[Clinical analysis of 3 cases with primary splenic diffuse large B-cell lymphoma].

The definition of primary splenic lymphoma is controversial, but it has been reported to be a rare disease that comprises less than 1% of all malignant lymphomas. Three cases of primary splenic diffuse large B-cell lymphoma treated at our institution are described here. Median follow-up was 34.6 months (range 8.7∼39.2) and median age at diagnosis was 72 years old (range 65∼73). In all three cases, the diagnosis was definitively established not by splenectomy but by ultrasonically guided percutaneous splenic tissue core biopsy. Using the Hans classifier, one of the cases was subclassified as the germinal center B-cell like (GCB) subtype and two as non-GCB subtype. One case was CD5-positive diffuse large B-cell lymphoma. Two patients were in Ann Arbor stage II and one was in stage III. Using the International Prognostic Index, one was categorized as Low/intermediate risk, one as high/intermediate risk, and one as high risk. All patients underwent eight cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisolone followed by irradiation therapy. These three patients attained complete response. Although the follow-up period to date has been short, all patients have maintained a complete response and are currently alive. To determine whether our management protocol is valid, further observations are needed.

Histiocytic sarcoma of the spleen: case report of asymptomatic onset of thrombocytopenia and complex imaging features.

Histiocytic sarcoma of the spleen, in which the malignant cells display morphologic and immunophenotypic features similar to those of mature tissue histiocytes, is a rare but potentially lethal condition that can remain asymptomatic or only mildly symptomatic for a long period of time. We studied a case of histiocytic sarcoma of the spleen in an 82-year-old woman with prolonged chronic thrombocytopenia that was non-responsive to steroid therapy. Ultrasonography, computed tomography, and magnetic resonance imaging showed a characteristically enlarged spleen and liver. Palliative irradiation therapy was clinically effective; however, disease progression proved lethal. Autopsy revealed the proliferation of tumor cells within the splenic sinus and the liver sinusoids, which displayed extreme hemophagocytosis and strong expression of the histiocytic markers CD68 (KP1 and PG-M1) and CD163. The postmortem diagnosis showed histiocytic sarcoma of the spleen with liver infiltration. This and previous reports indicate that early detection (facilitated by imaging and clinical features) and management may improve patient prognosis and survival. Histiocytic sarcoma of the spleen should be considered as a differential diagnosis in therapeutically unresponsive patients with chronic thrombocytopenia.

Primary histiocytic sarcoma of the spleen associated with hemophagocytosis.

We report a patient with primary histiocytic sarcoma of the spleen associated with prominent hemophagocytosis. Although thrombocytopenia, probably due to hemophagocytosis, was refractory to corticosteroid therapy, the transfusion of platelets, and splenic irradiation, partial splenic embolization was effective and facilitated splenectomy for a diagnosis. The majority of the spleen showed necrosis, but viable neoplastic cells with pleomorphic nuclei and abundant cytoplasm, showing occasional erythrocytes or leukocytes, were still discernible. The neoplastic cells expressed CD68, lysozyme, and S-100 protein, and were negative for lymphoid, myeloid, and epithelial cell markers. CD163, a monocyte/macrophage-specific molecule, was positive in only some of them. Despite multiagent chemotherapy, the patient died of the disease, showing a rapidly progressive clinical course. Although the preoperative diagnosis of primary splenic histiocytic sarcoma is difficult, it has been confirmed in patients with splenomegaly of unknown etiology that clinicolaboratory features suggestive of hemophagocytosis may be important clues suggestive to the disease. CD163 expression by neoplastic cells could be confirmed only after careful observation, because the molecule may only be seen in some of the neoplastic cells.

Early detection and integral resection are keys to extend survival in patients suffered from primary angiosarcoma of the spleen: A care-compliant case report and literature review.

RATIONALE: Primary angiosarcoma of the spleen (PAS) is a very rare malignant neoplasm that originates from endothelial cells of the splenic blood vessels. Without typical clinical presentations and specific radiological features, PAS is very difficult to be early identified and 1-year mortality is extremely high. Late detection and spleen rupture are considered as the most important risk factors for early metastasis. PATIENT CONCERNS: Without any obvious symptom, a 35-year-old woman was admitted with splenic neoplasm that was accidentally discovered through a routine physical examination. DIAGNOSES: The patient was first diagnosed as lymphoma by laboratory tests and imaging studies, but changed to PAS by histological examinations after the surgery. INTERVENTIONS: After careful preoperational assessment, a laparoscopic-assisted splenectomy was scrutinously performed and the entire spleen was removed without any rupture. OUTCOMES: The postoperative followed-up was uneventful until 3 years later, when she sought medical attention due to persisting back pain. Bone metastasis was consequently identified and the symptom was quickly alleviated after radiation therapy. However, intra-abdominal metastases leading to intestinal obstruction occurred 4.5 years after surgery. Following short palliative treatment, the patient passed away 4 years and 9 months after the operation due to multiple organ failure. LESSONS: PAS is an uncommon and aggressive splenic disease. Once suspected, PAS require prompt and precise surgical procedures to remove the tumor origin. Laparoscopic-assisted splenectomy was technically feasible and therapeutically harmless for PAS treatment compared with open surgery as long as the spleen was removed intact. However, more evaluation of this option will be needed due to limited experience by now. Early discovery, precautious plan, meticulous operation, close follow-up, and comprehensive treatment may significantly prolong the living period of this fatal disease.

[Splenic irradiation: apropos of 8 cases. Clinical indications and literature review]. / Radioterapia esplénica: a próposito de 8 casos. Indicaciones y revisión de la literatura.

Clinical indications of splenic irradiation in haematological disorders include the irradiation in lymphoproliferative disorders with spleen infiltration, palliative treatment of splenomegaly in malignant diseases like chronic lymphocytic leukaemia or myeloproliferative disorders, with the purpose of relief from abdominal pain associated with capsular enlargement size and decrease cytopenias secundaries to hypersplenism.This paper reports our experience with spleen irradiation in the Hospital General Universitario Gregorio Marañón in the last five years, and analyzes indications, results and toxicity, and an actual review of the literature.

Discrepancy in Programmed Cell Death-Ligand 1 Between Primary and Metastatic Non-small Cell Lung Cancer.

AIM: To investigate the discordance in the programmed cell death-ligand 1 (PD-L1) expression between primary and metastatic tumors and analyze the association between the discordance and the clinical factors in non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Twenty-one NSCLC patients who underwent surgery or biopsy for paired primary and metastatic lesions at our Institution from 2005 to 2016 were analyzed. Lesions with the PD-L1 expression being ≥5% were considered PD-L1-positive. RESULTS: The metastatic sites included the brain (n=16), adrenal gland (n=3), spleen (n=1) and jejunum (n=1). Negative conversion of the primary PD-L1-positive NSCLC and positive conversion of the primary PD-L1-negative NSCLC were observed in 3 (14%) and 2 (10%) cases, respectively. Radiotherapy for the metastatic brain lesion before its resection showed a significant relationship with the positive conversion of the primary PD-L1-negative NSCLC (p=0.048). CONCLUSION: Radiotherapy-derived effects may contribute to the positive conversion of the primary PD-L1-negative NSCLC.

[Clinical evaluation of ultrasound-guided percutaneous microwave ablation of splenic tumors].

OBJECTIVE: To investigate the feasibility, safety and efficacy of ultrasound-guided percutaneous microwave ablation (MWA) of splenic tumors. METHODS: Seven patients with 8 pathologically confirmed splenic tumors (including 2 metastases from the ovary and 4 from the lung, gastric adenocarcinoma, hepatocellular carcinoma, or rectal carcinoma; 1 hemangioma and 1 inflammatory pseudotumor) with sizes ranging from 1.3 to 6.2 cm (mean 3.1 ± 1.9 cm) were treated with MWA. A cooled shaft needle antenna was percutaneously inserted into the tumor under ultrasound guidance. A thermocouple was placed about 0.5 cm away from the tumor to monitor the temperature in real time during the ablation. The microwave emitting power was set at 50-60 W. The treatment efficacy was assessed by contrast-enhanced imaging at 1, 3 and 6 months following the procedure, and every 6 months thereafter. RESULTS: All the tumors were completely ablated in a single session and no complications occurred. No local tumor progression was observed during a median follow up time of 13 months (4 to 92 months). The ablation zone, well defined on contrast-enhanced imaging, was gradually reduced with time. A new metastatic lesion was detected in the spleen at 11 months after the ablation in a ovarian carcinoma patient and was successfully treated by a second MWA. The post-ablation survival of the patients with splenic metastasis was 13 months (range 4 to 92 months). No complications other than fever and abdominal pain were observed in these patients. CONCLUSION: Ultrasound-guided percutaneous MWA is a safe and effective minimally-invasive technique for treatment of splenic tumors in selected patients.

Clustering of non-Hodgkin's lymphomas. A case study.

Lymphomas developed in three genetically unrelated family members living in the same household over a period of one year. Two of the patients had diffuse histiocytic lymphoma, and one had nodular lymphocytic lymphoma. All three showed response to treatment initially, but two have had relapses and died. The "clustering" of lymphomas in this family suggests an environmental cause.

Treatment of subdiaphragmatic Hodgkin's disease: long-term results and side effects.

To evaluate the results, prognostic factors and especially side-effects of the treatment for subdiaphragmatic Hodgkin's disease (SHD) a retrospective study was conducted in the Haematology Departments and in the Cancer Centres of Nancy and Strasbourg between 1976 and 1990; 55 patients corresponding to the IA to IIB SHD stages were analysed. The median age was 45 years. In accordance with Ann Arbor classification, we observed 12 CS IA (21.3%), 2 CS IB (3.5%), 14 CS IIA (25.4%) and 27 CS IIB (49.7%). Twenty-five patients (45.4%) underwent laparotomy with spleen involvement in 10 cases. Fifteen patients (27.3%) had exclusive radiotherapy, 10 by inverted-Y field with or without splenic field, 5 by limited field to inguinal and homolateral iliac nodes. Forty patients had prior chemotherapy, 18 by MOPP protocol, 18 by hybrid MOPP/ABVD protocol and 4 by other schemes. The total dose delivered ranged from 26 to 45 Gy. With a median follow-up of 8 years, the overall and disease specific survival rates are respectively 61% and 83% at 10 years. Nine patients relapsed (16.4%), 4 among the 15 (26.6%) treated by exclusive irradiation and 5 among the 40 (12.5%) treated by combined therapy. We observed 8.3%, 21.4% and 18.5% of relapses respectively among the clinical stages IA, IIA and IIB. Eleven patients (20%) developed a second cancer. Twenty-six long-term complications were noted, nine of which concerned the digestive system. The only significant prognostic factor is age, with 10-year specific survival rates of 96% and 66% respectively for patients younger and older than 50 years (p=0.0003). Our data confirm that the most appropriate treatment for stage IA is exclusive radiotherapy and combined therapy for all other cases. With the use of CT-scan and eventually lymphography, the laparotomy is reserved only for cases with an uncertain diagnosis. Tobacco use is also clearly a risk factor in our series for late vascular complications and second cancers.

Absence of multiple local minima effects in intensity modulated optimization with dose-volume constraints.

This paper reports on the analysis of intensity modulated radiation treatment optimization problems in the presence of non-convex feasible parameter spaces caused by the specification of dose-volume constraints for the organs-at-risk (OARs). The main aim was to determine whether the presence of those non-convex spaces affects the optimization of clinical cases in any significant way. This was done in two phases: (1) Using a carefully designed two-dimensional mathematical phantom that exhibits two controllable minima and with randomly initialized beamlet weights, we developed a methodology for exploring the nature of the convergence characteristics of quadratic cost function optimizations (deterministic or stochastic). The methodology is based on observing the statistical behaviour of the residual cost at the end of optimizations in which the stopping criterion is progressively more demanding and carrying out those optimizations to very small error changes per iteration. (2) Seven clinical cases were then analysed with dose-volume constraints that are stronger than originally used in the clinic. The clinical cases are two prostate cases differently posed, a meningioma case, two head-and-neck cases, a spleen case and a spine case. Of the 14 different sets of optimizations (with and without the specification of maximum doses allowed for the OARs), 12 fail to show any effect due to the existence of non-convex feasible spaces. The remaining two sets of optimizations show evidence of multiple minima in the solutions, but those minima are very close to each other in cost and the resulting treatment plans are practically identical, as measured by the quality of the dose-volume histograms (DVHs). We discuss the differences between fluence maps resulting from those similar treatment plans. We provide a possible reason for the observed results and conclude that, although the study is necessarily limited, the annealing characteristics of a simulated annealing method may not be justified in clinical optimization in the presence of dose-volume constraints. The results of optimizations by the Newton gradient (NG) method with a quadratic cost function are reported in detail. An adaptive simulated annealing method, optimizing the same function, and the dynamically penalized likelihood method, optimizing a log likelihood function, have also been used in the study. The results of the latter two methods have only been discussed briefly, as they yielded the same conclusions as the NG method.

[Question of differential diagnosis in a case of chronic B-cell lymphopathy]. / Quesiti diagnostico-differenziali su un caso di linfopatia cronica di origine B cellulare.

We have reported the case of a woman aged 76 years suffering from pancytopenia, splenomegaly, relative lymphocytosis, lymphocytes with villous projection in the peripheral blood. On the basis of membrane phenotype, cytochemistry, ultrastructural examination of blood and marrow lymphocytes, differential diagnosis was between chronic lymphatic leukemia (CLL), CLL of mixed cell type, hairy cell leukemia (HCL), HCL variant, splenic lymphoma with circulating villous lymphocytes (SLVL), Non-Hodgkin lymphoma of mantle zone (NHL). The application of morphologic and immunological methods has reinforced the value of cytomorphology and has proved advantageous in increasing our understanding of the heterogeneity of B CLL itself. A new classification of chronic B leukemias has been proposed on the basis of clinical, cytomorphological, histological, cytochemical, immunological criteria: CLL; CLL of mixed cell type including cases with more than 10% and less than 55% prolymphocytes (CLL/P) and a less well defined form with pleomorphic lymphocytes (CLL/P) and a less well defined form with pleomorphic lymphocytes but less than 10% prolymphocytes; prolymphocytic leukemia (PLL); hairy cell leukemia (HCL); HCL variant; splenic lymphoma with circulating villous lymphocytes (SLVL); leukemic phase of NHL (follicular lymphoma, intermediate or mantle zone lymphoma, and others); lymphoplasmacytic lymphoma; plasma cell leukemia. Even if the application of cytomorphological and immunological criteria has increased our knowledge of the heterogeneity of chronic B leukemias, in some cases, as in the one reported, exact classification may be very difficult. However, on the basis of clinical and laboratory criteria this case can be classified as SLVL, notwithstanding some discrepancies of the immunophenotype.

Estimated background doses of [67Ga]-DTPA-USPIO in normal Balb/c mice as a potential therapeutic agent for liver and spleen cancers.

INTRODUCTION: The aim of this study was to evaluate the biodistribution of dextran-coated iron oxide nanoparticles labeled with gallium-67 (Ga) in various organs by intravenous injection in Balb/c mice. METHODS: Ultrasmall superparamagnetic iron oxide (USPIO) was successively labeled with Ga-chloride after chelation with freshly prepared cyclic DTPA-dianhydride. The labeling efficiency of USPIOs labeled with Ga is above 98%. Sixty-five mice were killed at 13 different time points. The percentage of injected dose per gram of each organ was measured by direct counting for 19 harvested organs of the mice. The medical internal radiation dose formula was applied to extrapolate data from mouse to human and to predict the absorbed radiation dose for various organs in the human body. RESULTS: The biodistribution of Ga-USPIO in Balb/c mice showed that 75% of the injected dose accumulated in the spleen and liver 15 min after injection. These nanoparticles remained in the liver for more than 7 days after injection, whereas their clearance was very fast from other organs. Extrapolating these data to the intravenous injection of Ga-USPIO in humans gave an estimated absorbed dose of 36.38 mSv/MBq for the total body, and the highest effective absorbed dose was seen in the liver (32.9 mSv/MBq). CONCLUSION: High uptakes of USPIO nanoparticles in the liver and spleen and their fast clearance from other tissues suggest that these nanoparticles labeled with a ß-emitter radioisotope could be suitable as treatment agents for spleen and liver malignancies only if the organ tolerance dose is not exceeded.

Treatment of splenic marginal zone lymphoma: splenectomy versus rituximab.

Splenic marginal zone lymphoma (SMZL) is an uncommon indolent B-cell lymphoma causing marked splenic enlargement with CD20-rich lymphoma cells infiltrating blood and bone marrow. In the pre-rituximab era, the treatment of choice for patients with symptomatic splenomegaly or threatening cytopenia was splenectomy, since chemotherapy had limited efficacy. Responses to splenectomy occurred in approximately 90% of patients. However, SMZL patients are often elderly and poor surgical risks. Since approval of rituximab, treatment of such patients with the anti-CD20 antibody both alone or in combination with chemotherapy has shown remarkable responses. In retrospective series of rituximab monotherapy totaling 52 patients, including both chemotherapy-naive and -refractory patients, overall responses of 88% to 100% were noted with marked and prompt regression of splenomegaly and improvement of cytopenias. Sustained responses occurred both with and without rituximab maintenance in 60% to 88% of patients at 3 years. Relapsed patients responded to second courses of rituximab monotherapy. Overall survival was comparable to that reported following splenectomy. Rituximab in combination with purine nucleosides may provide further improvement in progression-free survival; however, confirmatory prospective trials are necessary. These results suggest that splenectomy should no longer be considered as initial therapy for SMZL but rather as palliative therapy for patients not responsive to immunotherapy with or without chemotherapy.

Low-dose palliative splenic irradiation in haematolymphoid malignancy.

Patients are treated with palliative splenic irradiation (SI) to relieve pain, volume effects and the clinical consequences of hypersplenism. The case records of 19 patients treated with palliative SI at our centre, from April 2003 to November 2004, were reviewed. Twenty-two courses of SI were identified. The radiation doses delivered ranged from 150 to 800 cGy (median 450 cGy). The fraction sizes ranged from 25 to 100 cGy. Parallel-opposed anteroposterior-posteroanterior portals were the most common field arrangement. The target volume was reduced in 18 out of 22 courses. The percentage of field reduction ranged from 0 to 59.57% (mean 24.82%). Twelve of 14 courses were successful in achieving symptom palliation. Of the six patients who received SI for a combination of splenic symptoms and abnormal blood tests, five had symptomatic palliation but only one patient responded haematologically. Of two patients who were started on palliative SI for abnormal haematology alone, only one responded. In summary, 17 of 20 (85%) courses of SI initiated for symptom control resulted in effective palliation. Only two of eight (25%) courses of SI started for abnormal blood counts produced a desired response. To conclude, SI offers an effective and well-tolerated palliative treatment option.

[Clinical treatment of chronic lymphatic leukemia by means of extracorporeal blood irradiation]. / Klinische Heilung der chronischen lymphatischen Leukämie mittels extrakorporaler Blutbestrahlung?

A chronic lymphatic leukaemia (CLL) with hepato-splenomegaly was treated in a 76 years old female patient by means of extracorporeal irradiation of blood (ECIB), after which a complete involution of the tumour in the spleen had taken place. Leukocytes initially increased to 35,500/mm3, amounting to 10,700/mm3 later on. The patient died of pneumonia in general cachexia. No signs of CLL could be found macroscopically after autopsy. An involution of the lymphatic infiltration could be identified microscopically in the bone-marrow.

[Post-radiation nephritis. Study of the renal consequences of splenic irradiation for lymphoma]. / A propos des néphrites post-radiothérapiques. Etude du retentissement rénal de l'irradiation de la rate dans les hématosarcomes

The authors studied the left kidney consequences of splenic irradiation in 40 patients with lymphomas. The renal work-up performed before irradiation and every six months afterwards includes : blood pressure, biological tests, IVP and 197 Hg Neohydrine renal scan. Computer scan data processing showed a partial disfunction of left kidney in 16 patients with 18 month-follow up. Renal disfunction appeared within 8 to 10 months following spleen irradiation. During that period no clinical or radiological abnormalities were observed.

Late occurrence of malignancy in a ganglioneuroma 19 years following radiation therapy to a neuroblastoma.

Neuroblastoma is a common solid tumor of childhood. Maturation to a ganglioneuroma or regression has been reported to occur spontaneously or following minimal treatment. Malignant degeneration of such a ganglioneuroma is extremely rare. We present a report of a malignant tumor arising in a ganglioneuroma 19 years following abdominal radiation therapy for neuroblastoma.