Module 10

Malignancies of bone
Introduction
Malignant nonodontogenic tumors of the jaws,
both primary and metastatic, are rare in
comparison to tumors arising in the surrounding
soft tissues. Despite the infrequent occurrence
of these entities, a diagnosis of a malignant jaw
tumor has serious prognostic implications, often
signaling a treatment plan requiring major
therapeutic intervention. Often these lesions
present with signs and symptoms that suggest
intrabony malignancy to the clinician (see next
slide).
 Malignancy in the Jaws
Signs and Symptoms
• Paresthesia
• Pain
• Loose teeth, vertical mobility, premature loss
• Tooth resorption more likely than displacement
• Rapid growth
• Acquired malocclusion
• Radiographic changes
Uniformly widened periodontal membrane space
Ill-defined lesion
 Introduction – Cont.
Tumors in the jaw malignancy category
arise from either hard tissues
(osteosarcoma and chondrosarcoma),
marrow cavities (Ewing's sarcoma,
Burkitt's lymphoma, plasma cell
neoplasias), or soft tissues of distant
organs (metastatic malignancies).
Classification of malignancies of the jaws
Osteosarcoma
Parosteal & periosteal osteosarcomas
Chondrosarcoma
Mesenchymal chondrosarcoma
Ewing’s sarcoma
Burkitt’s lymphoma
Plasma cell neoplasms
Multiple myeloma
Solitary plasmacytoma
Metastatic carcinoma
 Module 10:
Malignancies of bone

Case 1
 History
A 17 year old male developed a
slight bony-hard left mandibular
swelling. There was also a
possible associated shifting of his
premolars in the area. His gingiva
appeared normal clinically.
Courtesy of Dr. M.A. Pogrel
 History of present illness
Based on the history, what are some questions that should
be asked of this patient?
Any trauma to the area?
Any recent dental work?
Any pain or paresthesia?
Duration of the swelling? Days, weeks, months?
Has the swelling been continuous or cyclic?

The patient answers “no” to the first three questions.

The swelling was noticed several weeks ago and has been continuous
and gradual.

Is malignancy possible?
Yes
Is it likely?
No
What would you like to do next?
 Describe the pathology in the panogram.
A relative radiolucency related to separation of the left mandibular premolars.
There is also marked widening of the periodontal ligament space.
Is osteomyelitis likely? No, there is no symptomatology, exudate, or etiologic factor to suggest this.
Note greater definition of the uniformly widened periodontal ligament spaces in this
periapical film.

What groups of lesions should be

considered in a differential diagnosis?

Benign fibro-osseous lesion

Odontogenic neoplasm
Malignancy (uniformly widened periodontal membrane space)
Decalcified tissue section

This material replacing Tooth

PDM suggests what
type of tissue?

Cartilage

Shrinkage
space
 High magnification of other tissue areas show
atypical cells making atypical cartilage and bone.

Diagnosis?

Chondroblastic osteosarcoma
Additional films obtained from the
patient’s dentist. Is there evidence
of tumor in older films?

1 year ago, probably

2 years ago, ?

Current film

2 years ago 1 year ago

Treatment included marginal resection of the
mandible and subsequent placement of implants.
 Osteosarcoma of the jaws
Key features
Etiology
Predisposing factors
Radiation, Paget’s disease
?polyostotic fibrous dysplasia
Genetic predisposition
Li-Fraumeni syndrome (germline p53 mutations)
Rothmund-Thompson synd. (auto recessive, skin, bone, cataracts)
Genes that may be altered
p53, Rb, MDM2, CDK4, c-fos, c-myc, SAS
Clinical features
Swelling, pain, paresthesia, PDL invasion
Mean age 30-35 yrs, range 5-85
Males = females, mandible > maxilla
Histopathology
Most are well differentiated
high grade lesions – poorer prognosis
Chondroblastic osteosarcoma most common subtype
Osteosarcoma and fracture of femur with Paget’s change
 Module 10:
Malignancies of bone

Case 2
 History
A 72 year old male presented with a
swelling between teeth #s 27 and 28.
He had no symptoms. The patient felt
well, although he was recently treated
for prostate cancer.

Courtesy of Dr. Nicky Hakimi

 Describe the clinical appearance this lesion

A predominantly red tumescence of the buccal gingiva measuring approximately 1

x 1.5 cm. Also there is a nodular swelling present on the lingual gingiva, and there
appears to be an associated bone loss in the area.
You complete the oral and neck
exam – there are no additional
findings. What would you like to
do next?

Describe the radiographic

appearance.

A radiolucency between teeth

27 & 28. The alveolar crest bone
and lamina dura are lost. The
inferior margin is ill-defined
 Differential diagnosis?

Periodontal abscess
Pyogenic granuloma
Peripheral giant cell granuloma
Peripheral odontogenic tumor
Metastatic cancer
(consider prostate because of history)
Biopsy specimen
Note nests of cells
 The nests of cells in this biopsy are not native to this site.
Do these cells exhibit epithelial, mesenchymal, or lymphoid features?

Epithelial, they are polygonal and show nested adherence.

The lesion does not exhibit features of any odontogenic tumors.

This coupled with the variation in size, shape and staining suggest that
this is a metastatic neoplasm. Metastatic prostate is certainly possible.
See immunohistochemical stains that follow.
Cells are intensely positive for keratins
confirming epithelial differentiation.
 Positive cytoplasmic staining (brown) for prostate-specific
antigen supports the diagnosis of metastatic prostate cancer.

PSA
 What are the malignancies that are
most likely to metastasize to the jaws?
Breast carcinoma
Lung carcinoma
Prostate adenocarcinoma
Colorectal carcinoma
Renal cell carcinoma
Adenocarcinoma of the breast metastatic to the jaws

Radiograph 1 year later shows failure of

chemotherapy to control malignancy.
Metastatic malignancy to the gingiva
 Module 10:
Malignancies of bone

Case 3
 History
A 47 yo man returned to his dentist 3
weeks after two root canal fillings. The
original swelling in his lip and vestibule that
he had before treatment failed to resolve.
He had been taking a broad spectrum
antibiotic since his endodontic procedure.
He has hypertension which is under
medical control.
Note persistent fullness in patient’s upper lip and maxillary vestibule
 Describe the radiographic appearance of the lesions

Irregular radiolucencies
associated with the apices of
teeth 8 & 9. The lesions have ill-
defined margins and there is a
suggestion of loculations. (The
shadow of the nares may be
superimposed on the lesions)

What should be done next?

Biopsy
The biopsy specimen shows an intense,
diffuse infiltrate of round cells with little
cytoplasm.
Atypical mitotic figures are frequently
found in high power fields.
Which of the following is suggested by the
microscopy?
Carcinoma, sarcoma, lymphoma
Lymphoma
 Non-Hodgkins lymphoma
• Malignant tumors of cells native to
lymphoid tissues
• 60% in lymph nodes; 40% extra-nodal
• Oral lesions are seen what sites?

Tonsil (MALT), palate, bone, other

What is MALT?
Mucosa Associated Lymphoid Tissue
 Non-Hodgkins lymphoma

There is a marked range of clinical behavior from

indolent to aggressive. This is based upon
lymphoma subtype. How are lymphoma subtypes
determined?
A combination of histopathology and
immunohistochemistry for lymphoid markers
 Non-Hodgkins lymphomas
INDOLENT AGGRESSIVE HIGHLY
AGGRESIVE
Age Adults Any Children

Tumor growth Slow Fast Very fast >95%

rate dividing
Bone marrow Yes Uncommon Common
involved
Natural history if Indolent, takes Kills patient in 1- Kills patient in
untreated years to kill 2 years weeks to months
Response to Poor Responsive Very responsive
treatment
 Non-Hodgkins lymphoma

What 2 factors determine prognosis for

patients with lymphomas?
Microscopic classification (subtype) and clinical stage (extent of disease)
 Module 10:
Malignancies of bone

Case 4
 History
A 26 year old Asian woman presents with a
chief complaint of a swollen jaw (left mandible).
 History of present illness
What are some pertinent questions that should be asked of the patient?

Duration?, Oral signs?, Symptoms? Recent trauma or dental work?, Systemic signs &
symptoms such as fever, malaise, lymphadenopathy? Allergies? Medications?

The swelling started about 3 months ago and

has shown steady growth since. Two weeks ago
she noticed gingival swelling along with a numb
lip and chin on the same side. She has no
history of trauma to the site or recent dental
treatment. She has been in excellent health. She
has no allergies and is taking is birth control
pills.
The left mandible is bony hard and is slightly painful to palpation.
There is no cervical lymphadenopathy.
The intraoral lesion is indurated and there is no exudate upon pressure.
A radiograph shows an ill-defined lucency
 Differential diagnosis?
Malignancy
Osteosarcoma, lymphoma/leukemia

Osteomyelitis
Acute exacerbation of chronic infection

Next step?
Biopsy
Low magnification shows relatively cellular lesion making osteoid
 High magnification shows atypical cells making osteoid.
There are no inflammatory cells.

Diagnosis?

Osteosarcoma

What type of treatment would likely be provided for this patient?

Surgery and possibly preoperative chemotherapy.

Radiation or chemotherapy therapy might be added if surgical margins are positive.
Surgical resection
Post-op radiogram
 Follow-up
The patient was treated initially with
surgery only. Two years after resection, a
mass developed in the anterior segment of
the patient’s mandible. Biopsy showed
recurrent tumor. The patient subsequently
received radiation and chemotherapy. Two
years later, she died of metastatic disease.
What are some of the signs and symptoms
of malignancies in the jaws?
• Paresthesia
• Pain
• Loose teeth, vertical mobility, premature loss
• Tooth resorption more likely than displacement
• Rapid growth
• Acquired malocclusion
• Radiographic changes
Uniformly widened periodontal membrane space
Ill-defined lesion
 Module 10:
Malignancies of bone

Case 5
 History
An 11 year old male developed
pain in association with right
hypermobile mandibular molars.
Speech, eating, and swallowing
have become difficult. He also
has premature occlusal contact
in his right posterior jaw.
Duration of problem – 3 weeks.
Note jaw asymmetry
Hypererupted & mobile molar
Note poorly defined radiolucency
Differential diagnosis
Malignancy vs. acute infection
Gross specimen
 Decalcified section

Note blue cellular areas

(see next image)
Microscopically, the blue areas are neoplastic lymphocytes with scattered macrophages.

This pattern is known as “starry sky” and suggests what diagnosis?

Burkitt’s lymphoma
One year post-chemotherapy,
No evidence of disease
 Burkitt’s lymphoma
In what age group is this disease seen?
Children

In what region is this disease endemic?

Africa

With what virus are many cases associated?

Epstein-Barr virus
 Burkitt’s lymphoma
Key features
High-grade, B-cell lymphoma
CD 10 (CALLA), 19, 20, 22+
c-myc (chromosome 8) dysregulation
translocation, usually t(8;14)
Highly responsive to intensive chemotherapy
Types
Endemic African
Children, >95% associated with EBV infection
Jaws >50%, abdomen
Sporadic North American
Young adults, 10-20% associated with EBV
Abdomen, jaws 10-20%
HIV immunodeficiency
Adults, 25% associated with EBV
Marrow, CNS, GI
 Module 10:
Malignancies of bone

Case 6
 History
Five years ago this 68 year old man
had a mass removed from his
maxilla. He had slight discomfort,
but no paresthesia. Biopsy was
read as osteocartilageneous
exostosis. A second biopsy of
recurrent tumor was read as
osteochondroma. He now returns
with another recurrence.
 The recurrent lesion is represented in this panogram.

Additional imaging indicated that the lesion was peripheral in location.

 Oral cavity

See magnified images below

On surgical removal, the surgeon also felt

that the lesion was only peripheral; i.e.
there was no involvement of the medullary
bone.

Cortex deep to image

Hypercellular zone

Osteoid
Pathologists felt that the lesion represented a low grade
bone-producing malignancy of peripheral origin. What
was their diagnosis?

Parosteal osteosarcoma
Juxtacortical osteosarcomas
Types
Parosteal osteosarcoma
Slow growing, well-differentiated neoplasm
Very good prognosis
Periosteal osteosarcoma
Also a peripheral lesion, but poorly
differentiated neoplasm
Rare in the jaws
Fair to good prognosis
Parosteal osteosarcoma of the condyle
Self assessment
Which of the following signs/symptoms would be least
likely associated with a malignant neoplasm within the
mandible?

A. Paresthesia
B. Pain
C. Vertical tooth mobility
D. Uniformly widened periodontal
membrane space
E. Sclerotic bony margins
Answer: E
 Neoplastic proliferation of plasma cells caused several
lucencies in the jaws and skull of a 52 year old patient. Which
of the following is also associated with this condition?

A. Abnormal serum electrophoresis

B. Increased sedimentation rate
C. Bence-Jones proteinuria
D. Monoclonal gammopathy
E. All the above
Answer: E
What is this type of malignancy called?
Multiple myeloma or plasma cell myeloma
Paresthesia of the lower lip would be least likely associated
with which of the following?

A. Acute abscess at apex of tooth #28

B. Lymphoma of the mandible
C. Metastatic melanoma to the mandible
D. Ossifying fibroma of the mandible
E. Multiple myeloma of the jaw

Answer: D
A poorly defined radiolucent lesion in the mandible of 28-
year-old HIV+ male was biopsied. It was a cellular
neoplasm composed of sheets of hyperchromatic
lymphoid cells with many atypical mitotic figures. This
suggests which of the following?

A. Squamous cell carcinoma

B. Fibrous dysplasia
C. Osteosarcoma
D. Lymphoma
Answer: D
What type of radiographic pattern does this osteosarcoma exhibit?

Sunburst pattern
Which of these jaw malignancies typically occurs
in children?
Osteosarcoma
Conventional
Juxtacortical
Parosteal & periosteal osteosarcomas
Chondrosarcoma
Conventional
Mesenchymal chondrosarcoma
Ewing’s sarcoma
Burkitt’s lymphoma
Plasma cell tumors
Multiple myeloma
Solitary plasmacytoma
Metastatic neoplasms
This patient 58 yo male presented with a slightly sensitive gingival mass.
What is your clinical differential diagnosis for this lesion?

Most likely
Pyogenic granuloma
Peripheral giant cell granuloma
Foreign body reaction

Least likely
Kaposi’s sarcoma
Metastatic cancer

The biopsy was read as carcinoma

probably metastatic. The patient
was subsequently diagnosed with
carcinoma of the esophagus.
 In adults, the jaws are occasionally the sites of metastatic
deposits from malignancies in distant organs. From which of
the following organs do malignancies typically metastasize
to the jaws?

A. Lung
B. Breast
C. Gastrointestinal tract
D. Prostate
E. All of the above
Answer: E
 Could the changes associated with tooth #19 be caused by periodontal disease?
Yes
What features in this radiograph would suggest the possibility of a malignancy in the jaw?
A widened periodontal membrane space which is somewhat uniform on the distal
roots and at the apical end of the mesial root of #19.

Initial presentation
The tooth was extracted and the patient returns 2 years later with a numb lip.
Biopsy of the edentulous site is illustrated in the next image.
The specimen shows atypical cells making osteoid which has undergone some
calcification (purple areas).

Probable diagnosis? Osteosarcoma – very likely present for at least two years
 This elderly male has a numb lip and an ill-defined radiolucency of his left ramus.
A biopsy (right) is contains an infiltrate of plasmacytoid cells. He was
subsequently found to have several punched out lesions of his skull. What is the
likely diagnosis for this patient?

Multiple myeloma

What test on his biopsy tissue could be done to confirm the diagnosis?

Immunohistochemical stains for kappa and lambda light chains to show monoclonality.
(advance to next slide)
Stain for kappa light chains is positive Stain for lambda light stains is negative

Does this confirm the diagnosis of multiple myeloma?

Yes, this is a monoclonal gammopathy

 Which of the following malignancies of the jaws
characteristically affects the older adult population?

A. Sarcoma
B. Burkitt's lymphoma
C. Ewing's tumor
D. Metastatic adenocarcinoma to jaws
E. None of the above

Answer: D
This lesion did not resolve after root canal therapy.
Does the biopsy (right) indicate periapical cyst?

No, the lesion is a solid epithelial proliferation.

This was subsequently determined to be
metastatic carcinoma of the breast.
 This patient has confirmed leukemia.
Does the tissue collected from around
the roots of # 15 suggest leukemic
involvement of the maxilla?

Yes, the nuclei of this infiltrate are highly

atypical (dark, angular, and variably sized).
Bone fracture, infection, and malignant transformation are
potential complications in the late stages of which of the
following?

A. Periapical granuloma
B. Periapical cemento-osseous dysplasia
C. Traumatic bone cyst
D. Osteoblastoma
E. Paget's disease

Answer: E
This is a biopsy specimen from the mandible of a 12 year old male who experienced
associated pain, swelling, and hypermobility of teeth 18 & 19. The duration of the
condition was three weeks. What neoplasm does the specimen suggest?

Lymphoid neoplasm – Burkitt’s lymphoma

Jaw pain and paresthesia of the lip suggest
which of the following?

A. Acute infection
B. Primary jaw malignancy
C. Metastatic malignancy
D. Either primary or metastatic
malignancy
E. All the above

Answer: E
End of module 10