Mediastinal tumors of peripheral nerve origin (so-called neurogenic tumors)

Abstract

The mediastinum can be the site of origin of a variety of benign and malignant tumors of peripheral nerve sheath origin. Although schwannoma is one of the most common tumors found in the posterior mediastinum, peripheral nerve sheath tumors are reported in all compartments of the mediastinum. The majority of peripheral nerve sheath tumors in the mediastinum as in other anatomic sites occur sporadically, and a subset of them, most notably neurofibromas, and to a lesser extent, schwannomas and malignant peripheral nerve sheath tumors, occur in patients with syndromes such as neurofibromatosis 1 (NF1). In this review, the characteristics of mediastinal nerve sheath tumors along with the histologic differential diagnosis are summarized. Primary emphasis is placed upon the use of morphologic criteria for establishing a definitive diagnosis with reference to photomicrographs to illustrate the classic and sometimes unusual features of this varied group of tumors. The judicious application of ancillary testing, most frequently immunohistochemistry, for separating peripheral nerve sheath tumors from each other and from their morphologic mimics is reviewed. Included in the review are the clinicopathologic features, clinical management and prognostic implications of benign and malignant mediastinal peripheral nerve sheath tumors.

Keywords: Mediastinal nerve sheath tumor; malignant peripheral nerve sheath tumor; schwannoma; thoracic nerve sheath tumor.

Figure 1

(A) Solid change in encapsulated schwannoma. (B) Grossly cystic change in a large schwannoma showing peripheral solid elements and capsule.

Figure 2

(A) Schwannoma demonstrating Antoni A and B areas with some hyalinized vessels (40×, H&E). (B) A cellular nodule within schwannoma composed primarily of Antoni A areas (40×, H&E).

Figure 3

(A) Ancient schwannoma showing hyalinized vessels and Verocay bodies (H&E, 40×). (B) Ancient schwannoma showing degenerative atypia and nuclear inclusions (200×, H&E).

Figure 4

(A) Nuclear enlargement and hyperchromatic chromatin within ancient schwannoma (400×, H&E). (B). Cellular nodule within a schwannoma with adjacent loose myxoid stroma (20×, H&E). (C). Cellular areas of schwannoma with atypical cells seen at high power in (A) (100×, H&E). (D) Atypical mitotic figure within schwannoma with degenerative atypia (400×, H&E).

Figure 5

(A) Gross appearance of cut surface of melanotic schwannoma. (B) Low power view of heavily melanotic pigment deposition in a melanotic schwannoma (40×, H&E).

Figure 6

(A) Melanotic schwannoma showing atypical cells with heavy melanotic pigment and foam cells (200×, H&E). (B) Slightly fasciculated appearance of melanotic schwannoma with large intranuclear inclusions and heavy melanin pigment (200×, H&E).

Figure 7

(A) Gross appearance of somewhat dumbbell shaped neurofibroma. (B,C) Low power views of myxoid and spindled Schwannian cells with associated collagen bundles (40×, H&E).

Figure 8

(A) Myxoid areas of plexiform neurofibroma with conventional appearing histology and Schwannian cells intimately associated with curved collagen bundles (40×, H&E). (B) Lower power view of plexiform neurofibroma (20×, H&E) .

Figure 9

(A) Lung biopsy of MPNST from a 23-year-old patient with neurofibromatosis 1 showing fasciculated spindle cells with undulating nuclei (40×, H&E); (B) Nuclear hyperchromasia and variably cellular areas (100×, H&E). (C) Nuclear loss of trimethylation marker H3k27me3, characteristic of high grade MPNST (100×, immunohistochenical stain for H3k27me3). MPNST, malignant peripheral nerve sheath tumor.

Figure 10

(A) High grade MPNST with herringbone pattern of fascicles of spindle cells with undulating nuclei, nuclear hyperchromasia, and easily found mitoses (100×, H&E). (B) MPNST showing intersecting fascicles and zones of hypercellularity (40×, H&E). MPNST, malignant peripheral nerve sheath tumor.

Figure 11

(A) High grade MPNST showing spindled Schwannian-like cells with mitotic figures and punctate single cell necrosis (400×, H&E). (B) Zones of geographic necrosis sharply juxtaposed with hypercellular fascicles of spindle cells (40×, H&E). MPNST, malignant peripheral nerve sheath tumor.

Figure 12

(A) Loss of H3k27me3 immunohistochemical expression in tumor cells of high grade MPNST (100×, PAP) and (B) scattered desmin positive cells (200×, PAP). MPNST, malignant peripheral nerve sheath tumor.