Primary bone tumors can be benign or malignant and affect people of a wide age range. Molecular profiling using techniques like next generation sequencing has helped distinguish tumors with overlapping features and identified recurrent genetic alterations specific to different tumor types. For example, chondrosarcomas commonly harbor mutations in IDH1 and IDH2, while giant cell tumor of bone has H3F3A alterations in over 95% of cases. This molecular information can provide diagnostic, prognostic and predictive insights and help guide targeted therapy development.
Lab Diagnosis of Chronic lymphoproliferative disorders (CLPD);Flowcytometric...Dr Siddartha
Lab Diagnosis of Chronic lymphoproliferative disorders (CLPD);Flowcytometric Evaluation
Basavatarakam Indo-American Cancer Hospital and Research Institute
This is a presentation on the topic of cytology of the breast, prepared by Dr Ashish Jawarkar, he is MD in pathology and a teacher at Parul institute of Medical sciences and research Vadodara.
pathology of round cell tumours of osseo articular system like ewings sarcoma, mesenchymal chondrosarcoma,small cell osteosarcoma, plasma cell neoplasms and other hematopoietic malignancies. how immunochemistry os playing pivotal role in differential diagnosis.
Lab Diagnosis of Chronic lymphoproliferative disorders (CLPD);Flowcytometric...Dr Siddartha
Lab Diagnosis of Chronic lymphoproliferative disorders (CLPD);Flowcytometric Evaluation
Basavatarakam Indo-American Cancer Hospital and Research Institute
This is a presentation on the topic of cytology of the breast, prepared by Dr Ashish Jawarkar, he is MD in pathology and a teacher at Parul institute of Medical sciences and research Vadodara.
pathology of round cell tumours of osseo articular system like ewings sarcoma, mesenchymal chondrosarcoma,small cell osteosarcoma, plasma cell neoplasms and other hematopoietic malignancies. how immunochemistry os playing pivotal role in differential diagnosis.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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
Title: Sense of Taste
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 structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
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!
2. BONE TUMORS
• Primary bone tumors comprise both benign
and malignant tumors affecting people with
wide age range.
• Benign are more common than malignant
tumors.
• Diagnosis heavily relay on imaging findings.
2
3. BONE TUMORS
• Thus, the diagnosis and treatment is best
accomplished with a multidisciplinary
approach consisting of surgeons, radiologists,
pathologists, and oncologists to produce
optimal patient care.
3
4. BONE TUMORS
• Traditionally, diagnosis has relied on
histopathological assessment of tumor tissue
combined with clinical and radiological
correlation.
• This has been supplemented with cytogenetic
analysis including karyotype analysis and
fluorescence in situ hybridization (FISH).
• Immunohistochemical analysis has played
little role in the diagnosis of bone tumors.
4
5. MOLECULAR GENETICS IN BONE
TUMORS
• Although recent molecular advances have
provided pathologists with specific targets
amenable to antibody interrogation in some
tumors such as GCT of bone and
chondroblastoma.
5
6. MOLECULAR GENETICS IN BONE
TUMORS
• Polymerase chain reaction (PCR) and
massively parallel next generation sequencing
(NGS) based assays have provided additional
tools for assessing molecular alterations in
bone tumors.
6
10. INTRODUCTION
• Large scale sequencing of DNA and RNA from
bone tumors has revealed many recurrent
alterations that are exclusively meant for
different tumor types.
• This has transformed the ability of pathologists to
distinguish tumors with overlapping histologic
features.
• These are now included as a part of laboratory
diagnostic armoury.
10
11. INTRODUCTION
• Next phase of research in this area is to
determine the genetic profiles of bone tumor
which can be employed as prognostic and
predictive markers .
• If targeted therapies can be developed against
these alterations.
11
12. CARTILAGINOUS TUMORS
• They are the M/C group of primary bone
tumor.
• Osteochondroma – bone surface.
• Enchondroma - central within medullary
cavity.
• Both can transform into chondrosarcoma.
12
13. OSTEOCHONDROMA
• Exostosis - M/C benign bone tumor.
• 85% are sporadic.
• 15% are part of Autosomal Dominant, Multiple
Hereditary Exostosis Syndrome.
• Endochondral in origin.
• M/C site - metaphysis near growth plate.
13
14. • Gross image of osteochondroma; notice the
hyaline cartilage cap overlying mature
cancellous bone.
• Low power view of osteochondroma (4x);
cartilage cap lined by perichondrium,
contiguous with mature bone.
14
15. OSTEOCHONDROMA
• M/E - Cap composed of mature hyaline cartilage with
overlying fibrous perichondrium.
• Germline loss of function mutation in EXT1 and EXT2.
• Reduced expression of EXT1 and EXT2 is observed in
sporadic cases too.
• These genes encode enzymes that synthesize heparan
sulfate glycosaminoglycans(GAGs).
15
16. MULTIPLE HEREDITARY EXOSTOSES (MHE)
• MHE is caused by germline mutation in the
EXT1 (at 8q24) or EXT2 (at 11p11–12) genes.
• These genes have been implicated in the
formation of both sporadic and hereditary
osteochondromas.
• Defects in EXT1 are roughly twice as common
as defects in EXT2.
16
17. CHONDROMA
• Benign tumor of hyaline cartilage.
• Endochondral in origin.
• Mutation in IDH1 and IDH2.
17
18. CHONDROSARCOMA
• Malignant cartilage producing tumor.
• Mutation in EXT gene.
• Sporadic chondrosarcoma harbour mutation
in IDH1 and IDH2.
• Silencing of CDKN2A locus by DNA
methylation is also observed.
18
19. CHONDROSARCOMA
• Whole genome sequencing of
chondrosarcoma revealed mutation in TP53
and CDKN2A.
• Detection of IDH 1/2 helps in differentiating
dedifferentiated chondrosarcoma with
osteosarcoma component from primary
osteosarcoma of bone.
• Since the treatment of both varies.
19
20. CHONDROSARCOMA
• IDH 1 mutation in chondrosarcoma also show
expression of brachyury – the diagnostic hallmark
of chordoma.
• HEY1-NCOA2 fusion – characteristic of
mesenchymal chondrosarcoma.
• An association between 6q13–21 chromosome
aberrations and locally aggressive behavior has
been described in chondrosarcomas.
20
21. CHONDROSARCOMA
• Central conventional and periosteal cartilaginous
tumor and dedifferentiated chondrosarcoma
harbour mutation in IDH 1 or 2.
• These mutant IDH 1 / 2 fails to convert isocitrate
to alpha ketoglutarate and leads to accumulation
of D-2-hydroxyglutarate (2HG).
21
22. CLEAR CELL CHONDROSARCOMA
• Cytogenetic analysis has shown recurrent
chromosome 9 and 20 abnormalities.
• IDH mutations are absent.
22
24. Dedifferentiated Chondrosarcoma
• Harbor IDH1/2 mutations.
• At the molecular level, the process of
anaplastic transformation is accompanied by
overexpression of TP53 and HRAS mutation.
24
25. MESENCHYMAL CHONDROSARCOMA
• It is non conventional chondrosarcoma representing
2%.
• M/C in vertebral bodies in head and neck region.
• They are strongly reactive for CD 99 and are
mistaken for Ewing’s.
• Fusion transcript in HEY1-NCOA2 is recently
identified using exon expression data by rapid
amplification of cDNA PCR.
• This is also detected by FISH and RTPCR. 25
27. MULTIPLE ENCHONDROMA
• It is a group of diseases with spectrum of overlapping
phenotype.
• M/C variant is Ollier disease.
• Second M/C is Maffucci syndrome.
• They have high risk of glioblastoma.
• >90 % have IDH 1 / 2.
• Germline alteration include PTPN11, which encodes
protein tyrosine phosphatase.
27
28. MULTIPLE ENCHONDROMA
• Non receptor type 11 and ACP5 encodes
tartrate resistant acid phosphatase.
• PTHR1 alteration is associated with multiple
enchondroma.
• IDH 1/2 mutation were first identified in 2008
in brain tumors.
• Now in recent times, a vaccine targeting
mutant IDH1 has been developed.
28
29. CHONDROMYXOID FIBROMA
• It is a benign nonconventional cartilaginous
tumor.
• Nord et al recently identified that structural
rearrangements involving promoter swapping
and gene fusion resulting in aberrant
expression of glutamate receptor gene, GRM1
which is a G protein coupled receptor.
https://jcmtjournal.com/article/view/3898 29
30. CHONDROMYXOID FIBROMA
• Cytogenetically, chondromyxoid fibroma is
characterized by rearrangements of
chromosome 6 at band q13 or q25.
• Aberrations in 6q13 map to the COL12A1
locus is also seen.
30
31. OSTEOCLAST RICH NEOPLASM
• In recent times, genetic alterations of number
of osteoclast rich lesions have been described.
• USP6 fusion transcript in 70% of ABC.
31
32. GIANT CELL TUMOR
OSTEOCLASTOMA
• H3F3A genetic alteration detected in >95% of
GCT.
• But H3F3B have never been detected in GCT
so far.
• GCT metastasing to lung showed G34W
alteration and TP53 was not detected.
32
33. GIANT CELL TUMOR
• Most cases exhibit chromosomal abnormalities,
usually in the form of telomeric association that
can involve a variety of chromosomes.
• Such as 11p, 13p, 14p, 15p, 19q, 20q, and 21p.
• Telomeric association is a rare form of
cytogenetic abnormality characterized by end-to-
end fusion of intact chromosomes.
33
39. OSTESARCOMA
• M/C primary malignant bone tumor.
• Bimodal age of distribution.
• M>F affected.
• Metaphyseal region.
• Osteosarcoma typically shows complex
karyotypes, with structural alterations (including
translocations) and numerical alterations (gain and
loss) involving multiple chromosomes.
39
40. OSTESARCOMA
Mutations in the following:
• RB mutation – 70% of sporadic cases.
• TP53 mutation.
• CDKN2A – encodes two tumor suppressor gene P16
and p14 are inactivated.
• MDM2 and CDK4 – inhibit p53 and RB function.
• Deletions and amplifications of chromosomes 3, 6,
and 8 result in gene alterations may have prognostic
significance, including LSAMP, RUNX2, and MYC.
40
41. HIGH GRADE OSTESARCOMA
• Recent studies show that in approx 20% of
cases show amplification of fibroblastic
growth receptor.
• This was found in cases which failed to
respond to chemotheraphy.
41
42. PARAOSTEAL AND LOW GRADE
CENTRAL OSTEOSARCOMA
• These are bone forming neoplasm.
• Low grade central osteosarcoma and fibrous dysplasia
cannot be easily differentiated since both have central
location.
• They are characterized by MDM2 gene amplification.
• Gene amplification can be detected by molecular
diagnostic techniques or MDM2 & CDK4 protein can be
detected by IHC if only decalcified tissue is available
42
43. FIBROUS DYSPLASIA
• Benign tumor with localized development
arrest.
• It is a mosaic disorder caused by substitution
of GNAS1 with frequent involvement of codon
201.
43
45. EWINGS SARCOMA
• Malignant bone tumor characterized by primitive
round cells without obvious differentiation.
• It is a round blue cell tumor involving bone and
soft tissue mostly in children.
• It is characterized by the fusion of EWSR1 with FLI1
in 85 % cases.
• EWSR1 – chr 22 and FLI1 – chr 11.
45
46. 46
(a) H&E morphology of Ewing sarcoma/PNET.
(b) The tumor shows CD99 membranous pattern.
(c) FLI-1p (nuclear pattern, positivity by IHC.
(d) Confirmatory test by EWSR1 (22q12) dual-color, break-apart rearrangement
probe fluorescence in situ hybridization (FISH).
Separated red and green arrows demonstrate the genetic alteration, while the
two joint arrows are indicative for the intact chromosome.
INTACT
CHR
47. EWINGS SARCOMA
• About 95% of cases of Ewing family of tumors show
on cytogenetic examination the reciprocal
translocation t(11;22)(q24;q12) or t(21;22)(q22;q12),
which results in the fusion of the EWSR1 gene at
22q12 with the FLI1 or ERG genes respectively.
• The most common fusion is the one that results in
“in frame linking” of EWSR1 exon 7 with FLI1 exon 6.
• This gene encodes a chimeric protein EWS/FLI1 that
binds to chromatin and dysregulates transcription
leading to uncontrolled growth and abnormal
differentiation. 47
48. EWINGS SARCOMA
• These translocations are useful diagnostically and can be
detected by RT-PCR, can also be detected by molecular
cytogenetic analysis (FISH).
• It has been demonstrated that those tumors harboring
ERG abnormalities are frequently negative for EWSR1.
• Two other “Ewing-like” sarcomas have been identified.
• CIC-DUX4 tumors closely resemble Ewing sarcoma
histologically and immunohistochemically but are
frequently positive for WT1 and harbor the
t(4;19)(q35;q13.1).
48
49. EWINGS SARCOMA
• These tumors appear to be even more clinically
aggressive than Ewing sarcoma.
• In the remaining 5% cases EWSR1 or FUS fuses with other
ETS and non-ETS family genes such as ETV1, ETV4, ERG,
NFATC2, SMARCA or SP3.
• The other recently discovered Ewing-like tumor is
characterized by the BCOR-CCNB3 gene fusion.
• These tumors contain both round cell and spindled cell
elements and often lack the diffuse membranous CD99
immunoreactivity seen in Ewing sarcoma.
49
50. PHOSPHATURIC MESENCHYMAL TUMOR
• Rare bone tumor common in patients with long
standing osteomalacia who are resistant to
vitamin D and Calcium.
• FGF23 has been found to have a role in
phosphate homeostasis.
• Removal of this tumor results in dramatic drop in
circulating levels of FGF23 and reversal of
osteomalacia.
• Recently FN1-FGFR1 gene fusion has been
observed in 60% cases.
50
51. PSEUDOMYOGENIC
HEMANGIOENDOTHELIOMA
• Unusual tumor occuring in sites like subcutis,
deep soft tissue and bone.
• Behaves in an indolent manner with multifocality
and rarely metastases.
• IHC – immunoreactive for CK, CD31, ERG can lead
to misdiagnosis.
• But SERPINE1-FOSB fusion gene helps in
diagnosis.
51
53. CHORDOMAS
• Expansile lobulated intraosseous mass that usually
permeates the cortex and invades adjacent soft
tissue.
• Cut surface is gelatinous to chondroid
• Grossly, this chordoma has a fleshy cut surface
with invasion of the adjacent soft tissue.
53
57. LANGERHANS CELL HISTIOCYTOSIS
• LCH should be regarded as a neoplastic disease.
• Recently, it has been shown that a relatively high
percentage of cases of LCH harbour BRAF V600E
mutations.
• Resulting in activation of the MAPK pathway.
• A smaller percentage of lesions have mutations in
the MAP2K1 gene. 57