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Modern Pathology : An Official Journal... Oct 2017Rosai-Dorfman disease is a histiocytic disorder with a poorly defined pathogenesis. Recent molecular studies have revealed recurrent mutations involving genes in the...
Rosai-Dorfman disease is a histiocytic disorder with a poorly defined pathogenesis. Recent molecular studies have revealed recurrent mutations involving genes in the MAPK/ERK pathway in Langerhans cell histiocytosis and Erdheim-Chester disease. However, cases of Rosai-Dorfman disease have rarely been assessed. We performed next-generation sequencing to assess 134 genes on 21 cases of Rosai-Dorfman disease, including 13 women and 8 men with a median age of 43 years (range, 3-82). In all, 13 had extranodal, 5 had nodal, and 3 had coexistent nodal and extranodal disease. The head and neck region was the most common area involved (n=7). Mutation analysis detected point mutations in 7 (33%) cases, including KRAS (n=4) and MAP2K1 (n=3). No mutations were identified in ARAF, BRAF, PIK3CA, or any other genes assessed. Immunohistochemistry demonstrated p-ERK overexpression in 3 cases, all harboring MAP2K1 mutations. Patients carrying mutated genes were younger (median age, 10 vs 53 years, P=0.0347) with more pediatric patients (4/7 vs 1/14, P=0.0251). The presence of mutations correlated with location being more common in the head and neck region; 6/7 (86%) mutated vs 1/14 (7%) unmutated cases (P=0.0009). All 5 (100%) mutated cases with available staging information had a multifocal presentation, whereas only 3/11 (27%) unmutated patients had multifocal disease (P=0.0256). Treatment information was available in 10 patients, including radical resection (n=4), resection and radiation (n=3), and cladribine-based chemotherapy (n=3). With a median follow-up of 84 months (range, 7-352), 7 remained in clinical remission and 3 had persistent disease. No correlation between mutation status and clinical outcome was noted. In summary, we detected mutually exclusive KRAS and MAP2K1 mutations in one-third of cases of Rosai-Dorfman disease suggesting this subgroup are clonal and involve activation of MAPK/ERK pathway. Our data contribute to the understanding of the biology of Rosai-Dorfman disease and point to potential diagnostic and therapeutic targets.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; DNA Mutational Analysis; Female; Histiocytosis, Sinus; Humans; MAP Kinase Kinase 1; Male; Middle Aged; Mutation; Proto-Oncogene Proteins p21(ras); Young Adult
PubMed: 28664935
DOI: 10.1038/modpathol.2017.55 -
Orphanet Journal of Rare Diseases May 2023Rosai-Dorfman disease (RDD) is a rare form of non-Langerhans cell histiocytic disease. The aim of this study was to review the characteristics of RDD using F-FDG PET/CT... (Review)
Review
BACKGROUND
Rosai-Dorfman disease (RDD) is a rare form of non-Langerhans cell histiocytic disease. The aim of this study was to review the characteristics of RDD using F-FDG PET/CT and determine its efficacy in the disease management.
RESULTS
A total of 28 RDD patients underwent 33 F-FDG PET/CT scans for systematic assessment and follow-up. The common involved sites included the lymph nodes (17, 60.7%), upper respiratory tract (11, 39.3%), and skin (9, 32.1%). Five patients had more lesions detected in PET/CT images than in CT and/or MRI, including inapparent nodules (n = 5) and bone destruction (n = 3). After thorough treatment evaluation using PET/CT, the treatment strategies of 14 patients (14/16, 87.5%) were changed. Five patients underwent PET/CT twice during follow-up and the SUVs were significantly decreased (15.3 ± 3.4 vs. 4.4 ± 1.0, p = 0.02), which demonstrated disease improvement.
CONCLUSIONS
F-FDG PET/CT contributed to displaying the holistic characteristics of RDD, in particular during initial assessment, treatment strategy adjustment, or efficacy evaluation, and could compensate for some disadvantages of CT and MRI images.
Topics: Humans; Histiocytosis, Sinus; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Retrospective Studies; Positron-Emission Tomography
PubMed: 37179326
DOI: 10.1186/s13023-023-02711-8 -
Orphanet Journal of Rare Diseases Oct 2020Rosai-Dorfman disease (RDD) and IgG4-related (IgG4-RD) disease are both rare diseases, but in some cases, RDD mimics IgG4-RD clinically and pathologically. RDD mimicking...
BACKGROUND
Rosai-Dorfman disease (RDD) and IgG4-related (IgG4-RD) disease are both rare diseases, but in some cases, RDD mimics IgG4-RD clinically and pathologically. RDD mimicking IgG4-RDs (RDD mimic IgG4-RD), referring to disease initially diagnosed as IgG4-RD but finally pathologically confirmed to be RDD, is a clinically rare and confusing disease. To summarize the characteristics of this disease, we prospectively analyzed the clinical features, laboratory parameters, pathological characteristics, treatment and prognosis of patients diagnosed with RDD mimic IgG4-RD. Moreover, by analyzing characteristics of RDD mimic IgG4-RD, RDD and IgG4-RD, we further compared the similarities and differences between RDD and IgG4-RD.
RESULTS
7 patients with RDD mimic IgG4-RD were included in this study and all of them had extranodal organ involvement, especially the central nervous system, which occurred in 5 patients (71.4%). Although serum IgG4 level was elevated in 6 cases (1360-54,100 mg/L), overall, it was still lower than that in IgG4-RD patients. Furthermore, we found a new cut-off value of serum IgG4 concentration for differentiating RDD and IgG4-RD with higher specificity. Pathological findings of RDD also showed features resembling IgG4-RD: IgG4-positive plasma cell enrichments were observed in all RDD mimic IgG4-RD patients, and the proportion of IgG4/IgG in tissues was 10-40% in 4 patients and more than 40% in 2 patients. However, none of the RDD mimic IgG4-RD patients or RDD patients displayed obliterative phlebitis or storiform fibrosis. Most of the RDD mimic IgG4-RD patients were treated with glucocorticoids combined with immunosuppressants, and a good prognosis was obtained following treatment.
CONCLUSIONS
RDD has clinical manifestations that mimic IgG4-RD. However, detailed differences in laboratory parameters and pathological characteristics are present between these two diseases. Our study underlines the necessity to rule out RDD while diagnosing IgG4-RD using pathological findings as the identification criteria and provides advice for both differentiating these two diseases and clinical treatment of RDD mimic IgG4-RD.
Topics: Autoimmune Diseases; China; Diagnosis, Differential; Fibrosis; Histiocytosis, Sinus; Humans; Immunoglobulin G; Immunoglobulin G4-Related Disease
PubMed: 33054782
DOI: 10.1186/s13023-020-01567-6 -
Cureus Mar 2020Rosai-Dorfman disease (RDD) is a rare medical condition with bilateral painless lymphadenopathy. We present the case of a young man diagnosed with a very unique...
Rosai-Dorfman disease (RDD) is a rare medical condition with bilateral painless lymphadenopathy. We present the case of a young man diagnosed with a very unique presentation of Rosai-Dorfman disease. A 40-year-old African-American man presented with a firm, non-tender, progressive chest and neck mass appeared three months ago. Imaging of the neck demonstrated an 8.6-cm anterior neck subcutaneous soft tissue mass extending into the anterior mediastinum through the sternum with erosive changes in the sternum and the lesion is abutting the right common carotid artery and innominate vein and surrounds the medial aspect of the clavicles bilaterally. Ultrasound (US)-guided biopsy showed marked polytypic-appearing plasma cell proliferation associated with relatively prominent histiocytes with hemophagocytosis/emperipolesis and focal neutrophils. There were S100+ histiocytes; however, findings were not typical for RDD. As that biopsy was not diagnostic, incisional biopsy with adequate sampling was performed. Surgical pathology demonstrated a very abnormal infiltrate with prominent histiocytes including areas with the features of extranodal RDD. BRAF V600E immunohistochemistry (IHC) was negative. Modified radical neck dissection, proximal sternal resection and superior mediastinal nodal dissection surgery was recommended. However, the patient refused the procedure. Typical manifestations are lymphadenopathy with fever that our patient did not experience. Bone involvement happens in 5-10% of cases. There is not enough data about blood vessel invasion which make our case unique. Treatment plan is still controversial. Clinical monitoring is recommended if the symptoms are tolerable as regression has been reported in many cases (20-50%). Surgery is reserved for patients with vital organ involvement or extra-nodal disease.
PubMed: 32313769
DOI: 10.7759/cureus.7328 -
Medicine Oct 2023Rosai-Dorfman disease is a benign lymphatic tissue proliferative disease with slow growth and is rarely observed in the clinic. Most of these patients present clinically... (Review)
Review
BACKGROUND
Rosai-Dorfman disease is a benign lymphatic tissue proliferative disease with slow growth and is rarely observed in the clinic. Most of these patients present clinically with enlarged lymph nodes. In patients with spinal extranodal Rosai-Dorfman disease, which is even rare than the disease of lymph nodes, patients may experience numbness and weakness in the extremities.
CASE PRESENTATION
We report a 32-year-old male patient with multi-segmental spinal Rosai-Dorfman disease. On admission, his left fingers had been numb for 2 months. Over a 2-month period, the limb numbness progressed from the left to the right hand. The patient underwent resection of the lesion and internal fixation of the C2-C7 spine. The postoperative outcomes were satisfied and no recurrence was observed at 1-year follow-up.
CONCLUSION
Spinal Rosai-Dorfman disease is a relatively rare tumor of which the pathogenesis is still unclear, and most patients have no specific clinical manifestations. Characteristic imaging findings can indicate this disease, however, a definitive diagnosis still depends on a pathological examination. Currently, total surgical resection of the tumor is a relatively effective and preferred treatment.
Topics: Male; Humans; Adult; Histiocytosis, Sinus; Hypesthesia; Lymphadenopathy; Cervical Vertebrae; Neoplasms
PubMed: 37904362
DOI: 10.1097/MD.0000000000035654 -
Journal of Medical Case Reports Mar 2024Rosai-Dorfman disease (RDD) is a form of non-Langerhans cell histiocytosis in which the activated histiocytes of the lymph nodes and other organs begin to accumulate...
BACKGROUND
Rosai-Dorfman disease (RDD) is a form of non-Langerhans cell histiocytosis in which the activated histiocytes of the lymph nodes and other organs begin to accumulate following excessive production. Bilateral, massive, and painless lymphadenopathy are classic presentations. Systemic RDD is already known to be a rare condition, but isolated cutaneous RDD is extremely rare. We presented a rare and unusual presentations of a disease.
CASE PRESENTATION
A 35-year-old Thai female with a 6-month history of a small acne-like lesion that rapidly progressed to 5 cm tumor-like lesions on the face within 3 months. Tissue histology showed a dense dermal infiltration of histiocytes with emperipolesis phenomenon. Immunohistochemistry was positive for S100 protein and CD68 and negative for CD1a. Oral prednisolone (50 mg/day) was initiated with a favorable outcome at the one-month follow-up. However, prednisolone yielded a partial response at 2-month follow-up, leading to application of another modality.
CONCLUSION
Although cutaneous Rosai-Dorfman disease is considered benign and well medical responded disease, patients with atypical presentation and rapid growing lesion may necessitate aggressive multimodal treatment.
Topics: Humans; Female; Adult; Histiocytosis, Sinus; Skin Diseases; Histiocytes; Lymphadenopathy; Prednisolone
PubMed: 38532442
DOI: 10.1186/s13256-024-04410-9 -
International Journal of... Oct 2021Rosai Dorfman disease is a rare histiocytic disorder of over-production of non-Langerhans histiocytes, which typically manifests with massive lymphadenopathy and...
Rosai Dorfman disease is a rare histiocytic disorder of over-production of non-Langerhans histiocytes, which typically manifests with massive lymphadenopathy and sinonasal involvement. We report a rare case of systemic and disseminated craniospinal Rosai Dorfman disease with intraparenchymal and leptomeningeal involvement, but no sinus or dural-based disease. The diagnosis was established by biopsy of a hypothalamic mass. Additionally, UCSF500 Next Generation Sequencing demonstrated a solitary pathogenic alteration affecting the BRAF oncogene, which supports the morphologic and immunohistochemical diagnosis of Rosai-Dorfman disease.
PubMed: 35291666
DOI: 10.18502/ijhoscr.v15i4.7482 -
Modern Pathology : An Official Journal... May 2019In 2008, we presented three cases of ALK-positive histiocytosis as a novel systemic histiocytic proliferation of early infancy with hepatosplenomegaly and dramatic...
In 2008, we presented three cases of ALK-positive histiocytosis as a novel systemic histiocytic proliferation of early infancy with hepatosplenomegaly and dramatic hematological disturbances. This series of 10 cases (including the original three cases) describes an expanded clinicopathological spectrum and the molecular findings of this histiocytic proliferation. Six patients had disseminated disease: five presented in early infancy with eventual disease resolution, and the sixth presented at 2 years of age and died of intestinal, bone marrow, and brain involvement. The other four patients had localized disease involving nasal skin, foot, breast, and intracranial cavernous sinus - the first three had no recurrence after surgical resection, while the cavernous sinus lesion showed complete resolution with crizotinib therapy. The lesional histiocytes were very large, with irregularly folded nuclei, fine chromatin, and abundant eosinophilic cytoplasm, sometimes with emperipolesis. There could be an increase in foamy histiocytes and Touton giant cells with time, resembling juvenile xanthogranuloma. Immunostaining showed that the histiocytes were positive for ALK, histiocytic markers (CD68, CD163) and variably S100, while being negative for CD1a, CD207, and BRAF-V600E. Next-generation sequencing-based anchored multiplex PCR (Archer® FusionPlex®) performed in six cases identified KIF5B-ALK gene fusion in five and COL1A2-ALK fusion in one. There was no correlation of gene fusion type with disease localization or dissemination. The clinicopathological spectrum of ALK-positive histiocytosis is broader than originally described, and this entity is characterized by frequent presence of KIF5B-ALK gene fusion. We recommend that every unusual histiocytic proliferative disorder, especially disseminated lesions, be tested for ALK expression because of the potential efficacy of ALK inhibitor therapy in unresectable or disseminated disease.
Topics: Adolescent; Adult; Cell Proliferation; Child, Preschool; Crizotinib; Female; Gene Fusion; Genetic Predisposition to Disease; Histiocytes; Histiocytosis; Hong Kong; Humans; Infant; Infant, Newborn; Male; Oncogene Proteins, Fusion; Phenotype; Protein Kinase Inhibitors; Singapore; Treatment Outcome; Victoria
PubMed: 30573850
DOI: 10.1038/s41379-018-0168-6 -
Actas Dermo-sifiliograficas Jun 2017
Topics: Adult; Facial Dermatoses; Histiocytosis, Sinus; Humans; Immunosuppressive Agents; Lymphocytes; Male; Methotrexate
PubMed: 28109522
DOI: 10.1016/j.ad.2016.10.018 -
BMC Cancer Feb 2019Langerhans cell histiocytosis (LCH) is a rare clonal disease, characterized by hyperproliferation of Langerhans cells. It may rarely involve the thyroid gland. Its... (Review)
Review
BACKGROUND
Langerhans cell histiocytosis (LCH) is a rare clonal disease, characterized by hyperproliferation of Langerhans cells. It may rarely involve the thyroid gland. Its association with papillary thyroid carcinoma (PTC) is extremely rare; with only few case reports available in the English literature. BRAF mutations are implicated in the development of papillary thyroid carcinoma, and have also been identified in Langerhans cell histiocytosis.
CASE PRESENTATION
Here we present a rare case of a 36-year-old Indonesian female patient with dysphagia associated with neck mass which was complicated by skin sinus formation. The diagnosis of PTC was rendered on fine needle aspiration (FNA). Debulking thyroidectomy revealed co-existeence of PTC and LCH. On subsequent molecular testing, BRAF V600E and V600K mutations were detected in tissues macrodissected from both lesions, respectively. To the best of our knowledge, this case is the first case to report two different BRAF mutations in tissues of a Langerhans cell histiocytosis and a papillary thyroid carcinoma co-existing in the thyroid gland. The patient received chemotherapy of etoposide combined with prednisone. At the most recent follow-up, the patient is in a stable clinical condition.
CONCLUSIONS
The coexistence of a PTC with LCH harboring BRAF mutation may suggest etiologic relation between the two conditions that involves the BRAF gene. Clinically, it may suggest an aggressive, locally advanced thyroid cancer, an impression that may reflect on the selected surgical management, chemotherapy and BRAF mutation-targeting therapy to these patients.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cell Proliferation; Cytoreduction Surgical Procedures; Deglutition Disorders; Etoposide; Female; Histiocytosis, Langerhans-Cell; Humans; Mutation; Prednisone; Proto-Oncogene Proteins B-raf; Thyroid Cancer, Papillary; Thyroid Gland; Thyroidectomy
PubMed: 30795755
DOI: 10.1186/s12885-019-5372-3