Extranodal Presentation Research Articles

Hairy cell leukemia with an atypical extranodal presentation: A clinicopathological analysis of four cases

Hairy cell leukemia with an atypical extranodal presentation: A clinicopathological analysis of four cases

An unusual presentation of unifocal Rosai-Dorfman disease and surgical treatment

Rosai-Dorfman disease (RDD) is a rare histiocytic disorder with an unclear aetiology, and commonly presents with painless, bilateral cervical lymphadenopathy. Extranodal presentation in the absence of nodal involvement has been reported to have a predilection for the head and neck with less than 20 cases involving the jaw bones and sinuses. We present an interesting case of unifocal RDD of the infratemporal space in the absence of nodal involvement in a 61-year-old female treated with surgical excision and adjuvant radiation therapy.

Clinicopathological and genetic landscape of plasmablastic lymphoma in Taiwan

Plasmablastic lymphoma (PBL) is an aggressive large B-cell lymphoma with a terminal B-cell differentiation phenotype and is frequently associated with immunodeficiency. We aimed to investigate the clinicopathological and immunophenotypic features, genetic alterations, and mutational landscape of PBL in Taiwan. We retrospectively recruited 26 cases. Five (5/18; 28%) patients were HIV-positive and 21 (81%) presented extranodally. There were two morphological groups: one with purely monomorphic large cells (85%) and the other comprising large cells admixed with plasmacytic cells (15%). Phenotypically, the tumors expressed MYC (8/10; 80%), CD138 (20/26; 77%), and MUM1 (20/20; 100%), but not CD20 (n = 26; 0%). Fourteen (54%) cases were positive for EBV by in situ hybridization; the EBV-positive cases were more frequently HIV infected (p = 0.036), with extranodal presentation (p = 0.012) and CD79a expression (p = 0.012), but less frequent light chain restriction (p = 0.029). Using fluorescence in situ hybridization, we identified 13q14 deletion, MYC rearrangement, and CCND1 rearrangement in 74%, 30%, and 5% cases, respectively, without any cases having rearranged BCL6 or IGH::FGFR3 fusion. In the 15 cases with adequate tissue for whole exome sequencing, the most frequent recurrent mutations were STAT3 (40%), NRAS (27%), and KRAS (20%). In conclusion, most PBL cases in Taiwan were HIV-unrelated. Around half of the cases were positive for EBV, with distinct clinicopathological features. Deletion of chromosome 13q14 was frequent. The PBL cases in Taiwan showed recurrent mutations involving JAK-STAT, RAS-MAPK, epigenetic regulation, and NOTCH signaling pathways, findings similar to that from the West.

Primary Pulmonary Diffuse Large B-Cell Lymphoma - a Rare Case Report

Background: Diffuse large B cell lymphoma (DLBCL) is an aggressive hematological malignancy, and a common histological form of non-Hodgkin's lymphoma. However, its extra-nodal presentation is seen in 30-40% of cases with involvement of gastrointestinal tract, skin, testes, adrenals and bone. ( Lugogo NL et al., 2006) A pulmonary manifestation is an extremely rare entity. We present an atypical case of DLBCL presenting as pleuritic chest pain with imaging consistent with bilateral pulmonary nodules suggestive of metastasis. Case description: A healthy 87 year old male former smoker with a history of type 2 diabetes mellitus, hypertension presented to the emergency department with pleuritic chest pain. There was no associated cough, shortness of breath, palpitations, nausea, dizziness or diaphoresis. No recent infections or B symptoms. He had a good appetite. He had prostate cancer 20 years ago and had a radical prostatectomy. Upon presentation, work up showed mild anemia (Hb 11.1 g/dL). Cardiac work up for chest pain was unremarkable. Chest X-Ray revealed mass like opacities in each lung with largest in left mid lung measuring up to 6 cm. CT chest with IV contrast revealed multiple lung nodules bilaterally with 2 largest in left upper lobe measuring 5.6 x 3.7 cm and 5.7 x 3.3 cm. Multiple other small nodules are present in both lung fields consistent with diffuse lung metastasis. No lymphadenopathy was noted. (Image 1) PET CT scan was significant for bilateral FDG avid lung lesions. No evidence of other FDG avid disease. CT guided biopsy of the left lung mass surprisingly revealed diffuse large B cell non-Hodgkin's lymphoma, non-germinal center type. (Image 1) Immuno-histochemistry showed atypical lymphocytes positively stained with CD20, BCL6, BCL2, PAX5 and MUM1. C-myc had 50% positivity. Ki67 had 90% proliferative index. FISH analysis was negative for MYC, BCL2 and BCL6; hence there was no double hit lymphoma detected. According to Lunago classification, patient had advanced stage disease with IPI (prognosis index) of 2. His ECOG PS score was 0. He was initiated on R-Pola-CHP. Given his age, Cyclophosphamide and Adriamycin doses were reduced as done with R-mini CHOP. Vincristine was avoided given neurotoxicity. Discussion: Primary pulmonary B-cell lymphomas (PP-BCLs) represent less than 3-4% of all extra-nodal NHL. They primarily affect the lung without evidence of extrapulmonary disease at the time of diagnosis. PP-DLBCL accounts for only 10% cases of PP-BCLs. ( Sanguedolce et al., 2021) Most cases have atypical presentation. Likewise, in our patient, he manifested with atypical chest pain without any B symptoms. Radiographic imaging can show variable findings of consolidation, single/multiple nodules, reticular interstitial infiltrate or bilateral ground glass opacities. In view of the insidious onset and lack of specificity in clinical symptoms, primary pulmonary lymphomas are frequently misdiagnosed as refractory pneumonia, lung abscess, asthma, primary lung cancer, or lung metastasis. ( Liu et al., 2020) Patients with DLBCL are typically treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). However, with this regimen, only 60% of patients are cured and the rest might relapse. In the POLARIX phase 3 trial, polatuzumab vedotin (a monoclonal antibody to CD79b ubiquitously expressed on B cells) combined with R-CHP significantly improved 2 year progression-free survival compared to the routine R-CHOP therapy in previously untreated DLBCL patients. ( Tilly et al., 2022) Given our patient's advanced stage disease, he was initiated on the Pola-R-CHP regimen. Doses of cyclophosphamide and doxorubicin were reduced as per the R-mini CHOP dose-reduced regimen for a physically fit elderly individual. Patient continues on therapy at the time of this abstract. In conclusion, primary pulmonary DLBCL is a rare entity with only a few case reports in literature. It should be considered in patients presenting with large pulmonary masses, mimicking metastatic disease.

Primary Ovarian Non-Hodgkin's Lymphoma: An 18-year Retrospective Institutional Study and Review of Literature from India.

Primary lymphomas of the female reproductive tract are rare and the ovarian extranodal presentation of non-Hodgkin's lymphoma (NHL) accounts for only 0.5% of all NHLs and 1.5% of all ovarian malignancies. We retrospectively reviewed the institutional medical oncology database for newly diagnosed NHL cases between 1999 and 2017. We aimed to study the clinical characteristics, pathology, and outcome of primary ovarian non-Hodgkin's lymphoma (NHL) cases presented to our institution. Weidentified three patients (3.7% of extranodal NHLs and 0.85% of all NHL patients) with primary ovarian NHL from 350 NHL patient records. They underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by six to eight cycles of (rituximab, adriamycin, cyclophosphamide, vincristine, prednisolone (R-CHOP/CHOP), and they attained complete remission. Given the heterogeneity of cancer incidence in India and the absence of state-wise cancer registries, our study argues a pressing need to develop a national representative registry for NHL for accurate incidence, mortality, and survival data. Additionally, fertility preservation is an important issue that must be discussed with women of fertile age and the parents of children.

Extranodal presentation of a MYC/BCL6 double-hit lymphoma with 11q aberration in an older patient

Extranodal presentation of a MYC/BCL6 double-hit lymphoma with 11q aberration in an older patient

ABCL-200 Primary and Secondary Extranodal Diffuse Large B-Cell Lymphoma: A Single-Center Survey from India

Approximately 30% of all non-Hodgkin lymphoma (NHL) cases arise from extranodal sites and almost half of them have diffuse large B-cell lymphoma (DLBCL) histology. Not only does the extranodal presentation require a site-specific diagnostic or therapeutic approach, but there is geographical variability in the overall frequency of extranodal presentation as well. To estimate the distribution of sites of extranodal DLBCL in patients treated at a tertiary care center in north India. This retrospective study was conducted at Dr. Bhim Rao Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi. Case files of patients (age >18 years) diagnosed with DLBCL at our institute between 2014 and 2018 were retrospectively studied and their sites of disease involvement were surveyed. A total of 550 patients were diagnosed with DLBCL during the study period, including 244 (44.3%) with nodal disease, 224 (40.7%) with extranodal involvement, and 82 (14.9%) with primary extranodal disease. A total of 306 (55.63%) patients have extranodal involvement, either primary or secondary. Among patients with primary extranodal DLBCL (n=82), the most common sites were gastrointestinal (n=36, 43.90%); the stomach was the most common region followed by the central nervous system (n=11, 13.4%), bone (n=8, 9.7%), head and neck area (n=7, 8.5%), breast (n=6, 7.3%), testis (n=4, 4.8%), and liver (n=4, 4.8%). The less commonly involved sites included the spleen (n=2, 2.4%), and one patient (1.2%) each had involvement in the prostate, pancreas, adrenal, and ovary. Bone was the most common site of secondary extranodal involvement observed in 32% of patients followed by gastrointestinal involvement in 30% of cases. Parallel to the incidence of DLBCL, the incidence of extranodal involvement, including primary and secondary extranodal presentation, is high in India. Bone is the most common site for secondary extranodal involvement, and the upper gastrointestinal system (stomach) is the most common site of primary extranodal lymphoma.

S2007 Chronic Lymphocytic Leukemia Presenting as Colonic Ulcers

Introduction: Chronic Lymphocytic Leukemia (CLL) accounts for 25% of leukemias. One can present with hepatomegaly, splenomegaly, and lymphadenopathy. CLL infiltration in the gastrointestinal (GI) mucosa is rare. Colonic CLL can develop late in the disease course with mild to no GI symptoms. Awareness of CLL and its various extra-nodal presentations allow for prompt diagnosis and treatment. Case Description/Methods: An 80-year-old female with untreated CLL presented with 2 months of rectal bleeding. She denied weight loss, anorexia, night sweats, blood thinners, and NSAID use. She had WBC 34.3, platelets 139, and a normal Hgb of 13.2. Colonoscopy showed ulcerations at the ileocecal valve and transverse colon, a 30 mm ascending colon polyp, and multiple 10-20 mm transverse and descending colon polyps. Pathology showed only chronic inflammation of the ulcerated regions, and a sessile serrated adenoma at the ascending colon. The remaining polyps were not removed due to concern for cancer and potential colectomy. A CT chest, abdomen, and pelvis was unremarkable. Tumor markers showed CEA 8 and normal Ca19-9 and Ca-125. Due to an unclear diagnosis, a second colonoscopy was performed with repeat biopsies and removal of all polyps in the descending and sigmoid colon. Pathology results were negative for inflammatory bowel disease and infection. The polyps were tubular adenomas and hyperplastic. However, immunohistochemical analysis was positive for CD5/CD43 and CD23, indicative of CLL in the ulcerated mucosa. Treatment options were discussed with surgery and oncology. The patient was offered right colon resection or endoscopic removal of the remaining polyps prior to chemotherapy (Figure). Discussion: Colorectal lymphomas are rare and account for 1% of all GI malignancies with CLL usually found proximal to the hepatic flexure. In this case, the presence of ulcerations and large polyps were concerning for colorectal cancer. However, the initial work-up was negative. After a repeat colonoscopy, testing for specific CLL markers was requested. In a review of literature, chemotherapy alone for colonic CLL had a perforation risk of 15%. While it is unclear if surgical treatment is beneficial, it is a potential option. Due to the high risk of perforation on chemotherapy, recommendations included right hemicolectomy or endoscopic removal of the remaining polyps prior to starting treatment. This demonstrates the importance of knowing the varying presentations of colonic CLL as its treatment may require multidisciplinary discussion.Figure 1.: Colonic ulcers located at the transverse colon (top left) and IC valve (top right). H&E stain of the colonic mucosa (bottom) that showed positive markers for CLL on IHC analysis.

NON-HODGKIN LYMPHOMA IN A MALE BREAST:A CASE REPORT

Breast lymphoma is a rare clinicopathological condition and can affect both sexes. Around 1% of all malignant breast tumours occur in males. The most common tumors of breast are ductal and lobular carcinomas. Extranodal presentation 1 can be seen in around one-third of patients of NHL. Breast involvement is a rare finding of extranodal lymphoma because of paucity of lymphoid tissue in breast. Breast lymphomas comprise about 0.4-0.5 % of all malignant tumors of breast, 0.38-0.7 % of all lymphomas and 1.7- 2.2 % of all 2 extranodal lymphoma. Breast lymphomas might present either as a primary presentation or as expression of systemic lymphoma. Around 44% of breast lymphomas are primary, 22% present with disseminated disease and 29% comprise 3 recurrence of pre-existing lymphomas.

Extranodal presentation in limited-stage diffuse large Bcell lymphoma as a prognostic marker in three SWOG trials S0014, S0313 and S1001.

Not available.

P1180: ARE EXTRANODAL LIMITED-STAGE DIFFUSE LARGE B-CELL LYMPHOMA MORE AGRESSIVE THAN NODAL FORMS?

Background: Limited-stage diffuse large B-cell lymphoma (DLBCL) is associated with favourable outcomes with overall survival of 70-80% at 10 years. Stage-modified IPI (sm-IPI) predicts the risk of relapse and death based on clinical factors that do not include extranodal (EN) involvement, although in some studies it has been associated with worse outcomes. Aims: To analyse the characteristics and outcomes of limited-stage DLBCL in a single center series and evaluate the prognostic impact of EN involvement. Methods: We conducted a retrospective analysis of consecutive patients with newly diagnosed stage I-II DLBCL treated with curative intent at a single centre from 2015 to 2019. Primary central nervous system (CNS) lymphoma, primary testicular lymphoma, primary mediastinal B-cell lymphoma and transformed lymphoma were excluded. Response to therapy was assessed according to Lugano criteria. Overall (OS) and progression free survival (PFS) were calculated by Kaplan-Meier method and comparisons done by the log rank test. Cumulative incidence of relapse was calculated using competing risk models and Gray test for group comparisons. Cox regression was used to identify prognostic factors for PFS. Results: Of 152 patients identified, 53 (35%) had EN disease and 99 (65%) were nodal (N). The most common EN sites were stomach (30%), sinus/nasal cavity (13%), skin and soft tissue (9%) and breast (9%). Seventy-two (47%) had low risk sm-IPI (45 N; 27 EN). Clinical characteristics were similar between both groups, except for stage (stage I in 50.9% of EN vs 32.3% of N cases) and bulky disease (EN 15.1% vs N 37.4%). All patients received R-CHOP (median 6 cycles; range 1-8). Eight patients, all with EN involvement (3 sinus/nasal cavity, 2 breast, 2 bone and 1 orbit), received CNS prophylaxis. Seventeen out of 152 patients received additional radiotherapy (RT), 71% of whom had nodal involvement; 16/17 were irradiated due to bulky disease and/or treatment with abbreviated immunochemotherapy. Globally, 89% patients had a complete response (CR) to treatment: 85% in the N and 96% in the EN group (p=0.212). Nine patients relapsed at a median of 18 (7-52) months after obtaining CR (6 from the N and 3 from the EN group). The 4-year cumulative incidence of relapse was similar: 11.2% (95%CI 9.0-13.9%) in EN and 6.7% (95%CI 5.9-7.5%) in N group (p=0.778). No gastric lymphomas relapsed. The most common sites of relapse were lymph nodes (3), soft tissue (3) and CNS (2). Nineteen (14 N; 5 EN) patients died at a median of 12 (0-47) months after starting treatment, mostly (52.6%) due to lymphoma progression. With a median follow-up of 43 months, 4-year OS and PFS were 87% and 82%, respectively. No significant survival differences were observed in patients with N or EN presentation with a 4-year PFS of 81.8% and 81.3% (p=0.428), respectively. On multivariable analysis adjusting for RT, sm-IPI and bulky disease, EN involvement was not associated with a decreased PFS compared with N involvement (HR 0.77; 95%CI 0.31-1.90; p=0.570). Image:Summary/Conclusion: Our study corroborates the very favourable outcomes of localized DLBCL. We could not find differences in PFS according to N and EN presentations when controlling for other prognostic factors. These results do not support different treatment strategies for EN disease; however, due to limited sample size the role of RT and the prognostic impact of specific locations cannot be fully ascertained.

Unexpected Rare Association of Secondary Breast, Thyroid, and Ovarian Lymphomas in a Female Patient with Burkitt Lymphoma: PET-CT Findings.

We report the case of a 15-year-old female, followed for Burkitt lymphoma with initial ovarian presentation. Positron emission tomography-computed tomography (PET-CT) with 18 F-fluorodeoxyglucose ( 18 F-FDG) performed to evaluate initial extension assessment showed an unexpected association with secondary breast, thyroid, and ovarian lymphomas. To our knowledge, this association is very rare, unusual, and these extranodal presentations have been reported in literature as a separate case report. Authors highlight performance of PET-CT with 18 F-FDG to determinate the secondary origin of this multiglandular involvement, to establish a lesional map of the whole body, and to contribute to the therapeutic decision.

Nodular lymphocyte predominant Hodgkin lymphoma with T-cell/histiocyte - rich large B-cell lymphoma pathohistological characteristics and extranodal presentation: Case report and literature review

Nodular lymphocyte predominant Hodgkin lymphoma appears in 5% of Hodgkin lymphoma. Because of major biological and clinical differences with classical Hodgkin lymphoma and close relationship to T-cell/histiocyte-rich large B-cell lymphoma, lately the term nodular lymphocyte predominant B-cell lymphoma is accepted. The presence of lymphocyte predominant cells with preserved B-cell phenotype and a lack of CD30 is the prerequisite for the diagnosis of nodular lymphocyte predominant Hodgkin lymphoma. Lymphocyte predominant cells are typically embedded in large nodules of B lymphocytes (growth patterns A and B), but variants that are characterized by lymphocyte predominant cells located outside the nodules, a Tcell- rich nodular growth pattern and T-cell-rich or B-cell-rich diffuse growth patterns, respectively, have also been described (growth patterns C, D, E, and F). Variant growth patterns are associated with the recurrence and progression of disease and should be recognized and specified in pathology reports. Broad B-cell immunohistochemical panel, including PAX5, CD79a, Bob.1, and Oct-2 is indicated in these cases to distinguish between nodular lymphocyte predominant Hodgkin lymphoma, classical Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma, which have significant differences in clinical behavior and treatment. There are different treatment approaches in patients with nodular lymphocyte predominant Hodgkin lymphoma depending on pathohistological type, clinical presentation and stage of the disease. Treatment may include active surveillance, radiation therapy, immunotherapy or chemotherapy. A multidisciplinary approach is beneficial to optimize the diagnosis and management of patients with nodular lymphocyte predominant Hodgkin lymphoma.

Immunohistochemical Characterisation of Cell of Origin in Diffuse Large B-cell Lymphoma and its Association with the Double Expressor Phenotype: A Retrospective Study

Introduction: Diffuse Large B-cell Lymphoma (DLBCL) is the most common type of Non Hodgkin Lymphoma (NHL) and is categorised into the Germinal Centre B-cell (GCB) and Activated B-cell (ABC/Non GCB) subtypes as per the Cell Of Origin (COO) model with the help of gene expression profiling/ immunohistochemistry. The non GCB subtype has been found to associate with the Double Expressor (DE) phenotype (i.e., co-expression of BCL-2 and c-myc by IHC and this association was substantiated and proven to be statistically significant in the present study. Aim: To categorise all DLBCL cases into GCB and Non GCB and further into DE and Non-DE by using Hans and Choi IHC alogrithm. Materials and Methods: A retrospective study of 50 patients was carried out with the help of archival material filed in the Department of Anatomic Pathology at Dharamshila Narayana Superspeciality Hospital, New Delhi, India from 1st January 2019 to 30th June 2020. The study was approved by Instituitional Ethics Committee (IEC). Chi-square test and Yates correction were used for statistical analysis. Results: The study cohort was divided into two Groups- group-A with nodal presentation and group-B with extranodal presentation. By using the Hans and Choi IHC algorithms, the cases were categorised into the GCB and non GCB subtypes in both the groups. The DE phenotype was determined in each case by the co-expression of c-myc (>40%) and BCL-2 (>50%) by IHC. By using the statistical chi-square test analysis and Yates correction, the association of DE was found to be statistically significant with non GCB type lymphomas and non DE with GCB lymphomas with p-value being 0.0005 and 0.00168, respectively. Conclusion: Due to the heterogeneity inherent in DLBCL, prediction of the DE phenotype and the COO by IHC is a sensitive tool and helps in the prognostication and therapeutic triage of patients. Hence, in all the cases diagnosed as DLBCL, a detailed morphological and IHC work up is mandatory to determine prognosis and possibly tailor therapy according to COO and DE phenotype.

Extranodal Presentation in Limited Stage DLBCL As a Prognostic Marker in Three Sequential SWOG Trials S0014, S0313 and S1001 (NCT00005089, NCT00070018, NCT01359592)

Extranodal Presentation in Limited Stage DLBCL As a Prognostic Marker in Three Sequential SWOG Trials S0014, S0313 and S1001 (NCT00005089, NCT00070018, NCT01359592)

Central Nervous System Involvement in Extranodal Natural Killer/T-Cell Lymphoma: Case Series

▪Introduction：Extranodal NK/T-cell lymphoma, nasal type (NKTCL) is an aggressive subtype of non-Hodgkin lymphoma that is characterized by extranodal presentation. Central nervous system (CNS) involvement in NKTCL is very rare and carries dismal outcome, but lacks clear consensus on optimal treatment. This study summarized the clinicopathological features, treatment patterns and survival outcomes of NKTCL patients with CNS involvement, in order to improve the understanding of CNS involvement in NKTCL.Methods: 1019 patients diagnosed with extranodal NKTCL, from August 2010 to January 2021 were reviewed, and patients with CNS involvement were included in the analysis. The CNS involvement was diagnosed either pathologically or clinically. Due to the difficulties and potential hazards of brain biopsy, pathologic confirmation of CNS involvement was conducted by identifying malignant cells in the cerebrospinal fluid (CSF) by cytology and flow cytometry analysis. Clinically diagnosed CNS involvement was based upon the characteristic radiographic findings by magnetic resonance imaging (MRI), computed tomography (CT) or positron emission tomography (PET/CT), Circulating EBV-DNA was detected by quantitative polymerase chain reaction (PCR). Overall survival (OS) was defined as time from confirmation of CNS disease to death from any cause or last follow up.Results: Among 1019 patients diagnosed with NKTCL, 14 cases (1.3%) with CNS involvement were included. The general characteristics of these patients are listed in Table 1. Of these 14 patients, the median age was 40.5 years (range, 14-57 years) at the time of diagnosis of CNS involvement. Approximately 71.4%(10/14）of patients were men. The median time between initial diagnosis of NKTCL and diagnosis of CNS involvement was 3.0 months (range, 0-141.0 months). 5 patients suffered CNS involvement at initial diagnosis of NKTCL. The other 9 CNS involvement were identified as disease progression. All patients underwent radiological examination, which disclosed the lesion location in CNS of 9 patient. The other 5 patients were diagnosed with CNS involvement by the examination of CSF. The elevated protein concentration and leukocytosis in CSF were identified in 8 and 2 patients, respectively. Among these patients with CNS involvement, the median number of treatment lines after the diagnosis of CNS involvement was 1.5 (range, 1-4). The best response was complete response (CR) in 11 patients, partial response (PR) in 1 patient, stable disease in 1 patient and progressive disease in 1 patient. CR was achieved when patients were treated with pegaspargase- containing regimens(n=4), anti-PD-1 antibodies-containing regimens(n=3), chidamide-containing regimens(n=2) and HD-MTX-containing regimens(n=2). After achieving CR, 2 patients received anti-PD-1 antibodies as maintenance treatment, with the duration of response of 26 and 72 months, respectively. With the median follow-up of 24.5 months (range, 4-72 months), 5 patients died of NKTCL, and the median OS was not reached. 9 patients presented with high circulating EBV-DNA level at diagnosis of CNS involvement, and the post-treatment EBV-DNA descended to the normal level in 7 patients, among whom 6 patients achieved CR.Conclusions: The incidence of CNS involvement in NKTCL is low. Compared with previous studies, more patients received anti-PD-1 antibodies- and chidamide-containing regimens, which may contribute to the improved response rate and survival outcomes. Measurement of dynamic changes in EBV-DNA levels during the treatment process can be applied to monitor the treatment response. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Atypical involvement of central nervous system in classic Hodgkin lymphoma: a case report

BackgroundHodgkin lymphoma is a systemic disease that commonly involves the cervical, supraclavicular, and mediastinal lymph nodes. The involvement of central nervous system in Hodgkin lymphoma is extremely rare, and diagnosis is usually established using distinct morphological and immunohistochemical staining on the tissue biopsied. Extranodal presentation of HL is a rare occurrence. It has been evident that prognosis is encouraging in patients with disease that is limited to just central nervous system initially or as relapse, compared with involvement of multiple sites of relapse.Case presentationWe herein report a case of a 35-year-old South-East Asian male with relapsed Hodgkin lymphoma. The patient developed a parotid gland lesion, cervical lymphadenopathy with significant weight loss, and intermittent night sweats. Along with spread to the central nervous system, there was a high suspicion of tuberculosis. Upon biopsy of his cervical lymph node, the patient was confirmed to have Hodgkin lymphoma. Immediate treatment began with six cycles of chemotherapy consisting of adriamycin, bleomycin, vinblastine, and dacarbazine. The patient received three cycles of chemotherapy consisting of ifosfamide, carboplatin, and etoposide but then was lost to follow-up. Five years later, the patient suffered a road traffic accident. Upon work-up, a right parietal space-occupying lesion with moderate cerebral edema and midline shift was found on computed tomography of the brain. The patient underwent resection of the space-occupying lesion of brain, with features consistent with classical Hodgkin lymphoma on histopathology examination. It is crucial for such lesions to be investigated meticulously to rule out any secondary disease process.ConclusionRelapsed Hodgkin lymphoma with central nervous system involvement is relatively rare with just over two dozen cases reported to date and is observed infrequently in developing nations. Therefore, space-occupying lesion should always be investigated, and biopsy of such lesions is gold standard to establish diagnosis. With timely appropriate therapy, complete remission can be achieved. However, large-scale studies would be prudent to explore the presentation, survival, and treatment options for patients with Hodgkin lymphoma involving the central nervous system.

PULMONARY ROSAI-DORFMAN DISEASE WITH NO LYMPH NODE INVOLVEMENT

TOPIC: Lung Pathology TYPE: Fellow Case Reports INTRODUCTION: Histiocytosis is a disorder when a collection of hematopoietic-derived cells multiply without regulation but is not considered malignant. The most recent classification was laid out by the World Health Organization in 2016 dividing them into multiple groups. Rosai-Dorfman disease typifies the R group and is unique in its presentation ranging from a solitary lesion or multifocal, systemic disease. CASE PRESENTATION: A 74-year-old male of African descent with a past medical history significant for tobacco abuse presented to the emergency department with hemoptysis that started 2 days prior to presentation. Patient was seen as outpatient due to hemoptysis in the past and CT chest showed a 4.2 cm mass in the left lower lobe, no lymphadenopathy; confirmed by another CT Chest in the emergency department. PET/CT at that time showed the mass had increased 18-FDG uptake with SUV 26.4. There was very high suspicion for lung carcinoma and bronchoscopy showed a friable, bleeding, pedunculated mass occupying LLL basal segmental airway. The mass was removed using a snare and forceps and the tumor base was cauterized with argon plasma coagulation. Pathology report of the mass showed proliferation of histocytes with immunostaining positive for S100 and CD68, but negative for CD1a consistent with the diagnosis of Rosai-Dorfman disease. The patient was started on definitive radiation therapy with resolution of his symptoms. DISCUSSION: Rosai-Dorfman disease (RDD) is a rare histiocytosis that is characterized as being multisystemic. First described in 1969 by Rosai and Dorfman, this was described as self-limiting painless lymph node enlargement seen in teenagers and young adults. Our patient presented in his late 70's and was of African descent. Recent publications coming from China with 25 cases of RDD showed that extranodal presentation less common in Asians compared to white/black patients, and the mean age was 45 years old. Pulmonary involvement of RDD usually involves mediastinal lymphadenopathy which our patient did not have; the PET/CT showed the disease was limited to the mass in the left lower lobe. Differentiating RDD with this presentation from malignant lung disease, especially on a patient with significant smoking history, is challenging. Histopathology will give the diagnosis - in RDD S-100 and CD68 are the common positive markers with negative CD1a ruling out Langerhans cell histiocytosis. Treatment with radiation therapy is described for localized disease-causing symptoms, our patient has had a good response with resolution of his symptoms. CONCLUSIONS: RDD is very rare to present in lungs alone with no lymphadenopathy and this presentation is difficult to differentiate from malignancy. Diagnosis is based on tissue sampling with immunohistochemistry staining characterized by (+) S-100 and CD68 with (-) CD1a. Radiation therapy is an effective treatment for symptomatic localized disease. REFERENCE #1: Abla O, Janka G. Histiocytic Disorders Cham: Springer International Publishing AG; 2017:30-33 REFERENCE #2: Ali A, Mackay D. Rosai-Dorfman disease of the lung. Thorax. 2009;64(10):908-909 REFERENCE #3: Kong Y, Kong J, Shi D et al. Cutaneous Rosai-Dorfman disease a clinical and histopathologic study of 25 cases in China. The American journal of surgical pathology. 2007;31(3):341-350 DISCLOSURES: No relevant relationships by Alfredo Iardino, source=Web Response No relevant relationships by Jill Ono, source=Web Response No relevant relationships by Arthur Oliver Romero, source=Web Response No relevant relationships by Ipsita Samanta, source=Web Response

ABCL-265: Detection of Triple Protein Expression in Diffuse Large B-Cell Lymphoma (DLBCL): A Single-Center Study

Background DLBCL is the most common type of NHL. Genetic studies have revealed that one molecular subtype that is resistant to treatment by standard protocols occurs when there are concurrent translocations in the c-Myc, BCL-2, and BCL-6 genes. Objective Our study aimed to detect the presence of triple protein expression in patients diagnosed with DLBCL at the Clinical Oncology Department in Menoufia University Hospital. We also aimed to explore the possible associations between c-Myc, BCL-2, and BCL-6 co-expression (TEL) and clinical, as well as epidemiological, data of included patients. Patients and Methods A tissue microarray platform was constructed using cores from selected areas of each specimen. 2-mm-diameter cores were duplicated and spaced 0.2 mm apart. Several four-micron-thick sections were prepared from blocks. Hematoxylin and eosin slides were reviewed to confirm pathological diagnosis according to criteria defined by WHO, and immunohistochemistry was used for the detection of c-Myc, BCL-2, and BCL-6 expression. Stained slides were assessed for the percentage of cellular expression for each marker. Median expression was used as the threshold value for defining high and low expression for each marker. DLBCL with high expression for c-Myc, BCL-2, and BCL-6 was defined as TEL. Results Tissue microarray blocks were constructed from paraffin blocks of 94 cases with confirmed diagnoses of DCBL. The median age for participants was 56 years. c-Myc, BCL-2, and BCL-6 showed high protein expression in 51% (n=47), 55% (n=51), and 52.7% (n=49), respectively. Median-based triple protein expression constituted 15% of the sample (n=14). TEL was significantly higher in patients with poor ECOG performance status (PS >2), extranodal presentation, and bone marrow infiltration. No associations between TEL and other patient or disease characteristics (age, gender, smoking history, family history, comorbidities, B symptoms, LDH, B2 microglobulin, stage, IPI, IPI risk group, and baseline neutrophil-lymphocyte ratio) were found. Conclusion Triple protein expression lymphoma is not uncommon among the studied sample, constituting around 45.1% of cases. This positive protein expression was commonly found in patients with poor performance status, creating a particular need for new treatment modalities.

Transferability Of Results From Randomized Trials To Clinical Practice: The Case Of Diffuse Large B Cell Lymphoma Patients Treated With R-CHOP When Comorbidities Are Present

BackgroundImmuno-chemotherapy with Rituximab and CHOP (R-CHOP) represents the standard of care for Diffuse Large B Cell Lymphoma DLBCL patients of any age. The clinical outcome of patients treated by this program has been reproducibly confirmed by many independent randomized clinical trials that recruited patients on the basis of restrictive inclusion/exclusion criteria. Few information is available about the short and long term outcome of patients who, in the daily clinical practice, are treated by R-CHOP despite the presence of one or more co-morbidities that should have been considered as exclusion criteria for the aforementioned clinical trials. AimTo evaluate the response rate, the early death as well as overall survival of DLBCL patients who received a front-line R-CHOP or R-CHOP/like programs despite the presence at diagnosis of one or more severe comorbidities. PatientsFrom April 2000 to March 2013 we evaluated 473 consecutive and unselected DLBCL homogeneously treated at our institution with R-CHOP or R-CHOP/like as first line treatment. These patients were males in 53%, had a median age of 64 years (range 18 -89), clinical stage III-IV in 54%, B symptoms in 31%, bone marrow involvement in 14%, Bulky disease (> 7 cm) in 34%, Extranodal presentation (>1 site) in 30%, ECOG (>2) in 25%, a high LDH level in 48% and high IPI (>2) in 42%. For the present analysis, patients were divided in group A (n=257) and B (n=216) according to whether they met or not clinical trial enrollment criteria respectively (as reported by Cunningham et al, Lancet 2013). Reasons for not meeting these criteria were the following organ dysfunctions: cardiovascular (75%), liver (35%), lung (14 %) and renal (5%) or the presence of a positive serology for HCV, HBV and HIV that were detected in 73%, 38% of and 10% of these patients, respectively. Of note, 41 patients (8%) had a previous solid tumor. Overall 63% of patients had only one comorbidity, 30% more than two and 6% more than three. ResultsGender and patients with bulky disease were equally distributed between group A and B. However, patients belonging to group A were younger (58 vs 70, p=0.0001), had a less advanced stage disease (stage III and IV 46% vs 54, p= 0,001), fewer B symptoms (45% vs 55%, p= 0,024), less BM infiltration (34% vs 65%, p= 0,002), less extranodal involvement (42% vs 57%, p= 0,004) and showed a better performance status (ECOG >2 41% vs 59%, p= 0,005), a lower proportion of cases with high LDH level (46% vs 54%, p= 0,002) and a better IPI (IPI >2, 40% vs 60%, p= 0,000). After 6 chemotherapy cycles, the response rate was slightly lower in group B (82% vs 89%, p=ns). The proportion of early deaths (events registered within 6 months from start of chemotherapy), was lower in group A (7/257, 2.7%) as compared to group B (22/216, 10.2%, p=0.001), independently of age (> or<60 year). Of note, the early death rate in group A reproduced that seen in several randomized clinical trials. Main reasons of early death were: bacterial infections, acute liver failure, myocardial infarction and progressive disease. The median time to early death was 1.8 months in group A as compared to 2.35 in group B (p= ns), respectively. By multivariate logistic regression analysis, corrected by age, IPI and bone marrow positivity, the presence of B symptoms (OR 3.32, 95% CI 1.23-9.01, p= 0.018) and the presence of any comorbidity (OR 3.13, 95% CI 1.07-9.14, p= 0.037) proved as strongly independent predictors of early deaths. The 2 year probability of overall survival was 87% and 72% (p= 0.0001) in group A and B, respectively (Figure 1). B symptoms, and the presence of any comorbidity and IPI >2 were also significantly affecting the long term overall survival (B symptoms, HR 1.59, 95% CI 1.04-2.43; any comorbidity, HR 1.71, 95% CI 1.12-2.61; IPI >2, HR 2.38, 95% CI 1.48-3.82). Based on this analysis, we finally identified three risk categories: low (no B symptoms, no comorbidity and no high IPI), intermediate (presence of either B symptoms or any comorbidity or high IPI) and high (co-presence of B symptoms, any comorbidity and High IPI) that were associated to a significantly different 2 year survival of 93%, 81% and 48% (p= 0.0000), respectively. ConclusionsThe clinical outcome of a large proportion of DLBCL patients treated in the daily clinical practice is negatively affected by comorbidities. This should be considered when analyzing transferability of results from randomized clinical trials into clinical practice. [Display omitted] Disclosures:Rambaldi:Roche, SpA, Italy: Consultancy, Honoraria.