ABSTRACT
Congenital infiltrating lipomatosis of the face (CILF) is a rare, congenital, nonhereditary facial overgrowth due to post-zygomatic activating mutations in PIK3CA gene. It is unilateral and involves hypertrophy of both the soft and hard tissue structures on the affected side of the face. This commonly results in early eruption of the teeth, hypertrophy of the facial bones, macroglossia, and proliferation of the parotid gland. Less than 80 cases of CILF have been reported in the literature so far. Treatment modalities include liposuction and surgical excision. However, since the hallmark of CILF is mutation in the PIK3CA gene, PI3K inhibitors may play a therapeutic role in CILF. We report a case of an 8-year-old boy with recurrent CILF of the scalp and nose, with PIK3CA H1047R mutation. We discuss the differential diagnoses, clinical outcomes, and management of this rare entity.
ABSTRACT
Cutaneous non-Langerhans cell histiocytosis (NLCH) is a rare and biologically benign entity that can be broadly classified into two categories: xanthogranuloma and non-xanthogranuloma. The xanthogranuloma family is characterized by a proliferation of histiocytes with both macrophage and dendritic cell differentiation, negative BRAF mutation, and rare Touton-type giant cells. Molecular studies have reported that mutations involved in the MAPK signaling pathways are implicated in the pathophysiology of histiocytoses. While LCH is associated with the somatic mutation of BRAF v600e, however, mutations and gene fusions in NLCH cases are undefined. We hereby present a 19-month-old female with recalcitrant nodular rashes diagnosed as NLCH with associated novel genetic mutation involving ANKRD26 and PDGFRB genes, as well as PDGFRB::CD74 fusion mRNA. Immunohistochemical staining showed strong and diffuse CD68 and CD163 positivity, and negative CD1a, CD207, ALK D5F3, S100 protein, and BRAF V600E (VE1). Albeit unknown significance, this case of an ANKRD26 and PDGFRB gene mutation in cutaneous NLCH has not been reported prior in the literature. Our case highlights the advantage of pathology and genetic studies in cutaneous NLCH to increase the understanding of this heterogeneous enigmatic disorder and identify further options in management.
Subject(s)
Histiocytosis, Non-Langerhans-Cell , Receptor, Platelet-Derived Growth Factor beta , Child , Female , Humans , Infant , Histiocytosis, Non-Langerhans-Cell/genetics , Histiocytosis, Non-Langerhans-Cell/pathology , Intercellular Signaling Peptides and Proteins/genetics , Mutation , Proto-Oncogene Proteins B-raf/genetics , Receptor, Platelet-Derived Growth Factor beta/genetics , Soft Tissue Neoplasms , XanthomatosisABSTRACT
Here, we report a case of a 3-year-old female who presented to clinic with an enlarging mass in the posterior cervical midline. The mass was present since birth and demonstrated no cutaneous stigmata. Plain film, CT, and MRI of the cervical spine (C3-C5) revealed enlargement of the spinal canal, soft tissue calcification, spinal dysraphism, and an intramedullary, predominantly fatty, mass. The mass had associated calcifications and a highly proteinaceous cyst. Surgical resection of the spinal lesion was subsequently performed. Histopathological evaluation revealed a mature teratoma. Cervical spinal teratomas in the pediatric population are rare entities with few cases currently reported in the literature. We conducted a systematic review to outline the current evidence detailing cases of intramedullary spinal cord teratomas. Six articles were included for final review. All patients in the included articles underwent maximal surgical resection with one patient also receiving chemotherapy and radiation. With our report, we aim to add to the literature on cervical intramedullary spinal cord teratomas in the pediatric population.
Subject(s)
Spinal Cord Neoplasms , Spinal Dysraphism , Teratoma , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/pathology , Cervical Vertebrae/surgery , Child , Child, Preschool , Female , Humans , Neck/pathology , Spinal Cord Neoplasms/diagnostic imaging , Spinal Cord Neoplasms/pathology , Spinal Cord Neoplasms/surgery , Teratoma/diagnostic imaging , Teratoma/pathology , Teratoma/surgeryABSTRACT
Brain tumors are the most common solid tumors of childhood, and the genetic drivers and optimal therapeutic strategies for many of the different subtypes remain unknown. Here, we identify that bithalamic gliomas harbor frequent mutations in the EGFR oncogene, only rare histone H3 mutation (in contrast to their unilateral counterparts), and a distinct genome-wide DNA methylation profile compared to all other glioma subtypes studied to date. These EGFR mutations are either small in-frame insertions within exon 20 (intracellular tyrosine kinase domain) or missense mutations within exon 7 (extracellular ligand-binding domain) that occur in the absence of accompanying gene amplification. We find these EGFR mutations are oncogenic in primary astrocyte models and confer sensitivity to specific tyrosine kinase inhibitors dependent on location within the kinase domain or extracellular domain. We initiated treatment with targeted kinase inhibitors in four children whose tumors harbor EGFR mutations with encouraging results. This study identifies a promising genomically-tailored therapeutic strategy for bithalamic gliomas, a lethal and genetically distinct brain tumor of childhood.
Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Glioma/genetics , Mutation/genetics , Adolescent , Antineoplastic Agents/therapeutic use , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Child , Child, Preschool , Epigenesis, Genetic/genetics , ErbB Receptors/genetics , Female , Glioma/drug therapy , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Protein Kinase Inhibitors/pharmacologyABSTRACT
Epileptogenic tumors affecting children and young adults are a morphologically diverse collection of neuroepithelial neoplasms that, as a group, exhibit varying levels of glial and/or neuronal differentiation. Recent advances in molecular profiling technology, including comprehensive DNA sequencing and methylation analysis, have enabled the application of more precise and biologically relevant classification schemes to these tumors. In this report, we describe a morphologically and molecularly distinct epileptogenic neoplasm, the polymorphous low-grade neuroepithelial tumor of the young (PLNTY), which likely accounts for a sizable portion of oligodendroglioma-like tumors affecting the pediatric population. Characteristic microscopic findings most notably include infiltrative growth, the invariable presence of oligodendroglioma-like cellular components, and intense immunolabeling for cluster of differentiation 34 (CD34). Moreover, integrative molecular profiling reveals a distinct DNA methylation signature for PLNTYs, along with frequent genetic abnormalities involving either B-Raf proto-oncogene (BRAF) or fibroblast growth factor receptors 2 and 3 (FGFR2, FGFR3). These findings suggest that PLNTY represents a distinct biological entity within the larger spectrum of pediatric, low-grade neuroepithelial tumors.
Subject(s)
Antigens, CD34/metabolism , Brain Neoplasms/complications , Brain Neoplasms/genetics , Epilepsy/etiology , Gene Expression Regulation, Neoplastic/genetics , Mutation , Neoplasms, Neuroepithelial/complications , Signal Transduction/physiology , Adolescent , Adult , Antigens, CD34/genetics , Brain Neoplasms/diagnostic imaging , Child , Child, Preschool , Epilepsy/genetics , Female , Glial Fibrillary Acidic Protein/metabolism , Humans , Male , Mitogen-Activated Protein Kinases/genetics , Mitogen-Activated Protein Kinases/metabolism , Neoplasms, Neuroepithelial/diagnostic imaging , Neoplasms, Neuroepithelial/genetics , Neuroglia/pathology , Oligodendroglioma/genetics , Proto-Oncogene Mas , Proto-Oncogene Proteins B-raf/genetics , Receptors, Fibroblast Growth Factor/genetics , Young AdultSubject(s)
Epigenesis, Genetic/genetics , Neoplasms, Neuroepithelial/pathology , Receptor, Fibroblast Growth Factor, Type 2/genetics , Adolescent , Adult , Brain Neoplasms/genetics , Child, Preschool , DNA Methylation , Epilepsy/etiology , Epilepsy/genetics , Female , Humans , Male , Oncogene Proteins, Fusion , Young AdultABSTRACT
Extraintestinal manifestations frequently affect patients with inflammatory bowel disease. They can involve virtually any organ, with the musculoskeletal and integumentary systems being the most common. Leukocytoclastic vasculitis is a rare extraintestinal manifestation of inflammatory bowel disease, especially at disease onset. It has been reported to occur in association with Crohn's disease and trimethoprim/sulfamethoxazole (TMP-SMX) exposure independently. We report a case of a 14-year-old female who developed leukocytoclastic vasculitis after exposure to TMP-SMX and was ultimately diagnosed with Crohn's disease. The patient presented with purpura, oral ulcers, abdominal pain, and intermittent bloody stools. Colonoscopy showed colonic inflammation, and biopsies revealed severe chronic active colitis with crypt abscesses. A skin biopsy confirmed the diagnosis of leukocytoclastic vasculitis. Management consisted of high-dose steroids and infliximab, with resolutions of her symptoms. This case emphasizes that extraintestinal manifestations are multifactorial in nature, with the example of an existing genetic predisposition through Crohn's disease and a triggering factor such as TMP-SMX.
ABSTRACT
The Journal retracts the article, Histopathologic Findings Associated with Miller-Dieker Syndrome: An Autopsy Report [...].
ABSTRACT
PURPOSE: Desmoplastic infantile gangliogliomas (DIGs) are rare tumors of infancy. Herein, we describe an unusual case of DIG diagnosed by prenatal ultrasound. METHODS: This 5-day-old newborn was delivered after a prenatal ultrasound revealed a large cystic mass in the left cerebral hemisphere along with an echogenic solid component. RESULTS: The tumor revealed a glial and neuronal proliferation in a background of desmoplasia more typical of DIG and a minor component with a more primitive, immature appearance to the glioneuronal elements. A significant component of the tumor was composed of pleomorphic eosinophilic spindle cells in whorls and interlacing fascicles that showed a strong, sharp, and diffuse positivity for desmin, thus mimicking rhabdomyosarcoma. However, the tumor cells were GFAP (+), INI-1 (+), and myogenin (-). Mitoses were seen both in the more spindle cell astroglial areas as well as the more primitive neuroepithelial cells. The MIB-1 proliferation index was brisk, exceeding 15 %, and in areas it was estimated to be as high as 30 %. Such high proliferation index has been described and accepted in the more primitive neuroepithelial areas, but not in the terminally differentiated, spindle cell astroglial areas as in our case. Our patient was incidentally diagnosed prenatally. To our knowledge, this case is the first documented congenital DIG diagnosed prenatally. CONCLUSIONS: This case highlights the pitfalls in diagnosing DIG, which can mimic a rhabdomyosarcoma. Furthermore, it underscores the importance of re-evaluating the grading of these tumors or at least segregating the variants where the prognosis may be more guarded.
Subject(s)
Desmin/biosynthesis , Ganglioglioma/metabolism , Rhabdomyosarcoma/diagnosis , Supratentorial Neoplasms/metabolism , Cesarean Section , Cytogenetics , Desmin/genetics , Diagnosis, Differential , Ganglioglioma/diagnosis , Ganglioglioma/ultrastructure , Humans , Image Processing, Computer-Assisted , Immunohistochemistry , Infant, Newborn , Ki-67 Antigen/analysis , Magnetic Resonance Imaging , Male , Microscopy, Electron , Neuroglia/pathology , Neuroglia/ultrastructure , Neurons/pathology , Neurons/ultrastructure , Prognosis , Rhabdomyosarcoma/ultrastructure , Supratentorial Neoplasms/diagnosis , Supratentorial Neoplasms/diagnostic imaging , Ultrasonography, PrenatalABSTRACT
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyper-inflammatory disorder that occurs due to immunologic dysregulation. HLH can be primary (hereditary) or secondary to infections, autoimmune diseases, immune deficiencies, metabolic diseases, drugs, or malignancies. Lymphoid neoplasms mostly accompany malignancy-associated HLH. We present a case of a 12-year-old boy with a history of precursor B lymphoblastic leukemia (B-ALL), who subsequently developed chemotherapy-induced acute myeloid leukemia (t-AML). The patient was admitted for febrile neutropenia and initial laboratory tests revealed hemophagocytic lymphohistiocytosis (HLH). The hospital course was complicated by multiple infections and septic shock. The patient received several broad-spectrum antimicrobials, dexamethasone, as well as a pericardial drain to drain the hemorrhagic pericardial effusion. Despite intervention, the patient expired, and an autopsy was performed. We provide a synopsis of the main autopsy findings.
ABSTRACT
Miller-Dieker syndrome (MDS) is a rare genetic disorder characterized by congenital lissencephaly (absent or diminished cerebral gyri), facial dysmorphisms, neurodevelopmental retardation, intrauterine fetal demise, and death in early infancy or childhood. We present a case of a 4-year-old girl with MDS (17p13.3p13.2 deletion) who was admitted to the hospital due to fever and increased secretions from her nose, mouth, and tracheostomy tube (as she had been on a ventilator and G-tube dependent since birth). During the course of hospitalization, she developed multiorgan failure, third spacing, and significant lactic acidosis. The patient had a cardiorespiratory arrest and expired after 4 months and 8 days of hospitalization. We provide a synopsis of the main autopsy findings, with a focus on the neuropathologic anomalies.
ABSTRACT
BACKGROUND: Neonatal acute liver failure (NALF) is a rare and life-threatening condition. It causes bilirubin to accumulate to a dangerous level in the body, causing permanent damage to vital organs such as the brain and lungs. In many cases, the etiology of NALF remains unknown. CASE PRESENTATION: We described a case of an 8-day-old baby girl who presented with poor oral intake, lethargy, and jaundice. Her clinical condition rapidly deteriorated with progression to multi-organ failure, and despite intensive resuscitation efforts, she expired. At autopsy, the most significant findings were liver necrosis, yellow hyaline membrane deposition in the lungs, and bilirubin deposition in the brain (kernicterus). CONCLUSIONS: NALF is a rare and potentially fatal condition necessitating prompt recognition and disease-specific treatment approaches. Toxic accumulation of bilirubin in the lungs can lead to hypoxia and precipitate further ischemic injury to the liver.
ABSTRACT
Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare gastric polyposis syndrome defined by numerous polyps (>100) in the fundus and body of the stomach with sparing of the lesser curvature and antrum. GAPPS is linked to a variant in the promoter 1B region of the APC gene. These variants carry a high risk of developing gastric adenocarcinoma, which can occur at an early age. We report a case of GAPPS discovered in a 16-year-old Hispanic girl after endoscopy detected extensive fundic gland polyposis. Genetic testing revealed a promoter 1B point mutation of the APC gene, variant c.-191T>G. Although similar variants have been reported (i.e., c.-191T>C, c.-195A>C, c.-192A>G) in association with GAPPS, variant c.-191T>G has not nor has GAPPS ever been described in a Hispanic individual before.
ABSTRACT
Extranodal marginal zone B-cell lymphomas (EMZLs), while relatively common in adults, are rare entities in the pediatric population. A subclass of the typically aggressive non-Hodgkin lymphomas, the few reported pediatric cases indicate that, as in adults, these tumors tend to be indolent. We present a case of EMZL arising in the conjunctivae in a 9-year-old male with bilateral disease. The patient was treated with surgical excision alone and has remained disease-free 6 years after the operation.
Subject(s)
Conjunctival Neoplasms/pathology , Lymphoma, B-Cell, Marginal Zone/pathology , Child , Conjunctival Neoplasms/surgery , Humans , Lymphoma, B-Cell, Marginal Zone/surgery , MaleABSTRACT
The FGFR1 gene encoding fibroblast growth factor receptor 1 has emerged as a frequently altered oncogene in the pathogenesis of multiple low-grade neuroepithelial tumor (LGNET) subtypes including pilocytic astrocytoma, dysembryoplastic neuroepithelial tumor (DNT), rosette-forming glioneuronal tumor (RGNT), and extraventricular neurocytoma (EVN). These activating FGFR1 alterations in LGNET can include tandem duplication of the exons encoding the intracellular tyrosine kinase domain, in-frame gene fusions most often with TACC1 as the partner, or hotspot missense mutations within the tyrosine kinase domain (either at p.N546 or p.K656). However, the specificity of these different FGFR1 events for the various LGNET subtypes and accompanying genetic alterations are not well defined. Here we performed comprehensive genomic and epigenomic characterization on a diverse cohort of 30 LGNET with FGFR1 alterations. We identified that RGNT harbors a distinct epigenetic signature compared to other LGNET with FGFR1 alterations, and is uniquely characterized by FGFR1 kinase domain hotspot missense mutations in combination with either PIK3CA or PIK3R1 mutation, often with accompanying NF1 or PTPN11 mutation. In contrast, EVN harbors its own distinct epigenetic signature and is characterized by FGFR1-TACC1 fusion as the solitary pathogenic alteration. Additionally, DNT and pilocytic astrocytoma are characterized by either kinase domain tandem duplication or hotspot missense mutations, occasionally with accompanying NF1 or PTPN11 mutation, but lacking the accompanying PIK3CA or PIK3R1 mutation that characterizes RGNT. The glial component of LGNET with FGFR1 alterations typically has a predominantly oligodendroglial morphology, and many of the pilocytic astrocytomas with FGFR1 alterations lack the biphasic pattern, piloid processes, and Rosenthal fibers that characterize pilocytic astrocytomas with BRAF mutation or fusion. Together, this analysis improves the classification and histopathologic stratification of LGNET with FGFR1 alterations.
Subject(s)
Neoplasms, Neuroepithelial/classification , Neoplasms, Neuroepithelial/genetics , Neoplasms, Neuroepithelial/pathology , Receptor, Fibroblast Growth Factor, Type 1/genetics , Adolescent , Adult , Aged , Brain Neoplasms/classification , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Child , Female , Humans , Male , Middle Aged , Mutation , Spinal Cord Neoplasms/classification , Spinal Cord Neoplasms/genetics , Spinal Cord Neoplasms/pathology , Young AdultABSTRACT
Angiocentric glioma, a rare brain neoplasm with features of ependymal differentiation, has only recently been recognized as a distinct clinicopathological entity. To date, all reported cases have involved tumors in the cerebral hemispheres, and the majority have presented with seizures. The authors report the case of a 5-year-old girl who presented with several cranial neuropathies and mild gait disturbance. An exophytic neoplasm arising from the posterior midbrain and causing obstructive hydrocephalus was identified, and surgical resection revealed a neoplasm with features of angiocentric glioma.
Subject(s)
Brain Neoplasms/pathology , Gait Disorders, Neurologic/etiology , Glioma/pathology , Hydrocephalus/diagnosis , Mesencephalon/pathology , Biopsy, Needle , Brain Neoplasms/complications , Brain Neoplasms/surgery , Child, Preschool , Female , Follow-Up Studies , Gait Disorders, Neurologic/diagnosis , Glioma/complications , Glioma/surgery , Humans , Hydrocephalus/etiology , Hydrocephalus/surgery , Immunohistochemistry , Magnetic Resonance Imaging , Mesencephalon/surgery , Neurosurgical Procedures/methods , Risk Assessment , Treatment OutcomeABSTRACT
Pontocerebellar hypoplasias are a group of autosomal recessive neurodevelopmetal disorders with varied phenotypic presentations and extensive genetic mutational landscape that are currently classified into ten subtypes. This classification is based predominantly on the genetic iterations as the phenotypic presentations are often broad and overlapping. Pontocerebellar hypoplasia type-3 (PCH3) is an autosomal recessive disorder characterized by a small cerebellar vermis, hyperreflexia, and seizures, described in Middle Eastern families in association with a homozygous truncating mutation of the PCLO gene in locus 7q11-21. This is a case of PCH, with previously unreported novel genetic alterations. The patient is a 1-week-old girl, born at term to a 26-year-old G4P0A3 woman in a nonconsanguinous relation. At birth, the baby was depressed and hypertonic with abnormal tonic-clonic movements of extremities. MRI revealed cerebellar and brainstem hypoplasia. Postmortem examination revealed a palmar simian crease. The cerebellum measured 2.5 cm from side to side and 1 cm from rostral to caudal. The vermis was rudimentary. Sectioning revealed a flattened linear fourth ventricle, scant abortive cerebellar foliae, and a markedly small cerebellum when compared with the cerebrum and with age-matched size. H&E-stained sections of cerebellum revealed scant rudimentary foliae. A rudimentary unilateral embolliform nucleus was identified. The remaining cerebellar nuclei were absent. Chromosomal microarray showed an interstitial duplication of 841 kB on chromosome 7q11.23. Locus 7q11.23 contains FGL2 and GSAP genes and is 5 MB upstream of the 7q11-21 region, suggesting a possible linkage. This novel genomic finding possibly represents a new familial variant of PCH closely associated with PCH-3 and further strengthens its association with the 7q11 locus.
ABSTRACT
An otherwise healthy 6-week-old girl who presented with an isolated left third cranial nerve palsy underwent MRI that revealed an enhancing mass intrinsic to the left third cranial nerve. Rapid enlargement of the lesion over 1 month led to subtotal neurosurgical resection of an atypical teratoid/rhabdoid tumor (AT/RT), a rare, highly aggressive malignancy of infancy closely related histologically to medulloblastoma and primitive neuroectodermal tumor. Despite aggressive chemotherapy, the patient died within 6 months of presentation. This is the first report of an AT/RT presenting as an isolated third cranial nerve palsy caused by tumor arising from within the nerve.