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Universit degli Studi di Padova Dipartimento di Medicina

Sezione di Anatomia Patologica Generale e Citopatologia

Adipocytic Tumours in children

Rita Alaggio

Basel Seminars in Pathology

Paediatric Pathology & Genetics

Basel, June 22nd 25th, 2016

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Outline

Classification of adipocytic tumors

Lipoblastoma

Lipoblastoma: Differential Diagnostic

Challenges

Liposarcoma

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WHO 2013 Classification

BENIGN

Lipoma

Lipoblastomatosis

Lipomatosis of Nerve

Lipoblastoma

Angiomyolipoma

Myolipoma of soft tissue

Chondroid lipoma

Spindle cell/Pleomorphic lipoma

Hybernoma

MALIGNANT

Atypical lipomatous tumor

Dedifferentiated liposarcoma

Myxoid liposarcoma

Pleomorphic liposarcoma

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WHO 2013 Classification

BENIGN

Lipoma

Lipoblastomatosis

Lipomatosis of Nerve

Lipoblastoma

Angiomyolipoma

Myolipoma of soft tissue

Chondroid lipoma

Spindle cell/Pleomorphic lipoma

Hybernoma

MALIGNANT

Atypical lipomatous tumor

Dedifferentiated liposarcoma

Myxoid liposarcoma

Pleomorphic liposarcoma

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Outline

Classification of adipocytic tumors

Lipoblastoma

Lipoblastoma: Differential Diagnostic Challenges

Liposarcoma

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Case 1 Multivacuolated and univacuolated lipoblasts

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Clinical History

Boy, 1.5 yr

expanding mass in the paravertebral

region

Main diameter 3 cm

Treatment: resection

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Clinical History

Boy, 1.5 yr

expanding mass in the paravertebral

region

Main diameter 3 cm

Treatment: resection

Diagnosis: Lipoblastoma

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Lipoblastoma

Lipoblastoma, a benign neoplasm of embryonal

white fat, is a localized or diffuse

(lipoblastomatosis) tumor with a tendency for

local recurrence if incompletely excised.

- WHO, 2013

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Lipoblastoma Clinical Features

90% before 3 years

40% 1st year of life

Rare in adolescents and adults

Sex: male predilection

Site: trunk, extremities Others: retroperitoneum, pelvis, abdomen,

head/neck, organs (lung, heart)

Benign clinical course 13-46% of relapse in incomplete resection

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Lipoblastoma (Courtesy of C. Coffin)

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Lipoblastomatosis (Courtesy of C. Coffin)

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Lipoblastoma

Histology

Lobulated architecture with fibrovascular septa

Lipoblasts in various stages of differentiation to mature fat with orientation from periphery to the center:

primitive stellate or spindle cells

multivacuolate lipoblasts

signet ring cells

Floret cells

Hibernoma like cells

Myxoid foci with plexiform vascular pattern, primitive mesenchymal cells

Chronic inflammation, mast cells

Fibrolipoma-like areas possible

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Lipoblastoma

Histology

Lobulated architecture with fibrovascular septa

Lipoblasts in various stages of differentiation to mature fat with orientation from periphery to the center:

primitive stellate or spindle cells

multivacuolate lipoblasts

signet ring cells

Floret cells

Hibernoma like cells

Myxoid foci with plexiform vascular pattern, primitive mesenchymal cells

Chronic inflammation, mast cells

Fibrolipoma-like areas possible

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Lipoblastoma

Histology

Lobulated architecture with fibrovascular septa

Lipoblasts in various stages of differentiation to mature fat with orientation from periphery to the center:

primitive stellate or spindle cells

multivacuolate lipoblasts

signet ring cells

Floret cells

Hibernoma like cells

Myxoid foci with plexiform vascular pattern, primitive mesenchymal cells

Fibrolipoma-like areas (eg in maturing lipoblastoma)

Chronic inflammation, mast cells

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Abdominal Lipoblastoma, age 2 yr. Resection

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Abdominal Lipoblastoma, age 2 yr. Recurrence, 5yr

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S100, CD34: positive nonspecific

Desmin: in primitive mesenchymal cells: a potential pitfall

PLAG1 protein: not liable

p16: negative

Lipoblastoma Immunohistochemistry

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Lipoblastoma (Cappellesso et al Hum Pathol 2016)

Desmin

S100

p16 -ve

p16 +ve (2 cases/30)

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Chromosome 8 aberrations typical, including extra copies in 10-15%

Breakpoints cluster to 8q11-13 involving PLAG1 in 8q12.1

Translocation partners vary:

3q12-13, COL1A2 in 7q21.3

HAS2 in 8q24.13

rarely COL3A1 and RAB2A*

others *Yoshida et al. Genes, Chromosomes & Cancer 53:606611 (2014)

Lipoblastoma Genetics

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Chromosomal Rearrangements

Increase of PLAG1 copy number

IGF2 Activation

Adipocytes Proliferation

Lipoblastoma: Genetic Alterations

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Chromosomal Rearrangements of PLAG1

HAS2 (hyaluronic acid synthase 2)

Check and transport of Ialuronic Acid

COL1A2 (collagen 1 alpha 2)

Involved in the formation of the

collagen in connective tissue,

bone and tendons

Potential role in collagen septae formation

? Potential role in the genesis of myxoid

component

?

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Developmental delay or abnormalities

Congenital malformations

Seizures

Sturge-Weber syndrome

Autism

Familial lipomas

Lipoblastoma Associated Conditions

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Outline

Classification of adipocytic tumors

Lipoblastoma

Lipoblastoma: Differential Diagnostic

Challenges

Liposarcoma

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Lipoma and variants

Primitive myxoid mesenchymal tumor of

infancy

Lipofibromatosis

Fibrous Hamartoma

Liposarcomas, especially myxoid and

myxoid-pleomorphic

Other fatty and myxoid tumors

Lipoblastoma Differential Diagnostic Challenges

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Lipoma Hibernoma

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Genetic aberrations in pediatric lipoma

Similar to adult lipomas

In literature less than 30 pediatric lipomas investigated:

11 with aberrations of the 12q14q15 region, with rearrangement of the HMGA2 gene in 3, 1 with anomaly of 6p21 region, resulting in a rearrangement of HMGA1

NFIB identified as a fusion partner of HMGA2 in pediatric lipoma. NFIB is a regulator of adipocyte differentiation; its inhibition

suppresses induction of adipogenic transcription factors, (PPAR, C/EBPa etc), and reduces accumulation of lipids during differentiation.

Cancer Genetics 208 (2015) 469481

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Lipoma and variants

Primitive myxoid mesenchymal tumor of

infancy

Lipofibromatosis

Fibrous Hamartoma

Liposarcomas, especially myxoid and

myxoid-pleomorphic

Other fatty and myxoid tumors

Lipoblastoma Differential Diagnostic Challenges

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Primitive myxoid mesenchymal tumor of infancy

Vimentin

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Initial diagnosis of Lipoblastoma (2/30 cases in Italian series)

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Lipoma and variants

Fibrous Hamartoma

Primitive myxoid mesenchymal tumor of

infancy

Lipofibromatosis

Liposarcomas, especially myxoid and

myxoid-pleomorphic

Other fatty and myxoid tumors

Lipoblastoma Differential Diagnostic Challenges

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Fibrous Hamartoma

In our series 2 originally diagnosed as lipoblastoma (out of 30 lipoblastomas)