The 2020 WHO Classification of Tumors of Bone: An Updated Review Overview • Selected new tumor entities and subtypes in the 2020 WHO classification of bone tumors • Newly identified molecular genetic alterations and immunohistochemistry markers • Tumors reclassified in the categorization of tumors • Tumors changed in ICD-O code or biological potential • Tumors removed in the 2020 WHO classification of bone tumors 2013 WHO classification 2020 WHO classification Tumours of soft tissue Tumours of soft tissue Tumours of bone Tumours of bone Undifferentiated small round cell sarcomas of bones and soft tissue Tumours of bone 2013 WHO Classification 1. Chondrogenic tumors 2. Osteogenic tumors 3. Fibrogenic tumors 4. Fibrohistiocytic tumours 5. Ewing sarcoma 6. Haematopoietic neoplasm 7. Osteoclastic giant cell-rich tumors 8. Notochordal tumors 9. Vascular tumors 10. Myogenic , lipogenic and epithelial tumours 11. Tumours of undefined neoplastic nature 12. Undifferentiated high grade pleomorphic sarcoma Tumours of bone 2020 WHO Classification 1. 2. 3. 4. 5. 6. 7. 8. • Chondrogenic tumors Osteogenic tumors Fibrogenic tumors Haematopoietic neoplasm Osteoclastic giant cell-rich tumors Notochordal tumors Vascular tumors Other mesenchymal tumours of bone Ewing sarcoma • • • • Fibrohistiocytic tumours Myogenic , lipogenic and epithelial tumours Tumours of undefined neoplastic nature Undifferentiated high grade pleomorphic sarcoma Chondrogenic Tumors Chondrogenic Tumors • 2013 WHO classification, the terminology “atypical cartilaginous tumor” (ACT) was introduced as a synonym for chondrosarcoma, grade 1 and classified as intermediate (locally aggressive) Site Term Biological potential Appendicular atypical skeletons (long and cartilaginous short tubular bones) tumor / ACT Intermediate Axial skeleton, (pelvis, scapula, and skull base) Malignant chondrosarcoma, grade 1 / CS1 Changes in Biological Potential in the Chondrogenic Tumors Tumor Entities 2013 WHO Classification 2020 WHO Classification Chondroblastoma Intermediate Benign tumor Chondromyxoid fibroma Intermediate Benign tumor Synovial chondromatosis Benign tumor Intermediate (locally aggressive) Molecular Genetic Alterations Tumour entities Genetic alteration Enchondroma IDH1 and IDH2 Osteochondroma EXT1 or EXT2 Chondroblastoma H3F3B p.Lys36Met (K36M) Chondromyxoid fibroma GRM1 rearrangements Primary central ACT/CS1 IDH1 and IDH2 Central chondrosarcoma, grade2 IDH1 and IDH2 and 3 Periosteal chondrosarcoma IDH1 and IDH2 Secondary peripheral ACT/CS1 EXT1 or EXT2 Dedifferentiated chondrosarcoma IDH1 and IDH2 Mesenchymal chondrosarcoma HEY1-NCOA2 Central Atypical Cartilaginous Tumor/ Chondrosarcoma, Grade 1 • Arising in medulla of bone • Etiology – Primary : Not associated with precursor – Secondary : Associated with enchondroma • IDH1 and IDH2 gene mutation • Histology – – – – Cellularity low Nuclei uniform, small, binucleation Mitosis abcent Permeate and entrap the preexisting lamellar bone trabeculae – Presence of soft tissue extention Central Atypical Cartilaginous Tumor/ Chondrosarcoma, Grade 1 Secondary Peripheral Atypical Cartilaginous Tumor/ Chondrosarcoma, Grade 1 • Neoplasm arising within the cartilaginous cap of a preexisting osteochondroma • Thick (>2 cm), lobulated cartilaginous cap • Nodules of cartilage apparently permeating soft tissues and separated from the main mass of the tumor. Central Chondrosarcoma Grades 2 and 3 • Present intramedullary • Histology – More cellular than ACT/CS1 with more pronounced nuclear atypia and show a variable extent of myxoid changes – Mitoses are present and binucleation and necrosis can occur • IDH 1, IDH2 ,TP53 mutation present Central Chondrosarcoma Grades 2 and 3 Mesenchymal Chondrosarcoma • High-grade, malignant, biphasic tumours • Sites – – bone, soft tissue, and intracranial sites. Intraosseous lesions mainly involve the jaw, ribs, ilium, vertebrae, and lower extremities • HEY1 and NCOA2 gene mutations present • Histology – Small to medium-sized, poorly differentiated round cells – Various proportions of islands of well-differentiated hyaline cartilage • IHC – S100 protein, CD99, and SOX9. – Aberrant expression of EMA, desmin, myogenin, and MYOD1 may be present – SMARCB1 (INI1) is retained Mesenchymal Chondrosarcoma Dedifferentiated Chondrosarcoma • Bimorphic histologic appearance with a conventional chondrosarcoma component and an abrupt transition to a highgrade, noncartilaginous sarcoma • Sites – femur (46%), pelvis (28%), humerus (11%), and scapula • Molecular features – TP53 and IDH mutations • Histology – cartilaginous portion can range from an enchondroma-like appearance to grade 1 or grade 2 chondrosarcomas – The high-grade dedifferentiated component usually has the appearance of a high-grade undifferentiated pleomorphic sarcoma or osteosarcoma Dedifferentiated Chondrosarcoma Osteogenic tumors Osteogenic tumors 2013 WHO Classification Osteoma • Osteoid osteoma • Osteoblastoma • Low-grade central osteosarcoma • • Conventional osteosarcoma • Telangiectatic osteosarcoma • Small cell osteosarcoma • Parosteal osteosarcoma • Periosteal osteosarcoma • High-grade surface osteosarcoma 2020 WHO Classification • Osteoma NOS • Osteoid osteoma NOS • Osteoblastoma NOS • Low-grade central osteosarcoma • Osteosarcoma NOS Conventional osteosarcoma Telangiectatic osteosarcoma Small cell osteosarcoma • Secondary osteosarcoma • Parosteal osteosarcoma • Periosteal osteosarcoma • High-grade surface osteosarcoma Molecular Genetic Alterations Tumour entities Genetic alteration Osteoid osteoma FOS & FOSB rearrangement Osteoblastoma FOS & FOSB rearrangement Low-grade central osteosarcoma MDM2 and CDK4 amplification Parosteal osteosarcoma MDM2 and CDK4 amplification Osteosarcoma NOS TP53 and RB1 Osteosarcoma NOS • Majority originate in the long bones of the extremities • Telangiectatic osteosarcomas also frequently develop around the knee ( 60%) and in the proximal humerus ( 20%). – They occur in the metaphysis, commonly with direct extension into the adjacent epiphysis and diaphysis • Small cell osteosarcoma more commonly develops in the diaphysis of long bones • IHC (Non specific) – SATB2, osteocalcin, osteonectin, osteoprotegerin, RUNX2, S100 protein Secondary Osteosarcoma • In the 2020 WHO classification, secondary osteosarcomas are subdivided into 6 subtypes 1. Osteosarcoma in PDB 2. Radiation-associated osteosarcoma 3. Infarct-related osteosarcoma 4. Osteosarcoma due to chronic osteomyelitis 5. Implant-related osteosarcoma 6. Osteosarcoma secondary to early postzygotic disorders such as fibrous dysplasia Fibrogenic Tumors Fibrogenic Tumors • In the 2020 WHO classification, there were no significant changes in the category of fibrogenic tumors Tumour entities Genetic alteration Desmoplastic fibroma CTNNB1 mutations Fibrosarcoma CDKN2A deletion Vascular tumours Vascular tumours 2013 WHO Classification Haemangioma • Epithelioid haemangioma • Epithelioid • haemangioendothelioma Angiosarcoma • 2020 WHO Classification Haemangioma NOS • Epithelioid haemangioma • Epithelioid • haemangioendothelioma NOS Angiosarcoma • Molecular Genetic Alterations Tumour entities Genetic alteration Epithelioid hemangioma FOS or FOSB rearrangements Epithelioid hemangioendothelioma WWTR1-CAMTA1, YAP1-TFE3 Epithelioid Hemangioma of Bone • Commonly affects the fourth decade. • It commonly involves long tubular bones, short tubular bones of the distal lower extremities, flat bones, and vertebrae • Histology – Lobular architecture. – Cells form vascular lumina or grow in solid sheets. – A subset of cases, referred to as atypical epithelioid hemangiomas, displays more solid growth, increased cellularity, nuclear pleomorphism, and necrosis. • IHC – CD31, CD34, FLI1, ERG, and factor VIII-related antigen. – Many cases are also positive for cytokeratin and EMA. – FOS or FOSB can be expressed in a subset of cases. Epithelioid Hemangioendothelioma of Bone • • Malignant neoplasm arising from bone • Histology Commonly arise in long tubular bones, especially in lower extremities, followed by the pelvis, ribs, and spine – – • • Composed of epithelioid endothelial cells within a myxohyaline stroma Tumor cells have moderate amounts of eosinophilic cytoplasm and round nuclei with inconspicuous nucleoli. Intracytoplasmic vacuoles are sometimes present. EHE with YAP1-TFE3 fusion is associated with distinct morphology – well-formed lumina and larger tumor cells with abundant, voluminous cytoplasm. – The myxohyaline stroma is usually absent or inconspicuous IHC – – CD31, CD34, ERG, FLI1, factor VIII-related antigen, D2-40, and PROX1. – TFE3 immunohistochemistry can be used to identify EHE with YAP1-TFE3 Nuclear staining for CAMTA1 is positive in 86% to 88% of cases and is highly specific. Osteoclastic giant cell-rich tumors Osteoclastic giant cell-rich tumors 2013 WHO Classification • Giant cell lesion of the small bone • Giant cell tumour of bone Fibrohistiocytic tumours • Non ossifying fibroma 2020 WHO Classification • • • • Aneurysmal bone cyst Non-ossifying fibroma Giant cell tumor of bone NOS Conventional giant cell tumor of bone • Giant cell tumor of bone, malignant • Most tumors previously considered giant cell lesion of the small bones represent a solid variant of ABC • Denosumab-treated giant cell tumor (GCT) is newly described as a variant of GCT Changes in Biological Potential Tumor Entities 2013 WHO Classification 2020 WHO Classification Aneurysmal bone cyst Intermediate (locally aggressive) Benign tumor Molecular Genetic Alterations Tumour entities Genetic alteration Aneurysmal bone cyst USP6 rearrangements Non-ossifying fibroma KRAS and FGFR1 mutations Giant cell tumor H3F3A p.Gly34Trp (p.G34W) mutations Aneurysmal Bone Cyst • Benign neoplasm of bone • Most common in children and adolescents. • It usually arises in the metaphysis of long bones, especially the femur, tibia, and humerus, and the posterior elements of vertebral bodies. • Histology – ABC is well circumscribed and contains blood-filled cystic spaces separated by fibrous septa composed of neoplastic (myo)fibroblastic spindle cells, scattered multinucleated osteoclast-type giant cells, and reactive woven bone. Non-ossifying Fibroma • Affects children or adolescents and undergoes spontaneous regression after puberty. • It commonly occurs in the metaphysis of long bones of the lower extremities, especially the distal femur, proximal tibia, and distal tibia. • Histology – Bland, spindle-shaped cells with a storiform growth pattern. – Multinucleated osteoclast-type giant cells, hemosiderin deposition, and foamy macrophages • In the 2013 WHO classification, tumors with morphology similar to NOF but occurring in the pelvis and non metaphyseal region of long bones, and in age groups unusual for NOF, have been designated as benign fibrous histiocytoma (BFH) of bone. • Current assessments indicate majority of BFH cases representing GCT of bone with regressive changes. Non-ossifying Fibroma Malignant Giant Cell Tumor • GCT of bone is a locally aggressive and rarely metastasizing neoplasm composed of neoplastic mononuclear stromal cells admixed with macrophages and osteoclast-like giant cells. • Malignant GCTs account for <10% of all GCTs. • Approximately 95% of GCTs harbor pathogenic H3.3A (H3F3A) mutations • Histology – malignant GCTs show a sarcomatous component juxtaposed to a conventional GCT. Denosumab-treated Giant Cell Tumor • Denosumab, a receptor activator of nuclear factor-κB ligand (RANKL) inhibitor is increasingly used in the treatment of GCT. • The treatment effect of denosumab in GCTs is marked depletion of osteoclastic giant cells and increased woven bone deposition . • Variable amounts of conventional GCT features may persist. • Denosumab-treated GCTs with abundant bone formation may mimic de novo osteosarcomas or secondary malignant GCTs. • unlike osteosarcomas or secondary malignant GCTs, denosumab-treated GCTs show less severe atypia, reduced mitotic activity, and lack of infiltrative growth pattern. Denosumab-treated Giant Cell Tumor Notochordal tumors Notochordal tumors 2013 WHO Classification 2020 WHO Classification • Benign notochordal cell • tumor Chordoma – Chordoma NOS – Chondroid chordoma – Dedifferentiated chordoma Benign • Benign notochordal cell tumor Malignant • Conventional chordoma /Chordoma NOS • Chondroid chordoma • Poorly differentiated chordoma • Dedifferentiated chordoma Notochordal Tumors • Chondroid chordoma is a variant of conventional chordoma and show a large area of the matrix mimics hyaline cartilaginous tumors. • Dedifferentiated chordoma is a chordoma with a biphasic appearance, characterized by conventional chordoma and high-grade sarcoma. • PDC is crucial as a new distinct subtype of chordoma. Tumour entities Genetic alteration Chordoma TBXT copy number gain Poorly differentiated chordoma SMARCB1 deletions Poorly Differentiated Chordoma • It typically arises in children and occasionally in young adults • The most common location is the skull base , followed by the cervical spine and rarely the sacrococcygeal region. • Histology – PDC is composed of cohesive sheets or nests of poorly differentiated epithelioid cells, often with a focal rhabdoid morphology. – Mitotic activity is increased – Geographical necrosis is often conspicuous. – Physaliphorous cells are absent. • IHC – tumor cells are positive for cytokeratin and brachyury with variable positivity for S100 protein. • A diagnostic feature is the loss of SMARCB1 (INI1) expression Poorly Differentiated Chordoma Other mesenchymal tumors of bone • • • • 2013 WHO Classification 2020 WHO Classification Myogenic, lipogenic and epithelial tumours Lipoma Adamantinoma Leiomyosarcoma Liposarcoma Other mesenchymal tumors of bone Lipoma Adamantinoma of long bone Leiomyosarcoma Hibernoma • • • • • Fibrocartilaginous mesenchymoma Simple bone cyst • Simple bone cyst Fibrous dysplasia • Fibrous dysplasia Osteofibrous dysplasia • Osteofibrous dysplasia Chondromesenchymal hamartoma • Chondromesenchymal hamartoma • Pleomorphic sarcoma, Undifferentiated high grade undifferentiated pleomorphic sarcoma Tumours of undefined neoplastic nature • • • • • Other Mesenchymal Tumors • In the 2020 WHO classification, adamantinoma is divided into three subtypes: 1. Classic 2. Ostiofibrous dysplasia (OFD) -like 3. Dedifferentiated adamantinoma. Tumor Entities 2013 WHO Classification 2020 WHO Classification OFD-like adamantinoma Malignant Intermediate (locally aggressive) Hibernoma Benign Fibrocartilaginous mesenchymoma Intermediate (locally aggressive) Hibernoma of Bone • Benign neoplasm composed of brown adipocytes that arise within or on the surface of bone. • Middle-aged and elderly adults • Affect the axial skeleton. • Histology – Brown fat cells are large, have numerous clear vacuoles that scallop central nuclei, and are surrounded by eosinophilic cytoplasm – The cells may be admixed with hematopoietic elements. • IHC – Express brown fat marker uncoupling protein 1. Hibernoma of Bone Fibrocartilaginous Mesenchymoma • It is a very rare, locally aggressive neoplasm • Affect children and adolescents • Frequently occurs in the metaphysis of long bones, followed by the iliac-pubic bones, vertebrae, ribs, and metatarsal bones. • It lacks GNAS , IDH1 and IDH2 mutations, and MDM2 amplification • Histology – FCM is characterized by spindle cell proliferation, hyaline cartilage nodules, and bone trabeculae – It may destroy the cortex and extend into the soft tissue. Fibrocartilaginous Mesenchymoma Dedifferentiated Adamantinoma • It involves the anterior metaphysis or diaphysis of the tibia • Dedifferentiated adamantinoma shows foci of classic adamantinoma and gradual transition to dedifferentiated areas composed of highly pleomorphic tumor cells with high mitotic counts • IHC – Epithelial components show coexpression of cytokeratin, EMA, vimentin, p63, and podoplanin. – Sarcomatoid components may or may not show some cytokeratin positivity Hematopoietic neoplasms Hematopoietic neoplasms 2013 WHO Classification • Plasma cell myeloma • Solitary plasmacytoma of bone • Primary non Hodgkin lymphoma of bone 2020 WHO Classification • Solitary plasmacytoma of bone • Primary non Hodgkin lymphoma of bone • Langerhans cell histiocytosis • Erdheim-Chester disease • Rosai-Dorfman disease Changes in Biological Potential Tumor Entities 2013 WHO Classification 2020 WHO Classification Langerhans cell histiocytosis Intermediate (locally aggressive) LCH NOS : Intermediate (locally aggressive) LCH Disseminated : Malignant Molecular Genetic Alterations Tumour entities Genetic alteration Langerhans cell histiocytosis BRAF V600E mutations Erdheim-Chester disease BRAF p.Val600Glu mutations Rosai-Dorfman disease NRAS, KRAS, MAP2K1 Langerhans Cell Histiocytosis • LCH is a clonal neoplastic proliferation of myeloid dendritic cells with a Langerhans cell phenotype. • LCH can be unifocal or multifocal or may be multisystem. • Histology – LCH cells have grooved, folded, indented, or lobed nuclei and moderately abundant, slightly eosinophilic cytoplasm. • IHC – LCH cells express CD1a, CD207 (langerin), S100 protein, CD68 Erdheim-Chester Disease • ECD is a clonal systemic histiocytosis with inflammation and fibrosis. • The median age at diagnosis is 55 years, • • • • multisystem disease. Long bones are involved in >90% of cases. Infiltration of the retroperitoneum (58%) or around the aorta (46%) Histology – infiltration of foamy, lipid-laden, and/or small mononuclear histiocytes associated with Touton giant cells, small lymphocytes, plasma cells, and neutrophils. – Fibrosis is usually present and is sometimes predominant. • IHC – Histiocytes are positive for CD163, CD68, and CD14 and negative for CD1a and CD207. Erdheim-Chester Disease UNDIFFERENTIATED SMALL ROUND CELL SARCOMAS OF BONE AND SOFT TISSUE UNDIFFERENTIATED SMALL ROUND CELL SARCOMAS OF BONE AND SOFT TISSUE 2013 WHO Classification • Ewing sarcoma 2020 WHO Classification • Ewing sarcoma • Round cell sarcoma EWSR1–non-ETS fusions • CIC-rearranged sarcoma with • Sarcoma with BCOR genetic alterations UNDIFFERENTIATED SMALL ROUND CELL SARCOMAS OF BONE AND SOFT TISSUE • Small round cell sarcomas histologically resembling ES but lacking fusions between the EWSR1 gene and ETS family of transcription factors. • The new chapter includes ES and 3 main categories 1. Round cell sarcoma with EWSR1–non-ETS fusions 2. CIC-rearranged sarcoma 3. Sarcoma with BCOR genetic alterations. • Although these tumors show overlapping histologic features, most exhibit characteristic molecular and clinical features. Ewing sarcoma • Small round cell sarcoma with gene fusions involving one member of the FET family of genes (usually EWSR1) and a member of the ETS family of transcription factors. • ES is the second most common malignant bone tumor in children and young adults, after osteosarcoma. • 85% - EWSR1- FLI1 fusions • 10% - EWSR1-ERG fusions. Round Cell Sarcomas with EWSR1–non-ETS Fusions • Round cell sarcomas with EWSR1–non-ETS fusions are rare, • EWSR1 or FUS fusions involving unrelated to the ETS gene family. • It occurs in children and adults . • The genes involved in EWSR1/FUS fusions include NFATC2 and PATZ1. 1. EWSR1-NFATC2 sarcomas arise predominantly in the long bones than soft tissue. 2. FUS-NFATC2 sarcomas occur exclusively in the long bones 3. EWSR1-PATZ1 sarcomas arise in the deep soft tissue of the chest wall and abdomen. Histology • EWSR1-NFATC2 and FUS-NFATC2 sarcomas – composed of small to medium-sized round and/or spindled tumor cells. – The tumor cells are predominantly arranged in cords, small nests, trabeculae, and pseudoacinar patterns – in fibrohyaline or myxohyaline stroma. – nuclear pleomorphism, prominent nucleoli, and cytoplasmic clearing can be seen. • IHC – diffusely express CD99 in half of cases, – PAX7 and NKX2.2 may be expressed. • EWSR1-PATZ1 sarcomas. – Tumor cells may show mild atypia with coarse chromatin – Necrosis and mitotic activity may or may not be evident. • IHC – Coexpression of myogenic markers (e.g., desmin, myogenin,MYOD1) and neurogenic markers (eg, S100 protein, SOX10,and GFAP) is present CIC-rearranged Sarcoma • High-grade round cell undifferentiated sarcoma defined by CICrelated gene fusions ( CIC-DUX4 ) • Wide age range , from children to elderly adults. • Most tumors occur in the deep soft tissues of the limbs, trunk, head, neck, and retroperitoneum. • Primary osseous involvement is rare (<5%). Histology • Diffuse sheets of undifferentiated round cells, with a lobulated growth pattern. Spindled or epithelioid tumor cells may be partially present. • The tumor cells often reveal a mild degree of nuclear pleomorphism with vesicular chromatin and prominent nucleoli and a moderate amount of lightly eosinophilic or clear cytoplasm. • The mitotic rate is usually high and necrosis is common. • Myxoid stromal changes are present in one-third of the cases. • IHC – express CD99 in a patchy pattern. – WT1 and ETV4 are expressed in most cases. – Diffuse and strong nuclear expression of DUX4 is consistently present. CIC-rearranged Sarcoma Sarcoma With BCOR Genetic Alterations • Sarcomas with BCOR genetic alterations are uncommon and are divided into 2 groups: 1. Sarcomas with BCOR-related gene fusions, BCOR-CCNB3 2. Sarcomas with BCOR internal tandem duplication (BCOR-ITD) 1. BCOR-CCNB3 sarcomas • predilection for children • common in bone than soft tissue • predilection for the pelvis, lower limbs, and paraspinal region. – composed of primitive small round to ovoid cells – arranged in solid sheets or a vague nesting pattern – surrounded by a rich capillary network. Histology 1. Sarcomas with BCOR-ITD • occur within the first year of life • mainly in the soft tissues of the trunk, retroperitoneum, head, and neck – variable degrees of cellularity – ranging from solid sheets of small primitive cells to – hypocellular areas of dispersed spindle cells, within a myxoid matrix and delicate vessels . • IHC – most cases show BCOR and CCNB3 positivity. – SATB2, TLE1 and cyclin D1 are also expressed – CD99 is positive in approximately 50% of cases. BCOR-ITD sarcomas Summery Category New Entities and Subtypes Biological Potential Notochordal tumors Poorly differentiated chordoma Malignant Other mesenchymal tumors of bone Hibernoma of bone Benign Fibrocartilaginous mesenchymoma Intermediate Dedifferentiated adamantinoma Malignant Undifferentiated small round cell sarcomas of bone and soft tissue Round cell sarcoma with EWSR1– Malignant non-ETS fusions CIC-rearranged sarcoma Malignant Sarcoma with BCOR genetic alterations Malignant New tumor entities and subtypes Tumor Entities WHO Classification WHO Classification Chondroblastoma Intermediate (rarely Benign tumor metastasizing) Chondromyxoid fibroma Intermediate (locally aggressive) Benign tumor Synovial chondromatosis Benign tumor Intermediate (locally aggressive) ACT/CS1 Intermediate (locally aggressive) ACT. Intermediate (locally aggressive) CS1. Malignant tumor Aneurysmal bone cyst Intermediate (locally aggressive) Benign tumor OFD-like adamantinoma Malignant tumor Intermediate (locally aggressive) Changes in Biological Potential Changes in Biological Potential Tumor Entities 2013 WHO Classification 2020 WHO Classification Langerhans cell histiocytosis Intermediate (locally aggressive) Langerhans cell histiocytosis NOS. : Intermediate Langerhans cell histiocytosis, disseminated : Malignant Erdheim-Chester disease Intermediate (locally aggressive) Malignant tumor Tumors removed Tumor Entities 2013 WHO Classification 2020 WHO Classification Benign fibrous histiocytoma Fibrohistiocytic tumor Removed Giant cell lesion of the small bones Osteoclastic giant cell rich tumor Removed Liposarcoma Lipogenic tumor Removed Thank you
