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Limited Renal Intravascular Lymphoma: A Case Report and Review of the Literature

Limited Renal Intravascular Lymphoma: A Case Report and Review of the Literature Hindawi Case Reports in Oncological Medicine Volume 2020, Article ID 7052536, 7 pages https://doi.org/10.1155/2020/7052536 Case Report Limited Renal Intravascular Lymphoma: A Case Report and Review of the Literature 1 2 3 Guillermo Enrique Quintero Vega, Daniel Osorio, José Antonio de la Hoz Valle, and Daniela Rodríguez Feria Department of Hematology, Hospital Universitario Fundación Santa Fe de Bogotá, Bogotá, Colombia Department of Hematology, Universidad de los Andes, Bogotá, Colombia Department of Clinical Research, Hospital Universitario Fundación Santa Fe de Bogotá, Bogotá, Colombia Correspondence should be addressed to Daniela Rodríguez Feria; dani.rod2256@gmail.com Received 23 February 2020; Revised 7 August 2020; Accepted 20 September 2020; Published 7 October 2020 Academic Editor: Katsuhiro Tanaka Copyright © 2020 Guillermo Enrique Quintero Vega et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin lymphoma. It is characterized by the proliferation of cancerous cells into the intraluminal space of the blood vessels. It has a low incidence rate of 0.095 cases per 1,000,000. The clinical presentation is insidious and unspecific, often delaying the diagnosis. IVLBCL can be diagnosed through body images and histopathology analysis. This neoplasm averages a 60% response rate to current chemotherapy treatment, favoring rituximab, and doxorubicin-based regimen if it is diagnosed in time. Here, we present the case of a 56-year-old man admitted to our hospital with a fever who was eventually diagnosed with IVLBCL. He presented to the consultation with anemia, fever, and splenomegaly. An infection panel, a bone marrow biopsy, and a PET-CT scan were performed and ruled out the possibility of infections and neoplasms. The patient later developed edematous syndrome. As a result, a renal biopsy was performed which tested positive for intravascular large B-cell lymphoma. Currently, the patient has been in complete remission for 33 months. Along with presenting this specific case, we also reviewed previously published cases of IVLBCL to illustrate the renal involvement of this pathology. 1. Introduction pathology is classified into three main variants: classical, cutaneous, and hemophagocytic [5]. Intravascular large B-cell lymphoma (IVLBCL) is a rare A diagnosis is made by conducting a surgical biopsy in the affected organ to determine if there has been infiltration subtype of large cell lymphoma that is characterized by the proliferation of cancerous cells into the intraluminal space by cancerous cells. Intravascular lymphoma (IVL) is positive of small to medium blood vessels while sparing the surround- in 91% of cases for B-cell phenotype (CD19, CD20, CD22, ing tissue, lymph nodes, and reticuloendothelial system. and CD79a) and has occasionally shown expression of CD5 IVLBCL’s incidence rate is 0.095 cases per 1,000,000 in the with this last marker being associated with a poor prognosis United States [1]. IVLBCL patients have a median age at [6]. Vieites et al. and Yamamoto et al. [7, 8] described diagnosis of 70 years (the age range is from 40 to 90 years segmental tandem triplication of the 18q21 and q22q25 of old). IVLBCL affects both males and females without a predi- chromosome 11 as genetic alterations of IVL. lection for one or the other [2]. Also, IVLBCL has a heteroge- The treatment consists of anthracycline-based chemo- neous clinical presentation depending on the organ that is therapy regimens which have a nearly 60% response rate compromised. The majority of patients present with systemic and a 3-year overall survival rate higher than 30% [3]. CNS- symptoms such as fever of an unknown origin, pain, weight directed therapy, such as rituximab-cyclophosphamide, vin- loss, and rapid deterioration [3]. Usually, the central nervous cristine, and doxorubicin, is recommended for patients with system (CNS) and the skin are commonly affected [4]. This neurologic symptoms. Prednisone regimens do not penetrate 2 Case Reports in Oncological Medicine (a) (b) (c) Figure 1: PET-CT scan. Initial PET-CT. (a) Shows the hypermetabolic lesions, which can be seen in the descending colon, and the augmented signaling of the liver without renal compromise is documented. (b, c) PET-CT scans showing nonenhancement of the kidney signal. the CNS [4]. However, this information comes from a small anti-neutrophil cytoplasmic antibody) was performed. The series of cases, and given the rare nature of this disease, there autoimmune panel was also negative. are no randomized controlled trials that compare these Additionally, bone marrow cultures for detecting bacterial treatment regimens [9]. The analysis of a small sample size and fungal infections were performed. Cultures for fungal and of patients favors rituximab and doxorubicin-based treat- bacteria (aerobic and anaerobic) were negatives after 48 days ments when adjusting for age and poor prognosis factors and 6 days of incubation, respectively. A polymerase chain such as elevated lactate dehydrogenase serum levels [10]. reaction for Mycobacterium detection was negative. Notably, patterns of recurrence seem to indicate that the A positron emission tomography-computerized tomog- same organ becomes compromised if it recurs. However, raphy (PET-CT) scan was conducted to rule out infectious the small number of case reports available is not enough disease, neoplasms, and inflammatory diseases; it showed a for statistical analysis [10]. focal hypermetabolic lesion in the colon and an augmented signal in both the spleen and the bone marrow (Figure 1). A colonoscopy found grade 1 internal hemorrhoids and 2. Case Report sigmoid diverticulitis with focal edema of the mucosa and In 2017, a 56-year-old man arrived at the emergency room small angiodysplasia without signs of bleeding. No tumors with fever, chills, dyspnea, arthralgia, and headache that he or polyps were observed. A biopsy was taken from edematous had been experiencing for 20 days before the medical consul- mucosa. Due to the possibility of insidious diverticulitis, a tation. He had mild anemia with a hemoglobin level of control CT scan was also ordered. The results of the colon biopsy, alpha-fetoprotein test, CA-19-9 blood test, and 9.7 g/dL (reference range (RR): 14-18 g/dL), lactate dehydro- genase with levels of 506 U/L (RR: 98-192 U/L), C-reactive carcinoembryonic antigen test were negative for malignancy. protein levels of 18,904 mg/dL (RR: 0.000-0.748 mg/dL), beta The control CT scan showed an enlarged liver along with splenomegaly, and thus, a liver biopsy was performed which 2 microglobulin levels of 5620.0 ng/mL (RR: 1000.0- 3000.0 ng/mL), and albumin levels of 1.8 g/dL (RR: 3.50- showed no alterations. Ten days after admission, the patient 4.80 g/dL). A physical examination showed fever, diaphoresis, developed edematous syndrome along with low serum albu- tachypnea, blood oxygen saturation level of 76%, lung noises, min, elevated serum triglycerides, and elevated urine protein and a palpable spleen one centimeter below the costal margin. levels. A renal biopsy was performed; it was positive for mono- clonal B-lymphocyte (CD20+, CD5+, BCL2+ and BCL6+, Because the patient presented with a fever, infectious dis- ease panels were performed including IgM and IgG antibodies CD3-, GRANZYME-, MUM1-, and CD10- KI67 80%) against Cytomegalovirus, rubella virus infection, Treponema infiltration inside the peritubular capillaries which is compat- pallidum, anti-Epstein-Barr virus-IgG and IgM, hepatitis B ible with an intravascular large B-cell lymphoma (Figure 2). and C, and tropical diseases (thick drop test). He was also The patient was classified with a poor prognosis and con- sidered high risk according to the Revised International Prog- tested for central nervous system infections using cerebrospi- nal fluid analysis. All panels and tests were negative. nostic Index (R-IPI) due to a compromised extranodal site, an The patient also presented anemia and a high level of ECOG performance status higher than 2, high levels of lactate lactate dehydrogenase; therefore, a hematological malig- dehydrogenase, and an Ann Arbor clinical stage of IV. The nancy was suspected. A bone marrow biopsy was conducted. karyotype analysis was normal, and the cytogenetic FISH assessment was negative for BCL2, MYC, and EBV. The bone marrow biopsy tested negative for hemophagocyto- sis. However, it showed grade II fibrosis. Therefore, a second After the diagnosis was made, the patient received 6 cycles bone marrow biopsy was performed, which did not show of chemotherapy treatment (1 every 21 days) with rituximab, fibrosis; thus, the fibrosis from the first biopsy was interpreted cyclophosphamide, vincristine, doxorubicin, prednisone, as an inflammatory condition. Also, an autoimmune panel intrathecal cytarabine, and methotrexate. This treatment resulted in improvements in his blood test (Figure 3). By the (Anas, rheumatoid factor, C3 and C4 levels, anti-DNA, and Case Reports in Oncological Medicine 3 (a) (b) (c) (d) (e) (f) Figure 2: Kidney biopsy. (a) Hematoxylin-eosin staining of the kidney showing the presence of large atypical lymphocytes with an irregular nucleus in the glomerulus and tubules. (b) PAS staining of the kidney showing the presence of lymphocytes in the peritubular capillaries. (c) CD20 staining showing the presence of atypical B-lymphocytes. (d) CD3 staining. (e) KI67 staining showing a proliferation (80%). (f) CD5 staining was positive in this patient and associated with a poor prognosis in IVLBCL. end of the treatment, the patient had achieved complete [8]. Not all patients can be categorized under the three vari- metabolic response evidenced by the PET-CT scan, normal ants of clinical manifestation. Additionally, PET-CT scans hemoglobin levels of 14.2 gr/dL, normalized renal function of patients with IVLBCL are difficult to analyze due to renal with a creatinine level of 1.01 mg/dL, and regular levels of excretion of the radioisotope [6]. This difficulty shows the urine protein. Currently, the patient remains in complete importance that histopathological studies in patients with metabolic response after 33 months. compromised organs have in diagnosing and characterizing the disease. This pathology is considered a rare disease; most of the 3. Discussion information about it comes from case reports, small case IVLBCL has been commonly characterized as an aggressive series, and expert opinions [1]. After conducting a literature disease with a poor overall survival rate, and many diagnoses review, we found 9 cases of renal IVLBCL [11–19] with a were determined during postmortem analysis. Even though higher presentation in female patients and a median age of presentation of 58. The main clinical manifestations in these medical advances have been made in the field of hematolog- ical malignancies, intravascular lymphomas continue to be a cases were fever, renal failure, proteinuria, and edema. In diagnostic challenge due to the undefined symptoms, vari- imaging studies, a majority of these patients had enlarged kid- able clinical presentations, and inconclusive imaging studies neys on CT scans and PET-CT exams that were negative for 4 Case Reports in Oncological Medicine Albumin (g/dl) 6th 4th 5th 3rd chemotherapy chemotherapy chemotherapy chemotherapy cycle cycle cycle 2nd cycle chemotherapy chemotherapy 1 1st st cycle cycle ch chemotherapy emotherapy 5 Diagnosis Diagnosis cycl cycle e o of IVLBCL f IVLBCL 4,5 3,5 2,5 1,5 0,5 (a) Hemoglobin (g/dl) 6th 5th 4th chemotherapy chemotherapy chemotherapy cycle cycle 3rd 2nd cycle 16 chemotherapy chemotherapy ch chemotherapy emotherapy cycle cycle cycle cycle 14 1 1st st Admission Admission c chemotherapy hemotherapy D Diagnosis iagnosis cyc cycle le 12 of I of IVLBCL VLBCL (b) Lactate dehydrogenase (U/L) Diagnosis of IVLBCL Admission dmission 1st chemotherapy 2 2nd nd 3rd 4th 5th 6th cycle chemothe chemotherapy rapy chemotherapy chemotherapy chemotherapy chemotherapy cy cycle cle cycle cycle cycle cycle (c) Figure 3: Evolution of the main laboratory parameters. The patient showed improvement in albumin, lactate dehydrogenase, and hemoglobin levels after the chemotherapy treatment. (a) The albumin levels of the patient showed improvement as a result of the treatment. (b) The hemoglobin levels show improvement as a result of the treatment. (c) The lactate dehydrogenase levels decreased as a result of the treatment. 22/04/2017 4/05/2017 24/04/2017 29/04/2017 1/05/2017 11/05/2017 6/05/2017 8/05/2017 18/05/2017 13/05/2017 15/05/2017 25/05/2017 20/05/2017 22/05/2017 1/06/2017 27/05/2017 29/05/2017 8/06/2017 5/06/2017 3/06/2017 15/06/2017 12/06/2017 10/06/2017 22/06/2017 19/06/2017 17/06/2017 29/06/2017 26/06/2017 24/06/2017 6/07/2017 3/07/2017 1/07/2017 13/07/2017 10/07/2017 8/07/2017 20/07/2017 17/07/2017 15/07/2017 27/07/2017 24/07/2017 22/07/2017 31/07/2017 3/08/2017 29/07/2017 7/08/2017 10/08/2017 5/08/2017 14/08/2017 17/08/2017 12/08/2017 21/08/2017 19/08/2017 24/08/2017 28/08/2017 26/08/2017 31/08/2017 4/09/2017 2/09/2017 7/09/2017 11/09/2017 9/09/2017 14/09/2017 18/09/2017 16/09/2017 21/09/2017 25/09/2017 23/09/2017 28/09/2017 2/10/2017 30/09/2017 5/10/2017 9/10/2017 7/10/2017 12/10/2017 16/10/2017 14/10/2017 23/10/2017 Case Reports in Oncological Medicine 5 Table 1: Patients with intravascular large B-cell lymphoma. Bone Clinical Case Age/gender Year CT/PET-CT marrow Renal biopsy Treatment Outcome manifestation biopsy Computed tomography Edema of his (CT) revealed markedly The proliferating cells lower enlarged bilateral were phenotypically Niitsu et al. extremities kidneys but no characterized to be CD3 NA R-CHOP CR 52 (M) 2008 [11] and mild lymphadenopathy. −, CD20+, CD5−, CD10 renal FDG-PET revealed no −, BCL2+, BCL6+, and dysfunction. abnormal uptake of MUM-1+. FDG. Fever, MCD with lymphoma nausea, D’Agati et al. cells within glomerular 62 (F) 1989 vomiting, NA NA Prednisone Death [12] capillaries, interstitial nephritic vessel, and interstitium. syndrome. Glomerular capillary Fever, lumina with large Axelsen et al. proteinuria, 60 (F) 1991 NA NA lymphoma cells; CAVP CR [13] CNS CD20+, UCHL-1−, involvement. and CD43−. The lymphoma cells were positive for CD20, PET-CT showed that CD45, CD34, CD31, Sekulic et al. Fever, 59 (M) 2016 this lesion had no Normal and immunoglobulin R-CHOP CR [14] albuminuria. increased FDG uptake. (Ig) M and were negative for cytokeratin, IgG, IgA, and CD56. Atypical large lymphoid cells in the glomerular capillaries were positive for CD20 and CD79a CT showed both Renal but negative for CD3 Hasegawa et al. kidneys were small with 65 (F) 2015 dysfunction, NA and CD10. R-CHOP Relapse [15] a long axis of 9 cm proteinuria. Lymphocytes in the bilaterally. tubulointerstitium were positive for CD3 but negative for CD20 and CD79a. The immunohistochemical analysis was positive for CD20, factor-8, and CT showed Anasarca leukocyte common Bilgili et al. hepatomegaly with 56 (F) 2013 edema, acute NA antigen (LCA) (CD45) R-CHOP CR [16] 168 mm size and renal failure. and negative for CD3, inguinal lymph nodes. CD30, HMB45, S100, CD117, cytokeratin, CK7, CK20, CEA, and EMA. Atypical CD20 positive Renal B-lymphocytes filling impairment, PET-CT showed diffuse the capillary lumens of Kamalanathan 77 (F) 2013 proteinuria, marrow activity but no NA nearly 50% of all R-CHOP CR et al. [17] lethargy, abnormal renal signal. glomeruli seen on the weight loss. biopsy indicating large B-cell lymphoma of 6 Case Reports in Oncological Medicine Table 1: Continued. Bone Clinical Case Age/gender Year CT/PET-CT marrow Renal biopsy Treatment Outcome manifestation biopsy nongerminal centre immunophenotype. Atypical lymphoid cells PET-CT shows foci with were positive for B-cell 41.5% Fever, high signal intensity in markers CD20 and immature bilateral bilateral kidneys, negative for CK, CD3, Bai et al. [18] 41 (F) 2011 cells of CHOP CR lower limb multiple vertebrae, CD45RO, and CD10. unknown fatigue. bilateral sacrum, and They were positive for origin. ilium. large B-cell lymphoma marker mum-1. The atypical large lymphoid cells showed positive stainings for leukocyte common antigen CD45, BCL-2, PET-CT revealed no Kameoka et al. BCL-6, B-cell-associated 40 (F) 2006 Proteinuria. significant uptake of NA R-CHOP CR [19] antigens including isotopes. CD20, CD79a, and MUM1 and showed negative stainings for CD3, CD5, CD10, or CD56. PET-CT showed a focal Intravascular B Fever, hypermetabolic lesion lymphoma (CD20+, headache, in the colon and CD5+, BCL2+ Y BCL6 Current case 56 (M) 2016 Normal R-CHOP CR dyspnea, augmented signal in +, CD3-, GRANZYME-, arthralgia. both spleen and bone MUM1- Y CD10- KI67 marrow. 80%). R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone; CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisolone; CAVP: cyclophosphamide, doxorubicin, vincristine, and prednisone; CR: complete response; NA: not available. the current opinion of some experts that positions a PET-CT malignancy. Regarding their histopathology, bone marrow biopsies were normal in almost all the patients, and kidney scan as an important tool for diagnosis and follow-up for biopsies showed atypical lymphocytes located primarily in IVLBCL, especially in patients with renal compromise [21]. the glomerulus, followed by peritubular and interstitial infil- Finally, elevated urine proteins along with the presentation trates (Table 1). In another study, Törnroth et al. [20] reported of the edematous syndrome were the sole manifestations that 44 cases of bilateral renal lymphoma in 2013. Imaging studies indicated the organ was compromised by the disease. revealed that 40 out of the 44 patients in their study had bilat- The introduction of novel agents, such as rituximab, into eral enlargement of their kidneys without proteinuria in the cancer treatment protocols, has led to a paradigm shift in nephrotic range. Six patients had bone marrow involvement the treatment of lymphomas, making an early diagnosis and while 16 had another organ compromised. The mortality rate consequent treatment of intravascular lymphoma even more for these cases was approximately 54.5%. important than ever to secure a better response to therapy Our patient presented with nonspecificsymptoms and [7]. In the small series of cases reviewed in the literature, we without neurological alterations or skin lesions, which led to found 46% of the subjects were treated with rituximab-based extended laboratory testing, a late diagnosis, and the delayed chemotherapy regimens, and all of them reached a complete initiation of chemotherapeutic treatment. Notable inconclu- response with only 1 subject experiencing a relapse of his sive tests, in this case, include a bone marrow biopsy which hematological disease. Also, the mortality rate of IVLBCL was negative for neoplasm and hemophagocytic syndrome as has decreased from 54% to 10% [11–19]. It is important to well as CT scans and PET-CT scans that did not show any perform, in certain specific cases, a histopathological diagno- sis in patients with a fever of unknown origin and/or long findings regarding the neoplasm. This case presents itself as atypical because the PET-CT scan performed was negative duration and organ dysfunction. In this case, the patient did for hypermetabolic lesions in the renal parenchyma. Even not have any infectious or autoimmune disease or any classi- upon retroactive revision of the images after the full diagnosis cal clinical presentation of malignancies. Even though the was reached, we were unable to identify suspicious images in patient’s imaging tests were negative, the presence of hema- the kidneys. This absence of findings comes as a surprise given tooncological conditions was determined by renal biopsy. Case Reports in Oncological Medicine 7 cular large B-cell lymphoma?,” Journal of Clinical Oncology, Ethical Approval vol. 26, no. 31, pp. 5134–5136, 2008. The case report has been approved by our local research [10] E. Fonkem, E. Lok, D. Robison, S. Gautam, and E. T. Wong, ethics committee. “The natural history of intravascular lymphomatosis,” Cancer Medicine, vol. 3, no. 4, pp. 1010–1024, 2014. Consent [11] N. Niitsu, D. Okamura, N. Takahashi et al., “Renal intravascu- lar large B-cell lymphoma with early diagnosis by renal biopsy: The patient signed an informed consent form for case a case report and review of the literature,” Leukemia Research, reports. vol. 33, no. 5, pp. 728–730, 2009. [12] V. D'Agati, L. B. Sablay, D. M. Knowles, and L. Walter, “Angiotropic large cell lymphoma (intravascular malignant Conflicts of Interest lymphomatosis) of the kidney: presentation as minimal change disease,” Human Pathology, vol. 20, no. 3, pp. 263– The authors have no conflicts of interest to declare. 268, 1989. [13] R. A. Axelsen, P. P. Laird, and M. Horn, “Intravascular large Authors’ Contributions cell lymphoma: diagnosis on renal biopsy,” Pathology, vol. 23, no. 3, pp. 241–243, 1991. GEQV, DO, DRF, and JADLHV contributed equally to this [14] M. Sekulic, S. Martin, A. Lal, and A. Weins, “Intravascular work. large B-cell lymphoma of the kidney,” Kidney International Reports, vol. 3, no. 6, pp. 1501–1505, 2018. References [15] J. Hasegawa, J. Hoshino, T. Suwabe et al., “Characteristics of intravascular large B-cell lymphoma limited to the glomerular [1] D. J. Rajyaguru, C. Bhaskar, A. J. Borgert, A. Smith, and capillaries: a case report,” Case Reports in Nephrology and B. Parsons, “Intravascular large B-cell lymphoma in the United Dialysis, vol. 5, no. 2, pp. 173–179, 2015. States (US): a population-based study using Surveillance, Epi- [16] S. G. Bilgili, D. Yılmaz, Y. U. Soyoral, A. S. Karadag, and demiology, and End Results program and National Cancer I. Bayram, “Intravascular large B-cell lymphoma presenting Database,” Leukemia & Lymphoma, vol. 58, no. 9, pp. 2080– with anasarca-type edema and acute renal failure,” Renal Fail- 2088, 2017. ure, vol. 35, no. 8, pp. 1163–1166, 2013. [2] M. Ponzoni, E. Campo, and S. Nakamura, “Intravascular large [17] M. Kamalanathan, D. Wright, R. Johnston, A. Webb, and B-cell lymphoma: a chameleon with multiple faces and many E. Kingdon, “Intravascular large B-cell lymphoma diagnosed masks,” Blood, vol. 132, no. 15, pp. 1561–1567, 2018. at renal biopsy,” Clinical Kidney Journal, vol. 6, no. 1, [3] M. Ponzoni, A. J. Ferreri, E. Campo et al., “Definition, diagno- pp. 100-101, 2013. sis, and management of intravascular large B-cell lymphoma: proposals and perspectives from an international consensus [18] X. Bai, X. Li, L. Wan, G. Wang, N. Jia, and J. Geng, “Intravas- meeting,” Journal of Clinical Oncology, vol. 25, no. 21, cular large B-cell lymphoma of the kidney: a case report,” pp. 3168–3173, 2007. Diagnostic Pathology, vol. 6, no. 1, p. 86, 2011. [4] A. J. Ferreri, E. Campo, J. F. Seymour et al., “Intravascular lym- [19] Y. Kameoka, N. Takahashi, A. Komatsuda et al., “Kidney-lim- phoma: clinical presentation, natural history, management ited intravascular large B cell lymphoma: a distinct variant of and prognostic factors in a series of 38 cases, with special IVLBCL?,” International Journal of Hematology, vol. 89, emphasis on the 'cutaneous variant',” British Journal of Hae- no. 4, pp. 533–537, 2009. matology, vol. 127, no. 2, pp. 173–183, 2004. [20] T. Törnroth, M. Heiro, N. Marcussen, and K. Franssila, “Lym- [5] A. J. Ferreri, G. P. Dognini, E. Campo et al., “Variations in clin- phomas diagnosed by percutaneous kidney biopsy,” American ical presentation, frequency of hemophagocytosis and clinical Journal of Kidney Diseases, vol. 42, no. 5, pp. 960–971, 2003. behavior of intravascular lymphoma diagnosed in different [21] D. Albano, R. Laudicella, P. Ferro et al., “The role of 18F-FDG geographical regions,” Haematologica, vol. 92, no. 4, pp. 486– PET/CT in staging and prognostication of mantle cell lym- 492, 2007. phoma: an Italian multicentric study,” Cancers, vol. 11, [6] A. Desclaux, E. Lazaro, J. B. Pinaquy, M. Yacoub, and J. F. no. 12, p. 1831, 2019. Viallard, “Renal intravascular large B-cell lymphoma: a case report and review of the literature,” Internal Medicine, vol. 56, no. 7, pp. 827–833, 2017. [7] B. Vieites, M. Fraga, E. Lopez-Presas, E. Pintos, A. Garcia- Rivero, and J. Forteza, “Detection of t(14;18) translocation in a case of intravascular large B-cell lymphoma: a germinal centre cell origin in a subset of these lymphomas?,” Histo- pathology, vol. 46, no. 4, pp. 466–468, 2005. [8] K. Yamamoto, A. Okamura, K. Yakushijin, Y. Hayashi, H. Matsuoka, and H. Minami, “Tandem triplication of the BCL2 gene in CD5-positive intravascular large B cell lym- phoma with bone marrow involvement,” Annals of Hematol- ogy, vol. 93, no. 10, pp. 1791–1793, 2014. [9] A. J. Ferreri, G. P. Dognini, S. Govi et al., “Can rituximab change the usually dismal prognosis of patients with intravas- http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Case Reports in Oncological Medicine Hindawi Publishing Corporation

Limited Renal Intravascular Lymphoma: A Case Report and Review of the Literature

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Hindawi Case Reports in Oncological Medicine Volume 2020, Article ID 7052536, 7 pages https://doi.org/10.1155/2020/7052536 Case Report Limited Renal Intravascular Lymphoma: A Case Report and Review of the Literature 1 2 3 Guillermo Enrique Quintero Vega, Daniel Osorio, José Antonio de la Hoz Valle, and Daniela Rodríguez Feria Department of Hematology, Hospital Universitario Fundación Santa Fe de Bogotá, Bogotá, Colombia Department of Hematology, Universidad de los Andes, Bogotá, Colombia Department of Clinical Research, Hospital Universitario Fundación Santa Fe de Bogotá, Bogotá, Colombia Correspondence should be addressed to Daniela Rodríguez Feria; dani.rod2256@gmail.com Received 23 February 2020; Revised 7 August 2020; Accepted 20 September 2020; Published 7 October 2020 Academic Editor: Katsuhiro Tanaka Copyright © 2020 Guillermo Enrique Quintero Vega et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin lymphoma. It is characterized by the proliferation of cancerous cells into the intraluminal space of the blood vessels. It has a low incidence rate of 0.095 cases per 1,000,000. The clinical presentation is insidious and unspecific, often delaying the diagnosis. IVLBCL can be diagnosed through body images and histopathology analysis. This neoplasm averages a 60% response rate to current chemotherapy treatment, favoring rituximab, and doxorubicin-based regimen if it is diagnosed in time. Here, we present the case of a 56-year-old man admitted to our hospital with a fever who was eventually diagnosed with IVLBCL. He presented to the consultation with anemia, fever, and splenomegaly. An infection panel, a bone marrow biopsy, and a PET-CT scan were performed and ruled out the possibility of infections and neoplasms. The patient later developed edematous syndrome. As a result, a renal biopsy was performed which tested positive for intravascular large B-cell lymphoma. Currently, the patient has been in complete remission for 33 months. Along with presenting this specific case, we also reviewed previously published cases of IVLBCL to illustrate the renal involvement of this pathology. 1. Introduction pathology is classified into three main variants: classical, cutaneous, and hemophagocytic [5]. Intravascular large B-cell lymphoma (IVLBCL) is a rare A diagnosis is made by conducting a surgical biopsy in the affected organ to determine if there has been infiltration subtype of large cell lymphoma that is characterized by the proliferation of cancerous cells into the intraluminal space by cancerous cells. Intravascular lymphoma (IVL) is positive of small to medium blood vessels while sparing the surround- in 91% of cases for B-cell phenotype (CD19, CD20, CD22, ing tissue, lymph nodes, and reticuloendothelial system. and CD79a) and has occasionally shown expression of CD5 IVLBCL’s incidence rate is 0.095 cases per 1,000,000 in the with this last marker being associated with a poor prognosis United States [1]. IVLBCL patients have a median age at [6]. Vieites et al. and Yamamoto et al. [7, 8] described diagnosis of 70 years (the age range is from 40 to 90 years segmental tandem triplication of the 18q21 and q22q25 of old). IVLBCL affects both males and females without a predi- chromosome 11 as genetic alterations of IVL. lection for one or the other [2]. Also, IVLBCL has a heteroge- The treatment consists of anthracycline-based chemo- neous clinical presentation depending on the organ that is therapy regimens which have a nearly 60% response rate compromised. The majority of patients present with systemic and a 3-year overall survival rate higher than 30% [3]. CNS- symptoms such as fever of an unknown origin, pain, weight directed therapy, such as rituximab-cyclophosphamide, vin- loss, and rapid deterioration [3]. Usually, the central nervous cristine, and doxorubicin, is recommended for patients with system (CNS) and the skin are commonly affected [4]. This neurologic symptoms. Prednisone regimens do not penetrate 2 Case Reports in Oncological Medicine (a) (b) (c) Figure 1: PET-CT scan. Initial PET-CT. (a) Shows the hypermetabolic lesions, which can be seen in the descending colon, and the augmented signaling of the liver without renal compromise is documented. (b, c) PET-CT scans showing nonenhancement of the kidney signal. the CNS [4]. However, this information comes from a small anti-neutrophil cytoplasmic antibody) was performed. The series of cases, and given the rare nature of this disease, there autoimmune panel was also negative. are no randomized controlled trials that compare these Additionally, bone marrow cultures for detecting bacterial treatment regimens [9]. The analysis of a small sample size and fungal infections were performed. Cultures for fungal and of patients favors rituximab and doxorubicin-based treat- bacteria (aerobic and anaerobic) were negatives after 48 days ments when adjusting for age and poor prognosis factors and 6 days of incubation, respectively. A polymerase chain such as elevated lactate dehydrogenase serum levels [10]. reaction for Mycobacterium detection was negative. Notably, patterns of recurrence seem to indicate that the A positron emission tomography-computerized tomog- same organ becomes compromised if it recurs. However, raphy (PET-CT) scan was conducted to rule out infectious the small number of case reports available is not enough disease, neoplasms, and inflammatory diseases; it showed a for statistical analysis [10]. focal hypermetabolic lesion in the colon and an augmented signal in both the spleen and the bone marrow (Figure 1). A colonoscopy found grade 1 internal hemorrhoids and 2. Case Report sigmoid diverticulitis with focal edema of the mucosa and In 2017, a 56-year-old man arrived at the emergency room small angiodysplasia without signs of bleeding. No tumors with fever, chills, dyspnea, arthralgia, and headache that he or polyps were observed. A biopsy was taken from edematous had been experiencing for 20 days before the medical consul- mucosa. Due to the possibility of insidious diverticulitis, a tation. He had mild anemia with a hemoglobin level of control CT scan was also ordered. The results of the colon biopsy, alpha-fetoprotein test, CA-19-9 blood test, and 9.7 g/dL (reference range (RR): 14-18 g/dL), lactate dehydro- genase with levels of 506 U/L (RR: 98-192 U/L), C-reactive carcinoembryonic antigen test were negative for malignancy. protein levels of 18,904 mg/dL (RR: 0.000-0.748 mg/dL), beta The control CT scan showed an enlarged liver along with splenomegaly, and thus, a liver biopsy was performed which 2 microglobulin levels of 5620.0 ng/mL (RR: 1000.0- 3000.0 ng/mL), and albumin levels of 1.8 g/dL (RR: 3.50- showed no alterations. Ten days after admission, the patient 4.80 g/dL). A physical examination showed fever, diaphoresis, developed edematous syndrome along with low serum albu- tachypnea, blood oxygen saturation level of 76%, lung noises, min, elevated serum triglycerides, and elevated urine protein and a palpable spleen one centimeter below the costal margin. levels. A renal biopsy was performed; it was positive for mono- clonal B-lymphocyte (CD20+, CD5+, BCL2+ and BCL6+, Because the patient presented with a fever, infectious dis- ease panels were performed including IgM and IgG antibodies CD3-, GRANZYME-, MUM1-, and CD10- KI67 80%) against Cytomegalovirus, rubella virus infection, Treponema infiltration inside the peritubular capillaries which is compat- pallidum, anti-Epstein-Barr virus-IgG and IgM, hepatitis B ible with an intravascular large B-cell lymphoma (Figure 2). and C, and tropical diseases (thick drop test). He was also The patient was classified with a poor prognosis and con- sidered high risk according to the Revised International Prog- tested for central nervous system infections using cerebrospi- nal fluid analysis. All panels and tests were negative. nostic Index (R-IPI) due to a compromised extranodal site, an The patient also presented anemia and a high level of ECOG performance status higher than 2, high levels of lactate lactate dehydrogenase; therefore, a hematological malig- dehydrogenase, and an Ann Arbor clinical stage of IV. The nancy was suspected. A bone marrow biopsy was conducted. karyotype analysis was normal, and the cytogenetic FISH assessment was negative for BCL2, MYC, and EBV. The bone marrow biopsy tested negative for hemophagocyto- sis. However, it showed grade II fibrosis. Therefore, a second After the diagnosis was made, the patient received 6 cycles bone marrow biopsy was performed, which did not show of chemotherapy treatment (1 every 21 days) with rituximab, fibrosis; thus, the fibrosis from the first biopsy was interpreted cyclophosphamide, vincristine, doxorubicin, prednisone, as an inflammatory condition. Also, an autoimmune panel intrathecal cytarabine, and methotrexate. This treatment resulted in improvements in his blood test (Figure 3). By the (Anas, rheumatoid factor, C3 and C4 levels, anti-DNA, and Case Reports in Oncological Medicine 3 (a) (b) (c) (d) (e) (f) Figure 2: Kidney biopsy. (a) Hematoxylin-eosin staining of the kidney showing the presence of large atypical lymphocytes with an irregular nucleus in the glomerulus and tubules. (b) PAS staining of the kidney showing the presence of lymphocytes in the peritubular capillaries. (c) CD20 staining showing the presence of atypical B-lymphocytes. (d) CD3 staining. (e) KI67 staining showing a proliferation (80%). (f) CD5 staining was positive in this patient and associated with a poor prognosis in IVLBCL. end of the treatment, the patient had achieved complete [8]. Not all patients can be categorized under the three vari- metabolic response evidenced by the PET-CT scan, normal ants of clinical manifestation. Additionally, PET-CT scans hemoglobin levels of 14.2 gr/dL, normalized renal function of patients with IVLBCL are difficult to analyze due to renal with a creatinine level of 1.01 mg/dL, and regular levels of excretion of the radioisotope [6]. This difficulty shows the urine protein. Currently, the patient remains in complete importance that histopathological studies in patients with metabolic response after 33 months. compromised organs have in diagnosing and characterizing the disease. This pathology is considered a rare disease; most of the 3. Discussion information about it comes from case reports, small case IVLBCL has been commonly characterized as an aggressive series, and expert opinions [1]. After conducting a literature disease with a poor overall survival rate, and many diagnoses review, we found 9 cases of renal IVLBCL [11–19] with a were determined during postmortem analysis. Even though higher presentation in female patients and a median age of presentation of 58. The main clinical manifestations in these medical advances have been made in the field of hematolog- ical malignancies, intravascular lymphomas continue to be a cases were fever, renal failure, proteinuria, and edema. In diagnostic challenge due to the undefined symptoms, vari- imaging studies, a majority of these patients had enlarged kid- able clinical presentations, and inconclusive imaging studies neys on CT scans and PET-CT exams that were negative for 4 Case Reports in Oncological Medicine Albumin (g/dl) 6th 4th 5th 3rd chemotherapy chemotherapy chemotherapy chemotherapy cycle cycle cycle 2nd cycle chemotherapy chemotherapy 1 1st st cycle cycle ch chemotherapy emotherapy 5 Diagnosis Diagnosis cycl cycle e o of IVLBCL f IVLBCL 4,5 3,5 2,5 1,5 0,5 (a) Hemoglobin (g/dl) 6th 5th 4th chemotherapy chemotherapy chemotherapy cycle cycle 3rd 2nd cycle 16 chemotherapy chemotherapy ch chemotherapy emotherapy cycle cycle cycle cycle 14 1 1st st Admission Admission c chemotherapy hemotherapy D Diagnosis iagnosis cyc cycle le 12 of I of IVLBCL VLBCL (b) Lactate dehydrogenase (U/L) Diagnosis of IVLBCL Admission dmission 1st chemotherapy 2 2nd nd 3rd 4th 5th 6th cycle chemothe chemotherapy rapy chemotherapy chemotherapy chemotherapy chemotherapy cy cycle cle cycle cycle cycle cycle (c) Figure 3: Evolution of the main laboratory parameters. The patient showed improvement in albumin, lactate dehydrogenase, and hemoglobin levels after the chemotherapy treatment. (a) The albumin levels of the patient showed improvement as a result of the treatment. (b) The hemoglobin levels show improvement as a result of the treatment. (c) The lactate dehydrogenase levels decreased as a result of the treatment. 22/04/2017 4/05/2017 24/04/2017 29/04/2017 1/05/2017 11/05/2017 6/05/2017 8/05/2017 18/05/2017 13/05/2017 15/05/2017 25/05/2017 20/05/2017 22/05/2017 1/06/2017 27/05/2017 29/05/2017 8/06/2017 5/06/2017 3/06/2017 15/06/2017 12/06/2017 10/06/2017 22/06/2017 19/06/2017 17/06/2017 29/06/2017 26/06/2017 24/06/2017 6/07/2017 3/07/2017 1/07/2017 13/07/2017 10/07/2017 8/07/2017 20/07/2017 17/07/2017 15/07/2017 27/07/2017 24/07/2017 22/07/2017 31/07/2017 3/08/2017 29/07/2017 7/08/2017 10/08/2017 5/08/2017 14/08/2017 17/08/2017 12/08/2017 21/08/2017 19/08/2017 24/08/2017 28/08/2017 26/08/2017 31/08/2017 4/09/2017 2/09/2017 7/09/2017 11/09/2017 9/09/2017 14/09/2017 18/09/2017 16/09/2017 21/09/2017 25/09/2017 23/09/2017 28/09/2017 2/10/2017 30/09/2017 5/10/2017 9/10/2017 7/10/2017 12/10/2017 16/10/2017 14/10/2017 23/10/2017 Case Reports in Oncological Medicine 5 Table 1: Patients with intravascular large B-cell lymphoma. Bone Clinical Case Age/gender Year CT/PET-CT marrow Renal biopsy Treatment Outcome manifestation biopsy Computed tomography Edema of his (CT) revealed markedly The proliferating cells lower enlarged bilateral were phenotypically Niitsu et al. extremities kidneys but no characterized to be CD3 NA R-CHOP CR 52 (M) 2008 [11] and mild lymphadenopathy. −, CD20+, CD5−, CD10 renal FDG-PET revealed no −, BCL2+, BCL6+, and dysfunction. abnormal uptake of MUM-1+. FDG. Fever, MCD with lymphoma nausea, D’Agati et al. cells within glomerular 62 (F) 1989 vomiting, NA NA Prednisone Death [12] capillaries, interstitial nephritic vessel, and interstitium. syndrome. Glomerular capillary Fever, lumina with large Axelsen et al. proteinuria, 60 (F) 1991 NA NA lymphoma cells; CAVP CR [13] CNS CD20+, UCHL-1−, involvement. and CD43−. The lymphoma cells were positive for CD20, PET-CT showed that CD45, CD34, CD31, Sekulic et al. Fever, 59 (M) 2016 this lesion had no Normal and immunoglobulin R-CHOP CR [14] albuminuria. increased FDG uptake. (Ig) M and were negative for cytokeratin, IgG, IgA, and CD56. Atypical large lymphoid cells in the glomerular capillaries were positive for CD20 and CD79a CT showed both Renal but negative for CD3 Hasegawa et al. kidneys were small with 65 (F) 2015 dysfunction, NA and CD10. R-CHOP Relapse [15] a long axis of 9 cm proteinuria. Lymphocytes in the bilaterally. tubulointerstitium were positive for CD3 but negative for CD20 and CD79a. The immunohistochemical analysis was positive for CD20, factor-8, and CT showed Anasarca leukocyte common Bilgili et al. hepatomegaly with 56 (F) 2013 edema, acute NA antigen (LCA) (CD45) R-CHOP CR [16] 168 mm size and renal failure. and negative for CD3, inguinal lymph nodes. CD30, HMB45, S100, CD117, cytokeratin, CK7, CK20, CEA, and EMA. Atypical CD20 positive Renal B-lymphocytes filling impairment, PET-CT showed diffuse the capillary lumens of Kamalanathan 77 (F) 2013 proteinuria, marrow activity but no NA nearly 50% of all R-CHOP CR et al. [17] lethargy, abnormal renal signal. glomeruli seen on the weight loss. biopsy indicating large B-cell lymphoma of 6 Case Reports in Oncological Medicine Table 1: Continued. Bone Clinical Case Age/gender Year CT/PET-CT marrow Renal biopsy Treatment Outcome manifestation biopsy nongerminal centre immunophenotype. Atypical lymphoid cells PET-CT shows foci with were positive for B-cell 41.5% Fever, high signal intensity in markers CD20 and immature bilateral bilateral kidneys, negative for CK, CD3, Bai et al. [18] 41 (F) 2011 cells of CHOP CR lower limb multiple vertebrae, CD45RO, and CD10. unknown fatigue. bilateral sacrum, and They were positive for origin. ilium. large B-cell lymphoma marker mum-1. The atypical large lymphoid cells showed positive stainings for leukocyte common antigen CD45, BCL-2, PET-CT revealed no Kameoka et al. BCL-6, B-cell-associated 40 (F) 2006 Proteinuria. significant uptake of NA R-CHOP CR [19] antigens including isotopes. CD20, CD79a, and MUM1 and showed negative stainings for CD3, CD5, CD10, or CD56. PET-CT showed a focal Intravascular B Fever, hypermetabolic lesion lymphoma (CD20+, headache, in the colon and CD5+, BCL2+ Y BCL6 Current case 56 (M) 2016 Normal R-CHOP CR dyspnea, augmented signal in +, CD3-, GRANZYME-, arthralgia. both spleen and bone MUM1- Y CD10- KI67 marrow. 80%). R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone; CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisolone; CAVP: cyclophosphamide, doxorubicin, vincristine, and prednisone; CR: complete response; NA: not available. the current opinion of some experts that positions a PET-CT malignancy. Regarding their histopathology, bone marrow biopsies were normal in almost all the patients, and kidney scan as an important tool for diagnosis and follow-up for biopsies showed atypical lymphocytes located primarily in IVLBCL, especially in patients with renal compromise [21]. the glomerulus, followed by peritubular and interstitial infil- Finally, elevated urine proteins along with the presentation trates (Table 1). In another study, Törnroth et al. [20] reported of the edematous syndrome were the sole manifestations that 44 cases of bilateral renal lymphoma in 2013. Imaging studies indicated the organ was compromised by the disease. revealed that 40 out of the 44 patients in their study had bilat- The introduction of novel agents, such as rituximab, into eral enlargement of their kidneys without proteinuria in the cancer treatment protocols, has led to a paradigm shift in nephrotic range. Six patients had bone marrow involvement the treatment of lymphomas, making an early diagnosis and while 16 had another organ compromised. The mortality rate consequent treatment of intravascular lymphoma even more for these cases was approximately 54.5%. important than ever to secure a better response to therapy Our patient presented with nonspecificsymptoms and [7]. In the small series of cases reviewed in the literature, we without neurological alterations or skin lesions, which led to found 46% of the subjects were treated with rituximab-based extended laboratory testing, a late diagnosis, and the delayed chemotherapy regimens, and all of them reached a complete initiation of chemotherapeutic treatment. Notable inconclu- response with only 1 subject experiencing a relapse of his sive tests, in this case, include a bone marrow biopsy which hematological disease. Also, the mortality rate of IVLBCL was negative for neoplasm and hemophagocytic syndrome as has decreased from 54% to 10% [11–19]. It is important to well as CT scans and PET-CT scans that did not show any perform, in certain specific cases, a histopathological diagno- sis in patients with a fever of unknown origin and/or long findings regarding the neoplasm. This case presents itself as atypical because the PET-CT scan performed was negative duration and organ dysfunction. In this case, the patient did for hypermetabolic lesions in the renal parenchyma. Even not have any infectious or autoimmune disease or any classi- upon retroactive revision of the images after the full diagnosis cal clinical presentation of malignancies. Even though the was reached, we were unable to identify suspicious images in patient’s imaging tests were negative, the presence of hema- the kidneys. This absence of findings comes as a surprise given tooncological conditions was determined by renal biopsy. 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Case Reports in Oncological MedicineHindawi Publishing Corporation

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