Clifford Blieden

Semaphorin7A promotes tumor growth and exerts a pro-angiogenic effect in macrophages of mammary tumor-bearing mice

Semaphorins are a large family of molecules involved in axonal guidance during the development of the nervous system and have been recently shown to have both angiogenic and anti-angiogenic properties. Specifically, semaphorin 7A (SEMA7A) has been reported to have a chemotactic activity in neurogenesis and to be an immune modulator through α1β1integrins. SEMA7A has been shown to promote monocyte chemotaxis and induce them to produce proinflammatory mediators. In this study we explored the role of SEMA7A in a murine model of breast cancer. We show that SEMA7A is highly expressed by DA-3 murine mammary tumor cells in comparison to normal mammary cells (EpH4), and that peritoneal elicited macrophages from mammary tumor-bearing mice also express SEMA7A at higher levels compared to those derived from normal mice. We also show that murine macrophages treated with recombinant murine SEMA7A significantly increased their expression of proangiogenic molecule CXCL2/MIP-2. Gene silencing of SEMA7A in peritoneal elicited macrophages from DA-3 tumor-bearing mice resulted in decreased CXCL2/MIP-2 expression. Mice implanted with SEMA7A silenced tumor cells showed decreased angiogenesis in the tumors compared to the wild type tumors. Furthermore, peritoneal elicited macrophages from mice bearing SEMA7A-silenced tumors produce significantly (p < 0.01) lower levels of angiogenic proteins, such as CXCL2/MIP-2, CXCL1, and MMP-9, compared to those from control DA-3 mammary tumors. We postulate that SEMA7A in mammary carcinomas may skew monocytes into a pro-tumorigenic phenotype to support tumor growth. SEMA7A could prove to be valuable in establishing new research avenues toward unraveling important tumor-host immune interactions in breast cancer patients.

Post-transplant lymphoproliferative disorder presented as small bowel intussusception in adult liver transplant patient.

Intestinal obstruction after liver transplant is a rare complication, with diverse clinical manifestations. Intestinal adhesion is the most common cause. However, internal hernia, abdominal wall hernia, and neoplasm are also reported. Intussusception is another rare cause of intestinal obstruction, which has been reported primarily in pediatric patients. Herein, we report a case of intestinal obstruction from intussusception in an adult liver transplant patient associated with post-transplant lymphoproliferative disorder.

Acute spontaneous tumor lysis syndrome as the initial presentation of ALK-positive diffuse large B-cell lymphoma

Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL) is a recently described, uncommon form of DLBCL, which has been seen primarily in young men and which presents with advanced disease. The fact that ALK-positive DLBCL is an uncommon diagnosis is likely due to the combined effects of this being an uncommon disease coupled with the challenges in the pathologic identification of this neoplasm. Prompt and accurate identification of this tumor is becoming increasingly important, however, as we enter the era of therapeutic ALK inhibitors, which are currently undergoing study in several clinical trials. Here, we report a case of ALK-positive DLBCL in a 39-year-old male patient who presented with spontaneous tumor lysis syndrome. We review the clinical, morphologic, immunohistochemical, and molecular aspects of this case and of ALK-positive DLBCL in general, with the purpose of bringing to light the existence of this disease and its potential future therapy.

Brainstem anaplastic glioma in patients with AIDS: a case report and review of the literature.

AIDS is an increasingly common diagnosis seen by neurologists and neurosurgeons alike. Although the more common brain lesions associated with AIDS are due to central nervous system lymphomas, toxoplasma encephalitis or progressive multifocal leukoencephalopathy, relatively recent clinical evidence has shown that AIDS-independent cerebral tumours can arise as well, albeit less commonly. Previous incidents have been reported with HIV and AIDS patients presenting with cerebral astrocytomas. To our knowledge, there has never been a report in the literature of a brainstem anaplastic glioma occurring in an AIDS or HIV patient. We report a 55-year-old patient with HIV and brainstem anaplastic glioma. Its presentation, diagnostic difficulty, scans, histology and subsequent treatment are discussed. We also review the relevant literature on gliomas in HIV/AIDS patients.

De novo acute myeloid leukemia with monocytoid blasts and erythrophagocytosis

Acute myeloid leukemia (AML) with t(8:16) is an infrequent acute leukemia subtype. It can occur de novo or more frequently therapy‐related. The presence of blasts with monocytoid morphology and erythrophagocytosis suggest the presence of the t(8;16).

Processing radical prostatectomies: an alternate-slice method is comparable with total embedding

Receipt of radical prostatectomy specimens in the histopathology laboratory is quite common in academic centers and community hospitals. Despite numerous processing protocols, there is not an accepted standard method of processing. There are potential disadvantages of total sampling of the prostate; however, other alternatives have not been proven to show significant advantages. We present a partial sampling method (alternate slice) and compare its results to the total embedding method. Consecutive radical prostatectomy specimens were selected to compare both histologic sampling methods. The primary method of sampling was total embedding. Subsequently, alternate slice sections from the anterior, middle, and posterior thirds of the gland were reviewed. Seminal vesicle, bladder neck, and margins were similarly evaluated in both methods. Total sampling resulted in an average of 30 blocks compared with 18 in the alternate slice method. Gleason correlation was 87.5%; extraprostatic extension correlation was 97.9%. There was complete correlation in margin status and perineural invasion. Pathologic staging correlation was 97.9%. In summary, this alternate slice method compares very favorably with the total embedding method.

Anaphylactic reaction to platelet transfusion as the initial symptom of an undiagnosed systemic mastocytosis: a case report and review of the literature

IntroductionThe association between anaphylactic reactions and systemic mastocytosis is well documented. However, platelet transfusion has not previously been reported as a potential elicitor of anaphylaxis in the context of systemic mastocytosis.Case presentationWe describe the clinicopathological findings of a 59-year-old Latin American man who presented to the emergency room with fatigue, leukocytosis, thrombocytopenia and mild hepatosplenomegaly. He developed two separate, temporally associated and severe anaphylactic reactions after receiving platelet transfusions. The result of a laboratory investigation for clerical errors and Coombs test was negative. Pre- and post-transfusion urine samples were negative for hemolysis. Bone marrow biopsy and aspirate smears performed demonstrated involvement by systemic mastocytosis, which had been previously undiagnosed.ConclusionsWe posit the transfusion reaction to be an anaphylactic reaction to transfused products as a result of heightened allergic sensitivity due to the underlying systemic mastocytosis. To the best of our knowledge, this is the first reported case of a severe anaphylactic-type reaction to blood products occurring in the setting of a previously undiagnosed systemic mastocytosis. Furthermore, it seems there are no published studies closely examining the relationship between hematopoietic neoplasms and transfusion reactions in general.

Acquired B cell immunophenotype of follicular dendritic cells in a B cell-depleted lymph node after treatment with rituximab

Dear Editor, We describe an unusual immunohistochemical finding in the lymph node of a 54-year-old man who underwent an excision of a neck mass after a recent therapy with rituximab for suspected recurrent follicular lymphoma (FL). The lymph node was B cell-depleted, and follicular dendritic cells (FDCs) within reactive germinal centers adopted a B cell immunophenotype as identified by immunohistochemical studies. To our knowledge, there is no previous description of this finding in the medical literature. A 54-year-old man was initially diagnosed in 2005 with a localized grade 3 FL in a cervical lymph node for which he received rituximab and localized radiation therapy. Seven years later, the patient presented with prolonged fever. Imaging studies showed diffuse mesenteric lymphadenopathy and a left parotid gland mass. An infectious workup was negative, and the patient was presumed to have recurrent FL. The patient received rituximab; however, the neck mass did not decrease in size. Fine-needle aspiration (FNA) of the left parotid gland mass was nondiagnostic, and he underwent an excision of the parotid gland 2 months after rituximab therapy. Histologic examination revealed a lymphoepithelial cyst in addition to atrophic salivary gland tissue. A small reactive lymph node was also identified in the specimen that did not demonstrate evidence of involvement by FL (Fig. 1). Immunohistochemical studies showed that the lymph node was partially depleted of B cells and that the FDCs were strongly positive for CD23 and CD20 andweakly and partially positive for CD19 (Fig. 1). The positive controls for CD19 and CD20 were reviewed and were adequate. The FDCs were negative for CD79a, PAX-5, CD10 and BCL-6 (Fig. 1). FDCs are stromal cells that form a network of processes in primary follicles and germinal centers. The origin of FDCs has not been established definitively, but it is believed that FDCs develop from local resident mesenchymal cells [1]. FDCs are in contact with B cells undergoing somatic hypermutation within the germinal center and are, in part, responsible for presenting opsonized antigens to B cells [2, 3]. FDCs have the ability to capture large amounts of antigen in the form of immune complexes in highly ordered units designated as iccosomes. FDCs can be recognized morphologically by the presence of double oval to rectangular shaped nuclei with vesicular chromatin and small nucleoli. FDCs express Fc receptors, such as FcgRIIb (CD32) and FceRII (CD23), and complement receptors, such as CR1 (CD35), CR2 (CD21), CR3 (CD11b/CD18), vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1), but are usually negative for CD19 and CD20 [4, 5]. In this case, we found that the lymph node was partially B cell depleted, and FDCs were positive for CD20 and, to a lesser extent, CD19. We surmise that the acquired B cell antigenicity of the FDC is the result of rituximab therapy inducing B cell apoptosis with release of CD19 and CD20 into serum followed by the capture of these B cell antigens from the serum by FDCs. The absence of CD79a and PAX5 in FDCs suggests that these antigens are processed differently following B cell apoptosis. The recognition of CD19 or CD20 staining of FDCs after rituximab therapy and, potentially, in circumstances of a high B cell turnover is of interest as this occurrence provides insights in lymph node pathophysiology and may prevent pathologists who may observe this C. Blieden : F. Vega (*) Section of Hematopathology, Department of Pathology and Laboratory Medicine, University of Miami/Sylvester Comprehensive Cancer Center, Building UMH, Pathology Department, Suite 4061, 1400 NW 12th Ave, Miami, FL 33136, USA e-mail: fvega@med.miami.edu

Suprasellar and sellar paraganglioma presenting as a nonfunctioning pituitary macroadenoma

It is extremely rare for paragangliomas to be present in the brain. We present a 44-year-old man with a suprasellar-sellar paraganglioma encasing the internal carotid arteries. We review all such tumors reported in the literature and conclude that paraganglioma should be kept in the differential diagnosis of unusual suprasellar-sellar lesions.

Acute Myeloid Leukemia with Translocation (8;16)(p11;p13): A Distinct Syndrome– Case Report and Literature Review

Acute myeloid leukemia with the translocation (8;16)(p11;p13) is a rare type of acute leukemia with a number of unique features including erythrophagocytosis, extramedullary disease, and poor prognosis with high relapse rate. These cases of AML are often categorized as M4, M5a, or M5b AML under the FAB system of AML classification. However, the clinical and pathological features of AML with t(8;16) (p11;p13) do not fit into any of these French- American-British (FAB) classification system subtypes, nor is it recognized as a recurrent genetic abnormality within the WHO classification system. Here, we report the case of a 50-year-old female with a history of low-grade carcinoid tumor on surveillance who developed de novo AML with histiocytic differentiation and t(8;16)(p11;p13). Immunohistochemistry and morphology of the patient’s bone marrow biopsy was not consistent with any specific AML subtype, which resulted in diagnostic and therapeutic delays. AML with t(8;16)(p11;p13) has been described a number of times in the literature as a unique leukemic syndrome based on clinical, cytochemical, and DNA microarray features. As such, AML with t(8;16)(p11;p13) should be added to the WHO classification system list of AML with recurrent genetic abnormalities.