Primary pleural hybrid cellular schwannoma/perineurioma: A case report

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Author's personal copy respiratory investigation 52 (2014) 269–273

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Short Communication

Primary pleural hybrid cellular schwannoma/perineurioma: A case report Danny Soria-Ce´spedes, MDa,n, Carlos Robles-Vidal, MDb, Arturo Go´mez-Gonza´lez, MDc, Rosalinda Pen˜aloza-Ramı´rez, MDa, Carlos Ortiz-Hidalgo, MDa,d a

Department of Surgical and Molecular Pathology, The American British Cowdray Medical Center, Mexico City, Mexico Department of Surgery, The American British Cowdray Medical Center, Mexico City, Mexico c Department of Internal Medicine, The American British Cowdray Medical Center, Mexico City, Mexico d Department of Tissue and Cell Biology, Universidad Panamericana, Mexico City, Mexico b

art i cle i nfo

ab st rac t

Article history:

Hybrid schwannoma/perineurioma is a recently characterized benign nerve sheath tumor,

Received 13 November 2013

most commonly affecting the lower limb and limb girdle. Hybrid tumors located in the

Received in revised form

subcutis of the trunk have not previously been reported to affect the pleura. We describe a

4 March 2014

52-year-old man with dyspnea and thoracic pain due to a large mass in the right pleura,

Accepted 5 March 2014

histologically composed of densely packed, S-100-positive spindle cells, intermixed with

Available online 22 April 2014

cells containing slender nuclei positive for epithelial membrane antigen, Glut-1, and claudin-1. To our knowledge, this is the first report of hybrid schwannoma/perineurioma in the pleura. & 2014 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.



Benign peripheral nerve sheath tumor types include schwannoma, perineurioma, and neurofibroma, derived from Schwann cells, perineurial cells, and a mixture of endoneurial components, respectively [1]. Schwannoma is composed of compact spindle cells with twisted nuclei that are strongly and diffusely positive for S-100 protein and negative for epithelial membrane antigen (EMA), CD34, Glut-1, and

claudin-1 [1]. Cellular schwannoma is a highly cellular variant of schwannoma, showing predominantly compact spindle cell proliferation, with few or no Verocay bodies, and is often associated with xanthomatous histiocytes and lymphoid clusters [2,3]. Perineuriomas are far less common than schwannomas and neurofibromas and consist of a proliferation of spindle cells with wavy nuclei that have extremely thin, elongated, and bipolar cytoplasmic processes and a storiform, focally whorled growth pattern. These tumor cells

Abbreviations: EMA, epithelial membrane antigen n Correspondence to: Department of Surgical and Molecular Pathology, The American British Cowdray Medical, Sur 136#116, Col. Las Américas, Mexico City 01120, Mexico. Tel./fax: þ52 55 52308171. E-mail addresses: [email protected] (D. Soria-Céspedes), [email protected] (C. Robles-Vidal), [email protected] (A. Gómez-González), [email protected] (R. Peñaloza-Ramírez), [email protected] (C. Ortiz-Hidalgo). 2212-5345/& 2014 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

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respiratory investigation 52 (2014) 269 –273

are positive for EMA, Glut-1, CD34, and claudin-1 and are generally negative for S-100 protein [1,4]. In recent years, a number of nerve sheath tumors showing areas of more than one histologic type have been described, and these tumors exhibit an abrupt transition and/or intimate admixture of peripheral nerve cell types. These composite tumors have been termed “hybrid” peripheral nerve sheath tumors. Well-documented examples have been reported that include hybrid schwannoma/neurofibroma, schwannoma/perineurioma, neurofibroma/perineurioma [5–8], and cellular schwannoma/perineurioma [9]. These hybrid tumors usually arise in the dermis and subcutis and have been reported to occur over a wide range of ages and anatomical sites [5]. The pathogenesis of these hybrid tumors remains unknown, but these tumors might be associated with localized microenvironmental changes or clonal genetic alterations in primitive tumor cells [8]. Intrathoracic peripheral nerve sheath tumors are rare and usually occur in the paraspinal region of the mediastinum,

where they involve spinal nerve roots and sympathetic ganglia, raising the possibility of a pleural tumor [10]. Herein, we describe the case of a 52-year-old man with a pleural tumor exhibiting morphological and immunohistochemical features of a hybrid cellular schwannoma/perineurioma.


Case report

A 52-year-old man presented to the ABC Medical Center in Mexico City with a history of dyspnea, thoracic pain, and sporadic cough for 3 months. There was no clinical evidence of neurofibromatosis or a history of other peripheral nerve sheath tumors. Computed tomography and 2-deoxy-2-[(18)F] fluoro-D-glucose positron emission tomography/computed tomography revealed an 18  11  10 cm3 bilobed mass in the right hemithorax that involved the visceral pleura, with a standard uptake value of 7.8 and extensive pleural effusion with ipsilateral lung collapse (Fig. 1 A–C). The tumor was

Fig. 1 – (A–C) Computed tomography and 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography/computed tomography revealing a mass located in the right hemithorax that involved the visceral pleura, with a standard uptake value of 7.8, ipsilateral pleural effusion, and lung collapse. (D) On sectioning, the cut surface showed a solid, firm, yellow/white fascicular mass. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

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Fig. 2 – The tumor was composed of highly proliferative spindle cells with plump nuclei distributed in fascicular and storiform growth patterns (A), with aggregates of xanthogranulomatous histiocytes (B) and lymphoid clusters (C). (D) A subset of cells with slender nuclei and elongated bipolar cytoplasmic processes were also present.

3. completely resected by an open thoracostomy and was macroscopically composed of two detached firm nodules with smooth outer surfaces. The first nodule measured 10  10  9 cm3, and the second measured 10  9  8 cm3; the total weight of the nodules was 1050 g. On sectioning, both nodules had firm, homogeneous cut surfaces, with white to yellow areas exhibiting small focal cysts (Fig. 1D). Histologically, both nodules had the same morphology: they were well circumscribed but non-capsulated; showed solid cellular proliferation and a storiform and fascicular pattern; were devoid of Verocay bodies; and were composed of spindle cells with plump nuclei, pale eosinophilic cytoplasm, and indistinct cell borders (Fig. 2A). Focal aggregates of xanthomatous histiocytes and lymphoid clusters were present, predominantly in the periphery of the tumor (Fig. 2B and C). Scattered throughout this cellular proliferation, a subset of cells with slender nuclei and elongated bipolar cytoplasmic processes were observed. These cells were arranged in focal perivascular whorls, were associated with variable amounts of collagenous stroma, and showed lymphocytic infiltration and focal cystic degeneration (Fig. 2D). The mitotic count was q1/10 high-power fields. No mast cells were observed. Immunohistochemically, both nodules were diffusely and intensely positive for S-100 protein (450% of cells) and showed multifocal positivity for EMA (425% of cells), Glut-1 (20% of cells), and claudin-1 (10% of cells). The cells positive for EMA, Glut-1, and claudin-1 had slender nuclei and elongated bipolar cytoplasm (Fig. 3). Staining for pancytokeratin and smooth muscle actin was uniformly negative. The cell proliferation index measured with Ki67 staining was less than 5%. On the basis of all of these findings, hybrid cellular schwannoma/ perineurioma was diagnosed.


Benign peripheral nerve sheath tumors are heterologous neoplasms that involve different components of the nerve sheath and present with different clinical, morphological, and immunohistochemical characteristics [1]. The most common benign peripheral nerve sheath tumors are schwannoma and neurofibroma, whereas perineurioma is much less common. Schwannomas and perineuriomas are composed of a single cell type (Schwann cells and perineurial cells, respectively), whereas neurofibroma is composed of an admixture of Schwann cells, perineurial-like cells, fibroblasts, and scattered intermingled axons as well as variable numbers of infiltrating mast cells [1]. In the last few years, benign tumors of the peripheral nerve sheath containing a mixture of Schwann cells and perineurial cells have been reported. These “hybrid nerve sheath tumors” present more than one histological type, with either a biphasic (the two distinct areas are identifiable) or monophasic pattern (areas composed of the two different components are intimately mixed), which may cause diagnostic difficulties because of this “hybrid” morphology and mixed immunohistochemical staining results [5–8,11]. These hybrid tumors have a wide anatomic distribution; however, Hornick et al. described 42 cases of hybrid schwannoma/perineurioma, primarily located in the lower limb and limb girdle (45%), followed by the upper limb and limb girdle (29%), the trunk (10%), the head and neck region (14%), and, in one case, the colon (2%) [5]. A case of multiple painful, soft tissue hybrid tumors has also recently been reported [6]. The hybrid tumors reported in the trunk were located in the subcutis of the chest wall, without affecting the pleura [5]. Yang et al. described

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Fig. 3 – Immunohistochemical analysis revealed that the tumor cells were positive for S-100 protein with multifocal expression of epithelial membrane antigen (EMA), Glut-1, and claudin-1. Staining for calretinin was positive only in reactive mesothelial cells.

10 cases of hybrid schwannoma/perineurioma; three were located in the dermis or subcutis of the trunk and none affected the pleura [7]. Our group previously described a case of a hybrid benign nerve sheath tumor showing features of cellular schwannoma and perineurioma in the left paravertebral region [9]. To our knowledge, this report is the first to describe hybrid cellular schwannoma/perineurioma in the pleura. The overall median age at diagnosis of patients with hybrid tumors was 38 years, and no association with neurofibromatosis 1 or 2 has been reported. In some series, there was a slight female predilection with a female-to-male ratio of approximately 1.2:1 [7]. There are no clear risk factors recognized for these tumors; radiation is the only previously reported risk factor, based on two cases where the tumor was located in the dermis of the lower leg and in the mons pubis [12]. The case we describe in this report involved a pleuralbased tumor composed of areas that were histologically similar to a cellular schwannoma but also contained perineurioma-like features, with both patterns confirmed by immunohistochemical studies. Staining for S-100 protein was diffusely and intensely positive in the spindle cells with plump nuclei, pale eosinophilic cytoplasm, and indistinct cell borders, with many intermixed slender cells positive for EMA, Glut-1, and claudin-1. According to Hornick et al., S-100 protein and EMA were diffusely positive in 450% of cells and 425% of cells, respectively; in this situation, double staining is useful in demonstrating that the tumor is composed of two different cell types [5]. Our patient had no clinical features of neurofibromatosis or schwannomatosis and had no history of radiation or a previous benign peripheral nerve sheath tumor in a different location. The pathogenetic basis of hybrid peripheral nerve sheath tumor is unclear and continues to be debated. Erlandson

postulated intermediate or transitional cells in some peripheral nerve sheath tumor cases, which might be able to differentiate into both cell types [13]. The main differential diagnoses for hybrid schwannoma/ perineuriomas in the thorax have been reported to include schwannoma, neurofibroma, perineurioma, solitary fibrous tumor, smooth muscle tumor, spindle cell carcinoma, thymoma, a sarcomatoid variant of mesothelioma, a leiomyomatoid variant of mesothelioma, and low-grade malignant peripheral nerve sheath tumor [5,12,14]. In all these cases, immunohistochemical staining was crucial in confirming the differentiation of the tumor cells. The biological behavior of hybrid tumors is similar to that of conventional benign schwannomas and perineuriomas, and they only rarely recur [5]. Rekhi and Jambhekar described a malignant counterpart of these hybrid tumors in the right thigh of a young adult man [15]. In general, the malignant counterpart tumor had a diverse histological appearance; the cells had a whorled and more rarely a palisading growth pattern, with areas of necrosis and mitotically active tumor cells. The tumor we describe in this report had no necrosis or pleomorphism and a low mitotic count. In summary, to our knowledge, we describe here the first case of hybrid cellular schwannoma/perineurioma in the pleura of a patient with no clinical features of neurofibromatosis or schwannomatosis.

Conflict of interest The authors have no conflicts of interest.

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