Histology and pathology of lymph nodes

1. Presented by
Dr. Anjum Baker
II MDS postgraduate
Dept. of Oral Pathology & Microbiology,VIDS&RC
SEMINAR#8

2. Contents
• Introduction
• Overview of Lymphoid organs
• Embryology of lymph nodes
• Anatomy of head and neck nodes
• Lymphatic drainage of oral cavity
• Clinical examination of head and neck nodes
• Histology of Lymph nodes including cytology
• Pathology of lymph nodes
oInfections
oReactive hyperplasias
oLymphoid neoplasms
oOthers

3. INTRODUCTION
• Lymphoid system is a part of the hematopoietic system represented by
thymus, lymph nodes and spleen
• Lymph nodes form a part of the immune system as well as the circulatory
system as it collects and drains lymph and are distributed along the course of
the larger lymphatic vessels.
• Lymph originates as blood plasma, in tissue capillary bed, plasma leaves the
circulatory system to become interstitial fluid.
• 90% of interstitial fluid is returned to capillary bed and drains via venous
channels.Remaining 10% is drained via lymphatic system and makes up the
lymph

4. LYMPHOID ORGANS
• CENTRAL/PRIMARY
• Where new lymphocytes are
produced
• Bone marrow
• Thymus
• PERIPHERAL/SECONDARY
• Where lymphocytes respond
to antigens
• Lymph nodes
• Spleen
• Tonsils
• Mucosa/skin associated
lymphoid tissue (MALT)

5. • EMBRYOLOGY
• Develops from lateral plate
mesoderm
• Lymphatic sacs develop from
endothelial outgrowths of large
central veins
• Sacs are invaded by mesenchymal
cells that proliferate and
aggregate
• Ist trimester end- foci of
lymphoblasts
• 2nd trimester end-Organisation
into cortex, medulla and primary
follicles

6. ANATOMY OF H&N NODES
•Distributed in 3 regions
•1. peripheral nodes
i. circular chain/cervical collar/horizontal superficial
ring
ii. deep inner circle/ horizontal deep ring
•2. Deep cervical nodes/vertical chain
•Waldeyer’s ring

7. PRINCIPAL H&N NODES
Rouviere in 1938 divided the nearly 300 lymph nodes of
head and neck into 10 principal groups
• SUPRAHYOID
• 1. Occipital
• 2. Mastoid
• 3. Parotid
• 4. Submandibular
• 5. Facial
• 6. Submental
• 7. Sublingual
• 8. Retropharyngeal
• 9. Anterior cervical
• 10. Lateral cervical
• INFRAHYOID
• 1. Anterior cervical
• A)Juxtrvisceral
• B) prelayngeal
• C) Pretracheal
• D) prethyroid
• E) Lateral tracheal
• 2. Lateral cervical
• A) Deep
• B) Superficial

8. WALDEYER’S RING
•Immunosurveillence organs of head and neck
•Palatine tonsils
•Lingual tonsils
•Tubal tonsil
•Phayngeal tonsil

9. LYMPHATIC DRAINAGE

10. CLINICAL EXAMINATION

11. CLINICAL FINDINGS
FINDING INTERPRETATION
Firm,tender,enlarged,warm Inflammation
Firm to fluctuant, nontender,enlarged,mobile, Chronic inflammation/chronic abscess
(TB,HIV etc)
Tensely filled balloon/grape Acute abscess
Nontender,enlarged,rubbery consistency Post infection
Firm,nontender,matted,fixed,slowly enlarging Malignancy
Diffuse bilateral involvement Systemic malignancy
Localised involvement Localised malignancy
Posterior cervical lymph node enlargement Upper respiratory tract infection

12. •SURGICAL DISSECTION

13. HISTOLOGY OF LYMPH NODES
•CAPSULE
•OUTER CORTEX
•INNER MEDULLA

16. •PRIMARY FOLLICLES
• In the absence of immune
stimulation
•SECONDARY FOLLICLES
OR GERMINAL CENTERS
• In the presence of immune
stimulation.

17. CELLS OF LYMPH NODES
A.SMALL
LYMPHOCYTES
 T/B cells
 Effector/memory
 Lineage- by location
in node (Lymphocyte
homing)
 Clumped chromatin-
non activated
 Stage of maturation-
IHC/molecular
techniques

18. B. GERMINAL CENTRE CELLS
• Replicating and post-replicating B cells
• I)Noncleaved cells, small and large
• Replicating populations- expanding antigen responsive cells.
• Round nuclei but larger than resting small lymphocyte
• Open or vesicular chromatin
• Recognizable nucleoli.
• Nucleus clear -->genetic material unwound for replication.
• Size, large or small compared nucleus of macrophage.
• 2)Small cleaved cells- ( CENTROCYTES)
• Nonreplicating population
• Post mitotic memory or plasma cell precursors
• Clumped chromatin
• Irregular folded and cleaved nuclear
profiles

19. REACTIVE GERMINAL CENTRE
MZ
LZ
DZ

21. 3.IMMUNOBLASTS
•Replicating large cells found outside the germinal
centers.
•May be of B or T cell type
•Have nuclear characteristics of replicating
lymphocytes- Vesicular chromatin ,Nucleoli

22. 4. ACCESSORY CELLS
I) Antigen processing cells
• Interdigitating reticulin cells- T cell paracortex
• Dendritic reticulin cells- B cell germinal centers
• Process and present antigen to B and T lymphocytes
• Invisible in normal lymph node
2) Macrophages
 Phagoctytic cells of lymph node
 Tingible body macrophages of germinal centers
 Medullary and subcapsular sinus macrophages-
Abundant pale cytoplasm
Oval nucleus, single small nucleolus

23. PATHOLOGY OF LYMPH NODES
•Infections
•Reactive hyperplasias
•Malignant lymphomas
•Metastatic tumors
•Others

24. INFECTIONS
•SPECIFIC
i. Bacterial-TB, syphilis, brucellosis
ii. Viral- infectious mononucleosis,PGL OF HIV,LGV
iii. Fungal- histoplasmosis, blastomycosis,coccidomycosis
iv. Parasitic- Filariasis,toxoplasmosis
• NONSPECIFIC
i. Acute
ii. Chronic

25. BACTERIAL INFECTIONS
Common Features
•Increase in no of Germinal centres
•Hyperplasia of paracorticalT cell zones
•Granulomatous lesion –caseous /non caseous
•Identification of causative organism is only by
culture/serology.

26. TUBERCULAR LYMPHADENITIS
• The characteristic morphological element is the tuberculous granuloma
(caseating tubercule) which maybe confluent.
• This consists of Langhan’s giant cells surrounded by epithelioid cells ,T cell
lymphocytes and fibroblasts.
• Granulomatous tubercules eventually develop central caseous necrosis and
tend to become confluent, replacing the lymphoid tissue.
• Stages ofTubercular Lymphadenitis -
• Lymphadenitis
• Periadenitis
• Cold abscess
• 'Collar stud' abscess
• Sinus
• Syphilitic lymphadenitis- Similar presentation but rare.

28. ACUTE NONSPECIFIC LYMPHADENITIS
• Prominent large reactive germinal centres
• Numerous mitotc figures
• Macrophages with particulate debris
• Pyogenic infection- neutrophils
• Necrosis at centre of follicle
• Severe infections- acute inflammatory cell infiltrate with
effacement of LN architecture
• Less severe infections- scattered neutrophil infiltrate in follicles and
accumulation in lymphoid sinuses
• Hyperplasia of endothelial cell lining sinuses

30. CHRONIC NONSPECIFIC LYMPHADENITIS
• Germinal centres in secondary follicles
• Chronic inflammatory cells-Macrophages, plasma cells and
eosinophils.
• Necrosis of entire follicles
• Fibrosis
• Thickened sinus walls
• Effacement of LN architecture

32. Infectious Mononucleosis
• EBV infection in young adults- lymphadenopathy
• Periperal blood lymphocytosis
• Diagnosis-Serology
• H/P
• Marked paracortical hyperplasia
• Early stages- follicular hyperplasia
• Increased population of small lymphocytes, plasmacytoid
lymphocytes,immunoblasts,R-S cells, histiocytes and plasma cells
• Foci of coagulative necrosis
• Late Stages- effacement of architecture ,sometimes only residual
follicles/patent sinuses can be identified
• DD- Lymphomas
• IHC- CD45+ (immunoblasts), CD15-(R-S Cells)

34. HIV INFECTION
 Persistent generalized lymphadenopathy
 H/P
 Initial marked reactive follicular hyperplasia
 Large bizzare germinal centres, Minimal/absent mantle zone
 Follicle lysis- small lymphocytes infiltrate GC
 Marked monocytoid B cell reaction in sinuses
 Paracortical regions are not prominent
 Chronic condition
 Involution of LN
 Lymphocyte depletion
 Only follicular dendritic cells remain
 Plasma cells, histiocytes and vascular network remains
 Wide patent sinuses
 Later stages- malignant neoplasms, increased histiocytes, MAC infections

36. REACTIVE HYPERPLASIAS
• 3 PROMINENT PATTERNS
1. Follicular hyperplasia
2. Paracortical hyperplasia
3. Sinus histiocytosis

37. A. Follicular Hyperplasia
• Increase in no and size of germinal centres,
• may involve paracortex and medullary areas
• Seen in-
• collagen vascular disorders
• Systemic toxoplasmosis
• Syphilis

39. B. Paracortical Hyperplasia
• Increase in interfollicular elements
• small compressed follicles
• Increased subcortical infiltrates
• Seen in
• SLE
• Viral infections( low grade)
• Drug reaction

41. C. Sinus Histiocytosis
• Expansion of medullary sinus histiocytes
• Selective proliferation of histiocytes
• Expanded patent sinuses
• Seen in-
• Malignancy adjacent to lymph nodes
• Chronic Infections

43. LYMPHOMAS
• Malignant neoplasms of lymphoid origin
• Divided into Hodgkin’s and Non-Hodgkin’s types
• All HL and 2/3rd of NHL occur in lymph nodes
• Lymphoid neoplasms show some degree ofT or B cell
differentiation
• Associated with immune system abnormalities
• Neoplastic cells can recapitulate behavior of normal counterparts

44. CLASSIFICATION
• Based on prognosis

45. WORKING FORMULATION
• Low grade
• ML, small lymphocytic
• ML, follicular small cleaved cell
• ML, follicular, mixed small and large cell
• Intermediate grade:
• ML, follicular, large cell
• ML, diffuse, small cleaved cell
• ML, diffuse, mixed small and large cell
• ML, diffuse, large cell
• High grade
• ML, immunoblastic
• ML, lymphoblastic
• ML, small non-cleaved cell (Burkitt's vs non-
Burkitt's)
• Miscellaneous (mycosis fungoides, true
histiocytic, etc.)
From 1982-1994, the classification used
in the United States
Based on:
The observed clinical history of
1200 patients.
Microsopic examination alone,
utilizing
Loss of normal nodal
architecture
The dominant cytologic cell
type observed under the
microscope
Presence or absence of
"follicularity" - mimicking of
normal lymphoid follicle
formation

46. CLASSIFICATION- REAL/WHO 2008
• REAL/WHO is a "disease” oriented rather than purely morphology
oriented classification, based on:
• Cell lineage: B vs T vs NK vs Histiocytic
• Stage of maturation of the presumed normal counterpart.
• Includes immunologic and molecular criteria in addition to purely
morphologic criteria of WF
• Each disease entity may have differing grades of aggressiveness
• Greatly expanded the list of entities; includes leukemias of
lymphoid origin

47. B-Cell Neoplasms T/NK-Cell Neoplasms Hodgkin's Lymphoma
Precursor B-cell lymphoblastic
leukemia/lymphoma
Precursor T cell lymphoblastic
leukemia/lymphoma
Lymphocyte p redominance,
nodular
Peripheral B-cell neoplasms Peripheral T-cell and NK-cell
neoplasms
Classical HL
B-cell CLL/SLL Predominantly
leukemic/disseminated
Lymphocyte rich classical HL
B-cell prolymphocytic leukemia T-cell prolymphocytic leukemia Nodular sclerosis
Lymphoplasmacytic lymphoma T-cell large granular lymphocytic
(LGL) leukemia
Mixed cellularity
Mantle cell lymphoma NK cell leukemia Lymphocyte dep letion
Follicular lymphoma Adult T-cell leukemia/lymphoma Unclassifiable classical HL
Extranodal marginal zone B-
cell lymphoma, MALT type (+/-
monocytoid B cells)
Predominantly nodal
Angioimmunoblastic T-cell
lymphoma
Nodal marginal zone B-cell
lymphoma (+/-monocytoid B
cells)
Peripheral T-cell lymphoma
unspecified
Splenic marginal zone B-cell
lymphoma (+/-villous
lymphocytes )
Anap lastic large cell lymphoma,
T/null-cell
Predominantly extranodal
Hairy cell leukemia Mycosis fungoides
Diffuse large B-cell lymphoma Sezary syndrome
Burkitt lymphoma Primary cutaneous (CD30+ T-cell
lymphoproliferative disorders)
Plasma cell myeloma Subcutaneous panniculitis-like T-
cell lymphoma
Plasmacytoma NK/T cell lymphoma, nasal and
nasal-type
Enteropathy-type intestinal T-cell
lymphoma
Hepatosplenic T-cell lymphoma
g/d (gamma/delta)
a /b (alpha/beta )

48. MAJOR LYMPHOID NEOPLASMS
OF LYMPH NODES
• i. Mantle cells/Mantle zone – Mantle cell lymphomas
• Ii. Germinal centre
Follicular lymphomas
Burkitt’s lymphomas
DLBCL
HL
iii. Marginal zone
DLBCL
Marginal zone lymphomas
Small lymphocytic lymphoma
Chronic lymphocytic leukemia
iv. PeripheralT cells
PeripheralT cell lymphomas
V. Paracortical regions – Anaplastic large cell lymphomas

51. CLINICAL FEATURES
•Lymphadenopathy
•Pain +/-
•Weight loss >10% body weight
•Fever>38^C
•Night sweats
•Malaise
•Pruritis
•Frequent Infections
‘B symptoms”

52. FNAC OF LYMPHOMAS
•Indications
• for metastasis
•recurrences and deep seated lymphomas
•C/I
• for primary lymphomas

53. LYMPHOMA REACTIVE HYPERPLASIA
K/L K/L

54. METASTATIC SCC LYMPHOMA
CYTOKERATIN

55. FNAC EVALUATION
•Quick stain –cytomorphology
••Flow/immunocytochemistry
••Proliferation Indexes
••Cytogenetics
http://www.mayoclinic.org/cond/lymphoma/fnac/con-20035937

56. MANTLE CELL LYMPHOMA
• DEFINITION
• CD5+ B cell malignant lymphoma with chromosomal translocation
t(11:14), rearranged Bcl-1 gene, Cyclin D1 overexpression and cytologic
features intermediate between small lymphocytic lymphoma and
follicular lymphoma.
• SYNONYMS
• Intermediate lymphocytic lymphoma/centrocytic lymphoma/SC cell
lymphoma
• ORIGIN
• Primary Follicles
• Mantle zone of secondary follicles

57. C/F
• 60-63YRS
• M:F=2:1TO 5:1
• Generalised lymphadenopathy
• B symptoms-Weight loss/fever/night sweats
• Early dissemination- most cases late stage with spleen & BM
involvement during diagnosis
• Extranodal sites-Waldeyer’s ring, SG,spleen,GIT
• Intermediate grade lymphoma

58. H/P
• Small to med sized lymphocytes with irregular nuclear contours,
condensed chromatin, inconspicuous nucleoli and scanty
cytoplasm
• Nucleus not as round as SLL nor as cleaved as FL
• SLL and F type cells <30%
• Immunoblasts – rare/absent
• Moderate mitotic rate
• Venules with hyalinised walls
• Non neoplastic plasma cells
• Epitheloid histiocytes

60. VARIANTS
• Mantle zone
• Nodular
• Diffuse
• Blastic

61. MANTLE ZONE PATTERN

62. NODULAR PATTERN

63. DIFFUSE PATTERN

64. BLASTICVARIANT

65. IHC
• B cell markers
• CD5, CD43
• Cyclin D1
• Bcl-1
Rx & Prognosis
Surgery,Chemotherapy, Radiation
Very poor prognosis in case of-
 Increased proliferation rate
 P53 mutation
 P16 inactivation
 Blastic variant
Median survival time- 3-4 yrs

66. FOLLICULAR LYMPHOMA
• DEFINITION
• Lymphomas composed of cleaved and non cleaved B cells
recapitulating the germinal centres of lymphoid follicles and growing
in a nodular pattern
• SYNONYMS
• Nodular lymphosarcoma/Germinal centre lymphoma/Nodular
lymphoma/Brill Symmer’s disease
• ORIGIN
• Naïve B cells of germinal centre

67. C/F
• Most common lymphoma after DLBCL
• Tumor of old age
• No male predominance as in other lymphomas
• Indolent disease, insidious onset
• Cervical and inguinal LN are most common sites
• Late Diagnosis with dissemination into BM,Liver,GIT

68. H/P
• Obliteration of normal LN architecture by nodules of uniform size
and shape involving cortex and medulla
• Involvement of perinodal fibroadipose tissue
• Total/ partial occupation of LN with nodules which sometimes lack
mantle zone-blurring of borders
• Closely packed nodules with little uninvolved tissue between them
• Monotonous monoclonal population
• Also forms nodular pattern if it metastasizes to other site.

71. GRADING
• Grade I- predominant small cleaved cell type
• Grade II- mixed small cleaved and large cell
• Grade III- predominant large cell type
AGGRESSIVETRANSFORMATION
To aggressive diffuse lymphomas usually after 6 months or more of
initial diagnosis
Can transform to DLBCL,BL,Diffuse mixed lymphoma or
immunoblastic lymphoma

72. Signet ring lymphomas
• Rare variant of FL
• Nodular/combined nodular and diffuse pattern
• Signet ring cells
• Intracytoplasmic inclusions- IIIr to Russel bodies c/d Dutcher bodies

73. IHC for FL
B cell markers-CD19,CD20,CD22,CD79
Bcl-2 overexpression
CD5-
Rx & Prognosis
Responsive to radiation and chemotherapy
Remission for avg of 19 years
Tendency for aggressive transformation

74. BURKITT’S LYMPHOMA
• Non Hodgkin’s B cell lymphoma of small noncleaved cell type,
associated with EBV infection
• Ist lymphoma in which cytogenetic abnormality was detected
• Variants
• Burkitt’s
• Non Burkitt’s
• Endemic to Africa
• Associated EBV infection in 90% cases
• Increased incidence in AIDS

75. Pathogenesis
• Immortalisation of EBV in B lymphocytes of infected patients
• Continuous stimulation of lymphocytes by EBV bearing B cells
• Reciprocal chromosomal translocation 8:14
• Rapid tumor growth with increased growth fraction and short
doubling time

76. C/F
• Mean age – 7 years
• M:F=2:1
• Jaw/ orbital bone -60% cases
• LN- abdominal followed by cervical
• AIDS associated – CNS involvement

77. HP/F
• Starry sky appearance- monomorphic neoplastic lymphoid cells
interspersed with histiocytes
• Tumor cells with uniform size-smaller than centroblasts, larger than
lymphocytes
• Thin rim of basophilic cytoplasm,small lipd vacuoles
• Increased mitosis- 4% of tumor cells
• Doubling time of 24-48 hrs
• Cellular necrosis,phagocytic histiocytes

79. Non Burkitt’s variant
• Lacks monotony of BL
• LesserTBM
• Less evident starry sky pattern
• Moderate pleomorphism

80. IHC
• IgM with Kappa & Lambda chains
• B cell markers +
• EBV demonstration in situ
RX & PROGNOSIS
• Usually poor prognosis
• Cyclophosphamide+Methotrexate-Good regression

81. DIFFUSE LARGE B CELL LYMPHOMA
• Heterogenous group of neoplasms characterized by a diffuse proliferation of
large neoplastic B lymphoid cells, with nuclear size at least twice that of a
small lymphocyte.
• Some are of follicle centre cell origin. It is unclear which combination of
positivity for CD10, bcl-2 & bcl- 6and t(14;18) may indicate derivation from a
follicle centre cell, either de novo or by transformation.
• Most common lymphoma
• Male predominance
• Mean age 60 years
• Genetics- Dysregulation of bcl-6, t(14:18) translocation
• Rapidly enlarging mass, aggressive
• Common site-Waldeyer’s ring, oropharyngeal lymphoid tissue

82. H/P
• Large cell size-4-5 times diameter of normal lymphocytes
• Diffuse pattern
• Round/oval nucleus which appears vesicular
• Anaplastic tumors may contain MNGC resembling RS cells

84. IHC
• CD19+,CD20+
• CD10,Bcl-6- variable expression
Rx & PROGNOSIS
• Rapidly fatal without treatment
• Chemotherapy-complete remission in 60% to 80% cases
• Adjuvant therapy with antiCD20 antibody- good response to Rx

85. MARGINAL ZONE LYMPHOMA
• DEFINITION
• Heterogenous group of B cell tumors that arise within lymph
nodes, spleen or extranodal tissues.
 May arise in SG of sjogren’s syndrome pts, thyroid of pts with
Hashimoto’s thyroiditis

86. H/P
Architectural effacement by atypical centrocyte like cells that
infiltrate around reactive B cell follicles in a marginal zone
distribution and spread to interfollicular area
May have a pattern resembling Follicular Lymphoma
Monocytoid B cells, Small lymphocytes, plasma cells, centroblasts
and immunoblasts in small numbers.

89. IHC
• B cell markers+, Bcl-10+
• CD11, Bcl-2 –
• RX AND PROGNOSIS
• Chemotherapy and Radiotherapy
• Good remission rates-92%

90. SMALL LYMPHOCYTIC LYMPHOMA/ CHRONIC
LYMPHOCYTIC LEUKEMIA
• SML & CLL differ only in the amount of peripheral blood lymphocytosis
• CLL- absolute lymphocyte count >5000/cu.mm
• Less common in Asians
• Mutation of Ig genes
• C/F
• B symptoms
• Ig spike

91. H/P
• Diffuse effacement of LN by small lymphocytes
• Round to irregular nuclei
• Scanty cytoplasm
• Mitotically active cells aggregate at proliferation centres- mostly
large lymphocytes- pathognomic feature
• ‘Smudge cells” in peripheral smears

94. IHC
• B cell markers+
• CD5+
• Rx & Prognosis
• Chemotherapy and radiotherapy
• CLL- Bone marrow transplant
• Intermediate grade neoplasm
• Good remission rates

95. HODGKIN’S LYMPHOMA
• DEFINITION
• A lymphoma characterized by a heterogenous cellularity comprising a
minority of specific neoplastic cells and a majority of reactive non-
neoplastic cells
• C/F
• Age-bimodal distribution;b/w 15-34 yrs & 54 yrs
• M>F
• Less common than NHLs in HIV pts
• Etiology-EBV infection is implicated as R-S cells are EBV+ in 40% to 50%
cases

96. • Cervical and supraclavicular nodes are commonly involved
• Usually contiguous spread
• Non contiguous spread in case of vessel invasion
• Enlarged LN- non painful, non tender
• Immune deficiency symptoms
• B symptoms

98. CLASSIFICATIONS

99. HP/F• Cell types
• 1. Non neoplastic cells
• Represent immune reaction to neoplastic cellular component
• Lymphocytes with small round nucleus and rare mitoses is predominant
• Majority are CD4+T cells
• Occasional histiocytes, fibroblasts, immunoblasts, plasma cells, neutrophils
and eosinophils are seen
• Eosinophils-constant and characteristic component of NS & MC types-
‘eosinophilic microabscesses’
• Epitheloid granulomas in 10% cases
• Increased no of epitheloid cells in MC type

100. • 2. Neoplastic cells
• Reed Sternberg cells are pathognomic
• Typical cells are 20-60 Microns in dm
• Variable amount of cytoplasm
• Large nuclei with thick nuclear membrane
• 2 nuclei- mirror image
• Single prominent eosinophilic nucleolus –owl eye app
• May show multipolar mitoses
• Mononucleated cells with prominent eosinophilc nucleolus-’Hodgkin cell”
• Constitute 1-3% of tumor volume

101. Origin of RS cells-Theories
• 1.Transformation of histiocytes/RE cells
• Capacity for phagocytosis
• CD21+
• Fc receptors present
• 2.From immunoblasts
• Ig gene rearrangements in RS cells
• CD15+,CD20+
• 3.Somatic mutation in GC cells
• 4.EBV RNA identified in some RS cells

102. RS cell variants
•Hodgkins cell- mononuclear
•Lacunar variant
•Mummified variant
•Anaplastic variant
•L H cells-pop corn cells

103. NODULAR SCLEROSISTYPE• Most common especially inYoung women
• Diagnostic criteria
• Lacunar cells- single/sheets
• Sclerosis- defining feature- broad interconnecting bands of collagen-
originate from capsule and divide LN into nodules of varying sizes and
shapes
• RS cells in variable numbers
• Phases- cellular phase to fibrotic phase
• SyncytialVariant of NS -Extreme form of cellular phase-Numerous RS
cells and Hodgkin’s cells arranged in clusters and sheets, Central
necrosis-Resembles melanoma/metastatic carcinoma

105. LYMPHOCYTE RICH
• Few RS cells and HC within a mass of lymphocytes and only few
eosinophils and neutrophils
• Incidence-6%
• Diagnostic-
• <5RScells/hpf
• Bad prognosis
• Survival 2-3 yrs
Post diagnosis

106. MIXED CELLULARITY
• Heterogenous cell population- lymphocytes, plasma
cells,histiocytes,eosinophils, HC,Rs cells with Moderate to diffuse fibrosis
• Common in young/elderly/AIDS pts
• Involves whole/large areas of LN
• Total loss of architecture
• Foci of necrosis
• Diagnostic criteria
• 5-15 RS & HC/hpf

107. LYMPHOCYTE DEPLETION
• Most aggressive form of HL, worst prognosis
• Older pts
• Short median survival(4-5 months posr diagnosis)
• Subtypes-
• 1. Diffuse Fibrosis
• 2. Reticular
• Diagnostic criteria
• RS & HC >15 cells/hpf

108. Diffuse Fibrosis
• Develops spontaneously or as a result of radiation or chemotherapy
• Poorly cellular structureless LN architecture
• Normal parenchyma replaced by fibrous tissue, scattered RS cells/residual
lymphocytes
• Spindle cells
• Bizzare RS cells
•Reticular subtype
• Hypercellular
• Normal LN architecture obliterated by pleomorphic RS cells/variants
• Eosinophils,neutrophils,macrophages
• Foci of necrosis, minimal fibrosis
• Characteristic capsule/perinodal invasion

110. NODULAR LYMPHOCYTE PREDOMINANT
• Also c/d paragranuloma
• Nodular lymphoproliferation with clinicopathological features of both HL and
low grade B cell lymphoma
• 2-6% of HL
• AggressiveTransformation to DLBCL has been reported
• Good prognosis
• 2 patterns

111. 1. Nodular
LN architecture replaced by large lymphocytic nodules, larger than seen in
reactive follicles/FL and composed entirely of small lymphocytes
LH cells-variant of RS cells with vesiculated multilobate nucleus- popcorn
cells
Epitheloid cells ,histiocytes
20% cases- enlarged follicles with increased B cells of mantle zone type-
progressive transformation of Germinal centres (PTGC zones-
pathognomic)
2.Diffuse-
Rarely seen
LH cells scattered without nodule formation

113. IHC
• RS cells & variants-
• CD15+,CD30+
• CD45-,CD20-,EMA-, B cell markers-
• LP nodular type-
• LH cells- CD45+, B cell markers+
•TREATMENT
• Surgery ,Chemotherapy,Radiotherapy

114. UNCLASSIFIABLE LYMPHOMAS
• Cannot be defined by combine morphologic, immunohistochemical
and genetic investigations

115. PRIMARY NONHEMATOLYMPHOID TUMORS OF LN
• A. Stromal
• Hemorrhagic spindle cell tumor
• Angiomyolipoma
• lymphangiomyoma
• Intranodal leiomyoma
• Inflammatory pseudotumor
• B. Vascular
• Kaposi’s sarcoma
• Hemangioma, epithelioid hemangioendothelioma,and angiosarcoma
• Lymphangioma
• C. Benign Epithelial and nevus inclusions- no atypia

116. METASTATIC NEOPLASMS IN LN
• Most common metastatic tumor in H&N region- SCC
• Others-Malignant melanoma,Thyroid Ca,
• Emreyonic small cell Ca,Adenocarcinoma,
• Renal clear cell Ca.
• HN Sarcomas almost always metastasize to LN
• The metastatic tumor often starts as isolated cellular clusters in the subcapsular
sinuses, with gradual replacement of the nodal parenchyma. may be
accompanied by a desmoplastic reaction or inflammatory reaction including
granuloma formation.
• Discrete metastasis – IHC panel
• Treatment modalities depend on nature of primary tumor

117. REFERENCES
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