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Hodgkin Lymphoma

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Dr. Adnan Arshad

pathology
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Presented by: -
Zunair Jamshaid
Samiullah chadharh
Duaa Naeem
Alma Akram
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 Definition:-
Hodgkin lymphoma is a type of lymphoma in which cancer originates from
a specific type of white blood cells called lymphocytes, it specifically affects
B-lymphocytes, causing them to accumulate in the lymph nodes
Name origin:-
It was named after Thomas Hodgkin , who first describe the condition in
1832.
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Etiology/Risk factor:-
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About half of cases Hodgkin lymphoma are due to Epstein-Barr virus and
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these are generally the classic form. Other risk factors include a family
history of the condition and having HIV/AIDS.
 Manifestations: -
Lymphadenopathy:-the most common symptom of Hodgkin is the
painless enlargement of one or more lymph nodes. The nodes may also
feel rubbery and swollen when examined. The nodes of neck and
shoulders(cervical and supraclavicular)are most frequently involved(80-
90%). The nodes of chest may also be affected, and these may be noticed
on chest radiograph.
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Systemic symptoms:- about one- third of people with Hodgkin disease

may also present with systemic symptoms , including.
• Itchy skin
• Low grade fever
• Night sweats
• Fatigue
 Unexplained weight loss of at least 10% of the person’s total body weight
in six months or less
These symptoms are categorized as B symptoms thus presence of these
indicate that the person’s stage 2B.
Hepatomegaly
Splenomegaly
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Hepatosplenomegaly
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Back pain(lower back specifically)

Pain following alcohol consumption(rare)only in 2-3% patients
Cyclical fever, people may be present with cyclical high-grade fever commonly known as
Pel-Ebstein Fever
Nephrotic syndrome
 Diagnostic methods: -
• Definitive diagnosis is by lymph node biopsy (usually excisional biopsy
with microscopic examination)
• Blood tests are also performed to assess function of major organs and to
assess safety for chemotherapy .positron emission tomography(PET) is
used to detect small deposits that do not show on CT scanning. PET
scans are also useful in functional imaging(by using a radio labeled
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glucose to image tissues of high metabolism)

• In some cases a Gallium scan may be used instead of PET scan.
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• The most common age of diagnosis is between 20 and 40 years old.

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Prognosis:-
The one year survival rate for patients with Hodgkin lymphoma is about 92%.
The five-year survival rate is about 82%. For people with stage 4 Hodgkin
lymphoma the survival rate is less, but you can still beat the disease in even
stage 4.
 Pathology: -
• Affected lymph nodes are enlarged, but their shape is preserved
because the capsule is not invaded. Usually the cut surface is white-
grey and uniform; in some histological subtypes a nodular aspect may
appear.

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• Microscopic examination of the lymph node biopsy reveals complete or

partial effacement of thr lymph node architecture by scattered large
malignant calls known as Reed-Sternberg cells(RSC) admix within a
reactive cell infiltrate composed of variable proportions of lymphocytes,
histiocytes, eosinophils and plasma cells. The Reed-Sternberg cells
are identified as large often binucleated cells with prominent nucleoli
and an unusual CD45-, CD30+, CD15+/- immunophenotype. In
approximately 50% of cases the Reed-Sternberg cells are infected by
the Epstein-Barr virus.
 • Characteristics of classic Reed-Sternberg cells include large size,
abundant, amphophilic, finely granular/homogenous cytoplasm,two
mirror-image nuclei each with an eosinophilic nucleolus and a thick
nuclear membrane. Almost all of these cells have an increased copy
number of chromosome 9p/9p24.1

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1. Hodgkin cell is a variant of RS cell, which has the same

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characteristics but is mononucleated.
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2. Lacunar RSC is large, with a single hyperlobulated nucleus, multiple,

small nucleoli and eosinophilic cytoplasm which is retracted around th
nucleus creating an empty space
3. Pleomorphic RSC has multiple irregular nuclei
4. “Popcorn” RSC is a small cell, with a very lobulated, small nuclei
5. Mummy RSC has a compact nucleus with no nucleolus and
basophilic cytoplasm
 
 Pathophysiology: -
 There is two classes of Hodgkin lymphoma which is furthur divided
into five types.Nodular sclerosing hodgkin lymphoma (NSHL), mixed
cellularity hodgkin lymphoma (MCHL), lymphocyte depleted hodgkin
lymphoma(LDHL), and lymphocyte rich hodgkin lymphoma(LRHL)
are the four types included to class “classical Hodgkin lymphoma”.
The fifth type, nodular lymphocyte-predominant Hodgkin lymphoma
(NLPHL), is a distinct class and has its own pathophysiology.

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 In classical Hodgkin lymphoma, the neoplastic cell is the Reed-

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Sternberg cell . Reed-Sternberg cells comprise only 1-2% of the total

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tumor cell mass. The remaining is composed of a variety of reactive,
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mixed inflammatory cells consisting of lymphocytes, plasma cells,

neutrophils, eosinophils, and histiocytes..
  Most Reed-Sternberg cells are of B-cell origin, derived from lymph
node germinal centres but no longer able to produce antibodies.

introduction
Hodgkin lymphoma cases in which the Reed-Sternberg cell is of T-
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cell origin are rare, accounting for 1-2% of classical Hodgkin

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lymphoma.
 The Reed-Sternberg cells consistently express the CD30 (Ki-1) and
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CD15 (Leu-M1) antigens. CD30 is a marker of lymphocyte activation

that is expressed by reactive and malignant lymphoid cells and was
originally identified as a cell surface antigen on Reed-Sternberg
cells. CD15 is a marker of late granulocytes, monocytes, and
activated T-cells that is not normally expressed by cells of B lineage.
 Types: -
There are two main types of Hodgkin lymphoma:
1. NODULAR PREVALENCE PREDOMINANT HODGKIN LYMPHOMA
2. CLASSICAL HODGKIN LYMPHOMA
Class 1
• Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL)
constitutes 5% of cases. It is a distinct clinical entity and is not considered
part of the classical Hodgkin lymphoma type. Typical Reed-Sternberg

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cells are either infrequent or absent in NLPHL. Instead, lymphocytic and

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histiocytic (L&H) cells, or "popcorn cells" (their nuclei resemble an

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exploded kernel of corn), are seen within a background of inflammatory

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cells, which are predominantly benign lymphocytes. Unlike Reed-
Sternberg cells, L&H cells are positive for B-cell antigens, such as
CD20, and are negative for CD15 and CD30.
• A diagnosis of NLPHL needs to be supported by immunohistochemical
studies, because it can appear similar to LRHL or even some non-
Hodgkin lymphomas.
 .Class 2
Classical Hodgkin lymphoma is classified into the following 4 types:
• Lymphocyte-depleted Hodgkin lymphoma (LDHL)
• Lymphocyte-rich classical Hodgkin lymphoma (LRHL)
• Nodular sclerosing Hodgkin lymphoma (NSHL)
• Mixed-cellularity Hodgkin lymphoma (MCHL)
Lymphocyte-depleted Hodgkin  Lymphocyte-rich
lymphoma: - classical Hodgkin

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• LDHL constitutes less than 1% of lymphoma: -

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cases. The infiltrate in LDHL is

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diffuse and often appears • LRHL constitutes 5% of cases.

hypocellular. Large numbers of
Reed-Sternberg cells and bizarre
sarcomatous variants are present.
• LDHL is associated with older age
and HIV-positive status. Patients
usually present with advanced-
stage disease. Epstein-Barr virus
(EBV) proteins are expressed in
many of these tumors. Many
cases of LDHL diagnosed in the
past were actually non-Hodgkin
lymphomas, often of the
anaplastic large-cell type.
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In LRHL, Reed-Sternberg cells
of the classical or lacunar type
are observed, with a
background infiltrate of
lymphocytes. It requires
immunohistochemical
diagnosis. Some cases may
have a nodular pattern.
Clinically, the presentation and
survival patterns are similar to
those for MCHL.
 Mixed-cellularity Hodgkin
Nodular sclerosing Hodgkin
lymphoma: -
lymphoma: -
• In MCHL, which constitutes 15-30%
• In NSHL, which constitutes 60-80% of of cases, the infiltrate is usually
all cases of Hodgkin lymphoma, the diffuse. Reed-Sternberg cells are of
morphology shows a nodular pattern. the classical type (large, with
Broad bands of fibrosis divide the bilobate, double or multiple nuclei,
node into nodules. The capsule is and a large, eosinophilic
thickened. The characteristic cell is the nucleolus). MCHL commonly
lacunar-type Reed-Sternberg cell, affects the abdominal lymph nodes

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which has a monolobated or and spleen. Patients with this
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multilobated nucleus, a small histology typically have advanced-
nucleolus, and abundant pale stage disease with systemic

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cytoplasm. symptoms. MCHL is the histologic

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• NSHL is frequently observed in type most commonly observed in
patients with human
adolescents and young adults. It immunodeficiency virus (HIV)
usually involves the mediastinum and infection.
other supradiaphragmatic sites.
 TREATMENT: -
• The main treatment for Hodgkin lymphoma is chemotherapy alone

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or chemotherapy followed by radiotherapy.

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• In some cases chemotherapy may be combined with steroid

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medication. Surgery isn’t generally used to treat the condition,

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except for the biopsy used to diagnose it.
• Survival rate:-The percentage of people who survive five years in
the united state is 86%. For those under the age of 20, rate of
survival are 97%. Radiation and some chemotherapy drugs
however, increase the risk of other cancers, heart disease, or lung
disease over the subsequent decades.
 Epidemiology: -

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Epidemiology
• Estimates suggest that around 1 in 25,000 people are affected

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by this cancer every year, and the condition accounts for just

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under 1% of all cancers that occur worldwide.

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• It generally develops among two age groups in particular, which
are those aged between 15 years and 35 years and those aged
over 55 years.
• In 2015, about 57,4000 people globally had Hodgkin
lymphoma, and 23,900 (4.2%)died. In the united states, 0.2%
of people are affected at some point in their life.
Research title : -
Treatment of Nodular Lymphocyte Hodgkin Lymphoma: The
Goldilocks Principle
Author: -
Washington University Medical Center, St Louis, MO
1

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CITATION:-

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DOI: 10.1200/JCO.19.02816 Journal of Clinical Oncology 38, no. 7

pathology
(March 01, 2020) 662-668.

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Published online January 10, 2020.
CASE PRESENTATION: -
• A healthy 32-year-old man with a 1-month history of left axillary
swelling and was found to have a 4-cm left axillary lymph node and no
B symptoms (fever, night sweats, and weight loss).
• Complete blood count, comprehensive metabolic panel, and lactate
dehydrogenase level normal
 Study and testing:-
• core needle biopsy showed effacement of the normal nodal
architecture, with a vague nodular infiltrate of small immature-
appearing lymphocytes interspersed with larger atypical cells
• an excisional lymph node biopsy to obtain additional tissue for
pathologic review for differentiation between T-cell–rich large B-cell
lymphoma (TCRLBCL) and nodular lymphocyte-predominant
Hodgkin lymphoma (NLPHL)
• (Fig A), including numerous large CD20-positive mononuclear

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“popcorn cells” (Figs B and C). Subtle progressive transformation of

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germinal centers was noted, as well as T-cell rosetting around large

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atypical cells, features characteristic of NLPHL (Fig D).

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Immunohistochemistry was similar to the core biopsy studies, and
flow cytometry showed no clonal B-cell population.
• Initial positron emission tomography–computed
tomography (PET-CT) scan of the chest showing (A)
left axillary and left subpectoral nodes, (B) a small
hypermetabolic pericardial node, and (C) a small
posterior costophrenic node. Interim PET/CT with
marked improvement in the (D) left axillary nodes and
resolution of the (E) pericardial and (F) costophrenic
node. End-of-treatment PET shows (G) a complete
remission.

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 CHALLENGES IN DIAGNOSIS AND
MANAGEMENT: -
The majority of patients with NLPHL are male (2.2:1) and present with
peripheral adenopathy and early-stage disease (75%).In contrast to

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classic Hodgkin lymphoma (cHL), bulky disease (13%-15%),
mediastinal involvement (7%-10%), B symptoms (4%-10%), and

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contiguous spread are uncommon in NLPHL.NLPHL comprises less

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than 5% of all patients with Hodgkin lymphoma (HL), with an
estimated 550 new patients diagnosed in the United States annually,
and has a bimodal age distribution, with disease peaks in childhood
and at age 30-40 years.Transformation to diffuse large B-cell
lymphoma occurs in 3%-14% of patients with NLPHL within 10 years
and in 30% at 20 years, with splenic involvement and prior
chemotherapy identified as risk factors.In one series, 39% of patients
with splenic involvement had evidence of histologic transformation
during the course of their disease.
Active Surveillance: -
Based on the favorable prognosis and concern for serious
late effects, the Children’s Oncology Group examined the
role of resection alone for patients with stage IA NLPHL.Of
52 patients with complete resection of a single node, 13
relapsed at a median of 11.5 months; 12 of 13 relapses
were stage IA. The 5-year EFS rate was 77.1% (95% CI,

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62.4% to 86.6%), sparing the majority of patients RT or

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systemic therapy.

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Conclusion: -
• With favourable outcomes and a variety of treatment approaches,
the guiding principle of therapy for NLPHL should continue to be “do
no harm”; in particular.
• favour minimizing therapies with potentially life-threatening late
effects. Like Goldilocks, the key is to identify the treatment that is
“just right,” not too much (BEACOPP, regional, or EFRT) or too little
(single-agent R in patients at increased risk for transformation).

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• For the patient presented, the challenge was the presence of non-

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contiguous stage II disease, specifically, involvement of small

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pericardial and cardio phrenic nodes (Figs 1B and 1C)

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• The combination chemotherapy choices for this patient were R-
CHOP, R-CVP, or R-ABVD.
• Although the data are sparse, ABVD-based regimens are inferior to
alkylator-based regimens in advanced-stage disease or early-stage
disease where consolidative RT is not feasible.
• choose between R-CHOP and R-CVP based on risk factors for
transformation, preferring R-CHOP in patients with intra-abdominal
disease.
• Link: -
• https://ascopubs.org/doi/full/10.1200/JCO.19.02816
• https://www.ncbi.nlm.nih.gov/pubmed/?term=31922929
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