Liver tumor concurrent with chronic myelocytic leukemia and extreme thrombocytosis: A rare case report

Background Chronic myelocytic leukemia (CML) may occasionally occur after organ transplantation or for solid tumors; Solid tumors secondary to biotherapy in CML have also been reported. However, the concurrence of solid tumor with CML and extreme thrombocytosis in an untreated patient is seldom reported. Case presentation We describe a 61-year-old woman transferred to liver surgery department for the discovery of a large mass in the liver and an elevated plasmic AFP. She was initially diagnosed with liver cancer. Blood tests indicated a marked increase of platelets(2464x10 9 /L). The chromosome examination of bone marrow biopsy indicated the existence of t(9;22) translocation, fluorescence in situ hybridisation (FISH) and PCR were both positive for the Bcr-Abl rearrangement. The diagnosis of CML was made. She received hydroxyurea and imatinib to treat CML, and platelet-lowering therapy, and then underwent a liver biopsy, which suggestted a moderately-poorly differentiated adenocarcinoma, or might be a hepatic metastatic carcinoma. However, the patient refused further pathological examination and primary site screening for the tumor. She died six and a half months after discharge. Conclusion: Here, we describe a rare case of liver cancer concurrent with CML and extreme thrombocytosis in an old patient. However, the exact relationship between the two tumors is still unclear, and more cases are desired.

there are even individual reports that platelets in CML patients can reach more than 10,000 × adenocarcinoma [11]. The underling mechanisms is unclear, but may be relevant to the chemotherapy induced DNA damage, multiple genetic alterations and increasing host susceptibility to oncogenic viruses due to immunosuppression [9]; 3) Secondary CML after treatment for solid tumors, the formation of CML after treatment for solid tumors have been reported in non-small cell lung cancer [12], thyroid carcinoma [13,14], breast cancer [15], and gastric adenocarcinoma [16,17]. Up to now, evidence is lacking as to the frequency of therapy-related CML complicating cytotoxic therapy. 4) CML after organ transplant, more than 30 cases of CML associated with organ transplants have been reported up to now, most of them developed after kidney transplants [18,19]. The development of CML in this situation may be associated with the postorgan transplant immunosuppressed state.
However, it remains controversial whether the incidence of CML in such patients is truly higher than the general population owing to the limited number of reported cases.
In this case report, we reported the concurrent of liver cancer with CML and extreme thrombocytosis in an untreated old woman.

Case Presentation
A 61-year-old woman was transferred to our hospital with complaints of upper abdominal pain accompanied by anorexia for four months. Doctors in local hospital found a large mass in her right hepatic lobe by magnetic resonance imaging (MRI) and an elevated plasma level of AFP to 216.5 ng/ml, and she was initially diagnosed with liver cancer and admitted to our liver surgery department. She had a 5-year history of hepatitis B, but has never been treated; she also had a 5year history of hypertension, and treated with indapamide tablet.
The physical examination on admission showed no jaundice, ascites, pedal edema or spider naevi, the liver and spleen are not touched below the costal margin. There were no obvious enlargement of superficial lymph nodes, and the remaining physical examination findings were unremarkable.
Laboratory tests at admission (Table 1) showed a hemoglobin level of 111 g/L, white blood cell count of 7.01 × 10 9 /L, and platelet count of 2464 × 10 9 /L. The liver function test results were serum alanine aminotransferase of 55 U/L, serum aspartate aminotransferase of 82 U/L, and globulin of 69 g/L. HBV-DNA was 2.11 × 10 7 IU/ml. AFP was 308.8 ng/ml. Abdominal color Doppler ultrasonography showed a large hypoechoic area of about 9.5 cm x 5.7 cm in the right lobe of the liver, which was irregular in shape, unclear in boundary and uneven in internal echo, and the distal part of the right hepatic vein was not clearly displayed due to the compression of the mass (Fig. 1A). Abdominal contrast-enhanced CT showed a slightly low-density lesion in the right lobe of the liver with a maximum diameter of about 9.1 × 5.5 cm, and was slightly uneven enhancement and delayed enhancement (Fig. 1B,C). Hilar and retroperitoneal lymph nodes were increased and enlarged. These imaging and biochemical examination results suggested a neoplastic lesion in the liver, particularly HCC. Table 1 The main laboratory test results at admission

Our values
Normal range WBC 7.01 × 10 9 /L 3.50-9.50 × 10 9 /L Neutrophils 3.28 × 10 9 /L 1.80-6.30 × 10 9 /L RBC 3.71 × 10 12 /L 3.80-5.10 × 10 12 /L Hb 111 g/L 115-150 g/L Platelet 2464 × 10 9 /L 125-350 × 10 9 /L AST 82 U/L 0-32 U/L ALT 55 U/L 0-33 U/L Total bilirubin ( showed that ESR was 95 mm/H, beta-2 microglobulin was 4.62 mg/L and anti-nuclear antibody was 1:320. No M protein was found in the test of monoclonal gamma globulin disease. A bone marrow aspiration and biopsy was performed to examine bone marrow, and results showed a hypercellular marrow with marked granulocytic and megakaryocytic hyperplasia( Fig. 2A December 2015 [21], and 87 of 1591 CML patients with extreme thrombocytosis were identified, with platelet count ranging from1054 × 10 9 /L to 4720 × 10 9 /L. CML patients with atypical clinical features and severe thrombocytosis were often mimicked with essential thrombocytosis (ET) as reported previously [22]. In our case, the patient's platelet count was as high as 3622 × 10 9 /L, but her erythrocyte and granulocyte series in peripheral blood were generally normal. However, FISH, chromosome examination and RT-PCR confirmed the diagnosis of CML. Moreover, bone marrow aspiration and biopsy revealed megakaryocytes that were smaller than normal cells and had a typical hyperlobated round nuclei in morphology. Therefore, we and other researchers propose that every case of ET should be tested for the Philadelphia chromosome to avoid missed diagnosis of CML [23].
The main pathogenesis of CML is the reciprocal translocation between chromosomes 9 and 22, which leads to the tyrosine kinase coding gene ABL of chromosome 9 translocated into BCR region of chromosome 22. An important result of this chromosome translocation is the product of fusion gene Abl-Bcr that encodes a deregulated tyrosine kinase resulting in manifestations of CML. Inhibition of Bcr-Abl oncogene expression and protein function are the primary treatment of CML based on its pathogenesis [24]. Bcr-Abl tyrosine-kinase inhibitors (TKI) are the first-line therapy for CML, among them, imatinib is one of the most classic, first-line drug [25]. In the recent study of Sora et al as mentioned previously, the majority of patients patients received a pre-treatment with hydroxycarbamide, and then treated with TKIs(63 patients received imatinib, 16 received dasatinib, and 8 were given nilotinib), 87% patients obtained a complete cytogenetic response (CCyR) or a major molecular response (MMR) after 12 months of treatment [21]. In our case, the patient received a pre-treatment with hydroxycarbamide and platelet-lowering therapy with anagrelide, but it did not achieve a relevant reduction in platelet count. However, when imatinib therapy was started, the platelet count rapidly decreased to the normal range. At the four-month follow-up after discharge, her platelet count remained in normal range.
Another issue in our report is the solid tumor complicating with CML in one patient. showing subsequently with a liver mass which was pathological diagnosed as Histiocytic sarcoma (HS) [26]. The liver mass showed a retained BCR-ABL1 translocation suggesting clonality between the CML and HS. Therefore, the author proposed that the concurrent expression of immunoglobulin heavy (IGH)-/light-chain rearrangements or cytogenetic markers common to the primary CML suggested an evolutionary mechanism involving lineage switching that could potentially be affected by genetic or epigenetic factors which may occur at the level of a progenitor or the malignant cell itself [26]. MS is a rare extramedullary presentation of neoplastic myeloid cells. They may occur before, concurrent with, or after the diagnosis of myeloproliferative disorders, such as AML or CML [27,28]. Norsworthy reviewed 51 cases of biopsy-proven MS involving the liver, biliary tree or pancreas [29], most cases presented with systemic disease, mainly in association with AML and CML. The main symptom includes jaundice, right upperquadrant abdominal pain, fatigue, anorexia, nausea and vomiting. Many cases were initially diagnosed as cholecystitis, pancreatitis or carcinoma, especially in those with unknown hematological diseases, and underwent surgery. As immunohistochemistry confirmed, the most commonly expressed cell surface markers of MS in these cases were myeloperoxidase (63%), CD68 (40%), CD45 (30%), CD34 (30%), CD43 (30%), CD117 (28%), CD33 (15%), lysozyme (15%) and CD13(8%) [29]. Unfortunately, for our case, there are no additional samples for further immunohistochemical detection of MS markers. Although the platelet count was reduced to a normal range, imatinib therapy did not reduce the size of the liver tumor.
In summary, we presented a rare case of liver cancer concurrent with CML and extreme thrombocytosis in an old patient. Although the exact pathological relationship between the liver cancer and CML in this case is unknown, we wish there are more reports on the concurrent CML and solid tumors like our case to explore the underline mechanisms.

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