Extranodal Rosai–Dorfman disease involving the heart: report of two cases

Sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease) is a rare disease that typically occurs in lymph nodes. While many body sites have been reported to be involved in extranodal manifestations of the disease, the cardiovascular system has been largely absent in this literature. We report two cases of Rosai–Dorfman disease that involves the heart. Case 1 was a 40-year-old man with chronic myelomonocytic leukemia who was incidentally noted to have Rosai–Dorfman disease on autopsy after succumbing to respiratory failure in the setting of adult respiratory distress syndrome. Case 2 was a 57-year-old woman known to have Rosai–Dorfman disease involving mediastinal lymph nodes and found to have a right atrial mass on workup for atypical chest pain. Both cases showed a similar histologic picture of large, multinucleated histiocytes with immunoreactivity to S100, emperipolesis, and marked plamacytosis. This study expands our knowledge of organs involved in extranodal Rosai–Dorfman disease.     

累及骨和软骨Rosai–Dorfman病2例报告并文献复习

目的:探讨2例累及骨和软骨的结外罗道(Rosai–Dorfman)病的临床病理特征、诊断及鉴别诊断。方法:复习分别位于右胫骨近端及甲状软骨的2例Rosai–Dorfman病患者的临床和影像学资料,行组织学观察及免疫组织化学分析,并复习相关文献。结果:39岁女性,右胫骨占位及38岁男性,甲状软骨肿物。影像学示前者右胫骨上段溶骨性骨质破坏;CT示后者甲状软骨前实性占位,与甲状软骨界限不清。光镜下前者病变在破碎骨小梁间生长,后者病变包绕并侵犯甲状软骨,并在软骨化骨骨小梁间侵袭性生长。低倍镜下组织细胞显著增生,与浸润的淋巴细胞、浆细胞形成明暗相间的结构,部分组织细胞体积较大,呈多边形或椭圆形;胞浆淡嗜酸性或空亮,泡状核,可见小核仁;部分胞浆内见吞噬完整的淋巴细胞和(或)浆细胞、中性粒细胞等。免疫组织化学标记组织细胞表达S–100蛋白和CD68,不表达CD1a。结论:累及骨和软骨的Rosai–Dorfman病罕见,临床及影像学检查均容易误诊。组织学形态及免疫组织化学检查是确诊的唯一依据。     

Extranodale Rosai-Dorfman-Erkrankung (Sinushistiozytose mit massiver Lymphadenopathie)

Sinus histiocytosis with massive lymphadenopathy (SHML) was described in 1969 by Rosai and Dorfman as an benign disorder of the lymph nodes. Involvement of extranodal sites by SHML may occur as part of a generalized disease involving lymph nodes as well as independently of the lymph node status. The clinical course is mostly benign and indolent, but in rare cases the SHML can cause death. We report 5 cases of extranodal Rosai Dorfman disease (ENSHML). The lesions were localized in the soft tissue of the extremities, the head and the skeleton. Histopathological examination revealed a lymphoplasmacellular infiltration and numerous histiocytes with an eosinophilic cytoplasma and vesicular nuclei with basophilic nucleoli. The histiocytes showed emperipolesis with multiple lymphocytes within the cytoplasm and occasionally phagocytosis of other inflammatory cells. The histiocytes were immunohistochemically positive for S 100 protein and macrophage-specific antibodies, but in paraffin material negative for CD1a. We briefly discuss aspects of differential diagnosis of this lesion, too.     

A lethal intracranial Rosai‐Dorfman disease of the brainstem diagnosed at autopsy

Rosai‐Dorfman disease (RDD) is a benign histiocytic proliferative disorder characterized by the accumulation of histiocytes in lymph nodes and various other organs. RDD seldom involves the central nervous system, and cases of purely intracranial RDD are particularly rare. We report a case of purely intracranial RDD involving the brainstem that was diagnosed at autopsy. A 68‐year‐old woman visited our hospital because of visual disturbances and loss of energy. Magnetic resonance imaging revealed an obscure mass in the brainstem. Despite exhaustive work‐ups, the etiology of the intracranial mass remained unclear. The patient died of respiratory depression, and an autopsy was performed for pathological investigation. Macroscopically, a pink pale mass 2.5 cm in diameter was found in the brainstem, with no attachment to the dura. Histologically, it was composed of histiocytic cells with incorporation of small lymphocytes (emperipolesis). Immunohistochemical staining revealed that the cells were positive for CD68 and S100 and negative for CD1a, consistent with a diagnosis of RDD. Purely intracranial RDD is extremely rare and considered benign. To date, nine cases (including ours) have been reported. To our knowledge, this is the first case of intracranial RDD with autopsy. Although generally considered benign, RDD involving the brainstem might be lethal.     

Case report of Rosai–Dorfman disease

This case report discusses the presentation of Rosai–Dorfman disease in a 4 year old female patient, who presented with bilateral level V lymphadenopathy of the cervical neck. The histopathology demonstrated numerous histiocytes, with characteristic emperipolesis. No granulomas or necrosis were identified. Micro-organisms were not identified on special stains, nor on culture. The patient was under observation and spontaneous remission occurred after six months.     

Intraosseous Rosai‐Dorfman disease diagnosed by touch imprint cytology evaluation: A case series

Sinus histiocytosis with massive lymphadenopathy, also known as Rosai‐Dorfman disease (RDD) is a rare benign disorder that primarily affects the lymph nodes. Localized lymphadenopathy is the most common clinical manifestation of this disorder. However, RDD has been described in several extra‐nodal sites including the head and neck region, soft tissue, skin, upper respiratory tract, gastro‐intestinal tract and central nervous system (CNS). Involvement of the bone is considered very rare, occurring in less than 10% patients. RDD is one of the histiocytoses and the differential diagnosis includes entities such as Langerhans cell histiocytosis and Erdheim‐Chester disease. In the rare intraosseous variant, the clinical and radiologic differential diagnosis is broader and includes neoplasms such as osteosarcoma and Ewing sarcoma. In this report, we describe three cases of extra‐nodal, intraosseous RDD where touch imprint cytology played a crucial role in diagnosis. Two of the cases initially presented with involvement of the head and neck region and later developed intraosseous disease; while the third patient presented with primary bone involvement. The diagnosis was established by core biopsy with touch imprints of the bone lesions. The cytologic samples showed numerous histiocytes, often with neutrophils within their cytoplasm (emperipolesis) in addition to lymphocytes and plasma cells. The diagnosis of RDD was confirmed with appropriate immunohistochemical stains. Our account of these three cases of intraosseous Rosai‐Dorfman disease highlights the role of cytology in the diagnosis of this rare entity.     

SINUS HISTIOCYTOSIS WITH MASSIVE LYMPHADENOPATHY (RO SAI AND DORFMAN) AND SIGNIFICANT SKIN INVOLVEMENT

Clinicopathological features of this female patient described here, showing unusual and extremely marked sinus histiocytosis of lymph nodes with considerable systemic lymphadenopathy, accompanying fever as well as acceleration of erythrocyte sedimentation rate fairly well coincided with the symptoms of "Sinus Histiocytosis With Massive Lymphadenopathy" (Rosai and Dorfman). The onset of the present case was in 1966 when the patient was 10 years of age, and she has been followed-up for over 10 years. While persisting to display active clinical manifestations, immunological abnormality with thymus involution was demonstrated — deterioration of cell-mediated immunity, but with non-remarkable humoral immunological data, except for hypergamma-globulinemia with elevation of IgG. In 1973 lymphadenopathy as well as skin eruption extended over the extremities and abnormalities of hematological and serological nature began to improve and at the present date the patient is uneventful. This is the first recorded case of "Sinus Histiocytosis With Massive Lymphadenopathy" (Rosai and Dorfman) in Japan. Considerable skin involvement in the upper and lower extremities was a significant feature and unique in this case.     

Paediatric histiocytic tumors

The histiocytoses are a diverse collection of uncommon diseases that include accumulations and proliferations of macrophages and dendritic cells. In this review we survey the majority of histiocytic proliferations that affect children. We emphasize the practical diagnostic features, differential diagnosis, and consider new information on Langerhans cell histiocytosis and related lesions. We describe the various non-Langerhans cell histiocytoses, especially the juvenile xanthogranuloma family of lesions including reticulohistiocytoma, Rosai–Dorfman disease, and overlap, combined and sequential histiocytic lesions.     

Benign non-infectious causes of lymphadenopathy: A review of cytomorphology and differential diagnosis

Fine‐needle aspiration (FNA) biopsy is a quick, cost‐effective, and safe diagnostic modality that provides answers to guide treatment and management in patients with lymphadenopathy. In adults and children, there are a range of non‐neoplastic, non‐infectious etiologies for lymphadenopathy. These include reactive lymphoid hyperplasia (RLH), dermatopathic lymphadenitis (DLN), Rosai‐Dorfman disease, Castleman disease, Kimura disease, Kikuchi‐Fujimoto disease, and lymphadenopathy associated with autoimmune and metabolic/storage disease. Other benign nodal entities that may be encountered include lymph node infarction, foreign body reactions, drug reactions, extramedullary hematopoeisis, and benign inclusions. This article reviews the practical role of FNA in the evaluation of these benign, non‐infectious causes of lymphadenopathy and focuses on their cytomorphology and differential diagnosis. Diagn. Cytopathol. 2012; © 2012 Wiley Periodicals, Inc.     

Nodal Langerhans cell histiocytosis with prominent eosinophilic emperipolesis

Multinucleated giant cells of osteoclastic type are known to occur in nodal and extranodal lesions of Langerhans cell histiocytosis (LCH). These giant cells are thought to be derived from phagocytic histiocytes, which correlate with the degree of necrosis in LCH lesions. Emperipolesis commonly seen in Rosai–Dorfman disease is a distinct phenomenon characterized by intact phagocytosed cells in an intracytoplasmic vacuole protected from proteolytic digestion. We present a case of emperipolesis of inflammatory cells especially of eosinophils by multinucleated giant cells of Langhans type in a lymph node involved by LCH—a finding that has not been described previously in the literature. Diagn. Cytopathol. 2015;43:1000–1002. © 2015 Wiley Periodicals, Inc.     

Rectal extranodal Rosai–Dorfman disease diagnosed by EUS‐FNA: A case report and review of the literature

Rosai–Dorfman disease (RDD), also known as “sinus histiocytosis with massive lymphadenopathy,” only rarely involves the gastrointestinal (GI) tract. Therefore, this unusual site of presentation can be challenging for the pathologist. We present a case of RDD manifesting as a rectal submucosal mass associated with rectal bleeding in a 54 year old woman. The diagnosis was made on cytologic preparations obtained through endoscopic ultrasound guided fine needle aspiration (EUS‐FNA) and subsequently confirmed by biopsy. To our knowledge, this is the first time extranodal RDD of the GI tract has been diagnosed by EUS‐FNA. A review of previously published cases of GI RDD is presented to increase awareness of this exceptional presentation. Diagn. Cytopathol. 2015;43:40–44. © 2014 Wiley Periodicals, Inc.     

Sinus histiocytosis with massive lymphadenopathy--a review of seven cases

Sinus histiocytosis with massive lymphadenopathy (SHML) also called as Rosai Dorfman disease is a rare histiocytic proliferative disorder of unknown etiology. Histological features currently define it. Persistent painless lymphadenopathy due to expansion of sinuses infiltrated with benign histiocytes and plasma cells and emperipolesis are the characteristic features of SHML. Our study includes seven cases (5 nodal and 2 extranodal) of SHML over a 5-year period whose slides and blocks were reviewed. IHC was performed on the main lesion, from a panel of S100, CD68, LCA, CD20, CD3, CD30, CD43, bcl2, cytokeratin and epithelial membrane antigen. In our series we have work up available in 7 cases out of which a detailed follow-up is available in 5 patients. Out of these 5 patients, 4 have a stable disease, while one developed histiocytic sarcoma after a gap of four years.     

Erdheim‐Chester disease with prominent pericardial effusion

Erdheim‐Chester disease (ECD) is a rare, non‐Langerhans form of histiocytosis of unknown origin with distinct clinicopathologic and radiographic features. Reports detailing the cytology of ECD are rare. We describe a case of ECD with pericardial effusion. Cytologic examination revealed a hypercellular specimen composed of clusters and singly dispersed foamy macrophages with round nuclei and inconspicuous nucleoli, admixed with lymphocytes, eosinophils, and Touton‐type multinucleated giant cells. Immunostains for CD68 were strongly positive in the foamy macrophages while S100 and CD1a were negative. The presence of foamy histiocytes, multinucleated giant cells, lymphocytes and eosinophils are also features of other systemic histiocytic disorders, including Langerhans cell histiocytosis (LCH), Rosai‐Dorfman disease (RDD) and sarcoidosis. To the best of out knowledge, this is the first report describing the cytological features of ECD in a pericardial effusion. Diagn. Cytopathol. 2014;42:530–534. © 2013 Wiley Periodicals, Inc.     

Sinus histiocytosis with massive lymphadenopathy. A histogenic analysis of histiocytes found in the fourth Japanese case

The present paper deals with immunohistochemical and ultrastructural study of the lymph nodes of sinus histiocytosis with massive lymphadenopathy (Rosai and Dorfman, SHML) of a 12-year-old Japanese boy. This is the fourth case in Japan. Osseous manifestation was also found in the bilateral ulnae. With hallmarks of S-100 protein and interdigitating cytoplasmic extensions, the phagocytizing histiocytes proliferating in the sinuses were considered to be derived mostly from interdigitating cells in the paracortex or T cell dependent area, which have heretofore been regarded as nonphagocytizing. Furthermore, it is most interesting that lymphoid cells bearing thymic cortical cell-antigen (OKT 6) were increasingly recognized in the patient's peripheral blood. These results suggested that SHML is a specialized reactive histiocytosis analogous to histiocytosis X and histiocytic medullary reticulosis.     

Sinus Histiocytosis With Massive Lymphadenopathy A Histogenic Analysis of Histiocytes Found in the Fourth Japanese Case

The present paper deals with immunohistochemical and ultrastructural study of the lymph nodes of sinus histiocytosis with massive lymphadenopathy (Rosai and Dorfman, SHML) of a 12-year-old Japanese boy. This is the fourth case in Japan. Osseous manifestation was also found in the bilateral ulnae. With hallmarks of S-100 protein and interdigitating cytoplasmic extensions, the phagocytizing histiocytes proliferating in the sinuses were considered to be derived mostly from interdigitating cells in the paracortex or T cell dependent area, which have heretofore been regarded as nonphagocytizing. Furthermore, it is most interesting that lymphoid cells bearing thymic cortical cell-antigen (OKT 6) were increasingly recognized in the patient's peripheral blood. These results suggested that SHML is a specialized reactive histiocytosis analogous to histiocytosis X and histiocytic medullary reticulosis.     

Progressive hearing loss associated with a unique cervical node due to a homozygous SLC29A3 mutation: a very mild phenotype

In 2008, SLC29A3 has been implicated in a syndromic form of genodermatosis: H syndrome. The major features encountered in H syndrome are Hearing loss, Hyperglycaemia, Heart anomalies, Hypertrichosis, Hyperpigmentation, Hepatomegaly and Hypogonadism. More recently, SLC29A3 mutations have been described in families presenting syndromes associating generalized histiocytosis to systemic progressive features: severe camptodactyly, hearing loss, hypogonadism, hepatomegaly, heart defects and skin hyperpigmentation. We have identified a homozygous missense SLC29A3 mutation in a patient presenting with only a progressive sensorineural hearing impairment and a single cervical node (Rosai Dorfman). SLC29A3 mutations appear to be involved in a large phenotypic continuum which should prompt physicians to study this gene even in mild clinical presentations.     

Rhinoscleroma associated with Rosai-Dorfman reaction of regional lymph nodes

Rhinoscleroma is an uncommon chronic, destructive infection of the respiratory mucosa caused by Klebsiella rhinoscleromatis. This coccobacillus can be found in the typical histiocytes, the Mikulicz cells . Extranasal and nodal involvement in this disease is rare, but documented. Rosai–Dorfman disease or sinus histiocytosis with massive lymphadenopathy is also a rare, non-hereditary disorder. Bilateral cervical lymphadenopathy with emperipolesis, as the main histological characteristic, is the most common presentation. It can also occur extranodally. We report a case of rhinoscleroma occurring in a 62-year-old woman since 1984, who developed parotid gland and lymph node involvement. The changes in the nasal mucosa and the parotid gland showed chronic inflammation with Mikulicz cells. In the lymph nodes, features characteristic of Rosai–Dorfman disease were seen. Taking into consideration the literature dealing with both of these diseases, we discuss that Rosai–Dorfman disease could be a special type of lymph node reaction and is not necessarily an entity of its own. Therefore, it should be known as Rosai–Dorfman lymph node reaction. Furthermore, there seems to be an interconnection between Rosai–Dorfman disease and rhinoscleroma.     

Role of fine-needle aspiration cytology in breast lymphoma

Lymphomas of the breast are rare and may mimic carcinoma clinically. We investigated the ability of fine-needle aspiration (FNA) biopsy combined with adjunctive flow cytometry (FC), immunofluorescence microscopy (IFM), and immunocytochemistry (ICH) to diagnose and eventually subclassify lymphomas of the breast according to the Revised European American Lymphoma/World Health Organization classification. We retrieved 21 breast aspirates from 19 patients with a cytologic diagnosis of lymphoma or plasmacytoma over a 10-year period (1992-2002), excluding 98 benign intramammary lymph nodes and 1 atypical lymphohistiocytic proliferation (Rosai Dorfman disease). FC was performed in 15/21 aspirates, IFM in 1/21, ICH in 3/21. Histologic follow-up (HF) was obtained for 10 patients, most of them with primary lymphoma. For the remaining nine patients without HF, flow cytometric analysis, comparative morphology, or remission after chemotherapy regimens supported the cytologic diagnosis. Of 19 patients, 11 patients had a secondary lymphoma (SL) and 8 patients had a primary lymphoma (PL). FNA and FC/IFM/ICH classified 7/8 PLs as B-cell lymphomas and 1/8 PLs as plasmacytoma. However, FNA could only subclassify 3 of 8 PLs. FNA and/or FC subclassified accurately 10/11 SLs. All cases were accurately immunophenotyped as B-, T-cell non-Hodgkin's lymphomas or plasmacytoma. World Health Organization classification was achieved in 3/8 PLs (42%) and 10/11 SLs (91%; P = 0.04). Subclassification (which has an impact on long-term management and prognosis) was significantly better in SL, when a previous histologic diagnosis had already been made, when compared to PL, of which 5/8 cases (62.5%) could not be accurately classified.