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1 Ophthalmic Pathology Evening Specialty Conference USCAP th March, 2017 Mukul K. Divatia, MD Assistant Professor Department of Pathology & Genomic Medicine Weill Cornell Medical College Houston Methodist Hospital Houston, TX USA Disclosure of Relevant Financial Relationships USCAP requires that all planners (Education Committee) in a position to influence or control the content of CME disclose any relevant financial relationship WITH COMMERCIAL INTERESTS which they or their spouse/partner have, or have had, within the past 12 months, which relates to the content of this educational activity and creates a conflict of interest. Dr. Divatia declase she has nothing to disclose. Clinical History 55 year-old woman presented with the following signs and symptoms: 1) right eye pain and proptosis, 2) eyelid swelling 3) abduction limitation progressive over several months Radiological Findings Orbital CT scan, MRI, and angiography showed i. a well-circumscribed, highly vascular mass situated adjacent to the optic nerve ii. displacing the globe laterally and downward iii. supplied by branches of the right ophthalmic artery Treatment Approach Histological Features Marked vascularity and high arterial flow within the mass Intra-arterial embolization of the ciliary feeding vessels was performed Followed by orbitotomy with resection of a 2.7 x 2 x 1.5 cm, irregularly shaped lesion with a glistening, bosselated and hypervascular surface 1
2 Polarizable material Mitotic activity- 6 mitoses/10 HPF Capsular infiltration 2
3 Differential Diagnosis 1.Dermatofibrosarcoma protuberans 2.Deep fibrous histiocytoma 3.Spindle cell lipoma 4.Cellular schwannoma 5.Monophasic synovial sarcoma 6.Malignant peripheral nerve sheath tumor 7.Spindle cell melanoma 8.Spindle cell/poorly differentiated carcinoma 9.Dedifferentiated liposarcoma CD34 CD99 IHC Profile bcl2 Ki-67 proliferation index STAT6 Diagnosis Malignant Solitary Fibrous Tumor s/p Onyx embolization Onyx (ethylene vinyl alcohol copolymer) embolization Preoperative onyx embolization reported for different types of vascular tumors of head and neck Aims to reduce hemorrhagic complications of surgery Vision-sparing preoperative onyx embolization of orbital meningiomas and SFTs has been reported 3
4 Onyx embolization May be performed transarterially or via direct, percutaneous tumor puncture Onyx is an ideal substance for embolizing orbital lesions like SFT Mechanism: Slow precipitation properties of Onyx allows deep penetration into smaller vessels within the tumor producing a diffuse infiltration and minimizing the need for repeated catheterizations Solitary Fibrous Tumor (SFT) Fibroblastic neoplasm that frequently arises in the pleura but can occur at almost any anatomic site Most cases of SFT reported as hemangiopericytoma (HP C) -a neoplasm with perivascular (pericytic) differentiation exhibiting a well-developed branching vascular pattern SFT-Salient Facts Clinical Features Usually well- circumscribed Composed of variably cellular and patternless distributions of bland spindle and ovoid cells within prominent collagenous stroma Diffuse positivity for CD34 Displays a broad spectrum of both morphology and biologic behavior Behavior of SFTs is unpredictable Propensity for aggressive behavior in a minority of cases to ensure adequate clinical follow-up Peak incidence: middle-aged adults (age range years) Most cases occur in 5 th -6 th decades M=F(except the fat-forming variant, M>F) More commonly encountered at extrapleural sites Most common extrapleural locations: retroperitoneum, deep soft tissues of extremities (thigh, axilla), abdominal cavity, and head and neck (including the orbit and meninges) Head and Neck SFTs Approximately 10% cases reported in head and neck region Symptoms due to to mass effect, based on size and site of tumor Tends to present relatively early with compression symptoms or local invasion in cases with malignant behavior Rarely, SFT may cause hypoglycemia due to the production of insulin-like growth factor I or II Treatment and Outcome of SFT Wide surgical resection is gold standard for localized disease Pre- or postoperative radiation therapy or adjuvant chemotherapy is not employed routinely Most SFTs pursue a benign clinical course 5% to 10% SFTs recur or metastasize Estimated recurrence rates for malignant SFTs are around 20-30% Locoregional recurrent disease is more frequent in patients with malignant histologic features compared with those with classical morphology 4
5 Prognosis is usually excellent for most SFTs without malignant histologic features SFTs with malignant features are associated with a poor outcome SFTs with bland histologic appearances at diagnosis can also behave aggressively with development of widespread metastatic disease A large case series by Demicco et al. has shown 5- and 10- year disease-specific survival rates of 89% and 73%, and overall 5- and 10-year metastasis-free rates of 74% and 55%, respectively Mod Pathol. 2012; 25: Genetics NAB2-STAT6 gene fusions Recurrent intrachromosomal rearrangements on chromosome 12q13 Fusion shows variable breakpoints and leads to nuclear expression of the C-terminal portion of STAT6 Genetics SFT- Classic type Different NAB2-STAT6 fusion types may be associated with separate clinicopathologic subgroups of SFTs NAB2ex4-STAT6ex2/3: Most common fusion variant classic pleuropulmonary SFTs with prominent fibrosis and usually indolent behavior and occurred in older patients NAB2ex6-STAT6ex16/17: Second commonest variant found in a relatively younger population, typical SFT from deep soft tissues and displayed more aggressive clinical behavior Am J Pathol. 2014; 184: Cellular SFT Myxoid SFT 5
6 Fat-forming SFT Giant cell rich variant of SFT (giant cell angiofibroma) Malignant SFT SFT with otherwise typical morphologic appearances with some or all of the following features: a) Infiltrative margins b) Hypercellularity c) At least focal pleomorphism d) Mitotic index greater than 4/10 hpf e) Necrosis f) Frequently associated with loss of CD34 expression Risk Stratification Mod Pathol. 2012; 25: Risk Stratification Patient age, tumor size, and mitotic index predicted both time to metastasis and disease-specific mortality, while necrosis predicted metastasis only A risk stratification model based on age, size, and mitotic index to detect patients at high risk for poor outcomes Small tumors with low mitotic rates are highly unlikely to metastasize Large tumors 15 cm, which occur in patients 55 years, with mitotic figures 4/10 high-power fields require close follow-up and have a high risk of both metastasis and death Dedifferentiated SFT Relatively newly defined concept in SFT Rare finding showing abrupt transition between typical SFT and areas with high-grade, anaplastic morphology Documented in pleural and soft tissue SFTs Morphology varies from spindle cell sarcoma (NOS) to undifferentiated pleomorphic sarcoma Heterologous dedifferentiation such as rhabdomyosarcoma and osteosarcoma can also be rarely seen 6
7 Immunohistochemical stains Differential diagnosis POSITIVE STAT6 CD34 Bcl2 CD99 Nuclear beta-catenin (40%) Focal EMA and SMA NEGATIVE CD31 Desmin h-caldesmon S100 protein Cytokeratins Predominantly Cellular Morphology (including Malignant Forms) 1. Dermatofibrosarcoma protuberans 2. Deep fibrous histiocytoma 3. Spindle cell lipoma 4. Cellular schwannoma 5. Monophasic synovial sarcoma 6. Malignant peripheral nerve sheath tumor 7. Spindle cell melanoma 8. Spindle cell/poorly differentiated carcinoma 9. Dedifferentiated liposarcoma Differential Diagnosis Predominantly Fibrous Morphology: 1. Desmoid Fibromatosis 2. Angiofibroma of soft tissue Predominantly Vascular Morphology: 1.Hemangioma with stromal hyalinization 2.Symplastic hemangioma Differential Diagnosis Fat-Forming Solitary Fibrous Tumor 1.Well-differentiated liposarcoma 2.Dedifferentiated liposarcoma, morphologically low grade 3.Myolipoma/lipoleiomyoma SFT with Stromal Giant Cells (Giant Cell Angiofibroma) 1. Giant cell fibroblastoma SFT: Things to remember Occurs mostly in middle-aged adults with a wide anatomic distribution May present with hypoglycemia Patternless architecture with variable cellularity; prominent stromal collagen; and ectatic, branching ( staghorn ) vessels Small unpredictable risk of metastasis (for conventional SFT) Histologically malignant SFT: 20% to 30% metastatic rate Most reliable criterion for malignancy: increased mitotic activity (>4 per 10 hpf) STA6 very helpful IHC marker for arriving at diagnosis Questions? 7
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