Bilateral adnexal masses: A case report of acute myeloid leukemia presenting with myeloid sarcoma of the ovary and review of literature.

•We report a case of a patient with acute myeloid leukemia (AML) presenting as myeloid sarcoma.•This patient with bilateral adnexal masses was managed via total robotic hysterectomy with bilateral salpingo-oophorectomy.•There are a limited number of reports of bilateral ovarian occurrences that exist in the literature.•Myeloid sarcoma of the ovaries may present with vaginal bleeding to dysmenorrhea, dysuria, and palpable abdominal mass.

Primary Effusion Lymphoma without an Effusion: A Rare Case of Solid Extracavitary Variant of Primary Effusion Lymphoma in an HIV-Positive Patient.

Primary effusion lymphoma (PEL) is a unique form of non-Hodgkin lymphoma, usually seen in severely immunocompromised, HIV-positive patients. PEL is related to human herpesvirus-8 (HHV-8) infection, and it usually presents as a lymphomatous body cavity effusion in the absence of a solid tumor mass. There have been very few case reports of HIV-positive patients with HHV-8-positive solid tissue lymphomas not associated with an effusion (a solid variant of PEL). In the absence of effusion, establishing an accurate diagnosis can be challenging, and a careful review of morphology, immunophenotype, and presence of HHV-8 is necessary to differentiate from other subtypes of non-Hodgkin lymphoma. Treatment involves intensive chemotherapy, and prognosis is usually poor. We present a rare case of a PEL variant in an HIV-positive patient who presented with extensive lymphadenopathy without any associated effusions.

NK cell enteropathy: a case report with 10 years of indolent clinical behaviour.

AIMS: Natural killer (NK) cell enteropathy is a recently described clinically indolent condition characterised by atypical NK cell infiltrates in the gastrointestinal mucosa that mimics malignant lymphoma. We report a case that highlights the indolent clinical behaviour by documenting absence of clinical progression over 10 years. METHODS AND RESULTS: We report the case of a 69-year old female who had clinically long-standing abdominal pain and recurrent mucosal ulcerations associated with atypical NK cell infiltrates. The clinical, morphologic and immunophenotypical findings in this case were diagnostic of NK cell enteropathy. Review of the patient's prior biopsies demonstrated that this persisted without clinical progression for 10 years, confirming the clinical indolent course. CONCLUSION: Recognition of NK cell enteropathy is important to avoid over-diagnosing this benign condition as an aggressive lymphoma.

Development of a Breast Cancer Treatment Program in Port-au-Prince, Haiti: Experiences From the Field.

PURPOSE: The nonprofit Project Medishare launched a breast cancer treatment program in Port-au-Prince in July 2013 to address the demand for breast cancer care in Haiti. We outline the development of the program, highlight specific challenges, and discuss key considerations for others working in global oncology. METHODS: We reflected on our experiences in the key areas of developing partnerships, building laboratory capacity, conducting medical training, using treatment algorithms, and ensuring access to safe, low-cost chemotherapy drugs. We also critically reviewed our costs and quality measures. RESULTS: The program has treated a total of 139 patients with breast cancer with strong adherence to treatment regimens in 85% of patients. In 273 chemotherapy administrations, no serious exposure or adverse safety events were reported by staff. The mortality rate for 94 patients for whom we have complete data was 24% with a median survival time of 53 months. Our outcome data were likely influenced by stage at presentation, with more than half of patients presenting more than 12 months after first noticing a tumor. Future efforts will therefore focus on continuing to improve the level of care, while working with local partners to spread awareness, increase screening, and get more women into care earlier in the course of their disease. CONCLUSION: Our experiences may inform others working to implement protocol-based cancer treatment programs in resource-poor settings and can provide valuable lessons learned for future global oncology efforts.

Epithelioid Myofibroblastoma of the Breast: A Report of Two Cases with Discussion of Diagnostic Pitfalls.

Mesenchymal lesions of the breast are uncommon lesions which present diagnostic dilemmas for even the most experienced pathologists. Here, we present two cases of the epithelioid-variant of myofibroblastoma which were misdiagnosed as malignant lesions. Careful integration of clinical presentation, imaging, and close examination of the gross, histologic, and immunohistochemical findings can assist in differentiating these challenging lesions and avoiding diagnostic pitfalls.

Developing aptamer probes for acute myelogenous leukemia detection and surface protein biomarker discovery.

BACKGROUND: The majority of patients with acute myelogenous leukemia (AML) still die of their disease. In order to improve survival rates in AML patients, new strategies are necessary to discover biomarkers for the detection and targeted therapy of AML. One of the advantages of the aptamer-based technology is the unique cell-based selection process, which allows us to efficiently select for cell-specific aptamers without knowing which target molecules are present on the cell surface. METHODS: The NB4 AML cell line was used as the target cell population for selecting single stranded DNA aptamers. After determining the affinity of selected aptamers to leukocytes, the aptamers were used to phenotype human bone marrow leukocytes and AML cells in clinical specimens. Then a biotin-labelled aptamer was used to enrich and identify its target surface protein. RESULTS: Three new aptamers were characterized from the selected aptamer pools (JH6, JH19, and K19). All of them can selectively recognize myeloid cells with Kd in the low nanomole range (2.77 to 12.37 nM). The target of the biotin-labelled K19 aptamer probe was identified as Siglec-5, a surface membrane protein in low abundance whose expression can serve as a biomarker of granulocytic maturation and be used to phenotype AML. More importantly, Siglec-5 expression can be used to detect low concentrations of AML cells in human bone marrow specimens, and functions as a potential target for leukemic therapy. CONCLUSIONS: We have demonstrated a pipeline approach for developing single stranded DNA aptamer probes, phenotyping AML cells in clinical specimens, and then identifying the aptamer-recognized target protein. The developed aptamer probes and identified Siglec-5 protein may potentially be used for leukemic cell detection and therapy in our future clinical practice.

Carcinosarcoma of the ureter with a small cell component: report of a rare pathologic entity and potential for diagnostic error on biopsy.

Carcinosarcomas of the ureter are rare biphasic neoplasms, composed of both malignant epithelial (carcinomatous) and malignant mesenchymal (sarcomatous) components. Carcinosarcomas of the urinary tract are exceedingly rare. We report a unique case of a carcinosarcoma of the ureter with a chondrosarcoma and small cell tumor component arising in a 68-year-old male who presented with microscopic hematuria. CT intravenous pyelogram revealed right-sided hydroureter and hydronephrosis with thickening and narrowing of the right ureter. The patient underwent robot-assisted ureterectomy with bladder cuff excision and subsequent adjuvant chemotherapy. The patient is disease-free at 32 months after treatment. We provide a brief synoptic review of carcinosarcoma of the ureter and bladder with utilization of immunohistochemical (IHC) stains and potential diagnostic pitfalls.

Xp11 Translocation Renal Cell Carcinoma: Unusual Variant Masquerading as Upper Tract Urothelial Cell Carcinoma.

Xp11 translocation renal cell carcinoma (TRCC) is a rare subtype of renal cell carcinoma characterized by chromosomal translocations involving the TFE3 gene located at the Xp11.2 locus. Initial cases were more common in children, but cases in older adults have begun to accrue and suggest a relatively more aggressive course. We report a case of Xp11 TRCC in a 63-year-old female patient with initial presentation mimicking upper urinary tract urothelial cell carcinoma, with biopsy proving TRCC. She underwent a radical nephrectomy and paracaval lymph node dissection and is followed up with the intent to initiate vascular endothelial growth factor-targeted therapy in case of recurrence.

Intrathyroidal parathyroid carcinoma: report of an unusual case and review of the literature.

Intrathyroidal parathyroid carcinoma is an exceedingly rare cause of primary hyperparathyroidism. A 51-year-old African American female presented with goiter, hyperparathyroidism, and symptomatic hypercalcemia. Sestamibi scan revealed diffuse activity within an enlarged thyroid gland with uptake in the right thyroid lobe suggestive of hyperfunctioning parathyroid tissue. The patient underwent thyroidectomy and parathyroidectomy. At exploration, a 2.0 cm nodule in the usual location of the right inferior parathyroid was sent for intraoperative frozen consultation, which revealed only ectopic thyroid tissue. No parathyroid glands were identified grossly on the external aspect of the thyroid. Interestingly, postoperative parathyroid hormone levels normalized after removal of the thyroid gland. Examination of the thyroidectomy specimen revealed a 1.4 cm parathyroid nodule located within the parenchyma of the right superior thyroid, with capsular and vascular invasion and local infiltration into surrounding thyroid tissue. We present only the eighth reported case of intrathyroidal parathyroid carcinoma and review the literature.

Sarcoidosis manifesting as a pseudotumorous renal mass.

A 53 year-old African American woman with a three-year history of pulmonary sarcoidosis had a follow-up computed tomographic scan to evaluate the status of her disease and response to treatment. On the scan, an abnormal, hypodense mass on the left renal superior pole, which was not present on previous scans, was incidentally discovered. The initial concern was of carcinoma, despite her lack of any urinary symptoms. She underwent further evaluation with magnetic resonance, and the enhancement pattern and the shape of the mass were more suggestive of lymphoma or infarction than a carcinoma. A review of literature revealed sparse case reports demonstrating sarcoidosis presenting as infiltrative granulomatous masses resembling tumors with nonspecific imaging qualities. This diagnosis was entertained and then proven by biopsy. Pseudotumorous renal sarcoid should be in the differential of renal masses, especially in patients with a history of sarcoidosis, as it alters clinical management.

Noninvasive evaluation of nuclear morphometry in breast lesions using multispectral diffuse optical tomography.

Breast cancer is the most prevalent cancer and the main cause of cancer-related death in women worldwide. There are limitations associated with the existing clinical tools for breast cancer detection and alternative modalities for early detection and classification of breast cancer are urgently needed. Here we describe an optical imaging technique, called multispectral diffuse optical tomography (DOT), and demonstrate its ability of non-invasively evaluating nuclear morphometry for differentiating benign from malignant lesions. Photon densities along the surface of the breast were measured to allow for the extraction of three statistical parameters including the size, elongation and density of nuclei inside the breast tissue. The results from 14 patients (4 malignant and 10 benign lesions) show that there exist significant contrasts between the diseased and surrounding normal nuclei and that the recovered nuclear morphological parameters agree well the pathological findings. We found that the nuclei of cancer cells were less-spherical compared with those of surrounding normal cells, while the nuclear density or volume fraction provided the highest contrast among the three statistical parameters recovered. This pilot study demonstrates the potential of multispectral DOT as a cellular imaging method for accurate determination of breast cancer.

Systemic Capillary Leak Syndrome as an Initial Presentation of ALK-Negative Anaplastic Large Cell Lymphoma.

Systemic capillary leak syndrome (SCLS) is a rare disease characterized by third spacing of plasma into the extravascular compartment, leading to anasarca, hemoconcentration, and hypovolemic shock. It has been rarely associated with lymphomas, and reports usually indicate that it occurs after antineoplastic treatment. We present the case of a patient with ALK-negative anaplastic large cell lymphoma who presented with SCLS as the initial manifestation of her lymphoma. The SCLS resolved with treatment of the malignancy with steroids and chemotherapy.

PTK7: a new biomarker for immunophenotypic characterization of maturing T cells and T cell acute lymphoblastic leukemia.

Protein tyrosine kinase-7 (PTK7) was recently identified as a surface protein expressed on hematopoietic cells. To determine if PTK7 is a useful biomarker in clinical practice for acute leukemia immunophenotyping and detection, we examined the PTK7 expression in human bone marrow and thymic specimens. Our results show that PTK7 expression in normal thymic T cells is tightly regulated during the maturational process, but in T cell acute lymphoblastic leukemia (T-ALL) the expected temporal relationship of expression between PTK7 and other maturational T cell markers is lost or disrupted. In addition, nearly all T-ALL cases expressed higher PTK7 levels than mature T cells in the human bone marrow specimens. Therefore, in conjunction with other T cell markers, PTK7 has utility as a biomarker for detecting minimal residual disease of T-ALL in the bone marrow.

Flow cytometric analysis of immunoglobulin heavy chain expression in B-cell lymphoma and reactive lymphoid hyperplasia.

The diagnosis of B-cell lymphoma (BCL) is often dependent on the detection of clonal immunoglobulin (Ig) light chain expression. In some BCLs, the determination of clonality based on Ig light chain restriction may be difficult. The aim of our study was to assess the utility of flow cytometric analysis of surface Ig heavy chain (HC) expression in lymphoid tissues in distinguishing lymphoid hyperplasias from BCLs, and also differentiating various BCL subtypes. HC expression on B-cells varied among different types of hyperplasias. In follicular hyperplasia, IgM and IgD expression was high in mantle cells while germinal center cells showed poor HC expression. In other hyperplasias, B cell compartments were blurred but generally showed high IgD and IgM expression. Compared to hyperplasias, BCLs varied in IgM expression. Small lymphocytic lymphomas had lower IgM expression than mantle cell lymphomas. Of importance, IgD expression was significantly lower in BCLs than in hyperplasias, a finding that can be useful in differentiating lymphoma from reactive processes.

Tumor endothelial marker 8 expression in triple-negative breast cancer.

BACKGROUND/AIM: Tumor endothelial marker 8 (TEM8) is a tumor endothelial-associated antigen that is having an increasingly recognized role in tumor biology. The expression of TEM8 in triple-negative breast cancer (TNBC) has not yet been characterized. MATERIALS AND METHODS: We hypothesize that TEM8 is overexpressed in TNBC and in metastatic TNBC in lymph nodes (LN) compared to normal breast tissue and normal lymphatic tissue, respectively. We studied expression of TEM8 in cases of primary (n=17) and metastatic (n=2) TNBC using immunohistochemical analyses. RESULTS: All cases demonstrated increased expression of TEM8 in tumor tissue compared to non-cancerous breast tissue. TEM8 was expressed at a higher level in the stroma adjacent to the TNBC in all cases, with focal immunoreactive areas within the tumor. TEM8 was not expressed in normal lymphoid tissue, but showed expression at sites of LN metastases. CONCLUSION: TEM8 would appear to represent a new biologic target for designing novel diagnostic or therapeutic approaches for TNBC.

Smoothelin immunohistochemistry is a useful adjunct for assessing muscularis propria invasion in bladder carcinoma.

AIMS: To prospectively evaluate the utility of smoothelin immunohistochemical expression for the evaluation of muscularis propria (MP) in diagnostic transurethral resection of bladder tumour (TURBT) specimens and cystectomies. METHODS AND RESULTS: Smoothelin immunohistochemistry was performed on a total of 26 TURBT and cystectomy specimens. All but two cases (24/26) demonstrated strong (3+) or moderate (2+) immunoreactivity of the MP with smoothelin. Muscularis mucosae (MM) never displayed strong (3+) reactivity, and in only one case did the MM have moderate (2+) reactivity; in this case the MP had strong (3+) reactivity. MM intensity mirrored the intensity of reactivity of blood vessels in all cases (26/26). Using moderate or strong immunoreactivity as a cut-off, smoothelin had a sensitivity of 92% for detecting MP and a specificity of 97% for distinguishing between MP and MM. In all unequivocal MP-invasive and lamina proporia-invasive cases by haematoxylin and eosin (H&E), smoothelin immunohistochemistry confirmed the original light microscopic diagnosis. In four cases in which there was equivocal MP involvement by H&E, smoothelin helped establish MP invasion. CONCLUSIONS: Smoothelin immunohistochemistry has diagnostic utility in the evaluation of MP invasion in urothelial carcinoma. Smoothelin could be used as an adjunct to traditional H&E-stained light microscopy and may help reduce the number of equivocal diagnoses.

Primary diffuse large B-cell lymphoma of the oral cavity: germinal center classification.

Primary lymphomas of the oral cavity are rare and the most frequent type is diffuse large B-cell lymphoma (DLBCL). Recently, several reports have highlighted the value of classifying DLBCL into prognostically important subgroups, namely germinal center B-cell like (GCB) and non-germinal center B-cell like (non-GCB) lymphomas based on gene expression profiles and by immunohistochemical expression of CD10, BCL6 and MUM-1. GCB lymphomas tend to exhibit a better prognosis than non-GCB lymphomas. Studies validating this classification have been done for DLBCL of the breast, CNS, testes and GI tract. Therefore we undertook this study to examine if primary oral DLBCLs reflect this trend. We identified 13 cases (age range 38-91 years) from our archives dating from 2003-09. IHC was performed using antibodies against germinal center markers (CD10, BCL6), activated B-cell markers (MUM1, BCL2) and Ki-67 (proliferation marker). Cases were sub-classified as GCB subgroup if CD10 and/or BCL6 were positive and MUM-1, was negative and as non-GCB subgroup if CD10 was negative and MUM-1 was positive. Immunoreactivity was noted in 2/13 cases for CD10, in 12/13 for BCL6, in 8/13 for MUM-1, and in 6/13 for BCL2. Therefore, 8/13 (58%) were sub-classified as non-GCB DLBCLs and 5/13 (42%) as GCB subgroup. All tumors showed frequent labeling with Ki-67 (range 40-95%). Four of the 8 patients with non-GCB subgroup succumbed to their disease, with the mean survival rate of 16 months. Two patients in this group are alive, one with no evidence of disease and another with disease. No information was available for the other 3 patients in this group. Four of the 5 patients in the GCB subgroup were alive with no evidence of disease and one patient succumbed to complications of therapy and recurrent disease after 18 months. In conclusion, our analysis shows that primary oral DLBCL predominantly belongs to the non-GCB subgroup, which tends to exhibit a poorer prognosis. These findings could allow pathologists to provide a more accurate insight into the potential aggressive behavior and poorer prognosis of these lymphomas.

Cutting edge: bacterial infection induces hematopoietic stem and progenitor cell expansion in the absence of TLR signaling.

Bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) can be activated by type I IFNs, TLR agonists, viruses, and bacteria to increase hematopoiesis. In this study, we report that endotoxin treatment in vivo induces TLR4, MyD88, and Toll/IL-1 resistance domain-containing adaptor-inducing IFN-beta (TRIF)-dependent expansion of BM HSPCs. Bacterial infection by Staphylococcus aureus or cecal ligation and puncture also induces HSPC expansion, but MyD88, TRIF, type I IFN, cytokine, PG, or oxidative stress pathways are not required for their expansion. S. aureus-induced HSPC expansion in MyD88(-/-)TRIF(-/-) mice is also normal, but is associated with BM remodeling as granulocyte stores are released peripherally. Importantly, reduction in BM cellularity alone can reproduce HSPC expansion. These data show in vivo HSPC responses to bacterial infection are complex and not absolutely dependent upon key inflammatory signaling pathways.

Thrombotic storm in Kimura disease.

We report herein a patient with Kimura disease who experienced life threatening visceral venous thromboses and a clinical course fitting the description of "thrombotic storm". Kimura disease is an indolent chronic inflammatory disease common in Asians and characterized by angiolymphoid proliferation with ample eosinophil infiltration, peripheral blood eosinophilia and elevated serum immunoglobulin E levels. The clinical course of the disease is thought to be benign. Our patient experienced a major thrombotic event with a thorough evaluation revealing no evidence of inherited thrombophilia or acquired conditions associated with visceral venous thromboembolism. Despite persisting eosinophilia and other manifestations of Kimura disease there have been no recurrent thrombotic events with continuous warfarin therapy over a 4-year period. This case highlights the occurrence of hypercoagulability in association with this unusual eosinophilic disorder.