Essential Dermatopathology Jinah Kim, MD, PhD Department of Pathology and Dermatology Stanford University Medical Center
OBJECTIVES Review clinical, pathologic and molecular aspects of bone and fat tumors Discuss the main diagnosbc features Discuss picalls and differenbal diagnosis
Tumors of Fat Lipoma Angiolipoma Spindle cell / Pleomorphic lipoma Myolipoma Hibernoma Lipoblastoma Liposarcoma
HMGA2-LPP fusion gene Italiano et al. Genes Chromosomes Cancer, 2008; 47(11);971-7
Angiolipoma Late teens or early twenbes Forearm is the most common site, followed by the trunk and upper arm MulBple subcutaneous small nodules, usually tender/ painful
Angiolipoma
Tumors of Fat Lipoma Angiolipoma Spindle cell / Pleomorphic lipoma Myolipoma Hibernoma Lipoblastoma Liposarcoma
Spindle cell lipoma Posterior neck, upper back and shoulders Well circumscribed
Spindle cell lipoma CD34 posibve, usually extensive Mast cells may be numerous
Spindle cell lipoma/ Pleomorphic lipoma
Spindle cell lipoma/ Pleomorphic lipoma
Spindle cell lipoma/ Pleomorphic lipoma
DDX: Mammary-type fibroblastoma Median age 55 years, 80% men Usually inguinal / groin region or along milk line, also abdominal wall, buttock, back, vaginal wall Slowly growing painless mass/ incidental Usually subcutis, but may be deeper McMenamin and Fletcher. Am J Surg Pathol. 2001 Aug;25(8):1022-9.
Mammary-type fibroblastoma
Mammary-type fibroblastoma
Mammary-type fibroblastoma Desmin+ CD34 CD34+ smooth muscle actin +/- Rb - STAT6 -
Giant cell fibroblastoma
Giant cell fibroblastoma Painless nodule or mass in subcubs Back of the thigh, inguinal region, chest wall Children younger than 5 years of age
Tumors of Fat Lipoma Angiolipoma Spindle cell / Pleomorphic lipoma Myolipoma Hibernoma Lipoblastoma Liposarcoma
Myolipoma of sos Bssue Benign tumor Mature smooth muscle Mature adipose
Myolipoma of soft tissue Rarely reported Vast majority female Sites of involvement Females: pelvic, retroperitoneal, suprapubic,inguinal Males: inguinal, abdominal wall, back
Myolipoma of sos Bssue SMA
Myolipoma of soft tissue Composed of mature fat and bland smooth muscle Muscle predominates in most cases Usually evenly interspersed Muscle in short fascicles Both components lack any atypical features
Myolipoma Spindle cells posibve for SMA, Desmin CD34, HMB45 negabve
Tumors of Fat Lipoma Angiolipoma Spindle cell / Pleomorphic lipoma Myolipoma Hibernoma Lipoblastoma Liposarcoma
Hibernoma Rare, painless Benign tumor of subcutis and deep soft tissue Arise from brown fat Interscapular, axillae, low neck Cytogenetic rearrangement 11q13
Tumors of Fat Lipoma Angiolipoma Spindle cell / Pleomorphic lipoma Myolipoma Hibernoma Lipoblastoma Liposarcoma
Lipoblastoma
Lipoblastoma First three years of life ExtremiBes are most commonly involved Slowly growing nodule/mass, well circumscribed in subcubs Circumscribed, benign tumor
Lipoblastoma Lobules of immature fat separated by septa Lipoblasts in various stages of development Plexiform vascular pattern
8q11-13 PLAG1 Lipoblastoma
Lipoblastoma
Tumors of Fat Lipoma Angiolipoma Spindle cell / Pleomorphic lipoma Myolipoma Hibernoma Lipoblastoma Liposarcoma
Atypical Lipomatous Tumor/ Well Differentiated Liposarcoma Most common adult sarcoma Adults (>40 years of age) Intermediate malignant Painless, slowly growing mass
ALT/ WDL Deep soft tissue (thigh, retroperitoneum) Head and neck cases are often initially misdiagnosed, 53% recur Usually NOT superficial Location is the most important prognostic factor
Atypical Lipomatous Tumor/ WD Liposarcoma Fibrous Smudge septa cell and (Atypical atypical stromal cell) cells
Atypical Lipomatous Tumor/ WD Liposarcoma Lipoblasts Cell size variability Adipoctye atypia Smudge cells
amplification of 12q13-15 MDM2 and CDK4
Liposarcoma De-differenBated Myxoid (spindle cell and round cell) Pleomorphic NOS
Atypical Lipomatous Tumor/ WDL High-grade Sarcoma Dedifferentiated Liposarcoma
De-differenBated Liposarcoma (Grade Progression) De-differenBaBon Progression in grade to a high-grade sarcoma UndifferenBated pleomorphic sarcoma
De-differenBated Liposarcoma 10% of WDL Retroperitoneum TransiBon from the ALT/WDL to sarcoma
Myxoid liposarcoma
Myxoid liposarcoma
Myxoid Liposarcoma Second most common liposarcoma (10% adult sarcomas) Deep soft tissue of extremity (thigh) Large painless mass in adults
Myxoid Liposarcoma FUS-DDIT3 EWSR1-DDIT3
Myxoid liposarcoma
Round cell liposarcoma
Pleomorphic liposarcoma
Tumors of Bone Osteoma cutis Osteoid osteoma Osteoblastoma Osteosarcoma
Tumors of Bone Primary osteoma cubs Absent preexisbng, associated lesion Secondary ossificabon Inflammatory TraumaBc NeoplasBc
Osteoma cutis
Osteoma cutis
Secondary ossification of pilomatricoma
DifferenBal diagnosis Calcinosis CuBs CarBlaginous tumors of the skin Foreign body Gouty tophus
Bone Tumors Relatively rare group of tumors Malignant bone tumors comprise ~0.2% of all types of cancer They represent an important percentage of potentially curable cancers following multimodal therapy
Clinical Presentation Usually nonspecific: Pain (any tumor; osteoid osteoma: severe pain, worse at night, relieved by aspirin) Mass (parosteal OS: painless, hard growing mass in popliteal fossa) Pathologic fracture Asymptomatic
Diagnostic Factors Age Sex Skeletal localizabon Specific bone Specific area of bone 1. Medullary cavity, cortex, juxtacorbcal 2. Epiphysis, metaphysis, diaphysis Radiographic appearance
Age Adolescence Osteosarcoma and Ewing s sarcoma Young adults Giant cell tumor Elderly Chondrosarcoma
Location KNEE ½ of osteosarcomas Giant cell tumor CENTRAL/AXIAL ½ of osteoblastomas
Radiologic Patterns Sclerotic margin is generally an indication of benign, slowlygrowing neoplasm Ill-defined margin is generally an indication of malignant, rapidlygrowing neoplasm
Radiologic Patterns Solid, ivory-like pattern is generally seen in malignant bone matrix-forming tumors Rings and arcs are generally seen in chondroid matrixforming tumors
Benign Bone-Forming Tumors
Osteoid Osteoma Vs Osteoblastoma. Long bones, femur & tibia. < 2 cm. Night pain. Responds to aspirin. Radiolucent lesion within sclerotic cortex. Vertebrae or long bone metaphysis. > 2 cm. Painful. Not responsive to aspirin. Expansile radio-lucency with mottling
PATHOLOGY Well-circumscribed Osteoid Osteoma Woven bone trabeculae/osteoid rimmed by innocuous osteoblasts (nidus) Fibrovascular stroma TREATMENT Surgical resection/curettage May recur if not completely removed
Osteoid osteoma
Osteoid Osteoma
3cm Osteoblastoma Histologically very similar to osteoid osteoma
Osteoblastoma
Malignant Bone tumors Osteosarcoma
Osteosarcoma Metaphysis of long bones Femur, tibia, humerus (56%); flat bones, spine (older patients) Hematogenous spread to lungs is common
Osteosarcoma Poorly circumscribed Bone destruction Cortical disruption Bone matrix Soft tissue extension Codman s triangle
Osteosarcoma Classification Histologic types Intramedullary Osteoblastic Conventional (high grade) Chondroblastic Low grade central Fibroblastic Mandibular Post-radiation Giant-cell rich Paget disease Small cell Telangiectatic Osteoblastoma-like Multicentric Surface Parosteal (juxtacortical) Periosteal High Grade Intracortical (very rare) Extraosseous (soft parts)
Osteosarcoma
Osteoblastic Osteosarcoma
Chondroblastic Osteosarcoma
Fibroblastic Osteosarcoma
Osteosarcoma PATHOGENESIS Inherited mutant allele of RB gene Hereditary RB: marked increase (1000X) in OS Mutation of p53 suppressor gene Li-Fraumeni: bone and soft tissue sarcomas, early onset breast cancer, brain tumors, leukemia Overexpression of MDM2 (5-10%); INK4 and p16 Sites of bone growth/disease Prior irradiation