SOX10 Immunostaining Research Articles

Genome Doubling Shapes High-Grade Transformation and Novel EWSR1::LARP4 Fusion Shows SOX10 Immunostaining in Hyalinizing Clear Cell Carcinoma of Salivary Gland

Hyalinizing clear cell carcinoma (HCCC) is a rare indolent malignant tumor of minor salivary gland origin with EWSR1::ATF1 rearrangement. Pathologically, the tumor cells possess a clear cytoplasm in a background of hyalinized stroma. Generally, the tumor cells are positive for p63 and p40 and negative for s100 and α-smooth muscle actin, suggesting that they differentiate into squamous epithelium and not into myoepithelium. In this study, we performed a detailed histopathological and genomic analysis of 6 cases of HCCC, including 2 atypical subtypes—a case of “high-grade transformation” and 1 “possessing a novel partner gene for EWSR1.” We performed a sequential analysis of the primary and recurrent tumor by whole-exome sequencing, RNA sequencing, Sanger sequencing, and fluorescence in situ hybridization to investigate the effect of genomic changes on histopathology and clinical prognosis. A fusion gene involving the EWSR1 gene was detected in all cases. Five cases, including the “high-grade transformation,” harbored a known EWSR1::ATF1 fusion gene; however, 1 case harbored a novel EWSR1::LARP4 fusion gene. This novel EWSR1::LARP4–fused HCCC has a SOX10-positive staining, which is different from the EWSR1::ATF1–fused HCCC. According to whole-exome sequencing and fluorescence in situ hybridization analysis, the “whole-genome doubling” and focal deletion involving CDKN2A, CDKN2B, and PTEN were detected in HCCC with “high-grade transformation.” Conclusively, we identified a novel partner gene for EWSR1, LARP4, in indolent HCCC. Importantly, “high-grade transformation” and poor prognosis were caused by whole-genome doubling and subsequent genomic aberrations.

S2666 Recurrence of Uveal Melanoma Presenting as Hepatic Metastases

Introduction: Uveal melanoma is considered a rare cancer with a stable incidence of 5.1 per million for many years. This is contrast to cutaneous melanoma that has had steadily increasing incidence since the 1970s. Due to the lack of lymphatics in the uveal tract, ocular melanomas spread hematogenously with the liver being a commonly affected organ. Case Description/Methods: A 69-year-old man presented to the hospital with progressive right upper quadrant pain over the past 3 weeks. He had a history of uveal melanoma status post enucleation in 2016 without evidence of recurrence on several years of follow up. On arrival to the hospital, the patient was hemodynamically stable with laboratory values significant for a bilirubin of 7.2 mg/dL (direct of 5.7 mg/dL), alkaline phosphatase of 212 IU/L, AST 90 U/L, and ALT 42 U/L. Computerized Tomography (CT) showed multiple hypoattenuating lesions in the liver without biliary obstruction. MRI demonstrated several different types of hepatic lesions. This included an increased T2 signal with heterogeneous enhancement measuring 16.2 x 9.7cm, several foci of arterial phase hyperenhancement with the largest measuring 4.4 x 5.3 cm, and several rim enhancing lesions. The patient received a liver biopsy with tumor cells positive for SOX 10 and Melan A (Figure) consistent with metastatic melanoma. He underwent complete staging, including a brain MRI, with only other findings of a sclerotic L1 lesion. The patient decided to pursue comfort care and was discharged to home. Discussion: We report here a case of recurrent melanoma of uveal origin presenting as hepatic metastases. Uveal melanoma has low incidence but carries a very poor prognosis as median overall survival is 4-15 months. Even if treated, there is a high risk of recurrence with metastatic disease, largely to the liver, with majority appearing within 10 years of initial treatment. Survival is directly related to the presence and progression of liver metastases. There are currently no guidelines for surveillance or standard of care treatment modalities for metastatic uveal melanoma. Our patient was closely monitored by his oncologist, and follow-up was discontinued after several disease-free years. This case demonstrates that patients with a history of uveal melanoma may benefit from continued surveillance with liver enzyme tests and liver imaging, akin to hepatocellular carcinoma screening. Heightened physician vigilance and patient awareness may aid in early diagnosis of recurrence.Figure 1:: A) Hematoxylin and eosin stain, B) SOX-10 immunostaining. The tumor cells are positive for SOX10, Melan A, negative for arginase and HSA. The results support the diagnosis of metastatic melanoma.

SOX10 commonly stains scar in Mohs sections

Sox10 immunostaining is used for the diagnosis and margin evaluation of melanocytic lesions. Sox10 was initially thought not to stain fibrohistiocytic processes. Consequently, it was believed to reliably distinguish desmoplastic melanoma from scar. However, recent data from formalin sections suggest Sox10 is less specific than previously thought. In this report, we demonstrate that Sox10-stained Mohs sections commonly show strong, fractional staining of scar. When using Sox10 with frozen section immunohistochemistry, Mohs practitioners should recognize the potential of this marker to stain scar to avoid overdiagnosis of desmoplastic melanoma.

CS-08 A CASE OF CD 57 NEGATIVE OLFACTORY GROOVE SCHWANNOMA IN WHICH SCHWANN / 2 E AND SOX10 WAS USEFUL FOR DISTINGUISHING FROM OEC TUMOR: A CASE REPORT AND REVIEW OF THE LITERATURES

INTRODUCTIONIn the case of the differentiate between olfactory groove schwannomas(OGS) and olfactory ensheathing cell (OEC) tumors, CD57 which is the marker which is specific for Schwann cell is useful. We experienced a case of OGS that was negative for CD57.CASE PRESENTATIONThis case was a 13-year-old girl. Medical history: She visited the pediatric department with a chief complaint of headache. On the magnetic resonance image (MRI), a tumorous lesion was found in the anterior skull base and was referred to our department. No dysosmia, visual impairment, or cafe au lait spots were observed. Past history: As a medical history, she has developed acute lymphocytic leukemia at the age of 1 and has achieved complete remission after chemotherapy. At that time, radiation treatment to the head was not performed. Neuroradiological findings: The tumor was strongly enhanced heterogeneously in Gadolinium (Gd) enhanced MRI and the angiography showed hypovascular. Progress after hospitalization: The tumor was clearly demarcated from the surrounding brain surface and adhered strongly to the cribriform plate. Eventually, all tumors were removed and the patient was discharged on the 10th postoperative day. Five years have passed since the operation, and no recurrence of the tumor has been confirmed by MRI. Pathological findings: Antoni A and Antoni B were seen by Hematoxylin & Eosin (H & E) staining. Immunostaining showed S-100 strong positive, Schwann / 2E and Sox10 positive, and CD57 negative. Discussion: In our case, CD57 (Leu7) was negative, but Schwann / 2E and Sox10 were positive, so OGS was diagnosed.CONCLUSIONWe experienced a case of OGS that was negative for CD57 (Leu7) but positive for Schwann / 2E and Sox10. For pathological differentiation between OGS and the OEC tumor, Schwann / 2E and Sox10 immunostaining would also be necessary in addition to H & E stain and CD57 (Leu7).

Clinical Neuropathology practice guide 6-2013: morphology and an appropriate immunohistochemical screening panel aid in the identification of synovial sarcoma by neuropathologists

Aims: Pathologists are under increasing pressure to accurately subclassify sarcomas, yet neuropathologists have limited collective experience with rare sarcoma types such as synovial sarcoma. We reviewed 9 synovial sarcomas affecting peripheral nerve diagnosed by neuropathologists and explored the morphologic and immunohistochemical differences between these and MPNST. Our goal was to make practical recommendations for neuropathologists regarding which spindle cell tumors affecting nerve should be sent for SYT-SSX testing. Methods: Clinical records and genetics were reviewed retrospectively and central pathology review of 9 synovial sarcomas and 6 MPNST included immunohistochemistry for SOX10, S100, BAF47, CK (lmw, pan, CK7, CK19), EMA, CD34, bcl2, CD99, and neurofilament. Results: Common synovial sarcoma sites were brachial plexus, spinal and femoral nerve, none were “intra-neural”, all had the SYT-SSX1 translocation, and 6/9 were monophasic with myxoid stroma and distinct collagen. Half of the monophasic synovial sarcomas expressed CK7, CK19 or panCK in a “rare positive cells pattern”, 8/9 (89%) expressed EMA, and all were SOX10 immunonegative with reduced but variable BAF47 expression. Conclusions: We recommend that upon encountering a cellular spindle cell tumor affecting nerve neuropathologists consider the following: 1) SYT-SSX testing should be performed on any case with morphology suspicious for monophasic synovial sarcoma including wiry or thick bands of collagen and relatively monomorphous nuclei; 2) neuropathologists should employ a screening immunohistochemical panel including one of CK7, panCK or CK19, plus EMA, S100 and SOX10, and 3) SYT-SSX testing should be performed on any spindle cell tumor with CK and/or EMA immunopositivity if SOX10 immunostaining is negative or only labels entrapped nerve elements.

Value of SOX10 Immunostaining in Tumor Diagnosis

SOX10 is a transcription factor that is essential for the generation of neural crest cells, their survival, and maintenance of pluripotency. Recent studies have shown that, among tumors, SOX10 is commonly expressed in melanomas, including desmoplastic melanomas, tumors with Schwann cell differentiation, and some salivary gland neoplasms, particularly those with myoepithelial differentiation. Because of its restricted expression, SOX10 has proved to be a useful immunohistochemical marker with a wide range of diagnostic applications in surgical pathology, some of which are briefly reviewed.

Acquisition of neuronal and glial markers by neural crest-derived cells in the mouse intestine.

Enteric neurons and glia arise from the neural crest. The phenotype of crest-derived cells was examined as they differentiated into neurons or glia in the mouse small and large intestine. Previous studies have shown that undifferentiated enteric crest-derived cells are Phox2b(+)/Ret(+)/p75(+)/Sox10(+), and at embryonic day (E) 10.5, about 10-15% of the crest-derived cells in the small intestine have started to differentiate into neurons. In the current study, by E12.5 and E14.5, about 25% and 47%, respectively, of Phox2b(+) cells in the small intestine were immunoreactive to the pan-neuronal protein, ubitquitin hydrolase (PGP9.5), and the percentage did not change dramatically from E14.5 onward. The differentiation of crest-derived cells into neurons in the colon lagged behind that in the small intestine by several days. Differentiating enteric neurons showed high Ret, low p75, and undetectable Sox10 immunostaining. Glial precursors were identified by the presence of brain-specific fatty acid binding protein (B-FABP) and detected first in the fore- and rostral midgut at E11.5. Glial precursors appeared to be B-FABP(+)/Sox10(+)/p75(+) but showed low Ret immunostaining. S100b was not detected until E14.5. Adult glial cells were B-FABP(+)/Sox10(+)/p75(+)/S100b(+). A nucleic acid stain (to identify all ganglion cells) was combined with immunostaining for PGP9.5 and S100b to detect neurons and glial cells, respectively, in the postnatal intestine. At postnatal day 0, fewer than 5% and 10% of cells in myenteric ganglia of the small and large intestine, respectively, were neither PGP9.5(+) nor S100b(+). Because some classes of neurons are not present in significant numbers until after birth, the expression of PGP9.5 by developing enteric neurons appeared to precede the expression of neuron type-specific markers.