rct.pptx

Round cell tumors
Dr Purva Pihulkar

Contents
• Non-Hodgkin’s Lymphomas
 Etiology
 Classification
 Clinical features
 Oral manifestations
 Staging
 Histologic features
 Types
• Diffuse large B cell lymphoma
• B-chronic lymphocytic leukemia/small lymphocytic lymphoma
• Follicular lymphoma
• Mantle cell lymphoma
• Lymphoplasmacytic lymphoma
• Marginal zone lymphoma
• Extranodular NK/T-cell Lymphoma
• Burkitt’s lymphoma

Non-Hodgkin’s Lymphomas
• The non-Hodgkin lymphomas include a diverse and complex group of
malignancies of lymphoreticular histogenesis and differentiation.
• In most instances, they initially arise within lymph nodes and tend to
grow as solid masses.
• The non-Hodgkin lymphomas most commonly originate from cells of
the B-lymphocyte series, with an estimated 85% of European and
American lymphoid neoplasms having this derivation.
• Tumors with a T-lymphocyte derivation are less common, whereas true
histiocyte-derived lymphomas are even rarer.

Etiology
• Genetic abnormalities like nonrandom chromosomal and molecular rearrangements play an
important role in the pathogenesis of many lymphomas and correlate with histology and
immunophenotype.
• Most lymphomas do not have a familial pattern; however, coexistence of multiple breast cancers,
ovarian cancer, sarcomas, and lymphomas in a family may suggest an inherited abnormality in
tumor suppressor genes.
• Environmental factors also seem to play a role in the development of NHL. Certain chemicals have
been linked to the development of NHL include a variety of pesticides and herbicides (e.g.
organophosphates, chlorophenols), solvents and organic chemicals (e.g. benzene, carbon
tetrachloride), and wood preservatives.

• Thus certain workers like pesticide applicators, workers in the
petroleum, rubber, plastics, and synthetic industries have a slightly
increased risk of NHL.
• Patients who receive cancer chemotherapy and/or radiation therapy are
at increased risk of developing NHL.
• Several viruses have been implicated in the pathogenesis of NHL,
including the Epstein-Barr virus in Burkitt’s lymphoma (especially in
endemic areas of Africa), sinonasal lymphoma in Asia and South
America, and lymphomas in immunocompromised patients; HTLV-1
Human T-lymphotropic Virus in adult T-cell lymphoma/leukemia; and
human herpesvirus 8 (HHV 8) in body cavity-based lymphomas in
patients with HIV infection.

• Immunodeficiency states that seem to predispose to NHL include
congenital immunodeficiency states (e.g. ataxia telangiectasia,
Wiskott–Aldrich syndrome, common variable
hypogammaglobulinemia, severe combined immunodeficiency (SCID)
as well as acquired immunodeficiency states (e.g. HIV infection,
iatrogenic immunosuppression for solid organ or bone marrow
transplant recipients).
• Connective-tissue disorders, including Sjögren syndrome,
rheumatoid arthritis, chronic lymphocytic thyroiditis, and systemic
lupus erythematosus (SLE) are also associated with increased risk of
NHL.

• The microscopic appearance of the lesional cells was used in the past to
classify the tumors as either lymphocytic or histiocytic.
• With the development of modern immunologic techniques, however, it is
now known that many of the lesions that had been classified as histiocytic
were in fact neoplasms composed of transformed B lymphocytes. In the
early 1980s, a group of American pathologists devised a classification
scheme, known as the Working Formulation for Clinical Use.
• Based on this classification, lymphomas were broadly grouped into three
categories:
• 1. Low grade
• 2. Intermediate grade
• 3. High grade

Clinical features
• Fifth of sixth decade
• Male predominance
• Cervical Lymphadenopathy, hepatosplenomegaly
• Head and neck region is the second most frequent
anatomical site of extranodal lymphomas after the
gastrointestinal tract.
• Swelling are soft and not adheres to underlying structures
or skin
• Fever, Night sweats, weight loss.

Signs:
• Patients complain of swelling or ulcer
• Dysphagia,
• sore throat,
• asymptomatic enlargement of one tonsil is common
Non-Hodgkin Lymphoma. The matted,
nontender lymph node enlargement in the
lateral cervical region represents a common
presentation of lymphoma.

Oral Manifestations of NHL
• In the oral cavity, lymphoma usually appears as extranodal disease. Although the oral lesions of
lymphoma are often a component of more widely disseminated disease, at times the lymphoma begins
in the oral tissues and has not spread to other sites.
• The malignancy may develop in the oral soft tissues or centrally within the jaws.
• Soft tissue lesions appear as nontender, diffuse swellings; they most commonly affect the buccal
vestibule, posterior hard palate, or gingiva .
• Such swellings characteristically have a boggy consistency. The lesion may appear erythematous or
purplish, and it may or may not be ulcerated.

Non-Hodgkin Lymphoma. One of the frequent
locations of extranodal lymphoma in the head and
neck area is the palate, where the tumor appears as a
nontender, boggy swelling. Note the overlying
telangiectatic blood vessels, a feature often seen with
malignancy.

• Patients who wear a denture that contacts the lesional site often complain
that their denture does not fit because it feels too tight.
• Lymphoma of bone may cause vague pain or discomfort, which might be
mistaken for a toothache. The patient may complain of paresthesia,
particularly with a mandibular lesion (so-called numb chin syndrome).
Non-Hodgkin Lymphoma. Ulcerated mass of
the left posterior maxilla.

• Radiographs usually show an ill-defined or ragged radiolucency,
although in the early stages, the radiographic changes may be
subtle or nonexistent.
• If untreated, then the process typically causes expansion of the
bone, eventually perforating the cortical plate and producing a soft
tissue swelling.
• Such lesions have been mistaken for a dental abscess, although a
significant amount of pain is not present in most cases.

Ann Arbor staging system
• In this system, stages I, II, III, and IV, adult NHL can be subclassified into A and B categories:
• B for those with well-defined generalized symptoms and
• A for those without such symptoms.
• The B designation is given to patients with any of the following symptoms:
o Unexplained loss of more than 10% of body weight in the six months before diagnosis
o Unexplained fever with temperatures above 38° C
o Drenching night sweats.

Stage I
Involvement of a single lymph node region (I) or localized involvement of a single extralymphatic
organ or site (IE).
Stage II
Involvement of two or more lymph node regions on the same side of the diaphragm (II) or localized
involvement of a single associated extralymphatic organ or site and its regional lymph nodes with
or without other lymph node regions on the same side of the diaphragm (IIE). The number of
lymph node regions involved may be indicated by a subscript (e.g. II3).
Stage III
Involvement of lymph node regions on both sides of the diaphragm (III) that may also be accompanied
by localized involvement of an extralymphatic organ or site (IIIE), by involvement of the spleen
(IIIS), or both (IIIS+E).
Stage IV
Disseminated (multifocal) involvement of one or more extralymphatic sites with or without associated
lymph node involvement or isolated extralymphatic organ involvement with distant (nonregional)
nodal involvement.

Histologic features
• Non-Hodgkin lymphomas are histopathologically characterized by a proliferation of
lymphocytic-appearing cells that may show varying degrees of differentiation, depending on
the type of lymphoma.
• Low-grade lesions consist of well-differentiated small lymphocytes. High-grade lesions tend to
be composed of less differentiated cells.
• All lymphomas grow as infiltrative, broad sheets of relatively uniform neoplastic cells that
usually show little or no evidence of lesional tissue necrosis.
• In some lesions, particularly those of B-lymphocyte origin, a vague semblance of germinal
center formation may be seen (i.e., a nodular or follicular pattern).

shows a diffuse infiltration of the
subepithelial connective tissue by
lymphoma.
shows lesional cells of lymphoma, consisting of
a population of poorly differentiated cells of
the lymphocytic series with minimal
cytoplasm

• Other lymphomas show no evidence of such differentiation, and
this pattern is termed diffuse. If the lymphoma arises in a lymph
node, then the tumor destroys the normal architecture of the node.
• An extranodal lymphoma destroys the normal adjacent host tissue
by infiltrating throughout the area.
• In the oral cavity, diffuse large B-cell lymphoma, which is considered
to be a high-grade lymphoma, is the most common diagnosis,
comprising approximately 60% of the cases.

Diffuse large B-cell lymphoma
Diffuse large B-cell lymphoma is a diffuse
proliferation of large neoplastic B lymphoid cells
with nuclear size equal to or exceeding normal
macrophage nuclei or more than twice the size of a
normal lymphocyte.

Clinical features:
• Most common type of NHL- 31% of all NHL
• 60-70% of aggressive lymphoid neoplasms.
• Most important lymphoma in adults -accounts for
50% of all adult NHLs
• Median age : 7th decade
• 15% of childhood lymphomas.
• Male predilection
• half of the patients have stage I/II disease

Site of involvement:
• May present nodal or extra nodal.
• Upto 40% extranodal
• Extranodal – GIT, Waldeyer ring
• Skin, Salivary gland, CNS, liver, spleen, kidney.
• Bone marrow-late, present as leukemic picture.
Cell of origin:
• Germinal center or postgerminal center B-cell.

Morphology:
• Large neoplastic B cells (3-4 times size of resting
lymphocytes), diffuse pattern of growth.
• Tumor cells are large (nuclear size comparable to
or greater than that of a histiocyte nucleus, or
more than twice the size of a small lymphocyte).

Morphologic variants:
Centroblastic:
• Large cells with round or oval vesicular nuclei with multiple
peripherlly located nucleoli, thin rim of amphophilic
cytoplasm
• Cytoplasm tends to be pale and modest in volume, resemble
“Centroblasts’ (seen in reactive germinal centers)

Centroblast - Large cells with round or oval vesicular
nuclei with multiple peripherlly membrane bound
nucleoli, thin rim of amphophilic cytoplasm.

• Immunoblastic:(Immunoblasts >90%)
– Cells with round or multiloculated large vesicular
nucleus with one or two centrally placed prominent
nucleoli.
– Broad rim of cytoplasm that can be either deeply
staining or clear.

• Immunoblast : Cells with round or multiloculated
large vesicular nucleus with one or two centrally
placed prominent nucleoli with pale/ clear cytoplasm

• Anaplastic:
– Large, round, oval, or polygonal cells with bizare
pleomorphic nuclei, multinucleation abundant
cytoplasm resembling RS cells.

Neoplastic cells with frequent nuclear multilobation

T-cell/histiocyte-rich large B-cell lymphoma
• Characterized by large neoplastic B cells dispersed within a background
of small T lymphocytes and histiocytes.
• Neoplastic cells accounts for <10% of the cell population.
• large neoplastic B cells usually show definite nuclear atypia, with round,
lobated, or irregularly folded nuclei and distinct nucleoli,and can
resemble L&H cells or Reed–Sternberg cells

Immunohistochemistry:
• Express pan-B cell antigens like CD-20, CD22,
CD79a, PAX-5.
Note presence of densely packed positive cells, staining
with uniform intensity for CD 20

Pathogenesis :
• Approx. 20% patients have rearrangement of BCL2
gene.
• Such cases may have transformed from a known or
occult follicular lymphoma, or have evolved to
DLBCL without a precursor phase of follicular
lymphoma.
• BCL6 and perhaps other unidentified genes play an
important role in the de novo pathway.
• BCL6 rearrangement occurs in about 30% of DLBCL

Special subtype associated with oncogenic
viruses:
• Immunodeficiency-associated large B-cell
lymphoma- end stages of HIV, post transplant
patient, EBV.
• Body cavity large cell lymphoma- HIV patient,
HHV8

Prognosis:
• Aggressive tumor, fatal if untreated.
• With intensive combination chemotherapy,
complete remission can be achieved in 60-80% of
patients.

B-chronic lymphocytic leukemia/small
lymphocytic lymphoma
Neoplasm of monomorphic small, round B lymphocytes in
peripheral blood, bone marrow and lymph nodes, admixed with
prolymphocytes, usually expressing CD5 and CD23.

Epidemiology:
• Constitutes only 4% of NHL
• Constitutes 30% of leukemias in Western countries
but quite uncommon in Asians
• Typically affects persons older than 50
• Male : Female ratio of 2 : 1.

Site of Involvement:
• CLL – Involvement of bone and peripheral blood at
the time of diagnosis and lymphocyte count > 10 x
109/l.
< 10 x 109/l – Diagnosis of CLL by morphology
and immunophenotyping.
• Diagnosis of SLL (not CLL) – Histologically in the
absence of bone marrow and blood involvement.
• Lymph nodes, Liver and spleen – typically infiltrated.
• Skin and breast – occasionally involved.

Clinical features:
• Often asymptomatic.
• Easy fatiguability, weight loss and anorexia
• Hypogammagloublinemia leading to increased
susceptibility to infection
• Autoimmune hemolytic anemia due to antibodies
against autologous RBCs
• Thrombocytopenia in a minority.

Morphology:
Lymph nodes:
• Sheets of small round lymphocytes and scattered ill-defined foci of
larger cells termed prolymphocytes diffusely efface involved lymph
nodes
A monotonous proliferation of small lymphocytes effaces the
architecture of the node.
The nuclear contours are regular, the chromatin is
clumped, and nucleoli are inconspicuous.

• Foci of mitotically active prolymphocytes are called
proliferation centers, their presence is pathognomonic for
CLL/SLL
proliferating center in lymph node involved
by small lymphocytic lymphoma.

Prognosis:
• Indolent
• The course & prognosis of CLL/SLL variable,
depends on clinical stage.
• Median age of survival is 4 to 6 years.
• Deletion of 11q and 17p correlates with higher stage
and poorer prognosis.

• Over time CLL/SLL tends to transform to more
aggressive tumors like prolymphocytic leukemia
(prolymphocytic transformation) or diffuse large B-
cell lymphoma (Richards Syndrome)
• Survival < 1yr.

Follicular lymphoma
Neoplasm of follicular center B cells (centrocytes /cleaved follicle
center cells (FCC) and centroblasts/noncleaved FCC, which has at least
a partially follicular pattern.
Postulated cell of origin:
• Germinal center B-cell.

Epidemiology:
• Constitute 40% of older adult NHLs in US. Lower
incidence in Asia.
• 70% of low grade lymphoma in US.
• Median age = 59 yrs.
• Male : female ratio = 1 : 1.7

Site of Involvement:
• Predominantly lymph node.
• Also involves spleen, bone marrow, peripheral blood
and Waldeyer’s ring
• Non haemopoetic extranodal sites like skin, soft
tissue and GIT – rarely.

Clinical features:
• Present as painless lymphadenopathy, which is
frequently generalized.
• Involvement of bone marrow in 85%.
• 1/3rd are diagnosed at stage I and II

Morphology:
• Lymph nodes are effaced by proliferations that have a
distinctly nodular appearance under low power.
• Tumor cells resemble normal germinal centre B cells.

• Predominant neoplastic cells are centrocyte-like cells
(slightly larger than resting lymphocyte with angular
cleaved nuclear contour. Nuclear chromatin is coarse
and condensed and nucleoli are indistinct)
• Mixed with variable number of centroblast-like cells
(3-4 times the size of a resting lymphocyte. Vesicular
chromatin, several nucleoli and modest amounts of
cytoplasm and resembles the mitotically active cells
found within the normal germinal centers)

 Grade 1 (1-5 centroblasts per high-power field)
 Grade 2 (6-15 centroblasts per high-power field)
 Grade 3 (more than 15 centroblasts per high-power
field).

Malignant follicular (grade
II) lymphoma : revealed
mixed small and large cell
lymphoma. Giemsa staining,
x600.
Malignant diffuse follicular
lymphoma (grade III) :
composed predominantly of
large cells.
Hematoxylin and eosin, x400.

Immunophenotype:
• Pan B-cell markers such as CD-19, CD-20.
CD 20 stain decorates the neoplastic nodule and identifies the cell as of
B-cell nature

Follicular lymphoma stained BCL2
 In addition, tumour cells express BCL2 protein, a feature that
distinguishes them from normal germinal centre B-cells which
are BCL-2 negative

Prognosis:
• Indolent course
• Not improved by aggressive treatment.
• Usual treatment is palliative chemotherapy or
radiotherapy if patient develops symptoms.
• Median survival is 7 to 9 years.
• 30 – 50% of follicular lymphoma transform to
diffuse large B-cell lymphoma

Mantle cell lymphoma
• B-cell neoplasm composed of monomorphous small to
medium sized lymphoid cells with irregular nuclei,
which morphologically closely resemble the
centrocytes /cleaved follicular center cells (FCC).
• Composed of B-cells that resemble the mantle zone of
normal lymphoid follicles.

Features:
• Constitute approx. 4% of all NHLs
• 5th to 6th decade.
• Occur mainly in males.
• Painless lymphadenopathy
• Lymph nodes followed by liver and spleen.
• Extranodal involvement: GIT, Waldeyer ring, Bone
marrow.

Morphology:
• Diffuse or vaguely nodular pattern of lymph node
involvement.
Mantle cell lymphoma surrounding a small
residual germinal center.

• Tumors cells are slightly larger than normal
lymphocytes and have an irregularly cleaved nucleus
and inconspicuous nucleoli. Resembles lymphoblasts.

• Mantle cell lymphoma is differentiated from CLL/SLL
by absence of proliferation centers and presence of
abnormally high levels of cyclin D1 protein.
Immunoreactivity for Cyclin D1 in mantle zone lymphoma

Prognosis:
• Aggressive tumors and incurable
• Median survival-3-5 years
• Histological transformation less frequent.

Lymphoplasmacytic lymphoma
• Neoplasm of small B lymphocytes, and plasma cells, and usually
involving bone marrow, lymph nodes and spleen, usually lacking CD5,
which has a serum monoclonal protein with hyperviscosity or
cryoglobulinemia in most of cases.
• Most commonly neoplastic plasma cells secrete IgM, often in sufficient
quantity to cause hyperviscosity syndrome called Waldenstrom
macroglobulinemia.

Epidemiology:
• Median age: 63 yrs
• Male predilection
• Bone marrow, lymph node, spleen.
• Extranodal- lung, GIT, skin.
Prognosis:
• Incurable
• Median age 4 yrs.

Clinical features:
• Non specific symptoms- weakness, fatigue, weight loss.
• Lymphadenopathy, hepatomegaly, splenomegaly- 50%
of cases.
• Anemia- bone infiltration or autoimmune hemolysis.
• Visual impairment
• Neurological problems- head ache, dizziness, deafness,
stupor.
• Bleeding

Morphology:
• Bone marrow contains a diffuse infiltrate of
lymphocytes, plasma cells, and plasmacytoid cells, often
accompanied by a reactive hyperplasia of mast cells.

Marginal zone lymphoma
Definition:
It is heterogenous group of lymphoma of B cells that variously
arise within lymph node, spleen or extranodal tissues.
• Initially recognized at mucosal site- Mucosa associated lymphoid
tissues (MALT)
Postulated cell of origin
• Postgerminal center memory B-cell

Etiology
• The marginal zone contains post germinal center B cells that have
undergone somatic hypermutation.
• Chronic and persistent immune stimulation, either of infective or
autoimmune nature, leads to the development of MALTomas.
• The postulated pathophysiologic mechanism of tumor development is
that chronic inflammation leads to the accumulation of antigen-
dependent B cells locally in the associated MALT.
• This growth is monoclonal, but continuous growth signal due to chronic
inflammation makes B cells prone to accumulating mutations.

• With time, the cells accumulate mutations, and the growth pattern transforms
from monoclonal to polyclonal, leading to the development of neoplastic B cells in
the marginal zone of the MALT.
• Following translocations are most commonly found in MALToma:
• t(14;18)(q32;q21)
• t(11;18)(q21;q21)
• t(3;14)(p13;q32)
• t(1;14)(p22;q32)
• Many of these mutations lead to the activation of nuclear factor-kappaB (NF-
kappaB), which increases the survival of neoplastic B cells in the marginal zone.

Epidemiology:
• 7-8% of B-cell lymphomas
• Median age:61
• M:F = 1:1.2
Precursor lesion/condition:
• Chronic inflammatory disorders of autoimmune or
infectious etiology.
E.g.; Hashimoto thyroiditis, Helicobacter gastritis.
• Regress if inciting agent is removed.

• GIT, stomach
• Lung, head and neck (ocular adenexae), skin,
thyroid, breast.
Ocular Adnexal Lymphoma (OAL)

Clinical features:
• Majority : Stage I & II
• Arise at extranodal sites with chronic inflammatory
disease.
• Remain localized, spread systematically late in
course.

Lymph node involvement by marginal zone B-cell lymphoma. There are
numerous residual germinal centers.
Morphology:
Lymphocyte infiltration around reactive B germinal
center, external to preserved mantle follicle, in a
marginal zone.

Lymph node involvement by marginal
zone B-cell lymphoma.
 Small to medium sized, slightly irregular
nuclei, moderately dispersed chromatin
and inconspicuous nucleoli resembling
centrocytes.

• Lies at the continuum between lymphoid hyperplasia and
full blown B-cell lymphoma
• Begins as reactive polyclonal reaction with acquisition of
mutation and chromosomal abberation over time, a
monoclonal neoplasm emerges that is still dependent on T-
helper cells for growth and survival.
Treatment
• Sensitive to radiotherapy
Prognosis
• Poor

Extranodular NK/T-cell Lymphoma
• Angiocentric T-cell lymphoma, Midline lethal granuloma,
Idiopathic midline destructive disease
• Rare, mostly characterized by aggressive nonrelenting destruction
of midline structures of the palate and nasal fossa.
• Postulated cell of origin
• Natural killer cell (common)
• Cytotoxic T-cell (rare)

Etiology
• EBV
Epidemiology:
• Asia, Mexico, South America
• Adults
• M>F
• Immunocompromised patients
Site of involvement
• Nasal cavity, nasopharynx, palate
• Skin, GIT, testis

Swelling of the palate may
precede the formation of a
deep, necrotic ulceration ,
which usually occupies a
midline position.
Clinical features:
Initial symptoms include nasal stuffiness or
epistaxis.

• Oronasal fistula, secondary
infections and life-
threatening hemorrhage
may be the complications

Morphology:
• Mixed infiltrate of a variety of inflammatory cells,
often arranged around blood vessels.

• Lesional process appears to invade and destroy
normal tissues in the area
• Necrosis , seen in some areas.
• Large, angular, lymphocytic cells with an atypical
appearance are usually identified as a component of
the cellular infiltrate

Treatment and prognosis:
• Localized lesions respond well to radiation therapy
• For patients with more disseminated disease,
combination chemotherapy is indicated.

Burkitt lymphoma (African jaw lymphoma)
• It is peculiar to the children of tropical central Africa.
• First reported by Denis Parsons Burkitt (1958–59).
• Burkitt’s lymphoma (BL) occurs endemically in parts of
Africa and Papua, New Guinea and is restricted to areas
with endemic malaria.
• It also occurs sporadically throughout the world.

• It is a high-grade B-cell neoplasm and has two major forms:
• Endemic (african) form.
• Nonendemic (sporadic) form.
• Burkitt’s lymphoma is a childhood tumor but it is observed
in adult patients too.
• Burkitt’s lymphoma is one of the fastest growing
malignancies in humans, with a very high growth fraction.

Pathogenesis
• The exact causes and mechanisms of Burkitt’s lymphoma are not
known.
• EBV is closely associated with the African form of Burkitt’s lymphoma.
• Some have postulated that, because of immunosuppression caused
by coexistent malaria or another infection, the host is unable to
generate an adequate T-lymphocyte response (i.e. EBV-specific
cytotoxic T cells) against B cells that are infected latently with EBV.
• This subsequently results in excessive B cell proliferation.

Clinical features
• The African form most often involves the maxilla or mandible.
• The involvement of abdominal organs, such as the kidneys,
ovaries, or retroperitoneal structures, is slightly less common.
• In contrast, the sporadic form usually involves abdominal organs,
with the most common involvement of the distal ileum, cecum, or
mesentery, and less common involvement of other abdominal
organs, pelvic organs, and facial bones.

• In the African form of Burkitt’s lymphoma, patients most often
present with swelling of the affected jaw or other facial bones,
loosening of the teeth, and swelling of the lymph nodes, which are
nontender and rapidly growing, in the neck or below the jaw.
• Abdominal presentation is slightly less common.
• Major signs of Burkitt’s lymphoma include a soft tissue mass
associated with the involvement of the jaw or other facial bones,
enlarged cervical lymph nodes, abdominal masses, and ascites.

• Patients with the sporadic form of Burkitt’s lymphoma most commonly
present with abdominal tumors causing swelling and pain in the affected
area.
• Some patients present with symptoms of bowel obstruction secondary to
an ileocecal intussusception caused by tumor growth.

• Because of the rapid growth of the Burkitt tumor, patients may quickly
manifest significant metabolic derangement and renal function impairment.
• Less common presentations of Burkitt’s lymphoma include an epidural
mass, skin nodules, CNS symptoms, and bone marrow involvement.
• Rare cases of Burkitt’s lymphoma can present as acute leukemia with fever,
anemia, bleeding, and adenopathy.

Radiographic features
Location
• African cases may involve one jaw or both the maxilla and mandible and affect the posterior parts of
the jaws. By contrast, American cases may not involve the facial bones but are more likely to affect
the abdominal viscera and testes.
Periphery and Shape
• The lesions may begin as multiple ill defined noncorticated radiolucencies that later coalesce into
larger ill-defined radiolucencies with an expansile periphery.
• They are of no specific shape, although they expand rapidly and have been likened to a balloon.
• This expansion breaches its outer cortical limits, causing gross balloonlike expansion with thinning of
adjacent structures and production of a soft tissue tumor mass adjacent to the osseous lesion.
• Lesions that abut the orbital contents or the maxillary sinus may show a smooth surface soft tissue
mass radiologically.

Internal Structure
• Burkitt ’ s lymphoma does not produce bone and rarely induces production of reactive bone within
its center. For this reason, the lesions are radiolucent in almost all cases. It is particularly radiolucent
in the jaw of a child.
Effects on Surrounding Structures
• Erupted teeth in the area of Burkitt ’ s tumor are grossly displaced, as are developing tooth crypts.
• Tumor cells within the crypt may displace the developing tooth bud to one side of its crypt.
• A tumor that is located apical to a developing tooth may cause it to be displaced such that it appears
to erupt with little if any root formation. After tumor involvement of the developing dental
structures occurs, root development ceases.
• Lamina dura of teeth in the area is destroyed, and cortical boundaries such as the maxillary sinus,
nasal fl oor, orbital walls, and inferior border of the mandible are thinned and later destroyed.
• The cortex of the inferior alveolar canal is lost, although it is diffi cult to see in the radiographs of a
normal pediatric patient in any case. If periosteum is involved, the border may show sunray
spiculation, although this is rare.

(A) Panoramic radiograph showing radiolucent osteolytic lesion
and the destruction of cortical bone in the left mandibular area.
(B) Periapical radiograph showing complete loss of the lamina dura
of the left mandibular primary second molar and permanent first
molar.

Histological features
• Monoclonal proliferation of B lymphocytes characterized
by small noncleaved cells that are uniform in appearance
and that produce a diffuse pattern of tissue involvement.
• Burkitt cells are homogeneous in size and shape, with
round to oval nuclei and slightly coarse chromatin, with
multiple nucleoli, and with intensely basophilic vacuolated
cytoplasm that contains neutral fat.

• The lesion on low-power magnification, a classic “starry-sky”
pattern is often appreciated—a phenomenon that is caused by the
presence of macrophages within the tumor tissue.
• These macrophages have abundant cytoplasm, which
microscopically appears less intensely stained in comparison with
the surrounding process. Thus these cells tend to stand out as
“stars” set against the “night sky” of deeply hyperchromatic
neoplastic lymphoid cells

(A): There is a diffuse infiltrate of atypical lymphoid cells with numerous mitoses
and a prominent starry‐sky pattern because of the presence of multiple tingible
body macrophages. (B): High‐power magnification shows that the neoplastic cells
are medium‐sized, round, and uniform, with nuclei that are similar in size to or
slightly smaller than the nuclei of the tingible body macrophages.

This low-power photomicrograph shows the classic “starry-sky”
appearance, a pattern caused by interspersed histiocytic cells
with abundant cytoplasm (“stars”) set against a background of
malignant, darkly staining lymphoma cells (“night sky”).

This high-power photomicrograph
demonstrates the undifferentiated, small, dark
lesional cells with numerous histiocytes.

Treatment and Prognosis
• combination chemo therapy and CNS prophylaxis (intrathecal
chemotherapy), the survival rate is now at least 60%.
• Patients with limited disease have a survival rate of 90%.
• Those with bone marrow and CNS involvement have a poor
prognosis.
• Adults with the disease, especially those in the advanced stage, do
more poorly than affected children.

MYCOSIS FUNGOIDES (CUTANEOUS T-CELL LYMPHOMA)
• It represents a lymphoma that is derived from T lymphocytes, specifically the T-
helper (CD4+) lymphocyte.
• Even though mycosis fungoides is the most common of these cutaneous lymphomas,
it is still a relatively rare malignancy.
• This condition exhibits a peculiar property called epidermotropism (i.e., a propensity
to invade the epidermis of the skin).
• Oral involvement, although infrequent, may also be present.

Clinical Features
• Mycosis fungoides is a condition that usually affects middleaged adult men; there is a 2
: 1 male-to-female ratio and a mean age at diagnosis of 55 to 60 years.
• The disease progresses through three stages, usually over the course of several years.
• The first stage, known as the eczematous (erythematous) stage, is often mistaken for
psoriasis of the skin because of the well-demarcated, scaly, erythematous patches that
characterize these lesions. Patients may complain of pruritus.
• With time, the erythematous patches evolve into slightly elevated, red lesions (plaque
stage). These plaques tend to grow and become distinct papules and nodules. At this
time, the disease has entered the tumor stage. Visceral involvement is also seen at this
point.

• The most commonly affected sites are the tongue, palate, and gingiva.
• The buccal mucosa, tonsils, lips, sinuses, and nasopharynx may also be
affected. The oral lesions present as erythematous, indurated plaques or
nodules that are typically ulcerated.
• Generally, these lesions appear late in the course of the disease and develop
after the cutaneous lesions.

• Sézary syndrome is an aggressive expression of mycosis fungoides
that essentially represents a dermatopathic T-cell leukemia.
• The patient has a generalized exfoliative erythroderma, as well as
lymphadenopathy, hepatomegaly, and splenomegaly. The lung,
kidneys, and CNS can also be involved.
• This condition follows a fulminant course and typically results in the
patient’s death within a short period of time; the median survival
for this form of the disease is 2 to 3 years.

Mycosis Fungoides. In the tumor stage of the
disease, patients with mycosis fungoides have
ulcerated nodules of the skin.
Mycosis Fungoides. The ulcerated
palatal lesions represent a rare
example of oral mucosal involvement
by mycosis fungoides.

Histopathologic Features
Eczematous Stage
• The early stages of mycosis fungoides may be difficult to diagnose
histopathologically because of the subtle changes that characterize
the initial lesions.
• A psoriasiform pattern of epithelial alteration is seen, with
parakeratin production and elongation of the epithelial rete ridges.
• Scattered, slightly atypical lymphocytic cells may be seen in the
connective tissue papillae, but such features are often mistaken for
an inflammatory process.

Plaque Stage
• With the development of the plaque stage, a more readily identifiable
microscopic pattern emerges.
• Examination of the surface epithelium reveals infiltration by atypical
lymphocytic cells, which are sometimes referred to as mycosis cells or
Sézary cells.
• These atypical lymphocytes classically form small intraepithelial
aggregates termed Pautrier microabscesses.

• The lesional cells have an extremely unusual nucleus because of the marked
infolding of the nuclear membrane, which results in what is termed a
cerebriform nucleus.
• This feature can best be appreciated when viewed in special semithin, plastic-
embedded microscopic sections.
atypical, malignant lymphoid cells of
mycosis fungoides that exhibit
cerebriform morphology (inset).

• The diagnosis of mycosis fungoides can be confirmed by
demonstrating positivity for CD4 (a cell surface marker for
T-helper cells) in the lesional cell population.
• In addition, T-cell receptor gene rearrangement analysis
should identify a monoclonal population of T lymphocytes.
A mixed infiltrate of eosinophils, histiocytes, and plasma
cells may be observed in the subepithelial connective
tissue.

Tumor Stage
As the condition progresses to the tumor stage, the diffuse infiltration of the
dermis and epidermis by atypical lymphocytic cells makes it easier to
identify as a malignant process.

Treatment and Prognosis
• Topical nitrogen mustard, topical carmustine, superpotent topical
corticosteroids, topical bexarotene (a synthetic retinoid), electron beam
therapy, or photochemotherapy (PUVA [8-methoxy-psoralen + ultraviolet A])
are effective in controlling mycosis fungoides during the early stages.
• Although mycosis fungoides is not considered to be curable, the disease is
usually slowly progressive. As a result, there is a median survival time of 8 to
10 years, and patients may die of causes unrelated to their lymphoma. Once
the disease progresses beyond the cutaneous involvement, the course
becomes much worse.
• The patient usually dies of organ failure or sepsis within 1 year.

Immunological markers
• lymphomas CD45,
• B cell markers (CD19, CD20,CD79a),
• T cell markers (CD3,CD5), CD23, cyclin D1, BCL2, anaplastic
lymphoma kinase, CD15, CD30, Ki67.
Rao IS. Role of immunohistochemistry in lymphoma. Indian J Med Paediatr Oncol. 2010;31(4):145-147. doi:10.4103/0971-5851.76201

Round Cell Liposarcoma (myxoid liposarcoma)
• Myxoid liposarcoma comprises about one-third of liposarcomas.
• lipoblast is a neoplastic cell that, to some extent, recapitulates the differentiation
cascade of normal fat.
• The earliest cells arise as pericapillary adventitial cells that closely resemble
fibroblasts.
• These spindled cells, endowed with ample endoplasmic reticulum, slowly acquire fat
droplets first at the poles of the cell and later throughout the cytoplasm.
• As fat accumulates in the cytoplasm, the cell loses its endoplasmic reticulum and
assumes a round shape. Gradually, the nucleus becomes indented and pushed to
one side of the cell. 110

111
Developing lipoblasts from a myxoid
liposarcoma, at an early stage of
differentiation (A) with fine vacuoles
fine vacuoles, an intermediate
stage
Formation of lipoblast

112
resembling mature white fat

Clinical features
• Myxoid liposarcomas account for about one-third to one- half of all
liposarcomas.
• 5th decade
• Site: tongue, submandibular area, cheek, FOM, soft palate
• Most cases present as a slowly growing, painless, nonulcerated
submucousal mass
113

Histopathology
• pure myxoid liposarcomas bear a marked
similarity to developing fetal fat.
• At low power, the lesion is a multinodular
mass of low cellularity with enhanced
cellularity at the periphery.
114

115
Multinodular appearance of a myxoid
liposarcoma.

116
Enhanced cellularity at the periphery of nodules in a myxoid
liposarcoma.

• Each nodule is composed of fusiform or round cells that lie
suspended individually in a myxoid matrix composed of hyaluronic
acid.
• The cells within pure myxoid liposarcomas characteristically are
small without a discernible nuclear pattern and without much
mitotic activity.
• Rarely, the nuclei are enlarged and hyperchromatic.
• A delicate plexiform capillary vascular network is present throughout
these tumors and provides an important clue for distinguishing them
from myxomas.
117

118
Myxoid liposarcoma with characteristic lipoblastic differentiation at the
periphery.

• The proliferating neoplastic cells recapitulate, albeit
imperfectly, the sequence of adipocyte differentiation.
• Immature spindled cells lacking obvious lipogenesis may be
seen next to multivacuolar and univacuolar lipoblasts.
• Although lipoblasts are usually easy to identify in these
liposarcomas, they may be especially prominent at the
periphery of the tumor nodules
119

120
Typical appearance of a myxoid liposarcoma.

121
Myxoid liposarcoma with arborizing vasculature and lipoblasts at varying
stages.

122
Myxoid liposarcoma with a larger number of mature
lipoblasts

• The hyaluronic acid-rich (Alcian blue-positive,
hyaluronidase-sensitive) stroma is present primarily in the
extracellular space but may also be found in individual
tumor cells.
• Frequently, the extracellular mucin forms large pools,
creating a cribriform or lace-like pattern in the tumor and,
infrequently, gross cysts.
• The cellular condensation at the rim of these pools
produces a pseudoacinar pattern.
123

124
Small pools of stromal mucin in myxoid
liposarcoma.

125
(A)Pools of stromal mucin in a myxoid liposarcoma forming a
sieve pattern.
(B) Pools of stromal mucin forming cysts.

126
Alcian blue staining of myxoid liposarcoma before (left) and after (right
hyaluronidase digestion. Stromal mucin staining is abolished following
enzyme treatment, indicating the presence of hyaluronic acid.

• As myxoid liposarcomas lose their differentiation, they assume an
increasingly round cell appearance, which is expressed in one of
two ways.
• Amid a myxoid backdrop, one encounters a pure round cell nodule
characterized by sheets of primitive round cells with a high
nuclear/ cytoplasmic ratio and a prominent nucleolus.
• The cells are so compact that they essentially lie back to back with
no intervening myxoid stroma, and the capillary vascular pattern,
though present, cannot be visualized easily.
128

• More commonly, however, the progression toward round cell areas is
reflected in a more gradual fashion.
• In these areas, the cellularity is clearly greater, and the cells are usually
larger with a more rounded shape.
• Round cell areas are diagnosed when the cells acquire a rounded shape, sit
back to back with overlapping nuclei, and obscure the vasculature.
• The term transitional has been used for cellular areas of a myxoid
liposarcoma that do not meet the criterion of a round cell.
• Transitional areas have not been correlated with an adverse outcome.
129

130
Myxoid liposarcoma with sharply demarcated
nodules of round cell liposarcoma.

131
Myxoid/round cell liposarcoma with progressive
transition, from somewhat cellular myxoid areas
(A)to borderline areas
(B) to round cell liposarcoma

132
(C, D) where cells have overlapping
nuclei and some residual myxoid
stroma.
Round cell areas without myxoid
stroma
(E) may be impossible to diagnose as
liposarcoma.

• Occasionally, round cell areas are characterized by branching
cords and rows of primitive small rounded cells or large cells
with an eosinophilic granular or multivacuolar cytoplasm
resembling malignant brown fat cells.
133

134
Cord-like pattern in a round cell liposarcoma.

135
Cord-like pattern and stromal hyalinization in a
round cell liposarcoma.

Histopathology
– Myxoid type:
• Low cellularity; round/ fusiform cells; lipoblasts
• Myxoid matrix – hyaluronic acid
• Haemorrhage, cartilaginous, osseous, leiomyomatous foci
– Round cell type:
• Loss of differentiation from myxoid type
• Sheets of primitive round cells
– as a foci in the myxoid type or pure round cell type
• High nuclear/cytoplasmic ratio
• No intervening myxoid stroma
• Occasional lipoblast: multi- or univacuolar cells
136

• Special stain:
• This will stain with alcian blue and is metachromatic
with toludine blue and cresyl violet. It is weakly positive
with meyer’s stain.
• Imunohistochemistry:
• adipocytes and lipoblasts are positive for vimentin and
S100.
• Other marker are MDM2, CDK4, caveolin (also seen in
smooth muscle neoplasm) and leptin (cytokine like
peptide)
137

Desmoplastic small round cell tumour
• rare neoplasm that was first described by
Gerald and Rosai in 1989.
• It is a high-grade tumor that mostly affects
abdominal cavity and visceral organs.
138

Clinical features
• Age - mainly affects young adults, with a peak incidence in the
second decade of life.
• Sex - male patients tend to outnumber female patients by 4 : 1.
• Site - In its most frequent intra-abdominal presentation
• usually causes abdominal pain associated with ascites, abdominal
distension and/ or intestinal obstruction.
139

Histopathology
• composed of sharply demarcated nests of varying size with small round or
oval cells embedded in a hypervascular desmoplastic stroma.
• Large tumor cell nests often have central necrosis.
• The neoplastic cells appear undifferentiated and have small
hyperchromatic nuclei with inconspicuous nucleoli and scant amounts of
eosinophilic cytoplasm.
• In most cases, the nuclei are relatively uniform, but some tumors show foci
with increased nuclear atypia, and rare tumors are composed
predominantly of markedly atypical cells.
140

141
Desmoplastic small round cell tumor. Nests of
undifferentiated tumor cells are surrounded by abundant
fibrous stroma.

• The cells may be arranged in a variety of patterns, including large nests
with central necrosis, tubular-like structures, trabeculae separated by
fibrovascular septa reminiscent of a zellballen pattern, and cords of single
cells similar to lobular carcinoma of the breast.
• Typically, the cellular aggregates are surrounded and separated by
abundant fibrous connective tissue with only a scattering of spindle-
shaped fibroblasts and myofibroblasts.
• Occasionally, the tumor cells have more abundant cleared-out or
vacuolated cytoplasm or even a signet ring-like appearance.
• A relatively common finding is the presence of rhabdoid-like foci in which
the tumor cells have paranuclear intracytoplasmic hyaline inclusions
composed of aggregates of intermediate filaments
142

143
Nests of undifferentiated tumor cells are separated by a
dense fibrous stroma in this desmoplastic small round cell
tumor.

144
Prominent desmoplastic stroma surrounds varying-sized
nests of tumor cells in a desmoplastic small round cell
tumor.

145
Desmoplastic small round cell tumor.
Larger tumor nests show central
necrosis.

146
Desmoplastic small round cell tumor. The
tumor cells appear undifferentiated and
have small hyperchromatic nuclei with
inconspicuous nucleoli.

147
Desmoplastic small round cell tumor. Cords
of cells are surrounded by a dense fibrous
stroma mimicking lobular carcinoma of the
breast.

148
Focus of cells with a rhabdoid
appearance in a desmoplastic small
round cell tumor.

– Nests of small round/ oval cells
– Cells:
• Hyperchromatic nuclei
• Scant cytoplasm
• Few cells – paranuclear hyaline inclusion
– intermediate filament
• Rare – signet cells
• Occasional nuclear atypia
– Cellular arrangement:
• Large nests – central necrosis
• Tubular
• Zellballen
• Cords
– Abundant fibrous connective tissue stroma
149

• Immunopositivity for desmin with a dot-
like staining pattern is almost always
observed.
150

151
Typical perinuclear globular pattern of desmin
immunoreactivity peculiar to desmoplastic small
round cell tumors.

• Histologically and cytologically, DSRCT must be distinguished from other small round
cell tumors, such as Ewing sarcoma/PNET, small cell carcinoma, lymphoma,
neuroblastoma, Wilms tumor, rhabdomyosarcoma, and malignant mesothelioma.
• Like DSRCT, Ewing sarcoma/PNET is composed of small round cells in nests or sheets.
Immunohistochemically, Ewing sarcoma/PNET is typically positive for MIC2 (CD99) and
vimentin, but negative for cytokeratins and myogenic markers.
• The characteristic reciprocal chromosomal translocation in Ewing sarcoma/PNET, t(11;
22)(q24;q12), involves the long arm of chromosome 11, in contrast to the translocation
observed in DSRCT, which involves the short arm of chromosome 11.

• Small cell neuroendocrine carcinoma demonstrates many cytologic and
histologic similarities to DSRCT, such as small round cells with nuclear
molding and absent or inconspicuous nucleoli.
• Clinically, small cell carcinoma is associated with a much older patient
population and usually originates in the lung.
• On histologic and cytologic examinations, the desmoplastic stroma is not a
feature of small cell carcinoma.
• On immunohistochemistry, small cell carcinoma demonstrates
immunoreactivity with epithelial markers, including TTF-1 and
neuroendocrine markers, but is negative for myogenic markers such as
desmin.

• Moreover, both embryonal and alveolar rhabdomyosarcomas may contain
small blue cells arranged in nests or sheets.
• However, nuclear molding and desmoplastic stroma are not characteristics
of rhabdomyosarcoma. Immunohistochemically, rhabdomyosarcoma is
positive for muscle markers including desmin, muscle specific actin, and
myoglobin, but usually negative for cytokeratins, S100 protein, and neural
markers.
• Neuroblastoma and Wilms tumor also share many morphologic features
with DSRCT, but they occur in very young children and cytogenetically lack
the specific chromosomal translocation.

Synovial Sarcoma
• Uncertain histogenesis
• Although it shows a histologic resemblance to developing synovium,
there is no evidence that the synovial sarcoma originates from
synovial tissue.
• Therefore, most occur unassociated with a joint.
• It occurs primarily in the paraarticular regions of the extremities,
usually in close association with tendon sheaths, bursae, and joint
capsules.
155

Clinical features
• Age- adolescents & young adults 15-45yrs
• Sex- Male predilection
• Site- Most are found in the lower extremity, particularly around the knee.
• Ten percent of cases are seen in the head and neck, particularly in the
paravertebral area. They may present as a retro- or parapharyngeal mass,
but they also can occur in the tongue, soft palate, and parotid.
• Clinical presentation- It presents as a painful but slow-growing mass, often
evolving over many years.
156

Radiographic features
• Radiographically, small calcifications may be
present; this feature can be helpful
diagnostically.
157

Histopathology
– Histological subtypes:
• Biphasic type:
– Epithelial and spindle cell morphologies
• Monophasic type:
– Fibrous type, i.e. spindle cell type
– Epithelial type
• Poorly differentiated round cell type
158

• Biphasic type-
• coexistence of morphologically different but histogenetically
related epithelial cells and fibroblast-like spindle cells.
• The epithelial cells are characterized by large, round or oval,
vesicular nuclei and abundant pale-staining cytoplasm with
distinctly outlined cellular borders.
• The cells are cuboidal to tall and columnar; they are arranged
in solid cords, nests, or glandular structures that contain
granular or homogeneous eosinophilic secretions.
159

160
Biphasic synovial sarcoma showing close apposition of
epithelial structures with malignant spindle cells.

161
Typical biphasic synovial sarcoma with
columnar epithelial cells surrounded by
spindle cell elements.

• The glandular spaces lined by epithelial cells must be distinguished
from cleft-like artifacts that are the result of tissue shrinkage.
• The surrounding spindle cell component consists mostly of well-
oriented, rather plump, spindle-shaped cells of uniform
appearance with small amounts of indistinct cytoplasm and oval
dark-staining nuclei.
• Generally, the cells form solid, compact sheets that are similar in
many respects to fibrosarcoma, except for the absence of long,
sweeping fascicles or a herringbone pattern and a more irregular
nodular arrangement.
162

163
Biphasic synovial sarcoma with
glandular epithelial structures
adjacent to a
malignant spindle cell component.
Biphasic synovial sarcoma. The
epithelial structures have
intraluminal eosinophilic
secretions.

• only the poorly differentiated forms of the tumor exhibit very high
mitotic counts.
• Commonly, the cellular portions of synovial sarcoma alternate with
less cellular areas displaying hyalinization, myxoid change, or
calcification.
• The collagen in the hyalinized zones may be diffusely distributed or
form narrow bands or plaquelike masses sometimes associated with
a markedly thickened basement membrane separating epithelial and
spindle-cell elements.
• Inflammatory elements and multinucleated giant cells are rare.
164

165
Fibrosarcoma-like area in a
synovial sarcoma. Note the
alternating darkly staining and
lightly staining regions, imparting a
marbled
appearance.
Fibrosarcoma-like area in a
synovial sarcoma. The spindle
cells are arranged in distinct
fascicles.

• Mitoses are infrequent but may be seen in both cell types.
• Calcifications may be present with or without ossification
in areas of hyaline; although only present in about 20% of
cases, this is a diagnostically important finding.
• Vascularity varies from dominant to scant.
• There may be replacement of the cellular component by
collagen or myxoid tissue.
166

• Monophasic type –
• more common than the biphasic
• Because this type is closely related to the biphasic type and merely
represents one extreme of its morphologic spectrum, the previously
mentioned morphologic features of the spindle-cell portion of the biphasic
type, such as cellular appearance, hyalinization, myxoid change, mast cell
infiltrate, hemangiopericytomatous vasculature, and focal calcification,
apply equally to the monophasic fibrous type.
167

168
High-magnification view of a monophasic
fibrous synovial sarcoma. The malignant
spindle cells are relatively uniform with

169
Uniform spindle cells in a
monophasic fibrous synovial
sarcoma.
Epithelioid area in a monophasic
fibrous synovial sarcoma. A small
group of cells have increased
amounts of eosinophilic cytoplasm
and appear more cohesive.

170
Predominantly epithelial-type synovial sarcoma. Most of this
tumor was composed of sheets of cohesive epithelioid cells with
only small foci of spindle-cell differentiation.

• Poorly differentiated round cell type – 3 types:
• (1) a large-cell or epithelioid pattern composed of variably sized rounded nuclei with
prominent nucleoli,
• (2) a small-cell pattern with nuclear features similar to other small round cell
tumors, and
• (3) a high-grade spindle-cell pattern composed of spindle-shaped cells with high-
grade nuclear features and a high mitotic rate
• The poorly differentiated synovial sarcoma consists of closely packed cells that are
often intermediate in form between epithelial and spindle cells.
171

• The tumor may be a predominantly large cell with round
nuclei and prominent nucleoli; it may be a small cell; or it
may have a high-grade spindle cell pattern with nuclear
atypia, numerous mitoses, and necrosis.
• There may be numerous thin-walled blood vessels, in
which case it may resemble hemangiopericytoma.
• Two types of mucins may be found: epithelial and
mesenchymal.
172

173
High-molecular-weight cytokeratin
immunoreactivity highlights the
epithelial
elements in this biphasic synovial

174
Focal immunoreactivity for
cytokeratin 7 in a monophasic
fibrous synovial sarcoma.

175
Strong nuclear TLE1 immunoreactivity
in a monophasic fibrous synovial
sarcoma.

• It is an aggressive B-cell malignancy highly associated with
HIV.
• A fraction of large B-cell lymphomas (LBCL) share a
plasmablastic differentiation with an aggressive behavior,
refractoriness to chemotherapy, and poor prognosis in most
cases.
• They are characterized by a gradual expression of
transcription factors associated with the plasmacytic
differentiation, CD38, CD138, MUM1, Blimp1, and XBP1,
with decreased expression of CD20 and PAX5.3
Plasmablastic lymphoma (PbL)

• PbL is more predominant in males (75% of the cases in the
various analyzed series).
• At diagnosis, PbL commonly presents in extranodal regions,
the most frequent being the oral cavity, the digestive tract,
and the skin.
• Most patients present at an advanced stage (III or IV), with
frequent bone marrow involvement and presence of B
symptoms (40% of patients).
• However, there are differences in the clinical presentation of
patients with different immunological status..

• Location of PbL in HIV-negative patients is more heterogeneous
than in HIV-positive patients, and bone marrow involvement, as
well as B symptoms are less frequent.
• Although lymph node involvement is less frequent at diagnosis, it
has been described in up to 30% of posttransplant patients.
• PbL can be diagnosed as the final event (transformation) of an
indolent lymphoproliferative syndrome.

• Round cell tumors are characterized by small, round, relatively
undifferentiated cells.
• Differential diagnosis of small round cell tumors is particularly
difficult due to their undifferentiated or primitive character.
• Tumors that show good differentiation are generally easy to
diagnose, but identification of the diagnostic, morphological
features is difficult when a tumor is poorly differentiated, therefore,
no definitive diagnosis may be possible.
• Fine-needle aspiration cytology (FNAC) plays an important role in
the diagnosis of these tumors
Diagnosis of round cell tomors

On the basis of round cell pattern
A. Diffuse round cell pattern
1. Ewing’s sarcoma
2. Primitive neuroectodermal tumor
(PNET)
3. Merkel cell carcinoma
4. Embryonal rhabdomyosarcoma (ERMS)
5. Small cell carcinoma
6. Lymphoma
7. Leukemic infiltrate.
B. Septate or lobulated round cell pattern
1. Small round cells are divided by
fibrous/fibrovascular septate
2. Ewing’s sarcoma 3. Alveolar
rhabdomyosarcoma (ARMS).

C.Alveolar/pseudoalveolar round cell pattern
This pattern includes focal, poor cohesion of the
round cell population resulting in pseudo
alveolar appearance
1. ARMS
2. PNET.
D. Round cell pattern with rosettes
A rosette’ is like a flower, with the cells being
arranged radially around a central area
1. Flexner’s (also called Flexner - Winterstein,
true rosettes) - contain clearly delineated
empty central lumen e.g., neuroblastoma,
PNET
2. Homer Wright rosette-center has no
lumen, but abundant fibrillary material
e.g., neuroblastoma.
E. Round cell pattern with
hemangiopericytomatous vascular pattern
e.g., poorly differentiated synovial sarcoma,
Mesenchymal chondrosarcoma.
F. Round cell pattern with other components

According to size of round cell
1. Small round cell
Squamous cell carcinoma, PNET, Ewing’s sarcoma, melanoma,
rhabdomyosarcoma (RMS), Langerhans cell disease, lymphoma,
adenocarcinoma, neuroendocrine carcinoma, Merkel cell
carcinoma, olfactory neuroblastoma
2. Large round cell
Squamous cell carcinoma, adenocarcinoma, melanoma, RMS,
lymphoid tumors, paraganglioma.

On the basis of origin
I. Neurogenic origin:
Ewing’s sarcoma/PNET,neuroblastoma,
retinoblastoma, medulloblastoma,
Merkel celltumor, paragangliomas,
small cell tumor of lung
II. Mesenchymal origin
1. Myogenic differentiation
a. ERMS b. ARMS.
2. Osteoid differentiation
a. Small cell osteosarcoma.
3. Chondroid differentiation a. Mesenchymal
chondrosarcoma.
4. Adipose tissue like differentiation a.
Myxoid/round cell liposarcoma.
Hematolymphoid origin
a. Lymphoma/“reticulum cell sarcoma.”
Malignant soft tissue tumors of uncertain type
a. Desmoplastic small round cell tumor
(DSRCT) b. Poorly differentiated synovial
sarcoma.

• Cytologically, these tumors are composed of a nearly uniform population of round
to oval cells with scanty, basophilic cytoplasm; mixed populations of small and
large cells are present in some tumors like neuroblastomas.
• These are also called small round blue cell tumors as the cells are blue, in the
sense that they have large hyperchromatic nuclei and a thin rim of cytoplasm.
• In general, these neoplasms consist of cells having diameters up to approximately
three times that of a small mature lymphocyte and typically possess only a single
hyperchromatic nucleus having finely granular, evenly distributed chromatin.
• Nucleoli can be unapparent, small, or quite prominent.
• The cytoplasm is generally scanty, resulting in a very high nuclear to cytoplasmic
ratio.

Ewing's Sarcoma and Primitive Neuroectodermal Tumor
• There is considerable clinical and histologic overlap between this tumor and
the PNET. Ewing's sarcoma arises within the bone, but can also occur within
the soft tissue (extraosseous Ewing's sarcoma) and PNET arises within soft
tissues.
• PNET is a small round cell malignancy of primitive, neuroectodermal tissue or
pluripotential, migratory neural crest cells that arises from the soft tissue or
bone, commonly affecting older children and adults.
• FNAC reveals the presence of tumor cells that are arranged in relatively small,
tight clusters with the presence of round or irregular nuclei lacking nucleoli.
These small blue cells have a high nucleocytoplasmic ratio. Two population of
cells have been described large chief cells and smaller dark cells.

Sharma S, Kamala R, Nair D, Ragavendra TR, Mhatre S, Sabharwal R, et al. Round cell tumors: Classification and
immunohistochemistry. Indian J Med Paediatr Oncol 2017;38:349-53.

Neuroblastoma.
(a) Cellular smears with dispersed
undifferentiated cells (MGG, ×200);
(b) Tumor cells are positive for NSE (IHC, 100);
(c) Tumor cells are negative for vimentin (IHC,
×100).

Immunohistochemistry of Round Cell Tumors
• CD 99
– CD 99 is a transmembrane glycoprotein of 30–32 KDa
– It plays a role in cellular adhesion and regulation of cellular proliferation
– It is specific for:
• Ewing's sarcoma – 90%
• Lymphoblastic lymphoma – 90%
• Synovial sarcoma – >75%
• Mesenchymal chondrosarcoma – 50%
• Osteosarcoma and desmoplastic round cell tumor – Rare
• Neuroblastoma – Never reported (-).
• NB 84
– It is sensitive marker for neuroblastoma (75%), Ewing's sarcoma (16%–25%)
– Also positive for RMS, WT, osteosarcoma, desmoplastic round cell tumor.
• S-100
– It is a marker for benign and malignant nerve sheath tumors
– Composed of two subunits α and β that combine to form 3 isotypes: α-α isotype found in the
myocardium, skeletal muscle and neurons, α-β isotype found in chondrocytes, glia and skin adnexae,
β-β isotype found in Langerhans and Schwann cells.

• Desmin
– It is the intermediate filament protein associated with both smooth and skeletal muscle differentiation
– Rarely expressed by myofibroblasts and their corresponding tumors
– In skeletal muscles desmin is localized to Z-zone between myofibrils when it serves as binding material for
contractile apparatus. In smooth muscles, it is associated with cytoplasmic dense bodies
– Desmin can also be expressed by nonmuscle cells including fibroblastic reticulum cells of lymph nodes,
submesothelial fibroblast, and endometrial stromal cells
– Expressed in PNET, desmoplastic round cell tumors, neuroblastoma, mesothelial cells and tumors, WT.
• Cytokeratins
– Used for distinguishing epithelial from nonepithelial tumors (lymphomas, sarcomas, melanomas)
– Expressed in: Carcinoma, epithelial sarcoma, leiomyosarcoma, mesothelioma
– Also expressed by round cell tumors such as Ewing's sarcoma/PNET, RMS, WT, desmoplastic round cell tumor.
• PAX 5
– PAX 5 is a member of the paired box transcription factors involved in the development and is expressed in
hematopoietic malignancies of B-cell lineage
– Expressed in cases of neuroendocrine carcinomas, urothelial tumors, Merkel cell carcinoma, glioblastoma, and
neuroblastoma
– Also positive for B-cell lymphoblastic lymphomas, WT and ARMS

Determining the cell size of Lymphoma
• In order to categorize the cell size, the neoplastic cells can
be compared with the reactive histiocytes interspersed
among the lymphoma cells.
• Small, medium-sized and large cells refer to cells with nuclei
smaller than, approximately the same size as, and larger
than those of the reactive histiocytes respectively.
• If histiocytes are not found, the endothelial cells nuclei can
be used instead as the “ruler” although they are certainly
less satisfactory because of their ovoid or elongated shape.
194

When classifying a lymphoma consider the
following:
• Cell size
• Nuclear configuration.
• Cytoplasmic characteristics
• Cellular organization{follicular vs. diffuse}
• Any other subsidiary feature.
195

Stains
Cells
cell membrane
all leucocytes except plasma
cells {which are negative or
variably positive}
For diagnosis of all lymphomas and leukemias
Negative for R.S cells in Classical Hodgkin’s Lymphoma
The general leucocyte marker is CD45RB
196

Most Useful Antibodies for
Assessment of Hematolymphoid
Proliferations
Problem to be addressed Recommended first line antibodies
B lineage? CD20 (or CD79a )
T lineage ? CD3
NK lineage ? CD56
Myeloid cell ? Myeloperoxidase
Follicular lymphoma Bcl – 2
B cell chronic lymphocytic leukemia CD5, CD23
Normal mantel zone cells IgD
197

Problem to be addressed Recommended first line antibodies
Mantel cell lymphoma Cyclin D1
Burkitt’s lymphoma Ki – 67
Anaplastic large cell lymphoma (ALCL) CD30, ALK – 1
Plasma cell CD20(negative), CD138 positive
Histiocyte CD68
Hodgkin’s lymphoma CD30, CD15
Langerhans cells S – 100 or CD1a
Follicular dendritic cell CD21 + CD35
198

Selected cell-typic markers commonly used in IHC
Muscle cells
Actin (pan-muscle specific or smooth muscle)
Caldesmon Desmin
Myoglobin Myogenin
MyoD
Hematopoietic cells
CD45 (common leukocyte antigen)
CD20 (B cells) CD79a (B cells)
CD15 (granulocytes, reed-sternberg cells)
CD68 (macrophage-monocytes)
CD3 (Tcells)
Myeloperoxidate (neutrophils)
Endothelial cells
Von Willebrand factor (factor VIII-related
antigen)
CD31
CD34
ERG
Neuroendocrine cells
Neuron-specific enolase
CD56
CD57
PGP5.5
Synaptophysin
Chromogranin
NeuroN
Neurofilaments

References
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Contributions, and Therapeutic Options. Anal Chem Insights. 2015;10(Suppl 1):1-10. Published
2015 Oct 29. doi:10.4137/ACI.S32730
• Rajendran A, Sivapathasundharam B. Shafer's Textbook of Oral Pathology. 7th ed. New Delhi:
Elsevier; 2012.
• Goldblum JR, Weiss SW. Enzinger and Weiss's Soft Tissue Tumors. 4th ed. Canada: Mosby; 2001.
• Sharma S, Kamala R, Nair D, et al. Round Cell Tumors: Classification and
Immunohistochemistry. Indian J Med Paediatr Oncol. 2017;38(3):349-353.
doi:10.4103/ijmpo.ijmpo_84_16
• Devoe K, Weidner N. Immunohistochemistry of small round-cell tumors. Semin Diagn Pathol. 2000
Aug;17(3):216-24. PMID: 10968707.
• Lopez A, Abrisqueta P. Plasmablastic lymphoma: current perspectives. Blood Lymphat Cancer.
2018;8:63-70. Published 2018 Oct 4. doi:10.2147/BLCTT.S142814

• Chang F. Desmoplastic small round cell tumors: cytologic, histologic, and immunohistochemical
features. Arch Pathol Lab Med. 2006 May;130(5):728-32.
• Sharma S, Kamala R, Nair D, Ragavendra TR, Mhatre S, Sabharwal R, et al. Round cell tumors:
Classification and immunohistochemistry. Indian J Med Paediatr Oncol 2017;38:349-53.
• Neville, Damm, Boquout; Oral & Maxillofacial Pathology; 2nd edition; 2004; Elsevier publications
• Cowson, Binnie, Speight, Barrett, Wright; Lucas’s pathology of tumors of oral tissues; 1998;
Churchill Livingstone press
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Sep;(2):1698-1700.
• John R. Goldblum, MD, FCAP, FASCP, FACG, Sharon W. Weiss, MD and Andrew L. Folpe, MD ;
Enzinger and Weiss's Soft Tissue Tumors ; 6th edition ; 2014 ; Elsevier publications
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doi:10.4103/0970-9371.54861

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