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Home , Burkitt lymphoma, Follicular lymphoma, Multiple myeloma

Lymphoproliferative disorders

Objectives: • To understand the general features of lymphoproliferative disorders (LPD) • To understand some benign causes of LPD such as • To understand the general classification of malignant LPD Important. • To understand the clinicopathological features of chronic lymphoid Extra.

• To understand the general features of the most common Notes (LPD) (Burkitt , , and ). •

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References:

Editing file 435 teamwork slides 6 girls & boys slides

Do you have any suggestions? Please contact us! @haematology436 E-mail: [email protected] or simply use this form Definitions Lymphoma (20min) Lymphoproliferative disorders: Several clinical conditions in which are produced in excessive quantities () increase in lymphocytes that are not normal Lymphoma: Malignant lymphoid mass involving the lymphoid tissues. (± other tissues e.g: skin, GIT, CNS ..) The main deference between Lymphoma & Leukemia is that the Lymphoma proliferate primarily in Lymphoid Tissue and Mass , While Leukemia proliferate mainly in BM& Peripheral blood : Malignant proliferation of lymphoid cells in marrow and peripheral blood. (± other tissues e.g: lymph nodes, , skin, GIT, CNS ..) BCL is an anti-apoptotic (prevent )

Lymphocytosis (causes) 1- Viral : 2- Some* bacterial 5- Chronic lymphocytic Infectious infection: (Pertussis, leukemia (CLL) mononucleosis, brucellosis) , * Usually bacterial give PMN 6- Other : rubella, hepatitis, 3- Immune : SLE, , adenoviruses, varicella Allergic drug reactions Hodgkin lymphoma The most common cause of 4- Other conditions:, lymphocytosis is viral splenectomy, infection dermatitis, hyperthyroidism metastatic carcinoma)

NO blasts! Mature Smear cell Reactive lymphocyte

Infectious mononucleosis (May predispose the patient to Lymphoma if it chronic)

An acute, infectious , caused by Epstein-Barr (EBV) characterized by: - - Sore throat

ميز Swollen lymph nodes (painful) - Atypical lymphocyte -

most common cause of lymphocytosis in children Affect young people (usually) Clinically, IM presents like ALL. But when we do blood smear we will find atypical lymphocytes and NO blasts and this will rule out ALL.

مستعجل\ة؟ اقفز\ إل الجدل (In a hurry? Skip to the table (slide 7 Malignant lymphoproliferative disorders

- CLL - Hairy cell This lecture is leukemia about - T- prolymphocytic B-Lymphocytes leukemia - Leukemic phase of Only! - lymphoma - Diffuse large B lymphoma Immature (ALL) - Follicular Malignant lymphoma Lymphoproliferative Lymphoid Leukemia - Multiple myeloma disease Mature Hodgkin

Lymphoma B- Cell 90%

Non-Hodgkin

B cell is more T- Cell 10% common but has better . You have to know which are T-cell -Adult T leukemia lymphoma or B-cell - Sezary syndrome* - Large anaplastic Journey of B-lymphocytes & that cause disorders:- T lymphoma In Leave bone marrow and are mature * نشع نظفحت ك مسا هيف T م عدا هذه

This circle is

Germinal center

Mantle zone

Key:

Disorder

Naïve Mutationمعنه

بلعربي قيل الخبرة

Cell type فـ عشن نحفظ الـ (surface Ig( حقت نربط بطل Markers الط ال م يتخرج يصير لقبه MD ه خبرته لس قية ) ) IgM & IgD)

Throughout the maturation where ever the disease occurs (at which stage) there will be specific findings For the mutations notice that they all have the number 14 so just memorise the other number. Chronic lymphocytic leukemia - Malignant neoplasm characterized by an increased number of small, mature lymphocytes in the blood (>5,000 ) and bone marrow (± spleen and lymph node) - The most common adult leukemia (~25% of adult ) - The median age is ~55 to 65 years. ( rare < 40 years). - 1.5 to 2 times more common in men than women. Features: - 40% of patients are asymptomatic at diagnosis. - Moderate lymphadenopathy and splenomegaly

- Lymphocytosis (>5,000): (Most important) Soccer ball - Small mature-appearing lymphocytes - soccer ball - smudge cells - PredispositionCondensed to infection nuclear chromatin - AutoimmuneNumerous phenomena (autoimmune hemolytic ) - Transformation to large cell lymphoma CLL Staging smudge cells Richters syndrome

Lymphoma

BurkittsHigh-grade non-Hodgkin's B-cell lymphoma which is rapidly growing (fastest growing tumor in humans) and highly aggressive with extremely short doubling time (24 hrs) but it has excellent response if we act quickly (see the picture) Types:- 1-Endemic: associated with chronic and EBV In equatorial Africa . It particularly affects the jaw, other facial bone and . 2-Sporadic: occurs throughout the world and affects GIT. 3--associated: associated with HIV infection or the use of immunosuppressive drugs. Morphology Genetics BMA

Homogenous medium Diffuse infiltration with Highly associated with t(8;14) size cells with round nuclei and deeply "starry sky Translocation of the c- proto- basophilic and ( engulfing at to immunoglobulin gene vacuolated cytoplasm the apoptotic cells) at The c-MYC is nuclear factor . Follicular Lymphoma Follicular Lymphoma Management - A malignant proliferation of B cells which has at least a partially follicular pattern. - Due to overexpression o f Bcl2 (anti عشا كذا اللفوسايت يصير لا تجع + apoptotic gene become . (caused by t(14;18 (ما توت - lymphoma (25% ). Median survival is around 10 years. Most common type of indolent Transformation to (DLBCL) - Indolent but incurable (some can occur exceptions) Immunophenotyping: May take long time to present but when it does

Positive for CD10, CD20 and Bcl2 (Negative for CD5 ( in most cases (تطبخ ع نر هدية) it is incurable

Presented as: 100%)

80%) Diagnosis • Lymphadenopathy60 %) • splenomegaly 40%). • BM involvement • blood involvement Multiple Myeloma Malignant B neoplasm characterized by a triad of abnormalities:

1. Accumulation of plasma cells in the bone marrow Pathogenesis 2. Lytic Bone (can cause & Fracture) 3. Production of a monoclonal immunoglobulin (Ig) or Ig fragments

Bone Lesions Accumulation Monoclonal Ig production

Dark basophilic لكش ظعلا لتأكم ا يكن فيه Fracture in cytoplasm & nucleus

is at the side Hodgkin Lymphoma Indolent (Idle) malignant lymphoma characterized by: 1- Presence of few large binucleated cells (Reed-Sternberg) surrounded by reactive cells (lymphocytes, plasma cells, eosinophils) 2- Involving in young adults (most often)RS Theycells become very huge!

Reed-Sternberg Lymph node Involvement

Diagnosis Possible Pathogenisis

CD 30 CD 15 Germinal center with EBV leads to These markers should be positive. dinucleate (RS cell) which in response lead to loss of apoptosis (accumulation) & recruit

Summary

Malignant Lymphoproliferative Disorders Mature Lymphoid Lymphoma leukemia Types Non Hodgkin lymphoma B- cell neoplasm CLL Hodgkin Multiple Mantle Follicular DLBCL Myeloma Cell Burrkits CD20, CD5 CD19, CD20 CD19, CD20 CD15 Markers CD138 CD19 CD23, CD5 CD10 CD30 CD56 CD20

t(3;14) t(8;14) t(14;18) Mature naïve B- BCL-6 t(11;14) Mutations C-myc BCL-2 Plasma cells cell IgM & IgD Centro- Cyklin D GC blast blasts

Diagnosis: rapidly growing and - a partially Malignant B Indolent (Idle) Lymphocytosis highly aggressive follicular neoplasm malignant (>5,000): with extremely pattern lymphoma - short doubling time characterized appearing (24 hrs) Presented as: by a triad of characterized lymphocytes• Small mature • Lympha- abnormalities: by: Morphology: denopathy 1- Presence of soccer ball 1- BMA: (100%) n of plasma few large •nuclear Condensed chromatin Homogenous • Spleno- cells•Accumulatio in the binucleated medium size cells megaly bone marrow cells (Reed- with round nuclei (80%) Sternberg) Features • Numerous and deeply • BM lesions surrounded by -Moderatesmudge cells basophilic and involve- • Lytic Bone reactive cells lymphadenopathy vacuolated ment of a (lymphocytes, and splenomegaly cytoplasm (60%) monoclonal• Production plasma cells, 2- Biopsy: Diffuse • Blood immunoglobu eosinophils) infiltration with involve- lin (Ig) or Ig 2- Involving "starry sky” ment fragments cervical lymph (Macrophages (40%) nodes in engulfing the young adults apoptotic cells) (most often)

Most common Types: Most common adult leukemia 1-Endemic: type of Male > Female associated with chronic malaria and lymphoma, Complications: EBV In equatorial butindolent incurable • Predisposition Africa. affects the (some to infection jaw, other facial exceptions). • Autoimmune bone and breast. phenomena 2-Sporadic: affects Transformati (autoimmune GIT. on to hemolytic 3- aggressive Notes anemia) Immunodeficiency lymphoma • Transformatio -associated: (DLBCL) can n to large cell associated with HIV occur lymphoma infection or immunosuppressive syndrome) drugs Richters rate: 90% at early phase 70% at advance disease MCQs:

1- Which of the following can cause Infectious Mononucleosis? a- Autoimmune b- Malaria c- E.Coli d- Epstein-Barr Virus

2- Ahmad is 35-Years old went to his family physician suffering from severe pain in his bones, After investigations his physician advised him to see Hematologist, the Hematologist told Ahmad that he has type of B-cells lymphoma, What is the most

a- CLL b- Multiple myeloma c-likely Burkitt diagnosis Lymphoma in Ahmads condition? d-Hodgkin Lymphoma

3- Khaled 25-Years old come to you to make general check-up, in CBC you find that his Lymphocyte number is more than 5000 (normal=1500-2700), in blood film you found Soccer ball appearance & Smudge cells, what is most likely diagnosis in this case? a- CLL b- Multiple myeloma c- Burkitt Lymphoma d-Hodgkin Lymphoma

4- Which type of lymphoma is featured by presence of Binucleated cells (Reed- Sternberg) & involves cervical lymph nodes mainly? a- CLL b- Multiple myeloma c- Burkitt Lymphoma d-Hodgkin Lymphoma

5- t(8;14) C-MYC is associated with which one of the following? c 5-

a- CLL b- Multiple myeloma d 4-

c- Burkitt Lymphoma d-Hodgkin Lymphoma a 3-

b 2- 1- d d 1- GOOD LUCK! Team members: Team Leaders: Khalid Al-Eisa Abdulaziz Al-Hussainy Abdulkarim Al-Harbi Jawaher Abanumy Safa Al-Osaimi