Neuroblastoma-like schwannoma is a subtype of schwannoma that is extremely rare with 25 previously reported cases [1]. This subtype was first described by Goldblum et al. [2] in 1994. According to the literature review conducted by KoubaaMahjoub et al., the lesion is thought to arise predominantly in females with a median age of 32.2 years [1] and most commonly involved the limbs. The rarity of this lesion and its most striking feature, rosette like formation, may lead to confusion with other benign and malignant entities characterized by rosettes and pseudorosettes, such as neuroblastoma, dendritic cell neurofibroma with pseudorosettes, hyalinizing spindle cell tumor with giant rosettes (low-grade fibromyxoid sarcoma) and Ewing sarcoma. We report a case of a 29-year-old woman with a schwannoma with neuroblastoma-like rosettes involving the chest wall soft tissue. The following case report emphasizes the need to have a high index of suspicion for this entity and the utility of morphologic clues and characteristic immunophenotype to avoid a diagnostic pitfall.

A 29-year-old woman presented with a left chest wall soft tissue lesion for 1 year. The lesion was surgically excised. Microscopic examination showed a well circumscribed, encapsulated lesion with many large rosette-like structures, composed of small round cells radially arranged around a central eosinophilic fibrocollagenous core (Figure 1A, Figure 1B, Figure 1C). These small cells were monomorphic, round to slightly elongated, with scant amount of cytoplasm, hyperchromatic nuclei, and prominent nucleoli. Perivascular hyalinized rosettes were also present. There were no mitoses or areas of necrosis identified. Immunohistochemical stain with S100 showed that these cells were strongly and diffusely positive with both cytoplasmic and nuclear staining (Figure 1D). These features were consistent with schwannoma with neuroblastoma-like rosettes. No areas with features of conventional schwannoma were identified within the lesion.

Neuroblastoma-like schwannoma is a rare subtype of schwannoma, with histological features resembling neuroblastoma. This subtype was initially described by Goldblum et al. [2] in 1994 in a case series of three cases. Few case reports followed [3],[4],[5],[6],[7],[8] highlighting a range of morphologic features from small, ovoid cells to epithelioid cells comprising the lesion. Although considered a sporadic lesion, two cases of neuroblastoma-like schwannomatosis have been reported [3],[9].

This lesion is characterized by a well circumscribed lesion with many large rosette-like structures, composed of small round cells radially arranged around a central eosinophilic fibrocollagenous core. However, smaller rosettes that somewhat resemble Homer-Wright rosettes have also been described in these lesions [2],[10],[11],[12]. The rarity of this lesion and its most striking feature, rosette-like formation, may lead to confusion with other entities characterized by rosettes and pseudorosettes, such as neuroblastoma, dendritic cell neurofibroma with pseudorosettes [6], hyalinizing spindle cell tumor with giant rosettes (low-grade fibromyxoid sarcoma) [6],[7] and Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET).

Neuroblastoma can be distinguished from neuroblastoma-like schwannoma by the absence of capsule, presence of true Homer-Wright rosettes 3,8 that are much smaller than the rosettes found in neuroblastoma-like schwannoma and that contain neuron-specific enolase positive fibrillary structures. S100 expression is only focal in the neuroblasts and stromal cells while it is strong and diffuse in neuroblastoma-like schwannoma [8].

Dendritic cell neurofibroma with pseudorosettes is a solitary well-circumscribed, painless lesion arising in the dermis on the extremities, trunk, and head. Histologically it is composed of small hyperchromatic lymphocyte-like cells surrounding larger cells with long dendritic extensions forming the pseudorosettes. The larger cells are more strongly positive for S100 protein than the smaller lymphocyte-like cells [13]. Distinguishing features between dendritic cell neurofibroma and neuroblastoma-like schwannoma includes small pseudorosettes with large cells in their centers that stain with S100 protein and CD34 in the former in contrast to the large rosettes with acellular centers, strong diffuse staining with S100 protein and absent CD34 staining in the latter [13].

Hyalinizing spindle cell tumor with giant rosettes, a variant of low-grade fibromyxoid sarcoma, typically arises below the fascia in the extremities and trunk. It has giant rosettes composed of epithelioid fibroblasts which are S100 immunoreactive, cuffed around a central hyalinized core of collagen [14],[15]. Features that help to distinguish low grade fibromyxoid sarcoma from neuroblastoma-like schwannoma include spindled cells in a whorling growth pattern, arcades of curvilinear blood vessels, MUC4 expression, lack of diffuse S100 reactivity and fibromyxoid sarcomatous areas in the former [15],[16],[17].

Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) is also included in the differential due to the presence of small round blue cell and Homer-Wright rosettes in Ewing sarcoma. This can be differentiated from neuroblastoma-like schwannoma by the lack of encapsulation, morphology of densely packed small round blue cells, membranous staining with CD99 and specific translocations associated with Ewing sarcoma [18]. In addition, tumor cells in Ewing sarcoma are mitotically active with ill-defined glycogen rich cytoplasm and often show areas of tumoral necrosis.

Neuroblastoma-like schwannoma is considered a neoplasm with benign behavior in most cases reported. No cases of recurrence or metastasis have been reported for this variant. Hence complete excision of this lesion is recommended as the choice of treatment [12]. However, a single case of malignant peripheral nerve sheath tumor arising in a patient with neuroblastoma-like schwannomatosis has been reported [9]. Hence due to the limited number of the reported cases and rarity of this lesion, additional studies with follow-up of the patients will help to better understand the pathophysiology and prognosis of this lesion and guide with adequate treatment.

In conclusion, neuroblastoma-like schwannoma is an unusual variant of schwannoma with relatively few reported cases which may be misinterpreted as a malignant neoplasm. This error can be avoided by awareness of the existence of this entity which is characterized by the presence of large rosette-like structures with small round, monomorphic cells radially arranged around a central eosinophilic fibrocollagenous core, absence of atypia and mitosis, and intense reactivity for S100.