Fibroblastic Connective Tissue Nevus Research Articles

Update on Superficial Spindle Cell Mesenchymal Tumors in Children.

The diagnosis of cutaneous and subcutaneous spindle cell neoplasms in children is often challenging and has potential therapeutic and prognostic implications. Although correctly diagnosing dermatofibrosarcoma protuberans and infantile fibrosarcoma is paramount, pathologists should not ignore a number of diagnostic pitfalls linked to mostly rare tumors with completely different clinical outcomes. In the last decade, a spectrum of novel entities has been described; information from molecular biology has helped to shape this new landscape for spindle cell tumors. Here, we review the most noteworthy neoplasms in this spectrum, with a focus on their histological similarities: fibroblastic connective tissue nevus, medallion-like dermal dendrocyte hamartoma, or plaque-like CD34-positive dermal fibroma, which share features with fibrous hamartoma of infancy; lipofibromatosis and lipofibromatosis-like neural tumor; and plexiform myofibroblastoma, a recently described neoplasm that should be distinguished from plexiform fibrohistiocytic tumor. These tumors also have genetic similarities, particularly gene rearrangements involving NTRK3 or NTRK1. These genetic features are not only essential for the differential diagnosis of infantile fibrosarcoma but are also of diagnostic value for lipofibromatosis-like neural tumors. The more recently described RET, RAF1, and BRAF gene fusions are also discussed.

Fibroblastic connective tissue nevus: Report of two cases

Fibroblastic connective tissue nevus: Report of two cases

Plexiform Myofibroblastoma: Clinicopathologic Analysis of 36 Cases of a Distinctive Benign Tumor of Soft Tissue Affecting Mainly Children and Young Adults.

The spectrum of benign superficial fibroblastic/myofibroblastic tumors continues to expand and includes entities such as plexiform fibrohistiocytic tumor, dermatomyofibroma and fibroblastic connective tissue nevus. Here, we describe a seemingly distinctive group of lesions which we have labeled "plexiform myofibroblastoma" (PM). PM is a rare superficial mesenchymal tumor of fibroblastic/myofibroblastic lineage that predominantly occurs in children and young adults. Thirty-six cases from the consultation archives of one of the authors have been studied to characterize the clinicopathologic characteristics of PM. 19 patients (53%) were female and 17 were male, with age at presentation ranging from congenital (2 cases) to 50 years of age (median: 9.5 y). Three patients had multiple lesions. Males tended to develop tumors during childhood (median: 2 y; range: congenital-37 y), while in females the age distribution was relatively uniform from childhood through adulthood (median age: 25 y; range: 4 mo to 50 y). Most tumors occurred in truncal locations (25/40), including the back (11), anterolateral chest wall (4), axilla (4), abdominal wall (4), perineum (1) and suprapubic region (1). Other tumor sites were the neck (10/40), occiput (2), lower extremity (2) and breast (1). The average greatest dimension was 2.7±1.7 cm (range: 0.6 to 8 cm). Three male patients, 2 of whom were brothers, presented between 6 months and 1 year of age with multiple lesions variably involving the back, occiput and axillae; these lesions spontaneously regressed after being present for about 2 years, with no evidence of recurrence at a mean follow-up of 11.4±3.2 years. Histologically, PM was composed of plexiform fascicles of fibroblastic/myofibroblastic spindle cells that ramify through the subcutis and reticular dermis. The bland neoplastic cells had indistinct cell borders, palely eosinophilic cytoplasm and ovoid or tapered nuclei. There was no histiocytoid component in any case, and no cases contained osteoclast-like giant cells. Twelve of thirty-four (35%) reviewed cases showed at least focal keloidal hyalinization, 6/34 (18%) contained somewhat fasciitis-like areas and 6/34 (18%) contained focal myxoid stroma. Immunohistochemical studies were positive for SMA (27/32 cases), desmin (9/21) and CD34 (13/24) and negative for β-catenin (0/14) and S-100 (0/22). EMA was weakly positive in 2/15 cases. An FGFR2 M535L tyrosine kinase domain variant of unknown significance was detected in 1/7 sequenced cases, and no somatic alterations, copy number alterations or gene fusions were detected in the other 6. Clinical follow-up data were available for 16/36 patients (44%; median duration: 5.5 y). Although most excisions had positive margins (11/16), only 1 patient developed a local recurrence 4 years after initial excision. No tumors metastasized. PM is a benign tumor with characteristic histology, epidemiology and anatomic site distribution. Because PM rarely recurs, a watchful waiting approach would be reasonable for lesions excised with positive margins.

Novel KHDRBS1-NTRK3 rearrangement in a congenital pediatric CD34-positive skin tumor: a case report

Cutaneous spindle-cell neoplasms in adults as well as children represent a frequent dilemma for pathologists. Along this neoplasm spectrum, the differential diagnosis with CD34-positive proliferations can be challenging, particularly concerning neoplasms of fibrohistiocytic and fibroblastic lineages. In children, cutaneous and superficial soft-tissue neoplasms with CD34-positive spindle cells are associated with benign to intermediate malignancy potential and include lipofibromatosis, plaque-like CD34-positive dermal fibroma, fibroblastic connective tissue nevus, and congenital dermatofibrosarcoma protuberans. Molecular biology has been valuable in showing dermatofibrosarcoma protuberans and infantile fibrosarcoma that are characterized by COL1A1-PDGFB and ETV6-NTRK3 rearrangements respectively. We report a case of congenital CD34-positive dermohypodermal spindle-cell neoplasm occurring in a female infant and harboring a novel KHDRBS1-NTRK3 fusion. This tumor could belong to a new subgroup of pediatric cutaneous spindle-cell neoplasms, be an atypical presentation of a plaque-like CD34-positive dermal fibroma, of a fibroblastic connective tissue nevus, or represent a dermatofibrosarcoma protuberans with an alternative gene rearrangement.

Fibroblastic Connective Tissue Nevus

Fibroblastic connective tissue nevus (FCTN) represents a rare and distinct benign cutaneous mesenchymal lesion of fibroblastic/myofibroblastic lineage, which broadens the spectrum of lesions presently recognized as connective tissue nevus. A series of 25 cases of FCTN has been analyzed to further characterize the clinicopathologic spectrum and immunohistochemical features of this entity. Sixteen patients were female (64%) and 9 were male (36%), with age at presentation ranging from 1.5 months to 58 years (median, 10 y). Most patients presented with a solitary, slowly growing, painless plaque-like or nodular skin lesion. Eleven cases (44%) arose on the trunk, 9 (36%) on the head and neck, and 5 (20%) on the limbs. The lesion was present for a median duration of 11.5 months (mean, 13.2 mo). Grossly, the lesions were tan-brown to tan-white, smooth, and firm. Their size ranged from 0.3 to 2.0 cm in greatest dimension (mean size, 0.67 cm; median, 0.6 cm). All tumors showed poor circumscription and were situated primarily in the reticular deep dermis, extending into the superficial subcutis in 13 cases (52%). The lesion was associated with papillomatous epidermis in 17 cases (70%) and the presence of adipose tissue in the reticular dermis in 14 cases (60.9%). All tumors were composed of a proliferation of bland intradermal fibroblastic/myofibroblastic cells with indistinct palely eosinophilic cytoplasm and tapering nuclei, with no significant cytologic atypia or pleomorphism, arranged in short-intersecting fascicles and entrapping appendages. No mitoses were identified. Immunostains showed positivity for CD34 in 20 of 23 cases (87%) and weak focal positivity for smooth muscle actin in 9 of 19 cases (47%). No case stained positively for desmin or S100 protein. Clinical follow-up was obtained for 14 patients (median duration, 4 y). No tumor recurred locally, even when surgical excision was incomplete. No lesion metastasized. FCTN occurs most commonly as a plaque on the trunk and head/neck of children, involves deep dermis and superficial subcutis, and stains mainly for CD34. FCTN most likely represents a localized developmental dermal anomaly; it is entirely benign and should not be confused with dermatofibrosarcoma protuberans or other neoplasms such as dermatomyofibroma.