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CHAPTER 3

So-called Fibrohistiocytic Tumours

Over the past 10 years, the concept of fibrohistiocytic differenti-

ation has been challenged and is now regarded as a poorly

defined morphological descriptor of histiocytic differentiation.

Pleomorphic malignant fibrous histiocytoma (MFH) was previ-

ously regarded as a distinct tumour type representing the most

common adult soft tissue sarcoma. Today, this term is synony-

mous with undifferentiated pleomorphic sarcoma, which has

become a diagnosis of exclusion accounting for less than 5% of

adult sarcomas. Similarly, the morphological features formerly

regarded as characteristic of the giant cell and inflammatory

variants of MFH are shared by a variety of other, specific tumour

types. Myxofibrosarcoma (formerly known as myxoid MFH) and

so-called angiomatoid MFH remain as distinctive and discrete

entities (see Chapters 2 and 9).

Cutaneous fibrous histiocytomas, dermatofibrosarcoma protu-

berans (best classified as a fibroblastic neoplasm) and atypical

fibroxanthoma are described separately in the Skin volume.

Since the localized and diffuse forms of giant cell tumour of ten-

don sheath have more in common with the descriptive category

of fibrohistiocytic lesions than with true synovium, they are for

now included in this chapter.

Giant cell tumour of tendon sheath

N. de St. Aubain Somerhausen

P. Dal Cin

The term giant cell tumour of tendon

sheath encompasses a family of lesions

most often arising from the synovium of

joints, bursae and tendon sheath {1027}.

These tumours are usually divided

according to their site (intra- or extra-

articular) and growth pattern (localized

or diffuse) into several subtypes, which

differ in their clinical features and biolo-

gical behaviour.

Sites of involvement

Localized giant cell tumours occur pre-

dominantly in the hand where they prob-

ably represent the most common neo-

plasm. Approximately 85% of the

tumours occur in the fingers, in close

proximity to the synovium of the tendon

sheath or interphalangeal joint. The

lesions may infrequently erode or infil-

trate the nearby bone {2160}, or rarely

involve the skin.

Other sites include the wrist, ankle / foot,

knee, and very rarely the elbow and the

hip {1492,2163}.

process based on animal models, the

common history of trauma, the predilec-

tion for the first three fingers of the right

hand {1492} and one X-inactivation

study suggesting polyclonality {2295}.

However, the finding of aneuploidy in

some cases {7}, the demonstration of

clonal chromosomal abnormalities

{1774}, and the fact that these lesions

are capable of autonomous growth

strongly support a neoplastic origin.

Definition

The localized type of giant cell tumour of

tendon sheath is a circumscribed prolif-

eration of synovial-like mononuclear

cells, accompanied by a variable num-

ber of multinucleate osteoclast-like cells,

foam cells, siderophages and inflamma-

tory cells, most commonly occurring in

the digits.

Macroscopy

Grossly, most localized giant cell

tumours are small (between 0.5 and 4

cm), although lesions of greater size may

be found in large joints. Tumours are well

circumscribed and typically lobulated,

white to grey with yellowish and brown

areas.

Clinical features

The most common presenting symptom

is that of a painless swelling. The

tumours develop gradually over a long

period and a preoperative duration of

several years is often mentioned .

Antecedent trauma is reported in a vari-

able number of cases (from 1 to 50%)

{1492,2163}.

Radiological studies usually demon-

strate a well circumscribed soft tissue

mass, with occasional degenerative

changes of the adjacent joint or erosion

of the adjacent bone {1046}.

ICD-O code

9252/0

Histopathology

Tumours are lobulated, well circum-

scribed and at least partially covered by

a fibrous capsule. Their microscopic

appearance is variable, depending on

the proportion of mononuclear cells,

multinucleate giant cells, foamy

macrophages, siderophages and the

amount of stroma. Osteoclast-like cells,

which contain a variable number of

nuclei (from 3-4 to more than 50), are

usually readily apparent but may be

Synonyms

Tenosynovial giant cell tumour, localized

type, nodular tenosynovitis.

Epidemiology

The localized form is frequent and the

most common subset of giant cell tu-

mours. Tumours may occur at any age

but usually between 30 and 50 years,

with a 2:1 female predominance {2163}.

Aetiology

Tenosynovial giant cell tumours initially

were regarded as an inflammatory

Fig. 3.01 Giant cell tumour of tendon sheath. A Typical admixture of histiocytoid cells, foamy cells and lymphocytes. In this case, giant cells are scanty. B Typical mononu-

clear histiocytoid cells with variably prominent eosinophilic cytoplasm and scattered osteoclastic giant cells.

110 Fibrohistiocytic tumours

Fig. 3.02 Giant cell tumour of tendon sheath. A Most cases show focal collections of xanthoma cells, while others (B) show extensive stromal hyalinization. C Small, his-

tiocyte-like cells with occasional nuclear grooves and larger cells with vesicular nuclei and abundant eosinophilic cytoplasm, frequently with a rim of haemosiderin.

inconspicuous in highly cellular tumours.

Most mononuclear cells are small, round

to spindle-shaped. They are character-

ized by pale cytoplasm and round or

reniform, often grooved nuclei. They are

accompanied by larger epithelioid cells

with glassy cytoplasm and rounded

vesicular nuclei. Xanthoma cells are fre-

quent, tend to aggregate locally near the

periphery of nodules and may be associ-

ated with cholesterol clefts.

Haemosiderin deposits are virtually

always identified. The stroma shows vari-

able degrees of hyalinization and may

occasionally have an osteoid-like

appearance. Cleft-like spaces are less

frequent than in the diffuse form {2163}.

Mitotic activity usually averages 3 to 5

mitoses per 10 HPF but may reach up to

20/10 HPF {2295}. Focal necrosis is

rarely seen.

(HHF35). A subset of desmin-positive

dendritic cells is reported in up to 50% of

cases {705}.

Multinucleate giant cells express CD68,

CD45 and markers such as tartrate

resistant acid phosphatase {449,1590}.

translocation partners have been

described, including 3q21, 5q31, and

11q11. In addition, two cases without

1p11-13 rearrangement had transloca-

tions involving 16q24, thus possibly rep-

resenting an alternative primary cytoge-

netic change. Numerical changes seem

to be rare. In particular, it should be

noted that gain of chromosomes 5 and 7,

which is common in the diffuse type giant

cell tumour {1477}, has not been

described in the localized form {1910}.

Ultrastructure

Ultrustructural studies have revealed an

heterogeneous cell population com-

posed of a majority of histiocyte-like

cells, accompanied by fibroblast-like

cells, intermediate cells, foam cells and

multinucleate giant cells {35,2163}.

Prognostic factors

Localized giant cell tumour is a benign

lesion with a capacity for local recur-

rence. Local excision is the treatment of

choice. 4 to 30 % of cases recur {1504,

1757,1774} but these recurrence are

usually non-destructive and are con-

trolled by surgical reexcision. It has been

suggested that recurrences develop

most often in highly cellular tumours or

lesions with a high mitotic count

{1757,2298}.

Genetics

Cytogenetic aberrations have been

described in 11 giant cell tumours of ten-

don sheath. A near- or pseudodiploid

karyotype was seen in all cases, mostly

with simple structural changes {1910}.

The short arm of chromosome 1 is fre-

quently involved, with a clustering of

breakpoints to the region p11-p13 in 7/11

cases. A recurrent t(1;2)(p11;q35-36)

has been identified, but several other

Immunophenotype

Immunohistochemically, mononuclear

cells are positive for CD68. Some cells

may also express muscle-specific actin

Fig. 3.03 Giant cell tumour of tendon sheath. A Localized giant cell tumours of tendons sheath are usually CD

68 positive. B Some cases of both localized and diffuse type contain numerous desmin-positive mononuclear

cells, sometimes with dendritic cytoplasmic porcesses.

Fig. 3.04 Giant cell tumour of tendon sheath. Partial

karyotype showing the characteristic t(1;2)(p13;q37)

translocation. Arrows indicate breakpoints.

Giant cell tumour of tendon sheath 111

Diffuse-type giant cell tumour

N. de St. Aubain Somerhausen

P. Dal Cin

Definition

Diffuse-type giant cell tumour is a

destructive proliferation of synovial-like

mononuclear cells, admixed with multi-

nucleate giant cells, foam cells,

siderophages and inflammatory cells.

The extraarticular form is defined by the

presence of an infiltrative soft tissue

mass, with or without involvement of the

adjacent joint.

The very uncommon malignant giant cell

tumour of tendon sheath is defined by

the coexistence of a benign giant cell

tumour with overtly malignant areas or by

the recurrence of a typical giant cell

tumour as a sarcoma.

poromandibular and spinal facet joints

{782,1899}. Extraarticular tumours most

commonly involve the knee region, thigh

and foot. Uncommon locations include

the finger, wrist, groin, elbow and toe {87,

1984,2164}.

Most extraarticular tumours are located

in periarticular soft tissues but these

lesions can be purely intramuscular or

predominantly subcutaneous {2164}.

sponge-like. The typical villous pattern of

pigmented villonodular synovitis is usual-

ly lacking in extraarticular tumours. The

latter have a multinodular appearance

and a variegated colour, with alternation

of white, yellowish and brownish areas.

Histopathology

Most tumours are infiltrative and grow as

diffuse, expansile sheets. Their cellularity

is variable: compact areas alternate with

pale, loose, discohesive zones. Cleft-like

spaces are common and appear either

as artefactual tears or as synovial-lined

spaces. Blood-filled pseudoalveolar

spaces are seen in approximately 10% of

cases.

In comparison with the localized form,

osteoclastic giant cells are less common

and may be absent or extremely rare in

up to 20% of cases. They are irregularly

distributed throughout the lesions and

are more easily found around haemor-

rhagic foci.

The mononuclear component comprises

two types of cells: small histiocyte-like

cells, which represent the main cellular

component, and larger cells. Histiocyte-

like cells are ovoid or spindle-shaped,

with palely eosinophilic cytoplasm. Their

nuclei are small, ovoid or angulated, con-

tain fine chromatin, small nucleoli and

frequently display longitudinal grooves.

Larger cells are rounded or sometimes

show dendritic cytoplasmic processes.

Their cytoplasm is abundant, pale to

deeply eosinophilic, often contains a

Clinical features

Patients complain of pain, tenderness,

swelling or limitation of motion.

Haemorrhagic joint effusions are com-

mon. The symptoms are usually of rela-

tively long duration (often several years).

Radiographically, most tumours present

as ill defined peri-articular masses, fre-

quently associated with degenerative

joint disease and cystic lesions in the

adjacent bone {542}. On magnetic reso-

nance imaging, giant cell tumours show

decreased signal intensity in both T1-

and T2-weighted images {1036}.

ICD-O code

9251/0

Synonyms

Pigmented villonodular synovitis, pig-

mented villonodular tenosynovitis.

Epidemiology

Diffuse-type giant cell tumours tend to

affect younger patients than their local-

ized counterpart. The age of patients

varies widely but most lesions affect

young adults, under the age of 40. There

is a slight female predominance {1523,

1984,2164}.

Aetiology

Although these lesions have been

regarded as reactive, the presence of

clonal abnormalities {1910} and the

capacity for autonomous growth are now

widely regarded as evidence for a neo-

plastic origin.

Sites of involvement

Intraarticular lesions affect predominant-

ly the knee (75% of cases), followed by

the hip (15%), ankle, elbow and shoul-

der. Rare cases are reported in the tem-

Macroscopy

Diffuse-type giant cell tumours are usual-

ly large (often more than 5 cm), firm or

Fig. 3.05 A Villous appearance of an intra-articular diffuse-type giant cell tumour. B Low magnification of a com-

pletely extra-articular tumour showing infiltration of the muscular and adipose tissue.

Fig. 3.06 Diffuse-type giant cell tumour with promi-

nent inflammatory component and numerous large

dendritic cells with abundant cytoplasm.

112 Fibrohistiocytic tumours

peripheral rim of hemosiderin granules

and occasionally shows a paranuclear

eosinophilic filamentous inclusion. Nuclei

are characterized by reniform or lobulat-

ed shape, thick nuclear membranes,

vesicular chromatin and eosinophilic

nuclei. The occasional predominance of

these larger cells may obscure the typi-

cal features of giant cell tumour and lead

to a diagnosis of sarcoma. Sheets of

foam cells are frequently observed, usu-

ally in the periphery of lesions and vari-

able amounts of haemosiderin are identi-

fied in most cases. Giant cell tumours

may also contain a significant lymphocyt-

ic infiltrate. The stroma shows variable

degrees of fibrosis and may appear

hyalinized, although this is usually less

marked than in the localized form.

Mitoses are usually identifiable and

mitotic activity of more than 5 per 10 HPF

is not uncommon {1984,2164,2239}.

There have been several reports of typi-

cal giant cell tumours recurring as a his-

tologically malignant neoplasms and a

few series included primary histological-

ly malignant tumours of the tendon

sheath resembling giant cell tumours

{187,637,1555,1941,1984}. These neo-

plasms tended to show significantly

increased mitotic rate (more than 20

mitoses / 10 HPF), necrosis, enlarged

nuclei with nucleoli, spindling of mononu-

cleated cells, the presence of abundant

eosinophilic cytoplasm in histiocyte-like

cells, and stromal myxoid change,

although none of these features could be

used in isolation as a criterion for malig-

nancy {187,637,1984}.

In addition, two cases with banal histol-

ogy which developed metastatic disease

(in the lungs or lymph nodes) have been

reported to date {1984,2239}.

Fig. 3.07 Diffuse-type giant cell tumour. A Pseudosynovial or 'pseudoglandular' spaces, surrounded by clusters

of xanthoma cells. B Pseudoalveolar spaces are commonly seen in diffuse-type giant cell tumours.

pseudodiploid karyotype. Rearrange-

ments of the 1p11-13 region have been

detected in eight of them, one had a

t(1;2)(p22;q35-37), and one had involve-

ment of band 16q24, suggesting a close

cytogenetic relationship with the local-

ized form of giant cell tumour {1910}.

One difference, however, between these

two entities, is that trisomies for chromo-

somes 5 and 7, usually as the sole anom-

alies, have been detected only in diffuse-

type giant cell tumours {1477}. The sig-

Immunophenotype

The immunohistochemical and ultra-

structural features of diffuse-type giant

cell tumour are similar to those of the

localized form. Mononuclear cells are

positive for CD68 and other macrophage

markers. Desmin stain highlights a popu-

lation of cells with dendritic features in 35

to 40% of cases; these frequently corre-

spond to the larger eosinophilic cells.

Giant cells are positive for CD68 and

CD45 {705,1590,1984}.

Fig. 3.08 Diffuse-type giant cell tumour. A Typical mononuclear histiocytoid cells, some of which have promi-

nent eosinophilic cytoplasm. B Note frequent nuclear grooves in the histiocytoid cells. Some tumour cells have

more prominent eosinophilic cytoplasm with haemosiderin granules.

Genetics

Chromosomal aberrations have been

described in 17 cases, all with a near- or

Diffuse-type giant cell tumour

113

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