplásica del músculo. El diagnóstico diferencial debe realizarse con el absceso del psoas, que puede originarse en una tiflitis si es secundario. No hemos podido encontrar registros de cáncer de cuello uterino como segundo cáncer primario luego de LLA.

Non-invasive follicular neoplasm with papillary-like nuclear features: a challenging and infrequent entity in Argentina.

PURPOSE: Non-invasive encapsulated follicular variant of papillary thyroid cancer was reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). These neoplasms have an extremely low malignant potential. The aim of this study was (1) to assess the prevalence of NIFTP in patients with papillary thyroid carcinoma, (2) to evaluate their outcomes, and (3) to determine their molecular profile. METHODS: Multicenter, descriptive, retrospective study. Patients with papillary thyroid cancer diagnosed from January 2006 to December 2016 from 11 referral centers were included. Diagnosis of NIFTP was based on criteria described by Nikiforov et al. in 2018. At least two pathologists agreed on the diagnosis. Two thousand six hundred and seventy-seven papillary thyroid cancer patients were included; 456 (17%) of them were follicular variant papillary thyroid cancer, and 30 (1.12%) fulfilled diagnostic criteria for NIFTP. RESULTS: Each of the 30 included patients underwent a total thyroidectomy, and 50% were treated with radioiodine (median dose 100 mCi). After a median follow-up of 37 months, 84% of patients had an excellent response, 3% had an indeterminate response and data was missing in the remaining 13%. No metastatic lymph nodes, distant metastases or recurrences were found. RAS mutations were detected in 4 patients (13%). CONCLUSION: The prevalence of NIFTP in our series is amongst the lowest reported. Excellent outcomes of patients underscore their low malignant potential. Molecular findings differ from other series, probably related to environmental or ethnic features of our population and the meticulous criteria for diagnosing NIFTP.

Bezafibrate therapy in primary biliary cholangitis refractory to ursodeoxycholic acid: a longitudinal study of paired liver biopsies at 5 years of follow up.

BACKGROUND: Ursodeoxycholic acid (UDCA) is the first-line therapy for primary biliary cholangitis (PBC). However, nearly 40% of patients have an incomplete response to UDCA. The addition of bezafibrate has shown biochemical benefit in this group of patients. AIM: To evaluate the long-term effects of UDCA in combination with bezafibrate on histological outcomes in patients with UDCA-refractory PBC. METHODS: Fifty-nine patients refractory to UDCA were included. Clinical parameters were monitored and paired liver biopsy (PLB) was performed after 5 years of follow-up. RESULTS: Of the total cohort, 49 subjects were analysed and 31 had PLB at 5 years. Values for serum ALP, AST, ALT and GGT significantly improved with UDCA-bezafibrate. This beneficial effect was observed at 12 months where 86% achieved ALP at normal levels. Analyses of PLB showed a significant decrease in liver damage as reflected by Ludwig (baseline 2.29 ± 1.2, to 1.84 ± 1 at year 5, P = 0.0242) and Ishak (baseline 6.19 ± 2.2 to 4.77 ± 2.2 at year 5, P = 0.0008) scores. Overall, regression of fibrosis was attained in 48% of patients. Furthermore, we observed a significant reduction in the proportion with cirrhosis from 19% at baseline to 3% at 5 years (P < 0.001). These beneficial effects were associated with better predictive risk scores using the GLOBE and UK-PBC prognosis models. CONCLUSIONS: Adding bezafibrate to UDCA in patients with UDCA-refractory PBC showed a significant decrease in fibrosis and inflammatory histological scores at 5 years. These beneficial effects warrant further evaluation in long-term cohort studies and controlled trials.

Expression of p16(INK4A) gene in human pituitary tumours.

Pituitary adenomas comprise 10-15% of primary intracranial tumours but the mechanisms leading to tumour development are yet to be clearly established. The retinoblastoma pathway, which regulates the progression through the cell cycle, is often deregulated in different types of tumours. We studied the cyclin-dependent kinase inhibitor p16(INK4A) gene expression at mRNA level in human pituitary adenomas. Forty-six tumour specimens of different subtypes, 21 clinically non-functioning, 12 growth hormone-secreting, 6 prolactin-secreting, 6 adrenocorticotropin-secreting, and 1 thyrotropin-secreting tumours were studied. All clinically non-functioning and most of the hormone-secreting tumours were macroadenomas (38/46). The RT-PCR assay and electrophoresis of the PCR-products showed that p16(INK4A) mRNA was undetectable in: 62% of non-functioning, 8% of growth hormone-secreting, 17% of prolactin-secreting and 17% of adrenocorticotropin-secreting adenomas. Forty percent of all macroadenomas and 25% of microadenomas had negative p16(INK4A) mRNA, the latter results suggest that the absence of p16(INK4A) product might be an early event in tumours with no expression of this suppressor gene. Within the non-functioning adenomas 63% were "null cell" and 37% were positive for some hormone, both subgroups showed similar percentage of cases with absence of p16(INK4A) mRNA. Our results show that clinically non-functioning macroadenomas have impaired p16(INK4A) expression in a clearly higher proportion than any other pituitary tumour subtype investigated. Other regulatory pathways may be implicated in the development of tumours with positive p16(INK4A) expression.

Brown tumors of the jaw: an atypical manifestation of primary hyperparathyroidism / Tumores pardos de mandíbula: una manifestación atípica de hiperparatiroidismo primario

Abstract Brown tumors represent the terminal stage of bone remodeling processes in primary hyperparathyroidism. Currently they are rare, and typically affect long bones, pelvis and ribs. Brown tumors may be not included in the initial differential diagnosis of bone disease, espe cially when they are present in atypical localizations. We reported two cases of oral brown tumors as the initial presentation of primary hyperparathyroidism. In the first case, a 44-year-old woman presented a painful and sessile lesion of 4x3 cm over the central body of the mandible which progressively increased in 4-month. The second case involved a 23-year-old woman who was referred with a 3-month history of a painful and ulcerated mass of 2 cm arising from left maxilla, episodes of gingival hemorrhage and difficulty of breathing. Both cases were solitary tumors with no evidence of palpable cervical lymphadenopathy. Incisional biopsy of oral tumors resul ted in giant cell and primary hyperparathyroidism was confirmed by laboratory tests. After parathyroidectomy, histology confirmed adenoma in both cases. Although this type of clinical presentation has almost disappeared in the recent decades, brown tumors should be consi dered in the differential diagnosis of bone oral masses.

Resumen Los tumores pardos son raros y, por lo general, afectan huesos largos, pelvis y costillas. Pueden no estar incluidos en el diagnóstico diferencial inicial como manifestación de enfermedad esquelética, es pecialmente cuando se presentan en localizaciones atípicas. Comunicamos dos casos de tumores pardos orales como presentación inicial de hiperparatiroidismo primario. En el primer caso, una mujer de 44 años presentó una lesión dolorosa y sésil de 4 × 3 cm sobre el cuerpo central de la mandíbula que aumentó de tamaño progresivamente en 4 meses. El segundo caso corresponde a una mujer de 23 años que acudió por presentar una masa dolorosa y ul cerada de 2 cm en maxilar izquierdo de 3 meses de evolución, episodios de hemorragia gingival y difi cultad para respirar. Todos fueron tumores solitarios sin evidencia de linfadenopatía cervical palpable. La biopsia incisional de los tumores orales resultó en células gigantes, y las pruebas de laboratorio confirmaron el hiperparatiroidismo primario. Tras la paratiroidectomía, la histología confirmó adenoma en ambos casos. Los tumores pardos representan la etapa terminal de los procesos de remodelación ósea en el hiperparatiroidismo primario. Aunque este tipo de presentación clínica casi ha desaparecido en las últimas décadas, los tumores pardos deben ser considerados en el diagnóstico diferencial de las masas óseas orales.

Ganglio centinela positivo en melanoma: factores predictivos y resultados del vaciamiento ganglionar / Positive sentinel lymph node in melanoma: predictive factors and results of completion lymph node dissection

RESUMEN Antecedentes: la biopsia del ganglio centinela (GC) es la técnica aceptada para determinar el pronóstico en estadios iniciales de melanoma cutáneo. La ventaja del vaciamiento ganglionar (VG) cuando el GC resulta positivo ha sido recientemente cuestionada. Objetivo: describir los porcentajes y factores asociados a metástasis en el GC, y en los ganglios no centinela (GnC) en los VG de pacientes con GC positivo. Material y métodos: se llevó a cabo un estudio retrospectivo de los registros clínicos y patológicos de 139 pacientes operados por melanoma cutáneo entre enero de 2012 y diciembre de 2019. Resultados: a 96 (69%) pacientes se les realizó biopsia de GC. El promedio de edad fue 61,7 años ± 17,5 (19-93); 53 (55,2%) fueron hombres. La lesión primaria estuvo ubicada en: extremidades 47 (49%), tronco 39 (40,6%), cabeza y cuello 10 (10,4%). El promedio de espesor de Breslow fue 5,01 mm (1,05- 50 mm) y se encontró ulceración en 35 casos (36,4%). El GC fue identificado en todas las oportunidades y en 39 (40,6%) fue positivo. Hubo asociación con el espesor ≥ 3 mm (p = 0,000017) y con la ulceración (p = 0,0011). A los pacientes con GC positivo se les efectuó el VG del territorio afectado: 23 axilar, 10 inguinal y 6 cervical. Veintitrés (59%) presentaron metástasis en GnC. Se asoció con el espesor (p = 0,022) y la ulceración (p = 0,019). Conclusión: existió un alto porcentaje de GnC positivos en la población estudiada, vinculado al espesor y la ulceración. Estas características, así como la dificultad de un estricto seguimiento, inducen a no abandonar el VG en pacientes con GC positivo.

ABSTRACT Background: Sentinel lymph node (SLN) biopsy is the technique accepted to determine the prognosis of early cutaneous melanomas. The advantage of lymph node dissection (LND) when SLN biopsy is positive has recently been questioned. Objective: The aim of this study is to describe the percentages and factors associated with SLN and non-sentinel node (NSN) metastases in LNDs of SLN-positive patients. Material and methods: The clinical records and pathology reports of 139 patients undergoing surgery for cutaneous melanoma between January 2012 and December 2019 were retrospectively reviewed. Results: Ninety-six (69%) patients underwent SLN biopsy. Mean age was 61.7 ± 17.5 years (19-93) and 53 (55.2%) were men. The primary lesion was located in the extremities in 47 (49%) cases, in the trunk in 39 (40.6%), and in the head and neck in 10 (10.4%). Mean Breslow thickness was 5.01 mm (1.05-50 mm) and ulceration was found in 35 cases (36.4%). The SLN was identified in all the cases and was positive in 39 (40.6%). There was an association with thickness ≥ 3 mm (p = 0.000017) and ulceration (p = 0.0011). Those patients with positive SLN biopsy underwent LND of the territory involved: axillary in 23, inguinal in 10 and cervical in 6. Twenty-three (59%) presented NSLN metastases and were associated with thickness (p = 0.022) and ulceration (p = 0.019). Conclusion: There was a high percentage of positive NSLN in the population studied which was associated with thickness and ulceration. These characteristics and the difficulty to achieve strict follow-up are the reasons for completion LND in SLN-positive patients.

Síndrome del psoas maligno secundario a cáncer de cuello uterino / Malignant psoas syndrome secondary to uterine cervical carcinoma

Resumen Una mujer de 40 años se internó de forma programada para recibir quimioterapia por una leucemia linfoblástica aguda (LLA) B común de alto riesgo, diagnosticada 10 meses antes a raíz de hemato mas y petequias en los miembros inferiores, y metrorragia. En ese momento, presentaba trombocitopenia y una ecografía ginecológica transvaginal normal. Al ingreso de la internación programada, se quejó de dolor inguinal izquierdo con irradiación al muslo e impotencia funcional de 3 meses de evolución, dolor en fosa ilíaca derecha y diarrea. En el examen físico tenía dolor a la palpación profunda en la fosa ilíaca derecha y signo del psoas positivo a la izquierda. La tomografía de abdomen y pelvis reveló una imagen compatible con un absceso del psoas izquierdo y signos de tiflitis. La biopsia del psoas izquierdo demostró infiltración por nidos y cordones de carcinoma escamoso queratinizante moderadamente diferenciado. El examen ginecológico dirigido evidenció anomalías macroscópicas del cuello uterino correlacionadas con el mismo diagnóstico histopatológico. Los se gundos cánceres primarios más frecuentemente asociados a LLA son linfoma de Hodgkin, cáncer escamoso de piel, tumores endocrinos, cáncer renal, linfoma no-Hodgkin y cáncer de mama. Las metástasis musculares de tumores sólidos son infrecuentes, y habitualmente provienen del pulmón, riñón, tiroides y melanoma. El síndrome del psoas maligno es causado por infiltración neoplásica del músculo. El diagnóstico diferencial debe realizarse con el absceso del psoas, que puede originarse en una tiflitis si es secundario. No hemos podido encontrar registros de cáncer de cuello uterino como segundo cáncer primario luego de LLA.

Abstract A 40-year-old woman was scheduled to receive chemotherapy for a high-risk common B-cell acute lymphoblastic leukemia (ALL), diagnosed 10 months earlier in the wake of lower limb bruising and petechiae, and metrorrhagia. At that time, she had thrombocytopenia and a normal transvaginal gynecological ultrasound. Upon admission, she complained of a 3-month history of incapacitating left groin pain radiated to the thigh, and right lower quadrant abdominal pain associated with diarrhea. On physical examination, she had tenderness in the right iliac fossa and a positive psoas sign on the left. Computerized scan of the abdomen and pelvis reported an image compatible with a left psoas abscess and signs of typhlitis. The biopsy of the left psoas muscle demonstrated infiltration by nests and cords of moderately differentiated keratinizing squamous carcinoma. Gynecological examination revealed macroscopic abnormalities of the cervix correlated with the same histopathological diagnosis. The second primary cancers most frequently associated with ALL are Hodgkin lymphoma, squamous skin cancer, endocrine tumors, kidney cancer, non-Hodgkin lymphoma, and breast cancer. Muscle metastases from solid tumors are rare, and usually arise from the lung, kidney, thyroid, and melanoma. Malignant psoas syndrome is caused by neoplastic infiltration of the muscle. The differential diagnosis should be made with a psoas abscess, which may arise from typhlitis if secondary. We have not been able to find records of cervical cancer as second primary cancer after ALL.

[Clinical experience in 37 cases of insulinoma]. / Experiencia clinica sobre 37 casos de insulinoma.

Insulinoma is the most frequent pancreatic islet cell tumor. Clinical manifestations include adrenergic and neuroglycopenic symptoms. Diagnosis is established through demonstration of inappropriately elevated insulin serum concentrations in the presence of hypoglycemia. The aim of this study is to show our experience in the management of insulinoma. Since 1988, 23 women (48 +/- 18 years) and 14 men (45 +/- 19 years) were studied. Seventy three percent of them suffered mainly from neuroglucopenic symptoms while 27% referred adrenergic signs. Mean duration of symptoms before diagnosis was 2.7 +/- 2 years. Mean fasting serum glucose was 32.4 +/- 8.7 mg/dl, insulin 38.2 +/- 39.7 microU/ml (RIA, n=11) or 23.8 +/- 18.1 microU/ml (chemoluminescence, n=26) and C-peptide 1.15 +/- 1.60 nmol/l (n=14). Twenty one patients developed clinical and/or biochemical hypoglycaemia within 9.0 +/- 5.2 hours of supervised fast. Preoperative localization was performed in 73% by imaging techniques, arterial calcium stimulation and/or intraoperative ultrasonography and palpation by the surgeon. Thirty six patients were operated on by conventional surgery in 25, or laparoscopic approach in 11 cases. In 22 patients, a solitary tumor was excised (61.1%). Six cases presented multiple insulinomas. Five patients had malignant insulinomas. In one case, a pattern of nesidioblastosis was found and 2 patients presented unspecific findings. In 3 patients another tumour (glucagonoma) was found (1 of them with MEN 1). One patient was treated with verapamil with good clinical response. Mean postoperative follow up was 60.4 +/- 59.9 months.

Dramatic clinical response to dabrafenib plus trametinib in anaplastic thyroid carcinoma and the challenges faced during the COVID-19 pandemic

SUMMARY Anaplastic thyroid carcinoma is the rarest tumor of the thyroid gland, representing less than 2% of clinically recognized thyroid cancers. Typically, it has an extremely rapid onset, fatal outcomes in most cases, and a median overall survival of 3 to 10 months despite aggressive multidisciplinary management. The presence of targetable mutations in anaplastic thyroid carcinoma patients is an opportunity for treatment when conventional therapeutics approaches are not effective, a frequent situation in the majority of patients. We present our experience in the management of a patient with unresectable anaplastic thyroid cancer who had a remarkable and rapid response to treatment with dabrafenib and trametinib during the COVID-19 pandemic. After four weeks of dabrafenib 150 mg twice daily plus trametinib 2 mg daily, he showed a dramatic reduction of the cervical mass around 90%. Nearly eight weeks under treatment with dabrafenib plus trametinib, the patient remains with minimal locoregional disease without distant metastases.

[Detection of micrometastases of colorectal carcinoma in lymph nodes]. / Detección de micrometástasis de carcinoma de colon en ganglios linfáticos.

Dissemination of lymph nodes is a known prognostic factor in colorectal carcinoma. Micrometastases in lymph nodes can be missed when studied by routine techniques. We analyzed 162 lymph nodes from 30 patients with colonic carcinoma and using routine techniques, they were classified as follows: two Dukes A; nineteen Dukes B; and nine Dukes C. A patient with benign colon disease served as negative control. Lymph nodes were all sectioned in halves, with one of the halves stored in liquid nitrogen for molecular biology examination by carcinoembryonic antigen expression. The other formalin-fixed and paraffin embedded halves were saved for both pathologic and immunohistochemical examination. For Dukes A and Dukes B tumors, reverse transcriptase-polymerase chain reaction (RT-PCR) had a 50% higher sensitivity in the detection of micrometastases. The expression of carcinoembryonic antigen (CEA) was detected in all Dukes C cases, which were considered as positive controls. These results showed that RT-PCR has a higher sensitivity in the detection of micrometastases than routine techniques, including immunohistochemistry.

Preliminary report on tumor stem cell/B cell hybridoma vaccine for recurrent glioblastoma multiforme.

BACKGROUND: Glioblastoma multiforme (GBM), the most aggressive glioma, presents with a rapid evolution and relapse within the first year, which is attributed to the persistence of tumor stem cells (TSC) and the escape of immune surveillance. Mixed leukocyte culture (MLC) cytoimplant has been shown to function as a powerful intratumor pro-inflammatory cytokine pump. Tumor B-cell hybridoma (TBH) vaccines have been shown to function as antigen-presenting cells. We evaluated the toxicity and efficiency of each treatment alone and in combination. PATIENTS AND METHODS: In an open study, 12 consecutive patients were evenly divided into 3 groups, each group receiving 3 different treatments. Patients in Group 1 were treated, after diagnosis, with debulking surgery (DS)+radiotherapy (Rx), and after the first relapse underwent DS+MLC treatment. Patients in Group 2 were similarly treated but after the first relapse underwent DS+MLC+TBH. Finally, patients in Group 3 were similarly treated but after the first relapse underwent DS+TBH. Nestin PAP stain assessed TSC participation in TBH. RESULTS: Treatment with MLC had strong and rapid therapeutic effects, but was limited in duration and induced various degrees of brain inflammation. Treatment with MLC+TBH acted synergistically, provoking a rapid, strong and lasting therapeutic response but also generating different degrees of brain inflammation. A lasting therapeutic effect without generating high degrees of brain inflammation occurred in patients treated with TBH vaccine alone. CONCLUSION: TSC vaccine consisting of TBH alone seems to have potent adjuvant reactions overcoming both persistence of tumor stem cells and immune escape of GBM without provoking an encephalitic reaction.

Experiencia clinica sobre 37 casos de insulinoma / Clinical experience in 37 cases of insulinoma

El insulinoma es el tumor neuroendocrino pancreático más frecuente. Se manifiesta por signos adrenérgicos y de neuroglucopenia. Su diagnóstico se confirma documentando la existencia de hipoglucemia junto a una inapropiada secreción de insulina. Desde 1988 fueron estudiados 23 mujeres (48 ± 18 años) y 14 varones (45 ± 19 años) con diagnóstico de insulinoma. La evolución de la enfermedad hasta el diagnósticofue de 2.8 ± 2.1 años. Veintisiete pacientes (73%) presentaron principalmente síntomas de neuroglucopenia, y el 27% refirió síntomas adrenérgicos. El laboratorio mostró glucemia en ayunas 32.4 ± 8.7 mg/dl, insulina (RIA) 38.2 ± 39.7 μU/ml (n=11), insulina (quimioluminiscencia) 23.8 ± 18.1 μU/ml (n=26), péptido C1.15 ± 1.6 nmol/l (n=14). El test de ayuno prolongado fue diagnóstico a las 9.0 ± 5.2 horas (n=21). La localizaciónpreoperatoria fue posible en el 73% por imágenes, arteriografía con estimulación de calcio y/o ecografía intraoperatoria. Once casos fueron operados por laparoscopia, y el resto por vía convencional. El diagnósticofue confirmado por histología e inmunohistoquímica. Veintidos pacientes (61.1%) presentaron insulinomas únicos(16 en cuerpo y cola, 6 en la cabeza y proceso uncinado), 6 eran portadores de insulinomas múltiples, 5 deinsulinomas malignos, 1 de nesidioblastosis del adulto y en 2 casos los hallazgos fueron incaracterísticos. En 3 pacientes se halló un glucagonoma asociado (1 de ellos con NEM1). Una paciente no fue operada recibiendotratamiento con verapamilo, con buena respuesta clínica. El seguimiento postquirúrgico fue de 60.4 ± 59.9 meses

Insulinoma is the most frequent pancreatic islet cell tumor. Clinical manifestations include adrenergic and neuroglycopenic symptoms. Diagnosis isestablished through demonstration of inappropriately elevated insulin serum concentrations in the presence ofhypoglycemia. The aim of this study is to show our experience in the management of insulinoma. Since 1988,23 women (48 ± 18 years) and 14 men (45 ± 19 years) were studied. Seventy three percent of them sufferedmainly from neuroglucopenic symptoms while 27% referred adrenergic signs. Mean duration of symptoms beforediagnosis was 2.7 ± 2 years. Mean fasting serum glucose was 32.4 ± 8.7 mg/dl, insulin 38.2 ± 39.7 μU/ml(RIA, n= 11) or 23.8 ± 18.1 μU/ml (chemoluminescence, n=26) and C-peptide 1.15 ± 1.60 nmol/l (n=14). Twenty one patients developed clinical and/or biochemical hypoglycaemia within 9.0 ± 5.2 hours of supervised fast. Preoperative localization was performed in 73% by imaging techniques, arterial calcium stimulation and/or intraoperative ultrasonography and palpation by the surgeon. Thirty six patients were operated on by conventional surgery in 25, or laparoscopic approach in 11 cases. In 22 patients, a solitary tumor was excised (61.1%). Six cases presented multiple insulinomas. Five patients had malignant insulinomas. In one case, a pattern of nesidioblastosis was found and 2 patients presented unspecific findings. In 3 patients another tumour(glucagonoma) was found (1 of them with MEN 1). One patient was treated with verapamil with good clinicalresponse. Mean postoperative follow up was 60.4 ± 59.9 months

Estesioneuroblastomas: estudio clínico-patológico, inmunohistoquímico y de ploidía nuclear / Esthesioneuroblastomas: clinico-pathological, immunohistochemical and nuclear ploidy study

Se presentaron 9 casos de estesioneuroblastomas (ENB), 5 varones y 4 mujeres cuyas edades promedio fueron 39 y 55 años respectivamente. Todos presentaban masas polipoides, friables, ubicadas a nivel de nariz y/o senos paranasales. El tratamiento consistió en 8 resecciones quirúrgicas locales, considerándose irresecable uno de los casos. Histológicamente los tumores se hallaban constituidos por células redondas, pequeñas y uniformes dispuestas en planchas y nidos con una matriz fibrilar de fondo, identificándose en un caso pseudorosetas de Homer-Wright. Los estudios inmunohistoquímicos fueron positivos para: enolasa neuronoespecífica (9); proteína S-100 (8); sinaptofisina (7); cromogranina (6); neurofilamentos (6); anticuerpo 013 (4); citoqueratina (1); proteína gliofibrilar ácida (1) y negativos para desmina y CD 45. La determinación del antígeno nuclear de proliferación celular mostró una actividad proliferativa baja en 6 casos (0 a 20 por ciento), y alta en los restantes 3(30 a 50 por ciento). El análisis de ADN reveló 3 tumores diploides y 6 aneuroploides. Un paciente falleció (tumor irresecable y diploide), y los restantes 8 se hallan vivos con seguimientos de 6 meses a 22 años. Se demostró la utilidad de un panel de anticuerpos en el diagnóstico de ENB y el posible valor pronóstico adverso de los histogramas diploides

Tumores papilares y quísticos del páncreas: estudio clínicopatológico, citopatológico, inmunohistoquímico y de ploidía nuclear / Papillary cystic tumors of the pancreas: clinico-pathological, cytopathological, immunohistochemical, and nuclear ploidy study

Se presentam 7 casos de tumores papilares y quísticos del páncreas (TPQ): 5 se presentaron en mujeres y 2 em hombres con edades entre 21 y 68 años (media 39). Clínicamente todos tenían una massa abdominal palpable, 3 tumores estaban localizados en la cabeza, 2 en el cuerpo, 1 en el istmo y el restante en la cola del órgano; 5 casos fueron tratados con resecciones quirúrgicas radicales y 2 sólo biopsias. En 4 casos se realizó punción aspiración preoperatoria, realizándose el diagnóstico en 3 de ellos. inmunohistoquímicamente tenían marcadores endocrinos y exocrinos apoyando estos datos la hipótesis de la diferenciación dual de estos tumores. La ploidía nuclear demostró 4 tumores diploides, 2 diploides-tetraploides y 1 aneuploide. Los TPQ son neoplasia de bajo grado factibles de ser diagnosticados por punción aspiración, con un fenotipo mixto (endocrino-exocrino) y con una predominancia de tumores diploides

Quistes de paratiroides / Prathyroid cysts

Antecedentes: Los quistes de paratiroides son reconocidos pero constituyen una entidad clínica infrecuente. Objetivo: Conocer su existencia para efectuar el diagnóstico preoperatorio y tener en cuenta otras alternativas terapéuticas. Lugar de aplicación: Servicio de Cirugía de Hospital Asociado a la Facultad de Medicina de la UBA. Diseño: Análisis retrospectivo. Población: 5 pacientes con quistes de paratiroides.Método: Análisis de historias clínicas. Resultados: Todos los pacientes pertenecían al sexo femenino. Dos de ellos se diagnosticaron durante operaciones en la glándula tiroides y los tres restantes por punción de un tumor de cuello e investigación de PTH en el líquido obtenido. Conclusiones: Los tumores de cuello y en especial los vecinos a la glándula tiroides deben ser punzados para su diagnóstico. La obtención de un líquido fluido y claro obliga a pensar en esta patología y a medir la concentración de PTH en el mismo

Adelantos en el manejo clínico-quirúrgico del feocromocitoma / Advances in clinical-surgical management of pheochromocytoma

Fue revisado el manejo y evolución de 25 pacientes operados por feocromocitoma entre 1977 y 1994. Tres de ellos fueron tratados inicialmente en otros centros y se presentaron con metástasis regionales y/o a distancia. Los restantes 22 recibieron tratamiento primario en nuestra institución. La edad promedio fue de 35 años, y quince (60 por ciento) fueron mujeres. La hipertensión asociada con ataques paroxísticos estuvo presente en 17 casos (68 por ciento), e hipertensión sostenida en 8 (32 por ciento). En todos los enfermos menos uno se encontraron niveles altos de ácido vainillilmandélico y de catecolaminas en orina de 24 horas. Todos los tumores pudieron ser localizados correctamente en el preoperatorio. Los métodos más comunmente usados fueron la tomografía computada, el centellograma con MIBG I 131 y la ecografía. Se consiguió un adecuado bloqueo alfa adrenérgico preoperatorio con dibencilina o con prazosin. Los feocromocitomas fueron resecados a través de una vía anterior transperitoneal en 20 casos ((80 por ciento) y de una vía posterolateral extraperitoneal en 5 (4 por ciento). El índice de malignidad de la serie fue del 23 por ciento. Todos los tumores malignos habían sido diagnosticados inicialmente como benignos. La bilateralidad ocurrió en el 16 por ciento, y existió asociación con carcinoma medular de tiroides en 13 por ciento. Los criterios morfológicos usados para predecir el comportamiento de estos tumores fueron de poca utilidad. Se confirmó la sensibilidad de los marcadores neuroendocrinos y la falta de valor pronóstico de la proteína S-100 y de la mutación de la proteína p53. Valores de proliferación superiores al 10 por ciento con PCNA serían un indicador útil de pronóstico adverso. El análisis de ADN reveló valores aneuploides en el 85 por ciento de los casos. Los tumores diploides o near-diploides mostraron un comportamiento clínico benigno