Letter to the Editor
Leukemic transformation of Langerhans cell sarcoma
Leucemización de sarcoma de células de Langerhans
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The visualization of Birbeck granules in the cytoplasm of the malignant cells by electronic microscopy is not always demonstrable in every case.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">2</span></a> BRAF V600E mutations are detected in only 25–57% of cases.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">3,4</span></a> We describe herein an exceptional case of leukemization of LCS.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 34 year-old woman was admitted because of acute abdominal pain, increased abdominal girth, mild weight loss, galactorrhea of one-month duration and appearance of subcutaneous nodules in face, upper extremities, trunk and back. Hemoglobin was 112<span class="elsevierStyleHsp" style=""></span>g/L (normal: 12–14<span class="elsevierStyleHsp" style=""></span>g/L); serum LDH was 646<span class="elsevierStyleHsp" style=""></span>U/L (normal <214), and serum prolactin 59.1<span class="elsevierStyleHsp" style=""></span>ng/mL (normal: 4.8–23). A CT scan showed moderate ascites and an adenopathic mesenteric and retroperitoneal conglomerate that sized 95<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>112<span class="elsevierStyleHsp" style=""></span>mm. A laparotomy was performed and histological study of the tumor biopsy showed a diffuse infiltration by atypical, blastic large cells of histiocytic appearance with broad vacuolated cytoplasm and some images of hemophagocytosis. The nuclei had marked indentations, immature chromatin and visible nucleoli. By immunohistochemistry, these cells were CD4/CD68/CD15/S100 positive and negative for pan-T, pan-B markers, CD1a, langerin, BCL6, CD30, MUM1, HMB45, melan A, CAM 5.2 and AE1/AE3 cytokeratines. The study of BRAF V600E mutation resulted negative. Flow cytometry (FC) study showed expression of CD1a/CD4/CD64/CD33/CD123/CD45/DR/CD11b and cytoplasmic lysozyme, but pan-B and pan-T markers, CD56, CD34, MPO, CD14 and TdT were negative. Karyotype was normal and TCR rearrangement was ruled out by PCR. On the basis of the histological and cytological findings and the CD1a expression by FC, a diagnosis of Langerhans cell sarcoma (LCS) was made. A cranial MRI performed to rule out pituitary tumor, and serial bone radiology were normal. The bone marrow biopsy showed no infiltration but the FC analysis found 2% of cells expressing the same immunophenotype as that observed in the tumor. A post-surgical eventration delayed the start of chemotherapy.</p><p id="par0015" class="elsevierStylePara elsevierViewall">One month later the patient consulted by malaise and clinical tonsillitis. Blood analysis showed 50.3<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span><span class="elsevierStyleHsp" style=""></span>L<span class="elsevierStyleSup">−1</span> leukocytes of which 73% were large cells with abundant slightly basophilic and vacuolated cytoplasm, irregular and indented nuclei with immature chromatin and visible nucleoli. Serum LDH was 3951<span class="elsevierStyleHsp" style=""></span>U/L (normal <214). FC showed infiltration of peripheral blood by 80% of cells with identical phenotype as that observed in the abdominal tumor. Electron microscopy of peripheral blood did not detect Birbeck granules but deeply cleaved and convoluted nuclei were seen in tumoral cells. Their cytoplasms had very scarce lysosomes as opposed to other types of histiocytic cells. A diagnosis of leukemization of LCS was done. The patient was treated with idarrubicin-cytarabin-etoposide induction chemotherapy and consolidation with cytarabin, reaching a complete remission and resolution of the galactorrhea and skin lesions. Then, an allogeneic hematopoietic stem cell transplantation was performed. Three months later, blood counts, bone marrow and physical examination were normal. However, 6 months after transplantation the subcutaneous nodules reappeared and the biopsy revealed a diffuse infiltrate with atypical histiocytes, with the same phenotype as that described in the original tumor, confirming a LCS relapse. Bone marrow and peripheral blood were not affected. One year after the diagnosis of LCS, the patient is receiving treatment with CHOEP chemotherapy.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Leukemization of cells of histiocyitc origin is exceptional.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">5–8</span></a> One of the reports on LCS leukemization<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">8</span></a> describes a case of leukemic transformation three months after the diagnosis, an evolution very similar to that observed in our patient, in which blasts appeared in peripheral blood two months after the diagnosis of LCS. In all the described cases of LCS leukemization the response to chemotherapy is usually transient, although in our patient 25 months have elapsed since diagnosis.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Botin T, Navarro JT, Juncà J, Mate JL. Leucemización de sarcoma de células de Langerhans. Med Clin (Barc). 2016;146:418–419.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib0045" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Langerhans cell sarcoma arising from Langerhans cell histiocytosis: a case report" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J.S. 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