Introduction, various types of Classification of spindle cell tumors

1. Good morning

2. Seminar on
Spindle cell tumors of the oral cavity
Part - I
By: Dr. Madhusudhanreddy
III year PG
VDC

3. Contents
• Introduction
• Causes for development of spindle cell tumors
• Various classifications proposed for spindle cell lesions
• Clinical and histological features of individual tumor
• Approach for diagnosis of spindle cell tumors

4. Introduction
• These lesions are highly variable both biologically and
clinically
• Clinical, histological, and immunohistochemical some
times electron microscopy
• Predominant cells – spindle cells / altered spindle cells
• Ranging from simple reactive to malignant lesions
• Uncommon - oral cavity,
• Common in other sites of the body.
– Head and neck
– Soft tissues of scalp
– Orbit
– Upper aerodigestive tract (UADT)
• Account for - 1% of all tumors in the oral regions.

5. Causes
• Spindle cells arise among actively dividing connective
tissue/epithelial cells
• Causes
– Genetic predisposition
– Chromosomal mutations
– Cellular genetic defects in Oncogene, tumor suppressor
genes
• Example NF1 in neurofibromatosis
– Exposure to radiation or certain chemicals,
– Trauma, and inflammation,
• All of which may stimulate the tissues to divide more
rapidly than normal.

6. Classification
• Classification – based on the tissue of origin into –
I. Tumors of fibrous origin
II. Tumors of Fibro histiocytic origin
III.Tumors of adipose tissue origin
IV.Tumors of Smooth muscle origin
V. Tumors of Skeletal muscle origin
VI.Tumors of Nerve tissue origin
VII.Tumors of Vascular origin
VIII.Tumors of Bone
IX. Tumors of epithelial origin

7. Benign Malignant
Fibroma Fibrosarcoma
Fibromatosis
Myofibroma
Benign Malignant
Fibrous
histiocytoma
Malignant fibrous
histiocytoma
Benign Malignant
Lipoma (spindle
cell and
pleomorphic
lipoma)
Dedifferentiated
liposarcoma
1. Fibroblastic tumors
2. Fibrohistiocytic tumors
3. Lipomatous tumors
Benign Malignant
Cellular
rhabdomyoma
Spindle cell
rhabdomyosarcoma
Benign Malignant
Leiomyoma
(angiomyoma)
Leiomyosarcoma
Benign Malignant
Spindle cell
hemangioendothelioma
Angiosarcoma
Kaposi
sarcoma
4. Smooth muscle tumors
5. Skeletal muscle tumors
6. Vascular tumors
Benign Malignant
Traumatic
neuroma
Neurofibrosarcoma
Neurofibroma
Schwannoma
Malignant
Fibroblastic osteosarcoma
Malignant
Synovial sarcoma
7. Neural tumors
8. Bone tumors
9. Synovial tumor
10. Epithelial tumors
Benign Malignant
Nevus
(intramucosal,
spitz nevus)
Melanoma
Spindle cell
carcinoma

8. • Histological patterns:
• Monomorphic - Uniform spindle cells
– Fascicles
– Storiform pattern or a ‘herringbone’ pattern
– Sometimes associated with a dense collagenous stroma.
• Pleomorphic - Spindle cells - variation in size and shape,
often with marked nuclear pleomorphism and tumour
giant cells.

9. • Biphasic - 2 distinct components
– Spindle cell areas
– Epithelioid areas
• Epithelioid areas may be sparse
• Myxoid - Spindle cell component may be conspicuous or
less easily identified, but it is set in a loose, myxoid stroma.
• Prominent inflammatory infiltrate.
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

10. Monomorphic spindle cell
lesion
Pleomorphic
spindle cell
lesion
Biphasic spindle
cell lesion
Myxoid pattern
MPNST MPNST MPNST
Leiomyosarcoma Leiomyosarcoma Leiomyosarcom
Synovial sarcoma Synovial sarcoma Synovial sarcoma
Solitary fibrous tumour Carcinosarcoma Schwannoma
Cellular schwannoma Myxoma
Vascular leiomyoma Inflammatory
myoblastic tumour
Nasopharyngeal angiofibroma Nodular fasciitis
Desmoid –type fibromatosis Myofibrosarcoma
Myofibroma/ Myofibromatosis
Myofibrosarcoma
Myoepithelioma
Odontogenic fibroma
• Sarcomatoid squamous carcinoma, Melanoma occurs in all the 4
patterns.

11. • Neural tumor
– Neurofibroma
– Schwannoma
– Traumatic neuroma
– Ancient Schwannoma
– Palisaded encapsulated neuroma
– Malignant peripheral nerve sheath
tumor
• Myofibroblastic tumors
– Myofibroma
– Inflammatory myofibroblastic
tumor
– Low-grade myofibroblastic
sarcoma
• Smooth muscle tumors
– Angiomyoma/vascular leiomyoma
• Fibroblastic tumors
– Solitary fibrous tumor
– Nodular fasciitis
– Fibromatosis
– Desmoplastic fibroma
– Fibrosarcoma
• Vascular tumors
– Vascular malformation
– Kaposi’s sarcoma
• Carcinomas
– Spindle cell SCC
• Other
– 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.

12. • Neural tumors
– Neurofibroma
– Neurilemmoma
– Palisaded encapsulated neuroma
– Traumatic neuroma
– Malignant peripheral nerve sheath
tumors
• Myofibroblastic tumors
– Myofibroma
– Inflammatory myofibroblastic
tumor
– Low grade myofibrosarcoma
• Muscle tumors
– Leiomyoma
– Vascular leiomyoma
– Leiomyosarcoma
– Rabdomyoma
– Rabdomyosarcoma
• Fibroblastic tumors
– Solitary fibrous tumor
– Fibromatosis
– Nodular fascitis
– Desmoplastic fibroma
– Fibrosarcoma
• Vascular tumors
– Spindle cell hemangioma
– Hemangiopericytoma
– Kaposi sarcoma
• Epithelial tumors
– Pleomorphic adenoma
– Spindle cell carcinoma
– Malignant melanoma
Thorakkal Shamim: A simple working type classification proposed for spindle cell neoplasma of oral cavity; journal
of cytology, 2013; vol- 30; issue- 1; 85

13. • Odontogenic tumors
– Ameloblastic fibroma
– Ameloblastic fibrosarcoma
– Central odontogenic fibroma
– Desmoplastic ameloblastoma
• Miscellaneous tumors
– Benign fibrous histiocytoma
– Malignant fibrous
histiocytoma
– Synovial sarcoma
– Ossifying fibromyxoid tumor
– Giant cell angiofibroma
– Blue nevus
Thorakkal Shamim: A simple working type classification proposed for spindle cell neoplasma of oral cavity; journal
of cytology, 2013; vol- 30; issue- 1; 85

14. Fibroblastic tumors
• Benign
• Fibroma
• Fibromatosis
• Myofibroma
• Malignant
• Fibrosarcoma

15. Fibroma

16. • Synonyms: Irritation fibroma; Traumatic fibroma; Focal
fibrous hyperplasia; Fibrous nodule
• Reactive fibrosis and scarring - bite trauma
• True neoplasm ?
• Common benign soft tissue neoplasm of the oral cavity.
• Reactive hyperplasia of the fibrous connective tissue, in
response to local irritation or trauma.

17. • Demographics:
• Age: Most common in the 4th to 6th decades of life.
• Sex: No sex predilection
• Site: Any oral site
• Common along the plane of occlusion, on the buccal
mucosa.
• Other sites – Labial mucosa, tongue & the palate.

18. Elevated smooth-
surfaced pink nodule
HyperkeratosisMillimeters to a few
centimeters
Asymptomatic
Clinical features

19. • Histopathology:
Pedunculated fibroma
Atrophy of the epithelium, PSSE
CT gradually blends
Collagen bundles – streaming pattern

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

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

22. • Differential diagnosis:
– Giant cell fibroma
– Solitary Neurofibroma (encapsulation)
– Palisaded encapsulated neuroma (encapsulation)
– Fibroepithelial polyp
– Epulis fissuratum
– Peripheral reactive lesions
– Peripheral odontogenic lesions
– Mucocele
• Treatment:
• Conservative surgical excision
• Recurrence is rare

23. Giant cell fibroma
• Not associated with any chronic irritation.
• It represents approximately 2% to 5% of all oral fibrous
• In 1974 Weathers and Callihan identified
• Demographics:
• Age: 10 – 30 years
• Sex: No gender predilection
• Site: Most commonly it occurs on the mandibular gingiva,
followed by tongue, and palate.

24. • Clinical features:
• It appears as an asymptomatic, sessile, or a pedunculated
nodule, usually less than 1 cm in size, with a bossilated or a
papillary surface.

25. • Histopathology:
Lobulated growth, hyperparakeratinized
SSE
Thin elongated rete ridges
Avascular CT

26. Stellate fibroblasts within the
superficial connective tissue
Mono or multinucleated Fibroblasts

27. • Differential diagnosis:
• Papilloma
• Retrocuspid papilla (Site specific)
• Irritational fibroma
• Treatment:
• Conservative surgical excision
• Recurrence is rare

28. fibromatosis

29. • Definition: Benign, recurring but nonmetastasizing, infiltrative,
fibroblastic proliferations arising in any part of the oral cavity.
• Fibromatosis
– Fibromatosis gingivae
– Juvinile fibromatosis
– Aggressive fibromatosis

30. Fibromatosis gingivae
• Synonyms: Elephantiasis gingivae; Hereditary gingival
fibromatosis; Congenital macrogingivae
• A diffuse fibrous over growth of gingival tissues.
• A slowly progressive - over growth of the gingival fibrous
connective tissue.
• Occur during shedding of deciduous teeth and early
eruption of permanent teeth

31. • Demographics:
• Age: Occurs before 20 yr of age
• Sex: No sex predilection
• Site: Maxillary gingiva is frequently effected
• Generalized or localized
• Delayed eruption

32. • Clinical features:
• May be familial or idiopathic.
• Hereditary condition – dominant autosomal gene.
• Sometimes Sporadic - with no familial background.
• Diffuse, smooth or nodular overgrowth of the gingival tissues
• Facial and lingual aspects of the attached and marginal gingiva
• Single quadrant or all quardents
• Painless, slowly progressive

33. • Other findings seen in conjunction with gingival
fibromatosis are
- Hyper trichosis
- Epilepsy
- Mental retardation
- Sensori neural deafness
- Hypo thyroidism
- Chondro dystrophia
- Growth hormone deficiency

34. • Can be associated with one of the several hereditary
syndromes like –
- Zimmermann-laband syndrome
- Murray-Puretic-Drescher syndrome
- Ruthefurd syndrome
- Multiple hamartoma syndrome (Cowden)
- Cross syndrome

35. • Dense hypocellular, hypovascular collagenous tissue
• Irregularly arranged interlacing bundles
• Epithelium – thing long rete ridges extending deep into CT
• Dystrophic calcification – some times seen.
• Electron microscopy demonstrates a mixture of both
fibroblasts and myofibroblast-like cells.
• Histopathology:

36. • Differential diagnosis:
• Plasma cell gingivitis
• Systemic granulomatosis causing gingival hyperplasias
• Amyloidosis
• Treatment:
• Conservative treatment – gingivectomy
• Recurrence is very often

37. Juvenile fibromatosis
• Fibromatoses – a broad group of fibrous proliferations
• Biologic behavior & histologic pattern – Intermediate
between those of benign fibrous lesions and fibrosarcoma.
• Head and neck - these lesions are called as – Juvenile
aggressive fibromatoses or extra abdominal desmoids.
• Lesions within the bone are called as – Desmoplastic
fibromas.

38. Clinical Features:
A firm, painless mass - rapid or
insidious growth.
occurs in children or in young adults
Most common in paramandibular soft
tissue can occur at other sites also.
Facial disfigurement
Destruction of the adjacent bone

39. Poorly circumscribed &
infiltrates the adjacent tissues
Streaming fascicles of spindled cells
highly cellular with
variable amount of collagen
Hyperchromatic and pleomorphic
nuclei are seldom seen
Histopathology:

40. Reactive to smooth muscle actin (SMA), Vimentin and
nonreactive for Desmin, S-100, cytokeratin

41. • Differential diagnosis:
• Dysplastic mesenchymal cells
– Fibrosarcoma
– Malignant fibrous histiocytoma (MFH)
– Fibroblastic osteosarcoma (if attached to bone)
• Treatment:
• A locally aggressive tumor.
• Wide excision, including a generous margin of the adjacent
normal tissues.
• Recurrence rate of for oral and paraoral fibromatses – 23%.
• No metastases.

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

43. Aggressive fibromatosis
• A non-metastasizing tumor-like fibroblastic growth
• Unknown pathogenesis
• It involves the voluntary muscles as well as aponeurotic &
fascial structures.
• The lesion has a strong tendency to local recurrence &
shows an aggressive infiltrating growth.

44. Clinical features:
• Commonly occurs in the shoulder girdle, thigh & buttock
of young adults.
• In oral cavity anterior maxilla - most common site
• Rapidly enlarging or Slow growth.
• Pain may or may not be present.
• When it is present near the bone, bone destruction occurs.

45. Cellular interlacing bundles
Elongated fibroblasts
• Histopathology:

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

47. Markers:
• Actin, desmin, & S-100 are negative – some cases may show
patchy expression.
Beta catanin

48. • Differential diagnosis:
• Reactive fibroblastic proliferation/ myofibroblastic
proliferation
• Desmoplastic fibroma
• Fibrosarcoma transformation of fibromatosis

49. • Treatment:
• Complete surgical excision, with generous margins of
normal tissue.
• Frequent recurrence
• Prolonged follow-up

50. Good morning

51. Myofibroblastictumors
• Myofibroma
• Nodular fascitis

52. • Main cell which are involved in tumor formation is – myofibroblasts
• Discovered in 1971
• Distinct biochemically, pharmacologicaly and immunohistochemically
• Features are typically of smooth muscle
• Myofibroblast is seen ultrastructurally
• Under light microscopy
– Large spindle cell
– Stellate with several cytoplasmic extensions
– Acidophillic or amphopillic and fibrillar cytoplasm
– Nucleus finely granular with conspicuous nucleoli

53. • Occurs both physiologically and pathologically
• Physiologically
– Developing human palatal mucosa
– Intestinal mucosa
– PDL of mouse and rat – tooth eruption
– Lymphnodes, spleen, bone marrow
– Pericytes
– Wound healing
• Pathologically
– Helps in tumor progression

54. Origin

55. pathogenesis

56. Myofibroma

57. • Also called as myofibromatosis
• A rare spindle cell neoplasm that consists of myofibroblasts
• It was originally described as a multicentric tumor process
affecting infants & young children
• The tumor occurs as a solitary mass & at any age.

58. Clinical features
• Demographics:
• Age: Newborns to old age
• Sex: Common in males M-F ratio - 1.5:1
• Site: Most common Tongue > buccal mucosa > palate >
gingiva > mandibular vestibule > retromolar area
• least common in the lip
• Occurs as an exophytic mass
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

59. Clinical features:
• Rare – in head & neck region.
• Usually a painless mass – some times exhibits a rapid
enlargement.
• Intra bony tumors create poorly defined radiolucent
defects.
• Some may be well defined or multilocular.

60. • Clinical differential diagnosis
• Tongue
– Irritation fibroma,
– Granular cell tumor
– Neurofibroma
– Schwannoma
• Buccal mucosa
– Lymphoid hyperplasia
– Lipoma
– Salivary gland tumors
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

61. Histopathology:
• Nodular fascicles may alternate with more cellular zones,
imparting a biphasic appearance to the tumor.
• Unencapsulated but circumscribed
• Has monomorphic and biphasic spindle cells

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

63. Scattered mitoses
Cells are positive for smooth muscle
actin

64. • Histological Differential diagnosis:
• Tongue
– Neurofibroma (S-100)
– Leiomyoma (desmin and h-caldesmon)
• Buccal mucosa
– Nodular fasciitis
– Fibrous histiocytoma (CD68)
– Solitary fibrous tumor (CD34 and CD99)
– Infantile/congenital fibrosarcoma
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

65. • Markers:
• Positive for vimentin and actin
• Negative for Desmin, CD34, h-caldesmon, cytokeratin and
S-100.
• Differential diagnosis:
Fibromatosis Leiomyoma Nodular fascitis Neural tumors Solitary fibrous
tumor
S-100 Patchy
positive
Negative Negative Positive Positive
SMA Negative Positive Positive Negative Negative
CD-34 Negative Negative Negative Negative positive
Desmin Negative Positive Negative Negative Negative
β-
Catanin
Positive Negative Negative Negative Negative

66. 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.

67. Nodular fascitis
• Definition: A pseudosarcomatous, self-limiting, reactive process
composed of fibroblasts and myofibroblasts
• Cause of NF is unknown
• Trauma is believed to be important
• Demographics:
• Age: Fourth and fifth decades of life,
• Sex: Equal gender distribution
• Site: Buccal mucosa, labial mucosa, tongue, Angle of the mandible,
inferior border of the mandible, zygomatic arch, anterior mandible

68. • Clinical features:
• 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: 1.
nodular fasciitis; J Oral Pathol Med (2005) 34: 426–35

69. • Clinical differential diagnosis
• Exophytic lesion, occasionally secondarily ulcerated,
especially when located in the buccal mucosa,
– Traumatic ulcer (chronic),
– Traumatic granuloma
– Salivary gland tumors,
– Various infectious processes (e.g. of bacterial or deep
fungal origin)
– Squamous cell carcinoma
Dan Dayan et al, Clinico-pathologic correlations of myofibroblastic tumors of the oral cavity: 1.
nodular fasciitis; J Oral Pathol Med (2005) 34: 426–35

70. • Clinical differential diagnosis
• Solitary, deep nodule
– Salivary gland tumors
– Solitary fibrous tumor
– Neurofibroma
– Schwannoma
– Intramuscular lipoma,
– Myofibroma
– Fibromatosis
Dan Dayan et al, Clinico-pathologic correlations of myofibroblastic tumors of the oral cavity: 1.
nodular fasciitis; J Oral Pathol Med (2005) 34: 426–35

71. Well delineated, unencapsulated with focal
areas of infiltration into the adjacent
tissues.
Histopathology
Spindle cells in myxoid background

72. • Histological differential diagnosis
– Neurofibroma
– Fibrous histiocytoma
– Fibromatosis
• 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: 1.
nodular fasciitis; J Oral Pathol Med (2005) 34: 426–35

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

74. • Treatment
• Local excision is the treatment of choice

75. FIBROSARCOMA

76. • Defination: a malignant tumor composed of Fibroblasts
arranged in a herringbone pattern, with varying amounts of
collagen in the background

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

78. • Clinical features:
• Large, deep-seated, slow-growing, solitary Mass
• May occur at site of prior injury, burn
• Radiotherapy (postirradiation fibrosarcoma)
• Associated with mobility of adjacent teeth and ulceration of
overlying mucosa.
• Pain and paresthesia - late symptoms indicating nerve
involvement

79. • Clinical differential diagnosis
• Squamous cell carcinoma
• Osteosarcoma

80. • Radiological features:
• If in contact with bone, may be visible periosteal reaction
• Purely osteolytic lesion without calcification
• Poorly defined, irregular margins
• Destruction of the cortical plates without expansion
• Misdiagnosed as an odontogenic abscess or cyst.

81. • Histological grading of fibrosarcoma
– Based on
• Cellularity
• Differentiation
• Mitotic activity
• Necrosis

82. Herring bone pattern
Histopathology:
Bipolar spindle cells scanty
cytoplasm

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

84. High grade fibrosarcoma
Closely packed and less well oriented cells
Round tumor cells with high grade nuclear
features

85. Marked vimentin positivity

86. • Differential diagnosis
• Benign:
– Fibromatosis
– Nodular fascitis
– Cellular BFH (VIIIa, CD68)

87. Lesion Cytokeratin S-100 CD 34 SMA
Fibrosarcoma Negative Negative Negative Positive Positive for Vimentin
MPNST Negative Positive Variable Negative
MFH Variable Negative Negative Negative Positive for Leu-3
Synovial sarcoma Positive Variable Negative Negative
Desmoplastic
leiomyosarcoma
Negative Negative Negative Positive
Malignant
melanoma
Negative Positive Negative Negative
Spindle cell
carcinoma
Positive Negative Negative Negative
Treatment
Wide local excision
Radical neck dissection

88. Fibrous histiocytic tumors

89. • Histiocytes – connective tissue macrophages.
• Also called sessile macrophages or resting migratory cells.
• Part of the mononuclear phagocyte system (MPS).
• Precursor cells – monocytes – derived from bone marrow.
• Function – phagocytose & store substances (scavenger
cells).
• Phagocytes have irregular shapes.
• They are flattened & often show pseudopodia-like
processes.

90. • Nuclei - Eccentrically located are smaller & more densely
structured than fibroblast nuclei.
• Apart from the usual cell organelles, there are small
vesicles, vacuoles, filaments & osmiophilic inclusions.
• These may be primary lysosomes, secondary lysosomes or
often also inclusions, which have become part of
phagolysosomes or residual bodies.

91. • Fibrohistiocytic tumors – cellular elements resemble both
fibroblasts & histiocytes.
• Originally, they were believed to be neoplasms of
histiocytes.
• But studies suggest that the phenotype of the neoplastic
cells most closely resembles that of fibroblasts.
• Thus, the term fibrohistiocytic is used, which describes its
histogenetic origin.

92. BENIGNFIBROUS HISTIOCYTOMA

93. • Diverse group of neoplasms – both fibroblastic & histiocytic
differentiation.
• The cell of origin – histiocyte
• Varied microscopic appearances – numerous alternative
diagnostic terms such as
- Dermatofibroma
- Sclerosing hemangioma
- Xanthogranuloma
- Fibroxanthoma
- Nodular subepidermal fibrosis
- Epithelioid histiocytoma
- Reticulohistiocytoma

94. Clinical features:
• Skin of the extremities – as a small,
firm nodule.
• Predominantly on the buccal mucosa
& vestibule.
• Middle-aged & older adults.
• Painless sub-mucosal nodule
• Variable size – a few millimeters to
several centimeters.
• Deeper tumors – larger & most lesions
cannot be easily moved

95. Submucosal aggrigation of Spindle-
shaped, fibroblast-like cells
Scattered rounded histiocytic cells and
Foamy histiocytes
Histopathology:

96. Spindle cells in BFH
Storiform arrangement of
histiocytes

97. Touton giant cells engulf lipid and
hemosiderin
Mixture of spindle cells and
xanthomatous cells

98. BFH with myxoid changes
Hemangiopericytoma like areas in
BFH

99. Plump spindle cells with
ocassionally mitotic figures
Factor XIIIa immunostaining of BFH

100. • Differential diagnosis:
• Xanthogranuloma or juvenile xanthogranuloma
– Proliferating sheets of histiocytes with few Touton giant
cells and foamy cytoplasm.
– Better circumscribed and less fibrosed
• Langerhan’s cell disease (Histiocytosis X)
– Multinucleated giant cells nuclei not pushed to the cell
periphery.
– Reactive histiocyte – after trauma
– Hyperlipidemia or hypercholesterolemia

101. • Above lesions are usually diagnosed during the first two
decades of life.
• The histiocytic cells of a xanthoma
– Typically express S-100 protein, while the lesional cells
of the fibrous histiocytoma do not
– Cholesterol clefts are commonly seen in the
xanthoma

102. • Benign fibrous histiocytoma is often confused with other
benign fibrous lesions like
- Nodular fasciitis
- Myofibroma
- Palisading encapsulated neuroma
- Neurofibroma
- Leiomyoma
- Spindle cell type of myoepithelioma.

103. • BFH should also be differentiated from aggressive forms of
fibrous and fibrohistiocytic neoplasms such as
- Dermatofibrosarcoma protuberans
- Malignant fibrous histiocytoma and
- Fibrosarcoma

104. • Treatment & Prognosis:
• Wide surgical excision.
• Recurrence rate – 5-10%
• Deeper & larger lesions – higher rate of recurrence

105. Malignent fibrous histiocytoma

106. • Definition: A high-grade, pleomorphic spindle cell sarcoma with
a storiform pattern; matrix calcification or ossification is not
present
• First described by O'Brien & Stout – 1964.
• Most common soft-tissue sarcoma of late adult life

107. • Demographics:
• More common in white patients than in patients of African
or Asian descent.
• Site: Mandible, maxilla, soft tissue of oral cavity
• Age: 5th & 6th decades, but an age range of 10-90 years
• Sex: Male-to-female ratio – 2:1

108. • Clinical features:
• United States – MFH accounts 20-24% of soft-tissue sarcomas
• Enlarging painless intramuscular soft-tissue mass, typically
5–10 cm in diameter
• Usually occurs -soft tissues of upper followed by lower
extremities. MFH in oral cavity is very rare

109. • Clinical differential diagnosis
• Rabdomyoma
• Leiomyoma
• Lipoma
• Liposarcoma

110. • Five histological subtypes of MFH
– Storiform/pleomorphic (most common),
– Myxoid,
– Giant cell,
– Inflammatory (usually retroperitoneal
– Angiomatoid (often located more superficially than
other varieties)

111. lesions show pleomorphic, spindle cells in
a storiform pattern
Predominately histiocytic-like pattern
with bizarre round cells and highly
pleomorphic nuclei
Histopathology:

112. Malignant spindle cell having abundant
eosinophilic cytoplasm with
hyperchromatic, pleomorphic nuclei
Positive expression for S-100 protein

113. • Differential diagnosis:
– Cellular benign fibrous histiocytoma
– Aggressive fibromatosis
– Fibrosarcoma

114. Markers:
• Histochemistry of the tumor reveals
- Vimentin positivity
- CD 68 positive
- Melanoma markers (S100, HMB45) negativity
• Carcinoma markers (cytokeratin AE1/3, EMA, CK7,
CK20), lymphoma markers (CD45, CD20, CD3, CD4,
CD43, CD5, CD30) and markers for specific sarcomas
(SMA, CD34, CD117, HHF35, & desmin) are all negative.
• Therefore, MFH has become a diagnosis of exclusion

115. • Treatment:
• Complete surgical ablation with disease-free margins
• Chemotherapy is often a helpful adjuvant
• 5-year survival rate is 34% to 50%

116. Lipomatous tumors

117. Lipomatous tumors
• Benign tumors
– Spindle cell lipoma/
Pleomorphic
– Vascular (angiolipoma)
– Lipoblastoma
– Hibernoma
– Chondroid type
– Myolipoma
– Myelolipoma
– Angiomyolipoma
• Malignant tumors
• Liposarcoma
• Classified by WHO as
– Well differentiated
(WDL)/Atypical lipomatous
neoplasm(ANL)
– Didifferentiated (DL)
– Myxoid/round cell (MRCL)
– Pleomorphic
– Spindle cell liposarcoma

118. Spindle cell/pleomorphic lipoma

119. • Enzinger and Harvey in 1975
• Both the lesions were grouped under “atypical lipomas”
• Defination: A spectrum of benign lesion composed of an
admixture of mature adipocytes, spindle cells, and
hyperchromatic multinucleated giant cells.
• Demographics:
• Site: Tongue, cheek/buccal mucosa, floor of mouth, lip, hard
palate, alveolar ridge, maxilla
• Age: mean age of 55 yrs
• Sex: males are more frequently effected

120. • Clinical features:
– Slow growing
– Solitary
– Circumscribed
– Painless
– Firm nodule

121. Clinical differential diagnosis
• Buccal mucosa
– Salivary gland tumors
– Solitary fibrous tumor
– Neurofibroma
– Schwannoma
– Intramuscular lipoma,
– Myofibroma
– Fibromatosis
• Tongue
– Irritation fibroma,
– Granular cell tumor
– Neurofibroma
– Schwannoma

122. Well circumscription
Mature adipocytes
Cellular area
Ropy collagen
Histopathology:

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

124. CD 34 positivity

125. • Differential diagnosis
• Nodular fascitis
• Schwannoma
• Neurofibroma
• Solitary fibrous tmor
• Hemangiopericytoma
• Myxoid liposarcoma
• Spindle cell liposarcoma
• Treatment
• Completely benign lesion
• Exceptionally recur
• Dedifferentiation and metastasis - no

126. Spindle cell liposarcoma

127. • 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

128. • Demographics:
• Age: 4 - 6th decade
• Sex: Male
• Site: Majorly effects cheeks
• Other sites: floor of the mouth, palate, gingiva,
mandible, tongue
• Clinical features:
• Painless
• Slowly enlarging mass

129. Clinical differential diagnosis
• Buccal mucosa
– Salivary gland tumors
– Solitary fibrous tumor
– Neurofibroma
– Schwannoma
– Intramuscular lipoma,
– Myofibroma
– Fibromatosis
• Tongue
– Irritation fibroma,
– Granular cell tumor
– Neurofibroma
– Schwannoma

130. Prominent spindle cells
Resembling SCL
Scattered lipoblasts
In various shapes and sizes
Histopathology:

131. Variable spindle cells devoid of
lipoblasts
Nuclear Atypia

132. • IHC Markers: S-100 positivity in lipogenic areas; nuclear
expression of MDM2 and CDK4
• Differential diagnosis
– Neural
– Fibroblastic
– Myofibroblastic
• Treatment
• Wide surgical excision is the treatment of choice
• Radiation therapy remains controversial

133. Smoothmuscle tumors

134. • Benign tumors
• Pilar
• Genital
• Vascular/Angiomyoma
• Leiomyoma of deep soft
tissue
• Retroperitonial
• Malignant tumors
• Cutaneous leiomyosarcoma
• Leiomyosarcoma of vascular
origin
• leiomyosarcoma of deep soft
tissue

135. Leiomyoma

136. • Definition: Benign mesenchymal tumor with smooth muscle
differentiation that is classified according to location as pilar,
genital, vascular, deep soft tissue and retroperitonial.
• In H&N regions smooth muscle tumors believed to arise from
the tunica media of the blood vessels
• Demographics:
• Age: middle age to older age
• Sex: females
• Site: Very rare, if present - hard palate, tongue, buccal mucosa

137. Clinical features:

138. • Clinical differential diagnosis
– Fibroma
– Neurofibroma
– Lipoma
– Leiomyosarcoma
– Mucocele
– Pleomorphic adenoma
– Lymphangioma
– Hemangioma
– Pyogenic granuloma

139. Monomorphic spindle cells with
cigar shaped nuclei
Stori form pattern
Masson trichrome
Histopathology:

140. VASCULAR LEIOMYOMA
Actin immunostain
Fascicles of spindle cells

141. Spindle cells are SMA positive
CD31 reveals many vessels
Other markers
Vimentin, Desmin, h-caldesmon

142. • Histological Differential diagnosis
– Fibromatosis
– Myofibroma
– Neurofibroma
– Schwannoma
– Special stains – collagen
– IHC – Vimentin, desmin, α-smooth muscle actin (SMA)
and muscle specific actin (MSA)
• Treatment
• Surgical excision
• No recurrence

143. Leiomyosarcoma

144. • Definition: Malignant mesenchymal tumor with smooth
muscle differentiation that can be categorized as cutaneous,
vascular, or arising in deep soft tissue or the retroperitoneum
• Demographics:
• Age: Middle-aged or older individual
• Sex: Females
• Site: any of the above mentioned sites

145. • Clinical features:
• Typically presents as a painless, lobulated, fixed mass of
the submucosal
• Secondary ulceration of the mucosal surface

146. • Clinical differential diagnosis
– Fibroma
– Neurofibroma
– Lipoma
– Leiomyosarcoma
– Mucocele
– Pleomorphic adenoma
– Lymphangioma
– Hemangioma
– Pyogenic granuloma

147. Fascicles of interlacing monomorphic
spindle-shaped cells with abundant
eosinophilic cytoplasm
Moderately large, blunt-ended
nuclei, often with mild atypia
Histopathology:
Leiomyosarcoma arising from a
blood vessel.

148. • One study on leiomyosarcoma of head and neck found that
– LMS are well circumscribed
– Focal areas of infiltration
– Mitotic activity – 1-50 MF per 10 high power fields
Montgomery E, Goldblum JR, Fisher C. Leiomyosarcoma of the head and neck: a
clinicopathological study. Histopathology 2002; 40: 518–25.
• IHC Markers:
• Positive for MSA, SMA, Desmin, h-caldesmon
• Negative for cytokeratin, CD34
• Few cases may also expresses cytokeratin, CD34

149. Differential diagnosis:

150. • Treatment
• Early surgical excision with radical neck dissection for
lymph node metastasis
• Chemotherapy and radiotherapy
• Recurrence and metastasis is about 50%

151. Referrences
• Brad . W . Neville , Douglas D . Damm , Carl M . Allen Oral and
maxillofacial pathology 2nd edition 2004
• SHAFER; Text book of oral pathology 5th edition 2006
• Enzinger and weiss; Soft tissue tumors fifth edition
• Douglas .R. Gnepp; Diagnostic surgical pathology of head and neck;
second edition
• Andrew L.Folpe, Carrie Y. Inwards; Bone and soft tissue pathology
foundation in surgical pathology.
• Sook-Bin Woo; Oral pathology A comprehensive atlas and text