Centrocytes (small cleaved cells)
• Small cells
• Cytoplasm - scant
• Irregular or cleaved nuclear
• Condensed chromatin
These cells are majority in
• Large cells
• Cytoplasm – moderate
• Nuclei – round
• Regular nuclear contour
• With open nuclear chromatin
Nucleoli – multiple and several
(bound to the membrane)
Tumors showing these cells
Malignant lymphoma is a neoplastic proliferative process of the
lymphopoietic portion of the reticuloendothelial system that
involves cells of either the lymphocytic or histiocytic series in
varying degrees of differentiation and occurs in an essentially
homogenous population of a single cell type. (Lukes)
EVOLUTION OF LYMPHOMA
• Rappaport (considered cytologicaland
• Lukes and Collins (immunophenotype)(1973)
• Kiel Classification(Europe)(1973)
• REAL Classification(1992)
• WHO classification(2001)
• Update of WHO classification(2008
Rappaport Classification (1966)
• First popularly used system
• Divided growth patterns into nodular and diffuse;
• Cells types into well differentiated, poorly differentiated (cleaved
follicular center cells), histiocytic (large cells) undifferentiated
(round; between lymphocytes and histiocytic), and Burkitt’s.
Lukes-Collins Classification (1973)
• Based on proposed cell of origin; follicular center cells, cleaved or
uncleaved; immunoblasts; B or T Cells
Kiel Classification (1973)
• Based on low and high grade, Centroblastic, Lymphoblastic,
• Low grade: Lymphocytic, Lymphoplasmacytoid, Centrocytic,
WORKING FORMULATION FOR CLINICAL
• Establish a common language of communication between
pathologists and clinicians rather than to represent specific
• An individual patient can progress from one histologic type to
Low Grade: Small lymphocytic, follicular small
cleaved,follicular mixed(small cleaved and large cell)
Intermediate Grade: follicular large cell, diffuse large cell,
diffuse small cleaved cell, diffuse mixed (small and large cell)
High Grade: Immunoblastic, lymphoblastic, small non-cleaved.
Misc : Composite, Mycosis fungoides, Histiocytic,
Extramedullary plasmacytoma, Others
REAL/ WHO 2001/ WHO 2008 CLASSIFICATION OF
B – CELL LYMPHOMAS
REAL/ WHO 2001/ WHO 2008 CLASSIFICATION
OF THE T/NK CELL LYMPHOMAS
2008 WHO Classification of Hodgkin Lymphoma
HL is a type of malignant lymphoma in which Reed-Sternberg cells
are present in a “characteristic background” of reactive
inflammatory cells of various types, accompanied by fibrosis of a
Tumors of B cell origin - germinal center or post germinal center B cells
• It was named after Thomas Hodgkin who first described it in 1832.
• Dorothy Reed & Carl Sternberg first described the malignant cells of
HL called Reed Sternberg cells.
• Cervical lymphadenopathy is the most common head and neck
presentation for Hodgkin's lymphoma (HL).
• extranodal HL typically associated with generalized disease & a
consequence of local spread from adjacent lymph nodes.
A possible model of pathogenesis
loss of apoptosis
Cytokines (such as IL-5, IL-10, IL-13, and
TGF-β) and chemokines (such as TARC, MDC,
IP-10, and CCL28) are secreted by Reed-
They lead to florid accumulation of reactive
cells in tissues involved by classical HL.
These reactive cells produce factors that
support the growth and survival of the
tumor cells and further modify the reactive
FORMATION OF REED STERNBERG CELLS
Infects B cells Which has undergone VDJ recombination somatic
Will express LMP1( protein encoded by EBV genome)
upregulates NF kb
Which rescues crippled germinal centre B cells that cannot express
Igs from apoptosis
Promote lymphocyte survival & proliferations
Produce reed sternberg cells
HODGKINS LYMPHOMA IN ORAL CAVITY
Primary / relaspsed HL in oral soft tissue & jaws are rare
oral mucosa – only 12 cases
jaw – extremely rare
The primary site - Waldeyer’s ring
• base of tongue
• posterior pharyngeal wall
DISSEMINATED HL more common – only 5 cases
(tongue, palate, tonsil)
A 71 year old male presented with
a swelling in the left mandibular
buccal vestibule and buccal
mucosa, lateral to his left mandible.
NON-HODGKIN’S LYMPHOMAS (nhls) represent a
heterogeneous group of malignancies that arise from the lymphoid
system which can involve
- both lymph nodes & lymphoid organs
- extranodal organs & tissues
In oral cavity:
NHLs of the oral cavity are rare
Account for only 2-3% of all the lymphomas reported.
Oral cavity - large B cell lymphoma – 60% Of cases
Anatomic location of thirty-one cases of NHL in the oral
region arising in soft tissues
Disease of oral cavity is extranodal.
• The disease can be due to Manifestation of disseminated disease
• Primary disease of the oral tissues and has not spread to other sites.
(Sole expression of the disease or the initial manifestation of
1. Oral soft tissues
2. Centrally within jaws.
Presentation – oral lesions grow rapidly and then ulcerate. Some cases
they can become large, fungating, necrotic, foul smelling masses.
Soft tissue mass
Non tender diffuse swellings. Most common
buccal vestibule, posterior hard palate or gingiva.
swellings have a boggy consistency.
Lesion may be erythematous or purplish. May or may not be ulcerated.
Lymphomas of bone in oral cavity
• vague pain or discomfort which might be mistaken form
• Tooth mobility and pain may develop.
• Parasthesia in the mandible (numb chin syndrome)
• Ulcerated – then bony expansion eventually perforating the
cortex producing a soft tissue swelling.
Systemic symptoms like fever, night sweats, weight loss and
fatigue, pruritis noted.
Of a total of 1,467 cases of extranodal NHL studied by Freeman and
417 (28percent) - head and neck region.
• Tonsils, 32 %
• Salivary glands 16.5 %
• Oral cavity 9.5 %
• Nasopharynx - 8.8 %
• Thyroid - 8.6 %
• Nose - 7.9 %
• characterized by 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 (>20 μm).
• 7th decade of life
• clinically a rapidly enlarging
• often symptomatic mass is typically seen
mediastinum, GIT, bone marrow, CNS, breast & testes.
Waldeyer's ring, maxillary alveolus, maxillary vestibule & posterior
DIFFUSE LARGE B-CELL LYMPHOMA
Centroblasts ( large atypical
pleomorphic lymphocytic nucleus
with multiple nucleoli)
Swelling in the anterior hard palate
with surface ulceration
SUBCLASSIFICATION OF DLBCL affecting oral cavity
CLINICAL, HISTOLOGICALAND IMMUNOLOGICAL DD
CLINICAL, HISTOLOGICALAND IMMUNOLOGICAL DD
Oral PBL is rare
recently described B-cell derived lymphoma
most commonly seen in patients with HIV infection.
characterised by a diagnostic triad of predilection for
1. Gingivo-buccal complex mucosa,
2. Classical plasmablastic morphology with the lack of neoplastic
3. A limited immunohistochemical panel
LCA (+/), CD138/VS38c diffuse positivity,
light chain restriction & high Mib-1(Ki 67) index.
Prognosis is usually poor regardless of the site of origin.
PBL has found a place in the World Health Organization
(WHO) 2000 classification as a distinct type of AIDS-related
lymphoma and is accepted to be a variant of DLBCL.
• highly aggressive NHL that has the highest cell proliferation rate
among human neoplasms.
• occurs predominantly in the first decades of life
• mostly in males
• with significant affinity for gnathic bones – 50 – 70% cases
• maxilla: mandible – 2:1
• Posterior segments of the jaw
• Sometimes – 4 quadrant involvement
Jaw involvement seems to be age related:
• 90% - 3 yrs old pt
• 25% - pts older than 15 yrs
There are three clinical variants of BL:
1. Endemic BL - children in Africa and Papua New Guinea as jaw or
2. Sporadic BL- no specific age or geographic predilection and occurs
with abdominal or nodal involvement
3. HIV associated BL
A retrospective review of patients with
Burkitt's lymphoma in the facial (1978 -
SITES: mandible, maxilla, palate
TUMOUR- facial swelling /exophytic mass
/ as an ulcer..
H/P: sheets of round cells
with vesicular nuclei &
condensed nuclei. Few
macrophages were seen
between the tumour cells .
MANTLE CELL LYMPHOMA
• MCL includes small-medium
sized lymphoid cells and
accounts for 6–10% of all B-cell
• Common extra-nodal sites -
• Waldeyer's ring, gastrointestinal
tract, bone marrow and
• INTRORAL: 9 cases
• Common site: palate….floor of
mouth…Base of tongue
Palatal MCL is mostly seen in
elderly people and may be
masked with the presence of
Follicular lymphomas accounts for one third of NHL.
• This is a low to intermediate grade lymphoma
• show a follicular architecture
• represents the neoplastic counterpart of germinal center B
Few case reports – in salivary glands
• Among lymphomas originating from salivary glands, the ratio of
follicular lymphoma is very low.
A case follicular lymphoma which
presented as a salivary gland
tumour – submandibular gland
• Destruction of salivary gland
• No acinar cell/ducts were seen.
• The entire mass was infiltrated
by proliferation of lymphocytes
which were arranged in sheets..
• neoplastic lymphocytes in a
neoplastic cells expressing strong
positivity for Bcl-2.
neoplastic cells expressing strong
positivity for CD20
EXTRANODAL MARGINAL ZONE B-CELL LYMPHOMA
• Lymphoma of MALT.
• Indolent lymphoma in mucosal sites and in extranodal tissues
including the gastrointestinal tract, salivary glands, lung, thyroid
gland, and skin.
• Any age-group or gender can be affected
• Associated with Sjogren's syndrome
• female predominance.
• Populated by lymphocytes such as T cells and B cells, as well
as plasma cells and macrophages
• Sheets of monocytoid B cells & includes lymphoepithelial
CD 19 +
CD 20 +
CD 10 – ( FOLLICULAR L)
CD 5 -- (MANTLE CELL
MYCOSIS FUNGOIDES –Cutaneous T-cell
• is a distinctive variant of NHL
• Characterized by a malignant proliferation of helper (CD4+)
T-lymphocytes & less commonly suppressor (CDS+) T-
• with a predilection to involve the skin.
• The mouth is an rare site
• only 31 cases of oral CTCL have been reported in English
• Oral lesions almost always develop after cutaneous
• ulcerated tumors, indurated plaques, papules, leukoplakia-like
lesions, nodules, and multiple erosions
• Dysphagia commonly associated
Oral lesions appear to be a late manifestation of mycosis
fungoides that arise on skin
• consist of a dense infiltrate of atypical
• characteristic Pautrier's microabscesses
can be found.
• These features are similar to those seen
in cutaneous lesions
EXTRANODAL NASAL-TYPE NATURAL KILLER (NK)/T-
Represents a rare entity
Typically originating in the nasal cavity
palate or midfacial region.
Signs and symptoms
• non-specific rhinitis and/or sinusitis
• nasal obstruction
• epistaxis, facial swelling
• development of deep necrotic ulceration in the midline of the
palate, causing an oronasal defect.
• Differential diagnosis: fungal infections, Wegener’s
granulomatosis, tertiary syphilis, other non-Hodgkin’s
lymphomas & malignant epithelial midline tumors.
LYMPHOMAS OFSALIVARY GLANDS
LYMPHOMAS – LYMPH NODES
EMBEDDED IN SG
1.7% - BRITISH SERIES OF 40 CASES OF SG TUMOURS
2.45% – AMERICAN SERIES OF 366 CASES
• LOW GRADE LYMPHOMA -
Predominant in all studies
• HIV/AIDS Associated – high grade
large cell lymphoma
• Parotid gland 80% of cases
• Submandibular gland (16%)
• Sublingual gland and minor salivary glands (2%).
• Lymphoid tissues closely asso with SG
• Especially parotid gland- 5 – 10 lymph node embedded
• Several lymph node – submaxillary gland
• SG acini & ducts present in medulla of upper cervical lymph
• These nodes – target for viral/bacterial infections
anti- immune diseases
Lymphomas – site for long standing benign lesions
COMMON – 1. Marginal zone Bcell L
Ann Arbor Staging System
• Stage I: Single lymph node region (I) or single extralymphatic organ or
• Stage II: > 2 lymph node regions on same side of diaphragm (II) or with
limited, contiguous extra lymphatic tissue involvement (IIE)
• Stage III: both sides of diaphragm involved, may include spleen (IIIS) or
local tissue involvement (IIIE)
• Stage IV: multiple/disseminated foci involved with > 1 extralymphatic
organs (i.e. bone marrow)
(A) or (B) designates absence/presence of “B” symptoms
*(E) Localized, solitary involvement of extralymphatic tissue, excluding liver
and bone marrow 80
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A: absence of B symptoms
B: fever, night sweats, weight loss
• Blood test
• Lactate Dehydrogenase (LDH)
• Bone Marrow Biopsy
• CT, and PET scans
• Flow Cytometry
• Fluorescence in Situ Hybridization (FISH): to detect changes in
• Polymerase Chain Reaction (PCR): to detect specific DNA
sequences that occur in some cancers
• DNA Microarray
Oral lymphoma often is a component of a disseminated disease process that may
involve regional nodes as well. Other times, it may represent a primary extranodal
disease confined to oral cavity or jaws, which is very rare
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• NEVILLE – Oral and maxillofacial pathology
• SHAFERS - Oral and maillofacial pathology
• ROBBINS – Basic pathology 8th edition
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