DISEASES OF LYMPH NODES

Dr. Jusuf Fantoni, SpPA., MSc.Path.

Learning Objectives :

1. The students should have the ability to understand normal function of lymph nodes. 2. The students would have the capability to understand the pathology & disease of lymph nodes.

WHEN LYMPH NODES CHALLENGED BY FOREIGN AGENTS OR MICROBIOLOGIC AGENTS , THEY UNDERGO REACTIVE CHANGES.

ACUTE LYMPHADENITIS
-

INFECTIONS

MOST SEEN IN THE CERVICAL REGION DUE TO

OF THE TEETH / TONSILS & THE AXILLA OR INGUINAL

REGIONS SECONDARY TO INFECTIONS IN THE EXTREMITIES

MORPHOLOGY

NODES BECOME SWOLLEN.

HISTOLOGICAL : LYMPHOID FOLLICLES PROMINENT WITH GEREMINAL CENTERS CONTAINING DEBRIS CONTAINING MACROPHAGES SOMETIMES NEUTROPHILS SEEN
CHRONIC NONSPECIFIC LYMPAHDENITIS

PRODUCE DIFFERENT MORPHOLOGIC ALTERATIONS

MORPHOLOGY FOLLICULAR HYPERPLASIA.

THIS IS CAUSED BY HUMORAL IMMUNE RESPONSES B-CELL RICH GERMINAL CENTERS ENLARGE, SURROUND ED BY THE MANTLE ZONE. IN THE CENTER, A DARK ZONE OF BLAST-LIKE B CELLS TINGIBLE MBODY MACROPHAGES

PLASMA CELLS, MACROPHAGES, NEUTROPHILS MAY BE FOUND IN THE PARAFOLLICULAR REGIONS HYPERPLASIA OF THE MONONUCLEAR PHAGOCYTES LINING THE LYMPHATIC SINUSES MAY BE CONFUSED WITH FOLLICULAR LYMPHOMA. SOMETIMES ACCOMPANIED BY MARGINAL ZONE BCELL

HYPERPLASIA ( THESE CELLS HAVE MODERATELY

ABUNDANT PALE CYTOPLASM & FOLDED / RENIFORM NUCLEI RESEMBLING MONOCYTES ( CALLED MONOCYTOID B CELLS ) ; THEY

APPEAR
TO BE MEMORY B CELLS.

PARACORTICAL LYMPHOID HYERPLASIA REACTIVE CHANGES WITHIN THE T-CELL REGIONS THAT ENCROACH ON, SOMETIMES EFFECE THE B-CELL FOLLICLES. WITHIN INTERFOLLICULAR REGIONS, IMMUNOBLASTS ARE SEEN, HYPERTROPHY OF SINUSOIDAL ENDOTHE-

LIAL CELLS
SINUS HISTIOCYTOSIS = DISTENTION & PROMINENCE OF THE SINUSOIDS. THOUGH NONSPECIFIC, THIS HYPERPLASIA MAY BE PROMINENT IN LYMPH NODES DARINING CANCERS. THE LINING ENDOTHELIAL CELLS MARKEDLY HYPER-

TROPHIED, MACROPHAGES GREATLY INCREASED,

RESULTING IN EXPANSION AND DISTENTION OF SINUSES.

LYMPHOID NEOPLASMS CONFUSING ASPECTS : (DIFFERENCE BETWEEN LEUKEMIA &

* LEUKEMIA = LYMPHOID NEOPLASMS PRESENTING LYMPHOMA )

WITH WIDESPREAD INVOLVEMENT OF THE BONE MARROW ACCOMPANIED BY THE PRESENCE OF LARGE NUMBERS OF TUMOR CELLS IN THE PERIPHERAL BLOOD * LYMPHOMA = PROLIFERATION ARISING AS DISCRETE TISSUE MASSES. TWO BIG GROUPS OF LYMPHOID NEOPLASMS ARE : HODGKIN LYMPHOMA & NON HODGKIN LYMPHOMA

TWO THIRDS OF NHL & VIRTUALLY ALL CASES OF HODGKIN LYMPHOMA PRESENT WITH NONTENDER NODAL ENLARGEMENT ( LOCALIZED OR GENERALIZED ). REMAINING ONE-THIRD OF NHL ARISE AT EXTRANODAL SITES ( E.G. SKIN, STOMACH,OR BRAIN ).
HISTORICALLY, SO MUCH CONTROVERSY & CONFUSION EVOKED IN THE CLASSIFICATION OF NHL & RELATED LYMPHOID NEOPLASMS. IN 1994, CAME THE REVISED EUROPEANAMERICAN CLASSIFICATION OF LYMPHOID NEOPLASMS ( REAL ). THIS CLASSIFICATION INCORPORATED IMMUNOPHENOTYPE, GENETIC ABERRATIONS WITH MORPHOLOGIC AND CLINICAL FEATURES.

THE WHO CLASSIFICATION OF THE LYMPHOID NEOPLASMS I. PRECURSOR B-CELL NEOPLASMS PRECURSOR LYMPHOBLASTIC LEUKEMIA / LYMPHOMA

II.

PERIPHERAL B-CELL NEOPLASMS CHRONIC LYMPHOCYTIC LEUKEMIA / SMALL LYMPHOCYTIC LYMPHOMA B-CELL PROLYMPHOCYTIC LEUKEMIA LYMPHOPLASMACYTIC LYMPHOMA SPLENIC AND NODAL MARGINAL ZONE LYMPHOMA EXTRANODAL MARGINAL ZONE LYMPHOMA MANTLE CELL LYMPHOMA FOLLICULAR LYMPHOMA MARGINAL ZONE LYMPHOMA HAIRY CELL LEUKEMIA PLASMACYTOMA / PLASMA CELL MYELOMA DIFFUSE LARGE B-CELL LYMPHOMA BURKITT LYMPHOMA

III. PRECURSOR T-CELL NEOPLASMS PRECURSOR T LYMPHOBLASTIC LEUKEMIA / LYMPHOMA

IV. PERIPHERAL T-CELL AND NK-CELL NEOPLASMS T-CELL PROLYMPHOCYTIC LEUKEMIA LARGE GRANULAR LYMPHOCYTIC LEUKEMIA MYCOSIS FUNGOIDES / SEZARY SYNDROME PERIPHERAL T-CELL LYMPHOMA, UNSPECIFIED ANAPLASTIC LARGE CELL LYMPHOMA ANGIOIMMUNOBLASTIC T-CELL LYMPHOMA ENTEROPATHY-ASSOCIATED T-CELL LYMPHOMA PANNICULITS-LIKE T-CELL LYMPHOMA HEPATOSPLENIC T-CELL LYMPHOMA ADULT T-CELL LEUKEMIA / LYMPHOMA NK / T-CELL LYMPHOMA, NASAL TYPE NK-CELL LEUKEMIA

V. HODGKIN LYMPHOMA CLASSICAL SUBTYPES - NODULAR SCLEROSIS - MIXED CELLULARITY - LYMPHOCYTE-RICH - LYMPHOCYTE DEPLETION LYMPHOCYTE PREDOMINANCE

CHRONIC LYMPHOCYTIC LEUKEMIA ( CLL ) / SMALL CELL LYMPHOCYTIC LYMPHOMA ( SLL ) INDISTINGUISHABLE MORPHOLOGICALLY, PHENOTYPICALLY, & GENOTYPICALLY. DIFFER ONLY IN THE DEGREE OF PERIPHERAL BLOOD LYMPHOCYTOSIS ( CLL : MORE THAN 4000 PER MM3 ). MORE IN WESTERN WORLD MORPHOLOGY
LYMPH NODE ARCHITECTURE IS DIFFUSELY EFFACED PREDOMONANT BY SMALL LYMPHOCYTES CONTAINING ROUND TO SLIGHTLY IRRGULAR NUCLEI WITH CONDENSED CHROMATIN AND SCANT CYTOPLASM. TUMNOR CELLS USUALLY INFILTRATE THE SPLENIC WHITE AND RED PULP AND THE HEPATIC PORTAL.

IMMUNOPHENOTYPE CLL/SLL TUMOR CELLS EXPRESS THE PAN B-CELL MARKERS CD19 AND CD20.
CHROMOSOMAL ABNORMALITIES & MOLECULAR GENETICS - CHROMOSOMAL TRANSLOCATION RARE - DELETIONS OF 13q12-14, TRISOMY 12 q CLINICAL FEATURES - age over 50 - CLL : LEUKOCYTE COUNT EXCESS OF 200,000 PER mm3 - hypogammaglobulinemia - MEDIAN SURVIVAL IS 4 6 YEARS - TRANSFORM TO LARGE B-CELL LYMPHOMA ( RICHTER SYNDROME )

FOLLICULAR LYMPHOMA - MOST COMMON NHL IN USA - MALE = FEMALE - NEOPLASTIC CELLS RESEMBLE NORMAL GERMINAL CENTER B CELLS.
MORPHOLOGY - PREDOMINANTLY NODULAR or NODULAR & DIFFUSE GROWTH PATTERN - TWO PRINCIPAL CELL TYPES IN VARYING PROPORTIONS : (1) SMALL CELLS WITH IRRGULAR OR CLEAVED NUCLEAR CONTOURS & SCANT CYTOPLASM ( = CENTROCYTES / SMALL CLEAVED CELLS ); (2) LARGER CELLS WITH OPEN NUCLEAR CHROMATIN, SEVERAL NUCLEOLI, & MODEST AMOUNT CYTOPLASM ( = CENTROBLASTS ).

- IN MOST CASES, SMALL CLEAVED CELLS MAKE UP THE MAJORITY OF THE CELLS - BONE MARROW INVOLVEMENT 85% --- PARATRABECULAR LYMPHOID AGGREGATES - SPLENIC WHITE PULP & HEPATIC PORTAL TRACTS FREUQENTLY INVOVED. IMMUNOPHENOTYPE - EXPRESS CD19, CD20, CD10 & SURFACE Ig - CD5 IS NOT EXPRESSED ( UNLIKE CLL/SLL ) - EXPRESS BCL2 MORE THAN 90% CASES - ALMOST ALL EXPRESS BCL6 ( = A TRANSCRIPTIONAL
REPRESSOR THAT REGULATES GERMINAL CENTER B CELL DEVELOPMENT ).

CYTOGENETICS & MOLECULAR GENETICS - HALLMARK : ( 14:18 ) TRANSLOCATION (90% CASES) ---- OVEREXPRESSION OF BCL2 PROTEIN ( = AN
ANTAGONIST OF APOPTOTIC CELL DEATH.

CLINICAL FEATURES - PAINLESS , GENERALIZED LYMPHADENOPATHY - ALTHOUGH INCURABLE, IT FOLLOWS AN INDOLENT COURSE - MEDIAN SURVIVAL IS 7 9 YEARS & IS NOT IMPROVED BY AGGRESSIVE THERAPY - 30% - 50% TRANSFORM TO DIFFUSE LARGE B-CELL LYMPHOMA

BURKITT LYMPHOMA 1. AFRICAN ( ENDEMIC ) BURKITT LYMPHOMA 2. SPORADIC (NONENDEMIC) BURKITT LYMPHOMA 3. A SUBSET OF AGGRESSIVE LYMPHOMAS IN HIV PATIENT ALL HISTOLOGICALLY IDENTICAL, BUT SOME CLINICAL, GENOTYPIC AND VIROLOGIC DIFFERENT.
MORPHOLOGY INVOLVED TISSUES ARE EFFACED BY A DIFFUSE INFILTRATE OF INTERMEDIATE-SIZED LYMPHOID CELLS, WITH OVAL OR ROUND NUCLEI, COARSE CHROMATIN, SEVERAL NUCLEOLI, & A MODERATE AMOUNT OF FAINTLY BASOPHILIC OR AMPHOPHILIC CYTOPLASM. A HIGH MITOTIC INDEX IS TYPICALM AS IS APOPTOTIC TUMOR CELL DEATH, ACCOUNTING FOR THE PRESENCE OF NUMEROUS TISSUE MACROPHAGES WITH INGESTED

DEBRIS

THESE BENIGN MACROPHAGES, DIFFUSELY DISTRIBUTED AMONG THE TUMOR CELLS & HAVE ABUNDANT CLEAR CYTOPLASM, CREATING A CHARACTERISTIC STARRY SKY PATTERN
IMMUNOPHENOTYPE = MATURE B CELLS EXPRESSING SURFACE IgM, MONO TYPIC KAPPA OR LAMBDA LIGHT CHAIN, CD19, CD20 AND CD10, AND BCL6, A PHENOTYPE CLOSELY RESEMBLES RAPIDLY DIVIDING B CELLS WITHIN THE DARK ZONES OF GERMINAL CENTERS. CYTOGENETIC AND MOLECULAR GENETIC FEATURES - TRANSLOCATIONS OF THE c-MYC GENE ON CHROMOSOME 8, THE PARTNER IS USUALLY THE IgH LOCUS ( t (8; 14)) - EBV DNA IS IDENTICAL IN ALL TUMOR CELLS, INDICATING THAT INFECTION PRECEDS CELLULAR TRANSFORMATION

CLINICAL FEATURES
- BOTH ENDEMIC & SPORADIC CASES FOUND LARGELY IN CHILDREN OR YOUNG ADULTS.

- MOST MANIFEST AT EXTRANODAL SITES

- ENDEMIC B L OFTEN INVOLVES MANDIBLE & UNUSUAL PREDILECTION FOR INVOLVEMENT OF ABDOMINAL VISCERA, PARTICULARLY KIDNEYS, OVARIES, & ADRENAL GLANDS - SPORADIC B L MOST OFTEN AS AN ABDOMINAL MASS INVOLVING THE ILEOCAECUM AND PERITONEUM. - VERY AGGRESSIVE BUT RESPONDS WELL TO SHORT-TERM, HIGH DOSE CHEMOTHERAPY

ANAPLASTIC LARGE CELL LYMPHOMA ( ALCL ) - UNIQUE - STRONG ASSOCIATTION WITH REARRANGEMENTS INVOLVING THE ALK GENE ON CHROMOSOME 2p23 - COMPRISES LARGE ANAPLASTIC CELLS, SOME OF WHICH TYPICALLY CONTAIN HORSESHOE-SHAPED NUCLEI AND VOLUMINOUS CYTOPLASM ( = HALLMARK CELLS ). - THE TUMOR CELLS SOMETIMES CLUSTER ABOUT VENULE & INFILTRATE LYMPHOID SINUSES, MIMICK ING THE APPEARANCE OF METASTATIC CARCINOMA.

- THOSE WITH ALK REARRANGEMENTS TEND TO

OCCUR IN CHILDREN OR YOUNG ADULTS, FREQUENTLY INVOLVE SOFT TISSUES, CARRY A VERY GOOD PROGNOSIS

HODGKIN LYMPHOMA
ARISES IN A SINGLE NODE OR CHAIN OF NODES, SPREAD FIRST TO THE ANATOMICALLY CONTIGUOUS NODES ( NHLS FREQUENTLY
OCCUR AT EXTRANODAL SITES & SPREAD IN AN UNPREDICTABLE FASHION ).

CHARACTERIZED BY THE PRESENCE OF NEOPLASTIC GIANT CELLS CALLED REED-STERNBERG CELLS THAT INDUCE THE ACCUKUMATION OF REACTIVE LYMPHOCYTES, HISTIOCYTES, & GRANULOCYTES. R-S CELLS ARE DERIVED FROM GERMINAL CENTER OR POST GERMINAL CENTER B-CELLS, INDICATING HLs ARE UNUSUAL TUMORS OF B-CELL

ORIGIN.
IT IS ONE OF THE MOST COMMON FORMS OF MALIGNANCY IN YOUNG ADULTS ( AVERAGE 32 YEARS). NOW CURABLE IN MOST CASES.

CLASSIFICATION. ( WHO ) NODULAR LYMPHOCYTE PREDOMINCE CLASSICAL : - NODULAR SCLEROSIS - MIXED CELLULARITY - LYMPHOCYTE DEPLETION - LYMPHOCYTE RICH

IN NODULAR LYMPHOCYTE PREDOMINANCE HL, THE R-S CELLS HAVE A CHARACTERISITC B-CELL IMMUNPHENOTYPE, DISTINCT FROM THAT OF THE CLASSICAL HL SYBTYPES ( WHICH ALL THE FOUR HAVE
A SIMILAR IMMUNPHENOTYPE ) MORPHOLOGY IDENTIFICATION OF R-S CELLS & THEIR VARIENTS IS ESSENTIAL FOR THE HISTOLOGIC DIAGNOSIS

R-S CELLS ARE LARGE & HAVE MULTIPLE NUCLEI OR A SINGLE

NUCLEUS WITH MULTIPLE NUCLEAR LOBES, EACH WITH A LARGE INCLUSION-LIKE NUCLEOLUS ABOUT THE SIZE OF A SMALL LYMPHOCYTE. THE CYTOPLASM IS ABUNDANT. SEVERAL

VARIANTS ARE RECOGNIZED : MONONUCLEAR VARIANTS

CONTAIN ONLY A SINGLE ROUND OR OBLONG NUCLEUS WITH A LARGE NUCLEOLUS; LACUNAR CELLS, SEEN PREDOMINANTLYIN THE NODULAR SCLEROSIS SUBTYPE, HAVE MORE DELICATE

FOLDED OR

MULTILOBATE NUCLEI SURROUNDED BY

ABUNDANT PALE CYTOPLASM THAT IS OFTEN DISRUPTED DURING THE CUTTING OF SECTIONS, LEAVING THE NUCLEUS SITTING IN AN EMPTY HOLE ( LACUNE ). IN CLASSICAL FORMS, R-S CELLS UNDERGO PECULIAT CELL DEATH, BECOME PYKNOTIC ,KNOWN AS MUMMIFICATION .

LYMPHO-HISTIOCYTIC VARIANTS ( L&H CELLS ) WITH POLYPOID NUCLEI RESEMBLING POPCORN KERNELS, INCONSPICUOUS NUCLEOLI, & MODERATELY ABUNDANT CYTOPLASM, ARE SPECIFIC TO THE LYMPHOCYTE PREDOMINANCE SUBTYPE. DIAGNOSIS OF HL IS COMPLICATED BY THE PRESENCE OF CELL SIMILAR OR IDENTICAL TO R-S CELLS IN OTHER CONDITIONS, SUCH AS INFECTIOUS MONONUCLEOSIS, SOLIS TISSUE CANCER & NHL. THUS, ALTHOUGH R-S CELLS ARE REQUISITE FOR THE DIAGNOSIS, THEY MUST BE PRESENT IN AN APPROPRIATE BACKGROUND OF NON-NEOPLASTIC INFLAMMATORY CELLS ( LYMPHOCYTES, PLASMA CELLS, EOSINOPHILS ). THE SPREAD OF HL IS PREDICTABLE : NODAL FIRST, THEN SPLE NIC DISEASE, HEPATIC DISEASE AND FINALLY MARROW INVOLVEMENT AND EXTRANODAL DISEASE.

FOR THIS REASON, THE STAGING OF HL IS NOT ONLY PREDICTIVE OF PROGNOSIS BUT ALSO GUIDES THE CHOICE OF THERAPY. SYMPTOMS : FEVER,NIGHT SWEATS & WEIGHT LOSS ARE CHARACTERICTIC OF HL ( ALSO BE SEEN IN OTHER LYMPHOID NEOPLASMS ).

HL, NODULAR SCLEROSIS TYPE. = THE MOST COMMON FORM OF HL ( 65% - 70% ). CHARACTERIZED BY THE PRESENCE OF : 1. VARIANT OF R-S CELL, THE LACUNAR CELL 2. COLLAGEN BANDS THAT DIVIDE THE LYMPHOID TISSUE INTO CIRCUMSCRIBED NODULES. THE FIBROSIS CAN BE SCANT OR ABUNDANT.

THE NEOPLASTIC CELLS ARE FOUND IN A POLYMORPHOUS BACKGROUND OF SMALL T LYMPHOCYTES, EOSINOPHILS, PLASMA CELLS AND MACROPHAGES. THE TUMOR CELLS HAVE A CHARACTERISTIC IMMUNOPHENOTYPE: POSITIVE FOR CD15 & CD30 AND NEGATIVE FOR CD45 AND B-CELL AND T-CELL MARKERS OCCURS EQUAL IN MALES AND FEMALES IT HAS A PROPENSITY TO INVOLVE THE LOWER CERVICAL, SUPRACLAVICULAR AND MEDIATINAL LYMPH NODES. RARELY ASSOCIATED WITH EBV. PROGNOSIS IS EXCELLENT

HL, MIXED CELLULARITY TYPE - 20% - 25% - DIFFUSE EFFACEMENT BY A HETEROGENOUS CELLULAR INFILTRATE, INCLUDES SMALL ;YMPHOCYTES, EOSINOPHILS,PLASMA CELLS & BENIGN MACROPHAGES, ADMIXED WITH NEOPLASTIC CELLS. - DIAGNOSTIC R-S CELLS & MONONUCLEAR VARIANTS ARE USUALLY PLENTIFUL - IMMUNOPHENOTYPE IS IDENTICAL TO NODULAR SCLEROSIS TYPE. - SMALLLYMPHOCYTES IN THE BACKGROUND ARE PREDOMIANTLY T-CELLS, EARLY NODAL DISEASE PREFERENTIALLY INVOLVES PARACORTICAL TCELL ZONE

- MORE COMMON IN MALES - STRONGLY ASSOCIATED WITH EBV, AS THE R-S CELLS CONTAIN EBV GENOMES IN AT LEAST 70% CASES. - MORE ASSOCIATED WITH OLDER AGE , SYSTEMIC SYMPTOMS SUCH AS NIGHT SWEATS AND WEIGHT LOSS, AND ADVANCED TUMOR STAGE. - PROGNOSIS IS VERY GOOD

HL, LYMPHOCYTE-RICH TYPE - UNCOMMON - REACTIVE LYMPHOCYTES MAKE UP THE VAST MAJORITY OF THE INFILTRATE.

- IN MOST CASES, LYMPH NODES ARE DIFFUSELY EFFACED, BUT VAGUE NODULARITY DUE TO THE PRESENCE OF RESIDUAL B-CELL FOLLICLES SOMETIMES SEEN. - THIS ENTITY IS DISTINGUISHED FROM THE LYMPHOCYTE PREDOMINANCE TYPE BY THE PRESENCE OF FREQUENT MONONUCLEAR AND DIAGNOSTIC R-S CELLS WITH THE CHARACTERISTIC CD45-, CD20-. CD15+, CD30+. - ASSOCIATED WITH EBV ( 45% CASES ) - VERY GOOD TO EXCELLENT PROGNOSIS

HL, LYMPHOCYTE DEPLETION TYPE

- LEAST COMMON ( LESS THAN 5% ) - PAUCITY OF LYMPHOCYTES - ABUNDANCE OF R-S CELLS OR THEIR PLEOMORPHIC VARIANTS - PHENOTYPE OF TUMOR CELLS IDENTICAL TO NODULAR SCLEROSIS & MIXED CELLULARITY TYPES PHENOTYPING IS CRITICAL FOR THE D/, SINCE MOST TUMORS SUSPECTED OF BEING LYMPHOCYTE DEPLETION HL ACTUALLY PROVE TO BE LARGE-CELL NON HODGKIN LYMPHOMA. - PREDOMINANTLY IN OLDER PATIENTS, HIV+ , PATIENTS IN NONINDUSTRIALIZED COUNTRIES - EBV ASSOCIATED - ADVANCED STAGE & SYSTEMIC SYMPTOMS (+) - OVERALL OUTCOME LESS FAVORABLE

HL, LYMPHOCYTIC PREDOMINANCE TYPE

- UNCOMMON ( 5% OF CASES ) - NODAL EFFACEMENT BY A NODULAR INFILTRATE OF SMALL LYMPHOCYTES ADMIXED WITH VARIABLE NUMBERS OF BENIGN HISTIOCYTES - TYPICAL R-S CELLS, EXTREMELY DIFFICULT TO FIND - MORE COMMON ARE SO-CALLED LYMPHOHISTIOCYTIC (L & H ) VARIANTS THAT HAVE A DELICATE, MULTILOBED NUCLEUS RESEMBLING A POPCORN KERNEL ( POPCORN CELL ). - OTHER CELLS SUCH AS EOSINOPHILS, NEUTROPHILS, & PLASMA CELLS ARE SCANTY / ABSENT - LITTLE EVIDENCE OF NECROSIS OR FIBROSIS

MULTIPLE FEATURES OF L&H R-S VARIANTS POINT TO AN ORIGIN FROM GERMINAL CENTER B CELLS. IN CONTRAST TO OTHER FORMS OF HL, L&H VARIANTS EXPRESS B-CELL MARKERS ( e.g.CD20 ) & THE GERMINAL CENTER-SPECIFIC TRANSCRIPTION FACTOR BCL6.
THE NODULAR PATTERN IS DUE TO THE PRESENCE OF EXPANDED B-CELL FOLLICLES, WHICH ARE POPULATED NOT ONLY WITH L&H VARIANTS, BUT ALSO WITH NUMEROUS REACTIVE B CELLS. L&H VARIANTS WITHIN INDIVIDUAL TUMORS HAVE IDENTICAL IgH GENE REARRANGEMENTS

3% - 5% TRANSFORM TO DIFFUSE LARGE B-CELL LYMPHOMA. EBV IS NOT ASSOCIATED MAJORITY ARE MALES, YOUNGER THAN 35 YEARS OF A AGE, WITH CERVICAL / AXILLARY LYMPHADENOPATHY MORE LIKELY TO RECUR, PROGNOSIS IS EXCELLENT