Panel Of Immunohistochemical Stains Research Articles

Combined utility of CD177, P53, CD105 and c-kit immunohistochemical stains improves the detection of myelodysplastic syndrome

The diagnosis of myelodysplastic syndrome (MDS) relies primarily on identifying peripheral blood cytopenia and morphologic dysplasia as well as detecting cytogenetic aberrations in a subset of patients. Accumulating data points to the importance of examining certain immunophenotypic changes characteristic of MDS, most of which are tested by flow cytometry. The role of immunohistochemistry in the diagnostic workup of MDS is less known. In this study, we used immunohistochemistry to survey the expression patterns of CD177, P53, CD105 and c- kit in a cohort of MDS bone marrow specimens (n = 57) and compared the results with a control group of patients who had cytopenia for other benign conditions (n = 49). MDS cases showed significant higher rates of: CD177-loss (13/57, 23% vs 1/49, 2%; P = .0016), P53 overexpression (8/57, 14% vs none; P = .005) and the presence of clusters of CD105-positive cells (6/57, 11% vs none; P = .021). Increased c-kit-positive cells was more common in MDS patients, but not statistically significant (17/57, 30% vs 8/49, 16%; P = .102). On multivariate analysis, only loss of CD177 expression was significantly higher in MDS group (P = .014). These findings suggest that a panel of immunohistochemical stains could serve as an adjunct tool in investigating unexplained cytopenias and warrant further comparative studies with flow cytometry.

Comparison of Immunohistochemistry Expression of CK7, HMWK and PSA in High-Grade Prostatic Adenocarcinoma and Bladder Transitional Cell Carcinoma.

Background & Objective:Prostate adenocarcinoma is the most common malignancy in males, and the urothelial bladder carcinoma is also prevalent. The histological characteristic of these two tumors is very similar in high-grade cases, and their differentiation is difficult. This study was performed to compare the immunohistochemistry panel of high-grade prostate adenocarcinomas and high-grade urothelial bladder carcinomas.Methods:In this cross-sectional study, 36 cases of prostate adenocarcinoma and 36 urothelial bladder carcinoma samples were collected from the pathology department of Shahid Beheshti Hospital in Hamedan. For each sample, expression of Cytokeratin 7, high-molecular-weight cytokeratin and Prostate-specific antigen markers was evaluated by immunohistochemistry. Comparison of expression of these markers in high-grade bladder tumors and prostate tumors was made by SPSS 25 using Chi-square test.Results:In this study, the Cytokeratin 7 positivity was seen in 88.9% of bladder cancer versus 27.8% of prostate cancer samples. High-molecular-weight cytokeratin positive immunoreactivity was noted in 55.6% of bladder cancer and 5.6% of prostate cancer samples. Prostate-specific antigen marker showed positive results in 94.4% of prostate cancer samples, but no positivity was evident in those of bladder cancer.Conclusion:A panel of immunohistochemical stains can be used to differentiate high-grade prostate adenocarcinoma from urothelial bladder carcinoma in those cases which are challenging to diagnose.

Clinicopathological Study of Primary Pediatric Gastrointestinal Lymphomas.

Background:Primary gastrointestinal lymphomas (PGIL) are uncommon in children and account for <5% of all pediatric malignancies. The objective of our study was to analyze the prognostic factors of pediatric PGILs with reference to its histological subtypes, stage, and outcomes using immunohistochemistry.Materials and Methods:Twenty cases were studied over 11 years. Clinicopathological profiles, histological details, and immunohistochemical (IHC) profiles were analyzed.Results:The mean age at the presentation was 6 years. Using IHC stains (CD CD10, CD19, CD20, CD3, terminal deoxynucleotidyl transferase, BCL 2 and 6, PAX 5, and MUM1), diffuse large B-cell lymphoma (DLBCL) was most prevalent (45%), followed by Burkitt lymphoma (35%) and lymphoblastic lymphoma (20%). DLBCLs (9) were classified using the Han's algorithm. Six were activated B-cell and 3 were germinal center B-cell subtypes. The cases of lymphoblastic lymphoma and those in Stage I disease had the best prognosis.Conclusion:Pediatric PGILs have variable presentation, outcomes, and diverse treatment modalities depending on the histological subtypes. A panel of IHC stains can be a useful adjunct for the categorization and prognosis of pediatric PGILs.

A Rare Case of Chronic Lymphoproliferative Disorder of NK Cells with an Unusual Expression of CD57

Abstract Introduction/Objective Natural Killer cells (NK-cells) malignancies are extremely rare and the two NK-cell disorders involving the peripheral blood and bone marrow include chronic lymphoproliferative disorder of NK-cells (CLPDNK) and aggressive NK-cell leukemia (ANKL). ANKL is EBV associated with a prevalence in Asian adults and a fulminant clinical course leading to death within 2 months. Methods A 76-year-old female with a history of iron deficiency anemia presented for evaluation of lymphocytosis (78 TH/mm) and negative EBV with extreme fatigue, weight loss, and worsening weakness from the past 8 months. Results The peripheral and bone marrow aspirate showed an increase in granular lymphocytes with bland nuclei and abundant pale-staining cytoplasm containing fine to coarse azurophilic granules with no evidence of nuclear atypia. Flow cytometry demonstrated an atypical lymphocytic cell population comprising &amp;gt;50% of total marrow and peripheral blood lymphocytes demonstrating loss of CD56 and diminished CD7 expression. The analysis showed atypical lymphocytes with the following immunophenotype: CD2, CD8 (the majority, at least 75%),CD7 (dim), CD38, CD11c (subset) with no expression of CD3, CD5, CD4, CD56, or CD11c. Flow cytometry is important as it helps in the phenotypic detection of aberrancy. A broad panel of immunohistochemical stains revealed scattered positivity for CD3, CD4, CD7, CD8, TIA-1, granzyme, perforin, and tryptase and negative for CD56 and CD57. Our top differential with a similar clinical course included T-cell large granular lymphocytic leukemia which is characterized by a clonal proliferation of mature cytotoxic T cells and also has an indolent course. They show CD3 positivity by flow cytometry along with co-expression of NK cell-associated markers (CD16 and CD57), and variable expression of other pan T cell markers such as CD2, CD5, CD7. It is found incidentally in patients having cytopenias with a persistent increase in circulating mature NK-cells. Of note, the PET scan revealed splenomegaly with no other significant findings.The patient was started on steroids and is currently doing well. Conclusion Thus, overall morphologic, immunophenotypic, and molecular results with negative expression of surface or cytoplasmic CD3 as well as the absence of TCR expression were most consistent with CLPD-NK with an unusual expression of CD57 expression detected in flow cytometry.

P16, Ki67, P53, and WT1 Expression in Uterine Smooth Muscle Tumors: An Adjunct in Confirming the Diagnosis of Malignancy in Ambiguous Cases.

The diagnosis of uterine smooth muscle tumors is sometimes difficult, as these tumors may show worrisome features, suspicious for but not diagnostic of malignancy. The recommended immunohistochemical panel in this setting is currently under debate. In this study, we aimed to find a panel of immunohistochemical stains that would be helpful in determining the correct diagnosis in ambiguous uterine smooth muscle tumors, with an emphasis on investigating the possible usefulness of the WT1 antibody. Uterine leiomyomas were found to be immunoreactive with WT1. Since a previous study reported on the lack of immunoreactivity of uterine leiomyosarcomas with WT1, we speculated that WT1 might be useful in this setting. We retrospectively reviewed the medical charts and slides of 91 patients: 22 with leiomyosarcoma, 15 with smooth muscle tumor of uncertain malignant potential, and 54 with leiomyoma. Immunohistochemical stains for WT1, p16, p53, and Ki67 were performed on each case. We found that immunoreactivity with p16 and Ki67 (>40% and >10% of the tumor cells, respectively) and loss of nuclear expression of WT1 (<10% of the tumor cells) were significantly more common in leiomyosarcomas (all P<0.001). Mutated p53 immunohistochemical staining pattern was significantly more prevalent in leiomyosarcomas than in leiomyomas (P<0.001). Thus, in diagnostically challenging uterine smooth muscle tumors, we recommend using an immunohistochemical panel composed of Ki67, p16, p53, and WT1. A positive result in either of the former 2 (p16 >40% and/or Ki67 >10%) has the strongest association with leiomyosarcoma (sensitivity: 95.5%, specificity=88.9%, positive predictive value=77.8%, negative predictive value=98.0%).

SAT-LB42 Bilateral Large Calcified Adrenal Leiomyoma Mimicking Adrenal Malignancy: A Rare Case Report With Literature Review

Background: Adrenal leiomyoma is a very rare benign soft tissue tumor, it is even more unusual if presenting bilaterally; 21 cases have been reported in the literature and only six had bilateral involvement; 5 in the pediatric population and only one in an adult patient. Radiological appearance may frequently be confused with malignancy especially if large, calcified and with central necrosis. We report a rare case of bilateral, large, calcified, non-functioning adrenal leiomyoma in a 20-year-old female, who was suspected for a malignancy preoperatively. Clinical Case: A 20 year-old-female presented with chronic abdominal discomfort, fatigue, and inability to gain weight. On examination, she was normotensive, underweight with BMI of 15.6 kg/m2, and there were no stigmata of Cushing’s syndrome, Addison’s disease or pheochromocytoma. A contrast CT scan of the abdomen revealed the presence of bilateral well-defined suprarenal lesions measuring 8.5 x 8.5 x 7.2 cm and 4.7 x 4.2 x 3.5 cm on the right and left side, respectively. The lesions showed large central areas of necrosis with multiple punctate calcifications and heterogenous peripheral enhancement. The radiological differential diagnosis included adrenal cortical carcinoma, adrenal metastasis, infectious etiology, and bilateral pheochromocytoma. Her hormonal assays showed normal free cortisol and catecholamine metabolites in the urine and normal serum androgens. Thus, the tumors were concluded to be non-functioning. Adrenal insufficiency was ruled out after a short Synacthen test. The patient underwent a successful right adrenalectomy. Resected specimen measured 10 x 9.5 x 7.5 cm. Histology revealed a well-circumscribed and pseudo-encapsulated smooth muscle tumor comprised of bland, spindle-shaped cells. The panel of immunohistochemical stains supported the diagnosis of leiomyoma. Postoperatively, the symptoms improved, she gained 4 kg weight over the following 4 months, and short Synacthen test confirmed an intact adrenal function. To avoid lifelong adrenal insufficiency and after discussion with the patient, we agreed to leave the left adrenal mass and follow it by serial imaging. There was only a minimal increase in the size over the following 4 years (5.5 x 4.5 x 3.8 cm). Conclusion: Adrenal leiomyoma is an extremely rare adrenal tumor and can be confused with adrenal malignancy. Therefore, it should be considered in the differential diagnosis of adrenal incidentalomas. In the case of bilateral etiology, permanent adrenal insufficiency and longterm replacement therapy can be avoided in certain population by removing the larger tumor and continuous follow-up for the other side.

Nodular histiocytic hyperplasia: A rare incidental finding that can be potentially misdiagnosed as malignancy

Introduction: Nodular histiocytic hyperplasia is a rare benign condition that occur most commonly in body cavities such pleura, peritoneum, pericardium and in hernial sacs. Morphologically, it comprises nodular florid proliferation of histiocytes which can mimic malignant neoplasms such as metastatic carcinoma and mesothelioma. Therefore, it is essential to recognize this entity to prevent a potential diagnostic pitfall.Aim: To familiarize pathologists with a rare entity to prevent a potential diagnostic pitfall. Material and Methods: A case of inguinal hernia sac with incidental nodular histiocytic hyperplasia was studied for detailed histopathological examination and expression of immunohistochemical markers. Results: Running a wide panel of immunohistochemical stains revealed that the proliferative cells are positive for the histiocytic markers CD68 and CD163 but negative for epithelial and mesothelial markers. Conclusion: Nodular histiocytic hyperplasia is a benign condition characterized by proliferation of histiocytes that were believed previously to be of mesothelial origin. It is essential to recognize this entity as it can be potentially misdiagnosed as a malignant neoplasm.

Primary Cutaneous Adenomyoepithelioma Ex Spiradenoma With Malignant Histologic Features, Epithelial-Myoepithelial Carcinoma Type: A First Case Report With Molecular Studies

Adenomyoepithelioma is an extremely rare primary cutaneous neoplasm. Although there is ample evidence on the existence of malignant adenomyoepithelioma in the breast, a malignant counterpart in the skin has not been documented. We report a primary cutaneous adenomyoepithelioma (pcAME) with malignant features arising from a spiradenoma in a 39-year-old female patient. The tumor was solid-cystic in appearance and entirely located in the subcutaneous tissue. Histologically, the tumor displayed foci of adenomatous changes and adenomyoepitheliomatous hyperplasia adjacent to a minute spiradenoma. Gradual increase of architectural complexity, cytologic atypia, mitotic activity, and infiltrative growth were observed in a significant portion of the neoplasm, indicative of transformation to adenomyoepithelioma and subsequently low- to high-grade salivary-type epithelial-myoepithelial carcinoma (EMCA). The intimate dual populations of ductal and myoepithelial cells were highlighted by a panel of immunohistochemical stains in all different components of the tumor. Molecular studies revealed a PIKCA3 mutation, a genetic aberration that has been documented in EMCA, particularly of breast origin. The current case documents for the first time a pcAME with malignant features arising from a spiradenoma and suggests adenomyoepithelioma ex spiradenoma as a possible tumorigenesis pathway of this rare cutaneous tumor.

A Report of Submucosal Intravascular Paraganglioma of the Gallbladder and Review of the Literature

Abstract Objectives The purpose of this case study and review of the literature is to allow pathologists to recall an appropriate differential diagnosis for submucosal epithelial tumors of the gallbladder. It is also important to note the immunohistochemical evaluation of a paraganglioma. Methods Intraoperative findings were multiple adhesions of the omentum to the gallbladder itself, with a mildly dilated cystic duct measuring 6 to 7 mm externally. The intraoperative cholangiogram was normal with no evidence of retained stones. The gallbladder was 9.5 cm and essentially unremarkable with no stones upon gross examination. Palpation revealed a 5 × 4 × 4-mm gray-tan cystic duct lymph node that was microscopically unremarkable. Microscopically, there was a 2.7-mm submucosal intravascular epithelioid tumor. Cytologically, the cellular infiltrate was cohesive, filled, and expanded a single submucosal vessel. A broad panel of immunohistochemical stains was performed, with the results listed below. Results Carbonic anhydrase IX: Negative; Monoclonal CEA: Negative; CK7: Negative; CK 20: Negative; Gata-3: Positive; Mart-1: Negative; OCT3/4: Strong diffuse positive; P 63: Negative; Pancytokeratin: Negative; PAX-8: Negative; S-100: Negative; WT1: Negative; PLAP: Negative; Hep par 1: Negative; AFP: Negative; CD117: Negative; CD 30: Negative; CDX2: Negative; Glypican 3: Negative; SALL4: Negative; Inhibin: Negative ERG: Negative; CD34: Negative; CD56: Strong diffuse positive; Synaptophysin: Strong diffuse positive; Chromogranin: Strong diffuse positive. Conclusion Expert opinion was requested to confirm the presumed diagnosis on this case. The consulting pathologist was in agreement that this was best classified as an intravascular paraganglioma. The patient was seen in follow-up and a CT of the chest, abdomen, and pelvis was ordered. Interestingly, a 1.9-cm enhancing upper pole right renal mass was identified. The patient was sent to urologic surgical consultation in which they believed this tumor to represent a stage 1a primary renal cell carcinoma and subsequently sent for radiofrequency ablation.

Dimensional Analysis of CD44High CD24Low and Ki67 in Triple Negative Breast Cancer.

AIM:To study the dimensional analysis CD44high CD24low and Ki67 in triple negative breast cancer (TNBC).METHODS:This cross-sectional study was performed on patients with breast cancer in Haji Adam Malik Hospital Medan from 2013 to 2016 to determine the frequency and pathologic features of TNBC by immunohistochemistry stained.RESULTS:By using immunohistochemistry staining panel of CD44, CD24, Twist, Claudin 7, CK5, CK8/18, EMA, E-Cadherin, Ki-67, a total 67 breast tumour samples with TNBC were classified as 9 stem-cells like 1 basal, 22 baso-luminal, and 23 luminal subtypesCONCLUSION:By using immunohistochemical staining panel, TNBC can be differentiated into stem cells like basal, baso-luminal and luminal subtypes. Didifferentiation and EMT can produce heterogeneity in TNBC subtypes and this will affect in handling TNBC. Stemness in stem cells- like subtypes are resistant to therapy. Therefore, TNBC needs special attention in order to assist in more optimal handling.

Advances in the cytologic diagnosis of gastroenteropancreatic neuroendocrine neoplasms.

Two-thirds of neuroendocrine neoplasms arising in the human body originate from the gastrointestinal system or pancreas. Gastroenteropancreatic neuroendocrine neoplasms are heterogeneous, comprising both well differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). The clinical presentation, molecular characteristics, and behavior are distinct for NETs and NECs. Fine-needle aspiration is an important modality for the primary diagnosis and staging of these neoplasms and can provide information of prognostic and therapeutic significance. Our evolving understanding of neuroendocrine neoplasm biology has led to several iterations of classification. In this review, new concepts and issues most relevant to cytology diagnosis of gastroenteropancreatic neuroendocrine neoplasms are discussed, such as newer detection methods that aid in diagnosis and staging, recent changes in World Health Organization classification, practical issues related to grading these neoplasms on cytology, guidelines for diagnostic reporting, and panels of immunohistochemical stains for the diagnosis of metastasis. The current understanding of genetic and epigenetic events related to tumor development and potential applications for cytology also are presented as they relate to prognostication and recent therapeutic advances.

Differentiating Intrarenal Ectopic Adrenal Tissue From Renal Cell Carcinoma in the Kidney.

Adrenal rest (AR) is the presence of ectopic adrenal cortical tissue, often identified incidentally during autopsy (20% of postmortem examination). In the kidney, AR can be found in 6% of the general population. Ectopic adrenal tissue is of no functional significance but may in some cases, pose a diagnostic challenge for the pathologist, especially in the context of renal clear cell renal cell carcinoma (RCC) and small needle biopsies. To investigate the utility of immunohistochemical stains in distinguishing AR from RCC. Archival cases of AR, in our institution, were reviewed and compared with a cohort of RCC cases using a panel of immunohistochemical stains, including PAX2, PAX8, calretinin, and inhibin. Nine of 10 (90%) cases of AR showed positive staining for inhibin and negative staining for calretinin, PAX2 and PAX8. One AR case was positive for PAX2 and PAX8 in addition to inhibin. All (100%) RCC cases were positive for PAX2 and PAX8, but negative for inhibin and calretinin. A panel of PAX2, PAX8 and inhibin may be useful markers for distinguishing AR from RCC. Calretinin was noncontributory in our study.

Solitary fibrous tumor occurring in the parotid gland: a case report

BackgroundSolitary fibrous tumor is an uncommon spindle cell neoplasm of unknown origin. It has been reported in many anatomic sites, with a rare occurrence in the head and neck region. Solitary fibrous tumors of the parotid gland are exceptional; their clinical and radiologic features are non specific, often mimicking more common salivary gland tumors. Pathologic examination and immunohistochemistry are required to make the correct diagnosis. The prognosis is favorable, with most tumors being benign, and complete surgical resection is the treatment of choice.Case presentationWe report the case of a 42-year-old man who presented with a painless mass involving the parotid gland. A parotidectomy was performed, and follow up was unremarkable. Gross examination showed a well circumscribed, firm tumor measuring 3,4 cm. Histologically, the tumor was composed of a spindle cell proliferation of variable cellularity, with staghorn vessels. A panel of immunohistochemical stains was performed, and confirmed the diagnosis of parotid gland solitary fibrous tumor.ConclusionIn this report we aim to increase awareness of this rare entity among clinicians and pathologists, and to emphasize the role of immunohistochemistry in confirming the diagnosis.

Application of Immunohistochemistry in Undifferentiated Neoplasms: A Practical Approach.

- Advances in interventional technology have enhanced the ability to safely sample deep-seated suspicious lesions by fine-needle aspiration procedures. These procedures often yield scant amounts of diagnostic material, yet there is an increasing demand for the performance of more ancillary tests, especially immunohistochemistry and, not infrequently, molecular assays, to increase diagnostic sensitivity and specificity. A systematic approach to conserving diagnostic material is the key, and our previously proposed algorithm can be applied aptly in this context. - To elaborate a simple stepwise approach to the evaluation of cytology fine-needle aspiration specimens and small biopsy tissue specimens, illustrating the algorithmic application of small panels of immunohistochemical stains in providing an accurate diagnosis with scant amounts of tissue, including the potential pitfalls that may arise while using immunohistochemical staining on small quantities of tissue. - The sources include literature (PubMed), the first Chinese American Pathologists Association Diagnostic Pathology Course material, and the review authors' research data as well as practice experience. Seven examples selected from the CoPath database at Geisinger Medical Center (Danville, Pennsylvania) are illustrated. - A stepwise approach to the evaluation of fine-needle aspiration and small biopsy tissue specimens in conjunction with a small panel of select immunohistochemical stains has been successful in accurately assessing the lineage/origin of the metastatic tumors of unknown primaries. The awareness of the common pitfalls of these biomarkers is essential in many instances.

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.

B-cell posttransplant lymphoproliferative disorder isolated to the central nervous system is Epstein-Barr virus positive and lacks p53 and Myc expression by immunohistochemistry

In this retrospective study from one institution, we performed a clinicopathological study of a cohort of patients with posttransplant lymphoproliferative disorder (PTLD) confined to the central nervous system. We also identified a comparison cohort of patients with de novo primary diffuse large B-cell lymphoma of the central nervous system. We performed a detailed morphologic review, evaluated Epstein-Barr virus (EBV) by in situ hybridization, and interpreted a panel of immunohistochemical stains in a subset of cases including Hans classification markers (CD10, BCL6, MUM1), p53, CD30, Myc, and BCL2. All 17 of the posttransplant and none of 11 de novo cases were EBV positive (P < .005). Morphologic patterns identified in the PTLD cases were monomorphic diffuse large B-cell lymphoma pattern (10 patients) and "T-cell-rich" pattern (7 patients). The monomorphic posttransplant cases were more likely to be Myc negative (P = .015) and CD30 positive (P < .005) than the de novo cases, and showed a similarly low rate of p53 positivity by immunohistochemistry. No prognostic factors for overall survival were identified. Central nervous system PTLD is EBV positive, typically lacks p53 and Myc expression by immunohistochemistry, and can present with numerous background T lymphocytes.

Oct2 and Bob1 are sensitive and specific markers in lineage determination of B cell lymphomas with no expression of conventional B cell markers.

Rare cases of B cell lymphomas do not express conventional B cell markers (CD20, CD79a and PAX5), and these types of lymphomas include anaplastic lymphoma kinase (ALK)-positive large B cell lymphoma, plasmablastic lymphoma, primary effusion lymphoma and the solid variant of primary effusion lymphoma, extracavitary human herpesvirus 8 (HHV8)-positive large B cell lymphoma. Establishing accurate diagnoses of these B cell lymphomas can be challenging, and often requires a large panel of immunohistochemical stains, molecular assays and cytogenetic studies. B cell-specific transcription factors, Oct2 and Bob1, have been shown to be expressed consistently in most, if not all, B cell lymphomas, and therefore we investigated the utility of Oct2 and Bob1 immunohistochemistry in lineage determination of the aforementioned B cell lymphomas. We selected 34 cases of previously diagnosed B cell lymphomas with no or weak expression of CD20, CD79a and PAX5. Oct2 and Bob1 were positive in 74% (25 of 34) and 85% (29 of 34) of the cases, respectively. When we combined the results of these two immunostains, 94% (32 of 34) cases expressed at least one of these two markers. We also included 51 control cases of non-B cell neoplasms, and none of them expressed either Oct2 or Bob1. Oct2 and Bob1 are very reliable in determining B cell lineage in the absence of expression of other pan-B cell markers, and it should provide great diagnostic benefit to include them both in a panel of immunohistochemistry to assess undifferentiated malignant neoplasms.

Epstein-Barr virus-negative diffuse large B cell lymphoma with aberrant expression of CD3 and other T cell-associated antigens: report of three cases with a review of the literature

Expression of CD3 ona mature B cell neoplasm, such as diffuse large B cell lymphoma (DLBCL), is extremely rare. When it is present, it will cause diagnostic confusion since the classification of lymphoid neoplasms is largely based on immunophenotyping to determine the cell lineage. We report three cases of DLBCL with CD3 and other T cell-associated antigens. A literature search identifies 30 additional cases of DLBCL expressing CD3, with the majority (78.6%) displaying cytoplasmic expression, while two of our cases demonstrate membranous staining. Additionally, expression of CD3 tends to be partial and weak in both our series and the reported cases. Of the 28 cases reported in the literature that were tested for Epstein Barr Virus (EBV), 16 (57.1%) are positive, suggesting an important role of EBV in promoting lineage ambiguity/infidelity, whereas, all three cases in our series are negative for the virus. All three cases in our series show homogeneous expression of multiple B cell specific antigens, while the reported cases show variable expression with some having B cell antigens downregulated, particularly in those cases with EBV association or anaplastic morphology. A low threshold for testing EBV status is advocated in DLBCL with phenotypic ambiguity along with panels of immunohistochemical stains and B/T cell receptor gene rearrangement analysis.

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.

A single EBUS-TBNA procedure can support a large panel of immunohistochemical stains, specific diagnostic subtyping, and multiple gene analyses in the majority of non–small cell lung cancer cases

Targeted therapies for pulmonary adenocarcinoma (ACA) necessitate specific subtyping and molecular testing of non-small cell lung carcinomas (NSCLC). However, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has decreased the tissue available for these assessments. While EBUS-TBNA specimens have previously been reported to successfully subtype NSCLC, allow immunohistochemistry (IHC), and support molecular diagnostics, no studies have documented the extent to which all objectives are possible in a single sample. Of 107 consecutive EBUS-TBNA specimens that were eligible for molecular testing, 98.8% had enough tissue for IHC, 80.2% received a definitive subtype, and 71.0% had both sufficient tissue to attempt molecular testing and technical success on multigene next-generation sequencing and ALK fluorescence in situ hybridization assays. Both subtyping and molecular diagnostics were possible in 57.9% of patients. The mean number of immunostains performed did not differ between patients with or without successful molecular testing (4.4 versus 4.6, P = .88). Only 40% of patients with insufficient tissue underwent repeat sampling. These findings indicate that a majority of EBUS-TBNA specimens provide sufficient tissue for subtyping pulmonary NSCLC, performing IHC, and completing multiple gene analyses. Although priorities must be assessed for each case individually, performance of IHC does not detract from completion of molecular diagnostics in general. Because most patients never undergo repeat sampling, the tissue yield of EBUS-TBNA should be improved to maximize evaluation for targeted therapies.