Leukemic infiltration of the ovary as an initial presentation of chronic myeloid leukemia in chronic phase

Introduction: We report a case of a newly diagnosed patient with chronic
 myeloid leukemia in chronic phase, with leukemic infiltration of the right
 ovary on disease presentation.Case report: The patient presented with
 abdominal pain, leukocytosis, and anemia. Peripheral blood smear was
 indicative of chronic myloid leukemia and cytoreductive treatment was
 started. Due to the worsening of the abdominal pain, a computerized
 tomography was done. It revealed a cystic tumor of the right ovary. The
 tumor was surgically removed. Bone marrow examination confirmed the
 diagnosis of chronic myloid leukemia in chronic phase. Immunohistochemical
 analysis of the ovarian tumor showed leukemic infiltration with 5% of
 blasts. The patient was treated with imatinib for one year. Due to treatment
 failure, imatinib was switched to nilotinib. Allogeneic stem cell
 transplantation is considered. Conclusion: This case points out the critical
 role of multidisciplinary team approach and close treatment monitoring to
 achieve the best possible outcome.


Abstract
Introduction: We report a case of a newly diagnosed patient with chronic myeloid leukemia in chronic phase, with leukemic infiltration of the right ovary on disease presentation.Case report: The patient presented with abdominal pain, leukocytosis, and anemia. Peripheral blood smear was indicative of chronic myloid leukemia and cytoreductive treatment was started. Due to the worsening of the abdominal pain, a computerized tomography was done. It revealed a cystic tumor of the right ovary. The tumor was surgically removed. Bone marrow examination confirmed the diagnosis of chronic myloid leukemia in chronic phase. Immunohistochemical analysis of the ovarian tumor showed leukemic infiltration with 5% of blasts. The patient was treated with imatinib for one year. Due to treatment failure, imatinib was switched to nilotinib.
Allogeneic stem cell transplantation is considered. Conclusion: This case points out the critical role of multidisciplinary team approach and close treatment monitoring to achieve the best possible outcome.

Case report
A 24-year-old woman referred to the doctor due to a sudden onset of abdominal pain and weakness. The pain was localized in the right lower quadrant. She had no significant previous medical history but reported that she lost around 5kg over the last four months.
Routine blood work showed leukocytosis and anemia. After a brief hospitalization in a regional hospital, she was transferred to a tertiary center. Upon admission to the Clinic of Hematology, the physical examination showed tenderness in the lower right quadrant and a palpable spleen 5 cm below the left costal margin. Her last period was fifteen days prior to admission.
Initial blood count showed an extreme leucocytosis with anemia and slight thrombocytosis (hemoglobin 69 g/l, white blood count 603 × 10 9 /l, platelets 464 × 10 9 /l).  Figure 2). The number of CD34+/CD117+ blasts was around 5%. One month after surgery, treatment with imatinib was started. Hematologic response was achieved after 2 months. The patient did not reach a complete cytogenetic response after six months of imatinib treatment (Table   1). An optimal cytogenetic and molecular response according to European LeukemiaNet (ELN) guidelines was not reached even after one year of imatinib treatment (Table 1) Gynecological follow up showed a normal finding. Due to treatment failure with imatinib, nilotinib 800mg/day was introduced. HLA typisation was performed only for the patient because she did not have siblings. We plan to repeat PCR and cytogenetics after six months of treatment with nilotinib and decide about allogeneic transplantation from unrelated matched donor.

Discussion
Leukemic infitration was previously described in CML, although the most common sites were lymph nodes, liver, spleen, and bones 1,3 . Ovaries and other parts of the genital system are rarely affected by CML, especially in young females. The finding of leukemic infiltration in the ovarian mass was quite surprising in our patient. Mostly, complex cystic masses in young females are hemorrhagic cysts, endometriomas, a tubo-ovarian abscess or ectopic pregnancy 4

. Solid masses can be benign or malignant ovarian tumors 4 .
Pathohistological examination of the tumor is crucial for obtaining the correct diagnosis.
Only morphological examination with hematoxylin and eosin stain can give an incorrect diagnosis 1 . Immunohistological positivity for myeloperoxidase, CD34 and CD117 was essential to determine cell origin and the number of blasts 1 . Fluorescent in situ hybridization (FISH) should be performed to prove the clonal origin of CML. In our case, it was not done due to technical difficulties.
In general, extramedullary leukemic infiltration indicates poor prognosis since it commonly represent extramedullary blast crisis. Extramedullary blast crisis is most common in acute leukemia and blastic phase of CML 1,3 . Usually, it happens simultaneously or precedes marrow blast crisis by a few months 3 . It is very rare as an initial presentation of CML and in CML-CP 3 . TKI revolutionized the treatment and outcome of CML inducing around 85% of maior cytogenetic responses after 12 months of treatment with imatinib 5 . The response rate is even higher on treatment with nilotinib 6 . However, imatinib does not improve the prognosis of blast crisis dramatically 1 . Cytotoxic treatment followed by an early allogeneic stem cell transplantation is needed to induce remission in these patients 1 .
In our opinion, our patient was not in extramedullary blast crisis since the number of blasts in the infiltrated tissue was around 5%. That was very important for the treatment decision.
Due to our country's regulations, imatinib was the only first-line treatment option.
Nilotinib was introduced because of imatinib treatment failure after one year. We continued TKI treatment because the patient was still in CML-CP but decided to do HLA typisation.
The decision about the timing of allogeneic transplantation will be based on the results of PCR and cytogenetics after six months on nilotinib.
Another dilemma about CML and the ovarian localization of extramedullary hematopoiesis is fertility and childbirth. There is no solid evidence that TKI treatment impairs fertility, but medication should probably be stopped before pregnancy because of teratogenicity 7