WBC Diseases, Lymph Nodes, Spleen, Thymus II (V1) PDF Lecture Notes

PATHOLOGY | TRANS 6B LE WBC Diseases, Lymph Nodes, Spleen,...

PATHOLOGY | TRANS 6B LE WBC Diseases, Lymph Nodes, Spleen, 01 Thymus II DR. ARACELI P. JACOBA, MD, FPSP | Lecture Date (10/04/2024) | Version 1 OUTLINE ▪ Leukemia: bone marrow proliferation that will spill I. Neoplastic Proliferations into the blood III. Peripheral Lesions A. Review of Hematopoiesis A. Peripheral B Neoplasm ▪ Contains both MYELOID & LYMPHOID stem cells, in Light of WBCs B. Peripheral T/NK Cells therefore neoplastic proliferation in the bone marrow B. Lymphoid Neoplasm IV. Review Questions can produce 2 types of leukemia depending on which II. Precursor Lesions V. References cell line proliferates A. Precursor T Lymphoma − Myelocytic type leukemia B. Precursor B Lymphoma 💬 − Lymphocytic type leukemia Must Lecturer Book Previous Youtube Note: Myeloid cells (e.g. neutrophils, monocytes, ❗️ Know 💬 📖 Trans 📋 🔺 Video basophils, eosinophil, RBC, and platelets) all originate from the same myeloid stem cell. → Lymph node or any nodal tissue: malignant LEARNING OBJECTIVES proliferation leads to LYMPHOMA ✔ To understand the pathogenesis (gene defects), ▪ Lymphoma: lymphoid proliferations arising from the laboratory abnormalities (including nodal tissues that form discrete tumor masses immunohistochemistry), and morphology and ▪ Malignant proliferation of nodal tissues produces symptomatology of diseases of WBC with emphasis on either B or T cell lymphoma, NOT LEUKEMIA lymphoma, leukemia, and multiple myeloma ▪ Contains only LYMPHOCYTES I. NEOPLASTIC PROLIFERATIONS − B cells reside in the lymphoid follicles: originate in AKA Tumoral Proliferations the bone marrow Usually monomorphic = ONLY ONE TYPE OF WBC − T cells reside in the parafollicular areas: originates in the thymus 📋 becomes malignant Neoplastic proliferation of WBC will take various clinical from the same myeloid stem cell. presentations and various morphology depending on what → From the point of view of cell origin: cell type is neoplastic. ▪ B lymphocytes will result into B cell lymphoma or Types according to cell origin: leukemia, being present in both the lymph node and → Lymphoid neoplasms: Tumors of Lymphocytes bone marrow → Myeloid Neoplasms: Tumors of Granulocytes ▪ T lymphocytes produces only a lymphoma being → Plasma Cell Dyscrasias: Tumors of Plasma Cells present only in the nodal tissue and the thymus → Histiocytosis: Tumors of Histiocytes ▪ Granulocytes are myeloid cells that produce only The cell that undergoes neoplastic proliferation (e.g. leukemia being present only in the bone marrow lymphocytes) will overgrow and wipe out all the other cells → B lymphocytes can exit the lymph node and become (like granulocytes) leaving only one cell type in the bone plasma cells. Malignant proliferation of plasma cells is marrow, lymph node, or blood. called multiple myeloma → Monocytes exit circulation and become macrophages or A. REVIEW OF HEMATOPOIESIS IN LIGHT OF WBCS histiocytes. Their proliferation is called histiocytosis → 4 types WBC proliferation: ▪ Leukemia ▪ Lymphoma ▪ Multiple Myeloma ▪ Histiocytosis 📋 Table 1. Location, Cell Origin, and Type of Lymphoid Neoplasm Location Type of Cell that Type of Neoplasm Proliferates Bone marrow Myeloid Myelogenous Leukemia B lymphocytes Lymphocytic Leukemia Lymph Node B lymphocytes B cell Lymphoma Lymph Node & T lymphocytes T cell Lymphoma Figure 1. Review of Hematopoiesis Thymus Granulocytes Leukemia WBCs have 2 origins hence, tumors of WBCs will have 2 manifestations. → Bone marrow: malignant proliferation leads to LEUKEMIA LE 1 TG 1 | Acin, Arteche, Armamento TE | Arellano, Ariate* AVPAA | Castro PAGE 1 of 16 TRANS 1 VPAA | Cambas PATHOLOGY | LE 1 WBC Diseases, Lymph Nodes, Spleen, Thymus II | Dr. Araceli P. Jacoba B. LYMPHOID NEOPLASM Lymphoid neoplasms arise from 2 areas in the body. From the lymph node and bone marrow. LYMPHOMA: neoplastic proliferation that arises from any nodal tissue whether nodal or extranodal sites that inherently contain lymphoid tissue like the brain, GIT or thyroid. Lymphomas are classified according to: 📋 → Cell type proliferating: B or T cell Thymus is the origin of T cell lymphomas → Cell maturity: precursor or peripheral ▪ Precursor lymphomas originate from immature, undifferentiated lymphoblasts ▪ Peripheral lymphomas originate from older, committed lymphoblasts LEUKEMIA – neoplastic proliferation that arises from the BM and spills into the peripheral blood. → They are classified according to acute and chronic. ▪ Acute Lymphocytic Leukemia (ALL) ▪ Chronic Lymphocytic Leukemia (CLL) Figure 2. Origin of the Different Types of B and T cell → Lymphocytic leukemia: tumors that arise from Lymphoma. [Lecturer’s PPT] lymphocytes in the BM. Precursor Tumors – tumors of primitive/ most immature → Myelogenous Leukemia: arise from granulocytes or cells myelocytes. → T cells: The precursor lesion originates from the thymus. 4 types of Lymphoid tumors: → B cells: The precursor cells originate from the BM. → Precursor B: tumors of immature B cells that are → CLP, BLB (Common Lymphocytic Precursor/PreB located in the bone marrow Lymphoblasts) are the most immature B cells → Precursor T: tumors of immature T cells that are seen Peripheral Lesions - These cells are starting to leave or in the thymus have left the site of origin to go to its final destination. → Peripheral B: tumors of mature B cells that are located → PTC origin of peripheral T cells. The cells have left the in the lymph node. The mantle zone contains B cells thymus and are located in the parafollicular areas of the originally from the BM but have later resided in the LN. nodes. → NBC, MC, and GC are the sources of Peripheral B cell → Peripheral T: tumors of mature T cells that are located tumors. in the parafollicular areas of the node but more 💬 specifically in other T cell areas in the body like the skin. CELL ANTIGENS IN WBC Note: majority of the lymphomas are B cells. In normal circulation, there are more T cells (80-90%) than B cells Cluster Designations (CD) are very important surface (10-29%). It is more of the B cells that become neoplastic. antigens on WBCs that help identify the type of lymphoid tumor. Table 2. WHO Classification of Lymphoid Tumors[Lecturer’s PPT] T cells are identified by lower numbers → CD4 and CD8 Precursor B cell B Lymphoblastic Leukemia B cells are identified by higher numbers (Pre B cell) (ALL) / Lymphoma → Important markers: CD10, CD19, CD20, and IgM in plasma cells Precursor T cell T Lymphoblastic Leukemia / ▪ Remember: your plasma cells are B cells (Pre T cell) Lymphoma Monocytes have several CDs → Remember the common ones: CD14 & CD64 Peripheral B cell Chronic Lymphocytic Leukemia (CLL) ❗️CD15 & CD30 Hodgkin’s Lymphoma Small Lymphocytic Leukemia All lymphoid tumors will be positive for CD45 (SLL) (Leukocyte Common Antigen or LCA) Burkitt’s Lymphoma → Importance: differentiates lymphomas from small cell Follicular Lymphoma carcinoma which has the same morphologic features Hairy Cell Leukemia ▪ Lymphomas: require medical chemotherapy only ▪ Carcinoma: requires surgery Peripheral T cell Adult T cell Lymphoma or NK cell NK-T cell Lymphoma Table 3. Cell Antigens in WBC[Lecturer PPT] Mycosis Fungoides / Sezary LCA CD45 Syndrome T cell CD1 Hodgkin’s CD5 Lymphoma CD4 / CD8 CD3 B cell CD10 - germinal center B PATHOLOGY WBC Diseases, Lymph Nodes, Spleen, Thymus II PAGE 2 of 16 PATHOLOGY | LE 1 WBC Diseases, Lymph Nodes, Spleen, Thymus II | Dr. Araceli P. Jacoba → Polymorphic appearance consisting of centrocytes, CD19, CD20 - Pre B, mature B centroblasts, macrophages, and small unstimulated CD23 - mature B lymphocytes in the periphery of the follicle. IgM - plasma cells Follicular lymphoma (malignant) → Monomorphic appearance showing only one cell type Monocyte/ CD11 whether it appears in the center or periphery of the Macrophage CD13 follicle. CD14 CD15 MAIN MANIFESTATIONS OF LYMPHOMAS CD33 CD64 LYMPHADENOPATHY → Main manifestation NK cell CD16 → Multiple, painless lymphadenopathy which may or may CD56 not be associated with nonspecific manifestations (fever, malaise, weight loss) Stem cell CD34 ▪ Manifestation should be differentiated from a benign lesion which is usually small, movable, and with Hodgkin’s CD15 evidence of inflammation like pain and redness CD30 → Take note of the following characteristics of lymphadenopathy in different conditions: ▪ Reactive Chronic Lymphadenitis GENERAL CHARACTERISTICS OF LYMPHOID TUMORS − involve only 1-2 nodes with sizes < 2 cm and are Monoclonal Population movable → There is only one cell type within the tumor, sharing the ▪ Lymphoma same antigen receptor gene configuration − multiple, large, coalescent nodes that are painless, Most lymphomas are B cell in origin (85-95%) and may be bilateral Each type has its own clinical presentation and Can have symptoms of extranodal involvement once behavior the tumor has spread to other organs Associated with immune abnormalities → Primary → There may be loss of protective immunity: cannot → Extension protect against infection despite elevated WBC → There may be breakdown in tolerance: produce autoimmune disorders Recapitulate behavior of normal counterparts → Homing characteristics of neoplastic cells ▪ E.g. T lymphocytes have homing characteristics in the skin and present mostly as tumors located in the 📋 Follicular lymphoma originates from cells that go to the skin germinal centers → Vascular recirculation 📋 Characteristic of lymphoid cells to spread and are ▪ Causes widespread dissemination systemic at the time of diagnosis Figure 4. Gross appearance of lymphomatous node[Lecturer’s PPT] Node is enlarged Cut section shows fish flesh surface that bulges above the cut surface Margins are irregular that an invade the capsule Figure 3. Reactive follicle producing follicular hyperplasia and malignant follicle in follicular lymphoma[Lecturer’s PPT] Follicular hyperplasia (benign) PATHOLOGY WBC Diseases, Lymph Nodes, Spleen, Thymus II PAGE 3 of 16 PATHOLOGY | LE 1 WBC Diseases, Lymph Nodes, Spleen, Thymus II | Dr. Araceli P. Jacoba → All precursor lesions will be positive for this marker A. PRECURSOR T LYMPHOMA It is a lymphoblastic lymphoma originating from very immature T cells of the thymus that have not differentiated to either CD4 or CD8, calling these blast cells as Double Negative Pre T Cells → Being present in the thymus, lymphoblastic lymphoma presence as a mediastinal mass. It is a rapidly enlarging symptomatic mass: a mediastinal (thymic) mass in 70% of cases corresponding to the location of the thymus Affects mostly adolescent males Symptoms mostly due to lymphadenopathy and splenomegaly It is aggressive and rapidly fatal if untreated Figure 5. Paratracheal LN identified by black carbon 60% - 80% remission if with treatment pigments[Lecturer’s PPT] Only 1 type: Acute Lymphoblastic Lymphoma Lymphomas affect any nodal group B. PRECURSOR B LYMPHOMA Gross findings will show multiple, massively enlarged, varying in sizes, coalescent nodes with a fish flesh It is a lymphoblastic leukemia that originates from the most appearance immature blast cells in the bone marrow called Common Lymphocytic Precursor (CLP) or Pre B Lymphoblast → The coalescence is due to the tumor extending beyond (BLB) the capsule to invade the adjacent node. Will present as a leukemia since it originates from the The black areas are carbon pigments indicating that these bone marrow are perihilar nodes in the lungs. Precursor B leukemia is aka Acute Lymphocytic Leukemia Common in children (< 15 years old, peaks at 4 years old) II. PERIPHERAL LESIONS Peripheral Lymphoma: Originate from older, committed lymphoblasts A. PERIPHERAL B NEOPLASM After B lymphoblasts matures, then progresses and enter the peripheral pool, then resides in the follicles of the nodes producing various types of Peripheral B Lymphomas → constitute the largest group of lymphomas Under Peripheral B Cells are the most number of tumors → each tumor has its own clinical presentation, course, Figure 6. Gross appearance of a lymph nodes involved by 💬 and chromosomal abnormalities. If they ask you the origin of a particular tumor, in all likelihood it's going to be a Peripheral B cell tumor non-Hodgkin lymphoma of the diffuse large cell type[Lecturer’s PPT] Peripheral B cell Neoplasms: This is from the gut, showing multiple enlarged paracolic 1. Small Lymphocytic Lymphoma/CLL nodes that are coalescent (Figure X) 2. Follicular Lymphoma Lymphomas are tumors that can arise de novo from any 3. Diffuse large B cell Lymphoma organ containing lymphoid tissue 4. Burkitt's Lymphoma → In the gut, the more common site of lymphomas is the 5. Extranodal Marginal zone lymphoma Ileum, because it contains several Peyer’s Patches 6. Mantle cell Lymphoma → It is also possible to have primary lymphoma of the 7. Hairy cell Leukemia tonsils, the brain, or the spleen or any organ where 8. Multiple Myeloma there is native lymphoid tissue. SMALL LYMPHOCYTIC LYMPHOMA II. PRECURSOR LESIONS A disease of the elderly (> 60 years old) WHO Classification of Lymphoid Tumors: More common in males (2:1 male:female ratio) → Precursor B cell (pre B cell) It is very indolent causing little or no manifestations at all ▪ B lymphoblastic Leu (ALL) / lymphoma Mostly asymptomatic and patients live as much as 4 to 10 → Precursor T cell (pre T cell) years after diagnosis ▪ T lymphoblastic lymphoma / Leu Can present as mild hepatomegaly or minimal → Peripheral B cell → Peripheral T cell or NK cell ❗️ lymphadenopathy Important characteristic: → Invades the bone marrow which later spills into blood → Hodgkin's Lymphoma Precursor Lymphoma (immature cells): producing a leukemia-like picture, calling it Chronic → Originate from immature undifferentiated lymphoblasts Lymphocytic Leukemia The marker for precursor lesions whether it be T or B is Being a mild disorder patients usually succumb to other Terminal Deoxynucleotidyl Transferase (TdT) causes outside of the disease but common complications may ensue. PATHOLOGY WBC Diseases, Lymph Nodes, Spleen, Thymus II PAGE 4 of 16 PATHOLOGY | LE 1 WBC Diseases, Lymph Nodes, Spleen, Thymus II | Dr. Araceli P. Jacoba Common complications of SLL: → Whole node is replaced by a monotonous sea of → Hypogammaglobulinemia with increased tendency to small lymphocytes infection Histology of SLL HPO (Figure X. Right side) → Hemolytic Anemia or Thrombocytopenia → Tumor cells made up of small round lymphocytes ▪ Due to the production of autoimmune antibodies by interspersed with slightly larger prolymphocytes cells non-neoplastic B-cells with a prominent nucleoli (black arrow) ▪ Recall: Warm AHA are caused by tumors like lymphomas CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) ❗️ → Transformation to Large B Cell (10%) A more aggressive lymphoma called Richter Syndrome Phenotypically, genotypically and clinically similar to SLL → Differs only in the degree of peripheral lymphocytosis WBC count: Low (↓) in SLL, High (↑) in CLL ▪ Shortens survival to 1 year after transformation Diagnosis depends on the CLL Absolute Lymphocyte Chromosome aberrations are rare Count = Total WBC count x Lymphocyte Differential Count → More consistent: deletions of chromosome 11q, 13q, → CLL: >4,000 (absolute lymphocyte count) 17p and trisomy 12 → E.g. WBC count of 20,000; Lymphocyte Count of 50% Immunophenotype is that of B cells ▪ 20,000 x 50% = 10, 000 ❗️ → CD19, CD20, CD23 (B cell markers) ▪ It is considered CLL or a leukemia rather than an SLL 📋 contains CD5 (T cell marker) or a lymphoma ▪ Present only 1 of 2 B-Cell tumors (SLL & Mantle cell CLL is the common leukemia in adults in the Western 📋 Lymphoma) world ▪ Helps in differentiation of SLL from other Peripheral B Chromosomal abnormality, age, sex, clinical picture cell lymphomas and prognosis is similar to SLL Since this is an indolent tumor, it is necessary to identify It is seen in elderly males with an indolent course with markers that will indicate a more aggressive course similar chromosomal abnormality (just like SLL) Poor Prognostic Factors → High tumor load (levels 200,000 and above) → Presence of chromosomal abnormalities Zap70 and 📋 Notch 1 mutation Zap70 - protein that augments signals produced by the Ig receptor 📋 → Deletion of 11q and 17p Lack of somatic hypermutation Treatment: → “Gentle” chemotherapy given only to symptomatic patients 📋 → Being a mild disorder, chemotherapy is not aggressive The growth of CLL/SLL cells is largely confined to proliferation centers, where tumor cells receive critical 📋 cues from microenvironment Proliferation centers: variable numbers of larger 📋 activated lymphocytes that gather in loose aggregates Pathognomonic for CLL/SLL Figure 8. SLL: Small cells mixed with “prolymphocytes”[Lecturer’s PPT] Refer to Figure 8: Shows an increase in WBC on the smears with small lymphocytes predominance. → Normal WBC count will show only 3 - 4 WBCs per oil immersion field with a mixture of both neutrophils and 💬 lymphocytes This slide shows a heavy load of WBC that is purely lymphocytic which could give you a clue to a diagnosis of lymphocytic leukemia. Smudge cells (black arrow) will give a clue on the → 📋 diagnosis These are pale cells that appear flattened, larger than the adjacent lymphocyte, no definite nuclei and Figure 7. SLL: Small cells mixed with “prolymphocytes”[Lecturer’s 📋 irregular smudged margins Monomorphic appearance of only lymphocytes in smear. No other cells present PPT] FOLLICULAR LYMPHOMA Histology of SLL will show diffuse effacement of nodal Most common type in the US (45%) architecture on LPO (Figure X. Left side) → Not very common in Asia including the Philippines → No follicles in the cortex Epidemiology: Usually seen in middle age, affecting → No sinuses in the medullary area males and females equally PATHOLOGY WBC Diseases, Lymph Nodes, Spleen, Thymus II PAGE 5 of 16 PATHOLOGY | LE 1 WBC Diseases, Lymph Nodes, Spleen, Thymus II | Dr. Araceli P. Jacoba ❗️ Strongly associated with the bcl-2 translocation seen in about 90% of cases affecting chromosome 14 and 18. Figure 10. Comparison of Follicular Lymphoma and Follicular Hyperplasia[Lecturer’s PPT] → Genetic Abn: t(14:18) bcl-2 proto oncogene (90%) Symptoms: Table 4. Comparison of Follicular Lymphoma and Follicular → Similar to all lymphomas with generalized painless Hyperplasia lymphadenopathy w/ BM involvement Follicular Lymphoma Follicular Hyperplasia → Involvement of extranodal sites is uncommon (GIT, Malignant Benign brain, or testis) Follicles show monomorphic Follicles are polymorphic ❗️ Prognosis/Course: Indolent, like SLL, with a long natural history (survival median of 7-9 years) but it is incurable cells No clear margin between Clear well defined margin germinal center and inactive between germinal center → Can progress to Diffuse Large B Cell Lymphoma (DLBL) mantle zone and inactive mantle zone ❗️ ▪ More aggressive Particularly in c-MYC gene is carried (bad gene) The median survival is less than 1 yr after transformation Pinpoint spaces occupied by the macrophages are Cells in the germinal center will show pinpoint pale lost areas due to the Symptoms wax and wane that is unaffected by treatment macrophage and the Treatment protocol: proliferation is limited by the → “Watch and Wait” attitude for treatment capsule → Because the disease is unaffected by treatment, Invasion of capsule and No invasion of capsule treatment is only given when patient is symptomatic adjacent fat Immunophenotype: B cells (CD10, C19, C20) with 📋 positivity (+) for Bcl 2 protein Histologic transformation occurs in 30 to 50% of follicular lymphomas, most commonly to diffuse large B cell lymphoma Figure 11. Histology: Mixture of centrocytes and centroblast[Lecturer’s PPT] Left picture: Spleen (gross) affected with Lymphoma → Expanded follicles : represented by prominent multiple small nodules Figure 9. Follicular Lymphoma LPO[Lecturer’s PPT] ▪ Not only in Follicular Lymphomas. Can also be seen ❗️→Figure X, note the following: Multiple nodular aggregates of lymphoblasts that in other forms of Lymphomas Right picture: Follicular Lymphoma (histology) → The cells recapitulate the centroblasts and centrocytes replace normal nodal architecture in a germinal center and are mixed with each other → Cortex and medulla all replaced by tumoral follicle compared to the polarized arrangement in a normal → Note invasion of the capsule and invasion of the germinal center where the centroblasts are near the adjacent adipose tissue (arrow) mantle zone and the centrocytes are in the center of the → Normal architecture of node with follicles limited to the germinal center. cortex is not seen in cases of lymphoma → Centrocytes ▪ are irregular cleaved nuclear outline → Centroblast: large cells w/ several nucleoli (with arrows) PATHOLOGY WBC Diseases, Lymph Nodes, Spleen, Thymus II PAGE 6 of 16 PATHOLOGY | LE 1 WBC Diseases, Lymph Nodes, Spleen, Thymus II | Dr. Araceli P. Jacoba Figure 13. Spleen affected by Diffuse Large B Cell Figure 12. Bcl-2 Stain; staining characteristics of Lymphoma[Lecturer’s PPT] a reactive follicle and a follicular lymphoma[Lecturer’s PPT] Left Picture: Spleen (gross) affected by Diffuse Large B Left Picture : Benign Follicle Cell Lymphoma → Bcl-2 stains only the inactive lymphocytes of the mantle → This tumor presents as a rapidly enlarging mass zone; none in the germinal center commonly affecting a node or an extranodal site. Note Right Picture: Malignant Follicle the fleshy or fish flesh appearance of the tumor on → All cells are stained in the central and peripheral zone sectioning → Bcl-2’s functions to antagonize apoptosis and promotes Right picture: Spleen (histology) affected by Diffuse Large survival of follicular lymphoma cells B Cell Lymphoma → Apoptosis and cell death is a normal occurrence in the → show large cells, larger than those seen in SLL or germinal center Follicular Lymphoma. ▪ Battlefield where soldiers die; lymphocytes die after ▪ 5x bigger than normal lymphocyte, with moderately doing its work of clearing the enemy abundant cytoplasm and nuclei with prominent ▪ Bcl-2 abnormality: persistence and immortality of nucleoli cells; causes tumor ▪ Increased mitosis in this tumor ▪ Difficult to differentiate from metastatic carcinoma − LCA and CD clusters for B cells will be needed to differentiate the two DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) − These cells resemble immunoblasts therefore Epidemiology: Affects elderly (median age of 60); small another term for this tumor would be percentage in pedia (5%) Immunoblastic Lymphoma Course and behavior: Aggressive tumor that is rapidly fatal BURKITT’S LYMPHOMA if untreated. Age: Children (30%) and young adults → Chemotherapy achieves complete remission in 60-80% → one of the fastest growing tumors in humans of patients. Achieves cured status in 50% of patients Histology: monotonous sea of round lymphocytes → Contrast with Follicular Lymphomas which is an interspersed by pale white macrophages; starry sky indolent, slow growing tumor but incurable and no appearance response to treatment Symptomatology: Endemic types affect facial bone & Symptoms: Rapidly enlarging symptomatic mass at a pelvic organs single nodal or extranodal site. → Mostly extranodal (2 patterns) → Nodal sites: Can be the tonsils and oropharynx, with ▪ Mandible abundant lymphoid tissues ▪ Pelvis: kidney, adrenals and ovary → Extranodal sites: GIT, skin, bone, brain, with secondary → Non-endemic or sporadic types affect the abdomen involvement of spleen and liver (ileocecal and peritoneum) → Spleen and liver: can be the origin of the tumor or Course and Prognosis: Very aggressive, responds well involved in secondary spread to chemotherapy → Affects more extranodal tissue rather than lymph nodes → Children and young adults can be cured; poorer in older Cytogenetics: Bcl-6 (30%) and Bcl-2 (10%) patients → This type of tumor has a good response to treatment but Immunophenotype: B cells, IgM, Bcl-6 presence of C-myc gene indicates poor prognosis/ high → B cell markers (CD10, CD19, CD20) plus IgM and BCL6 treatment failure Pathogenesis: t(8;14) of c-myc gene; EBV (Epstein-Barr Immunophenotype for B cells (CD19, C20, CD10) and Virus) Bcl 6 → All forms of Burkitt’s Lymphoma are highly associated → However Bcl 6 but seen only in as third of cases and not with a translocation of the MYC gene on chromosome 8 as consistent as Bcl 2 in Follicular Lymphomas that leads to increased MYC protein levels → BcL-6 controls differentiation and inhibits p-53 PATHOLOGY WBC Diseases, Lymph Nodes, Spleen, Thymus II PAGE 7 of 16 PATHOLOGY | LE 1 WBC Diseases, Lymph Nodes, Spleen, Thymus II | Dr. Araceli P. Jacoba → Includes Bone Marrow (40-60%), Spleen (50%), liver, GIT (lymphomatoid polyposis) ▪ It affects the Bone marrow in more than half of cases causing it to spill in the blood and spread to other organs. − Follicular Lymphoma or Small Lymphocytic Lymphoma: only affects the lymph nodes − Diffuse Large B-cell lymphoma (DLBCL): affects the extranodal organs − Mantle Cell Lymphoma (AKA Disseminated Lymphoma): Lymph nodes, extranodal organs and peripheral circulation are affected, making it an aggressive tumor that spreads widely ▪ When the GIT is involved, it produces multiple Figure 14. Types of Burkitt's Lymphoma[Lecturer’s PPT] polypoid lesions called lymphoid polyposis. ▪ Because of the extensiveness of the lesions with generalized lymphadenopathy and spread to other organs, it is called as disseminated lymphoma Course and prognosis: Very aggressive; incurable. Has poor prognosis → Survival rate of 3-5 years → Worst type of lymphoma Immunophenotype: → (+) CD19, CD20, CD5 → (-) CD23 ▪ distinguishes it from SLL which is also CD5 positive Genetic Abnormality: t(11:14), increased expression of cyclin D1 → Cyclin D1 mutation promotes G1 to S phase of cell Figure 15. Starry Sky pattern of Burkitt's Lymphoma[Lecturer’s cycle. Abnormality is present in almost all cases PPT] Starry Sky → Tumor is made up of a sea of round blue cells representing the “blue sky” interspersed by larger benign macrophages representing the “stars”. → Tumor has high mitotic index with numerous apoptotic cells; consistent with rapid growth Figure 17. Mantle Cell Lymphoma[Lecturer’s PPT] Mantle zone pattern → B-cells surrounding germinal centers → Prominence and proliferation of the lymphocytes in the Figure 16. Starry sky of Burkitt's Lymphoma 2[Lecturer’s PPT] mantle zone that surround a small, atrophic germinal center High mitotic count (white arrow → Homogeneous small lymphocytes w/o large cells Apoptotic debris (yellow arrows) resembling prolymphocytes (CLL) or centroblasts → The apoptotic debris can be seen engulfed by the (follicular lymphoma). macrophages or scattered between the tumor cells MARGINAL ZONE LYMPHOMA Macrophages with abundant white cytoplasm, representing also called Mucosa of Associated Lymphoid Tissue or the stars in a background of diffuse spread of dark blue MALToma. lymphocytes. 3 Characteristics of tumor → arise from chronic inflammation like those seen in Hashimoto's thyroiditis, PUD w/ H pylori, Sjogrens MANTLE CELL LYMPHOMA disease of salivary gland Epidemiology: Predominantly Elderly males (50-60 y/o) → remain localized for a long period of time Symptomatology: Generalized painless → can regress if inciting agent is removed lymphadenopathy with extranodal spread. ▪ The characteristics suggest that this type of lymphoma arising in chronically inflamed tissue lies in PATHOLOGY WBC Diseases, Lymph Nodes, Spleen, Thymus II PAGE 8 of 16 PATHOLOGY | LE 1 WBC Diseases, Lymph Nodes, Spleen, Thymus II | Dr. Araceli P. Jacoba a continuum between reactive hyperplasia to full Mantle Cell Older Disseminated Disease blown lymphoma. This is the reason why H. pylori males Aggressive should be treated to prevent occurrence of Marginal Zone Any age MALTOMA malignancy Prognosis: Very good, it is important to identify factors that As mentioned, one of the characteristics of this group of will cause it to behave otherwise. disorders is each that each type of lymphoma will have its Chromosomal abnormality: BCL2 mutation t(11:18) or own clinical presentation t(14:18) Small cell lymphoma (SLL) ▪ When present, regression is not possible and → Small: gives a clue that tumor is indolent transforms to more aggressive types of lymphoma Diffuse Large B cell Lymphoma ▪ Poor prognostic factors for MALTomas → “Large”: gives a clue that tumor is aggressive ▪ Specific for MALToma → Responsive to treatment CHROMOSOMAL ABNORMALITIES IN LYMPHOMA Follicular lymphoma → “Follicles”: gives a clue that tumor is indolent ▪ Normal nodes contains follicle ▪ Presence of follicles in this tumor: slow growing type of tumor Marginal Zone → Mildest form of lymphoma arising from long standing inflammation → Can regress once inciting agent is removed ❗lymphoblastic B. PERIPHERAL T CELL OR NK CELLS Precursor T or pre-T tumors is an acute lymphoma presenting as a mediastinal mass. → Immature T resides in the thymus therefore the main presentation is a mediastinal lesion → In comparison to precursor B, which resides in the bone marrow and presents as a leukemia Figure 18. Chromosomal abnormalities in Lymphoma[Lecturer’s → These tumors are those that have left the thymus and PPT] travel to either the paracortical areas of the lymph node Follicular or to its normal location in other parts of the body → Bcl2 prevents apoptosis of the germinal center cells → Neoplasms of Peripheral T-Cells: Most are very rare proliferation of the lymphocytes in the germinal center → Mycosis Fungoides/ Sezary Syndrome ▪ Most commonly seen in clinics Diffuse Large Cell → Extranodal NK/ T Cell lymphoma → Bcl6 inhibits expression of factors that promote germinal → Adult T cell Lymphoma/ Leukemia (CD4) center B-cell to mature → produce cells in → Anaplastic Large cell Lymphoma (ALK+) undifferentiated proliferative state → Large Granular T-cell Lymphocytic Leukemia Mantle Cell Notice that T cell tumors are characterized by mass lesions at a particular location such as the skin or → Cyclin D1 Promotes rapid mitosis due to shortening the nasopharynx. Those that present with lymphoma/leukemia G1 phase with rapid progression to S phase are very aggressive tumors Burkitt’s MYCOSIS FUNGOIDES → Warburg effect: MYC gene is a master transcriptional Indolent tumors that are limited to the skin for long periods regulator that alters metabolism to allow cells to of time biosynthesize all building blocks (protein, nucleotide, Infiltration of the skin by neoplastic CD4 T cells lipid) for mitosis from just glucose and glutamine to Prognosis: Indolent; good allow for rapid growth and mitosis. This is the reason → Localized to the skin for many years why cancer patients are cachectic. → Depends on the percentage of the body surface SUMMARY involved by the tumor Table 5. Summary of Clinical Behavior MYCOSIS FUNGOIDES: CLINICAL STAGES OF Type of CUTANEOUS LESIONS Age group Clinical Feature Lymphoma 1. Inflammatory phase (Patch Stage) SLL/CLL >60, males Indolent; Spills in blood Affect BM, liver spleen Follicular Middle age Indolent, incurable Lymphoma M=F Generalized lymphadenopathy DLBCL Elderly Rapidly growing mass pedia (LN or ExtraLN) Aggressive Burkitt’s Children Extranodal mass Aggressive PATHOLOGY WBC Diseases, Lymph Nodes, Spleen, Thymus II PAGE 9 of 16 PATHOLOGY | LE 1 WBC Diseases, Lymph Nodes, Spleen, Thymus II | Dr. Araceli P. Jacoba → Same CD4 lesion of the skin with infiltration of epidermis and dermis by malignant T cells Clinical picture: 2 of the 3 stages (patch and plaque stages) → Inflammatory and plaque phase only → Exfoliative erythroderma w/o tumor phase ▪ Reddish exfoliative patches ▪ Infiltrates blood → spreads to spleen and lymph node → lymphadenopathy and splenomegaly − Spreads through the body Course and Prognosis: Aggressive compared to indolent course of Mycosis fungoides Figure 19. Patch stage of Mycosis Fungoides [Lecture PPT] HISTOLOGY (MYCOSIS FUNGOIDES AND SEZARY SYNDROME) Flat-reddish patchy areas usually in the trunk They have the same histologic features Multiple, flat, map-like, reddish areas usually in the trunk There will be a thick infiltration of neoplastic lymphocytes Later progresses to involve the extremities seen as dark blue cells in the dermis. 2. Plaque Phase → Note that the malignant lymphocytes are immediately adjacent to the epidermis and invade it. Notice these dark blue cells migrating towards the outer surface of the epidermis Thick panned of atypical lymphocytes that aggregates in the superficial dermis with invasion of the epidermis seen in single cell or small clusters → Collection of neoplastic lymphocytes: Pautrier’s Microabscesses Figure 20. Plaque stage of Mycosis Fungoides [Lecture PPT] Elevation of the lesion from the skin surface Eczema like lesions raised above the skin forming indurated, irregularly outlined, erythematous plaques that may ulcerate 3. Tumor Phase Figure 22. Histology of Mycosis Fungoides & Sezary Syndrome showing Pautrier’s Microabscesses (black arrow) [Lecture PPT] EXTRANODAL NK/T CELL LYMPHOMA T cell lymphoma of the sinuses & nasopharynx: Tumor that causes extensive necrosis forming destructive masses in the nasopharynx and sinuses. → T cell tumors usually involve a particular site of the body ▪ CD4 T-cell tumors: Skin Figure 21. Tumor stage of Mycosis Fungoides [Lecture PPT] ▪ NK cell tumor: Nasopharynx or sinuses Lethal Midline Granuloma or Midline Malignant Lesion forms an enlarging mass/lesion on the skin Reticulosis Malignant lymphocytes forms a bulging, tumoral mass → Lethal: Characterizes the aggressiveness and instead of a flat, elevated lesion of the skin destruction brought about by the tumor → This stage is not seen in Sezary Syndrome → Midline: Location in the nasopharynx and sinuses → Sezary syndrome: invades the circulation to cause → Granuloma: Misnomer splenomegaly, and lymphadenopathy and can invade ▪ Extensive necrosis and the failure to find tumor cells other organs as well. wiped out by the necrosis was very typical for this lesion ❗ SEZARY SYNDROME Same histology as Mycosis Fungoides PATHOLOGY WBC Diseases, Lymph Nodes, Spleen, Thymus II PAGE 10 of 16 PATHOLOGY | LE 1 WBC Diseases, Lymph Nodes, Spleen, Thymus II | Dr. Araceli P. Jacoba ▪ The necrosis characterizes this tumor such that → Inflammatory there is difficulty identifying the tumor cells on biopsy. → Plaque Symptoms: Destructive masses of sinus & nasopharynx → Tumor Morphology: Atypical lymphocytes invading small blood Sezary Syndrome has no tumor phase vessels leading to necrosis and destruction of tissues Histology of MF and SS are the same → Histologic diagnosis will be difficult since it will only HTLV-1 directly causes adult T cell show extensive necrosis despite multiple biopsies Lymphoma/Leukemia Associated with EBV Prognosis: Aggressive HODGKIN’S LYMPHOMA → Respond to radiation but not to chemotherapy B cell Lymphoid neoplasms containing neoplastic giant cells (Reed-Sternberg cells) that induce accumulation of other inflammatory cells → This is part of the Peripheral B lymphoid neoplasms which has been separated from similar tumors of that classification due to its different clinical behavior, prognosis and histology → First human CA to be treated successfully with radiotherapy & chemotherapy Neoplastic giant cells (RS cells) that induce accumulation of other inflammatory cells Characteristics of Hodgkin's disease → Presence of Reed-Stenberg cells (RS cells) Figure 23. Extranodal NK/T Cell Lymphoma [Lecture PPT] → Polymorphic cells ▪ Recall: all previous lymphomas discussed have ADULT T-CELL LYMPHOMA/LEUKEMIA monomorphic cells CD4 T cell proliferation → Involve single axial LN chain → More systemic manifestations due to a greater leukemic ▪ Non-hodgkin's lymphoma affects multiple Lymph picture node groups unlike Hodgkin's Etiology: This disease is the only malignancy established → Spread is contagious and stereotyped to be directly caused by a virus. (others are only ▪ Spreads in an orderly fashion relationships) ▪ Progression is predictable/stereotype → Directly caused by HTLV-1 − Lymph Node → Spleen → Liver → Bone Marrow Symptoms: Skin lesions, hypercalcemia, general → Other organs lymphadenopathy, enlarged liver & spleen, Blood → Rare extranodal presentation lymphocytosis HL is different than other lymphomas because the → Main symptoms are concentrated on other lesions like neoplastic tumor cells which are the RS are few. lymphadenopathy, hepatosplenomegaly + Blood The predominant cells are the benign proliferating lymphocytosis (indicating spillage in blood presenting as cells adjacent to it due to the triggers sent by the RS. leukemia) + metabolic abnormality of hypercalcemia Figure 25 shows the diagrammatic representation of the → Hypercalcemia: manifest as muscle weakness, renal communication between the RS cells and other cells that (stones, polyuria), GIT (diarrhea, polydypsia) provide for its survival. These signals are the cytokines Morphology: Clover leaf or flower cells and chemokines triggered by RS cells and the responses → Multilobulated nuclei of other cells adjacent to it. Complication: Demyelinating disk of brain & spinal cord Course and prognosis: Highly aggressive; → Rapidly aggressive despite chemotherapy → Very poor prognosis Figure 24. Adult T-cell lymphoma/Leu pointing Clover Leaf or Flower Cell MUST KNOW 📋 Precursor T tumors reside in the thymus and its main Figure 25. Reed Sternberg Cells Communication presentation is a mediastinal lesion Precursor B tumors reside in the bone marrow and Prognosis: present as a leukemia → Stage I & IIA: 5 year survival rate (90%) Clinical stages of Mycosis fungoides (InPlaTu): PATHOLOGY WBC Diseases, Lymph Nodes, Spleen, Thymus II PAGE 11 of 16 PATHOLOGY | LE 1 WBC Diseases, Lymph Nodes, Spleen, Thymus II | Dr. Araceli P. Jacoba → Stage IVA & IVB: 5 year survival rate (70%) ▪ The prognosis of HL as a whole is very good with a 5 yr survival rate of close to 90% in the early stages. ▪ Even in the higher stages the 5yr survival rate remains high. ▪ This is due to the fact that the tumor cells are few and consist of only few RS which can easily be destroyed by chemotherapy. → This is the first tumor ever successfully treated with chemotherapy. Complication: → development of other malignancy after chemo and radiation (AML, MDS, Lung CA) Figure 27. Nodular Sclerosis MOLECULAR PATHOGENESIS MIXED CELLULARITY Activation of transcription factor NF-κB by EBV or other This will show a heterogenous cellular infiltrate which mechanisms includes T-lymphocytes, eosinophils, macrophages → Presence of NF-Kb which promotes lymphocytes admixed with a diagnostic RS (black arrow) and some survival and proliferation. Lympho-histiocytic variants (red arrow). → This transcription factor is stimulated by the EBV virus Usually present in Stage III and Stage IV but remains to which is common in cases of HL have a good prognosis Males greater than females. Biphasic age incidence = young adults and older adults Positive markers : classic type CD15 & CD30 Most are EBV positive Figure 26. Molecular Pathogenesis Several pathways like AKT, RAS, STAT, MAP, P13, cAMP are normally stimulated thru receptors on the cell surface. There will be independent proliferation & survival if the surface receptors are destroyed like what is seen in Figure 28. Mixed Cellularity Polycythemia vera with destruction of the JAK pathway LYMPHOCYTE RICH CLASSIFICATION OF HODGKIN’S LYMPHOMA Shows predominantly reactive lymphocytes making up the Classic Variants: CD 15+, CD 30+, Negative for other B majority of the cellular infiltrate mixed with RS. cell markers Uncommon variant. → Nodular Sclerosis Males greater than Females. → Mixed Cellularity Tends to be seen in older adults → Lymphocytic Depletion Good prognosis → Lymphocyte rich Positive: classic type markers CD15 CD30 Non-classic variant: CD 15-, CD30-, Positive B cell markers → Lymphocytic predominance (Histologically similar to lymphocyte rich) NODULAR SCLEROSIS There are well defined collagen bands of pink acellular tissue (black arrow) separating the lymph node into circumscribed tumor nodules. Inset shows lacunar cells that replaces the RS cells in this tumor. They are seen as large cells with clear space around the nuclei Most common subtype Very good prognosis. Equal occurrence in males and females. Affect young adults Positive markers: classic type CD15 and CD30 Figure 29. Lymphocyte Rich PATHOLOGY WBC Diseases, Lymph Nodes, Spleen, Thymus II PAGE 12 of 16 PATHOLOGY | LE 1 WBC Diseases, Lymph Nodes, Spleen, Thymus II | Dr. Araceli P. Jacoba → The best prognosis is noted in nodular sclerosis LYMPHOCYTIC PREDOMINANCE because the presence of collagen attempts to wipe out the tumor Uncommon variant. → RS cells are abundant in most subtypes except in Seen mostly in young males Nodular sclerosis where it is replaced by lacunar cells Histologically similar to lymphocyte rich with a → EBV is common to all subtypes except nodular predominance of reactive lymphocytes with LH variants sclerosis and lymphocytic predominance. (lympho-histiocytic variants at tip of black arrow) and few → The subtype commonly seen in HIV patients is RS cells (Note cleaved nuclei of LH) lymphocytic depletion. Immunohistochemistry: non classic markers CD 5 & CD30 negative CD20 positive REED STERNBERG CELLS RS cell is required for a diagnosis of Hodgkin's Lymphoma The classic RS: → Bilobed giant cell that is a mirror image of each other with a large nucleoli producing an “owl eye” appearance. Hodgkins is based on the identification of RS in a background of non-neoplastic inflammatory cells RS cells are the tumor cells in this lesion → they release cytokines & chemokines → induces accumulation of benign inflammatory cells which in turn feed the RS. Note that RS here appears with plasma cells, dendritic cells, fibroblasts, monocytes/macrophages (larger paler Figure 30. Lymphocytic Predominance cells) and T lymphocytes (small blue cells). → The T-lymphocytes are benign workers for the RS. Table 6. Summary of the Classification of Hodgkin → The RS cell is the neoplastic B cell. Lymphoma RS should be distinguished from similar cells seen in: Type Histology Clinical Feature Prognosi → Infectious mononucleosis s → Large cell Non Hodgkin Lymphoma Nodular Bands of M=F; Common Excellent sclerosis collagen in cervical & Stage 70% lacunar mediastinal 1-2 cells young adults, EBV (-) Mixed Many different M>F, EBV (+) Good cellularity cells, RS [70%] 25% plentiful lymphadenopathy, biphasic age incidence Lymphocyte Few Elderly males, Mod depletion 5% lymphocytes, HIV (+) aggressiv many RS and Most EBV (+) e variants Lymphocyte Many M>F Middle age Good to Figure 31. Reed Sternberg Cell rich lymphocytes, males enlarged excellent many RS LN, EBV (+) [40%] Lymphocyte Few RS/LH Young males, Very predominanc variant or good e 5% “popcorn” cell EBV- CD15 & CD30 cervical/axillary neg lymphadenopathy Summary of the subtypes of HL → The prognosis parallels the amount of lymphocytes in that particular type. → Those with less lymphocytes such as in lymphocytic Figure 32. L-R: Lacunar, LH, Mononuclear depletion have a poorer prognosis than the rest RS cells may produce other RS variants PATHOLOGY WBC Diseases, Lymph Nodes, Spleen, Thymus II PAGE 13 of 16 PATHOLOGY | LE 1 WBC Diseases, Lymph Nodes, Spleen, Thymus II | Dr. Araceli P. Jacoba → Lacunar cells: large cells with clear space around the a. Burkitt Lymphoma nucleus; seen in nodular sclerosis b. Hodgkin Lymphoma → LH: lymphohistiocytic variant or popcorn cells are large c. Mycosis Fungoides cells with infolding of the nuclear membrane; seen in d. Chronic Lymphocytic Leukemia lymphocytic predominance 2.. A 12-year-old boy has had increasing abdominal → Mononuclear variant: large cells with dark ink blot distention and pain for the past 3 days. An abdominal nuclei CT scan shows a 7-cm mass in the ileocecal valve. The resected mass microscopically shows sheets of IMMUNOHISTOCHEMISTRY OF HODGKIN’S intermediate-sized lymphoid cells, with nuclei having LYMPHOMA coarse chromatin, several nucleoli and many mitotic figures. A bone marrow biopsy sample is negative for this cell population. Cytogenetic analysis from the mall shows a t(8:14) karyotype. The tumor shrinks dramatically after a course of chemotherapy. Which of the following is the most likely diagnosis? a. Answer b. Answer c. Answer 3. A 12-month-old child was noted to have on and off infection. PBS showed several blasts in the smear and he was diagnosed to have ALL. What is his prognosis? a. No risk for relapse b. 90% Cure rate c. A very good prognosis Figure 33. Immunostain for CD15 d. A high risk of treatment failure Immunohistochemistry of Hodgkin's Lymphoma is Positive 4. A biopsy taken from a patient showed markers for B for CD 15 and CD 30 cells. Which of the following is NOT a possible Brown uptake is positive for CD 15 present only in RS diagnosis of the case? cells. None of the benign cells in background are positive a. Sezary syndrome for the stain b. Follicular Lymphoma c. Small Cell lymphocytic lymphoma STAGING OF LYMPHOMA (ANN ARBOR d. Hairy cell Leukemia CLASSIFICATION) 5. All of the following are true of the Reed Sternberg Determines the course, choice of therapy and cell, except: prognosis of the disease. a. It is multinucleated Stages are further divided depending on the presence or b. T expresses CD 15 and CD 30 absence of the following symptoms: c. It is of B-cell lineage → Fever d. It represents majority of the cells in the lymph node of → Night sweats Hodgkin lymphoma → Unexplained weight loss of >10% of normal body weight Stage I ANS: → only a single lymph node site or extranodal site is 1. C. Map-like reddish flat patches in the skin initially involved affecting non sun-exposed areas like the trunk and hips. Stage II 2. D. Burkitt’s Lymphoma usually affects the abdomen → two or more lymph node sites on one side of the (ileocecal and peritoneum) in the sporadic types. Affects diaphragm are involved, or limited contiguous t(8;14) of c-myc gene, aggressive and rapidly progressive extranodal site involvement but responds well to chemotherapy Stage III 3. D. (A) 95% of children with ALL obtain complete remission; → Lymph node sites on both sides of the diaphragm are (B) 75% to 85% are cured; (C) Age younger than 2 years involved, with splenic or limited contiguous extranodal leads to worse prognosis site involvement, or both 4. A. Arise from cutaneous T-cell lymphoma; B,C,D – Stage IV classified as Peripheral B lymphomas → Extensive involvement of extranodal sites, with or 5. A. Reed-Sternberg Cells are usually bilobed giant cells without lymph node involvement showing owl-eyed appearance V. REFERENCES III. REVIEW QUESTIONS WBC, Lymph Nodes, Spleen, Thymus I & II – Dr. Araceli P. Jacoba, MD, 1. A 45-year-old man has noted a change in the FPSP (Asynch) appearance of his skin over his shoulder for the past Trans 2026 6 months. On P.E., the skin is thickened and reddended. A punch biopsy of skin is performed and on microscopic examination, it shows thick, neoplastic T-lymphocytes in the dermis with invasion of the epidermis. Which of the following is the most likely diagnosis? PATHOLOGY WBC Diseases, Lymph Nodes, Spleen, Thymus II PAGE 14 of 16 PATHOLOGY | LE 1 WBC Diseases, Lymph Nodes, Spleen, Thymus II | Dr. Araceli P. Jacoba FORMATIVE QUIZ 1. 9/M is seen because of abdominal Peripheral Blood smear morphology pain and discomfort. PE shows the → Starry sky appearance right sided ovarian which was ▪ “Stars” are the macrophages resected. This was the histologic → One cell type is proliferating: B cells finding. Give your diagnosis. Table 5. Summary of Clinical Behavior Type of Age group Clinical Feature Lymphoma SLL/CLL >60, males Indolent; Spills in blood Affect BM, liver spleen Follicular Middle age Indolent, incurable C Lymphoma M=F Generalized lymphadenopathy DLBCL Elderly pedia Rapidly growing mass (LN or ExtraLN) Aggressive Burkitt’s Children Extranodal mass Aggressive Mantle Cell Older males Disseminated Disease a. Diffuse large cell lymphoma Aggressive b. Small Cell Lymphoma Marginal Zone Any age MALTOMA c. Burkitt’s Lymphoma d. Hodgkin’s Lymphoma Follicular Lymphoma 2. 27/M complains of slowly enlarging cervical neck mass. Patient afebrile P.E. shows a 2 x 1 movable mass on the posterior triangle of the neck. Mass was Figure. 34. Follicular lymphoma excised and sent for biopsy. Give → Malignant your diagnosis. → Follicles show monomorphic cells → No clear margin between germinal center and inactive mantle zone → Pinpoint spaces occupied by the macrophages are lost → Invasion of capsule and adjacent fat D Mantle Cell Lymphoma a. Follicular Lymphoma b. Mantle cell lymphoma c. Parafollicular hyperplasia d. Follicular hyperplasia Figure 35. Mantle Cell Lymphoma → Mantle Cell Lymphoma (AKA Disseminated Lymphoma): Lymph nodes, extranodal organs and peripheral circulation are affected, making it an aggressive tumor that spreads widely ▪ Because of the extensiveness of the lesions with generalized lymphadenopathy and spread to other organs, it is called as disseminated lymphoma PATHOLOGY WBC Diseases, Lymph Nodes, Spleen, Thymus II PAGE 15 of 16 PATHOLOGY | LE 1 WBC Diseases, Lymph Nodes, Spleen, Thymus II | Dr. Araceli P. Jacoba Table 2. WHO Classification of Lymphoid Tumors[Lecturer’s PPT] Precursor B cell B Lymphoblastic Leukemia (ALL) / Lymphoma (Pre B cell) Precursor T cell T Lymphoblastic Leukemia / Lymphoma (Pre T cell) Peripheral B cell Chronic Lymphocytic Leukemia (CLL) 3. 38 year old male multiple fixed Small Lymphocytic Leukemia (SLL) nodes in the neck. CT scan showed Burkitt’s Lymphoma posterior mediastinal masses. Follicular Lymphoma Biopsy of the neck node is as Hairy Cell Leukemia follows. Give the origin of the tumor. C Peripheral T cell or Adult T cell Lymphoma a. Precursor B NK cell NK-T cell Lymphoma b. Precursor T Mycosis Fungoides / Sezary Syndrome c. Peripheral B d. Peripheral T Hodgkin’s Lymphoma a. Precursor B - B lymphoblastic Leu (ALL)/ Lymphoma b. Precursor T - T lymphoblastic Leu/ Lymphoma c. Peripheral B - CLL, SLL, Follicular lymphoma, Burkitt's lymphoma, Hairy cell Leu d. Adult T cell lymphoma, NK-T cell lymphoma, Mycosis Fungoides/ Sezary Syndrome PATHOLOGY WBC Diseases, Lymph Nodes, Spleen, Thymus II PAGE 16 of 16