A Clinico-pathologic study of soft tissue tumors

Abstract:
Introduction: Soft tissue is nonepithelial, extraskeletal tissue of body. Soft tissue tumors are
rare neoplasms. Benign tumors are the most common. Malignant soft tissue tumors are
extremely rare constituting <1% of all cancers.
Aims: To study histopathological findings in soft tissue tumor specimens and grading of
malignant tumors for treatment stratification.
Methods and Materials: A cross sectional study was done to examine all the soft tissue
tumor specimens after routine processing for haematoxylin and eosin staining and special
stains and immunohistochemistry was used wherever necessary. WHO system of
classification was used to describe soft tissue tumors and FNCLCC grading system was
used for grading.
Results: Total of 250 soft tissue tumor specimens examined. Benign tumors were 213
(85.2%), intermediate 7 (2.8%) and malignant 30 (12%). Males were 141 and females 109
with M:F ratio of 1.3:1. Benign tumors most commonly occurred in 3 rd decade and malignant
tumors in 5th decade. The most common site was head and neck in benign tumors and trunk
in malignant tumors. Grade III tumors were most common in malignant tumors. IHC was
carried out in 13 specimens for further confirmation which helped in revising diagnosis in 3
patients. Grossly, 75% of the benign tumors were well circumscribed with size less than
5cm, whereas 60% of malignant tumors were more than 5cm in size.
Conclusion: Benign tumors outnumber malignant tumors by considerable margin. The
diagnosis and management of soft tissue tumors require a team perspective consisting of
clinical, radiological and pathological correlation. A careful gross examination Routine H&E
staining is the standard in diagnosis. Special stains and Immunohistochemistry are
supplementary.. Undifferentiated malignant neoplasms are a daunting diagnostic problem for

anatomical pathologists, calling for a tour de force in morphological skill, clinicopathological

correlation, and application of adjunctive laboratory studies like IHC and genetic analysis.
Grading is the best prognostic indicator of malignant soft tissue tumors and predictor of
metastasis outcome. It should be part of the pathologic report.

Key words: Soft tissue; tumors; histopathology;

Introduction:
Soft tissue can be defined as nonepithelial, extraskleletal tissue of the body, exclusive of the
reticuloendothelial system, glia and supporting tissue of various parenchymal organs. It is
represented by voluntary muscle, fat, fibrous tissue along with the vessels serving these
tissue and the peripheral system. They are derived from the embryonic mesoderm with
some contribution from neuroectoderm.(1).
Soft tissue tumors (STTs) are rare neoplasms. Benign tumors are the most common tumors
with annual incidence of 300 per 1 lakh population and they outnumber the malignant
counterparts by ratio of 100:1. The malignant soft tissue tumors also called sarcomas are
heterogenous groups of tumors constituting less than 1% of all cancers. (2)
Soft tissue tumors occur throughout the body with predilection to extremities accounting for
approximately 50% of cases. Other sites include head and neck, retroperitoneum and body
wall.
Majority of STTs occur sporadically and only a minority are associated with genetic defects.
Well recognized risk factors include various physical and chemical factors, ionizing radiation
exposure and inherited or acquired immunologic defects. All the tumors are thought to arise
as a result of acquired genetic alterations leading to abnormal quality or quantity of proteins
that control cellular proliferation and differentiation.
Soft tissue sarcomas become more common with increasing age with median age of 65yrs.
Sarcomas most commonly metastasize to lungs and skeleton by hematogenous
dissemination.
Most commonly followed soft tissue tumor classification worldwide is World Health
Organization system classification last published in 2002.(3). Histologic grading is the most
important prognostic factor and the best indicator of metastatic risk in adult soft tissue

sarcomas. (4). The most commonly used system for grading is French grading, a 3-tier
system mainly based on histologic type, subtype, tumor nerosis and mitotic activity. (5)
Routine light microscopy in Haematoxylin and Eosin (H&E) stained sections is still the gold
standard for the diagnosis of STTs. (6). However, immunohistochemistry (IHC) is helpful in
the prognosis of the tumors. (7).

Materials and Methods:

This study is a cross sectional study, carried out at the histopathology unit of department of
department of pathology for a period of two and half years from December 2008 to August
2011 after ethical committee approval. All the consecutive soft tissue tumor specimens
received during this period were studied.
The primary objective of the study was to study the histopathological findings in the soft
tissue tumors and secondary objective was to grade the malignant soft tissue tumors for the
treatment stratification.
A detailed gross examination of the soft tissue tumor specimen was performed to record the
tumor size, shape, color, consistency and distance from the deep seated margins. The
specimens were preserved in 10% formalin and allowed to fix for 24 hrs. The H&E stained
sections of all the specimens obtained by routine processing and paraffin embedding were
studied. Special stains such PAS(periodic acid Schiff), reticulin were used whenever
necessary and IHC was done in some tumors to confirm the diagnosis.
For the present study WHO classification of soft tissue tumors used and for grading
FNCLCC system was used. All the data was recorded on a pre-defined proforma

Results:
During the study period, 250 soft tissue tumor specimens were received at the
Histopathology unit of department of Pathology. Benign soft tissue tumors were 213 in
number, intermediate tumors were 7 and malignant tumors were 30 constituting 85.2%,
2.8% and 12% respectively (Table 1). The adipocytic tumors accounted for the majority of
soft tissue tumors (30%) followed by vascular tumors (26%) and neural tumors (17.2%). Of
the benign benign tumors, adipocytic tumors were the most common accounting for 35.2%.
Tumors of fibroblastic/myofibroblastic differentiation were most common in both intermediate
(57.1%) and malignant (26.7%) soft tissue tumors.
Sex distribution: There were 141 (56.4%) males and 109 (43.6%) females in the study. The
overall male to female (M:F) ratio was 1.3:1. Both benign and malignant tumors were more
common in males with ratio of 1.4:1 and 1.1:1 respectively whereas intermediate tumors
were more common in females with M:F ratio of 1:1.3. (Table 2, Graph 1). Age distribution:
Majority of the benign and intermediate tumors occurec in the 3 rd decade and malignant
tumors in the fifth decade. (Graph 2)
Grossly, 75% of the benign tumors were well circumscribed with size less than 5cm,
whereas 60% of malignant tumors were more than 5cm in size. Anatomical sites of benign
and malignant tumors is depicted in table 3 and 4.
When all the subgroups of tumors in benign tumors are considered lipomas were most
common (31.9%) followed by capillary hemangioma (13.1), Schwannoma (11.7%),
neurofibroma (8.5%), cavernous haemangioma (7.1%), lymphangioma (5.2%), pyogenic
granuloma (3.3%), giant cell tumor (GCT) tendon sheath (2.8%), fibroma (2.3%). In the
intermediate STTs group fibromatosis was the most common. In case of malignant tumors
dermatofibroma protuberans (23.3%) is most common followed by undifferentiated
pleomorphic sarcoma (16.7%), embryonal rhabdomyosarcoma and malignant peripheral

nerve

sheath

tumor

(MPNST)

each

10%

and

synovial

sarcoma

and

alveolar

rhabdomyosarcoma each 6.6%.

Histological grading was done in 30 malignant soft tissue sarcomas. Nine tumors were
Grade I, three were Grade II and 18 were Grade III tumors.
Further IHC studies (table 5) were performed in the 13 malignant tumors for further
confirmation. It was helpful only in 3 tumors where the initial diagnosis had to be revised
based on the IHC positivity. These tumors include infantile fibrosarcoma, Ewings/Primitive
neuroectodermal tumor (PNET) and intermediate grade STT were respectively revised into
embryonal rhabdomysarcoma (desmin, MyoD1 and Myogenin positive), clear cell sarcoma
(s-100, vimentin positive) and dermatofibrosarcoma protuberans (CD34, SMA positive).

Discussion:
The present study analysed a cross-section of consecutive 250 soft tissue tumor specimens
received at the Histopathology unit of Pathology department.
The age of the patients in this study ranged from 4months to 89yrs. However the peak
incidence for benign and malignant tumors was different being 3 rd decade and 5th decade
respectively.
The incidence of benign, intermediate and malignant tumors was 85.2%, 2.8% and 12%
respectively. The ratio of benign to malignant tumors was 7.1:1. Jenson OM (8) reported
lesser incidence of malignant tumors (5.4%) compared to benign tumors (94.6%) with
benign to malignant ratio of 18.5:1. This may be explained by inherent bias in the referral
population. However, Kransdorf MJ (9) reported increased percentage of malignant tumors
(39.8%) with benign to malignant ratio of 1.5:1 which may be due to case material referred to
highly specialized centres.
This variable frequency of distribution of benign and malignant tumors in different studies
may be due to long latent period appearance of the tumors and reporting to the clinicians.
The general consensus is that benign tumors outnumber the malignant counterparts by a
considerable margin.
The commonest benign tumor type was adipose tumor forming 35.2% of benign STTs which
is comparable to the study by Geetha D (10) et al i.e. 38.3%. But the incidence was much
higher 48.1% in study by Jensen OM (8) and much lower 16.7 in study of Kransdorf MJ (9).
Second most common benign tumor group was the vascular tumors with incidence of 30.5%
but in study by Geetha D (10) et al the incidence was 21.3% and study by Jensen OM (8)
was much lesser with incidence of 13.6%.
The commonest malignant tumor type was fibroblastic/myofibroblastic tumors accounting for
26.7% followed by fibrohistiocytic tumors at 20% in the present study. This is in contrast to

the studies of Jensen OM (8) and Kransdorf MJ (11) where fibrohistiocytic tumors were the
most

common

with

incidence

of

40.3%

and

25.7%

respectively

followed

by

fibroblastic/myofibroblastic tumors with incidence of 19.4% and 11.5% respectively.

There were 141 (56.4%) males and 109 females (43.6%) with M:F ratio of 1.3:1 and was
comparable to study by Kransdorf MJ (9) where the M:F ratio was 1.2:1. In the case of
benign tumor group there were 122 males and 91 females with a male to female ratio of
1.4:1 in contrast to the study of Jensen OM (8) where the male to female ratio was 0.9:1. In
case of malignant tumors there were 16 males and 14 females with a male to female ratio of
1.1:1 which was again in contrast to the study of Jensen OM (8) where the male to female
ratio was 2:1 indicating males were at two fold risk of malignant tumors.
Age distribution: The average age was 40yrs in benign tumors and 43.6yrs in malignant
tumors which were comparable to the study of Jensen OM. (8). The peak incidence of
benign tumors was 3rd decade and 5th decade for malignant tumors.
Site Distribution: In the present study, benign tumors occurred most commonly in the head &
neck (38%) region followed by upper extremity (22.2%), trunk (20.6%) and lower extremity
(19.2%). This is comparable with study by Dev G (12) et al where head and neck was
commonest site (32%) followed by upper extremity (26.6%), trunk (24.8%) and lower
extremity (16.6%). But this is in contrast to study of Kransdorf MJ (9) where the commonest
site was upper extremity (33.3%) followed by lower extremity(30.3), trunk (21.6%) and head
& neck (14.8%).
Malignant STTs have equal predilection for both upper and lower extremities 26.7% each in
contrast to the study of Kransdorf MJ (11) where the common site was lower extremity.
On gross examination, 75% of benign tumors were well encapsulated and presented with a
size less than 5cm while 60% malignant tumors measured more than 5cm whereas Jensen
OM (8) reported 95% and 75% repectively for benign and malignant tumor.

Conclusion:
The large majority of soft tissue tumors are benign with a very high cure rate after surgical
excision. Malignant mesenchymal neoplasms amount to less than 1% of the overall human
burden of malignant tumors but they are life threatening and may pose a significant
diagnostic and therapeutic challenge.
The diagnosis and management of soft tissue tumors require a team perspective consisting
of clinical, radiological and pathological correlation. Even though soft tissue sarcomas are
rare and usually present just as painless mass, the clinician must be able to diagnose it early
for better management.
A careful gross examination of the specimen and adequate sampling of the tumor is
essential. Special stains and IHC are helpful in addition to the routine haematoxylin and
eosin for the proper diagnosis of STTs.
Undifferentiated malignant neoplasms are a daunting diagnostic problem for anatomical
pathologists, calling for a tour de force in morphological skill, clinicopathological correlation,
and application of adjunctive laboratory studies like IHC and genetic analysis.
Grading is the best prognostic indicator of malignant soft tissue tumors and predictor of
metastasis outcome. It should be part of the pathologic report. Grading should be adapted to
the modern management of patients and complemented by radiologic and molecular
parameters.

References:
1. Weiss WS, Goldblum JR, Enzinger and Weisss Soft Tissue Tumours. 5 th ed.
St.Louis: Mosby;2008.
2. Rydholm A, Berg NO, Gullberg B et al. Epidemiology of soft tissue sarcoma in the
locomotor system. A retrospective population based study of the inter-relationships
between clinical and morphologic variables. Acta Pathol Microbial Immunol Scand.
1984;92:363-374.
3. Fletcher C.D.M., Unni K.K., Mertens F. (Eds.): World Health Organization
Classification of Tumors. Pathology and genetics of tumors of soft tissue and bone.
IARC Press:Lyon 2002.
4. Coindre JM. Grading of soft tissue sarcomas: Review and update. Arch Pathol Lab
Med 2006;130:1448-1453.
5. Trojani et al. ????(no Reference quoted????)
6. Suster S. Recent advances in the application of immunohistochemical markers for
the diagnosis of soft tissue tumors. Semin Diagn Pathol 2000;17(3):225-35.
7. Coindre JM. Immunohistochemistry in the diagnosis of soft tissue tumors.
Histopathology 2003;43:1-16.
8. Jensen OM. A consecutive 7 year series of 1331 benign soft tissue tumors:
Clinicopathologic data. Comparison with sarcomas. Acta orthop scand 1981;52:287293.
9. Kransdorf MJ. Benign soft-tissue tumors in a large referral population: Distribution of
specific diagnosis by age, sex and location. AJR 1995;164:395-402.
10. Geetha D et al (????reference????)/.
11. Kransdorf MJ. Malignant soft tissue tumors in a large referral population: distribution
of diagnosis by age, sex and location. AJR 1995;164:129-134.
12. Dev G, Banerjee AK, Aikat BK. Benign soft tissue tumors. Ind J Cancer 1974;2:336343.

Sl.No.

Tumors

1.

Adipocytic

2.

Fibroblastic/

Benig

Intermediate

Malignant

Total

75

30

75

30

14

5.6

1.6

3.2

26

10.4

myofibroblastic
3.

Fibrohistiocytic

2.8

0.4

2.4

14

5.6

4.

Smooth muscle

0.4

2.4

5.

Pericytic

0.4

0.4

6.

Skeletal muscle

7.

Vascular

65

26

0.4

66

26.4

0.4

0.4

1.2

0.8

10

43

17.2

1.2

46

18.4

8.

9.

Chondroosseous
Uncertain
differentiation

10.

Neural

Table1. Distribution of benign, intermediate and malignant soft tissue tumor

Sl.No.
1
2

Tumors
Adipocytic
Fibroblastic/

Males
46
15

%
18.4
6

Females
29
11

%
11.6
4.4

Total
75
26

3
4
5
6

myofibroblastic
Fibrohistiocytic
Smooth muscle
Pericytic
Skeletal muscle
a Vascular

9
1
3
37

3.6
0.4
1.2
14.8

5
6
2
29

2
2.4
0.8
11.6

14
6
1
5
66

7
8
9

Neural
Chondro-osseous
Uncertain

24
1
5

9.6
0.4
2

22
5

8.8
2

46
1
10

10

differentiation
Total

141

56.4

109

43.6

Table2. Sex distribution of all soft tissue tumors

Extremities
Sl.No.

Tumor type

Upper

Head

Lower

Trunk

and
neck

1.
2.
3.
4.
5.
6.
7.
8.

Adipocytic
Fibroblastic/myofibroblastic
Fibrohistiocytic
Smooth muscle
Vascular
Pericytic
Neural
Uncertain differentiation
Total

Prox
15
2
1
1
6
25

Dist
5
2
6
3
6
22

Table3. Anatomical sites of benign soft tissue tumors

Prox
10
4
6
4
3
26

Dist
2
1
6
1
4
15

26
2
8
8
44

17
7
1
41
15
81

Extremities
Sl.No.

Tumor type

Upper

Head

Lower

Trunk

and
neck

1.
2.
3.
4.
5.
6.
7.
8.

Fibroblastic/myofibroblastic
Fibrohistiocytic
Smooth muscle
Skeletal muscle
Neural
Vascular
Chondro-osseous
Uncertain differentiation
Total

Prox
4
1
5

Dist
1
2
3

Prox
3
1
1
5

Dist
4
4

Table 4. Site distribution of malignant soft tissue tumors

5
1
1
4
1
12

1
1

Sl.No

Age/Se

x
1.

25 Y/M

2.

38 Y/M

Site

HPD

IHC

MPNST

S-100, +ve

Forearm

Epitheloid

EMA, CD34+ve. S-

swelling

sarcoma

100 sparsely +ve.

Left thigh
mass

Desmin, MyoD1,
3.

40 Y/M

Retroperitone

Infantile

myogenin+ve.

al mass

fibrosarcoma

Revised diagnosisEmbryonal RMS

4.

60 Y/M

Left arm mass

Left hand

5.

25 Y/M

-recurrent
swelling

6.

25 Y/M

Mass upper
1/3 leg
Left forearm

7.

70 Y/M

8.

26 Y/M

mass
Cervical polyp

9.

19 Y/M

Left calf mass

Fungating

10.

50 Y/M

lesion over
the chest

11.

25 Y/M

12.

68 Y/F

Left foot
lesion
Pigmented
lesion over

MPNST
Calcifying synovial
sarcoma

S-100+ve
EMA, Mic-2 +ve
S-100, vimentin+ve.

Ewings/PNET

Revised diagnosisClear cell sarcoma

MPNST

S-100 +ve

Embryonal RMS
Mesenchymal

Desmin +ve
Mic2 +v. SMA focally

chondrosarcoma
Soft tissue

+ve
CD34, SMA+ve.

sarcoma

Revised diagnosis-

(intermediate

Desmatofibrosarco

grade)

ma protuberans

Ewings/PNET

FLI-1, Mic-2 +ve

Angiosarcoma

CD31 +ve

sacrum
13.

2 Y/M

Antrachoanal
polyp

Alveolar
rhabdomyosarco
ma

Desmin, MyoD1,
myogenin +

Table5. IHC studies of malignant soft tissue tumors

140

122

120
100

91

80

Male
Fe male

60
40
16
20

14

0
Be nign

Inte rme diate

Malignant

Graph1. Sex distribution of benign, intermediate and malignant soft tissue tumors

45

45
40
32

35
29

27

30

27

24

25
Be nign

20
15

12

12

10
5

Malignant

20-29

30-39

6
3

0
0-9

10-19

40-49

50-59

60-69

70-79

0
80-89

Graph2. Age distribution of benign and malignant soft tissue tumors