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Cervical Lymphadenopathy Mimicking Angioimmunoblastic T-Cell Lymphoma after Dapsone-Induced Hypersensitivity Syndrome

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A 36-year-old woman presented with erythematous confluent macules on her whole body with fever and chills associated with jaundice after 8 months of dapsone therapy. Her symptoms had developed progressively, and a physical examination revealed bilateral cervical lymphadenopathy and splenomegaly. Excisional biopsy of a cervical lymph node showed effacement of the normal architecture with atypical lymphoid hyperplasia and proliferation of high endothelial venules compatible with angioimmunoblastic T-cell lymphoma. However, it was assumed that the cervical lymphadenopathy was a clinical manifestation of a systemic hypersensitivity reaction because her clinical course was reminiscent of dapsone-induced hypersensitivity syndrome. A liver biopsy revealed drug-induced hepatitis with no evidence of lymphomatous involvement. Intravenous glucocorticoid was immediately initiated and her symptoms and clinical disease dramatically improved. The authors present an unusual case of cervical lymphadenopathy mimicking angioimmunoblastic T-cell lymphoma as an adverse reaction to dapsone.

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Most cited references 16

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Drug-induced pseudolymphoma and drug hypersensitivity syndrome (Drug Rash with Eosinophilia and Systemic Symptoms: DRESS).

Since the first description by Saltzstein in 1959, the denomination of drug-induced pseudolymphoma was used to describe two cutaneous adverse drug reactions with a histological picture mimicking malignant lymphoma. On the basis of clinical presentation, this term includes two different patterns: (1) hypersensitivity syndrome which begins acutely in the first 2 months after the initiation of the drug and associates fever, a severe skin disease with characteristic infiltrated papules and facial edema or an exfoliative dermatitis, lymphadenopathy, hematologic abnormalities (hypereosinophilia, atypical lymphocytes) and organ involvement such as hepatitis, carditis, interstitial nephritis, or interstitial pneumonitis. The cutaneous histological pattern shows a lymphocytic infiltrate, sometimes mimicking a cutaneous lymphoma, and the mortality rate is about 10%. When organ involvement exists, corticosteroids are often prescribed with dramatic improvement. Relapses may occur. (2) drug-induced pseudolymphoma which has a more insidious beginning with nodules and infiltrated plaques appearing several weeks after the beginning of the drug without constitutional symptoms. A pseudolymphoma pattern is seen on cutaneous histological slides. Complete improvement is usual after drug withdrawal, but a delayed lymphoma is possible. To decrease the ambiguity of the denomination of hypersensitivity syndrome, we propose the term of DRESS (Drug Rash with Eosinophilia and Systemic Symptoms).
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Clinicopathologic and genotypic study of extranodal nasal-type natural killer/T-cell lymphoma and natural killer precursor lymphoma among Koreans.

This study aimed to define genotypic profile and to describe the clinicopathologic features of nasal-type natural killer (NK)/T-cell lymphoma of nasal and extranasal origin and NK precursor lymphoma. NK/T-cell lymphomas from the upper aerodigestive tract (n = 45), skin (n = 2), gastrointestinal tract (n = 3), and soft tissue (n = 2) and NK precursor neoplasms (n = 3) were studied. Immunophenotype was analyzed by immunohistochemistry and flow cytometry. In situ hybridization with EBER 1/2 RNA probes was performed. T-Cell Receptor (TCR)-gamma gene rearrangement was analyzed by seminested polymerase chain reaction with heteroduplex analysis. Overall survival rate was correlated with clinicopathologic parameters and compared by Wilcoxon test. Clonal TCR-gamma gene rearrangement was detected in 3 of 31 upper aerodigestive and 1 of 2 skin tumors. When immunostained using paraffin embedded tissue, 6 upper aerodigestive lymphomas were negative for CD56 in which 4 cases lacked clonal TCR gene rearrangement. Epstein-Barr virus (EBV) mRNA was detected in 33 upper aerodigestive tumors including 26 of 29 nasal tumors (90%), and 7 of 10 extranasal tumors (70%). There was no histologic, immunophenotypic, or genotypic differences according to the lineage and EBV association in upper aerodigestive lymphomas. Among the patients with upper aerodigestive tumors, overall 1-year survival rate was 41%, and correlated well with the stage (P 0.05). Median survival rate of lymphomas from other sites excluding upper aerodigestive tract was not significantly different from that of upper aerodigestive lymphomas with same stage (P > 0.05). Unlike nasal-type NK/T-cell lymphomas, NK precursor lymphoma involved the bone marrow and lymph nodes at initial presentation or in the course of disease. Tumor cells were positive for TdT in all and myeloid markers in two. TCR gene rearrangement was germ line. Most upper aerodigestive nasal-type NK/T-cell lymphomas among Koreans are genotypically of NK derivation and few belong to T lineage. Presence or absence of EBV has no significant correlation with the histologic changes and the lineage of these lymphomas. Copyright 2000 American Cancer Society.
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The Dapsone Hypersensitivity Syndrome revisited: a potentially fatal multisystem disorder with prominent hepatopulmonary manifestations

4,4'-Diaminodiphenylsulphone (Dapsone) is widely used for a variety of infectious, immune and hypersensitivity disorders, with indications ranging from Hansen's disease, inflammatory disease and insect bites, all of which may be seen as manifestations in certain occupational diseases. However, the use of dapsone may be associated with a plethora of adverse effects, some of which may involve the pulmonary parenchyma. Methemoglobinemia with resultant cyanosis, bone marrow aplasia and/or hemolytic anemia, peripheral neuropathy and the potentially fatal dapsone hypersensitivity syndrome (DHS), the focus of this review, may all occur individually or in combination. DHS typically presents with a triad of fever, skin eruption, and internal organ (lung, liver, neurological and other systems) involvement, occurring several weeks to as late as 6 months after the initial administration of the drug. In this sense, it may resemble a DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms). DHS must be promptly identified, as untreated, the disorder could be fatal. Moreover, the pulmonary/systemic manifestations may be mistaken for other disorders. Eosinophilic infiltrates, pneumonitis, pleural effusions and interstitial lung disease may be seen. This syndrome is best approached with the immediate discontinuation of the offending drug and prompt administration of oral or intravenous glucocorticoids. An immunological-inflammatory basis of the syndrome can be envisaged, based on the pathological picture and excellent response to antiinflammatory therapy. Since dapsone is used for various indications, physicians from all specialties may encounter DHS and need to familiarize themselves with the salient features about the syndrome and its management.

Author and article information

Department of Internal Medicine, Gachon University Gil Hospital, Gachon University of Medicine and Science, Incheon, Korea.
[1]Department of Pathology, Gachon University Gil Hospital, Gachon University of Medicine and Science, Incheon, Korea.
[2]Department of Laboratory Medicine, Gachon University Gil Hospital, Gachon University of Medicine and Science, Incheon, Korea.
[3]Department of Pathology, Ewha Womans University School of Medicine, Seoul, Korea.
Author notes
Corresponding Author: Sanghui Park, M.D. Department of Pathology, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 158-710, Korea. Tel: +82-2-2650-5822, Fax: +82-2-2650-5822,
Korean J Pathol
Korean J Pathol
Korean Journal of Pathology
The Korean Society of Pathologists and The Korean Society for Cytopathology
December 2012
26 December 2012
: 46
: 6
: 606-610
© 2012 The Korean Society of Pathologists/The Korean Society for Cytopathology

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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