Spindle cell lesions of oral cavity

1. SPINDLE CELL
TUMOURS
Part 1
SHERIN JAMES

2. CONTENTS
•Introduction
•Types of spindle cells and its origin
•General considerations
•Pathogenesis
•Pretreatment evaluation
•Classification
•Description of lesion specific
•Treatment/Prognosis
•Conclusion

3. INTRODUCTION

4. ORIGIN OF SPINDLE CELLS ???
Epithelial Origin
Fibroblastic
Myofibroblastic Origin
Muscle Origin
Nerve Tissue Origin
Adipocytic Origin
Vascular Origin
Bone Origin
Odontogenic origin

5. FIBROBLASTS MYOFIBROBLASTS
SMOOTH MUSCLE SCHWANN CELL
OSTEOCYTE
MYOEPITHELIAL CELL
SPINDLE CELLS IN
NORMAL TISSUES

6. GENERAL CONSIDERATIONS
• For most of the spindle cell tumors of head and neck/oral cavity
etiology is unknown
• Various identified causes are:
– Exposure to ionizing radiation
– Inherited or acquired immunologic defects
– Environmental factors like - trauma
– Chemical carcinogens
– Oncogenic virus (Ex: HHV8- Kaposi’s sarcoma, EBV-smooth
muscle tumor in immunodeficiency syndrome patients)
– Genetic factor (Ex: Neurofibromatosis 1 and 2)

7. PRETREATMENT EVALUATION
• Clinical Examination
– Most lesions in the oral cavity arises as painless mass, this will
generally cause delay in diagnosis
– Suspected cases require Biopsy.
• Prior to biopsy depending on peripheral or intra-osseous lesion:
– Radiographic evaluation
– CT Scan
– CBCT in case of oral lesion
– MRI – gives better demonstration of soft tissue tumor
• Helps in clinical staging and helps to locate nerve of origin and
vessel involved in case of neural/vascular tumors.
• Inaccessible area FNAC advised, or incisional biopsy

8. CLASSIFICATION

9. A simple working type classification proposed for the spindle cell neoplasms of the oral cavity
Thorakkal Shamim: A simple working type classification
proposed for spindle cell neoplasma of oral cavity; journal of
cytology, 2013; vol- 30; issue- 1; 85
1

10. 1. Fibrous tissue origin
a) Benign: Fibroma, Nodular
fasciitis, Proliferative fasciitis
and myositis, solitary fibrous
tumor
b)Intermediate:
Fibromatoses, Infantile
fibromatoses, Desmoid tumor
c) Malignant: Fibrosarcoma,
Congenital or Infantile
fibrosarcoma
2. Fibrous histiocyte origin
a) Benign: Fibrous
histiocytoma
b) Intermediate:
Dermatofibrosarcoma,
Plexiform fibrous histiocytic
tumor
c) Malignant: Malignant
fibrous histiocytoma
3. Myofibroblast origin
a)Benign: Myofibroma, b)
intermediate: Inflammatory
myofibroblastic tumor
b)Malignant: Low grade
myofibrosarcoma
4. Muscle tissue origin
Benign: Leiomyoma.
Cellular rhabdomyoma
b) Malignant
i. Leiomyosarcoma,
5. Lipomatous origin
a) Benign: Spindle cell lipoma
b)Malignant: Dedifferentiated
liposarcoma
6. Epithelial origin
a) benign: spindle cell nevus
Malignant: Mal. Melanoma,
Spindle cell carcinoma
10. Vascular origin
a) Benign: Angiofibroma
b) Intermediate: Spindle cell
hemangioma,
Hemangiopericytoma
c) Malignant: Angiosarcoma,
Kaposi sarcoma
8. Neural origin
a) Benign: Traumatic
neuroma, Neurofibroma,
Schwannoma, PEN
b) Malignant: Malignant
peripheral nerve sheath
tumor
7. Osseous origin
Fibroblastic variant of
osteosarcoma,Desmoplastic
fibroma
9. Salivary gland
Myoepithelioma, Myoepithelial
carcinoma
11. Odontogenic origin
Odontogenic fibroma,
Odontogenic myxoma
12. Miscellaneous
Synovial sarcoma, diffuse mesothelioma, fibromyxoma
3/23/2023 10

11. Classified based on APPEARANCES AND THE
ARCHITECTURAL PATTERN.
• A. MONOMORPHIC SPINDLE CELL LESIONS:
• uniform spindle cells which may be arranged in fascicles, a storiform
pattern or a ‘herringbone’ pattern, or are sometimes associated with a
dense collagenous stroma.
• The most common are spindle cell squamous carcinoma and melanoma.
• B. PLEOMORPHIC SPINDLE CELL LESIONS:
• Spindle cells showing wide variation in size and shape, often with
marked nuclear pleomorphism and tumour giant cells.
• These malignancies can occur both in mucosal sites and as lymph node
metastases in the neck and parotid glands.
2
Catriona E Anderson, Awatif Al-Nafussi; Spindle cell lesions of the head and neck: an
overview and diagnostic approach. Diagnostic histopathology, 2009; 15:5 265 -272

12. • C. BIPHASIC SPINDLE CELL LESIONS:
• Two distinct components, spindle cell areas and epithelioid areas.
• Epithelioid areas may be sparse and several levels should be
examined in biopsies of spindle cell lesions in an attempt to identify
these elements.
• D. MYXOID SPINDLE CELL LESIONS:
• Spindle cell component may be conspicuous or less easily identified,
but it is set in a loose, myxoid stroma.
• Some tumours in this category may also have a prominent
inflammatory infiltrate.

14. 1. NEURAL TUMOR
– Neurofibroma
– Schwannoma
– Traumatic neuroma
– Palisaded encapsulated neuroma
– Malignant peripheral nerve sheath tumor
2. MYOFIBROBLASTIC TUMORS
– Myofibroma
– Inflammatory myofibroblastic tumor
– Low-grade myofibroblastic sarcoma
3. SMOOTH MUSCLE TUMORS
– Angiomyoma/vascular leiomyoma
Jordan RC, Regezi JA. Oral spindle cell neoplasms: a review of 307 cases. Oral Surg Oral Med
Oral Pathol Oral Radiol Endod. 2003;95:717-24.
3

15. 4. FIBROBLASTIC TUMORS
– Solitary fibrous tumor
– Nodular fasciitis
– Fibromatosis
– Desmoplastic fibroma
– Fibrosarcoma
5. VASCULAR TUMORS
– Vascular malformation
– Kaposi’s sarcoma
6. CARCINOMAS
– Spindle cell SCC
– Sarcoma NOS/Atypical spindle cell neoplasm
– Benign fibrous histiocytoma
Jordan RC, Regezi JA. Oral spindle cell neoplasms: a review of 307 cases. Oral Surg Oral Med
Oral Pathol Oral Radiol Endod. 2003;95:717-24.

16. TODAY!!!
• Fibroblastic
• Fibrohistiocytic
• Myofibroblastic
• Adipose tissue
• Epithelial

17. FIBROBLASTS

18. ORIGIN OF FIBROBLAST CELL
18

19. MYOFIBROBLASTS
Myofibroblasts are short, bipolar or tripolar, spindle shaped or
stellate cells with long cytoplasmic extensions, containing sparse to
moderate amounts of acidophilic cytoplasm with indistinct cell
margins, and ovoid, often indented, pale nuclei containing a small
nucleolus.
They have contractile elements and synthesize collagen,
fibronectin, and laminin.
Widely used marker- α-SMA,
Endoscalin, p311, integrin, osteopontin, periostin seems specific
for certain conditions.

20. ORIGIN OF MYOFIBROBLASTS
20

21. Lesion wise description

22. FIBROBLASTIC

23. FIBROBLASTIC
Fibroma
Giant cell fibroma
Fibromatosis
Solitary fibrous tumor
Nodular fasciitis
Fibrosarcoma

24. FIBROMA
• Synonyms:
• Reactive hyperplasia of the fibrous connective tissue, in response to local irritation
or trauma.

25. DEMOGRAPHICS & CLINICAL FEATURES:

27. HISTOPATHOLOGY:
Pedunculated fibroma
CT gradually blends
Collagen bundles – streaming pattern

29. Hyperkeratosis due to irritation
Dense, hyalinized collagen in
sclerotic fibroma

30. Collagen bundles in whirling pattern with numerous blood capillaries – less
inflammatory cell

31. TREATMENT:
• Conservative surgical excision
• Recurrence is rare

32. GIANT CELL FIBROMA
• Not associated with any chronic irritation.
• It represents approximately 2% to 5%of all oral fibrous
DEMOGRAPHICS:
• 10 – 30 years
• No gender predilection (Female )
• Most commonly it occurs on the mandibular gingiva, followed by tongue, and
palate.

33. CLINICAL FEATURES:
• It appears as an asymptomatic, sessile, or a pedunculated nodule
• Usually less than 1 cm in size
• Bosselated or a papillary surface.

34. HISTOPATHOLOGY:
 Corrugated, atrophic SSE
 Thin elongated rete ridges
 Vascular fibrous CT (loosely arranged)
 Numerous large STELLATE FIBROBLASTS with several Nuclei, in superficial
CT

35. Mono or multinucleated Fibroblasts
Stellate/spindle shaped fibroblasts within
the superficial connective tissue

36. H& E
10x and 40x

37. DIFFERENTIAL DIAGNOSIS:
• Retrocuspid papilla (Site specific)
• Papilloma
• Irritational fibroma
TREATMENT:
• Conservative surgical excision
• Recurrence is rare

38. FIBROMATOSES
• Fibromatoses comprise a broad group of benign fibrous tissue
proliferations of similar microscopic appearance whose biologic
behavior and histopathologic pattern is intermediate between
that of benign fibrous lesions and fibrosarcoma.
• In the soft tissues of the head and neck- frequently called
Juvenile aggressive fibromatoses or extraabdominal desmoids.

39. •These non-encapsulated lesions are locally aggressive in behavior
with a tendency for recurrence.
• They do not metastasize but presents with local infiltration into
the vital structures

40. CLINICAL FEATURES
• Enzinger and Weiss subdivide the fibromatoses into two broad
categories:
– Superficial (fascial) fibromatoses and
– Deep (musculo - aponeurotic) fibromatoses
40

41. Types of
fibromatoses
Deep
Abdominal
Extra
abdominal(Head
and Neck)
Intra-abdominal
Superficial Palmar/Plantar
Sporadic
(Familial
multicentric)
41

42. • Adjacent to the mandible, where underlying bone may be
eroded or destroyed by invasion.
• Can spread through fascial planes and invade surrounding
structures, causing pain, dysphagia, respiratory distress,
proptosis and epistaxis.
• When airway or major vessels are involved, there may be
life-threatening consequences
42

43. •A firm, painless mass - rapid or
insidious growth.
•Most common in para-mandibular
soft tissue.
•Facial disfigurement

44. PATHOGENESIS
• Remains unexplained.
• Some endocrinal disturbances, because these tumors are
characterized by high levels of estrogens and pituitary gonadotropins.
• Steroid hormones have an important role in the regulation or
fibroblastic activity and proliferation.
• Cases have occurred in surgical scars, in irradiated areas, in burn
scars, in regions of healed fractures, and in areas of previous trauma,
and one case occurred after a silicone implant.
• Occasional cases with familial history have been reported.

45. GROSS APPEARANCE
• Firm, glistening mass resembling scar tissue
• Margins are usually poorly circumscribed
45

46. HISTOPATHOLOGY
Non- encapsulated, poorly circumscribed, infiltrative lesion with a fascicular
growth pattern, usually striated musculature
Cellular proliferation of spindle shaped cells that are arranged in streaming
fascicles & associated with variable amount of collagen.
No atypia, mitotic figures.
Slit like vascular spaces seen

48. Low, paucicellular fibrous proliferation in
long fascicles, numerous slit-like vessels
Fibroblasts, spindled, dense, wavy nuclei
and minimal cytoplasm

49. •Some cases show moderate numbers of lesional cells in a background
stroma of abundant mature collagen, and others show minimal stroma with
large numbers of active mesenchymal cells.
•Occasionally normal-appearing mitotic figures may be found, but they
should not exceed 4 mitoses per high-power field.
Vesicular nuclei with minute
nucleoli, indistinct cytoplasm,
interstitial collagen

50. Streaming fascicles of spindled cells
highly cellular with variable amount of
collagen
Hyperchromatic and pleomorphic
nuclei are seldom seen

51. Cellular interlacing bundles
Elongated fibroblasts

52. Little or no Pleomorphism
Little or no mitotic activity
No inflammation.
Slit-like vascular spaces

53. H&E, 4x,10, 40x 53

54. IMMUNOHISTOCHEMISTRY
The spindle cells express vimentin, SMA and MSA
Some show desmin expression, β- catenin (adenomatous polyposis coli (APC)
gene) positivity
β- catenin

55. Reactive to smooth muscle actin (SMA), Vimentin
SMA

56. DIFFERENTIAL DIAGNOSIS
• Fibrosarcoma – one or more than one mitotic figure PHF
• Nodular fasciitis- Negative for β- catenin
• Leiomyoma - bright pink cytoplasm of smooth muscle, desmin+
56

57. TREATMENT:
• A locally aggressive tumor.
• Wide excision, including a generous margin of the adjacent normal tissues.
• Recurrence rate of for oral and paraoral fibromatoses – 23%.
• No metastases.

58. NODULAR FASCIITIS
(Pseudosarcomatous Fasciitis/ Infiltrative Fasciitis,
Subcutaneous Pseudosarcomatous Fibromatosis)
A benign and reactive fibroblastic growth extending as a solitary
nodule from the superficial fascia into the sub-cutaneous fat and
subjacent muscle.
It is closely related to “proliferative myositis” which occurs in
muscle.

59. Definition:
A pseudosarcomatous, self-limiting, reactive process
composed of fibroblasts and myofibroblasts
• Common benign mesenchymal lesion often misdiagnosed as a
sarcoma
• Etiology : unknown; trauma ??
• Recent molecular studies suggests that the cells are clonal, thus
confirms that it is a benign neoplasm.

60. DEMOGRAPHICS:
• Age: Fourth and fifth decades of life
• Sex: Equal gender distribution
• Site: Buccal mucosa, labial mucosa, tongue, Angle & inferior
border of the mandible, zygomatic arch, anterior mandible
• Trunk & extremities – most commonly involved.

61. CLINICAL FEATURES:
 Occur mostly in areas which serve as sites of origin and insertion of muscles of
mastication.
10 % - soft tissues of the head and neck region, usually presenting as a rapidly
enlarging mass. (skin of face & parotid sheath).

62. • Rapidly growing (1 to 2 months), sometimes painful nodule
• Exophytic lesion some times may be ulcerated
Dan Dayan et al, Clinico-pathologic correlations of myofibroblastic tumors of the oral
cavity: nodular fasciitis; J Oral Pathol Med (2005) 34: 426–35

63. GROSS APPEARANCE
• Depends on amount of myxoid or fibrous stroma, cellularity
• Well circumscribed, non-encapsulated lesion
• Cut surface is soft and gelatinous- if myxoid
• Rarely hemorrhagic areas are seen.

64. HP
• Zonation effect with hypocellular central region and hypercellular
periphery
• Composed of uniform, plump, immature, spindled to stellate
fibroblasts or myofibroblasts without atypia, with a feathery,
"tissue-culture" like growth pattern due to abundant ground
substance
• Mucoid / myxoid pools (microcysts), a very useful diagnostic
finding
• Cellular areas may have storiform or fascicular patterns (S or C
shaped)

65. Subcutaneous tumor is partially circumscribed nodule infiltrating focally along fascial planes

66. Focal infiltration into fat, with
evenly distributed granulation
tissue-like vessels throughout the
lesion

67. Gently curving C and S
shaped fascicles of
myofibroblastic cells exhibit
a characteristic "torn
Kleenex" pattern

68. Focal storiform pattern is suggestive of fibrous histiocytoma

69. Mitotic figures,
but no abnormal forms

71. A nodular growth contains plump fibroblasts with vesicular nuclei
in a haphazard to storiform arrangement.

72. Spindle cells in myxoid background

73. DD:
•Benign fibrous histiocytoma: in dermis, storiform pattern, infiltrative
borders with collagen trapping, sometimes prominent xanthoma cells
and often Touton giant cells, no myxoid microcysts
•Fibromatosis: infiltrates surrounding soft tissue, spindled cells are
parallel and separated by abundant collagen and arranged in broad
sweeping fascicles, no loose tissue culture appearance or myxoid
microcysts
•Sarcoma: nuclear atypia is prominent, necrosis, larger size usually

74. • Spindle cell shows both myofibroblastic and histiocytic immunoprofile
– SMA
– MSA
– Vimentin
– CD68
Dan Dayan et al, Clinico-pathologic correlations of myofibroblastic tumors of the oral
cavity: nodular fasciitis; J Oral Pathol Med (2005) 34: 426–35
SMA

75. Smooth muscle actin, vimentin that
shows strong and diffuse cytoplasmic
positivity

76. TREATMENT
• Local excision is the treatment of choice

77. SOLITARY FIBROUS TUMOR (SFT)
• The diagnosis of Hemangiopericytoma (HPC) was first described
by Arthur Purdy Stout and Margaret Murray in 1942  derived
from pericytes
• Solitary fibrous tumor (SFT) was originally described as a
primary tumor arising in the pleura, presumably as a tumor of
submesothelial fibroblasts
• Now recognized as ends of the spectrum within a single biologic
entity.

79. The recent discovery of the reproducible NAB2-STAT6 gene fusion,
resulting from a t(12q13) translocation in tumors previously classified as
both soft tissue SFT and HPC has largely ended the controversy..
The histologic features of HPC, using the Enzinger and Smith 1976
definition, include
(1) randomly distributed (“patternless”) ovoid to short spindle cells
(2) prominent thin-walled vasculature in a branching (“stag horn”) pattern.
 The tumor cells lack overt differentiation and show uniformly high
cellularity.
Mitotic activity is usually low (1-4 mf / 10 hpf)
while necrosis and pleomorphism are absent.

80. CLINICAL FEATURES
• Middle-aged adults (median age 50 years)
• Wide anatomic distribution; essentially arises from any soft tissue
or visceral location
• Rarely causes paraneoplastic hypoglycemia due to insulin-like
growth factor production
• Slow growing painless mass, usually benign; histologically
malignant tumors may be grossly infiltrative.

81. GROSS APPEARENCE

82. HISTOPATHOLOGY
• Patternless architecture of hypo- and hypercellular areas separated
by thick, hyalinized collagen with cracking artifact and stag horn
vessels
• Perivascular sclerosis
• Bland and uniform oval to spindle cells dispersed along thin
parallel collagen bands, cells have minimal cytoplasm, small
elongated nuclei and indistinct nucleoli
• Some have myxoid change, mast cells, adipose tissue or
multinucleated giant cells
• Minimal pleomorphism

83. Moderately cellular
fibroblastic appearance

84. Scant cytoplasm and uniform
spindled nuclei, note the thin bands
of intercellular collagen
Storiform growth

87. Typically circumscribed
neoplasms
(A) bland ovoid or spindled
fibroblastic cells in
“patternless” distributions
within variably collagenous
stroma (A-F) that frequently
shows areas of dense
hyalinization (C) as well as
interspersed large branching
or “staghorn”-shaped
thin-walled
hemangiopericytic vessels(D
Note the marked intertumoral
variation in cellularity, with
hypercellular stroma-poor
areas that alternate with more
sparsely cellular collagenous
areas (E). The cells are
typically uniform with
basophilic nuclei that are
hyperchromatic or vesicular
and scanty amphophilic
cytoplasm with indistinct cell
borders (E, F).

92. POSITIVE STAINS
•CD34 (90 - 95%),
•CD99 (70%),
•1/3 positive for bcl2, EMA and actin

93. DIFFERENTIAL DIAGNOSIS
•Benign neural tumors: S100+
•Smooth muscle tumors: fascicles of cells with more abundant
eosinophilic cytoplasm, blunted nuclei, desmin+, actin+
•Synovial sarcoma (monophasic): Ovoid cels, no thick collagen
bands; keratin+, t(X;18)

94. FIBROSARCOMA
“A malignant spindle cell tumor composed of Fibroblasts
arranged in a herringbone/ interlacing fascicular pattern, with
varying amounts of collagen in the background with no
expression of other connective tissue markers”

95. •Fibrosarcoma accounts for approximately 15% of all soft tissue sarcomas, of
which only 1% occur in the head and neck region.
•Men commonly affected
•4th decade
•Usually lower extremities (femur and tibia)
Also reported to arise from pre- existing lesions: fibrous dysplasia, chronic
osteomyelitis, bone infarct, Paget's disease & previously irradiated areas.
•Large painless mass, often of shorter duration, ulceration can be seen
•Soft tissue and bone lesion

96. CLINICAL FEATURES
• An infantile/congenital form (in children < 10 years) of
fibrosarcoma exists, defined in the World Health Organization
classification
• However, most are discovered at birth or within first year of
life.
• Unlike fibrosarcoma in adults, it has an excellent prognosis,
even in the face of metastatic disease at presentation, when
treated with a combination of neoadjuvant and adjuvant
chemotherapy and resection.
96

98. • DEMOGRAPHICS:
• Age: 30 – 50 yrs (wide age range), younger
• Sex: no sex predilection
• Site: Buccal mucosa, tongue – 1/4th of the oral lesions

100. GROSS FINDINGS
Typically, the lesions are solitary, multilobulated, fleshy masses 5–10 cm in
diameter when first detected.
About two-thirds of these tumors are located in skeletal muscle, <10% are
confined to the subcutis.
A multinodular white mass with areas of
hemorrhage and necrosis.

101. HISTOPATHOLOGY
Highly cellular fibroblastic proliferation in herringbone pattern (cells in columns
of short parallel lines with all the lines in one column sloping one way and lines in
adjacent columns sloping the other way).
fusiform or spindle-shaped cells that vary little in size and shape, have scanty
cytoplasm with indistinct cell borders, tapering elongated dark nuclei with
increased granular chromatin, variable nucleoli and are separated by interwoven
collagen fibers arranged in a parallel fashion.
Mitotic figures are frequent.
Collagen may be sparse.
Patterns:
Keloid-like (thick hyalinized collagen fibers), loose fascicular, focally
myxoid

102. HISTOLOGICAL GRADING OF FIBROSARCOMA
Based on
• Cellularity
• Differentiation
• Mitotic activity
• Necrosis

103. Histologic grading of fibrosarcomas is based on the cellularity and
differentiation, mitotic activity, and necrosis
Low-grade (well differentiated) fibrosarcomas are characterized by a uniform,
orderly appearance of the spindle cells associated with abundant collagen

104. Atypical uniform cells in herringbone pattern

105. Malignant, with coarse chromatin
but minimal pleomorphism

106. LOW GRADE
Minimal pleomorphism and low mitotic
index, but is more cellular than
fibromatosis
INTERMEDIATE GRADE:
intermediate features

107. HIGH GRADE:
high grade atypia and high mitotic index

108. HIGH GRADE FIBROSARCOMA
Closely packed and less well oriented cells
Round tumor cells with high grade nuclear
features

109. Herring bone pattern
Bipolar spindle cells
scanty cytoplasm

110. Low grade fibrosarcoma resembling
fibromatosis
Variation in shape and size
Mitotic activity moderate
Mild pleomorphism

113. H&E
Vimentin+

114. POSITIVE STAINS
•Reticulin stain demonstrates fibers surrounding each cell
•Phosphotungstic acid-hematoxylin demonstrates abundant
cytoplasmic fibrils
•Also vimentin, type 1 collagen, p53
•High Ki67
•May be CD34+ if arises from DFSP or solitary fibrous tumor

115. Immunohistochemistry/Cytogenetics and
Molecular Genetics
• Vimentin- positive
• Weak positive for smooth muscle actin- due to focal
myofibroblastic differentiation
• Little is know about molecular or cytogenetic alterations in
adult fibrosarcoma, but multiple complex chromosomal
rearrangement as be reported in infantile fibrosarcoma
(chromosomal change involving- t(2;19).

116. Marked vimentin positivity

118. Differential diagnosis
• Nodular fasciitis
• Cellular benign fibrous histiocytoma
• Fibromatoses
• Malignant peripheral nerve sheath tumor
• Malignant fibrous histiocytoma
• Monophasic fibrous synovial sarcoma

119. TREATMENT
Wide local excision
Radical neck dissection

120. HISTOLOGICAL VARIANTS OF
FIBROSARCOMA
Adult type fibrosarcoma
• Myxofibrosarcoma
• Sclerosing epitheliod type
• Hyalinising spindle cell type
Infantile fibrosarcoma
120

121. MYXOID TYPE OF FIBROSARCOMA
Spindle or stellate shaped cells deposited in a myxoid matrix composed of
predominantly of hyaluronic acid.
The cells have slightly eosinophilic cytoplasm and indistinct cell borders; the nuclei
are hyperchromatic, are mildly pleomorphic, and have only rare mitotic figures.
DD
1: Nodular fasciitis
2: Myxoma
3: Nerve sheath Myxoma
4: Spindle cell lipoma
5. Myxoid liposarcoma
6. Extraskeletal myxoid chondrosarcoma

123. FIBROMYXOID TYPE OF FIBROSARCOMA
•Composed of bland spindle-shaped cells with small hyperchromatic oval nuclei,
finely clumped chromatin, and one to several small nucleoli.
•The cells have indistinct pale eosinophilic cytoplasm and show only mild nuclear
pleomorphism with little mitotic activity.
•The cells are deposited in a fibrous and myxoid stroma that tends to vary in
different areas of the tumor

124. SCLEROSING EPITHELIOID TYPE OF
FIBROSARCOMA
The neoplastic cells are predominantly epithelioid in appearance and are arranged in
a variety of patterns, including nests, cords, strands, and occasionally acini or alveoli.
The cells have oval to round angulated nuclei with finely stippled or vesicular
chromatin, small basophilic nucleoli, and scanty cleared-out or faintly eosinophilic
cytoplasm

125. TREATMENT:
 Radical excision, radiation if residual tumor or positive margins
 Possibly chemotherapy, if high grade

126. FIBROHISTOCYTIC
TUMORS

127. BENIGN FIBROUS HISTIOCYTOMA
• Neoplastic lesion composed of mixture of fibroblastic and
histiocytic cells accompanied by varying number of
inflammatory cells, foam cells, MNG’s
• Cell of origin : Histiocyte.
127
Dermatofibroma
Sclerosing Hemangioma
Fibroxanthoma
Nodular sub-epidermal fibrosis

128. • Solitary - slow growing - firm nodule
• Typically seen in middle aged and older adults (5th decade).
• Common site: skin of the extremities : DERMATOFIBROMA
• Oral cavity: rare, if present: Buccal mucosa & vestibule.

129. HISTOPATHOLOGY
Fairly well-demarcated & often circumscribed at the periphery.
Cellular proliferation of spindle shaped fibroblast cells with plump, vesicular
nuclei in storiform pattern (cart wheel or matlike ) with rounded histiocytic-like cells
Lipid containing xanthoma cells & Tuoton multinucleated giant cells with
nuclei pushed to periphery.
A background of variably dense collagenous tissue & vascularity is seen.
Mixed inflammatory cells present

130. H&E
4x
10x
40x
10x
130

132. IMMUNOHISTOCHEMISTRY
POSITIVE
▸Vimentin
▸CD 68
▸SMA / CD 34: diffuse
Vimentin

133. VARIANTS of fibrous histiocytoma
• Cellular fibrous histiocytoma
• Epitheloid fibrous histiocytoma
• Aneursymal fibrous histiocytoma
• Atypical fibrous histiocytoma
133

134. DIFFERENTIAL DIAGNOSIS
• Nodular fasciitis
• Neurofibroma
• Leiomyoma
TREATMENT
Wide surgical excision
High rate of recurrence.
134

135. MALIGNANT FIBROUS
HISTIOCYTOMA/ PLEOMORPHIC
SARCOMA
• Malignant fibrous histiocytoma is a malignant neoplasm of
fibroblasts with a propensity to differentiate into histiocytic and
fibrohistiocytic cells.
• First described in 1964, by O'brien and Stout under the name
malignant fibrous xanthoma
• Histopathological features were first described by Kempson and
Kyriakos.
135

136. Clinical features
• Any age (50-70yrs)
• Firm submucosal mass expanding slowly or moderately fast
• Asymptomatic and may show ulceration
• Irregular nodular lesion measures less than 4cm
136

137. •Depending on the dominant morphology, it is currently
subclassified as:
•Pleomorphic storiform,
•Myxoid,
• Angiomatoid (aneurysmal),
•Inflammatory and
•Giant cell malignant fibrous histiocytoma
•Small group of undifferentiated sarcomas lacking differentiation
markers of other sarcomas; DIAGNOSIS OF EXCLUSION.

138. HISTOPATHOLOGY
•Basic to all MFH - proliferation of pleomorphic spindle shaped cells showing
fibroblastic morphology.
•Abnormal & frequent mitotic figures, necrosis & extensive cellular atypia.
•Storiform-pleomorphic type, with a predominantly storiform pattern

139. 139

140. The myxoid type is characterized by
myxoid areas in association with cellular
areas indistinguishable from ordinary MFH.

141. The giant cell type of MFH , also termed malignant giant cell tumor of soft parts is a
multinodular tumor composed of a mixture of spindled, rounded, and osteoclast-type
giant cells

142. CD68 stain of an inflammatory MFH with
staining of benign xanthoma cells
Inflammatory type of MFH - benign- and
malignant-appearing xanthoma cells, the
latter often assuming a gigantic size with
bizarre nuclei. Typically, these neoplastic cells
display phagocytosis of neutrophils. The
inflammatory component is characteristically
prominent and usually consists of a mixture
of acute and chronic inflammatory cells
with marked prominence on the former.

143. Immunohistochemistry/cytogenetic and molecular
genetic of UNDIFFERENTIATED PLEOMORPHIC
SARCOMA
• Immunohistochemistry is of little value in the diagnosis of
malignant fibrous histiocytoma because no specific marker for
these lesions exists.
• Factor XIII a or α-1- antichymotrypsin antibodies, CD68 are
positive
• Loss of 4q31 and 18q22 were found but are independent
predictors of metastasis.
143

144. TREATMENT:
• Radical surgical resection.
• 40% recur locally/ metastasize.

145. 145

146. MYOFIBROBLASTIC

147. MYOFIBROBLASTIC ORIGIN
Myofibroma
Inflammatory myofibroblastic tumor
Myofibrosarcoma

148. MYOFIBROMA & MYOFIBROMATOSIS
• The most common site of myofibroma is in the head and neck
region followed by the trunk, extremities and viscera
• Infantile myofibromatosis (multicentric myofibromatois) occurs
in infants and neonates.

149. CLINICAL FEATURES
• Age: 1st to 4th decade (Infants – Myofibromatosis)
• Sex: Common in males M-F ratio - 1.5:1
• Site: Most common Mandible >Tongue > BM >
palate > gingiva > mandibular vestibule > retromolar area
Marilena Vered et al, Clinico-pathologic correlations of myofibroblastic tumors of the
oral cavity. II. Myofibroma and myofibromatosis of the oral soft tissues; J Oral
Pathol Med (2007) 36: 304–14

150. Rare neoplasms with predilection for H& N region.
Occurs as an exophytic mass
Presents as painless mass that show rapid enlargement.
Radiographs:
radiolucent defects that are poorly defined, sometimes well defined & multilocular.

151. HISTOPATHOLOGY
Interlacing bundles of spindle cells with tapered or blunt ended nuclei and
eosinophilic cytoplasm.
Nodular fascicles may alternate with more cellular zones- giving a biphasic
appearance.
Centrally, the lesion is more vascular with hemangiopericytoma like appearance.
imparting a biphasic appearance to the tumor.
Has monomorphic and biphasic spindle cells

152. Hemangiopericytoma like areas
Interlacing bundles of spindle cells
blunt-ended nuclei & eosinophilic
cytoplasm

153. Scattered mitoses
Cells are positive for SMA

154. 154

155. IMMUNOHISTOCHEMISTRY
Positive for SMA, MSA
Negativity for DESMIN which rules out Leiomyoma & Leiomyosarcoma
SMA POSITIVE

156. MARKERS:
• Positive for vimentin and actin

157. DIFFERENTIAL DIAGNOSIS
• Nodular fasciitis
• Neurofibroma
• Fibrous histiocytoma
• Hemangiopericytoma
• Leiomyoma
• Leiomyosarcoma
157
Marilena Vered et al, Clinico-pathologic correlations of myofibroblastic tumors of the oral cavity.
II. Myofibroma and myofibromatosis of the oral soft tissues; J Oral Pathol Med (2007) 36: 304–
14

158. TREATMENT:
• Solitary tumors – surgical excision
• Recurrent tumors – re-excision.
• In some cases – spontaneous regression.
• Those involving the viscera or vital organs in infants – more aggressive &
may prove to be fatal.

159. INFLAMMATORY MYOFIBROBLASTIC
TUMOR (IMT)
• IMT is a rare neoplasm consisting of variable numbers of
inflammatory cells and myofibroblastic spindle cells
• It was first observed in the lung and described by Brunn in 1939
• Was so named by Umiker et al. in 1954 because of its clinical and
radiological behavior that mimics a malignant process.
• Liston et al. in 1981 was the first to report IMTs of oral cavity in
three children.
159

160. Described by various names
• Inflammatory pseudotumor (IPT),
• Plasma cell granuloma,
• Benign myofibroblastoma,
• Inflammatory fibrosarcoma,
• Histiocytoma,
• Xanthomatous granuloma, and
• Spindle cell pseudotumor, describing its heterogeneous nature
160

161. CLINICAL FEATURES
• Age: 2 to 82 years, with a mean of 35 years.
• Sex: Female
• Site: The buccal mucosa > retromolar area region > premolar
region > pterygoid and masseteric muscle > lingual alveolar
mucosa of the edentulous molar region > tongue> maxilla >
hard palate.
• In some cases localized to an extraction site.

162. • Size ranged from 0.5 to 5cm, rapid growth rate is an
alarming feature of oral IMT reportedly as short as 1 day, with
a majority of lesions of 2 months duration or less
• Well circumscribed, solitary nodule or mass, 40% of the tumor
were designated as firm or indurated and notably demonstrated
ulceration, characterized with varying degrees of erythema.
• Pain was reported with concurrent clinical ulceration. Some
patients experienced trismus

163. Most lesions are lobular, multinodular or bosselated.
Hard or rubbery cut surface, appears white, grey or tan-yellow.
Sometimes gritty sensation due to presence of calcification
GROSS APPEARANCE
163

164. HISTOPATHOLOGY
• Three main patterns
– Monomorphic spindle cells arranged in fascicles
– Myxoid, nodular fasciitis like areas
– Hypocellular hyalinized areas
• A variable infiltrate of inflammatory cells associated with the
tumor cells
164

165. Histopathology
H&E

166. Spindle shaped cells with fasciculated architecture
Hypocellular fibrous areas with numerous plasma cells
Concurrent fascitis-like foci

168. IMMUNOHISTOCHEMISTRY
SMA
MSA POSITIVE
DESMIN
ANAPLASTIC LYMPHOMA KINASE-1 (ALK-1)

169. Cytogenetics and molecular genetics of
myofibroblastic tumor
• Clonal rearrangement of ALK gene at 2q23.
• ALK gene codes for tyrosine kinase receptor that is a member
of insulin growth factor receptor superfamily.
• ALK rearrangement – constitutive expression and activation of
this gene with abnormal phosphorylation of cellular substrata
169

170. Differential diagnosis
• Inflammatory Leiomyosarcoma
• Inflamamtory fibrosarcoma
• Malignant fibrous histiocytoma
170

171. LOW GRADE MYOFIBROSARCOMA
• Malignant tumor of myofibroblast
• Indolent neoplasm that can recur and metastasize after long
period of time
171

172. CLINICAL FEATURES
 Usually affects adults and is uncommon in children.
 Intra oral tumors- usually slows growing & asymptomatic.
 Oral cavity-the tonsil, mandible, maxilla
Age: Affects young to middle aged adults.
Sex: No sex predilection
Site: 20-25% of cases arise in the head and neck region (especially the oral
cavity and tongue).
Painless growth, large mass.

173. A population of spindle-shaped cells showing vesicular nuclei with
fine stippled chromatin and a small nucleolus. The cytoplasm was pale
and eosinophilic with indistinct margins.
The cells will be arranged in variably orientated short fascicles or
vaguely storiform whorls , between individual skeletal muscle fibers.
A mild degree of nuclear pleomorphism, anisonucleosis, and
hyperchromatism will be seen.

174. A moderate amount of collagen was present in several foci, but
a myxoid or hyalinized stroma can also be seen.
Occasional lymphocytes, plasma cells, and mast cells.
The lack of significant atypia confuses with benign diagnosis
such as nodular fascitis, proliferative myositis, and Fibromatosis.

175. Histopathology of low grade myofibrosarcoma

176. Immunohistochemistry/Cytogenetics and Molecular
genetics of low grade myofibrosarcoma
SMA- POSITIVE
Calponin- Diffusely Positive
Desmin – Focal Positive
h-caldesmon- Negative
ALK – Negative (eliminates IMFT and leiomyosarcoma)
Comparative genomic hybridization shows gains of 1p11, 12p12.2 and 5p13.2.
176

177. DIFFERENTIAL DIAGNOSIS
• Nodular fasciitis
• Leiomyosarcoma
• Fibrosarcoma
• IMFT
177

178. ADIPOCYTIC ORIGIN

179. Spindle cell Lipoma
Spindle cell Liposarcoma

180. Lipomatous Tumors
• BENIGN TUMORS
– Spindle cell lipoma/
Pleomorphic
– Vascular (angiolipoma)
– Lipoblastoma
– Hibernoma
– Chondroid type
– Myolipoma
– Myelolipoma
– Angiomyolipoma
• MALIGNANT TUMORS
Liposarcoma

181. SPINDLE CELL/PLEOMORPHIC
LIPOMA
• Enzinger and Harvey in 1975
• Both the lesions were grouped under “atypical lipomas”
• Definition: A spectrum of benign lesion composed of an admixture
of mature adipocytes, spindle cells, and hyperchromatic
multinucleated giant cells.

182. DEMOGRAPHICS:
• Site: Tongue, cheek/buccal mucosa, floor of mouth, lip, hard
palate, alveolar ridge, maxilla
• Age: mean age of 55 yrs
• Sex: males
• Subcutaneous tissue of the posterior neck, shoulder, and back; oral
cavity- rare.
• Slow growing, typically solitary, circumscribed or encapsulated,
painless, firm nodule, usually centered in the subcutaneous tissue

183. • CLINICAL
FEATURES:
– Slow growing
– Solitary
– Circumscribed
– Painless
– Firm nodule

184. GROSS APPEARANCE
• Resembles usual type of lipoma, except for grey white
gelatinous foci, representing increased cellularity, some tumor
show myxoid areas, other show predominantly lipomatous
184

185. HISTOPATHOLOGY
Vary widely in its appearance.
Some tumors are predominantly composed of mature adipose tissue with only
scattered spindle cell or pleomorphic elements.
Other tumors are predominantly solid and lack any significant lipomatous
component
The classic spindle cell lipoma consists of a relative equal mixture of mature fat
and spindle cells.
The spindle cells are uniform with a single elongated nucleus and narrow, bipolar
cytoplasmic processes .
The cells may be haphazardly distributed but tend to be arranged in short, parallel
bundles.

186. HISTOPATHOLOGY
186

188. Cellular area
Ropy collagen
Well circumscription
Mature adipocytes

189. Myxoid change
Hyperchromatic multinucleated giant
cells
Bland spindle cells with elongated
nucleus

190. Immunohistochemistry/ cytogenetics and
molecular genetics of spindle cell lipoma
• Positive: strongly CD34 stains the nuclei of mature lipocytes.
• 55% to 75% of them show chromosomal aberrations.
• Harbor aberrations of 12q13-15.
• Gene HMGC located on 12q13-15 is affected
190

191. CD 34 positivity

192. DIFFERENTIAL DIAGNOSIS
• Nodular fascitis
• Neurofibroma
• Solitary fibrous tumor
• Hemangiopericytoma
• Myxoid liposarcoma
• Spindle cell liposarcoma
TREATMENT
• Completely benign lesion
• Exceptionally recur
• Dedifferentiation and metastasis - no

193. SPINDLE CELL LIPOSARCOMA
• Liposarcoma is a malignancy of fat cells
• Definition: Proliferation of mature adipocytes exhibiting marked variation
in cell size with at least focal nuclear atypia
• Variants - Enzinger and Weiss - developmental stage of the lipoblasts,
cellularity, pleomorphism
• – Well-differentiated
• – Myxoid
• – Round-cell
• – Pleomorphic
• – Spindle cell & Dedifferentiated 193

194. Age: 6th to 7th decade peak, men and women equally affected
Symptoms depends on anatomic location. Slow growing mass- presents for months
to even several years
Unusual variant of liposarcoma- consisting of loosely arranged fibroblast like spindle
cells

195. GROSS APPEARANCE
• Resembles normal fat, except for fibrous bands.
195

196. A very rare and unusual form of liposarcoma consisting almost entirely of
loosely arranged fibroblast-like spindle cells oriented along a single plane and
surrounded by a delicate reticulin meshwork.
At low power, the lesion bears a superficial similarity to spindle cell lipoma,
although it is far more cellular.

197. HISTOPATHOLOGY
In mature cells the vacuole
coalesce to form single vacuole
that sits on the slender nuclei
like a scoop of ice cream on a
cone.
197

198. Scattered lipoblasts
In various shapes and sizes
Prominent spindle cells
Resembling SCL

199. Nuclear Atypia
Variable spindle cells devoid of
lipoblasts

202. IMMUNOHISTOCHEMISTRY
• Express S-100 protein that may play a role in highlighting the
presence of lipoblasts.
• Expression of MDM2 and CDk4 play a diagnostic role.
202

203. DIFFERENTIAL DIAGNOSIS
• Fibrosarcoma
• Pleomorphic liposarcoma
203

204. • Treatment
• Wide surgical excision is the treatment of choice
• Radiation therapy remains controversial

211. SUMMARY
Spindle cell lesions of head & neck are diverse & diagnostically
challenging
High index of suspicion of spindle cell carcinoma for any
malignant tumor with spindle cells
Clinical correlation is valuable.
Pathologists should take particular care before rendering final
diagnosis.
Rule of thumb –in adults malignant spindle cell are more likely
to represent ca or melanoma than a true sa

212. REFERENCE:
 Enzinger and weiss; Soft tissue tumors. fifth edition
 Brad . W . Neville, Douglas D . Damm , Carl M . Allen. Oral and
maxillofacial pathology. 2nd edition 2004
 SHAFER, Text book of oral pathology. 6th edition 2006
 Regezi, Sciubba, Jordon. Oral Pathology.
 Douglas .R. Gnepp; Diagnostic surgical pathology of head and neck;
2nd edition
 Cawson’s essentials of Oral pathology. 7th edition.
 Contemporary oral & maxillofacial pathology. 2nd edition. J Philip
Sapp, Eversole.
 Textbook of oral pathology. Sanjay Saraf.