Kikuchi-fujimoto disease in the United States: three case reports and review of the literature [corrected].

Kikuchi-Fujimoto Disease (KFD), also known as histiocytic necrotizing lymphadenitis [corrected], is a benign, self-limiting disease that manifests primarily as cervical lymphadenopathy but may include low-grade fever, headache, and fatigue. There is a higher incidence of KFD in women aged 20-35 years and in Asian populations. A PubMed search revealed 590 articles that described KFD. Of these, 22 cases have been fully described in the United States. Ten of the 22 (45%) patients were male and 12 (55%) were female, with 20% Caucasian, 20% Asian American, and the remaining 60% of other ethnic backgrounds. In this study, we describe an additional 3 cases of KFD and discuss the diagnosis, pathology, and management of KFD.

Follicular lymphoma: current management and future directions.

BACKGROUND: Follicular lymphomas (FLs) are a heterogeneous group of lymphomas. No standard of care exists, and the management of these patients is highly individualized. METHODS: After reviewing the scientific literature pertaining to the prognosis and management of FLs, we describe recent developments in treatment and discuss future trends in the care of patients with this disease. RESULTS: With the exception of a subset of patients with limited-stage FL treated with radiation therapy, no curative treatment exists for the majority of patients with FL. The decision on when to start treatment is based on the presence of symptoms, bulky disease, or abnormalities in hematologic parameters that can be attributed to FL. Prognostic scoring systems such as the Follicular Lymphoma International Prognostic Index help in assessing prognosis but do not contribute to the decision on when to start treatment. There are numerous effective chemotherapeutic regimens for the treatment of advanced-stage FL, but none show a definitive improvement in overall survival. Maintenance and consolidation regimens have also been shown to be effective treatments of FL, with significant improvements in progression-free survival and possibly overall survival. CONCLUSIONS: Newer prognostic tests are in development that may help to guide the decision on which patients may benefit from early treatment. In addition, newer targeted agents that may improve on existing outcomes with less toxicity are currently being evaluated.

Primary cutaneous B-cell lymphomas: recent advances in diagnosis and management.

BACKGROUND: Primary cutaneous B-cell lymphoma (PCBCL) is a heterogeneous group of rare clonal B-cell lymphoproliferative disorders with distinct clinicopathologic features from more common nodal B-cell lymphomas. METHODS: We performed a systematic review of the relevant literature in the MEDLINE database and analyzed laboratory and clinical data. This review discusses the three most common types of PCBCL: primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle-center lymphoma (PCFCL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT). RESULTS: Skin biopsies with histology, immunohistochemistry, and molecular clonality studies are essential for a correct diagnosis of cutaneous B-cell lymphoma. Comprehensive lymphoma staging with laboratory and imaging studies and bone marrow aspiration and biopsy are important for determining the prognosis and differentiation of PCBCL from secondary skin involvement with systemic B-cell lymphomas. PCMZL and PCFCL are low-grade PCBCLs, with an estimated 5-year disease-specific survival rate of greater than 95%. Surgical excision or focal radiation therapy is sufficient to control stages T1 and T2 disease. Rituximab monotherapy is frequently used for patients with stage T3 disease. PCDLBCL, LT is an intermediate-grade B-cell lymphoma, with a 5-year disease-specific survival rate of approximately 50%. An anthracycline-based chemotherapy regimen with rituximab is usually required as initial therapy to improve outcomes. CONCLUSIONS: In less than a decade, significant progress has been made in our understanding of PCBCL. Novel classification, staging, and prognostic systems have resulted in more accurate diagnosis and prognosis. Although no randomized prospective studies have been conducted in PCBCL, therapies derived from systemic B-cell lymphomas have shown promising results.

Cutaneous manifestations in CMML: Indication of disease acceleration or transformation to AML and review of the literature.

Our retrospective analysis explored the role of leukemia cutis (LC) in disease progression of chronic myelomonocytic leukemia (CMML). Of 108 patients with CMML, 11 patients (10.2%) had LC including its equivalent (2 patients). Four of these patients developed acute myeloid leukemia (AML) within 0-4 months. The remaining 7 patients demonstrated increased monocytes (<20% blasts), with 3 demonstrating extramedullary involvement. Overall survival from LC to disease progression was 7.8 months. Overall survival from diagnosis to the last follow-up in patients with LC was 28.2 months, shorter than patients without LC (44 months). LC and its equivalent could predict disease progression to AML.

Nonnecrobiotic necrobiotic xanthogranuloma as an initial manifestation of paraproteinemia and small lymphocytic lymphoma in a patient with Sjögren syndrome.

We report a unique case of periocular nonnecrobiotic necrobiotic xanthogranuloma in a 52-year-old white woman with Sjögren syndrome who was subsequently found to have an immunoglobulin G paraproteinemia and coexisting small lymphocytic lymphoma. Therapy with fludarabine, cytoxan, and rituximab (FCR) resulted in a dramatic resolution of her sicca symptoms and periocular xanthogranulomas. This case further illustrates the association of hematolymphoid disorders with cutaneous xanthogranulomatous disease and the importance of additional appropriate laboratory and radiologic investigation for the accurate diagnosis of an underlying malignancy.

A comparative analysis of molecular genetic and conventional cytogenetic detection of diagnostically important translocations in more than 400 cases of acute leukemia, highlighting the frequency of false-negative conventional cytogenetics.

In this study, we correlated the results of concurrent molecular and cytogenetic detection of entity-defining translocations in adults with acute leukemia to determine the frequency of cryptic translocations missed by conventional cytogenetics (CC) and of recurrent, prognostically relevant translocations not detectable by multiplex reverse transcriptase-polymerase chain reaction (MRP). During a 5.5-year period, 442 diagnostic acute leukemia specimens were submitted for MRP-based detection of 7 common recurrent translocations: t(8;21), t(15;17), inv(16), t(9;22), t(12;21), t(4;11), and t(1;19), with a detection rate of 15.2% (67/442). CC was performed in 330 (74.7%) of 442 cases. In 7 of these 330 cases, CC missed the translocation detected by MRP. In 50 additional cases, CC revealed 1 of the MRP-detectable translocations (all were also MRP positive), yielding a false-negative rate of 12% (7/57) for the CC assay. The remaining 140 of 190 cases with clonal cytogenetic changes harbored abnormalities that were not targeted by the MRP assay, including 8 that define specific acute myeloid leukemia entities. This study revealed the frequent occurrence of false-negative, entity-defining CC analysis and highlighted the complementary nature of MRP and CC approaches in detecting genetic abnormalities in acute leukemia.

Mixed phenotype acute leukemia with t(11;19)(q23;p13.3)/ MLL-MLLT1(ENL), B/T-lymphoid type: A first case report.

The majority of cases of acute leukemia belong to a specific lineage origin, either lymphoid or myeloid, and therefore are classified as acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML), based on morphologic features and cytochemical and immunophenotypic profile of the blast cells. A minority of acute leukemias however, show no clear evidence of differentiation along a single lineage. These are now classified under acute leukemias of ambiguous lineage by the most recent WHO classification and account for <4% of all cases of acute leukemia [1]. They include leukemias with no lineage specific antigens (acute undifferentiated leukemias) and those with blasts that express antigens of more than one lineage to such degree that it is not possible to assign the leukemia to any one particular lineage with certainty (mixed phenotype acute leukemias). The latter can either be leukemias with two distinct populations of blasts, each expressing antigens of a different lineage (historically referred to as "bilineal" leukemias) or a single blast population expressing antigens of multiple lineages (historically referred to as "biphenotypic" acute leukemias) [2]. Acute leukemias of ambiguous lineage may harbor a variety of genetic lesions. Those with t(9;22)(q34;q11) or translocations associated with mixed lineage leukemias (MLL) gene, i.e., t(11;V)(q23;V), occur frequently enough and are associated with distinct features, that are considered as separate entities according to the recent WHO classification. Co-expression of myeloid and B-lymphoid antigens is most common in mixed phenotype acute leukemia (MPAL), followed by co-expression of myeloid and T-lymphoid antigens, accounting for 66-70% and 23-24% of MLLs, respectively. Coexpression of B- and T-lineage associated antigens or antigens of all three lineages is exceedingly rare, accounting for <5% of MLLs [3,4]. The requirements for assigning more than one lineage to a single blast population has been established by current WHO classification [1].

Hyaline-vascular castleman disease: a rare cause of solitary subcutaneous soft tissue mass.

Castleman disease (CD) is a rare lymphoproliferative disorder that primarily affects mediastinal, retroperitoneal, and cervical lymph nodes. Clinically, these lesions occur as a localized (unicentric) or less frequently as a systemic (multicentric) disease. Two main distinct histologic variants are recognized, the more common hyaline-vascular (HV) type and the plasma cell (PC) type. Extranodal Castleman disease, HV type (HVCD) is even less common. We describe a case of subcutaneous HVCD in a 57-year-old woman with a palpable chest mass and without systemic symptoms. Although the histologic findings are similar to those of HVCD in lymph nodes and other sites, a plethora of differential diagnosis is raised particularly with the more commonly occurring lymphoproliferative lesions in this location. This is one of the few bona fide cases of HVCD in subcutaneous location published to date. A review of the literature with an emphasis on pathogenesis of the disease subtypes is presented.

Splenomegaly with sea-blue histiocytosis, dyslipidemia, and nephropathy in a patient with lecithin-cholesterol acyltransferase deficiency: a clinicopathologic correlation.

A 31-year-old man with no significant medical history presented with a 5-day history of progressive left upper quadrant abdominal pain. Physical examination revealed a tender guarded abdomen, no icterus, and bilateral corneal "arcus senilis"-like changes. Laboratory workup showed a mild normocytic, normochromic anemia; and target cells were seen in the peripheral blood smear. Serum was turbid; and the lipid profile showed elevated total cholesterol, low high-density lipoprotein cholesterol, and elevated triglycerides. Urinalysis revealed nephrotic range proteinuria with microhematuria. An abdominal computed tomographic scan demonstrated a homogeneously enlarged spleen. The patient was discharged after symptomatic treatment to be followed as an ambulatory patient. Several days later, he returned with severe left upper quadrant pain and was admitted to the surgical service for further evaluation. A splenectomy was performed for a suspected splenic lymphoma. Upon gross examination, spleen was moderately enlarged, weighing 780 g. Sectioning revealed a beefy red cut surface without gross lesions. Wright-Giemsa-stained touch imprints showed many sea-blue histiocytes. A renal biopsy was also performed, demonstrating focal segmental glomerular sclerosis and mesangial expansion with extramembranous and intramembranous deposition of lipids. In the absence of hematologic malignancy and in light of the abnormal lipid profile, a disorder of lipid metabolism was suspected. Histologic and ultrastructural findings in the kidney and spleen raised the likelihood of lecithin-cholesterol acyltransferase (LCAT) deficiency, which was confirmed by the markedly decreased serum LCAT activity and serum LCAT mass. We describe a case with the triad of splenomegaly with sea-blue histiocytes, nephropathy, and dyslipidemia in a patient with LCAT deficiency.

Successful use of the anti-CD25 antibody daclizumab in an adult patient with hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and severe inflammatory disorder marked by abnormal cytotoxic T and natural killer cell activity, resulting in impaired clearance of pathogen, excessive cytokine production, and continued immune system activation. Soluble IL-2 receptor (sIL-2R or sCD25) is typically elevated in HLH and can serve as a marker of disease activity, although its role in the pathophysiology of the disease is unclear. Here we present a case of an adult patient with steroid-dependent HLH who was treated successfully with daclizumab, a monoclonal anti-CD25 antibody, allowing successful withdrawal of steroid therapy without an increase in symptoms.