Molecular Alterations in Pediatric Fibroblastic/Myofibroblastic Tumors: An Appraisal of a Next Generation Sequencing Assay in a Retrospective Single Centre Study.

BACKGROUND: Pediatric fibroblastic/myofibroblastic tumors (PFMTs) can be challenging to definitively classify. Large case series or diagnostic updates have not been recently published despite identification of molecular alterations that could improve diagnostic accuracy. Our review of the literature found that over two-thirds of the more than 30 types of PFMTs harbor recurrent molecular alterations. We performed an institutional review of PFMTs to highlight limitations of a predominantly morphological classification, and evaluated the utility of a next-generation sequencing assay to aid diagnosis. METHODS: PFMTs identified over a period of 12 years were reviewed, categorized per the new WHO classification, and tested using the Oncomine Childhood Cancer Research Assay. RESULTS: Eighty-seven specimens from 58 patients were reviewed; 50 were chosen for molecular analysis, 16 (32%) lacking definitive classification. We identified alterations, some novel, in 33% of assayed cases. Expected alterations were identified for most known diagnoses and mutations were identified in 6 of 16 tumors (38%) that were initially unclassified. CONCLUSION: We confirmed a significant subset of PFMTs remain difficult to classify using current criteria, and that a combined DNA/RNA assay can identify alterations in many of these cases, improving diagnostic certainty and suggesting a clinical utility for challenging cases.

Inflammatory myofibroblastic tumor of the central nervous system and its relationship to inflammatory pseudotumor.

Inflammatory myofibroblastic tumor (IMT) is a distinctive spindle cell lesion and occurs primarily in soft tissue. Recent evidence suggests a neoplastic nature, although historically, both neoplastic and nonneoplastic processes were combined in this category. Originally described as a nonneoplastic process, the term inflammatory pseudotumor (IP) has been used synonymously with IMT. IMTs have been linked to ALK gene (2p23) rearrangements, and some have suggested an association with the human herpesvirus 8 (HHV-8). IMT in the central nervous system (CNS) is rare, its characteristics are poorly defined, and its relation to similar tumors at other sites is unclear. To better characterize IMT within the CNS, we studied clinicopathologic features of 6 IMTs and compared them with 18 nonneoplastic lesions originally classified as IP. The IMT group consisted of 2 male and 4 female patients with a median age of 29 years. Of the six IMTs, 5 occurred within the cerebral hemispheres, and one was in the posterior fossa. All tumors were composed of neoplastic spindle cells and a variable amount of inflammatory infiltrate. Eighteen IPs included in this study consisted of predominantly inflammatory masses occasionally seen in the setting of systemic diseases. Only 1 IMT and none of the IPs recurred during the follow-up period. Four IMTs had either ALK protein overexpression or 2p23 rearrangement, and 1 case demonstrated both. None of the IPs were positive for ALK. Neither IMT nor IP cases demonstrated HHV-8 expression. We suggest that IMT in the CNS is distinct from the nonneoplastic IP, and distinguishing IMT from nonneoplastic lesions should enable better decisions for patient management.

Intranasal myopericytoma. A tumour with perivascular myoid differentiation: the changing nomenclature for haemangiopericytoma.

We present a case report of a patient who developed a sinonasal myopericytoma treated by surgical excision through a lateral rhinotomy. Some aggressive features on pre-operative computed tomography scanning and the complexity of recent changes in the histological nomenclature for these tumours led to consideration of adjuvant therapy. The close histological relationship between myopericytoma, myofibromatosis, solitary myofibroma and infantile haemangiopericytoma is discussed. This group of lesions constitute a single morphological spectrum with differentiation towards perivascular myoid cells (pericytes). Currently myopericytoma is the most appropriate and accepted term embracing all these entities. A review of the literature has been reassuring in identifying these tumours as benign but with a reasonably high rate of local recurrence (17 per cent). The treatment of choice is surgical excision with further excisions for local recurrence.

[Congenital myofibroma. A true hemangiopericytoma. A neonatal case with immunohistochemical and ultrastructural studies]. / Miofibroma congénito. Un hemangiopericitoma verdadero. Un caso neonatal con estudio inmunohistoquímico y ultraestructural.

We report the case of a male newborn infant with a pedunculated dermic tumor, located in the right malar region; who underwent a complete surgical resection of the tumor and had a satisfactory postoperative evolution. The histopathologic findings disclosed a subcutaneous tumor with a nodular aspect and a subendothelial intravascular growth, constituted by a dual population of small cells and spindle-shaped cells, distributed in a biphasic pattern. All tumor cells showed a strong pericellular reaction for PAS. The immunohistochemical studies revealed: diffuse cytoplasmic positivity for CD34 and Vimentin in all tumor cells, and only spindle-shaped tumor cells and less differentiated isolated neoplastic cells, presented cytoplasmic positivity for the smooth muscle alpha-actin. The electronic microscopy demonstrated a layer of basal membrane and in the citoplasm, numerous intermediate filaments with focal condensations. Based on all these findings, we conclude that this is a myofibroma, a "true hemangiopericytoma" with myofibroblastic differentiation. For this reason, we propose the term myofibropericytoma, in order to highlight its pericytic origin and its myofibroblastic differentiation. We emphasize the need to recognize this entity, in view of its low frequency and the possibility of a diagnostic mistake with other soft tissues tumors that display haemangiopericytoma-like features.

[Fibroblastic-myofibroblastic proliferations of childhood and adolescents]. / Proliférations fibroblastiques et myofibroblastiques de l'enfance et de l'adolescence.

Fibroblastic-myofibroblastic proliferations of childhood and adolescents form a clinical and morphologic spectrum from benign reactive processes and pseudosarcomas, to fibromatoses, to various types of sarcoma. The diagnosis is challenging because of clinical and morphologic similarities, lack of specific immunohistochemical markers for different types of fibroblastic-myofibroblastic tumors, and limited molecular genetic information. Careful attention to clinical, macroscopic, and histopathologic features permits classification in most cases. This review focuses on the pathologic features of fibroblastic-myofibroblastic tumors with a predilection for children and adolescents.

The spectrum of pediatric fibroblastic and myofibroblastic tumors.

Fibroblastic and myofibroblastic tumors in neonates, infants, and children provide a diagnostic dilemma in surgical pathology due to their relative rarity and similarity in appearances. These tumors may be congenital or occur early during the first years of life or later during the first and second decades of life. The morphologic, immunocytochemical, ultrastructural, cytogenetic, and molecular features of the more "common" pediatric fibroblastic and myofibroblastic tumors are reviewed. In addition, the importance of a multimodal approach to tumor diagnosis is emphasized, with correlation with treatment and outcome differences among these unique fibroblastic and myofibroblastic tumors. The importance of providing an accurate diagnosis with pediatric fibroblastic and myofibroblastic tumors cannot be overstated, because treatment, prognosis, follow-up, and outcome are based on the initial assessment of these fascinating, but oftentimes, perplexing tumors.