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
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.
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,  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,  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
several small series ranging from 6-20 cases,
.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.
A distinctive subset of PS occurs in congenital or childhood setting, which was previously considered
as a form of malignant peripheral nerve sheath tumor.  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.
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,  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
Val-Bernal et al (1 case),  and Lim et al (1 case) 
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.
In a recent cytogenetic report, Joste et al  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.
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