Spurious leukocytosis-simulating relapse of chronic myeloid leukemia after bone marrow transplant: Possible relationship to hypercholesterolemia and hyperbiliru binemia

A case of CD56/NCAM+ malignant lymphoma is reported. Only a rare malignant lymphoma cell showed azurophilic granules in the cytoplasm of Giesma-stained preparations, while electron microscopic examination revealed occasional cytoplasmic granules with paracrystalline inclusions. The most common phenotype seen in NK lymphomas, CD2+, CD3-, CD56+, CD16-, CD57-, was present in the case. Cases with this phenotype have been interpreted to represent either true NK lymphoma or T-cell lymphoma with NK expression. Genotyping, where performed, has shown TCR germline configuration. Our case showed TCRβ rearrangement indicating that the above phenotype can be associated with a peripheral T-cell lymphoma.     

Establishment of an IL-2-dependent cell line derived from 'nasal-type' NK/T-cell lymphoma of CD2+, sCD3−, CD3ɛ+, CD56+ phenotype and associated with the Epstein-Barr virus

A novel interleukin-2 (IL-2)-dependent cell line, HANK1, was established from a patient with CD56⁺ NK/T-cell lymphoma arising in the retroperitoneum. Morphologically, HANK1 is a pleomorphic large cell line with irregular nuclei, which contains azurophilic granules in the cytoplasm. Immunophenotypic analysis showed that HANK1 expressed CD2, CD3ɛ, CD56, TIA-1, granzyme B, and HLA-DR, but no other T-lineage markers. These features were the same as seen in the original tumour, and are highly characteristic of nasal and 'nasal-type' NK/T-cell lymphoma as described in the proposed W.H.O. classification. Genotypically, this cell line also demonstrated the germline configuration of the T-cell receptor β, γ and the immunoglobulin heavy chain genes and clonal integration of the Epstein-Barr virus (EBV) together with antigen expression with a type II latency pattern (LMP-1⁺ and EBNA2⁻). Furthermore, Southern blot analysis using the EBV termini as probes confirmed its derivation from the original lymphoma, and revealed that it contained multiple copies of the EBV genome. Dose-dependent growth on IL-2 was observed in an in vitro study with a doubling time of 3 d at maximal stimulation. These data indicate that HANK1 seemed to preserve the biological characteristics of the original tumour and therefore may serve as a good model for the further analysis of unusual 'nasal-type' NK/T-cell lymphoma.     

Primary CD56+ NK/T-cell lymphoma of the rectum accompanied with refractory ulcerative colitis

A case of primary NK/T-cell lymphoma of the rectum accompanied with ulcerative colitis (UC) in a 73-year-old man is reported. He had a 6-year history of repeated admission to our hospital for UC. Total colonoscopy performed 4 months after resolution of refractory UC complicated by cytomegalovirus colitis showed a markedly submucosal tumor in the rectum, which was histologically diagnosed as malignant lymphoma. The findings of computed tomography of the chest and abdomen, gallium scintigraphy, abdominal ultrasonography, and upper gastrointestinal endoscopy showed no abnormal lesions. Therefore, based on a diagnosis of localized rectal lymphoma with UC, proctocolectomy was performed. The resected specimen showed three submucosal tumors in the rectum with local nodal involvement. Histologically, the tumors were characterized by diffusely infiltrating sheets of large atypical lymphoid cells, which were negative for CD4, CD8, and CD20 but were positive for CD56, CD3, and granzyme B. The presence of Epstein-Barr virus (EBV) infection in neoplastic cells was shown by in situ hybridization for EBV-encoded early small RNA1 (EBER-1). Based on these findings, the patient was diagnosed with primary CD56+ NK/T-cell lymphoma of the rectum (stage IIE). This is the first case report of primary rectal NK/T-cell lymphoma accompanied with UC.     

Primary CD56+ T/NK cell lymphoma of the colon

Primary T/natural killer (NK) cell lymphoma of the colon is extremely rare. Despite the advances in histological and immunophenotypic studies, the diagnosis of primary T/NK cell lymphoma of the colon can be delayed because the early symptoms and colonoscopic findings may be very similar to those of inflammatory bowel diseases such an Crohn's colitis, and most physicians have little available information on this group of neoplasms. Moreover, florid nonspecific inflammatory infiltrates would not allow characterization of the tumor cells in such an inflammatory background. Herein, we describe a patient who initially presented with features that were clinically and colonoscopically similar to Crohn's colitis. Three months later, he had cecal bleeding and perforation, and primary T/NK cell lymphoma of the colon was diagnosed through immunophenotypic and genotypic studies of surgical specimens. Received: March 5, 2001 / Accepted: August 24, 2001 Reprint requests to: D.K. Lee     

Chromosome aberrations are restricted to the CD56+, CD3− tumour cell population in natural killer cell lymphomas: a combined immunophenotyping and FISH study

Natural killer (NK) cell lymphomas are a newly recognized entity of non-Hodgkin's lymphoma with a highly aggressive clinical course and strong association with Epstein-Barr virus (EBV) infection. Although no recurrent chromosome aberrations have been identified in NK-cell lymphoma, deletions of 6q and trisomy 7 have been described repeatedly in this type of lymphoma. In this study we attempted to determine the immunophenotypes of tumour cells with certain chromosome aberrations, i.e. deletions of 6q and trisomy 7, in three cases of NK cell lymphomas by means of combined immunophenotyping and fluorescence in situ hybridization (FISH). In all three cases clonal chromosome aberrations were detected only in CD56+ cells but not in CD3+ or CD5+ cells. However, not all CD56+ cells were shown to contain these chromosome aberrations. Double immunophenotyping combined with FISH confirmed that the chromosome aberrations occurred only in CD56+CD3- cells. This study indicates that chromosome aberrations in NK-cell lymphomas are restricted to the CD56+, CD3- and CD5- cell population and that NK-cell lymphomas are indeed derived from mature true NK cells and not from T lymphocytes.     

Sustained remission of multi-line relapsed extranodal NK/T-cell lymphoma,nasal type,following sintilimab and chidamide: A case report

Introduction:There is currently no optimal treatment modality for refractory or relapsed Extranodal NK/T-cell lymphoma, nasal type (ENKTL). In recent years, programmed cell death protein 1 (PD-1)/programmed cell – ligand 1 pathway blockade and histone deacetylase inhibitors have emerged as promising strategies for refractory or relapsed ENKTL. Accumulating evidence has shown that therapeutic effects of anti-PD-1 antibody could be enhanced by histone deacetylase inhibitors.Patient Concerns:A 52-year-old male patient was diagnosed with stage I ENKTL by biopsy on February 2010.Diagnosis:positron emission tomography–computed tomography (PET-CT) and biopsy were used to diagnose relapsed ENKTL in 2014.Interventions:The patient was treated with radiotherapy and six cycles of etoposide, prednisone, vincristine (Oncovin), cyclophosphamide and doxorubicin hydrochloride and achieved complete remission (CR) by PET-CT in August 2010. In November 2014, the patient was diagnosed with relapsed stage IV ENKTL and was treated with six cycles of alternative chemotherapy with the regimen of steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide and pegaspargase plus Gemcitabine, Oxaliplatin along with radiotherapy. The patient achieved remission and was placed on thalidomide maintenance treatment. Upon suspicion of relapse suggested by PET-CT, Autologous stem cell transplant was performed after BCNU, etoposide, Ara-C, and melphalan preconditioning on February 2016. Following relapse again in December 2016, the lesions of left femur were treated with radiotherapy and he received anti-PD-1 antibody. He was treated with 4 cycles of pegaspargase plus Gemcitabine, Oxaliplatin on August 2017. The patient''s condition improved. He received maintenance and consolidation therapy including lenalidomide, radiotherapy of the right nasal cavity and paranasal sinuses and antigen-specific reactive T cell infusions. PET-CT imaging showed there was high metabolic activity signal in the distal end of right femoral on August 2018 and the treatment regimen was adjusted to radiotherapy of the distal end of right femoral and systemic treatment of PD-1 antibody Sintilimab and chidamide 30 mg. After 5 months post-treatment, biopsy of nasopharynx showed no lymphoma cells. The patient continued the treatment of Sintilimab and chidamide 20 mg.Outcomes:PET-CT imaging showed his lesions obtained remission after 8 months post-treatment.Conclusion:Thus, combination of sintilimab and chidamide can be used to treat relapsed ENKTL following treatment failure from chemo-, radio-, and immuno-therapy. A clinical trial has been launched.     

Intestinal NK/T cell lymphoma: A case report

BACKGROUND The incidence of intestinal NK/T cell lymphoma(NKTCL) is extremely low, and the clinical symptoms are atypical, which makes it difficult to distinguish this disorder from Crohn's disease(CD), T lymphocyte proliferative disease, and other immune disorders. The misdiagnosis rate is high, and the patient's prognosis is poor.CASE SUMMARY In this case, the patient had repeated high fever, colonoscopy revealed multiple ulcers, and the initial diagnosis was CD. The patient's condition did not improve after treatment with hormones and infliximab, and she eventually died. Positron emission tomographic-computed tomographic and B-ultrasound were performed in our hospital and showed that multiple lymph nodes were enlarged. Immunohistochemi-stry showed that CD3 and Epstein-Barr virus encoded RNA expression was positive. Colonoscopy, tissue biopsy, and histopathology showed intestinal focal mucosal infiltration of heterotypic lymphocytes with an abnormal immune phenotype. On the basis of the patient's medical history, auxiliary examination, and pathological findings, digestive physicians and pathologists gave the diagnosis of NKTCL.CONCLUSION Clinicians need to improve their comprehensive knowledge of NKTCL, and combination of clinical symptoms, histological characteristics, as well as colonoscopy biopsies should be considered to improve the diagnosis and thereby reduce misdiagnosis.     

T-cell receptor Jβ1/Jβ2 locus rearrangements in an HTLV-1-positive T-cell lymphoma with complex chromosomal aberrations

We report a case of human T-cell lymphotropic virus type 1 (HTLV-1)-infected adult T-cell lymphoma that has multiple chromosomal abnormalities, including the presence of an additional 7q22-36, which contains the locus of the T-cell receptor (TCR) beta chain gene. Specific TCR Jβ1/Jβ2 gene rearrangements were detected in both marrow and peripheral blood DNA, with evidence of further evolution of the transformed clonal population within the peripheral lymphocytes. To our knowledge, this is the first case in which gene rearrangements have been associated with additional TCR loci. Consequently, it is advised that every effort should be made to correlate chromosomal abnormalities with gene rearrangement by molecular methods. © 1996 Wiley-Liss, Inc.     

A case of nasal‐type NK/T cell lymphoma in a patient with dermatomyositis

The association of malignancy with dermatomyositis is well known, and the frequency is reported to be up to 30%. However, cutaneous lymphoma associated with dermatomyositis has rarely been reported. We experienced a case of nasal‐type NK/T‐cell lymphoma in a 40‐year‐old woman with a 2‐year history of dermatomyositis. To our knowledge, this is the first report of cutaneous involvement of nasal‐type NK/T‐cell lymphoma developing in a dermatomyositis patient. When skin lesions are resistant to aggressive conventional treatment in dermatomyositis patients, we should consider the possibility of malignancy, especially cutaneous lymphoma.     

An unusual extranodal natural killer/T-cell lymphoma presenting as chronic laryngitis: A case report

Rationale:Nasal-type, extranodal natural killer (NK)/T-cell lymphoma is a rare lymphoma. The tumor usually shows ulcerative and necrotic lesions in the nasal cavities and sinuses. Tissue involvement outside the nasal cavity is uncommon.Patient concern:We describe a 30-year-old man with a 2-month history of hoarseness, weight loss, and dyspnea.Diagnosis:Magnetic resonance image (MRI) showed edema of the larynx with obliteration of the airway. Laryngoscopic examination described necrotic tissue in the glottis and larynx. The biopsy showed chronic, necrotizing laryngitis, with no granulomas, vasculitis, or atypical cells. The immunologic and microbiologic study was negative. Later, after immunosuppressive therapy, the patient presented erythema and diffuse enlargement of the right arm. MRI showed myositis of the biceps and brachial muscles. Infection was rule out, and direct microscopy showed an extensive muscle infiltration by mononuclear cells and abundant mitosis. Immunohistochemistry was positive for CD3, CD8, Ki 67 (90%), and CD56 compatible with extranodal NK/T cell lymphoma.Interventions:The patient initially received immunosuppression treatments (corticoids, cyclofosfamide, and Rituximab) with relapsing episodes. When lymphoma was diagnosed, chemotherapy was started.Outcomes:The patient died during chemotherapy.Lessons:Nasal-type, extranodal NK/T-cell lymphoma should be suspected even when there are no classical findings of neoplasms on histology. Immunohistochemistry is mandatory to rule it out.     

Effective high-dose chemotherapy combined with CD34+-selected peripheral blood stem cell transplantation in a patient with cutaneous involvement of nasal NK/T-cell lymphoma

The prognosis of nasal natural killer (NK)/T-cell lymphoma with cutaneous involvement especially is morbid despite intensive chemotherapy and radiotherapy. We treated a 52-yr-old Japanese woman with cutaneous dissemination of nasal NK/T-cell lymphoma. Six cycles of chemotherapy, irradiation to skin lesion were administered and complete remission (CR) was attained. High-dose chemotherapy (HDC; etoposide 750 mg/m(2) x 2 d, cyclophosphamide 60 mg/kg x 2 d, total body irradiation 12 Gy two daily fractions x 3 d) followed by CD34(+)-selected autologous peripheral blood stem cell transplantation (CD34(+)-APBSCT) was then prescribed. Complete remission (CR) was obtained and she has been free of disease for 34 months since CD34(+)-APBSCT. We suggest that marrow-ablative chemotherapy facilitated by autologous stem cell transplantation should be considered part of the primary therapy for subjects with a poor prognosis for nasal NK/T-cell lymphoma with cutaneous involvement.     

Hepatosplenic gamma-delta T-cell malignant lymphoma: report of the first case in childhood, including molecular minimal residual disease follow-up

Summary. We report the first case of T-cell 7.5⁺ hepatosplenic malignant lymphoma in childhood. Tumour-specific oligoprobes were developed against the single Vl-Jl rearrangement of the δ T-cell receptor (TCR) gene in order to perform minimal residual disease (MRD) studies. Molecular analysis in serial bone marrow samples proved to be of predictive value concerning the clinical outcome. Clonotypic DNA was not detected in peripheral blood during the course of the disease until a refractory terminal leukaemic phase took place 18 months after the diagnosis. This case demonstrates the usefulness of MRU studies to monitor the course of disease in at least some subsets of peripheral T-cell lymphomas.     

Pulmonary manifestations of peripheral T‐cell lymphoma: case report and review of the literature

Introduction: Peripheral T‐cell lymphomas (PTCL) represent approximately 10% of non‐Hodgkin's lymphomas. Pulmonary involvement is an uncommon manifestation of this heterogeneous group of malignancies. Methods: Report of a case. Results: This case report describes a 75‐year‐old man with fever, weight loss, anemia, enlargement of spleen and liver, atypical lymphocytes and pulmonary nodules. Lung biopsy showed lymphocytic infiltration of the lung parenchyma. T‐cell receptor gamma gene rearrangement by polymerase chain reaction confirmed the diagnosis of peripheral T‐cell lymphoma. Unfortunately, the patient died because of refractory and aggressive disease. Conclusion: Pulmonary and pleural involvement are seen in patients with PTCL and usually carry a poor prognosis. The subject of pulmonary involvement in peripheral T‐cell lymphoma is discussed. Please cite this paper as: Vahid B, Machare‐Delgado E and Marik PB. Pulmonary manifestations of peripheral T‐cell lymphoma: case report and review of the literature. The Clinical Respiratory Journal 2007; 1:114–117.     

Primary extranodal natural Killer/T-cell lymphoma in a child in the colon: A case report

Rationale:Primary extranodal natural killer (NK)/T-cell lymphoma (ENKTL) rarely occurs in childhood and adolescence. To the best of our knowledge, ENKTL of childhood in the gastrointestinal (GI) tract has not been reported yet.Patient concerns:A 12-year-old Chinese boy complained of abdominal pain and persistent fever for 1 month.Diagnosis:Grossly an ulcerated tumor with perforation was located at the proximal ascending colon, 5 cm × 4 cm × 1.5 cm in diameter. The tumor was poorly circumscribed, tan-white and solid. Histological evaluation revealed medium-sized atypical lymphoid cells with large areas of necrosis distributed throughout all layers of the colon. Small blood vessels with destroyed walls were surrounded by lymphoid cells. Immunohistochemistry (IHC) highlighted tumor cells as strongly positive for CD3, CD56, CD5, CD2, CD8, CD4, CD43, T-cell restricted intracellular antigen 1 (TIA-1) and granzyme B. The proliferation index, measured by Ki-67 expression was high with 60%. The In situ hybridization (ISH) for EBER was positive. TCR was negative. Therefore, the final diagnosis was ENKTL of childhood in the colon.Interventions:The patient underwent right hemicolectomy and ileocolostomy.Outcomes:We recommended further evaluation and treatment, but the patient and patient family rejected further treatment of his condition. The patient died within 1 month after being discharged from hospital as a result of his disease.Lessons:ENKTL of childhood in the GI tract is extremely rare. Due to the non-specific clinical symptoms, it is easy it is easy not to think of this differential diagnosis at early stage. If patients have GI symptoms, ENKTL cannot easily be ignored. It is necessary to diagnose ENKTL of childhood in the GI tract by morphology and immunohistochemistry, and to differentiate from the GI T-cell lymphomas. We hope this case may serve as a reference improving clinical diagnosis and treatment.     

Mantle cell lymphoma presenting with severe upper gastrointestinal bleeding: A case report

Introduction:Although it usually involves extranodal sites such as the gastrointestinal tract in more than 80% of cases, mantle cell lymphoma is considered a rare cause of gastrointestinal bleeding, especially severe and life-threatening bleeding.Patient concern:A 60-year-old man with peptic ulcer disease, who presented with severe upper gastrointestinal (GI) bleeding and large gastric ulcer.Diagnosis:Primary gastric mantle cell lymphoma.Interventions:He was treated conservatively with blood transfusion and started on Traneximic acid for 3 days. Then, the patient underwent urgent hemostatic radiotherapy.Outcomes:The patient became stable and kept in the hospital for monitoring with a definite diagnosis of stage IV Mantle cell lymphoma is made.Conclusion:Mantle cell lymphoma should be kept in mind when assessing massive upper GI bleeding, as an unusual cause of bleeding gastric ulcer, given that bleeding is an uncommon presenting feature of GI lymphoma.     

t(3;17)(q21;q25) in Epstein-Barr virus associated peripheral T-cell lymphoma: a paediatric case

We describe an immunocompetent 8-year-old boy with a serological profile indicating chronic infection by Epstein-Barr virus (EBV) who developed subcutaneous and pulmonary lesions related to a peripheral T-cell proliferation. No clonal rearrangement of T-cell receptor or immunoglobulin genes was seen. However, the finding of a t(3;17)(q21;q25) in 44 metaphases from one skin lesion demonstrated a clonal origin. We also showed that the proliferative T cells contained EBV genome leading to the diagnosis of EBV-associated peripheral T-cell lymphoma. Further cytogenetic and molecular studies are needed to identify genes implicated in the pathogenesis of this haematological malignancy.