Atlas of Soft Tissue Tumor Pathology

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Cyril Fisher

Atlas of Soft Tissue Tumor

Pathology
Cyril Fisher, MA, MD, DSc, FRCPath
Department of Histopathology
The Royal Marsden Hospital
London
United Kingdom

ISBN 978-1-4614-7024-3 ISBN 978-1-4614-7025-0 (eBook)

DOI 10.1007/978-1-4614-7025-0
Springer New York Heidelberg Dordrecht London

Library of Congress Control Number: 2013938302

© Springer Science+Business Media, LLC 2013

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Series Preface

“One Picture is Worth Ten Thousand Words”

- Frederick Barnard, 1927

Remarkable progress has been made in anatomic and surgical pathology during the last
10 years. The ability of surgical pathologists to reach a definite diagnosis is now enhanced by
immunohistochemical and molecular techniques. Many new clinically important histopatho-
logic entities and variants have been described using these techniques. Established diagnostic
entities are more fully defined for virtually every organ system. The emergence of personalized
medicine has also created a paradigm shift in surgical pathology. Both promptness and preci-
sion are required of modern pathologists. Newer diagnostic tests in anatomic pathology, how-
ever, cannot benefit the patient unless the pathologist recognizes the lesion and requests the
necessary special studies. An up-to-date Atlas encompassing the full spectrum of benign and
malignant lesions, their variants, and evidence-based diagnostic criteria for each organ system
is needed. This Atlas is not intended as a comprehensive source of detailed clinical information
concerning the entities shown. Clinical and therapeutic guidelines are served admirably by a
large number of excellent textbooks. This Atlas, however, is intended as a “first knowledge
base” in the quest for definitive and efficient diagnosis of both usual and unusual diseases.
The Atlas of Anatomic Pathology is presented to the reader as a quick reference guide for
diagnosis and classification of benign, congenital, inflammatory, nonneoplastic, and neoplastic
lesions organized by organ systems. Normal and variations of “normal” histology are illus-
trated for each organ. The Atlas focuses on visual diagnostic criteria and differential diagnosis.
The organization is intended to provide quick access to images and confirmatory tests for each
specific organ or site. The Atlas adopts the well-known and widely accepted terminology,
nomenclature, classification schemes, and staging algorithms.
This book Series is intended chiefly for use by pathologists in training and practicing surgi-
cal pathologists in their daily practice. It is also a useful resource for medical students, cyto-
technologists, pathologist assistants, and other medical professionals with special interest in
anatomic pathology. We hope that our trainees, students, and readers at all levels of expertise
will learn, understand, and gain insight into the pathophysiology of disease processes through
this comprehensive resource. Macroscopic and histological images are aesthetically pleasing
in many ways. We hope that the new Series will serve as a virtual pathology museum for the
edification of our readers.

Liang Cheng, MD
Series Editor
Atlas of Anatomic Pathology

v
Preface

The soft tissues are composed of connective tissue, fat, muscle, blood vessels, and nerves,
wherever they occur. Benign soft tissue tumors are relatively common, and malignant ones,
accounting for less than 1 % of all cancers and less than 1 % of all soft tissue tumors, are rela-
tively rare. Both types, however, may cause difficulties for the diagnostic surgical pathologist
who is trying to assess malignancy and predict behavior. Studies of large numbers of cases and
the application of modern pathologic techniques have led to a deeper understanding of and
diagnostic capability for these tumors. However, these discoveries also have resulted in multi-
plication of the number of entities, both from the description of new ones and the subdivision
of established ones. Reclassification and confusing changes in terminology also have occurred,
at times making the subject bewilderingly complex for the nonspecialist.
This atlas aims to illustrate the range of soft tissue tumor pathology and to provide essential
information about clinical features, morphology, and adjunctive diagnostic methods, especially
with reference to immunohistochemistry, molecular pathology, and cytogenetic studies, for
more than 150 tumor types. The contents are arranged by lineage or apparent line of differen-
tiation, when known, and broadly follow the World Health Organization classification of 2002.
We also have added new tumors not included in this classification, such as those showing nerve
sheath differentiation, mesenchymal tumors of skin, and more recently described entities. In
many chapters, the lesions are grouped as benign, intermediate (locally aggressive or rarely
[<2 %] metastasizing), or malignant. However, in cases in which benign lesions have similar
malignant counterparts, these are presented together to avoid repetition. Many soft tissue
tumors have characteristic chromosomal translocations or other consistent genetic abnormali-
ties, and if they do not correspond to the usual normal cell lineages, they are included in a sepa-
rate chapter, together with entities of unknown differentiation or uncertain lineage.
This atlas is intended as a succinct guide to a fascinating and challenging area of tumor
pathology, and it is hoped that it will be useful to both trainees and practicing pathologists
as well as clinicians, nurses, and allied health care practitioners in the fields of oncology,
orthopedics, and related clinical areas.

London, UK Cyril Fisher, MA, MD, DSc, FRCPath

vii
Contents

1 Tumors of Adipose Tissue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

1.1 Lipoblasts and Mimics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.2 Benign Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.3 Liposarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
2 Chondroid and Osseous Tumors of Soft Tissue . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.1 Benign Tumors and Tumor-Like Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
2.2 Malignant Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
3 Benign Fibroblastic and Myofibroblastic Lesions. . . . . . . . . . . . . . . . . . . . . . . . . 23
Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
4 Intermediate and Malignant Fibroblastic and Myofibroblastic Tumors . . . . . . 37
4.1 Intermediate Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
4.2 Malignant Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
5 Fibrohistiocytic Lesions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
5.1 Benign Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
5.2 Intermediate Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
5.3 Malignant Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
6 Genital Stromal Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
7 Mesothelial Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
7.1 Benign Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
7.2 Malignant Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
8 Myoepithelial Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
9 Nerve Sheath Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
9.1 Benign Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
9.2 Malignant Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
10 Neuroectodermal and Neural Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
10.1 Ewing Sarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
10.2 Neuroblastic Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106

ix
x Contents

11 Tumors of Pericytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107

Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
12 Skeletal Muscle Tumors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
12.1 Benign Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
12.2 Malignant Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
13 Smooth Muscle Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
13.1 Benign Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
13.2 Malignant Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
14 Vascular Lesions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
14.1 Benign Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
14.2 Intermediate Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
14.3 Malignant Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
15 Tumors of Uncertain Differentiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
15.1 Benign Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150
15.2 Intermediate Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154
15.3 Malignant Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
15.4 Gastrointestinal Stromal Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
16 Other Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171
Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
 Tumors of Adipose Tissue
1

Tumors of adipose tissue are the most frequently encountered features or context in which the vacuolated cells occur and
benign or malignant soft tissue tumors. Lipomas may occur use of appropriate immunohistochemical panels allow cor-
at almost any site and represent the most common benign rect diagnosis.
soft tissue neoplasm. Liposarcoma has a high incidence Liposarcomas are among the commonest soft tissue sar-
among malignant soft tissue tumors, but the term includes comas and occur mostly in adults. They appear as deep soft
several distinct lipogenic tumor types that vary clinically, tissue tumors in the proximal limbs, trunk, retroperitoneum
histogenetically, and genetically. These include tumors with and rarely the mediastinum and head and neck sites; they
increased copy numbers (gene amplification), specific trans- often attain a large size before presentation, especially when
locations, or complex karyotypes, but there are no significant they arise in the abdomen. The morphologic subtypes also
predisposing factors. have different genetic features. The atypical lipomatous
Lipoblasts are a distinctive feature of some liposarcomas, tumor (well-differentiated liposarcoma) has amplification of
but their presence is not necessary for the microscopic diag- the 12q13-15 chromosomal segment, which includes the
nosis of well-differentiated liposarcomas or myxoid liposar- genes MDM2, CDK4, and HMGA2. The same abnormality,
comas. However, diagnosis of pleomorphic sarcomas and with additional complex cytogenetic changes, is found in
round cell liposarcomas usually requires the demonstration dedifferentiated liposarcoma. Myxoid-round cell liposarco-
of lipoblastic differentiation, at least focally. Many other cell mas have (t12;16)(q13;p11) rearrangement with FUS-DDIT3
types may at times display cytoplasmic vacuolation and fusion gene formation, or t(12;22)(q13;q12) rearrangement
mimic lipoblasts, which may lead to their erroneous interpre- with EWSR1-DDIT3 fusion. Pleomorphic liposarcomas have
tation as liposarcomas. Appreciation of the associated complex karyotypes and variable genetic changes.

C. Fisher, Atlas of Soft Tissue Tumor Pathology, Atlas of Anatomic Pathology, 1

DOI 10.1007/978-1-4614-7025-0_1, © Springer Science+Business Media, LLC 2013
2 1 Tumors of Adipose Tissue

1.1 Lipoblasts and Mimics

Fig. 1.3 Lipoblasts. Univacuolated and bivacuolated lipoblasts are a

feature of well-differentiated liposarcoma
Fig. 1.1 Lipoblasts. Pleomorphic lipoblasts are the diagnostic feature
of this pleomorphic liposarcoma. They have one or more vacuoles that
are perfectly round and empty and frequently indent the nucleus. They
often are S-100 protein–positive but lack other markers

Fig. 1.4 Lipoblast mimics. Silicone in prostheses may leak into adja-
cent tissues and be phagocytosed by macrophages. This process and the
empty tissue spaces can mimic lipoblasts

Fig. 1.2 Lipoblasts. Multivacuolated lipoblasts are prominent in this

pleomorphic sarcoma. The nucleus is not seen in every cell, but the
cytologic appearances are distinctive

Fig. 1.5 Lipoblast mimics. Adenocarcinoma of the cervix, in which

the cells have clear vacuolated cytoplasm, is readily identified by a
positive epithelial marker
1.1 Lipoblasts and Mimics 3

Fig. 1.6 Lipoblast mimics, lymphoma. Both lymphoma and melanoma Fig. 1.8 Lipoblast mimics. This example of myxoinflammatory
may assume a signet-ring morphologic appearance. The former is easily fibroblastic sarcoma shows markedly vacuolated fibroblasts containing
identified by immunohistochemistry. Melanoma may be confused with stromal mucin. These cells are a typical feature of this tumor type
round cell liposarcoma, as both may have S-100 protein positivity

Fig. 1.7 Lipoblast mimics. Intracellular accumulation of myxoid Fig. 1.9 Lipoblast mimics. Epithelioid hemangioendothelioma is a
stromal secretion in myxofibrosarcoma may result in multivacuolated tumor of endothelial cells that may display intracytoplasmic “lumen”
fibroblasts, sometimes termed pseudolipoblasts. An important differ- formation. The abundant cytoplasm, the overall architecture, and the
ence from lipoblasts is that the vacuoles in these fibroblasts are not immunohistochemical demonstration of endothelial antigens help
empty but contain alcian blue–positive stromal material exclude the diagnosis of liposarcoma
4 1 Tumors of Adipose Tissue

1.2 Benign Tumors

Fig. 1.10 Lipoma. This is an encapsulated tumor that resembles nor-

mal fat in color and texture. Lipomas may occur anywhere; this tumor
is from the subcutaneous tissue of the upper back, which is a common
site. The cut surface is lobulated and has paler areas representing myx-
oid stromal change Fig. 1.12 Intramuscular lipoma. Skeletal muscle bundles are separated
by normal-looking differentiated adipose tissue. The infiltrative nature
of the lesion means that it may recur after incomplete excision, although
some examples have a circumscribed margin and are less likely to
recur

Fig. 1.11 Lipoma. This neoplasm is composed of differentiated adipo- Fig. 1.13 Lipoma arborescens. Lipomas may occur in any anatomic
cytes without nuclear atypia. Most of the cell appears empty because location, including within nerves and joints. The term lipoma arbore-
the fat is removed during processing, and there is only a thin rim of scens is used for lipomatous infiltration of synovium forming a multi-
cytoplasm. The nucleus is pushed to the margin of the cell nodular tumor within a joint, such as the knee. Lesions may be bilateral
or multiple
1.2 Benign Tumors 5

Fig. 1.14 Lipoma with myxoid change. This stromal change some- Fig. 1.16 Lipoma with bone. Heterologous benign mesenchymal ele-
times is seen in otherwise typical lipomas. They differ from myxoid ments such as bone, cartilage, or smooth muscle (myolipoma) may
liposarcomas, which have a plexiform vascular pattern and contain occur. No atypical features are seen
lipoblasts in various stages of differentiation

Fig. 1.15 Fibrolipoma. Fibrosis often is prominent as collagenous Fig. 1.17 Lipoma with extramedullary hemopoiesis. This is an occa-
bands divide the tumor into lobules sional finding, but the possibility of hematologic disease, such as
myelofibrosis, should be considered. Fatty tumors with a prominent
hemopoietic component have been termed extra-adrenal myelolipoma
6 1 Tumors of Adipose Tissue

Fig. 1.18 Angiolipoma. This is a circumscribed, thinly encapsulated, Fig. 1.20 Angiolipoma. Some examples have increased blood vessels
subcutaneous tumor that is often tender. It consists of normal fat with that form more solid masses with a minimal adipose tissue component
clusters of blood vessels that are more frequent toward the periphery of
the lesion

Fig. 1.19 Angiolipoma. The capillaries have variably thickened walls, Fig. 1.21 Myelolipoma of the adrenal gland. Mature adipose tissue is
with intervening spindle cells; in addition, some contain thrombi, with infiltrated by aggregates of normal hemopoietic cells. A rim of remain-
occasional neutrophils ing adrenal cortical tissue is seen at the bottom of the image. Myelolipoma
is most common in the adrenal gland but also occurs in other locations,
including the retroperitoneum and presacral region. It may be associated
with adrenal cortical tumors, obesity, and diabetes
1.2 Benign Tumors 7

Fig. 1.22 Spindle cell lipoma. Typically this occurs on the back of the
neck or shoulder region (and rarely at other sites) in adults as a slowly
growing subcutaneous tumor. It is encapsulated with white, yellow, and
myxoid-looking areas Fig. 1.25 Spindle cell lipoma. Myxoid change sometimes is promi-
nent in these tumors. This pattern of spindle cell lipoma is distinguish-
able from that of myxoid liposarcoma by the subcutaneous location, the
subcutaneous origin, and the absence of lipoblasts and the typical plexi-
form vascular pattern. In myxoid spindle cell lipoma, the cells are
evenly dispersed. The typical collagen bundles can be seen. Similar
tumors have been described as dendritic fibromyxolipomas

Fig. 1.23 Spindle cell lipoma. The image shows variable proportions of
mature adipose tissue, spindle cells, and wiry or ropy collagen fibers

Fig. 1.26 Spindle cell lipoma. Pseudoangiomatous change, with dilated

spaces, is a rare but distinctive occurrence

Fig. 1.24 Spindle cell lipoma. The cells are uniform with ovoid nuclei
and scanty cytoplasm, and they lack mitoses. Mast cells are a typical
feature. The spindle cells are arranged in short bundles and are CD34
positive on immunohistochemical testing. This tumor lacks a specific
translocation but frequently has chromosomal loss at 13q, including the
RB gene
8 1 Tumors of Adipose Tissue

Fig. 1.27 Pleomorphic lipoma. This tumor is clinically and genetically Fig. 1.29 Hibernoma. This is a benign neoplasm resembling normal
similar to spindle cell lipoma, and the two patterns may be present in the brown fat. It arises in adults at various sites, including the thigh, shoul-
same neoplasm. Pleomorphic lipoma has multinucleated floret cells, and der, back, and retroperitoneum. At low magnification, the tumor has a
enlarged hyperchromatic nuclei and lipoblasts sometimes are seen lobular pattern, defined by thin fibrous septa

Fig. 1.28 Pleomorphic lipoma. This may be distinguished from an Fig. 1.30 Hibernoma. The cells have numerous small fatty vacuoles,
atypical lipomatous tumor by the superficial location, encapsulation, and the small round nuclei often are centrally located. Some cells have
floret cells, and spindle cell lipomatous component, as well as by the a more granular cytoplasm. Genetically, hibernomas have rearrange-
absence of MDM2 and CDK4 amplification by fluorescence in situ ments at 11q13
hybridization (FISH) and immunohistochemical evaluation