Peripheral nerve sheath tumors of the breast.

Benign and malignant peripheral nerve sheath tumors can involve the breast, presenting as masses in the dermis, deep breast parenchyma or axillary soft tissue. Although the histologic features are frequently characteristic, diagnosis can be challenging on core needle biopsy, and the differential diagnosis includes a variety of other benign and malignant spindle cell lesions of the breast. Here, we review the key clinical and pathological features of breast schwannoma, neurofibroma, granular cell tumor, and malignant peripheral nerve sheath tumor.

Loss of H3K27 tri-methylation is a diagnostic marker for malignant peripheral nerve sheath tumors and an indicator for an inferior survival.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that can show overlapping features with benign neurofibromas as well as high-grade sarcomas. Additional diagnostic markers are needed to aid in this often challenging differential diagnosis. Recently mutations in two critical components of the polycomb repressor 2 (PRC2) complex, SUZ12 and EED, were reported to occur specifically in MPNSTs while such mutations are absent in neurofibromas, both in the setting of neurofibromatosis (NF) and sporadic cases. Furthermore, both SUZ12 and EED mutations in MPNSTs were associated with loss of H3K27 tri-methylation, a downstream target of PRC2. Therefore, we tested whether H3K27me3 immunohistochemistry is useful as a diagnostic and prognostic marker for MPNSTs. We performed H3K27me3 immunohistochemistry in 162 primary MPNSTs, 97 neurofibromas and 341 other tumors using tissue microarray. We observed loss of H3K27me3 in 34% (55/162) of all MPNSTs while expression was retained in all neurofibromas including atypical (n=8) and plexiform subtypes (n=24). Within other tumors we detected loss of H3K27me3 in only 7% (24/341). Surprisingly, 60% (9/15) of synovial sarcomas and 38% (3/8) of fibrosarcomatous dermatofibrosarcoma protuberans (DFSP) showed loss of H3K27 trimethylation. Only 1 out of 44 schwannomas showed loss of H3K27me3 and all 4 perineuriomas showed intact H3K27me3. Furthermore, MPNSTs with loss of H3K27 tri-methylation showed inferior survival compared with MPNSTs with intact H3K27 tri-methylation, which was validated in two independent cohorts. Our results indicate that H3K27me3 immunohistochemistry is useful as a diagnostic marker, in which loss of H3K27me3 favors MPNST above neurofibroma. However, H3K27me3 immunohistochemistry is not suitable to distinguish MPNST from its morphological mimicker synovial sarcoma or fibrosarcomatous DFSP. Since loss of H3K27 tri-methylation was related to poorer survival in MPNST, chromatin modification mediated by this specific histone seems to orchestrate more aggressive tumour biology.

Hybrid Epithelioid Schwannoma/Perineurioma.

We report a case of a 58-year-old who woman presented with a solitary slowly growing subcutaneous nodule covered by normally appearing skin on her left groin. Microscopically, the lesion was well circumscribed but unencapsulated, and showed biphasic cellular differentiation. One cell population was presented by small rounded (epithelioid) cells arranged singly, in small aggregates or short cords, whereas the second one was composed of cells with slender nuclei and delicate elongated bipolar cytoplasmic processes. On immunohistochemistry, the epithelioid component showed positive reaction for S-100 protein and negative for epithelial membrane antigen (EMA), thus compatible with schwannian differentiation and resembling epithelioid schwannoma. The other component showed a reverse immunophenotype being S-100 protein negative and EMA positive, thus corresponding to perineuriomatous differentiation. The clinicopathologic and immunohistochemical features of the lesion were compatible with hybrid epithelioid schwannoma/perineurioma, a rare morphological variant of peripheral nerve sheath tumors.

[Diagnostic value of STAT6 immunohistochemistry in solitary fibrous tumor/meningeal hemangiopericytoma].

OBJECTIVE: To investigate the diagnostic role of STAT6 immunohistochemistry in solitary fibrous tumors (SFT)/meningeal hemangiopericytomas (HPC). METHOD: Evaluated the expression of STAT6, vimentin, CD34, EMA, PR, S-100, CD56, GFAP and Ki-67 in a cohort of 37 SFT/meningeal HPC, 30 meningiomas and 30 schwannomas by immunohistochemistry staining. RESULTS: All SFT/meningeal HPC demonstrated nuclear positivity for STAT6, and the proportion of positive tumor cells ranged from 60% to 95%, with no significant difference cases.Vimentin was strongly positive in all cases. CD34, EMA and PR positivity was found in 32 cases, 1 case and 4 cases, respectively.S-100 protein, CD56 and GFAP were negative; Ki-67 labeling index was 1%-8%. However, the meningiomas and schwannomas were negative for STAT6. CONCLUSIONS: STAT6 is a relatively specific biomarker for SFT/meningeal HPC, and may be used in the diagnosis and differential diagnosis of SFT/meningeal HPC, especially for the atypical cases, and allows the precise pathologic diagnosis of SFT/meningeal HPC.

Diagnostic utility of SOX10 to distinguish malignant peripheral nerve sheath tumor from synovial sarcoma, including intraneural synovial sarcoma.

Synovial sarcoma and malignant peripheral nerve sheath tumor pose a significant diagnostic challenge given similar histomorphology. The distinction is further complicated by similar immunophenotype and especially by occasional synovial sarcomas that present as intraneural tumors. Although the presence of a t(X;18) rearrangement or expression of TLE1 can help confirm the diagnosis of synovial sarcoma, negative results for these tests are not diagnostic of malignant peripheral nerve sheath tumor. The SOX10 transcription factor, a putative marker of neural crest differentiation, may have diagnostic utility in this differential, but immunohistochemical data are limited. The goal of the present study was to determine the diagnostic utility of SOX10 to discriminate between synovial sarcoma and malignant peripheral nerve sheath tumor. Forty-eight cases of malignant peripheral nerve sheath tumor, all from patients with documented neurofibromatosis, and 97 cases of genetically confirmed synovial sarcoma, including 4 intraneural synovial sarcomas, were immunohistochemically stained for SOX10. The stain was scored for intensity and fraction of cells staining. Thirty-two of 48 malignant peripheral nerve sheath tumors (67%) were SOX10-positive. The majority of malignant peripheral nerve sheath tumors showed ≥2+ staining, but staining did not correlate with grade. By contrast, only 7/97 (7%) synovial sarcomas were SOX10-positive. Only three synovial sarcomas showed ≥2+ staining but, importantly, two of these were intraneural synovial sarcoma. Therefore, SOX10 is a specific (93%), albeit not very sensitive (67%), diagnostic marker to support a diagnosis of malignant peripheral nerve sheath tumor over synovial sarcoma. Furthermore, the stain needs to be interpreted with caution in intraneural tumors in order to avoid a potential diagnostic pitfall. It remains to be determined whether SOX10-positive cells in intraneural synovial sarcoma represent entrapped Schwann cells, synovial sarcoma cells or both.

Benign esophageal schwannoma compressing the trachea requiring esophagectomy: a case report.

We report a case of esophageal schwannoma in a 62-year-old woman with a 10-month history of dysphagia and dyspnea. Chest computed tomography showed a giant mediastinal mass with a maximum diameter of 9 cm, extrinsically compressing the trachea and esophagus. With a large esophageal mucosal defect and poor blood supply after removal of the tumor, we had to perform partial esophagectomy and esophagogastrostomy in the right thorax (Ivor-Lewis procedure). Pathologic and immunohistochemical examinations revealed a benign esophageal schwannoma.

[Olfactory ensheathing cell tumour: case report and literature review]. / Tumor de las células envolventes del olfatorio: caso clínico y revisión de la literatura.

Olfactory ensheathing cells are glial cells located in the olfactory bulb and nerve. Microscopically, both olfactory ensheathing cells and Schwann cells have similar morphological and immunohistochemical features. However, olfactory ensheathing cells are negative for Leu-7(CD-57), whereas Schwann cells are positive. We present the case of a 49 year-old male with a history of visual impairment and hyposmia. Radiological CT and MRI studies showed a subfrontal cystic extra-axial mass, which eroded the right cribriform plate, with heterogeneous contrast enhancement. Total excision of the tumour was performed by bifrontal craniotomy. Histological examination initially suggested a schwannoma, with immunohistochemical staining being positive for S-100 protein and negative for epithelial membrane antigen (EMA). However, the tumour was negative for Leu-7. Accordingly, the final diagnosis was olfactory ensheathing cell tumour. Herein, we describe the sixth case of intracranial olfactory ensheathing cell tumour and stress the important role of immunohistochemical techniques in obtaining a definitive diagnosis.

Intravascular schwannoma.

Schwannoma is defined as a benign nerve sheath neoplasm of Schwann cell origin. Cutaneous schwannoma typically manifests along the course of peripheral nerves as a solitary, well-defined, skin-colored nodule within the deep dermis or subcutis of the flexor aspects of the extremities. Schwannoma enlarges slowly and typically follows a benign course, with local recurrence and malignant transformation being exceedingly rare. Although involvement of the vasculature by neurofibroma has been rarely reported, intravascular schwannoma has not been documented to date. We present a unique case of cutaneous schwannoma, as confirmed by histological morphology and immunohistochemistry, within the dermal venous system. Presentation of this case is followed by a discussion of the differential diagnoses of schwannoma, the possible etiologies of the extension of this lesion into the vasculature, and the significance of such a phenomenon.

Lobular breast carcinoma metastasis to a superficial plexiform schwannoma as the first evidence of an occult breast cancer.

Tumor to tumor metastasis is a rare phenomenon, in which one, benign or malignant, tumor is involved by metastatic deposits from another. Most documented tumor to tumor metastases have been located intracranially, in which, in the majority of cases, either a breast or a lung carcinoma metastasized to a meningioma. Only 7 cases of metastases to schwannoma have so far been reported in the English literature, in 6 cases to an intracranial acoustic schwannoma and in a single case to a subcutaneous schwannoma. We present a case of dermal/subcutaneous plexiform schwannoma containing metastatic deposits of an occult lobular breast carcinoma, creating a unique schwannoma with epithelioid cells. Differential diagnosis of schwannoma with epithelioid cells includes malignant transformation of schwannoma and metastasis of a carcinoma or melanoma to schwannoma, epithelioid schwannoma, and schwannoma with glandular or pseudo glandular elements.

Orbital schwannoma with fluid-fluid levels on MRI.

A 40-year-old man presented with a progressively growing left orbital mass producing proptosis. Orbital MRI revealed a large bilobed mass that was isointense with respect to the extraocular muscles on T1-weighted images and demonstrated heterogenous contrast enhancement. T2-weighted images revealed a markedly heterogenous internal appearance with fluid-fluid levels. The mass was completely excised in one piece. Histopathologically, the encapsulated tumor consisted mostly of spindle-shaped tumor cells with elongated nuclei forming bundles without obvious mitosis. Richly cellular areas were consistent with the Antoni A pattern, and more hypocellular edematous areas were consistent with the Antoni B pattern. Hemorrhagic and cystic areas were seen within the tumor. The tumor cells stained diffusely positive with S-100 protein. Findings were consistent with the diagnosis of orbital schwannoma. Fluid-fluid levels are usually seen in some vascular and bone tumors and soft tissue lesions. Fluid-fluid levels have previously been reported to occur in intracranial but not in orbital schwannomas. This case demonstrates that orbital schwannoma can also display fluid-fluid levels on MRI, which were thought to be due to intralesional hemorrhage in this case.

Epibulbar schwannoma in a 17-year-old boy and review of the literature.

A healthy, 17-year-old boy presented with a 2-month history of an epibulbar mass on the left eye. Slit lamp examination showed an amelanotic, translucent, round, well-circumscribed, superonasal subconjunctival nodule. On ultrasound biomicroscopy, the tumor was acoustically hollow. The lesion was excised intact, and cryotherapy was applied to the surrounding conjunctiva. Histopathologic examination revealed a tumor composed of spindle cells with slender cytoplasmic processes and bland cigar-shaped nuclei, consistent with schwannoma. Immunohistochemistry showed positivity for S100 protein. The patient had no signs of neurofibromatosis. There was no tumor recurrence after 18 months. This case shows that conjunctival schwannoma can present as a translucent, well-circumscribed subconjunctival mass.