|Year : 2015 | Volume
| Issue : 2 | Page : 75-76
Sweet's Syndrome in Acute Lymphoblastic Leukemia with t (9:22)
Khushboo Dewan, Shailaja Shukla
Department of Pathology, Lady Hardinge Medical College and Associated Hospitals, New Delhi, India
|Date of Submission||04-Feb-2015|
|Date of Acceptance||06-Mar-2015|
|Date of Web Publication||28-Apr-2015|
Dr. Khushboo Dewan
26, Amit Apartments, Sector-13, Rohini, New Delhi 110085
Source of Support: None, Conflict of Interest: None
Sweet's syndrome (SS) is a rare disease diagnosed in children and is characterized by fever, erythematous skin lesions, and dense infiltration of neutrophils in the upper dermis without evidence of leukocytoclastic vasculitis on histopathology. It may occur secondary to infection, malignancy or drug intake. A case of a 9-year-old boy diagnosed as acute precursor B-cell lymphoblastic leukemia with BCR-ABL1 mutation and treated with induction chemotherapy and imatinib mesylate (IM) therapy is presented. After 8 weeks of consolidation chemotherapy, the patient developed painful and erythematous nodules where a biopsy showed dense neutrophilic infiltrate and edema in the papillary dermis consistent with SS. Whether SS is caused clinically by acute lymphoblastic leukemia, the presence of BCR-ABL1 mutation or due to IM therapy is discussed.
Keywords: Acute lymphoblastic leukemia, BCR-ABL1 mutation, imatinib mesylate, Sweet′s syndrome
|How to cite this article:|
Dewan K, Shukla S. Sweet's Syndrome in Acute Lymphoblastic Leukemia with t (9:22). Cancer Transl Med 2015;1:75-6
| Introduction|| |
Sweet's syndrome (SS) is characterized by an unexpected onset of painful and erythematous skin lesions, fever, increased erythrocyte sedimentation rate, elevated C-reactive protein, neutrophilia, and histopathological evidence of dense neutrophilic infiltrate in the upper dermis without evidence of leukocytoclastic vasculitis.  It is a rare disease diagnosed in children.  It is usually associated with an infection of the upper respiratory tract or gastrointestinal tract, inflammatory bowel disease, pregnancy (classical SS), an underlying acute myelogenous leukemia (AML), carcinomas of the genitourinary organs, breast and gastrointestinal tract (malignancy-associated SS [MASS]) or related to drug intake (drug-induced SS [DISS]).  Only a single case of its association in acute lymphoblastic leukemia (ALL) has been reported so far. 
| Case Report|| |
A 9-year-old boy was diagnosed with ALL with his peripheral blood examination revealing a total leukocyte count of 137,900 cells/μL and presence of 94% myeloperoxidase negative blasts. The blasts showed bright expression of CD10, CD79a, HLA-DR, CD34, and moderate expression of CD19, dim TdT, and CD22 expression on flow cytometry. BCR-ABL1 translocation was detected by fluorescence in situ hybridization and karyotyping. After 8 weeks of consolidation chemotherapy and imatinib mesylate (IM) therapy, the patient presented high fever and painful and erythematous tender nodules measuring 0.3-1 cm on the palmar aspect of both hands that developed into abscesses [Figure 1]. Peripheral blood showed the leukocytosis with total leukocyte count of 14,100 cells/μL with 68% neutrophils. Erythrocyte sedimentation rate was 62 mm/h. Bacterial culture from the abscess fluid was sterile. A skin biopsy from the lesion that was taken to rule out leukemic infiltration of the skin showed a dense neutrophilic infiltrate in the papillary dermis along with intense edema [Figure 2]. Many dilated small blood vessels and a few capillaries that were lined by swollen endothelial cells completely obliterating their lumen were seen [Figure 3]. Despite heavy neutrophilic infiltrate, there was no evidence of leukocytoclastic vasculitis and the overlying epidermis was unremarkable. Moreover, no blasts were identified morphologically and immunohistochemically. In view of the histopathological findings and the clinical presentation, a diagnosis of SS was made, and IM was withheld until the skin lesions healed. No steroid therapy was given to the patient. IM therapy was reinitiated after 6 weeks, and the patient responded well to the therapy. The patient is being followed up and has been healthy 1-year after the initial leukemic presentation.
|Figure 1. An abscess on the palmar aspect of right thumb measuring 0.8 cm in diameter|
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|Figure 2. Skin biopsy (HE, ×100) shows neutrophilic infiltrate in the papillary dermis along with intense edema|
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|Figure 3. Skin biopsy (HE, ×400) shows capillaries that are lined by swollen endothelial cells completely obliterating their lumina along with neutrophilic infiltrate in the papillary dermis|
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| Discussion|| |
Sweet's syndrome was first described by Sweet  as "acute febrile neutrophilic dermatosis" in 1964. Since then, several hundred cases of SS have been reported. SS has been described in different clinical settings: classical SS, MASS, and DISS. Classical SS predominantly affects women and is often preceded by infection of the upper respiratory tract or gastrointestinal tract. Around one-fifth of the patients with SS are associated with hematologic or solid malignancy.  MASS is most often seen in patients with AML.  It has also been described in patients with chronic myeloid leukemia (CML), chronic lymphocytic leukemia, myelodysplastic syndrome, and hairy cell leukemia. ,, A case of SS in ALL was reported by Tuncer  in 1988. In patients with hematologic disorders, SS can occur in one or more of the following forms: a drug-induced dermatosis, a paraneoplastic syndrome or with concurrent demonstrate leukemia cutis. DISS has been observed in patients following treatment with colony-stimulating factors, anti-neoplastics, and antibiotics. A temporal relationship between drug intake, clinical presentation/recurrence, and temporally related resolution of lesions after drug withdrawal is described.
The case under investigation is unique, for the patient had Philadelphia positive chromosome ALL, for which he was started on IM treatment and who later in the course of the disease developed SS. Whether SS is caused clinically because of ALL, the presence of BCR-ABL1 mutation, due to IM therapy or because of their interaction is an interesting question. Only a single case of SS in ALL has been reported so far, possibly as a paraneoplastic syndrome.  A number of cases of CML with SS have been reported, some of which were also treated with IM. In the case reported by Ayirookuzhi et al.,  the patient developed skin lesions of SS on 2 occasions immediately following IM therapy initiation and the symptom was relieved by discontinuation of IM and treatment with steroids. Although IM has been implicated to cause SS in many case reports, the patient under study tolerated IM therapy well, and the skin lesions developed only after 3 months of chemotherapy. Moreover, the patient is currently receiving IM therapy without developing any additional skin lesions. A lack of the temporal relationship between IM ingestion and skin lesions in this case discredits against the diagnosis of DISS. The absence of lymphoblasts infiltrating the skin rules out a co-existing leukemia cutis. A possibility of SS arising from a paraneoplastic syndrome in this case cannot be excluded.
To conclude, SS is rare in patients with ALL. This case is highlighted for the development of SS in a case of ALL with BCR-ABL1 mutation taking IM therapy. SS occurring from a paraneoplastic syndrome in this case is more likely over imatinib-induced SS.
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[Figure 1], [Figure 2], [Figure 3]