High-grade Histologic Subtypes Research Articles

Abstract IA009: Racial disparities in high grade endometrial cancers

Abstract Endometrial cancer (EC) is the most common gynecological cancer in the United States, with approximately 66,200 cases diagnosed annually. Incidence rates have been increasing over the past two decades, especially in non-white and younger populations. Additionally, population-based studies have shown that the increases are greatest among the more aggressive histologic subtypes. In unadjusted analyses, incidence rates are highest among non-Hispanic white women (NHW); however, when the greater prevalence of hysterectomies in non-Hispanic black women (NHB) is accounted for, the incidence among NHB women exceeds that of other racial and ethnic groups. In addition, survival after an EC diagnosis is significantly lower for NHB women at every stage of diagnosis, and for all histologic subtypes. EC is currently the 6th leading cause of cancer-related deaths among women but will likely overtake ovarian cancer (the 5th leading cause) before the end of the decade—it has already done so for NHB women. Factors influencing survival exist across the cancer care spectrum, starting at diagnosis and continuing through treatment and beyond. A portion of the differences in EC survival can be explained by the histologic subtype of the tumor. Low grade endometrioid ECs are the most common histologic type and tend to have a good prognosis. High grade tumors, such as serous cancers, are more common among NHB women and have poorer prognosis. A better understanding of the molecular characteristics of these more aggressive tumors is warranted, as they are increasing in incidence and cause a disproportionate amount of morbidity and mortality. To date, most studies that have included molecular profiling do not have large enough numbers or participants from diverse populations to examine whether mutations that may be clinically significant differ by race and ethnicity in high grade endometrial cancers. In a population of women with high grade EC (endometrioid, serous, clear cell, mixed) identified from two academic hospitals in Detroit, Michigan, we performed whole exome sequencing on tumor and normal tissue from 285 women. We hypothesized that somatic mutations in specific genes may vary by race and ultimately contribute to the survival disparity consistently identified in population-based studies. We report findings from the two most common high grade histologic subtypes, endometrioid (n=51 NHB, n=60 NHW) and serous (n=85 NHB, n=37 NHW). Established and emerging therapeutic targets were selected as a priori for the initial analysis. Tumor mutational burden (TMB), microsatellite instability status (MSI), mutations in genes in the PIK3 pathway, POLE, ARID1A and p53 were all examined. Findings highlight the need to consider histologic subtype in conjunction with race and ethnicity, as failure to do so may erroneously confound the estimates. Larger studies in diverse populations will be critical to disentangle the contribution of ancestry, histology and somatic mutations to the survival disparities seen after an EC diagnosis. Citation Format: Michele L. Cote. Racial disparities in high grade endometrial cancers [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA009.

Risk Factors for Recurrence of Stage I Epidermal Growth Factor Receptor Mutated Lung Adenocarcinoma

BackgroundWe aimed to clarify the risk factors for postoperative recurrence in patients with epidermal growth factor receptor (EGFR)-mutated stage I lung adenocarcinoma, using EGFR wild-type adenocarcinoma as a comparator, to select optimal candidates for adjuvant therapy with EGFR tyrosine kinase inhibitor (TKI). MethodsData of patients with pathologic stage I EGFR-mutated (n = 713) and wild-type (n = 673) adenocarcinoma who did not receive adjuvant therapy were retrospectively analyzed. The cumulative incidence of recurrence (CIR) was estimated using Gray’s method, and multivariable Fine-Gray competing risk models identified independent risk factors associated with recurrence. ResultsThe CIR did not differ significantly between patients with EGFR-mutated and wild-type adenocarcinoma (P = .32). Multivariable analysis revealed that greater size (cm) of invasive tumor (hazard ratio 1.539; 95% CI, 1.077-2.201), lymphovascular invasion (hazard ratio 5.180; 95% CI, 2.208-12.15), pleural invasion (hazard ratio 3.388; 95% CI, 1.524-7.533), and high-grade histologic subtype (hazard ratio 4.295; 95% CI, 1.539-11.99) were independent risk factors for recurrence in patients with EGFR-mutated adenocarcinoma. The 5-year CIR was significantly higher among patients with these factors (tumor size greater than 2 cm, 15.9%; lymphovascular invasion, 26.9%; pleural invasion, 39.3%; and high-grade subtype, 44.4%) than among patients without them (4.4%, 2.2%, 3.9%, and 5%, respectively; P < .001). For patients with EGFR wild-type adenocarcinoma, independent risk factors for recurrence were invasive tumor size, lymphovascular invasion, and pleural invasion, but not histologic subtypes. ConclusionsEven for patients with EGFR-mutated stage I lung adenocarcinoma, recurrence risk is stratified. Adjuvant therapy may be considered if they have high-risk factors for recurrence.

Novel Genetic Prognostic Signature for Lung Adenocarcinoma Identified by Differences in Gene Expression Profiles of Low- and High-Grade Histological Subtypes.

The 2021 WHO classification proposed a pattern-based grading system for early-stage invasive non-mucinous lung adenocarcinoma. Lung adenocarcinomas with high-grade patterns have poorer outcomes than those with lepidic-predominant patterns. This study aimed to establish genetic prognostic signatures by comparing differences in gene expression profiles between low- and high-grade adenocarcinomas. Twenty-six (9 low- and 17 high-grade adenocarcinomas) patients with histologically “near-pure” patterns (predominant pattern comprising >70% of tumor areas) were selected retrospectively. Using RNA sequencing, gene expression profiles between the low- and high-grade groups were analyzed, and genes with significantly different expression levels between these two groups were selected for genetic prognostic signatures. In total, 196 significant candidate genes (164 upregulated and 32 upregulated in the high- and low-grade groups, respectively) were identified. After intersection with The Cancer Genome Atlas–Lung Adenocarcinoma prognostic genes, three genes, exonuclease 1 (EXO1), family with sequence similarity 83, member A (FAM83A), and disks large-associated protein 5 (DLGAP5), were identified as prognostic gene signatures. Two independent cohorts were used for validation, and the areas under the time-dependent receiver operating characteristic were 0.784 and 0.703 in the GSE31210 and GSE30219 cohorts, respectively. Our result showed the feasibility and accuracy of this novel three-gene prognostic signature for predicting the clinical outcomes of lung adenocarcinoma.

Comparison of PD-L1 immunohistochemical assays and the significance of PD-L1 expression in thymoma.

Thymoma is a relatively rare malignancy, which is categorized as thymic epithelial tumor but known as the most common pathology that is developed in the anterior mediastinum. Complete resection is recommended for localized tumors and usually favorable prognosis can be obtained. However, poor survival period has been reported in unresectable cases exhibiting extensive invasion or distant metastasis, as effective chemotherapeutic regimens are restrained. We previously assessed expression of programmed death ligand 1 (PD-L1) and programmed death 1 (PD-1) and discussed their prospective application in the immunotherapy of thymic epithelial tumors. After our publication, additional studies using reliable PD-L1 antibodies, which are currently administered to predict efficacy of PD-1/PD-L1 blockade therapy were performed and further characterized PD-L1 in thymoma. Herein, recent knowledge in relation to the significance of PD-L1 expression in thymoma is reviewed based on recent findings using qualified PD-L1 clones. Most studies coherently found high expression of PD-L1 on the cell membrane and cytoplasm of tumor epithelial cells in accordance with previous reports, which is a predictive marker for effectiveness of anti-PD-1/PD-L1 drugs, even when approved PD-L1 antibodies were employed. On the other hand, PD-L1 expression on tumor infiltrating immune cells remains to be sufficiently determined. High PD-L1 expression can be expected in cases with high grade histological subtypes, such as type B2/B3 thymomas, or those with advanced stages III or IV of the disease. Interestingly, the level of PD-L1 expression was found to be upregulated after chemotherapy compared with that before, which could be explained by immunogenic cell death. The prognostic impact of PD-L1 expression in thymoma might be found only when thymic carcinoma patients were excluded. Furthermore, it also could be identified when we analyzed thymomas completely resected, distinct from biopsy and incompletely resected cases.

Early-stage clear cell ovarian cancer compared to high-grade histological subtypes: An outcome exploratory analysis in two oncology centers

Objectiveadvanced stage clear cell ovarian cancer (CCOC) carries a higher risk of relapse and death compared to other histological subtypes. The prognosis of early-stage CCOC is controversial. MethodsEarly-stage high-grade OC patients from two Italian oncologic centers were included. Patients with early-stage CCOC were compared with those with high-grade endometrioid (HGE) and serous (HGS) OC in terms of relapse-free interval (RFI), cancer-specific survival (CSS) and post relapse cancer-specific survival (prCSS). The Cox proportional hazard model and the restricted mean survival time were used. ResultsBetween 1981 and 2012, 134 patients with CC, 152 with HGE and 160 with HGS were treated at two referral centers. Median follow-up was 11.5 years. Ten years RFI rates were 80.6%, 72.1%, 60.6%, and CSS rates were 84.3%, 82.6%, 81.7% respectively. Adjuvant chemotherapy significantly improved RFI (aHR 0.61, 95%CI 0.40 to 0.91, P = 0.015). In the multivariable analysis HGS histotype was associated with a shorter RFI compared to CC, (Hazard Ratio [HR]: 1.81; 95%CI: 1.12–2.93; P = 0.016), whereas CSS was not statistically different. prCSS was longer in HGS compared to CCOC (HR, 0.36; 95% CI, 0.17–0.74; P = 0.006).According to the stage, IA/IB/IC1 HGSOC had a shorter RFI (HR, 2.13; 95% CI, 1.14–3.99; P = 0.018) compared to IA/IB/IC1 CCOC, but similar CSS. For prCSS, CC compared to HGS conferred a worse prognosis regardless of the initial stage. ConclusionsEarly-stage CCOC is associated with a longer RFI, similar CSS and a shorter prCSS compared to HGSOC. No prognostic differences were observed between CC and HGE OC. The relapse risk was the lowest in IA/IB/IC1 CC compared to HGS, whereas CC displayed poor sensitivity to chemotherapy after relapse.

Impacts of thoracoscopic surgery and high grade histologic subtypes on spread through air spaces in small stage I lung adenocarcinomas.

Spread through air spaces (STAS) as a pattern of invasion in lung adenocarcinomas had been recognized by WHO in 2015. Moreover, STAS was associated significantly with aggressive micropapillary or solid components when presented predominant pattern in lung adenocarcinomas, which had a poor prognostic significance. Small amounts of micropapillary or solid with components could also reduce overall survival and recurrence-free survival but its impact on STAS is unknown now. Some studies have demonstrated manipulations of surgeons and pathologists could affect STAS but the degree of these impacts is not clear. We reviewed resected small (≤ 2cm) stage I invasive lung adenocarcinomas by thoracoscopic surgery at our institution from January 2017 to October 2018 (n = 277). Micropapillary or solid pattern was considered to be present when the subtype occupied at least 1% of the entire tumor. Lobectomy and segmentectomy were performed using three portals thoracoscopic surgery. Statistical analysis was performed to analyze the correlations of STAS and clinicopathological characteristics. Moreover, we also analyzed the correlated factors of STAS in solid nodules. STAS was found in 59 of 163 (36.2%) lobectomy cases and 27 of 114 (23.7%) limited resection cases. Lobectomy group showed a higher incidence of STAS compared with limited resection group (p = 0.027), but the difference was disappeared in multivariate analysis, which showed that STAS was significantly correlated to solid nodules and presence of high grade histologic subtype (mircopapillary or solid). However, both lobectomy and presence of high grade histologic subtype were significantly correlated with STAS in solid nodules. The small amounts of high grade histologic subtypes were also associated with STAS. Thoracoscopic surgery could affect STAS to some degree.

Histologic subtyping in pathologic stage I-IIA lung adenocarcinoma provides risk-based stratification for surveillance.

BackgroundWe hypothesize that recurrence hazard following resection for stage I-IIA lung adenocarcinoma (ADC) varies according to histologic subtype, which may provide risk stratification for surveillance better than the current uniform follow-up protocol.ResultsPresence (≥5%) of high-grade histologic subtypes (MIP and/or SOL) was associated with a significantly higher recurrence hazard: (1) presence of either MIP or SOL was associated with a significant increase in recurrence hazard during the first two years after surgery; (2) presence of SOL was associated with an increase in recurrence hazard—in particular, distant recurrence hazard—during the first year after surgery; (3) absence of high-grade subtypes (515/1,572 patients) was associated with a very low recurrence hazard (<2% risk/year) during the first ten years after surgery.MethodsAll hematoxylin and eosin–stained tumor slides from pathologic stage I-IIA lung ADC (n = 1572) were reviewed for quantification of the percentage of each histological subtype. Recurrence hazard was estimated using the Kernel-Epanechnikov smoothing procedure. The association between recurrence hazard and high-grade histologic subtypes (micropapillary [MIP] and solid [SOL]) was assessed.ConclusionsOur findings suggest that histologic subtyping has utility for identifying recurrence hazard for surgically resected stage I-IIA lung ADC patients and provide rationale for establishing risk-based surveillance.

Genetic and clinicopathologic characteristics of lung adenocarcinoma with tumor spread through air spaces

ObjectiveThe World Health Organization Classification of Lung Tumors considers “Spread Through Air Spaces (STAS)” as a form of invasion in lung adenocarcinoma. However, its existence as an independent pathologic entity rather than an artifact caused by spreading through a knife surface is still controversial. Therefore, we performed comprehensive analyses on the genetic and clinicopathologic characteristics of lung adenocarcinoma with STAS. Materials and MethodsA total of 316 surgically resected lung adenocarcinoma cases were analyzed retrospectively. Detailed analyses were performed on clinical-histological-molecular features. Tumor STAS was defined as tumor cells within air spaces in the lung parenchyma beyond the edge of the main tumor. ResultsSTAS was observed in 160 cases (50.6%). STAS was significantly related to lymphovascular invasion, lymph node metastasis, higher stage, and high-grade histologic subtype. STAS was frequently found in tumors with wild-type EGFR or ALK-rearrangement. Logistic regression analysis showed that STAS was significantly associated with absence of lepidic component, presence of micropapillary component, cribriform predominant type, lymphovascular invasion, and wild-type EGFR. Multivariate survival analysis demonstrated that STAS was independently associated with shorter recurrence-free survival. STAS was also associated with recurrences to extrathoracic sites as well as intrathoracic sites. ConclusionSTAS is associated with certain pathological and molecular subtypes. STAS might be a parameter for tumor aggressiveness in that it is strongly associated with poor prognostic factors and recurrence, including to extrathoracic sites.

Preponderance of High-Grade Histologic Subtype in Autologous Metastases in Lung Adenocarcinoma.

Preponderance of High-Grade Histologic Subtype in Autologous Metastases in Lung Adenocarcinoma.

P1.03-084 Implications of 8th Edition TNM Proposal: Invasive vs. Total Size for T Descriptor in pT1a-2bN0M0 Lung Adenocarcinoma

The aim of this study was to conduct a clinicopathological comparative analysis of total tumor versus invasive tumor size in pT1a-2bN0M0 nonmucinous lung adenocarcinomas. Resected pT1a-2bN0M0 lung adenocarcinomas (1995-2012) based on 8th edition of TNM classification using total (N=1475) and invasive tumor size (N=1482) were included. Recurrence free probability [RFP] and lung cancer-specific survival [LCSS]) were compared between both pT-staging systems using Kaplan-Meier method. Use of invasive size for the T descriptor increased the number of pT1a tumors by 2 fold compared to use of total tumor size (316 vs. 161), with no difference in RFP and LCSS (RFP, 82% vs. 80%; LCSS, 94% vs. 93%). Use of invasive rather than total size also showed better stratification of lymphatic/vascular invasion and high-grade histological subtypes according to increasing pT stage. RFP and LCSS in invasive-size-based pT2b were lower than those in total-size-based pT2b (RFP, 44% vs. 60%; LCSS, 69% vs. 77%). In pT1a-2bN0M0 nonmucinous lung adenocarcinoma, the 8th edition TNM proposal to use invasive rather than total size for the pT descriptor gives better prognostic discrimination by capturing a larger number of patients with favorable prognosis (pT1a) and providing better stratification for pT2b.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

MA12.08 Clinicopathological Significance of Increasing Percentage of High-Grade Histological Subtypes in Lung Adenocarcinomas

MA12.08 Clinicopathological Significance of Increasing Percentage of High-Grade Histological Subtypes in Lung Adenocarcinomas

Intraoperative Radiation Therapy for Locally Advanced and Recurrent Soft-Tissue Sarcomas in Adults

To analyze the outcomes of and identify prognostic factors for patients treated with surgery and intraoperative radiotherapy (IORT) for locally advanced and recurrent soft-tissue sarcoma in adults from a single institution. We retrospectively reviewed 50 consecutive patients treated with IORT to 62 sites of disease. Primary sites included retroperitoneum-pelvis (78%), extremity (8%), and other (14%). Seventy percent of patients had recurrent disease failing prior surgery (70%) and/or radiation (32%). Mean disease-free interval (DFI) before IORT was 1.9 years (range, 2 weeks-5.4 years). The IORT was delivered with orthovoltage X-rays using individually sized beveled cone applicators. Clinical characteristics were as follows: mean tumor size, 10 cm (range, 1-25 cm); high-grade histologic subtype (72%); and mean dose, 1,159 cGy (range, 600-1,600 cGy). Postoperative radiation or chemotherapy was administered to 37% of IORT Sites and 32% of patients, respectively. Outcomes measured were infield control (IFC), locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and treatment-related complications. Mean and median follow-up of alive patients were 59 and 35 months, respectively. Kaplan-Meier 5-year IFC, LRC, DMFS, and DSS probabilities for the entire group were 55%, 26%, 51%, and 25%, respectively. Prognostic factors found to be significant (p < 0.05) on multivariate analysis were prior DFI and tumor size for LRC, extremity location and leiomyosarcoma histologic subtype for DMFS, and prior DFI for DSS. Our cohort had five Grade 3/4 complications associated with treatment or a 5-year Kaplan-Meier Grade 3/4 complication-free survival rate of 85%. IORT after tumor reductive surgery is well tolerated and seems to confer IFC in carefully selected patients.

Radioimmunoscintigraphy (RIS) with Bectumomab (Tc99m Labeled IMMU-LL2, Lymphoscan®) in the Assessment of Recurrent Non-Hodgkin's Lymphoma (NHL)

The efficacy of a Tc99m-labeled anti-lymphoma antibody fragment, bectumomab [LymphoScan], was retrospectively examined in the staging of recurrent or newly diagnosed non-Hodgkin's lymphoma (NHL) [7 patients] and to assess targeting before radioimmunotherapy (RIT) [14 patients]. Performance was graded relative to conventional imaging. Tumors included 7 low-grade, 11 intermediate-grade, and 3 high-grade histologic subtypes. Computed x-ray tomography, radiogallium imaging, FDG-PET, and bone marrow biopsy defined 117 sites. Bectumomab revealed 56% of these sites. In 4 patients bectumomab uncovered five sites not evident by conventional imaging. In addition, it uncovered one site in the brain, an area not covered in the standard work-up of asymptomatic patients. Bectumomab imaging most often failed in central abdominal and thoracic locations, and excelled in revealing disease in the head and neck. Relative to Ga67 citrate imaging, the performance of bectumomab was variable, with no clear relation to anatomic location; there was better targeting of low and intermediate grade NHL. Radiogallium out-performed bectumomab imaging in 23 sites, 19 of which were in patients with high or intermediate-grade disease. Bectumomab was superior to radiogallium at six sites, five of which involved low-grade tumor. Bectumomab shows promise as a pre-RIT probe for targeting of B-cell NHL. It excelled at defining small volume, low-grade disease. However, as a purely diagnostic agent, its performance was variable.

Non-Hodgkinʼs Lymphoma

Non-Hodgkin's lymphomas (NHL) represent a heterogenous group of diseases including low, intermediate and high grade histological subtypes. Most entities are sensitive to chemotherapy and radiotherapy. However, most relapsed patients are incurable with conventional treatment. The major reason for unsatisfactory long-term results in NHL is tumour cells that persist after standard treatment. New sensitive techniques have been developed to detect occult lymphoma cells. These cells might be eradicated by new immunotherapeutic agents with different modes of action, such as cytokines or antibody-based agents. In NHL, most experience has been accumulated with interferon-alpha, which seems to be effective against minimal residual disease (MRD). The experience with interleukin-2 and interleukin-3 is less convincing. Monoclonal antibodies have been used in their native form, or conjugated with radioisotopes or toxins to selectively destroy lymphoma cells. Such immunotoxins and radioisotope-coupled antibodies have shown promising results in early clinical trials, and are now being evaluated in patients with smaller tumour burdens.

Posttransplantation lymphoproliferative disorders in bone marrow transplant recipients are aggressive diseases with a high incidence of adverse histologic and immunobiologic features.

Posttransplantation lymphoproliferative disorders (PT-LPDs) occurring in T-cell depleted (TCD) allogeneic bone marrow transplant recipients seem to be different from those that arise in solid organ recipients in their early development, the high incidence of extensive dissemination at presentation, and their aggressive course and high fatality rate. We report a series of 10 patients with PT-LPDs after TCD allogeneic bone marrow transplant. We studied the correlation between the morphology of the lesions; their clonality based on immunoglobulin (Ig) heavy chain gene rearrangement analysis and immunohistochemistry; their proliferative activity as measured by immunoperoxidase staining for the proliferating cell nuclear antigen (PCNA) and the presence of p53 gene product overexpression. Histologically, our cases corresponded to the two morphologic categories of polymorphic B-cell lymphoma (PBCL, seven cases) and malignant lymphoma immunoblastic (ML-IB, three cases). Ig light-chain staining showed monoclonality in a minority of the cases, whereas Ig gene rearrangement analysis by polymerase chain reaction revealed B-cell clonality in three of seven cases of PBCL and in all three cases of ML-IB. The Epstein-Barr virus (EBV) genome, the expression of EBV latent membrane protein or both were found in all 10 specimens. High proliferative activity (PCNA > or = 66%) was found in all cases, with a mean PCNA value of 56% in PBCL and 84% in ML-IB. Five specimens were p53+ (two of seven PBCL and three of three ML-IB). Two of four PBCL cases resolved with the administration of donor leukocytes. All of the remaining patients died of the PT-LPD within a short time from admission. Our results show that the PT-LPDs after TCD bone marrow transplantation are characterized by a high frequency of high-grade histologic subtypes, frequent monoclonality, high proliferative activity, frequent overexpression of p53 gene product, and poor prognosis. These characteristics observed in only a minority of cases of PT-LPDs occurring after solid organ transplantation may account for the less aggressive clinical behavior observed in those diseases.

Durability of remission after ABMT for NHL: the importance of the 2-year evaluation point

Few series describing the results of autologous bone marrow transplantation (ABMT) for the treatment of non-Hodgkin's lymphoma report mature follow-up. We retrospectively reviewed 110 adults with NHL treated with ABMT from 1988 to 1993. Overall survival and relapse-free survival were 50% and 35%, respectively. Estimated median relapse-free survival was 16 months. There was no statistically significant difference in relapse-free or overall survival by low, intermediate, and high-grade histologies, as defined by the International Working Formulation. The most powerful negative prognostic variable was an elevated LDH at the time of transplant (relapse-free survival 17% vs 42% for those with a normal LDH). Forty-seven patients were in complete remission 2 years after transplant. Extended follow-up revealed that 100% of patients with high-grade histologies remained in complete remission, whereas patients with intermediate-grade and low-grade histologies remained at risk of relapse with longer follow-up. Of 22 patients with diffuse large cell lymphoma (LCL) or immunoblastic (IBL) histologies, eight of eight with IBL remain in continued remission, while four of 14 with LCL relapsed 24-48 months after ABMT. We conclude that patients with high-grade histologic subtypes of NHL who are in complete remission 2 years after ABMT are likely to be cured. However, patients with intermediate and low-grade histologic subtypes are at continued risk of relapse and require appropriate clinical surveillance for at least 48 months after ABMT.

Lymphomas of the oral soft tissues are not preferentially associated with latent or replicative Epstein-Barr virus

Epstein-Barr virus is periodically shed in the saliva of persons infected by the virus. Epstein-Barr virus has been implicated in the pathogenesis of certain subtypes of lymphoma, particularly high-grade lymphomas. Because high-grade subtypes represent the majority of lymphomas that arise in oral soft tissues, we hypothesized that Epstein-Barr virus might be preferentially associated with oral lymphomas. A series of 34 oral lymphomas were diagnosed according to the revised European-American classification scheme. They were examined for the presence of latent Epstein-Barr virus by EBER1 in situ hybridization and for expression of the Epstein-Barr virus replicative protein, BZLF1, by immunohistochemistry. Epstein-Barr virus EBER1 transcripts were detected in 11 of 31 oral lymphomas including 7 of 10 AIDS-related lymphomas and only 4 of 21 lymphomas that occurred in nonimmunocompromised persons. The Epstein-Barr virus-containing lymphomas were all high-grade histologic subtypes, that is, diffuse large cell, immunoblastic, or Burkitt's lymphomas. In contrast, Epstein-Barr virus was not detected in any of five low-grade oral lymphomas. In the single case of T-cell lymphoma in this study, EBER1 was expressed in the tumor cells. A switch from viral latency to replication, as measured by EBV BZLF1 expression, was identified in rare lymphoma cells in only four cases. This rate of viral replication was not higher than what has been reported in lymphomas arising at other anatomic sites. Although one of our lymphomas arose at a site of previous oral hairy leukoplakia, there was no other evidence that Epstein-Barr virus replication predisposed to development or persistence of oral lymphomas. These data suggest that even though Epstein-Barr virus is frequently found in oral secretions, neither latent nor replicative Epstein-Barr virus is present more commonly in oral lymphomas than in lymphomas arising in other anatomic sites, when controlling for immunodeficiency status.

Primary gastric lymphoma: a clinical and therapeutic evaluation of 82 patients.

Eighty-two patients with primary gastric (IE, II1E, and II2E) non-Hodgkin's lymphoma according to the Musshoff's staging system were treated with combined modality including surgery with/without radiotherapy between January 1985 and December 1991. According to the Updated Kiel classification 54 had high-grade histologic subtypes and 28 low-grade. The strategy throughout the study was to resect primary tumor: all patients underwent gastrectomy, 40 subtotal and 42 total gastrectomy. The resection permitted complete surgical staging utilizing three pathologic features: disease confined within or beyond the serosa, negative/positive regional lymph nodes, and negative/positive surgical margins. If there was no evidence of these pathologic factors, the patients who underwent surgery alone received no further radiotherapy. On the other hand, all patients who presented at least one of three pathologic factors were treated with adjuvant radiotherapy after the resection. All except 14 patients presented at least one of the pathologic features and 50 (61%) patients had involvement of the whole gastric wall. Radiotherapy included the gastric bed and para-aortic lymph nodes and, for the patients, who had positive regional lymph nodes in combination with the complete involvement of the gastric wall, the irradiation included the whole abdominal approach. The complete response rate was 97% and the 9-year disease-free survival was 93%. All but one of the 5 relapses occurred within 18 months stressing the need for more specific staging. Gastric resection with/without radiotherapy may still represent the primary therapeutic procedure in early stage gastric non-Hodgkin's lymphoma.

Renal involvement in patients with non‐Hodgkin's lymphoma: Clinical and pathological features in 23 cases

Twenty-three cases of renal or perirenal involvement by non-Hodgkin's lymphoma were identified from a retrospective review of computed tomography (CT) scans performed on patients at St Bartholomew's Hospital over an 8-year period. The histology, clinical features and survival of these patients were examined. Eighteen of the 23 patients had high grade histological subtypes according to the Kiel classification. The majority of cases were identified from scans performed at the time of presentation. In nine cases renal lymphoma was observed in the absence of detectable retroperitoneal lymphadenopathy. Staging was rarely altered by the finding of renal lymphoma as 21 of the 23 patients had involvement of other extranodal sites in addition to the kidney. Survival did not appear to be adversely affected by the presence of renal lymphoma at the time of initial diagnosis. During the same period no cases of renal involvement were identified in patients with Hodgkin's disease, although one patient had perirenal involvement.

Pulmonary Emboli in Patients Receiving Chemotherapy for Non-Hodgkin's Lymphoma

Combination chemotherapy has dramatically improved the prognosis of patients with intermediate and high grade histologic subtypes of non-Hodgkin's lymphomas. Treatment-related complications, however, are considerable, and a common problem encountered is respiratory distress or respiratory insufficiency. Usually these difficulties have been attributed to infectious etiologies or to chemotherapy-induced interstitial fibrosis, most often involving bleomycin. We describe five patients presenting with respiratory problems several weeks after the initiation of chemotherapy. These patients, who represent 3 percent of all patients treated with a single bleomycin-containing regimen for intermediate or high grade non-Hodgkin's lymphoma, were all initially thought to have chemotherapy-induced interstitial fibrosis but were found on subsequent evaluation to have pulmonary emboli. Of the three patients in whom pulmonary emboli were diagnosed antemortem, two had symptoms suggestive of pulmonary emboli and all were successfully treated and remained well and free of lymphoma for over 24 months. Two additional patients were diagnosed at autopsy. We suggest that pulmonary emboli may contribute significantly to the morbidity and mortality of patients undergoing chemotherapy for non-Hodgkin's lymphoma and recommend that patients presenting with respiratory difficulties be evaluated for pulmonary emboli.