5/25/19
Disclosure UCSF Current Issues in Pathology 2019 Company Relationship type Presage Biosciences Consultant A practical approach to well- differentiated adipocytic tumors
Andrew Horvai MD PhD Clinical Professor, Pathology UCSF, San Francisco, CA
Lipoblast Well-differentiated lipogenic tumors • Benign – Lipoma – Angiolipoma – Hibernoma – Lipoblastoma – Spindle cell / pleomorphic lipoma • Malignant and borderline – Atypical lipomatous tumor/ well-differentiated liposarcoma – Atypical spindle cell lipomatous tumor • Selected lesions that simulate malignancy – Intramuscular lipoma – Massive localized lymphedema – Fat necrosis Confirms lipogenic differentiation, NOT malignancy
1 5/25/19
Pedunculated thigh mass 64 year old man, thigh mass
Lipoma (conventional) 45 year old woman, painful forearm mass
• Most common soft tissue neoplasm of adults • Painless slow growingCLINICAL subcutaneous mass • Uniformly benign, no recurrence • Circumscribed, unencapsulated • Mature adipose tissue, uniform cell size PATHOLOGY • No atypia • Ancillary tests: S100+ • Variants – Intramuscular, lipomatosis,VARIANTS with metaplastic cartilage
2 5/25/19
Angiolipoma: PTAH Angiolipoma
• Subcutis of forearm, multifocal, painful, multifocal • Familial forms • Uniformly benign, no recurrence • Circumscribed, thinly encapsulated • Mature adipose tissue, peripheral or diffuse capillaries with fibrin • No atypia • Ancillary tests: PTAH • Variants – Cellular angiolipoma
Cellular angiolipoma 25 year old woman with right groin mass
CT Axial PET
3 5/25/19
25 year old woman with right groin mass Hibernoma • Rare, young adults • Proximal lower extremity, painless, subcut or intramusc • Uniformly benign, no recurrence • Circumscribed, usually unencapsulated • Rich capillary network • Mixture of – multivacuolated “brown” adipocytes, central round nucleus – multivacuolated “pale” adipocytes, central or peripheral ovoid nucleus – mature, univacuolated adipocytes • No atypia • Variants: eosinophilic, myxoid, fibrous-spindled
Hibernoma Brown Fat vs. Foam cells Pale cell Eosinophilic Brown Fat Foam cells of fat necrosis
4 5/25/19
9 month old with neck mass 9 month old with neck mass
MRI T1
PLAG FISH
PLAG FISH courtesy Dr. Bahrami, St. Jude Pathology
Lipoblastoma Lipoblastoma (2 month old)
• < 3 year old, deep soft tissue, slow growing • Infiltrative, may entrap muscle and fascia • < 5 cm, delicate fibrous septae, may be ill-defined • Lipoblastomatosis may recur (<20%), nondestructive • Nodules – Centrally mature fat – Peripherally myxoid with spindle cells and signet ring lipoblasts, increased vascularity • Ancillary tests: – PLAG fusions (-HAS2, -COL1A2) – No t(12;16) FUS-DDIT3 fusion • Variants: brown fat, “matured”
5 5/25/19
Lipoblastoma (2 year old) 50 year old man, 5 cm upper back mass
Upper back mass Spindle cell lipoma
• Subcutaneous, painless mass, upper back or neck most common but wide anatomic distribution • Middle aged, M>F • Uniformly benign • Circumscribed, unencapsulated • Variable amounts of – Mature fat – Short, blunt spindle cells – Ropy collagen – Floret giant cells – Lipoblasts • Ancillary studies: CD34+,Rb-, S100+ – del(16) or del(16q) • Variants: pleomorphic lipoma, metaplastic bone, angiomatous, low-fat/nonfat, Myxoid
6 5/25/19
Spindle cell lipoma Spindle cell lipoma Spindle cells Lipoblasts Mast cells Metaplastic bone and cartilage
Spindle cell lipoma Pleomorphic lipoma
Myxoid stroma, floret giant cells
7 5/25/19
Spindle cell lipoma Angiomatous spindle cell lipoma
Low fat High fat
Angiomatous spindle cell lipoma Spindle cell lipoma CD34
ER
Zamecnik M, Michal M. Pathol Int 2007 57:26-31
8 5/25/19
Spindle cell lipoma Spindle cell lipoma? Rb Atypical spindle cell lipomatous tumor
Rb
9 5/25/19
Atypical Spindle cell lipomatous tumor Atypical spindle cell lipomatous tumor
• Adults, proximal extremity, subcutis, 40% deep • Local recurrence ~10%, no metastasis • Similar components to spindle cell lipoma • Infiltration, increased atypia, mitoses, atypical mitoses • Ancillary tests: – CD34+ – Rb deletion – No MDM2 amplification, no DDIT3 rearrangement • Variants: Dedifferentiated atypical spindle cell lipomatous tumor
Atypical spindle cell lipomatous tumor 72 year old woman, retroperitoneal mass
CT - Axial
10 5/25/19
Well-differentiated liposarcoma / atypical 72 year old woman, retroperitoneal mass lipomatous tumor (WDL/ALT) • Superficial to deep soft tissue, retroperitoneum, scrotum, mediastinum • Slow growing mass or abdominal fullness • Outcome related to site, not histomorphology • Circumscribed or infiltrative, most >10 cm • Mature fat • Fine, hair-like collagen around individual fat cells or in fibrous septae • More variable adipocyte size than lipoma • Atypical, hyperchromatic spindle cells • Ancillary tests – 12q13-15 amplification – MDM2, CDK4, p16 overexpression
• Variants: Lipoma-like, sclerosing, myxoid, lipoleiomyosarcoma
WDL vs ALT WDL (lipoma-like) • Identical histology, genetics • Extremity: ALT • Body cavity, scrotum: WDL
100 10 year survival 100 Dedifferentiation
75 75
50 50
% Surviving 25 25 % Dedifferentiated 0 0 Acessible ST Retroperitoneum Acessible ST Retroperitoneum Location Location
Henricks et al Am J Surg Pathol 1997 21:271-281 McCormick et al Am J Surg Pathol 1994 18:1213-1223
11 5/25/19
WDL: atypical spindle cells WDL: Adipocyte size variability
Lipoma WDL
Lipoma vs. WDL/ALT: Ancillary tests When to do ancillary testing
CT - Axial
1. Recurrence 2. Deep extremity >10 cm >50 year old • Definitely a tumor? 3. Equivocal atypia • 4. Body cavity Adequately sampled? 5. Directed by treating physician
12 5/25/19
WDL: 12q13.3-15 amplification WDL: 12q13-15 amplification
CISH
FISH
aCGH
Weaver J, et al Mod Pathol. 2008 ;21(8):943-9. Horvai et al. 2009 Mod Pathol 22(S1): 14A
WDL: Immunohistochemistry Selected WDL mimics MDM2 CDK4 CDK4 • Intramuscular lipoma • Massive localized lymphedema • Fat necrosis
13 5/25/19
WDL mimics: intramuscular lipoma Intramuscular lipoma
MRI axial T1 fast spin echo
WDL mimics: Massive localized lymphedema Massive localized lymphedema
MRI Coronal T1
14 5/25/19
WDL mimics: Fat necrosis Fat necrosis
Adipocyte size variability Foam cells MDM2
Fat necrosis in WDL Take home messages
• Lipoblasts confirm lipogenic differentiation, not malignancy • Well-differentiated liposarcoma (WDL) and atypical lipomatous tumor (ALT) differ based on anatomic location • Immunohistochemistry and genetic studies are helpful in large, deep tumors to exclude WDL/ALT • Fat necrosis may mimic WDL but does not exclude it
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