individual spindle cell lesions of skeletal muscle origin, vascular origin, neural origin,

1. Good morning

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

3. • Part I seminar
I. Tumors of fibrous origin
II. Tumors of Fibro histiocytic origin
III.Tumors of adipose tissue origin
IV.Tumors of Smooth muscle origin

4. 7. Neural tumors
Benign Malignant
Traumatic
neuroma
Neurofibrosarcoma
Neurofibroma
Schwannoma
Benign Malignant
Cellular
rhabdomyoma
Spindle cell
rhabdomyosarcoma
Benign Malignant
Spindle cell
hemangioendothelioma
Angiosarcoma
Kaposi
sarcoma
5. Skeletal muscle tumors
6. Vascular tumors

5. Skeletal muscle tumors
• Benign
• Rabdomyoma
• Malignant
• Rabdomyosarcoma

6. Rabdomyoma

7. • Definition: Benign mesenchymal tumor with skeletal
muscle differentiation divided into the adult, fetal, and
genital types, according to degree of differentiation and
location
• Named by Zenker in 1864
• Rare benign tumor that exhibits mature skeletal muscle
differentiation.

8. • Demographics:
• Age: 4 years (age range - 3 days to 58 years)
• Sex: M:F ratio is 2.4:1
• Site: Histologic types
– Myxoid type – preauricular and post auricular
– Intermediate type – head and neck

9. • Clinical features:
• Kapadia et al
– 42% - younger than 1 year old
– 25% - congenital
– 50% - older than 15 years of age
• Symptoms: Solitary mass involving soft tissue or mucosa
• Some times fetal rhabdomyoma may be associated with
nevoid basal cell carcinoma syndrome.
• Adult Rhabdomyoma
• Fetal Rhabdomyoma
Douglas R.Gnepp; diagnostic surgical pathology of head and neck; second edition

10. • Clinical differential diagnosis
• Fibrosarcoma
• Leiomyosarcoma
• Rhabdomyosarcoma
• Kaposi sarcoma
• Lymphoma
• Neuroblastoma

11. Histopathology:
Varying size and shape of muscle cells
with bipolar nucleus and eosinophillic
cytoplasm in myxoid background
Mixture of undifferentiated and
Differentiated skeletal muscle cells

12. Cross striation in the in the myofibrils

13. • Cross striation – H&E stain, PTAH, Masson trichrome stain
• IHC markers – Desmin, Muscle specific actin (MSA)
• Histological differential diagnosis
• Spindle cell Rhabdomyosarcoma
• Infantile fibromatosis
• Treatment
• Total surgical excision is the treatment of choice
• Recurrence rate – up to 40% - incomplete excision

14. Rabdomyosarcoma

15. • Initially described by Weber in 1854.
• First published was probably a tongue lesion
• Accounts for 6% of all malignancies in children under 15
years of age
• RMS of the oral cavity accounts for 10 –12% of all the head
and neck RMS cases
• Definition: A primitive soft tissue sarcoma, showing a
variable degree of embryonic skeletal muscle differentiation
Ankita Tandon et al; Oral Rhabdomyosarcoma: A review; J Clin Exp Dent. 2012;4(5):e302-8.

16. • Demographics:
• Age: First and second decades
• Sex: Males have slight high predelection
• Site: Head and neck > Orbit (35%) > trunk and extremities
> intra-abdominal organs and genitourinary tract (23%)
• Oral cavity – Tongue > soft palate > hard palate > baccal
mucosa
• Signs and symptoms: pain, parasthesia, loss of teeth and
trismus
Ankita Tandon et al; Oral Rhabdomyosarcoma: A review; J Clin Exp Dent. 2012;4(5):e302-8.

17. Clinical features:
Smooth or lobulated surface, sometimes botryoid or grape cluster–like in
appearance and become fixed to surrounding tissues

18. • Clinical differential diagnosis
• Fibrosarcoma
• Leiomyosarcoma
• Rhabdomyosarcoma
• Alveolar soft-part sarcoma
• Kaposi sarcoma
• Lymphoma

19. Ovoid and spindled tumor cells with
dark nuclei in myxoid stroma
Cells are polygonal or elongated
with eosinophilic cytoplasm
Histopathology:

20. Moderate nuclear pleomorphism and
“strap” cell
More cellular area with mitotic
figures

21. Primitive and anaplastic muscle fibers

22. • Histological differential diagnosis
• Ewings sarcoma
• Neuroblastoma
• IHC markers:
– Desmin
– Myogenin/MyoD1
• Treatment
• Surgical excision
• Followed by chemotherapy and radiotherapy
• 66- 90% of 5 years survival rate

23. Vascular tumors
• Benign
• Spindle cell hemangioendothelioma
• Malignant
• Angiosarcoma
• Kaposi sarcoma

24. Spindle cell hemangioendothelioma

25. • Definition:
• Vascular tumor of intermediate malignancy
• Weiss and Enzinger described in 1986
• It was considered to be an intermediate or low-grade
malignancy, with a biologic behavior between a hemangioma
and an angiosarcoma
• Relatively uncommon lesion

26. • Fletcher et al, Imayama et al - nonneoplastic reactive
vascular proliferation
• Later Perkins and Weiss
– “spindle cell hemangioma” (SCH) - solitary lesions
– “spindle cell hemangiomatosis” - multifocal lesions
K.I. Tosios et al; Spindle cell hemangioma (hemangioendothelioma) of the head and neck: case report
of an unusual (or underdiagnosed) tumor; Oral Surg Oral Med Oral Pathol Oral Radiol Endod
2008;105:216-21

27. • Demographics:
• Age: Young Adults
• Sex: no sex predelection
• Site: dermis and subcutis of distal extremities, axilla,
trunk, vulva, penis, spleen, pancreas, bones, head and
neck

28. • Clinical features:
• Solitary tumor or multiple asymptomatic nodules
clustered
• Color - Normal or bluish
• Consistency - firm
• Size - few millimeters to a few centimeters - less than
2.0 cm.

29. Histopathology:
Spindle cell arranged in the form of
glomeruloid nests
Capillary hemangioma like areas

30. • Histological differential diagnosis
• Kaposi sarcoma
• Cavernous hemangioma
• Epithelioid hemangioma
• Intravascular papillary endothelial hyperplasia
• Kaposiform hemangioendothelioma
• Epithelioid and spindle cell hemangioma

31. • IHC markers:
• Vimentin
• CD31
• CD34
• SMA
• Factor VIII–related antigen,
• HAM-56

32. CD34
SMA

33. • Treatment
• surgical excision
• Recurrence may develop many years after the initial
excision
• No metastasis

34. Angiosarcoma

35. • Definition: Fully malignant sarcoma showing endothelial
differentiation.
• Rarely affecting the oral cavity
• Demographics:
• Age: 1 year to 20 years with an average of 7.3 years
• Sex: Equal sex predilection
• Site: Tongue > Parotid gland > Lip > Submandibular gland
> Palate

36. • Clinical features:
• Poorly demarcated
• Round or ovoid nodules
• Red-blue to purplish
• Painful
• Spontaneously bleeding
• Firm on palpation

37. • Clinical differential diagnosis
• Hemangioma
• Pyogenic granuloma
• Melanoma
• Erythroplakia
• Diffuse angiomatosis
• Atypical vascular proliferations after irradiation

38. Atypical polygonal or spindle cells
with hyperchromatic nuclei

39. Histopathology:
Clear-cut vasoformation and clearly
malignant endothelial cells
Sheet-like proliferation malignant
epithelioid cells, Mimicking Carcinoma

40. Pleomorphic tumor with rudimentary lumen
formation

41. • Histological differential diagnosis
• Haemangioma and its variants
• Pyogenic granuloma
• Spindle cell carcinoma
• Mucosal malignant melanoma
• Rhabdomyosarcoma
• Leiomyosarcoma
• Liposarcoma
• Synovial sarcoma
• Fibro-histiocytic sarcomas, MPNST and epithelioid
sarcoma
• Malignant myoepithelioma of salivary gland
• Anaplastic non-Hodgkin’s lymphoma with spindle cell
features
G. Favia et al; Angiosarcoma of the head and neck with intra-oral presentation. A clinico-pathological
study of four cases; Oral Oncology 38 (2002) 757–762

42. • IHC markers:
• Vimentin
• CD31
• CD34
• FLI-1 protein
• D2-40 and VEGFR-3
• Low-molecular-weight cytokeratin expression in 25%
of cases, particularly epithelioid tumors
G. Favia et al; Angiosarcoma of the head and neck with intra-oral presentation. A clinico-pathological
study of four cases; Oral Oncology 38 (2002) 757–762

43. Factor VIII-related antigen
Positive for CD34

44. MIB-1 labeling
CD31 immunostain for
angiosarcoma cells

45. • Treatment
• Radiotherapy of 4000–5000 rads,
• Followed by radical surgery - most effective procedure
• Prognosis
• Survival - longer in low grade angiosarcoma than high grade
angiosarcoma
• 50% - die within 15 months from the diagnosis
• 12% - survive 5 years or longer
• Death is usually due to uncontrolled local progression and/or
distant metastases to the lungs, liver and bone
G. Favia et al; Angiosarcoma of the head and neck with intra-oral presentation. A clinico-pathological
study of four cases; Oral Oncology 38 (2002) 757–762

46. Kaposi sarcoma

47. • Definition: Malignant vascular tumor caused by infection
with HHV-8, most often in immunocompromised patients
• Kaposi sarcoma (KS) - multifocal angioproliferative
disorder of vascular endothelium, primarily affecting
mucocutaneous tissues with the potential to involve viscera

48. Mahnaz Fatahzadeh; Kaposi sarcoma: review and medical management update; Oral Surg Oral Med
Oral Pathol Oral Radiol 2012;113:2-16
• Demographics:
Clinical
variants of KS
Etiology Age sex site
Classic KS - 5th decade older men
M:F, 17:1
Skin and extrimities
Endemic KS - children and
young
male
individuals
lymph node and soft
tissue
Iatrogenic KS - - - kidney transplant
patients
Epidemic KS Homosexual male
intravenous drug
Abusers
Adults Males skin,
mucosal
and visceral locations

49. Clinical features:
Solitary, mutifocal, or multicentric
macules, plaques, or nodules of different
sizes

50. Clinical features

51. • Clinical differential diagnosis
• Hemangioma
• Pyogenic granuloma
• Melanoma
• Erythroplakia

52. Histopathology:
Short fascicles of spindle cells
with abundant fresh hemorrhage
Spindle cells show mild nuclear
pleomorphism and mitotic activity

53. Proliferation of spindle cells with dilated vessels and
hemosiderin

54. Spindle cells with mild nuclear
atypia
Lumen formation and presence of
hyaline globules

55. • Histological differential diagnosis
• Angiosarcoma
• Sindle cell hemangioma
• Spindle cell sarcomas
• Hemangioma
• Pyogenic granuloma
• Angiopericytoma

56. • IHC markers
• CD31
• CD34
• FLI-1 protein
• D2-40 and VEGFR-3 expression in most cases
• HH V-8 LANA protein expression
D2-40

57. CD31 in majority of the cells
LANA1 of HHV8

58. • Treatment
• Treatment is divided into
– Local/regional therapy
– Systemic therapy
• Local/regional therapy
– Surgical excision
– Cryotherapy
– Sclerotherapy
– Intralesional vinca-alkaloids
– Radiotherapy
– Laser therapy
Mahnaz Fatahzadeh; Kaposi sarcoma: review and medical management update; Oral Surg Oral Med
Oral Pathol Oral Radiol 2012;113:2-16

59. • HAART
– NNRT-based therapy
(non-nucleoside reverse
transcriptase)
– PI-based therapy
(protease inhibitor)
• Chemotherapy
– Combination agent ABV
or ABVb
– Vincristine,
Vinblastine,Vinorebline
– Bleomycin
• Immune modulators
– Interferon-alpha
• Experimental & targeted
therapies
– Antiherpes therapy
– Angiogenic inhibitors (e.g.,
thalidomide)
– VEGF inhibitors
– Tyrosine kinase inhibitors
– Matrix metalloproteinases
Systemic therapy
Mahnaz Fatahzadeh; Kaposi sarcoma: review and medical management update; Oral Surg Oral Med
Oral Pathol Oral Radiol 2012;113:2-16

60. Neural tumors

61. • Benign
• Traumatic neuroma
• Neurofibroma
• Schwannoma
• Malignant
• Neurofibrosarcoma

62. Traumatic neuroma

63. • Definition: Disorganized proliferation of nerve in response
to injury or disruption.
• Occurs in the area of any nerve that has been surgically or
auto-amputated
• Demographics:
• Age: Middle-aged adults
• Sex: Slightly more common in females than in males
• Site: Mental foramen area
lateral tongue
lower lip

64. • Clinical features
• Patient has firm, painful nodule
• Constant or intermittent aching, a burning sensation,
or severe radiating pain
• Clinical differential diagnosis
• Traumatic fibroma
• Mucocele
• Solitary neurofibroma

65. Histopathology:
Nerve fibers of varying sizes with
fibrosis

66. Prominent fibrosis
Nerve fibers with thickened
endoneurium

67. • Histological differential diagnosis
• PEN
• Mucosal neuroma
• Morton’s neuroma
• Neurofibroma
• IHC markers
• S-100
• CD-57
• Treatment
• Excision

68. Neurofilament protein positivity
CD57 (Leu-7) in traumatic neuroma

69. Neurofibroma

70. • Definition:
• Neurofibromas are the most frequent benign neoplasms
originating from the peripheral nerve sheath and occur as
solitary or multiple tumours when associated to the von
Recklinghausen disease, better known as neurofibromatosis

71. • Demographics:
• Age: Most patients are younger than 45 years of age
• Sex: Females are more frequently affected,
• F:M ratio being 2:1.
• Site:
• Buccal mucosa, palate, alveolar ridge, vestibule and
tongue, lips and gingival
• Intraosseous lesions are quite rare.
• Most common site being the posterior mandible

72. • Clinical features
• ORAL NEUROFIBROMA - uncommon benign tumor
of the oral cavity
• Neurofibroma occurs as a
– Solitary lesion – unknown cause
– As part of the generalized syndrome of
neurofibromatosis (von Recklinghausen disease of
the skin) - inherited as an autosomal dominant trait
• 50% of cases are reported to be the result of
spontaneous mutation in
– Neurofibromatosis type 1 (NF1) gene
– Neurofibromatosis type 2 (NF2) gene

73. • Solitary oral lesions - non-ulcerated nodules, which
tend to be of same color of normal mucosa.
• Lesions associated with neurofibromatosis – solitary
lesions, iris Lisch nodules, cafe-au-lait spots and
freckling in the axillary region.

74. Intraoral involvement
Multiple tumors of the trunk
and cafe-au-lait spots

75. • Central neurofibromas
– Early stages – Asymptomatic
– Grow in size - Cause expansion of the cortical plates
of the mandible, with or without destruction,
– Pain and anesthesia or paresthesia of the lower lip
• Radiographically - Well-circumscribed or poorly
demarcated radiolucent lesion

76. • Clinical differential diagnosis
• Mucocele
• Lipoma
• Pleomorphic adenoma

77. Histopathology
Unencapsulated lesion
Spindle cells, curvilinear nuclei,
delicate collagen, and mast cells

78. S-100 positivity

79. • Histological differential diagnosis
• Nodular fasciitis (absence of thin wavy nucleus)
• Focal mucinosis
• Palasaded encapsulated neuroma
• IHC markers
• S-100
• CD34
• Neurofilament
• Factor VIII
• Treatment
• Surgical excision
• Malignant transformation - is reported to occur in 5%
to 16% of patients

80. Schwannoma

81. • Once termed “neurilemoma,” - Stout, 1935
• Benign tumor, apparently derived from the Schwann cells
• Definition: A peripheral nerve sheath tumor arising
eccentric to nerve
• Demographics:
• Age: 20 to 50 years common in 2nd and 3rd decades
• Sex: Female Sex Predilection
• Site: Tongue > Palate > Buccal mucosa
• Some times intraosseous – mandible
• Bone expansion, pain, parasthesia

82. Clinical features

83. • Clinical differential diagnosis
• Lipoma
• Fibroma
• Solitary neurofibroma
• Hemangioma
• Eosinophillic granuloma
• Epidermoid and dermoid cysts
• Epithelial hyperplasia
• Granular cell tumor
• Leiomyoma
• Lymphangioma
• Salivary gland tumors
Monoela D M et al; Intraoral schwannoma: case report and litrature review; indian journal of dental
res, 20(1), 2009.

84. Histological varients

85. Histopathology
Marked cystic degeneration of stroma
Encapsulation

86. • Verocay bodies – Antoni A pattern
Eosinophilic basement membrane
material between palisaded nuclei
Spindle cells – Antoni B pattern

87. Antoni A- nuclear palasading
Antoni A- without nuclear
palasading

88. Verocay bodies and adjacent Antoni
type B tissue
Delicately collagenized and myxoid
stroma

89. Spindle cell proliferation
perivascular hyalinization, mostly
Antoni type B tissue
Palisading of nuclei forming
unusual Verocay body

90. • Histological differential diagnosis
• Neurofibroma
• Melanoma
• Leiomyosarcoma
• MPNST
• Solitary fibrous tumor
• Solitary circumscribed neuroma
• IHC markers:
• S-100

91. S-100 positivity

92. • Treatment
• Conservative surgical excision
• No evidence of recurrence if completely excised
• Malignant transformation - controversial

93. Neurofibrosarcoma

94. • Definition: A malignant neoplasm with a poor
prognosis of perineural fibroblasts or schwann cells,
with propensity to rapidly extend along the associated
nerve trunk.
• WHO has grouped this lesion under the heading of
MPNSTs
– Mlignant schwannoma
– Malignant neurilemmoma
– Neurogenic sarcoma
– Neurofibrosarcoma

95. • Demographics
• Age: 20 – 50 yrs of age
• Sex: no sex predelection
• Site: any where in the body but most commonly in skin
• Clinical features
• Exact mechanism of occurance of the lesion is not yet
identified
• Occurs as a complication of neurofibromatosis I (15%)
• Or occurs denovo

96. • Mostly occurs in soft tissue
• Intraosseous neurofibrosarcoma
– Due to the nerve present in the neutrient canal
– Due invasion into the bone from soft tissue
– Symptoms include pain, parasthesia
Neurofibromatosis-I patient with
neurofibrosarcoma of the left cheek

97. Histopathology
Spindle cell proliferation with
numerous mitotic figures
Fascicles of spindle cells
resembling fibrosarcoma

98. Patchy positivity for S-100
Vimentin positivity

99. • Histological differential diagnosis
• Monophasic syanovial sarcoma
• Leiomyosarcoma
• Fibrosarcoma
• IHC markers
• S-100 (weak or negative)
• GFAP
• Neurofilament
• NSE
• Leu-7
• Myelin basic protein
• Ki67

100. • Treatment
• Highly aggressive tumor and difficult to treat
• Prognosis - Grade of tumor, tumor size
• Overall survival rate is 40-75%
• Early detection and appropriate treatment is crucial
for survival

101. 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
• Net source and articles