Intravascular T-cell Lymphoma Research Articles

234 Single-cell RNA sequencing reveals crosstalk between T cells and endothelial cells in a patient with intravascular T-cell lymphoma

234 Single-cell RNA sequencing reveals crosstalk between T cells and endothelial cells in a patient with intravascular T-cell lymphoma

O-130 - Single-cell RNA sequencing reveals crosstalk between T cells and endothelial cells in intravascular T-cell lymphoma

O-130 - Single-cell RNA sequencing reveals crosstalk between T cells and endothelial cells in intravascular T-cell lymphoma

Abstract 33: Epidemiology and clinicopathology of T-cell intravascular lymphoma (TIVL): Making the case for extra-nodal NK-T cell lymphoma-angiotropic type as a provisional entity

Abstract TIVL is a rare and often aggressive NK/T-cell lymphoma characterized by the presence of neoplastic lymphocytes that are restricted to the lumen of small vessels. It comprises 8-10% of all IVL. By the time a diagnosis is made, TIVL tends to be widely disseminated across multiple extra-nodal sites with frequent catastrophic consequences. In order to study the demographic characteristics, presentation and progression patterns, survival, and prognostic factors, we constructed a database that pooled cases between 1986 and 2019. Kaplan-Meier survival curves were constructed. Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinical factors on survival. A total of 81 patients with confirmed TIVL were identified. The median age was 53 (17-87) years with a peak incidence between ages 50 and 60. There was a slight male predominance with a male to female ratio of 1.5. Comprising 43% of reported cases, Asians were the most afflicted ethnic group. Skin (71%) was the most common site involved with TIVL followed by CNS (23%), and pulmonary and bone marrow involvement (8% each). The median overall survival of the whole group was 7 months. Sex and age did not seem to affect survival rates. When compared to supportive care, chemotherapy significantly improved survival (HR:0.15, p<0.0001). Skin only involvement had the highest survival rates whereas CNS and pulmonary involvement had the worst. When skin only involvement was associated with constitutional symptoms survival rates significantly declined. In a multivariate analysis, skin only involvement (HR:0.43, p=0.009) and not receiving treatment (HR:3.45, p=0.001) continued to have a significant association with survival. CD56+, CD30-, and TCR clonality each seems to adversely impact survival. However, they were of borderline non-statistical significance. Only the detection of EBER in the sample was found to significantly impact survival in a negative manner (p=0.016). Our results indicate that TIVL is an NK/T cell entity with distinct angiotropic pathology and aggressive clinical behavior and often poor outcomes. TIVL's B-cell counterpart is already recognized by the WHO lymphoma classification as a separate B-cell entity. It is our hope that these results serve as the basis for establishing Extra-Nodal NK/T Cell Lymphoma-Angiotropic Type as a provisional entity in order to further study and characterize this rare disease. Citation Format: Philip A. Haddad, Kevin Gallagher, Dalia Hammoud. Epidemiology and clinicopathology of T-cell intravascular lymphoma (TIVL): Making the case for extra-nodal NK-T cell lymphoma-angiotropic type as a provisional entity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 33.

Abstract 5799: Epidemiology and prognostic factors of primary paratesticular lymphoma (PPTL): A pooled case-series since 1980

Abstract PPTL involving the spermatic cord &/or epididymis and sparing the testicular parenchyma is an extremely rare and heterogeneous disease. It doesn't exceed 1.5-2% of all tumors of the spermatic cord. Old cases indicated that PPTL was highly lethal. Many significant changes in classification and treatment have occurred since these reports were published. This retrospective epidemiologic review was conducted to update our knowledge of PPTL using more recent cases that reflect the current state of medicine. This study included all published cases of PPTL in English between 1980-2019 attempting to explore the demographic characteristics, presentation and metastases patterns, types of therapies, and survival of patients with PPTL. The Kaplan-Meier method was used to estimate survival. Log-rank test and multivariate Cox regression models were used to assess the influence of demographic and clinical factors on survival. A total of 34 (27 spermatic cord, 6 epididymis, 1 seminal vesicle) patients with PPTL were identified. The median age was 65 years. A sharp increase in the reported PPTL cases aged 50 and above was noted, peaking within the 72-82 year age-bracket. Diffuse Large B- Cell Lymphoma (DLBCL) was the most prevalent histology (85%). Other types consisted of 1 PEL-like DLBCL, 2 Follicular lymphomas, 1 Marginal Zone Lymphoma, and 1 Intravascular T-cell Lymphoma. The majority presented with Ann-Arbor stage I (65%), followed by II (18%), IV (15%) and III (3%). Only one patient had B-symptoms. All cases presented with growing painless scrotal masses except 2 patients who reported pain including one with bilateral scrotal masses. The average tumor size was 6cm (3-8.5cm). When presenting with stage IV, the majority had involvement of the abdominopelvic and cervical/supraclavicular lymph nodes with additional prostate involvement in one patient and tonsillar involvement in another. All the patients underwent orchiectomy for diagnostic purposes followed by chemotherapy except one who was treated with primary radiation alone. Twenty-eight percent received radiation and only 12% received intrathecal chemotherapy. Median overall survival of the whole group was 12 months. Univariate analysis revealed that PPTL of the epididymis and cases reported after 1990 had significantly better survival. Early stages I&II was of borderline significance. While Age <50 seemed to have better survival, it did not reach statistical significance. However, in multivariate analysis, stage, reporting year, and age significantly impacted the survival of this cohort. This retrospective study presents an updated epidemiologic descriptive data and provides prognostic factors from a relatively recent PPTL cohort. Moreover, it clarifies the perception of the lethality of the disease as PPTL seems to have a similar median overall survival to testicular lymphoma. Citation Format: Philip A. Haddad. Epidemiology and prognostic factors of primary paratesticular lymphoma (PPTL): A pooled case-series since 1980 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5799.

Renal intravascular lymphoma in a dog

ABSTRACT: A 10-year-old male large mixed breed dog was presented with skin ulcers and fracture on the right hind limb caused by vehicle collision. Given required limb amputation, and as being a shelter senior dog, euthanasia was requested by the owner and a complete post-mortem examination was conducted immediately after death. Gross changes were consistent with marked bilateral nephromegaly. Histopathological examination of the kidneys revealed round cells filling blood vessels. Immunohistochemically, the round cells were positive for CD3 antibody. Based on these findings, in absence of involvement of the bone marrow and peripheral blood, and inexistence of primary extravascular masses, the tumor was classified as T-cell intravascular lymphoma. To the author’s knowledge, this is the first report describing intravascular lymphoma involving the kidneys alone in a dog.

Intravascular T-Cell lymphoma in a Fjordhorse

Intravascular T-Cell lymphoma in a Fjordhorse

Western Intravascular Lymphoma (IVL): Case Series of Published Reports Between 1994-2014

Introduction: IVL is rare entity that often associated with disseminated aggressive pattern and fatal clinical course. It is characterized byproliferation of clonal lymphoma cells within blood vessel lumina of various organs that can represent diagnostic challenge due to with non-specific symptoms. IVL is categorized as a subset of large cell non-Hodgkin lymphoma and divided into western and Asian types. We hereby present this systematic review to better describe the salient features of the western subtype, treatment options and overall prognosis. Methods:A systematic review of the Medline and Embase databases via OVID engine was conducted to search for primary articles and case reports under keywords “intravascular lymphoma”,” angiotropic lymphoma” and “malignant angioendotheliomatosis”. Search was limited to publications between January 1994 and April 2014 including all the following; human cases, English language, pathologically confirmed cases and western subtype. Asian variants and cases without sufficient information were excluded. End points were overall survival and treatment, in addition to description of western types and related demographics. Chi-square test was used to analyze categorical covariates data. Student T test was used to compare subgroups means for continuous covariates. Statistical analysis was performed using SAS 9.3 software. Results: A total of 155 patients (Pts) were identified with western type IVL. 53% of cases were males (n=82) and median age on presentation was 64 years (median for B-cell and T-cell IVL 64 & 54 respectively). B-cell IVL (77%, n=119) was the most common subtype (T-cell 9%, NK-cell 1%, unspecified 13%).All cases staged as stage IV with 14% bone marrow involvement (n=21). Presenting symptoms were fever (52%), neurological (51%), fatigue (46%), skin lesions (28%), night sweats (23%), weight loss (23%), edema (22%), gastrointestinal (14%), respiratory (14%), genitourinary (7%), musculoskeletal (5%) and cardiovascular (1%). Median over-all survival from diagnosis was 5 months (mean B-cell 10.8 months, T-cell 10.4,P=0.9472). Fifty seven percent of pts treated with chemotherapy (19% CHOP, 16% R-CHOP 25, and 21% other). Pts treated with chemotherapy had mean survival of 16 months (95% confidence interval [CI] 12-20 months) compared to 2 months (95% CI: 2-4 moths) for those who did not receive chemotherapy (P<0.0001). The median survival of B and T-cells was similar in chemo treated pts (10.4, 10.8 respectively, P=0.9472). Rituximab was used in 19% of pts while 10% treated with intravenous methotrexate (MTX) regimen. In B-cell pts treated with R-CHOP vs CHOP, the mean survival was 21.2 and 10.2 months respectively, P<0.0247, while those treated with MTX vs no MTX mean OS was 37.4 and 14.3 months respectively, P=0.115, and rituximab vs no rituximab mean OS were 19.5 and 14.7 respectively, P=0.2294. In all pts treated with chemotherapy, median survival of those who received MTX was 25 months (95% CI 11.3-38.7) versus a mean OS of 14.3 months (95% CI 10.4-10.8) for those who did not receive MTX (P=0.0232). Conclusions: Western IVL is an aggressive type of lymphoma with a relative poor prognosis. In this systemic review, we found no statistical difference in OS between B- and T-cell types. In chemotherapy treated B-cell IVL, MTX and rituximab clinically prolonged survival but were not statistically significant. However, those who received RCHOP had better OS than those who received CHOP therapy. In all pts treated with chemotherapy, MTX significantly prolonged survival. The addition of MTX to all patients with IVL and rituximab for B-cell IVL to the backbone of multi-agent chemotherapy maybe beneficial and the use of CNS directed therapy should be considered. DisclosuresNo relevant conflicts of interest to declare.

Cutaneous Intravascular Anaplastic Large T-Cell Lymphoma

Intravascular lymphoma (IVL) is a rare subtype of extranodal lymphoma. In the 2008 WHO classification of tumors of the hematopoietic and lymphoid tissues intravascular large B-cell lymphoma is included as a distinct entity. IVL of T-cell type is not included as a diagnostic category and is only mentioned in passing by Nakamura et al. as "a different entity" in their discussion of intravascular large B-cell lymphoma. T-cell IVL is rare, the majority of cases being of natural killer/T-cell phenotype. Exceptionally rare is primary cutaneous intravascular anaplastic large T-cell lymphoma. We present such a case in an otherwise well 39-year-old female having disease limited to the skin established after detailed staging investigations. This is only the third such case described in the literature. We report the clinicopathological features of this case and also review previously documented cases of cutaneous intravascular anaplastic large cell lymphoma.

Intravascular Large B-Cell Lymphoma (IVLBCL): A Study of 12 Cases with Special Emphasis on High Density Lipoprotein Cholesterol (HDL-C) Preceding Diagnosis

Abstract 5221 Background:Intravascular large B-cell lymphoma (IVLBCL) is a rare entity characterized by growth of neoplastic lymphocytes in the lumina of small blood vessels. Hallmarks of the disease include poor performance status, elevated lactate dehydrogenase levels, anemia, B symptoms and variable clinical presentation. In this study, we conducted a retrospective analysis of all identified cases of intravascular lymphoma that presented within a large integrated healthcare delivery system, reviewing clinical presentation, laboratory findings, pathological features and outcomes. Methods:Kaiser Permanente Northern California (KPNC) provides care to approximately 3.2 million members and maintains centralized database of all hospital and ambulatory visits, laboratory, pathology, radiology, and pharmacy records. We utilized electronic pathology record databases to identify all cases of intravascular lymphoma, defined by the World Health Organization from January 1995 - July 2010 using the following search terms: intravascular lymphoma, intravascular B-cell lymphoma, intravascular T-cell lymphoma, intra vascular lymphoma, malignant angioendotheliomatosis, and angiotropic large-cell lymphoma. Results:Twelve cases of IVLBCL were identified. Median age was 70 years, female to male ratio of 2 to 1. 50% were diagnosed in vivo. The median time of diagnosis from onset of symptoms was 1.5 months. Four patients underwent multiple biopsies prior to diagnosis. Of the six patients with in vivo diagnosis, three were made by bone marrow biopsy, one by small bowel resection, one by muscle biopsy, and one by abdominal fat pad biopsy.At the time of diagnosis, ten (83%) patients had B symptoms and seven (58%) patients had ECOG≥4. Other common organ systems involved on presentation included neurological (58%) and gastrointestinal symptoms or hepatic involvement (58%).Increased serum lactate dehydrogenase was seen in 92% of patients, anemia in 92% of patients and thrombocytopenia in 75% of patients. Elevated erythrocyte sedimentation rate seen in 67% of patients and elevated C-reactive protein in 58% of patients.Extremely low subnormal high density lipoprotein cholesterol level (HDL-C) was present in 10 of 11 patients with measured lipoprotein profiles. The median HDL-C was 22 mg/dl (range <4–56 mg/dl). Levels of low density lipoprotein cholesterol, total cholesterol and triglyceride levels were all within the normal range (median 61 mg/dl, 117 mg/dl and 230 mg/dl respectively).All patients had biopsy proven involvement of at least one organ. Four patients had complete autopsy. The sites of disease involvement included bone (4), gastrointestinal tract (4), renal (4), lymph node (3), spleen (3), central nervous system (2), liver (2), peripheral blood (1), hemophagocytosis syndrome (1).Four patients received chemotherapy. CHOP (1), R-CHOP (3). Overall survival was 8 days (CHOP); 38 days to >5 years (R-CHOP). The one patient in our cohort who achieved complete remission had localized bowel IVLBCL, treated with resection and three cycles of R-CHOP. Conclusions:Our cases represent a population-based ascertainment of IVLBCL within a large unselected clinic population. The clinical presentation and organ system involvement is variable. The disease is aggressive with poor outcomes. The unique finding in our series was the low HDL-C prior to diagnosis of IVLBCL. HDL-C may represent a possible preclinical indicator of this rare lymphoma. Disclosures:No relevant conflicts of interest to declare.

Skin manifestations of intravascular lymphoma mimic inflammatory diseases of the skin

Intravascular lymphoma (IVL) is fatal when it is diagnosed late in the course. Sometimes skin lesions enable early diagnosis, but criteria for diagnosis are not well established. To demonstrate the clinical spectrum of skin lesions of IVL and to correlate it with clinical outcome; to identify features differentiating between B-cell and T-cell IVL with skin involvement. Review of 97 articles reporting on total of 224 patients with IVL. Skin lesions were mentioned in 90 of 224 patients. They were nodules and/or plaques (49%) or macules (22.5%) of red (31%) or blue to livid (19%) colour on the leg (35%), the thigh (41%) and the trunk (31%). Telangiectases were present in only 20% of the patients. Oedema (27.5%) of the legs and pain (24%) were often accompanying. No criteria enabled distinction between lesions restricted to the skin and skin lesions concurrent with IVL in other organs, but when the disease was restricted to the skin, the prognosis was favourable (10% vs. 85% fatal outcome). Skin lesions of T-cell IVL are indistinguishable from those of B-cell IVL. Forty per cent of all patients with IVL have skin lesions, these being red, sometimes painful plaques located typically on the lower extremities, accompanied by oedema. A clinician risks misinterpreting these changes as thrombophlebitis, erythema nodosum or erysipelas. Neither clinical course nor differentiation of the lymphoma can be predicted from the morphology of skin lesions, but involvement of other organs at the time of diagnosis indicates a poor prognosis.

Intravascular large T-cell lymphoma: a case report of CD30-positive and ALK-negative anaplastic type with cytotoxic molecule expression

We reported a case of intravascular T-cell lymphoma (T-IVL) with anaplastic large cell morphology, the hemophagocytic syndrome, and an aggressive clinical course. Phenotypic analysis of the tumor cells revealed CD2+, CD3-, CD4+, CD5-, CD8-, CD30+, CD56-, T-cell receptor alpha/beta-, ALK-, TIA1+, granzyme B+, and perforin+. No association with Epstein-Barr virus was found by in situ hybridization. A review revealed that 25 cases of T-IVL have been reported in the available literature, only two of which were of CD30+ anaplastic large cell or cytotoxic T-cell type. The findings in the present case may highlight the unique clinicopathologic aspects of a subset of CD30-positive T-IVLs with an ALK-negative cytotoxic phenotype.

Intravascular T-cell lymphoma with bowel involvement: Case report and literature review

Intravascular lymphoma (IVL) is a rare form of non-Hodgkin lymphoma characterized by massive proliferation of large, neoplastic cells in small- and medium-sized blood vessels. Most cases of IVL are of B-cell immunophenotype; fewer than 15 cases of T-cell IVL have been reported. A 23-year-old male presented with acute abdominal pain, fever, and tender lower abdomen. Pathology at laparotomy revealed infiltration of colonic vessels with large lymphoid cells compatible with IVL. We reviewed all cases of IVL diagnosed at the Queen Elizabeth II Health Sciences Centre in Halifax, Nova Scotia, from August 1992 to August 2002. A literature review was also performed. Five additional cases of IVL were identified at this institution during a 10-year period. Three patients presented with neurological symptoms, and two with abdominal pain. In 4 of 5 cases, patients died of lymphoma within 3 months of presentation; one patient experienced a 10-month remission. While visceral involvement with IVL is common at autopsy, IVL presenting as an acute abdomen in an immunocompetent patient has not previously been described. Among the 15 cases of T-cell IVL reported in the literature, only two occurred in people under age 30. Given the rarity of T-cell IVL, it is remarkable that three cases of T-cell IVL have been diagnosed at our institution during a 10-year period.