Mutation characteristics of angioimmunoblastic T-cell lymphoma: an analysis of 75 cases / 中华病理学杂志

Objective: To investigate the characteristics of gene mutations in angioimmunoblastic T-cell lymphoma (AITL). Methods: Seventy-five AITL cases diagnosed at the Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from June 2021 to June 2023 were included. Their formalin-fixed and paraffin-embedded or fresh tissues were subject to targeted next generation sequencing (NGS). The sequencing data was collected, and the distribution and type of gene mutations were analyzed. Results: 492 potential driver mutations were identified in 74 out of the 84 genes. Targeted sequencing data for the 75 AITL patients showed that the genes with mutation frequencies of ≥10% were TET2 (89.3%), RHOA (57.3%), IDH2 (37.3%), DNMT3A (36.0%), KMT2C (21.3%), PLCG1 (12.0%), and KDM6B (10.7%). There were significant co-occurrence relationships between TET2 and RHOA, TET2 and IDH2, and RHOA and IDH2 gene mutations (P<0.05), respectively, while TET2 and KDM6B gene mutations were mutually exclusive (P<0.05). Conclusions: The study reveals the mutational characteristics of AITL patients using NGS technology, which would provide insights for molecular diagnosis and targeted therapy of AITL.

COVID-19 y leucemia/linfoma T del adulto, sinergia mortal / COVID-19 and adult T cell leukemia-lymphoma: a deadly synergy

La leucemia/linfoma T del adulto es una neoplasia maligna de mal pronóstico frecuente en población anciana. Se presenta el caso de una mujer de 44 años de edad, de Ayacucho, diagnosticada con el subtipo linfomatoso de esta enfermedad e infección por virus linfotrópico T humano-I; mostró síndrome oclusivo de vena cava superior con tratamiento de quimioterapia sistémica bajo régimen de dosis ajustada con rituximab más etoposido, prednisona, vincristina, ciclofosfamida y doxorubicina. Posteriormente ingresó en emergencia por presentar dificultad respiratoria, tos seca, disminución de la conciencia, hipercalcemia, tomografía de tórax con patrón heterogéneo consolidativo en ambos pulmones y PCR en hisopado nasofaríngeo positivo a COVID-19. Recibió tratamiento de hidroxicloroquina, azitromicina, corticoides e ivermectina con pobre respuesta, rápido deterioro y fallece días después. La leucemia/linfoma T del adulto a edad temprana es rara y está relacionada con infecciones crónicas como strongyloides o tuberculosis, susceptible ante el padecimiento de COVID-19.

Adult T cell leukemia-lymphoma is a common malignancy with a poor prognosis in the elderly population. We present a 44-year-old woman from Ayacucho who was diagnosed with a lymphoma subtype of this disease and a human T-lymphotropic virus-I infection; she showed superior vena cava occlusive syndrome with systemic chemotherapy treatment under an adjusted-dose regimen with rituximab plus etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin. Subsequently, she was admitted to the emergency service due to respiratory distress, dry cough, decreased consciousness, hipercalcemia, chest tomography with a heterogeneous consolidation pattern in both lungs and positive RT-PCR nasopharyngeal swab test for COVID-19. She received treatment with hydroxychloroquine, azithromycin, corticosteroids and ivermectin with a poor response, rapid deterioration and died later. Adult T cell leukemia-lymphoma at an early age is rare and is related to chronic infections such as strongyloides or tuberculosis, susceptible to COVID-19.

Composite B-cell and T-cell lymphomas: clinical, pathological, and molecular features of three cases and literature review / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Composite lymphoma (CL) involving B-cell lymphoma and T-cell lymphoma is extremely rare. Herein, we report three such cases using immunohistochemistry, flow cytometry, and the next-generation sequencing (NGS) to identify the pathological and molecular characteristics of CL. In the first case, the patient was admitted to hospital for generalized pruritic maculopapular rash over the whole body. An excisional biopsy of the skin lesions showed T-cell lymphoma. At the same time, the staging bone marrow (BM) biopsy revealed a diffuse large B-cell lymphoma (DLBCL). After R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapies, the patient produced a good response with substantial dissipation of the rashes and relief of skin. The other two patients were admitted to hospital due to lymphadenopathy and were diagnosed with DLBCL and follicular lymphoma (FL) after core needle biopsy of lymph nodes, BM biopsy, BM aspiration, and flow cytometry. Following R-CHOP and R-COP (rituximab, cyclophosphamide, vincristine, and prednisone) therapies, they achieved complete remission unconfirmed (CRu) and complete remission (CR). However, one or two years later, they suffered a relapse of lymphadenopathy. The shocking fact was that re-biopsy of lymphadenopathy revealed peripheral T-cell lymphoma (PTCL) and angioimmunoblastic T-cell lymphoma (AITL). NGS findings identified DNA methyltransferase 3a (DNMT3a), isocitrate dehydrogenase 2 (IDH2), Ras homolog gene family, member A (RHOA), splicing factor 3B subunit 1 (SF3B1), and tumor protein p53 (TP53) mutations. After immunochemotherapy, these patients achieved CRu and CR again. Nevertheless, they suffered a second relapse of T-cell lymphoma. Finally, they died due to progression of disease. We found that the occurrence of CL is associated with Epstein-Barr virus infection and DNMT3a, IDH2, and TP53 mutations, and the prognosis of the disease is closely related to the T-cell lymphoma components.

Efficiency and safety analysis of Plerixafor combined with granulocyte colony-stimulating factor on autologous hematopoietic stem cell mobilization in lymphoma / 中华血液学杂志

Objective: To evaluate the advantages and safety of Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) in autologous hematopoietic stem cell mobilization of lymphoma. Methods: Lymphoma patients who received autologous hematopoietic stem cell mobilization with Plerixafor in combination with G-CSF or G-CSF alone were obtained. The clinical data, the success rate of stem cell collection, hematopoietic reconstitution, and treatment-related adverse reactions between the two groups were evaluated retrospectively. Results: A total of 184 lymphoma patients were included in this analysis, including 115 cases of diffuse large B-cell lymphoma (62.5%) , 16 cases of classical Hodgkin's lymphoma (8.7%) , 11 cases of follicular non-Hodgkin's lymphoma (6.0%) , 10 cases of angioimmunoblastic T-cell lymphoma (5.4%) , 6 cases of mantle cell lymphoma (3.3%) , and 6 cases of anaplastic large cell lymphoma (3.3%) , 6 cases of NK/T-cell lymphoma (3.3%) , 4 cases of Burkitt's lymphoma (2.2%) , 8 cases of other types of B-cell lymphoma (4.3%) , and 2 cases of other types of T-cell lymphoma (1.1%) ; 31 patients had received radiotherapy (16.8%) . The patients in the two groups were recruited with Plerixafor in combination with G-CSF or G-CSF alone. The baseline clinical characteristics of the two groups were basically similar. The patients in the Plerixafor in combination with the G-CSF mobilization group were older, and the number of recurrences and third-line chemotherapy was higher. 100 patients were mobilized with G-CSF alone. The success rate of the collection was 74.0% for one day and 89.0% for two days. 84 patients in the group of Plerixafor combined with G-CSF were recruited successfully with 85.7% for one day and 97.6% for two days. The success rate of mobilization in the group of Plerixafor combined with G-CSF was substantially higher than that in the group of G-CSF alone (P=0.023) . The median number of CD34(+) cells obtained in the mobilization group of Plerixafor combined with G-CSF was 3.9×10(6)/kg. The median number of CD34(+) cells obtained in the G-CSF Mobilization group alone was 3.2×10(6)/kg. The number of CD34(+) cells collected by Plerixafor combined with G-CSF was considerably higher than that in G-CSF alone (P=0.001) . The prevalent adverse reactions in the group of Plerixafor combined with G-CSF were grade 1-2 gastrointestinal reactions (31.2%) and local skin redness (2.4%) . Conclusion: The success rate of autologous hematopoietic stem cell mobilization in lymphoma patients treated with Plerixafor combined with G-CSF is significantly high. The success rate of collection and the absolute count of CD34(+) stem cells were substantially higher than those in the group treated with G-CSF alone. Even in older patients, second-line collection, recurrence, or multiple chemotherapies, the combined mobilization method also has a high success rate of mobilization.

Primary central nervous system T-cell lymphoma in children and adolescents: a clinicopathological analysis of five cases / 中华病理学杂志

Objective: To study the clinicopathological characteristics, and further understand primary central nervous system T-cell lymphoma (PCNSTCL) in children and adolescents. Methods: Five cases of PCNSTCL in children and adolescents were collected from December 2016 to December 2021 at the First Affiliated Hospital of Zhengzhou University. The clinicopathological characteristics, immunophenotypic, and molecular pathologic features were analyzed, and relevant literatures reviewed. Results: There were two male and three female patients with a median age of 14 years (range 11 to 18 years). There were two peripheral T-cell lymphomas, not otherwise specified, two anaplastic large cell lymphoma, ALK-positive and one NK/T cell lymphoma. Pathologically, the tumor cells showed a variable histomorphologic spectrum, including small, medium and large cells with diffuse growth pattern and perivascular accentuation. Immunohistochemistry and in situ hybridization showed CD3 expression in four cases, and CD3 was lost in one case. CD5 expression was lost in four cases and retained in one case. ALK and CD30 were expressed in two cases. One tumor expressed CD56 and Epstein-Barr virus-encoded RNA. All cases showed a cytotoxic phenotype with expression of TIA1 and granzyme B. Three cases had a high Ki-67 index (>50%). T-cell receptor (TCR) gene rearrangement was clonal in two cases. Conclusions: PCNSTCL is rare, especially in children and adolescents. The morphology of PCNSTCL is diverse. Immunohistochemistry and TCR gene rearrangement play important roles in the diagnosis.

Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation treatment for T lymphoblastic leukemia/lymphoma / 中华血液学杂志

Objective: To analyze the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treating T lymphoblastic leukemia/lymphoma (T-ALL/LBL) . Methods: This study retrospectively evaluated 119 adolescent and adult patients with T-ALL/LBL from January 2006 to January 2020 at Peking University Third Hospital and Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Patients were divided into chemotherapy-only, chemotherapy followed by allo-HSCT, and chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) groups according to the consolidation regimen, and the 5-year overall survival (OS) and progression-free survival (PFS) rates of each group were compared. Results: Among 113 patients with effective follow-up, 96 (84.9%) patients achieved overall response (ORR), with 79 (69.9%) having complete response (CR) and 17 (15.0%) having partial response (PR), until July 2022. The analysis of the 96 ORR population revealed that patients without transplantation demonstrated poorer outcomes compared with the allo-HSCT group (5-year OS: 11.4% vs 55.6%, P=0.001; 5-year PFS: 8.9% vs 54.2%, P<0.001). No difference was found in 5-year OS and 5-year PFS between the allo-HSCT and auto-HSCT groups (P=0.271, P=0.197). The same results were achieved in the CR population. Allo-HSCT got better 5-year OS (37.5% vs 0) for the 17 PR cases (P=0.064). Different donor sources did not affect 5-year OS, with sibling of 61.1% vs hap-haploidentical of 63.6% vs unrelated donor of 50.0% (P>0.05). No significant difference was found in the treatment response in the early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP) and non-ETP populations. The ETP group demonstrated lower 5-year OS compared with the non-ETP group in the chemotherapy alone group (0 vs 12.6%, P=0.045), whereas no significant difference was found between the ETP and non-ETP groups in the allo-HSCT group (75.0% vs 62.9%, P=0.852). Multivariate analysis revealed that high serum lactate dehydrogenase level, without transplantation, and no CR after chemotherapy induction were independently associated with inferior outcomes (P<0.05) . Conclusion: Allo-HSCT could be an effective consolidation therapy for adult and adolescent patients with T-ALL/LBL. Different donor sources did not affect survival. Allo-HSCT may overcome the adverse influence of ETP-ALL/LBL on OS.

Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma in a 76-year-old Filipino Male: A case report

@#<p style="text-align: justify;"><strong>INTRODUCTION:</strong> Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma (PCAECTCL) is a rare subtype of cutaneous T-cell lymphoma characterized by widely distributed ulcerated lesions, epidermotropic infiltrates of CD8+ cytotoxic T cells, aggressive course, high tendency to spread to extranodal sites, poor response to conventional therapies and unfavorable prognosis.</p><p style="text-align: justify;"><strong>CASE REPORT:</strong> We report a 76-year-old Filipino male presenting with eight-month history of erythematous scaly patches evolving into widespread ulcerated nodules, unresponsive to topical and systemic steroids. Histopathology revealed prominent epidermotropism and lichenoid infiltrate of atypical lymphocytes. Immunohistochemistry showed positivity for CD3, CD8, Ki67 (5-15%), CD7, CD2; indeterminate for TIA-1, with high background staining; and was negative for CD20, CD30, CD4, CD5, CD56, granzyme-B, TdT, Epstein-Barr encoding region in situ hybridization (EBER-ISH), consistent with PCAECTCL. No overt metastasis was detected. The patient underwent interferon alfa 2B therapy followed by three full cycles of CHOP chemotherapy. Improvement was seen as thinning of plaques and nodules and re-epithelialization of ulcers however, severe anemia and leukopenia ensued with therapy. He then succumbed to septic shock secondary to pneumonia during the height of the COVID-19 pandemic.</p><p style="text-align: justify;"><strong>CONCLUSION:</strong> This case emphasizes that despite accurate diagnosis, polychemotherapy, and favorable response to therapy, complications may still arise contributing to the poor prognosis and low fi ve-year survival rate of this condition.</p><p style="text-align: justify;"><strong>KEYWORDS:</strong> T-cell lymphoma, CD8 positive, neoplasms</p>

Clinicopathological features and prognosis of cytotoxic T-cell lymphoma: analysis of 134 cases / 中华病理学杂志

Objective: To investigate the clinicopathological features and prognosis of cytotoxic T-cell lymphoma (CTL). Methods: The clinicopathological data of 134 CTL patients in Beijing Friendship Hospital Affiliated to Capital Medical University, the 989 Hospital of PLA Joint Logistics Support force (formerly the 152 Hospital) and the Fourth Hospital of Hebei Medical University from 2008 to 2020 were retrospectively collected. Immunophenotype, Epstein-Barr virus infection status and T cell receptor (TCR) clonality of tumor cells were assessed, and clinicopathological features and prognosis of patients were analyzed. Results: Among the 134 CTL patients, the male to female ratio was 1.7∶1.0, the median age was 49.5 years (range 3-83 years), and 100 cases (74.6%) were under 60 years old. Forty-six point nine percent of the patients (53/113) had B symptoms. Most of the patients presented with systemic superficial lymphadenopathy. According to the Ann Arbor staging system, 36.8% (39/106) of the patients were in stage Ⅰ-Ⅱ, and 63.2% (67/106) in stage Ⅲ-Ⅳ. The rate of extranodal involvement was 51.6% (66/128). Spleen was involved in 24.2% (31/128) of the cases. Morphology showed diffuse growth of abnormal lymphocytes, infiltrating and destroying normal tissue structure. Immunohistochemical staining showed that tumor cells expressed T cell antigens (CD2, CD3, CD5, and CD7), and 72.0% (77/107) of them had decreased or lost expression of one or more antigens. According to the numbers of CD4 and CD8 expression in tumor cells, 70 cases (52.2%) were grouped into CD8+>CD4+group. The expression rates of TIA-1 and granzyme B were 99.2% (119/120) and 79.8% (95/119), respectively. CD20 abnormal expression rate was 27.6% (37/134) and CD56 was negative in all cases. The median Ki-67 proliferative index was 45.0% (range 5%-80%). In situ hybridization of small RNA encoded by Epstein-Barr virus was negative. Clonal TCR gene rearrangement analysis was performed on 49 cases and was positive in all cases. Ninety-one patients were followed up for a median of 36 months (range, 1 to 240 months), and 40 of the 91 patients (44.0%) died. The twenty-three patients were in complete remission (including 13 cases with localized single extranodal mass). The 3-year and 5-year overall survival rates were 53.5% and 49.4%, respectively. Univariate analysis showed that B symptom, spleen involvement, extranodal involvement, clinical stage, CD8+>CD4+phenotype, abnormal expression of CD20 and Ki-67 proliferation index (>60%) were associated with overall survival (P<0.05). The multivariate Cox regression analyses showed that spleen involvement and CD8+>CD4+ phenotype were independent prognostic factors for overall survival in CTL patients. Conclusions: CTL are more commonly found in adult males under 60 years old, often accompanied by B symptom, with a high proportion of extranodal involvement and more CD8 positive phenotypes. Spleen involvement and CD8+>CD4+phenotype are independent predictors of CTL overall survival. Some patients with localized extranodal CTL may have a good prognosis.

Primary peripheral T-cell lymphoma of the cervix with mononeuritis multiplex: an unusual case presentation

Peripheral neuropathy (PN) is characterized by the injury to the peripheral nervous system of varied etiology. Lymphoma is one of the etiologies of PN, presenting various neurological manifestations. Neuropathy associated with peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) is unusual and fewer cases are documented in the literature. In addition, PTCL, NOS is extremely rare as primary in the female genital tract, especially uterine cervix, and exhibits aggressive clinical course with poor therapy response. We hereby describe a 47-year-old female who presented with fever and chills for 15 days. Clinical examination revealed left-sided lower motor neuron type of facial nerve palsy with Bell's phenomenon. Nerve conduction study of all four limbs illustrated asymmetrical axonal neuropathy (motor > sensory), suggesting mononeuritis multiplex. She developed vaginal bleeding during her hospital stay. Pelvic examination and imaging revealed a 4x3cm polypoidal mass on the posterior lip of the cervix, which was excised and diagnosed as extranodal primary PTCL, NOS based on morphology, immunohistochemistry, and in-situ hybridization findings. Besides, the cerebrospinal fluid (CSF) was infiltrated by the lymphoma cells, detected on cell block preparation. The patient succumbed to her illness within one week despite best efforts and the commencement of chemotherapy. No consent was obtainable for nerve biopsy and autopsy. Thus, we report an extremely rare case of primary extranodal PTCL, NOS of the uterine cervix with unusual presentation of mononeuritis multiplex. Further, we discussed the differentials of PTCL, NOS at this extranodal site.

Linfoma T intestinal epiteliotrópico monomórfico: Reporte de Caso / Monomorphic epitheliotropic intestinal T lymphoma: A case report / Linfoma T intestinal epiteliotrópico monomórfico: relato de caso

Introducción: El linfoma de células T intestinal epiteliotrópico monomórfico es una neoplasia derivada de linfocitos intraepiteliales. La etiología es desconocida, pero se ha asociado a enfermedad celíaca o a síndrome de malabsorción, aunque en la actualidad se considera un linfoma esporádico. La histopatología se caracteriza por linfocitos de tamaño intermedio a pequeño, con mínimo pleomorfismo, que generalmente expresan CD8 y CD56. Reporte de caso: Mujer de 60 años con dispepsia de larga evolución, fue ingresada por dolor abdominal agudo, diarrea, nausea, vómito bilioso y pérdida de peso. En los estudios se determinó anemia microcítica hipocrómica y desequilibrio hidroelectrolítico. Se evidenció por tomografía de abdomen una lesión nodular esplénica y engrosamiento concéntrico segmentario de yeyuno e íleon distal asociado a la presencia de líquido libre en cavidad abdominal, se consideró una masa tumoral. Evolución: Se realizó una laparotomía exploratoria con resección de yeyuno-transverso, en patología se determinó la presencia de 3 tumores: a nivel de yeyuno de 16x8.5x6 cm, en el íleon distal de 13x6.5x3 cm y en el ciego de 5x4x2cm con histología de linfoma no Hodgkin T de alto grado, intestinal primario, de tipo monomórfico epiteliotrópico (MEITL). Fue dada de alta diez días después. Dos semanas luego desarrollo sepsis de foco urinario, deshidratación, síndrome de intestino corto, hiper-amonemia y neumonía de focos múltiples con derrame pleural bilateral. Falleció al sexto día de hospitalización. Conclusiones: El MEITL es una neoplasia agresiva primaria intestinal de reciente identificación y pobre pronóstico. No se conocen en su totalidad los mecanismos moleculares asociados a esta entidad. El caso presentado demostró un curso clínico similar al reportado en la literatura.

Introduction: Monomorphic epitheliotropic intestinal T-cell lymphoma is a derived neoplasia of intraepithelial lymphocytes. The etiology is unknown, but it has been associated with celiac disease or malabsorption syndrome, although it is currently considered a sporadic lymphoma. Histopatholo-gy is characterized by medium to small lymphocytes with minimal pleo-morphism, which generally express CD8 and CD56. Case report: A 60-year-old woman with long-standing dyspepsia was admitted for acute abdominal pain, diarrhea, nausea, bilious vomiting, and weight loss. In the studies, hypochromic microcytic anemia and fluid and electrolyte imbalance were determined. A splenic nodular lesion and segmental concentric thickening of the jejunum and distal ileum associated with the presence of free fluid in the abdominal cavity was evidenced by abdominal tomography, it was considered a tumor mass. Evolution: An exploratory laparotomy was performed with transverse jejunum resection, in pathol-ogy the presence of 3 tumors was determined: at the jejunum level of 16x8.5x6 cm, in the distal ileum of 13x6.5x3 cm and in the cecum of 5x4x2cm with histology of high-grade non-Hodgkin T lymphoma, primary intestinal, epitheliotropic monomorphic type (MEITL). She was discharged ten days later. Two weeks later, she developed sepsis with a urinary focus, dehydration, short bowel syn-drome, hyper-amonemia, and multiple-focus pneumonia with bilateral pleural effusion. He died on the sixth day of hospitalization. Conclusions: MEITL is a recently identified aggressive primary intestinal neoplasm and poor prog-nosis. The molecular mechanisms associated with this entity are not fully known. The case presented showed a clinical course similar to that reported in the literature.

Introdução: O linfoma intestinal monomórfico epiteliotrópico de células T é uma neoplasia derivada de linfócitos intraepiteliais. A etiologia é desconhecida, mas tem sido associada à doença celíaca ou síndrome de má absorção, embora seja atualmente considerado um linfoma esporádico. A histopatologia é caracterizada por linfócitos médios a pequenos com pleomorfismo mínimo, que geralmente expressam CD8 e CD56. Relato do caso: Mulher de 60 anos com dispepsia de longa data foi admitida por dor abdominal aguda, diarreia, náuseas, vômitos biliosos e perda de peso. Nos estudos, foram determinados a anemia microcítica hipocrômica e o desequilíbrio hidroeletrolítico. Lesão nodular esplênica e espessamento concêntrico segmentar do jejuno e íleo distal associado à presença de líquido livre na cavidade abdominal foi evidenciado pela tomografia abdominal, considerada massa tumoral. Evolução: Foi realizada laparotomia exploradora com ressecção transversa do jejuno, na anatomia patológica foi determinada a presença de 3 tumores: ao nível do jejuno de 16x8,5x6 cm, no íleo distal de 13x6,5x3 cm e no ceco de 5x4x2cm com histologia de epiteliotrópico monomórfico monomórfico tipo linfoma T intestinal primário não-Hodgkin (MEITL). Ela teve alta dez dias depois. Duas semanas depois, desenvolvimento de sepse de foco urinário, desidratação, síndrome do intestino curto, hiperamonemia e pneumonia de foco múltiplo com derrame pleural bilateral. Ele morreu no sexto dia de internação. Conclusões: MEITL é uma neoplasia intestinal primária agressiva recentemente identificada e de mau prognóstico. Os mecanismos moleculares associados a esta entidade não são totalmente conhecidos. O caso apresentado apresentou evolução clínica semelhante à relatada na literatura.

Linfoma de células NK/T subtipo nasal ­ relato de caso / Nasal subtype NK/T cell lymphoma ­ case report

RESUMO O linfoma de células NK/T subtipo nasal tem baixa incidência e alta agressividade, mostrando-se necessário diagnóstico precoce. Tal se mostra desafiador devido à sua manifestação clínica inicial, semelhante a quadro infeccioso de vias aéreas superiores. Por meio deste estudo observacional descritivo, relatam-se casos deste linfoma acometendo paciente masculino e outro feminino, ambos com diagnóstico tardio e com envolvimento de vias aéreas superiores sem resposta à antibioticoterapia. À exame de imagem, apresentaram lesão expansiva em cavidade nasal e o diagnóstico se deu por meio de estudo histológico com marcadores imuno-histoquímicos de células NK atípicas e presença de vírus Epstein-Barr (EBV). PALAVRAS-CHAVE: Linfoma de células NK/T tipo nasal, Epstein-Barr vírus, linfoma não-hodgkin, linfoma de células T periférico

ABSTRACT Nasal subtype NK/T cell lymphoma has a low incidence and high aggressiveness, and early diagnosis is necessary. This is challenging due to its initial clinical manifestation, similar to an upper airway infection. Through this descriptive observational study, we report cases of this lymphoma affecting a male and a female patient, both with late diagnosis and involvement of the upper airways without response to antibiotic therapy. On imaging scan, they presented an expansive lesion in the nasal cavity and the diagnosis was made through histological study with immunohistochemical markers of atypical NK cells and the presence of Epstein-Barr virus (EBV). KEYWORDS: NK/T-cell lymphoma nasal type, Epstein-Barr virus, Lymphoma non Hodgkin, T-cell lymphoma

Linfoma pericárdico primario a células T/NK: reporte de un caso / Primary pericardial T/NK cell lymphoma: case report / Linfoma pericárdico primário de células T/NK: relato de um caso

Los linfomas cardíacos primarios son un subtipo muy poco frecuente de tumor en los cuales la lesión primaria se encuentra en el corazón. Los tumores suelen ser infiltrantes y se localizan en la aurícula derecha, seguidos del pericardio. Su mortalidad es notablemente alta y el diagnóstico tardío es el principal factor para su mal pronóstico. Describimos el caso de un paciente que presentó shock obstructivo por derrame pericárdico profuso causado por un tipo raro de tumor cardíaco primario, un linfoma pericárdico de células T/NK.

Primary cardiac lymphomas are a rare subtype of lymphomas in which the primary lesion is in the heart. The tumors are usually located in the right atria, followed by the pericardium and are frequently infiltrative. Mortality is remarkably high in this group and the delayed diagnosis is the main factor for its poor prognosis. We describe the case of a patient that presented with obstructive shock due to profuse pericardial effuse caused by a rare kind of primary cardiac tumor, a T/NK cell pericardial lymphoma.

Os linfomas cardíacos primários são um subtipo de tumor muito raro, no qual a lesão primária está no coração. Os tumores geralmente são infiltrativos e localizam-se no átrio direito, seguidos pelo pericárdio. Sua mortalidade é notavelmente alta e o diagnóstico tardio é o principal fator que produz seu mau prognóstico. Descrevemos o caso de um paciente que apresentou choque obstrutivo devido a um derrame pericárdico profuso causado por um tipo raro de tumor cardíaco primário, um linfoma pericárdico de células T/NK.

Exploring the Mechanism of Paclitaxel Inhibiting T-cell Lymphoma based on High-throughput Sequencing and Public Databases / 中国实验血液学杂志

OBJECTIVE@#To analyze gene expression profile of T cell lymphoma Jurkat cell line treated with paclitaxel by computational biology based on next generation sequencing and to explore the possible molecular mechanism of paclitaxel resistance to T cell lymphoma at gene level.@*METHODS@#IC50 of paclitaxel on Jurkat cell line was determined by CCK-8 assay. Gene expression profile of Jurkat cells treated with paclitaxel was acquired by next generation sequencing technology. Gene microarray data related to human T cell lymphoma were screened from Gene Expression Omnibus (GEO) database (including 720 cases of T cell lymphoma and 153 cases of normal tissues). Combined with the sequencing data, differential expression genes (DEGs) were intersected and screened. DAVID database was used for enrichment analysis of GO function and KEGG pathway to determine and visualize functional entries of DEGs, and protein-protein interactions network of DEGs was drawn. The levels of gene expression were detected and verified by RT-qPCR.@*RESULTS@#CCK-8 results showed that the proliferation of Jurkat cells was inhibited by paclitaxel depended on the concentration apparently. Treated by paclitaxel for 48 h, P<0.05 and |log2(FC)|≥1 were used as filter criteria on the results of RNA Sequencing (RNA-Seq) and GeoChip, 351 DEGs were found from Jurkat cells, including 323 up-regulated genes and 28 down-regulated genes. The GO functional annotation and KEGG pathway enrichment analysis showed that the role of paclitaxel was mainly concentrated in protein heterodimerization activity, nucleosome assembly and transcriptional dysregulation in cancer, etc. The results of RT-qPCR were consistent with those of the sequencing analysis, which verified the reliability of this sequencing.@*CONCLUSION@#Paclitaxel can affect the proliferation and apoptosis of T-cell lymphoma by up-regulating JUN gene, orphan nuclear receptor NR4A family genes and histone family genes.

Research Progression of Subcutaneous Panniculitis-like T-Cell Lymphoma--Review / 中国实验血液学杂志

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a very rare cutaneous malignant lymphoma derived from cytotoxic T cells that mainly involves subcutaneous adipose tissue rather than epidermis and dermis. It usually occurs in young and middle-aged population, and the etiology is currently unclear. Clinically, SPTCL is characterized by subcutaneous plaques, nodules, and skin ulcers with swell and ache, mainly presenting in limbs and trunk. SPTCL has been restricted to cases that express α/β phenotype, whereas cases with γ/δ phenotype are categorized to cutaneous γ/δ

Extranodal NK/T-cell lymphoma, nasal type with extensive cardiopulmonary involvement

Extranodal NK/T-cell lymphoma, nasal type (ENKTL-NT) is a rare type of Non-Hodgkin's lymphoma, which usually presents with extranodal involvement and affects the nasal/upper aerodigestive tract in the classical presentation. Herein, we report the case of a 31-year-old, previously healthy, male patient diagnosed with ENKTL-NT with the involvement of the lung parenchyma and heart. Unfortunately, due to the rapid disease progression, the diagnosis was performed only at the autopsy. The authors highlight the rare clinical presentation of this type of lymphoma, as well as the challenging anatomopathological diagnosis in necrotic samples.

Linfoma hepatoesplénico de células T en un paciente adolescente / Hepatosplenic T-cell lymphoma in an adolescent patient

Resumen Introducción: Los linfomas de células T son infrecuentes y se caracterizan por presentarse en la población de los adultos jóvenes. Además, suele acompañarse de patologías como la anemia moderada, hepatoesplenomegalia y trombocitopenia e infiltración sinusoidal por linfocitos T en células de médula ósea, bazo e hígado. Caso clínico: Se presenta un caso clínico de un adolescente que tiene los síntomas característicos de esta patología, con sospecha clínica y diagnóstico paraclínico confirmado con histoquímica de médula ósea. Conclusión: Es una entidad infrecuente de pronóstico desfavorable, hasta el momento el paciente está estable recibiendo tratamiento. Para utilizar el enfoque adecuado en el diagnóstico y brindar tratamiento, es necesario considerar todos los hallazgos clínicos.

Abstract Introduction: T-cell lymphomas are uncommon; these tend to be present in young adult patients. Additionally, this condition is characterized by the existence of pathologies like moderate anemia, hepatosplenomegaly disorder, thrombocytopenia and sinusoidal infiltration by T-Lymphocytes in bone marrow cells, spleen and liver. In this study a case of this rare lymphoma is going to be presented. Case report: A clinical case of an adolescent who presents the characteristic symptoms of this pathology is exposed. This clinical suspicion held a paraclinical diagnosis that was confirmed by histochemistry of bone marrow tests. Conclusion: It is an infrequent condition with an unfavorable prognosis. Until now the patient remains stable and is receiving treatment, the clinical findings of the disease raise awareness about the importance of carrying out the appropriate diagnosis procedures and providing treatment.

Histopathological and immunophenotypical characterization of canine multicentric lymphoma in Brazil: a study of 203 cases / Caracterização histopatológica e imunofenotípica do linfoma multicêntrico canino no Brasil: um estudo de 203 casos

The immunophenotype is regarded as an independent prognostic factor in high-grade lymphomas, seeing that lymphomas of T-cell origin are associated with shorter survival time. Although a number of studies have evaluated the immunophenotypical profile of lymphoma in the USA and Europe, Brazilian research on the matter remains scarce. Exact characterization of the histopathological type is crucial to establish proper treatment and prognosis. This study evaluated the database of immunohistochemistry laboratories that perform immunophenotyping of canine lymphoma in Brazil. A total of 203 cases of multicentric lymphoma were classified according to the WHO classification. Immunophenotyping was able to identify 71.4% lymphomas of B-cell line, 27.1% of T-cell line and 1.5% of non-B cells and non-T cell lines. Diffuse large B-cell lymphoma was the most common with 59.1% of the cases. Among T-cell lymphomas, lymphoblastic was the most common (11.33% of the cases). Even though canine lymphomas tend to be high-grade, indolent lymphomas comprised 11.82% of the cases and T-zone lymphoma was the most prevalent (8.86%). The immunophenotype of multicentric lymphoma in Brazil is similar to those in other parts of the world, which suggests similar etiologic factors to the development of this disease.(AU)

O imunofenótipo é considerado um fator prognóstico independente em linfomas de alto grau, visto que os linfomas de origem de células T estão associados a menor tempo de sobrevida. Apesar de vários estudos terem avaliado o perfil imunofenotípico do linfoma nos EUA e na Europa, a pesquisa brasileira sobre o assunto ainda é escassa. A caracterização exata do tipo histopatológico é crucial para estabelecer o tratamento e o prognóstico adequados. Este estudo avaliou a base de dados de laboratórios de imuno-histoquímica que realizam imunofenotipagem do linfoma canino no Brasil. Um total de 203 casos de linfoma multicêntrico foi classificado de acordo com a classificação da OMS. A imunofenotipagem foi capaz de identificar 71,4% dos linfomas da linhagem de células B, 27,1% da linhagem de células T e 1,5% das linhagens de células não B e não T. O linfoma difuso de grandes células B foi o mais comum em 59,1% dos casos. Entre os linfomas de células T, o linfoblástico foi o mais comum (11, 33% dos casos). Embora os linfomas caninos tendam a ser de alto grau, os linfomas indolentes representaram 11,82% dos casos e o linfoma da zona T foi o mais prevalente (8,86%). O imunofenótipo do linfoma multicêntrico no Brasil é semelhante ao de outras partes do mundo, o que sugere fatores etiológicos semelhantes ao desenvolvimento dessa doença.(AU)

Angioimmunoblastic T-cell lymphoma with fever, arthritis and skin pigmentation: A case report / 北京大学学报(医学版)

Angioimmunoblastic T-cell lymphoma is a rare T-cell lymphoma. The clinical manifestations are not specific. In addition to the common clinical manifestations of lymphomas such as fever, weight loss, night sweats and lymphadenopathy, it may also have skin rashes, arthritis, multiple serous effusions, eosinophilia and other systemic inflammatory or immune symptoms. The lymphoma cells of angioimmunoblastic T-cell lymphoma originates from follicular helper T cells, and the follicular structure of lymph nodes disappears. In the tumor microenvironment, in addition to tumor cells, there are a large number of over-activated immune cells, such as abnormally activated B cells, which produce a series of systemic inflammation or immune-related symptoms. This disease is rare and difficult to diagnose. This article reports a 36-year-old female. She got fever, joint swelling and pain, skin pigmentation, accompanied by hepatomegaly, splenomegaly, lymphadenopathy, anemia and other multiple-systems manifestations. The clinical manifestations of this patient were similar to autoimmune diseases such as adult onset Still's disease, rheumatoid arthritis, and systemic sclerosis, which made the diagnosis difficult. At the beginning of the disease course, the patient got arthritis and fever. And her white blood cells were significantly increased. Adult onset Still's disease should be considered, but her multiple-systems manifestations could not be explained by adult onset Still's disease. And her arthritis of hands should be distinguished with rheumatoid arthritis. However, the patient's joint swelling could get better within 3-7 days, and there was no synovitis and bone erosion on joint imaging examination. The rheumatoid factor and anti-CCP antibody were negative. The diagnostic evidence for rheumatoid arthritis was insufficient. The patient's skin pigmentation and punctate depigmentation were similar to those of systemic sclerosis. But the patient had no Raynaud's phenomenon, and her sclerosis-related antibody was negative. The diagnostic evidence for systemic sclerosis was also insufficient. After 3 years, she was finally diagnosed with angioimmunoblastic T-cell lymphoma by lymph node biopsy aspiration. This case suggests that the clinical manifestations of angioimmunoblastic T-cell lymphoma are diverse, and some symptoms similar to immune diseases may appear. When the patient's clinical symptoms are atypical and immune diseases cannot explain the patient's condition, and further evidence should be sought to confirm the diagnosis.