HODGKIN'S
DISEASE
HEMATOLOGY
by Reinaldo Dal Bello
Figueira Júnior
Hematology
Resident
The Federal University of Rio de Janeiro- Brazil
Definition
Hodgkin Disease is a neoplasm of lymphoid
tissue that is defined histopathologically by the presence of the
malignant Reed Sternberg cells with an appropriate cellular
background. The disease has been of great interest because of its
infectious disease like symptoms and findings, its epidemiologic
characteristcs, its associated immunologic abnormalities and its
responsiveness to therapy. Although it was a uniformly fatal disorder
when first recognized and remains one if untreated, the majority of
patients with Hodgkin’s Disease can now be cured of their neoplasm.
Epidemiology
It is more common in males (sex ratio aproximately 1.4:1),
especially before puberty (sex ratio 6 to 10:1). In the United States
and other developed countries there is a bimodal age specific
incidence rate, with an early peak in young adulthood and another in
advanced age. In Japan, the early peak is absent, presumably because
of a reduced incidence of the nodular sclerosis pathologic subtype.
There are other important
epidemiologic observations that correlate socioeconomic factors and
disease incidence. The disease is more common among individuals with
few or no siblings, among those having higher education, and among
urban than rural dwellers.
It has long been recognized
that Hodgkin’s Disease has a higher than expected incidence among
siblings. It has been estimated that a sibling of an affected patient
has a fivefold risk of developing the disease. Preliminary studies
suggested that there may be a region near the dR locus associated with
familial Hodgkin’s Disease.
The Epstein Barr virus has
also been documented by in situ hybridization studies to be found in
Reed Sternberg cells in a proportion of patients. These observations
need confirmation and explanation.
Etiology and Pathogenesis
Numerous attempts have been made to isolate a pathogenetic
microorganism from patients with Hodgkin’s Disease. Among the
leading candidates since the turn of the century have been
Mycobacterium tuberculosis, brucella, diphtheroids, and the herpes
viruses. None of thes potential causative agents has confirmed.
Whether or not Hodgkin’s
Disease is a true neoplasm corresponding to other human tumors has
long been a matter of debate. It is significant that the largest
portion of the tumor mass, responsible for the major clinical
findings, is composed of inflamatory, presumed non neoplastic cells.
Cells that meet accepted criteria of being neoplastic are often very
rare in Hodgkin’s Disease tissue. It may be that the mononuclear
variant of the diagnostic Reed Sternberg multinucleated giant cell is
the chief tumor cell in the disease. Past evidence favoring the
opinion that this cell is derived from the monocyte-macrophage system
rather than from a B or T lymphocyte precusor has recently been
chalenged.
A defect in cell mediate
immunity has been recognized in patients with Hodgkin’s Disease. A
relative lymphocytopenia is characteristic, especially in patients
with advanced and progressive disease. Untreated patients have a
relative T lymphocytopenia, T lymphocyte dysfunction, and a serum
factor that interferes with normal T lymphocyte reactions. B cell
function is normal.
Pathology
The minimum requirement for the pathological diagnosis of Hodgkin’s
Disease is the presence of characteristic giant cells of the Reed
Sternberg type in an appropriate histological setting. See Reed
Sternberg Cell (24 Kb).
The most reliable
characteristics of the Reed Sternberg cell are the large inclusion
like nucleloi and the double or multiple nuclei of large size. A
peculiar clear zone about the nucleolus is tipically large and
spherical, with smooth margins and homogeneous eosinophilic or
amphophilic staining characteristics. The Reed Sternberg cells may
vary considerably in their morphological apperance, depending on the
histological subtype.
This and other refinements
have permitted the development of the Rye histopathological
classification.
See(Table
1).
Clinical Manifestations
Constitutional symptoms may accompany the diagnosis of Hodgkin’s
Disease. Patients with fever in excess of 38°C, drenching night
sweats, and weight loss exceeding 10 percent of baseline body weight
during the 6 months preceding diagnosis are designated as having”B”disease.
Fevers are usually low grade and irregular. Rarely, a cyclic pattern
of high fevers for 1 to 2 weeks alternating with afebrile periods of
similar lengh is present at diagnosis. This classic Pel Ebstein fever
is virtually diagnostic. Generalized pruritus, often accompanied by
marked excoriation, may be present at diagnosis. Pain in involved
lymph nodes immediately after the ingestion of alcohol is a curious
complaint that is nearly specific to Hodgkin’s Disease. Patients
with intrathoracic disease may present with cough, chest pain, dyspnea,
and, rarely hemoptysis. Rarely, patients present with bone pain,
including the constellation of back pain accompained by signs and
symptoms of spinal cord compression.
A typical presentation is the
observation, usually by the patient, of a painless, enlarging mass,
most often in the neck but occasionally in the axilla or
inguinal-femoral region. On examination this is found to be a
discrete, rubbery, painless lymphadenopathy, frequently with enlarged
lymph nodes in close proximity. In other patients, a chest
roentgenogram, taken for a routine purpose, demonstrates a moderate or
even massive mediastinal enlargement with associated lower cervical
lymphadenopathy.
Hematological
Abnormalities
Anemia of a moderate degree may be found in patients who present
with widespread disease, often associated with systemic symptoms. This
is usually an anemia with normal indices, with a normal or low
reticulocyte count, and with a negative Coomb’s test. This may be
caused by extensive bone marrow involvement with the disease,
hypersplenism with splenomegaly, or rarely, a Coomb’s positive
hemolytic picture.
Bone marrow involvement can
only rarely be demonstrated by the usual marrow aspirate technique and
examination of marrow smears. The involvement is focal, often
associated with fibrosis. It may be found with increasing frequency as
the disease is or becomes more widespread with systemic symptoms and
is often associated with an elevated serum alkaline phosphatase,
radiologic evidences of bone involviment and unexplained pancytopenia
The erythrocyte sedimentation
rate is commonly elevated in patients with active disease and
sometimes may be the only evidence that the disease has been
inadequately treated or that clinical recurrence is imminent.
An absolute severe
lymphopenia, even in untreated patients, is seen in small percentage
of cases and, when present, is a poor prognostic sign.
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