Embryonal and alveolar rhabdomyosarcoma in adolescents/young adults, adults and older adults: a population-based cohort study.

BACKGROUND: The clinical characteristics, outcomes, and prognostic factors of adult embryonal rhabdomyosarcomas (ERMS) and alveolar rhabdomyosarcomas (ARMS), particularly the differences among adolescents/young adults (AYA), adults, and older adults, remain unclear. We assessed the clinicopathological features and survival outcomes of adult patients with ERMS and ARMS in Japan and to compare these features among AYA, adult, and older adult patients. METHODS: We retrospectively analyzed data from the Bone and Soft Tissue Tumor Registry of Japan and enrolled patients aged ≥15 years with ERMS and ARMS. Disease-specific overall survival (DOS) was estimated using the Kaplan-Meier method, and a Cox regression model was used to identify prognostic factors. RESULTS: Among 184 patients with ERMS and ARMS (median age, 27 years; interquartile range, 18-49 years), a high rate of distant and regional nodal metastases was initially observed in 65 (35%) and 66 (36%) cases, respectively. Older age and distant metastasis at first presentation were statistically poor prognostic factors, and histological subtype and site of tumor origin were not associated with DOS. In patients with localized ERMS and ARMS, older age and nodal metastasis were poor prognostic factors; the 5-year DOS rates of patients with and without nodal metastasis were 23% and 72%, respectively. CONCLUSIONS: Older patients with rhabdomyosarcoma had a dismal prognosis, and distant metastasis was a poor prognostic factor. The prognostic factors differed between adult and pediatric patients with rhabdomyosarcoma; biological analyses, such as genome analysis of adult rhabdomyosarcoma and clinical trials with pediatric oncologists, are needed to improve the prognosis of adult rhabdomyosarcoma.

Staufen1 controls mitochondrial metabolism via HIF2α in embryonal rhabdomyosarcoma and promotes tumorigenesis.

Elevated mitochondrial metabolism promotes tumorigenesis of Embryonal Rhabdomyosarcomas (ERMS). Accordingly, targeting oxidative phosphorylation (OXPHOS) could represent a therapeutic strategy for ERMS. We previously demonstrated that genetic reduction of Staufen1 (STAU1) levels results in the inhibition of ERMS tumorigenicity. Here, we examined STAU1-mediated mechanisms in ERMS and focused on its potential involvement in regulating OXPHOS. We report the novel and differential role of STAU1 in mitochondrial metabolism in cancerous versus non-malignant skeletal muscle cells (NMSkMCs). Specifically, our data show that STAU1 depletion reduces OXPHOS and inhibits proliferation of ERMS cells. Our findings further reveal the binding of STAU1 to several OXPHOS mRNAs which affects their stability. Indeed, STAU1 depletion reduced the stability of OXPHOS mRNAs, causing inhibition of mitochondrial metabolism. In parallel, STAU1 depletion impacted negatively the HIF2α pathway which further modulates mitochondrial metabolism. Exogenous expression of HIF2α in STAU1-depleted cells reversed the mitochondrial inhibition and induced cell proliferation. However, opposite effects were observed in NMSkMCs. Altogether, these findings revealed the impact of STAU1 in the regulation of mitochondrial OXPHOS in cancer cells as well as its differential role in NMSkMCs. Overall, our results highlight the therapeutic potential of targeting STAU1 as a novel approach for inhibiting mitochondrial metabolism in ERMS.

DICER1-mutated rhabdomyosarcoma of the ovary with teratoid features.

DICER1-mutated rhabdomyosarcoma is a rare, emerging entity with a predilection for the gynecologic and genitourinary tracts. We report here a case of DICER1-mutated rhabdomyosarcoma of the ovary in a 14 years old girl which displayed interspersed mature teratoid glands, neuroectodermal rosettes and immature blastematous-like tubes. Morphologically the sarcomatous component predominated, corresponding to a high grade spindle cell rhabdomyosarcoma with botryoid features. Islets of cartilage were present. The sarcomatous proliferation encased the teratoid glands, forming cambium layer-like arrangements. The sarcoma cells were Myogenin and MYOD1 positive, the neuroectodermal rosettes expressed SALL4 along with cytokeratins and EMA and were negative for Inhibin; immature blastematous-like tubes were negative for SALL4 and Inhibin. Whole RNA- and targeted DNA-sequencing revealed two DICER1 mutations in exon 26: c.5113G>A: p.(Glu1705Lys) and exon 12: c.1642C>T: p.(Gln548X). The sarcomatous component harbored a complex genetic profile while the teratoid component was diploid, none of the above displayed abnormality of 12p. DICER1-mutated sarcomas display pathological features similar to embryonal rhabdomyosarcomas, botryoid type. They also display heterogeneous features combining cartilage foci, teratoid mature glands, immature blastematous-like tubes and/or neuroectodermal components. Molecular testing remains necessary to confirm the diagnosis. Further studies need to clarify the nosology of DICER1-mutated sarcomas and devise specific therapeutic strategies.

Oral rhabdomyosarcoma, a rare malignant tumor mimicking an endodontic-periodontal lesion in an adult patient: a case report.

BACKGROUND: According to previous research, 2.8% of lesions clinically identified as endodontic pathosis were ultimately diagnosed as non-endodontic periapical lesions via histopathology, and 3.7% of these non-endodontic periapical lesions were malignant neoplasms. Rhabdomyosarcoma, a malignant tumor most commonly observed in children, is uncommon in the oral cavity. CASE PRESENTATION: This is a report of a rare case of embryonal rhabdomyosarcoma in a 41-year-old female, in which the lesion was in the maxillary gingiva. The biopsy reports confirmed the diagnosis of embryonal rhabdomyosarcoma. The wide excision of the tumor, free flap reconstruction, chemotherapy, and radiotherapy were performed. Clinical, radiological, and histopathological and management aspects of the neoplasm were also discussed. CONCLUSIONS: This case report aimed to create awareness that rhabdomyosarcoma is one of the differential diagnoses of periapical lesions.

Successful pregnancy in a female with embryonal rhabdomyosarcoma of the cervix who received biopsy and chemotherapy alone without recurrence after 16 years: a case report and literature review.

BACKGROUND: Embryonal rhabdomyosarcoma (ERMS) of the uterine cervix is rare, but the population affected is mostly underage females. The scope of surgery has now evolved from extensive to limited, and organ-preserving surgery combined with chemotherapy is recommended to preserve the patient's fertility. However, reports of birth outcomes are rare. CASE: A minor woman with cervical ERMS who underwent only an outpatient biopsy of the lesion had no residual lesion on subsequent multipoint cervical biopsy and refused radical surgery or cervical conization, after which the patient received a nonclassical regimen of chemotherapy. The patient stopped the chemotherapy on her own, but the patient conceived spontaneously 16 years later with a good pregnancy outcome and no recurrence. CONCLUSIONS: This case suggests that preservation of reproductive function is often feasible in immature women with cervical ERMS, and the prognosis is usually good as long as the primary tumour can be surgically removed and the lesion is free of residual disease. We also look forward to reports of subsequent growth and pregnancy outcomes in other children with reproductive tract RMS. In cervical ERMS, accurate evaluation of the disease and development of an individualized treatment plan are crucial, and the protection of reproductive function and psychological well-being deserves special attention.

Clinicopathologic and survival correlates of embryonal rhabdomyosarcoma driven by RAS/RAF mutations.

Embryonal rhabdomyosarcoma (ERMS) is the most common subtype of rhabdomyosarcoma (RMS). Among RMS subtypes, ERMS is associated with a favorable outcome with an overall survival of 70% at 5 years for localized disease. The molecular profile of ERMS is heterogeneous, including mostly point mutations in various genes. Therapeutic strategies have remained relatively consistent irrespective of the molecular abnormalities. In this study, we focus on a homogeneous RAS/RAF mutated ERMS subset and correlate with clinicopathologic findings. Twenty-six cases (16 males and 10 females) were identified from screening 98 ERMS, either by targeted DNA sequencing (MSK-IMPACT) or by Sanger sequencing. Fourteen (54%) cases had NRAS mutations, 6 (23%) had KRAS mutations, 5 (19%) had HRAS mutations, and 1 case (4%) had BRAF mutation. Median age at diagnosis was 8 years (range 1-70) with two-thirds occurring in the children. Tumor sites varied with H&N and GU sites accounting for 62% of cases. RAS isoform hot spot mutations predominated: NRAS p.Q61K (57%), KRAS p.G12D (67%), and HRAS (codons 12, 14, and 61). Additional genetic abnormalities were identified in 85% of the RAS-mutated cases. At last follow-up, 29% of patients died of disease and 23% were alive with disease. The 3-year and 5-year survival rates were 75% and 61% respectively. In conclusion, RAS mutations occur in 27% of ERMS, with NRAS mutations encompassing half of the cases. Overall RAS-mutant RMS does not correlate with age or site, but most tumors show an undifferentiated and spindle cell morphology.

Patients with completely resected nongenitourinary low-risk embryonal rhabdomyosarcoma are candidates for reduced duration low-intensity chemotherapy.

BACKGROUND: The survival of patients with localized embryonal rhabdomyosarcoma (RMS) completely resected at diagnosis is greater than 90%. Most patients have paratesticular, uterine, or vaginal RMS, limiting specific analyses of RMS localized in other anatomic regions. This international study was conducted to define the outcome for completely resected embryonal RMS at sites other than paratesticular, uterine, or vaginal primary sites. METHODS: A total of 113 patients aged 0-18 years were identified who were enrolled from January 1995 to December 2016 in Children's Oncology Group (COG) (64 patients) and European protocols (49). Genitourinary nonbladder and prostate RMS were excluded. The recommended chemotherapy was vincristine and actinomycin-D (VA) for 24 weeks or ifosfamide plus VA in the European protocols and VA for 48 weeks or VA plus cyclophosphamide in the COG protocols. RESULTS: The most common primary sites were nonparameningeal head and neck (40.7%), other (23.9%), and extremities (20.4%). In the COG studies, 42% of patients received VA and 58% VA plus cyclophosphamide. In Europe, 53% received VA and 47% ifosfamide plus VA. With a median follow-up of 97.5 months, the 5-year progression-free and overall survival was 80.0% (71.2%-86.4%) and 92.5% (85.6%-96.2%), respectively, without significant differences between chemotherapy regimens. Tumor size (< or >5 cm) significantly influenced overall survival: 96.2% (88.6%-98.8%) vs. 80.6% (59.5%-91.4%), respectively (p = .01). CONCLUSIONS: Survival of patients with nonalveolar RMS completely resected at diagnosis is excellent among tumors arising from nonparatesticular, uterine, and vaginal sites, and patients may be treated successfully with low-intensity chemotherapy. To reduce the burden of treatment, VA for 24 weeks may be considered in children with tumors <5 cm.

DICER1-associated embryonal rhabdomyosarcoma and adenosarcoma of the gynecologic tract: Pathology, molecular genetics, and indications for molecular testing.

Gynecologic sarcomas are uncommon neoplasms, the majority occurring in the uterus. Due to the diverse nature of these, the description of "new" morphological types and the rarity of some of them, pathological diagnosis and treatment is often challenging. Finding genetic alterations specific to, and frequently occurring, in a certain type can aid in the diagnosis. DICER1 is a highly conserved ribonuclease crucial in the biogenesis of microRNAs and mutations in DICER1 (either somatic or germline) have been detected in a wide range of sarcomas including genitourinary embryonal rhabdomyosarcomas (ERMS) and adenosarcomas. Importantly, DICER1-associated sarcomas share morphological features irrespective of the site of origin such that the pathologist can strongly suspect a DICER1 association. A review of the literature shows that almost all gynecologic ERMS reported (outside of the vagina) harbor DICER1 alterations, while approximately 20% of adenosarcomas also do so. These two tumor types exhibit significant morphological overlap and DICER1 tumor testing may be helpful in distinguishing between them, because a negative result makes ERMS unlikely. Given that germline pathogenic DICER1 variants are frequent in uterine (corpus and cervix) ERMS and pathogenic germline variants in this gene cause a hereditary cancer predisposition syndrome (DICER1 syndrome), patients diagnosed with these neoplasms should be referred to medical genetic services. Cooperation between pathologists and geneticists is crucial and will help in improving the diagnosis and management of these uncommon sarcomas.

Novel findings and expansion of phenotype in a mosaic RASopathy caused by somatic KRAS variants.

Mosaic KRAS variants and other RASopathy genes cause oculoectodermal, encephalo-cranio-cutaneous lipomatosis, and Schimmelpenning-Feuerstein-Mims syndromes, and a spectrum of vascular malformations, overgrowth and other associated anomalies, the latter of which are only recently being characterized. We describe eight individuals in total (six unreported cases and two previously reported cases) with somatic KRAS variants and variably associated features. Given the findings of somatic overgrowth (in seven individuals) and vascular or lymphatic malformations (in eight individuals), we suggest mosaic RASopathies (mosaic KRAS variants) be considered in the differential diagnosis for individuals presenting with asymmetric overgrowth and lymphatic or vascular anomalies. We expand the association with embryonal tumors, including the third report of embryonal rhabdomyosarcoma, as well as novel findings of Wilms tumor and nephroblastomatosis in two individuals. Rare or novel findings in our series include the presence of epilepsy, polycystic kidneys, and T-cell deficiency in one individual, and multifocal lytic bone lesions in two individuals. Finally, we describe the first use of targeted therapy with a MEK inhibitor for an individual with a mosaic KRAS variant. The purposes of this report are to expand the phenotypic spectrum of mosaic KRAS-related disorders, and to propose possible mechanisms of pathogenesis, and surveillance of its associated findings.

Magnetic resonance features and cranial nerve involvement in pediatric head and neck rhabdomyosarcomas.

PURPOSE: Rhabdomyosarcoma (RMS) is a malignant tumor frequent in children. The frequency and characteristics of cranial nerve involvement in pediatric head and neck (H&N) RMS have been scarcely reported. The aim of this study is to review a large cohort of pediatric head and neck RMS with an emphasis on cranial nerve involvement. METHODS: We retrospectively reviewed H&N RMS cases from 3 tertiary hospitals over a 10-year period. Cranial nerve involvement was defined as radiologically apparent tumor extension along a nerve and/or the presence of secondary signs. Scans were reviewed by two pediatric neuroradiologists, blinded to clinical data. RESULTS: A total of 52 patients met the inclusion criteria. Histologically, 39/52 were embryonal RMS, while 13/52 were alveolar RMS. Regional lymph nodes metastases were present in 19.2%. Cranial nerve involvement was present in 36.5%. Nerves were mainly involved as a direct extension of the mass through skull base foramina or after invasion of cavernous sinus, Meckel's cave, orbital apex, or stylomastoid foramen. CONCLUSION: Cranial nerve involvement is frequent in pediatric head and neck RMS and occurs secondary to "geographic" invasion due to direct extension through skull base foramina or cavernous sinus. These tumors never showed distant perineural metastatic disease as is seen in cases of adult head and neck carcinomas. This implies a different biological interaction between the nerves and these tumors in comparison to adult H&N tumors.

Metastatic embryonal rhabdomyosarcoma of the breast: A case report and literature review.

Rhabdomyosarcoma (RMS) is a common malignancy in children, but embryonal rhabdomyosarcoma (ERMS) deposits rarely occur in the breast in adults. Therefore, little is known about magnetic resonance imaging (MRI) features of breast metastases from RMS, especially the embryonal type. We reported a case of a 22-year-old woman who was diagnosed with ERMS at left foot 2 years ago and accepted operation and chemotherapy. She was confirmed to have breast metastases from the left foot. Successive imaging examinations were performed 3 months apart. Breast ultrasound indicated a benign lesion, and further examination did not reveal any bone metastases. However, predominant restricted diffusion and rim contrast enhancement on MRI combined with the patient's medical history suggested a malignancy of BI-RADS 5. After 3 months, breast ultrasound revealed masses detected last time became larger and lobulated. In addition, internal heterogeneous intensity and rim contrast enhancement with restricted diffusion were revealed on MRI. We speculated that typical MRI findings of breast metastases from RMS may include iso- to hypointensity on T1WI, heterogeneous hyperintensity on T2WI, and circular enhancement with restricted diffusion. Moreover, mild peritumoral edema, rapid expansion of necrosis, and ascending time-intensity curve detected on MRI may be features of the ERMS type.

Distinct clonal evolution in a case with anaplastic embryonal rhabdomyosarcoma.

BACKGROUND: Clonal evolution of malignancy is a complex process related to intratumoral heterogeneity, as recent studies have also demonstrated in rhabdomyosarcoma. The purpose of this study is to present a distinct clonal feature of a case with anaplastic embryonal type rhabdomyosarcoma (ERMS) using molecular analysis. METHODS: A five-year-old girl developed a metastatic pelvic tumor. We cultured neoplastic cells isolated from the biopsy sample. Next, to characterize the current case, we analyzed the biopsy sample, autopsy sample, and established cell line using combined modalities, including histopathological, cytogenetic, and molecular assay. We also undertook the backtrack mutation-specific polymerase chain reaction to reveal clonal composition. RESULTS: The histology of the biopsy sample was consistent with ERMS with focal anaplasia. We established a permanently growing cell line, ICH-ERMS-1, from the biopsy sample. On molecular analysis, the biopsied tissue revealed a missense mutation at codon 245 of TP53. In contrast, the autopsy tumor tissue and the cell line established from the biopsied tissue showed a missense mutation at codon 248. A backtrack study using mutation-specific polymerase chain reaction detected a TP53 codon 248 mutation in the original biopsy sample. All the specimens examined had a missense mutation at PTPN11 codon 69. CONCLUSIONS: This study highlights intratumoral heterogeneity and distinct clonal change related to the functional context in our anaplastic ERMS case, supporting the concept of intratumoral heterogeneity and clonal evolution. It requires further case collection to reveal whether p14ARF-p53-MDM2 tumor suppressor pathway alteration, considered a late event in ERMS tumorigenesis, is responsible for anaplasia in ERMS.

Loss of H3K27me3 occurs in a large subset of embryonal rhabdomyosarcomas: Immunohistochemical and molecular analysis of 25 cases.

Loss of histone 3 lysine 27 trimethylation (H3K27me3) has been described as a diagnostic marker for malignant peripheral nerve sheath tumor (MPNST), also discriminating MPNST with rhabdomyoblastic differentiation (malignant Triton tumor) from rhabdomyosarcoma (RMS). We studied the immunohistochemical expression of H3K27me3 in embryonal RMSs (ERMSs), performed methylation profiling in order to support the diagnosis and RNA-sequencing for comparison of the transcriptome of H3K27me3-positive and -negative cases. Of the 25 ERMS patients, 17 were males and 8 were females with an age range from 1 to 67 years (median, 6 years). None were known with neurofibromatosis type 1. One patient had Li-Fraumeni syndrome. Tumor localization included paratesticular (n = 9), genitourinary (n = 6), head/neck (n = 5), retroperitoneal (n = 4) and lower arm (n = 1). Five MPNSTs served as reference group. All ERMS had classical features including a variable spindle cell component. Immunohistochemical loss (partial or complete) of H3K27me3 was detected in 18/25 cases (72%). Based on methylation profiling, 22/22 cases were classified as ERMS. Using RNA sequencing, the ERMS group (n = 14) had a distinct gene expression profile in contrast to MPNSTs, confirming that the H3K27me3 negative ERMS cases do not represent malignant Triton tumors. When comparing H3K27me3-negative and -positive ERMSs, gene set enrichment analysis revealed differential expression of genes related to histone acetylation and normal muscle function with H3K27me3 negative ERMSs being associated with acetylation. Conclusion: Loss of H3K27me3 frequently occurs in ERMSs and correlates with H3K27 acetylation. H3K27me3 is not a suitable marker to differentiate ERMS (with spindle cell features) from malignant Triton tumor.

NRAS associated RASopathy and embryonal rhabdomyosarcoma.

RASopathies are a group of phenotypically overlapping disorders that arise from dysregulation of the RAS/MAPK pathway. These disorders include Noonan syndrome, Costello syndrome, cardiofaciocutaneous syndrome, and neurofibromatosis-Type 1. While somatic mutations in the three human Ras genes (KRAS, HRAS, and NRAS) are a common finding in a variety of cancers, germline mutations in each of the these genes cause developmental RASopathy phenotypes with mutations in specific genes typically correlating with specific phenotypes. We present the case of a germline heterozygous NRAS mutation producing a severe phenotype involving embryonal rhabdomyosarcoma, severe intellectual disability, and numerous melanocytic nevi in addition to more typical manifestations of Noonan syndrome. Additionally, the specific p.G12R NRAS mutation in this case is a common somatic mutation in cancer cells, and analysis of previously reported NRAS-RASopathy cases suggests that mutations at traditionally oncogenic codons are associated with elevated cancer risk not present with mutations at other sites.

Gynecologic and reproductive health in patients with pathogenic germline variants in DICER1.

OBJECTIVE: Germline pathogenic variation in DICER1 underlies a tumor-predisposition disorder with increased risk for cervical embryonal rhabdomyosarcoma and ovarian sex-cord stromal tumors, particularly Sertoli-Leydig cell tumors. The gynecologic and reproductive health of these females has not yet been described. METHODS: All female subjects recruited from November 2011 to July 2018 participating in an epidemiologic study of families with pathogenic DICER1 germline variation were included in this cross-sectional analysis. Participant evaluation included obstetric-gynecologic history, physical examination, hormone testing, pelvic ultrasound and record review. RESULTS: Of 64 females aged 2-72 years, fifteen underwent treatment for pleuropulmonary blastoma as children and three were treated for cervical embryonal rhabdomyosarcoma. Of nine patients reporting a history of ovarian tumors, all presented with virilization or amenorrhea; eight occurred in adolescence. Post-pubertal females with no history of ovarian tumors experienced normal pubertal development, reported regular menstrual cycles, were fertile and underwent natural menopause at median age of 52 years. Thirty-two of 33 women who tried to conceive successfully delivered liveborn children. Of these 32, 10 experienced pregnancy-related thyroid enlargement resulting in thyroidectomy within one year of pregnancy; nine others had undergone pre-pregnancy thyroidectomy. CONCLUSION: In these DICER1-carrier females, DICER1-related gynecological tumors occurred during childhood or adolescence in some after which women generally experienced healthy reproductive lives. Individual education and screening for these tumors is warranted. The high rate of DICER1-related multinodular goiter resulting in pre- and post-pregnancy thyroidectomy underscores the importance of thyroid monitoring during pregnancy to ensure maternal and fetal wellbeing.

One-Step Lower Leg Reconstruction with Vascularized Functional Vastus Lateralis Muscle Flap in the Treatment of Embryonal Rhabdomyosarcoma for a Six-Month-Old Boy: A Case Report.

Rhabdomyosarcoma (RMS) is a common soft tissue sarcoma in childhood, however, it is very rare in the neonatal period (0.4-2% of cases). This case depicts a boy, who presented with RMS at two weeks of age, but officially diagnosed at the age of three months. MRI and scintigraphy determined a soft tissue tumor in the soleus muscle, while biopsy confirmed embryonal RMS with high mitotic activity (Ki67 (monoclonal antibodies) ~80%). CWS (Cooperative Weichteilsarkom Studiengruppe)-2012 with I2VA (ifosfamide, vincristine, actinomycin) chemotherapy regimen was administered per protocol. Surgical treatment was performed at age of six months and 18 days. The operation consisted of radical tumor resection and total triceps surae with partial fibula resection. Immediate reconstruction of triceps muscle was accomplished using a vascularized functional musculocutaneous vastus lateralis flap. Functional outcome was measured using the Lower Extremity Functional Scale (LEFS) and the Foot and Ankle Outcome Score (FAOS) with the results of 92.5% and 99% respectively.

The clinical and radiologic features of paediatric rhabdomyosarcoma.

Rhabdomyosarcoma is the most common soft-tissue sarcoma in children. The most common sites are head and neck, genitourinary tract and extremities. In this review we outline the clinical and radiologic features of paediatric rhabdomyosarcoma, as well as imaging considerations and imaging of relapse.

DICER1 syndrome: Approach to testing and management at a large pediatric tertiary care center.

BACKGROUND: To expand the current knowledge of DICER1 syndrome and to propose criteria for genetic testing based on experience at a pediatric tertiary care center. PROCEDURE: This study involved a retrospective chart review of the 78 patients (47 probands and 31 family members) seen in the Cancer Genetics Program at The Hospital for Sick Children (SickKids) who were offered genetic testing for DICER1. RESULTS: Of 47 probands offered genetic testing for DICER1, 46 pursued testing: 11 (23.9%) carried a pathogenic variant and one proband (2.1%) carried a missense variant of uncertain significance with evidence for pathogenicity. Thirty-one family members of variant-positive probands were offered testing: eight of the 25 who agreed to testing carried their familial variant (32.0%). Overall, 20 patients were identified to have a variant in DICER1 (eight males, 12 females). Of these, 13 (65.0%) presented with clinical manifestations associated with the syndrome. The most common lesions were pleuropulmonary blastoma (PPB) (five of 20 patients, 25.0%) and pineoblastoma (three of 20 patients, 15.0%). The average age at which individuals were diagnosed with a primary neoplasm was 5.2 years (range 0.8-20 years, median 3.0). Surveillance at our institution, with a median follow-up time of 23 months, has identified PPB in two asymptomatic individuals. These lesions were identified at early stages, thus potentially reducing treatment-related morbidity and mortality. CONCLUSION: This study further delineates the DICER1 syndrome phenotype and demonstrates the feasibility of a DICER1 syndrome surveillance protocol for the early detection of tumors.

Vaginoscopic Resection for Vaginal Rhabdomyosarcoma during Early Infancy: A Case Report.

Embryonal rhabdomyosarcoma, a malignant soft tissue neoplasm, is 1 of the most common pediatric tumors of the vagina. Although radical surgery has been replaced with radiation therapy, chemotherapy, and conservative surgery, the use of vaginoscopy is still uncommon. We present the case of an infant who underwent vaginoscopic resection because of botryoid sarcoma at 9 months of age.

Clinicopathologic features of 300 rhabdomyosarcomas with emphasis upon differential expression of skeletal muscle specific markers in the various subtypes: A single institutional experience.

The present study was aimed at evaluating clinicopathologic and immunohistochemical (IHC) features of 300 rhabdomyosarcomas (RMSs), including differential IHC expression and prognostic value of myogenin and MyoD1 across various subtypes of RMSs. IHC expression of myogenin and MyoD1 was graded on the basis of percentage of tumor cells displaying positive intranuclear immunostaining i.e. grade 1 (1-25%); grade 2 (26-50%); grade 3 (51-76%) and grade 4 (76-100%).Clinical follow-up was available in 238 (79.3%) patients. Various clinicopathologic parameters were correlated with 3-year disease free survival (DFS) and overall survival (OS). There were 140 cases (46.7%) of alveolar RMS (ARMS), 90 of embryonal RMS (ERMS) (30%), 61 (20.3%) of spindle cell/sclerosing RMS and 9 cases (3%) of pleomorphic RMS. Most cases, barring pleomorphic RMSs, occurred in the first two decades (228 cases) (76%), frequently in males, in the head and neck region (126) (42%). By immunohistochemistry, desmin was positive in 292/299 (97.6%) tumors; myogenin in 238/267 (89.1%) and MyoD1 in 192/266 (72.2%) tumors. High myogenin expression (in ≥51% positive tumor cells) was significantly associated with ARMSs (95/121, 78.5%), as compared to other subtypes (48/117, 41%) (p value < 0.001). High MyoD1 expression (≥51% tumor cells) was seen in more cases of pure sclerosing, combined with spindle cell/sclerosing RMSs (10/10, 100%), as compared to the other subtypes (91/141, 67.4%) (p = 0.032). There was no significant difference between high myogenin expression and clinical outcomes. Patients without metastasis and harbouring tumors, measuring ≤5 cm showed a significant increase in OS, with p values = 0.01 and <0.001, respectively. ARMS was the most frequent subtype. There was a significant association between high myogenin expression and ARMSs and high MyoD1 expression and spindle cell/sclerosing RMSs. High myogenin expression did not correlate with clinical outcomes. Patients with smaller sized tumors and without metastasis had significantly better clinical outcomes.