This document provides an overview of diseases of white blood cells and lymphoid tissue. It begins with an outline of topics including various types of leukemia, lymphoma, myeloproliferative disorders, and other conditions. It then discusses specific diseases in more detail, covering neutrophil and lymphocyte disorders, the various types of leukemia (both acute and chronic myeloid and lymphocytic forms), lymphomas, myeloproliferative disorders like CML and polycythemia vera, and multiple myeloma. It provides information on clinical features, pathogenesis, diagnostic criteria and other details for many of these conditions.
Dear all, Pathologybasics is out with a new series of power point presentations on general Pathology.. Following is link presentation on seventh and the most difficult to understand chapter of robbins.. chapter 7,neoplasia. Any suggestions/feedback/constructive criticism are welcome on facebook.com/pathologybasics or pathologybasics@gmail.com
Dear all, Pathologybasics is out with a new series of power point presentations on general Pathology.. Following is link presentation on seventh and the most difficult to understand chapter of robbins.. chapter 7,neoplasia. Any suggestions/feedback/constructive criticism are welcome on facebook.com/pathologybasics or pathologybasics@gmail.com
Definition
Morphology and ultra structure
Types of giant cell
Formation of giant cell
Inclusion bodies of giant cell
Giant cell in detail
It’s a mass formed by the union of several distinct cells (usually macrophage).
And usually arise in response to an infection.
Merriam – Webster - Dictionary
Giant cell as an unusually large cell, especially a large multinucleated often phagocytic cell.
A) Cell wall :
Mature giant cell wall is from five to ten times thicker than the cell wall of the surrounding cells
Cell wall has irregular surface with numerous projections jutting into the cytoplasm.
B) Cytoplasm :
Its dense and granular and contain protein
Contain RNA
Traces of carbohydrate and fat.
Definition
Morphology and ultra structure
Types of giant cell
Formation of giant cell
Inclusion bodies of giant cell
Giant cell in detail
It’s a mass formed by the union of several distinct cells (usually macrophage).
And usually arise in response to an infection.
Merriam – Webster - Dictionary
Giant cell as an unusually large cell, especially a large multinucleated often phagocytic cell.
A) Cell wall :
Mature giant cell wall is from five to ten times thicker than the cell wall of the surrounding cells
Cell wall has irregular surface with numerous projections jutting into the cytoplasm.
B) Cytoplasm :
Its dense and granular and contain protein
Contain RNA
Traces of carbohydrate and fat.
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- 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
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
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
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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
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!
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
The Gram stain is a fundamental technique in microbiology used to classify bacteria based on their cell wall structure. It provides a quick and simple method to distinguish between Gram-positive and Gram-negative bacteria, which have different susceptibilities to antibiotics
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.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
5. NEUTROPHILS
• Normal TOTAL WBC count 6-11 K
• Neutrophils usually 2/3 of total normal
• Myeloblast Promyelocyte Myelocyte
Metamyelocyte Band (stab) Mature
Neutrophil (Poly, PMN, Neutrophilic Granulocyte)
• Produced in red (hematopoetic) marrow,
sequester (pool) in spleen, live in peripheral
blood, migrate OUT of vascular compartment PRN,
live a couple days normally
10. PELGER-HUET ANOMALY
• Genetic: Autosomal Dominant)
• Sometimes ACQUIRED (Pseudo-PELGER-HUET)
• All neutrophils look like BANDS
• NOT serious, mostly a cute incidental finding
11. CHEDIAK-HIGASHI SYNDROME
• Also genetic: Autosomal Recessive
• Abnormal LARGE irregular neutrophil granules
• Impaired lysosomal digestion of bacteria
• Associated with pigment and bleeding disorders
• CAN be serious, especially in kids
13. INADEQUATE PRODUCTION
• Stem cell suppression, e.g., aplastic anemias
• DRUGS, esp. CHEMO, MANY antibiotics,
aminopyrene, thio-uracil, phenylbutazone
• DNA suppression due to
megaloblastic/myelodysplastic states
• Kostmann Syndrome: (A-R) (genetic, congenital)
• Marrow usually shows granulocytic HYPOplasia, just as in RBC and PLAT decreased
production
14. INCREASED DESTRUCTION
• Immune mediated
– By itself (idiopathic), or as in SLE
– After “sensitization” by many drugs
• Splenic sequestration, hypersplenism
• Increased peripheral demand, as in
overwhelming infections, esp. fungal
• Marrow usually shows granulocytic
HYPER-plasia, just as in RBC and PLAT
increased destructions
15. Leukocytosis/Neutrophilia
•
•
•
•
Marrow and splenic pool size
Rate of release between pool and circulation
Marginating pool
Rate of WBCs (neutrophils/monocytes) leaving the
vascular compartment
• NON-vascular pools FIFTY times larger than the
vascular pools
• TNF/IL-1/cytokines stimulate T-cells to produce
CSF, the WBC equivalent of EPO
16. NEUTROPHIL INCREASES
(e.g., “NEUTROPHILIA”)
• BACTERIA
• TISSUE NECROSIS, e.g., MI
• DÖHLE BODIES and TOXIC
GRANULES are often seen with
NEUTROPHILIA
• Accompanied by a “LEFT” shift
18. BASOPHIL INCREASES
(i.e., “BASOPHILIA”)
• RARE. VERY RARE. Period.
• But if you want to remember
something at least, remember
myeloproliferative diseases in
which ALL cell lines are increased
Is there such a thing as a specific baso-penia?
ANS: NO
21. “MYELOPROLIFERATIVE”
disorders
• Also called “chronic” myeloproliferative disorders because
they last for years
• Differentiate: Myeloproliferative vs.
Myelodysplastic
• ALL marrow cell lines are affected, splenomegaly
• Proliferating cells do NOT suppress residual marrow
production, and go OUTSIDE marrow, and EXPAND
marrow to fatty appendicular marrow
• Associated with EXTRA-medullary hematopoesis
– Chronic Myelogenous “Leukemia” (CML)
– P. Vera
22. CML
• NOT AT ALL like an “acute” leukemia, but can
develop into an acute leukemia, as a condition
called a “blast crisis”
• Age: adult, NOT kids
• 90% have the “Philadelphia” chromosome, which
are aberrations on chromosome #9 (BCR) and #22
(ABL), the BCR-ABL “fusion”
23. CML
• Marrow 100% cellular, NOT 50%
• ALL cell lines increased, M:E ratio massively
increased, 50K-100K neutrophils with
SIGNIFICANT “left shift”, but not more
than 10% blasts
• SIGNIFICANT SPLENOMEGALY!!!!!
• Significant breakthrough with BCR-ABL kinase
inhibitors!!! (90% remissions)
24.
25.
26. Polycythemia Vera
• All cell lines increased, NOT just RBC
• HIGH marrow cell turnover stimulates
increased purines which often cause gout
(10%)
• BOTH thrombosis AND bleeding risks are
present because the increased platelets are
AB-normal
• Do not get “blast” crises, BUT can progress to
myelofibrosis
27.
28. ESSENTIAL THROMOCYTOSIS
• Platelet count often near 1 million/mm3
• Often a diagnosis of exclusion.
• The RAREST of all myeloproliferative
disorders
• Giant platelets usually. Why? Ans: Quicker
release from marrow (RPW/RDW)
(MPV/MCV)
• Massively increased megakaryocytes in the
marrow
29.
30. PRIMARY MYELOFIBROSIS
•
•
•
•
Rapid progressive marrow fibrosis
Oldest age group of all the MPD’s, >60
Can follow other MPD’s. Why?
Usually the most extensive extramedullary
hematopoesis because the marrow is NOT
the primary site of hematopoesis
• LEUKOERYTHROBLASTOSIS
• Like CML, 10-20% can progress to AML
31.
32. WBC/LYMPHOID DISORDERS
• Review of Normal WBC Structure/Function
• Benign Neutrophil and Lymphoid Disorders
• Leukemias
• Lymph Nodes
• Spleen/Thymus
• REVIEW
33. LEUKEMIAS
• MALIGNANT PROLIFERATIONS of WHITE
BLOOD CALLS
• In the case of neutrophilic precursors, the
primary process is marrow and peripheral
blood, but can involve any organ or tissue
which receives blood
• In the case of lymphocytes, there is an
intimate concurrence with malignant
lymphomas
34. Lymphocytic Leukemias vs. Lymphomas
• All leukemias of lymphocytes have lymphoma
counterparts
• Primary lymphomas can have “leukemic” phases,
including multiple myelomas
• Any myeloid leukemia can infiltrate a lymph node, or any
other site, but if/when it does it is NOT called a
lymphoma, but simply a myeloid infiltrate INTO a lymph
node
• ALL lymphomas are malignant proliferations of
lymphocytes
• ALL leukemias involve bone marrow changes
35. •
•
•
•
•
•
LYMPHOMAS
NODAL or EXTRANODAL
T or B
SMALL or LARGE CELLS
FOLLICULAR or DIFFUSE
Hodgkins or NON-Hodgkins
“F.A.B. classification” is currently popular
this week (FrenchAmericaBritish), for the
NON-Hodgkins lymphomas, also evolved into
the “International” classification
36. •
•
•
•
•
LEUKEMIAS
Acute or Chronic
Myeloid or Lymphocytic
Childhood or Adult
All involve marrow
All ACUTE leukemias suppress normal
hematopoesis, i.e., have anemia,
thrombocytopenia
• Most have predictable chromosomal aberrations
• Some can respond DRASTICALLY to chemo, most
notably ALL in children, even be cured!!!!
38. WHITE CELL NEOPLASMS Leuk/Lymph
• Many have predictable chromosomal
translocations
• Can arise in inherited and/or genetic diseases:
– Downs Syndrome (Trisomy 21)
– Fanconi’s anemia (hereditary aplastic anemia)
– Ataxia telangiectasia
• May have a STRONG viral relationship:
– HTLV-1 (lymphoid tumors)
– EBV (Burkitt Lymphoma)
– (in HIV): Human Herpesvirus-8 (KS) and B-Cell
Lymphomas
39. WHITE CELL NEOPLASMS Leuk/Lymph
• Can be caused by H. Pylori (gastric B-Cell
lymphomas)
• Can follow celiac disease (gluten
sensitive enteropathy T-Cell
lymphomas)
• Are common in HIV, B-Cell lymphomas,
CNS lymphomas
40. A.L.L./LYMPHOMAS*
• SUDDEN ONSET
• ANEMIA, BLEEDING, FEVER
• Bone pain, adenopathy, hepatosplenomegaly
• CNS: headaches, vomiting, nerve palsies
*
• ( NB: These are pretty much the clinical
symptoms of A.M.L. too and vice versa)
41. A.L.L./LYMPHOMAS
• “Lymphoblasts” which can give rise either to T or B cells
are the cells of malignant proliferation
• All lymphocytic leukemias CANNOT be classified
independently of lymphomas because they all have
lymphoma counterparts
• A.L.L. mostly in children
• Most have chromosomal changes, hyperploidy,
Philadelphia chromosome, translocations
• SIGNIFICANT response to chemo: 90% remission, 75%
CURE!!!
43. C.L.L.
• Unexplained sustained (months) lymph count of >
4000/mm3 is CLL, usually picked up on CBC
• M>F, age >60
• Lymphs look normal and are NOT blasts
• No need for marrow exam for dx, but progressive
involvement of marrow, nodes, and other organs is the
usual biologic behavior
• Liver can be involved portally or sinusoidally
• Translocations RARE, but trisomies and
deletions common
46. MULTIPLE MYELOMA
• DEFINED AS A MALIGNANT PROLIFERATION OF
PLASMA CELLS (i.e., former B-lymphocytes)
• Can have a “leukemic” phase, but the BONE
MARROW is the usual primary site of origin
• Usually have MONOCLONAL GAMMOPATHIES
• Secrete Heavy and Light chains, and Light chains
in the urine is known as Bence-Jones protein
• Usually have elevated IL-6 (bad prognosis)
47. PLASMA CELL classic features
• OVAL cytoplasm, ROUND
nucleus off to side
• Cartwheel/Clockface
chromatin
• Prominent Golgi or “Hoff”
49. MULTIPLE MYELOMA
• BONE DESTRUCTION
• Various deletions and translocations
• Plasma cells usually 1-3% of marrow, but >20% or plasma
cells in SHEETS is diagnostic
• Plasma cells usually look normal
• IgG >> IgA, other immunoglobulins are rare
• Staph, Strep, E. coli infections
• Bleeding*
• Amyloidosis
• RENAL FAILURE
52. M.G.U.S.
• Monoclonal Gammopathy of Unknown
Significance, i.e., no plasma cell
proliferation is found
• Age related
• 1% of 50-year olds, 3% of 70-year olds, etc.
• Same chromosomal aberrations as MM, but
generally follow a BENIGN course
53. Other “GAMMOPATHIES”
• Waldenstrom’s MACROglobulinemia IgM (associated with
lymphomas)
• Heavy Chain Disease (associated with
lymphomas)
• AMYLOID, follows MM and/or
chronic granulomatous diseases
54. •
•
•
•
A.M.L.
GENETIC ABERRATIONS INHIBIT DIFFERENTIATION
Many have various TRANSLOCATIONS
F.A.B. classifies them as M0 M7
MORE than 20% of BLASTS are needed in the
marrow for a diagnosis of acute leukemia!!! (i.e.,
ANY kind of BLAST
• NORMALLY, a marrow should have only about 1-2
% blasts
55. • M0
A.M.L.
Minimally differentiated
• M1 AUER rods rare
• M2 AUER rods common
• M3
(COMMON)
(COMMON)
Acute PRO-myelocytic leukemia
• M4 AMML (myelo-Mono cytic) (COMMON)
• M5
• M6
• M7
Monocytic
ErythroLeukemia
Acute Megakaryocytic leukemia
NOTE: Diagnosis is CONFIRMED by special markers, not just
visual identification
60. A.M.L.
• Anemia
• Thrombocytopenia (bleeding)
– Petechiae
– Ecchymoses
•
•
•
•
Fever
Fatigue
Lymphadenopathy
60% respond, BUT only 20 % are free of remission
after 5 years, WORSE than A.L.L.
61. MYELO-DYSPLASTIC SYNDROMES
• Increased risk of acute leukemias
• But, UNLIKE the myeloPROLIFERATIVE syndromes, NOT
a hypercellular marrow
• Spontaneous or drug related (even > 5 yrs!)
• Has marrow ABERRATIONS
– REFRACTORY ANEMIAS
– RINGED SIDEROBLASTS (Fe in mitochondria)
– Nuclear “BUDDING”
– EXCESS BLASTS, but LESS than 20%
– About, say, 25% develop into acute leukemias
67. BENIGN ENLARGEMENT
•
•
•
•
Also called LYMPHADENITIS, and HYPERPLASIA
Can be ACUTE (tender), or CHRONIC (non-tender)
Usually SUBSIDE in, say, less than 6 weeks
FOLLICULAR HYPERPLASIA is enlargement of the cortical
secondary follicles and increase in number of the cortical
secondary follicles
• SINUS HISTIOCYTOSIS is prominence in medullary sinuses
(also called “reticular” hyperplasia)
77. FEATURES of LYMPHOMAS
• The antigen receptor genes re-arrangement PRECEDES
malignant transformation, so the cells are
MONOCLONAL, NOT the usual POLYCLONAL
• 85% B-cell, 15% T-Cell
• The tumor cells congregate wherever T and B cell
congregate normally however
• DISRUPTED or “EFFACED” normal architecture,
obliterated subcapsular sinus
• HD/Non-HD staging CRUCIALLY IMPORTANT, esp. HD.
Why? HD grows (spreads) more “linearly”, i.e., more
“predictably”.
78. LATEST CLASSIFICATION
• NON-HODGKIN
– PRECURSOR B
– PERIPHERAL B
– PRECURSOR T
– PERIPHERAL T
• HODGKIN’S DISEASE (i.e., HODGKINS
LYMPHOMA)
NS, LP, MC, LD
86. STAGING, HD & NHD
• I
ONE NODE or NODE GROUP
• II
MORE than ONE, but on ONE side of diaph.
• III BOTH sides of diaph., but still in nodes only
• IV OUTSIDE of NODES, e.g., liver, marrow, etc.
• A
• B
No systemic symptoms
fever and/or night sweats and/or 10% weight loss
87. METASTATIC CARCINOMA
• Perhaps the single most important staging and
prognostic feature of tumors
• The metastatic cells FIRST enter into the
SUBCAPSULAR SINUS
• The tumor may replace the entire node and
enlarge it
• The tumor may be focal
• The tumor usually looks the same as it’s
primary or other metastases
• The tumor usually ENLARGES the node
95. SPLENIC FUNCTION
• REMOVE OLD BLOOD CELLS
• MAJOR SECONDARY ORGAN of the IMMUNE
SYSTEM
• HEMATOPOIESIS
• SEQUESTER (POOL) BLOOD CELLS
• 15% of body’s PHAGOCYTIC activity is in the
spleen (liver has >80)
96. SPLENOMEGALY
• CONGESTIVE vs INFILTRATIVE
• HYPERSPLENISM
–Anemia
–Leukopenia
–Thrombocytopenia
• DECISION for SPLENECTOMY
104. THYMOMAS
• ALL (most) thymomas show counterparts of
BOTH lymphoid as well as epithelial reticular
cells, hence, the classic name
“LYMPHOEPITHELIOMA”
– Benign thymoma: (encapsulated)
– Malignant Thymoma I: (locally invasive)
– Malignant Thymoma II: (easily metastasizable)
Classical features of peripheral white cells, recognition algorhythms
Linear topics
Grouped topics
Classical features of peripheral white cells, recognition points.
Many names, same cell
ALL blasts look the same on routine stains, whether they are myeloblasts, lymphoblasts, monoblasts, etc.
A blast is a blast is a blast is a blast is a blast is a blast is a blast is a blast is a blast is a blast is a blast is a blast is a blast!
Please remember you have all been conditioned to think a NUCLEOLUS is darker than the rest of the NUCLEUS, as it is on H&E, but in the usual stains we stain bone marrow smears or peripheral smears with, i.e., Wright or Giemsa respectively, the nucleoli are LIGHTER!!!
MYELOPEROXIDASE stains are often use to identify cells believed to be of MYELOID origin, such as blastic looking cells, because you cannot really tell for sure on Wright’s or Giemsa stains.
Are these substances part on innate or learned immunity? ANS: INNATE
Notice the parallel with anemia and thrombocytopenia.
Here is the tip of the iceberg: acetazolamidealloprinol, asparaginasecaptopril, carbamazepine, cephalosporins, chloramphenicol, chlordiazepoxide, chlorpropamide, chlorthalidone, cimetidine, cyclophosphamide, ethacrynic acid, fluorouracil, furosemide, gold salts, ibuprofenimipramine, indomethasone, meprobamate, methimazole, methotrexate, metronidazole, nitrofurantoin, penicillamine, penicillins, phenothiazines, phenylbutazone, phenytoin, procainamide, procarbazine, propylthiouracil, quinidine, quinine, rifampin, spironolactone, sulfonamides, sulindac, thioridazine, tolbutamide,k Vancomycin
TOXIC GRANULES are EXAGGERATIONS of the marrow’s normal granularity, DOHLE bodies are fragments of remaining dilated rough ER.
Neutrophilia can be viewed as a NONSPECIFIC index of acute infection, especially bacterial, but also tissue necrosis.
Following activation by an immune stimulus, eosinophils degranulate to release an array of cytotoxic granule cationic proteins that are capable of inducing tissue damage and dysfunction. These include:
1) major basic protein (MBP)
2) eosinophil cationic protein (ECP)
3) eosinophil peroxidase (EPO)
4) eosinophil-derived neurotoxin (EDN)
Not only are basophils RARE to find normally, but pure “basophilia” is also VERY rare.
When activated, basophils degranulate to release histamine, proteoglycans (e.g. heparin and chondroitin), and proteolytic enzymes (e.g. elastase and lysophospholipase). They also secrete lipid mediators like leukotrienes, and several cytokines
Why would monocytosis be linked to granulomatous diseases? Answer: Monocytes are macrophages in circulation, and granulomatous diseaseas are macrophage diseases. Is it surprising that many classical granulomatous diseases are also characterized by monocytosis, because macrophages are the CHIEF cells of granulomas? Answer: NO, not surprizing, it would be logical even!
Would it be a fair statement to say that whereas, neutrophilia is characterized by bacterial infections, lymphocytosis can be an index of many viral infections? Answer: Yes, it is fair, but there are many exceptions.
EXTRAMEDULLARY HEMATOPOESIS is most common in the spleen, liver, and lymph nodes.
Now we move from increases of peripheral blood leukocytes to increases of marrow in general, increases in cellularity (one dimension of expansion), increases from axial to appendicular skeleton (second dimension of expansion), and increases into other organs which do not normally make marrow in adults, such as liver and spleen and lymph nodes (third dimension of expansion).
CML is the CLASSIC prototype of all myeloproliferative diseases.
If a CML had much more than 10% blasts, you might suspect that the patient was going into a “blast crisis”.
This marrow is virtually 100% cellularity!!! This is the HALLMARK of CML, and all the cells are still marrow cells although blasts are INCREASED, i.e., more than 1-2 %. The “spaces” are NOT fat, they are blood vessels.
This marrow is virtually 100% cellularity!!! This is the HALLMARK of CML, and all the cells are still marrow cells although blasts are INCREASED, i.e., more than 1-2 %. The “spaces” are NOT fat, they are blood vessels.
This marrow is virtually 100% cellularity!!! This is the HALLMARK of CML, and all the cells are still marrow cells although blasts are INCREASED, i.e., more than 1-2 %. In this CML megakaryocytes are proliferating so what OTHER myeloproliferative disease could this be confused with? Ans: essential thrombocythemia (also called essential thrombocytosis)
This marrow is about 90% cellular and looks a lot like CML. This is P. vera
Note that this is NOT a marrow biopsy but a smear, so TRUE marrow cellularity cannot be assessed, however MOST of the cells are megakaryocytes!
Leukoerythroblastosis is an anemic condition resulting from space-occupying lesions in the bone marrow and characterized by the presence of immature granular leukocytes and nucleated erythrocytes in the circulating blood. Also called myelophthisic anemia.
Note most of the marrow looks “fibrotic”. What stain could help you confirm that this is fibrous tissue? (trichrome would stain collagen green)
CHRONIC leukemias, are essentially DIFFERENT from ACUTE leukemias, sorta.
The most life saving thing you can learn today is how to recognize a blast!
HUGE NUCLEUS
NUCLEOLI (stain LIGHTER not DARKER than the rest of the nucleus on Wright stain), How many nucleoli does that one blast cell have? Answer: 3
NO cytoplasmic differentiation
NOBODY IS GETTING OUT OF THIS ROOM ALIVE UNTIL THEY CAN IDENTIFY A BLAST CELL!
Ataxia-Telangiectasia is characterised by:
Early-onset progressive cerebellar ataxia (difficulty with control of movement)
Ocular apraxia (difficulty following objects across visual field)
Telangiectasias of the eyes and skin
Immunodeficiency, low immunoglobulin concentrations
Chromosomal instability
Hyper-sensitivity to ionizing radiation
Increased incidence of malignancies (primarily hematologic).
Raised alpha-fetoprotein levels.[4]
Absent thymic shadow on X-ray.
Ovarian dysgenesis
I will admit, these “blasts” DO look a little lymphocytic.
You can usually diagnose CLL simply from a CBC printout, but should verify the cells visually.
Many cells from CLL have a “smudge” or “basket” appearance. If you know what a NORMAL lymphocyte looks like, you can diagnose CLL purely by numbers! No marrow exam needed!
Why would a CLL have hypogammaglobulinemia? ANS: LYMPHS are the precursors of plasma cells!
An ironic thing is that the identification of plasma cells in the marrow for myeloma depends on how much they resemble NORMAL plasma cells! But do think the amount of monoclonal protein depends on how much they look and act like normal plasma cells? Ans: YES
Please memorize those THREE diagnostic features of plasma cells, the malignant plasma cells of MM look like normal plasma cells usually.
Ironically, most myelomas are recognized because they look like NORMAL plasma cells!
Normal on left, myeloma on right. Batman sign?
*The presence of large proliferations of monoclonal immune proteins are believed to interfere with normal coagulation.
Note the “lytic” lesions. Often the term “punched out” is used also.
What if you have a plasmacytoma but NO monoclonal gammopathy?
What if you have a monoclonal gammopathy but NO demonstrable proliferation of plasma cells?
What is the difference between a monoclonal and a polyclonal gammopathy? (monoclonals usually show a SPIKE on serum protein electrophoresis, SPE). Monoclonals are the result of malignant proliferations, polyclonals are generally the result of chronic inflammation.
Well, after CML, CLL, and ALL, all that is left is the BIG ONE!
Lets make this REAL easy…..ALL blasts look alike!!!! Why? Because there is NO cellular differentiation beyond the primitive stem cell appearance!
Don’t confuse M (myeloid), with simply M, myelocytic series!
AML’s are classified according to where the arrest occurs, i.e., the cells which proliferate in marrow and peripheral smear, and organs.
Blasts, blasts with AUER rods. Auer rods are clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of leukemic blasts. They are composed of fused lysosomes and contain peroxidase, lysosomal enzymes, and large crystalline inclusions.
Acute promyelocytic leukemia, remember promyelocytes have BOTH nucleoli AND nonspecific granules, true BLASTS do NOT have granules.
Do you remember that M3 has a high degree of association with DIC?
In AMML, M4, many of the peripheral leukemic cells look like monocytes, while in M5, Acute Monocytic Leukemia, MOST of them look like monocytes. M5 has also been called “Schilling”-type leukemia. (NOT the same Schilling of the B12 Schilling test)
In M6, many of the cells may resemble erythroid cells, in M7, many of the cells may resemble megakaryocytes. But in reality you would probably never think the blasts of M7 are related to megakaryocytes.
Note AMAZING similarity to ALL, clinically.
Surprised? Ans: NO
CCPP
Know the difference between a myelo-”proliferative” and a myelo-”dysplastic” disease.
Why does the phrase “effaced architecture” appear on my pathology reports of malignant lymphomas?
BENIGN FOLLICULAR HYPERPLASIA. Larger and more numerous than normal follicles. MEDULLA may be compromised.
BENIGN SINUS HISTIOCYTOSIS. The cortical area may be compromised. SINUS HISTIOCYTOSIS may be seen in reaction to cancer, even if there are NO tumor cells in the lymph node.
Mention Steve Swerdlow and link to his father!
Why does the pathologist often use the word “buttocks” cell, to describe a “cleaved” cell lymphoma?
“HAIRY” cell leukemia/lymphoma consists of lymphocytes which look hairy, but remember, on SEM ant TEM they all look hairy!
“Effacement” means any pattern in which follicles in the cortex and cords/sinuses in the medulla cannot be recognized because they are “effaced” or “obliterated”
Most pathologists HATE lymphoma classifications with a passion!
I HATE this slide.
I HATE this slide even worse.
If you feel the need to memorize this fine, but better to remember:
T markers <10
B markers 19-23
Mono/Mac teens
RS 15, 30
Prognosis of HD disease is related directly of percentage of lymphocytes and inversely to number of RS cells.
Prognosis of HD disease is related directly of percentage of lymphocytes and inversely to number of RS cells.
Prognosis of HD disease is related directly of percentage of lymphocytes and inversely to number of RS cells.
Prognosis of HD disease is related directly of percentage of lymphocytes and inversely to number of RS cells.
Prognosis of HD disease is related directly of percentage of lymphocytes and inversely to number of RS cells.
STERNBERG REED cells are called “lacunar” cells in one of the most common forms of HD called NODULAR SCLEROSING
If there was only one tiny microscopic focus of metastatic tumor cells in this lymph node, where would it most likely be?
The subcapsular sinus of the lymph node is the FIRST place you will spot a metastatic tumor nest!
We can also use the 50/50 principle generally for the spleen too: 50% “red” pulp, 50% “white” pulp.
RED PULP = RBCs (grossly and microscopically)
WHITE PULP = LYMPHS (grossly only, BLUE, microscopically)
Notice the “confluence” of WHITE pulp? Could this be lymphoma involvement? Ans: Yes Could this be granulomas? Ans: YES
Portal hypertension, prominence of RED pulp, i.e., red pulp >> 50%
What 3 malignancies have the highest preference for splenic metastases?
malignant melanoma
lymphomas
testicular germ cell tumors
Why is a splenic infarct a “pale” infarct? Answer: single end-artery blood source
Note all these are benign, except fot the lymphoma. The commonest MALIGNANT tumor primary to the spleen is a LYMPHOMA, by far!
Are you more likely to see accessory spleens with splenomegaly? Ans: YES
Hassal’s corpuscles are fused epithelial reticular cells
Benign (encapsulated), Malignant I (invasive), and Malignant II (easily metastasizable)
Note that the classification of thymomas has little to do with the appearance of the cells, but in the BEHAVIOR of the tumor grossly:
1) Encapsulated
2) Invasive
3) Metastatic