A US Multicenter Collaborative Study on Outcomes of Hematopoietic Cell Transplantation in Hepatosplenic T-Cell Lymphoma.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive type of peripheral T-cell lymphoma with median overall survival (OS) of approximately 1 year. Data on the effectiveness of hematopoietic cell transplantation (HCT) is limited, as is the choice between autologous HCT (auto-HCT) and allogeneic HCT (allo-HCT) in the treatment of this disease. To evaluate the outcome of patients with HSTCL who underwent either auto-HCT or allo-HCT, we performed a multi-institutional retrospective cohort study to assess outcomes of HCT in HSTCL patients. Fifty-three patients with HSTCL were included in the study. Thirty-six patients received an allo-HCT and 17 received an auto-HCT. Thirty-five (66%) were males. Median age at diagnosis was 38 (range 2 to 64) years. Median follow-up for survivors was 75 months (range 8 to 204). The median number of prior lines of therapy was 1 (range 1 to 4). Median OS and progression-free survival (PFS) for the entire cohort were 78.5 months (95% CI: 25 to 79) and 54 months (95% CI: 18 to 75), respectively. There were no significant differences in OS (HR: 0.63, 95% CI: 0.28 to 1.45, P = .245) or PFS (HR: 0.7, 95% CI: 0.32 to 1.57, P = .365) between the allo-HCT and auto-HCT groups, respectively. In the allo-HCT group, the 3-year cumulative incidence of relapse was 35% (95% CI: 21 to 57), while 3-year cumulative incidence of NRM was 16% (95% CI: 7 to 35). In the auto-HCT group, the 3-year cumulative incidence of relapse and NRM were 43% (95% CI: 23 to 78) and 14% (95% CI: 4 to 52), respectively. Both Auto-HCT and Allo-HCT are effective consolidative strategies in patients with HSTCL, and patients should be promptly referred for HCT evaluation.

Unusual Case of Splenic Metastasis in Adenosquamous Carcinoma of the Cervix Uteri: Diagnosis and Treatment Considerations.

BACKGROUND Due to several factors such as its specific cellular and biochemical microenvironment, the spleen is not a predestined organ of frequent metastatic colonization in the case of primary solid carcinoma. Hence, the mode of diagnosis and the preferred treatment of a lesion highly suspicious of splenic metastasis must be decided on a case-by-case basis, considering not only the biological tumor entity but also the stage of the primary disease. CASE REPORT In the present case, we demonstrate the clinical course of a 37-year-old female patient who initially presented to our clinic with irregular vaginal bleeding. A consecutive gynecological examination revealed a 3×3-cm large mass of the cervix uteri, and the subsequent histomorphological workup led to the diagnosis of an adenosquamous carcinoma of the cervix uteri. Therapeutically, the patient received multimodal treatment, namely radical hysterectomy with adjuvant radio-chemotherapy. After 1.5 years, the patient presented to our Emergency Department with intermittent left-sided abdominal pain. Subsequent abdominal imaging (computed tomography scan, magnetic resonance imaging, positron emission tomography) determined a metabolically active splenic lesion with a central necrosis - signs of malignancy in line with a splenic metastasis. Presentation and discussion of the case within our interdisciplinary tumor board led to the decision of splenectomy followed by chemotherapy, a procedure that could be considered as therapeutic treatment in such exceptional cases. CONCLUSIONS The collection and reporting of atypical clinical courses remains a key factor in precision medicine to enable the most evidence-based decision making in such cases.

Hepatosplenic T-cell lymphoma presented with massive splenomegaly and pancytopenia - a case report.

BACKGROUND: Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of peripheral T-cell lymphoma. Patients usually present with splenomegaly and pancytopenia but without lymphadenopathy. Immunohistochemistry (IHC) staining of bone marrow biopsy shows intra-sinusoidal infiltration of CD3 and CD56 T-lymphocytes. Current treatment strategy of HSTCL includes a CHOP regimen (cyclophosphamide, adriamycine, vincristine, prednisone) followed by autologous transplantation. CASE: A 28-year-old male presented with abdominal fullness, weight loss, and massive splenomegaly. Laboratory findings revealed pancytopenia. A CT scan of the abdomen displayed hepatomegaly and massive splenomegaly. The bone marrow pathology examination showed monotonous medium-sized lymphocytes with some cluster of atypical lymphocytes with loosely condensed chromatin and pale cytoplasm. The intra-sinusoidal location was more prominent after using IHC staining of CD3 and CD56, which are characteristics of HSTCL. We administered CHOP-based regiment every 3 weeks for 3 cycles; however, the response was a stable disease. Since the splenomegaly was still massive and compromised the patient, the multidisciplinary team decided to perform splenectomy. Unfortunately, the patient did not survive the surgery. CONCLUSION: Hepatosplenic T-cell lymphoma is a rare aggressive disease, which is part of peripheral T-cell lymphoma. CHOP-based chemotherapy appeared to be ineffective, and we need further studies to find the optimal treatment of HSTCL.

[Splenic lymphoma, diagnosis and treatment]. / Lymphomes spléniques : diagnostic et prise en charge.

Some common clinical situations, such as splenomegaly or lymphocytosis, or less common, such as autoimmune hemolytic anemia, cold agglutinin disease, or cryoglobulinemia can lead to the diagnosis of splenic lymphoma. Splenic lymphoma is rare, mainly of non-hodgkinian origin, encompassing very different hematological entities in their clinical and biological presentation from an aggressive form such as hepato-splenic lymphoma to indolent B-cell lymphoma not requiring treatment such as marginal zone lymphoma, the most frequent form of splenic lymphoma. These entities can be challenging to diagnose and differentiate. This review presents different clinical and biological manifestations suspicious of splenic lymphoma and proposes a diagnosis work-up. We extended the strict definition of splenic lymphoma (lymphoma exclusively involving the spleen) to lymphoma thant can be revealed by a splenomegaly and we discuss the differential diagnosis of splenomegaly.

Characteristics and survival outcomes of primary splenic cancers: A SEER population-based study.

ABSTRACT: Primary splenic cancers represent a small number of cancer cases and studies on its clinicopathological features and outcomes are limited. Splenic lymphomas and primary splenic angiosarcoma (PSA) are the 2 most common histological types of splenic cancers. This population-based study aimed to investigate the clinical characteristics and survival outcomes of patients with splenic lymphomas or PSA.Patients diagnosed with splenic lymphomas or PSA between 2000 and 2015 were identified from the Surveillance Epidemiology and End Results database of the National Cancer Institutes. Overall survival (OS) and cancer-specific survival (CSS) rates were calculated using the Kaplan-Meier method. A Cox proportional hazard models were used to identify independent predictors of cancer-specific mortality.A total of 700 patients with splenic lymphoma and 48 patients with PSA were included in this study. The median age of patients with splenic lymphoma was 65 years and 57 years for patients with PSA. For patients with splenic lymphoma, the most prevalent histological subtypes were splenic marginal zone lymphoma and diffuse large B-cell lymphoma. A total of 52.6% of the cases had stage IV disease based on the Ann Arbor staging system. Five-year OS and CSS were 76.9% and 83.4%, respectively. Multivariate analysis revealed that independent predictors of splenic lymphoma CSS included race, stage, chemotherapy, and histological subtype. However, a much shorter OS time was seen in the PSA cohort which had a 5-year OS of 11.8%, a median OS of 10.0 months and the 5-year CSS of 12.4%. Chemotherapy was correlated with better outcomes in patients with PSA. However, the survival benefits of surgery for splenic cancer were not statistically significant in our study.The current study is the largest cohort of primary splenic cancer presented in literature based on the Surveillance Epidemiology and End Results database and our large series describe the characteristics and survival outcomes of such rare diseases which may provide reliable information for further studies and clinicians.

Successful treatment of hepatosplenic T-cell lymphoma with fludarabine, high-dose cytarabine and subsequent unrelated umbilical cord blood transplantation.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of peripheral T-cell lymphoma that occurs most often in adolescents and young adults and is rare in children. Because of the aggressive clinical course, resistance to conventional chemotherapy and poor prognosis of HSTCL, an effective treatment has not been established. We report the case of a 3-year-old girl with HSTCL presenting with trilineage myelodysplasia. Although the HSTCL was refractory to conventional chemotherapy, remission was achieved with salvage chemotherapy that included fludarabine and cytarabine, which were shown to be effective in the drug sensitivity assay. After undergoing umbilical cord blood transplantation with a conditioning regimen consisting of etoposide, cyclophosphamide and total body irradiation, the patient has remained in complete remission for 8 years. Single-nucleotide polymorphism array analysis revealed heterozygous deletions of PAX5 (9p), ETV6 (12p) and homozygous deletions of CDKN2A (9p). Exome analysis showed a heterozygous nonsense c.2961C>G (p.Tyr987Ter) variant of the KMT2C gene. To improve the poor prognosis of HSTCL, the chemotherapeutic regimen can be selected for each patient on the basis of drug sensitivity and molecular genetic characteristics.

A Review on Splenic Diffuse Red Pulp Small B-Cell Lymphoma.

Splenic diffuse red pulp small B-cell lymphoma (SDRPL) is a rare disease, representing <1% of all non-Hodgkin lymphomas (NHL). The most common clinical manifestations include splenomegaly, lymphocytosis, and hemocytopenia. A diagnosis of SDRPL can be challenging, as it shares multiple clinical and laboratory features with splenic marginal zone lymphoma (SMZL), hairy cell leukemia (HCL), and HCL variant (HCL-v). Obtaining splenic tissue remains the gold standard for diagnosis. In the cases where splenic tissue is not available, diagnosis can be established by a review of peripheral blood and bone marrow studies. SDRPL is characterized by a diffuse involvement of the splenic red pulp by monomorphous small-to-medium sized mature B lymphocytes effacing the white pulp. The characteristic immunophenotype is positive for CD20, DBA.44 (20 to 90%), and IgG, and typically negative for CD5, CD10, CD23, cyclin D1, CD43, annexin A1, CD11c, CD25, CD123, and CD138. The Ki-67 proliferative index is characteristically low. Cyclin D3 is expressed in the majority of SDRPL in contrast with other types of small B-cell lymphomas, thus facilitating the recognition of this disease. There is no standard treatment regimen for SDRPL. Initial treatment options include splenectomy, rituximab monotherapy, or a combination of both. Chemoimmunotherapy should be considered in patients with advanced disease at baseline or progression.

New Insights into the Biology and Diagnosis of Splenic Marginal Zone Lymphomas.

Splenic marginal zone lymphoma (SMZL) is a small B-cell lymphoma, which has been recognized as a distinct pathological entity since the WHO 2008 classification. It classically presents an indolent evolution, but a third of patients progress rapidly and require aggressive treatments, such as immuno-chemotherapy or splenectomy, with all associated side effects. In recent years, advances in the comprehension of SMZL physiopathology have multiplied, thanks to the arrival of new devices in the panel of available molecular biology techniques, allowing the discovery of new molecular findings. In the era of targeted therapies, an update of current knowledge is needed to guide future researches, such as those on epigenetic modifications or the microenvironment of these lymphomas.

Clinical Characteristics, Treatment and Evolution of Splenic and Nodal Marginal Zone Lymphomas-Retrospective and Multicentric Analysis of Portuguese Centers.

INTRODUCTION: Treatment of Splenic (SMZL) and Nodal (NMZL) Marginal Zone Lymphoma is not consensual. Histologic transformation (HT) to aggressive lymphoma is a poorly understood event, with an unfavorable outcome. OBJECTIVES: Describe the clinical characteristics, treatment, outcomes and incidence of HT. METHODS: Characteristics of patients with SMZL and NMZL consecutively diagnosed in 8 Portuguese centers were retrospectively reviewed. Endpoints were overall survival (OS), time to first systemic treatment (TTFST), frequency of HT and time to transformation (TTT). RESULTS: This study included 122 SMZL and 68 NMZL, most of them received systemic treatment: 55.4% and 76.5%, respectively. Splenectomy was performed in 58.7% of patients with SMZL. Different treatment protocols were used. OS or TTFST did not differ significantly according to treatments. Given the small sample size, no conclusion can be made concerning the role of Rituximab in the treatment of NMZL and SMZL based in these results. HT was documented in 18 patients, mainly in SMZL, with a cumulative incidence at 5 years of 4.2%. We confirmed that age is a prognostic factor. CONCLUSION: Randomized prospective trials are needed to standardize treatment in MZL. Patients with HT did appear to have shorter OS in comparison with those who did not experience HT (OS 5 years of 68.4% vs. 80.4%), but the number of HT was too small to reach statistical significance.

Spleen angiosarcoma: a world review.

Introduction: Spleen angiosarcoma (SA) is a rare malignant neoplasm that arises from the splenic vascular endothelium, with only around 300 cases reported to date. Due to a limited number of reported cases, there is a paucity of data and a lack of understanding of its presentation, diagnosis, and management. In this study, we aim to provide a comprehensive review of SA.Areas covered: On 27 February 2021, a literature search was done in PubMed and Embase database. The search yielded 122 articles involving 205 patients. The focus was on patient demographics, risk factors, clinical presentations, investigation results, preliminary diagnoses, therapies provided, and patient outcomes. These factors were analyzed to identify possible risk factors, diagnostic modalities, and therapeutic principles that were not mentioned before.Expert opinion: The clinical presentation or investigation results of patients with SA are often nonspecific. Hence, they may not be sufficient to clinch the diagnosis of SA if used alone. The authors recommend a triple assessment of clinical examination, imaging findings, and pathology to diagnose SA with high accuracy. Splenectomy should be the mainstay of management, with chemotherapy and radiotherapy considered as adjuncts, especially in the presence of metastases.

Clinical features and treatment outcomes of 14 patients with hepatosplenic γ δ T-cell lymphoma.

BACKGROUND: Hepatosplenic γ δ T-cell lymphoma (HSTCL) is a rare subtype of peripheral T-cell lymphoma (PTCL) with aggressive clinical behavior. To date, no standard therapy for HSTCL has been established. This study analyzed the clinical features, treatment, and prognosis for patients with HSTCL to determine the best therapeutic approach. METHODS: We reviewed the clinical characteristics, treatments, and responses to treatment of patients in our center between January 2001 and June 2021, and also reviewed related literature. RESULTS: Median patient age was 38 years (range 16-60 years) and the patients included eight males and six females. HSTCL in these patients typically presented with B symptoms (71.4%), splenomegaly (100%), and hepatomegaly (50.0%), but lymphadenopathy was extremely rare. In these patients, routine laboratory testing showed elevated lactate dehydrogenase (71.4%), liver dysfunction (42.9%), and decreased fibrinogen (35.7%). In the induction phase, five of the 14 patients received chemotherapy regimens containing anthracycline (CHOP, or CHOP plus bortezomib or Chidamide), and six were treated with non-CHOP chemotherapy. Seven patients responded to induction treatment, four of whom received allogeneic hematopoietic cell transplantation and then achieved a complete response in the consolidation phase. survival time of patients who received alloHCT range from 10 to 27 months. CONCLUSION: Hepatosplenic γ δ T-cell lacks a standard therapy and is often refractory to conventional chemotherapy regimens. Intensive induction chemotherapy followed by hematopoietic cell transplantation may improve the prognosis of HSTCL.

Synchronous splenic metastases from squamous cell carcinoma of oesophagus: a case report and review of literature.

Synchronous splenic metastases from oesophageal squamous cell carcinomas are extremely rare. Most of the cases of splenic metastases reported in the literature are mainly metachronous and occur usually from adenocarcinoma primary. The treatment options range from splenectomy to palliative chemotherapy with standard doses in fit individuals. However, in cases with poor performance status, the management is often the best supportive care only due to the fear of tolerance and toxicities with standard dose chemotherapy. Herein, we report a case of squamous cell carcinoma of the distal thoracic oesophagus in a poorly fit elderly male diagnosed with synchronous splenic metastases and successfully treated with palliative chemotherapy with reduced flat doses and radiotherapy with no significant toxicities.

Splenic marginal zone lymphoma associated with hepatitis B virus infection, remission after viral treatment, and splenectomy: A case report and review of the literature.

We report the case of a patient diagnosed with a splenic marginal zone lymphoma with a simultaneous finding of hepatitis B virus infection, who responded to antiviral treatment and splenectomy. We highlighted this association described in the literature and its possible causal role, as well as the available therapeutic choices.

Outcomes of Hepatosplenic T-Cell Lymphoma: The Mayo Clinic Experience.

BACKGROUND: Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of peripheral T-cell lymphoma accounting for less than 1% of non-Hodgkin lymphomas. It is generally associated with poor prognosis. PATIENTS AND METHODS: We performed a cohort study of patients with HSTCL treated at the Mayo Clinic between 1996 and 2020 exploring the clinical characteristics and therapeutic outcomes. RESULTS: Twenty-two cases of HSTCL were identified with a median (range) age at diagnosis of 45.5 (15.5-80.6) years and a male predominance (15/22, 68.2%). Clinical characteristics include massive splenomegaly in 16 patients (73%), hepatic involvement in 13 (59%), and chronic immunosuppressed state in 8 (36%). Phenotypically, lymphoma cells had gamma/delta T-cell receptor expression in 18 (82%) and alpha/beta in 4 patients. Cytogenetic abnormalities included isochromosome 7q (i7q) in 8 (62%) of 13 and trisomy 8 in 4 (44%) of 9. The median (range) follow-up of surviving patients was 33 (2.5-137) months. The median progression-free and overall survival were 9.5 months (95% CI, 1.8, 16.3) and 12.4 months (95% CI, 4.9, 18.5), respectively. Long-term survival was seen in 4 (18%) of 22 patients, with survival of 55, 74, 95, and 137 months. Moreover, 3 of 4 long-term survivors had splenectomy as part of initial treatment, and 2 of 4 long-term survivors received an allogeneic hematopoietic cell transplant (allo-HCT). CONCLUSION: Liver involvement and chronic immunosuppression were associated with shorter survival. Although splenectomy and allo-HCT have anecdotal benefit in the literature, our data do not show a statistically significant benefit of splenectomy and/or allo-HCT, likely as a result of our small sample size.

Acquired Angioedema due to C1 Inhibitor Deficiency Preceding Splenic Marginal Zone Lymphoma: Further Insights from Clinical Practice.

BACKGROUND: Acquired angioedema due to C1 inhibitor deficiency (AAE-C1-INH) is a very rare disease. In clinical practice, it may be difficult to differentiate AAE-C1-INH from hereditary angioedema due to C1-INH deficiency (HAE-C1-INH). In both conditions, patients are at an increased risk of death from asphyxiation due to upper airway obstruction. The association of AAE-C1-INH with lymphoproliferative and autoimmune diseases, and with presence of anti-C1-INH antibodies has been well documented, and treatment of the underlying condition may result in complete remission of angioedema. OBJECTIVES: To discuss the clinical evaluation, diagnosis, and treatment outcomes of AAE-C1-INH in the context of the care of 2 patients with recurrent isolated angioedema. METHODS: Two patients were followed up prospectively at our clinic. Measurements of C3, C4, C1-INH, and C1q levels were carried out by nephelometry, and the functional activity of C1-INH was determined by a chromogenic assay. Hematological investigation included morphological and immunophenotyping analysis of peripheral blood, bone marrow, and spleen histopathology. Sequencing of the 8 exons and adjacent intronic regions of the SERPING1 gene was performed using the Sanger method. RESULTS: Two patients were diagnosed with AAE-C1-INH associated with splenic marginal zone lymphoma during follow-up. CONCLUSIONS: Close follow-up, including detailed clinical history, physical examination, and laboratory tests, of our patients with AAE-C1-INH was essential for the early diagnosis and successful treatment of the lymphoproliferative disease, leading to the resolution of the angioedema attacks.

Outcomes of 43 small breed dogs treated for splenic hemangiosarcoma.

OBJECTIVE: To determine outcome and prognostic factors in small breed dogs in which hemangiosarcoma was diagnosed and whether outcomes differed between small and large breed dogs with splenic hemangiosarcoma. STUDY DESIGN: Bi-institutional retrospective study. ANIMALS: Forty-three small breed (<20 kg) and 94 large breed client-owned dogs. METHODS: Medical records were reviewed to identify dogs treated with splenectomy for splenic hemangiosarcoma. Data acquired included signalment, preoperative staging, bloodwork results, surgical findings, histopathologic findings, administration of chemotherapy, presence/absence of metastatic disease, and survival time (ST). Cox proportional hazards regression analysis was performed to assess prognostic factors associated with survival. RESULTS: The overall median ST was 116 days and 97 days for small and large breed dogs, respectively. The ST for dogs treated with surgery and chemotherapy was 207 and 139 days for small and large breed dogs, respectively. The disease-free interval (DFI) was 446 and 80 days for small and large breed dogs, respectively. Dog size was associated with DFI (P = .02) but not with ST (P = .09). The presence of metastasis at diagnosis was associated with decreased ST in small (P = .03) and large (P = .0009) breed dogs. Administration of chemotherapy (P = .02) was associated with increased ST (P = .02) in small breed dogs. CONCLUSION: The ST was not different in small and large breed dogs with splenic hemangiosarcoma treated with splenectomy and chemotherapy. CLINICAL SIGNIFICANCE: Prognosis remains poor despite aggressive therapies in small and large breed dogs.

A case of hepatosplenic T-cell lymphoma successfully treated by HLA haploidentical stem cell transplantation.

We report a case of hepatosplenic T-cell lymphoma (HSTL) transplanted from an HLA-haploidentical daughter. A 51-year-old man was referred due to liver function test abnormalities and fever. He was confirmed to have γδ-type HSTL by bone marrow and liver biopsies. He was treated with five cycles of a CHOP regimen. Although metabolic complete response (CR), as defined by positron emission tomography, was achieved, his bone marrow still contained tumor cells on polymerase chain reaction (PCR). He underwent transplantation using unmanipulated peripheral blood stem cells from his HLA-haploidentical daughter. The preconditioning regimen consisted of fludarabine, melphalan, busulfan and antithymocyte globulin. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and short-term methotrexate. Neutrophil engraftment was achieved on day 14. His bone marrow exhibited a completely female phenotype by fluorescence in situ hybridization, and no lymphoma cells were detected by PCR on day 30. Although he developed grade II acute GVHD on day 47, it was successfully treated by prednisolone. He has a limited type of skin chronic GVHD and still receives oral immunosuppressive therapy. He remains in CR four years after transplantation.