Plasma ctDNA Monitoring of a PTCH1-Mutant Metastatic Adult Medulloblastoma Showing a Durable Benefit With Vismodegib.

Adult medulloblastoma (MB) is a rare disease affecting 0.6 persons per million adults over 19 years of age. The SHH-activated/TP53-wild type is the most common subtype, accounting for 60% of adult MBs, being characterized by mutations in PTCH1, SMO, or the TERT promoter. Several small studies demonstrate objective but short-lived responses to SMO inhibitors such as vismodegib or sonidegib. Like other oncogene-addicted solid tumors, detection of the corresponding drivers through liquid biopsy could aid in the molecular diagnosis and monitoring of the disease through less invasive procedures. However, most studies have only evaluated cerebrospinal fluid as the ctDNA reservoir, and very limited evidence exists on the role of liquid biopsy in plasma in patients with primary central nervous system tumors, including MB. We present the case of a 26-year-old patient with a recurrent MB, in which next-generation sequencing (FoundationOne CDx) revealed a mutation in PTCH1, allowing the patient to be treated with vismodegib in second line, resulting in a durable benefit lasting for 1 year. Using an in-house digital PCR probe, the PTCH1 mutation could be tracked in ctDNA during treatment with first-line chemotherapy and while on treatment with vismodegib, demonstrating a precise correlation with the radiological and clinical behavior of the disease.

Histopathologic Changes in Congenital Corneal Stromal Dystrophy: Report of 4 Cases in 2 Families.

Corneal dystrophies are hereditary diseases affecting the corneal tissue; they are bilateral, symmetrical and unrelated to environmental or systemic conditions. Congenital corneal stromal dystrophy is a very rare autosomal dominant dystrophy that is caused by a mutation in the DCN gene that encodes decorin (a proteoglycan of the extracellular matrix). We herein report 4 cases of congenital stromal corneal dystrophy in 2 families, highlighting the previously undescribed histopathologic features, the possible differential diagnosis of this entity and the key role played by decorin staining in its diagnosis.

Durable benefit and change in TCR clonality with nivolumab in a Lynch syndrome-associated glioma.

Germline replication-repair deficient (gRRD) gliomas are exceptional events, and only a few of them have been treated with immune checkpoint inhibitors (ICIs). Contrary to sporadic gliomas, where ICIs have failed to show any objective benefit, the very few patients with gRRD gliomas treated with ICIs to date seem to benefit from programmed-death-1 (PD-1) inhibitors, such as nivolumab or pembrolizumab, either in terms of durable responses or in terms of survival. T-cell immunohistochemistry (IHC) and T-cell receptor (TCR) repertoire using high-throughput next-generation sequencing (NGS) with the Oncomine TCR-Beta-SR assay (Thermo Fisher Scientific) were analyzed in pre- and post-nivolumab tumor biopsies obtained from a patient with a Lynch syndrome-associated glioma due to a germline pathogenic hMLH1 mutation. The aim was to describe changes in the T-cell quantity and clonality after treatment with nivolumab to better understand the role of acquired immunity in gRRD gliomas. The patient showed a slow disease progression and overall survival of 10 months since the start of anti-PD-1 therapy with excellent tolerance. A very scant T-cell infiltrate was observed both at initial diagnosis and after four cycles of nivolumab. The drastic change observed in TCR clonality in the post-nivolumab biopsy may be explained by the highly spatial and temporal heterogeneity of glioblastomas. Despite the durable benefit from nivolumab, the scant T-cell infiltrate possibly explains the lack of objective response to anti-PD-1 therapy. The major change in TCR clonality observed after nivolumab possibly reflects the evolving molecular heterogeneity in a highly pre-treated disease. An in-deep review of the available literature regarding the role of ICIs in both sporadic and gRRD gliomas was conducted.

Detection of IDH1 Mutations in Plasma Using BEAMing Technology in Patients with Gliomas.

Molecular testing using blood-based liquid biopsy approaches has not been widely investigated in patients with glioma. A prospective single-center study enrolled patients with gliomas ranging from grade II to IV. Peripheral blood (PB) was drawn at different timepoints for circulating tumour DNA (ctDNA) monitoring. Next-generation sequencing (NGS) was used for the study of isocitrate dehydrogenase 1 (IDH1) mutations in the primary tumor. Beads, Emulsion, Amplification and Magnetics (BEAMing) was used for the study of IDH1 mutations in plasma and correlated with the NGS results in the tumor. Between February 2017 and July 2018, ten patients were enrolled, six with IDH1-mutant and four with IDH1 wild-type gliomas. Among the six IDH-mutant gliomas, three had the same IDH1 mutation detected in plasma (50%), and the IDH1-positive ctDNA result was obtained in patients either at diagnosis (no treatment) or during progressive disease. While the false-negative rate reached 86% (18/21), 15 out of the 18 (83%) plasma-negative results were from PB collected from the six IDH-mutant patients at times at which there was no accompanying evidence of tumor progression, as assessed by MRI. There were no false-positive cases in plasma collected from patients with IDH1 wild-type tumors. BEAMing detected IDH1 mutations in the plasma of patients with gliomas, with a modest clinical sensitivity (true positivity rate) but with 100% clinical specificity, with complete agreement between the mutant loci detected in tumor and plasma. Larger prospective studies should be conducted to expand on these findings, and further explore the clearance of mutations in PB from IDH1-positive patients in response to therapy.

Invaginación colocólica por anisakiasis, una causa infrecuente de obstrucción intestinal / Colonic intussusception caused by anisakiasis. A rare cause of obstruction

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[Symptomatic exaggerated placental site after first trimester abortion]. / Lecho placentario amplio sintomático tras aborto del primer trimestre.

Exaggerated placental site, a trophoblastic benign lesion, is characterized by an extensive infiltration of the endometrium, myometrium and arterial walls by intermediate trophoblast cells. Trophoblastic benign lesions are often an incidental finding in the anatomopathological study, but may be associated with severe bleeding especially in relation to trauma. Case report: Multigravida 39 years old with excessive uterine bleeding after medical treatment of abortion. Once expelled gestational vesicle is seen sonographically a uterine cavity occupied by a heterogeneous endometrium with maximum anteroposterior diameter of 21 mm, plenty of color map, reaching myometrium. B-HCG serum is 164 mlU/ml. During hysteroscopy a massive bleeding happens and its necesary to use an intrauterine catheter to stop it. Computed tomography angiography shows suggestive findings of uterine vascular malformation. A hysterectomy as a diagnostic and definitive treatment is made and pathology reports an exaggerated placental site.

Adenocarcinoma intestinal secundario de vejiga que simula clínicamente neoplasia primaria. Dos patrones clinicopatológicos diferenciados / Secondary adenocarcinoma of the bladder. Two differentiated clinicopathological patterns

Los adenocarcinomas secundarios de vejiga urinaria son tumores infrecuentes, y representan menos del 2% de todas las neoplasias malignas de vejiga. El origen colorrectal es el más habitual. La infiltración vesical secundaria puede suceder por extensión directa o por metástasis a distancia. Desde el punto de vista clínico, suelen manifestarse como los tumores vesicales primarios, y en el estudio histológico inicial plantean un desafío morfológico con los adenocarcinomas primitivos de vejiga urinaria. El presente estudio analiza las características clinicopatológicas de estas 2 formas de afectación vesical secundaria, y propone el uso de un panel inmunohistoquímico básico para el diagnóstico diferencial de estos adenocarcinomas. El diagnóstico específico de adenocarcinoma primario frente a infiltración vesical secundaria (invasión directa o metastásica) tiene relevantes connotaciones pronósticas y es decisivo en la toma de decisiones terapéuticas (AU)

Secondary adenocarcinoma of the urinary bladder is rare, representing less than 2% of all malignant bladder neoplasms. The most common origin of the primary tumour is colorectal. The bladder may be affected either by direct invasion or metastases. Secondary tumours present in the same way as primary bladder neoplasms and the initial histopathological diagnosis can prove challenging. The present study analyzes the clinicopathological features of both types of secondary bladder involvement and proposes the use of a basic immunohistochemical panel for their differential diagnosis. A correct differential diagnosis between primary adenocarcinoma of the bladder and secondary infiltration by either direct invasion or metastasis is important for both prognosis and therapy (AU)

Linfadenitis cervical aislada por leishmaniasis con patrón «Piringer-Kuchinka-like» en un paciente inmunocompetente / Isolated cervical "Piringer-Kuchinka-like" lymphadenitis due to leishmaniasis in an immunocompetent patient

La linfadenitis cervical aislada por leishmaniasis es una forma de presentación peculiar que clínicamente simula una enfermedad maligna, fundamentalmente linfoma. Los criterios citológicos de la linfadenitis por leishmanias son característicos, y los cuerpos de Leishman-Donovan son la clave diagnóstica de esta entidad, con rasgos citológicos e histológicos similares a los descritos como linfadenitis de Piringer- Kuchinka. Presentamos este caso por tratarse de una presentación clinicopatológica inusual en una paciente inmunocompetente(AU)

Isolated cervical lymphadenitis due to leishmaniasis is rare and clinically may resemble malignant disease. The characteristic cytology with the presence of Leishman-Donovan bodies provides the most important diagnostic clue. Microscopically, it has similar features to toxoplasmosis (Piringer-Kuchinka) lymphadenitis. We present a case of leishmaniasis in an immunocompetent patient with an unusual clinicopathological presentation(AU)