Sinus histiocytosis with massive lymphadenopathy associated with malignant lymphoma

Sinus histiocytosis with massive lymphadenopathy (SHML) is a distinct benign clinicopathological entity, characterized by painless enlargement of lymph nodes due to sinus histiocytosis. Here, we report a case of SHML with diffuse large B-cell lymphoma. A 64-year-old man was admitted to our hospital because of fever. He presented with enlargement of a small cervical lymph node and huge abdominal paraaortic lymphadenopathy. Cervical lymph node biopsy revealed SHML and bone marrow biopsy showed infiltration of large B-cell lymphoma. Several cases of SHML associated with lymphoma have been documented to date, but this type of simultaneous occurrence has not yet been reported.     

Morphological,ultrastructural, and genetic characterization of an unusual T-cell lymphoma in a patient with sinus histiocytosis with massive lymphadenopathy

Sinus histiocytosis with massive lymphadenopathy (SHML) is a rare benign disease of unknown etiology. It is rarely associated with malignant lymphoma. This report documents the first case of a T-cell lymphoma, which developed in a patient with a 10-year history of SHML. The disease was complicated by hypereosinophilia and massive retroperitoneal lymphadenopathy. Histological examination of a cervical lymph node biopsy during the terminal phase identified a lymphoma composed of cells with morphological plasmacytoid features. Ultrastructurally, the tumor cells showed poorly developed cytoplasm, nuclei with peripheral chromatin clumping, and inconspicuous nucleoli. Cytogenetic studies showed two related clones. On immunohistochemical staining tumor cells were positive with monoclonal antibodies (mAb) CD3 and CD45RO. Southern blotting analysis identified clonal rearrangements in the T-cell receptor (TCR) alpha, beta and gamma genes. Thus, T-cell lineage of the tumor cells was established. In situ hybridization of interleukin-2 (IL-2) and interleukin-5 (IL-5) cDNA probes on tissue sections identified the synthesis of IL-5 by the eosinophils, suggesting an autocrine pathway of eosinophilopoiesis leading to hypereosinophilia in this patient. ©1995 Wiley-Liss, Inc.     

Evidence for a polyclonal nature of the cell infiltrate in sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease)

Summary. Sinus histiocytosis with massive lymphadenopathy (SHML), or Rosai-Dorfman disease, is rare histiocytic disorder of known origin which shares several cell markers with Langerhans'cell histiocytosis (LCH). Although Rosai-Dorfman cells exhibit an aberrant immunophenotype, the indolent clinical course of SHML suggests a reactive disorder rather than a neoplastic process. Until recently this was prevailing opinion concerning LCH also, but recent studies have detected clonal histiocytes in all forms of this latter condition, which is therefore considered a clonal neoplastic disorder with highly variable biologial behaviour. To determine whether the histiocytic proliferation in SHML is polyclonal or clonal we used X-linked polymorphic loci to assess clonality in lesional tissues in two women. Polymorpic regions of the human androgen receptor (HUMARA) locus were amplified by polymerase chain reaction (PCR) analysis. The HUMARA locus was informative in both cases and, following digestion with methylation-sensitive enzymes, typical polyclonal X-inactivation patterns were observed. Since abnormal cells accounted for >90% lesional tissue cells, we conclude that Rosai-Dorfman histiocytic proliferation was polyclonal in the women studied.     

Gamma/delta T-cell hepatosplenic lymphoma: review of the literature, diagnosis by flow cytometry and concomitant autoimmune hemolytic anemia

 Hepatosplenic gamma/delta T-cell lymphoma is recognized as a subset of peripheral T-cell lymphoma in the REAL classification. Histologically these tumors are characterized by a mixture of small to medium-sized atypical lymphocytes. To date, approximately 15 cases of hepatosplenic γδ T-cell lymphoma have been reported. Affected individuals are usually young adults with a median age of 34 years. Patients commonly present with B symptoms and hepatosplenomegaly, but an absence of lymphadenopathy. The disease follows an aggressive course with median survival of 12–14 months and poor response to combination chemotherapy agents. Occasionally, the occurrence of frank blast transformation constitutes a terminal event for the patient. Although cytopenias are relatively common, nonimmune hemolytic anemia has been reported in one patient only. This is the first report of autoimmune hemolytic anemia associated with hepatosplenic γδ T-cell lymphoma. Received: 16 October 1996 / Accepted: 5 December 1996     

Extranodal multifocal Rosai–Dorfman disease: response to 2-chlorodeoxyadenosine treatment

Rosai–Dorfman disease (RDD) or “sinus histiocytosis with massive lymphadenopathy” is a rare lymphoproliferative disorder of unknown etiology. The disease usually presents with painless lymphadenopathy with occasional extranodal involvement in various organs. We report a case of a 36-year-old man with a history of non-Hodgkin lymphoma (NHL), who recently presented with inguinal lymphadenopathy. Following the diagnosis of RDD on lymph node biopsy, he developed symptoms of spinal cord compression due to a mass lesion discovered at T6-7 vertebral level. 18F-Fluorodeoxyglucose (18FDG) positron emission tomography (PET-CT) revealed extensive disease with lung, renal and bone involvement. The patient received a short course of steroid therapy for cord compression findings and 2-chlorodeoxyadenosine (2-CdA) treatment was initiated for long-term disease control. He had a dramatic sustained response to treatment with six courses of 2-CdA. These results suggest that 2-CdA can be an effective treatment of choice and positron emission tomography with 18FDG can be used for determining the extent of disease and for follow-up in RDD.     

Treatment of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): report of a case and literature review

Sinus histiocytosis with massive lymphadenopathy (SHML) is a rare disorder of unknown etiology, usually associated with lymph node enlargement in various superficial or deep sites. It usually shows a prolonged clinical course with occasional exacerbation and remission phases. We describe the long-term follow-up of a case of SHML that showed typical clinical features and in which various therapeutic strategies were attempted. Chemotherapy and alpha-interferon (IFN) were ineffective; surgery was ultimately required with satisfactory results. From an extensive literature review we found different treatment strategies in SHML in the 80 cases published between 1969 and 2000. Spontaneous resolution of adenopathies is frequently observed: 32 out of 40 cases which did not receive chemotherapy, radiotherapy, or surgery were healthy at the time of publication. Radiotherapy alone showed conflicting results: 3 complete remissions (CR) were obtained in the 9 patients treated. Surgical debulking when required was effective--8/9 CR--while chemotherapy showed generally negative results. IFN has been previously employed in only one case. In conclusion, clinical observation without treatment is advisable when possible. In the presence of vital organ compression and/or extranodal localization with important clinical signs, surgical debulking may be necessary. Radiotherapy has shown limited efficacy, while chemotherapy is in general ineffective. More experience is needed to evaluate the role of IFN.     

Detection of human herpesvirus 6 in tissues involved by sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease).

After preliminary serologic data demonstrated elevated antibody titers to human herpesvirus (HHV) 6 in patients with sinus histiocytosis with massive lymphadenopathy (SHML) or Rosai-Dorfman disease, tissues were examined from 9 patients with classical SHML to search for evidence of HHV-6 infection. Involved tissues from 7 of the 9 patients had detectable HHV-6 by in situ hybridization: Tissue from 1 had detectable Epstein-Barr virus genome but no HHV-6 and tissue from another had no detectable HHV-6 or Epstein-Barr virus. These studies suggest that HHV-6 and, to a lesser extent, Epstein-Barr virus may be involved in the etiology of SHML.     

Enthesitis-related arthritis in Kikuchi–Fujimoto disease

Histiocytic necrotizing lymphadenitis or Kikuchi–Fujimoto disease (KFD) is a rare, benign and self-limiting disorder that characteristically presents with fever and cervical lymphadenopathy. Articular manifestations in the form of arthralgias are common but frank arthritis is distinctly rare and dactylitis has not been reported yet. Herein, we describe a young boy who presented with arthritis and dactylitis as the initial manifestation of KFD. A 14-year-old boy presented with a two-week history of fever, generalized lymphadenopathy and asymmetric polyarthritis, enthesitis and dactylitis of the toes. Two years earlier he presented with arthritis of the knee and ankle joints, which lasted for 12 months. However, he had been asymptomatic for one year. Investigations revealed anemia, leukopenia and raised acute phase reactants. Work-up for infectious etiology, systemic lupus erythematosus and leukemia and lymphoma was negative. Excision biopsy of the cervical lymph node confirmed KFD. Fever, lymphadenopathy and leukopenia dissipated with nonsteroidal anti inflammatory drug therapy, but the arthritis persisted. A trial of methotrexate led to the resolution of the arthritis.     

Disseminated form of Rosai-Dorfman disease. A case report

INTRODUCTION: Extranodal involvement in sinus histiocytosis with massive lymphadenpathy (SHML) or Rosai-Dorfman disease is common, seen in 43% of cases. We present a case of disseminated form of SHML with thyroid, renal, bone and lung involvement. EXEGESIS: A 53-year-old woman presented with cervical lymphadenopathy and a large palpable mass in the submandibular area. A thyroid nodule was palpable. Laboratory data showed an increase of the erythrosedimentation rate and a polyclonal hypergammaglobulinemia. Histopathological examination of a cervical lymph node biopsy showed typical features of SHML. CT scan showed enlargement mediastinal lymph node, mass of the right lung and infiltrative mass in the right renal hilium. Radiographs revealed lytic lesions in the right proximal tibia and left patella. Histopathology of a biopsy from the kidney mass and thyroidectomy displayed typical characteristics of SMHL. The patient was treated by steroids with a markedly regression of the kidney and renal masses. CONCLUSION: Multiple extranodal involvement in SMHL is rare, the prognosis may be poor when lesions are massive and involve vital organs.     

Rosai-Dorfman Disease of the Central Nervous System: Report of 6 Cases and Review of the Literature

Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy (SHML), is an uncommon benign idiopathic lymphoproliferative disorder. The histologic hallmark of RDD is the finding of emperipolesis displayed by lesional histiocytes. While RDD most commonly affects lymph nodes, extranodal involvement of multiple organs has been reported, including the central nervous system (CNS). However, CNS involvement in RDD is rare and is not well characterized. As a result, therapeutic approaches to CNS involvement in RDD are not well established. Herein we report 6 cases of RDD with isolated CNS involvement and review the literature on RDD with CNS involvement. One of the presented cases exhibited intramedullary involvement of the spinal cord—a very rare form of RDD with CNS involvement.     

Treatment of angioimmunoblastic lymphadenopathy with dysproteinemia using 2-chlorodeoxyadenosine

 Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is an atypical lympho-proliferative disorder with borderline features that often constitute a diagnostic challenge for the hematopathologist and a therapeutic dilemma for the treating clinician. Morphologically, the involved lymph nodes in this disorder are characterized by abnormal infilitration by immunoblasts and plasma cells, often in clusters or sheets. Regressed follicles may be seen; these are referred to as "burned out." Neovascularization is prominent, and a background of inflammatory cells is usually present. AILD was originally thought to represent an exaggerated autoimmune response. Because of the short median survival of the patients and the demonstration of T-cell clonality, AILD now is considered an aggressive lymphoma and is recognized as a subset of peripheral T-cell lymphoma by the REAL classification. In this article we present a patient with AILD who achieved durable patrial remission after treatment with one cycle of 2-chlorodeoxyadenosine. Received: 16 March 1994 / Accepted: 8 July 1996     

Spontaneous tumor lysis syndrome with resolution of pancytopenia and disappearance of lymphadenopathy in a patient with peripheral T cell lymphoma unspecified

Tumor lysis syndrome is a well-described, serious complication of chemotherapy administered to treat malignancies. However, a very rare event resulting in the spontaneous necrosis of a tumor prior to therapy can also occur, which is termed spontaneous tumor lysis syndrome (STLS). We present a case of a 27-year-old male who presented to the hospital with epistaxis, dyspnea, and cervical lymphadenopathy. Laboratory findings included progressive pancytopenia, hyperuricemia, and acute renal failure. Bone marrow biopsy showed a T cell lymphoid neoplasm that had entirely infiltrated the marrow stroma. The patient was diagnosed with STLS in the setting of a T cell lymphoma with bone marrow infiltration. The patient was immediately treated with a blood transfusion and hemodialysis. After this urgent treatment, the patient’s pancytopenia resolved and the lymphadenopathy disappeared spontaneously. One month post-treatment, the patient’s cervical lymphadenopathy recurred and peripheral T cell lymphoma, not otherwise specified, was confirmed. STLS has previously been reported, however, most known cases of STLS did not show a decreased tumor burden resulting from massive tumor cell death. We present a rare case of STLS with resolution of pancytopenia and disappearance of lymphadenopathy in a patient with peripheral T cell lymphoma not otherwise specified.     

Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) of the pancreas: first case report.

Rosai-Dorfman Disease is a histiocytic proliferative disorder which primarily affects lymph nodes. Extranodal involvement occurs in about one half of the patients and the head and neck area represents the region most commonly involved. We present the case of a 48 year-old female who was found with a pancreatic mass during evaluation for abdominal pain. She underwent a distal pancreatectomy and splenectomy. Her pathology showed sinus histiocytosis with massive lymphadenopathy (SHML) involving the pancreas and lymph nodes and focally the spleen. The histiocytes characteristically contained one or more viable lymphocytes in the cytoplasm. The lymphocytes had penetrated the cytoplasm in a process known as "emperipolesis", where the lymphocytes continued to have free movement in the histiocyte. The histiocytic cells were positive with S-100 protein and CD68. Rosai-Dorfman Disease (SHML) can affect the peripancreatic lymph nodes with possible secondary pancreatic involvement and present as a pancreatic mass.     

Autoimmune Lymphoproliferative Syndrome: Response to Mycophenolate Mofetil and Pyrimethamine/Sulfadoxine in a 5-Year-Old Child

Autoimmune Lymphoproliferative Syndrome (ALPS) is a rare inherited disorder of disrupted lymphocyte homeostasis characterized by chronic splenomegaly and lymphadenopathy of early onset, hypergammaglobulinemia (Ig G and Ig A), autoimmune phenomena, and expanded populations of TCR-α/β+, CD3+, CD4-, CD8-T cells (Fisher et al. Cell 81:935–946; 1995), called double negative T-cells [(DN) T cells]. We discuss a case of ALPS which showed good response to immunosuppressant drug Mycophenolate-Mofetil in combination with Pyrimethamine/Sulfadoxine.     

Spontaneous splenic rupture in two patients with a blastoid variant of mantle cell lymphoma

 Spontaneous rupture of the spleen is a rare complication of hematological malignancies, occurring most commonly in patients with acute leukemia, but it has been documented in chronic leukemias and also in lymphomas. We report two patients with histologically and immunohistochemically confirmed mantle cell lymphoma (MCL) who experienced a spontaneous splenic rupture. An 80-year-old woman and a 51-year-old man had a blastoid variant of MCL and responded poorly to conventional treatment. Both patients recovered after splenectomy. The woman died of progressive lymphoma 2 months later. An allogeneic bone marrow transplantation was performed in the man with a good initial result, but an aggressive relapse was seen only 6 months later and he died of progressive lymphoma. In view of our data, we suggest special caution when MCL is complicated by rapid progression and severe splenomegaly. Although it is a rare phenomenon, the risk of splenic rupture should be kept in mind. Received: 2 September 1996 / Accepted: 16 October 1996     

Multiple M components in two patients with splenic lymphoma with villous lymphocytes

Splenic lymphoma with villous lymphocytes (SLVL) is a rare lymphoproliferative disorder characterized by the presence of typical lymphoid cells with villous projections and monoclonal immunoglobulin (M-Ig) in about 30% of patients. The simultaneous presence of more than one M-Ig in SLVL has not been reported. We present two patients with SLVL, each with three serum M components associated with the presence of rheumatoid factor (RF) and antiphospholipid antibodies (APLA) together with fatal thromboembolic events. Both patients presented with splenomegaly and typical bone marrow cytology with 30–50% infiltration of lymphoid cells that had the characteristics of villous lymphocytes. Immunohistochemistry of bone marrow histology showed CD20++, CD43−/+, CD5−, IgM+, lambda+ and kappa−. In serum, two M-IgMλ components were combined with M-IgGλ in case 1 and with M-IgAλ in case 2. In both cases, M-IgM displayed RF as well as lupus anticoagulant activity and free monoclonal lambda (λ) light chains were present. In addition to M-IgM, in case 1 M-IgG also behaved like an APLA. One patient was splenectomized. Both patients suffered thromboembolic complications and died 3 and 8 months after presentation with signs of massive pulmonary thromboembolism.     

Angiotropic B-cell lymphoma with hemophagocytic syndrome associated with syndrome of inappropriate secretion of antidiuretic hormone

 A case of angiotropic B-cell lymphoma associated with hemophagocytic syndrome (HPS) has been reported. In addition to fever, pancytopenia, hepatosplenomegaly, and lack of lymphadenopathy, unique clinical features, such as syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and pulmonary infarction, were manifested. Both soluble interleukin-2 receptor (sIL-2R) and IL-6 were elevated in the patient's sera in addition to an increase of serum lactate dehydrogenase and ferritin. In contrast, tumor necrosis factor-α and interferon-γ were within normal ranges. Serum antibodies against Epstein-Barr virus and cytomegalovirus showed a past infection pattern. An autopsy examination revealed systemic intravascular proliferation of lymphoma cells with a B-cell phenotype, confirming the diagnosis of angiotropic B-cell lymphoma. Moreover, SIADH was suggested to result from the infiltration of tumor cells into the pituitary gland. Triple association of angiotropic B-cell lymphoma, HPS and SIADH is quite rare. Therefore, the present case seems to be helpful for clarifying the mechanism for HPS of non-Hodgkin's lymphoma with B-cell origin. Received: 22 June 1999 / Accepted: 25 February 2000     

Fatal Mucor pneumonia after treatment with 2-chlorodeoxyadenosine for non-Hodgkin's-lymphoma

 Fungal infections, in addition to bacterial and opportunistic infections such as Pneumocystis carinii pneumonia, may evolve in patients with infectious complications due to iatrogenic immunosuppression. Aside from common Candida and Aspergillus species, rare fungi like Mucor must be considered in patients with neutropenia or prolonged impaired T-cell function. Here we report on a patient with a low grade lymphoma who was treated with 2-chlorodeoxyadenosine because of disease progression. After recovery from Pneumocystis carinii pneumonia he presented again with clinical signs of pneumonia. No pathogen was found on bronchoscopy and he died rapidly. In the lungs a massive necrosis was seen in which nonseptated hyphae identified as Mucor species were demonstrated. Received: 3 January 1996 / Accepted: 29 April 1996     

Multilobated B cell lymphoma (Pinkus variant) with isolated muscular localization in a patient with systemic sclerosis: a case report

 The association of systemic sclerosis (SSc) and non-Hodgkin's lymphoma (NHL) is a rare event whose pathogenesis remains to be clarified. We describe a case of NHL in a patient with SSc, in whom the NHL was particular in terms of clinical presentation (primitive muscle and bone involvement) and histologic type (large multilobated B-cell variant). The lymphoma was clinically aggressive but responded well to therapy. Surveillance for the development of "atypical" NHL is suggested in SSc cases. Received: 21 September 1995 / Accepted: 23 February 1996     

Angioimmunoblastic lymphadenopathy of the colon with malignant transformation

Angioimmunoblastic lymphadenopathy (AILD) is a rare disorder characterized by lymphadenopathy, constitutional symptoms, skin rashes, and a variety of hematologic disorders. Its occurrence in the colon is rare. Late in the disease, immunosuppression occurs, and there is an increased risk of malignant transformation. We present a case of AILD of the colon with eventual transformation into malignant lymphoma.