Recent advances in soft tissue tumors classification:
- Soft tissue tumors classification has significantly changed due to advances in immunohistochemistry, cytogenetics and molecular genetics.
- The 2013 WHO classification incorporated these advances and additional tumor types. It dismantled concepts like 'malignant fibrous histiocytoma' and incorporated gastrointestinal stromal tumors and peripheral nerve sheath tumors.
- Major changes included removing the term 'malignant fibrous histiocytoma' and recognizing additional rare tumor types based on genetic abnormalities. Classification aims to better reflect current understanding of tumor biology and genetics.
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.
Soft tissue pathology is rapidly changing
Novel molecular findings
Tumors previously known under one rubric are reclassified with relative frequency
Lesions that for decades were thought to be reactive now are discovered to possess gene rearrangements
Features of previously unknown or incompletely described tumors are coalesced and synthesized into new entities
Relative rarity of soft tissue tumors only adds to the challenge
of keeping abreast of all of these advances
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.
Soft tissue pathology is rapidly changing
Novel molecular findings
Tumors previously known under one rubric are reclassified with relative frequency
Lesions that for decades were thought to be reactive now are discovered to possess gene rearrangements
Features of previously unknown or incompletely described tumors are coalesced and synthesized into new entities
Relative rarity of soft tissue tumors only adds to the challenge
of keeping abreast of all of these advances
Presentation about lipoma and liposarcoma, origin, cause, description, diagnosis, treatment with pictures that help the better understanding of the topic.
Speak, Malady: An Autobiography of Cancer, Proton Beam Radiation, and Chordom...Adam Baer
Harper's Magazine essay on Cancer Narratives, Cancer Essays, Proton Beam Radiation Therapy, Cancer History, the Inability to "Cure" Cancer, Chordoma, and The Emperor of All Maladies by Siddhartha Mukherjee -- Adam Baer
Detailed Description about soft tissue sarcoma.
Deals with topics including etiology, histopathology,clinical presentation ,staging and prognostic factors and management methods including surgery and adjuvent therapy .
Soft tissue sarcomas are a heterogeneous group of malignant tumours derived from primitive mesenchymal cells.
They are aggressive tumours which are locally invasive and recurrent.
They are named based on the cell of origin .
They require multimodal treatment including surgery and certain adjuvent therapies
Malignant Bone Tumours - A lecture for undergraduate students and demonstrators / Tutors featuring general aspects and three common malignant bone tumours viz. Osteosarcoma, Ewing's Sarcoma and Multiple Myeloma
Similar to Recent advances in soft tissue tumors (20)
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
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.
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
- 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
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.
2. • Soft tissue tumours represent a heterogeneous group of mesenchymal lesions
• Substantial developments in immunohistochemistry, cytogenetics & molecular genetics
have caused a significant change in the classification and diagnosis
• In 2002, for the first time extensive genetic data were incorporated in WHO classification
• Concepts of so-called ‘malignant fibrous histiocytoma’ and ‘haemangiopericytoma’ began
to be dismantled
Evolving classification of soft tissue tumours
3. • The new WHO classification of soft tissue tumours was published in 2013
• The changes in the 2013 classification are somewhat less dramatic than 2002
• There have been substantial steps forward in molecular genetic and cytogenetic
characterization of this family of tumours
• The new classification also now incorporates gastrointestinal stromal tumours and
peripheral nerve sheath tumours.
• WHO felt that these groups of lesions fitted better under the heading of ‘Soft tissue
tumours’
Evolving classification of soft tissue tumours
4. WHO working group divides soft tissue tumors into four categories:
• Benign: do not recur locally and almost always cured by complete local excision
• Intermediate(locally aggressive): Recur locally and are associated with an infiltrative
locally destructive growth pattern
• Intermediate (rarely metastasizing): often locally aggressive & show well documented
ability to give rise to distant metastasis. The risk of such metastasis is <2%
• Malignant: have significant risk of distant metastasis (ranging from 20% to almost 100%
depending upon histological type and grade
5. Staging and Grading
• Unlike with other tumors the staging of soft tissue tumors is largely determined by grade
• There is no generally agreed upon scheme for grading soft tissue tumors
• Most widely used grading systems are French Federation of Cancer Centers Sarcoma
Group (FNCLCC) and National Cancer Institute (NCI)
• Both has 3 grades and are based on mitotic activity, necrosis and differentiation which
correlate well with the prognosis.
• In addition to these criteria, NCI system requires the quantification of cellularity and
pleomorphism for certain subtypes of sarcomas
6. FNCLCC grading system
• The TNM staging system recommends
the FNCLCC system
• Grading of MPNST, embryonal and
alveolar RMS, angiosarcoma, myxoid
chondrosarcoma, alveolar soft part
sarcoma, clear cell sarcoma, and
epithelioid sarcoma is not recommended
9. • Term small cell liposarcoma is deleted
• It simply represent histological continuum of high grade myxoid liposarcoma
• This concept is supported by the presence of same genetic abnormalities, most
commonly t(12;16), which fuses the DDIT3 (CHOP) gene on 12q13 with the FUS (TLS)
gene on 16p11
• The other minor change was deletion of the category of ‘mixed-type liposarcoma
• Represent unusual morphological patterns of de-differentiated liposarcoma.
11. • Nodular fasciitis, proliferative fasciitis and proliferative myositis, are in fact neoplastic
• Earlier, their nosological status was uncertain,
• These lesions have been found to have a consistent gene fusion, MYH9–USP6, indicating that
they are clonal neoplasms
• USP6 fusion genes have been identified in structurally related aneurysmal bone cyst
• Another major change is inclusion of the closely related entities giant cell fibroblastoma and
dermatofibrosarcoma protuberans (DFSP)
• Giant cell fibroblastoma was included in the intermediate (locally aggressive) category and
DFSP was included in the rarely metastasizing category
FIBROBLASTIC / MYOFIBROBLASTIC TUMOURS
12. • DFSP are characterized by the presence of supernumerary ring chromosomes.
• These ring chromosomes were shown to contain an ‘occult’ translocation t(17;22) resulting
in fusion of the COL1A1 and PDGFB genes
• There is a close relationship between low-grade fibromyxoid sarcoma (LGFMS) and
sclerosing epithelioid fibrosarcoma (SEF)
• Genetically, subsets of SEF, show identical findings as in LGFMS like t(7;16)(FUS–CREB3L2/L1)
• It is unclear whether FUS and EWSR1-negative SEF represent an entity distinct from LGFMS,
or a form of morphological progression
FIBROBLASTIC / MYOFIBROBLASTIC TUMOURS
14. • The major but not unexpected change here has been the final removal of the term
‘malignant fibrous histiocytoma’(MFH)
• MFH was initially regarded as a true histiocytic neoplasm, showing facultative fibroblastic
differentiation.
• Existence of MFH as a discrete entity (rather than a final common pathway for a variety
of poorly differentiated sarcomas) was itself challenged in a number of studies
• So-called ‘malignant fibrous histiocytoma’, now classified as ‘undifferentiated
pleomorphic sarcoma
FIBROHISTIOCYTIC TUMOURS
15. SMOOTH MUSCLE TUMOURS
• No major changes in this category
• Angioleiomyoma (vascular leiomyoma) was reallocated to the category of pericytic
(perivascular) tumours
• Deep leiomyoma
• Genital leiomyoma
• Leiomyosarcoma
16. PERICYTIC (PERIVASCULAR) TUMOURS
• Glomus tumour
• Myopericytoma
• Angioleiomyomas
• In the 2002 classification, the group of myopericytomas had been incorporated under
this heading for the first time
• It is now acknowledged that myofibroma/myofibromatosis also represent the spectrum
of myopericytic neoplasms
• It show predominantly myofibroblastic-like cytomorphology and prominent stromal
hyalinization
• Angioleiomyomas (vascular leiomyomas) were placed in this category and they form a
morphological continuum with the myoid end of the spectrum of myopericytomas
18. SKELETAL MUSCLE TUMOURS
• Spindle cell rhabdomyosarcoma had been regarded previously as a variant of embryonal
RMS, based on its generally good prognosis
• Spindle cell RMS is related very closely to sclerosing RMS, neither of these lesions is truly
related to embryonal rhabdomyosarcoma
• Neither spindle cell nor sclerosing RMS shows any genetic overlap with either embryonal
or alveolar rhabdomyosarcoma
• Recently rearrangements of the NCOA2 gene have been identified in infantile cases of
spindle cell rhabdomyosarcoma
• Sclerosing cell RMS appear to be less chemosensitive than other RMS, the prognosis is
worse in adults than in children.
20. Vascular tumors
• Introduction of a new entity pseudomyogenic haemangioendothelioma
• Also known as epithelioid sarcoma-like haemangioendothelioma
• Very distinctive tumour, arising in the extremities of adolescents, young adults and
multicentric in more than 50% of patients.
• They have a remarkably pseudomyogenic morphological appearance which would not
suggest endothelial differentiation at first
• Immunohistochemistry and electron microscopy support their vascular nature
• These tumours also harbour a distinctive t(7;19)(q22;q13) chromosomal translocation.
21. GASTROINTESTINAL STROMAL TUMOURS
• Approximately 80% of GISTs harbour oncogenic mutations in KIT, and 8–10% harbour
oncogenic mutations in PDGFRA,
• A new group of GISTs as been recognized in recent years, being characterized by loss of
function of the succinate dehydrogenase (SDH) complex
• These SDH-deficient GISTs, lack mutations in either KIT or PDGFRA
• Account for the important subset of tumours known as paediatric-type GIST
• Arise exclusively in the stomach, they can be multifocal, clinically very indolent
• The mechanism of SDH deficiency seems likely to be epigenetic (perhaps related to
methylation status). Only a small subset harbour a mutation in one of the SDH genes
23. NERVE SHEATH TUMOURS
• The current WHO classification included tumours previously classified under cranial and
peripheral nerves, head and neck and skin tumours
• This represents an important initiative to present the diverse family of mesenchymal
tumors into a single reference source
• One distinct group of newly recognized tumours included in the category of benign
nerve sheath tumours were hybrid nerve sheath tumours
• By far the most common among which is hybrid schwannoma/perineurioma
• However, rare examples of hybrid neurofibroma/schwannoma are also recognized
25. TUMOURS OF UNCERTAIN DIFFERENTIATION
• Principal changes have been the addition of several recently recognized ‘entities
• In the benign category, acral fibromyxoma and atypical fibroxanthoma are now included
• Added into the intermediate (locally aggressive) category is haemosiderotic
fibrolipomatous tumour
• Haemosiderotic fibrolipomatous tumour have been shown to harbour the chromosome
translocation t(1;10)(p22;q24)
26. • A new addition in the intermediate (rarely metastasizing) category is phosphaturic
mesenchymal tumour,
• A tumour type which has been recognized for many years but which had not been defined
clearly until more recently
• PNET has been dropped as a synonym for Ewing sarcoma in order to minimize confusion
• Malignant mesenchymoma is not included in the current classification.
• Most cases reported previously probably represent heterologous line of differentiation in
specific sarcomas
TUMOURS OF UNCERTAIN DIFFERENTIATION
28. UNDIFFERENTIATED/UNCLASSIFIED SARCOMAS
• A subset of sarcomas cannot be classified into any presently defined categories and
account for up to 20% of all sarcomas
• A significant subset of radiation-associated sarcomas fall into this category.
• These lesions show no definable line of differentiation
• In round cell category, genetic subsets which almost certainly represent discrete
entities are already beginning to be recognized,
• Most notably those characterized by CIC–DUX4 gene fusion, due to t(4;19) or t(10;19)
• It remains to be seen whether these cases represent one or more separate entities, or
whether they are better classified as variants of Ewing sarcoma.
30. • Immunohistochemistry is an integral component in the proper analysis of soft tissue
tumours
• The diagnostic approach consists in ruling out a non-mesenchymal tumor followed by
trying to define mesenchymal cell lineage.
• It is best used as a diagnostic adjunct following careful assessment of histopathology
and formulation of differential diagnosis
• The effective use of immunohistochemistry specifically assesses the differential
diagnostic possibilities
31. Basic panel of antibodies
• Cytokeratin
• EMA
• S100
• Desmin
• SMA
• Vimentin
• CD 34
• CD 31
• CD 99
• Bcl 2
• LCA
• An initial panel of antibodies is often required in order to establish the broad lineage
• The initial battery of IHC markers should always include:
32. Cytokeratin
• Collection of more than 20 proteins.
• Grouped by their mol. wt. into acidic and basic subfamilies.
• Their expression is not restricted to carcinomas.
Cytokeratin expression in soft tissue tumors
33. • Aberrenat CK expression can be found in many other sarcomas
• Significant percentage of smooth muscle and vascular tumors show CK positivity
34. EPITHELIAL MEMBRANE ANTIGEN( EMA)
• It is expressed in a variety of ductal, secretory and other epithelial cells
• EMA is also expressed in meningothelial and perineurial cell membranes
• EMA is useful in detecting epithelial differentiation in soft tissue tumours
• It is typically detectable in synovial sarcoma, epithelioid sarcoma, myoepithelioma
and many metastatic carcinomas
• Some other sarcomas, such as leiomyosarcoma, MPNST and rarely angiosarcomas, can
also be positive, and this has to be considered in the differential diagnosis.
35. SMOOTH MUSCLE ACTIN(SMA)
• SMA has specificity for smooth muscle cells. It is also expressed in the pericytes,
glomus cells, myofibroblasts and myoepithelial cells.
36. DESMIN
• Desmin is useful in the diagnosis of skeletal muscle and smooth muscle tumours
• Desmin can also be present in myofibroblasts, therefore myofibroblastic tumours such
as desmoid fibromatosis can be focally positive
• Desmin is expressed strongly in many other tumours, most important examples include
desmoplastic small round cell tumour, which show perinuclear dots like positivity
• Ewing sarcoma occasionally show desmin positivity
37. • Belongs to family of calcium binding proteins
• Expressed in Glia, Schwann cells, Melanocytes, histiocytes, Chondrocytes, lipocytes,
muscle, myoepithelial cells
• Diagnostic value in melanomas, peripheral nerve sheath tumors
• MPNST- only patchy and weak
• Other tumors expressing it-
• Malignant melanoma
• Synovial Sarcoma
• RMS
• LMS
• Adipocytic tumors
• Chondrocytic tumors
• Myoepithelioma
S-100 protein
38. Applications for CD34 shown by pairs of tumors with potential histological resemblance
CD 34
39. CD99
• Uniformly express CD99 with a characteristic membranous pattern in Ewing sarcoma
• But it is not so specific
• Positivity is seen in lymphomas, RMS, Mesothelioma, synovial sarcoma, solitary fibrous
tumor, desmoplastic small round cell tumor etc.
Bcl-2
• It is a family of protein involved in the apoptosis pathway in cell grown and death
• Positive in Solitary fibrous tumor, Synovial sarcoma, DFSP
• CD31 has been the gold standard as a marker for endothelial differentiation
• Diagnosis of malignant vascular tumours like epithelioid haemangioendothelioma,
angiosarcomas and Kaposi sarcoma is aided by demonstration of CD31
CD 31
40. Novel immunohistochemical markers in soft tissue tumors
• Until recently, the primary purpose of immunohistochemistry was simply to attempt to
demonstrate a line of differentiation
• Most traditional markers show relatively limited specificity
• Over the last decade, much more specific immunohistochemical markers for soft tissue
tumors have been developed
• These useful new diagnostic markers can separated into three general categories:
• (1) lineage-restricted transcription factors,
• (2) protein correlates of molecular alterations
• (3) diagnostic markers identified by gene expression profiling.
• Antibodies are helpful and relatively specific diagnostic markers
41. Myogenin, MyoD1 expression in rhabdomyosarcomas
a) Alveolar RMS showing a solid growth pattern. b) strong nuclear staining in nearly all tumor cells.
c) Embryonal RMS composed of round-short spindled cells in myxoid stroma d) Only a subset of tumor cells is positive
• Myogenin & MyoD1 are myogenic
transcriptional regulatory proteins
expressed early in skeletal muscle
differentiation
• Considered sensitive and specific
markers for RMS
42. ERG & FLI1(ETS family transcription factors)
• Expression of two related ETS family transcription factors is relatively restricted to
endothelial cells and derived neoplasms
• The most common translocation in Ewing sarcoma is t(11;22), found in ~90% of cases and
it leads to EWSR1-FLI1 fusion and overexpression of the FLI1 protein
• FLI1 is also expressed in endothelial cells and derived neoplasms, lymphoblastic
lymphomas, and occasionally in a wide range of mesenchymal neoplasms
• Given its lack of specificity, FLI1 immunohistochemistry is not particularly helpful in
differential diagnosis
43. (a) Poorly differentiated cutaneous angiosarcoma infiltrating dermal collagen.
(b) ERG shows strong nuclear staining in tumor cells.
• ERG(ETS-related gene) is a highly sensitive and specific marker for endothelial differentiation
44. Brachyury
• It is a transcriptional activator involved in the development of the notochord
• Nuclear expression of brachyury is a consistent feature of chordoma
• Helpful in distinguishing chordoma from chondrosarcoma, metastatic carcinoma and
myoepithelial tumors
Epithelioid cells with abundant eosinophilic
cytoplasm, cytoplasmic vacuoles, and scant
myxoid stroma.
45. SOX10 (SRY-related HMG-box 10) expression
a) Neurofibroma with buckled nuclei and prominent collagenous stroma b) SOX10- positive in the Schwann cell
c) MPNST with fascicular architecture, tapering nuclei & high mitotic rate d) Nucleopositivity is + in a small no of cells.
• Important for
embryonicdevelopment and cell
fate determination of the neural
crest and PNS
• Specific marker for
neuroectodermal neoplasms
• Consistently expressed in benign
nerve sheath tumors, clear cell
sarcoma, and melanoma
• SOX10 shows lower sensitivity for
MPNST(30–50%)
46. SATB2 expression
spindled-to-epithelioid cells with scattered osteoclast- like
giant cells and scant osteoid deposition.
• SATB2(special AT-rich sequence-binding protein 2) is
a nuclear matrix protein
• Plays a critical role in osteoblast lineage commitment
• SATB2 is a sensitive & specific immunohistochemical
marker of osteoblastic differentiation in bone and
soft tissue tumors
• SATB2 expression is also a feature of benign
osteoblastic neoplasms, other sarcoma types with
osteosarcomatous differentiation like
dedifferentiated chondrosarcoma dedifferentiated
liposarcoma
47. β-Catenin staining in desmoid
fibromatosis
Desmoid fibromatosis composed of bland myofibroblastic spindle cells
arranged in long fascicles.
• β-Catenin is the product of the CTNNB1 gene
involved in the Wnt signaling pathway
• Mutations in CTNNB1 are found in 85–90% of
sporadic desmoid tumors
• It is consistently negative in other intra-abdominal
mesenchymal neoplasms (including GISTs and
smooth muscle tumors)
• it is not entirely specific
• A subset of solitary fibrous tumors (20– 40%) and
low-grade myofibroblastic sarcomas (30%) also
show nuclear staining
48. • Atypical lipomatous tumor and dedifferentiated liposarcoma are characterized by
supernumerary ring and giant marker chromosomes, composed of amplified
material from the long arm of chromosome 12 (q13~15)
• Within which several oncogenes are located, leading to overexpression of MDM2
and CDK4.
• Nuclear reactivity for MDM2 and CDK4 is highly Sensitive, but is not entirely specific
• Some spindle cell and pleomorphic sarcomas (such as MPNST, myxofibrosarcoma,
and rhabdomyosarcoma) show nuclear staining in a subset of cases
• Combined positive staining for both MDM2 and CDK4 is much more specific.
MDM2 and CDK4 expression
49. MDM2 and CDK4 expression in liposarcomas
Well-differentiated liposarcoma (MDM2) Dedifferentiated liposarcoma(CDK4) Dedifferentiated liposarcoma (MDM2)
so-called ‘inflammatory MFH
50. • SMARCB1 is a member of the SWI/SNF multisubunit chromatin remodeling complex
• It plays a fundamental role in regulating transcription.
• SMARCB1 is ubiquitously expressed in normal cells.
• Biallelic inactivation of SMARCB1 is a defining feature of malignant rhabdoid tumors
• Homozygous deletion of the SMARCB1 locus is common in epithelioid sarcoma(95%)
• Loss of SMARCB1 expression is seen in 50% of epithelioid MPNST and a subset of
myoepithelial carcinomas, myxoid chondrosarcomas and poorly differentiated chordomas
SMARCB1 (INI1)-deficient tumors.
52. (a) SDH-deficient GISTs arise in the stomach and show a multinodular growth pattern. (b) Similar to conventional GISTs, KIT is strongly positive. (c) Most
SDH-deficient GISTs are dominated by epithelioid cytomorphology. (d) Loss of SDHB protein expression confirms the diagnosis. Note the granular
cytoplasmic staining in endothelial cells, which serve as an internal control.
Succinate dehydrogenase (SDH)-deficient GIST
• The SDH complex participates in both the citric acid cycle (oxidation of
succinate to fumarate) and the electron transport chain(complex II).
• Mutations in SDH subunit genes lead to loss of protein expression and
enzyme function
53. TFE3 expression
(a) Alveolar soft part sarcoma composed of epithelioid cells with abundant eosinophilic cytoplasm and a nested
architecture. (b) Strong nuclear staining for TFE3 is a characteristic finding.
• Alveolar soft part sarcoma harbors the translocation t(X;17), which leads to the ASPSCR1-TFE3 fusion
and overexpression of the TFE3 protein
• TFE3 rearrangements have recently been identified in a small subset of PEComas and a distinctive
subset of epithelioid hemangioendotheliomas
54. ALK expression in inflammatory myofibroblastic tumor.
IMTs composed of plump spindle cells arranged in loose fascicles with prominent stromal
lymphocytes. B) Cytoplasmic staining for ALK is observed in 50% of cases. (c) Epithelioid
inflammatory myofibroblastic sarcoma with amphophilic cytoplasm, prominent nucleoli, myxoid
stroma,stromal neutrophils. (d) There is a characteristic nuclear membrane pattern of ALK staining
• ~50% of inflammatory myofibroblastic
tumors (IMTs) harbour rearrangements of
the ALK locus
• Pattern of ALK staining appears to correlate
with the fusion partner
• Most translocations (involving the fusion
partners TPM3, TPM4, CARS, ATIC, SEC31A,
and CLTC) result in cytoplasmic staining
• Nuclear membrane pattern of staining is
seen with the RANBP2 fusion partner
• It is also positive in some RMS & MPNST
55. • Recently, a NAB2-STAT6 fusion has been identified by
several independent groups as a consistent feature of
solitary fibrous tumors
• So-called ‘meningeal hemangiopericytoma’ also
harbors this fusion gene, supporting the classification
of this tumor type with SFT
• NAB2-STAT6 fusion leads to high-level nuclear
expression of the STAT6 protein
• By immunohistochemistry, nearly all cases of solitary
fibrous tumor show strong nuclear staining for STAT6
56. DOG1 (discovered on GIST1) expression
a) Epithelioid GIST of the stomach with a PDGFRA mutation. (b) KIT is negative in tumor cells. Note the strong
membranous staining in occasional mast cells, which serve as an internal control.c) DOG1 is positive membranous
• Also known as ANO1 (anoctamin 1) and TMEM16A, this protein is a calcium-activated
chloride channel expressed in normal interstitial cells of Cajal
• DOG1 was shown to be highly expressed in GIST by gene expression profiling
• DOG1 is a highly sensitive and specific marker for GIST
57. Monophasic synovial sarcoma composed of fascicles of
uniform spindle cells, Strong nuclear staining for TLE1 is
TLE1(transducin-like enhancer of split 1)
expression
• TLE1 is a transcriptional corepressor that inhibits Wnt
signaling
• Using gene expression profiling, TLE1 was found to be an
excellent discriminator of synovial sarcoma from other
sarcoma types
• TLE1 shows moderate-strong, diffuse nuclear staining in
the majority of synovial sarcomas(80–90%)
• It is only positive in a small subset of MPNST and solitary
fibrous tumors (usually with only weak staining)
58. • MUC4 is a high-MW transmembrane glycoprotein expressed on the surface of some
glandular epithelial cell types.
• This epithelial mucin is highly expressed by low-grade fibromyxoid sarcoma (LGFMS)
• Characterized by the t(7;16) translocation, resulting in FUS-CREB3L2 rearrangement, or
rarely t(11;16), resulting in FUS-CREB3L1 fusion
• Hybrid tumors with both LGFMS and SEF components, as well as ~70% of ‘pure’ SEF
cases, are strongly positive for MUC4
MUC4 expression in fibroblastic sarcomas
59. MUC4 expression in fibroblastic sarcomas
(a) Low-grade fibromyxoid sarcoma showing a storiform-to-whorled growth pattern and bland spindle cell morphology. (b) Strong cytoplasmic staining for MUC4 is
highly specific for this tumor type among spindle cell neoplasms
(c) Sclerosing epithelioid fibrosarcoma composed of cords of epithelioid cells embedded in a densely hyalinized stroma. (d) MUC4 is positive in most cases.
62. Approach to the diagnosis of soft tissue tumors
Sarcomas may be divided into groups based on their primary histologic growth pattern:
• Round Cell Soft Tissue Sarcomas
• Epithelioid Soft Tissue Sarcomas
• Fascicular Spindle Cell Sarcomas
• Pleomorphic Sarcomas
• Myxoid Soft Tissue Sarcomas
69. • Molecular genetics of STS has developed at a rapid pace in recent years.
• The more current textbooks including the WHO edition reserve specific sections to
include recent cytogenetic and molecular data
• Diagnostic approaches were supplemented with reliable molecular diagnostic tools,
detecting tumour type-specific genetic alterations
• Successful application of techniques to formalin-fixed paraffin- embedded tissue made it
possible to subject a broader range of clinical material to molecular analysis
70. Sarcomas can be divided into two major genetic groups
• Soft tissue sarcomas with specific genetic alterations & relatively simple karyotypes:
• 15–20% bear specific reciprocal translocations (used as diagnostic markers)
• Specific somatic mutations (e.g., cKIT & PDGFR in GIST)
• Specific amplifications (e.g., MDM2 & CDK4 amplification in the liposarcoma)
• Soft tissue sarcomas with non-specific genetic alterations & complex karyotypes
• Genetic abnormalities like chromosomal numerical changes, translocations, gene
amplifications or large deletions can be apparent at the cytogenetic level (karyotyping,FISH)
• Small deletions, insertions or point mutations, require molecular genetic techniques (PCR
and sequence analysis)
71. Molecular genetic techniques
• The most common techniques currently used in molecular diagnostics include:
• Direct metaphase cytogenetics or karyotyping
• Fluorescence in-situ hybridization(FISH)
• Reverse transcriptase-polymerase chain reaction (RT PCR)
74. • Comparative genomic hybridization, DNA chip microarray analysis, direct genome
sequencing are currently remain in the realm of research tools.
• Next-generation sequencing (NGS) technologies also known as second-generation
sequencing, deep sequencing, massively parallel sequencing
• It obtain simultaneously both width (i.e multiple nucleotide sequences are analysed at
the same time) & depth (i.e each target nucleotide sequence is analysed several times)
• Allow detection of rare, mosaic variants in the analysis of genetic material.
New approach to identify gene fusions
75. Gene fusions in soft tissue tumours
• One-third of all sarcomas are characterized by specific recurrent chromosomal
translocations
• In 1992 the first sarcoma-associated gene fusion the EWSR1–FLI1 chimera resulting
from t(11;22)(q24;q12) in Ewing sarcoma was discovered
• New gene fusions were added at a fairly constant rate, and now amount to 94 fusions
in more than 30 distinct entities
76. • Approximately 85-90% of EWS/PNET harbour t(11;22)
• This translocation juxtaposes the EWS gene from chromosome 22 and the FLI1
gene from chromosome 11,
• There is generation of a chimeric gene encoding a functional fusion protein
composed of the transcriptional activating domain of EWS and the DNA binding
domain of FLI1.
• The resultant fusion gene is oncogenic and includes the N-terminal transactivation
domain of EWS and the C-terminal DNA binding domain of the FLI-1 gene.
77. FISH using the EWSR1 (22q12) dual colour, break-apart rearrangement probe
• The probe consists of a mixture of two FISH
DNA probes
• The first is a 500-kb probe labelled in
spectrum orange and flanks the 5’ side of the
EWSR1 gene extending inward to intron 4
• The second probe is a 1100-kb labelled in
spectrum green and flanks the 3’ side of the
EWSR1 gene.
• The known breakpoints within the EWSR1
gene are restricted to introns 7’ to 10’
In normal cells , a two-signal pattern is expected to reflect
two intact copies of EWSR1.
In abnormal cells, a fusion signal, one green and one orange
signal pattern will be expected.
78. • The Ewing sarcoma breakpoint region 1 (EWSR1; also known as EWS) represents one
of the most commonly involved genes in sarcoma translocations
• It is involved in a broad variety of mesenchymal lesions which includes:
• Ewing’s sarcoma,
• Desmoplastic SRCT,
• Clear cell sarcoma
• Angiomatoid fibrous histiocytoma
• Myxoid chondrosarcoma
• Subset of myxoid liposarcoma
• Myoepithelial tumours
• Low-grade fibromyxoid sarcoma,
• Sclerosing epithelioid fibrosarcom
• EWSR1 is a promiscuous gene that can fuse as 5′ partner with many different genes.
81. • Molecular results should be used as validation of the morphological differential diagnosis,
corroborated with immunohistochemical findings and clinical information
• In spite of overwhelming cytogenetic and molecular data that gene fusions are highly
specific markers, questioned have been raised about their specificity
• The molecular heterogeneity of fusion transcripts has been suggested to have a
prognostic role in certain sarcoma types.
• In Ewing’s sarcoma, the presence of type 1 EWS-FLI1 fusion was shown to have a better
survival benefit compared with other fusion transcript types
• Similarly, the presence of PAX7- FOXO1A was associated with a favourable prognosis in
alveolar rhabdomyosarcoma, compared with the more common PAX3-FOXO1A variant
82. Sarcomas with oncogenic mutations
• Constitutive activation of either KIT or PDGFRA receptor tyrosine kinase by oncogenic
mutations is a central pathogenic event in GISTs
• Malignant rhabdoid tumours show inactivating mutations of hSN5 ⁄ INI1 tumour
suppressor gene on chromosome 22q11.
83. Sarcomas with complex karyotypes
• Two-thirds of soft tissue sarcomas lack a recurrent genetic signature and are
characterized by numerous aberrations, including chromosomal losses and gains.
• Most of the adult spidle cell and pleomorphic sarcomas belong to this group
• There is high prevalence of p53 checkpoint alterations, including p53 inactivating
mutations, homozygous deletion of CDKN2A, MDM2 amplifications
• There is markedly elongated and heterogeneous telomeres, that maintain telomeres in a
telomerase-independent manner
• This mechanism of telomere dysfunction might contribute to the chromosomal
aberrations found in complex sarcomas
86. Targeted therapies for sarcomas
• The modalities of treatment include surgery and radiotherapy for local control and
chemotherapy for distant metastasis
• Recognition of different pathogenetic mechanisms, numerous targeted treatments
are currently being investigated.
• Chemotherapeutic agents are designed to modulate, inhibit, or interfere with the
function of specific molecular targets that are crucial to the malignancy of tumors
• In general, standard chemotherapy options are still quite limited for sarcoma
• The role of adjuvant chemotherapy in soft tissue sarcoma is still a matter of debate
due to the inconsistent benefit noted in randomized prospective clinical trials
87. • The best and most well established example in sarcoma is the use of tyrosine kinase
inhibitor as a targeted therapy for GIST