Chromosome 17p deletion in a case of T‐cell acute lymphoblastic lymphoma
Authors: Maryam Movassaghian, Aliyah R. Sohani, Steven L. McAfee, Ashley M. Perry, Paola Dal Cin, Cynthia McLaughlin, Amir T. Fathi
Journal: American Journal of Hematology (2014)

A 25-year-old, previously healthy female presented with pleuritic chest pain, dyspnea, and dry cough. Auscultation of the lungs demonstrated an absence of breath sounds on the left. Imaging with computed tomography (CT) and positron emission tomography (PET) modalities confirmed a large pleural effusion, but also revealed an anterior PET-avid mediastinal mass, measuring 11.2 cm by 6.0 cm, with a small pericardial effusion. There was also near-complete opacification of the left lung and a rightward mediastinal shift with displacement of adjacent structures. She was hospitalized and underwent placement of a left pleural chest tube. The pleural fluid was exudative and cellular, consisting of 12% atypical lymphoid cells expressing cytoplasmic CD3, CD7, CD34, but not surface CD3 or TdT. She then underwent a biopsy of a left internal mammary node, with pathological evaluation confirming a diagnosis of T-cell acute lymphoblastic lymphoma (Image 1A). Cytogenetic analysis revealed multiple abnormalities including a chromosome 17p deletion (Image 1B), which was confirmed by interphase fluorescence in situ hybridization (FISH) demonstrating p53 deletion in 88% of nuclei (Image 1C). An immunostain for p53 showed positive staining in approximately 2% of tumor cell nuclei (Image 1D). Of note, peripheral blood counts were normal, with no atypical circulating cells. A bone marrow biopsy revealed morphologically normal maturing trilineage hematopoiesis; however, <1% T-lymphoblasts were identified by flow cytometric analysis. The patient's cerebrospinal fluid (CSF) did not demonstrate disease involvement. Pathologic and cytogenetic findings of mediastinal mass biopsy. The specimen is composed of a diffuse infiltrate of medium-sized atypical lymphoid cells with oval nuclei, dispersed chromatin, occasional small nucleoli, and scant cytoplasm (A, H&E, ×1000). Frequent mitotic figures are seen (arrows). Cytogenetic abnormalities revealed multiple abnormalities with the dominant clone showing the following abnormal karyotype, including a deletion involving the short arm of chromosome 17 (B, arrow): 47,XX,+4,+14,del(17)(p1?3),−20[cp7]. A separate related minor clone was also present: 89 ∼ 91<4n>,idem,−X,−X,der(15)t(7;15)(q11.2;p11.2)×2, −21[cp3]. FISH analysis using a probe specific for the region containing TP53 on chromosome 17p confirmed TP53 loss in 44 of 50 interphase nuclei (C). An immunohistochemical stain for p53 revealed strong positive staining in approximately 2% of tumor cell nuclei (D, ×400). The patient was initiated on induction therapy with the hyper-CVAD regimen 1 consisting of alternating schedules of cytotoxic agents, including cyclophosphamide, doxorubicin, vincristine, dexamethasone, and high doses of cytarabine and methotrexate. Currrently, she is in the midst of chemotherapy, and imaging after two cycles has revealed a dramatic response. T-cell lymphoblastic lymphoma is a high grade neoplasm predominantly occurring in adolescents or young adults and typically manifesting as a mediastinal mass with or without pleural effusions. Due to common morphological and immunophenotypic features with lymphoblastic leukemia, it is grouped in the same category per the World Health Organization classification 2, only distinguished by the extent of bone marrow infiltration. We here report a case of T-cell lymphoblastic lymphoma, manifesting as a mediastinal mass and pleural effusion, with an unusual karyotypic abnormality of 17p deletion. Across hematologic malignancies, karyotypic abnormalities can provide insight on the clinical course, prognosis, as well as type and extent of therapies. In particular, loss of the short arm of chromosome 17, a segment containing the TP53 gene, is generally associated with advanced disease, decreased response to treatment, and shorter survival 3. A variety of chromosomal alterations can lead to loss of TP53, including deletions of the short arm of chromosome 17, del(17p), deletion of one entire chromosome 17, or balanced translocations involving the short arm of chromosome 17. In various lymphoid malignancies, del (17p) has been associated with disease progression and poor prognoses 4, 5. In contrast to other hematologic tumors, 17p deletion has been rarely 6 reported in T-cell lymphoblastic malignancies, and little is known about its prognostic impact. Our patient presented in a typical fashion with mediastinal mass and pleural effusions. She responded to initial treatment, but it is not known whether this alteration will have an impact on therapeutic response and future outcomes. Current efforts are under way to proceed with a matched donor allogeneic stem cell transplant (SCT). Additional experience and study is needed to learn about this uncommon alteration in T-cell lymphoblastic lymphoma and to determine whether it shares the high-risk features seen with other hematologic malignancies. Such data may help inform the appropriate type and extent of therapy for those with T-cell lymphoblastic lymphoma, a disease with currently suboptimal outcomes among adult patients.