Essential Dermatopathology. Jinah Kim, MD, PhD Department of Pathology and Dermatology Stanford University Medical Center

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1 Essential Dermatopathology Jinah Kim, MD, PhD Department of Pathology and Dermatology Stanford University Medical Center

2 OBJECTIVES Review clinical, pathologic and molecular aspects of bone and fat tumors Discuss the main diagnosbc features Discuss picalls and differenbal diagnosis

3 Tumors of Fat Lipoma Angiolipoma Spindle cell / Pleomorphic lipoma Myolipoma Hibernoma Lipoblastoma Liposarcoma

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5 HMGA2-LPP fusion gene Italiano et al. Genes Chromosomes Cancer, 2008; 47(11);971-7

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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

8 Angiolipoma

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10 Tumors of Fat Lipoma Angiolipoma Spindle cell / Pleomorphic lipoma Myolipoma Hibernoma Lipoblastoma Liposarcoma

11 Spindle cell lipoma Posterior neck, upper back and shoulders Well circumscribed

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14 Spindle cell lipoma CD34 posibve, usually extensive Mast cells may be numerous

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16 Spindle cell lipoma/ Pleomorphic lipoma

17 Spindle cell lipoma/ Pleomorphic lipoma

18 Spindle cell lipoma/ Pleomorphic lipoma

19 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 Aug;25(8):

20 Mammary-type fibroblastoma

21 Mammary-type fibroblastoma

22 Mammary-type fibroblastoma Desmin+ CD34 CD34+ smooth muscle actin +/- Rb - STAT6 -

23 Giant cell fibroblastoma

24 Giant cell fibroblastoma Painless nodule or mass in subcubs Back of the thigh, inguinal region, chest wall Children younger than 5 years of age

25 Tumors of Fat Lipoma Angiolipoma Spindle cell / Pleomorphic lipoma Myolipoma Hibernoma Lipoblastoma Liposarcoma

26 Myolipoma of sos Bssue Benign tumor Mature smooth muscle Mature adipose

27 Myolipoma of soft tissue Rarely reported Vast majority female Sites of involvement Females: pelvic, retroperitoneal, suprapubic,inguinal Males: inguinal, abdominal wall, back

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30 Myolipoma of sos Bssue SMA

31 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

32 Myolipoma Spindle cells posibve for SMA, Desmin CD34, HMB45 negabve

33 Tumors of Fat Lipoma Angiolipoma Spindle cell / Pleomorphic lipoma Myolipoma Hibernoma Lipoblastoma Liposarcoma

34 Hibernoma Rare, painless Benign tumor of subcutis and deep soft tissue Arise from brown fat Interscapular, axillae, low neck Cytogenetic rearrangement 11q13

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38 Tumors of Fat Lipoma Angiolipoma Spindle cell / Pleomorphic lipoma Myolipoma Hibernoma Lipoblastoma Liposarcoma

39 Lipoblastoma

40 Lipoblastoma First three years of life ExtremiBes are most commonly involved Slowly growing nodule/mass, well circumscribed in subcubs Circumscribed, benign tumor

41 Lipoblastoma Lobules of immature fat separated by septa Lipoblasts in various stages of development Plexiform vascular pattern

42 8q11-13 PLAG1 Lipoblastoma

43 Lipoblastoma

44 Tumors of Fat Lipoma Angiolipoma Spindle cell / Pleomorphic lipoma Myolipoma Hibernoma Lipoblastoma Liposarcoma

45 Atypical Lipomatous Tumor/ Well Differentiated Liposarcoma Most common adult sarcoma Adults (>40 years of age) Intermediate malignant Painless, slowly growing mass

46 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

47 Atypical Lipomatous Tumor/ WD Liposarcoma Fibrous Smudge septa cell and (Atypical atypical stromal cell) cells

48 Atypical Lipomatous Tumor/ WD Liposarcoma Lipoblasts Cell size variability Adipoctye atypia Smudge cells

49 amplification of 12q13-15 MDM2 and CDK4

50 Liposarcoma De-differenBated Myxoid (spindle cell and round cell) Pleomorphic NOS

51 Atypical Lipomatous Tumor/ WDL High-grade Sarcoma Dedifferentiated Liposarcoma

52 De-differenBated Liposarcoma (Grade Progression) De-differenBaBon Progression in grade to a high-grade sarcoma UndifferenBated pleomorphic sarcoma

53 De-differenBated Liposarcoma 10% of WDL Retroperitoneum TransiBon from the ALT/WDL to sarcoma

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55 Myxoid liposarcoma

56 Myxoid liposarcoma

57 Myxoid Liposarcoma Second most common liposarcoma (10% adult sarcomas) Deep soft tissue of extremity (thigh) Large painless mass in adults

58 Myxoid Liposarcoma FUS-DDIT3 EWSR1-DDIT3

59 Myxoid liposarcoma

60 Round cell liposarcoma

61 Pleomorphic liposarcoma

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63 Tumors of Bone Osteoma cutis Osteoid osteoma Osteoblastoma Osteosarcoma

64 Tumors of Bone Primary osteoma cubs Absent preexisbng, associated lesion Secondary ossificabon Inflammatory TraumaBc NeoplasBc

65 Osteoma cutis

66 Osteoma cutis

67 Secondary ossification of pilomatricoma

68 DifferenBal diagnosis Calcinosis CuBs CarBlaginous tumors of the skin Foreign body Gouty tophus

69 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

70 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

71 Diagnostic Factors Age Sex Skeletal localizabon Specific bone Specific area of bone 1. Medullary cavity, cortex, juxtacorbcal 2. Epiphysis, metaphysis, diaphysis Radiographic appearance

72 Age Adolescence Osteosarcoma and Ewing s sarcoma Young adults Giant cell tumor Elderly Chondrosarcoma

73 Location KNEE ½ of osteosarcomas Giant cell tumor CENTRAL/AXIAL ½ of osteoblastomas

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75 Radiologic Patterns Sclerotic margin is generally an indication of benign, slowlygrowing neoplasm Ill-defined margin is generally an indication of malignant, rapidlygrowing neoplasm

76 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

77 Benign Bone-Forming Tumors

78 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

79 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

80 Osteoid osteoma

81 Osteoid Osteoma

82 3cm Osteoblastoma Histologically very similar to osteoid osteoma

83 Osteoblastoma

84 Malignant Bone tumors Osteosarcoma

85 Osteosarcoma Metaphysis of long bones Femur, tibia, humerus (56%); flat bones, spine (older patients) Hematogenous spread to lungs is common

86 Osteosarcoma Poorly circumscribed Bone destruction Cortical disruption Bone matrix Soft tissue extension Codman s triangle

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88 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)

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90 Osteosarcoma

91 Osteoblastic Osteosarcoma

92 Chondroblastic Osteosarcoma

93 Fibroblastic Osteosarcoma

94 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