Mesotheliomas in Children.

Mesotheliomas are rare and aggressive tumors that originate from mesothelial cells. Although exceedingly rare, these tumors may occur in children. Different from adult mesotheliomas, however, environmental exposures particularly to asbestos do not appear to play a major role in mesotheliomas in children, in whom specific genetic rearrangements driving these tumors have been identified in recent years. These molecular alterations may increasingly offer opportunities for targeted therapies in the future, which may provide better outcomes for these highly aggressive malignant neoplasms.

NEMO-NDAS: A Panniculitis in the Young Representing an Autoinflammatory Disorder in Disguise.

ABSTRACT: A 15-month-old full-term boy of African descent with an asymptomatic sickle cell trait presented with episodes of transient erythematous subcutaneous nodules involving the entire body except the face, since 2 weeks of age. The skin lesions evolved to areas of lipoatrophy and hyperpigmentation. An initial skin biopsy, studied at a different department at 2 months, was initially misinterpreted as subcutaneous fat necrosis of the newborn, despite the lack of the typical radiated crystals and needle-shaped clefts characterizing that entity. At 4 months of age, he developed systemic inflammatory manifestations, including fever, a new rash, significant periorbital edema, and failure to thrive. An extensive workup showed leukocytosis, hypercalcemia, elevated inflammatory markers, hypertriglyceridemia, and transaminitis. A new skin biopsy of the eyelid was diagnosed as neutrophilic lobular panniculitis with necrotic adipocytes. An initial whole-exome sequencing did not identify any causative mutations, but a WES reanalysis focused on autoinflammatory disorders was requested based on additional clinicopathologic data and revealed a mosaic intronic mutation in IKBKG c. 671+3 G > C. This mutation encodes an mRNA missing exon 5 resulting in NF-kB essential modulator (NEMO) Δ-exon 5-autoinflammatory syndrome (NDAS). NEMO-NDAS is one of the systemic autoinflammatory diseases that may appear as an unexplained panniculitis in young children, who should be monitored for immunodeficiency and/or autoinflammatory diseases. The differential diagnosis of autoinflammatory disorders should be considered in such cases incorporating the use of the whole-genome/exome sequencing in the investigation. The inhibitor of kappa-B kinase regulatory subunit gamma (IKBKG) is located on chromosome Xq28 and encodes the NEMO, a critical molecule upstream of NF-kB activation.

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.

Ovotesticular Disorder of Sex Development: Approach and Management of an Index Case in the Dominican Republic.

Disorders of sex development (DSD) are a group of congenital conditions associated with anomalous development of internal and external genital organs. Ovotesticular disorder of sex development (OT-DSD) is a condition in which a child is born with both testicular tissue (that possesses variable fertility potential within seminiferous tubules) and ovarian tissue (with primordial follicles). These tissues may be co-existent in the same gonad (ovotestis) or independently in separate gonads. Here, we report the clinical case of a 21-month-old boy that we met during a humanitarian surgical mission performed at Hospital Dr. Francisco Moscoso Puello, Santo Domingo, Dominican Republic. The child was referred for management of hypospadias, cryptorchidism, and symptomatic right inguinal and umbilical hernias. With further chromosomal evaluation, the diagnosis of SRY-negative OT-DSD was made, and shared decision-making was used to determine the timing of gender assignment, reconstruction, and the child's long-term care team. OT-DSD is an uncommon condition with unclear causes. Once a DSD condition is suspected at birth, a complete investigation should be performed, encompassing a descriptive examination, a basic electrolyte and hormonal profile, genetic assessment, and pelvic ultrasound. Consultation with a multidisciplinary team is warranted, including pediatric urology or pediatric surgery with urologic training, endocrinology, genetics, psychology, pathology, and the patient's pediatrician at minimum before surgical reconstruction. It is crucial to involve the patient and their family with shared decision-making before surgery or gender assignment.

EWSR1-ATF1 Fusion in a Myoepithelial Carcinoma of Soft Tissue With Small Round Cell Morphology: A Potential Diagnostic Pitfall.

Myoepithelial tumors of soft tissue are rare mesenchymal neoplasms that overlap with their salivary gland and skin counterparts at both the histopathologic and molecular levels. EWSR1 gene rearrangements with various fusion partners represent a common genetic event in myoepithelial tumors of soft tissue, whether benign or malignant, and may prove useful as a diagnostic tool in difficult cases. However, the number of diagnostic entities with EWSR1 gene rearrangements has grown considerably in recent years, and there is significant morphologic and immunophenotypic overlap amongst this group, underscoring the importance of fusion testing to detect fusion partners that are characteristic of discrete diagnostic entities. Herein, we report a malignant myoepithelial tumor of soft tissue/myoepithelial carcinoma with an undifferentiated round cell morphology arising in a pediatric patient with a EWSR1-ATF1 gene fusion.

Pediatric Testicular Hemangioma in a 10-Year-old: A Rare Entity That May Mimic Malignancy With Appraisal of the Literature.

Capillary hemangioma is a rare benign lesion in the testicle, particularly in pediatrics. It can mimic malignancy, leading to radical orchiectomy. We present a case of a testicular hemangioma in a child, and review the literature on testicular hemangiomas in this age group. A hypervascular testicular lesion without elevated tumor markers may warrant intraoperative biopsy to direct surgical management, which may include testis-sparing surgery if amenable.

Phenotype and immunophenotype of the most common pediatric tumors.

Pediatric tumors are heterogenous and can be quite varied in appearance. However, those in the infamous "small round blue-cell tumor" group, with their hyperchromatic nuclei and small amount of cytoplasm can be challenging, and their diagnosis and prognostication require cost-efficient and focused immunohistochemistry and ancillary testing. Ideally, ample material should be obtained for routine histology and ancillary testing, including immunohistochemistry, fluorescent in situ hybridization, fresh tissue for cytogenetic studies, and snap-frozen tumor for DNA/RNA extraction both for routine molecular testing (ie, reverse-transcription PCR studies), as well as future research study protocols (genome wide studies, targeted gene sequencing). This review focuses on the main pediatric tumors with emphasis on immunophenotype, keeping in mind that a directed panel approach yields the highest yield with combination of clinical history, histologic features, and ancillary molecular testing.

Pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue associated with granulomatous inflammation in a child with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome).

Patients with immunodeficiency disorders have an increased incidence of lymphoproliferative disorders; however, only 4 such patients with DiGeorge/chromosome 22q11.2 deletion syndrome have been reported. We report a case of a pulmonary Epstein-Barr virus-negative extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue in a child with this syndrome.

Pediatric chronic sclerosing sialadenitis: Küttner tumor.

Chronic sclerosing sialadenitis is an uncommon cause of salivary gland enlargement mainly occurring in the fifth and seventh decade of life. In the Western population, chronic sclerosing sialadenitis has been characterized as an IgG4-related disease. Although rare, this lesion occurs in children. To increase awareness about this entity in the pediatric age group, we report the case of an 11-year-old boy with a hard, 4.0-cm circumscribed mass in the right submandibular gland. Histologically there was marked distortion of the gland architecture by a dense lymphocytic infiltrate and extensive fibrosis with septa that crossed and distorted the gland, leaving atrophic acini and dilated, irregular ducts. The lymphoid infiltrate formed multiple follicles with active germinal centers, numerous plasma cells, and areas with diffuse arrangement. Immunophenotyping showed abundant CD20- and CD3-positive lymphocytes; cytokeratin AE1/AE3 highlighted the distorted architectural pattern; IgG staining showed large numbers of positive cells infiltrating the interstitium and surrounding the atrophic acini and ducts. IgG4 staining revealed a large proportion of positive infiltrating elements. Küttner tumor belongs to the group of IgG4-related sclerosing diseases. The differential diagnosis includes pleomorphic adenoma and other salivary gland neoplasms. Its recognition in children is important clinically because this entity is amenable to steroid treatment, and additional work up and follow up is warranted to stave off other IgG4-related diseases/complications.

A novel presentation of diffuse lung disease caused by congenital hypothyroidism.

A term infant was born with respiratory distress, and subsequent imaging, histopathologic, and hormonal studies confirmed congenital hypothyroidism. This report is intended to alert pediatricians to the possibility of congenital hypothyroidism as a cause of respiratory symptoms of unknown cause in neonates with respiratory distress.