CD30 Positivity Research Articles

Histopathological and Clinical Features of Methotrexate-Associated Lymphoproliferative Disorders and Post-Transplant Lymphoproliferative Disorders

Objective: To study histopathological and clinical features of methotrexate-associated lymphoproliferative disorders (MTX-LPD) and post-transplant lymphoproliferative disorders (PTLD).Material and Methods: A retrospective study on 30 cases of MTX-LPD and 2 cases of PTLD from 2006 to 2021.Results: By histopathology, the MTX-LPD group had 21 cases of lymphoma (MTX-Lymphoma) and 9 cases of reactive changes (MTX-Reactive). The PTLD group included diffuse large B-cell lymphoma and polymorphic PTLD (1 case each). The distinctive findings in MTX-Lymphoma and PTLD were association with Epstein-Barr virus (EBV) (8/12 cases, 66.7%) and CD30 positivity (13/18 cases, 72.2%). The MTX-LPD group had median MTX dosage of 10 mg/week, median MTX cumulative dosage of 2,613.75 mg, and median duration of MTX usage of 2,186 days. The 14 MTX-LPD and PTLD patients has median duration to response after the varied interventions of 47 days and the time to the first complete remission (CR) of 126 days. The MTX-Reactive patients had a significantly higher absolute lymphocyte count, younger median age, fewer B symptoms, higher rate of single site involvement, less extranodal involvement, shorter duration to response, less time to enter CR, and higher CR rate than the MTXLymphoma patients (p < 0.05).Conclusion: Histopathology in MTX-LPD and PTLD patients can vary from reactive changes to lymphoma. EBV study and CD30 immunostaining help identify MTX-LPD and PTLD. History of MTX usage and other causes of immunodeficiency should be considered before diagnosing lymphoma. MTX discontinuation or reduction of immunosuppressant dosage are recommended before administrating combined chemotherapeutic agents in unresponsive cases.

ORAL PLASMABLASTIC LYMPHOMA IN A PATIENT WITH AIDS: A CASE REPORT

Plasmablastic lymphoma is a rare and aggressive large B-cell lymphoma, commonly associated with acquired immunodeficiency syndrome. A 31-year-old man reported a painful and bleeding lesion in the oral cavity that had evolved over 3 weeks. The patient had human immunodeficiency virus infection and was not undergoing antiretroviral therapy. On examination, we observed a swelling on the left side of the face, caused by an exophytic mass in the upper gingiva extending from the anterior region to the tuberosity. The lesion was reddish with areas of necrosis. Radiographic exams showed an extensive osteolytic lesion in the left maxilla with involvement of the maxillary sinus. An incisional biopsy was performed, and the microscopic exam revealed a lymphoid malignant neoplasm with intense pleomorphism and abundant mitosis. Immunohistochemistry showed positivity for CD45, CD10, MUM1, CD38, CD138, and CD30, confirming the diagnosis of plasmablastic lymphoma. Antiretroviral therapy was started, and the patient was referred for cancer treatment. Plasmablastic lymphoma is a rare and aggressive large B-cell lymphoma, commonly associated with acquired immunodeficiency syndrome. A 31-year-old man reported a painful and bleeding lesion in the oral cavity that had evolved over 3 weeks. The patient had human immunodeficiency virus infection and was not undergoing antiretroviral therapy. On examination, we observed a swelling on the left side of the face, caused by an exophytic mass in the upper gingiva extending from the anterior region to the tuberosity. The lesion was reddish with areas of necrosis. Radiographic exams showed an extensive osteolytic lesion in the left maxilla with involvement of the maxillary sinus. An incisional biopsy was performed, and the microscopic exam revealed a lymphoid malignant neoplasm with intense pleomorphism and abundant mitosis. Immunohistochemistry showed positivity for CD45, CD10, MUM1, CD38, CD138, and CD30, confirming the diagnosis of plasmablastic lymphoma. Antiretroviral therapy was started, and the patient was referred for cancer treatment.

GLI1 -Rearranged Enteric Tumor : Expanding the Spectrum of Gastrointestinal Neoplasms With GLI1 Gene Fusions.

GLI1 encodes a transcription factor that targets cell cycle regulators affecting stem cell proliferation. GLI1 gene fusions were initially described in pericytomas with a t[7;12] translocation and more recently in gastric plexiform fibromyxomas and gastroblastomas. This study describes the clinicopathologic, immunohistochemical, and molecular features of three intestinal-based neoplasms harboring GLI1 gene fusions. We studied three unique mesenchymal small bowel tumors. Paraffin embedded tumor tissues from these cases and 62 additional tumor samples that included a plexiform fibromyxoma were sequenced using a targeted RNAseq method to detect fusion events. The study patients included two women and one man who were 52, 80, and 22 years of age at the time of diagnosis. The tumors involved the submucosa and muscularis propria of the duodenum, jejunum, and ileum. All 3 tumors contained a proliferation of monotonous oval or spindle cells with scattered, somewhat dilated vessels. Two cases showed epithelioid structures such as glands, tubules, or nests. Immunohistochemical analysis revealed cytokeratin expression in the epithelioid components of both tumors displaying these features, and variable numbers of mesenchymal cells. Diffuse CD56 positivity was seen in the mesenchymal component of 2 tumors and desmin and smooth muscle actin staining in the other tumor. Immunostains for S-100 protein, DOG-1, and CD117 were negative in all cases. GLI1 fusions with different partner genes were detected in all tumors, and in the plexiform fibromyxoma, used as a control. Validation by fluorescence in situ hybridization was performed. None of the tumors have recurred or metastasize after surgery. We describe novel GLI1 fusions in 3 mesenchymal neoplasms of the small intestine, including 2 with biphenotypic features. Thus far, all cases have pursued indolent clinical courses. We propose the term " GLI1 -rearranged enteric tumor" to encompass this group of unique neoplasms of the small intestine that harbor GLI1 gene fusions and expand the spectrum of gastrointestinal neoplasms with these alterations.

Clinical and Epidemiological Profile of Elderly Hodgkin's Lymphoma in India.

BackgroundHodgkin’s lymphoma (HL) is a curable malignancy that commonly involves the younger population. However, HL can rarely occur in the elderly population (≥60 years) and probably has different biology as compared to the younger counterparts. There was a paucity of data on the clinical and epidemiological profile of the elderly subset with HL in Indian patients who are misdiagnosed and empirically treated as tuberculosis. We have done an analysis of this subset of elderly patients who were registered at our institute.MethodsA retrospective chart analysis of HL patients who presented to our center from 2008 to 2016 was conducted. Twenty-eight patients with HL of age ≥60 years were included in this study.ResultsElderly HL comprised 18.67% of the total HL patients registered during this period. The majority were male patients, and the mean age of presentation was 65.9±5.6 years. A Charlson Comorbidity Index (CCI) of ≥2 was seen in 30.77% of the patients. Among these, 84.62% of the patients presented with advanced-stage disease, and 57.69% of the patients presented with B symptoms, which was significantly associated with a high-risk international prognostic score (IPS). Histology-wise, mixed cellularity classical Hodgkin’s lymphoma (MCCHL) and nodular sclerosis classical Hodgkin’s lymphoma (NSCHL) were equally represented (30.76%). Of the patients, 50% had extranodal disease, with the liver being the most frequent site involved. One patient each had bone marrow involvement and bulky disease. CD30, CD15, and CD20 positivity was seen in 84.61%, 50%, and 26.92% of cases, respectively.ConclusionAmong elderly HL patients, males were more commonly represented than females, and patients more often presented with advanced disease and B symptoms and less often with bulky disease and mediastinal mass. Mixed cellularity classical HL is more common in the elderly subset, and significant comorbidities are present in a higher number of elderly HL patients.

Abstract 1995: β-Hydroxy-β-methylbutyrate promotes immunotherapy response and pro-inflammatory macrophage polarization in a mouse model of pancreatic cancer

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) continues to represent a critical unmet therapeutic need in the US, and is exacerbated by obesity. Current chemotherapeutic regimens poorly control PDAC progression, and immunotherapy has yet to be widely successful against PDAC. Obesity promotes a potently protumor PDAC microenvironment including suppression of antitumor immune response. The purpose of our studies was to test whether dietary supplementation with β-hydroxy-β-methylbutyrate (HMB), shown to be safe and well tolerated in cancer patients, could offset obesity-mediated exacerbation of PDAC and promote antitumor immunosurveillance. Methods: Lean and obese C57BL/6 mice were treated with HMB alone or in combination with anti-PD1 immunotherapy following subcutaneous injection of Panc02 PDAC cells. Bone marrow-derived macrophages (BMDM) were treated with HMB in vitro with or without lipopolysaccharide (LPS). Tumor/macrophage transcriptomic analysis using Affymetrix arrays followed by gene set enrichment was performed, and tumor microenvironment immune cell composition was determined by mass cytometry. Results: a) HMB cooperates with obesity and immunotherapy to reduce PDAC progression, as indicated by reduced tumor growth with the combination regimen of HMB + anti-PD1 relative to obese or anti-PD1 immunotherapy treated mice without HMB supplementation; b) HMB mitigates PDAC immunosuppression and promotes tumor immune surveillance, as demonstrated by induction of an antitumor immune-related gene expression profile in response to HMB supplementation; c) HMB promotes pro-inflammatory polarization of tumor-associated macrophages and BMDM, as shown by increased CD38 positivity and reduced Arg1 positivity in tumor-associated macrophages from HMB supplemented mice relative to control. Further, BMDM transcriptional response to HMB alone or HMB in combination with LPS paralleled that of BMDM treated with LPS relative to untreated LPS. Conclusion: Overall, our findings suggest HMB is an adjuvant for antitumor immune responses in PDAC. Moreover, HMB promotes immune surveillance in PDAC, synergizing with immunotherapy. Hence, HMB-induced suppression of PDAC tumor growth and promotion of immune surveillance may offer significant synergy with chemotherapies or immunotherapies in PDAC. Funding: This work was supported by R35CA197627 to SDH. Citation Format: Michael F. Coleman, Kristyn A. Liu, Alexander J. Pfeil, Suhas K. Etigunta, Xiaohu Tang, Laura M. Lashinger, Zhengrong Cui, Stephen D. Hursting. β-Hydroxy-β-methylbutyrate promotes immunotherapy response and pro-inflammatory macrophage polarization in a mouse model of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1995.

A real-world experience: Outcomes among relapsed/refractory diffuse large B cell lymphoma patients with CD20 loss.

e19570 Background: Despite novel therapies for relapsed/refractory (R/R) DLBCL, outcomes among this cohort remain poor. A prior study indicated that patients who lost CD20 expression after treatment have earlier disease progression, but whether this translates to inferior outcomes remains unknown. We hypothesized that R/R DLBCL patients who lost CD20 expression upon disease relapse would have worse survival and response rates compared to those who retained expression. Methods: We performed a retrospective cohort study of R/R DLBCL patients seen at the University of Michigan between 2007-2021. Inclusion criteria were patients ≥ 18 years old, diagnosis of CD20 positive (+) DLBCL (de novo or transformed), relapsed/refractory disease, and CD20 status available at relapse on flow cytometry/immunohistochemistry. Overall survival (OS) was defined as time from first relapse to death and relapse-free survival (RFS) was time from first relapse to death or next treatment; both of which were estimated with Kaplan Meier analysis. Overall response rate (ORR) was complete response or partial response after first salvage therapy. Descriptive statistics with univariate and multivariate analyses were also performed. Results: 98 patients were included (65% male) with median age at diagnosis of 62 years. Majority of patients had stage III/IV disease at diagnosis (85%), 45% with GCB subtype and 7% with high-grade lymphoma. At diagnosis, all patients had CD20+ disease. Median time from diagnosis to first relapse was 7 months and median time from completion of induction treatment to first relapse was 2.4 months. Among the 98 patients, 84 were CD20+ at first relapse, 12 were CD20 negative and the remaining 2 patients were indeterminate and excluded from survival analyses. The estimated OS in the CD20+ group was 17.9 months (95% CI 14.0, 41.8) compared to 10.6 months in the CD20 negative group (95% CI 6.9, Not Reached). Although median OS in the CD20+ group was longer, a two-sample log-rank test failed to identify a significant difference in OS between the two groups (p = 0.085). The estimated RFS in the CD20+ group was 3.5 months (95% CI 3.3, 3.9) compared to 4.4 months in the CD20 negative group (95% CI 2.6, Not Reached, p = 0.739). ORR among CD20+ and CD20 negative patients was 64% and 50%, respectively. Of patients who became CD20 negative at relapse, 100% received anti-CD20 directed therapy thereafter, as part of salvage or with conditioning prior to transplant. Conclusions: Patients with DLBCL who relapse and maintain CD20 positivity seem to have a trend towards longer OS, though this was not statistically significant in our analysis. Our study was limited given the retrospective data collection and small sample size which may have limited our ability to detect a statistical significance in outcomes. In the future, we will plan to expand our study to involve other academic institutions and reassess outcomes among these cohorts.

Intraindividual variability of CD30 expression in mycosis fungoides -implications for diagnostic evaluation and therapy.

To evaluate the frequency, subcellular localization, and variability of CD30 expression in mycosis fungoides. This retrospective multicenter study investigated 135 biopsy specimens of 95 patients with mycosis fungoides for CD30 expression and CD30 staining pattern in relation to histomorphologic criteria, eosinophils, and tumour stage. We used two different CD30 cutoffs: (i) any CD30 positivity (important for in-label treatment with an anti-CD30 antibody-based drug), and (ii) ≥10% (most commonly used cutoff in therapy studies). The histologic slides were digitally evaluated with a slide viewer. None of the patients were treated with an anti-CD30 antibody-based drug. We found any CD30 expression in 90% of the samples (tumour cells and tumour microenvironment). More than 60% of the samples had CD30 expression ≥10%. CD30 staining was predominantly cytoplasmic and membranous, a Golgi pattern was only found in three samples. In patients with multiple biopsies (69 samples), a highly variable CD30 expression was found, especially in biopsies taken at different timepoints. CD30 and eosinophils were more common in advanced disease stage and cytoplasmic CD30 staining in intraepidermal lymphocytes was significantly associated with the presence of eosinophils. 90% of mycosis fungoides biopsies showed CD30 expression and are principally eligible for anti-CD30-antibody treatment. Because of the high intraindividual variability, investigation of multiple tissue samples for CD30 expression improves the assessment of this therapeutic target. Analysis of only a single skin biopsy might lead to misinterpretation of CD30 and bears the risk of inadequate and potentially unfavourable therapeutic decisions.

Unique Clinical and Pathologic Characteristics of Poorly Differentiated Primary Pleuro-Pulmonary Synovial Sarcoma

Primary pleuro-pulmonary synovial sarcoma is rare and poses a diagnostic challenge particularly when poorly differentiated. We present 15 cases of poorly differentiated primary pleuro-pulmonary synovial sarcoma and compare and contrast results with previously published series on usual better differentiated tumors. Clinical and radiologic findings were similar to usual pulmonary synovial sarcoma with typical imaging features. 7 of 10 patients with outcome data died of disease within 5 years. Histologically, tumors had densely cellular fascicles, hyalinized stroma, hemangiopericytoma-like vasculature, and focal myxoid change. Round cell and rare rhabdoid morphology were unique to poorly differentiated tumors. Immunohistochemistry demonstrated at least focal expression of pancytokeratin, EMA, CK7, CK5/6, calretinin, and CD56, and diffuse positivity with CD99 and bcl-2. Ten primary pulmonary synovial sarcomas with tissue available for study were positive for t(x;18), with a more even distribution of SS18/SSX1 and SS18/SSX2 tumors compared with better differentiated lung synovial sarcomas. In conclusion, our study confirms that clinical, histological, and immunohistochemical data from poorly differentiated primary pleuro-pulmonary synovial sarcoma is similar to better differentiated tumours but special caveats remain for accurate histopathologic diagnosis.

Best Practices in CD30 Immunohistochemistry Testing, Interpretation, and Reporting: An Expert Panel Consensus.

Although CD30 testing is an established tool in the diagnostic workup of lymphomas, it is also emerging as a predictive biomarker that informs treatment. The current definition of CD30 positivity by immunohistochemistry is descriptive and based on reactivity in lymphomas that are defined by their universal strong expression of CD30, rather than any established threshold. Challenges include inconsistencies with preanalytic variables, tissue processing, pathologist readout, and with the pathologist and oncologist interpretation of reported results. To develop and propose general best practice recommendations for reporting CD30 expression by immunohistochemistry in lymphoma biopsies to harmonize practices across institutions and facilitate assessment of its significance in clinical decision-making. Following literature review and group discussion, the panel of 14 academic hematopathologists and 2 clinical/academic hematologists/oncologists divided into 3 working groups. Each working group was tasked with assessing CD30 testing by immunohistochemistry, CD30 expression readout, or CD30 expression interpretation. Panel recommendations were reviewed and discussed. An online survey was conducted to confirm the consensus recommendations. CD30 immunohistochemistry is required for all patients in whom classic Hodgkin lymphoma and any lymphoma within the spectrum of peripheral T-cell lymphoma are differential diagnostic considerations. The panel reinforced and summarized that immunohistochemistry is the preferred methodology and any degree of CD30 expression should be reported. For diagnostic purposes, the interpretation of CD30 expression should follow published guidelines. To inform therapeutic decisions, report estimated percent positive expression in tumor cells (or total cells where applicable) and record descriptively if nontumor cells are positive.

The different predictive effects of the intensity and proportion of CD20 expression on the prognosis of B-lineage acute lymphocyte leukemia.

The prognostic effects of the CD20 positivity have been studied extensively in B‐lineage acute lymphocyte leukemia (B‐ALL) patients, but the results remain controversial. The aim of this study is to investigate the different predictive effects of the intensity and proportion of CD20 expression on the prognosis for B‐ALL patients by retrospective analysis. The mean fluorescence intensity (MFI) and percentage of CD20 on B‐ALL cells from 206 patients with B‐ALL were dynamically measured by flow cytometry, and their optimal cut‐off values were determined using the receiver operating characteristic curve. Changes in MFI and percentage of CD20 at various time points and their relationship with prognosis were analyzed. We found that a low baseline CD20 MFI or high CD20 proportion was significantly associated with shorter 5‐year overall survival and progression‐free survival, and the combination of these two factors could more accurately predict worse survival for B‐ALL patients. Furthermore, low CD20 MFI or a high CD20 proportion had different predictive effects for ALL patients with different clinical characteristics and could serve as an independent risk factor for adverse prognosis. There were significant decreases in both the intensity and proportion of CD20 after recurrence in the absence of rituximab treatment, particularly with CD20 intensity. Notably, the decrease of CD20 intensity after recurrence indicated a more shortened survival time. Finally, we conclude that a low intensity or high proportion of CD20 expression may be used as an indicator for inferior prognosis for B‐ALL patients. CD20 intensity is more likely to be a more universal biomarker for worse prognosis.

Landscape of NOTCH1 mutations and co-occurring biomarker alterations in chronic lymphocytic leukemia

NOTCH1 is one of the most frequently mutated genes in chronic lymphocytic leukemia and has emerged as a marker of poor prognosis. In addition to coding NOTCH1 mutations involving exon 34, non-coding NOTCH1 mutations involving the 3′ UTR have been described in a limited number of chronic lymphocytic leukemia (CLL) patients and were associated with adverse outcomes. In this study, 1574 CLL patients were assessed using targeted sequencing with a 29 gene panel and the results were correlated with prognostic characteristics. NOTCH1 mutations were detected in 252 (16%) patients, including both coding (220/252, 14%), non-coding (24/252, 1.5%) and a mixture of coding and non-coding (8/252, 0.5%) NOTCH1 mutations. NOTCH1 mutations were more commonly seen in patients with unmutated IGHV, ZAP70 positivity and CD38 positivity. Mixed NOTCH1 mutations were also more commonly seen in patients with unmutated IGHV and ZAP70. There was no association between mixed NOTCH1 mutations and CD38 expression in this cohort. The most common cytogenetic alteration detected in patients with coding and mixed NOTCH1 mutations was trisomy 12, whereas del13q was the most common cytogenetic alteration detected in patients with non-coding NOTCH1 mutation. The most common gene mutations co-occurring with coding NOTCH1 mutations were: TP53 (23.2%), SF3B1 (16.4%) and SPEN (10%). The most common gene mutations co-occurring with non-coding NOTCH1 mutations were: SF3B1 11(34.4%), ATM 4(12.5%) and TP53 4(12.5%). CLL patients with clonal coding and non-coding NOTCH1 mutations had a significantly shorter time-to-first treatment than patients with wild type NOTCH1 (4.3 vs 10.0 years and 0.9 vs 10.0 years respectively, p < 0.05). Similarly, CLL patients with subclonal coding NOTCH1 mutations had a significantly shorter time-to-first treatment than patients with wild type NOTCH1 (5.6 vs 10.0 years, p < 0.05). CLL patients with subclonal non-coding NOTCH1 mutations also had a shorter time-to-first treatment than patients with wild type NOTCH1 mutations, however, the difference was not significant (5.1 vs 10.0 years, p = 0.15). These data confirm that both coding and non-coding NOTCH1 mutations carry adverse prognostic impact and need to be included in sequencing assays performed for the prognostic workup of CLL patients.

CD56-Negative Extranodal Natural Killer/T-Cell Lymphoma: A Retrospective Study in 443 Patients Treated by Chemotherapy With or Without Asparaginase.

ObjectiveExtranodal natural killer/T cell lymphoma (NKTCL) is an aggressive EBV-related lymphoma, originating from NK cells or T cells. Previous study demonstrated that CD56 negative NKTCL should be recognized as a distinct subtype. In this study, the value of CD56 in NKTCL is validated in the era of asparaginase, and genomic analysis was done to dissect the differences between CD56-negative and positive NKTCL.Methods443 patients with newly diagnosed NKTCL were enrolled in this retrospective study, and correlation between CD56 positivity and survival outcomes was analyzed. The gene sequencing data was downloaded (http://www.biosino.org/node/project/detail/OEP000498), and bioinformatics analysis was done to delineate the tumor microenvironment and differentially expressed genes.ResultsCD56 was expressed in 337 patients (76.1%). Within a median follow-up time of 51 months, the 5-year overall survival (OS) and progression free survival (PFS) rates were 63.8% and 51.9%, respectively. For the whole cohort, patients who were CD56-positive had superior OS (5-year OS, 86.2% vs. 51.9%, p=0.019) and PFS (5-year PFS, 55.9% vs. 40.1%, p=0.016). For patients in early stage disease, CD56 positivity was associated with superior OS and PFS (p=0.008 and 0.005, respectively). In patients who received non-asparaginase-based chemotherapy, CD56-negative was associated with shorter OS and PFS (p<0.001), and in patients who received asparaginase-based chemotherapy, CD56-negative was not related to inferior OS and PFS (p=0.093 and p=0.829, respectively). The genomic analysis demonstrated that CD56 positive NKTCL probably originated from NK cells and CD56 negative NKTCL originated from T cells. CD56 positive NKTCL had significantly higher proportion of resting NK cells, activated NK cells, and activated CD8+ and CD4+ T cells in the tumor microenvironment.ConclusionsCD56 negative NKTCL differs from CD56 positive NKTCL in both the tumor microenvironment and survival outcomes, and asparaginase-based treatment may overcome the poor prognosis brought by CD56 negativity.

Use of ifosfamide, carboplatin and etoposide in combination with brentuximab vedotin or romidepsin based on CD30 positivity in relapsed/refractory peripheral T-cell lymphoma.

BackgroundRelapsed/refractory peripheral T‐cell lymphoma (R/R PTCL) has a poor prognosis. Romidepsin (Ro) and brentuximab vedotin (Bv), combined with ifosfamide, carboplatin, and etoposide (ICE) has not been significantly studied in PTCL.AimWe report outcomes of Bv‐ICE in CD30 (+) and Ro‐ICE in CD30 (−) R/R PTCL treated in “Blinded for peer review” Cancer Center.Methods and ResultsWe retrospectively identified R/R PTCL patients treated with BV‐ICE or romidepsin‐ICE from May 2016 to September 2019. Out of 13 R/R PTCL patients, 6 were treated with Bv‐ICE and 7 with Ro‐ICE. Bv‐ICE had an overall response rate (ORR) of 66.7%, with all the patients achieving a complete response. ORR was 71.4% for Ro‐ICE with 57.1% of patients achieving a complete response. Two patients treated with Bv‐ICE and three treated with Ro‐ICE received transplantation.ConclusionIn our experience, treatment with Bv‐ICE and Ro‐ICE based on CD30 positivity is feasible and effective to treat patients with R/R PTCL.

The prognostic relationship between CD56 expression and newly diagnosed multiple myeloma

Objective: To evaluate the prognostic value of CD56 expression in newly diagnosed MM (NDMM). Methods: A total of 332 NDMM patients were enrolled in Beijing Chaoyang Hospital, Capital Medical University from January 1, 2011 to January 1, 2021, with a median age of 60 years and a male to female ratio of 1.2∶1. CD56 expression on myeloma cells was detected by flow cytometry before induction therapy. Overall survival (OS) and progression-free survival (PFS) data were collected. In order to reduce the confounding factors, the propensity score matching technique was used to match CD56 positive versus negative patients at a ratio of 1∶1. Results: Among 332 patients, CD56 positivity rate was 65.1% (216/332). Patients with CD56 expression had significantly longer median OS (58.4 vs. 43.1 months, P=0.024) and PFS (28.7 vs. 24.1 months, P=0.013) than those with negative CD56. Univariate Cox proportional hazards regression analyses showed that CD56 expression was positively correlated with OS (HR=0.644, 95%CI 0.438-0.947, P=0.025) and a favorable prognostic factor for PFS (HR=0.646, 95%CI 0.457-0.913,P=0.013). The favorable effect of CD56 expression on PFS was confirmed in multivariate analysis (HR=0.705, 95%CI 0.497-0.998, P=0.049), but OS was not affected (P>0.05).In the propensity score matching analysis, 194 patients with 97 in each group were identified. CD56 positivity consistently predicted longer PFS (34.2 vs.25.1 months, P=0.047), but not OS (63.4 vs.43.1 months, P=0.056). Conclusion: These results demonstrate that CD56 expression is a favorable prognostic factor for PFS of newly diagnosed MM patients.

Lymphoid hyperplasia with a polyp form of the gallbladder macroscopically mimicking carcinoma

Lymphoid hyperplasia is a type of tumor-like hyperplasia of lymphoid tissue. There have been few reports on lymphoid hyperplasia of the gallbladder. Here, we report a case of lymphoid hyperplasia with a polyp form of the gallbladder macroscopically mimicking carcinoma. Liver dysfunction was diagnosed in a 75-year-old woman who presented with a gallbladder mass measuring 20mm during an annual health checkup. Antibody tests for infectious diseases were positive for anti-HBs and anti-HBc antibodies. Accordingly, a laparoscopic cholecystectomy was performed. Macroscopically, the mass was a papillary/sessile tumor (29 × 25mm) located in the fundus of the gallbladder. Histologically, the tumor was accompanied by an erosion on a portion of the surface layer, while the remaining epithelium showed regenerative changes and mild hyperplasia. No atypia was observed in the constituent epithelium. Hyperplasia of the polarized lymphoid follicles was observed in the interstitium, and tingible body macrophages were scattered in the germinal center. Immuno-histologically, the germinal center showed CD20 positivity, weak CD10 positivity, Bcl-2 negativity, and a high Ki-67 index (MIB-1). These findings suggested that the proliferating lymphoid follicles were reactive rather than neoplastic. Therefore, we diagnosed the patient with lymphoid hyperplasia of the gallbladder and chronic cholecystitis.

Primary Mantle Cell Lymphoma of Pancreas- Rare Case

Primary pancreatic lymphomas (PPLs) are rare cancers that have a complicated histological classification. Sufficient sample volumes are required to adequately diagnose and decide the best treatment for PPLs. A 54-year-old man with primary pancreatic mantle cell lymphoma is described in this case study. Percutaneous biopsy was used to extract histological samples. Atypical small to medium round cells predominated in the tumor cells, which had diffuse CD20 and cyclin D1 positivity. Chemotherapy was used on the patient, and he went into complete remission as a result. Because it provides adequate samples for testing, a percutaneous biopsy could be a valuable and safe diagnostic tool for PPLs.

Patients with Classical Hodgkin Lymphoma with Less Than 10.5 CD20-Positive Reed-Sternberg Cells in 10 High-Power Fields Have Better Prognosis.

The CD20 immunoexpression in classical Hodgkin lymphoma (CHL) is variable and it may represent an intersection between the pathophysiology of CHL and the clinical prognosis of patients. Retrospective study with 174 patients with pathological diagnosis of CHL. Clinical data were reviewed from medical records. Immunophenotypic study with CD20 were performed in two ways: hotspot count and in 10 high-power fields (HPF). The data were tabulated and the p value less than 0.05 was considered significant. The CD20-positive phenotype was found in 45 (25.9%) of the total of 174 patients with available material. Patients with CD20 positivity on neoplastic cells tend to heal earlier, particularly those with less than 10.5 cells/10 HPF (p = 0.037). Patients with CHL with less than 10.5 CD20-positive Reed-Sternberg cells in 10 HPF have better prognosis.

Classical Hodgkin’s Lymphoma Presenting as Erythroderma

Hodgkin’s Lymphoma (HL) with direct cutaneous involvement is uncommon, unlike non specific paraneoplastic skin changes, which can occur during the course of the disease. Direct cutaneous infiltration commonly affects the chest and manifests as papules and plaques. Nodules in some patients may ulcerate. Paraneoplastic manifestations can be eczematous itchy papules or lichenified plaques adjacent to the affected lymph nodes. Authors’ reported a case of a 31-year-old female with erythroderma, of 4 months duration, who did not respond to treatment with corticosteroids and cyclosporine. Skin biopsy showed minimal epidermotropism without mitotic cells. Immunohistochemistry (IHC) showed CD3, CD4, CD5 and CD8 positivity and CD15, CD 20 negativity. She had frequent exacerbations while on treatment with steroids. Amongst this confusing clinical picture, it was the emergence of an axillary lymph node, after two months of initiating treatment which on histopathology was compatible with HL and on IHC positive for CD3, CD20 and CD30 and negative for CD15. These findings confirmed the diagnosis as classical HL. This case is being reported to highlight the importance of thorough clinical examination with particular reference to lymph node screening.

HISTOMORPHOLOGIC SPECTRUM OF HODGKIN AND NON-HODGKIN LYMPHOMAS ACCORDING TO WHO CLASSIFICATION 2016 IN A TERTIARY CARE HOSPITAL IN MAHARASHTRA

Introduction: Lymphoma is a group of lymphoproliferative malignancies that can originate in B lymphocytes, T lymphocytes, or natural killer (NK) lymphocytes. They account for 3% of all cancer types. The WHO's 2008 World Health Organization (WHO) classification of hematopoietic and lymphoid tumors was refined in 2016. This study screened surgically excised or biopsied specimens for lymphoma in lymphadenopathy. This research aimed to classify lymphomas in India based on histopathological and immunohistochemical findings. Methods: The study included 71 cases suspected/probable/proven to have lymphomas and H and E-suggestive lymphoid malignancies were recruited. Clinical details, histopathological reports, and lymphoma panel IHC status were analyzed. Age, sex, biopsy site, B-symptom history, and clinical findings were recorded. Paraffin blocks were prepared from biopsy specimens in buffered formalin using standard automated methods. All cases' slides were examined to confirm lymphoma. Tissue blocks were selected for IHC staining. All the slides were evaluated and classified as per the WHO 2016 lymphoma classification. Results: The mean age of the patients was 44.58 years, and 54 patients were males, while 17 were females. 61 of 71 cases were detected to be of NHL and 10 cases were of HL. The majority of NHL cases were formed by B cell neoplasms, constituting 72.1%, whereas T cell neoplasms constituted 24.6%. 2 of 61 cases showed CD56 positivity apart from T-cell markers and were categorized as T/NK cell NHL. As per WHO classification, different types of NHL and HL were classified. Among NHL, follicular lymphoma (FL) was predominant with 15 cases, while in CHL, mixed cellularity CHL prevalence was high. Ki67 expression in 15 cases of FL showed 1 case of grade 1, 3 cases of grade 2 and 2 cases of grade 3 follicular lymphoma with a Ki67 index of more than 40%. Conclusion: Histomorphology and immunohistochemistry helps diagnose lymphoma. NHL was more common among nodal and extranodal lymphomas. The NHL and HL were dominated by men. Follicular lymphoma (FL) was the most common subtype of B-cell NHL. Most HL patients had mixed-cellularity CHL.

Utility of a new notation to visualize flow cytometry analysis results: first preliminary comparison with immunohistochemistry to detect CD30 expression on T-cell lymphoma cells

BackgroundIt is important to confirm CD30 expression in T-cell lymphoma cases, but immunohistochemical staining for CD30 is not commonly performed and no comparison has been done between the results of flow cytometry (FCM) and immunohistochemical staining for CD30. Therefore, we devised a notation that we termed proportion of immunoreactivity/expression for FCM (PRIME-F notation), based on the cellular proportion showing different antigen-antibody reactivity.MethodsWe retrospectively compiled 211 cases of T-cell lymphoma, assessed via FCM, from major hospitals in Miyagi Prefecture from January 2012 to January 2019, and compared 52 of these cases with the immunohistochemical immunoreactive (IR) pattern of CD30 (PRIME-I notation). The PRIME-F notation was divided into five levels: notations starting with “-” followed by 3, 2, and 1 “>” correspond to level-I, level-II, or level-III; notations starting with “(dim)+” correspond to level-IV; and those starting with “+” or “(bright)+” correspond to level-V.ResultsThe 52 cases of PRIME-F notation with “+” included 16 cases of peripheral T-cell lymphoma (PTCL/NOS), 3 of follicular T-cell lymphoma (FTL), 3 of angioimmunoblastic T-cell lymphoma (AITL), 6 of extranodal NK/T-cell lymphoma/nasal type (ENKL), 18 of adult T-cell lymphoma (ATL), and 6 cases of anaplastic large cell lymphoma (ALCL). Eight of the 52 cases were immunohistochemically CD30-negative. In the PRIME-F level-I to III group (excluding false-positive cases), 21.7% (5 out of 23 cases) were < 10% positive for CD30 upon immunohistochemistry (IHC). Contrarily, in the level-IV & -V group, no CD30 positivity rate of < 10% upon IHC was found (0%) (p = 0.0497). In level-IV, 42.9% of cases presented a CD30 negative rate > 1/3 upon IHC, while in level-V, only 7.1% (one out of 14 cases) did. The CD30 negative rate tended to be low (p = 0.0877) in level-V.ConclusionsTo our knowledge, this is the first report describing the correspondence between FCM and immunohistochemistry findings for CD30 through newly proposed notations. The PRIME-F and PRIME-I notations for CD30 showed a minor positive correlation. The PRIME notation is considered universally applicable to antibodies, and notations of both FCM and IHC show great potential for big data.