Neural tumors

Published on 08/03/2015 by admin

Filed under Dermatology

Last modified 22/04/2025

Print this page

This article have been viewed 2654 times

Chapter 22

Neural tumors

Tammie Ferringer

Neurofibroma

Key features

• Loose arrangement with pale myxoid stroma

• Haphazard spindle cells with small wavy or S-shaped nuclei

• Mast cells are numerous

Neurofibromas may occur as solitary lesions. Multiple widespread neurofibromas characterize neurofibromatosis (von Recklinghausen’s disease) in which they are seen in association with café-au-lait macules, axillary freckling, and pigmented hamartomas of the iris (Lisch nodules).

Fig 22-1 Neurofibroma

Fig 22-2 Neurofibroma

Diffuse neurofibroma

Key features

• At scanning magnification, diffuse replacement of dermis and infiltration of fat

• Higher magnification shows features typical of neurofibroma

Differential Diagnosis

Dermatofibrosarcoma protuberans has a similar growth pattern and can be myxoid, bearing a considerable resemblance to diffuse neurofibroma. Both may be CD34 positive, but S100 staining of the neurofibroma can distinguish the two. Spindle cell lipoma can appear similar, but occurs as an encapsulated nodule.

Plexiform neurofibroma

Key features

• Large fascicles of neurofibroma surrounded by perineurium

• Often embedded within a diffuse neurofibroma

Plexiform neurofibroma clinically resembles a “bag of worms” and is considered pathognomonic of neurofibromatosis. Both diffuse and plexiform neurofibromas probably result from loss of heterozygosity, where segmental loss of the remaining normal allele for the NF1 gene results in a localized complete lack of tumor suppressor protein.

Fig 22-3 Plexiform neurofibroma

Fig 22-4 Plexiform neurofibroma

Schwannoma (neurilemmoma)

Key features

• Deep dermal or subcutaneous tumors with perineural capsule

• Arise within a nerve, displacing axons to the periphery, causing pain

• Antoni A tissue contains parallel rows of nuclei separated by acellular areas (Verocay bodies)

• Antoni B tissue represents a degenerative change with edematous stroma, typically just below the capsule

Fig 22-5 Schwannoma

Fig 22-6 Schwannoma (Verocay bodies)

Fig 22-7 Psammomatous melanotic schwannoma

Fig 22-8 Ancient schwannoma

Psammomatous melanotic schwannoma is a variant with psammoma bodies and melanin. It is associated with Carney’s complex (myxomas, spotty pigmentation, and endocrinopathy).

“Ancient” schwannoma

Key features

• Benign schwannoma with hyperchromatic pleomorphic nuclei

• No mitoses are present

These “ancient” changes in schwannomas represent a degenerative phenomenon. The absence of mitotic figures and absence of an expansile growth pattern distinguish benign ancient schwannoma from malignant peripheral nerve sheath tumors (MPNST). Typically, MPNSTs arise from neurofibromas, rather than schwannomas.

Neuromas

Neuromas are nerve sheath tumors with a roughly 1 : 1 ratio of axons to Schwann cells.

Fig 22-9 Traumatic neuroma

Traumatic neuroma

Key features

• Multiple nerve fascicles embedded within a fibrous scar

• Clefts between fascicles

Traumatic neuromas occur most commonly on the extremities where mechanical injuries are most frequent. Longitudinal growth of the regenerating nerve trunk results in complex folding. In cross-section, this appears as multiple discrete nerve fascicles.

Fig 22-10 Traumatic neuroma

Palisaded encapsulated neuroma

Key features

• Superficial dermal tumors with a thin, delicate capsule

• Fascicles of spindle cells separated by clefts

Palisaded encapsulated neuromas are solitary painless papules that occur most commonly on the lower central face. The name is somewhat of a misnomer, as there is usually no palisading and only an inconspicuous capsule. Histologically, they resemble the mucosal neuromas of multiple endocrine neoplasia syndrome type 2b, an autosomal-dominant syndrome caused by a mutation of the RET proto-oncogene. In addition to the multiple mucosal neuromas, the syndrome is characterized by a marfanoid habitus, medullary carcinoma of the thyroid, pheochromocytoma, and hyperparathyroidism.

Differential Diagnosis

Unlike schwannomas, palisaded encapsulated neuromas are superficial tumors with adjacent sebaceous glands and small vellus follicles typical of facial skin. Schwannomas lack the fascicles with clefts seen in palisaded encapsulated neuromas.

Fig 22-11 Palisaded encapsulated neuroma

Fig 22-12 Palisaded encapsulated neuroma

Fig 22-13 Supernumerary digit

Supernumerary digit (rudimentary polydactyly)

Key features

• Acral papule with nerve bundles

• Bone or cartilage may be present

Supernumerary digit presents as a congenital papule, typically located at the base of the fifth digit along the ulnar border.

Differential Diagnosis

Acquired digital fibrokeratoma is also an acral papule; however, there are no nerve bundles and large stellate factor XIIIa-positive dendrocytes may be present. There is often longitudinal streaking of collagen.

Merkel cell carcinoma (primary neuroendocrine carcinoma of the skin, trabecular carcinoma)

Key features

• Composed of small blue cells with scant cytoplasm and tightly packed nuclei in sheets or a trabecular array

• Nuclear molding, apoptotic cells, and mitoses are often present

• Synaptophysin, chromogranin, and neuron-specific enolase+

• CK20+ in a paranuclear dot pattern

Membrane-bound dense core granules on electron microscopy are characteristic. Metastatic small (oat) cell carcinoma of the lung also consists of small blue cells, but CK20 is typically negative and thyroid transcription factor (TTF-1) is positive. Also in the differential diagnosis of small blue cell tumors is lymphoma, which can be distinguished by positivity for hematopoietic markers. Melanoma is S100 positive. Neuroblastoma often demonstrates elongated, angulated “carrot-shaped” blue cells and may form rosettes.

Fig 22-14 Merkel cell carcinoma

Differential Diagnosis

The microscopic differential diagnosis for “small blue cell” tumors can be remembered by the mnemonic “LEMONS”:

• Lymphoma

• Ewing’s sarcoma

• Merkel cell carcinoma/melanoma

• Oat cell carcinoma of the lung

• Neuroblastoma

• Small cell endocrine carcinoma

Fig 22-15 Merkel cell carcinoma

Granular cell tumor

Key features

• Sheets of large polygonal cells with abundant eosinophilic granular cytoplasm with central nucleus

• Discrete round eosinophilic giant lysosomal granules (pustulo-ovoid bodies of Milian)

• Overlying pseudoepitheliomatous hyperplasia can be mistaken for squamous cell carcinoma

• S100+

Granular cell tumors are Schwann cell-derived tumors that can occur anywhere, but most commonly on the tongue. The granules within the cytoplasm are phagolysosomes. Bland cytology can be a poor predictor of biologic behavior, and large tumors should be regarded as potentially malignant.

Fig 22-16 Granular cell tumor with pseudoepitheliomatous hyperplasia

Fig 22-17 Granular cell tumor

Fig 22-18 Myxoid neurothekeoma

Fig 22-19 Myxoid neurothekeoma

Neurothekeoma

Neurothekeomas are benign neoplasms that are divided into myxoid, mixed, and cellular types. The myxoid type is strongly S100 positive, whereas those on the cellular end of the spectrum are composed of undifferentiated cells with partial features of Schwann cells, smooth muscle cells, myofibroblasts, and fibroblasts.

Myxoid neurothekeoma (nerve sheath myxoma)

Key features

• Multiple myxoid lobules containing sparse stellate cells

• S100+

Cellular neurothekeoma

Key features

• Nests and fascicles of epithelioid or spindled cells

• Myxoid stroma is absent or sparse

• S100− but S100A6+

Fig 22-20 Cellular neurothekeoma

The cellular variant is negative for S100 and desmin, but sometimes positive for smooth muscle actin, neuron-specific enolase, and factor XIIIa. It is frequently positive for NK1/C-3, S100A6, and PGP9.5 with antigen retrieval. S100A6 also stains histiocytic tumors, including atypical fibroxanthoma, as well as Spitz nevi.

Differential Diagnosis

Histologically, cellular neurothekeomas may be confused with melanocytic lesions such as dermal Spitz nevi. S100 positivity strongly favors the melanocytic lesion. The variable reactivity for factor XIIIa in cellular neurothekeoma can result in confusion with epithelioid fibrous histiocytoma. S100A6 positivity can lead to confusion with spindled atypical fibroxanthoma. Of the two, atypical fibroxanthoma is less likely to demonstrate fascicles of tumor cells. Epithelioid pilar leiomyomas may also be considered in the differential diagnosis due to the variable smooth muscle actin positivity in cellular neurothekeomas. However, the absence of desmin in cellular neurothekeoma aids in the distinction.