Concurrent Langerhans Cell Histiocytosis Research Articles

A case of langerhans cell histiocytosis associated with mantle cell lymphoma

Langerhans Cell Histiocytosis (LCH), which is caused by neoplastic clonal proliferation of Langerhans cells, may be associated with various malignant neoplasms, especially lymphomas, in rare cases. In literature some studies observed an unexpected number of second malignancies, both prior to and after the diagnosis of MCL. Here, we report a case with concurrent LCH and mantle cell lymphoma (MCL) in a same lymph node. To the best of our knowledge, this is the second reported case of LCH associated with mantle cell lymphoma in a lymph node.

Occult Langerhans Cell Histiocytosis Presenting with Papillary Thyroid Carcinoma, a Thickened Pituitary Stalk and Diabetes Insipidus.

Etiologies of a thickened stalk include inflammatory, neoplastic, and idiopathic origins, and the underlying diagnosis may remain occult. We report a patient with a thickened pituitary stalk (TPS) and papillary thyroid carcinoma (PTC) whose diagnosis remained obscure until a skin lesion appeared. The patient presented with PTC, status postthyroidectomy, and I131 therapy. PTC molecular testing revealed BRAF mutant (V600E, GTC>GAG). She had a 5-year history of polyuria/polydipsia. Overnight dehydration study confirmed diabetes insipidus (DI). MRI revealed TPS with loss of the posterior pituitary bright spot. Evaluation showed hypogonadotropic hypogonadism and low IGF-1. Chest X-ray and ACE levels were normal. Radiographs to evaluate for extrapituitary sites of Langerhans Cell Histiocytosis (LCH) were unremarkable. Germinoma studies were negative: normal serum and CSF beta-hCG, alpha-fetoprotein, and CEA. Three years later, the patient developed vulvar labial lesions followed by inguinal region skin lesions, biopsy of which revealed LCH. Reanalysis of thyroid pathology was consistent with concurrent LCH, PTC, and Hashimoto's thyroiditis within the thyroid. This case illustrates that one must be vigilant for extrapituitary manifestations of systemic diseases to diagnose the etiology of TPS. An activating mutation of the protooncogene BRAF is a potential unifying etiology of both PTC and LCH.

Classical hodgkin lymphoma (nodular sclerosis type) associated with langerhans cell histiocytosis: a case report on fine-needle aspiration cytologic features

Langerhans cell histiocytosis (LCH) can be associated with a variety of malignant neoplasms, the most common being malignant lymphoma, especially Hodgkin lymphoma (HL). In the present report we describe the fine needle aspiration (FNA) cytologic features of a case with concurrent LCH and HL in a lymph node. A 20-year-old man presented with an enlarged left upper cervical lymph node. FNA smears from the swelling revealed numerous CD1a+ and S-100+ Langerhans histiocytes (LCs) along with many eosinophils, neutrophils, and lymphocytes; there were also large atypical cells with enlarged nuclei having prominent nucleoli. The cytodiagnosis was LCH and the possibility of association with or trans-differentiation into a lymphoma was suggested. The histopathological diagnosis of the excised lymph node was classical Hodgkin lymphoma-nodular sclerosis type (CHL-NS) with LCH. The lacunar type Reed-Sternberg (RS) cells were positive for CD30 and CD15 while the LCs were positive for CD1a and S-100 protein. PET/CT imaging of vertex to mid-thigh demonstrated hypermetabolic lymph nodes in the neck, abdomen, thorax and pelvis as well as pulmonary nodules and a splenic mass. The patient received courses of chemotherapy and two years later, the enhanced CT of neck, chest, abdomen and pelvis revealed regressive course of the disease.

A case of Langerhans cell histiocytosis following acute basophilic leukemia

Dear Editor, Langerhans cell histiocytosis (LCH) is a class of histiocytic cell neoplasm with a clonal neoplastic proliferation of Langerhans-type cells that express CD1a, langerin, and S100 protein and show evidence of Birbeck granules by ultrastructural examination [1]. Concurrent LCH and malignancy have been reported occasionally. LCH occurred before or after malignancies including acute lymphoblastic leukemia, acute myeloid leukemia, and several solid tumors such as malignant lymphoma, retinoblastoma, lung carcinoma, ependymoma, hepatocellular carcinoma, Askin tumor, etc. [2–5]. We present the case of a 38-year-old patient who was diagnosed with LCH following acute basophilic leukemia (ABL). A 38-year-old male presented to the emergency department with a 2-month history of indigestion, nausea, and easy fatigue. Complete blood count with differential showed a white blood cell count of 13,500/μL with 13 % blasts and 14 % basophils, 8.4 g/dL hemoglobin, and a platelet count of 110,000/μL. Hepatosplenomegaly and multiple lymphadenopathies were noted. Bone marrow (BM) aspirates showed 15.6 % leukemic blasts and 11.6 % basophils. Since marked dilution of BM aspirate specimens, the proportion of blasts and basophiles were inaccurate. However, the BM cellularity was approximately 100 % with leukemic blasts. The blasts were of medium-to-large size, had round or cleaved nuclei, contained one or two nucleoli, and a had small amount of bluish cytoplasm. Some blasts had basophilic granules (Fig. 1). Flow cytometric analysis confirmed the presence of the surface markers CD34, CD13, CD33, CD117, and CD65. The blasts showed negative reaction for myeloperoxidase, periodic acid stain, and nonspecific esterase but metachromatic positivity after staining with toluidine blue. Electron microscopy confirmed the presence of basophilic granules in blasts (Fig. 1). The karyotype analysis demonstrated trisomy 16 (47,XY,+16[3]/46,XY[17]). The patient was diagnosed with ABL and received induction chemotherapy. Three months after induction chemotherapy, multiple erythematous indurated patches were observed on the left lower abdomen. Skin biopsy showed evidence of diffuse neutrophilic infiltration with papillary dermal edema and eczematous lesions, without evidence of cancer or fungal infection. Follow-up of BM studies revealed a normocellular marrow with 4.0 % blasts. However, marked increase of histiocytic cells, including immature forms, was noted. The histiocytic cells were clustered in a nodular pattern on the BM clot section. They were of medium-to-large size, with grooved or lobulated nuclei, inconspicuous nucleoli, and moderate amount of homogeneous pinkish cytoplasm. The histiocytic cells were positive for CD1a, S100, and CD68 marker proteins by immunohistochemistry staining (Fig. 2). Based on the morphology and immunohistochemical staining profiles, the patient was diagnosed with BM involvement of LCH. However, a primary lesion of LCH was not found. The patient underwent haploidentical BM transplantation; however, his clinical course continued to deteriorate with systemic fungal infection, necrotizing pneumonia, and hemodynamic instability. Despite aggressive treatment, the patient expired 7 months after diagnosis of ABL. T.-D. Jeong : S. Jang (*) :C.-J. Park :H.-S. Chi Department of Laboratory Medicine, College of Medicine, University of Ulsan and Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, South Korea e-mail: ssjang@amc.seoul.kr

Co-occurrence of Langerhans cell histiocytosis and Rosai–Dorfman disease: possible relationship of two histiocytic disorders in rare cases

Rosai–Dorfman disease and Langerhans cell histiocytosis are both disorders of accessory immune cells. Two cases have been previously reported of concurrent Langerhans cell histiocytosis and Rosai–Dorfman disease. In this report, we characterize the findings and selected molecular studies in nine additional cases. Histology was reviewed. Immunohistochemical stains were performed on all cases in which slides or blocks were available. A combination of CD1a, S-100, CD3, CD20, langerin, CD68, CD163, CD21, CD35 and CD123 immunohistochemical stains were performed. High-resolution array comparative genomic hybridization was performed on six samples from five cases. In these cases, seven were female and two male, with an average age of 25 years (15 months−59 years). A majority of the cases were identified in lymph node. Areas of Langerhans cell histiocytosis had a typical appearance with the existence of bland ‘coffee-bean’ nuclei, clear cytoplasm and associated eosinophils. The immunophenotype was typical, including expression of CD1a, S100, CD68 and langerin. In areas of Rosai–Dorfman disease, there was emperipolesis seen in all cases. Cells were intermediate-large in size with large round nuclei and ample clear or pale cytoplasm. The lesional cells were positive for S100, CD68, CD163, without expression of langerin or CD1a. Array comparative genomic hybridization showed gains and/or losses in four of the six samples. One case showed no gains or losses and one additional case showed gains and losses in the Langerhans cell histiocytosis, while no abnormalities were discovered in the Rosai–Dorfman disease component. These findings are comparable to those seen in previous studies of Langerhans cell histiocytosis. We report the clinical and pathologic findings of the combination of Langerhans cell histiocytosis and Rosai–Dorfman disease. Furthermore, we suggest on the basis of evidence from our cases that, when simultaneous, the two entities may be pathophysiologically related.

Concurrent Langerhans Cell Histiocytosis and B-Lineage Lymphoid Proliferation in the Bone Marrow

We present three cases of concurrent Langerhans cell histiocytosis (LCH) and B-lineage lymphoid cell infiltrations and/or nodules in the bone marrow. The first patient was a 25-month-old boy who presented with LCH on the right shoulder and multiple osteolytic lesions. Bone marrow biopsy showed the presence of LCH and two large lymphoid nodules of B-lineage, which were located in the paratrabecular region. Both LCH and the lymphoid nodules resolved after treatment with prednisone, vinblastine, methotrexate, and cyclophosphamide. The second patient was a 7-month-old girl who presented with LCH in the scalp and bone marrow. In spite of the treatment, a follow-up bone marrow analysis performed after 16 months showed LCH and increased B-lineage lymphoid cells in the interstitial area. The third patient was a 26-month-old girl, and imaging studies revealed reddish skin lesions and multiple osteolytic lesions. Skin biopsy and bone marrow biopsy did not show the presence of LCH; however, we initiated the treatment on the basis of the results of imaging studies. The follow-up study after 6 months showed the presence of LCH and large, patchy infiltration of B-lymphoid cells. We report three rare cases of concurrent bone marrow involvement of LCH and B-lineage lymphoid proliferation, which strongly suggest lymphoid malignancy. Further, clonal changes should be studied to elucidate the common pathogenic mechanism between the two diseases.

Concurrent Langerhans cell histiocytosis and myelodysplasia in children

Background Langerhans cell histiocytosis (LCH) is characterized by the proliferation of abnormal histiocytes (Langerhans cells), whose origin as a reactive process or a neoplastic disorder is still poorly understood. Although LCH has been recorded as being associated with malignant neoplasms, concurrence of LCH and myelodysplastic syndrome has not been reported so far. Procedure We report on four children aged 23, 25, 26, and 53 months with multisystem LCH with organ dysfunction (bone marrow and liver) whose bone marrow pictures, taken at diagnosis, revealed the presence of myelodysplastic abnormalities (RA, RAEB, RAEB-t). Results We suggest that the commonly used expression of “organ dysfunction,” which refers to clinical and functional alterations, could be explained by a myelodysplastic-like disorder. Conclusions The contemporary presence of both events may provide a better understanding of the pathogenesis of LCH, especially in young children with multisystem disease and organ dysfunction, who are known to have a very poor outcome. Med. Pediatr. Oncol. 35:421–425, 2000. © 2000 Wiley-Liss, Inc.