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Papers by Ashleigh Allen

Journal of Neurosurgery: Case Lessons, 2022

BACKGROUND Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor with a high ... more BACKGROUND Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor with a high likelihood of distant metastasis. Approximately 30 cases of MCC brain metastasis have been reported. The authors report a case of MCC brain metastasis with imaging findings mimicking primary central nervous system lymphoma. OBSERVATIONS A 69-year-old asymptomatic White female with a past medical history of rheumatoid arthritis and MCC of the right cheek with no known regional or distant spread presented with a right frontal lobe lesion discovered incidentally on a surveillance scan. Brain magnetic resonance imaging revealed a vividly enhancing homogeneous lesion with restricted diffusion on diffusion-weighted imaging and corresponding apparent diffusion coefficient maps. Imaging characteristics suggested a highly cellular mass consistent with primary central nervous system lymphoma; however, given the likelihood of metastasis, resection was recommended. An intraoperative frozen section s...

Survival curve showing a trend toward shorter progression-free survival of CNS DLBCL man... more Survival curve showing a trend toward shorter progression-free survival of CNS DLBCL manifesting a perivascular pattern of infiltration.</p

H&E-stained section of a CNS DLBCL exhibiting a diffuse pattern of infiltration (A),... more H&E-stained section of a CNS DLBCL exhibiting a diffuse pattern of infiltration (A), CD20 expression (B), and MYC expression by 80% of neoplastic cells (C). H&E-stained section of a CNS DLBCL exhibiting a perivascular pattern of infiltration (D), CD20 expression (E), and MYC expression by 30% of neoplastic cells (F). All photomicrographs were taken at 40x magnification.</p

H&E-stained section of a case exhibiting morphologic features intermediate between D... more H&E-stained section of a case exhibiting morphologic features intermediate between DLBCL and Burkitt lymphoma (A), 80% MYC expression by the neoplastic cells (B), non-GCB COO subtype - BCL6+ (C) and MUM1/IRF4+ (D), and displaying two normal MYC loci by FISH (two fused signals) (E). H&E-stained section of a case showing immunoblastic morphology (F), 50% MYC expression by the neoplastic cells (G), non-GCB COO subtype - BCL6+ (H) and MUM1/IRF4+ (I), and displaying MYC rearrangement by FISH (one split signal, red and green, and one fused signal) (J). H&E-stained section of a DLBCL showing anaplastic morphology (K), 60% MYC expression by the neoplastic cells (L), GCB COO subtype - CD10+ (M) and BCL6+ (N), and increased copies of MYC by FISH (5 fused signals) (O). Photomicrographs of all H&E-stained sections were taken at 400x magnification and all others at 40x magnification.</p

Abbreviations: MXT, methotrexate. WBRT, whole brain radiation therapy. R-MVP, rituximab,... more Abbreviations: MXT, methotrexate. WBRT, whole brain radiation therapy. R-MVP, rituximab, methotrexate, procarbazine, and vincristine.*Normal range of LDH: 115–221 units/L.Clinical Characteristics of CNS DLBCL.</p

Archives of Pathology & Laboratory Medicine, 2022

Context.— In the early 1980s, a monoclonal antibody termed Ki-1 was developed against a cell line... more Context.— In the early 1980s, a monoclonal antibody termed Ki-1 was developed against a cell line derived from a patient with Hodgkin lymphoma. This antibody detected a limited number of benign activated lymphocytes in lymphoid tissue, whereas in Hodgkin lymphoma it appeared to be nearly specific for Reed-Sternberg cells and their mononuclear variants. Subsequent studies showed that Ki-1 expression defined a new type of lymphoma that was later designated anaplastic large cell lymphoma with or without anaplastic large cell kinase expression/translocation. In the past 30 years, numerous new lymphoma entities have been defined, many of which are variably positive for CD30. Many virally transformed lymphoproliferative disorders are also frequently positive for CD30. Objective.— To illustrate the broad spectrum of CD30+ hematologic malignancies and to provide an update of CD30-targeted therapies. Data Sources.— Personal experiences and published works in PubMed. Conclusions.— Because of ...

Annals of Clinical and Laboratory Science, Aug 29, 2019

De novo CD5-positive diffuse large B- cell lymphoma (CD5+ DLBCL) is a subtype of DLBCL found pred... more De novo CD5-positive diffuse large B- cell lymphoma (CD5+ DLBCL) is a subtype of DLBCL found predominantly in older individuals. This particular subtype has been associated with a female pre- dominance and a more aggressive clinical course. Conversely, this entity has not been described in the pe- diatric population. We report a case of a 12 year-old boy who presented with an ileocecal intussusception. Radiologic, morphologic, and immunophenotypic analysis revealed an isolated extranodal mass consistent with a CD5+ DLBCL, germinal center cell phenotype. Fluorescent in situ hybridization analysis was nega- tive for cMYC, BCL6, BCL2, MLL, and IGH/CCND1 rearrangement and showed loss of one copy of MLL in 32% cells. The patient was treated with four cycles of cyclophosphamide, vincristine, prednisolone, methotrexate, and doxorubicin and achieved complete remission. To the best of our knowledge, this is the first detailed report of a de novo CD5+ DLBCL occurring in a child.

Diagnostic Cytopathology, 2020

Malignant mesothelioma, a neoplasm arising within the serosal surfaces, has been linked closely t... more Malignant mesothelioma, a neoplasm arising within the serosal surfaces, has been linked closely to asbestos exposure. We present a case of 72‐year‐old male with a 27 year work‐related history of asbestos exposure who presented with dyspnea. Chest computed tomography scan showed a large, right pleural effusion with compressive right lung atelectasis. Biopsies, subsequent pleurectomy and lung wedge resections revealed epithelioid malignant mesothelioma with associated focal non‐keratinizing squamous‐cell carcinoma, supported by extensive immunohistochemical stains and molecular studies. The patient was treated with 6 cycles of carboplatin/pemetrexed, showing no new metastases. Seven months post‐treatment, the patient presented with progressive dyspnea and large pleural effusions. Bilateral pleural fluid was collected and showed malignant epithelioid cells, morphologically similar to the patient's pleural neoplastic cells. However, the tumor was positive for squamous cells markers ...

Leukemia Research, 2014

C-myc protein expression has been studied in mature B-cell lymphomas and overexpression has been ... more C-myc protein expression has been studied in mature B-cell lymphomas and overexpression has been associated with poor prognosis. We sought to determine the prognostic significance of c-myc protein expression in BALL. We found ≥20% c-myc expression to predict risk of persistent disease in all age groups (odds ratio 7.487, p = 0.013). There was no statistically significant association between c-myc expression and risk of relapse or death in our study. Routine c-myc immunostaining may help identify higher risk patients and guide management of BALL. Additional studies are needed to further determine the molecular mechanisms and role of c-myc expression in BALL .

PLoS ONE, 2014

Primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) is a rare, aggres... more Primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) is a rare, aggressive subtype of DLBCL, the biology of which is poorly understood. Recent studies have suggested a prognostic role of MYC protein expression in systemic DLBCL, but little is known about the frequency and significance of MYC protein expression in CNS DLBCL. Hence, we investigated MYC protein expression profiles of CNS DLBCL and assessed the relationship between MYC expression and a variety of histopathologic, immunophenotypic, genetic, and clinical features. Fifty-nine CNS DLBCL diagnosed at our institution over the past 13 years were evaluated. The majority of cases (80%) showed centroblastic morphology, and 12 (20%) displayed a perivascular pattern of infiltration. According to the Hans criteria, 41 (69%) cases had a non-germinal center B-cell and 18 (31%) had a germinal center B-cell cell-of-origin (COO) phenotype. Mean MYC protein expression was 50% (median: 50%, range: 10-80%). Forty-three cases (73%) showed MYC overexpression (>40%), and 35 (60%) showed MYC/BCL2 coexpression. MYC overexpression was seen in the single case harboring MYC translocation and in the cases showing increased copies of MYC (27%); however, no significant difference in mean MYC expression was seen between groups harboring or lacking MYC aberrations. In our series, age was associated with a significantly increased risk of death, and the perivascular pattern of infiltration was associated with a significantly increased risk of disease progression. Neither MYC expression (with or without BCL2 coexpression) nor other variables, including COO subtype were predictive of clinical outcome. Our findings indicate that the proportion of CNS DLBCL overexpressing MYC is higher compared to systemic DLBCL, and MYC overexpression appears to be independent of genetic MYC

Reviews in Medical Microbiology, 2014

Plasmodium falciparum is a leading cause of severe disease in all age groups worldwide. Resistanc... more Plasmodium falciparum is a leading cause of severe disease in all age groups worldwide. Resistance to drug treatment is becoming increasingly common. This is resulting in a global health crisis as this dangerous disease is becoming increasingly difficult to treat. As a result, the effect of exchange transfusion is now of great interest to researchers and physicians who deal with treating malaria. This review describes the benefits and risks of exchange transfusion as adjunct therapy for patients with severe P. falciparum malaria. The true worth of this treatment has not been fully elucidated and further study is needed.

Leukemia Research, 2013

Early T-cell precursor-ALL (ETP-ALL) is a subtype of TALL with a poor prognosis in children. We a... more Early T-cell precursor-ALL (ETP-ALL) is a subtype of TALL with a poor prognosis in children. We analyzed ETP-ALL compared to conventional T-ALL/LBL in both adults and children to determine any differences in clinical outcomes, based on the following parameters: induction failure, relapse, and survival. Patients with ETP-ALL have a higher risk of relapse, especially in children (in all patients, HR = 4.08, p = 0.127, and children, HR = 11.63, p = 0.025). ETP-ALL seems to have an increased risk of adverse outcomes, particularly in children. Larger studies are needed to better determine the prognosis of this subtype of TALL .

Leukemia & lymphoma, Jan 31, 2015

Follicular lymphoma (FL) is the second most common type of B-cell lymphoma in adults in the Weste... more Follicular lymphoma (FL) is the second most common type of B-cell lymphoma in adults in the Western hemisphere. FL can occur within lymph nodes or at extranodal sites, and is typically characterized by a follicular growth pattern, and a variable mixture of centrocytes and centroblasts. FL expresses Band follicle center cell markers, and the majority show aberrant expression of BCL2. Characteristically, cytogenetic analysis shows translocation t(14;18)(q32;q21)(BCL2/IGH) leading to the overexpression of BCL2 in 80% of cases [1]. Myxoid changes refer to the deposition of mucopolysaccharides in stromal tissues. Such changes can be seen in a variety of conditions, including neoplastic (e.g. myxoid chondrosarcoma) and non-neoplastic (e.g. degenerative change in heart valves). Myxoid changes have been rarely reported in lymphomas, mostly as single case reports [2–9]. Herein, we report the case of a patient with a longstanding history of FL, with multiple relapses, whose lymphoma eventually relapsed in the groin showing pseudopapillary features with prominent myxoid changes. The relapsed lymphoma lacked CD20 expression and the typical follicular growth pattern; however, the lymphoma had the characteristic germinal center cell phenotype with aberrant BCL2 expression and t(14;18) translocation. The patient is a 51-year-old male diagnosed with FL, low grade, at the age of 31 in a cervical lymph node (LN). Five years after initial diagnosis, another enlarged neck LN was detected (not biopsied). The patient was presumed to have relapsed disease and received monthly rituximab  8 achieving a complete clinical response (CR). One year later, a neck LN biopsy showed FL, grade 3a, with follicular growth pattern. The lymphoma expressed CD20 (by both immunohistochemistry and flow cytometry), CD10 and BCL2. The patient was followed expectantly for 3 years and then received weekly rituximab  4 when he developed a parotid mass and cervical lymphadenopathy (LAN) (not biopsied) with a partial CR. He had persistent disease treated with 3000 cGy of radiation with excellent local control. One year later, he presented with lacrimal gland enlargement in association with cervical, chest and inguinal LAN (not biopsied). He received weekly rituximab  4 with regression and then received rituximab maintenance every 6 months (weekly  4) for three more cycles. One year after completing this treatment, a palatal lesion was biopsied at an outside institution revealing lymphoma (not specified), and he had a partial CR to weekly rituximab  4. Two years later, he presented with an occipital mass, clinically thought to be a recurrence, and was treated with weekly rituximab  4 achieving a partial CR. One year later, the occipital mass enlarged, prompting addition of four cycles of monthly rituximab/bendamustine, achieving a complete CR, followed by 12 cycles of rituximab maintenance every 2 months. The patient remained in remission for 15 months until he noted enlarged LNs in his neck and groin. After a non-diagnostic biopsy, an excisional biopsy of an inguinal lesion was performed. This biopsy showed a neoplastic cellular proliferation with pseudopapillary features in a myxoid stroma throughout the entirely examined biopsy [Figures 1(A) and 1(B)]. LN architecture was not identified. Architecture typical of FL or similar to that present in the patient’s prior biopsies was not identified. The neoplastic cells were medium-sized and had overall oval-to-round nuclei and coarsely clumped chromatin, lacking typical features of either centrocytes or centroblasts. Sparse, apoptotic debris was noted [Figure 1(C)]. Based on routine histology alone, the differential diagnosis included a soft tissue neoplasm, a metastatic tumor (e.g. carcinoma) or a very unusual histomorphology of lymphoma (given the patient’s history). The cells were positive for the following markers by immunohistochemistry (IHC): CD45, CD19 (partial), CD79a, PAX5, CD10, BCL6, LMO2 and HGAL [Figures 1(D) and 1(E)]. In addition, the cells showed bright, aberrant expression of BCL2 [Figure 1(F)]. They were negative for CD20, MUM1 and CD23. No follicular dendritic cell networks were identified on CD21 and CD23 immunostains. The Ki67 proliferation index was 40%. All epithelial (p63, CK, CK/CAM, CK5, CK7, CK20, LMWCK, HMWCK) and melanoma (S100, Melan-A) markers tested were negative. The myxoid stroma stained positive for Alcian Blue but not mucicarmine [Figure 1(A), inset]. Flow cytometry detected a