1. Hodgkin’s Lymphoma or Disease (HD)

2. Pathology of lymph nodes
A. Infections
1. Bacterial
2. Fungal, mycobacterial
B. Reactive hyperplasias
1. Exaggerations of normal histology. Expansion of all regions or selective expansion of one. Some types characteristic of certain diseases, but most not
2. Follicular hyperplasia increase in number and size of germinal centers, spread into paracortex, medullary areas
a. Collagen vascular diseases,
b. Systemic toxoplasmosis,
c. Syphillis
3. Interfollicular hyperplasia- paracortex-
a. Skin diseases
b. Viral infections
c. Drug reactions
4. Sinus histiocytosis- expansion of the medullary sinus histiocytes-
a. Adjacent cancer
b. Infections
C. Sarcoidosis
D. Metastatic tumors
E. Malignant lymphomas (Non-Hodgkins' lymphomas-NHLs) and Hodgkin's lymphoma

3. Classification Non-Hodgkin’s Lymphoma Hodgkin’s Lymphoma T cell NHL
B cell NHL
Miscellaneous NHL
Hodgkin’s Lymphoma
   Nodular sclerosis Hodgkin lymphoma
   Mixed cellularity Hodgkin lymphoma
Lymhocyte predominant Hodgkin Lymphoma
   Lymphocyte-rich classical Hodgkin lymphoma
   Lymphocyte depleted Hodgkin lymphoma

4. Hodgkin’s Lymphoma (Hodgkin's disease) (Thomas Hodgkin ;1832)
Less common than NHL;
approximately 10,000 cases per year
Incidence with respect to age bimodal, with one peak in late adolescence, young adulthood, second peak in sixth decade A potentially curable malignant lymphoma with distinct histology, biologic behavior, and clinical characteristics.
Young adults (male predominance)
particularly evident in children, where 85% of the cases are males.

5. Palpable, painless, firm lymphadenopathy (rubbery adenopathy):
Clinical findings
Palpable, painless, firm lymphadenopathy (rubbery adenopathy):
cervical area (60-80%),
axilla (6-20%),
inguinal area (6-20%).
Waldeyer ring or occipital or epitrochlear areas is observed infrequently.
Splenomegaly may be present.
Patients may have hepatomegaly.

6. Central nervous system (CNS) symptoms or signs may be due to paraneoplastic syndromes, including
cerebellar degeneration,
neuropathy,
Guillain-Barré syndrome,
multifocal leukoencephalopathy.

7. Fever (classic Hodgkin's fever is the "Pel-Ebstein fever", or intermittent spiking fever)
Pruritus
Eosinophilia
A complication of AIDS.

8. ETIOLOGY
The etiology of HD is unknown.
Infectious agents, especially the Epstein-Barr virus (EBV)
Previous history of Epstein-Barr Virus Infectious Mononucleosis
Almost 100% of HIV-associated HD cases are EBV-positive.
Patients with HIV infection have a higher incidence
However, HD is not considered an AIDS-defining neoplasm.
Genetic predisposition
Approximately 1% of patients with HD have a family history of the disease.
HLA-DP alleles are more common.
It is now agreed that Hodgkin lymphoma is a neoplasm arising from germinal center B cells.

9. A malignant disease with four histologic subtypes; to make the diagnosis need to see an acceptable Reed-Sternberg cell (the malignant cell of Hodgkin's disease) in the proper reactive cellular background, consisting of
small lymphocytes,
histiocytes,
plasma cells,
eosinophils.

11. Reed-Sternberg cell
The Reed-Sternberg cells represent a clonal proliferation of B lymphocytes that derive from the germinal centers of lymph nodes and that have lost their ability to express their antibodies because of the introduction of multiple somatic mutations.
Large binucleated cell
with large, red owl-eye nucleoli (same size as a small lymphocyte) with surrounding halo
multilobed nucleus (often appears "binucleate"), with lobes appearing as mirror images of one another
Pink-to-lavender cytoplasm.

15. Reed-Sternberg variants
Mononuclear Reed-Sternberg-like cells ("Hodgkin cells") have single-lobed nuclei and one nucleolus. They may be seen in any variant of Hodgkin's disease.
LP cells ("L&H cells") have scanty cytoplasm, big knobby nuclei, and small nucleoli. They are seen in lymphocyte predominance Hodgkin's disease.
Lacunar Reed-Sternberg cells have abundant, pale cytoplasm, and single, hyperlobated nucleus with small nucleoli. They are seen in nodular sclerosis Hodgkin's disease.
Polylobated Reed-Sternberg cells (popcorn cells) look like good Reed-Sternberg cells, except that the nucleoli aren't so impressive. They are typical of mixed cellularity Hodgkin's disease.
Pleomorphic Reed-Sternberg cells are anaplastic versions of the familiar form. They make up the bulk of the tumor in lymphocyte depletion Hodgkin's disease.

16. Lymphocytic and Hystiocytic (LH) cell variant Reed Sternberg cells in HD(pop-corn cells)

17. Lacunar variant

18. Clinical Differences Between Hodgkin and Non-Hodgkin Lymphomas
More often localized to a single axial group of nodes (cervical, mediastinal, para-aortic)
More frequent involvement of multiple peripheral nodes
Orderly spread by contiguity
Noncontiguous spread
Mesenteric nodes and Waldeyer ring rarely involved
Mesenteric nodes and Waldeyer ring commonly involved
Extranodal involvement uncommon
Extranodal involvement common

19. WHO Classification of HD
Microscopical types :
Lymphocyte predominant (at low stage)
Lymphocyte rich
Nodular Sclerosis (often a mediastinal mass).
Mixed cellularity (at low or high stage).
Lymphocyte depleted (at high stage).
Until the late stages of the disease, the tumor masses are composed primarily of inflammatory cells responding to the cancer.

20. Lymphocyte (B)
Reed-Sternberg cells
Other cells
Differential diagnosis
Lymphocyte predominance
Monotonous, Small cells
Rare (LP cells)
Small lymphocyte
Histiocytes
Small lymphocytic lymphoma
Mixed cellularity
Mixture of cells
Many (polylobated)
Lymphocytes, plasma cells, eosinophils, histiocytes
Infectious mononucleosis
Lymphocyte depletion
Less lymphocyte
Present (pleomorphic)
Anaplastic B-cells, lots of fibers, few lymphocyte
Nodular sclerosis
Less cell more fiber (collagen extending into the node)
Present (lacunar)
cellular islands containing lymphocytes, histiocytes, eosinophils, and plasma cells

21. Clinical Features Frequency Prognosis
Hodgkin's Disease
Type
Clinical Features
Frequency
Prognosis
Nodular sclerosis
Painless Lymphadenopathy,
more common in women
Most frequent type (68%)
Good, most are stage I or II
Mixed cellularity
Most frequent in older persons, second most frequent overall (23%)
Fair, most are stage III
Lympho-cyte predomi-nance
Young males, cervical nodes
diffuse or vaguely nodular
Uncommon (7%)
Lympho-cyte depletion
Uncommon (2%)
Poor, most are stage III or IV
Painless Lymphadenopathy
Painless Lymphadenopathy

22. Nodular Sclerosing HD

23. Lymphocyte predominant HD

24. Lymphocyte depledet HD

26. Immunhistochemistry RS cells are expressing CD-15

27. Positive staining for CD15 (Leu-M1) and CD30 (Ki-1)
Negative staining for CD45

28. Staging Stage I one node group or organ
Stage II one side of the diaphragm
Stage III both sides of the diaphragm
Stage IV marrow, or two extra-lymphatic organs.
Hodgkin's disease spreads predictably along contiguous groups of lymph nodes.
As it spreads, there may be transformation:
Lymphocyte predominance turns into mixed cellularity or lymphocyte depletion.
Mixed cellularity turns into lymphocyte depletion.
Nodular sclerosis generally keeps its type.

29. Hodgkin’s disease; cervical lymph node involvement

30. Hodgkin's Disease - Staging
Stage 1
Only a single lymph node site or extranodal site is involved
Stage 2
Two or more lymph node sites on one side of the diaphragm are involved, or limited contiguous extranodal site involvement
Stage 3
Lymph node sites on both sides of the diaphragm are involved, with splenic or limited contiguous extradodal site involvement, or both
Stage 4

32. Hodgkin’s Disease (Liver&Lymph node)

35. Complications of HD Mostly during or after treatment.
Irradiation-related complications:
Cardiac complications (coronary artery disease, chronic pericarditis, pancarditis, valvular heart disease, and defects in the conduction system)
Pulmonary complications (dyspnea)
Breast cancer
Hypothyroidism
Immunodeficiency
Chemotherapy-reladed complications:
Cardiac complications (congestive heart failure)
Pulmonary complications (interstitial pneumonitis)
Bone marrow complications (Myelodysplasia, acute myeloid leukemia)
Infertility
Non-Hodgkin lymphoma.

36. Infectious complications
Sepsis: Patients who have undergone splenectomy are predisposed to bacterial sepsis secondary to encapsulated microorganisms (especially pneumococcal organisms)
Herpes zoster.
Other complications:
Lung cancer
Malignant melanoma
Other cancers.

37. Thank you!