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Pleomorphic Lipoma • Chondroid Lipoma PATHOLOGY UPDATE: SurgicalDiagnostic Pearls for the Practicing Pathologist Friday, October 7, 2016 Aria® Resort & Casino • Las Vegas, Nevada Educational Symposia TABLE OF CONTENTS Friday, October 7, 2016 The Trouble with Fat: Diagnostic Issues in Well-Differentiated Lipomatous Tumors (John R. Goldblum, M.D.) ................ 1 Practical Approach to Melanocytic Tumor (Steven D. Billings, M.D.) .................................................................. 15 Reporting of Prostate Cancer in Needle Biopsy Specimens: Gleason Grading and More (David J. Grignon, M.D., FRCP(C)) ..................................................................... 45 Unraveling the Mesenchymal Madness in Gynecologic Tumors (Kristen A. Atkins, M.D.) ........................................ 73 REGISTER TODAY - 2017 Pathology Symposia 1 2 The Trouble With Fat: Diagnostic Issues in Well-Differentiated Lipomatous Tumors John R. Goldblum, M.D. Chairman, Department of Pathology, Cleveland Clinic Professor of Pathology, Cleveland Clinic Lerner College of Medicine Cleveland, Ohio Benign Lipomatous Tumors Lipomatous Tumors of Intermediate Malignancy • Lipoma • Angiomyolipoma • Lipoblastoma • Myelolipoma Atypical lipomatous tumor • Angiolipoma • Hibernoma (Well-differentiated liposarcoma) • Myolipoma • Spindle cell / pleomorphic lipoma • Chondroid lipoma Liposarcoma Malignant Lipomatous Tumors • Atypical lipomatous tumor (well-differentiated liposarcoma) • Dedifferentiated liposarcoma • lipoma-like • Myxoid liposarcoma • sclerosing • Round cell liposarcoma • inflammatory • spindle cell • Pleomorphic liposarcoma • dedifferentiated • Mixed-type liposarcoma • Myxoid / round cell liposarcoma • Liposarcoma, NOS • Pleomorphic liposarcoma 3 Pseudolipoblasts • Fat atrophy • Hibernoma cells • Silicone reaction • Signet ring cells • Fixation artifact • Neoplastic fat infiltration Well-differentiated Lipomatous Tumors • The most common consultation we receive • Pleomorphic/spindle cell lipoma vs ALT • Intramuscular lipoma vs ALT • Lipoma with fat necrosis vs ALT • Good rule: the larger and deeper the lesion, the more likely it is to be an ALT (but there are exceptions) • Deeply located benign tumors (intramuscular lipoma) • Superficial ALT 4 5 CD34 CD34 Spindle Cell / Pleomorphic Lipoma Pleomorphic Lipoma • Well-circumscribed subcutaneous mass Differential Diagnosis • Shoulder, neck, back • Atypical lipomatous tumor • Striking male predominance • No recurrence / metastasis • Pleomorphic sarcoma • CD34-positive • Common cytogenetic abnormality (16q¯, 13q¯) 6 ALT/WDL: A Historical Perspective Evans (1979) Evans (1979) Recur Dediff Mets Died Subcutis (9) 0 0 0 0 Subcutis Deep soft tissue Retroperitoneum Deep soft tissue (13) 69% 0 0 0 Retroperitoneum (8) 62% 0 0 37% Atypical lipoma Atypical intra- WDL muscular lipoma ALT/WDL: A Historical Perspective Weiss (1992) Weiss & Rao (1992) Recur Dediff Mets Died Subcutis Deep soft tissues Retroperitoneum Deep soft tissue 43% 6% 0% 0% (46) Atypical lipoma WDL WDL Retroperitoneum 91% 17% 17% 33% (23) Weiss SW et al, AJSP 1992 ALT/WDL: Lumper or Splitter? • Lumpers • Call all tumors (regardless of site) ALT • Call all tumors (regardless of site) WDL • Splitters • Superficial (subcutis) Atypical lipoma • Deep (deep soft tissue/retro) WDL * Requires communication and understanding between pathologist and surgeon/oncologist! 7 When To Suspect ALT/WDL • Large and deep fatty tumor (when it comes in buckets!) • Retroperitoneal fatty tumor (with rare exceptions) • MRI heterogeneity (surgeon is suspicious) • Fibrous bands • Atypia (hyperchromasia) identified at low power *Don’t look for lipoblasts!! Courtesy of Dr. F. Pédeutour MDM2 amplification 8 Problematic Lipomatous Tumors MDM2 FISH: Indications % Cases • Tumor size > 10 cm (62%) • Equivocal atypia (48%) • Deep location (28%) • Recurrence (11%) • Other (clinical suspicion) (4%) • Multiple indications 48% • Single indication 52% MDM2 Clay MR et al. AJSP, 2015 Problematic Lipomatous tumors MDM2 FISH: Multi vs Single Indication Problematic Lipomatous Tumors Recommendations for MDM2 FISH Indications ALT PL/SCL Lipoma Multiple (144) 65 (45%) 15 (11%) 64 (44%) • Recurrent well-differentiated lipomatous tumors Single (157) 43 (27%) 36 (23%) 79 (50%) • Lipomatous tumors with equivocal cytologic atypia • Retroperitoneal, intra-abdominal and pelvic tumors • Combo of size >10 cm, deep location and equivocal atypia was almost always ALT (13/14 cases) • Deep extremity tumors >10 cm in patients >50 years • Size >10 cm and deep location almost always ALT Clay MR et al. AJSP, 2015 Clay MR et al. AJSP, 2015 Problematic Lipomatous Tumors Pleomorphic Lipoma vs ALT Cases That May Not Require FISH PL ALT/WDL • Superficial tumors Atypical cells Yes Yes • Lipomatous tumors of the hands and feet Floret cells characteristic sometimes • Tumors in unusual locations with no other indicators Ropey collagen Yes No • Small retroperitoneal tumors with no other indicators CD34 Yes Rare cells (requires validation in larger series of cases) MDM2 ampl No Yes Dedifferentiation No Sometimes Clay MR et al. AJSP, 2015 9 ALT / WDL Low-grade sarcoma (no metastatic capability) incomplete excision complete excision Local recurrence Cured! Tumor progression Metastasis Differential Diagnosis • DDL without sampled low- grade (WDL) component • DDL with no residual low- grade (WDL) component (overgrowth by high-grade component) • Non-DDL pleomorphic sarcoma • Does it matter? • How can you tell? Retroperitoneal Mass 10 Dedifferentiated Liposarcoma Dedifferentiated Liposarcoma McCormick et al: 32 cases Henricks et al: 155 cases • Location: 19/32 (59%) in retroperitoneum or Site Recurrence Mets Died of disease Median f/u paratesticular Retroperitoneum (88) 41 (47%) 16 (18%) 30 (34%) 2.8 yrs • De novo dedifferentiation in 30/32 (94%) Accessible deep soft tissue (27) 9 (33%) 4 (15%) 3 (11%) 3.5 yrs • Follow-up: 3 mos – 33 years (mean: 5.6 years) Total (130) 53 (41%) 22 (17%) 36 (28%) 3 yrs • Metastasis in 4/27 (15%) Henricks et al. AJSP, 1997 McCormick D et al AJSP, 1994 Dedifferentiated Liposarcoma Dedifferentiated Liposarcoma Deep Thoughts MDM2/CDK4 Amplification IHC • DDL has a lower metastatic rate than other Diagnosis MDM2/CDK4 (a-CGH/RT-PCR) MDM2 CDK4 Both pleomorphic sarcomas as a whole Dediff Liposarcoma 53/55 (96%) 52 51 49 Simulators • Therefore, it is important to distinguish DDL from • Myxofibrosarcoma 8/13 (62%) 8 3 2 other pleomorphic sarcomas, including UPS • Leiomyosarcoma 5/32 (16%) 2 1 1 • MPNST 2/6 (33%) 6 1 1 • Most (if not all) UPS (“MFH”) of the retroperitoneum • “MFH” 3/39 (8%) 3 1 1 are actually DDL Binh MD et al AJSP, 2005 Well-differentiated Lipomatous Tumors Liposarcoma Cytogenetics Category Cytogenetics Lipoma 12q, 6p, 13q ALT/WDL Ring/giant marker chromosomes (12q13-15) Hibernoma 11q Dedifferentiated Additional complex Lipoblastoma 8q aberrations Spindle / pl lipoma 16q, 13q Myxoid/round cell t(12;16)(q13;p11) ALT / WDL ring chromosomes (12q) Pleomorphic Complex aberrations 11 Problematic Lipomatous Tumors MDM2 FISH: Tumor size > 10 cm Final Dx based on FISH No. cases (%) ALT 68 (36%) PL/SCL 14 (7%) Lipoma 105 (56%) • 51/68 ALTs had at least one other indication for FISH • 17/68 cases tested and proved to be ALT based on size alone • All >50 yrs • All in deep soft tissues of extremities • No tumor in superficial soft tissue tested for size alone was ALT Clay MR et al. AJSP, 2015 Problematic Lipomatous Tumors Problematic Lipomatous Tumors MDM2 FISH: Equivocal Atypia MDM2 FISH: Deep Location (retro/abd/pelvic) Final DX based on FISH No. cases (%) Final DX based on FISH No. cases (%) ALT 72 (50%) ALT 30 (35%) PL/SCL 44 (30%) PL/SCL 6 (7%) Lipoma 29 (20%) Lipoma 50 (58%) • Most common sole indication to FISH (72 cases) • 9 cases in which deep location was sole indicator: all • 7 cases in hands and feet all classified as PL/SCL benign Clay MR et al. AJSP, 2015 Clay MR et al. AJSP, 2015 Problematic Lipomatous Tumors Problematic Lipomatous Tumors MDM2 FISH: Recurrence MDM2 FISH: Unusual Features (n=12) • Unusual location (e.g. epiglottis)* Final Dx based on FISH No. cases (%) • Clinical concern by surgeon ALT 18 (55%) PL/SCL 3 (9%) • Worrisome imaging findings Lipoma 12 (36%) • Unusual morphologic features (e.g. myxoid features) • All recurrent superficial tumors were benign (n=7) *only case which proved to be ALT Clay MR et al. AJSP, 2015 Clay MR et al. AJSP, 2015 12 Liposarcoma Category Cytogenetics ALT/WDL Ring/giant marker chromosomes (12q13-15) Dedifferentiated Additional complex aberrations Myxoid/round cell t(12;16)(q13;p11) Pleomorphic Complex aberrations 13 14 15 16 General Rules for Melanocytic Tumors • Low power examination – Symmetry Practical Problems in • Junctional component • Dermal component Melanocytic Tumors • Pigmentation • Inflammation Steven D. Billings • Medium Power examination – Circumscription Cleveland Clinic, Cleveland, OH – Growth pattern [email protected] • Epidermis: nested vs. single cell • Dermis: regular nests vs. irregular nests or confluent • Maturation: do the melnocytes get smaller deeper in the dermis? General Rules for Melanocytic General Rules for Melanocytic Tumors Tumors • High power examination • The best special stain is H&E – Upward (pagetoid) spread of melanocytes – Levels often helpful – Cytology • Do not sign out difficult cases when you • Nevoid are tired • Epithelioid – Friday afternoon rule • Spindled • Pleomorphic • Do not be a hero – Dermal mitotic activity – Show cases to colleagues – Get consults when necessary Histology Issues • Orientation important for
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