notes by dr Claudio Italiano
Hodgkin's disease (MdH) is a neoplasm of the lymphatic system that affects the
lymph nodes, whose management is very complex and multidisciplinary.
In the United States each year there are 7,500 new cases of MdH; HIV + patients have a higher incidence and the same applies to patients with Epstein-Barr virus infection. The same applies to those who have had infectious mononucleosis in particular in patients who have a high antibody titre against the viral-parasitic EBV antigen. It has also been seen that Reed-Stenberg cells contain the EBV genome within them, therefore, there is a correlation between EBV and MdH infection. However, other factors may also intervene in the genesis of the disease, such as other viral factors, environmental exposure and environmental occupation, for example wood processing and genetic factors. Histopathology. The diagnosis of MdH requires a lymph node sample processed appropriately and controlled by an experienced haematopathologist. The identification of the Reed-Stenberg cell in the context of a cell population consisting of lymphocytes, eosinophils and histiocytes allows the diagnosis to be made. The MdH is unique in histopathology because the tumor cells are rare, while the inflammatory component is the majority. For this reason it is difficult to identify R-S cells. They are characterized by a nucleus with a binocular binuclear structure, and we talk about "pop-corn" cells or cells with glasses ", cells that have the characteristics of a macrophage or a lymphocyte. It is a hyperploid cell, with the following genetic markers: CD30 or Ber-H2 and CD-15 or Leu M-1.
Some rare times, in the type of MdH with lymphocyte
component, rare form, (LPHD) the infiltrate consists of polyclonal B
lymphocytes. On the other hand, the type of MdH with nodular sclerosis NSHD
is the most widespread type that affects young women, with
sopranosphragmatic presentations. The differential characteristic is the
presence of large birefringent collagen bands that divide the cellular
process into macroscopic nodules. MdH with mixed cellularity or MCHD is the
second most frequent histological type. It affects males and generally
presents either generalized lymphadenopathy or extranodal disease, with
frequent R-S cells and poor bands. The other form is a lymphocyte depletion
or LDHD is rare and is characterized by numerous R-S cells, with diffuse
fibrosis and necrosis. This form is associated with HIV infection. However,
it should be emphasized that the diagnosis is based on lymph node biopsy
findings and not extranodal sites.
According to the Ann Arbor system we have:
Stage I: The tumor in this phase is found only in a single lymphatic or in a
single extra-lymphatic organ (stage Ie);
Stage II: The tumor mass invades two or even more lymphatic regions on the
same side of the diaphragm. Other lymph node sites may be involved. If an
extra-lymphatic organ is involved, stage IIe is defined;
Stage III: The neoplasm extends both above and below the diaphragm. This stage
is subdivided into III1 (involvement of the lymph nodes above the renal
vessels such as the hilares, the portals, the celiacs and the portals), III2 (involvement
of the lower lymph nodes such as the para-aortic, the iliac and the pelvic),
IIIe (involvement of a extra-lymphatic organ) and IIIs (involvement of
[[spleen]);
Stage IV: Widespread tumor to bone marrow, liver or more than two
extra-lymphatic organs.
Each stage is subclassified into:
A: in the absence of symptoms;
B: if accompanied by the triad of Pel-Ebstein fever, recurrent night sweats
and weight loss of at least 10% in 6 months.Diagnosi differenziale.
The MdH is characterized by a lymph node diffusion with sopradiaframmatic
localization in more than 80% of the subjects, with involvement of the
anterior mediastinum. Only in the remaining 10-20% of cases the localization
is below the diaphragm. Mediastinal presentation is often the only site
involved and this makes diagnosis difficult because we need to think about
other mediastinal pathologies: aggressive non-Hodgkin's lymphomas, thymomas,
germ cell tumors, infections such as tuberculosis, sarcoidosis. Unlike
non-Hodgkin's lymphomas, the symptomatology of MdH may be poor or silent, and
sometimes it begins with coughing and with large mediastinal masses that
obstruct the trachea and cause dyspnoea and dysphonia.
MdH can begin with cervical, supraclavicular, axillary or inguinal
lymphadenopathy. On the other hand, non-Hodgkin's lymphoma forms affect the
preauricular, occipital, epitrochlear, posterior mediastinal and popliteal
sites. However, it is necessary to make a differential diagnosis with other
conditions that determine lymphadenopathy such as infections and reactive
lymphadenopathy, neoplasms involving the cervico-facial district, the lungs
and the thyroid, the breast and the autoimmune disorders.
The treatment of MdH is highly specialized and reserved for hematology centers.
In recent years studies have taken place that have led to new medical
knowledge, and in 1970 a new approach of the MOPP polychemotherapy combination
was established, and it is believed that chemotherapy is also indicated in the
initial stages. In the past radiotherapy was performed up to stage III.
Radiotherapy
Hodgkin's lymphoma, however, also responds discreetly to radiotherapy, with
linear accelerators (practice introduced in 1962) or alternatively,
telobalotherapy by irradiation from overlapping fields, after the vital organs
are protected. The doses are 40-45 Gy.
Above all ABV, ABVD and MOPP are used, ie treatments with multiple drugs, in
fact the monochemotherapy is not used because it does not provide satisfactory
results. Recently, the use of the known forms with Stanford V is being compared.
In the ABVD protocol there are:
• Doxorubicin;
• Bleomycin;
• Vinblastine;
• Decarbazine.
In the MOPP protocol there are:
• Mecloretamine;
• Vincristina;
• Procarbazin;
• Prednisone.
• Stem cell transplantation
Currently under clinical trials, it is used only if the chemotherapy has not led
to satisfactory results, for the moment it involves high toxicity.
Other therapies
The exact classification of anti-CD20 antibodies and the use of SGN-35
immunotoxin are still in progress.