—  SPECIALTY CONFERENCE  —

Bone & Soft Tissue Pathology

Case 1 - Deep-seated Plexiform Schwannoma

Cristina R. Antonescu
Memorial Sloan-Kettering Cancer Center
New York, NY


Click on each slide thumbnail image for an enlarged view
Clinical History
A 36-year old man presented with right thigh pain and swelling. An MRI showed a large lobulated mass with a high signal on T2-weighted images, located in the right vastus lateralis muscle. A resection of the mass was performed.


Case 1 - Figure 1 - MRI showing a large lobulated mass with a high signal on T2-weighted images, located in the right vastus lateralis muscle
Case 1 - Figure 2 - Gross appearance of the resection specimen showing a 9 cm multinodular mass, with a yellow-tan fleshy cut surface



Case 1 - Figure 3 - Low power microscopic appearance of the lesion shows a macronodular growth of tightly packed uniform spindle cells
Case 1 - Figure 4 - High power illustrates compacted fusiform cells with ill-defined cell borders, eosinophilic cytoplasm and hyperchromatic, elongated nuclei

Diagnosis: Deep-seated Plexiform Schwannoma

Differential Diagnosis: The main differential diagnosis of plexiform schwannoma (PS) includes plexiform neurofibroma, schwannomas with intralesional nodularity, and malignant peripheral nerve sheath tumor (MPNST).

Plexiform neurofibroma is one of the more commonly occurring plexiform neural tumors and is a 'sin qua non' for the diagnosis of neurofibromatosis type 1. Morphologically, they are usually hypocellular lesions with a myxoid background and showing well defined nodules. Although most of the plexiform neurofibromas are not difficult to differentiate from PS because of their classic morphology, some of the plexiform neurofibromas can show presence of cellular areas with schwannian nodules including nuclear palisading which can raise the question of schwannoma. It is extremely important, in these circumstances, to differentiate between the two lesions due to the clinical consequence as well as the potential for a malignant transformation, which is well known to occur in plexiform neurofibroma, but has not been reported to occur in PS. In our experience, use of immunohistochemical stains for S100 protein, neurofilament, laminin and collagen type IV can be helpful in differentiating the two entities. Schwannomas show diffuse and uniform staining for S100 protein, laminin, and collagen type IV, with positivity for neurofilament restricted to the subcapsular areas as opposed to neurofibromas that show patchy positivity for S100 and positivity for neurofilament within the tumor nodules.

MPNSTs arising either in a plexiform neurofibroma or de novo in a multinodular pattern can show increased cellularity and mitotic activity, features typical of PS. In these circumstances, the presence of an underlying benign component can be extremely helpful and should be looked for by extensive sampling of the lesion. In addition, immuno-histochemical stains for S100 protein, laminin and collagen type IV can be useful as they show diffuse and strong positivity in PS, while are weak and patchy in the MPNSTs.

Schwannomas, both conventional and cellular types, can exhibit intralesional nodularity simulating a plexiform / multinodular growth pattern. The presence of the loose Antoni B type areas in between the cellular nodules can accentuate the multinodular appearance. In our experience, close observation to the presence of fibrous capsule around the nodules as well as identifying non-lesional stromal tissue in between the nodules can help to differentiate these schwannomas. In addition, use of immunohistochemical stains for S100, laminin and collagen type IV, all of which are absent in the intervening stromal tissue, can help to distinguish between the lesional nodules and the intervening stromal tissues.

In cutaneous locations, the differential diagnosis also includes a neurothekeoma, which usually shows a nodular growth pattern with loose myxoid stroma. The absence of cellular areas, vascular pattern and absence of S100 staining can be helpful in differentiation.

Discussion
Plexiform schwannoma (PS) is the least common variant of schwannoma that exhibits a characteristic plexiform or multinodular growth pattern. In the original description as an abstract by Harkin et al in 1978, [1] 6 cases of multinodular / plexiform schwannoma were reported occurring in patients aged 9 to 39. None of the cases were associated with neurofibromatosis. With a follow up period of 1.5 to 6 years, there was no recurrence and they concluded that these lesions are benign and should be differentiated from plexiform neurofibroma and MPNSTs. The first reported case in the English literature came from Woodruff et al in 1983, [2] of a vulvar PS occurring in a 26-year-old woman. Since then, close to a hundred cases have been reported in the English literature [2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22] , including several small series ranging from 6-20 cases, [3, 4, 5, 12, 20] .The overwhelming majority of these cases are located superficially (dermal and sub-cutaneous) and only 10% are in non-cutaneous (deep soft tissue and viscera) locations.

Morphologically, PS can display either a conventional, cellular or mixed appearance. However, the frequent cellular morphology associated with hyperchromatic nuclei, increased mitoses, and plexiform growth can be often unsettling for the practicing pathologist. They are typically not associated with neurofibromatosis although rare associations with neurofibromatosis type 2 have been described. [4, 10, 12]

A distinctive subset of PS occurs in congenital or childhood setting, which was previously considered as a form of malignant peripheral nerve sheath tumor. [9] We have recently reported our experience with cellular PS in infants and children, showing that in spite of certain worrisome morphologic features, such as increased cellularity, hyperchromasia, and mitotic activity, these tumors show a benign behavior and have no metastatic potential, and therefore should be classified as benign PS. [20]

Most of the reported cases of PS are not associated with neurofibromatosis. The only association with von Recklinghausen's disease was reported by Iwashita et al, [4] when they reported a clinical diagnosis of neurofibromatosis type 1 in 2 of their 20 cases. A subsequent review of these cases at a later stage revealed that these patients developed vestibular schwannomas indicating that these patients, in fact, had neurofibromatosis type 2 (NF2). Six additional cases of PS were reported by Ishida et al (4 cases), [10, 12] Val-Bernal et al (1 case), [10] and Lim et al (1 case) [23] to be associated with NF2. Most of NF2 associated cases showed multiple, dermal and subcutaneous PSs. Furthermore, Shishiba et al reported one patient with multiple cutaneous schwannomas in schwannomatosis, with some of the cutaneous lesions having a multinodular architecture. [24]

In a recent cytogenetic report, Joste et al [25] showed trisomy of chromosomes 17 and 18 in a PS. They noted that this finding, although similar to conventional and cellular schwannomas in showing numerical chromosomal abnormalities, differed from cellular schwannomas in the lack of involvement of chromosome 22. MPNSTs, in contrast, are hyperdiploid to tetraploid, with complex karyotypes, extensive and variable cytogenetic heterogeneity involving most chromosomes, and in particular chromosomes 17 and 22. We are not certain, based on a single case, that the findings reported are characteristic of PS. Additional studies would be helpful to determine this association.

References

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