Newly identified phenotypes in a FIP1L1/PDGFRA‐associated paediatric HES patient: thrombocytosis, mHPA, young stroke and blindness

Abstract

specimens taken from the right forearm revealed non-specific superficial perivascular infiltration of inflammatory cells without spongiosis (Fig. 1b). Laboratory findings including aspartate aminotransferase and alanine aminotransferase were within normal limits and no eosinophilia was observed. Thus, one of the most apparent differential diagnoses was drug eruption, and all medications, including MMC therapy, were discontinued immediately.After discontinuation of all drugs and starting topical steroid therapy (betamethasone dipropionate; Shionogi & Co., Ltd., Osaka, Japan, for 3 days), the generalized erythema was remarkably improved with no recurrences. Neither patch tests nor druginduced lymphocyte stimulation tests (DLST) for all drugs, including MMC, were positive. However, from his clinical course, intravesical instillation of MMC was the leading candidate for the factor affecting his generalized erythema. Therefore, we performed a rechallenge test with intravesical instillation of MMC (5 mg, or half the previous dosage). After 24 h, generalized erythema had developed (Fig. 1c), and we considered that the rechallenge test was positive and immediately stopped MMC instillation. Topical steroid therapy resulted in prompt recovery to normal skin.In the present case, although DLST and patch test were negative, the patient's generalized erythema was assumed to be due to MMC treatment, as determined by rechallenge test. In general, the reliability of DLST in drug eruption is relatively low, and positive rates for the test have been reported to range from 60% to 70%. 2 Drug patch tests are positive in only 30-50% of patients with suspected drug eruption. 3 Therefore, from the present work, we conclude that a careful evaluation of clinical course, and in some cases also a rechallenge test, is very important for diagnosis of drug eruption.

Case Report: Pediatric myeloid/lymphoid neoplasm with eosinophilia and PDGFRA rearrangement: The first case presenting as B-lymphoblastic lymphoma

“…After the FIP1L1-PDGFRA fusion gene was identified, the diagnosis was modified to FIP1L1-PDGFRApositive CEL and the authors declared the intent of initiation of imatinib if their patient exhibits a second relapse (4). All subsequent reported pediatric cases included imatinib in their treatment plan (5,(7)(8)(9)(10)(11)(12)(13)(14). Favorable outcomes were reported in all cases except the case presenting as T-LBL that was reported by Oberley et al in 2017 (10).…”

Sustained Complete Molecular Remission With Imatinib Monotherapy in a Child Presenting With Blast Phase FIP1L1‐PDGFRA‐Associated Myeloid Neoplasm With Eosinophilia

“…Given the varied presentation, the World Health Organization now classifies these malignancies under the category of “myeloid/lymphoid neoplasms with eosinophilia (MLN‐Eo) and rearrangement of PDGFRA , PDGFRB , or FGFR1 , or with PCM1‐JAK2 ” 1 . This disease is extremely uncommon in children and only 8 FIP1L1‐PDGRFA cases have previously been described 2–9 …”

“…1 Among the eight pediatric FIP1L1-PDGFRA cases summarized in Table 1, seven presented as chronic MPNs with eosinophilia, while one presented as T-ALL/T-LLy without eosinophilia. [2][3][4][5][6][7][8][9] Only 1/7 chronic MPN cases had elevated BM blasts at 10%. 8 This disease rarely presents in blast phase, defined by >20% PB/BM blasts and/or extramedullary disease.…”

“…1 This disease is extremely uncommon in children and only 8 FIP1L1-PDGRFA cases have previously been described. [2][3][4][5][6][7][8][9] A rare presentation of this entity, only previously reported in adults, is blast phase disease with >20% blasts in the peripheral blood (PB) or bone marrow (BM), and/or as extramedullary disease. 1,10,11 Such a presentation is often difficult to distinguish from AML, and is typically accompanied with massive splenomegaly and peripheral eosinophilia.…”

Literature reviews of stroke with hypereosinophilic syndrome

“…We searched PubMed to identify case reports of stroke with HES and found 97 cases that have been reported from January 2000 to October 2021 [2] , [4] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , …”