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Dermatologic Manifestations of Neurilemmoma (Schwannoma) Workup

  • Author: Kara Melissa T Torres, MD, DPDS; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Jan 21, 2015
 

Laboratory Studies

Microscopic examination of the tumor biopsy tissue and clinicopathologic correlation establishes the correct diagnosis. The diagnostic microscopic features are described in Histologic Findings.

Masson trichrome stain can be used to demonstrate the presence of longitudinal striations observed in smooth muscle tumors to differentiate a cutaneous leiomyoma from a neurilemmoma, which lacks striations.

Immunostaining using anti–S-100 protein antibody confirms the presence of Schwann cells. In addition, vimentin, myelin basic protein, glial fibrillary acid protein (GFAP), and neuron-specific enolase (NSE) are expressed in most cases.[18, 21] On rare occasions, benign schwannomas may express alpha-smooth muscle actin.[28]

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Imaging Studies

With routine radiographic examination, neurilemmomas generally appear as sharply circumscribed tumor masses.

CT scan images show circumscribed, low-attenuation masses with uniform or heterogeneous contrast enhancement.

MRI reveals a high T2 signal and heterogeneous contrast enhancement.

Both CT scan images and MRI show that large tumors often have areas of cystic changes. Benign neurilemmomas do not show active irregular invasion of bone, as is observed in malignant peripheral nerve sheath tumors.

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Histologic Findings

The correct diagnosis of neurilemmoma is established by microscopic examination of tumor biopsy tissue.

Gross appearance

Cutaneous neurilemmomas present usually as a solitary dermal or subcutaneous nodule. However, lesions may be protruding or pedunculated.[29] In general, these lesions are firm, smooth-surfaced, and smaller than 10 cm. Most neurilemmomas affect small nerves. The smaller examples are rounded, somewhat elastic in consistency, and milky-white or semitranslucent. The larger tumors are lobulated irregularly and, by virtue of secondary degenerative changes, become partly or mainly cystic with calcification (ie, ancient change). Areas of hemorrhage and opaque creamy-yellow tumorous tissue are observed on the cut surface (see the image below)

A larger neurilemoma (5 cm in diameter) arising fr A larger neurilemoma (5 cm in diameter) arising from a peripheral nerve showing irregularly lobulated and secondary degenerative changes, ie, partly cystic with calcification (the so-called ancient change). Hemorrhage and opaque creamy-yellow areas of tumor are also seen on this cut surface.

Some tumors manifest as a firm rubbery nodule with a whorled appearance on the cut surface, resembling smooth muscle tumors of the uterus. The plexiform or multinodular variant, which accounts for approximately 5% of neurilemmomas, may be discernible upon gross examination (see the images below).

Cut surface of an intradermal plexiform (nodular) Cut surface of an intradermal plexiform (nodular) variety of neurilemoma. The plexiform variants of neurilemoma are rare. The area of nodularity is clearly discernible. Courtesy of the Atlas of Tumor Pathology Armed Forces Institute of Pathology Fascicles, Tumors of the Peripheral Nervous System. Used with permission
A low-power photomicrograph of a dermal plexiform A low-power photomicrograph of a dermal plexiform neurilemoma showing nodular aggregates of tumor cells and surrounding loose, myxomatous fibrous stroma. Hematoxylin and eosin stain at 50X magnification.

Microscopic appearance

Most tumors are unilocular masses surrounded by a fibrous capsule composed of epineurium and residual nerve fibers. While this capsule is evident in most tumors, those arising in mucosa (eg, nose, nasopharynx), the central nervous system, and viscera often lack a capsule. Intradermal neurilemmomas and the plexiform or multinodular growth pattern similar to a plexiform neurofibroma are rare. Histologically, the characteristic feature of a neurilemmoma is the pattern of alternating Antoni type A and B areas.

Antoni type A areas (as shown in the image) consist of compact, spindle-shaped cells with twisted nuclei, indistinct cytoplasmic borders, and, occasionally, clear intranuclear vacuoles.

Photomicrograph of a neurilemoma from an area with Photomicrograph of a neurilemoma from an area with a typical Antoni type A pattern. The palisaded benign Schwann cells show nuclear crowding, with cell processes radiating toward the centers of aggregated tumor cells. Inconspicuous loose fibrous stroma is present at the periphery. Hematoxylin and eosin stain at 150X magnification.

The cells are arranged in short bundles or interlacing fascicles with nuclear palisading, whirling of the cells, and Verocay bodies. Verocay bodies are formed by 2 compact rows of well-aligned nuclei and cell processes that are arranged in a roughly oval shape (see the image below). Verocay bodies are more distinctive of schwannomas than the Antoni A and Antoni B patterns, but they are not seen in all schwannomas.

A photomicrograph showing a characteristic Verocay A photomicrograph showing a characteristic Verocay body of a neurilemoma, consisting of tight, discrete aggregates of spindle-shaped, palisaded nuclei with a central fibrillary area, representing collections of cytoplasmic processes of tumorous Schwann cells. Courtesy of the Atlas of Tumor Pathology Armed Forces Institute of Pathology Fascicles, Tumors of the Peripheral Nervous System. Used with permission.

Mitotic figures are rare. S-100 protein, an acidic protein commonly found in the supporting cells of the central and peripheral nervous system, is demonstrated in neurilemmomas, particularly in the Antoni type A areas. Antoni B areas are less cellular and are often disorderly. The capsule is typically positive for epithelial membrane antigen (EMA).[29] The spindle or oval cells are arranged haphazardly in the loose matrix with microcystic changes, inflammatory cells, and delicate collagen fibers. Prominent, irregularly spaced blood vessels are present in the stroma. The psammomatous melanotic neurilemmoma (schwannoma) shows, in addition to the above features, melanin deposition and concentric calcified bodies (psammoma bodies).

Schwannomas have been variably observed to be GFAP and occasionally keratin positive, with antibodies reacting with multiple keratins (pankeratins, keratin cocktail (CK) (AE1/AE3). Both markers highlighted the cellular Antoni A areas, particularly adjacent to the capsule, myxoid or degenerative areas, and perivascularly. In recent studies of a large series of retroperitoneal schwannomas, 84% of the tumors stained positive for both AE1/AE3 and GFAP. However, the tumor cells were negative for specific keratin polypeptides (K). The findings can be attributed to cross reactivity of AE1/AE3 with other intermediate filament proteins, such as GFAP.[30] Schwannomas contain Leu7 and S-100 protein.

Ultrastructural examination of the tumor reveals almost exclusively a single cell type (ie, Schwann cells). They have characteristic thin cell processes that arrange in undulating layers and are continuous from the cell body. The Schwann cell surface is coated with basal lamina composed of electron-dense material measuring approximately 50 nm (see the image).

Transmission electron micrograph of Antoni type A Transmission electron micrograph of Antoni type A tumor tissue consisting of prominent arrays of Schwann cell processes with basement membrane substance coated on their surfaces. Note the centrally located nucleus with vesicular nuclear chromatin. Uranium acetate and lead citrate stain at 15,000X magnification.

The basal lamina lies in stacks between the cells along with typical and long-spacing collagen fibrils with a 130-nm periodicity. These collagen fibrils are often referred to as a Luse body (see the image).

A transmission electron micrograph of a Luse body, A transmission electron micrograph of a Luse body, ie, typical collagen fibrils and adjacent basement substance. Note the long-spaced, 130-nm periodicity. Uranium acetate and lead citrate stain at 52,500X magnification. Courtesy of the Atlas of Tumor Pathology Armed Forces Institute of Pathology Fascicles, Tumors of the Peripheral Nervous System. Used with permission.

The cytoplasm contains a flattened and sometimes invaginated nucleus, microfibrils, rare lysosomes, and scattered mitochondria. In Antoni B areas, the Schwann cells have increased numbers of lysosomes and myelin figures and fragmented basal lamina.

Immunohistochemical staining using anti–S-100 protein antibody demonstrates uniformly and intensely positive staining of Schwann cells in the tumor (see the image).

A photomicrograph of a dermal neurilemoma with ant A photomicrograph of a dermal neurilemoma with anti–S-100 protein immunostaining. The tumorous Schwann cells exhibit uniformly positive staining. Immunoperoxidase stain at 150X magnification.

This technique serves as an important diagnostic tool, and, in severely degenerated neurilemmomas, S-100 protein stain is most valuable for confirming the diagnosis.

The results of immunostaining for myelin proteins used to identify benign and malignant Schwann cell tumors have been variable.

Histologic differential diagnosis

Neurofibroma

The loose, myxomatous Antoni type B tissue of a neurilemmoma may mimic a neurofibroma. However, neurofibromas lack the thick collagenous capsule of neurilemmomas and instead are surrounded by a variably thickened perineurium and epineurium. Neurofibromas also lack the Antoni type A and B patterns and Verocay bodies typical of neurilemmomas. Neurofibromas are composed of a mucinous matrix containing scattered, myelinated, and nonmyelinated axons along with a heterogeneous cell population including Schwann cells, fibroblasts, and perineural cells. Consequently, immunoreactivity for S-100 protein is observed in only a portion of the cells comprising a neurofibroma, as opposed to uniform reactivity throughout a neurilemmoma.

Palisaded encapsulated neuroma

This is an uncommon, generally solitary, asymptomatic intraneural neuroma that may arise in early childhood or adulthood. It appears as a firm, rubbery, skin-colored or pink papule commonly affecting the "butterfly area" of the face. Palisaded encapsulated neuromas are bulbous expansions of a peripheral nerve. They appear as well-circumscribed, ovoid, or rounded nodules in the dermis, which, in contrast to neurilemmomas, contain a greater number of axons and Schwann cells in interlacing fascicles along with characteristic cleftlike spaces.

Schwannoma

These are distinguished from astrocytoma and ependymoma by their abundant parenchymal reticulin, which is positive for type IV collagen. Schwannomas have characteristic contiguous basement membranes along the exterior surfaces of their cells. Although occasionally focal positive staining for GFAP may be present, negative GFAP staining supports the diagnosis of schwannoma. Astrocytomas are generally GFAP positive.

Fibrous meningiomas

These lack typical meningeal whorls and psammoma bodies, and they can be difficult to differentiate from schwannomas. EMA is a useful immunomarker for distinguishing the 2 tumors. Meningiomas are reactive with EMA, while schwannomas (except for their surrounding capsules) are not. GFAP can sometimes be used, because some schwannomas are positive but meningiomas are negative.

Cutaneous leiomyoma

Leiomyomas are benign smooth muscle tumors. They are not derived from neural tissue and generally lack the thick, hyalinized capsule and vasculature of a neurilemmoma. Palisading resembling Verocay bodies may be observed. The blunt-ended nuclei and densely eosinophilic cytoplasm of smooth muscle cells showing distinct cell borders and perinuclear halos help distinguish them from Schwann cells (with their more tapered, spindle-shaped nuclei).

Immunohistochemical stains readily distinguish leiomyomas from neurilemmomas, the former staining with myogenic cell markers, such as smooth muscle actin and desmin, and the latter showing positive staining with S-100. It should be noted that schwannomas have been reported to express actin.[28] Masson trichrome stain may be used to demonstrate the longitudinal striations characteristic of smooth muscle tumors. The ultrastructural features of smooth muscle cells are also highly characteristic, being bounded by a basement membrane and often containing parallel arrays of abundant cytoplasmic microfilaments (actin) with interspersed fusiform dense bodies and pinocytotic vesicles.

Palisaded myofibroblastoma

These contain palisaded cells and Verocay bodies that may mimic neurilemmomas. However, palisaded myofibroblastomas involve lymph nodes, contain fibroblastic and myofibroblastic elements, and are negative for S-100 protein staining.

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Contributor Information and Disclosures
Author

Kara Melissa T Torres, MD, DPDS Visiting Research Fellow, Ackerman Academy of Dermatopathology

Kara Melissa T Torres, MD, DPDS is a member of the following medical societies: Philippine Dermatological Society

Disclosure: Nothing to disclose.

Coauthor(s)

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael J Wells, MD, FAAD Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Lester F Libow, MD Dermatopathologist, South Texas Dermatopathology Laboratory

Lester F Libow, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Texas Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Acknowledgements

Günter Burg, MD Professor and Chairman Emeritus, Department of Dermatology, University of Zürich School of Medicine; Delegate of The Foundation for Modern Teaching and Learning in Medicine Faculty of Medicine, University of Zürich, Switzerland

Günter Burg, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, International Society for Dermatologic Surgery, North American Clinical Dermatologic Society, and Pacific Dermatologic Association

Disclosure: Nothing to disclose.

Grace F Kao, MD Clinical Professor of Dermatopathology, Department of Dermatology, University of Maryland School of Medicine and George Washington University Medical School; Director, Dermatopathology Section, Department of Pathology and Laboratory Medicine, Veterans Affairs Maryland Healthcare System, Baltimore, Maryland

Grace F Kao, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and International Society of Dermatopathology

Disclosure: Nothing to disclose.

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A schematic illustration of the essential microscopic features of a neurilemoma (schwannoma). A solid lesion arises within a nerve composed of a single fascicle (top). The tumor is composed of Schwann cell proliferation within the epineurium and peripherally displaced nerve fibers, resulting in nodular eccentric growth (middle). No capsule is formed in the early growth phase. The larger tumor (bottom) slightly increases the size of the parent nerve and eventually becomes separated from surrounding fascicles by a capsule formed from the perineurium and epineurium. Occasional axons are present.
A small, clinically freely movable neurilemoma found in the subcutaneous tissue. Note the pale-yellow, somewhat-translucent cut surface. The tumor also exhibits a slight nodular growth pattern on the cut surface. Courtesy of the Atlas of Tumor Pathology Armed Forces Institute of Pathology Fascicles, Tumors of the Peripheral Nervous System. Used with permission.
A larger neurilemoma (5 cm in diameter) arising from a peripheral nerve showing irregularly lobulated and secondary degenerative changes, ie, partly cystic with calcification (the so-called ancient change). Hemorrhage and opaque creamy-yellow areas of tumor are also seen on this cut surface.
Cut surface of an intradermal plexiform (nodular) variety of neurilemoma. The plexiform variants of neurilemoma are rare. The area of nodularity is clearly discernible. Courtesy of the Atlas of Tumor Pathology Armed Forces Institute of Pathology Fascicles, Tumors of the Peripheral Nervous System. Used with permission
A low-power photomicrograph of a dermal plexiform neurilemoma showing nodular aggregates of tumor cells and surrounding loose, myxomatous fibrous stroma. Hematoxylin and eosin stain at 50X magnification.
Photomicrograph of a neurilemoma from an area with a typical Antoni type A pattern. The palisaded benign Schwann cells show nuclear crowding, with cell processes radiating toward the centers of aggregated tumor cells. Inconspicuous loose fibrous stroma is present at the periphery. Hematoxylin and eosin stain at 150X magnification.
A photomicrograph showing a characteristic Verocay body of a neurilemoma, consisting of tight, discrete aggregates of spindle-shaped, palisaded nuclei with a central fibrillary area, representing collections of cytoplasmic processes of tumorous Schwann cells. Courtesy of the Atlas of Tumor Pathology Armed Forces Institute of Pathology Fascicles, Tumors of the Peripheral Nervous System. Used with permission.
Transmission electron micrograph of Antoni type A tumor tissue consisting of prominent arrays of Schwann cell processes with basement membrane substance coated on their surfaces. Note the centrally located nucleus with vesicular nuclear chromatin. Uranium acetate and lead citrate stain at 15,000X magnification.
A transmission electron micrograph of a Luse body, ie, typical collagen fibrils and adjacent basement substance. Note the long-spaced, 130-nm periodicity. Uranium acetate and lead citrate stain at 52,500X magnification. Courtesy of the Atlas of Tumor Pathology Armed Forces Institute of Pathology Fascicles, Tumors of the Peripheral Nervous System. Used with permission.
A photomicrograph of a dermal neurilemoma with anti–S-100 protein immunostaining. The tumorous Schwann cells exhibit uniformly positive staining. Immunoperoxidase stain at 150X magnification.
Solitary cutaneous plexiform neurilemoma shown on photomicrograph.
Management algorithm for schwannoma nerve graft.
 
 
 
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