Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • 2024-04

    • In most patients with MCL multi organ involvement with organ

    2019-05-17

    In most patients with MCL, multi-organ involvement with organ damage is seen [2–5,10]. In most cases, the BM is the primary site of disease evolution [13]. However, only a smaller subset of patients with MCL present with circulating MC, and only very few cases present with rapidly increasing numbers of MC in the peripheral blood. In our patient, leukocyte counts increased rapidly within a very short time, and most of the expanding leukocytes were immature MC and metachromatic blasts, suggesting a high proliferation rate of MC. Indeed, we found that a substantial proportion of neoplastic MC (20%) in our patient stained positive for Ki-67, a proliferation-associated antigen that is usually not expressed in neoplastic MC in SM. The rapid proliferation of MC was also supported by the very high serum tryptase level that had increased rapidly shortly before and at the time of her relapse. In advanced SM, MC exhibit a characteristic phenotype, including CD25 and CD30 [1–3,14]. In our patient, neoplastic MC stained positive for CD117 (KIT) and tryptase, but most MC did not react with cetrimonium bromide against CD25 and CD30. This was a somehow unexpected result. Notably, CD30 has been considered to serve a marker of aggressive MC neoplasms [14]. However, apparently, CD30 is not expressed in MC in all cases of MCL. Otherwise, the phenotype of MC was found to correspond well with an aggressive type of SM. In fact, MC did not express chymase and CD2. The LFA-2 antigen (CD2) is of special interest, as it has been described already that CD2 levels are lower in advanced SM (compared to indolent SM=ISM) and may even decrease in MC with the progression of the disease from ISM to ASM or MCL. In most patients with SM, a transforming mutation in codon 816 of KIT is detectable. In the vast majority of ISM and ASM patients, KIT D816V is found [8,15–18]. However, in MCL, other mutations in KIT, including rare codon 816 mutations are detectable. In our patient, the KIT mutation D816H was detectable in neoplastic cells. This KIT mutant may trigger differentiation of MC in the same way as KIT D816V. However, this mutation is unable to explain the rapid malignant expansion of the clone. Rather, additional mutations and lesions are considered to be responsible for malignant proliferation of MC in MCL [1,2,5]. In our patient, we were able to detect additional lesions by karyotyping. In particular, we were able to detect a t(7;10)(q22;q26) translocation in neoplastic cells. Whether this lesion was involved in malignant progression remains unknown. Alternatively, additional mutations and lesions contributed to malignant expansion of MC in this case. Because of drug resistance, the overall prognosis of MCL remains dismal and the survival is short in most cases [1–4,19,20]. Therefore, patients with MCL are candidates for chemotherapy and SCT. In our patient, we were surprised to see that the patient´s leukemia responded well to induction chemotherapy. We selected the FLAG protocol because this chemotherapy regimen is well known to work well in a subset of patients with chemotherapy-refractory acute leukemias. In our patient, we obtained an almost complete remission after two cycles of FLAG. At that time we prepared the patient for SCT. However, unfortunately, the patient relapsed after her third cycle of FLAG and died from cerebral bleeding 5 months after diagnosis.
    Contributions P.V. designed the study, wrote the paper and approved the final version of the manuscript. G.E., K.B., H.H., and I.S. isolated mast cells and contributed flow cytomtery staining experiments. S.C.R. performed immunohistochemistry and molecular studies. G.H. performed molecular studies and KIT mutation analyses. R.T. and I.S. performed cytomorphologic investigations. L.M. performed histopathology, chromosome analyses and FISH. W.R.S. contributed the patient, analyzed clinical variables and performed treatment. C.M. provided molecular data and logistic support. H.P.H. contributed immunohistochemical evaluations as well as logistic support.