Are All Mutations the Same? A Rare Case Report of Coexisting Mutually Exclusive KRAS and BRAF Mutations in a Patient with Metastatic Colon Adenocarcinoma.

29-year-old Hispanic woman presented to the clinic with complaints of abdominal pain, nausea, fatigue, and constipation. Laboratory tests indicated the presence of iron deficiency anemia and transaminitis. Imaging evaluation revealed marked hepatomegaly with multiple hepatic metastases and pelvic lymphadenopathy. Biopsy of the hepatic lesions showed adenocarcinoma positive for pan-cytokeratin, CMA5.2, villin, and CDX2. She was positive for tumor markers CA 19-9, CA-125, and CEA. Upon further evaluation, she was found to have colorectal cancer positive for KRAS and BRAF mutations. Unfortunately, her disease progressed rapidly and she expired within 3 months from the time of her first diagnosis. KRAS and BRAF mutations are rare enough to be considered virtually mutually exclusive but coexistent mutations appear to be a distinct molecular and clinical subset with aggressive course of illness, which is in dire need of new treatment strategies. Panitumumab and Cetuximab are approved for patients with wild type KRAS CRC. Vemurafenib is a potent inhibitor of the kinase domain in mutant BRAF and its use in BRAF mutated colon cancer remains to be well established. Our report highlights the need to obtain tissue samples from these patients for analysis and to evaluate the benefit of Vemurafenib in colorectal cancers.

Myelodysplastic Syndrome with concomitant t(5;21)(q15;q22) and del(5)(q13q33): case report and review of literature.

Chromosomal abnormalities lead to the development of hematologic malignancies such as Myelodysplastic Syndrome (MDS). Known chromosomal changes causing MDS include deletion of the long arm of chromosome 5, runt-related transcription factor 1 (RUNX1) also known as acute myeloid leukemia 1 protein (AML1), and very rarely fusion genes involving RUNX1 at t(5;21)(q15;q22). We present a case of a 71-year-old female with MDS, refractory anemia with excess blasts, type 1, with a combination of two cytogenetic abnormalities, specifically a concomitant translocation between chromosomes 5q15 and 21q22 and deletion of chromosome 5q13q33. Fluorescence in-situ hybridization (FISH) using a probe for RUNX1 (AML1), localized to 21q22, showed three FISH signals for RUNX1, consistent with rearrangement of RUNX1. Therapy was started with Lenalidomide leading to normal blood counts. Most significantly, repeat cytogenetics revealed normal karyotype and resolution of deletion on the long arm of chromosome 5 and a t(5;21). FISH negative for deletion 5q. The results altogether meet criteria for a complete cytogenetic remission (CR). We report a new case of t(5;21)(q15;q22) involving the RUNX1 gene and del(5)(q13q33) in a MDS patient, a combination of chromosomal abnormalities heretofore not reported in the literature. RUNX1 rearrangement is usually associated with an adverse prognosis in AML and MDS. Deletions of 5q are typically associated with poor prognosis in AML, however it is usually associated with a favorable prognosis in MDS. Our patient responded very well to Lenalidomide therapy with achievement of CR. Lenalidomide is approved for treatment of anemia in low and intermediate risk MDS with del (5q), however based on a search of literature it seems that RUNX1 mutations are also more prominent in patients who have responded to Lenalidomide therapy. MDS is a genomically unstable disease. Hence, it is conceivable that our patient started with a 5q minus syndrome and then acquired the second hit RUNX1 translocation leading to an accelerated phase of myeloid neoplasm or refractory anemia with excess blasts, type 1. Hence, the temporal relationship between acquisition of del 5q and RUNX1 rearrangement may have influenced the clinical outcome and possibly response to therapy.

Skin Recurrence of Transformed Mycosis Fungoides Postumbilical Cord Blood Transplant despite Complete Donor Chimerism.

Background. Allogeneic stem cell transplant is the treatment of choice for systemic cutaneous T-cell lymphoma (CTCL) which provides graft-versus-lymphoma effect. Herein we discuss a case of recurrence of CTCL skin lesions after cord blood transplant in a patient who continued to have 100% donor chimerism in bone marrow. Case Presentation. A 48-year-old female with history of mycosis fungoides (MF) presented with biopsy proven large cell transformation of MF. PET scan revealed multiple adenopathy in abdomen and chest suspicious for lymphoma and skin biopsy showed large cell transformation. She was treated with multiple cycles of chemotherapy. Posttherapy PET scan showed resolution of lymphadenopathy. Later she underwent ablative preparative regimen followed by single cord blood transplant. Bone marrow chimerism studies at day +60 after transplant showed 100% donor cells without presence of lymphoma. However 5 months after transplant she had recurrence of MF with the same genotype as prior skin lesion. Bone marrow chimerism study continued to show 100% donor cells. Conclusion. A differential graft-versus-lymphoma effect in our case prevented lymphoma recurrence systemically but failed to do so in skin. We hypothesize that this response may be due to presence of other factors in the bone marrow and lymph node microenvironments preventing recurrence in these sites.