Mousa A. Al-Abbadi

Primary testicular diffuse large B-cell lymphoma belongs to the nongerminal center B-cell-like subgroup: a study of 18 cases

The most common type of primary testicular lymphoma is diffuse large B-cell type, which has the potential for aggressive clinical behavior. Diffuse large B-cell lymphoma can be further subclassified into two major prognostic categories: germinal center B-cell-like and nongerminal center B-cell-like. Such distinction is made possible using the immunohistochemical expression of CD10, Bcl-6 and MUM1. The aim of this study was to stratify primary testicular lymphoma of the diffuse large B-cell type according to this scheme. Immunohistochemical stains for CD10, Bcl-6 and MUM1 were performed on 18 cases of primary testicular lymphoma of diffuse large B-cell type. Subclassification was carried out as previously described where CD10 and/or Bcl-6 positivity and negativity for MUM1 were considered indicative of germinal center B-cell-like type and the opposite expression as nongerminal center B-cell-like type. The proliferative activity was determined using immunostaining with the Ki-67 antibody. Of 18 cases, 16 (89%) were found to belong to the nongerminal center B-cell-like type. Two cases (11%) were classified as germinal center B-cell-like type; one had a CD10-positive, Bcl-6-positive and MUM1-negative profile, and the other was CD10 negative, Bcl-6 positive and MUM1 negative. The former occurred in a 38-year-old patient who was human immunodeficiency virus positive. All the cases expressed high proliferative activity (≥50% Ki-67 labeling). We conclude that most (89%) primary testicular lymphomas of the diffuse large B-cell type belong to the nongerminal center B-cell-like subgroup and have high proliferative activity.

Most primary central nervous system diffuse large B-cell lymphomas occurring in immunocompetent individuals belong to the nongerminal center subtype: a retrospective analysis of 31 cases.

Primary central nervous system lymphomas are rare neoplasms characterized by a dismal prognosis relative to other extranodal lymphomas. Approximately 98% of primary central nervous system lymphomas are of B-cell origin, and most belong to the diffuse large B-cell type. Recently, diffuse large B-cell lymphomas have been subcategorized into germinal center and nongerminal center types based on gene expression profiles and immunohistochemical expression of CD10, Bcl-6, and MUM1. Studies have shown that the overall survival rate of the germinal center group is better than that of the nongerminal center lymphomas. In this study, 31 cases of primary central nervous system lymphomas of the diffuse large B-cell type were retrieved, reviewed, and immunostained for CD10, Bcl-6, MUM1, and Ki-67. Subclassification was carried out as described earlier, where CD10 and/or Bcl-6 positivity and negativity for MUM1 were considered characteristic of germinal center subtype and the opposite expression of nongerminal center subtype. Furthermore, the proliferative activity was semiquantitatively assessed using percent positive cells staining with Ki-67. Of the 31 cases examined, 26 (84%) were found to belong to the nongerminal center type. The Ki-67 index in these 26 cases ranged from 30 to 90% (mean, 69%). Five cases were categorized as the germinal center subtype. They had an Ki-67 index between 70 and 90% (mean, 78%). Interestingly, none of our patients were known to be HIV positive. One patient had a 10-year history of orthotopic liver transplant. We also performed fluorescence in situ hybridization analysis on formalin-fixed material and found that 38% of the cases where tissue was available had abnormalities of MYC/IGH and/or IGH/BCL2. We conclude that most primary central nervous system diffuse large B-cell lymphomas are of the nongerminal center origin. Regardless of the germinal center status, all cases showed a high proliferative rate. A statistically significant difference in the overall survival between the two groups was not seen.

Cytokeratin and Epithelial Membrane Antigen Expression in Angiosarcomas: An Immunohistochemical Study of 33 Cases

CONTEXT Expression of epithelial cell markers can occur in mesenchymal tumors and has been reported in angiosarcomas with variable frequency. In these situations, establishing the diagnosis becomes problematic. OBJECTIVE To determine the expression of cytokeratin and epithelial membrane antigen in angiosarcoma. DESIGN To address this issue, 33 well-documented cases of angiosarcomas were retrieved from the archival material of Shands Hospital at the University of Florida, Gainesville, and Jackson Memorial Hospital at the University of Miami, Miami, Florida. These cases were all reviewed and studied using a cytokeratin cocktail (CAM 5.2 and AE1/AE3) and epithelial membrane antigen using standard immunohistochemical techniques. All 33 cases had available material for cytokeratin analysis; however, only 20 cases had enough material for epithelial membrane antigen staining. RESULTS In the 33 cases studied, the age range of the patients was 2 to 88 years (mean, 63 years). There were 23 (70%) men and 10 (30%) women. One (3%) of 33 was cytokeratin-immunoreactive and 2 (10%) of 20 were epithelial membrane antigen-immunoreactive. CONCLUSION Cytokeratin and epithelial membrane antigen immunoreactivity in angiosarcomas is infrequent but may be encountered. Interpretation of such expression should be done with caution and in conjunction with the characteristic clinical and morphologic features of the tumor as well as the expression of endothelial cell antigens.

Morphological and molecular features of astroblastoma, including BRAFV600E mutations, suggest an ontological relationship to other cortical-based gliomas of children and young adults

Background. Astroblastomas (ABs) are rare glial tumors showing overlapping features with astrocytomas, ependymomas, and sometimes other glial neoplasms, and may be challenging to diagnose. Methods. We examined clinical, histopathological, and molecular features in 28 archival formalin-fixed, paraffin-embedded AB cases and performed survival analyses using Cox proportional hazards and Kaplan–Meier methods. Results. Unlike ependymomas and angiocentric gliomas, ABs demonstrate abundant distinctive astroblastic pseudorosettes and are usually Olig2 immunopositive. They also frequently exhibit rhabdoid cells, multinucleated cells, and eosinophilic granular material. They retain immunoreactivity to alpha thalassemia/mental retardation syndrome X-linked, are immunonegative to isocitrate dehydrogenase-1 R132H mutation, and only occasionally show MGMT promoter hypermethylation differentiating them from many diffuse gliomas. Like pleomorphic xanthoastrocytoma, ganglioglioma, supratentorial pilocytic astrocytoma, and other predominantly cortical-based glial tumors, ABs often harbor the BRAFV600E mutation, present in 38% of cases tested (n = 21), further distinguishing those tumors from ependymomas and angiocentric gliomas. Factors correlating with longer patient survival included age less than 30 years, female gender, absent BRAFV600E , and mitotic index less than 5 mitoses/10 high-power fields; however, only the latter was significant by Cox and Kaplan–Meier analyses (n = 24; P = .024 and .012, respectively). This mitotic cutoff is therefore currently the best criterion to stratify tumors into low-grade ABs and higher-grade anaplastic ABs. Conclusions. In addition to their own characteristic histological features, ABs share some molecular and histological findings with other, possibly ontologically related, cortical-based gliomas of mostly children and young adults. Importantly, the presence of BRAFV600E mutations in a subset of ABs suggests potential clinical utility of targeted anti-BRAF therapy.

Expression of cytomegalovirus in glioblastoma multiforme: Myth or reality?

Abstract A role for human cytomegalovirus (HCMV) in the pathogenesis of glioblastoma multiforme (GBM) was proposed more than a decade ago and has since generated a considerable debate as a possible therapeutic target. We investigate the presence of HCMV in the specimens of patients with GBM treated in our centre. This is a retrospective cohort study to investigate the presence of HCMV by routine immunohistochemical stains and polymerase chain reaction (PCR)-based molecular analysis on formalin-fixed-paraffin-embedded tissue of all patients with GBM treated in our hospital in 2009–2013 (5 years). The evaluation of positivity by immunohistochemistry (IHC) was semi-quantitative. The molecular analysis was performed by extracting the tumour DNA from representative paraffin-embedded tissue blocks and amplified for detection by a sensitive real time PCR (RT-PCR) CMV assay. During the study period, we treated 45 patients with GBM; however, adequate pathology tissue materials were available only for 32 patients. All the pathology material was reviewed and the diagnosis was confirmed. All the cases were found to be negative for CMV expression by our IHC and RT-PCR CMV assay. Our study has shown no expression of CMV in GBM. Our results were similar to other recent reports that concluded insufficient evidence to recommend routine testing for CMV in GBM or treatment as an add-on therapy.

Anaplastic Carcinoma Arising in a Mucinous Cystic Neoplasm Masquerading as Pancreatic Pseudocyst

Mucinous cystic neoplasms (MCN) of the pancreas can vary from benign to premalignant and malignant. Preoperative diagnosis is essential to offer the patient appropriate treatment. Occasionally these cases may harbor anaplastic carcinoma while clinically masquerade as a pseudocyst. Here in, we report an unusual case of a 37‐year old female presented with recurrent abdominal pain that was suspected clinically and by imaging studies to have a pseudocyst. EUS‐FNA with internal drainage of the cyst was performed. Cytological evaluation of the cyst fluid showed numerous inflammatory cells composed mainly of many neutrophils admixed with macrophages reminiscent of the usual pseudocyst content but there were scattered rare dyscohesive malignant cells which were highly pleomorphic with multinucleation. Immunostains on the cell block showed immunoreactivity of these cells including the multinucleated cells for Cam 5.2 and AE1/AE3 and focally for Ber‐Ep4, Moc −31, and CA19‐9. The subsequent resection confirmed the presence of anaplastic (undifferentiated) carcinoma (AC) arising in a MCN of the pancreas. Diagn. Cytopathol. 2016;44:538–542.

Fine-Needle Aspiration Followed by Core-Needle Biopsy in the Same Setting: Modifying Our Approach

Fine-needle aspiration biopsy (FNAB) is a well-established initial diagnostic tool. However, in some instances limitations and shortcomings arise, making it insufficient for determining a specific diagnosis. Consequently, patients have to undergo another diagnostic procedure. The second procedure is either repeat FNAB, core-needle or open biopsy, and can be inconvenient and costly. In some centers, the FNAB is immediately followed by core-needle biopsy (CNB) in the same setting after assuring adequacy on the initial FNAB utilizing rapid on-site specimen evaluation (ROSE). It is argued that implementing such an approach will eventually have additional critical advantages that include the following: (a) it is more convenient to patients to have both procedures in one visit, (b) the tissue procured by both procedures will be more adequate, enabling cytopathologists to reach an accurate diagnosis, and (c) it is ultimately a cost-effective approach if we take into consideration the avoidance of a potential second more invasive diagnostic procedure. Since we are living in an era of patient-centered medicine coupled with cost-cutting strategies, we present here a brief review of the topic with analysis of this alternative approach, review of the pertinent literature and shed light on a few scenarios that justify this approach.

Microscopic dysgerminoma associated with anti-Ma2 paraneoplastic encephalitis in a patient with gonadal dysgenesis.

We present a 27-yr-old female with gonadal dysgenesis (46, XY), who presented to our hospital with poor consciousness, aphasia, restlessness, and visual hallucination. Physical examination revealed normal breast development and normal external female genetalia. Computed tomography scan of the head and neck revealed the presence of brain edema, hydrocephalous, and a localized hypodense lesion in the hypothalamus. Her serum was positive for the anti-Ma2, which is associated with paraneoplastic encephalitis syndrome. Computed tomography of the abdomen revealed the presence of a 7.5×5.3×3.0 cm solid pelvic mass. Interestingly, a single microscopic focus of dysgerminoma was identified in a background of stromal fibrosis and focal dystrophic calcifications. No ovarian stroma or testicular tissue was identified. To our knowledge, this is the first case of gonadal dysgenesis presenting with anti-Ma2 paraneoplastic encephalitis with dysgerminoma. A discussion about paraneoplastic encephalitis with a microscopic dysgerminoma associated with anti-Ma2 antibody is presented.

Basics of cytology.

This overview is intended to give a general outline about the basics of Cytopathology. This is a field that is gaining tremendous momentum all over the world due to its speed, accuracy and cost effectiveness. This review will include a brief description about the history of cytology from its inception followed by recent developments. Discussion about the different types of specimens, whether exfoliative or aspiration will be presented with explanation of its rule as a screening and diagnostic test. A brief description of the indications, utilization, sensitivity, specificity, cost effectiveness, speed and accuracy will be carried out. The role that cytopathology plays in early detection of cancer will be emphasized. The ability to provide all types of ancillary studies necessary to make specific diagnosis that will dictate treatment protocols will be demonstrated. A brief description of the general rules of cytomorphology differentiating benign from malignant will be presented. Emphasis on communication between clinicians and pathologist will be underscored. The limitations and potential problems in the form of false positive and false negative will be briefly discussed. Few representative examples will be shown. A brief description of the different techniques in performing fine needle aspirations will be presented. General recommendation for the safest methods and hints to enhance the sensitivity of different sample procurement will be given. It is hoped that this review will benefit all practicing clinicians that may face certain diagnostic challenges requiring the use of cytological material.

Differential diagnosis between pancreatic neuroendocrine and solid pseudopapillary neoplasms on endoscopic ultrasound-guided fine-needle aspiration. An immunohistochemical study

Objectives: To evaluate the role of applying a limited panel of immunohistochemical stains on the cellblock preparation from samples obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the aim of differentiating solid pseudopapillary neoplasms (SPNs) from neuroendocrine tumors (NETs). Methods: We retrospectively retrieved all the EUS-FNAs of the pancreas that have a diagnosis of NET or SPN that were performed at 2 tertiary care hospitals in Riyadh, Kingdom of Saudi Arabia from May 2004 to December 2014. Diff-Quik, Papanicolaou, and Immunohistochemistry stains on cellblock preparations were performed. Results: Twenty cases were available (16 pancreatic neuroendocrine tumors (pNETs) and 4 SPNs). The pNETs were immunoreactive for synaptophysin, chromogranin A and CD56 while E-cadherin was diffusely to focally cytoplasmic positive. β-catenin was negative or showed focal cytoplasmic immunoreactivity. In comparison, SPNs were positive for vimentin, CD10, CD-56, focally positive for progesterone receptors and synaptophysin, and revealed nuclear immunostaining for β-catenin. They were negative for chromogranin A and E-cadherin. Conclusion: Based on EUS-FNA samples, nuclear immunoreactivity for β-catenin with loss of membranous immunostaining for E-Cadherin can potentially facilitate differentiating SPNs from pNETs.