LYMPH NODE.docx

LYMPH NODE +-----------------------------------+-----------------------------------+ | LYMPHOID HYPERPLASIAS | | +===================================+===================================+ | FOLLICULAR HYPERPLASIAS | - Reactive follicular...

LYMPH NODE +-----------------------------------+-----------------------------------+ | LYMPHOID HYPERPLASIAS | | +===================================+===================================+ | FOLLICULAR HYPERPLASIAS | - Reactive follicular | | | hyperplasia | | | | | | - Toxoplasmosis | | | | | | - Cytomegalovirus (CMV) | | | | | | - Human immunodeficiency virus | | | (HIV) | | | | | | - Rheumatoid arthritis | | | | | | - Syphilis | | | | | | - Progressive transformation of | | | germinal centers | | | | | | - Castleman disease, hyaline | | | vascular type | | | | | | - Castleman disease, plasma | | | cell type | +-----------------------------------+-----------------------------------+ | SINUS HYPERPLASIAS | - Whipple disease | | | | | *W-H-V* | - Hemophagocytic syndrome | | | | | | - Vascular transformation of | | | lymph node sinuses | +-----------------------------------+-----------------------------------+ | PARACORTICAL HYPERPLASIAS | - Infectious mononucleosis | | | | | *D-I-A* | - Atypical immunoblastic | | | reaction | | | | | | - Dermatopathic lymphadenopathy | +-----------------------------------+-----------------------------------+ | NECROTIZING GRANULOMATOUS | - Cat scratch disease | | LYMPHADENITIS | | | | - Lymphogranuloma venereum | | *Cat* | | | | - Tularemia | | *LiTer* | | | | - Yersinia | | *Yes* | | | | - Tuberculosis (TB) | | *Fun* | | | | - Fungal infection | | *Tubol* | | +-----------------------------------+-----------------------------------+ | NECROTIZING NONGRANULOMATOUS | - Kikuchi --Fujimoto disease | | LYMPHADENITIS | | | | - Systemic lupus erythematosus | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **MALIGNANT LYMPHOMA/LEUKEMIA** | | | | | | **(WHO CLASSIFICATION)** | | +===================================+===================================+ | HODGKIN LYMPHOMA | **Nodular lymphocyte predominant | | | Hodgkin lymphoma** | | N-C | | | | **Classic Hodgkin lymphoma** | | cHL | | | | - Nodular sclerosis Hodgkin | | - *NMLL* | lymphoma (NSHL) | | | | | | - Mixed cellularity Hodgkin | | | lymphoma (MCHL) | | | | | | - Lymphocyte-rich classic | | | Hodgkin lymphoma (LRCHL) | | | | | | - Lymphocyte-depleted Hodgkin | | | lymphoma (LDHL) | +-----------------------------------+-----------------------------------+ | PRECURSOR B- AND T- CELL | B-lymphoblastic leukemia/lymphoma | | NEOPLASMS | | | | T- lymphoblastic | | | leukemia/lymphoma | +-----------------------------------+-----------------------------------+ | MATURE B- CELL NEOPLASMS | Chronic lymphocytic leukemia | | | (CLL)/ small | | | | | | lymphocytic lymphoma (SLL) | | | | | | B-cell prolymphocytic leukemia | | | (B-PLL) | | | | | | Lymphoplasmacytic | | | lymphoma/Waldenstrom | | | | | | Splenic marginal zone lymphoma | | | | | | Hairy cell leukemia | | | | | | Plasma cell neoplasms | | | | | | Extranodal marginal zone lymphoma | | | of mucosa- | | | | | | associated lymphoid tissue (MALT | | | lymphoma) | | | | | | Nodal marginal zone B-cell | | | lymphoma | | | | | | Follicular lymphoma (FL) | | | | | | Mantle cell lymphoma | | | | | | Diffuse large B-cell lymphoma | | | | | | Mediastinal (thymic) large B-cell | | | lymphoma | | | | | | Burkitt lymphoma | +-----------------------------------+-----------------------------------+ | MATURE T-CELL AND NK-CELL | T-cell prolymphocytic leukemia | | NEOPLASMS | (T-PLL) | | | | | | Aggressive NK-cell leukemia | | | | | | Adult T-cell leukemia/lymphoma | | | | | | Extranodal NK-/T-cell lymphoma, | | | nasal type | | | | | | Enteropathy-associated T-cell | | | lymphoma (EATL) | | | | | | Hepatosplenic T-cell lymphoma | | | | | | Subcutaneous panniculitis-like | | | T-cell lymphoma | | | | | | Mycosis fungoides/Sezary syndrome | | | (MF/SS) | | | | | | Angioimmunoblastic T-cell | | | lymphoma | | | | | | Peripheral T-cell lymphoma, not | | | otherwise specified | | | | | | Anaplastic large-cell lymphoma | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | HISTIOCYTIC LYMPH NODE TUMORS | Histiocytic sarcoma | | | | | | Langerhans cell histiocytosis | | | | | | Langerhans cell sarcoma | | | | | | Sinus hyperplasia with massive | | | lymphadenopathy | | | | | | Interdigitating dendritic cell | | | sarcoma | | | | | | Follicular dendritic cell sarcoma | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **SPINDLE CELL LESIONS OF LYMPH | Bacillary angiomatosis | | NODE** | | | | Kaposi sarcoma | | | | | | Palisaded myofibroblastoma | | | | | | Inflammatory pseudotumor of lymph | | | node | +-----------------------------------+-----------------------------------+ REACTIVE FOLLICULAR HYPERPLASIA --------------------------------- ------------------------ Etiology Cannot be identified DDX Follicular lymphoma FCC bcl2 negative Follicular hyperplasia Homogenous F. lymphoma Absent cell polarity F. lymphoma Increased follicular density F. lymphoma FCC not light restricted F. hyperplasia +-----------------------------------+-----------------------------------+ | TOXOPLASMOSIS | | +===================================+===================================+ | Prevalence | Young females | +-----------------------------------+-----------------------------------+ | MOT | **Exposure to oocysts in cat | | | feces** or by ingestion of poorly | | | cooked meat. | +-----------------------------------+-----------------------------------+ | Symptoms | **flu-like or asymptomatic** | +-----------------------------------+-----------------------------------+ | Site of involvement | Posterior cervical nodes | +-----------------------------------+-----------------------------------+ | TOXO TRIAD | - **[Florid] | | | follicular hyperplasia** | | | | | | - **[Monocytoid B-cell | | | hyperplasia]** | | | expanding and surrounding | | | sinuses | | | | | | - **Paracortical epithelioid | | | histiocyte clusters** that | | | encroach on germinal centers | +-----------------------------------+-----------------------------------+ | NECROSIS? | **[ABSENT ]** | +-----------------------------------+-----------------------------------+ | CONFIRMATORY TEST | **[SEROLOGY ]** | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | CYTOMEGALOVIRUS | | +===================================+===================================+ | Microscopic | - **Florid follicular | | | hyperplasia** | | **First 2 may also be seen in | | | TOXO triad** | - **Monocytoid B-cell | | | hyperplasia expanding | | | sinuses** (CMV inclusions may | | | sometimes be identified here) | | | | | | - +/− immunoblastic | | | proliferation (may be | | | atypical) | +-----------------------------------+-----------------------------------+ | Confirmatory | - **Serology** | | | | | | - **IHC** | | | | | | - **ISH** | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | HIV | | +===================================+===================================+ | EARLY STAGE | - **Florid reactive lymphoid | | | hyperplasia** with absent | | | mantle zones and follicle | | | lysis of dendritic cell\] | | | meshwork, and increased T | | | cells) | | | | | | - **Monocytoid B-cell | | | hyperplasia expanding | | | sinuses** | | | | | | - Epithelioid histiocyte | | | clusters | | | | | | - Increased plasma cells and | | | polykaryocytes (large | | | multinucleated giant cells) | | | in interfollicular zones | +-----------------------------------+-----------------------------------+ | LATE STAGE | - Regressively transformed | | | germinal center | | | | | | - Depletion of lymphocytes from | | | paracortex | +-----------------------------------+-----------------------------------+ | **[POP QUIZ]** | | +-----------------------------------+-----------------------------------+ | **Monocytoid B-cell hyperplasia | **TOXO, CMV, HIV** | | expanding sinuses** | | +-----------------------------------+-----------------------------------+ | **Epithelioid histiocyte | EARLY STAGE | | clusters** | | +-----------------------------------+-----------------------------------+ | **Large multinucleated giant | Polykaryocytes | | cells** | | | | - SEEN IN EARLY STAGE | +-----------------------------------+-----------------------------------+ | **Depletion of lymphocytes from | LATE STAGE | | paracortex** | | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | RA | | +===================================+===================================+ | MICROSCOPIC | - Florid follicular hyperplasia | | | | | | - Marked interfollicular | | | plasmacytosis (plasma cells | | | also present within follicles | | | | | | - Clusters of neutrophils in | | | sinuses | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | SYPHILIS (LUETIC LYMPHADENITIS) | | +===================================+===================================+ | Microscopic | - Florid follicular hyperplasia | | | | | | - **Interfollicular | | | plasmacytosis** | | | | | | - Epithelioid granulomas | | | | | | - Thick, fibrotic capsule -- | | | perivascular plasma cells | | | | | | - **+/− arteritis/phlebitis** | +-----------------------------------+-----------------------------------+ | Confirmatory | - Serology | | | | | | - IHC | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | PROGRESSIVE TRANSFORMATION OF | | | GERMINAL | | | | | | CENTERS | | +===================================+===================================+ | Rarely precedes, accompanies, or | nodular lymphocyte predominant | | follows | Hodgkin lymphoma (NLPHL) | | \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\ | | | _\_\_\_\_\_\_ | | +-----------------------------------+-----------------------------------+ | Microscopic | Associated with reactive | | | follicular hyperplasia in the | | | same node | | | | | | Large follicles with | | | **[indistinct germinal | | | center/mantle zone]** | | | borders due to infiltration of | | | germinal centers by [mantle zone | | | lymphocytes] | | | | | | Residual centroblasts may mimic | | | LP cells of NLPH | +-----------------------------------+-----------------------------------+ | Ddx | - NLPHL | | | | | | - Follicular lymphoma- floral | | | variant | | | | | | - Mantle cell lymphoma | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **CASTLEMAN DISEASE: PLASMA CELL | | | VARIANT** | | +===================================+===================================+ | Clinical | POEM syndrome | +-----------------------------------+-----------------------------------+ | Site of involvement | - abdominal cavity and | | | mediastinum | | | | | | - peripheral lymph nodes, | | | | | | - extranodal sites | +-----------------------------------+-----------------------------------+ | Microscopic | Florid follicular hyperplasia | | | with **regressive transformation | | | of germinal centers** | | | | | | **Marked interfollicular | | | plasmacytosis** that extends to | | | | | | the lymph node capsule | | | | | | When multicentric, may be | | | HHV8-positive | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **CASTLEMAN DISEASE: HYALINE | | | VASCULAR TYPE** | | +===================================+===================================+ | Definition | Usually solitary mediastinal | | | mass, may involve other | | | | | | Sites | +-----------------------------------+-----------------------------------+ | Microscopic | **[Atrophic germinal | | | centers]** | | | (regressively transformed) | | | | | | with expanded mantle zones | | | composed of concentric | | | | | | layers of lymphocytes | | | | | | Multiple regressively transformed | | | germinal centers in one "cloud" | | | of mantle zone lymphocytes | | | | | | **Hyalinized blood vessels | | | penetrate into follicles** | | | | | | interfollicular vascularity | | | increased. | | | | | | Few interfollicular plasma cells | | | or transformed lymphocytes | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **WHIPPLE DISEASE** | | +===================================+===================================+ | Age and sex predilection | Middle aged adults | | | | | | M\>F | +-----------------------------------+-----------------------------------+ | Etiology | infectious disease of small bowel | | | (etiologic agent: | | | | | | **Tropheryma whipplei , formerly | | | called Tropheryma whippelii)** | +-----------------------------------+-----------------------------------+ | Site | - small bowel | | | | | | - abdominal lymph nodes, | | | | | | - +/− peripheral lymph nodes | +-----------------------------------+-----------------------------------+ | Microscopic | Sinuses distended by **[large | | | lipid vacuoles]** | | | surrounded by vacuolated | | | histiocytes | +-----------------------------------+-----------------------------------+ | Stain | PAS+ | | | | | | - PAS+ bacilli present within | | | histiocyte cytoplasm in | | | | | | - sinuses and in germinal | | | centers | +-----------------------------------+-----------------------------------+ | DX | PCR | | | | | | EM | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | HEMOPHAGOCYTIC SYNDROME | | +===================================+===================================+ | Affected? | Immunocompromised hosts | +-----------------------------------+-----------------------------------+ | Etiology | Usually due to viral infection, | | | may result from | | | | | | bacterial, fungal, or parasitic | | | infection | +-----------------------------------+-----------------------------------+ | May complicate certain lymphomas | - Subcutaneous | | | panniculitis-like T-cell | | | lymphoma | | | | | | - ALCL | | | | | | - Extranodal NK-/T-cell | | | lymphoma, nasal type | +-----------------------------------+-----------------------------------+ | Site of involvement | - lymph nodes | | | | | | - spleen | | | | | | - bone marrow | +-----------------------------------+-----------------------------------+ | Microscopic | Sinuses distended **[by | | | benign-appearing | | | histiocytes]** | | | | | | **[containing phagocytized | | | erythrocytes]** or | | | other | | | | | | hematopoietic elements | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | VASCULAR TRANSFORMATION OF LYMPH | | | NODE SINUSES | | +===================================+===================================+ | Clinical | Lymph node enlargement | | | | | | Sometimes associated with deep | | | venous thrombosis in adjacent | | | vein | +-----------------------------------+-----------------------------------+ | Microscopic | Sinuses distended by | | | proliferating anastomosing | | | | | | vascular channels, often with | | | fibrosis | | | | | | Capsule spared | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | INFECTIOUS MONONUCLEOSIS | | +===================================+===================================+ | MICROSCOPIC | Paracortical expansion (**EBV+ B | | | cells located in the | | | paracortex**) | | | | | | **FOCAL NECROSIS** | | | (toxoplasma---absent necrosis) | | | | | | Sinuses distended by atypical | | | lymphocytes, monocytoid B cells, | | | and/or immunoblasts | | | | | | +/− follicular hyperplasia | +-----------------------------------+-----------------------------------+ | CYTOLOGY | Sinuses distended by atypical | | | lymphocytes, | | | | | | monocytoid B cells, and/or | | | immunoblasts | +-----------------------------------+-----------------------------------+ | CONFIRMATORY | SEROLOGY | | | | | | EBV+ immunoblasts by In-sity | | | hybridization (EBER) or IHC (LMP) | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | ATYPICAL IMMUNOBLASTIC REACTION | | +===================================+===================================+ | MICROSCOPIC | Similar to IM | +-----------------------------------+-----------------------------------+ | Causes | - reaction (**especially | | | hydantoin):** eosinophils | | | often numerous | | | | | | - **Herpes simplex:** viral | | | inclusions may be seen in and | | | around necrotic areas | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **CAT SCRATCH DISEASE** | | +===================================+===================================+ | SITE | AXILLARY NODE | | | | | | CERVICAL NODES | +-----------------------------------+-----------------------------------+ | Etiology | Bartonella henselae | +-----------------------------------+-----------------------------------+ | Microscopic | Central **stellate abscesses** | | | containing neutrophils, | | | surrounded by **palisaded | | | histiocytes and fibroblasts** ; | | | sparse to no smultinucleated | | | giant histiocytes | | | | | | +/− follicular hyperplasia (IM | | | also) | | | | | | +/− monocytoid B cells distending | | | sinuses | +-----------------------------------+-----------------------------------+ | Stain | Bacilli (found in necrotic areas) | | | stain positively with | | | Warthin--Starry stain | +-----------------------------------+-----------------------------------+ | Confirmatory | PCR | +-----------------------------------+-----------------------------------+ **LYMPHORANULOMA VENEREUM** ----------------------------- ------------------------------------------------------------------------------------- Etiology Chlamydia trachomatis MOT SEXUALLY TRANSMITTED SITE Involves **inguinal lymph nodes in males and pelvic lymph nodes in females** MICROSCOPIC Morphologically indistinguishable from cat scratch disease, tularemia, and Yersinia Confirmatory PCR **TULAREMIA** --------------- -------------------------- MOT TICK BITE SITE **axillary lymph nodes** CONFIRMATORY **SEROLOGY/ CULTURE** **YERSINIA** -------------- ------------------------------------------------------------------------------------------ CLINICAL Clinical history of **abdominal pain and diarrhea**, ***signs suggesting appendicitis*** SITE MESENTERIC NODE **TUBERCULOSIS** ------------------ -------------------------------------------------------------------------------------------- MICROSCOPIC **Necrotizing granulomas with [central caseous necrosis] without neutrophils** DX **AFB+ bacilli** present in necrotic areas (may be difficult to find); PCR may help **FUNGAL INFECTION** ---------------------- -------------------------------------------------------------------------------------------------------------------------- MICROSCOPIC Morphologically **similar to TB**, but granulomas more commonly **contain neutrophils and karyorrhectic nuclear debris** STAIN GMS +, PAS + +-----------------------------------+-----------------------------------+ | **KIKUCHI-FUJIMOTO DISEASE** | | +===================================+===================================+ | SYNONYM | Synonym- **Histiocytic | | | necrotizing lymphadenitis** | +-----------------------------------+-----------------------------------+ | CLINICAL | YOUNG adult FEMALE | +-----------------------------------+-----------------------------------+ | SITE | CERVICAL LN | +-----------------------------------+-----------------------------------+ | MICROSCOPIC | **Patchy cortical and | | | paracortical necrosis** with | | | extensive karyorrhectic debris | | | and histiocytes | | | [centrally] | | | | | | **Immunoblasts, histiocytes, and | | | plasmacytoid monocytes | | | [periphery]** | | | | | | **No granulocytes, few plasma | | | cells** | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **SYSTEMIC LUPUS ERYTHEMATOSUS** | | +===================================+===================================+ | Clinical | Young adult female | +-----------------------------------+-----------------------------------+ | Site | Cervical Or Generalized | | | Lymphadenopathy | +-----------------------------------+-----------------------------------+ | **MICROSCOPIC** | Follicular hyperplasia | | | | | | Interfollicular zones contain | | | increased plasma cells and | | | immunoblasts | | | | | | Areas of necrosis may contain | | | neutrophils or plasma cells | | | | | | Hematoxylin bodies (composed of | | | DNA aggregates, polysaccharides, | | | and immunoglobulin) found within | | | areas of necrosis and walls of | | | blood vessels | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **HODGKIN'S LYMPHOMA** | | +===================================+===================================+ | DEFINITION | Malignant lymphoma that is | | | typically of B-cell origin | +-----------------------------------+-----------------------------------+ | EPID | young adults 20-30, older 50-70 | +-----------------------------------+-----------------------------------+ | ETIOLOGY | - Immunosuppression (e.g., | | | HIV), | | | | | | - EBV infection, Autoimmune | | | diseases | +-----------------------------------+-----------------------------------+ | Clinical features: | - PAINLESS ADENOPATHY---ABOVE | | | THE DIAPHRAGM | | | | | | - **[Contiguous spread | | | ]** | | | | | | - LN in the upper portion of | | | the body | | | | | | - **B symptom** | | | | | | - Pel-Ebstein fever | | | | | | - Alcohol-induced pain | | | | | | - Pruritus | | | | | | - **No hepatosplenomegaly** | | | | | | - No leukemic cells | | | | | | - RS cells | | | | | | - Good prognosis | | | | | | - ABVD, BEACOPP | | |  | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **NODULAR LYMPHOCYTE PREDOMINANT | | | HODGKIN LYMPHOMA** | | +===================================+===================================+ | Age | Median mid 30s (wide age range) | +-----------------------------------+-----------------------------------+ | Sex | male \> female (2.5:1) | +-----------------------------------+-----------------------------------+ | Site involved | Localized involvement of | | | peripheral nodes | | | | | | - Cervical | | | | | | - Supraclavicular | | | | | | - Axillary | | | | | | Occasionally preceded, | | | accompanied, or followed by | | | **[progressive transformation of | | | germinal centers | | | (PTGC)]** | +-----------------------------------+-----------------------------------+ | **Clinical course** | Vast majority have complete | | | response to therapy | | | | | | **May relapse or develop other | | | lymphoma, especially large B-cell | | | lymphoma** | +-----------------------------------+-----------------------------------+ | **MICROSCOPIC** | **Low power** | | | | | | - Macronodules +/− diffuse | | | areas, often with rim of | | | uninvolved lymph node | | | | | | **High power** | | | | | | - Neoplastic cells: | | | | | | | | | | | | - Scattered LP (lymphocyte | | | predominant) cells (large | | | cells with multilobated | | | vesicular nuclei, delicate | | | chromatin, small nucleoli, | | | and scant **[wispy | | | cytoplasm]**) set | | | into the macronodules | +-----------------------------------+-----------------------------------+ | **RS cells** | **Classic RS cells rare or | | | absent** | +-----------------------------------+-----------------------------------+ | **Background cells:** | - Macronodules composed of | | | small B cells with normal | | | mantle zone phenotype | | | accompanied by histiocytes | | | | | | - Rare plasma cells, | | | eosinophils, or neutrophils | +-----------------------------------+-----------------------------------+ | **IMMUNOHISTOCHEMISTRY: POSITIVE | - LP cells | | IN NLPHL** | | | | - CD45+ | | | | | | - CD19, CD20, CD22, CD79a+, | | | PAX5+ | | | | | | - EMA Positive | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **CLASSIC HODGKIN LYMPHOMA:** | | | | | | **[NODULAR SCLEROSIS] | | | HODGKIN LYMPHOMA** | | +===================================+===================================+ | Age | Young adults | +-----------------------------------+-----------------------------------+ | Sex | F\>M | +-----------------------------------+-----------------------------------+ | Sites of involvement | **lower cervical**, | | | **supraclavicular**, and | | | **anterior mediastinal lymph** | | | nodes are most common | +-----------------------------------+-----------------------------------+ | Prognosis | **Poorer prognosis: higher stage, | | | greater bulk of disease** | +-----------------------------------+-----------------------------------+ | Clinical course | often curable (**95% of patients | | | presenting at stage I and II,** | | | [50--70% of patients present at | | | stage III and IV)] | +-----------------------------------+-----------------------------------+ | **MICROSCOPIC** | Low power | | | | | | - Nodular pattern with fibrous | | | band separating nodules, +/− | | | diffuse areas, +/− necrosis | | | | | | - May be interfollicular | | | | | | High power | | | | | | - Hodgkin and RS cells (HRS | | | cells) | | | | | | - Lacunar cells (RS cell | | | variants) common | | | | | | | | | | | | - multilobated nuclei, small | | | nucleoli, and abundant pale | | | cytoplasm that retracts with | | | formalin fixation | | | | | | | | | | | | - Classic RS cells may be rare | | | | | | - Background cells | | | | | | | | | | | | - Lymphocytes (mostly T cells) | | | | | | - Eosinophils | | | | | | - Histiocytes | | | | | | - plasma cells | | | | | | - **neutrophils (associated | | | with B symptoms)** | | | | | | - and fibroblasts. | | | | | | Hodgkin lymphoma (HL) is | | | classified as NS type whenever | | | there are collagen bands and | | | lacunar cells, regardless of all | | | else | +-----------------------------------+-----------------------------------+ | **IHC** | HRS cells | | | | | | CD30+ **VS NLPHL (-)** | | | | | | **Usually CD15+** (paranuclear, | | | cytoplasmic, and/or membranous | | | staining pattern), at least in a | | | subset of | | | | | | CD45-- **(vs NLPHL 45 +)** | +-----------------------------------+-----------------------------------+ | **GENETICS** | Whole tissue DNA: **polyclonal** | | | | | | DNA isolated from isolated single | | | HRS cells: **usually monoclonal | | | Ig gene rearrangements** | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **CLASSIC HODGKIN LYMPHOMA:** | | | | | | **MIXED CELLULARITY HODGKIN | | | LYMPHOMA** | | +===================================+===================================+ | Age | adults (wide age range); Sex: M | | | \> F | +-----------------------------------+-----------------------------------+ | Presentation | higher stage (lymph nodes, | | | spleen, liver, bone marrow often | | | involved) | +-----------------------------------+-----------------------------------+ | MICROSCOPIC | Architecture | | | | | | - Diffuse or vaguely nodular | | | | | | - Lymph node capsule intact | | | | | | - No broad bands of fibrosis | | | | | | - May be interfollicular | +-----------------------------------+-----------------------------------+ | Cytology | HRS cells **(also with NSHL)** | +-----------------------------------+-----------------------------------+ | RS cells | Classic RS cells common: | | | | | | - large cells with large single | | | or multiple nuclei that often | | | have more than one lobe, a | | | single prominent eosinophilic | | | nucleolus per lobe, and | | | abundant cytoplasm | | | | | | o Lacunar cells absent | | | | | | o Background cells | +-----------------------------------+-----------------------------------+ | Cells | Lymphocytes, epithelioid | | | histiocytes, eosinophils, | | | neutrophils, and plasma cells | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **CLASSIC HODGKIN LYMPHOMA:** | | | | | | **LYMPHOCYTE-RICH CLASSIC HODGKIN | | | LYMPHOMA** | | +===================================+===================================+ | Age | adults; Sex: M \> F | +-----------------------------------+-----------------------------------+ | Presentation | usually lower stage (I or II) | +-----------------------------------+-----------------------------------+ | **MICROSCOPIC** | Architecture | | | | | | - Nodular or diffuse | | | involvement | +-----------------------------------+-----------------------------------+ | **Cytology** | **Neoplastic cells:** infrequent | | | classic RS cells, +/− lacunar | | | variants | +-----------------------------------+-----------------------------------+ | **Background cells:** | **numerous lymphocytes with | | | occasional histiocytes, | | | eosinophils, or plasma cells** | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **CLASSIC HODGKIN LYMPHOMA:** | | | | | | **LYMPHOCYTE-DEPLETED HODGKIN | | | LYMPHOMA** | | +===================================+===================================+ | Prevalence | Rare | +-----------------------------------+-----------------------------------+ | Age | Older adults | +-----------------------------------+-----------------------------------+ | Seen in | Also seen in HIV+ patients and | | | patients from developing | | | countries | +-----------------------------------+-----------------------------------+ | Site of involvement | abdominal lymph nodes, spleen, | | | liver, bone marrow | | | | | | - **Extranodal sites involved | | | in HIV+ individuals (usually | | | EBV+)** | +-----------------------------------+-----------------------------------+ | **MICROSCOPIC** | Architecture | | | | | | - Depleted appearance with | | | disorganized collage | +-----------------------------------+-----------------------------------+ | **Cytology** | **[INNUMERABLE RS | | | CELLS]**, bizarre | | | multinucleated cells, and RS cell | | | variants of no special type | | | | | | Minimal reactive elements | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **IMMUNOHISTOCHEMISTRY** | | +===================================+===================================+ | **NLPHL** | **NSHL** | +-----------------------------------+-----------------------------------+ | **[LP Cells ]** | HRS cells | | | | | CD45+CD19, CD20, CD22, CD79a+, | **CD20−/+** | | PAX5+ | | | | **CD45--** | | EMA Positive | | | | **PAX5+** | | Rimmed by **CD279+** small T | | | cells | T-cell-associated antigens | | | usually( --) | | Increased background **CD57+** | | | small T cells | ALK-- | | | | | May be kappa light chain | CD 15 + | | restricted. | | | | CD 30+ | | Usually EBV negative | | | | | | CD 15 -- | | | | | | CD 30 - | | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | NON-HODGKIN LYMPHOMA | | +===================================+===================================+ | Incidence | Increases with age (peak \> 50 | | | years) | +-----------------------------------+-----------------------------------+ | Etiology | - **Infections** (HIV, EN, | | | HTLV-1, HCV, H. Pylori) | | | | | | - **Autoimmune diseases** | | | (e.g., Hashimoto thyroiditis, | | | rheumatic disease) | | | | | | - **Chromosomal translocation** | +-----------------------------------+-----------------------------------+ | Classification based on: | - **Cell type** (B cell, T | | | cells, natural killer (NK) | | | cells) | | | | | | - **Location** (nodal or | | | extranodal) | | | | | | - **Tumor grade** | | | | | | **Note: HL B cell onleee** | +-----------------------------------+-----------------------------------+ | Spread | **Noncontiguous spread** | | | | | | **Vs HL contiguous** | | | | | | Adenopathy + Extranodal (Multiple | | | lymph node groups) | | | | | | - Lymph nodes throughout the | | | body, but can also arise in | | | normal organs | | | | | | - **VS HL painless, localized | | | abov ethe diaphragm** | +-----------------------------------+-----------------------------------+ | Clinical features: | **Nodal disease** | | | | | | - B symptoms | | | | | | - Lymphadenopathy | | | | | | - Mass | | | | | | - Hepatosplenomegaly (vs HL | | | ABSENT) | | | | | | - Cytopenias(bleeding) | | | | | | **Extranodal disease:** | | | | | | - GI | | | | | | - Neuro | | | | | | - cutaneous involvement | | | | | | **+leukemic phase** (VS HL | | | absent) | +-----------------------------------+-----------------------------------+ | Histology | **Majority are neoplastic cells | | | of B Cell lineage** | +-----------------------------------+-----------------------------------+ | Prognosis | **Worse (high LH, HIgh beta2 | | | microglobulin)** | +-----------------------------------+-----------------------------------+ | Treatment | **CHOP, radiotherapy** | +-----------------------------------+-----------------------------------+ **PRECURSOR B- AND T-CELL NEOPLASMS** +-----------------------------------+-----------------------------------+ | **LYMPHOBLASTIC | | | LEUKEMIA/LYMPHOMA,** | | | | | | **NOT OTHERWISE SPECIFIED** | | +===================================+===================================+ | AGE | children \> adults | +-----------------------------------+-----------------------------------+ | Presentation | **[Acute lymphoblastic | | | leukemia]** (bone | | | marrow and peripheral blood | | | involvement) **-- more common.** | | | | | | Pancytopenia, adenopathy, | | | hepatosplenomegaly, bone pain | | | | | | **[Lymphoblastic | | | lymphoma] ( solid | | | tumor \[lymph node, skin, | | | bone\],** +/− minimal bone | | | marrow, or peripheral blood | | | involvement) **-- less common.** | | | | | | Mediastinum rarely involved in | | | B-LBL | +-----------------------------------+-----------------------------------+ | Clinical course | Highly aggressive | | | | | | Often curable with chemotherapy | +-----------------------------------+-----------------------------------+ | Postulated cell of origin: | Precursor B lymphoblasts | +-----------------------------------+-----------------------------------+ | **MICROSCOPIC** | **Low power (lymph node)** | | | | | | - Architecture efface | | | | | | - Invasion of **[perinodal fat | | | common]** | | | | | | - Tumor involves paracortex, | | | may spare reactive follicles | | | | | | High power | | | | | | - Monotonous population of | | | lymphoblasts: | | | | | | - Frequent mitoses | | | | | | - +/− starry-sky pattern | | | (tingible body macrophages) | | | | | | - T and B phenotypes | | | morphologically | | | indistinguishable | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **T-LYMPHOBLASTIC | | | LEUKEMIA/LYMPHOMA** | | +===================================+===================================+ | Age | adolescents and young adults | +-----------------------------------+-----------------------------------+ | SEX | M \> F | +-----------------------------------+-----------------------------------+ | Presentation | rapidly enlarging mediastinal | | | (thymic) mass, +/− | | | lymphadenopathy, SVC syndrome, | | | pericardial and pleural effusions | +-----------------------------------+-----------------------------------+ | Bone marrow involvement \>25% = | precursor T- lymphoblastic | | | leukemia | +-----------------------------------+-----------------------------------+ | Clinical course: | highly aggressive but potentially | | | curable | +-----------------------------------+-----------------------------------+ | MICROSCOPIC | **[Monotonous population of | | | lymphoblasts]** | | | | | | Numerous mitoses, **tangible body | | | macrophages (starry sky)** | | | | | | Morphologically indistinguishable | | | from B-LBL | +-----------------------------------+-----------------------------------+ **B.3. MATURE B-CELL NEOPLASMS** +-----------------------------------+-----------------------------------+ | **CHRONIC LYMPHOCYTIC LEUKEMIA/** | | | | | | **SMALL LYMPHOCYTIC LYMPHOMA** | | +===================================+===================================+ | Age | older adults (median age 60--65 | | | years) | +-----------------------------------+-----------------------------------+ | Sex | M\>F (slight) | +-----------------------------------+-----------------------------------+ | **CLINICAL COURSE** | Indolent **[but not | | | curable]** with | | | available therapy | +-----------------------------------+-----------------------------------+ | **Median survival** | **60-70 months** | +-----------------------------------+-----------------------------------+ | **May t[ransform] to | **diffuse [large B-cell lymphoma | | \_\_\_\_** | ]**(DLBCL); poor | | | prognosis; risk increases over | | | time | | | | | | May also develop de **[novo | | | DLBCL]**; better | | | prognosis than transformation | +-----------------------------------+-----------------------------------+ | **Postulated cell of origin** | **40--50%** -- naive B cell | | | (germline variable region IG | | | genes) | | | | | | **50--60%** -- postgerminal | | | center B cell (variable region IG | | | genes contain somatic mutations) | +-----------------------------------+-----------------------------------+ | **PROGNOSIS** | **Poorer prognosis** | | | | | | - Extensive clinical disease | | | | | | - Low ECOG performance status | | | | | | - Increased number of large | | | cells (prolymphocytes and | | | paraimmunoblasts) | | | | | | - **17p deletion, 11q | | | deletion** | | | | | | - **Germline IGHV genes** | | | | | | - Elevated LDH | | | | | | - **Elevated serum β 2 | | | -microglobulin level** | | | | | | **Better prognosis** | | | | | | - Low stage | | | | | | - High ECOG performance status | | | | | | - **Mutated IGHV genes** | | | | | | - Isolated 13q deletion | | | | | | - Lack of expression of | | | CD38/ZAP-70 (controversial) | +-----------------------------------+-----------------------------------+ | **Microscopic** | **Low power** | | | | | | - Effaced architecture although | | | residual follicles may be | | | present | | | | | | - Pale zones (proliferation | | | centers) alternating with | | | darker zones | | | | | | - **Monotonous population of | | | small lymphocytes** | +-----------------------------------+-----------------------------------+ | **IMMUNOPHENOTYPE** | - CD19, CD20 (weak), CD79a+ | | | | | | - CD23+ | | | | | | - **CD5**+, CD43+ | | | | | | - sIg weakly + (M + / − D), | | | immunoglobulin light chain | | | restricted | | | | | | - **CD10--** | | | | | | | | | | | | - **Cyclin D1--** | +-----------------------------------+-----------------------------------+ | **Genetics** | - Ig heavy and light chain | | | genes are rearrange | | | | | | - **NOTCH1 mutation (10--15%)** | | | | | | - **SF3B1 mutation (10--15%)** | | | | | | - Trisomy 12 -- common -- | | | intermediate prognosis | | | | | | - 13q abnormalities (13q14) -- | | | most common -- slightly | | | better prognosis if sole | | | abnormality | | | | | | - 11q deletion -- poorer | | | prognosis | | | | | | | | | | | | - 17p deletion -- poorer | | | prognosis | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **B-CELL PROLYMPHOCYTIC | | | LEUKEMIA** | | +===================================+===================================+ | CLINICAL | Often present with **higher WBC | | | count and splenomegal**y | +-----------------------------------+-----------------------------------+ | MICROSCOPIC | 65% of blood lymphocytes are | | | prolymphocytes\` | +-----------------------------------+-----------------------------------+ | Prolymphocytes | clumped chromatin with | | | **[prominent single | | | nucleolus]**; defined | | | on the basis of peripheral blood | | | involvement, not tissue sections | +-----------------------------------+-----------------------------------+ | IMMUNOPHENOTYPE | Strong sIg+ | | | | | | **CD5 may be negative (VS CLL | | | (+)** | | | | | | CD23 usually absent (VS CLL (+) | +-----------------------------------+-----------------------------------+ | GENETICS | Abnormalities involving MYC | | | (translocations and/or extra | | | copies) common | +-----------------------------------+-----------------------------------+ | PROGNOSIS | More aggressive clinical course | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **LYMPHOPLASMACYTIC LYMPHOMA/** | | | | | | **WALDENSTROM MACROGLOBULINEMIA** | | +===================================+===================================+ | AGE | Age: older adults (median 63 | | | years) | +-----------------------------------+-----------------------------------+ | SEX | M \> F (slight) | +-----------------------------------+-----------------------------------+ | WM | clinical diagnosis characterized | | | by **monoclonal IgM serum | | | paraprotein** , bone marrow-based | | | disease, and **+/-- | | | hyperviscosity signs/symptoms** | +-----------------------------------+-----------------------------------+ | PATHOLOGIC DX | LYMPHOPLASMACYTIC LYMPHOMA | | | | | | - Lymphoplasmacytic lymphoma | | | may present with | | | lymphadenopathy without bone | | | marrow involvement | | | | | | - WM monoclonal immunoglobulin | | | serum or urine (usually IgM, | | | occasionally IgG or IgA) | +-----------------------------------+-----------------------------------+ | OTHER MANIFESTATION | Autoimmune hemolytic anemia, | | | autoimmune thrombocytopenia, | | | coagulation factor inhibitors, | | | and cryoglobulinemia may be | | | present | +-----------------------------------+-----------------------------------+ | SITES OF INVOLVEMENT | **[Lymph nodes, bone marrow, | | | spleen]** (usually | | | stage III or IV at presentation) | | | | | | Peripheral blood lymphocytosis | | | may be present | +-----------------------------------+-----------------------------------+ | CLINICAL COURSE | **[Similar to | | | CLL/SLL]** | | | | | | Indolent but **not curable** with | | | available therapy CLL IS ALSO NOT | | | CURABLE | +-----------------------------------+-----------------------------------+ | MAY TRANSFORM TO | **[May transform to : | | | ]** | | | | | | DIFFUSE LARGE B-CELL LYMPHOMA | | | (\~10%) -- POOR PROGNOSIS---SAME | | | WITH CLL | +-----------------------------------+-----------------------------------+ | MICROSCOPIC | Diffuse or parafollicular | | | proliferation of **[small | | | lymphocytes,]** | | | plasmacytoid lymphocytes | | | (**lymphocytic-like nuclei, | | | plasma cell-like cytoplasm**), | | | and plasma cells | | | | | | - SMALL LYMPHO | | | | | | - PLASMACYTOID LYMPHO | | | | | | - PLASMA CELL | +-----------------------------------+-----------------------------------+ | Abnormal immunoglobulin | - **Dutcher bodies** | | production manifested by | (intranuclear immunoglobulin | | | inclusion) | | | | | | - **Russell bodies** | | | (extracellular hyaline | | | immunoglobulin bodies) | | | | | | - Crystalline immunoglobulin | | | deposits (intracytoplasmic or | | | extracellular) | | | | | | - Amyloid deposits | | | | | | - Intercellular light chain | | | deposits, mimicking amyloid | | | | | | Sinuses spared (may contain | | | immunoglobulin | | | | | | Mast cells frequently seen | | | | | | Iron-containing epithelioid | | | histiocytes may be present | +-----------------------------------+-----------------------------------+ | **GENETICS** | **Ig heavy and light chain genes | | | are rearranged** | | | | | | **MYD88 L265P somatic mutation | | | :** present in \>90% of LPL; is | | | also occasionally present in | | | other small B-cell lymphomas | | | (**e.g., splenic MZL, CLL/SLL)** | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **SPLENIC MARGINAL ZONE | | | LYM