Morphologic Spectrum of Rhabdomyomatous Mesenchymal Hamartomas (Striated Muscle Hamartomas) in Pediatric Dermatopathology.

BACKGROUND: Rhabdomyomatous mesenchymal hamartomas (RMHs), also termed striated muscle hamartomas, are rare benign tumors of skin and subcutis, which mostly occur at birth with a predilection for the head and neck. Simple surgical excision is the treatment modality of choice with excellent prognosis. OBJECTIVE: To review the spectrum of the different clinical and pathologic features of RMHs in pediatric patients and recognize their characteristics to avoid confusion with other lesions in their list of differential diagnosis. METHODS: Six cases of RMH diagnosed at our institution from 2009 to 2021 were retrieved from our files and reviewed retrospectively after anonymization by an honest broker. This review is IRB-approved by the University of Pittsburgh School of Medicine, study STUDY19080192. RESULTS: The patients' age ranged from 6 days to 8 years, with a female predominance (2:1). In all cases, the lesion was present at birth. All lesions, except for 2, occurred in the head and neck regions. One patient had multiple additional small nodules in the face, whereas all others presented with solitary RMHs. The size of the lesions varied, and their composition included bundles of skeletal muscle (the landmark finding) associated with variable amounts of adipose, fibrous, vascular, nerve, and adnexal structures. CONCLUSIONS: RMH is a benign hamartomatous lesion with a variable phenotypic spectrum. RMHs predominate in the head and neck. Familiarity with these lesions, including their presentation in less frequent anatomical sites, is important to avoid diagnostic misinterpretations and potential overtreatment. This study represents one of the largest series of RMHs in the literature, including an unusual case in a perianal location.

Paraspinal Desmoid Tumor in a Pediatric Patient with No Surgical History: A Case Report.

Desmoid tumors are locally aggressive, benign neoplasms originating in connective tissues. Although the exact pathophysiology remains unknown, antecedent trauma or surgery are believed to be important contributing factors. The occurrence of paraspinal desmoid tumor in pediatric patients is extremely uncommon. Here, we present an exceedingly rare case of a pediatric patient with no surgical or family history who developed a paraspinal desmoid tumor. A 9-year-old female patient presented with 4 months of progressive back pain, right lower extremity weakness, and numbness. Spinal imaging revealed a left epidural paraspinal mass compressing her thoracic spinal cord and extending into the left thoracic cavity. A multidisciplinary approach with neurosurgery and thoracic surgery enabled gross total resection of the lesion. The patient had complete resolution of her symptoms with no signs of residual tumor on postoperative imaging. Pathology revealed a desmoid tumor that avidly stained for beta-catenin. On her last follow-up, she developed a recurrence, to which she was started on sorafenib therapy. Desmoid tumors are rare connective tissue neoplasms that often occur after local tissue trauma, such as that caused by surgery. This report presents a rare case of a pediatric paraspinal desmoid tumor that occurred in a patient with no surgical or family history. Such tumors should undergo surgical resection for symptomatic relief and tissue diagnosis. Close clinical and radiographic surveillance are essential in these patients due to the high recurrence rates of desmoid tumor.

Morphologic and Ancillary Studies of Pediatric Acinic Cell Carcinoma: A Single Institute Experience.

BACKGROUND: Acinic cell carcinoma (AciCC) is the second most common pediatric malignant salivary gland tumor. However, there are limited pathology publications about this tumor in the pediatric population. METHODS: We describe four pediatric AciCC cases diagnosed between 2000 and 2021 in our institute. Reticulin histochemistry plus immunohistochemistry for NR4A3 and DOG1 were performed on all cases. RESULTS: Histologically, all four cases featured a tumor-associated lymphoid proliferation and collagenous stroma, in which two formed central scars. The tumors were predominantly solid, with a lobular pattern and variably sized dilated spaces, including one case with focal microcysts. High-grade transformation was not observed in any of our cases. Reticulin stain and immunohistochemistry for NR4A3 showed distinct features between AciCC and non-neoplastic salivary gland parenchyma. DOG1 immunohistochemistry confirmed the acinar origin of AciCC. CONCLUSIONS: Our study reveals that pediatric AciCCs often present with tumor-associated lymphoid proliferation (TALP) and sclerosis. Special stains such as reticulin histochemistry and NR4A3 immunohistochemistry are helpful to separate tumor from adjacent benign parenchyma. The ancillary study is helpful for the diagnosis of small specimens. Our study is limited by its low case number, but we hope that our results will promote more studies on this rare salivary gland tumor in the pediatric population.

Congenital panfollicular nevus associated with polydactyly.

A 2-year-old girl presented with ulnar-sided duplication of the left thumb distal to the interphalangeal joint and syndactyly of the first web space. She also had several asymptomatic pink-tan cutaneous papules, involving the first and second ray of the left hand and wrist, clinically resembling a linear epidermal nevus. Microscopically, the papules were composed of well-circumscribed aggregates of basaloid epithelium within the dermis. No normal hair follicles were identified. Follicular germ and papillae were identified, representing abortive attempts at hair follicle formation. The features were remarkably similar to a novel entity described by Finn and Argenyi as congenital panfollicular nevus. In our case, the congenital panfollicular nevus was associated with distal thumb polysyndactyly, which may suggest an important link between limb patterning and hair follicle development.

Multimodality management of metastatic patients with soft tissue sarcomas may prolong survival.

OBJECTIVES: Patients who develop metastatic disease from soft tissue sarcoma have a poor prognosis. The purpose of this study was to identify metastatic survival rates and identify prognostic variables that predict for these outcomes. METHODS: Between 2000 and 2010, 182 patients with stage I to IV primary soft tissue sarcomas of the extremity and trunk were treated with multimodality treatment. Fifty-five patients developed or presented with metastasis. We retrospectively analyzed prognostic factors for metastatic survival. Metastatic survival between groups was compared with the log-rank test. Survival curves were estimated by Kaplan-Meier plots. Multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Median follow-up was 3.1 years. Median metastatic survival was 24.2 months. Median metastatic survival in those undergoing multimodality therapies was 40 versus 22 months in those receiving single modality treatments. In single predictor Cox models, age, stage, number of lung metastases, location of metastases, and primary disease were significant for metastatic survival. On multivariate analysis, number of pulmonary metastases, histology, stage, and location of primary disease predicted for metastatic survival. Patients who had pulmonary-only disease had improved metastatic survival versus those that had extrapulmonary with or without pulmonary metastatic disease (38 vs. 15 mo). Patients who had ≤5 pulmonary metastasis had improved metastatic survival versus those that had >5 pulmonary lesions (55 vs. 22 mo). CONCLUSIONS: This analysis shows that >5 pulmonary metastasis, malignant fibrous histiocytoma histology, stage III disease, and proximal lower extremity sarcomas are associated with decreased metastatic survival. Moreover, aggressive multimodality management of metastatic disease may prolong metastatic survival.

Prognostic variables in patients with primary soft tissue sarcoma of the extremity and trunk treated with neoadjuvant radiotherapy or neoadjuvant sequential chemoradiotherapy.

BACKGROUND: Neoadjuvant radiotherapy (NRT) is an effective strategy to treat soft tissue sarcomas (STS). However, the role of neoadjuvant chemoradiotherapy (NCRT) remains to be determined. METHODS: From May 1999 to July 2010, 112 patients with localized STS of the extremity and trunk who were treated with NRT or NCRT followed by surgery were retrospectively reviewed. Clinical outcomes including overall survival (OS), disease-free survival (DFS), and distant metastasis free survival (DMFS) were calculated using Kaplan-Meier survival analyses. Prognostic variables were determined by univariate (UVA) and multivariate analyses (MVA). RESULTS: Median follow-up was 37 months. Median RT dose was 50 Gy. Forty-nine patients received NCRT. Overall limb-preservation rate was 99% and local control was 97%. The estimated 3-year OS, DFS, and DMFS were 86%, 68%, and 72%, respectively. Age was the only variable to predict for OS, DFS and DMFS on UVA. Age ≥ 70 predicted for poor OS, stage III disease predicted for poor DFS and DMFS, and the addition of chemotherapy predicted for improved DMFS on MVA. CONCLUSIONS: Excellent rates of local control and limb-preservation were observed in patients with primary STS treated with neoadjuvant therapy followed by surgery. Neoadjuvant sequential chemotherapy followed by radiotherapy may be considered for young patients with stage III STS.

Unusual pulmonary findings in mucolipidosis II.

We report undescribed pulmonary findings in a child with mucolipidosis II (ML-II). Children with ML-II bear significant pulmonary morbidity that may include extensive pulmonary fibrosis, persistent hemosiderosis as well as pulmonary airway excrescences as they reach preschool age.

Malignant gastrointestinal neuroectodermal tumor: clinicopathologic, immunohistochemical, ultrastructural, and molecular analysis of 16 cases with a reappraisal of clear cell sarcoma-like tumors of the gastrointestinal tract.

The clinical, histologic, immunophenotypic, ultrastructural, and molecular features of a distinctive gastrointestinal tumor are described. Sixteen patients, 8 women and 8 men aged 17 to 77 years (mean age, 42 y; 63% less than 40 y) presented with abdominal pain, intestinal obstruction, and an abdominal mass. Mean tumor size was 5.2 cm (range, 2.4 to 15.0 cm). The tumors arose in the small bowel (10), stomach (4), and colon (2) and were histologically characterized by a sheet-like or nested population of epithelioid or oval-to-spindle cells with small nucleoli and scattered mitoses. Five cases showed focal clearing of the cytoplasm. Scattered osteoclast-type multinucleated giant cells were present in 8 cases. The tumor cells were positive for S-100 protein, SOX10, and vimentin in 100% of cases, for CD56 in 70%, for synaptophysin in 56%, for NB84 in 50%, for NSE in 45%, and for neurofilament protein in 14% of cases. All cases tested were negative for specific melanocytic, gastrointestinal stromal tumors, epithelial, and myoid markers. Ultrastructural examination of 5 cases showed features of primitive neuroectodermal cells with clear secretory vesicles, dense-core granules, occasional gap junctions, and no evidence of melanogenesis. EWSR1 gene rearrangement was assessed by fluorescence in situ hybridization in 14 cases. Twelve cases (86%) showed split EWSR1 signal consistent with a chromosomal translocation involving EWSR1. One case showed extra intact signals, indicating that the nuclei possessed either extra copies of the EWSR1 gene or chromosome 22 polysomy. Only 1 case showed no involvement of the EWSR1 gene. Six cases demonstrated rearrangement of the partner fusion gene ATF1 (46%), and 3 showed rearrangement of CREB1 (23%); 2 cases lacked rearrangement of either partner gene. Clinical follow-up was available in 12 patients and ranged from 1.5 to 106 months. Six patients died of their tumors (mean survival, 32 mo; 83% less than 24 mo). At last follow-up, 4 patients were alive with regional, lymph node, and liver metastases, and 2 patients were alive with no evidence of disease. The tumor described here is an aggressive form of neuroectodermal tumor that should be separated from other primitive epithelioid and spindle cell tumors of the gastrointestinal tract. The distinctive ultrastructural features and absence of melanocytic differentiation serve to separate them from soft tissue clear cell sarcomas involving the gastrointestinal tract. The designation "malignant gastrointestinal neuroectodermal tumor" is proposed for this tumor type.

Caracterización de mutaciones en el gen de la adenilosuccinato liasa (ASL) en un paciente con epilepsia, retardo psicomotor y autismo / Characterization of mutations in the gene of the adenilosuccinato liasa (ASL) in a patient with epilepsy, psicomotor retardation and aautismo

Analiza que la enzima adenilo succinato liasa cataliza dos pasos en la vía de doce pasos desde fosforibosil pirofosfato (PRPP) a monofosfato de inosina (IMP) y monofosfato de adenosina (AMP). La deficiencia de ASL (McKussick 103050) es el primer defecto reportado de humanos en la vía de síntesis de novo de las purinas. Es un error innato del metabolismo,autosónico recesivo, caracterizado por retardo mental, características de autismo, epilepsia, desgaste muscular y retardo sicomotor, junto con la prescencia en líquidos corporales de dos compuestos, succinil adenosina (S-Ado) y succinil aminoimidazol carboximida ribósico (SAICAribósido), derivados desfosforilados de dos metabolitos intermedios de la vía de síntesis de novo de las purinas. Un paciente con características clínicas y de laboratorio de deficiencia severa de ASL...