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Well-differentiated systemic mastocytosis with KIT K509I mutation and uterus infiltration in an Asian woman with good response to imatinib

Zhao, Duo-Duo1; Zhang, Lu1; Li, Wen-Qin2,3; Duan, Ming-Hui1; Zhuang, Jun-Ling1; Zhou, Dao-Bin1

Section Editor(s): Guo, Li-Shao

doi: 10.1097/CM9.0000000000000355
Correspondence
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1Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medicine Sciences, Beijing 100730, China

2Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medicine Sciences, Beijing 100730, China

3Department of Pathology, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830000, China.

Correspondence to: Dr. Lu Zhang, Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medicine Sciences, Beijing 100730, ChinaE-Mail: pumczhanglu@126.com

How to cite this article: Zhao DD, Zhang L, Li WQ, Duan MH, Zhuang JL, Zhou DB. Well-differentiated systemic mastocytosis with KIT K509I mutation and uterus infiltration in an Asian woman with good response to imatinib. Chin Med J 2019;132:00–00. doi: 10.1097/CM9.0000000000000355

Received 15 March, 2019

Online date: July 22, 2019

This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

To the Editor: We report a 27-year-old woman with a 2-month history of irregular uterine bleeding between periods. Blistering on the head was noted in the patient at the age of 2 months, and she gradually developed red maculopapular lesions over her neck and back during puberty, which were itchy after exposure to physical friction. On admission, physical examination had revealed diffuse faint maculopapular rash mainly on the neck and back [Figure 1]. Pelvic examination showed a smooth red lump (5 cm) on the cervix. No abnormality was detected in the complete blood count. Afterwards, the cervical lump was resected and confirmed to be the infiltration of mature mast cells (MCs) after careful pathological investigation. Additionally, a skin nodule biopsy also indicated mass aggregation of MCs, and a bone marrow (BM) biopsy showed a mass of round MCs with abundant cytoplasmic granules. The MCs accounted for about 22.5% of all cells in the aspirate smears. Flow cytometry immunophenotypic analysis on BM suggested that an aberrant MC population had represented 10% of the total analyzed cells, which was positive for CD117, CD33, and CD9, partially positive for CD2 and CD68, and negative for CD25. Genetic test through exome-wide sequencing for the receptor tyrosine kinase (KIT) gene had revealed K509I mutation.

Figure 1

Figure 1

The patient was treated with imatinib mesylate at a dose of 100 mg daily for nearly 3 months and then 400 mg daily for another 3 months. Fortunately, the patient could attain complete remission in BM and the symptoms were dramatically improved.

Systemic mastocytosis (SM) represents a group of disorder characterized by the expansion and accumulation of neoplastic MCs in one or more organ systems,[1] which frequently occurs in adults. In the World Health Organization (WHO) 2016 updated classification,[2] SM is further classified into indolent SM, smoldering SM (SSM), SM with an associated clonal hematologic non-MC-lineage disease, aggressive SM (ASM), and MC leukemia. In 2004, Akin et al[3] first reported a case of ASM associated with CD25/CD2 BM MCs that had normal morphology, along with a germline mutation (F522C) of KIT, and the patient showed dramatic response to imatinib. Since then, a few similar cases have been reported and this new disease variant is named well-differentiated SM (WDSM). Typically, sensitive response to tyrosine kinase inhibitor therapy is commonly seen among those patients with wild-type KIT or some molecular alterations of KIT.[3–5]

The clinical course and prognosis of SM are determined by the WHO-designated variant rather than the WD morphology of MCs. In our case, the patient was clearly diagnosed with smoldering SM-WDSM (SSMWDSM) based on her obvious symptoms and skin signs, mature MCs involvement in BM and uterus, as well as KIT K509I mutation. To the best of our knowledge, this is the first known case of WDSM in Asia and also the first report of well-differentiated MCs invasion of the uterus.

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Declaration of patient consent

The informed consent was obtained from the patient in this case, and the patient has given her consent in the form for her images and other clinical information to be reported in the journal. The patient understands that her name and initial will not be published and due efforts will be made to conceal the identity of the patient, although anonymity cannot be guaranteed.

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Funding

This work was supported by a grant from the Institutional Research Funding provided by the Fundamental Research Funds for the Central Universities (No. 3332018036).

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Conflicts of interest

None.

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References

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3. Akin C, Fumo G, Yavuz AS, Lipsky PE, Neckers L, Metcalfe DD. A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib. Blood 2004; 103:3222–3225. doi: 10.1182/blood-2003-11-3816.
4. Alvarez-Twose I, González P, Morgado JM, Jara-Acevedo M, Sánchez-Muñoz L, Matito A, et al. Complete response after imatinib mesylate therapy in a patient with well-differentiated systemic mastocytosis. J Clin Oncol 2012; 30:e126–e129. doi: 10.1200/JCO.2011.38.9973.
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