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Hodgkin's DiseaseAuthor: Reinaldo Dal Bello Figueira Júnior, MD |
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.
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.
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.
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.
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.
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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