Non hodgkins lymphomas are of two cell types
T-cells
And B-cells
T-cells constitute only 10% of all Non-hodgkins lymphomas.
T cell lymphomas
Basic introduction of the T -cells-development , maturation and functions.
Cell of origin of various nodal and extranodal lymphomas
WHO classification revised 4th edition
Precursor lymphomas-
T-cell prolymphoblastic leukemia/lymphoma
Nodal lymphomas - Angioimmunoblastic lymphoma
Anaplastic lymphoma (ALK+&ALK-)
Peripheral T cell lymphoma - NOS
Extranodal lymphomas-
EN-Nk T-cell lymphoma nasal type
Intestinal lymphomas
EATL
METL
Hepatosplenic lymphoma
Leukemic lymphomas
Adult T cell leukemia
T-cell prolymphocytic leukemia
T cell large granular lymphocytic leukemia
Cutaneous lymphomas
Mycosis fungoides
Sezary syndrome
Summary:
CD8+/CD4- in Extranodal lymphomas: Hepatosplenic lymphomas, MEITL, T-LGL
CD4+/CD8- with diffuse CD30+ is ALCL .
CD4+/CD8- with TFH and TF dendritic markers + is AITL.
CD4+/CD8- with HTLV exposure is ATLL.
CD4+/CD8- with loss of CD7 with cutaneous manifestations+ epidermotropism+spongiosis is Mycosis fungoides.
Waste basket category is PTCL-NOS
CD4+CD8-CD10-PD1- with lymphocytosis is T-PLL
References
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
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
various cutaneous lymphomas though having low incidence but need to be diagnosed accurately. they can be mimiced by many non neoplastic conditions of skin. so discussing both T and B cell lymphomas
1. Cutaneous T-cell pseudolymphomas
A) Primarily with stripe-like infiltration (the majority of cases)
Lymphomatoid drug eruption (most cases);
Lymphomatoid contact dermatitis;
Actinic reticuloid;
Nodular scabies (individual cases);
Idiopathic forms;
Clonal cutaneous T-cell pseudolymphomas.
B) Primarily with nodular infiltration (a small percentage
of the cases)
Drug-induced – mainly by anti-convulsive drugs
Persistent nodules after insect bites;
Nodular scabies (the majority of cases).
2. Cutaneous B-cell pseudolymphomas (with nodular infiltration)
Cutaneous lymphocytoma from Borrelia burgdorferi;
Cutaneous lymphocytoma after antigens injection;
Cutaneous lymphocytoma resulting from tattoo;
Cutaneous lymphocytoma after Herpes zoster;
Idiopathic forms;
Clonal cutaneous B-cell pseudolymphomas
For undergradutes
Revise structure of lymph node and spleen
Classify non-neoplastic lesions
Various histological patterns
Etiologies of each lesion / pattern
There are several important changes in the WHO 5th edition hemato-lymphoid with a paradigm shift towards genetic diagnosis along with morphological aspects. Precursor lesions of Clonal hematopoiesis, CHIP and CCUS are formally included, Changes include those in AML, MPN, JMML is now a part of MPN, MDS-MPN, ALAL etc.
various cutaneous lymphomas though having low incidence but need to be diagnosed accurately. they can be mimiced by many non neoplastic conditions of skin. so discussing both T and B cell lymphomas
1. Cutaneous T-cell pseudolymphomas
A) Primarily with stripe-like infiltration (the majority of cases)
Lymphomatoid drug eruption (most cases);
Lymphomatoid contact dermatitis;
Actinic reticuloid;
Nodular scabies (individual cases);
Idiopathic forms;
Clonal cutaneous T-cell pseudolymphomas.
B) Primarily with nodular infiltration (a small percentage
of the cases)
Drug-induced – mainly by anti-convulsive drugs
Persistent nodules after insect bites;
Nodular scabies (the majority of cases).
2. Cutaneous B-cell pseudolymphomas (with nodular infiltration)
Cutaneous lymphocytoma from Borrelia burgdorferi;
Cutaneous lymphocytoma after antigens injection;
Cutaneous lymphocytoma resulting from tattoo;
Cutaneous lymphocytoma after Herpes zoster;
Idiopathic forms;
Clonal cutaneous B-cell pseudolymphomas
For undergradutes
Revise structure of lymph node and spleen
Classify non-neoplastic lesions
Various histological patterns
Etiologies of each lesion / pattern
There are several important changes in the WHO 5th edition hemato-lymphoid with a paradigm shift towards genetic diagnosis along with morphological aspects. Precursor lesions of Clonal hematopoiesis, CHIP and CCUS are formally included, Changes include those in AML, MPN, JMML is now a part of MPN, MDS-MPN, ALAL etc.
Lymphoma is a cancer of lymphocytes. The most common place for abnormal lymphocytes is in lymph nodes (glands) particularly
under the arms, in the neck and in the groin.
Lymphoma is solid tumors of the immune system arising from cells of lymphoid tissues; lymphocytes, histiocytes, and reticulum cells. It can happen anywhere in the immune system, but usually in lymph nodes, spleen, marrow, and tonsils. Location and the behavior of lymphomas separate them from leukemia.The malignancy starts and restricted to lymphoid tissues and progress to involve the BM and appears in PB, at this stage it may be named, “lymphosarcoma cell leukemia.
Lymphoma by Sunil Kumar Daha (Hodgkins and Non-Hodgkins)sunil kumar daha
Please find the power point onLymphoma . I tried to present it on understandable way and all the contents are reviewed by experts and from very reliable references. Thank you
REFERENCES
cancer.org | 1.800.227.2345
Advances in the diagnosis and management
of lymphoma
Zachary H Word1
Matthew J Matasar1,2
1
Lymphoma Service, Department of
Medicine, Memorial Sloan–Kettering
Cancer Center, 2
Department of
Medicine, New York Presbyterian
Hospital, New York, NY, USA
Correspondence: Matthew J Matasar
Memorial Sloan–Kettering Cancer Center,
1275 York Avenue, New York,
NY 10065, USA
Tel +1 212 639 8889
Fax +1 646 422 2291
Email matasarm@mskcc.org
Lymphoma and CLL Forms
Parameswaran Hari, MD, MS
CLymphoma 101: The Basics
Neha Mehta-Shah, MD, MSCI
Assistant Professor
Department of Medicine
Division of Oncology
IBMTR , Milwaukee
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.
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
- 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
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
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These lecture slides, by Dr Sidra Arshad, offer a quick overview of 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 leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
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. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
8. INTRODUCTION
• Mature T- and Natural killer (NK)- cell malignancies are rare, accounting
for 10 – 12% of all Non-Hodgkin's lymphoma.
• More common in Asia and linked to EBV viral infection (NK-cell
lymphomas) and human T-cell leukaemia virus (HTLV-1) (adult T-cell
leukaemia/lymphoma).
• More aggressive than B-cell lymphomas.
9. WHO CLASSIFICATION OF PRECURSOR LYMPHOID NEOPLASMS
• T-Lymphoblastic leukemia/lymphoma
• Early T-cell Precursor lymphoblastic leukemia
• Nk-lymphoblastic leukemia/lymphoma
10. T-LYMPHOBLASTIC LEUKEMIA/LYMPHOMA
(Precursor T-lymphoblastic leukaemia/ lymphoma)
• Definition : Refers to neoplasm of immature lymphoid cells
(lymphoblasts) of T-cell lineage.
• Age : Most common in adolescents and young adults
Median age of 28 years.
• SEX: Males > Females.
• Clinical findings : Widespread lymphadenopathy (neck, axillae and
supraclavicular).
• Mediastinal mass is common
• Hepatosplenomegaly often present.
11. T-Lymphoblastic leukemia
T-ALL T-LBL
• Involving Bone marrow and
Blood
• 15% of childhood ALL cases
• 25% of cases of adult ALL
• Involving Thymus or Nodal or
Extra nodal
• 85–90% of all LBLs
12. Peripheral blood smear and Bone Marrow
• Anemia
• Granulocytopenia,
• Lymphoblasts >25%
• Thrombocytopenia
13. LYMPH NODE
• Architecture : Effaced
• Capsule & Para cortex :
Involved
• Pattern : Multinodular –
mimicking Follicular
lymphoma.
Starry Sky -
mimicking Burkitt lymphoma.
• Lymphoblasts : Medium sized-
round or Convoluted nuclei -
High N: C ratio, Frequent
mitotic figures.
14. TdT, CD34, CD1a & CD99 are positive
(suggest Precursor T-lymphoblasts)
CD7, CD3(cytoplasmic), CD2, CD5
(Immature markers) are often positive.
CD4, CD8 & CD10 are Positive
• The most common recurrent
cytogenetic abnormality
involves the αδ TR loci at
14q11.2.
• β locus at 7q35, and the γ locus
at 7p14-15, with a variety of
partner genes
• Deletions of (9q)
CYTOGENETICS
15. CRITERIA FOR DIAGNOSIS
1. Frequently associated with mediastinal mass
2. Relatively uniform cell population with high mitotic rate
3. Variable number of round - convoluted (deeply indented) nuclei
4. Dense, finely granular chromatin, mostly inconspicuous nucleoli
5. Scanty, pale, fragile cytoplasm.
6. Immunophenotype: TdT, most often CD3 (cytoplasmic) and CD7;
Often CD4 and CD8 double positive or double negative; variable positivity
with CD1a, CD34, CD10.
7. 50-70% abnormal karyotype.
16. WHO CLASSIFICATION
• Mycosis fungoides
• Sézary syndrome
• Primary cutaneous CD30+ T cell lymphoproliferative disorders
• Lymphomatoid papulosis
• Primary cutaneous anaplastic large cell lymphoma
• Primary cutaneous gamma delta cell lymphoma
• Primary cutaneous CD8+ aggressive epidermotropic cytotoxic
T cell lymphoma
• Primary cutaneous acral CD8+ T cell lymphoma*
• Primary cutaneous CD4+ small / medium T cell
lymphoproliferative disorder*
• Peripheral T cell lymphoma, NOS
• Angioimmunoblastic T cell lymphoma
• Follicular T cell lymphoma*
• Nodal peripheral T cell lymphoma with T follicular helper
phenotype*
• Anaplastic large cell lymphoma, ALK+
• Anaplastic large cell lymphoma, ALK-*
• Breast implant associated anaplastic large cell lymphoma*
MATURE T-CELL AND NK CELL NEOPLASMS
• T cell prolymphocytic leukemia
• T cell large granular lymphocytic leukemia
• Chronic lymphoproliferative disorder of NK cells
• Aggressive NK cell leukemia
• Systemic Epstein-Barr virus+ T cell lymphoma of
childhood*
• Hydroa vacciniforme-like lymphoproliferative disorder*
• Adult T cell leukemia / lymphoma
• Extranodal NK / T cell lymphoma, nasal type
• Enteropathy associated T cell lymphoma
• Monomorphic epitheliotropic intestinal T cell lymphoma*
• Indolent T cell lymphoproliferative disorder of the GI
tract*
• Hepatosplenic T cell lymphoma
• Subcutaneous panniculitis-like T cell lymphoma
21. MICROSCOPIC
• Lymph node: Three most common
features are
1. Diffuse pattern with Partial or
complete architecture effacement.
2. Numerous arborizing blood vessels,
lined by hyperplastic endothelial
cells.
3. Polymorphous population of cells
with a variable number of small and
large size with Hyperchromatic
nuclei and clear cytoplasm.
4. Numerous reactive cells including
plasma cells, eosinophils,
immunoblasts, small lymphocytes
and follicular dendritic cells.
22. • Subdivided into 3 histological patterns
TYPE-I
• Architecture-
Partially
preserved and
hyperplastic
follicles with
tingible body
macrophages
and indistinct
mantle zones
• Seen in 10-20%
of cases
TYPE-
II
• Architecture-
Preserved
mostly with
residual follicles.
• In half of the
cases
TYPE-III
• Architecture-
Completely
effaced without
residual
follicles.
• In remaining
cases.
23.
24. IMMUNOPHENOTYPE
• T cell antigens: εCD3, CD4, CD5 and CD7.
• Follicular dendritic cells: CD21, CD23, CD35
• TFH markers: CXCL13, CD10, PD1 & BCL6
• EBER (Epstein-Barr virus encoded small RNAs)
• Loss of sCD3 is more common in bone marrow and peripheral blood
compared to lymph nodes.
• CD8 –Ve and loss of CD7 is also observed
25. CYTOGENETICS/MOLECULAR STUDIES
• Karyotypic abnormalities in 90% of
the cases.
• Trisomy of chromosomes 3,5 and
21. Gain of chromosome X.
• Monoclonal T-cell receptor gene
rearrangements γ or β in 80%-90%
of AILT cases.
• Next generation sequencing panel
showed TET2, DNMT3, RHOA and
IDH2 mutations.
DIFFERENTIAL DIAGNOSIS
• Reactive lymphoid hyperplasia
• Classic hodgkins lymphoma, mixed
cellularity
• Peripheral T cell lymphoma –NOS
• EBV+ diffuse large B cell lymphoma, NOS
26. ANAPLASTIC LARGE – CELL LYMPHOMA-ALK POSITIVE
(Malignant Histiocytosis)
• Definition:
A peripheral T cell lymphoma consisting of large lymphoid cells with abundant
amphophilic cytoplasm, often horseshoe shaped nuclei, an ALK (anaplastic
lymphoma kinase) gene translocation, expression of ALK protein (CD246) and
CD30
• Constitutes 10-20% of childhood lymphomas.
• Age : First 3 decades of life
• SEX : M: F - 1.5 :1
• LOCALIZATION : Lymph nodes & extra nodal sites.
27. PATHOGENESIS
• Neoplastic cells are activated mature cytotoxic T cells (CD30+)
• Oncogenic translocations result in constitutive activation of the ALK tyrosine
kinase
• Resulting fusion proteins are shown to be involved in different downstream signalling
pathways including RAS/ERK, PI3K/Akt and JAK/STAT.
28.
29. MICROSCOPY
• Small-medium-large anaplastic cells
• Interfollicular T zones and subcapsular
sinuses infiltration
• Cohesive growth pattern
• Intrasinusoidal infiltration pattern
• Anaplastic large cells with abundant
cytoplasm, wreath-like or multiple nuclei,
open chromatin, multiple nucleoli,
perinuclear eosinophilic region
(prominent Golgi zone)
• Cells with horseshoe / kidney / embryo
shaped nuclei are referred to as
“hallmark cells”.
• Brisk mitotic activity
30. • Lympho histiocytic (10%)
• Numerous histiocytes and small lymphocytes, occasional
erythrophagocytosis
• Small cell (5 - 10%)
• Predominantly small cells with irregular nuclei, hallmark cells present (tend
to be perivascular), occasional fried egg cells, rare signet ring cells
• Hodgkin-like (1 - 3%)
• Mimics nodular sclerosis classic Hodgkin lymphoma;
• Hypocellular
• Small cell types may have hypocellular, granulation tissue-like appearance
• Composite pattern (10 - 20%)
• More than one pattern.
VARIANTS
33. CYTOGENETICS /MOLECULAR DIAGNOSIS
• Clonal T cell receptor (TCR) gene rearrangement seen in 90%
• All translocations result in upregulation of ALK protein
• ALK translocation results in activation of the downstream oncogenic
transcription factor, STAT3
• STAT3 activation regulates availability of hypoxia inducible factors involved in
tumor growth and metastasis
• t(2;5)(p23;q35): ALK and NPM (75 - 85%)
• t(1;2)(q25;p23): tropomyosin 3 (TPM3) and ALK (13%)
• inv(2)(p23;q35): ALK and ATIC (1%)
35. ALK NEGATIVE ANAPLASTIC LARGE CELL LYMPHOMA
• Morphologically similar to ALK +ALCL but is ALK negative.
• Common in Adults (40-65 years)
• Sites: Both lymph nodes and extra nodal sites, including bone, soft
tissue and skin
• Etiology : Unknown
PATHOPHYSIOLOGY:
• Recurrent rearrangement involving the TP63 gene
• STAT3 activating mutations
• DUSP22 rearrangements
36. MICROSCOPY
• Morphologically indistinguishable from ALCL, ALK positive
• Effaced architecture with solid, cohesive sheets of neoplastic cells
• May show preserved lymph node architecture with neoplastic cells
growing intrasinusoidally or only within the T cell areas
• Large cells with round to indented nuclei, deeply staining cytoplasm,
with prominent Golgi zone
• Hallmark cells (cells with eccentric, horseshoe or kidney shaped nuclei)
• Cases with DUSP22 rearrangements show smaller, monomorphic cells
with central nuclear pseudo inclusions (doughnut cells)
39. PERIPHERAL T-CELL LYMPHOMA (NOS)
(lymphoepithelioid lymphoma; Lennert lymphoma)
• Definition: Mature T cell lymphoma that does not meet WHO classification
criteria of other mature T cell lymphoma entities
• Heterogeneous category of nodal and extra nodal mature T-cell
lymphomas. (Wastebasket category)
• AGE : Adults, and has an aggressive clinical course.
• PTCL-U can be preceded by an immunologic disorder such as Hashimotos
thyroiditis, Immune thrombocytopenic purpura and Rheumatoid arthritis.
• Cell of origin: Activated mature T cells (CD4+ memory T cell)
40. LYMPH NODE
• Effacement of the normal
architecture.
• Para cortical or diffuse infiltrates
• Polymorphous to monomorphic.
• Most cases consist of medium-large
cells with irregular, pleomorphic,
hyperchromatic, or vesicular nuclei;
prominent nucleoli; and many
mitotic figures.
• Clear cells and Reed-
Sternberg―like cells can also be
seen. Rare cases have a
predominance of small lymphoid
cells with atypical, irregular nuclei.
• An inflammatory background is
often present.
41. MOLECULAR SUBTYPES
•GATA3 subtype (35% of PTCL, NOS):
• ≥ 50% tumor cells positive for GATA3 or
CXCR3 by IHC
• Associated with monomorphic
morphology with minimal inflammatory
background
• Very poor overall survival
•TBX21 subtype (58% of PTCL, NOS):
• ≥ 20% tumor cells positive for TBX21 or
CCR4 by IHC
• Associated with polymorphous
morphology
• Longer overall survival
42. Lymphoepithelioid variant
•Typically shows a diffuse infiltrate
of small cells with subtle nuclear
atypia numerous epithelioid
histiocytes which often form
clusters
•Correlates with TBX21 molecular
subtype
•May have better prognosis than
other PTCL, NOS subsets
43. • Extra nodal – Diffuse
infiltration with similar
cells
• SKIN : Infiltration in the
dermis and subcutis, often
producing nodules, which
may undergo central
necrosis.
Epidermotropism,
angiocentricity, and
adnexal involvement are
sometimes seen.
44. IMMUNOPHENOTYPING
• Pan T cell antigens CD3, CD5 and/or CD7 +ve.
• CD4+/CD8-
• Cases may be double positive or double negative for CD4 and CD8
• TCR alpha/beta
• CD30 : Variable (heterogeneous)
• ALK –ve
• T follicular helper markers -ve (CD10, BCL6, PD1, CXCL13)
• EBER -ve
45. MOLECULAR DIAGNOSIS
• PCR demonstrates
clonal rearrangement of
TCR genes.
• Next generation
sequencing shows
recurrent alterations of
TP53, TET2, CDKN2A ...
DIFFERENTIAL DIAGNOSIS
• Classic hodgkins lymphoma
• ALK negative Anaplastic large cell
lymphoma
• Angioimmunoblastic T cell lymphoma
• Adult T cell leukemia/ lymphoma
• Mycosis fungoides
47. EXTRA NODAL NK /T CELL LYMPHOMA –NASAL TYPE
(Polymorphic reticulosis/Malignant midline reticulosis/Lethal midline granuloma/Angiocentric T cell
lymphoma)
• DEFINITION : Aggressive extranodal lymphoma of NK / T cell origin
characterized by angiotropism and angiodestruction, necrosis and association
with Epstein-Barr virus (EBV)
• AGE : 5th to 7th decade.
• SEX : M:F – 2:1
• SITES : Nasal cavity (mc), GIT, Skin, Testis, Lung, Spleen and liver
• Clinical features : Nasal / upper airways obstruction, purulent discharge,
epistaxis and facial mass with surrounding edema, Pleural effusion and
elevated serum LDH
48. PATHOPHYSIOLOGY
• Nk cells infected by EBV secrete IL9 and IL10 which promote cell
activation and proliferation.
• Frequent 30 base pair deletion in LMP1 gene leads to a decrease in
immune recognition
49. LYMPH NODE
• Monotonous population of cells
• Paracortex or medullary
infiltration.
• Moderate cytoplasm, folded
nuclei and indistinct nucleoli.
• Coagulative necrosis
• Frequent mitosis
50. SKIN
• Dense and atypical lymphoid
infiltrate in dermis and subcutis
• Frequent mitoses, necrosis and
angioinvasion
• Association with microthrombi
• Involvement of hair follicles and
sweat glands
52. ENTEROPATHY ASSOCIATED T CELL LYMPHOMAS
• Definition : Intestinal lymphoma derived from intraepithelial T cells
which occurs in patients with celiac disease
• Age : 6th to 7th decade
• SEX : M=F In few areas Female preponderance.
• SITES : Small intestine more frequent
Jejunum > Ileum or Duodenum
• Clinical features :
Abdominal pain, diarrhoea and vomiting, Malabsorption, Fever,
Fatigue, Weight loss.
53. MICROSCOPY
• Intestinal involvement:
Ulcerated lesion with diffuse
and pleomorphic infiltrate of
medium to large cells ,
angulated nuclei, prominent
nucleoli and abundant
cytoplasm.
Mitotic figures and necrosis
are common.
Angiotropism.
Background inflammatory
cells.
Features of celiac disease –
Mucosa adjacent to EATL.
• Lymph node : Sinusoidal
pattern.
54. MONOMORPHIC EPITHELIOTROPHIC INTESTINAL T-CELL LYMPHOMA
• Definition : Previously known as Type-II enteropathy associated T-cell lymphoma,
is a mature intestinal T-cell lymphoma.
• Arise from intraepithelial T-lymphocytes & lacks association with Celiac disease.
• Rare, aggressive disease
• Median age in the sixth decade
• M:F = 2:1
• Sites : Small bowel, especially the jejunum, followed by ileum
• Clinical features : Abdominal pain, Obstruction or Perforation, weight lss,
diarrhea & gastro intestinal bleeding.
55. GROSS
• Neoplastic lymphocytes are relatively
monotonous, intermediate in size, with
round or slightly irregular nuclear contours,
dispersed chromatin, inconspicuous nucleoli
and scant rim of pale cytoplasm
• Prominent epitheliotropism as well as
transmural infiltrate are characteristic
• Few inflammatory cells are noted in the
background.
MICROSCOPY
56.
57. • Spleen tyrosine kinase (SYK) was
overexpressed in MEITL.
• Extra signals for MYC at 8q24 are
commonly seen
• Proliferation index (Ki67) was
approximately 90% Differential Diagnosis
• Enteropathy associated T cell
lymphoma (EATL)
• Mycosis fungoides with gastrointestinal
involvement
Positive: surface CD3, CD8, CD56,
granzyme B and TCRδγ
Negative: CD4, CD5, surface TCRαβ
Cytogenetics/Molecular diagnosis
58. HEPATOSPLENIC T CELL LYMPHOMA
(Erythrophagocytic Tγ lymphoma)
• Definition : Rare, aggressive extra nodal neoplasm that originates from cytotoxic T
cells; it usually expresses the T cell receptor (TCR) γδ (gamma delta)
• More common in young adult men, median age ~35 years.
• M > F
• Clinical findings : Hepatomegaly and splenomegaly, Moderate anemia,
Thrombocytopenia and Neutropenia, Lymphadenopathy is uncommon.
59. Pathophysiology
• Neoplastic clonal proliferation of γδ T cells induced by the
upregulation of the JAK / STAT (STAT3 and STAT5B) and PI3K
signaling pathways
(Or)
• Mutations of chromatin modifiers (SETD2, INO80 and ARID1B)
61. Cytogenetics/Molecular diagnosis
• Gamma delta origin: biallelic
rearrangement of TRG
• Mutations in JAK / STAT pathway
• Isochromosome (7q) or ring
chromosome 7
• Trisomy 8
Differential Diagnosis
• Splenic marginal zone lymphoma
• T-cell large granular lymphocytic
leukemia
TCRγδ in 80% of cases
CD2+, CD3+, CD7+, CD56+, CD8+/-,
CD4-, CD5-,
Variable CD16 and CD94 (dim or negative)
63. ADULT T CELL LEUKEMIA/LYMPHOMA
• Definition : Aggressive T cell neoplasm of mature CD4+ T cells
associated with human T lymphotropic virus 1 (HTLV1)
• SITES : Widespread lymph node involvement in most
• Systemic: Spleen and extranodal sites including the skin, peripheral blood.
• Age : Adults average 58 years
• SEX : M: F – 1.5:1
64. PATHOPHYSIOLOGY
• Cell of origin is peripheral CD4+ T regulatory αβ T cell (CD4+ CD25+
FoxP3+)
• ATLL patients suffer from profound immunodeficiency
65. Clinical manifestation Acute (mc) Lymphomatous Smouldering Chronic
Lymphocytosis Increased No No Mildly increased
Blood abnormal
lymphocyte
Increased No* > 5% Mildly increased
Increased LDH Yes No No Minimal
Hypercalcemia Yes Variable No No
Skin rash Variable: > 50% Variable: > 50% Erythematous rash Rash, papules
Lymphadenopathy Generalized Yes No Mild
Hepatosplenomegaly Usually present Often present No Mild
Bone marrow
infiltration
May be present No No No
Median survival < 1 year < 1 year > 2 years > 2 years
SHIMOYAMA CLASSIFICATION FOR CLINICAL VARIANTS
66. MICROSCOPY
PERIPHERAL BLOOD:
• Medium to large sized
lymphocytes with multilobulated
nuclei (flower cells), condensed
chromatin, absent or small
nucleoli, scant slightly basophilic
cytoplasm
67. BONE MARROW
• Pattern of marrow involvement
can be diffuse, interstitial or
sinusoidal
• Often evidence of bone resorption
and osteoclastic activity
• Bone trabeculae: may show
remodelling
• Lytic bone lesions can be present
even in the absence of tumoral
bone infiltration
68. LYMPH NODE
• Involves paracortical T cell zones
• Diffuse architectural effacement
• May be subdivided according to
cell type and pattern
• Pleomorphic medium and
large cell type / pattern (most
common)
• Anaplastic large cell-like
• Hodgkin lymphoma-like: seen
in early phase of some adult T
cell lymphoma
69. SKIN LESIONS
• Epidermal infiltration with
Pautrier-like micro-abscesses is
common.
• Hyperparakeratosis is variably
present in the overlying epidermis
• Dermal infiltration: mainly
perivascular but larger tumor
nodules with extension to
subcutaneous fat may be
observed
• Papules and nodules: composed
of larger cells that replace dermis
70. IMMUNOPHENOTYPING
• ATLL is neoplasm of mature T
cells, CD2+, CD3+, CD5+,TCR
αβ+, CD1a-, CD7-, CD10-, PD-1-
• ~ 90% of cases are CD4+ CD8-
DIFFERENTIAL DIAGNOSIS
• Peripheral T cell lymphoma –NOS
• Angioimmunoblastic T-cell
lymphoma
• Anaplastic large cell lymphoma
71. T-PROLYMPHOCYTIC LEUKEMIA
(T cell chronic lymphocytic leukemia (small cell variant of T cell prolymphocytic leukemia)
• Definition : Aggressive, mature T cell leukemia, composed of small to medium sized
mature T cells, with high white blood cell (WBC) count and widespread organ
involvement
• Rare (2% of mature lymphocytic leukemias)
• Adults and elderly (> 30 years) Median age: 65 years
• Sites : Peripheral blood, bone marrow, lymph nodes, spleen, liver, skin
• Clinical picture : Hepatosplenomegaly, lymphadenopathy, Anemia & thrombocytopenia,
high leukocyte count (>100 x 109/L) with skin and mucosal lesions.
72. Pathophysiology
• Overexpression of TCL1 family of proteins (which
stimulate AKT / protein kinase B driven
proliferation)
• Functional deficit of ATM
73. PERIPHERAL SMEAR
• Lymphocytosis with small
to medium sized
lymphocytes with
cytoplasmic blebs,
clumped chromatin and
variably prominent
central nucleolus
• Small cell variant in 25%
• Cerebriform variant in 5%
75. Cytogenetics/Molecular diagnosis
• Clonal T cell receptor gene
rearrangements
• TCL1A / TCL1B rearrangement:
inv(14)(q11;q32) in 80%,
t(14;14)(q11;q32) in 10%
• Rarely MTCP1 rearrangement
t(X;14)(q28;q11)
• Complex karyotype in 70 - 80%;
• Mutations in ATM gene on 11q23 in
80 - 90%
Differential diagnosis
• Adult T-cell leukemia/ lymphoma
• T-cell large granular lymphocytic leukemia
Mature CD3 positive T cells, usually
express pan T markers CD2, CD5 and
CD7; positive for CD52
CD4+, CD8- in 60%
76. T-CELL LARGE GRANULAR LYMPHOCYTIC LEUKEMIA
• DEFINITION: A chronic T cell lymphoproliferative disorder- clonal proliferation of mature
cytotoxic T cells without an identified cause. Presenting with cytopenia.
• 2 - 5% of mature lymphocytic leukemias
• Gender : M = F
• Age : Elderly with a median age of 60 years
• SITES : Peripheral blood, bone marrow, spleen, liver
• Clinical Features :
• Majority have neutropenia or anemia
• 30% are asymptomatic but regular complete blood count reveals lymphocytosis and
cytopenia
• Splenomegaly , autoimmune disorders- Rheumatoid arthritis(most common)
• Associated with other hematologic malignancies such as B cell lymphoma, myelodysplastic
syndrome and aplastic anemia
77. PATHOPHYSIOLOGY
• Oligo clonal expansion of cytotoxic large granular T cells in response to antigen
stimulation
• Upregulation of cellular survival signals or downregulation of apoptotic pathways
• STAT3 / STAT5b mutation as a secondary event
• Other secondary events - Resistance to Fas / FasL mediated cell death.
78. BONE MARROW
CD3+ CD8+
granzyme B+
TIA1+
No abnormal lymphocytic infiltration by
H&E
IHC demonstrates Intra-sinusoidal pattern
79. PERIPHERAL SMEAR
• Increased lymphocytes
containing small to
intermediate sized
reticulated nuclei and
fine to coarse azurophilic
cytoplasmic granules
80. Cytogenetics/Molecular studies
• Clonal T cell receptor (TCR) gene
rearrangements
• STAT3 mutation in 40 - 50% of T cell large
granular lymphocytic leukemia
• STAT5b mutation in 2% of T cell large
granular lymphocytic leukemia
Differential diagnosis
• Chronic lymphoproliferative disorder
of NK cells
• Peripheral T cell lymphoma
Mature CD3 positive T cells,
usually coexpress NK cell
associated markers (CD16 and
CD57)
CD4- CD8+
82. MYCOSIS FUNGOIDES
• DEFINITION : Peripheral T cell lymphoma derived from Mature, post-
thymic T lymphocytes
• Presents as cutaneous patches and can progress to plaques, tumors and
erythroderma
• EPIDEMIOLOGY : M>F ; Median age - 50yrs
• SITES: Bathing trunk distribution.
• CELL OF ORIGIN: Effector Memory T cells
83. MICROSCOPY
• Early lesions are histologically
indistinguishable from inflammatory skin
diseases
• Band-like papillary dermal lymphoid
infiltrate
• Intraepidermal lymphocytes out of
proportion with spongiosis
(epidermotropism) ± Pautrier
microabscesses
• Lymphocytes in the junction and within the
epidermis may have haloes & variable
nuclear pleomorphism, nuclear contour
irregularity (cerebriform cytomorphology
can be difficult to appreciate on biopsies)
and hyperchromasia
85. STAGING (ISCL & EORTC)
Skin
T1
Limited patches, papules or plaques covering <
10% of the skin surface:
T1a: patch only
T1b: plaque with or without patch
T2
Patches, papules or plaques covering ≥ 10% of
the skin surface:
T2a: patch only
T2b: plaque with or without patch
T3 One or more tumors (≥ 1cm diameter)
T4
Confluence of erythema covering ≥ 80% body
surface area
Node
N0 No clinically abnormal peripheral lymph node
N1
Clinically abnormal peripheral lymph nodes;
histopathology Dutch grade 1 or NCI LN0-2
N1a: clone negative
N1b: clone positive
N2
Clinically abnormal peripheral lymph nodes;
histopathology Dutch grade 2 or NCI LN3
N2a: clone negative
N2b: clone positive
N3
Clinically abnormal peripheral lymph nodes;
histopathology Dutch grade 3 - 4 or NCI LN4;
clone positive or negative
Nx
Clinically abnormal peripheral lymph nodes with
no histological confirmation
Visceral
M0
No visceral organ
involvement
M1
Visceral involvement (must
have pathological
confirmation)
Peripheral Blood (PB)
B0
Absence of significant
blood involvement: ≤ 5%
Sézary cells in PB
B0a: clone negative
B0b: clone positive
B1
Low blood tumor burden: >
5% Sézary cells in PB and
does not meet criteria of B2
B1a: clone negative
B1b: clone positive
B2
High blood tumor burden: ≥
1000/µL Sézary cells in PB
with clone positive
86. IMMUNOHISTOCHEMISTRY
• Diagnosis of exclusion
• Mature T cell phenotype ( CD45RO+, TCRβ+, CD2+, CD3+, CD4+
[frequent], CD5+, CD7+) is most commonly observed
• Loss of CD2 or CD5 favors mycosis fungoides
• Partial loss of CD7 is common.
• TCR gamma, CD8 & EBER are negative.
87. SEZARY SYNDROME
• Definition : Leukemic variant of cutaneous T cell lymphoma (CTCL)
defined by the presence of erythroderma, generalized
lymphadenopathy and clonal T cells with cerebriform nuclei (Sézary
cells)
• If same clone expressed in skin, lymph node and Peripheral blood –
Stronger diagnosis
• Cell of origin : Effector memory T cells (CD45RO)
88. PATHOPHYSIOLOGY
• Abnormalities in pathways:
NFκB / JAK STAT activation, cell
cycle dysregulation / apoptosis
and DNA structural
dysregulation affecting gene
• Chemokine receptors:
CCR4/CCR10
• Overexpression of CD47
CLINICAL FEATURES
• Erythroderma
• Alopecia
• Nail dystrophy
• Pruritis
Note: Clinical presentation with
erythroderma with < 1 x 109/L is
defined as pre-Sézary and some
patients progress to SS
89. MICROSCOPY
• SS is histologically similar to mycosis fungoides but sometimes epidermotropism is not
present
• May range from limited to superficial perivascular lymphocytic and eosinophilic
dermatitis with or without spongiosis (atopic-like lesions)
• Pautrier microabscesses are not common
• Peripheral blood
• Sézary cells: Atypical lymphocytes of intermediate to large size and cerebriform
nuclei
• Lymph node
• Complete effacement of the nodal architecture by monotonous infiltrating
population of Sézary cells
• Large cell or blastoid morphology may occur in advanced stages.