Unexpected finding of intravascular large B-cell lymphoma by a skin biopsy

Guillen-Climent, Santiago; García-Vázquez, Alejandro; Martínez-Ciarpaglini, Carolina

doi:10.1016/j.medcle.2020.04.062

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A) Haematoxylin-eosin stain (x100) with intimal hyperplasia (arrow) and lymphocytic infiltrate predominantly in the adventitia and (x400) clustered macrophages (*). 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A histopathology study confirmed the clinical diagnosis of the condition and revealed large, atypical lymphocytes with a prominent nucleolus in the lumens of the small blood vessels of the hypodermis. These cells showed positive immunostaining for CD20, BCL2, BCL6, and MUM, and negative staining for CD3 and CD10. The diagnosis of IVLBCL was reached based on these findings. Treatment of the condition consisted in six cycles of R-CHOP chemotherapy and four cycles of intrathecal therapy with methotrexate, cytarabine, and hydrocortisone, achieving a complete response. The patient’s disease-free interval at the time of writing this paper is 18 months.Case 2A 71-year-old woman presenting with a fever of unknown origin (FUO), asthenia, night sweats, and a weight loss of eight kilograms. She had elevated levels of C-reactive protein, lactate dehydrogenase, and beta-2-microglobulin. An infectious or autoimmune etiology was ruled out. A blind skin biopsy of her right thigh was performed, and the histopathology study of the collected sample revealed large, atypical lymphocytes with a prominent nucleolus in the lumens of the small and medium blood vessels of the hypodermis. An immunohistochemistry study revealed positivity for CD20, BCL6, and CD79a, and negativity for CD3 and CD10. Based on these findings, a diagnosis of IVLBCL was reached, and six cycles of treatment with R-CHOP and four cycles of intrathecal therapy with methotrexate, cytarabine, and hydrocortisone were administered, achieving a complete response. The patient relapsed after a disease-free interval of 15 months and was consequently treated with an additional six cycles of R-GEMOX (rituximab, gemcitabine, and oxaliplatin), achieving a complete response once again.Intravascular VLBCL consists in a malignant intravascular proliferation of large B-cells. It is a rare condition that occurs most frequently in the seventh decade of life.<a class="elsevierStyleCrossRefs" href="#bib0005">1,2</a>Its clinical manifestations are heterogeneous and are classified into different variants. The classic variant is the most common one, predominant in Western countries, and usually manifests with cutaneous and neurological involvement, FUO, and systemic symptoms. The cutaneous variant is more prevalent in Europe and associated with an improved prognosis. The hemophagocytic variant is more prevalent among Asians and is associated with the worst prognosis.<a class="elsevierStyleCrossRefs" href="#bib0005">1,3</a>Its cutaneous manifestations include indurated, painful, ill-defined erythematous-purpuric plates; plates similar to those caused by cellulitis; ulcerated nodules; and palpable purpura.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Furthermore, IVLBCL can infiltrate dermal and subcutaneous blood vessels without associated clinical manifestations.<a class="elsevierStyleCrossRefs" href="#bib0010">2,4</a>Its histological findings are large B-cells of centroblastic appearance occupying the lumens of the small and medium blood vessels of the dermis and hypodermis. These cells express B-markers such as CD20 and CD79a, tend to show positivity for MUM1 and BLC2, and, in some cases, for BCL6, CD5, and CD10.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>Because it is not associated with characteristic signs or symptoms, the diagnosis of IVLBCL is hard to reach, and in more than half of cases it is established through an autopsy.<a class="elsevierStyleCrossRefs" href="#bib0005">1,2</a> This condition should be suspected in a patient with FUO, neurological alterations, and cutaneous manifestations.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> The diagnostic usefulness of a blind skin biopsy has been demonstrated in cases presenting with FUO. Thus, it is advisable to perform multiple biopsies including subcutaneous cell tissue.<a class="elsevierStyleCrossRefs" href="#bib0005">1–5</a> The exact percentage of cases of IVLBCL diagnosed by a blind skin biopsy is unknown and there are no guidelines indicating the preferred locations on which this technique should be applied. However, considering the skin regions that are most frequently affected by this condition, the thighs, legs, and trunk may be suitable locations.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> Post-treatment blind skin biopsies were also performed in the cases presented in this paper, with no histopathological findings of IVLBCL being detected. Therefore, we believe that a blind skin biopsy may be an additional technique that may be applied to define the type of therapeutic response achieved in cases of IVLBCL. Finally, it must be noted that IVLBCL could be an incidental finding in histopathological exams of non-lymphoid skin lesions as in one of the cases described in this paper.In conclusion, we have herein presented two cases of IVLBCL in which a blind skin biopsy was crucial for reaching the diagnosis in the study of both a case of FUO and a case without an initial clinical suspicion. Because IVLBCL is a very rare disease whose clinical manifestations and laboratory findings are only indicative, a histopathology study is required for confirming the diagnosis and starting treatment early." "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Case 1" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Case 2" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Guillen-Climent S, García-Vázquez A, Martínez-Ciarpaglini C. Hallazgo casual de un linfoma de células grandes B intravascular tras una biopsia cutánea a ciegas. Med Clin (Barc). 2021;157:56–57." ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cutaneous B-cell lymphoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Goyal" 1 => "R.E. LeBlanc" 2 => "J.B. Carter" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.hoc.2018.08.006" "Revista" => array:6 [ "tituloSerie" => "Hematol Oncol Clin North Am" "fecha" => "2019" "volumen" => "33" "paginaInicial" => "149" "paginaFinal" => "156" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30497672" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intravascular large B cell lymphoma presenting as fever of unknown origin and diagnosed by random skin biopsies: a case report and literature review" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. di Fonzo" 1 => "D. Contardo" 2 => "D. Carrozza" 3 => "P. Finocchietto" 4 => "A. Rojano Crisson" 5 => "C. Cabral" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.12659/AJCR.903816" "Revista" => array:6 [ "tituloSerie" => "Am J Case Rep" "fecha" => "2017" "volumen" => "18" "paginaInicial" => "482" "paginaFinal" => "486" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28461685" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intravascular large B-cell lymphoma: a chameleon with multiple faces and many masks" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M. Ponzoni" 1 => "E. Campo" 2 => "S. Nakamura" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2017-04-737445" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2018" "volumen" => "132" "paginaInicial" => "1561" "paginaFinal" => "1567" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30111607" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The use of blind skin biopsy in the diagnosis of intravascular B-cell lymphoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E.N. Le" 1 => "M.R. Gerstenblith" 2 => "A.C. Gelber" 3 => "R.L. Manno" 4 => "P.D. Ranasinghe" 5 => "R.J. Sweren" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2008.03.010" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2008" "volumen" => "59" "paginaInicial" => "148" "paginaFinal" => "151" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18406005" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intravascular B-cell lymphoma: the role of skin biopsy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "C.R. Barnett" 1 => "S. Seo" 2 => "S. Husain" 3 => "M.E. Grossman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/DAD.0b013e31816c745f" "Revista" => array:6 [ "tituloSerie" => "Am J Dermatopathol" "fecha" => "2008" "volumen" => "30" "paginaInicial" => "295" "paginaFinal" => "299" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18496438" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015700000003/v3_202201060717/S2387020621003363/v3_202201060717/en/main.assets" "Apartado" => array:4 [ "identificador" => "43309" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015700000003/v3_202201060717/S2387020621003363/v3_202201060717/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020621003363?idApp=UINPBA00004N"]

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Vol. 157. Issue 3.

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Medicina Clínica (English Edition) follows the Recommendations for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals

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