Out of BCR-ABL negative myeloproliferative neoplasm (MPNPh- ) patients, 3%-14% display a concomitant monoclonal gammopathy of unknown significance (MGUS). In most cases, the diagnosis of plasma cell dyscrasia is either synchronous with that of MPNPh- or occurs later on. We present a 50-year-old patient with type 2 CALR Lys385Asnfs*47 mutation positive essential thrombocythemia (ET) who developed symptomatic multiple myeloma (MM) 13 years after the diagnosis of ET during PEG-INF2α treatment. The NGS study performed at the time of the MM diagnosis revealed the HRAS Val14Gly/c.41T〉G mutation and the wild type CALR, JAK2 and MPL gene sequence. In the presented case, the complete molecular remission of ET was achieved after 16 months of PEG-INF2α treatment. The origin of MM cells in MPNPh- patients remains unknown. Published data suggests that type 2 CALRins5 up-regulate the ATF6 chaperone targets in hematopoietic cells and activate the inositol-requiring enzyme 1α-X-box-binding protein 1 pathway of the unfolded protein response (UPR) system to drive malignancy. It cannot be excluded that endoplasmic reticulum stress induced by the increased ATF6 resulted in an abnormal redox homeostasis and proteostasis, which are factors linked to MM. The presented case history and the proposed mechanism of mutant CALR interaction with UPR and/or ATF6 should initiate the discussion about the possible impact of the mutant CALR protein on the function and genomic stability of different types of myeloid cells, including progenitor cells.

BACKGROUND: Essential thrombocythemia (ET) is an uncommon myeloproliferative neoplasm. It is more common in females; 20% of them are below 40 years old. The optimal management of ET during pregnancy and postpartum periods is still not well established.
METHODS: We report a case of a young lady with type 2 calreticulin-mutant ET who developed a marked rebound in her platelet count (reaching 2030 × 103/μL) 2 weeks after premature delivery of her baby (24th week of gestation). She was on Pegylated Interferon alfa 2-a during pregnancy (her platelet was around 500 × 103/μL during the second trimester), but she had stopped it on her own from the 20th week of gestation.
METHODS: Postpartum rebound of platelet count due to medication non-compliance.
RESULTS: We resumed her regular Pegylated Interferon, and subsequently, her platelet count reduced dramatically within 4 weeks to an acceptable level (684 × 103 /μL).
CONCLUSIONS: The guideline is still not well-established regarding the optimal approach for postpartum rebound of platelet count in patients with ET. It is still unclear if the platelet count will fall spontaneously without intervention after the rebound phase. Further research is required to establish the optimal management of ET during the postpartum phase. This case emphasizes the importance of platelet count follow-up during the postpartum period and outlines our management approach in such cases.

Priapism is a rare presentation and complication of ET that might be underreported. In ET, priapism can present as an ischemic or stuttering type. These patients are more likely to be anemic and have a high platelet count.

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Hemorrhagic stroke associated with essential thrombocythemia (ET) is very infrequent. Herein, we report a case of a 33-year-old woman with a 2-year history of ET who developed intracerebral and subarachnoid hemorrhage. Angiography demonstrated severe vessel irregularity in the bilateral cerebral arteries. Molecular genetic testing revealed a calreticulin mutation. To our knowledge, hemorrhagic stroke has been reported in only six other patients with ET, and this is the first report of hemorrhagic stroke in an ET patient with a calreticulin mutation. We review the current literature and discuss the possible underlying mechanisms.

Sclerosing extramedullary hematopoietic tumor (SEMHT) is a rare disease that was originally named fibrous hematopoietic tumor or myelosclerosis. The process typically occurs in patients with a history of chronic myeloproliferative disorders and may afflict the skin, lung, breast, gastrointestinal tract, breast, kidney, lymph node, and thyroid gland. In this article, we report the case of a 37-year-old female with more than 5 years history of acute B-cell lymphoblastic leukemia who presented with right upper quadrant pain and tenderness. Computed tomography scan showed multiple new ring-enhancing low-density lesions within the right and left hepatic lobes. A computed tomography-guided liver core biopsy was performed on one of the new liver lesions and showed extramedullary hematopoiesis with atypical megakaryocytes and sinusoidal capillarization with associated fibroblastic proliferation. Numerous atypical megakaryocytes were scattered in the background of haphazard collagen deposition. No significant blasts or a leukemic process were identified. Bone marrow aspiration and biopsy showed extensive reticulin fibrosis (MF-3), trilineage dysplasia, increased blasts (10% to 19%), and hypercellularity (close to 100%), which was consistent with MDS-EB-2. Cytogenetics was reported as follows: 44~46,XX,-3,add(3)(p13),-5,-6,-7,17,del(17)(p12),+1~5mar[cp9]/46,XX. Molecular analysis was negative for both JAK2 V617F and CALR exon 9 activating mutations. In summary, we contributed a new case of SEMHT diagnosis in a synchronous presentation with poor clinical evolution associated chromosome 7 deletion and intact JAK2 and CALR exon 9. Care should be taken when diagnosing intraabdominal and retroperitoneal soft tissue masses with the history of hematological disorders.

Essential thrombocythemia (ET) is rare in children, and pediatric guidelines are lacking. Therefore, we aimed to evaluate ET diagnosis and treatment in a pediatric cohort.
Data of patients with ET from three hospitals were reviewed. Molecular diagnosis included JAK2V617F, CALR, and MPL mutations. Patients were evaluated for acquired von Willebrand syndrome (AVWS). Follow-up included clinical symptoms, adverse events, and treatment.
Twelve children (median age: 8 years, range 1-14.5) were included. Mean lag period between the first documentation of thrombocytosis until ET diagnosis was 36 months. Six patients were positive for JAK2V617F and two for CALR mutations. In six of nine patients, AVWS was diagnosed. At diagnosis, only 33% of patients started therapy with aspirin (n = 4) and hydroxyurea (n = 2). In three of eight untreated patients, therapy was added during follow-up. The cohort was followed for a median of 32.5 months (range: 4-108 months). Clinical follow-up disclosed vascular complications in 4 of 12 patients (deep vein thrombosis, n = 1; transient ischemic attack, n = 3). Two females experienced excessive bleeding; both were diagnosed with AVWS. Neither leukemia nor myelofibrosis evolved in our cohort.
Increased awareness to pediatric ET is warranted, as delayed diagnosis is common. Compared to adults, AVWS may be more prevalent among children with ET.

Splenomegaly is a key clinical manifestation of myelofibrosis, and splenectomy is currently indicated in patients with drug refractory, symptomatic splenomegaly or with the aim of improving refractory cytopenias. Transformation to acute myeloid leukemia occurs in up to 20% of patients with myelofibrosis, while cases of myeloid sarcoma have been reported very unfrequently. In this manuscript, we report the case of a 60-year-old man with a history of primary myelofibrosis who underwent splenectomy because of drug-refractory massive splenomegaly, systemic symptoms and anemia. At the opening of the peritoneal cavity, the spleen resulted massively enlarged and tenaciously entrapped by a pervasive neoplastic-like tissue. The extensive involvement of the abdomen fatally complicated the surgical procedure. At postmortem examination, the spleen showed a diffuse infiltration of immature cells that were also found in the peritoneum, bowel, liver, lungs and myocardium. After immunohistochemical, cytogenetic, flow cytometric and molecular characterization of neoplastic population, a diagnosis of disseminated myeloid sarcoma of the spleen was made. This case report highlights a very unusual case of myeloid sarcoma originating from the spleen in a patient with myelofibrosis who had no evidence of bone marrow or peripheral blood involvement by leukemic cells. Molecular characterization showed that leukemic cells originated from the founding clone of the chronic phase. The sarcoma could not be suspected based on clinical findings and was diagnosed only at the time of surgical procedure and autopsy. This case suggests that leukemic transformation of myelofibrosis can originate outside the bone marrow and, presumably rarely, present as a granulocytic sarcoma.

Myeloproliferative neoplasms (MPNs) are classified as chronic myeloid leukemia (CML) and Philadelphia chromosome-negative MPN. In MPN cases, the presence of a BCR-ABL1 translocation with a coexisting mutation is exceptionally rare. Herein, we report the first documented patient with CML harboring CALR mutation in Korea. A 33-year-old woman was referred to our hospital in February 2015 with splenomegaly, leukocytosis, and thrombocytosis. She was diagnosed with CML and started receiving nilotinib. In October 2015, a major molecular response was observed, but thrombocytosis persisted. A repeat bone marrow (BM) examination revealed no specific findings. However, as thrombocytosis worsened, we changed nilotinib to dasatinib. In May 2019, owing to persistent thrombocytosis, we repeated the BM examination and found CALR mutation (15.97%) on the MPN-next generation sequencing (NGS) test. We then retrospectively performed repeat MPN-NGS testing using the BM aspirate sample obtained in 2015 and found CALR mutation (10.64%).

BACKGROUND: Concurrent calreticulin (CALR) mutation and BCR-ABL1 fusion are extremely rare in chronic myelogenous leukemia; to date, only 12 cases have been reported.
METHODS: A 57-year-old male who had an 11-year history of essential thrombocytosis presented to our hospital with leukocytosis and marked splenomegaly for 3 months.
METHODS: Chronic myelogenous leukemia with myeloid fibrosis arising on the background of essential thrombocytosis harboring both BCR-ABL1 fusion and type-1 like CALR mutation.
METHODS: Imatinib was started at 300 mg daily and increased to 400 mg daily after 3 months; interferon was added after 12 months.
RESULTS: Partial cytogenetic response was achieved after 3 months of imatinib therapy and complete cytogenetic response was achieved after 1 year of treatment. However, CALR mutation was still present with a stable mutational allele burden.
CONCLUSIONS: In this case report and review of additional 12 cases with simultaneous presence of CALR-mutation and BCR-ABL1 fusion, we highlighted the importance of integrating clinical, morphological, and molecular genetic data for classifying atypical myeloid neoplasms.