Study of the Utility of Myeloid Cell Nuclear Differentiation Antigen (MNDA) in the Diagnosis of Marginal Zone Lymphoma.

Myeloid cell nuclear differentiation antigen (MNDA) is normally expressed on myelomonocytic cells and a subset of B lymphocytes. It was found to be differentially expressed between nodal marginal zone lymphoma (MZL) and follicular lymphoma (FL). However, MNDA has not been widely used as a diagnostic marker in clinical practice. To validate its utility, we studied the expression of MNDA by immunohistochemistry in 313 cases of small B-cell lymphomas. Our results showed that MNDA was positive in 77.9% of MZL, 21.9% of mantle cell lymphoma, 28.9% of small lymphocytic lymphoma/chronic lymphocytic leukemia, 2.6% of FL, and 25% of lymphoplasmacytic lymphoma. MNDA positivity varied from 68.0% to 84.0% among the 3 MZL subtypes, with extranodal MZL having the highest percentage. There was a statistically significant difference in MNDA expression between MZL and FL, mantle cell lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia, or lymphoplasmacytic lymphoma. CD43 expression was slightly more frequent in MNDA-negative MZL than in MNDA-positive MZL. Combined use of CD43 and MNDA improved the diagnostic sensitivity for MZL from 77.9% to 87.8%. There was a trend of positive correlation between MNDA and p53 in MZL. In conclusion, MNDA is preferentially expressed in MZL among small B-cell lymphomas and it is a useful marker for the differentiation of MZL and FL.

Primary spinal extranodal NK/T-cell lymphoma diagnosed by fine-needle aspiration and core biopsy.

We report an extremely rare case of primary spinal extranodal NK/T-cell lymphoma (PSENKTL). A 54-year-old man presented with fever of unknown etiology for 2 months, with clinical evidence of hemophagocytic lymphohistiocytosis. Imaging studies revealed multiple spinal lesions without evidence of disease in other body sites. Fine-needle aspiration and core biopsy (FNACB) of a paraspinal mass showed a monotonous population of intermediate lymphocytes with abundant cytoplasm with fine granules, round to slightly irregular nuclei, and inconspicuous nucleoli. Core biopsy revealed diffuse infiltration by cells with a NK cell phenotype, positive Epstein-Barr virus-encoded small RNA, and negative T-cell receptor gene rearrangement. Bone marrow biopsy showed the presence of hemophagocytosis without evidence of lymphoma. The disease disseminated to the small bowel late in the clinical course and the patient died shortly after admission. This unusual case was diagnosed by FNACB and raised awareness of ENKTL as a differential diagnosis in spinal lesions.

Utility of TRPS-1 immunohistochemistry in diagnosis of metastatic breast carcinoma in cytology specimens.

INTRODUCTION: At present, GATA binding protein 3 (GATA-3) is the most frequently used diagnostic immunohistochemical (IHC) marker for breast carcinoma (BC). However, it is not specific and has very low sensitivity for triple-negative BC (TNBC). SRY-box transcription factor 10 (SOX-10) and trichorhinophalangeal syndrome type 1 (TRPS-1) have been suggested for inclusion in the diagnostic workup of TNBC. TRPS-1 has not been established in cytology specimens as a diagnostic IHC marker for metastatic BC (MBC). Hence, in the present study we evaluated the utility of TRPS-1 in diagnosing MBC in cytology specimens. MATERIALS AND METHODS: MBC cases diagnosed on cytology specimens from January to October 2020 were included in the present study. Only cases with hormonal status available and ≥20 tumor cells on cell blocks were included in the study. The cell blocks were assessed for TRPS-1, GATA-3, and SOX-10 IHC marker positivity (intensity and percentage of tumor cells). The results were correlated with the specimen type (fine needle aspiration [FNA] versus body fluid) and various BC prognostic subgroups. RESULTS: We analyzed 61 cases, including 33 body fluid and 28 FNA (13 lymph node, 10 bone, 2 liver, 2 soft tissue, and 1 lung) specimens. TRPS-1 had 97.2% positivity in ER/PR+ (estrogen receptor/progesterone receptor-positive) MBC compared with GATA-3, which had 100% positivity in the same group. TRPS-1 showed high positivity in 35 of 37 cases (94.6%) and intermediate positivity in 1 (2.6%) and was negative/low positive in 1 case (2.7%). In contrast, GATA-3 showed high positivity for all 37 cases (100%). SOX-10 showed positivity in only 1 of 37 cases (2.7%), with intermediate positivity. In the HER2+ (human epidermal growth factor receptor 2-positive) group, TRPS-1 showed high positivity in 5 of 7 cases (71.4%), intermediate positivity in 1 case (14.3%), and negativity in 1 case (14.3%). However, GATA-3 showed high positivity in 6 of 7 cases (85.7%) and negative/low positivity in 1 case (14.3%). SOX-10 was negative in all 7 cases. In TNBC, TRPS-1 showed high positivity in 16 of 17 cases (94%) and intermediate positivity in 1 (5.9%), and GATA-3 showed high positivity in 9 (53%), intermediate positivity in 2 (11.8%), and low positive/negative in 6 of the 17 cases (35.3%). TRPS-1 expression was significantly higher than GATA-3 expression for the number of positive cases (P = 0.07), mean percentage of positive tumor cells (P = 0.005), and intensity of reactivity (P = 0.005). SOX-10 expression was present in only 5 of 17 cases (29%), with a mean percentage of positivity in the tumor cells of 26.5% and intensity of 0.8. No differences were found in the IHC results between the different specimen types (FNA versus fluid) in any group. CONCLUSIONS: TRPS-1 is a highly sensitive new diagnostic IHC marker for breast carcinoma, with a similar positivity rate in ER/PR+ and HER2+ BC compared with GATA-3 and a higher positivity rate than GATA-3 and SOX-10 in TNBC in cytology specimens. In particular, when only a few clusters of tumor cells are present on the cell block, TRPS-1 can be highly useful, because its mean percentage of positive tumor cells and intensity are higher than those of other IHC markers.

Intravascular Large B Cell Lymphoma of the Breast: A Rare Entity.

Intravascular large B-cell lymphoma (IVLBCL) is a rare and high-grade disease of neoplastic lymphoid cells within the vascular lumina of small- to medium-sized vessels. The disease carries a grim prognosis despite robust treatment protocols. We discuss the case of a 58-year-old female who presented with mammographic screening abnormality which led to more investigations and ultimately to this diagnosis. The patient had no prior history of a lymphoma or in situ and invasive carcinoma of the breast. To our knowledge, IVLBCL of the breast is a very rare and an unusual location for this type of a lymphoma and so far, only five reported cases. Through our case report, we not only discuss the case but also review literature on this rare entity.

Human Papillomavirus (HPV) Detection by Chromogenic In Situ Hybridization (CISH) and p16 Immunohistochemistry (IHC) in Breast Intraductal Papilloma and Breast Carcinoma.

PURPOSE: This study explored human papillomavirus (HPV) amplification in breast benign and malignant lesions by chromogenic in situ hybridization (CISH) and the concordance of p16 expression by immunohistochemistry. PATIENTS AND METHODS: The presence of HPV6/11 and HPV16/18 in 33 cases of intraductal papilloma, 34 cases of ductal carcinoma in situ (DCIS), and 56 cases of invasive breast carcinoma (IBC) was evaluated using matched-background breast parenchyma and breast reduction as control groups. Association with clinicopathologic factors including prognosis was assessed. RESULTS: HPV 6/11 was observed in 0 cases (0%) of breast reduction, one case (3%) of intraductal papilloma, 11 cases (32.4%) of DCIS, and eight cases (14.3%) of IBC. HPV 16/18 was detected in three cases of (9.1%) breast reduction, six cases (18.8%) of intraductal papillomas, 14 cases (41.2%) of DCIS, and 25 cases (44.6%) of IBC. There was no difference in the HPV status between intraductal papilloma and breast reduction. HPV amplification in intraductal papilloma did not associate with developing atypia or carcinoma after long-term follow-up. However, HPV 6/11 and HPV 16/18 amplification was significantly higher in both DCIS and IBC when compared with breast reduction (P < .05). Compared with background breast parenchyma, HPV 16/18 amplification was significantly higher in both DCIS and IBC (P = .003 and P = .013, respectively). No correlation between p16 immunohistochemical staining and either of the HPV CISH testing was found (P > .05). CONCLUSION: HPV infection was detected in both breast lesions and background parenchyma. HPV infection may play a role in the pathogenesis of breast cancer but is not associated with intraductal papilloma. Immunohistochemical stain for p16 is not a good surrogate marker for HPV infection in breast lesions.

Evaluating of HPV-DNA ISH as an adjunct to p16 testing in oropharyngeal cancer.

AIM: Current guidelines recommend p16 immunohistochemistry (IHC) for testing human papillomavirus (HPV) in oropharyngeal carcinoma (OPSCC). We evaluated the value of adding DNA in situ hybridization (ISH) to p16 IHC. METHODS: Fifty patients with OPSCC were analyzed. Concordance between HPV-DNA ISH and p16 IHC was measured by Gwet's agreement coefficient. RESULTS: p16 IHC was positive in 35/48 (72.9%), negative in 8/48 (16.7%) patients. Wide spectrum DNA-ISH was positive in 9/23 (39%) and negative in 14/23 (60.9%) patients. High-risk 16/18 (HR) HPV DNA-ISH was positive in 11/23 (47.8%) and negative in 12 (52.2%) patients. The agreement between HPV DNA-ISH and p16 IHC is fair (Gwet's AC1 = 0.318). CONCLUSION: The agreement between p16 IHC and HPV-DNA ISH was fair. However, ISH sensitivity was low. Our findings add to the current data that p16 IHC testing is reliable and may be enough as a stand-alone test for HPV detection in OPSCC.

Applying the Paris system for reporting urine cytology to challenging cytology cases.

BACKGROUND: Implementing the Paris system for reporting urine cytology (TPS) can substantiate atypical diagnosis while improving standardization and risk stratification. This study evaluates its performance and reproducibility in challenging cases and examines whether focused education of morphological features can improve outcomes. METHODS: In our prior study, urine cytology cases diagnosed as "atypical" with surgical follow-up were used. Cases showing poor agreement in that study were collected for this one. Representative photographs of each case were taken and distributed via online questionnaires. Participants were asked to render an initial diagnosis and evaluate the presence of several morphological features. Educational material was distributed, followed by additional questionnaires. RESULTS: Three participants evaluated 40 cases before and after educational materials. TPS diagnoses were significantly more specific (0.23 vs 0.59, P = 0.004) and more accurate (0.43 vs 0.66, P = 0.0125) than diagnoses made with our institutional system. Fewer overall cases were diagnosed as "atypical" with TPS. TPS education resulted in slightly, though not significantly, more specific diagnoses (0.25 vs 0.59, P = 0.083). Interobserver agreement decreased for nuclear-to-cytoplasmic (N/C) ratio, TPS diagnoses and initial diagnoses, and increased for all other features. TPS resulted in downgrading of cases with biopsy-proven low grade urothelial neoplasm (LGUN) from "atypical" to negative for high grade urothelial carcinoma (NHGUC) (P = 0.018). CONCLUSIONS: Use of TPS in challenging urine cytology cases can improve specificity, risk stratification, and diagnostic accuracy while decreasing the number of "atypical" diagnoses. Though training can help cytopathologists better apply these criteria, it is unclear how to effectively improve evaluation of N/C ratio.

Diagnosis of Lymphoma Using Fine-Needle Aspiration Biopsy and Core-Needle Biopsy: A Single-Institution Experience.

OBJECTIVE: The objective is to study the efficacy of fine-needle aspiration biopsy (FNAB) and core-needle biopsy (CNB) in the diagnosis of lymphoma in a single institution. STUDY DESIGN: We retrospectively reviewed 635 FNAB/CNB cases performed in our institution to rule out lymphoma during a 4-year period and collected the relevant clinical and pathological information for statistical analysis. RESULTS AND CONCLUSIONS: This cohort comprised 275 males and 360 females, with a median age of 57 years. Among the 593 cases with adequate diagnostic materials for lymphoma work-up, 226 were positive for lymphoma, 286 were negative for lymphoma, and 81 were nondiagnostic. Each case had an FNAB, and 191 cases also underwent a CNB. The subclassification rate according to the WHO (2008) was 67% overall, 81% for the FNAB with CNB group, and 40% for the FNAB group. In the FNAB with CNB group, the subclassification rates for cases with and without a history of lymphoma were not significantly different. A definitive diagnosis of lymphoma relied on ancillary studies, but was not affected by location, or the needle gauge of CNB. Follow-up data revealed a high diagnostic accuracy of FNAB with CNB. In conclusion, the use of FNAB and CNB with ancillary studies is effective in providing a definitive diagnosis of lymphoma in our experience at the Northwell Health System.

Aggressive natural killer cell leukemia mimicking interstitial lung diseases with the activation of the mitogen-activated protein kinase pathway.

Aggressive natural killer (NK) cell leukemia (ANKL) is a rare form of leukemia with an aggressive clinical course. It commonly involves the peripheral blood, bone marrow, liver, and spleen but rarely involves the lungs. We report a 36 year-old woman who presented with pulmonary lesions we suspected to be interstitial lung disease on an imaging study. A lung biopsy showed extensive lymphoid infiltrate growing along pre-existing alveolar septa without destroying the alveolar spaces. Further workup revealed hepatomegaly, borderline splenomegaly, and multiple lymphadenopathies. Her laboratory tests showed leukocytosis, anemia, thrombocytopenia, abnormal liver enzymes, and elevated lactate dehydrogenase. A bone marrow (BM) aspirate smear revealed many intermediate to large lymphocytes with dispersed chromatin, basophilic cytoplasm, and some azurophilic granules. A BM biopsy showed hypercellularity with interstitial lymphoid infiltrate in a background of trilineage hematopoiesis and histiocytosis with hemophagocytosis. Immunohistochemical studies performed on both the lung and BM biopsies showed the neoplastic cells to be positive for CD2, CD3, CD7, CD56, granzyme B, phosphor-MAPK (pMAPK), EBER (Epstein-Barr Virus-encoded small RNA) by in situ hybridization; they were negative for CD4, CD5, CD8, CD30, LMP1, and phospho-STAT3 (pSTAT3). A flow cytometry analysis of the BM aspirate identified a population of atypical lymphocytes with the NK cell phenotype. Molecular studies were negative for T-cell receptor gene rearrangements, and the neoplastic cells displayed a complex karyotype. The patient responded initially to chemotherapy but died of multiorgan failure two months after the diagnosis. We present a case of ANKL mimicking interstitial lung disease with the activation of MAPK pathway.

Composite Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia and Follicular Lymphoma: A Clinicopathological Study of Six Cases.

BACKGROUND: Composite small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) and follicular lymphoma (FL) is extremely rare, and only 13 cases have been reported previously. METHODS: We identified 6 cases of composite SLL/CLL and FL in our database and studied their clinical, histologic, immunophenotypic, and cytogenetic features. A literature review of the existing cases was also conducted. RESULTS: The patients included 4 males and 2 females, with a median age of 72 years. Four patients presented with lymphadenopathy and 2 with extranodal diseases. Lymphocytosis was seen in 2 cases. Serum lactate dehydrogenase levels were within normal range in all but one case. There were 2 histologic patterns: SLL/CLL predominant pattern (type I) and FL predominant or mixed pattern (type II). The type I pattern was exclusively associated with in situ follicular neoplasia (ISFN). The SLL/CLL showed typical morphology and immunophenotype in all the cases. The FL component included low grade (n = 3), ISFN (n = 2), and primary cutaneous FL (n = 1). Four cases had staging bone marrow biopsies including 3 cases with involvement by SLL/CLL and 1 case with involvement by SLL/CLL and FL. Four patients received treatments, one was under clinical surveillance, and one had no available information. All patients were alive after a median follow-up of 22 months. CONCLUSIONS: This is the largest case serial of composite SLL/CLL and FL. The CL affects elderly individuals, presents with advanced clinical stage, and appears to have a relatively indolent clinical course.

CD5-Positive Intravascular Large B-Cell Lymphoma in a Patient with Wilson's Disease: Case Report and Review of the Literature.

Intravascular large B-cell lymphoma (IVLBCL) is a rare extra-nodal B-cell lymphoma that proliferates within small/intermediate blood vessels and capillaries while sparing large blood vessels and organ parenchyma. Clinical presentation is highly variable and may include B symptoms, neurological deficits, and/or cutaneous findings. The diagnosis of IVLBCL is difficult due to multiorgan involvement and nonspecific symptoms. We describe the case of a 68-year-old male who presented with progressive weakness, confusion, and falls. He had a past medical history of liver cirrhosis secondary to Wilson's disease. Physical exam and laboratory results revealed a lethargic man with jaundice, hepatic encephalopathy, and abnormal liver/kidney function tests. He expired after a short hospital course in the setting of hepatic and renal failure. Postmortem examination revealed large neoplastic lymphoid cells involving multiple organ blood vessels; however skin and neurologic involvement was absent. The neoplastic cells demonstrated B-cells positive for CD5, rendering a diagnosis of IVLBCL. Our case represents the occurrence of IVLBCL with CD5-positivity in a patient with Wilson's disease, diagnosed at autopsy demonstrating the challenging nature of diagnosing IVLBCL.

The impact of subdividing the "atypical" category for urinary cytology on patient management.

INTRODUCTION: The purpose of the study is to determine the impact of subdividing the "atypical" cytology interpretation into two groups: Atypical urothelial cells of uncertain significance (AUC-US) and Atypical urothelial cells suspicious for high-grade urothelial carcinoma (AUC-H/SHGUC), on management of patients with no prior history of UC. MATERIALS AND METHOD: This is a retrospective study of "atypical" urine cytology with subsequent tissue examination occurring within six months. Cytology reports with "atypical" interpretation were reclassified into AUS-UC and AUC-H based on morphologic features identified by the Johns Hopkins system and the Paris system for urine cytology. Follow-up and categorical outcomes were compared between the reclassified AUC-US and AUC-H groups. RESULTS: There was no significant difference (P < 0.4539) in the rate of cytology follow-up, the follow-up cytology result (P < 0.1845), or time between follow-up cytologies (P < 0.0869) between the reclassified atypical group of AUC-H and AUC-US. There was a significant association (P < 0.0001) of rate of malignancy with the reclassified AUC-H (87.18%) compared to the AUC-US (58.68%) groups. CONCLUSION: There was no difference in follow-up between the AUC-H and AUC-US, however there was a difference in the rates of malignancy in the two groups. The AUC-H group is similar to the SHGUC group of the Paris system and can be considered as such, whereas the AUC-US group should continue to be considered atypical. We conclude that reclassification of the "atypical" category into AUC-US and AUC-H/SHGUC can reduce the rate of atypia and help in focused follow-up and targeted management. Diagn. Cytopathol. 2016;44:477-482. © 2016 Wiley Periodicals, Inc.

Two-tiered subdivision of atypia on urine cytology can improve patient follow-up and optimize the utility of UroVysion.

BACKGROUND: The annual incidence of urothelial carcinoma continues to increase, and it is projected that greater than 70,000 new cases will occur in the year 2015. However, as much as 23% of cytologic specimens will demonstrate some degree of atypia without meeting the criteria for urothelial carcinoma and thus will be reported as atypical. METHODS: The authors conducted 2 laboratory information searches and 1 survey. In total, 311 patients who had atypical cytology-biopsy pairs available were identified from the initial data search. The second data search identified 942 patients who had fluorescence in situ hybridization (FISH) results available. RESULTS: There was fair agreement between FISH results and cytology results (κ = 0.34; 95% confidence interval, 0.27-0.41). The analysis did not reveal any benefits of using additional atypical subcategories beyond the 2 suggested in the literature. It was determined that 2 strategies would provide an optimal balance: standardizing patient management and facilitating the adoption of universally recognized templates. CONCLUSIONS: When combining cytology and the 2-tiered atypical classification system with FISH testing, a marked increase in sensitivity and an accompanying decrease in specificity were observed compared with either test individually. Thus, highly sensitive FISH testing may help to identify high-risk patients among those in the group with uncertain atypical findings.

Mantle cell lymphoma with in situ or mantle zone growth pattern: a study of five cases and review of literature.

We present two rare cases of in situ mantle cell lymphoma ("in situ MCL") and three cases of MCL with mantle zone growth pattern (MCL-MZGP). The patients include four males and one female, with a median age of 66 years (range, 52 to 86 years). Two present with isolated lymphadenopathy and three with multiple lymphadenopathy. At presentation, the complete blood count (CBC) and serum lactate dehydrogenase (LDH) are normal in all cases. Histologic examination reveals an in situ pattern in two cases and a mantle zone growth pattern in three cases. The staging bone marrow biopsies show minimal involvement by lymphoma in one case and no morphologic evidence of lymphoma in four cases. All cases are positive for cyclin D1, including two with typical MCL phenotype and three with CD5-negativity. Four out of five cases express kappa light chain. FISH study for t(11;14) is performed in three cases, of which one is positive and two are inconclusive. For four patients with a median follow-up of 38 months, three are in clinical remission and one has persistent disease. In conclusion, the "in situ MCL" is associated with incidental finding, indolent clinical course and lower tumor burden. The predominant usage of kappa light chain and frequent CD5-negativity observed in our cases are unusual. We review the clinical and laboratory features of "in situ MCL" cases in the literature.

Clinical evaluation of a novel bipolar radiofrequency ablation system for renal masses.

UNLABELLED: What's known on the subject? and What does the study add? With the advancement of minimally invasive surgery, the management of small renal masses (SRM) has dramatically changed. Ablative technology such as radiofrequency ablation (RFA) and cryoablation have emerged as viable alternative modalities to extirpative surgery. RFA is one of the most studied and applied energy-based, needle-ablative treatment modalities, with encouraging mid- and long-term oncological outcomes. Monopolar devices have several shortcomings. The electrodes are susceptible to the cooling effect of nearby blood vessels that act as a 'heat sink', limiting the extent of tissue ablation and forming lesions with asymmetric borders and 'skip lesions'. Therefore, it is difficult to monitor and accurately predict the size of ablated lesions. A novel bipolar radiofrequency ablation (BRFA) device has been recently developed to address concerns with monopolar systems (Trod Medical, Paris, France). The BRFA system addresses the limitations of monopolar RFA, in terms of lesion size, targeting, consistency and concerns about cell death in the ablated area. We evaluated the BRFA device in 10 patients undergoing laparoscopic partial or radical nephrectomy. The present study demonstrates the safety and efficacy of a novel BRFA device. A BRFA device can produce a defined reproducible lesion with a precise transition zone to normal tissue. The area of ablated tissue exhibited completely devitalized cells and precise transition zone. With these characteristics, the potential advantages of this new technology during RFA ablation of SRM include less collateral damage and more complete ablation without skip lesions. This has the potential to lower rates of local recurrence and reduce incidence of skin burns. Further follow-up studies are necessary to determine its oncological efficacy. OBJECTIVE: To evaluate a novel bipolar radiofrequency ablation (BRFA) system for the destruction of kidney tumours in patients. MATERIALS AND METHODS: Bipolar radiofrequency ablation (BRFA) was used to ablate renal masses in 10 patients undergoing laparoscopic radical or partial nephrectomy. The probe was placed percutaneously and laparoscopically guided into the tumour after routine laparoscopic exposure. The electrical current was continuously adjusted by the generator to overcome disruption from increasing impedance created from desiccated tissue. The specimens were then excised in routine fashion and analysed by a single pathologist. Lesion size and shape, and size of the transition zone to viable tissue were measured via nicotinamide adenine dinucleotide (NADH) staining. RESULTS: Ablation was successful in all 10 tumours. Mean time to set up and place the probe was between 2 and 4 min. Duration of ablation was 200 s. None of the ablated tissue showed signs of viable cells by histological examination and NADH staining. The mean size of the ablation zone was 6.26 cm(3), with regular borders and a tapered cylindrical shape similar to the shape of the outer coil. The width of the transition zone, or area spanning complete tissue ablation to the first viable cells, ranged from 10 to 60 µm. There were no complications noted due to the ablation. CONCLUSIONS: A BRFA device can produce a defined reproducible lesion with a precise transition zone to normal tissue. The area of ablated tissue exhibited completely devitalized cells and precise transition zone.