Hematological Malignancies

(Lymphoma)
Dr. Naveed Khawaja
HOD/ Associate Professor Oral Pathology
 Contents
Ref book: Contemporary OMFP

Hematological Malignancies (blood neoplasm)

1. Hodgkin’s lymphoma CH 12/ P-406
2. Non-Hodgkin’s lymphoma CH 12/ P-409
3. Burkitt’s lymphoma CH 12/ P-414
4. Multiple Myeloma CH 12/ P-415
5. Plasmacytoma CH 12/ P-415
6. Langerhans cell Histiocytosis CH 4/ P-124
 Learning Outcomes
• Should know definitions
• Should know the concept of the
diseases by pathogenesis/ origin
• Clinical and radiographic features
are an important
• Histopathology – main diagnostic
feature but brief
• Treatment is also an important.
 Multiple Myeloma (MM)
• A disseminated neoplasm of differentiated B lymphocytes (plasma cells)
located within bone.
• Represents a third type of lymphoma that arises from bone marrow-based
B cells, specifically those that have undergone terminal differentiated into
plasma cells.
• It eventually becomes disseminated, involving multiple skeletal sites.
 Clinical features
• Affects me and women equally and usually arise
during the fourth, fifth and sixth decades of life.
• A characteristic feature is deep bone pain due to
osteolytic lesions encountered in various bones.
• Radiographically, their radiolucent lesions are
relatively well defined, not corticated around
their boundaries.
 Radiographic features
• In the jaws, the disease may stimulate a toothache.
• Dental radiographs show coin-shaped, punched-out
radiolucencies or widespread osseous destruction.
• Radiographic margins are “mouth-eaten” without
cortication.
• Teeth within the area of malignancy may become
loose.
 Histopathology (MM & SP)
• Multiple myeloma and solitary plasmacytoma
show the same microscopic features.
• Diffuse sheets of atypical plasma cells are
encountered with minimal fibrous stroma;
instead, small capillary channels course
among the plasma cells.
• Importantly, binucleated forms are common,
• mitotic figures may be observed, and
• some degree of nuclear pleomorphism exists.
 Multiple Myeloma
• Cell population is usually homogenous.
• Furthermore, the plasma cells of inflammation are polyclonal and will therefore
express к and λ immunoglobulin light chains using immunohistochemistry.
• It (being a disseminated disease of immunoglobulin-secreting plasma cells) effects a
change in serum immunoglobulin levels. The total gamma globulins will be
increased; on serum immunoelectrophoresis, a monoclonal spike representing a single
immunoglobulin class will account for the increased levels.
• Light chains from immunoglobulins are often excreted into the urine in myeloma and
are referred to as Bence Jones protein.
 Treatment
• Carries a poor prognosis despite intensive chemotherapy.
• Multidrug regimens are used to arrest cell division in an attempt to
eliminate the disease.
• Total body radiation with bone marrow transplantation is another
treatment option.
 Solitary Plasmacytoma (SP)
• A single tumor of plasma cells often located in the soft tissue of the upper
air passages.
• The plasmacytoma (solitary) represents a clonal proliferation of plasma
cells in the extramedullary site.
• Some patients have survived for many years with solitary extramedullary
plasmacytoma, whereas others have eventually developed disseminated
multiple myeloma.
• The solitary plasmacytoma occurs as a pendulous
mass, usually identified within nasopharynx.
• Involvement of oral mucosa is extremely rare.
• These plasma cell tumors are usually brought to the
patient’s attention by such symptoms as
nasal speech or nasal stuffiness.
 How they are different?
• Solitary plasmacytoma and multiple myeloma are types of cancer that
form from plasma cells. Plasma cells are white blood cells that work as
part of the immune system. Normally, these cells produce antibodies,
which are proteins that help recognize and fight infection.
• However, genetic defects can occur that cause plasma cells to multiply
uncontrollably, giving rise to a group of diseases known as plasma cell
neoplasms (plasma cell cancers) such as solitary plasmacytoma and
multiple myeloma.
 Histopathology (MM & SP)
• Multiple myeloma and solitary plasmacytoma
show the same microscopic features.
• Diffuse sheets of atypical plasma cells are
encountered with minimal fibrous stroma;
instead, small capillary channels course
among the plasma cells.
• Importantly, binucleated forms are common,
mitotic figures may be observed, and some
degree of nuclear pleomorphism exists.
Langerhans’s Cell Histiocytosis (LCH)

• A probable neoplastic proliferation of Langerhans type of histiocytic cells

with a wide spectrum of biologic behavior ranging from a single lesion of
mandible to diffusely distributed bone lesions in combination with organ
and other soft tissue lesions; consists of S-100 and CD1a-positive
histocytes containing Birbeck granules and accompanying accumulations
of eosinophils.
• Principal cells of histiocytic system are
• Mononuclear phagocyte
• Dendritic Langerhans cell
• Lymph node follicular dendritic cell
• The cell type most common involved in a proliferative disorder
is Langerhans cell, and disease is designated as Langerhans cell
histiocytosis (LCH)
• It is estimated that LCH occurs at the rate of 0.2 to 0.5 cases per 100,000
children per year.
• Lesions with same basic histopathologic features were originally
considered three separate diseases under Histiocytosis X.
• Letter-Siwe disease
• Hand-Schuller-Christian disease
• Eosinophilic granuloma
• Langerhans cell histiocytosis (named in 1987 by histiocyte society).
• Idiopathic histiocytosis
• Langerhans cell granuloma
• Langerhans cell disease
• The studies leading to these conclusions used DNA technology on cells
from each of the clinical disease types and determined that cells were a
single clonal proliferation of CD1a-positive Langerhans cell.
 Clinical features
• Chronic focal
• A solitary lesion in one bone but occasionally in multiple bones, with no soft tissue or organ
involvement (previously designated as eosinophilic granuloma).
• Chronic disseminated
• Involving multiple bones, organ, lymph nodes, and occasionally skin (previously designated
as Hand-Schuller-Christian disease).
• Acute disseminated
• Involving most organs, lymph nodes, bone marrow, and skin of infants (previously
designated as Letter-Siwe-disease).
 Radiographic features
• Chronic focal form of LCH in oral cavity occur with the
greatest frequency.
• Common in teenagers and young adults as an area of
discomfort in which radiographs reveal a solitary
intraosseous punch out lesion around and beneath the roots.
• The lesions may involve several teeth and appear as focal
areas of advanced periodontal disease in which the teeth
seem to be floating in space because of the lack of
surrounding bone.
• In edentulous or nontooth-bearing areas, the lesion
presents as a demarcated radiolucency.
• In other areas, the lesion closely resembles a large
periapical abscess with teeth erroneously treated
endodontically.
• Chronic disseminated form (Hand-Schuller-Christian
disease) has bone lesion similar to the chronic focal
form and also soft tissue lesions; common under 10
years of age.
• The status of acute disseminated form (Letter-Siwe-
disease) is in question, because many believe that cases
attributed to this form may represent other disease
processes such as acute forms of lymphoma, common in
infants who follow a rapidly fatal course because of
extensive involvement of skin and visceral organs by
anaplastic cells.
 Histopathology
A
A. Large sheets of Langerhans histiocytic cells
with eosinophilic cytoplasm and centrally
placed nuclei with occasional multinucleated
cells interspersed with other inflammatory cells.
B. Presence of abundant focal concentrations of B
eosinophils, that is useful in differentiating
common periapical and periodontal
inflammatory lesions.
• The presence of Birbeck granules (BG)
confirms a diagnosis of LCH. These
intracytoplasmic structures are unique in
mononuclear Langerhans histocytic cells and
appear either as elongated thin rods or tennis
racket shaped.
• Ultrastructure of Langerhans histiocytes
reveal rods and tennis racket-shaped
intracytoplasmic structure.
• Using immunochemistry, the
mononuclear histiocytic cells are S-100
and CD1a-positive staining (brown) with
S-100 immunostain.
 Treatment
• Eosinophilic granuloma
• easily accessible to surgical intervention, thorough curettage is treatment of choice.
• For more diffusely located inaccessible lesions
• Chemotherapy with cytotoxic agents is commonly used.
• Recurrence and the development of new lesions are often problematic,
requiring long-term follow-up
 Clinical aspects
Oral manifestations are important to know to diagnosis.
Should know histopathological diagnostic features.
All are non-odontogenic even teeth and gingiva involved, have to know
differential points.
Could be encountered in differential diagnosis with odontogenic lesions.
• Most tumours are solitary, many can independently involve more than one
jaw quadrant.
• Tooth displacement and root resorption are common.
• In AIDS patients, non-Hodgkin lymphoma is second most prevalent
neoplasm.
• Similar microscopic features to Burkitt lymphoma.