- A 45-year-old female presented with a tumor on her fibula. An initial biopsy showed spindle-shaped cells forming interlacing fascicles with areas of nuclear pleomorphism. This was diagnosed as an atypical fibrous histiocytoma. - The tumor was then excised. The excised specimen showed variably pleomorphic cells, mitotic figures, and necrosis. Differential diagnoses included malignant peripheral nerve sheath tumor, synovial sarcoma, and fibrosarcoma. - Immunohistochemistry showed the tumor was positive for EMA and patchy positive for S-100, suggesting synovial sarcoma or malignant peripheral nerve sheath tumor. It was negative for TLE-

1. Fibular Tumour in a
45 year old Female
Dr P Tandon
Dr Mousumi Sharma
Dr Pooja Jaiswal

2. Initial Biopsy - Gross
• Multiple grayish white tissue
pieces measuring 9.0 x 4.0 x 0.7
cm in aggregate were received.
• It included soft tissue pieces and
bony pieces.
• Multiple tissue bits were
embedded in 5 blocks

3. Initial biopsy (Microscopic)
• Tumour mass formed of interlacing fascicles
of spindle shaped cells.
• Storiform pattern seen.
• In most of the places, tumour cell nuclei
appeared bland.
• However near bony tissue, some nuclear
pleomorphism was seen.
• No abnormal mitotic figures/ areas of necrosis
were present.

4. Initial Biopsy (Storiform pattern)

5. Hypocellular areas with bland nuclei

6. Initial Biopsy (Nuclear pleomorphism)

7. Initial Biopsy (Nuclear pleomorphism)

8. Storiform pattern
Storiform pattern is seen in:
– Reactive fibro-histiocytic proliferations
– Sclerotic fibroma
– Deep dermatofibroma
– Solitary fibrous tumour
– Fibromatosis
– Dermato-fibrosarcoma protuberans,
– Low-grade fibromyxosarcoma
– Malignant fibrous histiocytoma.

9. Diagnosis:
Atypical fibrous histiocytoma.
(Biological behavior unpredicatable.
Follow up indicated)

10. Excised specimen (Gross)
• Resected upper end of fibula with
surrounding soft tissue measuring 7.0 x 4.0 x
3.0 cm in size received.
• An ill-defined predominantly solid, grayish
white to yellowish mass seen near upper end
of fibula.
• It was destroying cortex of the bone and
infiltrating into the surrounding muscle
tissue.
• A total of 10 blocks were taken from different
areas.

11. Excised
Specime
n
(Gross)

12. Excised Specimen (Gross)

13. Excised Specimen (Microscopic)
• Tumour formed of spindle shaped cells is seen
• Variable cell morphology was evident in different
areas of the tumour.
• In some areas - tumour cells appear bland, arranged
in interlacing fascicles, focal storiform pattern seen.
• In other areas- tumour cells pleomorphic, nuclei
enlarged with prominent nucleoli.
• 2-3 mitotic figures/hpf present, necrosis seen.
• Tumour cells invading surrounding skeletal muscle
bundles.

14. Excised specimen

15. Excised specimen

16. Excised specimen

17. Excised specimen

18. Excised specimen

19. Excised specimen

20. Excised specimen

21. DIFFERENTIAL DIAGNOSIS OF MALIGNANT
SPINDLE CELL SARCOMA
• Leiomyosarcoma
• Fibrosarcoma
• MPNST
• Monophasic synovial sarcoma
• Myofibrosarcoma
• Spindle cell rhabdomyosarcoma
• In visceral organs possibility of
– Sarcomatoid carcinoma
– Melanoma
– Follicular dendritic cell sarcoma

22. Histopathological Diagnosis
Primary Spindle cell malignancy of
Fibula. Possibilities include:
• Malignant Fibrous Histiocytoma.
• Malignant Peripheral Nerve Sheath
Tumour.
• Fibrosarcoma
• Leiomyosarcoma
Further IHC work up indicated.

23. Slides and blocks
referred to RMLIMS ,
Lucknow for
immunohistochemistry
and opinion

25. Antibody MPNST Synovial Sarcoma MFH
Fibro
-sarcoma
EMA
SP - 0%
WP - 13%
SP - 74%
WP - 17%
-ve
-ve
S -100
SP - 48%
WP - 09%
SP - 35%
WP - 13%
-ve
-ve
SMA - ve - ve +/- -ve
CD - 56 +/- +/- -ve -ve
TLE -1 WP - 18%
Sens: 85 -100%
Spec: 75 - 96%
-ve
-ve
Desmin +/- - ve +/- -ve
IHC Profile of tumors under
consideration

26. Present case: - Interpretation of IHC
results
Antibody Result Interpretation
EMA Positive
Favor synovial sarcoma +++
Favor MPNST +
S -100 Patchy Positive
Favor synovial sarcoma +
Favor MPNST +
SMA
Patchy positive
Not helpful
CD 56 Negative Not helpful
TLE - 1 Negative Disfavor synovial sarcoma +++
Desmin Negative Disfavor leiomyosarcoma +++

27. MPNST vs Synovial sarcoma
• Majority of peripheral nerve sheath tumours
are benign.
• 50% arise in a setting of neurofibromatosis 1‑
and are seen mostly in soft tissue.
• Primary peripheral nerve sheath tumours of
bones are mostly benign and rare.
• In a study at Mayo Clinic, out of 3987 primary
bone tumors, six were of nerve sheath origin
and all were benign schwannomas. (Wirth
1977).

28. • Malignant tumours of peripheral nerve sheath (MPNST)
are also seen mostly in soft tissues and patients of
NF1 or persons exposed to irradiation are at increased
risk .
• Overall incidence of MPNST is ~ 0.0001%.
• In bone, primary intraosseous MPNST (PI MPNST) is
extremely rare and only 30 cases have been reported
till date.
• Of these, about 50% were seen in mandible and fifteen
cases are reported from bones of the extremities
(Suguwara 2017).
• Dx of MPNST within NF 1 context is easier. However,‑
most of the cases of PI MPNST have been sporadic.

29. • SS is a relatively common malignant tumour in soft
tissues, representing 5-10% of all soft tissue
sarcomas. Initially it was believed to be of synovial cell
origin.
• Now a days the term is considered to be a misnomer
because SS can occur at sites where no synovial
tissue is seen. Its immuno-histological and EM profile
is also different from that of synovial cells.
• WHO classification - Tumour of uncertain
histogenesis.
• Primary intraosseous synovial sarcoma is a very rare
entity. Till 2014, a total of 10 cases have been reported.

30. • Morphologically, MPNST is confused mostly with monophasic
synovial sarcoma (SS).
• Distinction between the two is clinically important because SS
are chemosensitive. Distinction can often be achieved with the
help of IHC.
• Traditionally, immunoreactivity to schwann cell markers like
S-100 is used to characterize MPNST. But, positivity is
reported in only 30 - 50% of tumours.
• To further confound matters, S-100 positivity is seen in ~ 35%
cases of SS.
• Another marker, TLE - 1 can be used to distinguish SS from
MPNST. TLE - 1 positivity is seen in > 85% cases of SS.
However, weak and variable staining of TLE-1 is seen in
MPNST also.

31. • Although TLE -1 staining is not wholly specific for SS, its
sensitivity means that it is useful in excluding the diagnosis of
synovial sarcoma when the result is negative (Fisher 2010).
• Other IHC markers associated with MPNST, such as bcl2, CD56
and nestin are also expressed in a significant proportion of SS
cases (FC Eliber et al 2008).
• In such instances, molecular studies have been found useful.
• SS shows a specific balanced translocation: t(X;18).
• The translocation results in the fusion of SS18 to the SSX1,
SSX2 or SSX4 gene
• Detection of this specific translocation by FISH technique has
been employed as a reliable diagnostic method in making a
distinction between SS and other histological mimics.

32. Take home message
• Clinical presentation of a rare disease can
be deceptively similar to more common
disorders. Hence one must always be alert
to the possibility of a rare disorder.
• It is essential to correlate histological
picture with clinico- radiological findings. If
discrepancy exists, review is indicated and
patient needs to be investigated further.
• In different areas, tumours sometimes have
variable morphology. A small biopsy may
offer misleading information.

33. • Recent lab techniques have become essential
to provide evidence based diagnosis in
Pathology. The practice of attaining a dx
based solely on HE based morphology is
proving to be obsolete in many cases.
• Molecular diagnosis of tumors is the future of
Pathology and may also prove to be the future
of patient management in oncology.
• It is possible that molecular profile of a
tumour may become the sole differentiating
criteria of tumor classification in near future

34. Thank You