ABSTRACT
Background: Febrile lymphadenopathy not responding to first line antibiotics in a patient hailing from or with a history of travel to tuberculosis endemic countries is often primarily diagnosed as extra-pulmonary tuberculosis. However, histiocytic necrotizing lymphadenitis or Kikuchi-Fujimoto Disease(KFD) presents with similar clinical features. Etiological theories of KFD include viral agents, autoimmunity, and physicochemical factors such as leaking implants. Although KFD has classically been described in young Asian females, recent studies show men and women can be equally affected, with cases increasingly being reported from the USA and Europe as well. Availability bias amongst physicians can lead to misdiagnoses, especially in patients from tuberculosis endemic countries. Objectives: To describe a case of misdiagnosis of KFD in an adolescent. Design/Method: Case report. Results: A 16-year-old male from a tuberculosis endemic country, with a history of asthma, eczema and excision of omental infarct, presented with sub-occipital lymphadenopathy which resolved with antibiotics. Six months later, he complained of tender left cervical lymphadenopathy, associated with fever and fatigue, which lasted for a month. Two courses of antibiotics failed to decrease symptoms. Based on his clinical history, he was started on empirical anti-tubercular medications despite negative tests for tuberculosis. However, his symptoms began to worsen after three weeks of this treatment, and he developed high evening rise of temperature associated with chills, night sweats, frontal headache, pedal edema and generalized pruritic maculopapular rash. Laboratory workups revealed leukopenia (WBC:3830/μL);elevated Erythrocyte sedimentation rate (29 mm/h), C-reactive protein (68.6 mg/dL), Aspartate Aminotransferase(95 U/L) and Alanine Aminotransferase(61 U/L). Rapid antigen test for SARS-CoV2 was negative, and no appreciable levels of SARS-CoV-2 IgG antibodies were detected. Investigations for Tuberculosis, EBV, CMV, Dengue, Malaria, Typhoid, Leptospirosis and Scrub typhus were all negative. Chest X-ray and abdomen ultrasound scan were normal. Histopathological analysis of the excised cervical lymph nodes demonstrated crescentic histiocytes and karyorrhexis in a background of coagulative necrosis. Neutrophils, granulomas and acid-fast bacilli were absent. Immunohistochemistry was positive for CD3, CD20, CD68;and negative for CD15, CD30 and PAX-5. A diagnosis of KFD was made, and patient was given supportive treatment only. His symptoms rapidly resolved within 48 hours, with complete resolution by three months. Conclusion: It is important to raise awareness of KFD, a benign and self-limiting condition with good prognosis, which has many clinical symptoms mimicking grave conditions like extra-pulmonary tuberculosis, SLE and lymphomas. Timely histopathological analysis can help avoid anxiety surrounding a misdiagnosis and adverse reactions due to unnecessary toxic treatments.
ABSTRACT
Introduction: Diffuse Large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, which accounts for approximately 30% of all non-Hodgkin lymphoma cases. Spontaneous remission of DLBCL is exceedingly rare, with only a handful of case reports that describe the phenomenon present in the literature. Specialists are investigating similar cases to find out whether the SARS-CoV-2 infection triggered an antitumor immune response, as has been described with other infections in the context of high-grade non-Hodgkin lymphoma. We report one case of an elderly woman with EBV positive DLBCL diagnosed with PCR-positive SARS-CoV-2 pneumonia in the course of the disease and their outcomes. Case report: A 81 years-old woman, was referred to the consult ambulatory of intern medicine with progressive cervical, axillary and inguinal lymphadenopathy with local pain, fever and weight loss. The biopsy of an axillary lymph node demonstrated diffuse atypical lymphoid infiltrate. Immunohistochemistry stains showed positive CD20, CD30, Bcl-2 and MUM-1. It was negative for CD3, CD10, Bcl-6, c-Myc and CMV. The Ki-67 proliferation index was 80%. Epstein-Barr virus (EBV) stain were positive. These findings were consistent with DLBCL, EBV positive, clinical Stage IIIB and R-IPI 4 (poor prognosis and high risk). Since PET-CT was unavailable, thorax and abdomen computed tomographies were performed and revealed enlarged lymph node on pulmonary hilum, pathological lymph node enlargement in the axillary and supraclavicular chains bilaterally and peri aortocaval adenomegaly, extending along the bilateral femoral iliac vessels (larger lymph nodes of 2.5cm). She was treated with 4 cycles of R-CVP (rituximab with cyclophosphamide, vincristine and prednisone). When an interim PET-CT was performed, disease progression was revealed (Lugano score 5). Therefore, considering patient age and clinical status, treatment scheme was changed to R-mini-CHOP (rituximab with reduced doses of cyclophosphamide, doxorubicin, vincristine and prednisone), achieving partial response after 4 cycles (Lugano score 4). A month after this evaluation, she was admitted to the Emergency Department with diarrhea, fever and was diagnosed with PCR-positive SARS-CoV-2 pneumonia. After 6-days hospitalization with no significant ventilatory impairment, she was discharged. No corticosteroid or immunochemotherapy was administered. Two months later, she had no palpable lymphadenopathy and a PET/CT scan revealed widespread resolution of the lymphadenopathy and reduced metabolic uptake throughout (Lugano score 1). After a 7-months follow-up, the patient still has no clinical relapse. Discussion: The putative mechanisms of action include cross-reactivity of pathogen-specic T cells with tumour antigens and natural killer cell activation by inammatory cytokines produced in response to infection. It is important to consider that the more cases of SARS-CoV-2 infection in patients with non-Hodgkin lymphoma, the more likely it is to analyze lymphoma remissions and demonstrate the exact mechanism of pathogen-specific T cells with tumor antigens. Conclusion: Because spontaneous remission of DLBCL associated with SARS-CoV-2 infection is a new event, careful investigation of these cases is important, because the information gained may lead to new therapeutic targets or treatment strategies for future patients.
ABSTRACT
Introdução: O linfoma não-Hodgkin (LNH) é a neoplasia hematológica mais comum, mais frequente em homens e em países subdesenvolvidos. De acordo com estudo do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), o LNH corresponde à 80% dos linfomas, destes 50% linfoma difuso de grandes células B (LDGCB), com idade média de 59,6 anos, 33% de acometimento extranodal, 62% de doença avançada, IPI (Índice Internacional de Prognóstico) intermediário alto de 24% e alto de 19% para portadores de LDGCB. Objetivos: Relatar caso de paciente diagnosticada com LNHDGCB double hit gástrico durante investigação ambulatorial de síndrome dispéptica e sua abordagem. Materiais e métodos: Levantamento de prontuário, descrição e discussão de relato de caso clínico, por meio de uma revisão integrativa utilizando bases de dados PUBMED, MEDLINE, BVS e SCIELO. Relato de caso: Feminina, 47 anos, sem comorbidades, com queixa de epigastralgia pós-prandial há 9 meses e perda ponderal de 15 kg no período, sem outros sinais e sintomas. Há 2 meses, em investigação com gastroenterologista foi realizada EDA com biópsia de lesão gástrica associada a painel imuno-histoquímico (BCL6, CD20, CD30, MYC e Ki-67 positivos) compatíveis com LNHDGCB gástrico com alto índice proliferativo, além de tomografia de abdome total com contraste, evidenciando infiltração em lobo hepático esquerdo e hilo esplênico (estádio IV), sendo encaminhada ao serviço de hematologia há aproximadamente 15 dias. Atualmente, paciente segue em programação de quimioterapia com R-da-EPOCH após término de isolamento contactante Covid. Discussão: O linfoma double-hit (LDH) é uma neoplasia de alto grau e agressiva, que integra o subgrupo de LDGCB e se traduz na translocação do gene MYC combinada à translocação gênica adicional de BCL2, BCL3, BCL6 ou CCND1. Nesses casos, há maior tendência de infiltração de medula óssea e sistema nervoso central, além de prognóstico reservado associado ao alto índice de proliferação celular, elevação de DHL sérica, acometimento acima de 70 anos, apresentação clínica em estádio avançado e má resposta terapêutica. O diagnóstico é realizado por meio de biópsia excisional do local suspeito, estudo imuno-histoquímico, e, preferencialmente, acrescido da pesquisa FISH (hibridação in situ por Fluorescência) para MYC, BCL2 e BCL6. O estadiamento obedece a classificação Lugano, baseada no antigo sistema Ann Arbor: envolvimento de região linfonodal única (I);duas ou mais regiões linfonodais do mesmo lado do diafragma (II);regiões linfonodais em ambos lados do diafragma (III);sítio extranodal fora do sistema linfático (IV). O tratamento quimioterápico envolve ciclos de R-da-EPOCH (rituximabe, dose ajustada de etoposídeo, prednisona, doxorrubicina, ciclofosfamida e vincristina) a cada 21 dias. A Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH) considera R-da-EPOCH o tratamento padrão-ouro, porém, durante a pandemia Covid, diante da indisponibilidade de leitos e/ou bombas de infusão portáteis para tratamento ambulatorial, orienta levar em consideração a terapia com R-CHOP, seguido de estratégias de consolidação, que incluem TCTH, a fim de não atrasar o tratamento. Conclusão: O LNHDGCB double hit pode acometer jovens, em sítio extranodal e exige abordagem diferenciada por sua agressividade e alto grau associados a prognóstico reservado. Apesar disso, com as novas terapêuticas e estadiamento clínico precoce é uma neoplasia potencialmente tratável e curável, cujo tratamento pode se beneficiar do uso de técnicas citogenéticas para pesquisa de translocações gênicas.
ABSTRACT
Introduction: Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of lymphomas associated with poor outcomes following anthracycline-based chemotherapy, even when consolidative autologous stem cell transplantation (ASCT) is used. CD30 expression is universal in anaplastic large cell lymphoma (ALCL) and is frequently expressed in other PTCL subtypes. Brentuximab vedotin (BV) is a CD30-directed antibody drug conjugate that prolongs progression-free survival (PFS) and overall survival (OS) when combined with cyclophosphamide, doxorubicin, and prednisone (CHP) as compared to CHOP chemotherapy (Horwitz, 2020). Although a majority of pts treated with BV-CHP remained in durable remission (5y PFS 51%), there is room for improvement. Based on retrospective studies that demonstrated improved outcomes in younger pts, the addition of etoposide to CHOP (CHOEP) is commonly used as initial therapy for PTCL. We performed a multicenter phase 2 trial to evaluate the safety and efficacy of adding etoposide to BV-CHP (CHEP-BV) followed by BV consolidation in pts with newly diagnosed CD30-expressing PTCL. Methods: Adults with newly diagnosed CD30+ (≥ 1% of tumor cells by local pathology) PTCL were eligible, including pts with ALK+ ALCL and IPI score ≥ 2, ALK-negative ALCL, PTCL not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), adult Tcell leukemia/lymphoma (ATLL), among others. After accrual of 28 pts, the protocol was amended to allow enrollment of 20 additional pts with CD30+ non-ALCL PTCL (with ALCL allowed in Canada). Pts could receive prephase steroids and/or 1 cycle of CHOPequivalent chemotherapy prior to study entry. 6 pts were treated in a safety lead-in cohort and all pts received CHEP-BV at the recommended phase 2 dose: 6 x 21-day cycles of CHP+BV (1.8mg/kg) on d1 and etoposide 100mg/m2 on d1-3. G-CSF prophylaxis was mandatory. Pts in response after CHEP-BV could receive BV consolidation (1.8mg/kg q3w) for up to 10 additional cycles (16 total BV cycles) either after ASCT or CHEP-BV if no ASCT was performed. The co-primary endpoints were safety and the CR rate (Deauville score 1-3) by PET-CT after CHEP-BV assessed by investigators according to the 2014 Lugano classification. Secondary endpoints were PFS and OS. Results: Accrual has completed and 48 pts were enrolled;all were evaluable for toxicity, 46 were evaluable for efficacy. 16 pts had ALCL (13 ALK+, 3 ALK-) and 32 had non-ALCL PTCL subtypes, including 18 with AITL, 11 with PTCL NOS, 2 with T-follicular helper PTCL, and 1 with ATLL. Baseline characteristics are shown in Table. 43 pts completed CHEP-BV, 2 had progressive disease (PD) prior to completion, 1 pt discontinued CHEP-BV early (MD discretion), 1 pt died due to COVID-19, and 1 remains on CHEP-BV. Of 43 pts who completed CHEP-BV, 24 proceeded to ASCT and 19 did not. 33 (74%) pts received BV consolidation (20 after ASCT, 13 directly after CHEP-BV) and completed a median 8 of the planned 10 cycles (range, 1-10). 13 pts completed all cycles of consolidation;19 pts discontinued early-12 due to adverse events (AE), 5 due to PD, and 2 due to patient/physician choice. The most frequent CHEP-BV related AEs (all grades, G) include fatigue (73%), peripheral sensory neuropathy (67%), anemia (62.5%), nausea (56%), neutropenia (50%), lymphopenia (44%), leukopenia (42%), thrombocytopenia (40%), elevated transaminases (33%). The most common G3+ AEs were neutropenia (37.5%), febrile neutropenia (23%), lymphopenia (21%), anemia (19%), thrombocytopenia (19%). There were 5 deaths, 4 due to PD and 1 due to COVID-19 infection during C3 of CHEP-BV. The interim (n=46) ORR and CR rates (after 3 CHEP-BV cycles, except 1 pt after 2) were 96% and 59% (27 CR, 17 PR), respectively. At completion of CHEP-BV (n=46), the ORR was 91% with 80% CR (37 CR, 5 PR, 4 PD). The ORR/CR rates in ALCL (n=16) vs non-ALCL (n=30) pts were 94%/94% vs 90%/73%, respectively. The ORR/CR rates in pts with CD30 expression 1-9% (n=15) vs 10+% (n=31) were 93%/67% and 90%/87%, respectively. The median follow-up in surviving pts is 1 .1 months (range, 0.9-32.5). The overall 18mo PFS and OS were 61% and 89%;18mo PFS by subgroup: ALCL 81%, non-ALCL 49%, CD30 1-9% 48%, CD30 10+% 67%. Landmark 1y PFS from end of CHEP-BV in responding pts (n=41) was 82% in pts who underwent ASCT vs 48% in pts who did not Conclusions: In a cohort of pts with mostly non-ALCL CD30-expressing PTCL, CHEP-BV (+/-ASCT) followed by BV consolidation was tolerable and effective.