RESUMEN
Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm most often arising from the pleura and rarely in extra-pleural locations, including the gastrointestinal tract. We describe two cases of a SFT presenting as submucosal colonic lesion and review the literature on this lesion. One submucosal lesion was localized in the cecum and was 10 mm in size. The second lesion presented as a 17 mm submucosal rectal lesion. Both lesions presented as well-circumscribed submucosal lesions arranged in short fascicles, blending with abundant collagenous stroma. In both cases, the spindle cells were positive for CD34, STAT6 and CD99, and molecular studies showed NAB2:STAT6 fusion supporting the diagnosis of SFT. Both patients are alive and well 10 and 5 years post-excision, respectively. In conclusion, SFT can occur in the colon as a submucosal lesion and should be included in the differential diagnosis of colonic mesenchymal lesions.
Asunto(s)
Neoplasias del Colon , Tumores Fibrosos Solitarios , Humanos , Tumores Fibrosos Solitarios/patología , Tumores Fibrosos Solitarios/cirugía , Tumores Fibrosos Solitarios/diagnóstico , Tumores Fibrosos Solitarios/diagnóstico por imagen , Masculino , Neoplasias del Colon/patología , Neoplasias del Colon/cirugía , Neoplasias del Colon/diagnóstico , Persona de Mediana Edad , Femenino , Factor de Transcripción STAT6/análisis , Factor de Transcripción STAT6/metabolismo , Anciano , Antígenos CD34/análisis , Antígenos CD34/metabolismo , Colonoscopía , Mucosa Intestinal/patología , Mucosa Intestinal/diagnóstico por imagen , Diagnóstico Diferencial , Proteínas RepresorasRESUMEN
Gastroblastoma is a rare gastric biphasic tumor composed of mesenchymal and epithelial elements in variable proportions. These tumors usually arise in the gastric antrum of children and young adults and are reported to harbor a recurrent MALAT1::GLI1 fusion. Herein we report a case of gastroblastoma in a 19-year-old male who presented with intermittent epigastric abdominal discomfort. Antrectomy revealed a 5.6-cm multi-lobulated, tan-pink mass with solid and focally cystic areas involving the submucosa, muscularis propria, and subserosa. All tumor cells demonstrated immunoreactivity for GLI-1, CD56, and vimentin; epithelial elements expressed pancytokeratins (AE1/AE3 and Oscar), and mesenchymal cells demonstrated focal positivity for CD10. Next generation sequencing revealed a novel ACTB::GLI1 fusion without evidence of the recurrent MALAT1::GLI1 fusion. Nine months after surgery, the patient is well without evidence of recurrence or metastases. To our knowledge, this is the first case of gastroblastoma harboring this novel ACTB::GLI1 fusion.
Asunto(s)
Actinas , Proteínas de Fusión Oncogénica , Neoplasias Gástricas , Proteína con Dedos de Zinc GLI1 , Humanos , Masculino , Adulto Joven , Biomarcadores de Tumor/genética , Fusión Génica/genética , Proteínas de Fusión Oncogénica/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Resultado del Tratamiento , Proteína con Dedos de Zinc GLI1/genética , Actinas/genéticaAsunto(s)
Leucemia Linfocítica Granular Grande , Neutropenia , Linfocitos T CD4-Positivos/metabolismo , Citometría de Flujo , Humanos , Leucemia Linfocítica Granular Grande/diagnóstico , Leucemia Linfocítica Granular Grande/genética , Mutación/genética , Neutropenia/diagnóstico , Neutropenia/genética , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismoRESUMEN
Anti-epidermal growth factor receptor (EGFR) antibodies and anti-programmed cell death 1 protein (PD-1) antibodies have been used separately to treat metastatic cutaneous squamous cell carcinoma (cSCC). While two anti-EGFR antibodies have similar clinical activity, cetuximab is administered weekly, whereas panitumumab is administered every two weeks. This report details findings using panitumumab in combination with anti-PD-1 antibody in patients with relapsed refractory cSCC. Three consecutive patients with poor performance status and rapidly progressive recurrent cutaneous squamous cell carcinoma (cSCC) of the face or scalp signed informed consent to receive an anti-PD-1 antibody with the option to add panitumumab were there inadequate response. After 2, 5, and 7 cycles of anti-PD-1 antibody treatment, respectively, panitumumab was added and the combination was continued for 27, 7, and 5 cycles, respectively. Fatigue, rash, and hypomagnesemia were reported, consistent with expectations for either agent alone. All three patients achieved durable complete response. The favorable clinical outcomes support further evaluation of the combination of anti-PD1 and anti-EGFR antibodies to control refractory cSCC of the face or scalp. J Drugs Dermatol. 2021;20(8):901-904. doi:10.36849/JDD.6175.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Panitumumab/uso terapéutico , Neoplasias Cutáneas , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Humanos , Recurrencia Local de Neoplasia , Neoplasias Cutáneas/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológicoRESUMEN
A case of a well-demarcated plaque measuring 11 cm without satellites of several years' duration is presented. It showed typical histologic findings of dermatofibroma, prompting a diagnosis of plaque-like dermatofibroma. The relationship to multiple clustered dermatofibromas and plaque-like myofibroblastic tumor is discussed.
RESUMEN
BACKGROUND: CD49f (integrin α6) is a useful marker for minimal residual disease (MRD) detection in B lymphoblastic leukemia and has recently been suggested to mediate infiltration of the central nervous system by leukemic B lymphoblasts. However, data regarding expression of CD49f protein in B lymphoblastic leukemia are limited, and whether CD49f protein expression varies among genetic subgroups of B lymphoblastic leukemia is unknown. METHODS: CD49f protein expression was characterized by flow cytometry in a series of 40 cases of B lymphoblastic leukemia, which included the genetic subgroups: KMT2A-rerranged, BCR-ABL1+, ETV6-RUNX1+, hypodiploidy, and hyperdiploidy. RESULTS: Expression of CD49f differed significantly among the five genetic subgroups studied, whether assessed by percentage of blasts positive for the antigen (p = .0001, Kruskal-Wallis) or median fluorescence intensity (MFI) (p = .0001, Kruskal-Wallis). Moreover, the percentage of CD49f+ blasts and MFI of CD49f were significantly lower in KMT2A-rearranged cases than in cases without KMT2A rearrangement (p = .0002 for both, Mann-Whitney). CONCLUSIONS: CD49f protein expression varies among genetic subgroups of B lymphoblastic leukemia, and is distinctly low in KMT2A-rearranged cases.
Asunto(s)
N-Metiltransferasa de Histona-Lisina/genética , Integrina alfa6/genética , Proteína de la Leucemia Mieloide-Linfoide/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , HumanosRESUMEN
Burkitt-like lymphoma with 11q aberration is a recently recognized diagnostic entity in the Revised 4th Edition of the World Health Organization (WHO) classification of lymphoid neoplasms. This diagnosis should be considered and cytogenetic array performed in patients with high-grade B-cell non-Hodgkin lymphomas without MYC rearrangement.
RESUMEN
Post-transplant lymphoproliferative disorder (PTLD) is an uncommon, but well-described complication after liver transplantation. Most recently, Hepatitis C virus (HCV) has been implicated in the development of PTLD. A HCV-negative 62-year-old man with autoimmune hepatitis received a HCV nucleic acid amplification test-positive liver graft from a 73-year-old brain-dead donor (D+/R-). After his recovery from the operation, the patient was treated for HCV and achieved an undetectable viral load. He was readmitted 6 months after transplant with a spontaneous perisplenic hematoma, weight loss, failure to thrive, low-grade fevers, and abnormal liver function tests. He had a rapid clinical deterioration and expired shortly after admission. His liver biopsy demonstrated EBV-negative monomorphic B-cell PTLD. Our case is the first to report an aggressive early-onset EBV-negative monomorphic B-cell PTLD in a HCV D+/R- liver transplant. This case illustrates the paucity of knowledge on HCV seroconversion and its involvement in EBV-negative monomorphic B-cell PTLD development.
Asunto(s)
Linfocitos B/patología , Hepatitis C/transmisión , Trasplante de Hígado/efectos adversos , Trastornos Linfoproliferativos/diagnóstico , Seroconversión , Trasplantes/virología , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Humanos , Trastornos Linfoproliferativos/virología , Masculino , Persona de Mediana Edad , Donantes de Tejidos , Carga ViralRESUMEN
Eosinophilic solid and cystic renal cell carcinoma (ESCRCC) is a recently described distinct renal neoplasm known to occur almost exclusively in female patients with or without tuberous sclerosis complex (TSC). We report a case of ESCRCC with 2 synchronous angiomyolipomas, including 1 angiomyolipoma with epithelial cysts (AMLEC), a rare cystic variant of AML that typically arises sporadically in the absence of TSC, in a 46-year-old woman with TSC. Besides additional copy number alterations identified in ESCRCC via molecular karyotyping, we also report a unique histologic feature of TSC-associated ESCRCC previously not described in detail, with formation of semicircular multinucleated neoplastic giant cells engulfing an additional intact neoplastic cell, simulating emperipolesis. To the best of our knowledge, this is the first reported case of ESCRCC with concurrent AMLEC in a patient with TSC, confirmed through additional genetic testing showing a germline heterozygous mutation in TSC1. Awareness of ESCRCC helps avoid the pitfall of a diagnosis of unclassified renal cell carcinoma, a typically much more aggressive tumor.
Asunto(s)
Angiomiolipoma/diagnóstico , Carcinoma de Células Renales/diagnóstico , Neoplasias Renales/diagnóstico , Riñón/patología , Neoplasias Primarias Múltiples/diagnóstico , Esclerosis Tuberosa/complicaciones , Angiomiolipoma/genética , Angiomiolipoma/cirugía , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/cirugía , Variaciones en el Número de Copia de ADN , Diagnóstico Diferencial , Femenino , Pruebas Genéticas , Mutación de Línea Germinal , Células Gigantes/patología , Heterocigoto , Humanos , Cariotipificación , Riñón/citología , Riñón/cirugía , Neoplasias Renales/genética , Neoplasias Renales/cirugía , Persona de Mediana Edad , Neoplasias Primarias Múltiples/genética , Neoplasias Primarias Múltiples/cirugía , Nefrectomía , Resultado del Tratamiento , Esclerosis Tuberosa/diagnóstico , Esclerosis Tuberosa/genética , Proteína 1 del Complejo de la Esclerosis Tuberosa/genéticaRESUMEN
BACKGROUND: Results of molecular studies are redefining the diagnosis and management of a wide range of skin disorders. Dermatology training programs maintain a relative gap in relevant teaching. OBJECTIVE: To develop a curriculum in molecular diagnostics, genomics and personalized medicine for dermatology trainees at our institution. The aim is to provide trainees with a specialty-appropriate, working knowledge in clinical molecular dermatology. METHODS: The Departments of Dermatology and Pathology and Laboratory Medicine collaborated on the design and implementation of educational objectives and teaching modalities for the new curriculum. RESULTS: A multidisciplinary curriculum was developed. It comprises: (i) assigned reading from the medical literature and reference textbook; (ii) review of teaching sets; (iii) two 1 hour lectures; (iv) trainee presentations; (v) 1-week rotation in a clinical molecular pathology and cytogenetics laboratory; and (vi) assessments and feedback. Residents who participated in the curriculum to date have found the experience to be of value. CONCLUSIONS: Our curriculum provides a framework for other dermatology residency programs to develop their own specific approach to molecular diagnostics education. Such training will provide a foundation for lifelong learning as molecular testing evolves and becomes integral to the practice of dermatology.
Asunto(s)
Curriculum , Dermatología/educación , Genómica/educación , Patología Molecular/educación , Medicina de Precisión , HumanosRESUMEN
A preterm infant presenting with a congenital cardiac malformation and thrombocytopenia was found to have a karyotype showing a terminal deletion of the long arm of chromosome 11 of the segment 11q24.1-11qter consistent with Jacobsen syndrome. The infant was later diagnosed with Paris-Trousseau syndrome, commonly associated with Jacobsen syndrome. Because children with cardiac malformations often require high-risk surgical procedures in the early neonatal period, those with platelet dysfunction require prompt identification at birth.
Asunto(s)
Síndrome de Deleción Distal 11q de Jacobsen/complicaciones , Anomalías Múltiples , Femenino , Humanos , Recién Nacido , CariotipoAsunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Trisomía/genética , Biomarcadores de Tumor/genética , Cromosomas Humanos Par 8/genética , Femenino , Humanos , Persona de Mediana Edad , Síndromes Mielodisplásicos/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , PronósticoRESUMEN
The X-linked form of Opitz syndrome (OS) affects midline structures and produces a characteristic, but heterogeneous, phenotype that may include severe mental retardation, hypertelorism, broad nasal bridge, widow's peak, cleft lip/cleft palate, congenital heart disease, laryngotracheal defects, and hypospadias. The MID1 gene was implicated in OS by linkage to Xp22. It encodes a 667 amino acid protein that contains a RING finger motif, two B-box zinc fingers, a coiled-coil, a fibronectin type III (FNIII) domain, and a B30.2 domain. Several mutations in MID1 are associated with severe OS. Here, we describe an intelligent male with a milder phenotype characterized by hypertelorism, broad nasal bridge, widow's peak, mild hypospadias, pectus excavatum, and a surgically corrected tracheo-esophageal fistula. He has an above average intelligence and no cleft lip/palate or heart disease. We identified a novel mutation in MID1 (P441L) which is in exon 8 and functionally associated with the FNIII domain. While OS phenotypes have been attributed to mutations in the C-terminal part of MID1, little is currently known about the structure-function relationships of MID1 mutations, and how they affect phenotype. We find from a literature review that missense mutations within the FNIII domain of MID1 are associated with a milder presentation of OS than missense mutations elsewhere in MID1. All truncating mutations (frameshift, insertions/deletions) lead to severe OS. We used homology analysis of the MID1 FNIII domain to investigate structure-function changes caused by our missense mutation. This and other missense mutations probably cause disruption of protein-protein interactions, either within MID1 or between MID1 and other proteins. We correlate these protein structure-function findings to the absence of CNS or palatal changes and conclude that the FNIII domain of the MID1 protein may be involved in midline differentiation after neural tube and palatal structures are completed.
Asunto(s)
Proteínas de Microtúbulos/química , Proteínas de Microtúbulos/metabolismo , Mutación/genética , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Síndrome de Smith-Lemli-Opitz/genética , Síndrome de Smith-Lemli-Opitz/patología , Factores de Transcripción/química , Factores de Transcripción/metabolismo , Adulto , Secuencia de Aminoácidos , Sistema Nervioso Central/fisiopatología , Fibronectinas/química , Humanos , Masculino , Proteínas de Microtúbulos/genética , Modelos Moleculares , Datos de Secuencia Molecular , Proteínas Nucleares/genética , Fenotipo , Estructura Terciaria de Proteína , Síndrome de Smith-Lemli-Opitz/fisiopatología , Relación Estructura-Actividad , Factores de Transcripción/genética , Ubiquitina-Proteína LigasasRESUMEN
DAXX, a modulator of apoptosis and a repressor of basal transcription, was identified in a two-hybrid screen as a protein capable of interacting with a trimeric form of human heat shock factor 1 (HSF1). In human cells, DAXX interacted with HSF1 essentially only during stress, i.e., when factor trimerization occurred. Several lines of experimentation suggested that DAXX is an important mediator of HSF1 activation: (i) overexpression of DAXX enhanced basal transactivation competence of HSF1 in the absence of a stress; (ii) a DAXX fragment exerted dominant-negative effects on HSF1 activation by different types of stress; (iii) induction of heat shock or stress protein (HSP)70 by heat stress was defective in a cell line lacking functional DAXX; and (iv) RNA interference depletion of DAXX also substantially reduced heat induction of HSF1 activity and HSP70 expression. HSF1 transactivation competence is repressed by an HSP90-containing multichaperone complex that interacts with trimeric factor. Overexpressed HSF1, known to be largely trimeric, only marginally increased HSF1 activity on its own but potentiated the activating effect of DAXX overexpression. Expression of a nonnative protein capable of competing for multichaperone complex also synergistically enhanced activation of HSF1 by DAXX. These observations suggest a model in which DAXX released from its nuclear stores during stress opposes repression of HSF1 transactivation competence by multichaperone complex through its interaction with trimerized HSF1. Our identification of DAXX as a mediator of HSF1 activation raises the question whether DAXX produces some of its pleiotropic effects through modulation of HSP levels.