Sujata Gaitonde

Multifocal, extranodal sinus histiocytosis with massive lymphadenopathy: An overview

CONTEXT This article provides an overview of the major pathologic manifestations of sinus histiocytosis with massive lymphadenopathy, including patient characteristics and current knowledge about its pathogenesis, with an emphasis on multifocal and extranodal presentation. Sinus histiocytosis with massive lymphadenopathy is a rare, nonneoplastic, idiopathic, proliferative histiocytic disorder; recognition of this disorder is important to avoid misinterpretation and subsequent unnecessary treatment. This is especially true for primary extranodal manifestation of this rare disorder. Although accurate diagnosis of this entity requires a correlation of clinical, radiologic, laboratory, and pathologic studies in most cases, it remains a disorder primarily defined by its histopathologic features and pathologic manifestations, which are key to the diagnosis. OBJECTIVE To summarize the scientific literature, provide a concise review, and emphasize the diagnostic histopathologic features of extranodal sinus histiocytosis with massive lymphadenopathy. DATA SOURCES A comprehensive literature review was undertaken to summarize the clinical and pathologic features of this disorder. CONCLUSIONS Sinus histiocytosis with massive lymphadenopathy is characterized by a rare, acquired, nonmalignant proliferation of distinctive histiocytes that present with lymphadenopathy or extranodal disease, primarily in children and young adults. It exhibits a broad range of clinical presentations, thus eliciting a wide differential diagnosis. The diverse clinical manifestations and frequent association with subtle or severe immunologic abnormalities suggest an immune-mediated cause. Additional studies are needed to characterize the interplay between death receptors and cytotoxic mediators and to further elucidate the loss of immune hemostasis that may underlie idiopathic histiocytic proliferations such as this.

Effects of extensive splenomegaly in patients with myelofibrosis undergoing a reduced intensity allogeneic stem cell transplantation

Changes in spleen size postallogeneic haematopoietic stem cell transplantation (HSCT) in patients with primary myelofibrosis have been poorly characterized. We analysed 10 patients with myelofibrosis and splenomegaly following a reduced‐intensity allogeneic HSCT. All patients fully engrafted donor cells including five patients with extensive splenomegaly. Extensive splenomegaly was associated with a prolonged time to neutrophil and platelet recovery. In all 10 patients, a progressive reduction of splenomegaly was documented within 12 months post‐transplant and paralleled the reduction of marrow fibrosis. These findings suggest that myelofibrosis patients with extensive splenomegaly may proceed with allogeneic HSCT without prior splenectomy.

Acute myelogenous leukemia with t(6;9)(p23;q34) and marrow basophilia: an overview.

Acute myelogenous leukemia (AML) with chromosomal translocation (6;9)(p23;q34) is a rare disease with poor prognosis and distinct clinical and morphologic features. t(6;9) results in a chimeric fusion gene between DEK (6p23) and CAN/NUP214 (9q34). FLT3-ITD mutation is one of the most frequent mutations in AML and correlates with poor clinical outcome. Prevalence of FLT3-ITD is as high as 70% among patients with t(6;9) AML, and patients with t(6;9) AML and FLT3-ITD mutations usually have higher white blood cell counts, higher bone marrow blasts, and significantly lower rates of complete remission. t(6;9) is most commonly associated with AML-FAB-M2 and is considered by some researchers to be a separate disease entity because of its distinct clinical and morphologic features and poor prognostic implication. Distinct morphologic features of this entity include marrow basophilia and myelodysplasia, and immunophenotypically, the blast cells are positive for CD9, CD13, CD33, and HLA-DR; are usually positive for CD45 and CD38; and may be positive for CD15, CD34, and terminal deoxynucleotidyl transferase.

Unique immunologic patterns in fibromyalgia

BackgroundFibromyalgia (FM) is a clinical syndrome characterized by chronic pain and allodynia. The diagnosis of FM has been one of exclusion as a test to confirm the diagnosis is lacking. Recent data highlight the role of the immune system in FM. Aberrant expressions of immune mediators, such as cytokines, have been linked to the pathogenesis and traits of FM. We therefore determined whether cytokine production by immune cells is altered in FM patients by comparing the cellular responses to mitogenic activators of stimulated blood mononuclear cells of a large number of patients with FM to those of healthy matched individuals.MethodsPlasma and peripheral blood mononuclear cells (PBMC) were collected from 110 patients with the clinical diagnosis of FM and 91 healthy donors. Parallel samples of PBMC were cultured overnight in medium alone or in the presence of mitogenic activators; PHA or PMA in combination with ionomycin. The cytokine concentrations of IFN-γ, IL-5, IL-6, IL-8, IL-10, MIP-1β , MCP-1, and MIP1-α in plasma as well as in cultured supernatants were determined using a multiplex immunoassay using bead array technology.ResultsCytokine levels of stimulated PBMC cultures of healthy control subjects were significantly increased as compared to matched non-stimulated PBMC cultures. In contrast, the concentrations of most cytokines were lower in stimulated samples from patients with FM compared to controls. The decreases of cytokine concentrations in patients samples ranged from 1.5-fold for MIP-1β to 10.2-fold for IL-6 in PHA challenges. In PMA challenges, we observed 1.8 to 4-fold decreases in the concentrations of cytokines in patient samples.ConclusionThe cytokine responses to mitogenic activators of PBMC isolated from patients with FM were significantly lower than those of healthy individuals, implying that cell-mediated immunity is impaired in FM patients. This novel cytokine assay reveals unique and valuable immunologic traits, which, when combined with clinical patterns, can offer a diagnostic methodology in FM.

Pulmonary extramedullary hematopoiesis in patients with myelofibrosis undergoing allogeneic stem cell transplantation

We examined the lung function of 11 patients with intermediate/high risk myelofibrosis undergoing allogeneic hematopoietic stem cell transplantation (HSCT). In 3 patients, chest computerized tomography (CT) scans revealed multiple pulmonary nodules with extramedullary hematopoiesis that disappeared

Primary Pancreatic Sinus Histiocytosis With Massive Lymphadenopathy (Rosai-Dorfman Disease): An Unusual Extranodal Manifestation Clinically Simulating Malignancy

Abstract Sinus histiocytosis with massive lymphadenopathy (SHML), also called Rosai-Dorfman disease, is a rare entity. Its etiology and pathogenesis are still essentially unclear. The histologic hallmark of this disease is proliferation of distinctive histiocytes within lymph node sinuses and in extranodal sites. Approximately 23% of patients with SHML, documented in the SHML Registry, presented with disease primarily in extranodal sites, and very few cases of SHML (<1%) involving the gastrointestinal system have been described in the literature. We report an unusual case of primary pancreatic SHML with infiltration of the process into peripancreatic, perinephric, and perisplenic adipose tissue, simulating malignancy.

EBV positivity in primary cutaneous large B-cell lymphoma with immunophenotypic features of leg type: An isolated incidence or something more significant?

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Primary low grade follicular lymphoma of cranial vault mimicking lipoma at presentation.

the whole axilla field. In a recently published systematic review of radiation-induced bullous pemphigoid [4], 27 cases were found. The majority (89%) experienced blistering confined to the irradiated area, and there was no report of mucosal pemphigus. As in this case, most of the reported cases were breast carcinoma (78%). The use of hormonal therapy was reported in five cases. Although a possible correlation between PV and tamoxifen cannot be excluded, there is no reported case of tamoxifen-induced PV without radiotherapy. In the current case, the patient continued the tamoxifen treatment, which did not interfere with the PV recovery. It is unclear how radiation therapy acts as a triggering mechanism to induce PV. Several theories have been proposed. One is that radiotherapy itself changes antigenic properties and induces autoantibody formation through the alteration of the basal membrane with unmasking of the antigen [4,9]. Another possible explanation is that patients who developed PV after radiation may already have circulating low-titer anti-basement membrane antibodies, and the tissue damage through radiotherapy may enhance the deposition of antibodies [4,9]. This may explain the rarity of this radiation-induced side effect. The unusual development of mucosal ulcers after radiotherapy should raise a suspicion of this diagnosis.

Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type, in a Patient with a Constitutional 11q Terminal Deletion Disorder

Background: Most cases of constitutional 11q terminal deletion disorder are children. Malignancy is a potential concern, as these children reach adulthood. However, since the majority of patients are young, their risk of developing malignancy in adulthood is essentially unknown. Aim: To report the first hematologic malignancy [extranodal natural killer (NK)/T-cell lymphoma, nasal type] arising in the trachea of a patient with constitutional 11q terminal deletion disorder. Our patient is the oldest patient reported in the literature. It is of note that this cytogenetic abnormality has not been described as a recurring abnormality in extranodal NK/T-cell lymphoma. Case Report: A 36-year-old male with congenital psychomotor retardation was transferred to our hospital. Pathologic evaluation was diagnostic of extranodal NK/T-cell lymphoma, nasal type. Staging marrow was negative for lymphoma, but cytogenetic analysis revealed a constitutional deletion of chromosome 11 at band q23 [46,XY,del(11)(q23)(c)]. This abnormality was present in a subsequent bone marrow specimen, along with an acquired abnormality, namely an extra copy of part of the long arm of chromosome 1 translocated to the short arm of chromosome 14. Conclusion: Patients with 11q terminal deletion disorder who reach adulthood may be predisposed to develop neoplasias by virtue of the constitutional deletion.

Conjunctival marginal zone b-cell lymphoma in a 13-year-old child

Ocular adnexal lymphoma is a hematopoietic tumor that arises in the conjunctiva, orbit, eyelid, lacrimal gland, or lacrimal sac. The treatment options in children have not been addressed in the literature. The authors describe a 13-year-old child with ocular adnexal lymphoma and discuss the treatment options.