10. 10
Centrocytes (small cleaved cells)
• Small cells
• Cytoplasm - scant
• Irregular or cleaved nuclear
contours
• Condensed chromatin
These cells are majority in
follicular lymphoma
Centroblasts
• 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
Follicular lymphoma
12. 12
Definition
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)
MALIGNANT
LYMPHOMAS
NON
HODGKINS
Lymphomas Leukemias
HODGKINS
14. EVOLUTION OF LYMPHOMA
CLASSIFICATION
• Rappaport (considered cytologicaland
architectural features)(1966)
• Lukes and Collins (immunophenotype)(1973)
• Kiel Classification(Europe)(1973)
• WorkingFormulation(USA)
• REAL Classification(1992)
• WHO classification(2001)
• Update of WHO classification(2008
15. CLASSIFICATION
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,
Immunoblastic
• Low grade: Lymphocytic, Lymphoplasmacytoid, Centrocytic,
Centroblastic
16. WORKING FORMULATION FOR CLINICAL
USE (1982)
• Establish a common language of communication between
pathologists and clinicians rather than to represent specific
disease entities.
• An individual patient can progress from one histologic type to
another
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
17. REAL/ WHO 2001/ WHO 2008 CLASSIFICATION OF
B – CELL LYMPHOMAS
18. REAL/ WHO 2001/ WHO 2008 CLASSIFICATION
OF THE T/NK CELL LYMPHOMAS
22. 22
Definition (WHO)
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
variable degree.
Histogenesis
Tumors of B cell origin - germinal center or post germinal center B cells
HODGKIN LYMPHOMA
• 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.
24. A possible model of pathogenesis
germinal
centre
B cell
transforming
event(s)
loss of apoptosis
RS cell
inflammatory
response
EBV?
cytokines
24
25. 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-
Sternberg cells.
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
cell response.
25
26. 26
FORMATION OF REED STERNBERG CELLS
EBV
Infects B cells Which has undergone VDJ recombination somatic
hypermutation
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
37. 37
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
• Nasopharynx
• Tonsil
• base of tongue
• posterior pharyngeal wall
DISSEMINATED HL more common – only 5 cases
(tongue, palate, tonsil)
38. 38
A 71 year old male presented with
a swelling in the left mandibular
buccal vestibule and buccal
mucosa, lateral to his left mandible.
NODULAR
SCLEROSIS
40. 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
45. 45
Oral manifestations
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
generalized disease).
Oral sites
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.
46. 46
Lymphomas of bone in oral cavity
• vague pain or discomfort which might be mistaken form
toothache.
• 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.
47. 47
Of a total of 1,467 cases of extranodal NHL studied by Freeman and
co-workers
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 %
48. 48
• 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
Extraoral sites:
mediastinum, GIT, bone marrow, CNS, breast & testes.
Oral site:
Waldeyer's ring, maxillary alveolus, maxillary vestibule & posterior
palate.
DIFFUSE LARGE B-CELL LYMPHOMA
49. 49
Centroblasts ( large atypical
pleomorphic lymphocytic nucleus
with multiple nucleoli)
Swelling in the anterior hard palate
with surface ulceration
53. 53
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
plasma cells
3. A limited immunohistochemical panel
CD20 negativity
LCA (+/), CD138/VS38c diffuse positivity,
light chain restriction & high Mib-1(Ki 67) index.
Prognosis is usually poor regardless of the site of origin.
PLASMABLASTIC LYMPHOMA
54. 54
Plasmablastic lymphoma
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.
55. 55
BURKITT LYMPHOMA
• 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
56. 56
There are three clinical variants of BL:
1. Endemic BL - children in Africa and Papua New Guinea as jaw or
orbital masses
2. Sporadic BL- no specific age or geographic predilection and occurs
with abdominal or nodal involvement
3. HIV associated BL
57. 57
A retrospective review of patients with
Burkitt's lymphoma in the facial (1978 -
1997) .
SITES: mandible, maxilla, palate
TUMOUR- facial swelling /exophytic mass
/ as an ulcer..
58. 58
H/P: sheets of round cells
with vesicular nuclei &
indistinct cytoplasm
interspersed with
lymphocytes with
condensed nuclei. Few
macrophages were seen
between the tumour cells .
60. 60
MANTLE CELL LYMPHOMA
• MCL includes small-medium
sized lymphoid cells and
accounts for 6–10% of all B-cell
lymphomas.
• Common extra-nodal sites -
RARE
• Waldeyer's ring, gastrointestinal
tract, bone marrow and
peripheral blood.
• 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
prosthesis
62. 62
Nuclei of small cells have
distinct hyperchromatism.
Mild nuclear
pleomorphism is also
evident
Diffuse small cell
lymphocytic infiltration is
the predominant component
on histology.
63. 63
Tumoral cells stained diffusely
positive with CD20
Tumoral cells showed nuclear
positivity with cyclin D1
staining
65. 65
FOLLICULAR LYMPHOMA:
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
lymphocytes.
Few case reports – in salivary glands
• Among lymphomas originating from salivary glands, the ratio of
follicular lymphoma is very low.
66. 66
A case follicular lymphoma which
presented as a salivary gland
tumour – submandibular gland
• Destruction of salivary gland
architecture.
• No acinar cell/ducts were seen.
• The entire mass was infiltrated
by proliferation of lymphocytes
which were arranged in sheets..
• neoplastic lymphocytes in a
follicular pattern.
68. 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
69. 69
• Sheets of monocytoid B cells & includes lymphoepithelial
formations
IMMUNOPHENOTYPE
CD 19 +
CD 20 +
CD 10 – ( FOLLICULAR L)
CD 5 -- (MANTLE CELL
L)
70. 70
MYCOSIS FUNGOIDES –Cutaneous T-cell
lymphoma/SEZARY SYNDROME
• is a distinctive variant of NHL
• Characterized by a malignant proliferation of helper (CD4+)
T-lymphocytes & less commonly suppressor (CDS+) T-
lymphocytes.
• with a predilection to involve the skin.
• The mouth is an rare site
• only 31 cases of oral CTCL have been reported in English
literature
• Oral lesions almost always develop after cutaneous
lesions
72. 72
Clinical presentation
• 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
73. 73
• consist of a dense infiltrate of atypical
pleomorphic lymphocytes.
• characteristic Pautrier's microabscesses
can be found.
• These features are similar to those seen
in cutaneous lesions
74. 74
EXTRANODAL NASAL-TYPE NATURAL KILLER (NK)/T-
CELL LYMPHOMA
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.
76. 76
LYMPHOMAS OFSALIVARY GLANDS
LYMPHOMAS – LYMPH NODES
LYMPHOID TISSUES
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
77. 77
• Parotid gland 80% of cases
• Submandibular gland (16%)
• Sublingual gland and minor salivary glands (2%).
79. 79
PATHOGENESIS:
• 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
nodes
• These nodes – target for viral/bacterial infections
anti- immune diseases
Lymphomas – site for long standing benign lesions
Sjogrens lymphadenopathies
HIV lymphadenitis
COMMON – 1. Marginal zone Bcell L
2. DLBCL
80. Ann Arbor Staging System
• Stage I: Single lymph node region (I) or single extralymphatic organ or
site (IE)
• 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
81. Stage I Stage II Stage III Stage IV
Staging of lymphoma
A: absence of B symptoms
B: fever, night sweats, weight loss
81
82. DIAGNOSIS
• Blood test
• Lactate Dehydrogenase (LDH)
• Biopsy
• Bone Marrow Biopsy
• CT, and PET scans
83. • Immunohistochemistry
• Flow Cytometry
• Fluorescence in Situ Hybridization (FISH): to detect changes in
specific chromosomes.
• Polymerase Chain Reaction (PCR): to detect specific DNA
sequences that occur in some cancers
• DNA Microarray
84. 84
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
85. 85
REFERENCES:
• IOACHIMS – Lymph node pathology 4th edition
• NEVILLE – Oral and maxillofacial pathology
• SHAFERS - Oral and maillofacial pathology
• ROBBINS – Basic pathology 8th edition
• Eisenbud L,Oral presentations in non-Hodgkin's lymphoma: a
review of thirty-one cases. Part II. Fourteen cases arising in
bone. Oral Surg Oral Med Oral Pathol. 1984;57:272–80.
• Kolokotronis , et al. Localized B-cell non-Hodgkin's lymphoma of
oral cavity and maxillofacial region: A clinical study. Oral Surg Oral
Med Oral Pathol Oral Radiol Endod. 2005;99:303–10.
86. 86
• Vega F, Lin P, Medeiros LJ: Extranodal lymphomas of the head
and neck. Ann Diagn Pathol 9:340, 2005
• Wertheim L, Smith GS. Mycosis fungoides. Arch Dermatol
Syphilol 1948; 57: 625 ± 635.
• Tolman MM. Mycosis fungoides in a 56-year-old woman. Arch
Dermatol Shypilol 1949; 60: 929 ± 930.
• Cho G, Suh IS, Tak KS, Park YK, Ko EY, Sung HM, et al.
Primary Parotid Non-Hodgkin’s lymphoma: Case report. J
Korean Cleft Palate-Craniofac Assoc 2010;11:99-102.
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HIV-associated lymphoblastic lymphoma in the oral cavity: a
case report. J Oral Maxillofac Surg 2007: 65: 1361–1364
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