Plexiform Cellular Schwannoma in Infancy and Childhood: A Clinicopathological Study of Seven Cases of an Underrecognized Nerve Sheath Tumor with a Tendency Toward Local Recurrence

Abstract

Plexiform cellular schwannoma (PCS) is very rare, and it is not completely understood. We present our experience with 7 additional cases of PCS in infancy and childhood to further characterize its distinctive clinicopathological features. There were 5 females and 2 males with a mean age of 28 months (ranging, 2 months to 8 years). The involved sites included the left forearm ( n = 2), sacrococcygeal region ( n = 2), retroperitoneum ( n = 1), thoracic spinal canal and thoracic cavity ( n = 1), and neck ( n = 1). Tumor sizes ranged from 3 to 13 cm in maximum diameter (mean, 7.1 cm). Histologically, all tumors consisted of abundant spindle cells arranged in a multinodular or plexiform growth pattern, possessing elongated, hyperchromatic nuclei and pale eosinophilic cytoplasm with indistinct cell margins. Mitotic figures were easily identified, with a mean count of 4 per 10 consecutive high power fields (HPF). Immunohistochemically, all tumors were strongly and diffusely positive for S100 protein, SOX10 and H3K27me3. The Ki-67 index ranged from 5% to 30% (mean, 15%). Follow-up (available in 6 cases) revealed that 5 patients experienced local recurrence and were treated by re-excision. There was no evidence of recurrence and metastasis in 3 patients, and the other 2 were alive with the disease. In conclusion, PCS is an uncommon nerve sheath tumor predominantly occurring in infants and children, featuring a plexiform or multinodular growth pattern and exhibiting a tendency toward local recurrence. PCS is easily mistaken as malignant peripheral nerve sheath tumor (MPNST) due to its locally aggressive behaviors and worrisome features, including hypercellularity, hyperchromatism and high proliferative activity. Increased awareness of its potential occurrence and greater familiarity with its characteristic features are helpful for both clinicians and pathologists to avoid misdiagnosis and unnecessary overtreatment.

Practical Approach to Histological Diagnosis of Peripheral Nerve Sheath Tumors: An Update

“…Plexiform schwannomas represent an uncommon variant of schwannoma (about 5% of all cases) that characteristically exhibit a multinodular/plexiform architecture, often appreciated at macroscopic examination ( Table 11 ). Unlike plexiform neurofibromas, which most often arise within the context of classical NF1 and are virtually pathognomonic to NF1, most plexiform schwannomas are (at least initially) isolated/solitary, with only a few cases arising within the context of NF2-related schwannomatosis (NF2/MERLIN schwannoma predisposing syndrome) [ 1 , 4 , 9 , 24 , 25 , 26 , 27 , 28 , 29 ]; one must think, however, in the cases of truly isolated/solitary lesions (after extensive work-up), about mosaicism for the schwannomatoses genes ( Table 7 ). They commonly affect the skin (dermis/subcutis) of the head and neck region and the distal extremities; more rarely, deep soft tissues are involved.…”

“…Histologically, the hallmark is the multinodular/plexiform growth pattern. Apart from this peculiar growth pattern, plexiform schwannoma is usually a cellular schwannoma, being mainly composed of Antoni A areas ( Figure 16 ) [ 24 , 25 , 26 , 27 , 28 , 29 ]. Pathologists should be aware of this hypercellularity to avoid a misdiagnosis of sarcomatous transformation/overgrowth in a plexiform schwannoma.…”

“…Pathologists should be aware of this hypercellularity to avoid a misdiagnosis of sarcomatous transformation/overgrowth in a plexiform schwannoma. The rare occurrence of plexiform schwannomas in deeper soft tissues or in large peripheral nerves may represent a further diagnostic challenge, as they may exhibit increased cellularity and mitotic count and thus pose differential diagnostic problems with malignant peripheral nerve sheath tumors [ 24 , 25 , 26 , 27 , 28 , 29 ]. The absence of tumor necrosis, significant nuclear atypia, and the relatively low number of mitoses are in contrast with malignancy [ 1 ].…”