- Fundic Gland Polyps in the Pediatric Population. [Journal Article]
- PDPediatr Dev Pathol 2017 Jan 01; :1093526617706816
- We retrospectively studied the clinical and histologic features of pediatric fundic gland polyps (FGPs) in 16 patients. FGPs had an endoscopic prevalence of 0.25% in 8527 pediatric gastric biopsies. ...
We retrospectively studied the clinical and histologic features of pediatric fundic gland polyps (FGPs) in 16 patients. FGPs had an endoscopic prevalence of 0.25% in 8527 pediatric gastric biopsies. Five patients had familial adenomatous polyposis (FAP). The median age of onset was 17.7 years in FAP and 17.3 years in sporadic patients. All syndromic patients were asymptomatic and FGPs were identified during surveillance for existing or concurrent colon polyps. They did not take antacids. In comparison, all 11 sporadic FGPs were identified during evaluation of symptomatic patients who had taken antacids (median duration 21 months). Syndromic FGPs can be multiple at single endoscopy and were more likely to recur, while sporadic FGPs were often single. None of the sporadic patients had recurrence of FGPs or a subsequent diagnosis of FAP during a median follow-up of 20.5 months. The dilated fundic glands were lined by parietal and chief cells only in majority (22/41, 53.7%) of syndromic FGPs, while additional tall mucinous lining cells were found in all sporadic FGPs. Syndromic FGPs did not have parietal cell hypertrophy in the background oxyntic mucosa. Nuclear immunopositivity for beta-catenin was essentially absent in all the FGPs. In conclusion, FGPs were rare in pediatric patients. In syndromic patients, FGPs are asymptomatic and did not precede colon polyps. Prolonged antacid intake seems to be associated with development of sporadic FGPs. Cellular components of dilated fundic glands and background parietal cell hypertrophy can be useful features to eliminate concern for syndromic polyposis.
- Malignant Rhabdoid Tumor of Soft Tissue. [Journal Article]
- PDPediatr Dev Pathol 2017 Jan 01; :1093526617706814
- Introduction Malignant rhabdoid tumor (MRT) is defined as a high-grade sarcoma derived from an uncertain cell of origin. Its diagnosis is associated with poor prognosis and patient's life expectancy ...
Introduction Malignant rhabdoid tumor (MRT) is defined as a high-grade sarcoma derived from an uncertain cell of origin. Its diagnosis is associated with poor prognosis and patient's life expectancy is greatly reduced. Material and method Here, we describe a unique case of 9-month-old boy who presented with a large MRT arising from the soft tissue of the neck. Following intensive multimodal treatment, the patient benefited from a 25 years' remission until the discovery of multiple liver metastases. Conclusion MRT of soft tissue needs to be distinguished from other soft tissue neoplasms, as MRT is highly aggressive and is usually associated with a poor outcome. In addition, this is the longest remission time reported in a patient with soft tissue MRT and this might be related to the use of early intensive multimodal treatments.
- An Unusual Presentation of a Cervical Paraspinal Leiomyoma in an Adolescent Female. [Journal Article]
- PDPediatr Dev Pathol 2017 Jan 01; :1093526617706815
- Objective We describe an apparently unique case of an extra-uterine leiomyoma in the cervical paraspinus including its evaluation and management. Methods A 14-year-old girl was referred to the neurol...
Objective We describe an apparently unique case of an extra-uterine leiomyoma in the cervical paraspinus including its evaluation and management. Methods A 14-year-old girl was referred to the neurology clinic for an abnormal head CT following a concussion. MRI revealed a homogenously enhancing left cervical paraspinal mass. The patient underwent complete resection and subsequent genetic testing and counseling were obtained to determine the presence of Li-Fraumeni Syndrome (LFS) or Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) mutations. Result Histopathological examination proved that the tumor was a benign leiomyoma. Genomic testing for Fumarate Hydratase Gene, HLRCC, TP53 mutations or deletions, and LFS sequencing were negative. Further testing showed no immunosuppression. Conclusions To the best of our knowledge, this is the only case of paraspinal leiomyoma to have been reported to date. We emphasize the importance of considering immunosuppression, LFS, or HLRCC as an underlying cause in extra-uterine leiomyata.
- Congenital Hypothalamic "Hamartoblastoma" Versus "Hamartoma". [Journal Article]
- PDPediatr Dev Pathol 2017 Jan 01; :1093526617701338
- Pallister Hall syndrome (PHS) is a rare malformative disorder that is due to truncating functional repressor mutations in GLI3. Since the seminal publication in 1980, hypothalamic tumors have been re...
Pallister Hall syndrome (PHS) is a rare malformative disorder that is due to truncating functional repressor mutations in GLI3. Since the seminal publication in 1980, hypothalamic tumors have been recognized to be a cardinal feature of PHS. In their original description of the neuropathologic features of PHS, Clarren et al. coined the term "hamartoblastoma" to characterize what they deemed to be a dual malformative and neoplastic mass of the hypothalamus. In subsequent published cases/series of PHS, the term "hamartoma" was often substituted for hamartoblastoma given what appeared to be a benign natural history of this lesion. Additional confusion in the literature has ensued since most hypothalamic hamartomas (HH) encountered on the clinical neuropathology service are "isolated" in nature (ie, no other congenital malformations) and present in a very different and stereotypical fashion with gelastic seizures and/or precocious puberty. While genomic investigations of isolated HH have begun to uncover a mutational profile of these cases, GLI3 mutations have only been recognized in a small subset of isolated HH. Herein, we describe the autopsy findings from a 21-week gestational age fetus with features of PHS. Moreover, we provide a detailed description of the hypothalamic tumor affecting this fetus and propose a novel subclassification of HH, distinguishing syndromic from isolated forms based upon the presence or absence of neocortical-like areas.
- Submucosal Colonic Lipoblastoma Presenting With Colo-colonic Intussusception in an Infant. [Journal Article]
- PDPediatr Dev Pathol 2017 Jan 01; :1093526617705271
- Lipoblastoma is a benign adipose tumor typically presenting in infancy in superficial soft tissues of extremities. Intestinal complications secondary to intraabdominal or retroperitoneal involvement ...
Lipoblastoma is a benign adipose tumor typically presenting in infancy in superficial soft tissues of extremities. Intestinal complications secondary to intraabdominal or retroperitoneal involvement are exceedingly rare. We describe a unique case of a primary intestinal lipoblastoma arising from the submucosa of the transverse colon in an otherwise healthy 18-month-old boy. He presented with a history of reducible rectal prolapse, rectal bleeding, and episodic abdominal pain and was initially treated for constipation. Imaging identified a short colo-colonic intussusception, confirmed at laparotomy, and a fatty mass thought to arise from the mesentery. Pathological examination of the resected transverse colon revealed a submucosal tumor composed of a mixture of mature adipose tissue, foci of myxoid mesenchymal tissue with desmin positive, HMGA2 negative spindle cells, and scattered lipoblasts, characteristic of lipoblastoma. Lipoblastoma should be considered as a potential albeit rare cause of intussusception in young children, where a pathologic lead point is infrequently identified.
- Pediatric Non-vestibular Schwannoma. [Journal Article]
- PDPediatr Dev Pathol 2017 Jan 01; :1093526617703540
- While the clinicopathologic features of pediatric vestibular schwannomas, often in the context of neurofibromatosis type 2 (NF2), have been well studied, there is less data regarding the characterist...
While the clinicopathologic features of pediatric vestibular schwannomas, often in the context of neurofibromatosis type 2 (NF2), have been well studied, there is less data regarding the characteristics of pediatric non-vestibular schwannomas (NVS). Additionally, the rate of loss of SMARCB1/INI1 expression in this population has not been systematically evaluated. Our institutional archives were searched for cases of NVS arising in patients 18 years or younger. Clinicopathologic features including SMARCB1/INI1 status were assessed for each case. Twenty-three NVS from 9 males and 13 females (age range, 2 months to 18 years) were identified, and sites included paraspinal (n = 10), head and neck (n = 6), extremities (n = 4), trunk (n = 1), mediastinum (n = 1), and retroperitoneum (n = 1); 22 cases were Antoni A predominant with 6 cases comprising solely Antoni A tissue. The mitotic rate of the tumors ranged from 0 to 10/10 high-power fields (HPFs), and 3 tumors had mitotic rates of ≥4 mitoses/10 HPFs. Two tumors showed plexiform architecture. No NVS showed diffuse atypia, calcifications, microcystic/reticular architecture, epithelioid morphology, pseudoglandular change, neuroblastoma-like features, or necrosis. All tumors tested (23/23) showed retained nuclear expression of SMARCB1/INI1. Follow-up was available in 21 patients (range 1 week to 194 months), and 5 tumors recurred. Pediatric NVS have a relatively homogeneous appearance with a predominance of Antoni A areas. Pathologists should be aware that schwannomas in this age group may be cellular with mitotic rates of ≥4/10 HPFs to avoid misclassification as a spindle cell sarcoma.
- BCOR-CCNB3 Undifferentiated Sarcoma-Does Immunohistochemistry Help in the Identification? [Journal Article]
- PDPediatr Dev Pathol 2017 Jan 01; :1093526617698263
- Recent methodology has enabled the identification of some new genetic subgroups within the melting pot of lesions presently classified by the 2013 WHO classification as "undifferentiated/unclassified...
Recent methodology has enabled the identification of some new genetic subgroups within the melting pot of lesions presently classified by the 2013 WHO classification as "undifferentiated/unclassified sarcomas". One of these subgroups is characterized by a paracentric inversion of the X chromosome with consequent formation of a BCOR-CCNB3 fusion. Clinical and pathological features of these tumors overlap with the Ewing sarcoma family as well as other soft tissue sarcomas, thus making them difficult to diagnose. To investigate the morphological and immunohistochemical characteristics of BCOR-CCNB3 positive sarcoma, we reviewed two sarcoma series, comprising 632 and 121 cases. The 11 tumors harboring the BCOR-CCNB3 fusion, identified by CCNB3 immunohistochemistry and/or RT-PCR, were reevaluated for morphological characteristics and further immunohistochemical investigations for CCNB3, SATB2, and Pax8 were performed. Tumors harboring a BCOR-CCNB3 fusion (11/753) occured exclusively in males, with a mean age at diagnosis of 12.9 years, and were mainly axially located. In this group of either spindled or round cell tumors, vesicular nuclei with finely dispersed chromatin, inconspicuous nucleoli and an arciform vascular pattern were pathognomonic. More than 50% of cases stained positive for SATB2 and Pax8, raising the hypothesis of a potential use of these markers in the identification of BCOR-CCNB3 positive undifferentiated/unclassified sarcomas. CCNB3 was confirmed as a useful ancillary immunohistochemical marker.
- Advancing Clinicopathologic Diagnosis of High-risk Neuroblastoma Using Computerized Image Analysis and Proteomic Profiling. [Journal Article]
- PDPediatr Dev Pathol 2017 Jan 01; :1093526617698603
- A subset of patients with neuroblastoma are at extremely high risk for treatment failure, though they are not identifiable at diagnosis and therefore have the highest mortality with conventional trea...
A subset of patients with neuroblastoma are at extremely high risk for treatment failure, though they are not identifiable at diagnosis and therefore have the highest mortality with conventional treatment approaches. Despite tremendous understanding of clinical and biological features that correlate with prognosis, neuroblastoma at ultra-high risk for treatment failure remains a diagnostic challenge. As a first step towards improving prognostic risk stratification within the high-risk group of patients, we determined the feasibility of using computerized image analysis and proteomic profiling on single slides from diagnostic tissue specimens. After expert pathologist review of tumor sections to ensure quality and representative material input, we evaluated multiple regions of single slides as well as multiple sections from different patients' tumors using computational histologic analysis and semiquantitative proteomic profiling. We found that both approaches determined that intertumor heterogeneity was greater than intratumor heterogeneity. Unbiased clustering of samples was greatest within a tumor, suggesting a single section can be representative of the tumor as a whole. There is expected heterogeneity between tumor samples from different individuals with a high degree of similarity among specimens derived from the same patient. Both techniques are novel to supplement pathologist review of neuroblastoma for refined risk stratification, particularly since we demonstrate these results using only a single slide derived from what is usually a scarce tissue resource. Due to limitations of traditional approaches for upfront stratification, integration of new modalities with data derived from one section of tumor hold promise as tools to improve outcomes.
- Novel NLRC4 Mutation Causes a Syndrome of Perinatal Autoinflammation With Hemophagocytic Lymphohistiocytosis, Hepatosplenomegaly, Fetal Thrombotic Vasculopathy, and Congenital Anemia and Ascites. [Journal Article]
- PDPediatr Dev Pathol 2017 Jan 01; :1093526616686890
- Autoinflammatory diseases are caused by pathologic activation of the innate immune system. Primary hemophagocytic lymphohistiocytosis (HLH) is an aggressive syndrome of excessive immune activation ca...
Autoinflammatory diseases are caused by pathologic activation of the innate immune system. Primary hemophagocytic lymphohistiocytosis (HLH) is an aggressive syndrome of excessive immune activation caused by monogenic mutations resulting in cytotoxic cell defects and subsequent failure to eliminate activated macrophages. Secondary HLH is often diagnosed in cases without a known Mendelian inheritance. However, some cases of "secondary" HLH have been shown to harbor mutations with partial dysfunction of the cytotoxic system. Recently, macrophage intrinsic abnormalities caused by NLRC4 inflammasome mutations have been linked to autoinflammation and recurrent macrophage activation syndromes resembling a primary HLH. We report a case of a former 28-week preterm infant with congenital anemia, ascites, and a heavy edematous placenta with fetal thrombotic vasculopathy, who developed hepatosplenomegaly and unexplained systemic inflammation with laboratory features of HLH in the early postnatal course and died at 2 months of age. Postmortem examination confirmed the hepatosplenomegaly with marked sinusoidal hemophagocytosis, along with striking hemophagocytosis in the bone marrow and lymph nodes. There was extensive acute and chronic ischemic bowel disease with matted bowel loops, fibrous adhesions, and patchy necrotizing enterocolitis features. Whole exome sequencing analysis demonstrated a novel mosaic heterozygous NLRC4 512 C> T (p.Ser171Phe) de novo mutation predicated to cause a dominant, gain-of-function mutation resulting in a constitutively active protein. The assembly of NLRC4-containing inflammasomes via an induced self-propagation mechanism likely enables a perpetuating process of systemic macrophage activation, presumed to be initiated in utero in this patient.
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- Esophageal Squamous Papilloma in a Pediatric Patient With Helicobacter pylori Gastritis. [Journal Article]
- PDPediatr Dev Pathol 2017 Jan 01; :1093526617701798