7. • The significance of the tumor-like bony lesions
is that their appearance may mimic that of
malignant bone tumors, which gives rise to
differential diagnostic problems, since they
are much more common.
8. Solitary bone cyst
• It is a fluid filled cyst of unknown etiology.
• Commonly in males under the age of 20.
• Usually occurs in long bones.
• Sites- Proximal humerus, proximal femur, pelvis and
calcaneus (short bone).
• Some investigators have shown that the fluid has a
biochemical composition similar to that of serum,
suggesting that it forms from venous obstruction and
subsequent extravasation of blood.
9. • Gross-
• Most are centered in metaphysis and they migrate
away from epiphysis.
• Well delineated cyst filled with straw colored or
blood stained serous fluid and is lined by smooth
brown fibrous membrane.
• Cortex in thinned out.
• Periosteal bone proliferation in areas of fracture only.
• Fracture- Haemorrhagic fluid.
10. Gross appearances of solitary bone
cyst.
A triangular lesion located in the
upper end of the tibia. There has been
secondary hemorrhage, leading to an
appearance not too dissimilar to that
of an aneurysmal bone cyst.
Gross appearances of solitary bone
cyst.
A large lesion located in the upper
metaphysis of the humerus.
11. • Microscopy-
• Cyst wall lacks true cell lining.
• And consists of thin layer of fibrous tissue, composed
of scattered fibroblasts, collagen fibers, fibrin
deposits, which can undergo mineralization and
resemble cementum.
• In case of previous pathologic fracture- Cyst wall may
be thickened and may contain reactive fibroblasts,
osteoclast type giant cells, haemosiderin deposits
and reactive woven bone.
12.
13. Typical solitary bone cyst of upper end of humerus abutting
against epiphyseal plate complicated by fracture.
(Soap bubble appearance).
14. • Diagnosis-
• May be difficult if:
– reparative changes following fracture.
– recurrent lesion after bone grafting.
– articular cartilage included in curettings.
• Becomes clear if history and radiographs available.
• Differential diagnosis-
• Aneurysmal bone cyst.
15. Aneurysmal bone cyst
• First described by Jaffe and Lichtenstein in 1942.
• Seen in patients between 10-20 years of age.
• Slightly common in females.
• It is a cystic lesion of bone most common in the
vertebrae, flat bones and shaft of long bones.
• Exceptions-
• Osseous ABC in a soft tissue locations and within the wall
of major artery.
16. • ABC may arise denovo- Primary ABC.
• Or areas resembling ABC can be found in other
benign and malignant bone tumors- Secondary ABC
such as in association with
GCT of bone.
Chondroblastoma.
Osteoblastoma.
Fibrous dysplasia and osteosarcoma.
17. Pathogenesis
• Elusive.
• Occasionally:
preceding trauma with fracture or subperiosteal
hematoma.
preexisting bone lesion as result of changed
hemodynamics.
• Usually no underlying lesion.
might be result of sampling or cyst destruction of
preexisting lesion
• Insulin-like growth factor-1.
• Nonrandom cytogenetic aberrations suggest that
some are true neoplasms (17p11-13, 19q22).
18. • Grossly-
• Multiple blood filled cystic spaces separated by thin
tan white septa.
• Solid tan white areas- Either represents a solid
portion of ABC, or a primary lesion that has
developed secondary ABC like change.
• X-ray-
• Lytic, involves metaphysis of long bones, is eccentric
and shows blow-out appearance with extension into
soft tissues.
• Periosteal new bone formation.
19. Aneurysmal bone cyst of lower end of ulna.
The large blood-filled cavities expand the metaphysis.
21. • Microscopy-
• Large spaces:
• filled with blood
• no endothelial lining
• delimited by cells:
with morphologic, ultrastructural, and
immunohistochemical features of fibroblasts,
myofibroblasts and histiocytes.
these cells also occupy septa that separate the cysts.
• row of osteoclasts often immediately beneath surface.
• Deposition of peculiar degenerated calcifying fibromyxoid
tissue: great diagnostic significance.
• Septa also contains blood vessels, foci of osteiod and bone.
22. Aneurysmal bone cyst of lower end of ulna.
It is showing two cavities lined by osteoclast-like multinucleated giant
cells. The intervening stroma is cellular but contains no neoplastic osteoid.
23. Aneurysmal bone cyst with multiple large giant cells
and reactive bone at the periphery.
24. Solid Variant Of Aneurysmal Bone Cyst
• Features of ABCs in association with solid areas
composed of:
fibrous tissue
new bone formation
osteoclasts
• Sometimes solid areas with this mixed appearance are
seen in the absence of typical ABC features.
• Locations include:
small bones of hand and feet, vertebrae, sacrum.
less commonly long bones:
• tend to have a metaphysical location.
25. Gross appearance of so-called ‘solid variant’ of aneurysmal bone cyst.
A few hemorrhagic cystic areas are present at the periphery.
27. Metaphyseal fibrous defect
• It is a non-neoplastic process, possibly related to
defect in ossification.
• Occurs under the age of 10 years.
• Classically involves metaphysis in skeletally immature
individuals.
• Fibrous cortical defect- When confined to cortex.
• Lesion enlarges and extends into the adjacent
medullary cavity- Non-ossifying fibroma.
28. • Sites- Distal femur, proximal and distal tibia.
• Associated syndromes- Neurofibromatosis and Jaffe
Campanacci syndrome.
• Asymptomatic and are discovered incidentally.
29. • Grossly-
• Lesion is tan brown on color with areas of yellow
discoloration.
• Cystic changes may be present.
• Haemorrhage and necrosis due to pathological
fracture.
30. • X ray-
• Eccentric, lytic lesion centered within the
metaphyseal cortex and adjacent medullary cavity of
long tubular bones.
• Well demarcated with sclerotic margins with internal
trabeculations.
• Trabeculations are incomplete and are the result of
scalloping of the affected cortex.
• As the patient grows, the lesion becomes
incorporated into the diaphysis.
31. Metaphyseal fibrous defect of
lower end of tibia.
Sharp delineation and sclerotic
margins.
Large metaphyseal fibrous defect
expanding lower tibial metaphysis.
32. Microscopy
• Spindle fibroblasts arranged in storiform pattern.
• Spindle cell have cytologically bland nuclei, that have
pointed ends and eosinophillic cytoplasm.
• Osteoclast type giant cells.
• Few mitosis.
• Haemosiderin deposits and foamy macrophages.
33. Metaphyseal fibrous defect.
The predominant element is a spindle cell of fibroblastic appearance. There
are also irregularly scattered osteoclasts.
34. Fibrous dysplasia and related lesions
• First described by Albright in 1937.
• Most common of the fibro-osseous tumours.
• It is a benign medullary fibro-osseous lesion which may
involve one or more bones.
• It has been likened to a localized developmental arrest-
all components of normal bone are present but they do
not differentiate into their mature structures.
36. • Two forms:
• Monostotic:
– More common and usually occurs in older children
and young adults.
– most commonly affects rib, femur, tibia, jaw bones,
calvarium and humerus.
– If craniofacial skeleton is involved disfigurement
occurs.
– Monostotic disease does not evolve into the
polystotic form.
37. • Polyostotic .
• Manifests at slightly earlier age.
• May be unilateral or bilateral.
• Bones affected in decreasing order of frequency are
femur, skull, tibia, humerus, ribs, fibula, radius, ulna,
mandible and vertebrae.
• Craniofacial involvement in 50% of the cases and
extensive skeletal disease in 100% patients.
38. • Have propensity to
involve shoulder and pelvic girdles,
resulting in crippling deformities (Shepherd –crook
deformity of the proximal femur) and
spontaneous, often recurrent fractures.
Mazabraud syndrome- with soft tissue myxomas.
McCune-Albright syndrome (2-3%)- Cafe-au-lait skin
pigmentation and endocrinopathies(sexual precocity,
hyperthyroidism, pituitary adenomas that secrete GH
and primary adrenal hyperplasia).
39. • Occurs due to somatic mutation occurring during
embryogenesis that involves gene that codes for
Guanine nucleotide binding protein (G protein).
• G protein normally couples receptors to the effector
enzyme adenylyl cyclase and the mutation causes
consecutive activation of the enzyme so that there is
excess production of cyclic AMP, which leads to
hyperfunction of cells in involved tissues.
• In bone this abnormality causes a proliferation of
osteoprogenitor cells while at the same time
inhibiting their differentiation.
• This leads to overproduction of fibrous matrix and
woven bone formation.
40. • Grossly-
• Well circumscribed.
• Gritty and leather like consistency.
• Occasionally cystic areas may be seen.
• In minority of cases nodules of pearly white cartilage
are seen.
41. Fibrous dysplasia of the rib.
The lesion forms a fusiform, expanded mass that is
grayish white.
42. • X ray-
• Classic groundglass appearance.
• Can be radiolucent or radiodense depending on
amount of bone present and degree of
mineralization.
• In appendicular skeleton- Well defined margins of
the lesion and surrounded by rim of sclerotic bone.
• Craniofacial skeleton- less well defined and blends
with surrounding bone.
44. Fibrous dysplasia in the upper arm (humerus).
Left, An X-ray showing fibrous dysplasia.
Center, magnetic resonance image of the same area.
Right, X-ray of the same bone one year later with a fracture (at tip
of arrow).
45. Microscopy
• Cellular fibrous tissue surrounding irregular,
curvilinear bony trabeculae.
• The bony trabeculae are discontinuous and are
composed of woven bone that is formed directly
from the spindle cells with minimal osteoblastic
rimming.
• Fibrous tissue is composed of cytologically bland,
plump spindle cells without atypia and mitotic
figures.
46. • Spindle cells can be arranged in storiform pattern, in
areas devoid of bone with collection of foamy
histiocytes mimicking xanthoma/fibroxanthoma.
• Collagen fibers (Sharpey’s-like fibers) are seen
extending from fibrous tissue into the lesional bone.
• Cellular nodules of hyaline or myxoid cartilage can be
seen.
• Cartilage predominates- Fibrocartilagenous
dysplasia.
• Matrix ressembling cementum may be found in
lesions of cranio-facial skeleton.
50. Osteofibrous dysplasia
• It is a self limited benign fibro-osseous of bone
characteristically involving cortical bone of the
anterior mid-shaft of tibia during infancy and
childhood.
• Also known as Kempson-Campanacci lesion or
cortical fibrous dysplasia.
• Occurs from 3 weeks to 35 years of life.
• Associated with trisomy 7 and 8.
51. • Gross-
• < 1cm to > 10 cm
• Solid, yellow-white, gritty and centered in cortex
which in expanded and attenuated.
• Microscopy-
• Irregular curvilinear trabeculae of woven bone,
which in the periphery merge with pre-existing
lamellar cancellous bone.
• Trabeculae of woven bone is rimmed by osteoblasts.
• Intervening stroma is composed of bland spindle
cells embedded within the collagenous matrix.
53. Osteofibrous dysplasia.
The low-power view is similar to that of fibrous
dysplasia, but on high power there was osteoblastic
rimming of the bone trabeculae.
55. • X ray-
• Well delineated, intracortical lucency that is
surrounded by areas of sclerosis which may extend
into the medullary cavity.
• It may also manifest as multiple lytic foci scattered
along the anterior cortex of tibia resulting in anterior
bowing.
57. • Differential diagnosis-
• Admantinoma.
• Impossible to distinguish these tumors from
admantinoma on FNAC.
• Histological confirmation is necessary.
• Osteofibrous dysplasia is positive for vimentin, S-100
and Leu-7.
• Isolated keratin positive mast cells have been
mentioned.
• A tumor should be defined as OFD like admantinoma
when keratin positive epithelial cells are found.
58. Osteofibrous dysplasia Fibrous dysplasia
Common sites Tibia Femur, pelvis, ribs
Age 0-10 After 10 years
Bowing of tibia Frequent Absent
Spontaneous regression Possible Likely in monostotic cases
Tendency to reoccur
before 10 years of age
High High if polystotic
Low if monostotic
Progression during
infancy and childhood
Moderate Variable but can be marked
Histology Zonal architecture: Lamellar
bone peripherally, Woven
bone centrally, Bone lined
by osteoblasts, contiguous
with cortex
Bone, usually without
prominent osteoblast
rimming, separated from
cortex , woven bone
Molecular biology Not defined Mutations of the alpha
subunits of the G- protein
system
59. Myositis ossificans
• Myositis ossificans progressiva-
• Very rare congenital progressive disease in which
groups of tendons and muscle, usually around major
joints, become progressively calcified and ossified,
producing severe functional disability.
• Microscopy reveal poorly organized bone, both
lamellar and woven and dense fibrous scar tissue.
• Poorly formed cartilage can also be seen.
60. • Myositis ossificans circumscripta-
• Patients present with lump is muscle.
• History of trauma in only half of the patients.
• Common locations- flexor muscles of the upper arm,
quadriceps femoris, adductor muscle of the thigh,
gluteal muscles and soft tissues of the hand.
61. • Gross-
• Shell of bony tissue with more or less soft red brown
central area.
• Usually 2-5 cm in diameter and adherent to the
surrounding muscle.
64. • Microscopy-
• In the central part of the lesion, an irregular mass of
active mesenchymal cells with foci of interstitial
haemorrhage.
• Haemosiderin laden macrophages.
• Degenerative muscle fibers.
• Whole lesion is intensely vascular, the vessels being
dilated channels lined by endothelium but without
any formed media or adventitia.
• Small foci of osteoid production/cartilage can also be
seen.
65. • At the periphery there are more clearly defined
trabeculae.
• The bone is usually of the primitive woven type with
large, round and crowded osteocytes.
• In long standing cases- Bone is mature and has a
lamellar pattern.
• X ray-
• Periosteal reaction and faint soft tissue calcification
within 3-6 weeks of injury.
• Gradually replaced by mature heterotopic bone by
10-12 weeks.
69. Differential diagnosis
• Sarcoma.
• Myositis ossificans is most mature at its periphery
and least mature at its center, the opposite is true of
a soft tissue osteosarcoma.
70. Langerhan’s cell histiocytosis
• It is defined as an intraosseous mass of proliferating
Langerhans cells.
• They are dendritic cells and normally populate the
skin, mucosal surfaces, lymph nodes, where they
function as antigen presenting cells.
• Single or multpile lesions restricted to the skeleton
have been termed as eosinophilic granuloma.
71. • Common during first three decades of life.
• Males are affected more than females.
• The disease usually manifests in skeleton, skin, lung
and lymph nodes.
• In skeleton most common- skull, jaw, vertebral
bodies, ribs, pelvis and long bones.
• 3 major categories-
• Solitary bone involvement.
• Multpile bone involvement (with or without skin).
• Multiple organ involvement (Bone, liver, spleen and
others).
72. • Associated syndromes-
• Hand-Schuller-Christian disease-
• Multifocal bone disease associated with exopthalmos
and diabetes insipidus.
• Letterer-Siwe disease-
• Aggressive disseminated form of the disorder that
occurs in infants.
73. • Gross-
• Non-specific, gritty, tan appearance.
• Microscopy-
• The proliferating Langerhan’s cells are ovoid/round,
histiocyte like cells, 10-15 um in diameter that are
arranged in aggregates, sheets or within loose
fibrous stroma.
• Cells have eosinophilic cytoplasm and contain
central, ovoid coffee bean shaped nuclei.
74. • Coffee bean appearance is produced by deep
indentations, clefts and folds of the nuclear
membranes which form linear grooves that traverse
the length of the nuclei.
• Most of the Langerhan’s cells are mononuclear but
some cells contain multiple nuclei, which tend to be
centrally located.
• Accompanying infiltrate of eosinophils which may be
so dense that it obscures underlying Langerhan’s
cells.
75. • Lymphocytes, plasma cells, macrophages,
neutrophils, osteoclast-type giant cells can also be
seen.
• Necrosis if prominent is usually a complication of a
pathologic fracture.
• Langerhans cells strongly express CD1a and S-100
protein.
76. This cell from Langerhans’ cell histiocytosis of bone
contains several Birbeck's granules (arrows)
78. Langerhans’ cell histiocytosis.
Polymorphic appearance resulting from an admixture of Langerhans’
cells, nonspecific histiocytes, lymphocytes, and eosinophils. There is a
mild atypia in the Langerhans’ cells that can simulate a malignant
process.
84. Poor prognostic factors
• Young age (< 18 months).
• Hepatomegaly.
• Anaemia.
• Thrombocytopenia.
• Bone marrow involvement.
• Haemorrhagic skin lesions.
85. Rosai-Dorfman’s disease
• Sinus histiocytosis with massive lymphadenopathy.
• Involves skin, upper respiratory tract, lymph node
and bone.
• Second and third decade of life.
• In bones- Skull, facial bones, ribs and vertebrae.
86. • X ray-
• Well circumscribed radiolucency confined within the
bone without soft tissue or periosteal reactions.
Microscopy-
• Heterogenous population of histiocytes,
lymphocytes, plasma cells and neutrophils which can
form microabcsess like foci.
• Histocytes may demonstrate vacuolar cytoplasm and
cellular phagocytosis (erythrophagocytosis and
leukophagocytosis).
• Emperipolesis- Phagocytosis of RBCs, plasma
cells/neutrophils is hallmark of disease.
89. References
• Rosai and Ackerman’s Surgical Pathology,
Ninth edition.
• Silverberg’s Principles and Practice of Surgical
Pathology and Cytopathology, fourth edition.
• Diagnostic Histopathology of tumors by
Christopher Fletcher, third edition.
