LYMPHOMAS

LYMPHOMAS ARE MALIGNANT NEOPLASMS

CHARACTERIZED BY THE PROLIFERATION OF CELLS
NATIVE TO THE LYMPHOID TISSUES THAT IS
LYMPHOCYTES, HISTIOCYTES AND THEIR PRECURSORS

TWO DISTINCT CLINICOPATHOLOGIC GROUPS ARE DISTINGUISHED:

• I. HODGKIN’S LYMPHOMA OR HODGKIN’S DISEASE (HD).
• II. NON-HODGKIN ‘S LYMPHOMAS (NHL).
 NON – HODGKIN’S LYMPHOMAS. MAIN FEATURES
• The usual presentation of non-hodgkin’s lymphomas (NHL) is a localized or generalized lymphadenopathy.
• However, in about one-third of cases it may be primary in other sites where lymphoid tissue is found, for example,
in the oropharyngeal region, bone marrow, gut and skin.
• All forms of lymphoma have the potential to spread from their origin in a single node or chain of nodes to the
other nodes, and eventually to disseminate to the spleen, liver and the bone marrow.
• There are some important principles of classification of NHL.
• As all tumors of the immune system, NHLs may originate in t-cells, b-cells, or histiocytes.
• The vast majority of NHL is of b-cells origin; the remainder is in large part of t-cells tumors.
• Tumors of histiocytes or macrophages are quite uncommon.
• Histologically, the lymphoma cells exhibit two different growth patterns: they are either clustered into identifiable
nodules (nodular lymphoma) or spread diffusely throughout the node (diffuse lymphoma). In general, nodular (or
follicular) architecture is associated with a significantly superior prognosis to that of diffuse pattern.
• It may be recalled that normal b cells form follicles within lymph nodes; malignant b cells tend to recapitulate this
behavior with nodule formation. Not surprisingly, therefore, nodular lymphomas are composed exclusively of B
cells.
There are some categories of NHL. Every of this category includes
some subtypes of leukemias with their own morphological features:

1. Low-grade.
2. Intermediate-grade.
3. High – grade.
 LOW-GRADE LYMPHOMAS

• THIS CATEGORY INCLUDES THREE TUMORS: SMALL LYMPHOCYTIC LYMPHOMA;

FOLLICULAR, PREDOMINANTLY SMALL CLEAVED CELL LYMPHOMA; AND
FOLLICULAR, MIXED (SMALL CLEAVED AND LARGE CELL) LYMPHOMA.
 SMALL LYMPHOCYTIC LYMPHOMA (SLL)
• THIS PATTERN MAKES UP APPROXIMATELY 4% OF ALL NHLS AND IS THE ONLY
LOW-GRADE LYMPHOMA THAT DOES NOT HAVE A FOLLICULAR ARCHITECTURE.
• MICROSCOPICALLY: SLL CONSISTS OF COMPACT, SMALL, APPARENTLY
UNSTIMULATED LYMPHOCYTES WITH DARK-STAINING ROUND NUCLEI, SCANTY
CYTOPLASM, AND LITTLE VARIATION IN SIZE. MITOTIC FIGURES ARE RARE, AND
THERE IS LITTLE OR NO CYTOLOGIC ATYPIA.
• INVOLVEMENT, OF BONE MARROW TO PRESENT IN ALMOST ALL CASES, AND IN
ABOUT 60% OF PATIENTS THE NEOPLASTIC CELLS SPILL OVER INTO BLOOD,
EVOKING A CHRONIC LYMPHOCYTIC LEUKEMIA-LIKE PICTURE.
 FOLLICULAR LYMPHOMAS

• THERE ARE TWO CYTOLOGIC SUBGROUPS OF LOW-GRADE FOLLICULAR LYMPHOMAS: FOLLICULAR SMALL CLEAVED
CELL AND FOLLICULAR MIXED CELL TYPE.
• THE NEOPLASTIC B CELLS TEND TO RECAPITULATE NORMAL LYMPHOID FOLLICLES, AND HENCE THEY RESEMBLE
THE CELLS SEEN WITHIN NORMAL GERMINAL CENTERS.
• SMALL-CLEAVED CELLS ARE SLIGHTLY LARGER THAN NORMAL LYMPHOCYTES, WITH SCANTY CYTOPLASM. THE
MOST DISTINCTIVE FEATURE THAT DIFFERENTIATES THE TUMOR CELLS FROM SMALL NORMAL LYMPHOCYTES IS
THEIR IRREGULAR “CLEAVED” NUCLEAR CONTOUR, CHARACTERIZED BY PROMINENT CLEFTS, INDENTATIONS, AND
LINEAR ENFOLDING.
• THE NUCLEAR CHROMATIN IS COARSE AND CONDENSED, AND NUCLEOLI ARE INDISTINCT. MITOSES ARE
INFREQUENT.
• FOLLICULAR, MIXED LYMPHOMAS CONSTITUTE A SMALL PROPORTION OF ALL FOLLICULAR CENTER CELL TUMORS.
 INTERMEDIATE-GRADE LYMPHOMAS

THERE ARE FOUR TUMORS IN THIS CATEGORY - ONE WITH A

FOLLICULAR ARCHITECTURE AND THE OTHER THREE WITH
A DIFFUSE PATTERN. THE DIFFUSE INTERMEDIATE-GRADE
LYMPHOMAS ARE DISTINGUISHED ON THE BASIS OF THEIR
CELLULAR COMPOSITION.
 HIGH-GRADE LYMPHOMAS
THERE ARE 3 TYPES OF LYMPHOMAS IN THIS CATEGORY:
• Large cell immunoblastic lymphomas;
• Lymphobtastic lymphoma, a tumor that occurs in adolescents and is associated
with a characteristic clinical presentation;
• Small noncleaved lymphomas, which include Burkitt's lymphoma and related b-
cell neoplasms.
 AFRICAN LYMPHOMA OR BURKITT'S
SOLUTION DESERVE SPECIAL ATTENTION
AMONG LYMPHOSARCOMAS
THE TUMOR CONSISTS OF SMALL LYMPHOCYTE-LIKE CELLS, AMONG
WHICH THERE ARE LARGE MACROPHAGES WITH LIGHT CYTOPLASM,
WHICH GIVES THE IMPRESSION OF A PECULIAR APPEARANCE OF THE
"STARRY SKY«. THE OCCURRENCE OF AFRICAN LYMPHOMA IS
ASSOCIATED WITH A HERPES-LIKE VIRUS THAT WAS FOUND IN THE LYMPH
NODES OF PATIENTS. VIRUS-LIKE INCLUSIONS ARE FOUND IN TUMOR
LYMPHOBLASTS.
BURKITT'S LYMPHOMA
 MYCOSIS FUNGOIDES
• MULTIPLE TUMOR NODES CONSIST OF
PROLIFERATING LARGE CELLS WITH A SIGNIFICANT
NUMBER OF MITOSES.
• PLASMA CELLS, HISTIOCYTES, EOSINOPHILS, AND
FIBROBLASTS ARE ALSO FOUND IN THE TUMOR
INFILTRATE. TUMOR NODES ARE SOFT, PROTRUDE
ABOVE THE SURFACE OF THE SKIN, RESEMBLE THE
SHAPE OF A MUSHROOM, AND ARE EASILY COVERED
WITH ULCERS.
• SUCH NODES ARE FOUND NOT ONLY IN THE SKIN, BUT
ALSO IN THE MUCOUS MEMBRANES, MUSCLES, AND
INTERNAL ORGANS.
• PREVIOUSLY, THE DEVELOPMENT OF THE TUMOR WAS
ASSOCIATED WITH THE INVASION OF MYCELIUM OF
MUSHROOMS, HENCE THE ERRONEOUS NAME OF THE
DISEASE.
 SÉZARY'S DISEASE
 T-LYMPHOCYTIC LYMPHOMA OF THE SKIN
WITH LEUKEMIA; REFERS TO SKIN
LYMPHOMAS.

 DAMAGE TO THE BONE MARROW, THE

APPEARANCE OF TUMOR CELLS IN THE
BLOOD, WHICH IS OBSERVED IN SÉZARY'S
DISEASE, SERVED AS THE BASIS FOR ITS
ATTRIBUTION IN SOME CASES TO CHRONIC
LYMPHOCYTIC LEUKEMIA.

 LYMPHOCYTIC INFILTRATION OF THE SKIN

ENDS WITH THE FORMATION OF TUMOR
NODES ON THE FACE, BACK, AND LEGS. IN
TUMOR INFILTRATES OF THE SKIN, BONE
MARROW, AND BLOOD, ATYPICAL
MONONUCLEAR CELLS WITH SICKLE-SHAPED
NUCLEI ARE FOUND - CELLS OF SEZARY.

 SOMETIMES SLIGHT TUMOR INFILTRATION OF

LYMPH NODES, SPLEEN, KIDNEYS, AND LIVER
IS POSSIBLE.
 HODGKIN’S DISEASE OR LYMPHOGRANULOMATOSIS

• HODGKIN’S DISEASE (HD) IS A DISORDER INVOLVING PRIMARILY THE LYMPHOID

TISSUE. IT ARISES ALMOST INVARIABLY IN A SINGLE NODE OR CHAIN OF NODES AND
SPREAD CHARACTERISTICALLY TO THE ANATOMICALLY CONTIGUOUS NODES.
• IT’S SEPARATED FROM NHL FOR SEVERAL REASONS.

1. First it is characterized morphologically by the presence of distinctive neoplastic giant

cells called reed-sternberg’s cells, admixed with a variable inflammatory infiltrate.
2. Second, it is often associated with somewhat distinctive clinical features, including
systemic manifestations such as fever. Finally, the target cell of neoplastic transformation
has yet to be identified with certainty.
 MORPHOLOGY

• A DISTINCTIVE TUMOR GIANT CELLS KNOWN AS THE REED-STERNBERG CELL (RS) IS CONSIDERED TO BE THE
ESSENTIAL NEOPLASTIC ELEMENT IN ALL FORMS OF HD, AND THEIR IDENTIFICATION IS ESSENTIAL FOR THE
HISTOLOGIC DIAGNOSIS.
• CLASSICALLY IT IS A LARGE CELL, MOST OFTEN BENUCLEATE OR BELOBED, WITH TWO HALVES OFTEN
APPEARING AS MIRROR IMAGES OF EACH OTHER.
• AT OTHER TIMES THERE ARE MULTIPLE NUCLEI, OR THE SINGLE NUCLEUS IS MULTILOBADE AND POLYPOID.
THE NUCLEUS IS ENCLOSED WITHIN THE ABUNDANT AMPHOPHILIC CYTOPLASM. PROMINENT WITHIN THE
NUCLEI ARE LARGE, INCLUSION-LIKE, “OWL-EYED” NUCLEOLI GENERALLY SURROUNDED BY A CLEAR HALO.
• VARIANTS OF RS CELLS INCLUDE UNINUCLEATED CELLS WITH PROMINENT NUCLEOLI, AND LACUNAR CELLS.
THE LACUNAR CELL IS LARGE WITH SINGLE HYPERLOBATED NUCLEUS CONTAINING MULTIPLE SMALL
NUCLEOLI AND AN ABUNDANT, PALE-STAINING CYTOPLASM.
• THE ORIGIN OF HD IS UNKNOWN. THE ACCUMULATED PHENOTYPIC AND MOLECULAR STUDIES SUGGEST
THAT HD IS HETEROGENEOUS WITH RESPECT TO BOTH THE CELL TYPE INVOLVED AND THE ETIOLOGIC
AGENTS. THE NODULAR FORM OF LYMPHOCYTE PREDOMINANCE TYPE IS CLEARLY B-CELL NEOPLASM;
OTHERS MAY ARISE FROM B-CELLS OR T-CELLS.
CELL TYPES IN LYMPHOGRANULOMATOSIS
 THE DEVELOPMENT OF
LYMPHOGRANULOMATOSIS GOES THROUGH
FOUR STAGES
I/ LOCAL STAGE (FIRST): ONE GROUP OF LYMPH NODES (I) OR ONE EXTRALYMPHATIC ORGAN (IE) IS
AFFECTED.
II/ REGIONAL STAGE (SECOND): 2 OR MORE GROUPS OF LYMPH NODES ARE AFFECTED, WHICH ARE LOCATED
ON ONE SIDE OF THE DIAPHRAGM (II) OR ONE EXTRALYMPHATIC ORGAN AND ITS REGIONAL LYMPH NODES
(IIE).
III/ GENERALIZED STAGE (THIRD): AFFECTED LYMPH NODES THAT ARE LOCATED ON BOTH SIDES OF THE
DIAPHRAGM (III). ADDITIONALLY, ONE EXTRALYMPHATIC ORGAN (IIIE), THE SPLEEN (IIIS), OR BOTH (IIIE +
IIIS) MAY BE AFFECTED.
IV/ DISSEMINATED STAGE (FOURTH): ONE OR MORE EXTRALYMPHATIC ORGANS (LUNGS, PLEURA, BONE
MARROW, LIVER, KIDNEYS, GASTROINTESTINAL TRACT AND OTHERS) WITH OR WITHOUT SIMULTANEOUS
INVOLVEMENT OF THE LYMPH NODES.
 There are some subtypes of HD according to the
Rye classification:

1.Lymphocytic predominance HD. Characterized by a diffuse or vaguely nodular infiltrate of mature lymphocytes
admixed with variable numbers of benign histiocytes. Scatterd among these cells are the distinctive RS cells. Most
patients are under 35 years of age and have an excellent prognosis.
2.Mixed cellularity HD is a common form of HD. Typical RS cells are plentiful. Usually there is heterogenous cellular
infiltrate, which includes eosinophils, plasma cells, and histiocytes.
3.Lymphocyte depletion HD. This uncommon pattern is characterized by a paucity of lymphocytes, RS and their
pleomorphic variants, and also massive foci of necrosis and sclerosis. The reticular variant is cellular and contains highly
anaplastic, atypical RS cells. Patients are usually older and have a very poor prognosis.
4.Nodular sclerosis HD. In this variant, fine or dense collagenous bands subdivide the lymphoid tissue into
circumscribed nodules. There are varying proportions of lacunar cells and lymphocytes; classic RS cells are rare. Most
patients are young with an excellent prognosis