Rosai-Dorfman disease mimicking cavernous hemangioma: a case report.

A 31-year-old female presented to the clinic with a 2 year history of proptosis of the right eye. She was diagnosed with cavernous hemangioma during her initial ophthalmologic consult and was advised monitoring. However, after a considerable increase in proptosis, she underwent an excision biopsy of the right orbital mass. A diagnosis of Rosai Dorfman disease was made after the histopathology report revealed a fibrosclerotic tissue with histiocytic proliferation showing emperipolesis that is mixed with numerous small lymphocytes and plasma cells. Rosai Dorfman disease is a rare disease presenting with lymphadenopathy and sinus histiocytosis. Orbital involvement can be the principal manifestation with proptosis as the most common presentation. Resection of the orbital lesion helped in the resolution of the mild ophthalmic symptoms but since the disease has other systemic associations, a complete systemic workup should be done to monitor recurrence.

Immunopathology of Kikuchi-Fujimoto disease: A reappraisal using novel immunohistochemistry markers.

AIMS: Kikuchi-Fujimoto disease (KFD) is a self-limited disease characterised by destruction of the lymph node parenchyma. Few studies have assessed the immunohistological features of KFD, and most employed limited antibody panels that lacked many of the novel immunohistochemistry markers currently available. METHODS AND RESULTS: We used immunohistochemistry to reappraise the microanatomical distribution of plasmacytoid dendritic cells (pDCs), follicular helper T cells and cytotoxic T cells, B cells, follicular dendritic cell (FDC) meshworks, and histiocytes in lymph nodes involved by KFD. The study group consisted of 138 KFD patients (89 women; 64.5%) with a median age of 27 years (range, 3-50 years). Cervical lymph nodes were most commonly involved, in 108 (78.3%) patients. The numbers of pDCs were increased, predominantly around and within apoptotic areas and the paracortex, and tapering off within xanthomatous areas. pDCs formed sizeable tight clusters, most notably around apoptotic/necrotic areas. T cells consisted mostly of CD8-positive cells with predominant expression of T-cell receptor-ß. There were notable increases in the numbers of CD8-positive T cells within lymphoid follicles, and their numbers correlated with alterations in FDC meshworks (P < 0.001). The number of follicular helper T cells was decreased within distorted FDC meshworks. CD21 highlighted frequent distortion of FDC meshworks, even in lymph node tissue that was distant from apoptotic/necrotic areas. Distorted FDC meshworks spanned all morphological patterns, and FDC meshwork characteristics (intact; distorted; remnant/nearly absent) correlated with morphological patterns (P < 0.01). CONCLUSIONS: The immunohistological landscape of KFD is complex and characterised by increased numbers of pDCs that frequently cluster around apoptotic/necrotic foci, increased numbers of cytotoxic T cells, and substantial distortion of FDC meshworks.

Herpes simplex infection simulating Richter transformation: a series of four cases and review of the literature.

AIMS: Richter transformation (RT) occurs in 5-10% of patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL), and is associated with a poor outcome. The histological manifestations of RT are variable, and include an increase in the proportion of prolymphocytes, immunoblasts, and other pleomorphic cells, along with an increased proliferation rate and often necrosis. Rarely, superimposed herpes simplex virus (HSV) infection involving lymph nodes in patients with CLL/SLL may mimic RT clinically and histologically. In this study, we describe four cases of CLL/SLL with superimposed HSV lymphadenitis, and we review the literature. METHODS AND RESULTS: We describe the clinicopathological and immunophenotypic findings of four cases of CLL/SLL with superimposed HSV infection. The patients presented with B-type symptoms, and laboratory and imaging findings suggested progression of lymphoma. Histologically, there were geographical areas of necrosis and increased numbers of prolymphocytes and immunoblasts, in some areas forming sheets, with increased mitotic figures and a high proliferation (Ki67) rate. However, the necrotic regions were associated with acute inflammatory cells and larger cells, mostly necrotic, showing viral cytopathic effects. Therapy with antiviral agents resulted in improvement of clinical symptoms and laboratory and imaging findings. Additionally, we identified 11 cases of CLL/SLL with superimposed HSV infection described in the English-language literature, and integrated the cases that we report here into this wider context. CONCLUSIONS: Herpes simplex virus infection of lymph nodes in patients with CLL/SLL results in clinicopathological and radiological findings that may mimic RT. It is essential to refrain from misclassifying these cases as RT, as patients can respond remarkably well to antiviral therapy.

Starry Sky Pattern in Hematopoietic Neoplasms: A Review of Pathophysiology and Differential Diagnosis.

The starry sky pattern is a distinctive histologic feature wherein a rapidly proliferating hematolymphoid neoplasm contains scattered histiocytes with abundant pale cytoplasm in a background of monomorphic neoplastic cells. The cytoplasm of these histiocytes typically contains cellular remnants, also known as tingible bodies, incorporated through active phagocytosis. Although common and widely recognized, relatively little is known about the pathophysiological underpinnings of the starry sky pattern. Its resemblance to a similar pattern seen in the germinal centers of secondary follicles suggests a possible starting point for understanding the molecular basis of the starry sky pattern and potential routes for its exploitation for therapeutic purposes. In this review, we discuss the historical, pathophysiological, and clinical implications of the starry sky pattern.

Histologic transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma.

Although generally considered a clinically indolent neoplasm, CLL/SLL may undergo transformation to a clinically aggressive lymphoma. The most common form of transformation, to DLBCL, is also known as Richter syndrome. Transformation determines the course of the disease and is associated with unfavorable patient outcome. Precise detection of transformation and identification of predictive biomarkers and specific molecular pathways implicated in the pathobiology of transformation in CLL/SLL will enable personalized therapeutic approach and provide potential avenues for improving the clinical outcome of patients. In this review, we present an overview of the pathologic features, risk factors, and pathogenic mechanisms of CLL/SLL transformation. Am. J. Hematol. 91:1036-1043, 2016. © 2016 Wiley Periodicals, Inc.

Bone Marrow Involvement in Patients With Nodular Lymphocyte Predominant Hodgkin Lymphoma.

The spectrum of bone marrow lesions in patients with nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) has not been evaluated systematically. In this study, we analyzed a cohort of 262 NLPHL patients who underwent staging bone marrow evaluation or targeted bone biopsy as a part of their initial diagnostic workup, among which lymphoma was detected in 24 (9.2%) patients. Eleven patients had bone marrow findings of NLPHL (few large B cells in a background of small B cell and T cell), and 13 patients had either T-cell/histiocyte-rich large B-cell lymphoma (large B cells in a background of T cells and histiocytes) or typical diffuse large B-cell lymphoma (sheets of large B cells). Bone marrow involvement was more common in patients with variant NLPHL histologic patterns in the lymph node as compared with those who had classic patterns (12/18 vs. 4/16; P=0.02). An additional 27 NLPHL patients had bone marrow specimens involved by lymphoid aggregates composed of small T cells and B cells without large B cells; this subgroup had a longer event-free survival than patients with lymphoma in the bone marrow (145 vs. 35 mo). Disease recurrence or progression was more frequent in patients with bone marrow involvement by either NLPHL or LBCL, compared with patients who had lymphoid aggregates (13/21 vs. 8/26; P=0.04). In conclusion, staging bone marrow sampling detects lymphoma in a sizeable subset of NLPHL patients, particularly those with variant histologic patterns. Lymphoid aggregates lacking large B cells in staging bone marrow specimens from NLPHL patients can be regarded as clinically benign without impact on stage, outcome, or risk stratification.

Characteristics and clinical implications of reactive germinal centers in the bone marrow.

Reactive germinal centers (GCs) in the bone marrow (BM) have been described in patients with autoimmune disorders, infections, malignancies, and following certain drug therapies, or as an isolated finding without obvious underlying disease. In this study, we describe the clinical conditions in which reactive GCs occur in BM samples, and their topography and accompanying laboratory and ancillary findings in the setting of a cancer center. We identified 32 BM specimens with reactive GCs with an estimated frequency less than 0.02% over a 12-year period. Fifteen (46.9%) BM specimens had concurrent hematolymphoid neoplasms: most often a variety of small B-cell lymphomas, but also myelodysplastic syndromes. One (3.1%) case was involved by metastatic melanoma. Isolated reactive GCs were observed in 16 (50%) patients. Most BM specimens (n = 25; 78.1%) showed only one reactive GC with a size ranging from 20 to 500 µm, and most GCs (29/32) were nonparatrabecular. GCs were positive for CD10 and BCL6, and were negative for BCL2. CD3 and CD5 demonstrated T cells surrounding the GC and CD21, and CD23 highlighted follicular dendritic cells. Reactive GCs are uncommon and can be seen in association with hematolymphoid and other types of neoplasms or as an isolated finding. Reactive GCs are usually located in a nonparatrabecular distribution. A panel of immunohistochemical stains is useful to confirm the nonneoplastic nature of these GCs to avoid misdiagnosis as lymphoma or as histologic evidence of transformation in a patient with small B-cell lymphoma in the bone marrow.

Immunophenotypic Shifts in Primary Cutaneous γδ T-Cell Lymphoma Suggest Antigenic Modulation: A Study of Sequential Biopsy Specimens.

Primary cutaneous γδ T-cell lymphoma (PCGD TCL), an aggressive type of lymphoma, accounts for approximately 1% of all primary cutaneous lymphomas. We have occasionally observed changes in T-cell antigen expression (immunophenotypic [IP] shift) over time, a phenomenon that is considered rare in T-cell lymphoma including cutaneous T-cell lymphoma. Therefore, we assessed sequential biopsies of PCGD TCL for possible IP shifts of the lymphoma cells. We searched for cases of PCGD TCL with consecutive biopsies to perform a comprehensive immunohistochemical analysis of paired specimens. A median of 12 markers per case was tested. We evaluated the percentage of neoplastic lymphocytes and determined the differential expression of antigens (gain, loss, increase or decrease). We identified 9 patients with PCGD TCL with consecutive biopsies. All (100%) cases had IP shifts of at least 1 antigen, whereas overall 22 pairs of markers were shifted: gain of reactivity occurred in 7 (31.8%) and loss in 3 (13.6%); increased reactivity in 4 (18.2%) and decreased in 8 (36.4%). Molecular analysis of TCRγ showed identically sized monoclonal rearrangements between biopsy pairs in 4/4 (100%) patients. There was no correlation between IP shifts and the clinical appearance of lesions, histopathologic or cytologic features, or molecular rearrangements. IP shifts are common in PCGD TCL, occurring in all patients in this study and involving a variety of antigens. IP shifts do not seem to be linked to changes in the T-cell clone and are without obvious clinical or morphologic correlates. The occurrence of IP shifts in PCGD TCL suggests that antigen modulation may be involved in pathogenesis. IP shifts are somewhat frequent in T-cell lymphoma; however, it does not suggest a second neoplasm, and molecular studies can be used to determine clonal identity.

High-grade Transformation of Low-grade B-cell Lymphoma: Pathology and Molecular Pathogenesis.

Patients with low-grade (clinically indolent) lymphomas are at risk to undergo transformation to high-grade (clinically aggressive) lymphoma, although transformation only occurs in a subset of patients. When transformation occurs it is a critical event that determines the course of disease and is associated with unfavorable patient outcomes. Accurate detection of transformation, predictive biomarkers, and identification of specific molecular pathways implicated in the pathobiology of transformation will facilitate personalized therapeutic approaches and underpin advances in clinical outcomes. In this article, we present an update of the clinical and pathologic diagnostic criteria for low-grade B-cell lymphoma transformation and discuss the molecular alterations involved in the pathogenesis of this biological phenomenon.