Malignant struma ovarii: next-generation sequencing of six cases revealed Nras, Braf, and Jak3 mutations

Poli, Roberta; Scatolini, Maria; Grosso, Enrico; Maletta, Francesca; Gallo, Marco; Liscia, Daniele; Nelva, Anna; Cesario, Flora; Forte, Giuseppe; Metović, Jasna; Volante, Marco; Arvat, Emanuela; Papotti, Mauro

doi:10.1007/s12020-020-02438-7

Cited by 15 publications

(23 citation statements)

References 39 publications

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“…Recurrent JAK3 V722I is reported in malignant struma ovarii, which is a specific ovarian teratoma. 17 Consistent with JAK3 V722I, the mutation site of JAK3 I688F is located in the same protein domain (protein kinase 1), thus potentially harboring a similar function.…”

Section: Discussionmentioning

confidence: 93%

Acute Mast Cell Leukemia Preceded by Malignant Mediastinal Germ Cell Tumor: A Case Report and Literature Review

Wang¹,

Chen²,

Lin³

et al. 2022

CMAR

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Background Mast cell leukemia (MCL) is a highly life-threatening and extremely rare subtype of systemic mastocytosis (SM). MCL often genetically contains one or more somatic mutations, particularly activating mutations of KIT . This study reported on an acute MCL patient who had a rare phenotype and genetic mutants with a history of primary malignant mediastinal germ cell tumor (GCT). Case Presentation A 30-year-old Asian male patient who underwent two rounds of surgery and chemotherapy with a history of primary mediastinal GCT (PM-GCTs) was admitted to our hospital due to persistent chest pain and severe fatigue. The diagnosis of acute MCL was confirmed via morphology analysis and chemical staining of marrow aspirate, as well as via marrow biopsy, with the addition of C-findings that included splenomegaly and cytopenia. The atypical MCs were phenotypically positive for CD117 and CD9 but weakly positive for CD2 and negative for CD25. Next-generation sequencing of the marrow aspirate identified heterozygous mutations in TP53 P301Qfs*44, FLT3 R973X, SETBP1 N272D, and JAK3 I688F, whereas mutations in KIT were not found. Although the initial therapy of corticosteroids, ruxolitinib, and dasatinib-based regimens was effective, he died of acute respiratory distress syndrome after the first cycle of chemotherapy with cladribine and cytarabine. The patient’s survival time was 2.4 months after the initial presentation of MCL. Conclusion In this case, MCL preceded by PM-GCTs had similar clinical symptoms and morphological manifestations but distinctly different genetic profiles than primary MCL. The characteristic morphology of MCL provides the most pivotal evidence that led our diagnosis in the correct direction. A competing hypothesis is that there is a common embryonal cancer stem cell between PM-GCTs and secondary MCL, and the latter is gradually developed in the context of additional “driver mutations”.

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Section: Discussionmentioning

confidence: 93%

Acute Mast Cell Leukemia Preceded by Malignant Mediastinal Germ Cell Tumor: A Case Report and Literature Review

Wang¹,

Chen²,

Lin³

et al. 2022

CMAR

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“…JAK3 mutation is regarded as a driver mutation that is frequently reported in T lineage acute lymphoblastic leukemia [25,26]. Recurrent JAK3 V722I is reported in malignant struma ovarii, a speci c ovarian teratoma [27]. Consistent with JAK3 V722I, the mutation site of JAK3 I688F is located in the same protein domain, protein kinase 1, potentially harboring a similar function.…”

Section: Discussionmentioning

confidence: 99%

Acute Mast Cell Leukemia Preceded by Malignant Mediastinal Germ Cell Tumor: A Rare Case Report and Literature Review

Wang¹,

Chen²,

Lin³

et al. 2021

Preprint

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Background: Mast cell leukemia (MCL) is a highly life-threatening and extremely rare subtype of systemic mastocytosis (SM). MCL, divided into de novo subtype and secondary to mastocytosis subtype, often genetically contains one or more somatic mutations, particularly the activating mutations of KIT. In this study, an acute MCL case was reported, who had rare phenotype and genetic mutants with a history of primary malignant mediastinal germ cell tumor (GCT).Case presentation: A male patient aged 30, who underwent two rounds of surgery and chemotherapy with a history of malignant mediastinal GCT, was admitted to our hospital due to persistent chest pain and severe fatigue. The diagnosis of acute MCL was confirmed by morphology analysis and chemical staining of marrow aspirate and biopsy, with the addition of C-findings including splenomegaly and cytopenia. The atypical MCs phenotypically expressed CD9, but no CD2 and CD25. Next gene sequencing of marrow aspirate identified heterozygous mutations in TP53 P301Qfs*44, FLT3 R973X, SETBP1 N272D, and JAK3 I688F, whereas the mutations in KIT were not found. Although the initial therapy of corticosteroids and dasatinib-based regimen was effective, he died of acute respiratory distress syndrome after the first cycle of chemotherapy with cladribine and cytarabine. The survival time of the patient was 2.4 months after the initial presentation of MCL. Conclusion: In this case, MCL preceded by malignant mediastinal GCT has similar clinical symptoms and morphological manifestations but distinctly different genetic profiles in contrast to primary MCL. The characteristic morphology of MCL provides the most pivotal evidence that led our diagnosis in the right direction. A hypothesis was speculated that there is a common embryonal cancer stem cell between primary malignant GCT and secondary de novo MCL, whereas the latter is gradually developed in the context of additional “driver mutations”.

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“…Oncogene mutations including KRAS , NRAS , BRAF and JAK3 have been reported. 31 , 32 It would be beneficial to investigate the mutations of ovarian germ cell tumors in guiding postoperative treatment.…”

Section: Discussionmentioning

confidence: 99%

Struma Ovarii Associated with Ascites and Elevated CA125: Two Case Reports and Review of the Literature

Wang¹,

He²,

Yang³

et al. 2022

IJWH

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Struma ovarii is a rare variety of specialized monodermal mature ovarian teratoma, it is composed predominantly of thyroid tissue. Ascites is present in one third of patients. The combination of struma ovarii, marked ascites and elevated CA125 is a rare condition, which may mimic ovarian cancer. We described two cases presenting with pelvic mass, ascites and elevated serum CA125 levels, frozen section and final pathology turned out to be struma ovarii. Ascites disappeared and the level of CA125 returned to normal level after operation. One of the cases was associated with pleural effusion, leading to a condition called pseudo-Meigs’ syndrome. Then we reviewed the related literatures to explore the possible mechanism of ascites and pleural effusion, the reason of CA125 elevation and imaging manifestations of struma ovarii. In conclusion, struma ovarii should be considered in the differential diagnosis preoperatively, when presented with pelvic mass, ascites and an elevated CA125 level.

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Malignant struma ovarii: next-generation sequencing of six cases revealed Nras, Braf, and Jak3 mutations

Cited by 15 publications

References 39 publications

Acute Mast Cell Leukemia Preceded by Malignant Mediastinal Germ Cell Tumor: A Case Report and Literature Review

Acute Mast Cell Leukemia Preceded by Malignant Mediastinal Germ Cell Tumor: A Case Report and Literature Review

Acute Mast Cell Leukemia Preceded by Malignant Mediastinal Germ Cell Tumor: A Rare Case Report and Literature Review

Struma Ovarii Associated with Ascites and Elevated CA125: Two Case Reports and Review of the Literature

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