1. SPINDLE CELL TUMORS OF
THE ORAL CAVITY
PART 2
SHERIN JAMES
5/30/2023

2. CONTENTS
 Introduction
 Classification
 Description of lesion specific
 Treatment/Prognosis
 Conclusion
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3. INTRODUCTION
3

4. CLASSIFICATION
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5.  I) APPEARANCE & ARCHITECTURAL PATTERN
 II) SPINDLE CELL LESIONS PRESENTING AT UPPER
AERODIGESTIVE TRACT MUCOSAL SITES
 III) WORKING CLASSIFICATION
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6. 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
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7. 7

8. LESION WISE DESCRIPTION
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9. MUSCLE TISSUE ORIGIN
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10. SMOOTH MUSCLE FIBERS
 Found mainly in relation to viscera, present in the tunica
media of large and small arteries and veins
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11. ORIGIN OF SMOOTH MUSCLE FIBERS
Smooth muscle of aorta and
pulmonary arteries - neural
crest origin
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12. MICROSCOPY OF SMOOTH MUSCLE
FIBERS
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14. SKELTAL MUSCLE FIBRES
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• Myofibers in longitudinal section.
Striations produced by the sarcomeres
are clearly visible.
•One of the earliest signs of myofiber
necrosis is the loss of these striations.

17. LEIOMYOMA
 The common sites are posterior
portion of the tongue, followed by
palate, cheeks, gingiva, lips and
salivary glands.
 Oral lesions are slow growing,
painless, often pedunculated
 Central leiomyoma are rare-
mandible
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18. HISTOPATHOLOGY
 Bundles or fascicles of spindled cells with eosinophilic and
possibly fibrillary cytoplasm
 Nuclei are blunt ended and elongated with fine chromatin,
indistinct nucleolus and variable cytoplasmic vacuole at one end
 Bundles of fibres appear to form WHORLS because of their
fascicular arrangement in varying planes.
 Minimal atypia
 Few mitotic figures 5/30/2023
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19.  Masson trichrome: to differentiate muscle from collagen
 Muscle: bright red
19

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Oblong nuclei have rounded ends
Bundles of elongate cells with
eosinophilic

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VARIANTS :
Solid leiomyoma
Vascular leiomyoma (Angiomyoma)
Epitheliod leiomyoma

22. IMMUNOHISTOCHEMISTRY
 SMA, MSA, Desmin, Vimentin, Actin and myosin
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SMA+

23. DIFFERENTIAL DIAGNOSIS
 Myofibroma
 Hemangiopericytoma
 Neurofibroma
 Leiomyosarcoma
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24. LEIOMYOSARCOMA
 Leiomyosarcomas account for 6-7% of all the soft tissue
sarcomas.
 Tongue, cheek, gingiva, soft palate, upper lip, and floor of
mouth.
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25. CLINICAL FEATURES
 Small well circumscribed, slow growing, painful, rubbery or
semi-firm, lobulated mass, firmly adherent to the surrounding
tissues.
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26. HISTOPATHOLOGY
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 Fascicular growth pattern (bundles intersect at right angles).
 Palisading of spindle cells with eosinophilic fibrillary cytoplasm,
focal granularity.
 Nuclei are cigar-shaped and blunt-ended with variable atypia,
often with cytoplasmic vacuoles at both ends of nuclei (unlike
neural lesions)
 Mitotic figures are common. (5 > 10 HPF)
 Ischemic areas showing stromal fibrosis and hyalinisation.

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•May have hemangiopericytoma-
like vasculature, nuclear
palisading, myxoid change.
•Often infiltrates into adjacent
tissue
Massons trichrome showing longitudinal
striations. ( red hair like streaks in
cytoplasm)

28. 4x 10x
40x 10x

29. IMMUNOHISTOCHEMISTRY/ GENETIC
FINDINGS
 SMA
 Muscle specific actin
 Desmin
 H-caldesmon
 RB1 gene has been implicated in some cases of leiomyosarcoma.
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30. DIFFERENTIAL DIAGNOSIS
 Fibrosarcoma
 MPNST
 Myofibroblastic tumors
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31. RHABDOMYOMA
 Benign neoplasm of striated muscle with varying degree of
differentiation and maturity.
 Well circumscribed/ encapsulated.
TYPES OF RHABDOMYOMA
 Adult
 Fetal (Spindle cells)
 Genital type
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32.  70% occurs in men (5:1 ratio)
 Oral cavity- palate, floor of the mouth, tongue
 Appears as a nodular mass and grows to many centimeters.
 Fetal variant: young children with male predilection
 Face, periauricular region, nasopharynx.
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Polygonal, vacuolated glycogen containing cells, fine granular
deeply acidophilic cytoplasm

34.  Less mature, pleomorphic, polygonal muscle cells with spindle shaped
cells.
 More cellular, with myxoid stroma.
 Myxoid/ Classic, Intermediate/ Cellular/ Juvenile Fetal
Rhabdomyoma.
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Undifferentiated round mesenchymal cells and
immature skeletal muscle cells within myxoid or

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The bipolar, immature skeletal muscle cells
have tapered eosinophilic cytoplasmic
processes and closely resemble the
myotubular stage of striated muscle
development, and the undifferentiated cells
have minimal cytoplasm and round or oval
nuclei
Mucosal tumors have a pseudo
cambium layer of plasma cells and
lymphocytes resembling embryonal
rhabdomyosarcoma, but there is no
atypia and no mitotic figures

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DIFFERENTIAL DIAGNOSIS
•Infantile fibromatosis: deep location, fascicles of spindle cells, no
cross striations, no undifferentiated cells
•Spindle cell variant of embryonal rhabdomyosarcoma: resembles
cellular variant of fetal rhabdomyoma but has cellular pleomorphism
and tumor cell necrosis

37. SPINDLE CELL RHABDOMYOSARCOMA
(VARIANT OF EMBRYONAL
RHABDOMYOSARCOMA)
 Rhabdomyosarcoma (RMS) originates from immature cells that
are destined to differentiate into striated skeletal muscle
 More common in young children; 60% soft tissue sarcoma in
childhood.
 Embryonal type most common in first 10 yrs of life (60%) -
spindle cell variant and botryoid variant
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38. 5/30/2023
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39. CLINICAL FEATURES
 It presents as a rapidly growing soft tissue mass.
 The clinical symptoms produced are based on their location.
 Chiefly from orbital, facial and cervical musculature.
 The head and neck lesions can cause proptosis, diplopia,
sinusitis, or unilateral deafness, depending on their location
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40. HISTOPATHOLOGY
Bizarre large cells are seen called
racket cells, strap cells and
ribbon cells
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41. bland spindle cells are characteristic
May be paucicellular with fibrotic stroma
containing undifferentiated round and
spindle
cells mixed with differentiating

42. IHC/CYTOGENETICS AND MOLECULAR
GENETICS
 Positive: Desmin, Troponin D, Myolobin, MyoD1, Myogenin.
 Structural rearrangement of chromosomes with LOH in
11p15.
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43. DIFFERENTIAL DIAGNOSIS
 Fibrosarcoma: herringbone pattern, may have similar morphology
but no rhabdomyoblasts, negative for skeletal muscle markers
 Infantile fibromatosis: deep location, fascicles of spindle cells, no
cross striations, no undifferentiated cells
 Leiomyosarcoma: usually high grade, cigar shaped nuclei, mitotic
figures and necrosis, no rhabdomyoblasts, often positive for
caldesmon, negative for myoglobin
 Rhabdomyoma: benign tumor of skeletal muscle differentiation, no
rhabdomyoblasts, no pleomorphism, no necrosis
44

44. NEURAL ORIGIN
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45. NERVE FIBER
 Within endoneurium sheath there are schwann cells
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48. MICROSCOPY OF NERVE FIBER
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49. TRAUMATIC NEUROMA
 Exuberant attempt at repair of damaged nerve trunk
 Small nodule or swelling of mucosa, typically near mental
foramen, slow growing, rarely reaches to greater size
 Pressure causes pain
50

50. HISTOPATHOLOGY OF TRAUMATIC
NEUROMA
51
Cross linked nerve bundles of medium size

51. 52 Schwann cells. B: Perineural
cells

52. 53
Luxol fast blue stain show some fibers to be myelinated

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S100+
Haphazard nerves within mature
collagenous scar with entrapped
smooth muscle

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55. DIFFERENTIAL DIAGNOSIS OF
TRAUMATIC NEUROMA
 Neurofibroma
 Neurilemmoma
 PEN
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56. NEURILEMMOMA (Neurinoma/
Lemmoma/ Perineural fibroblastoma)
 Benign neoplasm that is derived from proliferation of
schwann cells of the neurilemma or nerve sheath
 Slow growing, encapsulated tumor
 Asymptomatic mass
 Tongue common site
 Intraosseous lesion – Mandible.
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57. HISTOPATHOLOGY
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 Biphasic: compact hypercellular Antoni A areas and myxoid
hypocellular Antoni B areas (may be absent in small tumors)
 Cells are narrow, elongate, wavy with tapered ends interspersed
with collagen fibres.
 Nuclear palisading around fibrillary process (Verocay bodies)
are often seen in cellular areas
 Large irregularly spaced vessels are most prominent in Antoni
B areas

58. 59 Black arrow: Antoni A; blue arrow: Antoni B

59. 60 parallel arrays of nuclei forming a Verocay body
Verocay body showing horizontal rows of palisaded nuclei separated by areas of acellular pink
basement membrane like material.

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61. 5/30/2023
Verocay bodies
Encapsulated biphasic nerve sheath tumor
derived from Schwann cells with highly
ordered cellular component (Antoni A) that
palisades (Verocay bodies), plus myxoid
component (Antoni B)

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63. HISTOLOGICAL VARIANTS OF
SCHWANNOMA
 Cellular schwannoma
 Plexiform schwannoma
 Ancient schwannoma
 Telengectactic schwannoma
 Epitheloid schwannoma
 Melanotic schwannoma
 Pacinian schwannoma
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64. IMMUNOHISTOCHEMISTRY OF
SCHWANNOMA
 Positive: S-100, SOX10 (excellent for neural crest cell derivative)
 Occasionally Leu-7 and glial fibrillary acidic protein positive.
 Type IV collagen (stains abundant parenchymal reticulin
, CD34 (Antoni B areas) and calretinin (Antoni A areas)
 Silver stain shows minimal axons.
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65. DIFFERENTIAL DIAGNOSIS OF
SCHWANNOMA
 Leiomyosarcoma
 MPNST
 Plexiform neurofibroma- neurofibroma lacks capsule
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66. 5/30/2023
 Occurs even without neurofibromatosis, tumors usually have
epithelioid features and often areas of benign schwannoma.
 Transforms to MPNST, angiosarcoma or epithelioid malignant
change (EMC)
 Most common sites are limb, limb girdles, head / neck
 Schwannoma with MPNST: benign schwannoma with no other
primary tumor that may have metastasized to schwannoma,
histologically malignant cells resembling epithelioid MPNST; 5 year
survival < 20%
MALIGNANT TRANSFORMATION:

67. NEUROFIBROMA
 Most common type of peripheral nerve neoplasm
 Arises from- schwann cells, perineural fibroblasts.
 Appears as slow growing, soft painless lesion of varying size
 Three growth pattern observed: localised, diffuse or plexiform
 Palate, buccal mucosa and alveolar ridge
 Mandibular nerve is involved (intraosseous)
68

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Proliferation of all elements of peripheral nerves
Schwann cells with wire like collagen fibrils (wavy serpentine
nuclei, pointed ends), stromal mucosubstances, mast cells, Wagner-
Meissner corpuscles, Pacinian corpuscles, axons (highlight with silver
or acetylcholinesterase stain, NSE, neurofilament), fibroblasts and
collagen
HISTOPATHOLOGY

69. 70
 Perineurial cells in plexiform types, mitotic figures are rare
 May be infiltrative, have myxoid areas, contain melanin pigment,
have epitheloid morphology
 No Verocay bodies, no nuclear palisading
 No hyalinized thickening of vessel walls.

70. The cells are associated intimately with
wire like strands of collagen that is
correlated to “shredded carrots”.
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71. HISTOLOGIC VARIANT OF
NEUROFIBROMA
 Plexiform neurofibroma
 Pigmented neurofibroma
 Epitheloid neurofibroma
 Granular cell neurofibroma
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Plexiform neurofibroma

72. IMMUNOHISTOCHEMISTRY
 Strongly S-100 protein positive.
 Conventional and plexiform neurofibromas may also contain
variable numbers of EMA-positive perineurial cells and
CD34-positive fibroblasts
 Toluidine blue for mast cell (histochemical staining)
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73. DIFFERENTIAL DIAGNOSIS
 Traumatic neuroma,
 Solitary circumscribed neuroma,
 Schwannoma,
 Benign fibrous histiocytoma.
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74. PALISADED ENCAPSULATED
NEUROMA
 SOLITARY CIRCUMSCRIBED NEUROMA
 Generally considered reactive than a neoplasm
 Striking predilection for face
 Nose and cheek common areas
 Oral cavity - hard palate and maxilla
 5-7th decade of life, no gender predilection
 Smooth surface, painless, dome shaped nodule <1cm.
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Circumscribed dermal tumour underl-
ying an uninterrupted or
attenuated epidermis

76. 77
loose matrix and fascicles of spindled cells,
which resemble schwannoma
A split between the tumour and the
surrounding dermis is often seen

77. consists of solid proliferation of schwann cells and lack variety of stromal changes like mucoid,
myxoid changes some places they resemble schwannoma showing palisaded arrangement of cells
78

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79. IMMUNOHISTOCHEMISTRY OF PEN
 Silver stains for axons and luxol fast blue stain for myelin
will confirm the presence of Neural tissue within the tumor
 IHC : S-100 positive
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80. MALIGNANT PERIPHERAL NERVE
SHEATH TUMOR
 Malignant schwannoma, Malignant neurilemmoma,
Neurogenic sarcoma, Neurofibrosarcoma
 Malignant tumor arising from or differentiating toward cells of
the peripheral nerve sheath.
 Spindle cell malignancy of peripheral nerve schwann cells.
 It is found in at least 4% of patients with neurofibromatosis I.
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 Mostly 20-50 years
 Neck, tongue, soft palate.
 Central- mandible more common
 The tumor is an enlarging mass that sometimes exhibits rapid
growth.
 Paresthesia, muscle atrophy, and weakness may be present,
depending on whether a major nerve trunk is involved.
 Recur locally, distant metastases frequent

82.  CRITERIA that must be satisfied before a diagnosis is made is that
the tumor is histologically malignant and is identified arising :
1. from a peripheral nerve
2. from a neurofibroma schwannoma, ganglioneuroma,
ganglioneuroblastoma or pheochromocytoma
3. in a patient with NF-I and exhibiting the same histologic feature as
MPNSTs found originating from a peripheral nerve
4. in a patient without NF-1 but having the same histologic features as
well as demonstrating immunoreactivity for S-100 protein. In 50-
70% of cases, S-100 protein reactivity is found in scattered tumor
cells
83

83. Monomorphic serpentine cells (nuclear contour of schwann cells).
Frequent mitotic figures, cellular and nuclear pleomorphism.
Spindle cells in sweeping fascicles with hypocellular & myxoid areas.
May have glandular differentiation (positive for keratin, EMA, CEA,
chromogranin); if so, presume malignant
Note: some have no discernable Schwannian features at any level
HISTOPATHOLOGY OF MPNST

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85. VARIANTS OF MPNST
 Epitheliod
 Mesenchymal (Triton tumor)
 Glandular
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86. IHC / CYTOGENETICS AND
MOLECULAR GENETICS - MPNST
 Positive: S-100, Leu-2, myelin basic protein
 Up-regulation of gene involved in schwann cell
differentiation- SOX10
 Down regulation of – SOX9 and TWIST1
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87. DIFFERENTIAL DIAGNOSIS OF MPNST
 Leiomyosarcoma
 Synovial sarcoma- EMA, CK7 positive
 Fibrosarcoma
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88. VASCULAR ORIGIN
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89. PERICYTES
 Also known as “Rouget cells” (Charles Rouget)
 Zimmerman termed it as pericytes
 Present around small blood vessels, wrapped around the basal
surface of the endothelium
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90. ORIGIN OF PERICYTES
 It has recently been shown that perivascular cells (i.e, pericytes or smooth
muscle cells) and endothelial cells can be derived from a common
progenitor cell.
 Incubation of these progenitor cells with PDGF-BB stimulates their
differentiation into pericytes/smooth muscle cells,
 Whereas VEGF stimulates their differentiation into endothelial cells.
 It has been suggested that pericyte may also be derived from smooth
muscle cells, fibroblasts, endothelial cells, and the bone marrow
 Being derived from multiple cell types, it is now apparent that pericytes
have multilineage potential and are capable of differentiating into a
variety of different cell type.
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92. SPINDLE CELL HEMANGIOMA
 In 1986, Weiss and Enzinger described a unique vascular tumor with
combined features of both cavernous hemangioma and Kaposi
sarcoma.
 The spindle cell hemangioendothelioma was considered to be an
intermediate or low-grade malignancy, with a biologic behavior
between a hemangioma and an angiosarcoma.
 It affects almost exclusively the dermis and subcutis of the distal
extremities
 Spindle cell hemangioma presents as a solitary tumor or as multiple
nodules clustered within the same region.
95

93. 96
Multifocal SCHs have been
associated with Maffucci
syndrome,
Von Willenbrand disease,
acute myelomonocytic
leukemia, early-onset varicose
veins, and epithelioid
hemangioendothelioma.

94. HISTOPATHOLOGY
Composed of thin walled cavernous
vessels lined by flat endothelial cells and
contain mixture of erythrocytes and
thrombi.
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Between cavernous spaces are bland spindle
areas are seen resembling kaposis sarcoma.

95. 98
Well defined submucosal mass with cavernous spaces (C), solid (S)
areas, and large phleboliths (P) (40x).

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Irregular cavernous spaces lined by flat
endothelial cells
Spindle-shaped cells in solid areas
arranged in short interlacing
fascicles and slit-like spaces

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(A) Cavernous hemangiomatous component
(B) Component of spindle cell hemangioma

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Bland spindle cell proliferations between vascular lumina with extravasated
erythrocytes (similar to Kaposi's sarcoma), but also with vacuolated cells and
epithelioid endothelial cells (unlike Kaposi's sarcoma)

99. DIFFERENTIAL DIAGNOSIS
 Kaposi’s Sarcoma- rarely contains cavernous vessels with thrombi
and phleboliths and lacks epithelioid cells, and the spindle cells
react for the endothelial marker CD34.
 On the other hand, SCH does not present the hyaline globules seen
in Kaposi sarcoma, and does not express human herpes virus 8
latent nuclear antigen.
 Vascular malformations
102
IHC
Spindle cells are negative for endothelial markers
 and react for vimentin, and occasionally for actin, desmin, factor
XIIIa, lysozyme, alpha-1-antithrypsine, and HAM-56 antigen.

100. KAPOSI’S SARCOMA
 Angioreticuloendothelioma, MIHSK
 Multicentric proliferation of vascular and spindle cell
components- Moritz Kaposi (1872)
 Predominantly associated with HIV infection
 Four major clinical presentation: classic, endemic (African),
immunosuppression associated (transplant), AIDS related
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4 DISTINCT CLINICAL SETTINGS

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Classic (Mediterranean) Kaposi sarcoma (KS)
M > F, 40 - 70 years, Mediterranean or Ashkenazi origin
Usually lower extremities
Soft bluish nodules of palate, gingiva.
Endemic (African) KS
Adults and children in equatorial Africa
Lymphadenopathic form is aggressive
AIDS associated (epidemic) KS
Disseminated mucocutaneous / visceral lesions-Aggressive
Palatal and gingival mucosa.
Immmunosuppression asso: KS
(autoimmune disease, drugs, post-transplant)
CMI – lost in host

103. HISTOPATHOLOGY
Patch stage
Signs of a subtle vasoformative process composed of newly formed slit-like
or somewhat jagged vascular spaces.
The protrusion of native microscopic vascular structures into the lumens of
more ectatic neoplastic channels results in the characteristic promontory sign.

104. Plaque stage
More diffuse vascular infiltrate, accompanied by greater cellularity.
 The lesional cells tend to be more spindled and arranged in short, sometimes
haphazard fascicles. Fascicles cut in cross section demonstrate a sieve-like app:
Intra- and extracellular hyaline globules.
The arrows indicate so-called "autolumination", with paranuclear vacuoles
containing RBCs

105. Nodular stage
• The dermis is expanded by a solid tumor nodule.
• Fascicles of relatively monomorphic spindled cells, with slit-like vascular
channels containing erythrocytes.

106. Hyaline globules
Submucosal spindle cell proliferation with intervening slit-like spaces.
Slit-like spaces contain erythrocytes.
Eosinophilic PAS+ hyaline bodies in tumor cells or extracellular.
Extravasated erythrocytes, hemosiderin laden macrophages
Variable chronic inflammatory cell infiltrate.

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108. 5/30/2023
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Skin showing a stratified squamous epithelium with a fibrocollagenous
stroma within which are seen proliferating plump spindle cells with
slit-like vascular channels

109. IMMUNOHISTOCHEMISTRY
 Positive: CD34, CD31, Factor VII, FLI-1, vascular endothelial growth
factor receptor-3
 HHV8 latency associated nuclear antigen: most specific; stippled
nuclear staining
 Endothelial markers: factor VIII related antigen, CD34, CD31
(PECAM1), FLI1
 Lymphatic markers: D2-40 (binds podoplanin antigen
, LYVE1, VEGFR3, Prox1
 BCL2
 Iron stain highlights hemosiderin
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NEWER HISTOLOGIC VARIANTS:
anaplastic, bullous,
 ecchymotic,
 glomeruloid,
 hyperkeratotic,
intravascular,
keloidal,
lymphangioma-like,
 micronodular,
 pigmented,
pyogenic granuloma-like,
 telangiectatic,
with myoid nodules,
with sarcoid-like granulomas

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 Early (patch stage) KS
 Fibrous histocytoma
 Targetoid hemosiderotic hemangioma
 Nodular KS
 Bacillary angiomatosis: HHV8
negative, Bartonella
quintana (visible on silver stains),
well formed vascular spaces,
neutrophilic infiltrate
 Fibrohistiocytic tumors
 Dermatofibrosarcoma protuberans
 Fibrous histiocytoma
 Other spindle cell malignancies: all
HHV8 negative
 Angiosarcoma: marked atypia,
variable CK+
 Fibrosarcoma
 Leiomyosarcoma: atypia, necrosis,
smooth muscle markers+
 Spindle cell melanoma: melanoma
markers+
 Other vascular tumors:
 Kaposiform
hemangioendothelioma
 Spindle cell hemangioma
 Plaque stage KS
 Microvenular hemangioma
 Targetoid hemosiderotic hemangioma
 Tufted angioma
DIFFERENTIAL DIAGNOSIS

112. PROGNOSTIC FACTORS
Disseminated KS is often fatal
AIDS related and African KS are more aggressive than Mediterranean KS
Iatrogenic KS may regress when immunosuppression is discontinued
TREATMENT
Mainly palliative, based on extent of disease:
External beam radiation, laser therapy, cryotherapy, photodynamic therapy
Topical alitretoin gel, topical immunotherapy (imiquimod), intralesional
chemotherapy (vinblastine), surgical excision
IV chemo / immunotherapy (e.g. liposomal anthracyclines and taxanes),
interferon alpha, HAART if HIV+

113. SALIVARY GLAND
ORIGIN
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114. MYOEPITHELIAL CELLS
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115. ORIGIN OF MYOEPITHELIAL CELLS
126

116. MICROSCOPY OF MYOEPITHELIAL CELLS
Ultrastructure
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117. MYOEPITHELIOMA
 Tumor entirely composed of myoepithelial cells
 Accounts for less than 1% of salivary gland tumor
 Parotid common, followed by palate, lip and cheek
 Between 30-50yrs age
 Equal gender distribution
 Asymptomatic slow growing mass
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118. HISTOPATHOLOGY
129

119. IMMUNOHISTOCHEMISTRY OF
MYOEPITHELIOMA
 S-100 protein, actin, myosin, vimentin and
 Neuron-specific enolase.
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120. DIFFERENTIAL DIAGNOSIS OF
MYOEPITHELIOMA
 Fibroma,
 Fibrous histiocytoma
 Leiomyoma
 Neurofibroma
 Schwannoma
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121. MYOEPITHELIAL CARCINOMA
 Defined as malignant epithelial neoplasm whose tumor
cells demonstrate cytologic differentiation toward
myoepithelial cells and lacks ductal or acinar differentiation
 Painless mass, common in parotid,
 Maxillary gingiva and alveolar mucosa
 Equal sex predilection, adult age
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122. HISTOPATHOLOGY OF
MYOEPITHELIAL CARCINOMA
 Similar to myoepithelioma
 Quite cellular, more suggestive of
sarcoma than carcinoma
 Some part of stroma shows myxoid
appearance
 IHC;
CK, S100, SMA, GFAP (glial
fibrillary acidic protein)
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123. SYNOVIAL SARCOMA
 Synovial sarcoma is a morphologically, clinically and
genetically distinct entity that may occur at any site
 3rd and 5th decades of life
 Male female ratio 3:2
 common site of involvement is the lower extremity
 Oral lesions occur in the tongue, soft palate, cheek and parotid
 Deep seated, slow growing, palpable mass that may or may
not be associated with pain
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125. CELLULAR ELEMENTS AND THE DEGREE
OF DIFFERENTIATION
 Biphasic (epithelioid and spindle cell)
 Monophasic spindle cell
 Monophasic epithelioid type
 Poorly differentiated (round cell) type - Enzinger
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126. GROSS APPEARANCE OF SYNOVIAL
SARCOMA
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 Pink well demarcated fleshy mass with solid/hemorraghic
areas and cystic components with areas of calcification.
 Increase in calcification is associated with good prognosis.

127. 141
Biphasic have spindle cells and plump epithelial cells forming glands /
cords
Monophasic lack the epithelial cells
Spindle cells are arranged in plump fascicles with hyalinization and
distinct lobulation accompanied by mast cells, occasional osseous or
cartilaginous metaplasia, focal whorling
May have hemangiopericytomatous vascular pattern
HISTOPATHOLOGY

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142
A tumour composed of
spindle cells showing a fascicular
arrangement

129. MONOPHASIC FIBROUS SYNOVIAL
SARCOMA
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Typically, there are densely cellular
sheets or vague fascicles, with
occasional nuclear palisading.
Many tumours display, at least focally,
a prominent haemangiopericytomatous
vascular pattern.. Myxoid change is
usually focal and rarely diffuse and
predominant, with alternating hypocellular
and more cellular areas, and microcyst
formation. Mast cells can be abundant.

130. IMMUNOHISTOCHEMISTRY OF
SYNOVIAL SARCOMA
 Positive: CK, EMA, Bcl2, S-100, CD99
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TLE1 highly specific (transducer like
enhancement of spilt 1

131. DIFFERENTIAL DIAGNOSIS OF
SYNOVIAL SARCOMA
 MPNST
 Fibrosarcoma
 Hemangiopericytoma
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133. FIBROBLASTIC
OSTEOSARCOMA
 Osteosarcoma is a malignancy of mesenchymal cells able to
produce osteoid or immature bone.
 It is uncommon and represents 6-8% of all osteosarcomas.
 It occurs most often in the third and fourth decades of life.
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134. 148
Approximately 25% of osteosarcomas consist predominantly of spindle tumor
cells and can be classified as fibroblastic osteosarcoma. Osteoid production is
minimal and seen focally; although in this case, osteoid matrix was readily found.
Fibroblastic osteosarcomas are highly vascular and may resemble
hemangiopericytoma.

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149
Mesenchymal cells with spindle to ovoid shaped nuclei with variable degree of
atypical features and minimum amount of bone production.

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150
1. Storiform pattern of arrangement of fibroblasts with atypical; spindle cells.
2. Osteoclasts like giant cells closely associated with tumour osteoid.
3. markedly cellular lesion with proliferating fibroblasts.
4. Presence of few reactionary giant cells.

137. GRADING AND STAGING OF
MALIGNANT TUMORS
 American joint committee on cancer (AJCC) and
musculoskeletal tumor society developed a staging system
based on
 Size of primary tumors(T)
 Involvement of lymph node (N)
 Presence of metastasis (M)
 Type and grade of sarcoma (G)
 In 1997 other features were added
 Tumor depth
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138. 2010 AJCC staging of soft tissue malignancy (7th edition)
Primary tumor(T)
Tx Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor size 5cmm or less in dimension
T1a Superficial tumor
T1b Deep tumor
T2 Tmor more than 5cmm in dimension
T2a Superficial tumor
T2b Deep tumor
Regional lymphnode
Nx Regional lymphnode cannot be assessed
N0 No regional lymphnode involved
N1 Metastasis to regional lymphnode
Distant Metastasis
M0 No distant metastasis
M1 Distant metastasis
Histological grade
Gx Grade cannot be assessed
G1 Grade 1
G2 Grade 2
G3 Grade 3
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139. TREATMENT AND PROGNOSIS
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140. Fibrous tissue origin
Tumor Treatment Recurrence Prognosis
Nodular fascitis Surgical excision 1% Good
Proliferative fascitis and myositis Surgical excision Rare Good
Fibromatosis Conventional 23% Good /
recurrence
Infantile fibromatosis Marginal excision 60% Good
Desmoid tumor Wide local excision High Varied
Fibrosarcoma Wide excision 53% Worse
Congenital or infantile fibrosarcoma Wide excision Early local
recurrance-33%
Metastatic rate-
10%
Good
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141. Fibrous histiocyte origin
Tumor Treatment Recurrence Prognosis
Fibrous
histiocytoma
Local excision 5% Good
Dermatofibrosarco
ma
Wide local excision 10-20% Varied
Plexiform fibrous
histiocytic tumor
Wide excision 12.5-40% Good
Malignant fibrous
histiocytoma
Wide surgical
excision
Local recurrence-
10-31%
Metastatic rate- 31-
35%
5 yr suvival-60-70%
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142. Lipomatous origin
Tumor Treatment Recurrence Prognosis
Spindle cell lipoma Local excision Rare
Dedifferentiated
liposarcoma
Wide excision Local recurrence -
41%
Metastatic rate-
17%
Death in 28%
Smooth muscle origin
Leiomyoma Complete excision Local recurrence Good
Leiomyosarcoma Local recurrence-
10-25%
Metastatic rate-
45%
5 yr mortality-64%
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143. SKELETAL MUSCLE ORIGIN
Tumor Treatment Recurrence Prognosis
Cellular rhabdomyoma Excision Rare
Spindle cell rhabdomyosarcoma Total excision - Poor
5 yr mortality-
80%
BLOOD VESSEL ORIGIN
Spindle cell hemangioma 60%
Hemangiopericytoma - 40-50% 5 yr survival-
85-93%
Angiosarcoma Local surgical
excision
25% 5 yr survival-
43%
Kaposi’s sarcoma Surgical
excision and
radiation
- 10 yr survival-
50%
Mortality rate-
10-20%
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144. Uncertain origin
Tumor Treatment Recurrence Prognosis
Synovial sarcoma Excision;
radiotherapy
40% 5 yr survival-
36-76%
NEURAL ORIGIN
Neurofibroma Local.
Metastatic rate-2-
3%
5 yr survival-
44%
Schwannoma Excision 5%
OSSEOUS ORIGIN
Fibroblastic variant of
osteosarcoma
Local-50%
Metastatic rate-
61.5%
Poor
Desmoplastic fibroma Wide surgical 17%
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147. SCREENING PANEL FOR MONOMORPHIC
SPINDLE CELL TUMORS
Antibody Synovial
sarcoma
MPNST Fibrosarcoma Leiomyosarcoma Solitary
fibrous
tumor
Cytokeratins + _ _ Rare Rare
S-100 Variable + _ Rare _
CD34 _ Variable _ Rare +
Smooth
muscle actin
_ _ Variable
(myofibroblasti
c pattern)
Positive _
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149. SUMMARY
Spindle cell lesions of head & neck are diverse & diagnostically
challenging
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 carcinoma or melanoma than a true sarcoma.

150. 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.

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