Prevalence of lung cysts in adolescents and adults with a germline DICER1 pathogenic/likely pathogenic variant: a report from the National Institutes of Health and International Pleuropulmonary Blastoma/DICER1 Registry.

BACKGROUND: Pleuropulmonary blastoma (PPB), the hallmark tumour associated with DICER1-related tumour predisposition, is characterised by an age-related progression from a cystic lesion (type I) to a high-grade sarcoma with mixed cystic and solid features (type II) or purely solid lesion (type III). Not all cystic PPBs progress; type Ir (regressed), hypothesised to represent regressed or non-progressed type I PPB, is an air-filled, cystic lesion lacking a primitive sarcomatous component. This study aims to evaluate the prevalence of non-progressed lung cysts detected by CT scan in adolescents and adults with germline DICER1 pathogenic/likely pathogenic (P/LP) variants. METHODS: Individuals were enrolled in the National Cancer Institute Natural History of DICER1 Syndrome study, the International PPB/DICER1 Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Individuals with a germline DICER1 P/LP variant with first chest CT at 12 years of age or older were selected for this analysis. RESULTS: In the combined databases, 110 individuals with a germline DICER1 P/LP variant who underwent first chest CT at or after the age of 12 were identified. Cystic lung lesions were identified in 38% (42/110) with a total of 72 cystic lesions detected. No demographic differences were noted between those with lung cysts and those without lung cysts. Five cysts were resected with four centrally reviewed as type Ir PPB. CONCLUSION: Lung cysts are common in adolescents and adults with germline DICER1 variation. Further study is needed to understand the mechanism of non-progression or regression of lung cysts in childhood to guide judicious intervention.

Outcomes in ovarian Sertoli-Leydig cell tumor: A report from the International Pleuropulmonary Blastoma/DICER1 and Ovarian and Testicular Stromal Tumor Registries.

OBJECTIVE: Sertoli-Leydig cell tumors (SLCTs) are rare sex cord-stromal tumors, representing <0.5% of all ovarian tumors. We sought to describe prognostic factors, treatment and outcomes for individuals with ovarian SLCT. METHODS: Individuals with SLCT were enrolled in the International Pleuropulmonary Blastoma/DICER1 Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Medical records were systematically abstracted, and pathology was centrally reviewed when available. RESULTS: In total, 191 participants with ovarian SLCT enrolled, with most (92%, 175/191) presenting with FIGO stage I disease. Germline DICER1 results were available for 156 patients; of these 58% had a pathogenic or likely pathogenic germline variant. Somatic (tumor) DICER1 testing showed RNase IIIb hotspot variants in 97% (88/91) of intermediately and poorly differentiated tumors. Adjuvant chemotherapy was administered in 40% (77/191) of cases, and among these, nearly all patients received platinum-based regimens (95%, 73/77), and 30% (23/77) received regimens that included an alkylating agent. Three-year recurrence-free survival for patients with stage IA tumors was 93.6% (95% CI: 88.2-99.3%) compared to 67.1% (95% CI: 55.2-81.6%) for all stage IC and 60.6% (95% CI: 40.3-91.0%) for stage II-IV (p < .001) tumors. Among patients with FIGO stage I tumors, those with mesenchymal heterologous elements treated with surgery alone were at higher risk for recurrence (HR: 74.18, 95% CI: 17.99-305.85). CONCLUSION: Most individuals with SLCT fare well, though specific risk factors such as mesenchymal heterologous elements are associated with poor prognosis. We also highlight the role of DICER1 surveillance in early detection of SLCT, facilitating stage IA resection.

Anaplastic sarcoma of the kidney (DICER1-sarcoma of the kidney): A report from the International Pleuropulmonary Blastoma/DICER1 Registry.

BACKGROUND: Anaplastic sarcoma of the kidney (ASK) is a DICER1-related neoplasm first identified as a distinctive tumor type through the evaluation of unusual cases of putative anaplastic Wilms tumors. Subsequent case reports identified the presence of biallelic DICER1 variants as well as progression from cystic nephroma, a benign DICER1-related neoplasm. Despite increasing recognition of ASK as a distinct entity, the optimal treatment remains unclear. METHODS: Individuals with known or suspected DICER1-related tumors including ASK were enrolled in the International Pleuropulmonary Blastoma/DICER1 Registry. Additionally, a comprehensive review of reported cases of ASK was undertaken, and data were aggregated for analysis with the aim to identify prognostic factors and clinical characteristics to guide decisions regarding genetic testing, treatment, and surveillance. RESULTS: Ten cases of ASK were identified in the Registry along with 37 previously published cases. Staging data, per Children's Oncology Group guidelines, was available for 40 patients: 13 were stage I, 12 were stage II, 10 were stage III, and five were stage IV. Outcome data were available for 37 patients. Most (38 of 46) patients received upfront chemotherapy and 14 patients received upfront radiation. Two-year event-free survival (EFS) for stage I-II ASK was 81.8% (95% confidence interval [CI]: 67.2%-99.6%), compared with 46.6% EFS (95% CI: 24.7%-87.8%) for stage III-IV (p = .07). Two-year overall survival (OS) for stage I-II ASK was 88.9% (95% CI: 75.5%-100.0%), compared with 70.0% (95% CI: 46.7%-100.0%) for stage III-IV (p = .20). Chemotherapy was associated with improved EFS and OS with hazard ratios of 0.09 (95% CI: 0.02-0.31) and 0.08 (95% CI: 0.02-0.42), respectively. CONCLUSION: ASK is a rare DICER1-related renal neoplasm. In the current report, we identify clinical and treatment-related factors associated with outcome including the importance of chemotherapy in treating ASK. Ongoing data collection and genomic analysis are indicated to optimize outcomes for children and adults with these rare tumors.

Sarcomatoid Morphology in Pediatric Langerhans Cell Neoplasm Does Not Always Predict Aggressive Clinical Course.

Langerhans cell sarcoma (LCS), a rare malignant neoplasm in the general category of myeloid neoplasms characterized by overtly malignant Langerhans cells (LC) with conspicuous mitotic activity including atypical forms. Although most cases occur in adults, rare examples of LCS have been reported in children with variable clinical outcome. We present 2 childhood cases of Langerhans cell neoplasm with high grade sarcomatous features and OSBPL9::BRAF fusion and BRAF V600E mutation.

Type I and Ir pleuropulmonary blastoma (PPB): A report from the International PPB/DICER1 Registry.

BACKGROUND: Pleuropulmonary blastoma (PPB) is the most common lung cancer of infancy and early childhood. Type I PPB is a purely cystic lesion that has a microscopic population of primitive small cells with or without rhabdomyoblastic features and may progress to type II or III PPB, whereas type Ir lacks primitive small cells. METHODS: Children with suspected PPB were enrolled in the International PPB/DICER1 Registry. Pathology was centrally reviewed, and follow-up was ascertained annually. RESULTS: Between 2006 and 2022, 205 children had centrally reviewed type I or Ir PPB; 39% of children with type I and 5% of children with type Ir PPB received chemotherapy. Outcomes were favorable, although 11 children (nine with type I and two with type Ir PPB) experienced progression to type II/III (n = 8) or regrowth of type I PPB at the surgical site (n = 3), none of whom received chemotherapy before progression. Age and cyst size in combination were more suitable than either factor alone in predicting whether a particular lesion was type I or Ir PPB. CONCLUSIONS: For young children with type I PPB, outcomes are favorable, but complete resection is indicated because of the risk for progression. Chemotherapy may be useful in a subset of children at increased risk for recurrence/progression. Efforts to risk stratify children with type I PPB to optimize outcomes while reducing treatment-related side effects are underway.

Health-related quality of life in children and adolescents with pleuropulmonary blastoma: A report from the International PPB/DICER1 Registry.

PURPOSE: Pleuropulmonary blastoma (PPB) is the most common lung cancer of infancy and early childhood and is associated with germline DICER1 variants. Type I and Ir PPB are cystic lesions treated surgically, with a subset of children with type I receiving chemotherapy. Type II and III are more aggressive lesions, treated with surgery, intensive chemotherapy and potentially radiation. We sought to assess health-related quality of life (HRQoL) in children with PPB and known germline DICER1 variants. METHODS: Children with a diagnosis of PPB or germline DICER1 pathogenic variant without history of PPB or other DICER1-related neoplasm (DICER1+ only) were enrolled in the International PPB/DICER1 Registry. Parent reports for participants aged 2-17 years for the PedsQL v.4 and PedsQL Multidimensional Fatigue Scale v.3 were collected. Fatigue, physical, and psychosocial function scores were compared. RESULTS: Analysis included 84 participants (PPB type Ir = 20, type I = 15, type II/III = 27, DICER1+ only = 22). Total fatigue scores of participants with type I and II/III PPB were lower compared to DICER1+ only, with effect size larger in type II/III (-0.82 vs. -0.40). Total psychosocial and physical functioning scores were lower in participants with type I and type II/III PPB compared to DICER1+ only, with larger effects noted in type II/III. Female sex was suggestive of worse HRQoL for both type I/Ir and type II/III cohorts. CONCLUSIONS: These data demonstrate the importance of regular HRQoL assessment in patients with a history of PPB as well as the importance and feasibility of studying HRQoL in children with rare tumors.

Assessing the role of positron emission tomography and bone scintigraphy in imaging of pleuropulmonary blastoma (PPB): A report from the International PPB/DICER1 Registry.

BACKGROUND: Pleuropulmonary blastoma (PPB) is the most common primary lung neoplasm of infancy and early childhood. Given the rarity of PPB, the role of positron emission tomography (PET) and bone scintigraphy (bone scans) in diagnostic evaluation and surveillance has not been documented to date. Available PET and bone scan data are presented in this study. PROCEDURES: Patients with PPB enrolled in the International PPB/DICER1 Registry and available PET imaging and/or bone scan reports were retrospectively abstracted. RESULTS: On retrospective analysis, 133 patients with type II and III (advanced) PPB were identified with available report(s) (PET scan only = 34, bone scan only = 83, and both bone scan and PET = 16). All advanced primary PPB (n = 11) and recurrent (n = 8) tumors prior to treatment presented with 18 F-fluorodeoxyglucose (FDG)-avid lesions, with median maximum standardized uptake values of 7.4 and 6.7, respectively. False positive FDG uptake in the thorax was noted during surveillance (specificity: 59%). Bone metastases were FDG-avid prior to treatment. Central nervous system metastases were not discernable on PET imaging. Sensitivity and specificity of bone scans for metastatic bone disease were 89% and 92%, respectively. Bone scans had a negative predictive value of 99%, although positive predictive value was 53%. Four patients with distant bone metastases had concordant true positive bone scan and PET. CONCLUSION: Primary, recurrent, and/or extracranial metastatic PPB presents with an FDG-avid lesion on PET imaging. Additional prospective studies are needed to fully assess the utility of nuclear medicine imaging in surveillance for patients with advanced PPB.

Congenital Pulmonary Airway Malformations With a Reconsideration and Current Perspective on the Stocker Classification.

Congenital cystic pulmonary lesions (CCPLs) are represented by the following entities: congenital pulmonary airway malformation (CPAM), formerly congenital cystic adenomatoid malformation, extra- and intralobar sequestration (EIS), congenital lobar emphysema (overexpansion), and bronchogenic cyst. The developmental model of CPAM histogenesis by Stocker proposed perturbations designated as CPAM type 0 to type 4 without known or specific pathogenetic mechanisms along the airway from the bronchus to the alveolus. This review highlights mutational events either at the somatic level in KRAS (CPAM types 1 and possibly 3) or germline variants in congenital acinar dysplasia, formerly CPAM type 0, and pleuropulmonary blastoma (PPB), type I, formerly CPAM type 4. The potential for overt malignant progression exists in the case of PPB type I and CPAM type 1 in some cases to well-differentiated mucinous adenocarcinoma. On the other hand, CPAM type 2 is an acquired lesion resulting from interruption in lung development secondary to bronchial atresia. The latter is also regarded as the etiology of EIS whose pathologic features are similar, if not identical, to CPAM type 2. These observations have provided important insights into the pathogenetic mechanisms in the development of the CPAMs since the Stocker classification.

The Placenta and Neonatal Encephalopathy with a Focus on Hypoxic-Ischemic Encephalopathy.

Background: Placental examination is important for its diagnostic immediacy to correlate with maternal and/or fetal complications and parturitional difficulties. In a broader context, clinicopathologic studies of the placenta have addressed a range of pathogenetic questions that have led to conclusive and inconclusive results and interpretations. Methods: Recent standardized morphologic criteria and terminology of placental lesions have facilitated the ability to compare findings from studies that have focused on complications and outcomes of pregnancy. This review is an evaluation of recent studies on placental lesions associated with hypoxic-ischemic encephalopathy (HIE). Conclusion: No apparent consensus exists on whether it is fetal inflammation with the release of cytokines or chronic maternal and/or fetal vascular malperfusion is responsible for HIE with a lowering of the threshold for hypoxic ischemia. The counter argument is that HIE occurs solely as an intrapartum event. Additional investigation is necessary.

DICER1-associated hepatic cystic neoplasm with pleuropulmonary blastoma-like features: a novel clinicopathologic diagnosis.

This report documents a unique multicystic neoplasm of the liver in an 8-month-old boy with a heterozygous germline pathogenic DICER1 variant. This neoplasm, initially considered most likely a mesenchymal hamartoma based on imaging, demonstrated the characteristic histologic pattern of embryonal rhabdomyosarcoma residing in the subepithelial or cambium layer-like zone of the epithelial-lined cysts. Thus, although the differential diagnosis includes mesenchymal hamartoma, a young child with a multicystic mass lesion in the liver, lung, or kidney should both raise the possibility of a germline pathogenic DICER1 variant and also not be mistaken for one of the other hepatic neoplasms of childhood.

DICER1 tumor predisposition syndrome: an evolving story initiated with the pleuropulmonary blastoma.

DICER1 syndrome (OMIM 606241, 601200) is a rare autosomal dominant familial tumor predisposition disorder with a heterozygous DICER1 germline mutation. The most common tumor seen clinically is the pleuropulmonary blastoma (PPB), a lung neoplasm of early childhood which is classified on its morphologic features into four types (IR, I, II and III) with tumor progression over time within the first 4-5 years of life from the prognostically favorable cystic type I to the unfavorable solid type III. Following the initial report of PPB, its association with other cystic neoplasms was demonstrated in family studies. The detection of the germline mutation in DICER1 provided the opportunity to identify and continue to recognize a number seemingly unrelated extrapulmonary neoplasms: Sertoli-Leydig cell tumor, gynandroblastoma, embryonal rhabdomyosarcomas of the cervix and other sites, multinodular goiter, differentiated and poorly differentiated thyroid carcinoma, cervical-thyroid teratoma, cystic nephroma-anaplastic sarcoma of kidney, nasal chondromesenchymal hamartoma, intestinal juvenile-like hamartomatous polyp, ciliary body medulloepithelioma, pituitary blastoma, pineoblastoma, primary central nervous system sarcoma, embryonal tumor with multilayered rosettes-like cerebellar tumor, PPB-like peritoneal sarcoma, DICER1-associated presacral malignant teratoid neoplasm and other non-neoplastic associations. Each of these neoplasms is characterized by a second somatic mutation in DICER1. In this review, we have summarized the salient clinicopathologic aspects of these tumors whose histopathologic features have several overlapping morphologic attributes particularly the primitive mesenchyme often with rhabdomyoblastic and chondroid differentiation and an uncommitted spindle cell pattern. Several of these tumors have an initial cystic stage from which there is progression to a high grade, complex patterned neoplasm. These pathologic findings in the appropriate clinical setting should serve to alert the pathologist to the possibility of a DICER1-associated neoplasm and initiate appropriate testing on the neoplasm and to alert the clinician about the concern for a DICER1 mutation.

Phenotypic similarities within the morphologic spectrum of DICER1-associated sarcomas and pleuropulmonary blastoma: Histopathologic features guide diagnosis in the LMIC setting.

Extrapulmonary DICER1-associated sarcomas (DS) can harbor morphological features overlapping with pleuropulmonary blastoma. We report three children with intracranial and genital tract sarcomas, suspected to have DS based on a heterogeneous yet defining combination of spindle-cell sarcomatous and blastemal morphology, with rhabdomyomatous differentiation. Foci of immature cartilage at diagnosis (n = 2/3) and increased neuroepithelial differentiation at recurrence (n = 1) were noted. Morphological suspicion prompted somatic testing at reference centers, confirming likely biallelic, loss-of-function, and "hotspot" missense DICER1 variants in all three tumors. This can serve as a model for this diagnosis in resource-limited settings and has implications for germline testing, surveillance, and tumor management.

Rosette-like formations in melanocytic neoplasms: A case report and literature review.

Homer-Wright-like rosettes are a common finding in neural tumors but seldom seen in melanocytic nevi and melanoma. We report a case of a 23-year-old male with a compound melanocytic nevus with such rosette-like structures and summarize the current literature on this histopathological feature in melanocytic neoplasms. A symmetric, well-circumscribed, compound nevus consisting of aggregations of epithelioid melanocytes with eccentric nuclei and central eosinophilic cytoplasm, resembling Homer-Wright rosettes, was present on biopsy. Immunohistochemical stains strongly supported a melanocytic entity and were negative for NTRK1/2/3, a fusion protein potentially associated with rosette-like structures. We found 17 other cases of benign melanocytic nevi, including 9 atypical Spitz tumors and 6 Spitz nevi, and 11 malignant melanomas, including 3 Spitz melanomas and 4 metastases. We observed remarkable diversity among lesion morphologies containing rosettes, as well as level of prominence and cytology of the rosettes themselves. This case illustrates the morphologic malleability of neural-crest-derived lesions to share microscopic and phenotypic attributes.

Calretinin Staining in Anorectal Line Biopsies Accurately Distinguished Hirschsprung Disease in a Retrospective Study.

INTRODUCTION: The absence of submucosal ganglion cells does not reliably distinguish Hirschsprung disease from non Hirschsprung disease in anorectal line biopsies. Calretinin staining might be helpful in these biopsies. To determine its value, we analyzed calretinin positive mucosal neurites in anorectal line biopsies. METHODS: Two pediatric pathologists, without access to patient data, evaluated calretinin positive mucosal neurites in anorectal line junctional mucosa in archival rectal biopsies contributed by 17 institutions. A separate investigator compiled patient information and sent data for statistical analysis. RESULTS: Biopsies with anorectal junctional mucosa from 115 patients were evaluated for calretinin positive mucosal neurites. 20/20 Hirschsprung disease biopsies were negative. 87/88 non Hirschsprung disease biopsies and 7/7 post pullthrough Hirschsprung disease neorectal biopsies were positive. Statistical analysis of the 108 non pullthrough biopsies yielded an accuracy of 99.1% (sensitivity 100%, specificity 98.9%). Age range was preterm to 16 years. Biopsy size was less than 1 mm to over 1 cm. CONCLUSIONS: Absence of calretinin positive mucosal neurites at the anorectal line was highly accurate in distinguishing Hirschsprung disease from non Hirschsprung disease cases in this blinded retrospective study. Calretinin staining is useful for interpreting biopsies from the physiologic hypoganglionic zone up to the anorectal line.

Juvenile Xanthogranuloma: A Comparative Immunohistochemical Study of Factor XIIIa, CD11c, and CD4.

ABSTRACT: Juvenile xanthogranuloma is a group C and L non-Langerhans cell histiocytosis, and its cell of origin is still debatable. The expression of CD11c, a more recently described macrophage marker, and CD4 have not been studied comprehensively. This study aimed to expand immunophenotypic profile and hence our understanding of the origin of these lesions. The surgical pathology archive was searched for the cases with the pathologic diagnosis of "xanthogranuloma" from 1995 to 2019. Immunohistochemical (IHC) stains were performed for factor XIIIa, CD11c, and CD4. Morphologically, each lesion was classified into early classic, classic, or transitional subtypes. Seventy-seven cases were included with the median age of 7.8 years (male:female 1.3:1). Uniform positivity was noticed for CD4 (n = 77), CD68 (n = 37), CD163 (n = 5), and vimentin (n = 4) stains. Other stains included CD11c 75/77 (97.4%), factor XIIIa 71/76 (93.4%), S-100 protein 4/23 (17.4%), and CD1a 0/18 (0%). Despite insignificant association between morphologic subtype and main studied IHC stains, factor XIIIa reactivity was highest in transitional lesions and CD11c showed higher reactivity in early classic lesions. CD11c and CD4 are sensitive markers and showed promising results in the diagnosis of juvenile xanthogranuloma compared with factor XIIIa. Despite different reactivity of factor XIIIa and CD11c in various morphologic subtypes, such association was statistically insignificant.

Juvenile and adult xanthogranuloma: A 30-year single-center experience and review of the disorder and its relationship to other histiocytoses.

BACKGROUND: Juvenile xanthogranuloma (JXG) is the most common type of non-Langerhans cell histiocytosis whose cell of origin, etiology and pathogenesis are not fully understood. We aimed to provide an update on histopathologic and immunophenotypic profile of this well-characterized entity whose relationship to the other histiocytoses has received renewed attention in light of recent molecular genetic studies. MATERIALS AND METHODS: A retrospective review of all the cases with the pathologic diagnosis of "xanthogranuloma" was performed on our archives from 1989 to 2019. RESULTS: A total of 525 patients with 547 lesions diagnosed as JXG were identified with the median age of 4.5 years, a male predominance (M:F ratio 1.3:1) and a predilection for the head and neck region (40.8%). Cutaneous lesions comprised 76.8% cases and another 15.7% presented within soft tissues. The most common non-soft tissue, extracutaneous lesions included the brain (2.6%), and lungs (1.8%). Three basic histopathologic patterns were identified: early classic (EJXG) (14.2%), classic (CJXG) (45.3%), and transitional JXG (TJXG) (40.5%). Multinucleated giant cells, either Touton or non-Touton, were most frequently present in CJXG followed by TJXG. Mitosis was rare (<1/10 high-power field) among different patterns. There was an association among the patterns and lymphocytic infiltrates (P = 0.036), and presence of Touton or non-Touton giant cells (P < 0.001 for both) but not for mitotic count (P = 0.105) or eosinophilic infiltrates (P = 0.465). Additionally, there was a correlation between age groups and presence of non-Touton giant cells (P = 0.012) but not for Touton cells (P = 0.127). We have demonstrated that immunophenotypic expression of the lesion was not associated with age at diagnosis nor morphologic pattern: factor XIIIa 192/204 (94.1%), CD11c 75/77 (97.4%), CD4 82/84 (97.6%), CD68 200/201 (99.5%), CD163 15/15 (100%), CD1a 1/110 (0.9%), S-100 48/152 (31.6%), CD31 15/21 (71.4%), and vimentin 104/105 (99.0%). CONCLUSION: We have documented in a substantial series of cases of JXG that there is a correlation between one of the three basic histopathologic patterns with age at diagnosis, but with a consistent immunophenotype among the three patterns. Considering sensitivity and specificity rates, we suggest that a combination of CD11c, CD4, CD1a and either CD163 (preferred) or CD68 stains provides more specific diagnostic yield in the differentiation of JXG from other histiocytic disorders. JXG is also discussed in terms of its relationship and distinction from other similar histiocytic disorders in the context of MAPK/ERK pathway mutations.

Pseudo-Roberts Syndrome: An Entity or Not?

Background: Roberts syndrome is a genetic disorder characterized by tetra-phocomelia with abnormalities of ESCO2. We report a male stillborn with tetra-phocomelia and no ESCO2 mutation. Case report: Pre- and post-natal imaging and autopsy findings included schizencephaly, phocomelia of four limbs, micrognathia, oligodactyly, and cardiopulmonary malformations. Microcephaly on pre-natal imaging was not confirmed by autopsy examination. Karyotype, prenatal chromosome microarray and ESCO2 gene testing were normal. Conclusion: Given the various skeletal anomalies found on autopsy and imaging evaluations, at least phenotypically, our case appeared to conform into Roberts syndrome spectrum. Since the infant did not have the mutation associated with this disorder, this infant could be labeled as the first report of a pseudo-Roberts syndrome because many of his phenotypic anomalies are characteristic of Roberts syndrome in absence of the ESCO2 gene mutation.

Infantile Fibrosarcoma and Other Spindle Cell Neoplasms of Infancy. A Review of Morphologically Overlapping yet Molecularly Distinctive Entities.

BACKGROUND: Regardless of age at presentation, many soft tissue neoplasms have overlapping histopathologic and immunophenotypic features to serve as a diagnostic challenge. CASE REPORT: We reported a case of a spindle cell neoplasm in an infant, which was initially considered a vascular anomaly clinically and an eventual biopsy revealed marked inflammation with a spindle cell component that was resolved as an infantile fibrosarcoma with an ETV6 break-apart. CONCLUSION: The context of this case lead to a further consideration of various other spindle cell neoplasms arising predominantly in the soft tissues during the infancy period as defined by the first two years of age. Though sharing similar morphologic features, these tumors can be categorized into several molecular genetic groups, which have provided both diagnostic and pathogenetic insights as well as treatment options in some cases.

Vascular Malformation and CAP Polyposis: A New Insight into Pathophysiology or Fortuitous Association?

INTRODUCTION: CAP polyposis is a benign colorectal process presenting with multiple colorectal polyps with a "CAP" of inflammatory granulation tissue whose etiology has remained largely unknown. CASE: A 24-year-old male presented with a long-standing history of repeated multiple sessile colonic polyps over a period of 17 years. RESULTS: The numerous polyps showed consistent histologic features of superficial erosion with a surface "CAP" of granulation tissue with minimal submucosa to evaluate over this period. A left hemicolectomy disclosed an extensive vascular malformation. CONCLUSION: The underlying vascular malformation may have an etiologic correlation to the overlying CAP polyps in this patient. Future cases may benefit from an evaluation of the underlying submucosa for the presence of possible vascular malformation likely to be missed on superficial polypectomy.

Confirmation of Xp22.11 Duplication as a Germline Susceptibility Alteration in a Wilms Tumor Arising in Horseshoe Kidney.

BackgroundThere is strong evidence of a genetic contribution to Wilms tumor, such as WT1 gene variation or epigenetic changes at chromosome locus 11p15. A previous genome wide association study (GWAS) of Wilms tumor identified other significant association loci including Xp22. Case report: A 4-year-old girl developed a Wilms tumor of the left isthmus of a horseshoe kidney. Chromosomal microarray analysis (CMA) of peripheral blood showed a 563 kb copy number gain at Xp22.11 that included PRDX4 and ZFX. PRDX4 has been shown to play an active role in the tumorigenesis of malignant neoplasms in various organs. Beckwith-Wiedemann methylation analysis and WT1 sequencing were negative. Whole exome sequencing of peripheral blood revealed pathogenic variant in PMS2 gene (c.765C > A), which is consistent with Lynch syndrome. Conclusion: We report a case of Wilms tumor with germline Xp22.11 duplication which further supports this locus as germline susceptibility alteration for Wilms Tumor.