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1806 Part XI: Malignant Lymphoid Diseases Chapter 110: Heavy-Chain Disease 1807

HISTOPATHOLOGY the γ-HCD protein does not vary in parallel with the associated pro-
In contrast to α-HCD, γ-HCD has no consistent morphologic pattern cess, and relapse can occur without the reappearance of the pathologic
4
and a variety of underlying lymphoproliferative disorders have been protein.
described. The most frequent histopathologic finding is a pleomor-
16
phic malignant lymphoplasmacytic proliferation in marrow and lymph α-HEAVY-CHAIN DISEASE DEFINITION
nodes. These lymphocytoid plasma cells express pan–B-cell markers
and cytoplasmic γ-HC without light chains and are negative for CD5 AND HISTORY
and CD10. 17 α-HCD is a proliferative disorder of B-lymphoid cells involving the
Lymphoma without any consistent morphologic type was diag- IgA secretory immune system, especially the gastrointestinal tract. It is
nosed in 18 (38 percent) of 47 patients in whom lymph nodes were defined by the recognition of internally deleted monoclonal α chains
examined. A lymphoplasmacytic proliferation was present in 36 per- devoid of light chains.
cent and hyperplastic nodes and plasmacytoma in 11 percent each; In the first case description of α-HCD, in 1968 by Seligman and
there was one case of Hodgkin lymphoma and one of probable Hodgkin colleagues, an Arab woman had severe malabsorption resulting from a
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lymphoma. Plasmacytic infiltration may be found in the salivary glands lymphoplasmacytic infiltrate in the small bowel. Since then, more than
6
or thyroid. 4,5,18
400 cases have been reported.
DIFFERENTIAL DIAGNOSIS EPIDEMIOLOGY
All patients presenting with a lymphoplasmacytic proliferative disorder The majority of reported cases have been from northern Africa, Israel,
should be evaluated for γ-HCD.
and surrounding Middle Eastern countries. A common variable for
patients with α-HCD is a low socioeconomic status. In a study of the
THERAPY distribution of monoclonal gammopathies in Tunisia published in 1990,
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17 percent of 198 cases were attributed to α-HCD. In a later study of
Because γ-HCD is a heterogeneous condition, the choice of therapy 270 cases observed between 1992 and 2000 at the university hospi-
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depends on the clinical findings. In an asymptomatic patient with a tal of Sfax in Tunisia, only 2.2 percent were attributed to α-HCD, a
monoclonal γ-HC, no therapy is indicated. Any associated autoim- finding that might be partially explained by improved socioeconomic
mune disease should be managed with standard therapy for that specific conditions. Similarly, a persistent decrease in the incidence of immu-
disease type. In symptomatic patients with a low-grade lymphoplas- noproliferative small intestinal disease (IPSID) since 1986 as a result
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macytic malignancy, a trial of chlorambucil may be beneficial. Melpha- of improving sanitation has been reported from Iran and Greece. α-
lan and prednisone can be used, if the proliferation is predominantly HCD has a predilection for young adults. The prevalence of the disease
plasmacytic. A trial of cyclophosphamide, vincristine, and prednisone is slightly higher in males than in females.
with or without doxorubicin is reasonable for patients with evidence
of a progressive lymphoplasmacytic proliferative process or high-
grade lymphoma. One patient achieved a complete response after six ETIOLOGY AND PATHOGENESIS
courses of fludarabine. Successful treatment of γ-HCD with low-dose The cause of α-HCD is unknown. The disease might be considered
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etoposide has been reported. CD20 expression has been analyzed in a model showing the complex interactions of the environment with
20
only seven cases and was detected in six of the seven, including one in genetic factors and the infection–immunity–cancer interrelationships
which CD20 expression appeared transient. 5,21–23 Rituximab monother- originating from the same proliferating clone. Although the mecha-
apy was given in two cases, resulting in clinical responses in both. In nisms leading to the development of a clonal population synthesizing
5,21
two other cases, a combination of rituximab with chemotherapy had the structurally abnormal IgA are still speculative, the lymphoplas-
an antitumor effect in lymphoplasmacytic-type γ-HCD. 22,24 In local- macytic infiltration of the intestinal mucosa is likely a response of the
ized extramedullary plasmacytomas treated with radiation or surgical alimentary tract immune system to protracted luminal antigenic stim-
4
removal (or both), complete clinical and serologic remission has been ulation. A causal relationship between infection and pathogenesis is
achieved. supported by the observation that α-HCD can respond to broad-spec-
trum antibiotics. Using molecular strategies, Campylobacter jejuni was
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COURSE AND PROGNOSIS detected in five of seven patients with α-HCD. However, no specific
microorganism has been found in other clinical studies. The putative
The clinical course of γ-HCD is extremely variable and ranges from an agent may be present only at the onset of the disease and absent at
asymptomatic, benign, or transient process to a rapidly progressive neo- diagnosis.
plasm leading to death within a few weeks. Patients with the features of
only a monoclonal gammopathy have remained clinically well for 2 to CLINICAL FEATURES
7 years of followup. Spontaneous disappearance of the γ-HCD pro-
5,25
tein has been reported. The median duration of survival in a series of In most cases, patients who have α-HCD present with the digestive
4
23 patients was 7.4 years (range: 1 month to more than 21 years). 5 form. The disease is characterized by malabsorption manifested by
The amount of serum γ-HCD protein usually parallels the severity diarrhea, weight loss, and abdominal pain. Ascites, tetany, edema,
of the associated malignant process. Disappearance of the monoclo- and clubbing may be present. Hepatosplenomegaly and peripheral
nal component from serum and urine associated with apparent com- lymphadenopathy are infrequent. Fever is uncommon. Amenor-
plete response has been induced by chemotherapy, radiotherapy, or rhea, alopecia, and growth retardation in children and adolescents
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surgical removal of a localized process. In some instances, however, correlate with the duration and the severity of the malabsorptive

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