Presentation on bone tumors for undergraduate 2nd year MBBS medical students. The information for this presentation has been taken from texbook of Robbins & Cotran Pathologic Basis of Disease 8th ed.
Presentation on bone tumors for undergraduate 2nd year MBBS medical students. The information for this presentation has been taken from texbook of Robbins & Cotran Pathologic Basis of Disease 8th ed.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
CDSCO and Phamacovigilance {Regulatory body in India}NEHA GUPTA
The Central Drugs Standard Control Organization (CDSCO) is India's national regulatory body for pharmaceuticals and medical devices. Operating under the Directorate General of Health Services, Ministry of Health & Family Welfare, Government of India, the CDSCO is responsible for approving new drugs, conducting clinical trials, setting standards for drugs, controlling the quality of imported drugs, and coordinating the activities of State Drug Control Organizations by providing expert advice.
Pharmacovigilance, on the other hand, is the science and activities related to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems. The primary aim of pharmacovigilance is to ensure the safety and efficacy of medicines, thereby protecting public health.
In India, pharmacovigilance activities are monitored by the Pharmacovigilance Programme of India (PvPI), which works closely with CDSCO to collect, analyze, and act upon data regarding adverse drug reactions (ADRs). Together, they play a critical role in ensuring that the benefits of drugs outweigh their risks, maintaining high standards of patient safety, and promoting the rational use of medicines.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
2. Parts of bones
1. Epiphysis : ends of bone
2. Diaphysis : shaft
3. Metaphysis : epiphysial end of diaphysis
Macroscopically the architecture of bone may
be
1. Compact
2. cancellous/spongy/trabeculae
NORMAL BONE
4. Introduction
• Primary bone tumors are rare;
• Non-neoplastic conditions, metastatic disease, and
lymphohematologic malignancies, which may simulate
primary bone tumors, by far outnumber genuine bone tumors.
5. Predominant tissue Benign Malignant
Bone forming Osteoma
Osteoid osteoma and
osteoblastoma
Osteosarcoma
-central
-peripheral
-parosteal
Cartilage forming Chondroma
Osteochondroma
Chondroblastoma
Chondromyxoid
fibroma
Chondrosarcoma
-Juxtacortical chondrosarcoma
-Mesenchymal chondrosarcoma
-Dedifferentiated chondrosarcoma
-Clear cell chondrosarcoma
-Malignant chondroblastoma
Marrow tumors -Ewing sarcoma
-Primitive neuroectodermal tumor of
bone (PNET)
-Malignant lymphoma of bone
-Myeloma
WHO Histologic Classification of Bone Tumors
6. Osteoma
• Osteoma is
proliferation
a benign neoplasm characterized by a
of either compact or cancellous bone,
usually in an endosteal or periosteal location.
• Exclusively in the flat bones of skull and face
• May protrude inside paranasal sinus( particulary
frontal & ethmoidal) & block normal drainage of
sinus.
7. Clinical features
• Age: 40- 50 years
• males> female (2:1)
• c/p: slow growing tumor.
• Periosteal origin → circumscribed swelling → obvious asymmetry.
• Endosteal origin → expansion of the cortical plates.
• Multiple osteomas of the jaws, as well as of long bones and skull,
are a characteristic manifestation of Gardner syndrome.
8. GARDNER SYNDROME
• It is an autosomal dominant disorder.
• Mutation in APC gene
• characterized by the triad of colonic polyposis, multiple
osteomas and mesenchymal tumors of the skin and soft tissues
including epidermal inclusion cyst, lipoma, fibroma, and
fibromatosis
9. Histologic Features.
• Composed of extremely dense, mature lamellar bone.
• Bone formed appears normal
• Well circumscribed.
• Myxomatous tissue also may be intermingled on rare
occasions.
10.
11. Compact and trabecular bone is present beneath intact mucosa at the left of the field.
B, Compact cortical-type bone of the osteoma shown in A contains haversiansystems
12. Treatment and Prognosis
• Symptomatic lesions→ local
excision.
• No recurrence after surgical removal.
13. Osteoid osteoma
• Benign tumor of bone.
Clinical Features.
• Age:10-30 years
• Sex: males:female - 2:1.
• Site: Frequently in the femur or in the tibia; may also be
seen in humerus, bones of hand and feet , vertebrae and
fibula.
14. .
• Most of them are centred in cortex (85%)
• Chief symptoms → intense pain → sharply localized, worse at
night , classically, relieved by NSAIDs
• Unaccompanied by clinical or laboratory evidence of infection
15. • Radiographically tumor
contains radiolucent central
nidus that is seldom larger
than 1.5 cm and that may or
may not contain a dense
centre.
• Peripheral sclerotic reaction
may be seen in cortical
tumors.
16. Pathologic Features
• In its active growth phase
• Grossly appears as a discrete, round to
oval lesion marked by a cherry-red or
reddish-brown color. Friable ,easily
distinguished from the adjacent bone.
• In its mature phase → more
calcification and bone production, the
lesion is hard and gritty and blends with
the bone around it.
17. Histologic Features
• Characteristic and consists of a central nidus , which is sharply
delineated composed of compact osteoid tissue, varying in degree
of calcification and woven bone lined by plump osteoblasts
• growing within highly vascularized connective tissue.
• Osteoclasts and foci of bone resorption are also usually evident.
18. A, Nidus of osteoid osteoma abuts thickened mature bone. B, Osteoid trabeculae, some
partially calcified, within the nidus of an osteoid osteoma. The trabeculae are rimmed with
plump osteoblasts with occasional osteoclasts. The stroma is hemorrhagic.
19. • May be due to presence of entrapped and proliferating nerves
within and around the nidus.
• ↑Levels of prostaglandin E2 produced by osteoblasts in the
nidus; this is presumably the cause of pain and vasodilatation.
• Pain is completely eliminated by removal of nidus.
Causes of pain in osteoid osteoma
22. Osteoblastoma
• Osteoblastoma accounts →1% of primary bone tumors.
• It is typically a slow-growing, benign bone tumor.
• Osteoblastoma frequently lacks the characteristic pain and the
halo of sclerotic bone associated with osteoid osteoma.
23. Clinical Features
• Age: in young persons, 10-30 years.
• Sex: Males>Females.
• C/P: characterized clinically by pain and swelling.
pain → more generalized and less likely relieved by salicylates.
• Most common site → vertebral column. Other sites include
tibia, femur , humerus , pelvis and ribs.
• Occurs mostly in medullary cavity.
24. • Well defined radiolucent lesions
with haphazardly distributed foci
of mineralization.
• Size is often > 2cm
• Perilesional reactive bone is
typically less pronounced.
25. Pathologic Features.
On gross examination,
• Well delineated.
• Hemorrhagic
• Gritty or granular consistency with
cystic regions.
26. Histologic Features
Sharply circumscribed
Anastomosing trabeculae of woven bone lined by actively
proliferating osteoblasts
The moderate numbers of multinucleated giant cells
scattered throughout the tissue
Loose fibrovascular stroma
27. • In the less mature lesion → abundance of connective tissue
stroma in which osteoclast-type giant cells and small foci of
osteoid are present, some in a lacelike pattern.
• With maturation → progressive mineralization of the osteoid
with conversion to trabeculae of coarse woven bone, rimmed by
plump osteoblasts. The trabeculae may fuse to form an
anastomosing, netlike pattern.
• The osteoblasts usually lack any significant atypia, having
round to oval regular nuclei, often with prominent nucleoli.
Mitotic activity is infrequent.
28. A, Nidus of osteoblastoma shows active production of osteoid trabeculae, some in the early stage
of bone formation. The trabeculae are lined with enlarged osteoblasts with occasional osteoclasts.
Numerous dilated capillaries are present in the stroma. B, Large epithelioid osteoblasts, in
osteoblastoma, have abundant cytoplasm and large nuclei containing prominent nucleoli.
Formation of lacelike osteoid is seen.
29. Aggressive Osteoblastoma
It is primarily defined by epithelioid osteoblasts,
cells with abundant eosinophilic cytoplasm twice
the size of conventional osteoblasts. These cells
are frequently arranged in sheets with little or no
intervening osteoid
Cytologically, the neoplastic osteoblasts have
abundant basophilic, finely granular cytoplasm
with a perinuclear holo of less dense cytoplasm
and an eccentric vesicular nucleus with a solitary
prominent nucleolus
32. OSTEOSARCOMA / OSTEOGENIC SARCOMA
• Osteosarcoma is the third most common
adolescence, occurring less frequently
cancer in
than only
lymphomas and brain tumors.
• Most common primary malignant tumour of bone
• It is a malignant neoplasm in which the neoplastic cells
produce bone.
34. • Environmental factors:
Ultraviolet and ionising radiation
Viral origin: simian virus 40 (SV40)
• Transcription Factors
Excess MDM2 amplification, Hypermethylation of P14/ARF
Overexpression of Myc & PRIM1 gene
• Growth Factor
Dysregulated expression of growth factors such as TGF, IGF, and
CTGF leads to the accelerated proliferation of cells.
35. • Genetic predisposition
Alterations in genetic pathways including Rb, p53, SAS (sarcoma
amplified sequence)
Protein expression of the defective/amplified genes results in loss of
control of cell proliferation and differentiation
• Syndromes – Li-Fraumeni syndrome
- Rothmund-Thompson syndrome
36. Clinical features
• Sex- M>F (3:2)
• Age – Bimodal distribution ;
10 to 25 years of age ; 2nd peak seen after 40 years
• Site - metaphysial growth plates of extremities of long bones
distal femur>proximal tibia>proximal humerus>skull or jaw
> pelvis
• Painful, progressively increasing mass
• Sudden fracture of bone is first symptom
37. Radiographically – large
destructive , mixed lytic and
blastic mass with infiltrative
margins
Codman triangle- triangular
shell of reactive bone
CODMAN TRIANGLE
39. Gross pathology
• Osteoblastic - white-tan, yellow in color, bony hard to firm
in consistency
• Chondroblastic - translucent lobules
• Fibroblastic - tan colored with soft or firm in consistency
Contain areas of hemorrhage and cystic degenration
Surrounding cortex frequently destroyed producing soft
tissue mass,
Spreads extensively in medullary canal, infiltrating and
replacing the marrow.
40. • Periosteal reaction in
form of codman
triangle or sunburst
appearance can be
seen grossly
• Infrequently penetrate
epiphyseal plate and
enter the joint
• Distant metastasis to
lungs, other bones,
pleura through blood
41. Histological features
• Presence of osteoid formation by malignant osteoblasts
• Stromal cells are spindle shaped and atypical with
irregularly shaped nuclei
• The amount of matrix material produced in the tumor
varies considerably.
• Mitotic activity with frequent abnormal forms
• Destroy pre-existing bony trabeculae or grow around them in an
appositional fashion
42. • Osteoid produced by tumor cells is
eosinophilic, glassy, irregular border and
presence of osteoblasts
• In some ; thin , tubular , anastomosing
highly basophilic microtrabeculae
present
• Morphological variation- osteoid sparse
or dense, surrounded by bizzare cells or
acellular, or rosette like,
• tumor cells grow diffusely , nested or
pseudopapillary arrangement,
• vessels scanty or numerous, tumor cells
may be spindle or oval or round and may
be multinucleate. Cartilage may be
immature, mineralized or highly myxoid.
44. Lacelike streamers of pink osteoid
produced by malignant stromal cells
(osteoblasts).
Area in a conventional
osteosarcoma shows a combination
of osteoid, malignant cartilage, and
spindle cell fibrous zones
45. Other Variants :
Telangiectatic osteosarcoma- large cavernous, dilated vascular
channels, Aggressive course, detected by presence of numerous
blood filled spaces separated by septa containing highly pleomorphic
mononuclear and multinucleated giant cells accompanied by
abundant mitotic activity.
Small cell osteosarcoma- small , uniform , round or spindeloid cells
, look like ewings but osteogenesis by the tumour cell is
distinguishing.
Low grade central osteosarcoma- very bland looking, resemble
fibrous dysplasia. GNAS1 gene mutation consistently found in
fibrous dysplasia is generally absent in low grade central
osteosarcoma.
46. Telangiectatic osteosarcoma resemble an
aneurysmal bone cyst. Blood filled cystic
spaces are separated by delicate septa.
Benign giant cells resembling osteoclasts
are seen in about 25% of osteosarcomas.
48. • 1) juxtacortical osteosarcoma
(parosteal)
• Slightly older age group
• Grows very slowly
• Forms large lobulated mass
with tendency to encircle
bone
• Microscopicallly there is
disorderely pattern of well
formed bone, osteoid,
occasional cartilage and a
highly fibrous bland stroma.
• d/d-myositis ossificans(
orderly pattern of maturation)
• Prognosis very good Chromosomal study : 12q 13-15
corresponding to CDK4 & MDM2
49. 2) periostel osteosarcoma-:
Located in upper tibial shaft or femur and have presented as
small lucent lesions on the bone surface, bony spicules
arranged perpendicular to shaft
The lesions are limited to the cortex and only rarely invade
the medullary cavity. Prognosis good.
Microscopically the tumors are relatively high grade
osteosarcomas with a prominent cartilagenous component.
3) osteosarcoma of jaw-:
Patients affected are slightly older(34yrs)
Most lesions show a prominent chondroblastic component.
Prognosis good.
50.
51. 1)presence of paget disease- highly malignant
2)specific bone involved- osteosarcoma of jaw and
distal extremities have better prognosis
Osteosarcoma of other cranial facial bones and
vertebrae have very poor prognosis.
3) multifocal osteosarcoma- almost uniformly fatal
4)osteoblasic, chondroblastic, fibroblastic types-
chondroblastic type is less responsive to
chemotherapy.
5) microscopic variants-telangiectatic osteosarcoma
has worse prognosis while well differentiated has
better prognosis.
PROGNOSTIC FACTORS
52. 6) serum elevation of ALP- have an increased metastaic rate.
7) aneuploidy- most osteosarcomas are hyperploid or
aneuploid whereas vast majority of benign bone tumours are
diploid, however periosteal and well differentiated
osteosarcomas are usually diploid.
8) heat shock protein- heat shock protein 72 correlates with
good response to neoadjuvant chemotherapy
9) RB gene expression- loss of heterozygosity of RB gene is
a poor prognostic factor.
10)HER2/neu expression-correlate with poor prognosis.
11)p-glycoprotein-a/w increased rate of systemic relapse.
53. IHC-:
• strong alkaline phosphatase activity
• Consistently express actin,vimentin,
• positive for SMA & desmin, keratin, s-100
• Osteonectin,osteocalcin & osteopontin
positivity, BMA, Bone GLA protein
54. CHONDROMA-:
Benign tumours of hyaline cartilage most
frequently in small bones of hand and feet
particularly proximal phalanges that usually
occur in bones of enchondral origin.
When arise within medullary cavity k/a
enchondromas and when on the surface of
bone k/a juxtacortical chondromas.
Diagnosed in 20-50 yrs of age
Appear as solitary metaphyseal lesions of
tubular bones of hand and feet.
55. Radiographically , radiolucent nodule
of cartilage with central calcification
thins but doesn’t penetrate the cortex.
u/l multiple enchondromas referred as
ollier disease
Multiple enchondrma+ soft tissue
hemangioma= maffuci syndrome.
Pathogenesis-:
Heterozygous mutation in IDH1 and
IDH2 genes leads to synthesis of 2-
hydroxyglutarate which diffuses into
neighbouring cells with normal IDH
genes, thereby causing oncogenic
epigenetic changes in genetically
normal neighbours.
56. m/e-:
composed of well circumscribed
nodules of hyaline cartilage
containing cytomorphologically
benign chondrocytes, foci of
myxoid changes, calcification,
enchondral ossification.
Juxtacortical are more cellular
t/t-:
Observation and curettage
Maffuci sydrome also associated
with risk of developing ovarian
cacinoma and brain gliomas.
57. A, Chondroma. Strands of epithelium-like cells with abundant eosinophilic cytoplasm
reside in a blue-gray mucinous stroma. B, Area of chondroma with tumor cells showing
cytoplasmic vacuolation with the formation of multivacuolated physaliferous cells.
58. OSTEOCHONDROMA-:
Also k/a exostosis
Most frequent benign bone tumor.
Benign cartilage capped tumor that is attached to
underlying skeleton by bony stalk.
Solitary lesion usuallly first diagnosed in late adolscents
and early adulthood but multiple exostosis during
childhood.
Usually asymptomatic but may lead to deformity or
interfere with fxn of adjacent structures.
59. Men are affected more
Arise from metaphysis near the growth plate of
long tubular bones , especially near the knee.
Present as slow growing masses, which c/b painful
if they impinge on a nerve or if the stalk is #.
Average greatest dia is approx 4 cm but may reach
sizes of 10 cm or more.
Characterstically , there is a cap of cartilage
covered by fibrous membrane, which is continuous
with the periosteum of the adjacent bone.
Its average thickness is about 0.6 cm , rare for it to
exceed 1 cm.
60. Total bulk of lesion is made up of mature bone trabeculae
located beneath the cartilagnous cap and containing normal
bone marrow.
Pathogenesis-:
Loss of function mutations in either the EXT1 or the EXT2
gene which l/t reduce synthesis of heparan sulfate
glycosaminoglycans. Hence disruption of chondrocyte
differentiation and local skeletal development.
Clinical course-:
Stop growing at the time of growth plate closure
Symptomatic tumors are cured by simple excision
61.
62. CHONDROBLASTOMA-:
Males under 20 years of age
Quite painful
Epiphyseal and may extend upto
metaphysis
Distal end of femur, proximal end of
tibia, proximal end of humerus
Radiographically , sharply delineated
lytic appearance
m/e-:
Small tumours of round shapes are
accompanied by scattered osteoclast l/t
erroneous diagnosis of giant cell tumour.
Limited capacity for the production of
cartilagenous matrix
63. Shape of the cell is usually polyhederal or spindle
limited capacity for production of cartilaginous
matrix with cell membrane thick nuclei vary in
shape from round to indented and lobulated(
resemble Langerhan cells).
Small zones of focal calcification which range from
network of thin lines(chicken wire ) to obivous
deposits surrounded by giant cells.
Immunohistochemical positivity for s-100 & sox-9
64. M/E of chondroblastoma small
tumor cell of round shape are
accompanied by scatterd
osteoclasts
65. CHONDROMYXOID FIBROMA-:
Usually occurs in long bone of a young adult
Radiographically, sharply defined and may attain a large
size.
Usually located in the medullary portion of the bone, but a
juxtacortical variant arising on bone surface has been
described.
GROSS- solid and yellowish white or tan , replaces bone,
thins the cortex
m/e- hypocellular lobules with a myxochondroid appearance
, seperated by intersecting bands of highly cellular tissue
composed of fibroblast like spindle cell and osteoclasts
66. Large pleomorphic cells may result
in erroneous diagnosis of
chondrosarcoma.
Mitotic figures are exceptional
Reactivity for s-100 protein is the
rule.
Immunoreactivity for sox9 and type
2 collagen positivity.
t/t- en bloc excision
Soft tissue extension or
implantation may occur but no
distant mets.
67. CHONDROSARCOMA-:
Two major categories on the basis of
microscopic criteria-:
1) conventional chondrosarcoma
2) chondrosarcoma variants
Conventional chondrosarcoma-:
b/w 30-60 years of age
Second most common malignant matrix
producing tumour of bone.
Further subdivided as central, peripheral and
juxtacortical.
68. Central-
Located in medullary cavity
Radiographically, osteolytic lesion with splotchy calcification
Ill defined margins, fusiform thickening & perforation of the
cortex- 3 imp diagnostic signs
Pelvic bones, shoulder girdles and ribs are most common
locations.
Peripheral-
Arise de novo or from cartilagenous cap of a preexsisting
osteochondroma.
Signs of malignancy in osteochondroma- inc growth during
adolscence, a diameter over 8 cm and cartilagenous cap that is
irregular and thicker than 3 cm.
Radiograph- large, heavily calcified center surrounded by lesser
denser periphery with splotchy calcification
69. Juxtacortical -:
Involves shaft of long bones, ch by cartilagenous lobular
pattern with areas of spotty calcification and enchondral
ossification.
well differentiated
Moderately differentiated
Poorly differentiated
In well differntiated chondrosarcoma, the nuclei are
plump and hyperchromatic; there may be two or more
nuclei per cell and two or more cells per lacunae.
Chondrosarcoma distinguished from osteosarcoma by
lack of direct bone formation by the tumor cells.
70.
71. gross appearance of a secondary peripheral chondrosarcoma
arising from an osteochondroma of the scapula. The cartilage
cap is thick and highly irregular, and the lesion
72. IHC-:
S-100, ER, Sox9 positivity
BCL2 is positive in over half of the cases whereas
it is negative in 95% of osteochondromas.
Also show positivity for MCM6 and CXCR4
Overexpression of TP53 is seen in high grade
tumors.
Soft tissue implantation following biopsy is a well
known complication of chondrosarcoma.
Recurrence often of a higher microscopic grade
than the original tumor.
High grade chondrosarcoma metastatize early
particularly to the lungs .
73.
74. CHONDROSARCOMA VARIANTS
1) CLEAR CELL-
Contains sheets of large, malignant chondrocytes that
have abundant clear cytoplasm , numerous osteoclast type
giant cells and intralesional reactive bone formation,
S100
Radio- lytic, expansile and well marginated
2) MYXOID (CHORDOID SARCOMA)
Can occur in bone but more common in soft tissue.
Morphologically reminiscent of chordoma b/c rows of
cuboidal cells seperated by myxoid background.
S-100 and vimentin positivity but negative for
keratin(chordoma positive
75. 3.DEDIFFERENTIATED
Edge of an island of well differentiated cartilage is surrounded
by highly pleomorphic sarcoma containing tumor giant cells
Antichymotrypsin, actin, desmin, myoglobin, myogenin
Anaplasia due to P53 or HRAS mutation
4. MESENCHYMAL
Composed of islands of well differentiated hyaline cartilage
s/b sheets of small round cells which can mimic ewing
sarcoma.
C/F-:
Painful, progressively enlarging masses.
Grade 1 chondrosarcoma rarely metastatize whereas 70% of
grade 3 tumors spread hematogenously, especially to lungs.
76. On low magnification, clear cell chondrosarcomas often contain large areas of
woven bone and numerous multinucleated giant cells. The defining cells are large
and contain either eosinophilic or clear cytoplasm, large nuclei, and a prominent
central
77. Microscopic features of dedifferentiated
chondrosarcoma. The low-grade chondroid
component can be seen in the medullary cavity,
and the high-grade component is present in the
soft tissue.
78.
79. Highly malignant small round cell tumour
b/w 5-20 years
2nd most common group of bone sarcomas in
children
Predilection for occurrence in boys.
ES includes 3 variants-
1) classic ewing sarcoma
2)Soft tissue ewing sarcoma
3) PNET
Ewing sarcoma
80. Common neuroectodermal
origin
Common cytogenetic
translocation t(11;22)
(q24;12)
CD 99 cosistently expressed
by cells of ES/PNET.
Morphology -:
Arise in medullary cavity
Invade the cortex,
periosteum and soft tissue
Soft, tan-white and
frequently contain area of
hmg and necrosis.
Gross
appearance
of Ewing
sarcoma.It
has typical ill
defined
quality
81. m/e –
Uniform, small, round cells
that are slightly larger than
lymphocytes
Have scant cytoplasm, which
may be clear because it is rich
in glycogen.
Homer-wright rosett indicative
of neural differentiation
Necrosis may be prominent
Relatively few mitotic figures
in relation to dense cellularity
of the tumour.
82. IHC-
Consistent positivity for vimentin
Frequent reactivity for LMWK
NSE, protein gene product 9.5, Leu 7(CD57),
secretogranin II, neurofilament positivity.
Molecular genetics-
95% of cases of ES/PNET shows reciprocal translocation
t(11;22) (q24;q12) or t(21;22) (q22;q12) which results in
fusion of the EWS with FLI 1.
Inactivation of INK4A in upto one third of cases which
stablizes chimeric oncoprotein EWS/FLI1 and a/w worse
prognosis.
83. Clinical feature-:
usually arise in diaphysis of long tubular bones.
Femur and flat pelvis bone
Painful enlarging mass, affected site tender, warm
and swollen.
Fever, inc ESR, anaemia and leukocytosis
Radiographically, periosteal rxn produces layers of
reactive bones deposited in onion skin fashion
84. t/t-:
Chemotherapy and surgical excision with or without
irradiation.
Prognostic factor
1)Osseous versus extraosseous-
ES of bone has better prognosis
2)soft tissue extension,metastses-poor prognosis
3)neural differentiation-poor
4)type of gene fusion transcript- EWS-FLI1 fusion
has better prognosis.
5) overexpression of TP53, MYC amplification,
INK4A deletion- poor prognosis.
85. Uncommon benign but locally aggressive neoplasm
20-40 years
> common in women
Epiphysis of long bone is classic location
Lower end of femur, upper end of tibia and lower end of
radius is common location.
Radiographically, entirely lytic , expansile lesion in
the epiphysis, usually without peripheral bone sclerosis
or periosteal reaction.
GCT( osteoclastoma)
86. PATHOGENESIS-
Neoplastic cells express high level of
RANKL, which promotes prolifertaion
of osteoclast precursor and their
differentiation into mature osteoclast
via RANK expressed by these cells.
87. Gross-
Cut surface is solid and tan or light
brown, traversed by fibrous
trabeculae, and often contains
hemorrhagic areas
M/E
2 main component – stromal cells
and giant cells
Giant cells are usually large and
have over 20 or 30 nuclei , most of
them arranged towards the centre
Neoplastic stromal cells share
features of mesenchymal cells. At
ultrastructural level resemble
fibroblast or osteoblast.
88.
89.
90. Most true giant cell tumors express TP63
whereas this is true for only a small minority of
the lesions that simulate it.
Main microscopic differences between true
giant cell tumor and so called variants in the
spatial relationship between the giant and
stromal cells.
Former tends to be distributed regularly and
uniformly in giant cell tumor whereas in the
lesion that simulate it , foci contining numerous
clumped giant cells alternate with larger areas
completely lacking this component.
91. Upper portion of shaft of humerus or
femur
M>F, <20yrs
Metaphyseal, cortex thin
Cyst contains clear or yellow fluid lined
by smooth fibrous membrane
M/E- well-vascularized connective
tissue, hemosiderin and cholesterol
clefts, bone surrounding cyst dense with
irregular cement line.
Solitary bone cyst
92.
93. 10-20 years of age
> common in females
Mainly in vertebrae and flat bones
Shaft of long bone
Soft tissue location & wall of major artey
Radiographically , eccentric expansion of the
bone, with erosion and destruction of the
cortex and a small peripheral area of periosteal
new bone formation.
Aneurysmal bone cyst
94. Grossly – spongy haemorrhagic mass
covered by a thin shell of reactive bone,
which may extend into the soft tissue.
M/E- large spaces filled with blood are
seen. Don’t have endothelial lining but
are rather delimited by cells with the
morphologic, ultrastructural and
immunohistochemical features of
fibroblast, myofibroblast and histiocytes.
A row of osteoclast immediately beneath
the surface.
95. Gross appearance
of an aneurysmal
bone cyst, which
contains multiple
blood-filled cystic
structures.
96. d/d-
Solitary bone cyst
Giant cell tumor
Hemangioma
Teangiectatic osteosarcoma
Giant cell reparative granuloma( lesions located in jaw)
Chondroblastoma
Pathogenesis -:
IGF-1 may play role in its pathogenesis
Chromosomal translocation, USP6 (ubiquitin specific
protease gene on chromosome 17p13 can be fused with
number of partner gene- CDH1, TRAP 150, ZNF9
97. T/T-
En bloc resection or curettage with
bone grafting
Lesions containing fibromyxoid areas
and immatre osteoid are more likely to
reccur.
98. Adolescent, long tubular bones, eccentric,
sharply delimited, near epiphysis
When loose and associated with intramedullary
components known as nonossifying or
nonosteogenic fibromas.
Gross- Granular, brown or dark red
M/E- cellular masses of fibrous tissue arranged
in storiform pattern, scattered osteoclasts and
collection of foamy and hemosiderin laden
macrophages
Metaphyseal fibrous
defect(nonossifying fibroma)
99.
100. Two forms-
1) monostotic variety- seen in older children and young
adults, most commonly affects rib, femur and tibia.
2) polyostotic type- u/l distribution a/w endocrine
dysfunction, precocious puberty in female individuals and
areas of cutaneous hyperpigmentation(McCune-Albright
syndrome).
All c/b activating mutation in GNAS1 gene .
Mutation during embryonic life likely to result in Mc-
Cune Albright while mutation in postnatal life likely to
cause monostotic disease.
Fibrous dysplasia
101. Radiographs-fusiform, expanded mass with
thinning of the cortex.
Grossly-ts cuts with a gritty consistency and is
grayish white, cortical bone often is thinned and
expanded.
M/E-
Narrow, curved and misshaped bone trabeculae,
often having a characterstic fishhook configuration,
are interspersed with fibrous tissue of variable
cellularity. The coarse fiber (woven) bone present in
this condition doesn’t transform into lamellar bone,
suggesting that fibrous dysplasia represent a
maturation defect .
104. Infiltration by a cell of accessory immune
system known as langerhans cell, accompanied
by admixture of eosinophils, giant cells,
neutophils, foamy cells and areas of fibrosis.
Langerhans cells- nuclei often lobulated or
indented, sometimes with a longitudnal groove,
acidophilic cytoplasm, intracytoplasmic birbeck
granules.
Diagnostic IHC marker-s-100 protein, CD1a
and langerin(CD 207)
Langerhans cell
histiocytosis
105. Divided in 3 main categories on basis of type and
extent of organ involvement-
1) solitary bone involvement
2) multiple bone involvement
3) multiple organ invovement
Solitary bone invovement( eosinophilic
granuloma)-:
Young adults mc affected
Any bone c/b involved except hand and feet
Mc sites are cranial vault, jaw, humerus, rib and
femur.
Radiographically, osteolytic lesion often in
metaphyseal area of long bones, sometime a/w
periosteal bone proliferation.
106. Radiologically c/b confused with metstaic
carcinoma or ewing sarcoma.
After # or trauma may extend into adjacent soft
tissue.
Extremely radiosensitive
Long term prognosis excellent
multiple bone involvement/ polyostotic
eosinophilic granuloma-:
Depending on location bony infiltration may result
in proptosis, diabetes insipidus, chronic otitis
media or combination
Hand-Schuller-Christian disease has been applied
to this variety.
107. Histologic features of Langerhans cell
histiocytosis include large, ovoid Langerhans
cells with surrounding inflammation rich in
eosinophils.
108. Involve tibia, femur, ulna, fibula
In shaft or metaphysis
R/D- single or multiple lytic areas surrounded by
marked sclerosis
GROSS- poorly defined may extend to soft tissue
M/E- solid nests of basloid cells with palisading at
periphery
Keratin 14 & 19 +ve, In contrast to synovial
sarcoma, chordoma and epitheloid sarcoma –ve for
CK8 & 18
ADAMANTINOMA OF
LONG BONE