Osteosarcoma is the most common bone cancer that typically affects the legs of teenagers and young adults. It arises from bone-forming cells and presents with bone pain and swelling. Diagnosis is made through x-rays, biopsy, and microscopic examination showing malignant bone-forming cells. Treatment involves chemotherapy before and after surgery to remove the tumor. Outcomes have improved but many patients still experience recurrence.

3. Etiology
 The gene affected is also associated with
familial retinoblastoma.

4. Clinical features
 Age: Osteosarcoma is the most common bone cancer
in children. Average age at diagnosis is 15.
Osteosarcoma is also common in people over age 60.
 Sex: Boys and girls are just as likely to get
this tumor until the late teens, when it occurs more
often in boys

5.  Site: Most common in:
 Shin (near the knee)
 Thigh (near the knee)
 Upper arm (near the shoulder)
 Osteosarcoma occurs most commonly in large
bones in the area of bone with the fastest growth rate.
However, it can occur in any bone.

6. Symptoms
 Bone fracture (may occur after a routine movement)
 Bone pain
 Limitation of motion
 Limping (if the tumor is in the leg)
 Pain when lifting (if the tumor is in the arm)
 Tenderness, swelling, or redness at the site of the
tumor

7. Grading
 High-grade osteosarcomas:
 These are the fastest growing types of osteosarcoma. Show
a large number of mitotic figures.
 Most osteosarcomas that occur in children and teens are
high grade. There are many types of high-grade
osteosarcomas (although the first 3 are the most common).
 Osteoblastic
 Chondroblastic
 Fibroblastic
 Mixed
 Small cell
 Telangiectatic

8. ..contd.
 High-grade surface (juxtacortical high grade)

9. ..contd
 Other high-grade osteosarcomas include:
 Pagetoid: a tumor that develops in someone
with Paget disease of the bone
 Extra-skeletal: a tumor that starts in a part of the
body other than a bone
 Post-radiation: a tumor that starts in a bone that
had once received radiation therapy

10.  Intermediate-grade osteosarcomas: These
uncommon tumors fall in between high-grade and
low-grade osteosarcomas. (They are usually treated as
if they are low-grade osteosarcomas.)
 Periosteal (juxtacortical intermediate grade)

11.  Low-grade osteosarcomas: These are the slowest
growing osteosarcomas. The tumors look more like
normal bone and show few mitotic figures.
 Parosteal (juxtacortical low grade)
 Intramedullary or intraosseous well
differentiated (low-grade central)

12. X-ray
 medullary and cortical bone destruction
 wide zone of transition, permeative or moth-eaten
appearance
 aggressive periosteal reaction
 sunburst type
 Codman triangle
 lamellated (onion skin) reaction: less frequently seen
 soft-tissue mass
 tumor matrix ossification/calcification
 variable: reflects a combination of the amount of tumour
bone production, calcified matrix, and osteoid
 ill-defined "fluffy" or "cloud-like" cf. to the rings and arcs of
chondroid lesions

13. HP
 The tumor cells vary from
 spindled to polyhedral;
 their nuclei are pleomorphic and hyperchromatic.
 Mitotic figures are easily demonstrable, and atypical
mitotic figures also may be identified.
 The tumor cells are engaged in the production of
extracellular matrix that may be osseous,
cartilaginous, or fibrous in various proportions.

14. ..contd
 The production of bone or osteoid directly by tumor
cells at least somewhere in the tumor is the absolute
requirement for diagnosis

15. ..contd
 conventional osteosarcoma has been divided into
osteoblastic, chondroblastic, and fibroblastic subtypes
depending on the predominant type of extracellular
matrix

16. Treatment
 Before surgery to remove the tumor, chemotherapy is
usually given. This can shrink the tumor and make
surgery easier. It may also kill any malignant cells that
have spread to other parts of the body.
 Surgery is used after chemotherapy to remove any
remaining tumor. In most cases, surgery can remove
the tumor while saving the affected limb. This is called
limb-sparing surgery. In rare cases, more involved
surgery (such as amputation) is necessary.

19.  Hodgkin’s lymphoma is a rare cancer of the lymphatic
system

20. Predisposing factors
 Reduced immunity – patients with HIV or those
taking immunosuppressive drugs, for example, are at
an increased risk.
 Previous exposure to the Epstein-Barr virus (causes
glandular fever) can increase the risk of Hodgkin’s
lymphoma later on in life.

21.  the B-lymphocytes multiply at an abnormal rate and
accumulate in the lymph nodes.
 These cells are referred to as Reed-Sternberg cells and
they are detected on microscopic examination of a
lymph node biopsy.
 The Reed-Sternberg cell is not present in other forms
of lymphoma, which are referred to as non-Hodgkin’s
lymphoma.

22. Clinical features
 Age: aged between 20 and 34 years or those aged
between 70 and 79 years.
 Sex: The incidence of this condition is slightly higher
among men than among women.
 Site: affects groups of lymph nodes, such as those
found in the neck, armpits or groin.

23. Symptoms
 swelling is usually painless, it can cause an aching
sensation in some individuals.
 More general symptoms include the following:
 Fever
 Weight loss
 Night sweats
 Fatigue
 Coughing
 Itchy skin
 The most commonly occurring of these symptoms are
night sweats, fever and weight lost – symptoms which are
referred to as B symptoms

24.  Hodgkin’s disease is divided into four main types,
depending on the histological features identified during
microscopy and these are described below.
 Lymphocyte predominant type – The lymphocyte is the
main cell present. This type of Hodgkin’s lymphoma is
uncommon, but is associated with the most optimal
prognostic outlook.
 Nodular sclerosing type – Microscopic examination
reveals well-defined nodules distinguished by their fibrous
strands. This common form of Hodgkin’s disease accounts
for around 70% of cases and is often associated with a
positive prognostic outlook.

25.  Mixed cellularity type – This type is more common across
populations from Asia and the Middle East and accounts
for only 20% of cases in the UK, for example. This form of
Hodgkin’s disease is associated with a less positive
prognosis and requires an aggressive treatment approach.
 Lymphocyte depleted type – This form is associated with
the worst prognosis. Reed-Sternberg cells predominate, the
lymphocytes are severely depleted and the reactive
background is reduced. This aggressive form of Hodgkin’s
disease accounts for only 5% of cases overall.

26. Histopathology
 Microscopic examination of the lymph node may reveal
partially or complete scattering with Reed-Sternberg cells,
amongst a mixed background of reactive lymphocytes,
plasmocytes, eosinophils, granulocytes and histiocytes.
 The extent to which the presence of these other cells is only
reactive and whether or not the Sternberg-Reed cells are
the only malignant cells, is still under debate.
 However, histology experts do agree that the Reed-
Sternberg cells or a variant of these cells needs to be
identified in a biopsy in order for a diagnosis of Hodgkin’s
lymphoma to be confirmed.

28.  The Reed-Sternberg cells are typically about 20 to
50μm in size, with a finely granular and homogenous
cytoplasm, a thick nuclear membrane and an
eosinophilic nucleus. In around half of cases, these
Reed-Sternberg cells are infected with Epstein-Barr
virus.

29. [HODGKIN LYMPHOMA, NODULAR SCLEROSIS]. More examples of RS cells are shown, some mononucleated and some bi-nucleated. The RS cells are surrounded by small lym

30. Lab diagnosis
 patients have abnormal cells in their bone marrow at
the time they are diagnosed with Hodgkin’s
lymphoma.
 This can reduce the number of healthy blood cells
that are produced and circulated in the bloodstream.
 This reduction in the level of healthy blood cells can
lead to problems such as breathlessness, bleeding
disorders such as nosebleed, and an increased risk of
infection.

31. Treatment
 Hodgkin lymphoma can usually be treated successfully
with chemotherapy alone, or chemotherapy followed
by radiotherapy
 Rituximab is a type of biological therapy called a
monoclonal antibody

33.  The non-Hodgkin's lymphomas include a broad range
of neoplasms derived from the T cells and B cells and
their precursors in the lymphoid system. Although
they are not among the most common cancers, the
lymphomas have engendered a great deal of interest
among researchers because of their interesting biology
and responsiveness to therapy.

34.  The non-Hodgkin's lymphomas include at least ten
major subtypes of diseases with different morphologic
characteristics and clinical behavior. Based upon
survival characteristics, it is convenient to divide the
lymphomas into three broad categories,
 low grade,
 intermediate grade, and
 high grade.

35. ..contd
 The low grade lymphomas usually arise in middle age
or older individuals (median age, 55 years). They are
derived from B cells and often have a follicular
architectural pattern. They usually present with
advanced stages of disease, often by virtue of bone
marrow involvement.

36.  The intermediate grade lymphomas include the
common large cell lymphomas (follicular or diffuse)
and diffuse mixed cell lymphoma.
 The lymphomas, together with the high grade
immunoblastic lymphoma, are often grouped together
for the development of management strategies.
 These lymphomas may be derived from B cells or T
cells. They occur over a broader age range than the low
grade lymphomas and they are much more aggressive
in their natural behavior.

37.  Over the years, various classification systems have
been used to differentiate lymphoma types
including the Rappaport Classification (used until the
70's), the Working Formulation, the National Cancer
Institute Working Formulation, and the Revised
European-American Lymphoma Classification
(REAL).
 World Health Organization's International
Classification of Diseases (WHO ICD) is normally
followed nowadays.

40.  Burkitt’s lymphoma is a relatively rare and aggressive
form of non-Hodgkin’s lymphoma.
 These lymphomas are very similar to the leukemias.
The type of malignant cell present is called a B-cell and
Burkitt's is often referred to as a B-cell lymphoma or
leukemia.

41. Eitiology
 Burkitt lymphoma was first discovered in children in
certain parts of Africa, but it also occurs in the United
States.
 The African type of Burkitt lymphoma is closely
associated with the Epstein-Barr virus (EBV), the main
cause of infectious mononucleosis. The North
American form of Burkitt lymphoma is not linked to
EBV.
 People with HIV have an increased risk for this
condition.

42. Clinical features
 Age: Common in children
 Sex: Burkitt lymphoma is most often seen in males.
 Site:
 Burkitt lymphoma may first be noticed as a swelling
of the lymph nodes (glands) in the neck, groin, or
under the arm.
 In the types commonly seen in the United States
abdomen is commonly affected. The disease can also
start in the ovaries, testes, brain, and spinal fluid.

43. Symptoms
 The swollen lymph nodes are often painless, but can
grow very rapidly.
 Symptoms include:
 Fever
 Night sweats
 Unexplained swollen lymph nodes
 Unexplained weight loss

44. Staging and grading
 Burkitt lymphoma can start in areas outside the lymph nodes.
These are extranodal sites.
 Stage 1
 One group of lymph nodes is affected.
 Stage 2
 Two or more groups of lymph nodes are affected on the same
side of the diaphragm..
 Stage 3
 Lymph nodes above and below the diaphragm are affected.
 Stage 4
 The lymphoma has spread outside the lymph nodes to other
areas such as the liver or lungs, or the brain or spinal cord (the
central nervous system).

45. ..contd
 Grading
non-Hodgkin lymphomas are also divided into one of
two groups, depending on how quickly they grow:
 indolent (low-grade), which are usually slow-
growing
 aggressive (high-grade), which grow quickly.
 Burkitt lymphoma is an aggressive lymphoma that
needs to be treated quickly.

46. Histopathology
 Burkitt lymphoma (BL) is defined by the new World
Health Organization (WHO) classification as a highly
aggressive non-Hodgkin lymphoma (NHL) composed of
 Monomorphic medium-sized B cells with basophilic
cytoplasm, non-cleaved round nuclei with coarse
chromatin and 2-5 distinct nucleoli and numerous mitotic
figures.
 The tumor cells exhibit a high mitotic rate and a high
degree of apoptosis with diffuse sheets and starry-sky
pattern (stars are tingible body macrophages) imparted by
numerous benign histiocytes with phagocytosis of
apoptotic cellular debris

47. ● Bone marrow: usually diffuse infiltration of
interstitium, with some preservation of adipose tissue;
prominent mitotic figures; starry sky feature seen in
lymph nodes is rare in marrow

48. Lab diagnosis
 Immunohistochemical stains positive for CD45 or
leukocyte common antigen (LCA).
 Markers for B-lymphocyte CD20, and CD79a, also
positive, and the Pan T-cell marker CD3 is negative.

50. Treatment
 Chemotherapy used to treat and if it does not respond
to chemotherapy alone, a bone marrow transplant may
be done.

52.  Fibrosarcoma is an uncommon, malignant spindle cell
neoplasm.

53. Clinical features
 Age: It presents in adults,30 to 60 years old
 Sex: affects men and women equally.
 Site: It originates in fibrous tissues of the bone and
invades long or flat bones such as femur, tibia, and
mandible. It also involves periosteum and overlying
muscle.

54. Presentation
 The most common clinical presentation is that of a
localized, painful mass.

55. Histopathology
 Low, intermediate and high grade tumor.
 Depending on the differentiation, tumor cells may
resemble mature fibroblasts (spindle-shaped),
secreting collagen, with rare mitoses.
 These cells are arranged in short fascicles which split and
merge, giving the appearance of "fish bone" known as a
herringbone pattern.
 Poorly differentiated tumors consist of more atypical cells,
pleomorphic, giant cells, multinucleated, numerous
atypical mitoses and reduced collagen production.
Presence of immature blood vessels (sarcomatous vessels
lacking endothelial cells) favors metastasis.

56. Treatment
 Radiation therapy is used in conjunction with surgery
for soft-tissue fibrosarcomas, with or without
chemotherapy.

58.  Chondrosarcoma is a malignant tumor that produces
cartilage matrix.
 Primary chondrosarcoma is very uncommon, arises
centrally in the bone, and is found in children.
 Secondary chondrosarcoma arises from benign
cartilage defects such as osteochondroma or
enchondroma.
 Chondrosarcoma can also be classified as
intramedullary, which generally arise from
enchondromas, and surface which arise from
osteochondromas.

59. Clinical features
 Age: Chondrosarcoma is most commonly seen in
adults aged 30 to 70 years, with the peak age of
incidents being sometime around 40 to 60.
 Sex: Chondrosarcoma has a male to female ratio of 1.5
to 1.
 Site: It is most common in the femur, humerus, ribs
and on the surface of the pelvis.

60. Symptoms
 The presentation of chondrosarcoma depends on the
grade of the tumor.
 A high-grade, fast growing tumor can present with
excruciating pain.
 A low grade, more indolent tumor is more likely, to
present as an older patient complaining of hip pain
and swelling.

61. X ray
 On plain radiographs, chondrosarcoma is a fusiform,
lucent defect with scalloping of the inner cortex and
periosteal reaction.

62. Histopathology
 chondrosarcoma is differentiated from benign
cartilage growths by
 enlarged plump nuclei,
 multiple cells per lacunae,
 binucleated cells, and
 hyperchromic nuclear pleomorphism.

63. ..contd.
 Chondrosarcoma is graded from 1 (low) to 3 (high).
 Low grade chondrosarcoma is very close in appearance
to enchondromas and osteochondromas and has
occasional binucleated cells.
 High grade chondrosarcomas have increased
cellularity, atypia and mitoses.

64. Treatment
 Treatment of chondrosarcoma is wide surgical
excision. There is a very limited role for chemotherapy
or radiation.

66.  Kaposi sarcoma (KS) is a cancer that develops from the
cells that line lymph or blood vessels.

67. Etiology
 Researchers have discovered that Kaposi's sarcoma is
caused by a herpes virus, called Human Herpes Virus 8
(HHV-8).

68. Clinical features
 Age: depends on the type
 Sex: No def sex predilection
 Site: It usually appears as tumors on the skin or on
mucosal surfaces such as inside the mouth, but tumors
can also develop in other parts of the body, such as in
the lymph nodes , the lungs, or digestive tract.

69. Presentation
 The most visible signs of Kaposi's sarcoma are lesions on
the skin, which are not life threatening.
 These are flat and painless, aren't itchy, and don't drain.
 They appear as red or purple spots on white skin and
bluish, brownish, or black on dark skin.
 They may grow into raised bumps or grow together.
Unlike bruises, they don't turn white when pressed on
them.
 In some people, these growths change slowly. In others,
new spots may show up each week.
 If KS spreads elsewhere, it can cause other symptoms and
can be life threatening.

70.  Types of Kaposi’s sarcoma
 Epidemic (AIDS related)
 Endemic
 Classic (Mediterranean) Kaposi sarcoma
 Iatrogenic (transplant-related) Kaposi sarcoma

71. Endemic (African) Kaposi sarcoma
 Endemic KS occurs in people living in Equatorial
Africa and is sometimes called African KS.
 KSHV (Kaposi sarcoma associated herpesvirus)
infection is much more common in Africa than in
other parts of the world, so the risk of KS is higher.
 Other factors in Africa that weaken the immune
system (such as malaria, other chronic infections, and
malnutrition) also probably contribute to the
development of KS, since the disease affects a broader
group of people that includes children and women.

72. ..contd.
 Endemic KS tends to occur in younger people (usually
under age 40). Rarely a more aggressive form of
endemic KS is seen in children before puberty.
 This type usually affects the lymph nodes and other
organs and can progress quickly.

73. Epidemic
 When HIV damages the immune system, people who
also are infected with a certain virus (the Kaposi
sarcoma associated herpesvirus or KSHV) are more
likely to develop KS.
 KS is considered an “AIDS defining” illness. This
means that when KS occurs in someone infected with
HIV, that person officially has AIDS (and is not just
HIV-positive).

74. Classic (Mediterranean) Kaposi
sarcoma
 Classic KS occurs mainly in older people of
Mediterranean, Eastern European, and Middle Eastern
heritage. Classic KS is more common in men than in
women.
 Patients typically have one or more lesions on the legs,
ankles, or the soles of the feet. Compared to other
types of KS, the lesions in this type do not grow as
quickly, and new lesions do not develop as often.

75. Iatrogenic (transplant-related)
Kaposi sarcoma
 When KS develops in people whose immune systems
have been suppressed after an organ transplant, it is
called iatrogenic, or transplant-related KS.
 Most transplant patients need to take drugs to keep
their immune system from rejecting (attacking) the
new organ.
 But by weakening the body’s immune system, these
drugs increase the chance that someone infected with
KSHV (Kaposi sarcoma associated herpesvirus) will
develop KS.

76. Kaposi sarcoma in HIV negative
men who have sex with men
 There have been reports of KS developing in men who
have sex with men who are not infected with HIV.
 In this group, the cases of KS are often mild, similar to
cases of classic KS.

77. Histopathology
 Patch Stage:
 Flat lesion characterized by proliferation of numerous jagged
vascular spaces in the dermis ;
 The vascular spaces are parallel to the epidermis ;
 The slit like vessels are present around preexisting blood vessel
, skin adnexa and between collagen fibres. ( 'Promontory sign' ) ;
 Vessels are lined by plump, mildly atypical endothelial cells;
 Perivascular lymphocytes and plasma cells ;
 Extravasated red blood cells and hemosiderin may be
present ;
 The features resemble granulation tissue.

78.  Plaque Stage:
 Spindle cells are more prominent than those in the
'patch stage' ;
 Dermal proliferation of the spindle cells together
with poorly defined slit-like blood vessels ;
 Involves the reticular dermis and even the subcutis ;
 Hemosiderin deposition is prominent ;
 Eosinophilic globules are present .

79.  Nodular Stage:
 Well defined lesion characterized by prominent
interlacing bundles of spindle cells around slit like blood
vessels and extravasation of red blood cells ; These
features are more prominent than those in the 'plaque
stage' ;
 Dilated thin walled vessels are present at the periphery ;
 Mitotic figures are present ;
 Eosinophilic hyaline globules are present (intra and extra
cellular) ;
 These are PAS- positive and stain bright red with
Mallory's trichrome.

80. Treatment
 Freezing with liquid nitrogen
 Radiation treatment
 Surgical removal
 Injection with anti-cancer drugs like Doxil or
alpha interferon
 Treatment with Panretin gel (retinoic acid)

82.  Multiple myeloma is a cancer formed by malignant
plasma cells. Normal plasma cells are found in the
bone marrow and are an important part of the
immune system.

83. Clinical features
 Age: 50-70 yrs
 Sex: M>F 2:1

84. Symptoms
 These symptoms are generally referred to using the
acronym CRAB. CRAB stands
for Calcium, Renal, Anemia, and Bone damage

85. ..contd.
 High levels of calcium in the blood come from affected
bones leaking calcium. Too much calcium can cause
extreme thirst, nausea, constipation, confusion, and
appetite loss.
 Kidney failure can be caused by high levels of M protein.
 Anemia-related fatigue occurs due to few red blood cells.
This happens when myeloma cells replace red cells in the
bone marrow.
 Bone injuries and fractures occur when myeloma cells
invade the bone. Osteolytic bone fractures appear to be
punched out areas on X-rays. They often cause bone pain--
especially in the back, pelvis, ribs, and skull.

86. Presentation
 bone pain:
 initially intermittent, but becomes constant
 worse with activity/weight bearing, and thus is worse during
the day
 Presentation may also be with a complication, including:
 pathological fracture:
 vertebral compression fracture
 long bone fracture (e.g. proximal femur)
 amyloidosis
 recurrent infection: e.g. pneumonia due to leukopaenia
 plasmacytomas typically progress to multiple myeloma

87. X RAY
 numerous, well-circumscribed lytic bone lesions
(more common):
 punched out lucencies e.g. pepperpot skull or raindrop
skull
 endosteal scalloping
 generalized osteopenia (less common):
 often associated with vertebral compression
fractures/vertebra plana

88. Lab diagnosis
 reverse albumin/globulin ratio (low albumin, high
globulin)
 monoclonal gammopathy (IgA and/or IgG peak)
 proteinuria: Bence Jones proteins in urine (Ig light
chains)
 hypercalcaemia
 decreased or normal ALP unless there is a pathologic
fracture due to impaired osteoblastic function.

89. ..contd
 In multiple myeloma, the overgrowth of plasma cells
in the bone marrow can crowd out normal blood-
forming cells, leading to low blood counts.
 This can cause anemia – a shortage of red blood cells.
People with anemia become pale, weak, and fatigued.
 Multiple myeloma can also cause the level of platelets
in the blood to become low (called thrombocytopenia).
This can lead to increased bleeding and bruising.
 Another condition that can develop is leukopenia – a
shortage of normal white blood cells. This can lead to
problems fighting infections.

90. ..contd.
 People with multiple myeloma have a monoclonal
gammopathy, but not everyone with monoclonal
gammopathy has multiple myeloma.
 It can also occur in other diseases, such as
Waldenstrom macroglobulinemia and some
lymphomas. It can also occur in a disorder known
as monoclonal gammopathy of undetermined
significance (MGUS), which does not cause problems
like multiple myeloma does.

91. Treatment
 Chemotherapy is administered orally or intravenously
to kill myeloma cells.
 Stem cell transplants can be used for treatment after
high doses of radiation.
 Radiation therapy is used to kill myeloma cells.

93.  Plasmacytoma refers to a tumour consisting of
abnormal plasma cells that grows within the soft tissue
or bony skeleton. It can be present as a discreet solitary
mass of abnormal plasma cells, in which case it is
termed a "solitary" plasmacytoma or it can be present
as part of a systemic disorder - called multiple
myeloma.

94.  There is a localised build-up of abnormal plasma cells
in the bone.

95.  Solitary plasmacytomas do not have the typical
features of myeloma, which include low red blood cell
counts, elevated calcium levels in the blood, or
reduced kidney function.

96. Etiology
 It is not known what causes plasmacytomas.

97. Clinical features
 Age: Most commonly occurs in middle-aged or elderly
people and is very rare under the age of 30.
 Sex: Solitary plasmacytomas occur more commonly in
men than women.
 Site: Most commonly, these tumors develop in the
spinal column but they may also develop in the pelvis,
ribs, arms, face, skull, femur (thigh), and sternum
(breast bone).

98. Symptoms
 Solitary bone plasmacytomas may cause bone pain or
fractures. Symptoms depend on where the tumour is
located.

99. Histopathology
 a biopsy reveals a single tumour inside the bone or
tissue comprising abnormal plasma cells

100. Lab diagnosis
 Bone marrow biopsy shows no evidence of myeloma;
and
 blood tests show no signs of anaemia, high calcium or
reduced kidney function due to the M-protein.

101. Treatment
 The treatment used most commonly for both types of
plasmacytoma is radiotherapy. This is possible because
by definition, "solitary plasmacytomas" are localised
 Surgery is rarely necessary but may be required in
situations where plasmacytoma involvement of the
bone causes skeletal instability and high risk of
fracture.